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"Dual Pandemics": Intersecting Influences of Anti-Black Racism and the COVID-19 Pandemic on the Mental Health of Black Youth

5 days 1 hour ago
CONCLUSION: The simultaneous occurrence of the COVID-19 pandemic and instances of systemic anti-Black racism in the form of police violence presented "dual pandemics" for the Black community, profoundly impacting the mental health of Black youth and adding urgency and impetus to its prioritization. Results of this study indicate that it is critical to explore each event individually as well as the combined impact on the mental health of Black youth, particularly from a racial perspective.
Samah Osman

Shortcut learning in medical AI hinders generalization: method for estimating AI model generalization without external data

1 week ago
Healthcare datasets are becoming larger and more complex, necessitating the development of accurate and generalizable AI models for medical applications. Unstructured datasets, including medical imaging, electrocardiograms, and natural language data, are gaining attention with advancements in deep convolutional neural networks and large language models. However, estimating the generalizability of these models to new healthcare settings without extensive validation on external data remains...
Cathy Ong Ly

Exploring opportunities to strengthen rural tuberculosis health service delivery: a qualitative study with health workers in Tibet autonomous region, China

1 week 1 day ago
CONCLUSIONS: The quality of TB care could be improved across the care cascade in Tibet and other high-burden, remote settings by strengthening primary care through ongoing training, greater support and inclusion of community health workers and by leveraging technology to create a circle of care. Future formative and implementation research should include the perspectives of health workers at all levels to improve care organisation and delivery.
Victoria Haldane

DyMMM-LEAPS: An ML-based framework for modulating evenness and stability in synthetic microbial communities

1 week 3 days ago
There have been a growing number of computational strategies to aid in the design of synthetic microbial consortia. A framework to identify regions in parametric space to maximize two essential properties, evenness and stability, is critical. In this study, we introduce DyMMM-LEAPS (Dynamic Multi-species Metabolic Modeling - Locating Evenness And stability in large Parametric Space), an extension of the DyMMM framework. Our method explores the large parametric space of genetic circuits in...
Ruhi Choudhary

Integrative multi-omics analyses to identify the genetic and functional mechanisms underlying ovarian cancer risk regions

1 week 5 days ago
To identify credible causal risk variants (CCVs) associated with different histotypes of epithelial ovarian cancer (EOC), we performed genome-wide association analysis for 470,825 genotyped and 10,163,797 imputed SNPs in 25,981 EOC cases and 105,724 controls of European origin. We identified five histotype-specific EOC risk regions (p value <5 × 10^(-8)) and confirmed previously reported associations for 27 risk regions. Conditional analyses identified an additional 11 signals independent of the...
Eileen O Dareng

Natural compound screening predicts novel GSK-3 isoform-specific inhibitors

1 week 5 days ago
Glycogen synthase kinase-3 (GSK-3) plays important roles in the pathogenesis of cardiovascular, metabolic, neurological disorders and cancer. Isoform-specific loss of either GSK-3α or GSK-3β often provides cytoprotective effects under such clinical conditions. However, available synthetic small molecule inhibitors are relatively non-specific, and their chronic use may lead to adverse effects. Therefore, screening for natural compound inhibitors to identify the isoform-specific inhibitors may...
Firdos Ahmad

Long-range order enabled stability in quantum dot light-emitting diodes

1 week 6 days ago
Light-emitting diodes (LEDs) based on perovskite quantum dots (QDs) have produced external quantum efficiencies (EQEs) of more than 25% with narrowband emission^(1,2), but these LEDs have limited operating lifetimes. We posit that poor long-range ordering in perovskite QD films-variations in dot size, surface ligand density and dot-to-dot stacking-inhibits carrier injection, resulting in inferior operating stability because of the large bias required to produce emission in these LEDs. Here we...
Ya-Kun Wang

CRISPR-Cas genome editing in ex-vivo human lungs to rewire the translational path of genome-targeting therapeutics

1 week 6 days ago
The ongoing advancements in CRISPR-Cas technologies can significantly accelerate the preclinical development of both in vivo and ex-vivo organ genome-editing therapeutics. One of the promising applications is to genetically modify donor organs prior to implantation. The implantation of optimized donor organs with long-lasting immunomodulatory capacity holds promise for reducing the need for lifelong potent whole-body immunosuppression in recipients However, assessing genome-targeting...
Kumi Mesaki

Pathway-based, reaction-specific annotation of disease variants for elucidation of molecular phenotypes

2 weeks ago
Germline and somatic mutations can give rise to proteins with altered activity, including both gain and loss-of-function. The effects of these variants can be captured in disease-specific reactions and pathways that highlight the resulting changes to normal biology. A disease reaction is defined as an aberrant reaction in which a variant protein participates. A disease pathway is defined as a pathway that contains a disease reaction. Annotation of disease variants as participants of disease...
Marija Orlic-Milacic

Canadian Network for Mood and Anxiety Treatments (CANMAT) 2023 Update on Clinical Guidelines for Management of Major Depressive Disorder in Adults: Réseau canadien pour les traitements de l'humeur et de l'anxiété (CANMAT) 2023 : Mise à jour des lignes…

2 weeks ago
CONCLUSIONS: The CANMAT 2023 updated guidelines provide evidence-informed recommendations for the management of MDD, in a clinician-friendly format. These updated guidelines emphasize a collaborative, personalized, and systematic management approach that will help optimize outcomes for adults with MDD.
Raymond W Lam

Annotation of nuclear lncRNAs based on chromatin interactions

2 weeks 1 day ago
The human genome is pervasively transcribed and produces a wide variety of long non-coding RNAs (lncRNAs), constituting the majority of transcripts across human cell types. Some specific nuclear lncRNAs have been shown to be important regulatory components acting locally. As RNA-chromatin interaction and Hi-C chromatin conformation data showed that chromatin interactions of nuclear lncRNAs are determined by the local chromatin 3D conformation, we used Hi-C data to identify potential target genes...
Saumya Agrawal

Using Dimensionality Reduction to Visualize Phenotypic Changes in High-Throughput Microscopy

2 weeks 1 day ago
High-throughput microscopy has enabled screening of cell phenotypes at unprecedented scale. Systematic identification of cell phenotype changes (such as cell morphology and protein localization changes) is a major analysis goal. Because cell phenotypes are high-dimensional, unbiased approaches to detect and visualize the changes in phenotypes are still needed. Here, we suggest that changes in cellular phenotype can be visualized in reduced dimensionality representations of the image feature...
Alex X Lu

Guidelines for releasing a variant effect predictor

2 weeks 4 days ago
Computational methods for assessing the likely impacts of mutations, known as variant effect predictors (VEPs), are widely used in the assessment and interpretation of human genetic variation, as well as in other applications like protein engineering. Many different VEPs have been released to date, and there is tremendous variability in their underlying algorithms and outputs, and in the ways in which the methodologies and predictions are shared. This leads to considerable challenges for end...
Benjamin J Livesey

Identification of environmental and methodological factors driving variability of Pepper Mild Mottle Virus (PMMoV) across three wastewater treatment plants in the City of Toronto

2 weeks 4 days ago
PMMoV has been widely used to normalize the concentration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, influenza, and respiratory syncytial virus (RSV) to account for variations in the fecal content of wastewater. PMMoV is also used as an internal RNA recovery control for wastewater-based epidemiology (WBE) tests. While potentially useful for the interpretation of WBE data, previous studies have suggested that PMMoV concentration can be affected by various...
Eyerusalem Goitom

Functional and structural characterization of an IclR family transcription factor for the development of dicarboxylic acid biosensors

2 weeks 5 days ago
Prokaryotic transcription factors (TFs) regulate gene expression in response to small molecules, thus representing promising candidates as versatile small molecule-detecting biosensors valuable for synthetic biology applications. The engineering of such biosensors requires thorough in vitro and in vivo characterization of TF ligand response as well as detailed molecular structure information. In this work, we functionally and structurally characterize the Pca regulon regulatory protein (PcaR)...
Chester Pham

Final outcomes analysis of the cell product SQZ-PBMC-HPV Phase 1 trial in incurable HPV16+ solid tumors shows improved overall survival in patients with increased CD8+ T cell tumor infiltration

2 weeks 5 days ago
Cancer vaccines strive to induce robust, antigen-targeted, T-cell-mediated immune responses but have struggled to produce meaningful regression in solid tumors. An autologous cell vaccine, SQZ-PBMC-HPV, was developed by SQZ Biotechnologies using microfluidic squeezing technology to load PBMCs with HPV16 E6 and E7 antigens in HLA-A*02+ patients. The SQZ-PBMC-HPV-101 Phase 1 trial (NCT04084951) enrolled patients with incurable HPV16+ cancers. Here, we present a post hoc analysis of the...
Alice N Weaver