Cyclin E1/CDK2 activation defines a key vulnerability to WEE1 kinase inhibition in gynecological cancers.

Upregulation of Cyclin E1 and subsequent activation of CDK2 accelerates cell cycle progression from G1 to S phase and is a common oncogenic driver in gynecological malignancies. WEE1 kinase counteracts the effects of Cyclin E1/CDK2 activation by regulating multiple cell cycle checkpoints. Here we characterized the relationship between Cyclin E1/CDK2 activation and sensitivity to the selective WEE1 inhibitor azenosertib.

Can clinical findings at admission allow withholding of antibiotics in patients hospitalized for community acquired pneumonia when a test for a respiratory virus is positive?

Background: Current guidelines recommend empiric antibiotic therapy for patients who require hospitalization for community-acquired pneumonia (CAP). We sought to determine whether clinical, imaging or laboratory features in patients hospitalized for CAP in whom PCR is positive for a respiratory virus enable exclusion of bacterial coinfection so that antibiotics can be withheld.

Methods: For this prospective study, we selected patients in whom an etiologic diagnosis was likely to be reached, namely those who provided a high-quality sputum sample at or shortly after admission, and in whom PCR was done to test for a respiratory virus.

Continent catheterizable channels: Does "hitching" the bladder reduce complications?

Background: Continent catheterizable channels (CCC) are a mainstay for reconstruction in patients with neurogenic bladders. Common complications include false passage, channel stenosis/difficult catheterization, channel incontinence, and stomal stenosis. This may result in the need for surgical revision or replacement.

Rhinoconjunctivitis Symptoms in Children and Adolescents with Asthma: A Longitudinal Clustering Analysis.

Background: Rhinoconjunctivitis phenotypes are conventionally described based on symptom severity, duration and seasonality and aeroallergen sensitization. It is not known whether these phenotypes fully reflect the patterns of symptoms seen at a population level.

Objective: To identify phenotypes of rhinoconjunctivitis based on symptom intensity and seasonality using an unbiased approach and to compare their characteristics.

Comparative species delimitation of a biological conservation icon.

The United States Endangered Species Act (ESA) of 1973 set a precedent for biodiversity conservation across the globe. A key requirement of protections afforded by the ESA is the accurate delimitation of imperiled species. We present a comparative reference-based taxonomic approach to species delimitation that integrates genomic and morphological data for objectively assessing the distinctiveness of species targeted for protection by governmental agencies.

Characterization of DNA methylation clock algorithms applied to diverse tissue types.

Background: DNA methylation (DNAm) data from human samples has been leveraged to develop "epigenetic clock" algorithms that predict age and other aging-related phenotypes. Some DNAm clocks were trained using DNAm obtained from blood cells, while other clocks were trained using data from diverse tissue/cell types. To assess how DNAm clocks perform across non-blood tissue types, we applied DNAm algorithms to DNAm data generated from 9 different human tissue types.

BIS Guided Titration of Sevoflurane in Pediatric Patients Undergoing Elective Surgery: A Randomized Controlled Trial.

Background: In pediatric patients, the use of processed EEG monitoring may reduce the amount of anesthesia administered while maintaining adequate depth of anesthesia.

Aims: The primary aim of this study was to evaluate whether use of a BIS monitor to guide sevoflurane administration might reduce the average end tidal sevoflurane concentration used in children 4-18 years of age.

Methods: Participants in three age groups (4-8, 9-12, and 13-18 years) were randomized to either the BIS guided group or the control group.

Refining breast cancer genetic risk and biology through multi-ancestry fine-mapping analyses of 192 risk regions.

Genome-wide association studies have identified approximately 200 genetic risk loci for breast cancer, but the causal variants and target genes are mostly unknown. We sought to fine-map all known breast cancer risk loci using genome-wide association study data from 172,737 female breast cancer cases and 242,009 controls of African, Asian and European ancestry. We identified 332 independent association signals for breast cancer risk, including 131 signals not reported previously, and for 50 of them, we narrowed the credible causal variants down to a single variant.

High-density multielectrode arrays bring cellular resolution to neuronal activity and network analyses of corticospinal motor neurons.

Corticospinal motor neurons (CSMN), located in the motor cortex of the brain, are one of the key components of the motor neuron circuitry. They are in part responsible for the initiation and modulation of voluntary movement, and their degeneration is the hallmark for numerous diseases, such as amyotrophic lateral sclerosis (ALS), hereditary spastic paraplegia, and primary lateral sclerosis. Cortical hyperexcitation followed by in-excitability suggests the early involvement of cortical dysfunction in ALS pathology.

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.

Phase II Parallel Arm Study of Sacituzumab Govitecan-Hziy in Patients With Advanced Thymoma or Thymic Carcinoma.

Background: Thymic epithelial tumors (TETs), including thymoma and thymic carcinoma, are rare thoracic tumors of the anterior mediastinum. For those with advanced disease, platinum-based chemotherapy is used as first-line treatment. However, there is no standard regimen established for TET at progression after initial therapy, and treatment options for advanced/recurrent TETs are limited.

Liver Fibrosis and Cardiovascular Events.

Objectives: Liver fibrosis represents a common sequela of nonalcoholic fatty liver disease (NAFLD) and other chronic liver diseases. Noninvasive liver fibrosis scores (LFSs) aim to evaluate the severity of liver fibrosis. Whether LFSs can predict the risk of future cardiovascular events (CVEs) remains unclear.

Neutrophil extracellular traps promote pre-metastatic niche formation in the omentum by expanding innate-like B cells that express IL-10.

Disseminated cancer cells in the peritoneal fluid often colonize omental fat-associated lymphoid clusters but the mechanisms are unclear. Here, we identify that innate-like B cells accumulate in the omentum of mice and women with early-stage ovarian cancer concomitantly with the extrusion of chromatin fibers by neutrophils called neutrophil extracellular traps (NETs). Studies using genetically modified NET-deficient mice, pharmacologic inhibition of NETs, and adoptive B cell transfer show that NETs induce expression of the chemoattractant CXCL13 in the pre-metastatic omentum, stimulating recruitment of peritoneal innate-like B cells that in turn promote expansion of regulatory T cells and omental metastasis through producing interleukin (IL)-10.

An Activation Failure: Factors Associated With Undertriage of Pediatric Major Trauma Victims.

Introduction: Undertriage of children contributes to poorer clinical outcomes. The objective of this study was to determine factors associated with undertriage of pediatric major trauma victims.

Methods: We performed a retrospective cross-sectional study of children (aged < 16 ys) using the 2021 American College of Surgeons National Trauma Data Bank.

On the emergence of machine-learning methods in bottom-up coarse-graining.

Machine-learning methods have gained significant attention in the computational chemistry community as a viable approach to molecular modeling and analysis. Recent successes in utilizing neural networks to learn atomistic force-fields which 'coarse-grain' electronic structure have inspired similar applications to the thermodynamic coarse-graining of chemical and biological systems. In this review, we discuss the current viability and challenges in using machine-learning methods to represent coarse-grained force-fields, as well as the utility of machine-learning in various aspects of coarse-grained modeling.

Disentangling Sources of Momentum Fluctuations in Xe+Xe and Pb+Pb Collisions with the ATLAS Detector.

High-energy nuclear collisions create a quark-gluon plasma, whose initial condition and subsequent expansion vary from event to event, impacting the distribution of the eventwise average transverse momentum [P([p_{T}])]. Disentangling the contributions from fluctuations in the nuclear overlap size (geometrical component) and other sources at a fixed size (intrinsic component) remains a challenge. This problem is addressed by measuring the mean, variance, and skewness of P([p_{T}]) in ^{208}Pb+^{208}Pb and ^{129}Xe+^{129}Xe collisions at sqrt[s_{NN}]=5.

The Pelvic Floor Disorders Network: Evolution Over Two Decades of Female Pelvic Floor Research.

Importance: This review aimed to describe research initiatives, evolution, and processes of the Eunice Kennedy Shriver National Institute of Child Health and Human Development-supported Pelvic Floor Disorders Network (PFDN). This may be of interest and inform researchers wishing to conduct multisite coordinated research initiatives as well as to provide perspective to all urogynecologists regarding how the PFDN has evolved and functions.

Study Design: Principal investigators of several PFDN clinical sites and Data Coordinating Center describe more than 20 years of development and maturation of the PFDN.

Innate Immune Activation with Multifunctional Nanoparticles for Cancer Immunotherapy.

Immune checkpoint blockade (ICB) has revolutionized the treatment of many cancers by leveraging the immune system to combat malignancies. However, its efficacy is limited by the immunosuppressive tumor microenvironment and other regulatory mechanisms of the immune system. Innate immune modulators (IIMs) provide potent immune activation to complement adaptive immune responses and help overcome resistance to ICB.

Effect of sign language learning on temporal resolution of visual attention.

The visual environment of sign language users is markedly distinct in its spatiotemporal parameters compared to that of non-signers. Although the importance of temporal and spectral resolution in the auditory modality for language development is well established, the spectrotemporal parameters of visual attention necessary for sign language comprehension remain less understood. This study investigates visual temporal resolution in learners of American Sign Language (ASL) at various stages of acquisition to determine how experience with sign language affects perceptual sampling.

Multi-institutional development and testing of attention-enhanced deep learning segmentation of thyroid nodules on ultrasound.

Purpose: Thyroid nodules are common, and ultrasound-based risk stratification using ACR's TIRADS classification is a key step in predicting nodule pathology. Determining thyroid nodule contours is necessary for the calculation of TIRADS scores and can also be used in the development of machine learning nodule diagnosis systems. This paper presents the development, validation, and multi-institutional independent testing of a machine learning system for the automatic segmentation of thyroid nodules on ultrasound.

Clinical Manifestations.

Background: The multisite SuperAging Research Initiative (SRI) was established in 2021 to identify resilience and resistance factors promoting cognitive healthspan through a harmonized multidisciplinary protocol with prospective data collection. The designation of SuperAger is reserved for individuals age 80+ with episodic memory performance that is at least average for those 2-3 decades younger. Research studies of this relatively uncommon phenotype allow for investigations of fundamental importance to the neurobiology of brain aging, resilience, resistance, and avoidance of cognitive decline related to "average aging" and more severe impairments associated with Alzheimer's and related dementias (ADRD).

Clinical Manifestations.

Background: Similar neuroimaging abnormalities are reported in post-COVID patients and patients with AD. Moreover, COVID-19 and Alzheimer's Disease (AD) share genetic vulnerabilities and have similar cognitive symptoms of COVID (e.g.