Probing mechanical selection in diverse eukaryotic genomes through accurate prediction of 3D DNA mechanics.

Connections between the mechanical properties of DNA and biological functions have been speculative due to the lack of methods to measure or predict DNA mechanics at scale. Recently, a proxy for DNA mechanics, cyclizability, was measured by loop-seq and enabled genome-scale investigation of DNA mechanics. Here, we use this dataset to build a computational model predicting bias-corrected intrinsic cyclizability, with near-perfect accuracy, solely based on DNA sequence.

A cell atlas of the human fallopian tube throughout the menstrual cycle and menopause.

The fallopian tube undergoes extensive molecular changes during the menstrual cycle and menopause. We use single-cell RNA and ATAC sequencing to construct a comprehensive cell atlas of healthy human fallopian tubes during the menstrual cycle and menopause. Our scRNA-seq comparison of 85,107 pre- and 46,111 post-menopausal fallopian tube cells reveals substantial shifts in cell type frequencies, gene expression, transcription factor activity, and cell-to-cell communications during menopause and menstrual cycle.

Left atrial myxoma metastasizing to the brain: a case report and review of literature.

Cardiac myxomas, the most common primary cardiac tumors, are believed to originate from multipotent mesenchymal cells. Approximately 75% of myxomas occur within the left atrium, increasing the risk of systemic thromboembolic events. While typically benign, atrial myxomas can rarely metastasize to the brain, with fewer than 60 cases reported.

Prevalence of Substance Use and Sleep-Related Problems Among Driver Victims Involved in Road Traffic Accidents Presenting to a Tertiary Care Hospital in India.

Background: Road traffic accidents (RTAs) are a critical public health problem leading to significant morbidity, mortality, and socioeconomic losses. Despite known risk factors like substance use and sleep-related problems, there is limited research on the prevalence of these factors among drivers who met with RTAs. Hence, this study aimed to gain insight into the prevalence of substance use and sleep-related problems among this population attending a trauma center in the northern State of India.

Amoebae: beyond pathogens- exploring their benefits and future potential.

Amoebae, fascinatingly diverse protists, showcase a dual nature that positions them as both friends and foes in our world. These organisms, defined by their distinctive pseudopodia, span a spectrum from harmful to helpful. On the darker side, species like pose serious health risks, causing intestinal and liver diseases, while the infamous "brain-eating" leads to fatal primary amoebic meningoencephalitis (PAM), with a daunting 97% mortality rate.

Effects of Large Language Model-Based Offerings on the Well-Being of Students: Qualitative Study.

Background: In recent years, the adoption of large language model (LLM) applications, such as ChatGPT, has seen a significant surge, particularly among students. These artificial intelligence-driven tools offer unprecedented access to information and conversational assistance, which is reshaping the way students engage with academic content and manage the learning process. Despite the growing prevalence of LLMs and reliance on these technologies, there remains a notable gap in qualitative in-depth research examining the emotional and psychological effects of LLMs on users' mental well-being.

Cell-type-resolved chromatin accessibility in the human intestine identifies complex regulatory programs and clarifies genetic associations in Crohn's disease.

Crohn's disease (CD) is a complex inflammatory bowel disease resulting from an interplay of genetic, microbial, and environmental factors. Cell-type-specific contributions to CD etiology and genetic risk are incompletely understood. Here we built a comprehensive atlas of cell-type- resolved chromatin accessibility comprising 557,310 candidate cis-regulatory elements (cCREs) in terminal ileum and ascending colon from patients with active and inactive CD and healthy controls.

Genomic Biomarkers Associated with Enfortumab Vedotin Outcomes for Patients with Advanced Urothelial Carcinoma: Analysis of UNITE Study Data.

Enfortumab vedotin (EV) is used as monotherapy or combined with pembrolizumab in advanced urothelial carcinoma (aUC), but biomarker data associated with EV outcomes are limited. We identified 170 patients in the UNITE study who received EV monotherapy and had molecular biomarker data available. Outcomes for groups with and without a particular biomarker were compared using logistic regression (unadjusted) for the objective response rate (ORR), and a log-rank test and Cox proportional-hazard models (CPHMs) for progression-free survival (PFS) and overall survival (OS) from EV initiation.

Impact of microplastics on aquatic flora: Recent status, mechanisms of their toxicity and bioremediation strategies.

The accumulation of microplastics (MPs) in aquatic environments has occurred pervasively. The MPs affect almost all the aquatic plants including the aquatic microorganisms, ultimately disturbing the food chain. Aquatic flora attracts MPs due to the formation of several chemical bonds and interactions, including hydrogen bonds, electrostatic, hydrophobic, and van der Waals.

Potential of a newly isolated lytic bacteriophage to control Pseudomonas coronafaciens pv. garcae in coffee plants: Molecular characterization with in vitro and ex vivo experiments.

Traditionally, control of coffee plant bacterial halo blight (BHB) caused by the phytopathogen Pseudomonas coronafaciens pv. garcae (Pcg) involves frequent spraying of coffee plantations with non-environmentally friendly and potentially bacterial resistance-promoting copper products or with kasugamycin hydrochloride. In this study we report a leap forward in the quest for a new ecofriendly approach, characterizing (both physicochemically and biologically) and testing both in vitro and ex vivo a new lytic phage for Pcg.

Systems analysis and improvement to optimize opioid use disorder care quality and continuity for patients exiting jail (SAIA-MOUD).

Background: Between 2012-2022 opioid-related overdose deaths in the United States, including Washington State, have risen dramatically. Opioid use disorder (OUD) is a complex, chronic, and criminalized illness with biological, environmental, and social causes. One-fifth of people with OUD have recent criminal-legal system involvement; > 50% pass through WA jails annually.

Longitudinal Testing of Circulating Tumor DNA in Patients With Metastatic Renal Cell Carcinoma.

Purpose: Tumor-informed circulating tumor DNA (ctDNA) has shown promise as a biomarker for treatment response monitoring (TRM) in a variety of tumor types, with the potential to improve clinical outcomes. We evaluated ctDNA status and dynamics during surveillance and as part of TRM with clinical outcomes in both patients with clear cell renal cell carcinoma (ccRCC) and non-clear cell renal cell carcinoma (nccRCC) treated with standard-of-care immunotherapy or targeted therapy regimens.

Methods: This was a multicenter retrospective analysis of real-world data obtained from commercial ctDNA testing (Signatera, Natera, Inc) in patients with metastatic RCC.

Availability, storage capacity, and diffusion: Stationary states of an asymmetric exclusion process connected to two reservoirs.

We explore how the interplay of finite availability, carrying capacity of particles at different parts of a spatially extended system, and particle diffusion between them control the steady-state currents and density profiles in a one-dimensional current-carrying channel connecting the different parts of the system. To study this, we construct a minimal model consisting of two particle reservoirs of finite carrying capacities connected by a totally asymmetric simple exclusion process (TASEP). In addition to particle transport via TASEP between the reservoirs, the latter can also directly exchange particles via Langmuir kinetics-like processes, modeling particle diffusion between them that can maintain a steady current in the system.

Low-density Lipoprotein Receptor is an important host factor in flaviviral entry and replication in neurons.

Flaviviruses, which are transmitted by mosquitoes, are arthropod-borne infections that are pathogenic to both humans and animals, posing a significant global threat to public health. So far, various endocytic pathways have been reported for flaviviral entry; however, the role of cellular factors in viral replication and entry remains uncertain. Here in this study, we identified the role of Low-density lipoprotein receptor, which has long been established as a cholesterol carrier for neurons but remained unexplored as an essential host factor for JEV/WNV replication.

Open-World Games' Affordance of Cognitive Escapism, Relaxation, and Mental Well-Being Among Postgraduate Students: Mixed Methods Study.

Background: Open-world games, characterized by their expansive and interactive environments, may offer unique cognitive escapism opportunities, potentially leading to relaxation and enhanced well-being. These games, such as "The Legend of Zelda: Breath of the Wild" and "The Legend of Zelda: Tears of the Kingdom," allow players to experience a sense of freedom and autonomy, which can reduce stress and improve mental health. While previous research has examined the general impact of video games on mental well-being, specific studies on the effects of open-world games among postgraduate students are limited.

Harnessing the FBXW7 somatic mutant R465C for targeted protein degradation.

Targeted protein degradation (TPD) is a pharmacological strategy that eliminates specific proteins from cells by harnessing cellular proteolytic degradation machinery. In proteasome-dependent TPD, expanding the repertoire of E3 ligases compatible with this approach could enhance the applicability of this strategy across various biological contexts. In this study, we discovered that a somatic mutant of FBXW7, R465C, can be exploited by heterobifunctional compounds for targeted protein degradation.

FVIIa-PAR2 SIGNALING FACILITATES IMMUNE ESCAPE BY REDUCING PHAGOCYTIC POTENTIAL OF MACROPHAGES IN BREAST CANCER.

Background: Treatment of breast cancers with immunotherapy has so far achieved limited success. Traditional immunotherapies focusing on cytotoxic T cells have attained modest success, while the approval of phagocytic checkpoint blockers is still pending. Coagulation proteases are crucial elements pertaining to cancer growth and proliferation, but their relevance in altering the immunological topography in tumours remain largely uncharted.

Perspectives on Integrating Biological Assessments to Address the Health Effects of Childhood Adversities.

A majority of adults in the United States (US) report a range of stressful and potentially traumatic childhood experiences (e.g., physical or sexual abuse, witnessing violence, neglect).

Thrombin confers chemotherapeutic resistance by promoting transcriptional induction and post-translational stabilization of pro-survival MCL1 in TNBC.

The association between idiopathic venous thrombosis and occult cancer is widely recognized. However, the comprehensive understanding of how thrombin, generated during the process of thrombosis, possesses the potential to augment the malignant phenotype is still not well understood. The coagulation protease thrombin mediates its effects by cleaving protease-activated receptor 1 (PAR1), a receptor abundantly expressed on the surface of triple-negative breast cancer (TNBC) cells.

p21 Is a Novel Downstream Target of 40S Ribosomal S6 Kinase 2.

: The ribosomal S6 kinase 2 (S6K2) acts downstream of the mechanistic target of rapamycin complex 1 and is a homolog of S6K1 but little is known about its downstream effectors. The objective of this study was to use an unbiased transcriptome profiling to uncover how S6K2 promotes breast cancer cell survival. : RNA-Seq analysis was performed to identify novel S6K2 targets.

Expanding the diagnostic toolbox for complex genetic immune disorders.

Laboratory-based immunology evaluation is essential to the diagnostic workup of patients with complex immune disorders, and is as essential, if not more so, depending on the context, as genetic testing, because it enables identification of aberrant pathways amenable to therapeutic intervention and clarifies variants of uncertain significance. There have been considerable advances in techniques and instrumentation in the clinical laboratory in the past 2 decades, although there are still "miles to go." One of the goals of the clinical laboratory is to ensure advanced diagnostic testing is widely accessible to physicians and thus patients, through reference laboratories, particularly in the context of academic medical centers.

A double-blind, randomized, placebo-controlled trial of individualized homeopathic medicinal products in the treatment of nocturnal enuresis in children.

Context: Nocturnal enuresis (NE) is a very common problem in childhood. The prevalence rate varies from 3.5% to 56.