Δευτέρα 23 Ιανουαρίου 2023

Role of craniofacial phenotypes in the response to oral appliance therapy for obstructive sleep apnea

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Abstract

Background

Mandibular advancement device (MAD) is a good alternative for patients with obstructive sleep apnea (OSA). However, the treatment response varies among individuals.

Objective

This study aimed to explore the role of craniofacial features in the response to MADs to improve prognostication and patient selection.

Methods

The retrospective trial contained 42 males aged 41.5±9.0 years, and with an apnea-hypopnea index (AHI) of 21.5±13.8 events/h. According to the mandibular plane angle, participants were divided into three groups: low angle (n=13), average angle (n=14), and high angle (n=15). Under monitor of home sleep testing, adjustable MADs were used to titrate the mandible forward from 0 mm with an increment of 0.5 mm every day. The polysomnography outcomes, mandibular protrusion amounts, changes in upper airway MRI measurements, and nasal resistance were compared among three groups.

Results

The normalization rate (AHI < 5 /h) was 92.3%, 57.1%, and 46.7% respectively in the low, average, and high angle groups (p=0.027). The effective protrusion where AHI was reduced by half was 20 (11.3~37.5) %, 31.3 (23.6~50) %, and 50 (36.9~64.9) % of the maximal mandibular protrusion, in the low, average, and high angle groups (p=0.004). Multivariate logistic regression revealed that increased gonion angle (OR=0.878) and baseline AHI(OR=0.868) can reduce the probability of normalization.

Conclusion

The high mandibular plane angle might be an unfavorable factor to MAD treatment and more protrusion was needed to achieve a 50% reduction in AHI. Vertical craniofacial pattern (gonion angle) and baseline AHI constituted the model for predicting the effect of MADs.

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Single-cell transcriptomic analyses provide insights into the cellular origins and drivers of brain metastasis from lung adenocarcinoma

alexandrossfakianakis shared this article with you from Inoreader
Abstract
Background
Brain metastasis (BM) is the most common intracranial malignancy causing significant mortality, and lung cancer is the most common origin of BM. However, the cellular origins and drivers of BM from lung adenocarcinoma (LUAD) have yet to be defined.
Methods
The cellular constitutions were characterized by single-cell transcriptomic profiles of 11 LUAD primary tumor (PT) and 10 BM samples (GSE131907). Copy number variation (CNV) and clonality analysis were applied to illustrate cellular origins of BM tumors. Brain metastasis-associated epithelial cells (BMAECs) were identified by pseudotime trajectory analysis. By using machine-learning algorithms, we developed the BM-index representing the relative abundance of BMAECs in the bulk RNA-seq data, indicating high risk of BM. Therapeutic drugs targeting BMAECs were predicted based on the drug sensitivity data of cancer cell lines.
Results
Differences in macrophage s and T cells between PTs and BMs were investigated by single-cell RNA (scRNA) and immunohistochemistry and immunofluorescence data. CNV analysis demonstrated BM was derived from subclones of PT with a gain of chromosome 7. We then identified BMAECs and its biomarker, S100A9. Immunofluorescence indicated strong correlations of BMAECs with metastasis and prognosis evaluated by the paired PT and BM samples from Peking Union Medical College Hospital (PUMCH). We further evaluated the clinical significance of BM-index and identified 7 drugs that potentially target BMAECs.
Conclusions
This study clarified possible cellular origins and drivers of metastatic LUAD at single cell level, and laid a foundation for early detections of LUAD patients with a high risk of BM.
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GBMdeconvoluteR accurately infers proportions of neoplastic and immune cell populations from bulk glioblastoma transcriptomics data

alexandrossfakianakis shared this article with you from Inoreader
Abstract
Background
Characterising and quantifying cell types within glioblastoma (GBM) tumours at scale will facilitate a better understanding of the association between the cellular landscape and tumour phenotypes or clinical correlates. We aimed to develop a tool that deconvolutes immune and neoplastic cells within the GBM tumour microenvironment from bulk RNA sequencing data.
Methods
We developed an IDH wild-type (IDHwt) GBM-specific single immune cell reference consisting of B cells, T cells, NK cells, microglia, tumour associated macrophages, monocytes, mast and DC cells. We used this alongside an existing neoplastic single cell-type reference for astrocyte-like, oligodendrocyte- and neuronal-progenitor like and mesenchymal GBM cancer cells to create both marker and gene signature matrix-based deconvolution tools. We applied single-cell resolution imaging mass cytometry (IMC) to ten IDHwt GBM samples, five paired primary and recur rent tumours, to determine which deconvolution approach performed best.
Results
Marker based deconvolution using GBM tissue specific markers was most accurate for both immune cells and cancer cells, so we packaged this approach as GBMdeconvoluteR. We applied GBMdeconvoluteR to bulk GBM RNAseq data from The Cancer Genome Atlas and recapitulated recent findings from multi-omics single cell studies with regards associations between mesenchymal GBM cancer cells and both lymphoid and myeloid cells. Furthermore, we expanded upon this to show that these associations are stronger in patients with worse prognosis.
Conclusions
GBMdeconvoluteR accurately quantifies immune and neoplastic cell proportions in IDHwt GBM bulk RNA sequencing data and is accessible here: https : // gbmdeconvoluter.leeds.ac.uk
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Κυριακή 22 Ιανουαρίου 2023

Vitamin D levels in the assessment of Crohn's disease activity and their relation to nutritional status and inflammation

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background

Crohn's disease (CD) is frequently associated with malnutrition, inflammation, and a deficiency of vitamin D (VD) with the relationships between these symptoms being poorly defined. Vitamin D is a modulator of the immune system and is associated with the onset of CD and disease activity. The level of serum VD may have potential in the assessment of CD activity. This study aimed to evaluate the relationships between VD, nutritional status, and inflammation, and to identify more accurate VD thresholds.

Methods

The study included 76 outpatients with CD diagnosed between October 2018 and October 2020 and 76 healthy volunteers. Levels of serum 25(OH)D and nutritional indicators, as well as biochemical and disease activity assessments were conducted.

Results

Patients with CD and healthy participants were found to differ significantly in their 25(OH)D levels as well in levels of nutritional and inflammatory indicators. The optimal VD cut-off value was found to be 46.81 nmol/L for CD development and 35.32 nmol/L for disease activity. Levels of 25(OH)D were correlated with both nutritional status and inflammation.

Conclusions

The VD level is likely to be a useful additional tool in the evaluation of CD patients and predicting the disease activity and clinical response. The VD level may relate both to the nutritional status and levels of inflammation in CD patients, as well as disease progression.

This article is protected by copyright. All rights reserved.

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Impact of air pollutants on influenza−like illness outpatient visits under COVID−19 pandemic in the sub−center of Beijing, China

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Objective

This study aimed to explore the association between air pollutants and outpatient visits for influenza−like illnesses (ILI) under the coronavirus disease 2019 (COVID−19) stage in the sub−center of Beijing.

Methods

The data on ILI in the sub−center of Beijing from 1 January 2018 to 31 December 2020 were obtained from the Beijing Influenza Surveillance Network. A generalized additive Poisson model was applied to examine the associations between the concentrations of air pollutants and daily outpatient visits for ILI when controlling meteorological factors and temporal trend.

Results

A total of 171,943 ILI patients were included. In the pre−COVID−19 stage, an increased risk of ILI outpatient visits was associated to a high air quality index (AQI) and the high concentrations of particulate matter less than 2.5 (PM2.5), particulate matter 10 (PM10), sulphur dioxide (SO2), nitrogen dioxide (NO2), and carbon monoxide (CO), and a low concentration of ozone (O3) on lag0 day and lag1 day, while a higher increased risk of ILI outpatient visits was observed by the air pollutants in the COVID−19 stage on lag0 day. Except for PM10,the concentrations of other air pollutants on lag1 day were not significantly associated with an increased risk of ILI outpatient visits during the COVID−19 stage.

Conclusion

The findings that air pollutants had enhanced immediate effects and diminished lag-effects on the risk of ILI outpatient visits during the COVID−19 pandemic, which is important for the development of public health and environmental governance strategies.

This article is protected by copyright. All rights reserved.

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Torque teno virus (TTV): a gentle spy virus of immune status, predictive marker of seroconversion to COVID‐19 vaccine in kidney and lung transplant recipients

alexandrossfakianakis shared this article with you from Inoreader

Abstract

To date, no comprehensive marker to monitor the immune status of patients is available. Given that Torque teno virus (TTV), a known human virome component, has previously been identified as a marker of immunocompetence, it was retrospectively investigated whether TTV viral load may also represent a marker of ability to develop antibody in response to COVID-19-BNT162B2 vaccine in solid organ transplant recipients (SOT). Specifically, 273 samples from 146 kidney and 26 lung transplant recipients after successive doses of vaccine were analyzed. An inverse correlation was observed within the TTV copy number and anti-Spike IgG antibody titer with a progressive decrease in viremia the further away from the transplant date. Analyzing the data obtained after the second dose, a significant difference in TTV copy number between responsive and non-responsive patients was observed, considering a 5 log10 TTV copies/ml threshold to discriminate between the two groups. Moreover , for 86 patients followed in their response to the second and third vaccination doses a 6 log10 TTV copies/ml threshold was used to predict responsivity to the booster dose. Although further investigation is necessary, possibly extending the analysis to other patient categories, this study suggests that TTV can be used as a good marker of vaccine response in transplant patients.

This article is protected by copyright. All rights reserved.

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Does baseline EEG activity differ in the transition to or from a chronic pain state?

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background and aim

Identifying EEG brain markers might yield better mechanistic insights into how chronic pain develops and could be treated. An existing longitudinal EEG study gave us the opportunity to determine whether the development of pain is accompanied by less alpha power—ie, a 'relaxed' brain state—and vice versa.

Methods

Five-minute resting EEG with the eyes open was measured 2 times in 95 subjects at T0 (baseline) and T1 (6 months later). Based on the Short-Form Health Survey and Brief Pain Inventory questionnaire, subjects were divided into 4 groups: staying pain-free (n = 44), developing chronic pain (n = 8), becoming pain-free (n = 15), and ongoing chronic pain (n = 28). The EEG data of 14 electrodes were analyzed by multilevel regression.

Results

The group that developed chronic pain demonstrated less power in the lower-frequency bands over time during the resting state EEG, whereas the transition to a pain-free state had the opposite pattern. Thus, the a priori hypothesis was confirmed.

Conclusions

Transitions in pain states are linked to a change in baseline EEG activity. Future research is needed to replicate these results in a larger study sample and in targeted clinical populations. Further, these results might be beneficial in optimizing neurofeedback algorithms for the treatment of chronic pain.

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