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1.
PLoS One. 2020 Jan 15;15(1):e0227867. doi: 10.1371/journal.pone.0227867. eCollection 2020.
Factors related to met needs for rehabilitation 6 years after stroke.
Ytterberg C1,2,3, Kristensen HK3,4, Tistad M1,5, von Koch L1,2.

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Abstract

INTRODUCTION:

Research on stroke rehabilitation mainly concerns the first year of recovery, and there is a lack of knowledge regarding long-term rehabilitation needs and associated factors.
AIM:

The aim was to explore the perceived needs for rehabilitation services of people six years after stroke and factors associated with having rehabilitation services needs met.
METHODS:

The study was a 6-year follow up of a prospective study on the rehabilitation process after stroke. Data on perceived needs for rehabilitation, personal factors, disease specific factors, and patient-reported disability were collected through face-to-face interviews in the participants' homes. Logistic regression models were created to explore associations between having rehabilitation services needs met in 11 problem areas (dependent variable) and the independent variables: involvement in decisions regarding care and treatment, sex, age, sense of coherence, self-defined level of private financing, stroke severity, frequency of social everyday activities, perceived impact of stroke, and life satisfaction.
RESULTS:

The 121 participants had a mean age of 63 years at stroke onset and 58% were men. In all problem areas the majority (53-88%) reported having needs met at six years after stroke, however 47% reported unmet needs regarding fatigue and 45% regarding mobility. A lower perceived impact on participation was found to be associated with having rehabilitation services needs met in seven problem areas: mobility, falls, pain, fatigue, concentration, memory, and sight. The strongest association for having needs met was found for the independent variable, involvement in care and treatment, within the three problem areas mobility, falls, and speaking.
CONCLUSION:

In a long-term perspective, there were several modifiable factors associated with having rehabilitation services needs met. The most prominent were perceived involvement in care and treatment, and perceived participation. These factors had a stronger association with having rehabilitation services needs met than disease specific factors six years after stroke.
PMID: 31940423 DOI: 10.1371/journal.pone.0227867

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Select item 319404222.
PLoS One. 2020 Jan 15;15(1):e0227623. doi: 10.1371/journal.pone.0227623. eCollection 2020.
Economic compensation interventions to increase uptake of voluntary medical male circumcision for HIV prevention: A systematic review and meta-analysis.
Kennedy CE1, Yeh PT1, Atkins K1, Fonner VA2, Sweat MD2, O'Reilly KR2, Rutherford GW3, Baggaley R4, Samuelson J4.

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Abstract

BACKGROUND:

Economic compensation interventions may help support higher voluntary medical male circumcision (VMMC) coverage in priority sub-Saharan African countries. To inform World Health Organization guidelines, we conducted a systematic review of economic compensation interventions to increase VMMC uptake.
METHODS:

Economic compensation interventions were defined as providing money or in-kind compensation, reimbursement for associated costs (e.g. travel, lost wages), or lottery entry. We searched five electronic databases and four scientific conferences for studies examining the impact of such interventions on VMMC uptake, HIV testing and safer-sex/risk-reduction counseling uptake within VMMC, community expectations about compensation, and potential coercion. We screened citations, extracted data, and assessed risk of bias in duplicate. We conducted random-effects meta-analysis. We also reviewed studies examining acceptability, values/preferences, costs, and feasibility.
RESULTS:

Of 2484 citations identified, five randomized controlled trials (RCTs) and three non-randomized controlled trials met our eligibility criteria. Studies took place in Kenya, Malawi, South Africa, Tanzania, Uganda, Zambia, and Zimbabwe. Meta-analysis of four RCTs showed significant impact of any economic compensation on VMMC uptake (relative risk: 5.23, 95% CI: 3.13 to 8.76). RCTs of food/transport vouchers and conditional cash transfers generally showed increases in VMMC uptake, but lotteries, subsidized VMMC, and receiving a gift appeared somewhat less effective. Three non-randomized trials showed mixed impact. Six additional studies suggested economic compensation interventions were generally acceptable, valued for addressing key barriers, and motivating to men. However, some participants felt they were insufficiently motivating or necessary; one study suggested they might raise community suspicions. One study from South Africa found a program cost of US$91 per additional circumcision and US$450-$1350 per HIV infection averted.
CONCLUSIONS:

Economic compensation interventions, particularly transport/food vouchers, positively impacted VMMC uptake among adult men and were generally acceptable to potential clients. Carefully selected economic interventions may be a useful targeted strategy to enhance VMMC coverage.
PMID: 31940422 DOI: 10.1371/journal.pone.0227623

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Select item 319404213.
PLoS One. 2020 Jan 15;15(1):e0227646. doi: 10.1371/journal.pone.0227646. eCollection 2020.
Liganded T3 receptor β2 inhibits the positive feedback autoregulation of the gene for GATA2, a transcription factor critical for thyrotropin production.
Hirahara N1, Nakamura HM2, Sasaki S2, Matsushita A2, Ohba K3, Kuroda G2, Sakai Y2, Shinkai S2, Haeno H4, Nishio T5, Yoshida S5, Oki Y6, Suda T2.

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Abstract


The serum concentration of thyrotropin (thyroid stimulating hormone, TSH) is drastically reduced by small increase in the levels of thyroid hormones (T3 and its prohormone, T4); however, the mechanism underlying this relationship is unknown. TSH consists of the chorionic gonadotropin α (CGA) and the β chain (TSHβ). The expression of both peptides is induced by the transcription factor GATA2, a determinant of the thyrotroph and gonadotroph differentiation in the pituitary. We previously reported that the liganded T3 receptor (TR) inhibits transactivation activity of GATA2 via a tethering mechanism and proposed that this mechanism, but not binding of TR with a negative T3-responsive element, is the basis for the T3-dependent inhibition of the TSHβ and CGA genes. Multiple GATA-responsive elements (GATA-REs) also exist within the GATA2 gene itself and mediate the positive feedback autoregulation of this gene. To elucidate the effect of T3 on this non-linear regulation, we fused the GATA-REs at -3.9 kb or +9.5 kb of the GATA2 gene with the chloramphenicol acetyltransferase reporter gene harbored in its 1S-promoter. These constructs were co-transfected with the expression plasmids for GATA2 and the pituitary specific TR, TRβ2, into kidney-derived CV1 cells. We found that liganded TRβ2 represses the GATA2-induced transactivation of these reporter genes. Multi-dimensional input function theory revealed that liganded TRβ2 functions as a classical transcriptional repressor. Then, we investigated the effect of T3 on the endogenous expression of GATA2 protein and mRNA in the gonadotroph-derived LβT2 cells. In this cell line, T3 reduced GATA2 protein independently of the ubiquitin proteasome system. GATA2 mRNA was drastically suppressed by T3, the concentration of which corresponds to moderate hypothyroidism and euthyroidism. These results suggest that liganded TRβ2 inhibits the positive feedback autoregulation of the GATA2 gene; moreover this mechanism plays an important role in the potent reduction of TSH production by T3.
PMID: 31940421 DOI: 10.1371/journal.pone.0227646

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Select item 319404204.
PLoS One. 2020 Jan 15;15(1):e0227814. doi: 10.1371/journal.pone.0227814. eCollection 2020.
Pre-collecting lymphatic vessels form detours following obstruction of lymphatic flow and function as collecting lymphatic vessels.
Asano K1,2, Nakajima Y3, Mukai K3, Urai T4, Okuwa M3, Sugama J5, Konya C6, Nakatani T3.

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Abstract

BACKGROUND:

Previously, we showed that lymphatic vessels (LVs) formed detours after lymphatic obstruction, contributing to preventing lymphedema. In this study, we developed detours using lymphatic ligation in mice and we identified the detours histologically.
METHODS AND RESULTS:

Under anesthesia, both hindlimbs in mice were subcutaneously injected with Evans blue dye to detect LVs. We tied the right collecting LV on the abdomen that passes through the inguinal lymph node (LN) at two points. The right and left sides comprised the operation and sham operation sides, respectively. Lymphography was performed to investigate the lymph flow after lymphatic ligation until day 30, using a near-infrared fluorescence imaging system. Anti-podoplanin antibody and 5-ethynyl-2'-deoxyuridine (EdU) were used to detect LVs and lymphangiogenesis. Within 30 days, detours had developed in 62.5% of the mice. Detours observed between two ligation sites were enlarged and irregular in shape. Podoplanin+ LVs, which were located in the subcutaneous tissue of the upper panniculus carnosus muscle, connected to collecting LVs at the upper portion from the cranial ligation site and at the lower portion from the caudal ligation site. EdU+ cells were not observed in these detours. The sham operation side showed normal lymph flow and did not show enlarged pre-collecting LVs until day 30.
CONCLUSIONS:

Detours after lymphatic ligation were formed not by lymphangiogenesis but through an enlargement of pre-collecting LVs that functioned as collecting LVs after lymphatic ligation. Further studies are required to explore the developmental mechanism of the lymphatic detour for treatment and effective care of lymphedema in humans.
PMID: 31940420 DOI: 10.1371/journal.pone.0227814

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Select item 319404195.
PLoS One. 2020 Jan 15;15(1):e0227857. doi: 10.1371/journal.pone.0227857. eCollection 2020.
Staging dementia based on caregiver reported patient symptoms: Implications from a latent class analysis.
Yuan Q1, Tan TH1, Wang P1, Devi F1, Ong HL1, Abdin E1, Harish M2, Goveas R2, Ng LL3, Chong SA1, Subramaniam M1,4.

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Abstract

BACKGROUND:

Tailoring interventions to the needs of caregivers is an important feature of successful caregiver support programs. To improve cost-effectiveness, group tailoring based on the stage of dementia could be a good alternative. However, existing staging strategies mostly depend on trained professionals.
OBJECTIVE:

This study aims to stage dementia based on caregiver reported symptoms of persons with dementia.
METHODS:

Latent class analysis was used. The classes derived were then mapped with disease duration to define the stages. Logistic regression with receiver operating characteristic curve was used to generate the optimal cut-offs.
RESULTS:

Latent class analysis suggested a 4-class solution, these four classes were named as early (25.9%), mild (25.2%), moderate (16.7%) and severe stage (32.3%). The stages based on the cut-offs generated achieved an overall accuracy of 90.8% compared to stages derived from latent class analysis.
CONCLUSION:

The current study confirmed that caregiver reported patient symptoms could be used to classify persons with dementia into different stages. The new staging strategy is a good complement of existing dementia clinical assessment tools in terms of better supporting informal caregivers.
PMID: 31940419 DOI: 10.1371/journal.pone.0227857

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Select item 319404186.
PLoS One. 2020 Jan 15;15(1):e0227773. doi: 10.1371/journal.pone.0227773. eCollection 2020.
The impact of computed radiography and teleradiology on patients' diagnosis and treatment in Mweso, the Democratic Republic of Congo.
Crumley I1, Halton J1, Greig J2, Kahunga L3, Mwanga JP3, Chua A4, Kosack C1.

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Abstract

INTRODUCTION:

High quality diagnostic imaging can provide increased diagnostic accuracy and help guide medical decision-making and management, however challenges for radiology in resource-limited settings are numerous. Diagnostic imaging and teleradiology have financial and logistical implications, so evidence of impact is crucial. We sought to test the hypothesis that the implementation of computed radiography with teleradiology consultation support will significantly change diagnoses and treatment plans in a resource limited setting.
METHOD:

Paired before-after study to determine the therapeutic impact of an add-on diagnostic test. 'Preliminary Plan' and 'Final Plan' forms allowed direct comparison of diagnosis and treatment plans at initial consultation and following radiography and teleradiology. Consecutive consenting patients were included until the sample size (600) was reached. Changes in both diagnosis and treatment plan were analysed in the whole cohort, with sub-analyses of children aged <5 years, and cases of chest radiography.
RESULTS:

Final analysis included 536 cases. Diagnosis changed following radiography and teleradiology in 62% of cases, and treatment plans changed in 61%. In chest radiography cases, 70% of diagnoses and 62% of treatment plans changed, while in children <5 years 66% of diagnoses and 58% of treatment plans changed. Reduced final treatment plans were most common for exploratory surgery (72% decrease), surgical orthopaedic intervention (62% decrease), and TB treatment (52% decrease), allowing more conservative medical or surgical management in 61 cases. Increased final treatment plans were highest in the orthopaedic and interventional surgery and referral categories. Of 42 cases requiring interventional surgery in the final plan, 26 (62%) were identified only after radiography and teleradiology. 16 additional cases were indicated for orthopaedic surgery, 10 cases required patient transfer, and TB treatment was indicated in 45 cases. A change in the original prescription plan occurred in 41% of 536 cases, with one or more prescriptions stopped in 28% of all cases.
CONCLUSION:

We found that computed radiography with teleradiology had significant clinical value in this resource-limited setting, with the potential to affect both patient outcomes and treatment costs through providing improved diagnostics and avoiding unnecessary treatments and medications.
PMID: 31940418 DOI: 10.1371/journal.pone.0227773

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Select item 319404177.
PLoS One. 2020 Jan 15;15(1):e0227822. doi: 10.1371/journal.pone.0227822. eCollection 2020.
In vivo expression of peptidylarginine deiminase in Drosophila melanogaster.
Mahneva O1, Risley MG1,2, John C1, Milton SL1, Dawson-Scully K1, Ja WW3,4.

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Abstract


Peptidylarginine deiminase (PAD) modifies peptidylarginine and converts it to peptidylcitrulline in the presence of elevated calcium. Protein modification can lead to severe changes in protein structure and function, and aberrant PAD activity is linked to human pathologies. While PAD homologs have been discovered in vertebrates-as well as in protozoa, fungi, and bacteria-none have been identified in Drosophila melanogaster, a simple and widely used animal model for human diseases. Here, we describe the development of a human PAD overexpression model in Drosophila. We established fly lines harboring human PAD2 or PAD4 transgenes for ectopic expression under control of the GAL4/UAS system. We show that ubiquitous or nervous system expression of PAD2 or PAD4 have minimal impact on fly lifespan, fecundity, and the response to acute heat stress. Although we did not detect citrullinated proteins in fly homogenates, fly-expressed PAD4-but not PAD2-was active in vitro upon Ca2+ supplementation. The transgenic fly lines may be valuable in future efforts to develop animal models of PAD-related disorders and for investigating the biochemistry and regulation of PAD function.
PMID: 31940417 DOI: 10.1371/journal.pone.0227822

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Select item 319404168.
PLoS One. 2020 Jan 15;15(1):e0227851. doi: 10.1371/journal.pone.0227851. eCollection 2020.
Expression of concern: Compensatory increase of transglutaminase 2 is responsible for resistance to mTOR inhibitor treatment.
PLOS ONE Editors.
PMID: 31940416 DOI: 10.1371/journal.pone.0227851

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Select item 319404159.
PLoS One. 2020 Jan 15;15(1):e0227837. doi: 10.1371/journal.pone.0227837. eCollection 2020.
Chemical analysis of snus products from the United States and northern Europe.
Lawler TS1, Stanfill SB1, Tran HT1, Lee GE2, Chen PX3, Kimbrell JB3, Lisko JG1, Fernandez C1, Caudill SP1, deCastro BR1, Watson CH1.

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Abstract

INTRODUCTION:

Snus is an oral tobacco product that originated in Sweden. Snus products are available as fine-cut loose tobacco or in pre-portioned porous "pouches." Some snus products undergo tobacco pasteurization during manufacturing, a process that removes or reduces nitrite-forming microbes, resulting in less tobacco-specific nitrosamine content in the product. Some tobacco companies and researchers have suggested that snus is potentially less harmful than traditional tobacco and thus a potential smoking cessation aid or an alternative to continued cigarette consumption. Although snus is available in various countries, limited information exists on snus variants from different manufacturers.
METHODS:

Moisture, pH, nicotine, and tobacco-specific N'-nitrosamines (TSNAs) were quantified in 64 snus products made by 10 manufacturers in the United States and Northern Europe (NE). Reported means, standard errors, and differences are least-square (LS) estimates from bootstrapped mixed effects models, which accounted for correlation among repeated measurements. Minor alkaloids and select flavors were also measured.
RESULTS:

Among all product types, moisture (27.4%-59.5%), pH (pH 5.87-9.10), total nicotine (6.81-20.6 mg/g, wet), unprotonated nicotine (0.083-15.7 mg/g), and total TSNAs (390-4,910 ng/g) varied widely. The LS-mean unprotonated nicotine concentration of NE portion (7.72 mg/g, SE = 0.963) and NE loose (5.06 mg/g, SE = 1.26) snus were each significantly higher than US portion snus (1.00 mg/g, SE = 1.56). Concentrations of minor alkaloids varied most among products with the highest total nicotine levels. The LS-mean NNN+NNK were higher in snus sold in the US (1360 ng/g, SE = 207) than in NE (836 ng/g, SE = 132) countries. The most abundant flavor compounds detected were pulegone, eucalyptol, and menthol.
CONCLUSION:

Physical and chemical characteristics of US and NE products labeled as snus can vary considerably and should not be considered "equivalent". Our findings could inform public health and policy decisions pertaining to snus exposure and potential adverse health effects associated with snus.
PMID: 31940415 DOI: 10.1371/journal.pone.0227837

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Select item 3194041410.
PLoS One. 2020 Jan 15;15(1):e0227628. doi: 10.1371/journal.pone.0227628. eCollection 2020.
Spatial and climatic variables independently drive elevational gradients in ant species richness in the Eastern Himalaya.
Marathe A1,2, Priyadarsanan DR1, Krishnaswamy J1, Shanker K1,3.

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Abstract


Elevational gradients are considered important for understanding causes behind gradients in species richness due to the large variation in climate and habitat within a small spatial extent. Geometric constraints are thought to interact with environmental variables and influence elevational patterns in species richness. However, the geographic setting of most mountain ranges, particularly continuity with low elevation areas may reduce the effect of geometric constraints at lower elevations. In the present study, we test the effects of climatic gradients and continuity with the low elevation plains of the eastern Himalayan mountain range on patterns of species richness. We studied species richness of ants (Hymenoptera: Formicidae) on an elevational gradient between 600m and 2400m in the Eastern Himalaya-part of Himalaya biodiversity hotspot. Ants were sampled in nine elevational bands of 200m with four transects in each band using pitfall and Winkler traps. We used regression models to identify the most important environmental variables that predict species richness and used constrained null models to test the effects of contiguity between the mountain range and plains. We find a monotonic decline in species richness of ants with elevation. Temperature was a more important predictor of species richness than habitat complexity. Geometric constraints model weighted by temperature with a soft lower boundary and hard upper boundary best explained the species richness pattern. This suggests that a combination of climate and geometric constraints drive the elevational species richness patterns of ants.
PMID: 31940414 DOI: 10.1371/journal.pone.0227628

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Select item 3194041311.
PLoS One. 2020 Jan 15;15(1):e0227440. doi: 10.1371/journal.pone.0227440. eCollection 2020.
Relation of fibroblast growth factor receptor 2 expression to hepatocellular carcinoma recurrence after liver resection.
Jun BG1, Lee WC2, Jang JY2, Jeong SW2, Chang Y2, Lee SH3, Kim YD1, Kim SG4, Cheon GJ1, Kim YS4, Kim HS3, Jin SY5.

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Abstract

BACKGROUND:

Hepatocellular carcinoma (HCC) recurrence after liver resection depends upon the stage and histological grade of the tumor and the expression of certain biomarkers. However, it remains unclear which of these factors has the highest predictive value regarding HCC recurrence after surgical resection.
METHODS:

This study investigated the associations among clinicopathological characteristics, expression of biomarkers, and HCC recurrence after liver resection. Fifty-four patients having undergone liver resection for HCC were enrolled prospectively, and their data were analyzed retrospectively. Evaluated variables were clinical data, laboratory findings, modified Union for International Cancer Control (UICC) stage, vascular invasion, histological differentiation, and immunohistochemical staining for fibroblast growth factor receptor 2 (FGFR2), vascular endothelial growth factor, and tumor-necrosis-factor-related apoptosis-inducing ligand receptors 1 and 2.
RESULTS:

Mean patient age was 58.6 years (range, 30-71), and the mean and SD for follow-up duration were 51.2 ± 34.8 months. Cumulative 1-, 3-, and 5-year recurrence rates were 32.9%, 53.6%, and 68.1%, respectively. In univariate analysis, FGFR2 (p = 0.026) and Edmonson-Steiner grade (E-S grade) (p = 0.030) were associated with recurrence after resection in HCC patients. In multivariate analyses, increased FGFR2 expression (p = 0.017) was the only significant predictor of HCC recurrence.
CONCLUSIONS:

High FGFR2 expression had marginal association with poor E-S grade (p = 0.056). More intensive surveillance of HCC recurrence is warranted in HCC patients with increased FGFR2 expression.
PMID: 31940413 DOI: 10.1371/journal.pone.0227440

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Select item 3194041212.
PLoS One. 2020 Jan 15;15(1):e0227735. doi: 10.1371/journal.pone.0227735. eCollection 2020.
Wind energy development and wildlife conservation in Lithuania: A mapping tool for conflict assessment.
Morkūnė R1, Marčiukaitis M2, Jurkin V1,3, Gecevičius G4, Morkūnas J1,5, Raudonikis L5, Markevičius A2, Narščius A1, Gasiūnaitė ZR1,3.

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Abstract


The paper presents a mapping tool aiming to identify and minimise potential conflicts between onshore wind energy development and wildlife conservation in Lithuania. It merges current information on the distribution, conservation status and sensitivity of birds and bats to wind power with an integrated evaluation of wind resources (modelled wind speed), special planning status and technical perspectives of wind energy development. The paper includes assessment of the selected wildlife species which were described as sensitive to wind power (69 breeding and 43 migratory bird species and 17 bat species bats in the country). Used species level information allowed the precise identification of sensitive territories and might be used to mitigate negative wind farm effects using special measures based on species behavior. Finally, we delivered overlaps as possible conflicts among the most promising wind farm areas and the areas with high sensitivity in relation to bird and bat distribution. These overlaps point to the required attention and relevant decisions that are needed to ensure sustainable development of wind energy throughout the country. We suggest this tool for initial determination of appropriate areas for wind energy development in the country and as supplement to Environmental Impact Assessment.
PMID: 31940412 DOI: 10.1371/journal.pone.0227735

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Select item 3194041113.
PLoS One. 2020 Jan 15;15(1):e0227603. doi: 10.1371/journal.pone.0227603. eCollection 2020.
Mitochondrial DNA variations and mitochondrial dysfunction in Fanconi anemia.
Solanki A1, Rajendran A2, Mohan S3, Raj R3, Vundinti BR1.

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Abstract


In-vitro studies with different Fanconi anemia (FA) cell lines and FANC gene silenced cell lines indicating involvement of mitochondria function in pathogenesis of FA have been reported. However, in-vivo studies have not been studied so far to understand the role of mitochondrial markers in pathogenesis of FA. We have carried out a systematic set of biomarker studies for elucidating involvement of mitochondrial dysfunction in disease pathogenesis for Indian FA patients. We report changes in the mtDNA number in 59% of FA patients studied, a high frequency of mtDNA variations (37.5% of non-synonymous variations and 62.5% synonymous variations) and downregulation of mtDNA complex-I and complex-III encoding genes of OXPHOS (p<0.05) as strong biomarkers for impairment of mitochondrial functions in FA. Deregulation of expression of mitophagy genes (ATG; p>0.05, Beclin-1; p>0.05, and MAP1-LC3, p<0.05) has also been observed, suggesting inability of FA cells to clear off impaired mitochondria. We hypothesize that accumulation of such impaired mitochondria in FA cells therefore may be the principal cause for bone marrow failure (BMF) and a plausible effect of inefficient clearance of impaired mitochondria in FA.
PMID: 31940411 DOI: 10.1371/journal.pone.0227603

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Select item 3194041014.
PLoS One. 2020 Jan 15;15(1):e0227647. doi: 10.1371/journal.pone.0227647. eCollection 2020.
Characterization of METTL16 as a cytoplasmic RNA binding protein.
Nance DJ1, Satterwhite ER1, Bhaskar B1, Misra S1, Carraway KR1, Mansfield KD1.

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Abstract


mRNA modification by N6-methyladenosine (m6A) is involved in many post-transcriptional regulation processes including mRNA stability, splicing and promotion of translation. Accordingly, the recently identified mRNA methylation complex containing METTL3, METTL14, and WTAP has been the subject of intense study. However, METTL16 (METT10D) has also been identified as an RNA m6A methyltransferase that can methylate both coding and noncoding RNAs, but its biological role remains unclear. While global studies have identified many potential RNA targets of METTL16, only a handful, including the long noncoding RNA MALAT1, the snRNA U6, as well as the mRNA MAT2A have been verified and/or studied to any great extent. In this study we identified/verified METTL16 targets by immunoprecipitation of both endogenous as well as exogenous FLAG-tagged protein. Interestingly, exogenously overexpressed METTL16 differed from the endogenous protein in its relative affinity for RNA targets which prompted us to investigate METTL16's localization within the cell. Surprisingly, biochemical fractionation revealed that a majority of METTL16 protein resides in the cytoplasm of a number of cells. Furthermore, siRNA knockdown of METTL16 resulted in expression changes of a few mRNA targets suggesting that METTL16 may play a role in regulating gene expression. Thus, while METTL16 has been reported to be a nuclear protein, our findings suggest that METTL16 is also a cytoplasmic methyltransferase that may alter its RNA binding preferences depending on its cellular localization. Future studies will seek to confirm differences between cytoplasmic and nuclear RNA targets in addition to exploring the physiological role of METTL16 through long-term knockdown.
PMID: 31940410 DOI: 10.1371/journal.pone.0227647

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Select item 3194040915.
PLoS One. 2020 Jan 15;15(1):e0227765. doi: 10.1371/journal.pone.0227765. eCollection 2020.
Knowledge, beliefs, and concerns about bone health from a systematic review and metasynthesis of qualitative studies.
des Bordes J1, Prasad S2, Pratt G3, Suarez-Almazor ME1, Lopez-Olivo MA1.

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Abstract

BACKGROUND:

Patients with low bone density or osteoporosis need information for effective prevention or disease management, respectively. However, patients may not be getting enough information from their primary care providers or other sources. Inadequate disease information leaves patients ill-informed and creates misconceptions and unnecessary concerns about the disease.
OBJECTIVE:

We systematically reviewed and synthesized the available literature to determine patient knowledge, beliefs, and concerns about osteoporosis and identify potential gaps in knowledge.
METHODS:

A systematic search was conducted for full-text qualitative studies addressing understanding, literacy, and/or perceptions about osteoporosis and its management, using Medline, EMBASE, Web of Science, Cochrane Library, CINAHL, ERIC, PsychINFO, Psyc Behav Sci Collec, and PubMed, from inception through September 2016. Studies were selected by two reviewers, assessed for quality, and themes extracted using the Joanna Briggs Institute data extraction tool. Thematic analysis was used to identify themes and subthemes.
RESULTS:

Twenty-five studies with a total of 757 participants (including 105 men) were selected for analysis out of 1031 unique citations. Selected studies were from Australia, Canada, Denmark, Norway, the United Kingdom, and the United States. Four main themes emerged: inadequate knowledge, beliefs and misconceptions, concerns about osteoporosis, and lack of information from health care providers. Participants had inadequate knowledge about osteoporosis and were particularly uninformed about risk factors, causes, treatment, and prevention. Areas of concern for participants included diagnosis, medication side effects, and inadequate information from primary care providers.
CONCLUSION:

Although there was general awareness of osteoporosis, many misconceptions and concerns were evident. Education on bone health needs to reinforce areas of knowledge and address deficits, misconceptions, and concerns.
PMID: 31940409 DOI: 10.1371/journal.pone.0227765

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Select item 3194040816.
PLoS One. 2020 Jan 15;15(1):e0226966. doi: 10.1371/journal.pone.0226966. eCollection 2020.
Subterranean Deuteraphorura Absolon, 1901, (Hexapoda, Collembola) of the Western Carpathians - Troglomorphy at the northern distributional limit in Europe.
Parimuchová A1, Žurovcová M2, Papáč V3, Kováč Ľ1.

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Abstract


An integrative approach employing molecular, morphological and geographical data were applied to species delimitation among Deuteraphorura congeners occupying caves of the Western Carpathian Mts. A new species of Deuteraphorura from the Western Carpathians is described. D. muranensis sp. nov. belongs among species with 4 pso at the hind margin of the head and possesses highly troglomorphic features. It is conspicuous with its distinctly elongated claws and long, hair-like body chaetae. The status of the new species was confirmed by DNA barcoding based on the mitochondrial COI marker. Populations of D. kratochvili (Nosek, 1963), the most widespread species, were studied in detail. Both ABGD and PTP analyses brought results congruent with geography, i.e. the molecular and geographic distance of the populations were positively correlated. However, some molecular separation based on pairwise distance and the number of substitutions was indicated within two of the studied populations. Despite the indistinct morphological differences, the tested populations were well isolated both geographically and genetically, which indicates that each studied population may represent a cryptic species. The troglomorphy of cave Collembola at the northernmost border of the distribution of cave-adapted species in the Europe is discussed. It is clear that the level of troglomorphy is closely associated with conditions of the microhabitat occupied by the individual subterranean species. The results of our study enhance the importance of the Western Carpathians regarding the diversity pattern of obligate cave species in Europe.
PMID: 31940408 DOI: 10.1371/journal.pone.0226966

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Select item 3194040717.
PLoS One. 2020 Jan 15;15(1):e0227640. doi: 10.1371/journal.pone.0227640. eCollection 2020.
Comparison of blood lactate and perceived exertion responses in two matched time-under-tension protocols.
Vargas-Molina S1,2, Martín-Rivera F3, Bonilla DA4, Petro JL5, Carbone L6, Romance R2, deDiego M1, Schoenfeld BJ7, Benítez-Porres J2.

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Abstract

PURPOSE:

The aim of this study was to compare the concentration of blood lactate [bLa-] and the subjective perception of exertion of trained men in a moderate repetition protocol (MRP) versus a high repetition protocol (HRP) equated for time under tension.
METHODS:

A sample of 40 healthy young men (aged, 23.2 ± 4.0 years; height, 177.3 ± 7.0 cm; BMI, 24.3 ± 2.2) performed two sessions of 8 sets of bicep curls with a one-week recovery interval between the trials. In the HRP protocol, 20 repetitions were performed with a cadence of 2 seconds of eccentric and 1 second of concentric, while in the MRP protocol 10 repetitions were performed with 4 seconds of eccentric and 2 seconds of concentric. Cadences were controlled by a metronome. At the beginning and end of each of the sessions, blood lactate was taken at 2, 15, and 30 minutes, and rating of perceived exertion (OMNI-RES) was assessed immediately after completion of each session.
RESULTS:

There were [bLa-] differences between protocols in the MRP 2 min, (5.2 ±1.4); 15 min, (3.2 ±1.2); 30 min, (1.9 ±0.6); p< 0.05, and the HRP 2 min, (6.1 ±1.6); 15 min, (3.7 ±1.1); 30 min, (2.2 ±0.6); p<0.01. OMNI-RES was higher in HRP, (8.8 ±0.7) than in MRP, (7.7 ±0.9). Additionally, a correlation was found between the RPE and [bLa-] values in the HRP protocol (rs = 0.35, p < 0.01).
CONCLUSIONS:

Training protocols with high times under tension promote substantial increases in metabolic stress, however, our findings indicate that HRP generates more [bLa-] than MRP. In addition, there were higher RPE values in the HRP protocol compared to MRP in single-joint exercises.
PMID: 31940407 DOI: 10.1371/journal.pone.0227640

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Select item 3194040618.
PLoS One. 2020 Jan 15;15(1):e0227696. doi: 10.1371/journal.pone.0227696. eCollection 2020.
Association of benzodiazepines, opioids and tricyclic antidepressants use and falls in trauma patients: Conditional effect of age.
Cordovilla-Guardia S1,2, Molina TB3, Franco-Antonio C1,2, Santano-Mogena E1,2, Vilar-López R4,5.

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Abstract

INTRODUCTION:

The relationship between benzodiazepines, opioids and tricyclic antidepressants and trauma is of great importance because of increased consumption and the growing evidence of a positive association among older adults. The objective of this study was to determine the effect size of the association between the consumption of psychotropic medications /opioids and falls in patients who have suffered trauma by studying the role of other variables in this relationship.
METHOD:

From 2011 to 2016, the presence of benzodiazepines, opioids and tricyclic antidepressants and other drugs in 1060 patients admitted for trauma at a level I trauma hospital was analysed. Multivariate models were used to measure the adjusted effect size of the association between consumption of benzodiazepines, opioids and tricyclic antidepressants and falls, and the effect of age on this association was studied.
RESULTS:

A total of 192 patients tested positive for benzodiazepines, opioids and tricyclic antidepressants, with same-level falls being the most frequent mechanism of injury in this group (40.1%), with an odds ratio of 1.96 (1.40-2.75), p < 0.001. Once other covariates were introduced, this association was not observed, leaving only age, gender (woman) and, to a lesser extent, sensory conditions as variables associated with falls. Age acted as an effect modifier between benzodiazepines, opioids and tricyclic antidepressants and falls, with significant effect sizes starting at 51.9 years of age.
CONCLUSIONS:

The association between the consumption of benzodiazepines, opioids and tricyclic antidepressants and falls in patients admitted for trauma is conditioned by other confounding variables, with age being the most influential confounding variable.
PMID: 31940406 DOI: 10.1371/journal.pone.0227696

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Select item 3194040519.
PLoS One. 2020 Jan 15;15(1):e0227678. doi: 10.1371/journal.pone.0227678. eCollection 2020.
A scoping review of importation and predictive models related to vector-borne diseases, pathogens, reservoirs, or vectors (1999-2016).
Sadeghieh T1,2, Waddell LA1, Ng V1, Hall A1,2, Sargeant J2,3.

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Abstract

BACKGROUND:

As globalization and climate change progress, the expansion and introduction of vector-borne diseases (VBD) from endemic regions to non-endemic regions is expected to occur. Mathematical and statistical models can be useful in predicting when and where these changes in distribution may happen. Our objective was to conduct a scoping review to identify and characterize predictive and importation models related to vector-borne diseases that exist in the global literature.
METHODS:

A literature search was conducted to identify publications published between 1999 and 2016 from five scientific databases using relevant keywords. All publications had to be in English or French, and include a predictive or importation model on VBDs, pathogens, reservoirs and/or vectors. Relevance screening and data characterization were performed by two reviewers using pretested forms. The data were analyzed using descriptive statistics.
RESULTS:

The search initially identified 19 710 unique articles, reports, and conference abstracts. This was reduced to 428 relevant documents after relevance screening and data charting. About half of the models used mathematical techniques, and the remainder were statistical. Most of the models were predictive (87%), rather than importation (5%). The most commonly investigated diseases were malaria and dengue fever. Around 12% of the publications did not report all the parameters used in their model. Only 29% of the models incorporated the impacts of climate change.
CONCLUSIONS:

A wide variety of mathematical and statistical models on vector-borne diseases exist. Researchers creating their own mathematical and/or statistical models may be able to use this scoping review to be informed about the diseases and/or regions, parameters, model types, and methodologies used in published models.
PMID: 31940405 DOI: 10.1371/journal.pone.0227678

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Select item 3194040420.
PLoS One. 2020 Jan 15;15(1):e0227689. doi: 10.1371/journal.pone.0227689. eCollection 2020.
Estimating the population size of female sex workers and transgender women in Sri Lanka.
Bozicevic I1, Manathunge A2, Dominkovic Z1, Beneragama S2, Kriitmaa K3.

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Abstract


We implemented population size estimation of female sex workers (FSW) and transgender women (TGW) in Sri Lanka in 2018 using several approaches (geographical mapping, service and unique object multiplier and a modified Delphi method during the stakeholder consensus meeting). Mapping was done in 49 randomly selected Divisional Secretariats, which provided a basis for extrapolation of size estimates to the national level. Two types of adjustments were applied on the mean (minimum-maximum) population estimate obtained during mapping: (1) an adjustment for mobility to reduce double counting of FSW and TGW frequenting multiple spots, obtained during mapping; (2) an adjustment for "a hidden population", obtained from surveys among FSW and TGW. For the multiplier method, we used data from services of non-governmental organisations that FSW and TGW were in contact with, and surveys based on respondent-driven sampling. Surveys were carried out in the cities of Colombo (FSW, TGW), Kandy (FSW), Galle (FSW) and Jaffna (TGW). We estimated that there are 30,000 FSWs in Sri Lanka, with a plausible range of 20,000-35,000, which implies a prevalence of FSW of 0.56% (0.37-0.65%) among adult females. This study provided baseline estimates of 2,200 TGW in the country, with a plausible range of 2,000-3,500, which is 0.04% (0.04-0.07%) of adult male population. Our estimates of the proportional contribution of the FSW and TGW populations among the adult population in Sri Lanka are consistent with the The Joint United Nations Programme on HIV/AIDS (UNAIDS) recommended estimates for Asia and the Pacific. The results provide an important point for macro- and micro-level planning of HIV services, allocating programme resources and assessing programme coverage and quality.
PMID: 31940404 DOI: 10.1371/journal.pone.0227689

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Select item 3194040321.
PLoS One. 2020 Jan 15;15(1):e0227679. doi: 10.1371/journal.pone.0227679. eCollection 2020.
Assessment of climate change impact on the malaria vector Anopheles hyrcanus, West Nile disease, and incidence of melanoma in the Vojvodina Province (Serbia) using data from a regional climate model.
Mihailović DT1, Petrić D2, Petrović T3, Hrnjaković-Cvjetković I4,5, Djurdjevic V6, Nikolić-Đorić E7, Arsenić I1, Petrić M8,9,10, Mimić G11, Ignjatović-Ćupina A2.

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Abstract


Motivated by the One Health paradigm, we found the expected changes in temperature and UV radiation (UVR) to be a common trigger for enhancing the risk that viruses, vectors, and diseases pose to human and animal health. We compared data from the mosquito field collections and medical studies with regional climate model projections to examine the impact of climate change on the spreading of one malaria vector, the circulation of West Nile virus (WNV), and the incidence of melanoma. We analysed data obtained from ten selected years of standardised mosquito vector sampling with 219 unique location-year combinations, and 10 years of melanoma incidence. Trends in the observed data were compared to the climatic variables obtained by the coupled regional Eta Belgrade University and Princeton Ocean Model for the period 1961-2015 using the A1B scenario, and the expected changes up to 2030 were presented. Spreading and relative abundance of Anopheles hyrcanus was positively correlated with the trend of the mean annual temperature. We anticipated a nearly twofold increase in the number of invaded sites up to 2030. The frequency of WNV detections in Culex pipiens was significantly correlated to overwintering temperature averages and seasonal relative humidity at the sampling sites. Regression model projects a twofold increase in the incidence of WNV positive Cx. pipiens for a rise of 0.5°C in overwintering TOctober-April temperatures. The projected increase of 56% in the number of days with Tmax ≥ 30°C (Hot Days-HD) and UVR doses (up to 1.2%) corresponds to an increasing trend in melanoma incidence. Simulations of the Pannonian countries climate anticipate warmer and drier conditions with possible dominance of temperature and number of HD over other ecological factors. These signal the importance of monitoring the changes to the preparedness of mitigating the risk of vector-borne diseases and melanoma.
PMID: 31940403 DOI: 10.1371/journal.pone.0227679

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Select item 3194040222.
PLoS One. 2020 Jan 15;15(1):e0227682. doi: 10.1371/journal.pone.0227682. eCollection 2020.
Evaluation of questionnaire as an instrument to measure the level of nutritional and weight gain knowledge in pregnant women in Poland. A pilot study.
Mierzejewska E1, Honorato-Rzeszewicz T1, Świątkowska D2, Jurczak-Czaplicka M3, Maciejewski T2, Fijałkowska A4, Szulc-Kamińska J2, Czach A2, Nałecz H3, Szostak-Węgierek D5, Szamotulska K1.

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Abstract


Pregnancy is a period in life in which women are willing to improve their lifestyle. Providing proper information for these women is crucial for their health and the health of their offspring. Clear information about weak points in their nutritional and weight gain knowledge is the first step for proper health care assistance. There are a few previous studies evaluating the nutritional and weight gain knowledge of pregnant women. In the few studies available, different approaches were taken and there was no wider discussion on the content of the questionnaires attempting to measure level of knowledge. The aim of this study, designed in a pilot fashion, was to test the adequacy of the questionnaire as a research instrument in a group of 139 pregnant Polish women. The developed instrument is a 33-item questionnaire comprising four domains: weight gain, importance of nutrients, quality and quantity of food intake. The results of this study indicate that the questionnaire is stable and internal consistency is acceptable (Cronbach's alpha > 0.7) for dimensions with more than four items. For dimensions with less than four items, internal consistency was poor (Cronbach's alpha < 0.7). The cumulative explained variance for domains weight gain, importance of nutrients, quantity and quality of food intake was 54.74%, 42.74%, 54.42% and 48.99% respectively. Results from validity, reliability and factor analysis indicate that the questionnaire is adequate for its purpose.
PMID: 31940402 DOI: 10.1371/journal.pone.0227682

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Select item 3194040123.
PLoS One. 2020 Jan 15;15(1):e0227681. doi: 10.1371/journal.pone.0227681. eCollection 2020.
Healthcare utilization of Mexican-American Medicare beneficiaries with and without Alzheimer's disease and related dementias.
Downer B1,2, Al Snih S1,2, Raji M2,3, Chou LN4, Kuo YF2,4, Markides KS2,5, Ottenbacher KJ1,2.

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Abstract

BACKGROUND:

Older adults with Alzheimer's disease and related dementias (ADRD) are high-risk to experience hospitalizations and emergency room (ER) admissions. Mexican-Americans have a high prevalence of ADRD, but there is limited information on the healthcare use of older Mexican-Americans with ADRD. We used data from a cohort of older Mexican-Americans that has been linked with Medicare files to investigate differences in hospitalizations, ER admissions, and physician visits according to ADRD diagnosis. We also identify sociodemographic, health, and functional characteristics that may contribute to differences in healthcare utilization between Mexican-American Medicare beneficiaries with and without an ADRD diagnosis.
METHODS AND FINDINGS:

Data came from the Hispanic Established Populations for the Epidemiological Study of the Elderly that has been linked with Medicare Master Beneficiary Summary Files, Medicare Provider Analysis and Review files, Outpatient Standard Analytic files, and Carrier files. The final analytic sample included 1048 participants. Participants were followed for two years (eight quarters) after their survey interview. Generalized estimating equations were used to estimate the probability for one or more hospitalizations, ER admissions, and physician visits at each quarter. ADRD was associated with higher odds for hospitalizations (OR = 1.65, 95%CI = 1.29-2.11) and ER admissions (OR = 1.57, 95%CI = 1.23-1.94) but not physician visits (OR = 1.23, 95%CI = 0.91-1.67). The odds for hospitalizations (OR = 1.24, 95%CI = 0.97-1.60) and ER admissions (OR = 1.27, 95%CI = 1.01-1.59) were reduced after controlling for limitations in activities of daily living and comorbidities.
CONCLUSIONS:

Mexican-American Medicare beneficiaries with ADRD had significantly higher odds for one or more hospitalizations and ER admissions but similar physician visits compared to beneficiaries without ADRD. Functional limitations and comorbidities contributed to the higher hospitalizations and ER admissions for older Mexican-Americans with ADRD.
PMID: 31940401 DOI: 10.1371/journal.pone.0227681

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Select item 3194040024.
PLoS One. 2020 Jan 15;15(1):e0227756. doi: 10.1371/journal.pone.0227756. eCollection 2020.
Multidimensional Scales of Perceived Self-Efficacy (MSPSE): Measurement invariance across Italian and Colombian adolescents.
Basili E1, Gomez Plata M2, Paba Barbosa C3, Gerbino M1, Thartori E1, Lunetti C1, Uribe Tirado LM4, Ruiz García M4, Luengo Kanacri BP5, Tamayo Giraldo G6, Narvaez Marin M6, Laghi F2, Pastorelli C1.

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Abstract


Multidimensional Perceived Self-Efficacy Scale for Children has been developed as an important tool to measure Self-Efficacy in school contexts. The present study assesses the measurement invariance of the MSPSE across two samples of Italian and Colombian adolescents using Multi-sample Confirmatory Factor Analysis. Participants were Italian (N = 564) and Colombian (N = 645) students attending the 7th grade (age 12-13) drawn from a residential community near Rome and three Colombian cities: Medellin, Manizales and Santa Marta. Findings from gender invariance provide high support for full and partial invariance among Colombian and Italian adolescents respectively. Cross-national comparison showed partial scalar invariance between Italy and Colombia, with Italian students perceiving themselves as more efficacious on Academic, Social and Self-Regulatory dimensions. MSPSE's structural validity has been confirmed, along with its three-factor-structure across gender, for the Italian and Colombian samples. The findings support the invariance and the validity of this scale to measure Self-Efficacy in school contexts from a cross-cultural perspective.
PMID: 31940400 DOI: 10.1371/journal.pone.0227756

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Select item 3194039925.
PLoS One. 2020 Jan 15;15(1):e0227036. doi: 10.1371/journal.pone.0227036. eCollection 2020.
A little good is good enough: Ethical consumption, cheap excuses, and moral self-licensing.
Engel J1, Szech N1,2,3.

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Abstract


This paper explores the role of cheap excuses in product choice. If agents feel that they fulfill one ethical aspect, they may care less about other independent ethical facets within product choice. Choosing a product that fulfills one ethical aspect may then suffice for maintaining a high moral self-image in agents and render it easier to ignore other ethically relevant aspects they would otherwise care about more. The use of such cheap excuses could thus lead to a "static moral self-licensing" effect, and this would extend the logic of the well-known dynamic moral self-licensing. Our experimental study provides empirical evidence that the static counterpart of moral self-licensing exists. Furthermore, effects spill over to unrelated, ethically relevant contexts later in time. Thus, static moral self-licensing and dynamic moral self-licensing can exist next to each other. However, it is critical that agents do not feel that they fulfilled an ethical criterion out of sheer luck, that is, agents need some room so that they can attribute the ethical improvement at least partly to themselves. Outsiders, although monetarily incentivized for correct estimates, are completely oblivious to the effects of moral self-licensing, both static and dynamic.
PMID: 31940399 DOI: 10.1371/journal.pone.0227036

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Select item 3194039826.
PLoS One. 2020 Jan 15;15(1):e0227727. doi: 10.1371/journal.pone.0227727. eCollection 2020.
Structure-function analyses of candidate small molecule RPN13 inhibitors with antitumor properties.
Anchoori RK1,2, Tan M3, Tseng SH1, Peng S1, Soong RS1, Algethami A1, Foran P1, Das S1,4, Wang C5, Wang TL1, Liang H1, Hung CF1, Roden RBS1,2,6.

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Abstract


We sought to design ubiquitin-proteasome system inhibitors active against solid cancers by targeting ubiquitin receptor RPN13 within the proteasome's 19S regulatory particle. The prototypic bis-benzylidine piperidone-based inhibitor RA190 is a michael acceptor that adducts Cysteine 88 of RPN13. In probing the pharmacophore, we showed the benefit of the central nitrogen-bearing piperidone ring moiety compared to a cyclohexanone, the importance of the span of the aromatic wings from the central enone-piperidone ring, the contribution of both wings, and that substituents with stronger electron withdrawing groups were more cytotoxic. Potency was further enhanced by coupling of a second warhead to the central nitrogen-bearing piperidone as RA375 exhibited ten-fold greater activity against cancer lines than RA190, reflecting its nitro ring substituents and the addition of a chloroacetamide warhead. Treatment with RA375 caused a rapid and profound accumulation of high molecular weight polyubiquitinated proteins and reduced intracellular glutathione levels, which produce endoplasmic reticulum and oxidative stress, and trigger apoptosis. RA375 was highly active against cell lines of multiple myeloma and diverse solid cancers, and demonstrated a wide therapeutic window against normal cells. For cervical and head and neck cancer cell lines, those associated with human papillomavirus were significantly more sensitive to RA375. While ARID1A-deficiency also enhanced sensitivity 4-fold, RA375 was active against all ovarian cancer cell lines tested. RA375 inhibited proteasome function in muscle for >72h after single i.p. administration to mice, and treatment reduced tumor burden and extended survival in mice carrying an orthotopic human xenograft derived from a clear cell ovarian carcinoma.
PMID: 31940398 DOI: 10.1371/journal.pone.0227727

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Select item 3194039727.
PLoS One. 2020 Jan 15;15(1):e0227423. doi: 10.1371/journal.pone.0227423. eCollection 2020.
Sustainability effects of motor control stabilisation exercises on pain and function in chronic nonspecific low back pain patients: A systematic review with meta-analysis and meta-regression.
Niederer D1, Mueller J2.

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Abstract

STUDY DESIGN:

Systematic review with meta-analysis and meta-regression.
BACKGROUND AND OBJECTIVES:

We systematically reviewed and delineated the existing evidence on sustainability effects of motor control exercises on pain intensity and disability in chronic low back pain patients when compared with an inactive or passive control group or with other exercises. Secondary aims were to reveal whether moderating factors like the time after intervention completion, the study quality, and the training characteristics affect the potential sustainability effects.
METHODS:

Relevant scientific databases (Medline, Web of Knowledge, Cochrane) were screened. Eligibility criteria for selecting studies: All RCTs und CTs on chronic (≥ 12/13 weeks) nonspecific low back pain, written in English or German and adopting a longitudinal core-specific/stabilizing sensorimotor control exercise intervention with at least one pain intensity and disability outcome assessment at a follow-up (sustainability) timepoint of ≥ 4 weeks after exercise intervention completion.
RESULTS AND CONCLUSIONS:

From the 3,415 studies that were initially retrieved, 10 (2 CTs & 8 RCTs) on N = 1081 patients were included in the review and analyses. Low to moderate quality evidence shows a sustainable positive effect of motor control exercise on pain (SMD = -.46, Z = 2.9, p < .001) and disability (SMD = -.44, Z = 2.5, p < .001) in low back pain patients when compared to any control. The subgroups' effects are less conclusive and no clear direction of the sustainability effect at short versus mid versus long-term, of the type of the comparator, or of the dose of the training is given. Low quality studies overestimated the effect of motor control exercises.
PMID: 31940397 DOI: 10.1371/journal.pone.0227423

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Select item 3194039628.
PLoS One. 2020 Jan 15;15(1):e0227329. doi: 10.1371/journal.pone.0227329. eCollection 2020.
Correction: Amphibians on the hotspot: Molecular biology and conservation in the South American Atlantic Rainforest.
Amaral CRL, Chaves ACS, Borges Júnior VNT, Pereira F, Silva BM, Silva DA, Amorim A, Carvalho EF, Rocha CFD.

Abstract


[This corrects the article DOI: 10.1371/journal.pone.0224320.].

Erratum for
Amphibians on the hotspot: Molecular biology and conservation in the South American Atlantic Rainforest. [PLoS One. 2019]
PMID: 31940396 DOI: 10.1371/journal.pone.0227329

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Publication type


Select item 3194039529.
PLoS One. 2020 Jan 15;15(1):e0227358. doi: 10.1371/journal.pone.0227358. eCollection 2020.
The diagnostic accuracy of liver fibrosis in non-viral liver diseases using acoustic radiation force impulse elastography: A systematic review and meta-analysis.
Lin Y1, Li H1, Jin C1, Wang H1, Jiang B2.

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Abstract

BACKGROUND:

Acoustic radiation force impulse (ARFI) imaging is an ultrasound-based elastography method that has been studied in the staging of hepatic fibrosis, especially in chronic hepatitis. However, the diagnostic accuracy of ARFI in non-viral hepatopathies, such as autoimmune hepatitis and non-alcoholic fatty liver disease, has not been systematically determined.
AIM:

To systematically assess the diagnostic accuracy of ARFI in non-viral hepatopathies.
METHODS:

The databases of PubMed, Embase, Cochrane Library and clinicaltrials.gov were systematically searched for candidate studies reporting the diagnostic accuracy of ARFI for hepatic fibrosis. The pooled estimates of the sensitivity, specificity, diagnostic odds ratio, and positive and negative likelihood ratios were calculated with the summary receiver operating curve (sROC) performed using STATA software.
RESULTS:

In detail, a total of 29 diagnostic studies were included for further analysis. The quality of the included studies was relatively high using QUADAS method. The pooled sensitivity and specificity were 0.79 (0.73, 0.83) and 0.81 (0.75, 0.86), with AUROC 0.87 (0.83, 0.89) for the staging of significant fibrosis (F≥2). Meanwhile, for the staging of severe fibrosis (F≥3), the pooled sensitivity and specificity were 0.92 (0.87, 0.95) and 0.85 (0.80, 0.89), with AUROC 0.94 (0.92, 0.96). Furthermore, the pooled sensitivity and specificity were 0.89 (0.79, 0.95) and 0.89 (0.85, 0.92), with AUROC 0.94 (0.92, 0.96) for ARFI in staging cirrhosis (F = 4), which were similar to the data for severe fibrosis. No significant publication bias was present in this study.
CONCLUSION:

This meta-analysis demonstrated that ARFI exerted satisfactory diagnostic performance in staging non-viral hepatic fibrosis, especially severe fibrosis (F≥3) and cirrhosis (F = 4).
PMID: 31940395 DOI: 10.1371/journal.pone.0227358

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Select item 3194039430.
PLoS One. 2020 Jan 15;15(1):e0227406. doi: 10.1371/journal.pone.0227406. eCollection 2020.
Head impulse compensatory saccades: Visual dependence is most evident in bilateral vestibular loss.
Pogson JM1,2, Taylor RL1,2, McGarvie LA1,3, Bradshaw AP1, D'Souza M4, Flanagan S5,6, Kong J2,7,8, Halmagyi GM1,2, Welgampola MS1,2.

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Abstract


The normal vestibulo-ocular reflex (VOR) generates almost perfectly compensatory smooth eye movements during a 'head-impulse' rotation. An imperfect VOR gain provokes additional compensatory saccades to re-acquire an earth-fixed target. In the present study, we investigated vestibular and visual contributions on saccade production. Eye position and velocity during horizontal and vertical canal-plane head-impulses were recorded in the light and dark from 16 controls, 22 subjects after complete surgical unilateral vestibular deafferentation (UVD), eight subjects with idiopathic bilateral vestibular loss (BVL), and one subject after complete bilateral vestibular deafferentation (BVD). When impulses were delivered in the horizontal-canal plane, in complete darkness compared with light, first saccade frequency mean(SEM) reduced from 96.6(1.3)-62.3(8.9) % in BVL but only 98.3(0.6)-92.0(2.3) % in UVD; saccade amplitudes reduced from 7.0(0.5)-3.6(0.4) ° in BVL but were unchanged 6.2(0.3)-5.5(0.6) ° in UVD. In the dark, saccade latencies were prolonged in lesioned ears, from 168(8.4)-240(24.5) ms in BVL and 177(5.2)-196(5.7) ms in UVD; saccades became less clustered. In BVD, saccades were not completely abolished in the dark, but their amplitudes decreased from 7.3-3.0 ° and latencies became more variable. For unlesioned ears (controls and unlesioned ears of UVD), saccade frequency also reduced in the dark, but their small amplitudes slightly increased, while latency and clustering remained unchanged. First and second saccade frequencies were 75.3(4.5) % and 20.3(4.1) %; without visual fixation they dropped to 32.2(5.0) % and 3.8(1.2) %. The VOR gain was affected by vision only in unlesioned ears of UVD; gains for the horizontal-plane rose slightly, and the vertical-planes reduced slightly. All head-impulse compensatory saccades have a visual contribution, the magnitude of which depends on the symmetry of vestibular-function and saccade latency: BVL is more profoundly affected by vision than UVD, and second saccades more than first saccades. Saccades after UVD are probably triggered by contralateral vestibular function.
PMID: 31940394 DOI: 10.1371/journal.pone.0227406

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Select item 3194039331.
PLoS One. 2020 Jan 15;15(1):e0227408. doi: 10.1371/journal.pone.0227408. eCollection 2020.
Pepsin promotes laryngopharyngeal neoplasia by modulating signaling pathways to induce cell proliferation.
Niu K1, Guo C2, Teng S3, Zhou D2, Yu S1, Yin W1, Wang P1, Zhu W1, Duan M4.

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Abstract


Pepsin plays an important role in laryngopharyngeal reflux (LPR), a risk factor for the development of hypopharyngeal squamous cell carcinomas (HPSCC). However, the role of pepsin in HPSCC is not clear. We show by immunohistochemistry that pepsin positivity occurs in a significant proportion of human primary HPSCC specimens, and in many cases matched adjacent uninvolved epithelia are negative for pepsin. Pepsin positivity is associated with nodal involvement, suggesting that pepsin may have a role in metastasis. Treatment of FaDu cancer cells with pepsin increased cell proliferation, possibly by inducing G1/S transition. We also observed significant changes in expression of genes involved in NF-kappaB, TRAIL and Notch signaling. Our data suggest that pepsin plays an important role in HPSCC and that targeting pepsin could have potential therapeutic benefits.
PMID: 31940393 DOI: 10.1371/journal.pone.0227408

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Select item 3194039232.
PLoS One. 2020 Jan 15;15(1):e0227008. doi: 10.1371/journal.pone.0227008. eCollection 2020.
The earliest farming communities north of the Carpathians: The settlement at Gwoździec site 2.
Czekaj-Zastawny A1, Rauba-Bukowska A1, Kukułka A2, Kufel-Diakowska B3, Lityńska-Zając M1, Moskal-Del Hoyo M4, Wilczyński J5.

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Abstract


The appearance of the Linear Pottery Culture (LBK) on Poland territory initiated the process of neolithization in the area. However, as we will see in this article, this colonization took place later than previously thought. The stage, which in Poland is called as the early phase, actually corresponds only to the Fomborn/Ačkovy stage of LBK, and the earliest dating currently indicates around 5350 BC. Due to the small number of sites from this phase excavated on a large scale in Poland, this stage of the culture's development is poorly known. The Gwoździec Project is focused on the earliest stage of LBK settlement in south-eastern Poland. Excavation at the site was finished in 2018. Therefore, the article presents preliminary results of interdisciplinary analyzes, such as research on ceramics, flint production and use, and botanical remains. They point to various aspects of the economy of these early agricultural communities and significantly enrich the knowledge of this period in Central Europe. They also expose the chronological development of the oldest LBK development stage in Poland.
PMID: 31940392 DOI: 10.1371/journal.pone.0227008

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Select item 3194039133.
PLoS One. 2020 Jan 15;15(1):e0227419. doi: 10.1371/journal.pone.0227419. eCollection 2020.
Machine learning models for identifying preterm infants at risk of cerebral hemorrhage.
Turova V1, Sidorenko I2, Eckardt L3, Rieger-Fackeldey E4, Felderhoff-Müser U3, Alves-Pinto A1, Lampe R1.

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Abstract


Intracerebral hemorrhage in preterm infants is a major cause of brain damage and cerebral palsy. The pathogenesis of cerebral hemorrhage is multifactorial. Among the risk factors are impaired cerebral autoregulation, infections, and coagulation disorders. Machine learning methods allow the identification of combinations of clinical factors to best differentiate preterm infants with intra-cerebral bleeding and the development of models for patients at risk of cerebral hemorrhage. In the current study, a Random Forest approach is applied to develop such models for extremely and very preterm infants (23-30 weeks gestation) based on data collected from a cohort of 229 individuals. The constructed models exhibit good prediction accuracy and might be used in clinical practice to reduce the risk of cerebral bleeding in prematurity.
PMID: 31940391 DOI: 10.1371/journal.pone.0227419

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Select item 3194039034.
PLoS One. 2020 Jan 15;15(1):e0226784. doi: 10.1371/journal.pone.0226784. eCollection 2020.
Selection of memory clinic patients for CSF biomarker assessment can be restricted to a quarter of cases by using computerized decision support, without compromising diagnostic accuracy.
Rhodius-Meester HFM1,2, van Maurik IS1,3, Koikkalainen J4, Tolonen A5, Frederiksen KS6, Hasselbalch SG6, Soininen H7, Herukka SK7, Remes AM7,8,9, Teunissen CE10, Barkhof F11,12, Pijnenburg YAL1, Scheltens P1, Lötjönen J4, van der Flier WM1,3.

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Abstract

INTRODUCTION:

An accurate and timely diagnosis for Alzheimer's disease (AD) is important, both for care and research. The current diagnostic criteria allow the use of CSF biomarkers to provide pathophysiological support for the diagnosis of AD. How these criteria should be operationalized by clinicians is unclear. Tools that guide in selecting patients in which CSF biomarkers have clinical utility are needed. We evaluated computerized decision support to select patients for CSF biomarker determination.
METHODS:

We included 535 subjects (139 controls, 286 Alzheimer's disease dementia, 82 frontotemporal dementia and 28 vascular dementia) from three clinical cohorts. Positive (AD like) and negative (normal) CSF biomarker profiles were simulated to estimate whether knowledge of CSF biomarkers would impact (confidence in) diagnosis. We applied these simulated CSF values and combined them with demographic, neuropsychology and MRI data to initiate CSF testing (computerized decision support approach). We compared proportion of CSF measurements and patients diagnosed with sufficient confidence (probability of correct class ≥0.80) based on an algorithm with scenarios without CSF (only neuropsychology, MRI and APOE), CSF according to the appropriate use criteria (AUC) and CSF for all patients.
RESULTS:

The computerized decision support approach recommended CSF testing in 140 (26%) patients, which yielded a diagnosis with sufficient confidence in 379 (71%) of all patients. This approach was more efficient than CSF in none (0% CSF, 308 (58%) diagnosed), CSF selected based on AUC (295 (55%) CSF, 350 (65%) diagnosed) or CSF in all (100% CSF, 348 (65%) diagnosed).
CONCLUSIONS:

We used a computerized decision support with simulated CSF results in controls and patients with different types of dementia. This approach can support clinicians in making a balanced decision in ordering additional biomarker testing. Computer-supported prediction restricts CSF testing to only 26% of cases, without compromising diagnostic accuracy.
PMID: 31940390 DOI: 10.1371/journal.pone.0226784

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Select item 3194038935.
PLoS One. 2020 Jan 15;15(1):e0227294. doi: 10.1371/journal.pone.0227294. eCollection 2020.
Evaluation of KRAS, NRAS and BRAF mutations detection in plasma using an automated system for patients with metastatic colorectal cancer.
Franczak C1, Witz A1, Geoffroy K1, Demange J1, Rouyer M1, Husson M1, Massard V2, Gavoille C2, Lambert A2, Gilson P3, Gambier N4,5, Scala-Bertola J4,5, Merlin JL3, Harlé A3.

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Abstract

BACKGROUND:

Cell-free DNA detection is becoming a surrogate assay for tumor genotyping. Biological fluids often content a very low amount of cell-free tumor DNA and assays able to detect very low allele frequency mutant with a few quantities of DNA are required. We evaluated the ability of the fully-automated molecular diagnostics platform Idylla for the detection of KRAS, NRAS and BRAF hotspot mutations in plasma from patients with metastatic colorectal cancer (mCRC).
MATERIALS AND METHODS:

First, we evaluated the limit of detection of the system using two set of laboratory made samples that mimic mCRC patient plasma, then plasma samples from patients with mCRC were assessed using Idylla system and BEAMing digital PCR technology.
RESULTS:

Limits of detection of 0.1%, 0.4% and 0.01% for KRAS, NRAS and BRAF respectively have been reached. With our laboratory made samples, sensitivity up to 0.008% has been reached. Among 15 patients' samples tested for KRAS mutation, 2 discrepant results were found between Idylla and BEAMing dPCR. A 100% concordance between the two assays has been found for the detection of NRAS and BRAF mutations in plasma samples.
CONCLUSIONS:

The Idylla system does not reach as high sensitivity as assays like ddPCR but has an equivalent sensitivity to modified NGS technics with a lower cost and a lower time to results. These data allowed to consider the Idylla system in a routine laboratory workflow for KRAS, NRAS and BRAF mutations detection in plasma.
PMID: 31940389 DOI: 10.1371/journal.pone.0227294

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Select item 3194038836.
PLoS One. 2020 Jan 15;15(1):e0226954. doi: 10.1371/journal.pone.0226954. eCollection 2020.
Muscarinic modulation of M and h currents in gerbil spherical bushy cells.
Gillet C1, Kurth S2, Kuenzel T1,2.

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Abstract


Descending cholinergic fibers innervate the cochlear nucleus. Spherical bushy cells, principal neurons of the anterior part of the ventral cochlear nucleus, are depolarized by cholinergic agonists on two different time scales. A fast and transient response is mediated by alpha-7 homomeric nicotinic receptors while a slow and long-lasting response is mediated by muscarinic receptors. Spherical bushy cells were shown to express M3 receptors, but the receptor subtypes involved in the slow muscarinic response were not physiologically identified yet. Whole-cell patch clamp recordings combined with pharmacology and immunohistochemistry were performed to identify the muscarinic receptor subtypes and the effector currents involved. Spherical bushy cells also expressed both M1 and M2 receptors. The M1 signal was stronger and mainly somatic while the M2 signal was localized in the neuropil and on the soma of bushy cells. Physiologically, the M-current was observed for the gerbil spherical bushy cells and was inhibited by oxotremorine-M application. Surprisingly, long application of carbachol showed only a transient depolarization. Even though no muscarinic depolarization could be detected, the input resistance increased suggesting a decrease in the cell conductance that matched with the closure of M-channels. The hyperpolarization-activated currents were also affected by muscarinic activation and counteracted the effect of the inactivation of M-current on the membrane potential. We hypothesize that this double muscarinic action might allow adaptation of effects during long durations of cholinergic activation.
PMID: 31940388 DOI: 10.1371/journal.pone.0226954

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Select item 3194038737.
PLoS One. 2020 Jan 15;15(1):e0227040. doi: 10.1371/journal.pone.0227040. eCollection 2020.
Variance based weighting of multisensory head rotation signals for verticality perception.
Dakin CJ1, Kumar P1, Forbes PA2, Peters A1, Day BL1.

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Abstract


We tested the hypothesis that the brain uses a variance-based weighting of multisensory cues to estimate head rotation to perceive which way is up. The hypothesis predicts that the known bias in perceived vertical, which occurs when the visual environment is rotated in a vertical-plane, will be reduced by the addition of visual noise. Ten healthy participants sat head-fixed in front of a vertical screen presenting an annulus filled with coloured dots, which could rotate clockwise or counter-clockwise at six angular velocities (1, 2, 4, 6, 8, 16°/s) and with six levels of noise (0, 25, 50, 60, 75, 80%). Participants were required to keep a central bar vertical by rotating a hand-held dial. Continuous adjustments of the bar were required to counteract low-amplitude low-frequency noise that was added to the bar's angular position. During visual rotation, the bias in verticality perception increased over time to reach an asymptotic value. Increases in visual rotation velocity significantly increased this bias, while the addition of visual noise significantly reduced it, but did not affect perception of visual rotation velocity. The biasing phenomena were reproduced by a model that uses a multisensory variance-weighted estimate of head rotation velocity combined with a gravito-inertial acceleration signal (GIA) from the vestibular otoliths. The time-dependent asymptotic behaviour depends on internal feedback loops that act to pull the brain's estimate of gravity direction towards the GIA signal. The model's prediction of our experimental data furthers our understanding of the neural processes underlying human verticality perception.
PMID: 31940387 DOI: 10.1371/journal.pone.0227040

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Select item 3194038638.
PLoS One. 2020 Jan 15;15(1):e0227315. doi: 10.1371/journal.pone.0227315. eCollection 2020.
Radiomics signature for prediction of lateral lymph node metastasis in conventional papillary thyroid carcinoma.
Park VY1, Han K1, Kim HJ2, Lee E3, Youk JH4, Kim EK1, Moon HJ1, Yoon JH1, Kwak JY1.

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Abstract

PURPOSE:

Preoperative neck ultrasound (US) for lateral cervical lymph nodes is recommended for all patients undergoing thyroidectomy for thyroid malignancy, but it is operator dependent. We aimed to develop a radiomics signature using US images of the primary tumor to preoperatively predict lateral lymph node metastasis (LNM) in patients with conventional papillary thyroid carcinoma (cPTC).
METHODS:

Four hundred consecutive cPTC patients from January 2004 to February 2006 were enrolled as the training cohort, and 368 consecutive cPTC patients from March 2006 to February 2007 served as the validation cohort. A radiomics signature, which consisted of 14 selected features, was generated by the least absolute shrinkage and selection operator (LASSO) regression model in the training cohort. The discriminating performance of the radiomics signature was assessed in the validation cohort with the area under the receiver operating characteristic curve (AUC).
RESULTS:

The radiomics signature was significantly associated with lateral cervical lymph node status (p < 0.001). The AUC of its performance in discriminating metastatic and non-metastatic lateral cervical lymph nodes was 0.710 (95% CI: 0.649-0.770) in the training cohort and was 0.621 (95% CI: 0.560-0.682) in the validation cohort.
CONCLUSIONS:

The present study showed that US radiomic features of the primary tumor were associated with lateral cervical lymph node status. Although their discriminatory performance was slightly lower in the validation cohort, our study shows that US radiomic features of the primary tumor alone have the potential to predict lateral LNM.
PMID: 31940386 DOI: 10.1371/journal.pone.0227315

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Select item 3194038539.
PLoS One. 2020 Jan 15;15(1):e0227034. doi: 10.1371/journal.pone.0227034. eCollection 2020.
Post-weaning infant-to-mother bonding in nutritionally independent female mice.
Stroobants S1,2, Creemers J3, Bosmans G4, D'Hooge R1,2.

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Abstract


Infant-parent attachment is highly selective and continues beyond essential care in primates, most prominently in humans, and the quality of this attachment crucially determines cognitive and emotional development of the infant. Altricial rodent species such as mice (Mus musculus) display mutual recognition and communal nursing in wild and laboratory environments, but parental bonding beyond the nursing period has not been reported. We presently demonstrated that socially and nutritionally independent mice still prefer to interact selectively with their mother dam. Furthermore, we observed gender differences in the mother-infant relationship, and showed disruption of this relationship in haploinsufficient Nbea+/- mice, a putative autism model with neuroendocrine dysregulation. To our knowledge, this is the first observation of murine infant-to-mother bonding beyond the nursing period.
PMID: 31940385 DOI: 10.1371/journal.pone.0227034

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Select item 3194038440.
PLoS One. 2020 Jan 15;15(1):e0226194. doi: 10.1371/journal.pone.0226194. eCollection 2020.
Content shared on social media for national cancer survivors day 2018.
Cherian R1, Le G1, Whall J2, Gomez S3, Sarkar U1.

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Abstract

BACKGROUND:

Studies estimate that the number of cancer survivors will double by 2050 due to improvements in diagnostic accuracy and treatment efficacy. Despite the growing population of cancer survivors, there is a paucity of research regarding how these individuals experience the transition from active treatment to long-term surveillance. While research has explored this transition from more organized venues, such as support groups for cancer survivors, this paper explores the discourses surrounding cancer survivorship on social media, paying particular attention to how individuals who identify as cancer survivors represent their experience.
METHODS:

We identified social media posts relating to cancer survivorship on Twitter and Instagram in early June 2018, in order to coincide with National Cancer Survivorship Day on June 3, 2018. We used nine pre-selected hashtags to identify content. For each hashtag, we manually collected the 150 most recent posts from Twitter and the 100 most recent plus the top 9 posts from Instagram. Our preliminary sample included 1172 posts; after eliminating posts from one hashtag due to irrelevance, we were left with 1063 posts. We randomly sampled 200 of these to create a subset for analysis; after review for irrelevant posts, 193 posts remained for analysis (118 from Instagram and 75 from Twitter). We utilized a grounded theory approach to analyze the posts, first open-coding a subset to develop a codebook, then applying the codebook to the rest of the sample and finally memo writing to develop themes.
RESULTS:

Overall, there is substantial difference in the tone and thematic content between Instagram and Twitter posts, Instagram takes on a more narrative form that represents journeys through cancer treatment and subsequent survivorship, whereas Twitter is more factual, leaning towards advocacy, awareness and fundraising. In terms of content type, 120 posts (62%) of the sample were images, of which 42 (35%) were images of the individual posting and 28 (23%) were images of patients posted by family or friends. Of the remaining images, 14 (12%) were of support groups and 7 (6%) were of family or friends. We identified four salient themes through analysis of the social media posts from Twitter and Instagram: social support, celebrating milestones and honoring survivors, expressing identity, and renewal vs. rebirth.
DISCUSSION:

We observed a marked relationship between physical appearance, functional status and survivorship. Additionally, our findings suggest the importance of social support for cancer patients and survivors as well as the role social media can pay in identity formation.
CONCLUSION:

Our findings suggest that individuals who identify as survivors on social media define their identity fluidly, incorporating elements of physical, emotional and psychological health as well as autonomy.
PMID: 31940384 DOI: 10.1371/journal.pone.0226194

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Select item 3194038341.
PLoS One. 2020 Jan 15;15(1):e0227291. doi: 10.1371/journal.pone.0227291. eCollection 2020.
Tuberculosis recurrences and predictive factors in a vulnerable population in Catalonia.
Brugueras S1,2,3, Molina VI4, Casas X4, González YD4, Forcada N4, Romero D4, Rodés A5, Altet MN4, Maldonado J4, Martin-Sánchez M6, Caylà JA7, Orcau À1,2,7, Rius C1,2,3, Millet JP1,2,4,7.

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Abstract

BACKGROUND:

Patients with a history of tuberculosis (TB) have a high probability of recurrence because long-term cure is not always maintained in successfully treated patients. The aim of this study was to identify the probability of TB recurrence and its predictive factors in a cohort of socially vulnerable patients who completed treatment in the TB referral center in Catalonia, which acts as the center for patients with social and health problems.
METHODS:

This retrospective open cohort study included all patients diagnosed with TB who were admitted and successfully treated in Serveis Clínics between 2000 and 2016 and who remained disease-free for a minimum of 1 year after treatment completion. We calculated the incidence density of TB recurrences per person-years of follow-up. We also estimated the cumulative incidence of TB recurrence at 1, 2, 5, and 10 years of follow-up. Bivariate analysis was conducted using Kaplan-Meier curves. Multivariate analysis was conducted using Cox regression. Hazard ratios (HR) were calculated with their 95% confidence intervals (95%CI).
RESULTS:

There were 839 patients and 24 recurrences (2.9%), representing 0.49 per 100 person-years. The probability of a recurrence was 0.63% at 1 year of follow-up, 1.35% at 2 years, and 3.69% at 5 years. The multivariate analysis showed that the predictive factors of recurrence were age older than 34 years (aHR = 3.90; CI = 1.06-14.34 at age 35-45 years and aHR = 3.88; CI = 1.02-14.80 at age >45 years) and resistance to at least one anti-TB drug (aHR = 2.91; CI = 1.11-7.65).
CONCLUSIONS:

Attention should be paid to socially vulnerable persons older than 34 years with a previous episode of resistant TB. Surveillance resources should be directed toward adequately treated patients who nevertheless have a high risk of recurrence.
PMID: 31940383 DOI: 10.1371/journal.pone.0227291

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Select item 3194038242.
PLoS One. 2020 Jan 15;15(1):e0227285. doi: 10.1371/journal.pone.0227285. eCollection 2020.
Quantitative PCR provides a simple and accessible method for quantitative microbiota profiling.
Jian C1, Luukkonen P2,3, Yki-Järvinen H2,3, Salonen A1, Korpela K1.

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Abstract


The use of relative abundance data from next generation sequencing (NGS) can lead to misinterpretations of microbial community structures, as the increase of one taxon leads to the concurrent decrease of the other(s) in compositional data. Although different DNA- and cell-based methods as well as statistical approaches have been developed to overcome the compositionality problem, and the biological relevance of absolute bacterial abundances has been demonstrated, the human microbiome research has not yet adopted these methods, likely due to feasibility issues. Here, we describe how quantitative PCR (qPCR) done in parallel to NGS library preparation provides an accurate estimation of absolute taxon abundances from NGS data and hence provides an attainable solution to compositionality in high-throughput microbiome analyses. The advantages and potential challenges of the method are also discussed.
PMID: 31940382 DOI: 10.1371/journal.pone.0227285

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Select item 3194038143.
PLoS One. 2020 Jan 15;15(1):e0227053. doi: 10.1371/journal.pone.0227053. eCollection 2020.
Intra-host symbiont diversity in eastern Pacific cold seep tubeworms identified by the 16S-V6 region, but undetected by the 16S-V4 region.
Breusing C1,2, Franke M3, Young CR2.

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Abstract


Vestimentiferan tubeworms are key taxa in deep-sea chemosynthetic habitats worldwide. As adults they obtain their nutrition through their sulfide-oxidizing bacterial endosymbionts, which are acquired from the environment. Although horizontal transmission should favor infections by various symbiotic microbes, the current paradigm holds that every tubeworm harbors only one endosymbiotic 16S rRNA phylotype. Although previous studies based on traditional Sanger sequencing have questioned these findings, population level high-throughput analyses of the symbiont 16S diversity are still missing. To get further insights into the symbiont genetic variation and uncover hitherto hidden diversity we applied state-of-the-art 16S-V4 amplicon sequencing to populations of the co-occurring tubeworm species Lamellibrachia barhami and Escarpia spicata that were collected during E/V Nautilus and R/V Western Flyer cruises to cold seeps in the eastern Pacific Ocean. In agreement with earlier work our sequence data indicated that L. barhami and E. spicata share one monomorphic symbiont phylotype. However, complementary CARD-FISH analyses targeting the 16S-V6 region implied the existence of an additional phylotype in L. barhami. Our results suggest that the V4 region might not be sufficiently variable to investigate diversity in the intra-host symbiont population at least in the analyzed sample set. This is an important finding given that this region has become the standard molecular marker for high-throughput microbiome analyses. Further metagenomic research will be necessary to solve these issues and to uncover symbiont diversity that is hidden below the 16S rRNA level.
PMID: 31940381 DOI: 10.1371/journal.pone.0227053

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Select item 3194038044.
PLoS One. 2020 Jan 15;15(1):e0227060. doi: 10.1371/journal.pone.0227060. eCollection 2020.
The effect of diet on the gastrointestinal microbiome of juvenile rehabilitating green turtles (Chelonia mydas).
Bloodgood JCG1,2, Hernandez SM1,2, Isaiah A3, Suchodolski JS3, Hoopes LA4, Thompson PM5, Waltzek TB5, Norton TM6.

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Abstract


Threatened and endangered green turtles (Chelonia mydas) are unique because as juveniles they recruit from pelagic to near-shore waters and shift from an omnivorous to primarily herbivorous diet (i.e. seagrass and algae). Nevertheless, when injured and ill animals are admitted to rehabilitation, animal protein (e.g. seafood) is often offered to combat poor appetite and emaciation. We examined how the fecal microbiome of juvenile green turtles changed in response to a dietary shift during rehabilitation. We collected fecal samples from January 2014 -January 2016 from turtles (N = 17) in rehabilitation at the Georgia Sea Turtle Center and used next generation sequencing to analyze bacterial community composition. Samples were collected at admission, mid-rehabilitation, and recovery, which entailed a shift from a mixed seafood-vegetable diet at admission to a primarily herbivorous diet at recovery. The dominant phyla changed over time, from primarily Firmicutes (55.0%) with less Bacteroidetes (11.4%) at admission, to primarily Bacteroidetes (38.4%) and less Firmicutes (31.8%) at recovery. While the microbiome likely shifts with the changing health status of individuals, this consistent inversion of Bacteroidetes and Firmicutes among individuals likely reflects the increased need for protein digestion, for which Bacteroidetes are important. Firmicutes are significant in metabolizing plant polysaccharides; thus, fewer Firmicutes may result in underutilization of wild diet items in released individuals. This study demonstrates the importance of transitioning rehabilitating green turtles to an herbivorous diet as soon as possible to afford them the best probability of survival.
PMID: 31940380 DOI: 10.1371/journal.pone.0227060

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Select item 3194037945.
PLoS One. 2020 Jan 15;15(1):e0227173. doi: 10.1371/journal.pone.0227173. eCollection 2020.
Multiple paedomorphic lineages of soft-substrate burrowing invertebrates: parallels in the origin of Xenocratena and Xenoturbella.
Martynov A1, Lundin K2,3, Picton B4,5, Fletcher K6, Malmberg K3,7, Korshunova T1,8.

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Abstract


Paedomorphosis is an important evolutionary force. It has previously been suggested that a soft-substrate sediment-dwelling (infaunal) environment facilitates paedomorphic evolution in marine invertebrates. However, until recently this proposal was never rigorously tested with robust phylogeny and broad taxon selection. Here, for the first time, we present a molecular phylogeny for a majority of the 21 families of one of the largest nudibranch subgroups (Aeolidacea) and show that the externally highly simplified vermiform nudibranch family, Pseudovermidae, with clearly defined paedomorphic traits and inhabiting a soft-substrata environment, is a sister group to the complex nudibranch family, Cumanotidae. We also report the rediscovery of one of the most enigmatic nudibranchs-Xenocratena suecica-on the Swedish and Norwegian coasts 70 years after it was first found. Xenocratena was described from the same location and environment in the Swedish Gullmar fjord as one of the most enigmatic vermiform organisms, Xenoturbella bocki, which represents either an original simple bilaterian body plan or secondary simplification of a more complex organisation. Our results show that Xenocratena suecica reveals an onset of parallel paedomorphic evolution so we have proposed the new family, Xenocratenidae fam. n., to accommodate the molecular and morphological disparities we discovered. The paedomorphic origin of another aeolidacean family, Embletoniidae, is also demonstrated for the first time. Thus, by presenting three independent lineages from non-closely related aeolidacean families, Xenocratenidae fam. n., Cumanotidae and Embletoniidae, we confirm with phylogenetic data that a soft-substrata burrowing-related environment strongly favours paedomorphic evolution. We suggest criteria to distinguish ancestral and derived characters in the context of modifications of ontogenetic cycles. Applying an evolutionary model of the soft substrate-driven multiple paedomorphic origin of several families of nudibranch molluscs we propose that it is plausible to extend this model to other marine invertebrates and suggest that the ancestral organisation of the enigmatic metazoan, Xenoturbella, might correspond to the larval part of a complex ancestral bilaterian ontogenetic cycle with sedentary/semi-sedentary adult stages and planula-like larval stages.
PMID: 31940379 DOI: 10.1371/journal.pone.0227173

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Select item 3194037846.
PLoS One. 2020 Jan 15;15(1):e0226275. doi: 10.1371/journal.pone.0226275. eCollection 2020.
Valuing natural habitats for enhancing coastal resilience: Wetlands reduce property damage from storm surge and sea level rise.
Rezaie AM1, Loerzel J2, Ferreira CM1.

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Abstract


Storm surge and sea level rise (SLR) are affecting coastal communities, properties, and ecosystems. While coastal ecosystems, such as wetlands and marshes, have the capacity to reduce the impacts of storm surge and coastal flooding, the increasing rate of SLR can induce the transformation and migration of these natural habitats. In this study, we combined coastal storm surge modeling and economic analysis to evaluate the role of natural habitats in coastal flood protection. We focused on a selected cross-section of three coastal counties in New Jersey adjacent to the Jacques Cousteau National Estuarine Research Reserve (JCNERR) that is protected by wetlands and marshes. The coupled coastal hydrodynamic and wave models, ADCIRC+SWAN, were applied to simulate flooding from historical and synthetic storms in the Mid-Atlantic US for current and future SLR scenarios. The Sea Level Affecting Marshes Model (SLAMM) was used to project the potential migration and habitat transformation in coastal marshes due to SLR in the year 2050. Furthermore, a counterfactual land cover approach, in which marshes are converted to open water in the model, was implemented for each storm scenario in the present and the future to estimate the amount of flooding that is avoided due to the presence of natural habitats and the subsequent reduction in residential property damage. The results indicate that this salt marshes can reduce up to 14% of both the flood depth and property damage during relatively low intensity storm events, demonstrating the efficacy of natural flood protection for recurrent storm events. Monetarily, this translates to the avoidance of up to $13.1 and $32.1 million in residential property damage in the selected coastal counties during the '50-year storm' simulation and hurricane Sandy under current sea level conditions, and in the year '2050 SLR scenario', respectively. This research suggests that protecting and preserving natural habitats can contribute to enhance coastal resilience.
PMID: 31940378 DOI: 10.1371/journal.pone.0226275

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Conflict of interest statement


Select item 3194037747.
PLoS One. 2020 Jan 15;15(1):e0227108. doi: 10.1371/journal.pone.0227108. eCollection 2020.
Signatures of medical student applicants and academic success.
Baron T1,2, Grossman RI3, Abramson SB4, Pusic MV2, Rivera R3, Triola MM2, Yanai I1.

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Abstract


The acceptance of students to a medical school places a considerable emphasis on performance in standardized tests and undergraduate grade point average (uGPA). Traditionally, applicants may be judged as a homogeneous population according to simple quantitative thresholds that implicitly assume a linear relationship between scores and academic success. This 'one-size-fits-all' approach ignores the notion that individuals may show distinct patterns of achievement and follow diverse paths to success. In this study, we examined a dataset composed of 53 variables extracted from the admissions application records of 1,088 students matriculating to NYU School of Medicine between the years 2006-2014. We defined training and test groups and applied K-means clustering to search for distinct groups of applicants. Building an optimized logistic regression model, we then tested the predictive value of this clustering for estimating the success of applicants in medical school, aggregating eight performance measures during the subsequent medical school training as a success factor. We found evidence for four distinct clusters of students-we termed 'signatures'-which differ most substantially according to the absolute level of the applicant's uGPA and its trajectory over the course of undergraduate education. The 'risers' signature showed a relatively higher uGPA and also steeper trajectory; the other signatures showed each remaining combination of these two main factors: 'improvers' relatively lower uGPA, steeper trajectory; 'solids' higher uGPA, flatter trajectory; 'statics' both lower uGPA and flatter trajectory. Examining the success index across signatures, we found that the risers and the statics have significantly higher and lower likelihood of quantifiable success in medical school, respectively. We also found that each signature has a unique set of features that correlate with its success in medical school. The big data approach presented here can more sensitively uncover success potential since it takes into account the inherent heterogeneity within the student population.
PMID: 31940377 DOI: 10.1371/journal.pone.0227108

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Conflict of interest statement


Select item 3194037648.
PLoS One. 2020 Jan 15;15(1):e0227304. doi: 10.1371/journal.pone.0227304. eCollection 2020.
Evaluating two decision aids for Australian men supporting informed decisions about prostate cancer screening: A randomised controlled trial.
Pickles K1, Kazda L1, Barratt A1, McGeechan K1, Hersch J1, McCaffery K1.

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Abstract

BACKGROUND:

Australian clinicians are advised to 'offer evidence-based decisional support to men considering whether or not to have a PSA test'. This randomised trial compared the performance and acceptability of two new decision aids (DAs) to aid men in making informed choices about PSA screening.
METHODS:

~3000 Australian men 45-60 years with varying educational attainment were recruited via an online panel and randomised to view one of two online decision aids (one full length, one abbreviated) and completed a questionnaire. The primary outcome was informed choice about PSA screening.
FINDINGS:

Significantly more men in the long DA group (38%) made an informed choice than men who received the shorter DA (33%) (95% CI 1.1% to 8.2%; p = 0.008). On knowledge, the long DA group scored, on average, 0.45 points higher than the short DA group (95% CI 0.14 to 0.76; p = 0.004) and 5% more of the participants achieved an adequate knowledge score (95% CI 1.9% to 8.8%; p = 0.002). Men allocated the long DA were less likely to intend to have a PSA test in the future (53%) than men in the short DA group (59%). Both DAs rated highly on acceptability.
CONCLUSIONS:

Both DAs were useful and acceptable to men regardless of education level and both supported informed decision making. The long version resulted in higher knowledge, and a higher proportion of men able to make an informed choice, but the differences were small. Long DAs may be useful for men whose informational needs are not satisfied by a short DA.
PMID: 31940376 DOI: 10.1371/journal.pone.0227304

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Conflict of interest statement


Select item 3194037549.
PLoS One. 2020 Jan 15;15(1):e0227293. doi: 10.1371/journal.pone.0227293. eCollection 2020.
Barriers in the access, diagnosis and treatment completion for tuberculosis patients in central and western Nepal: A qualitative study among patients, community members and health care workers.
Marahatta SB1, Yadav RK1, Giri D1, Lama S1, Rijal KR2, Mishra SR3, Shrestha A4, Bhattrai PR4, Mahato RK5, Adhikari B6,7.

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Abstract

BACKGROUND:

Nepal has achieved a significant reduction of TB incidence over the past decades. Nevertheless, TB patients continue to experience barriers in access, diagnosis and completion of the treatment. The main objective of this study was to explore the factors affecting the access to the health services, diagnosis and the treatment completion for TB patients in central and western Nepal.
METHODS:

Data were collected using in-depth interviews (IDI) with the TB patients (n = 4); Focus Group Discussions (FGDs) with TB suspected patients (n = 16); Semi Strucutred Interviews (SSIs) with health workers (n = 24) and traditional healers (n = 2); and FGDs with community members (n = 8). All data were audio recorded, transcribed and translated to English. All transcriptions underwent thematic analysis using qualitative data analysis software: Atlas.ti.
RESULTS:

Barriers to access to the health centre were the long distance, poor road conditions, and costs associated with travelling. In addition, lack of awareness of TB and its consequences, and the belief, prompted many respondents to visit traditional healers. Early diagnosis of TB was hindered by lack of trained health personnel to use the equipment, lack of equipment and irregular presence of health workers. Additional barriers that impeded the adherence and treatment completion were the need to visit health centre daily for DOTS treatment and associated constraints, complex treatment regimen, and the stigma.
CONCLUSIONS:

Barriers embedded in health services and care seekers' characteristics can be dealt by strengthening the peripheral health services. A continuous availability of (trained) human resources and equipment for diagnosis is critical. As well as increasing the awareness and collaborating with the traditional healers, health services utilization can be enhanced by compensating the costs associated with it, including the modification in current DOTS strategy by providing medicine for a longer term under the supervision of a family member, peer or a community volunteer.
PMID: 31940375 DOI: 10.1371/journal.pone.0227293

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Select item 3194037450.
PLoS One. 2020 Jan 15;15(1):e0226779. doi: 10.1371/journal.pone.0226779. eCollection 2020.
Reconstructing Krassilovia mongolica supports recognition of a new and unusual group of Mesozoic conifers.
Herrera F1, Shi G2, Mays C3,4, Ichinnorov N5, Takahashi M6, Bevitt JJ7, Herendeen PS1, Crane PR8,9.

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Abstract


Previously unrecognized anatomical features of the cone scales of the enigmatic Early Cretaceous conifer Krassilovia mongolica include the presence of transversely oriented paracytic stomata, which is unusual for all other extinct and extant conifers. Identical stomata are present on co-occurring broad, linear, multiveined leaves assigned to Podozamites harrisii, providing evidence that K. mongolica and P. harrisii are the seed cones and leaves of the same extinct plant. Phylogenetic analyses of the relationships of the reconstructed Krassilovia plant place it in an informal clade that we name the Krassilovia Clade, which also includes Swedenborgia cryptomerioides-Podozamites schenkii, and Cycadocarpidium erdmanni-Podozamites schenkii. All three of these plants have linear leaves that are relatively broad compared to most living conifers, and that are also multiveined with transversely oriented paracytic stomata. We propose that these may be general features of the Krassilovia Clade. Paracytic stomata, and other features of this new group, recall features of extant and fossil Gnetales, raising questions about the phylogenetic homogeneity of the conifer clade similar to those raised by phylogenetic analyses of molecular data.
PMID: 31940374 DOI: 10.1371/journal.pone.0226779

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