Associations between genetically predicted levels of blood metabolites and pancreatic cancer risk

AlexandrosSfakianakis shared this article with you from Inoreader Associations between genetically predicted levels of blood metabolites and pancreatic cancer risk via International Journal of Cancer Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive solid malignancies, which is featured by systematic metabolism. Thus, a better understanding of metabolic dysregulation in PDAC is important to better characterize its etiology. Here, we performed a large metabolome-wide association study (MWAS) to systematically explore associations between genetically predicted metabolite levels in blood and PDAC risk. Using data from 881 subjects of European descent in the TwinsUK Project, comprehensive genetic models were built to predict serum metabolite levels. These prediction models were applied to the genetic data of 8,280 cases and 6,728 controls included in the PanScan (I, II, and III) and PanC4 consortia. After assessing the metabolite-PDAC risk associations by a slightly modified TWAS/FUSION framework, we identified five metabolites (including two dipeptides) showing significant associations with PDAC risk at false discovery rate (FDR)<0.05. Integrated with gut m icrobial information, two-sample Mendelian randomization (MR) analyses were further performed to investigate the relationship among serum metabolites, gut microbiome features, and PDAC. The flavonoid-degrading bacteria Flavonifractor sp90199495 was found to be associated with metabolite X – 21849, and it was also shown to be associated with PDAC risk. Collectively, our study identified novel candidate metabolites for PDAC risk, which could lead to new insights into the etiology of PDAC and improved treatment options. View on Web

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Exosomes: Mediators in Microenvironment of Colorectal Cancer

AlexandrosSfakianakis shared this article with you from Inoreader Exosomes: Mediators in Microenvironment of Colorectal Cancer via International Journal of Cancer Abstract Tumor microenvironment, the soil where tumor thrives, plays a critical role in the development and progression of colorectal cancer (CRC). Various cell signaling molecules in the environment promote tumor angiogenesis, immune tolerance and facilitate immune escape. Exosomes, as messengers between tumor and host cells, are considered key mediators involved in the tumor-accelerating environment. However, the exosome-mediated communication networks in the CRC microenvironment are still largely unclear. In this review, we summarized the relationship between TME and CRC based on recent literature. Then, we revealed the unique impacts and signal molecules of exosomes on account of their regulatory role in the flora, hypoxia, inflammatory, and immunological microenvironment of CRC. Finally, we summarized the therapeutically effective of exosomes in CRC microenvironment and discussed their current status and prospects, aiming to provide new molecular targets and a theoretical basis for th e CRC treatment. View on Web

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Identification of target proteins for breast cancer genetic risk loci and blood risk biomarkers in a large study by integrating genomic and proteomic data

AlexandrosSfakianakis shared this article with you from Inoreader Identification of target proteins for breast cancer genetic risk loci and blood risk biomarkers in a large study by integrating genomic and proteomic data via International Journal of Cancer Abstract Genome-wide association studies (GWAS) have identified around 200 loci associated with breast cancer risk. However, protein targets for these loci remain largely unknown. Identifying protein targets and biomarkers can improve the understanding of cancer biology and etiology and identify high-risk individuals for cancer prevention. In this study, we investigated genetically predicted levels of 1,142 circulating proteins with breast cancer risk in 133,384 cases and 113,789 controls of European ancestry included in the Breast Cancer Association Consortium (BCAC). We identified 22 blood protein biomarkers associated with the risk of overall breast cancer at a false discovery rate (FDR) <0.05, including nine proteins encoded by genes located at least 500kb away from previously reported risk variants for breast cancer. Analyses focusing on 124 encoding genes located at GWAS-identified breast cancer risk loci found 20 proteins associated with overall breast cancer risk and one protein associated with triple-negative breast cancer risk at FDR <0.05. Adjustment for the GWAS-identified risk variants significantly attenuated the association for 13 of these proteins, suggesting that these proteins may be the targets of these GWAS-identified risk loci. The identified proteins are involved in various biological processes, including glutathione conjugation, STAT5 signaling, and NF-κB signaling pathways. Our study identified novel protein targets and risk biomarkers for breast cancer risk. View on Web

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Pain mitigation and management strategies for anti‐GD2 infusions: An expert consensus

AlexandrosSfakianakis shared this article with you from Inoreader Pain mitigation and management strategies for anti‐GD2 infusions: An expert consensus via Pediatric Blood & Cancer Abstract Monoclonal antibodies (mAbs) targeting disialoganglioside 2 (GD2) are an important treatment advance for high-risk neuroblastoma, including in patients with refractory or relapsed disease. Dinutuximab and dinutuximab beta are administered for ≥8 hours (and up to 10 days for dinutuximab beta), whereas naxitamab is administered over 0.5 to 2 hours as tolerated. As acute pain is a class effect of anti-GD2 mAbs, effective pain management is crucial to successful treatment. Here, we provide an overview of current pain-management strategies for anti-GD2 mAb infusions, with a focus on strategies suitable for naxitamab infusions, which cause a more rapid onset of often severe pain. We discuss opioid analgesics, ketamine, gabapentin, and other similar agents and nonpharmacologic approaches. Potential future pain-management options are also discussed, in addition to the use of sedatives to reduce the anxiety that may be associated with infusion-related pain. In this expert conse nsus paper, specific guidance for pain management during naxitamab infusions is provided, as these infusions are administered over 0.5 to 2 hours and may not need overnight hospitalization based on the physician's assessment, and require rapid-onset analgesia options suitable for potential outpatient administration. View on Web

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Neonatal intestinal obstruction in Hoyeraal–Hreidarsson syndrome with novel RTEL1 variants

AlexandrosSfakianakis shared this article with you from Inoreader Neonatal intestinal obstruction in Hoyeraal–Hreidarsson syndrome with novel RTEL1 variants via Pediatric Blood & Cancer View on Web

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The adult outcome of childhood quasi‐autism arising following extreme institutional deprivation

AlexandrosSfakianakis shared this article with you from Inoreader The adult outcome of childhood quasi‐autism arising following extreme institutional deprivation via Journal of Child Psychology and Psychiatry Background Rutter and colleagues' seminal observation that extended early life exposure to extreme institutional deprivation can result in what he termed quasi-autism (QA), informed both our understanding of the effects of adversity on development and the nature of autism. Here we provide the first detailed analysis of the adult outcomes of the group of institutionally deprived-then-adopted children identified as displaying QA. Methods Twenty-six adult adoptees identified with QA in childhood (Childhood QA+) were compared to 75 adoptees who experienced extended institutional deprivation (>6 months) but no QA (Childhood QA−), and 116 adoptees exposed to Low/No institutional deprivation. The outcomes were child-to-adult developmental trajectories of neuro-developmental symptoms (autism, attention-deficit/hyperactivity disorder (ADHD), disinhibited social engagement (DSE) and cognitive impairment), adult functioning, life satisfaction and mental health. Results Childhood QA+ was associated with elevated and persistent trajectories of broad-based autism-related difficulties, ADHD and DSE symptoms and low IQ, as well as adult mental health difficulties and functional impairment, including high rates of low educational attainment and unemployment. Life satisfaction and self-esteem were unaffected. Autism-related communication problems, in particular, predicted negative adult outcomes. Childhood QA+ was still associated with poor outcomes even when ADHD, DSE and IQ were controlled. Conclusions Early and time-limited institutional deprivation has a critical impact on adult functioning, in part via its association with an early established and persistent variant of autism, especially related to communication difficulties. Apparent similarities and differences to non-deprivation related autism are discussed. View on Web

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Characterization of Microvascular Invasion in Hepatocellular Carcinoma Using Computational Modeling of Interstitial Fluid Pressure and Velocity

AlexandrosSfakianakis shared this article with you from Inoreader Characterization of Microvascular Invasion in Hepatocellular Carcinoma Using Computational Modeling of Interstitial Fluid Pressure and Velocity via Journal of Magnetic Resonance Imaging Background Most solid tumors show increased interstitial fluid pressure (IFP), and this increased IFP is an obstacle to treatment. A noninvasive model for measuring IFP in hepatocellular carcinoma (HCC) is an unresolved issue. Purpose To develop a noninvasive model to measure IFP and interstitial fluid velocity (IFV) in HCC and to characterize the microvascular invasion (MVI) status by using this model. Study Type Retrospective. Population A total of 97 HCC patients (mean age 57.6 ± 10.9 years, 77.3% males), 53 of them with MVI and 44 of them without MVI. Field Strength/Sequence A 3-T, three-dimensional spoiled gradient-recalled echo. Assessment MVI was defined as microscopic vascular invasion of small vessels within the peritumoral liver tissue. The volumes of interest (VOIs) were manually delineated and enclosed the tumor lesion and healthy liver parenchyma, respectively. The extended Tofts model (ETM) was used to estimate permeability parameters from all the VOIs. Subsequently, the continuity partial differential equation (PDE) was implemented and IFP and IFV were acquired. Statistical Tests Wilcoxon signed-ranks tests, histogram analysis, Mann–Whitney U test, Fisher's exact test, least absolute shrinkage and selection operator (LASSO) logistic regression, receiver operating characteristic (ROC) curve analysis with the area under the curve (AUC), Youden index, DeLong test, and Benjamini–Hochberg correction. A P value <0.05 was considered statistically significant. Results The HCC lesions exhibited elevated IFP and reduced IFV. There were no significant differences in any measured demographic and clinical features between the MVI-positive and MVI-negative groups, except for tumor size. Nine IFP histogram analysis-derived parameters and seven IFV histogram analysis-derived parameters could be used to characterize the MVI status. LASSO regression selected five features: IFP maximum, IFP 10th percentile, IFP 90th percentile, IFV SD, and IFV 10th percentile. The combination of these features showed the highest AUC (0.781) and specificity (77.3%). Data Conclusion A noninvasive IFP and IFV measurement model for HCC was developed. Specific IFP- and IFV-derived parameters exhibited significant association with the MVI status. Evidence Level 3. Technical Efficacy Stage 2. View on Web

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Effectiveness and Accuracy of MRI‐Ultrasound Fusion Targeted Biopsy Based on PI‐RADS v2.1 Category in Transition/Peripheral Zone of the Prostate

AlexandrosSfakianakis shared this article with you from Inoreader Effectiveness and Accuracy of MRI‐Ultrasound Fusion Targeted Biopsy Based on PI‐RADS v2.1 Category in Transition/Peripheral Zone of the Prostate via Journal of Magnetic Resonance Imaging Background MRI-ultrasound fusion targeted biopsy (MRI-TBx) improves the clinically significant prostate cancer (csPCa) detection with fewer cores. However, whether systematic biopsy-guided by transrectal ultrasound (TRUS-SBx) can be omitted when undergoing MRI-TBx in transition zone (TZ) and peripheral zone (PZ) remains unclear. Purpose To assess the performance and effectiveness of MRI-TBx based on PI-RADS v2.1 for csPCa diagnosis in TZ and PZ, respectively. Study Type Retrospective. Subjects A total of 309 selected cases (median age 70 years) with 356 lesions who underwent both MRI-TBx and TRUS-SBx were enrolled. Field Strength/Sequence A 3.0 T, multiparametric MRI (mp-MRI) including T2-weighted turbo-spin echo imaging (T2WI), diffusion-weighted spin-echo echo planar imaging (DWI), dynamic contrast-enhanced MRI with time-resolved T1-weighted imaging (DCE). Assessment Mp-MRI was assessed by two radiologists using PI-RADS v2.1. The csPCa detection rates provided by MRI-TBx, TRUS-SBx and combined biopsy in TZ and PZ were calculated, respectively. Statistical Tests McNemar test was used to compare the csPCa detection rates in TZ and PZ, respectively. The frequencies and distribution of all detected prostate cancers by different biopsy methods were also compared. P < 0.05 was considered statistically significant. Results Among 356 lesions in 309 patients, 208 (68 in TZ, 140 in PZ) were pathologically confirmed as csPCa. In TZ, there were significant differences for csPCa detection with PI-RADS 3 between combined biopsy and TRUS-SBx (23.5% vs. 15.3%), MRI-TBx (23.5% vs. 16.3%), respectively. MRI-TBx detected 23% (19/83) cases missed by TRUS-SBx in which 68% (13/19) were csPCa. In PZ, there were no statistical differences between MRI-TBx and combined biopsy with PI-RADS 3–5 (P = 0.21, 0.25, 0.07, respectively). In 9% (14/152) cases only detected by MRI-TBx, 86% (12/14) were clinically significant. Five percent (7/152) of cases only detected by TRUS-SBx were completely nonclinically significant. Data Conclusion MRI-TBx played a positive role on csPCa diagnosis in TZ, but combined biopsy might be the best choice especially in the subgroup PI-RADS 3. In PZ, MRI-TBx had an advantage over TRUS-SBx for csPCa detection. Evidence Level 2. Technical Efficacy Stage 2. View on Web

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WHOLE‐GENOME SINGLE MOLECULE REAL‐TIME SEQUENCING OF SARS‐CoV‐2 OMICRON

AlexandrosSfakianakis shared this article with you from Inoreader WHOLE‐GENOME SINGLE MOLECULE REAL‐TIME SEQUENCING OF SARS‐CoV‐2 OMICRON via Journal of Medical Virology ABSTRACT New variants and genetic mutations of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome can only be identified using accurate sequencing methods. Single molecule real-time (SMRT) sequencing has been used to characterize Alpha and Delta variants, but not Omicron variants harbouring numerous mutations in the SARS-CoV-2 genome. This study assesses the performance of a target capture SMRT sequencing protocol for whole genome sequencing (WGS) of SARS-CoV-2 Omicron variants and compared it to that of an amplicon SMRT sequencing protocol optimized for Omicron variants. The failure rate of the target capture protocol (6%) was lower than that of the amplicon protocol (34%, p<0.001) on our dataset, and the median genome coverage with the target capture protocol (98.6% [IQR: 86-99.4]) was greater than that with the amplicon protocol (76.6% [IQR: 66-89.6], (p<0.001)). The percentages of samples with >95% whole genome coverage were 64% with the target capture pro tocol and 19% with the amplicon protocol (p<0.05). The clades of 96 samples determined with both protocols were 93% concordant and the lineages of 59 samples were 100% concordant. Thus, target capture SMRT sequencing appears to be an efficient method for WGS, genotyping and detecting mutations of SARS-CoV-2 Omicron variants. This article is protected by copyright. All rights reserved. View on Web

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Concerns on Bebtelovimab (LY‐CoV1404) used to neutralize Omicron subvariants

AlexandrosSfakianakis shared this article with you from Inoreader Concerns on Bebtelovimab (LY‐CoV1404) used to neutralize Omicron subvariants via Journal of Medical Virology Abstract Bebtelovimab (LY-CoV1404) is a monoclonal antibody showing remarkable neutralizing capacity against all SARS-CoV-2 variants of concern (VOCs) as of June 2022, including the Omicron variant and its subvariants This article is protected by copyright. All rights reserved. View on Web

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