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A population-based analysis of the molecular landscape of glioma in adolescents and young adults reveals insights into gliomagenesis

2 days 5 hours ago
Gliomas are a major cause of cancer-related deaths in adolescents and young adults (AYAs; ages 15-39 years). Different molecular alterations drive gliomas in children and adults, leading to distinct biology and clinical consequences, but the implications of pediatric- versus adult-type alterations in AYAs are unknown. Our population-based analysis of 1,456 clinically and molecularly characterized gliomas in patients aged 0-39 years addresses this gap. Pediatric-type alterations were found in 31%...
Julie Bennett

Asciminib remained superior vs bosutinib in late-line CML-CP after nearly 4 years of follow-up in ASCEMBL

2 days 5 hours ago
The efficacy of and disease control afforded by tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia in chronic phase (CML-CP) has led to increased longevity and thus continued pursuit of alternative therapies that are efficacious and maximize tolerability. The 24- and 96-week analyses from ASCEMBL demonstrated superior efficacy, safety, and tolerability of asciminib compared with bosutinib in later-line therapy, meeting primary and key secondary objectives, respectively. With nearly 4...
Michael J Mauro

Cytoscape Web: bringing network biology to the browser

1 week 1 day ago
Since its introduction in 2003, Cytoscape has been a de facto standard for visualizing and analyzing biological networks. We now introduce Cytoscape Web (https://web.cytoscape.org), an online implementation that captures the interface and key visualization functionality of the desktop while providing integration with web tools and databases. Cytoscape Web enhances accessibility, simplifying collaboration through online data sharing. It integrates with Cytoscape desktop via the CX2 network...
Keiichiro Ono

PRMT5 promotes full-length HTT expression by repressing multiple proximal intronic polyadenylation sites

1 week 2 days ago
Expansion of the CAG trinucleotide repeat tract in exon 1 of the Huntingtin (HTT) gene causes Huntington's disease (HD) through the expression of a polyglutamine-expanded form of the HTT protein. This mutation triggers cellular and biochemical pathologies, leading to cognitive, motor, and psychiatric symptoms in HD patients. Targeting HTT splicing with small molecule drugs is a compelling approach to lowering HTT protein levels to treat HD, and splice modulators are currently being tested in the...
Manisha Yadav

Predicting Relapse of Depressive Episodes During Maintenance Treatment: The Canadian Biomarker Integration Network in Depression (CAN-BIND) Wellness Monitoring in Major Depressive Disorder Study: Prédire la rechute d'épisodes dépressifs pendant le…

1 week 2 days ago
BackgroundRelapse rates in major depressive disorder (MDD) remain high even after treatment to remission. Identifying predictors of relapse is, therefore, crucial for improving maintenance strategies and preventing future episodes. Remote data collection and sensing technologies may allow for more comprehensive and longitudinal assessment of potential predictors.MethodsThe Canadian Biomarker Integration Network in Depression Wellness Monitoring for MDD (CBN-WELL) study was a prospective,...
Raymond W Lam

Supporting Adolescents and Young Adults through Digitally Mediated Type 1 Diabetes Transition Care: A Qualitative Descriptive Study

1 week 2 days ago
CONCLUSIONS: The design of digital technologies to support T1D transition care should consider methods for standardizing holistic care delivery and integrating hybrid diabetes care visits to support access to transition care. These findings can inform future transition intervention development that leverages existing transition guidelines, targets holistic care model integration, and considers quantitative diabetes metrics in conjunction with broader life experiences of AYA when providing...
Noor El-Dassouki

Measured intrapatient radiomic variability as a predictor of treatment response in multi-metastatic soft tissue sarcoma patients

1 week 3 days ago
Radiomics offers a non-invasive approach to tumor characterization, yet its application in metastatic cancers is limited by intertumor heterogeneity-variability in radiomic phenotypes across lesions within the same patient. We introduce Measured Intrapatient Radiomic Variability (MIRV), a novel metric quantifying heterogeneity using standard-of-care imaging. Applied to 397 metastatic soft-tissue sarcoma (STS) patients from the SARC021 trial, MIRV was calculated from pretreatment CT scans using...
Caryn Geady

A TATA-box binding protein binds single stranded DNA in two modes: to poly(G) tracts and to flexible DNA regions

1 week 3 days ago
The TATA-box binding protein (TBP) homolog from Giardia intestinalis (gTBP) is highly divergent, lacking key phenylalanines crucial for binding and unwinding double-stranded DNA. Surprisingly, we determined that gTBP exhibits unconventional DNA binding properties and preferentially binds to single stranded DNA (ssDNA) using a DNA-binding pocket that is narrower relative to other eukaryotic TBPs. Additionally, we showed that gTBP binds in two distinct modes, which we call the A and B modes, that...
Kieran Freitag

Human papilloma virus (HPV) mediated cancers: an insightful update

1 week 3 days ago
Human papillomavirus (HPV), a DNA virus, is a well-documented causative agent of several cancers, including cervical, vulvar, vaginal, penile, anal, and head & neck cancers. Major factors contributing to HPV-related cancers include persistent infection and the oncogenic potential of particular HPV genotypes. High-risk HPV strains, particularly HPV-16 and HPV-18, are responsible for over 70% of cervical cancer cases worldwide, as well as a significant proportion of other genital and head and neck...
Sadaf Khursheed Baba

Pathogenesis and transmission of SARS-CoV-2 D614G, Alpha, Gamma, Delta, and Omicron variants in golden hamsters

1 week 4 days ago
Since the emergence of SARS-CoV-2 in humans, novel variants have evolved to become dominant circulating lineages. These include D614G (B.1 lineage), Alpha (B.1.1.7), Gamma (P.1), Delta (B.1.617.2), and Omicron BA.1 (B.1.1.529) and BA.2 (B.1.1.529.2) viruses. Here, we compared the viral replication, pathogenesis, and transmissibility of these variants. Replication kinetics and innate immune response against the viruses were tested in ex vivo human nasal epithelial cells (HNEC) and induced...
Andra Banete

Single-cell Transcriptional Atlas of Human Hematopoiesis Reveals Genetic and Hierarchy-Based Determinants of Aberrant AML Differentiation

1 week 4 days ago
We present a single-cell reference atlas of human hematopoiesis and a computational tool for rapid mapping and classification of healthy and leukemic cells. Applied to AML, this has enabled single-cell analysis at the scale of hundreds of patient samples, revealing the full breadth of derailment of differentiation in AML. See related commentary by Berger and Penter, p. XX.
Andy G X Zeng

Regioselective, Lewis Acid-Catalyzed Ring-Openings of 2,3-Aziridyl Alcohols with Azoles

2 weeks ago
Methods for regioselective ring-opening reactions of N-sulfonyl-protected aziridyl alcohols with azole nucleophiles have been developed. Several classes of azoles, including indazole, substituted pyrazole, benzotriazole, and tetrazole, have been employed as reaction partners, giving rise to C3-selective opening and >3:1 N-selectivity. BF(3)•OEt(2) is the optimal catalyst for most substrate combinations, although examples where diphenylborinic acid (Ph(2)BOH) provides higher yields, or where the...
Benjamin Zheng

Artificial intelligence-driven genotype-epigenotype-phenotype approaches to resolve challenges in syndrome diagnostics

2 weeks ago
BACKGROUND: Decisions to split two or more phenotypic manifestations related to genetic variations within the same gene can be challenging, especially during the early stages of syndrome discovery. Genotype-based diagnostics with artificial intelligence (AI)-driven approaches using next-generation phenotyping (NGP) and DNA methylation (DNAm) can be utilized to expedite syndrome delineation within a single gene.
Christopher C Y Mak

Geometrically focused training and evaluation of organs-at-risk segmentation via deep learning

2 weeks ago
CONCLUSION: We developed and evaluated a new geometric metric, wDSC, as a better indicator of D2cm³ accuracy, which has the potential to become a surrogate for dosimetric accuracy in cervical brachytherapy. The model with DP loss showed non-statistically significant improvements in geometric and dosimetric performance. This work also holds the potential to be used for precise OARs delineation in adaptive radiotherapy.
Ruiyan Ni

Observation of tt[over ¯] Production in Pb+Pb Collisions at sqrt[s_{NN}]=5.02  TeV with the ATLAS Detector

2 weeks ago
Top-quark pair production is observed in lead-lead (Pb+Pb) collisions at sqrt[s_{NN}]=5.02 TeV at the Large Hadron Collider with the ATLAS detector. The data sample was recorded in 2015 and 2018, amounting to an integrated luminosity of 1.9 nb^{-1}. Events with exactly one electron and one muon and at least two jets are selected. Top-quark pair production is measured with an observed (expected) significance of 5.0 (4.1) standard deviations. The measured top-quark pair production cross section is...
G Aad

Overture: an open-source genomics data platform

2 weeks 1 day ago
CONCLUSIONS: By making these tools freely available, we can accelerate the development of reliable genomic data management across the research community quickly, flexibly, and at multiple scales. Overture is an open-source project licensed under AGPLv3.0 with all source code publicly available from https://github.com/overture-stack and documentation on development, deployment, and usage available from www.overture.bio.
Mitchell Shiell

Advancing curation of viral life cycles, host interactions, and therapeutics in Reactome

2 weeks 2 days ago
Reactome (reactome.org) is a manually curated, peer-reviewed, open-source, open-access pathway knowledgebase of essential human cellular functions. Reactome includes viral life cycles that capture a broad range of virus-induced human pathology. Here, we describe a workflow using collaborative curation strategies, orthoinference procedures, and literature triage to rapidly create reliable molecular models of emergent viruses. The resulting pathway data set rigorously details viral infection...
Lisa Matthews

The Clinical Utility of Biomarkers in Diagnosing Major Depressive Disorder in Adults: A Systematic Review of Literature From 2013 to 2023

2 weeks 3 days ago
CONCLUSION: A large variety of biomarkers were available to diagnose MDD, with the best performing biomarkers intrinsically related to the pathophysiology of MDD. Potential for future research lies in investigating the joint sensitivity of the best performing biomarkers identified via machine learning methods and establishing the causal effect between these biomarkers and MDD.
Shi-Han Ang
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1 hour 38 minutes ago
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