High-throughput determination of exchange rates of unmodified and PTM-containing peptides using HX-MS.

Despite the widespread use of MS for hydrogen/deuterium exchange measurements, no systematic, large-scale study has been conducted to compare the observed exchange rates in protein-derived, unstructured peptides measured by MS to the predicted exchange rates calculated from NMR-derived values and how neighboring residues and post-translational modifications influence those exchange rates. In this study, we sought to test the accuracy of predicted values by performing hydrogen exchange measurements on whole cell digests to generate an unbiased dataset of 563 unique peptides derived from naturally-occurring protein sequences. A remarkable 97% of observed exchange rates of peptides are within two-fold of predicted values.

Event-driven PrEP beyond cisgender men who have sex with men.

Despite advancements in existing antiretroviral-based prevention strategies, including daily oral, locally acting, and injectable options, there is a pressing need for more inclusive and flexible event-driven pre-exposure prophylaxis (PrEP) strategies for all. Event-driven or intermittent dosing of PrEP in populations beyond cisgender men who have sex with men would offer a promising alternative by fitting prevention into the diverse lifestyles of affected populations and thereby advancing health equity. Evidence from PrEP clinical trials, pharmacokinetic studies, modelling studies, and real-world observational research suggests that event-driven PrEP could be a flexible and inclusive option, yet optimal dosing has not been established across sex and gender spectrums.

A phase I study of temsirolimus in combination with metformin in patients with advanced or recurrent endometrial cancer.

Introduction: Molecular alterations in the PI3K/AKT and Ras/Raf/MEK/ERK pathways are frequently observed in patients with endometrial cancers. However, mTOR inhibitors, such as temsirolimus, have modest clinical benefits. In addition to inducing metabolic changes in cells, metformin activates AMPK, which in turn inhibits the mTOR pathway.

Impact of water, sanitation, and hygiene indicators on enteric viral pathogens among under-5 children in low resource settings.

Poor water, sanitation, and hygiene (WASH) are the primary risks of exposure to enteric viral infection. Our study aimed to describe the role of WASH conditions and practices as risk factors for enteric viral infections in children under 5. Literature on the risk factors associated with all-cause diarrhea masks the taxa-specific drivers of diarrhea from specific pathogens, limiting the application of relevant control strategies.

Germline and Somatic Genomic Testing for Metastatic Prostate Cancer: ASCO Guideline.

Purpose: To evaluate evidence on germline and somatic genomic testing for patients with metastatic prostate cancer and provide recommendations.

Methods: A systematic review by a multidisciplinary panel with patient representation was conducted. The PubMed database was searched from January 2018 to May 2024.

Hospital Dermatology: Review of Research in 2023-2024.

Inpatient consultative dermatologists play a critical role in the care of hospitalized patients with skin disease. Our review of the 2023-2024 dermatology literature identified several areas of active investigation relevant to inpatient dermatology. In this article, we highlight advances in the understanding of severe cutaneous adverse drug reactions, diagnosis and prevention of skin and soft tissue infections, and management of autoimmune blistering diseases (AIBDs).

NXP800 activates the unfolded protein response, altering AR and E2F function to impact castration-resistant prostate cancer growth.

Purpose: Advanced prostate cancer (PCa) is invariably fatal with the androgen receptor (AR) being a major therapeutic target. AR signaling inhibitors have improved overall survival for men with advanced PCa, but treatment resistance is inevitable and includes reactivation of AR signaling. Novel therapeutic approaches targeting these mechanisms to block tumor growth is an urgent unmet clinical need.

Superstable lipid vacuoles endow cartilage with its shape and biomechanics.

Conventionally, the size, shape, and biomechanics of cartilages are determined by their voluminous extracellular matrix. By contrast, we found that multiple murine cartilages consist of lipid-filled cells called lipochondrocytes. Despite resembling adipocytes, lipochondrocytes were molecularly distinct and produced lipids exclusively through de novo lipogenesis.

Enhancing engagement in HIV care among adolescents and young adults: A focus on phone-based navigation and relationship building to address barriers in HIV care.

Structural, psychological, and clinical barriers to HIV care engagement among adolescents and young adults living with HIV (AYAH) persist globally despite gains in HIV epidemic control. Phone-based peer navigation may provide critical peer support, increase delivery flexibility, and require fewer resources. Prior studies show that phone-based navigation and automated text messaging interventions improve HIV care engagement, adherence, and retention among AYAH.

Individual and organizational factors associated with public health workforce competencies to advance health equity.

Little is known about how to develop public health workforce capacity for health equity work. We explored associations of individual and organizational characteristics of local public health departments (LHDs) with competencies essential for advancing health equity. Data included responses of 29,751 staff from 742 LHDs in 48 states to the 2021 Public Health Workforce Interests and Needs Survey, plus LHD characteristics and county demographics.

Dissociable roles of central striatum and anterior lateral motor area in initiating and sustaining naturalistic behavior.

Understanding how corticostriatal circuits mediate behavioral selection and initiation in a naturalistic setting is critical to understanding behavior choice and execution in unconstrained situations. The central striatum (CS) is well poised to play an important role in these spontaneous processes. Using fiber photometry and optogenetics, we identify a role for CS in grooming initiation.

Eye posture and screen alignment with simulated see-through head-mounted displays.

When rendering the visual scene for near-eye head-mounted displays, accurate knowledge of the geometry of the displays, scene objects, and eyes is required for the correct generation of the binocular images. Despite possible design and calibration efforts, these quantities are subject to positional and measurement errors, resulting in some misalignment of the images projected to each eye. Previous research investigated the effects in virtual reality (VR) setups that triggered such symptoms as eye strain and nausea.

Registry versus claims-based index dates for studies of cancer diagnosis in administrative data.

Purpose: Studies of healthcare encounters leading to cancer diagnosis have increased over recent years. While some studies examine healthcare utilization before the cancer registry date of diagnosis, relevant pre-diagnosis interactions are not always immediately prior to this date due to date abstraction guidelines. We evaluated agreement of a registry date with a claims-based index and examined Emergency Department (ED) involvement in cancer diagnosis as an example of possible pre-diagnostic healthcare misclassification that could arise from improper date choice.

CAGI6 ID panel challenge: assessment of phenotype and variant predictions in 415 children with neurodevelopmental disorders (NDDs).

The Genetics of Neurodevelopmental Disorders Lab in Padua provided a new intellectual disability (ID) Panel challenge for computational methods to predict patient phenotypes and their causal variants in the context of the Critical Assessment of the Genome Interpretation, 6th edition (CAGI6). Eight research teams submitted a total of 30 models to predict phenotypes based on the sequences of 74 genes (VCF format) in 415 pediatric patients affected by Neurodevelopmental Disorders (NDDs). NDDs are clinically and genetically heterogeneous conditions, with onset in infant age.

Adaptation in the Alleyways: Candidate genes under potential selection in urban coyotes.

In the context of evolutionary time, cities are an extremely recent development. Although our understanding of how urbanization alters ecosystems is well-developed, empirical work examining the consequences of urbanization on adaptive evolution remains limited. To facilitate future work, we offer candidate genes for one of the most prominent urban carnivores across North America.

A dataset and benchmark for hospital course summarization with adapted large language models.

Objective: Brief hospital course (BHC) summaries are clinical documents that summarize a patient's hospital stay. While large language models (LLMs) depict remarkable capabilities in automating real-world tasks, their capabilities for healthcare applications such as synthesizing BHCs from clinical notes have not been shown. We introduce a novel preprocessed dataset, the MIMIC-IV-BHC, encapsulating clinical note and BHC pairs to adapt LLMs for BHC synthesis.

Antibody-Drug Conjugates in Breast Cancer: The Road Towards Biologically-Informed Selection and Sequencing.

Purpose Of Review: In this review, we discuss evidence supporting the use of antibody-drug conjugates (ADCs) in breast cancer treatment, describe novel ADCs and combination regimens under development, and examine our current understanding of resistance mechanisms and biomarkers to guide ADC selection and sequencing.

Recent Findings: Three ADCs have proven benefit in patients with metastatic breast cancer: trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd), and sacituzumab govitecan (SG). There are over two hundred investigational ADCs on the horizon, as pre-clinical studies work to identify novel ADC targets and structures.

Using minimally invasive tissue sampling (MITS) and Determination of Cause of Death (DeCoDe) to establish etiologies of community respiratory deaths among Zambian infants and children.

In low-to-middle income countries, acute lower respiratory infection (ALRI) remains the leading infectious cause of death among infants and children under 5 years old. Case-control studies based on upper respiratory sampling have informed current understandings of ALRI etiologies; in contrast, minimally-invasive tissue sampling (MITS) offers a method of directly interrogating lower respiratory tract pathogens to establish etiologic distributions. This study performed in the post-mortem setting used MITS and a Determination of Cause of Death (DeCoDe) panel to elucidate causes of fatal pneumonia in the community in Lusaka, Zambia.

FDA-approved therapies for chronic GVHD.

Despite novel prophylactic regimens, chronic graft-versus-host disease (cGVHD) remains a challenging complication after allogeneic hematopoietic cell transplantation. Chronic GVHD can affect multiple organs and reduces quality of life, and treatment can cause serious side effects. In the last ten years, the drugs ibrutinib, ruxolitinib, belumosudil and axatilimab were FDA-approved for cGVHD.

Phase 2 Open-Label Trial of Brentuximab Vedotin with Pembrolizumab in PD-1 Pretreated Metastatic Non-Small Cell Lung Cancer and Metastatic Cutaneous Melanoma.

Purpose: Brentuximab vedotin (BV) is hypothesized to selectively deplete T regulatory cells (Tregs) that express CD30 and re-sensitize tumors to anti-(PD-1) therapy. This study evaluated responses to BV+pembrolizumab post PD-1 and explored corresponding biomarkers.

Methods: 55 patients with metastatic non-small cell lung cancer (NSCLC) and 58 with metastatic cutaneous melanoma received ≥1 dose of BV+pembrolizumab.

Breast Cancer Susceptibility Gene Sequence Variations and Development of Contralateral Breast Cancer.

Importance: Heterogeneity in development of estrogen receptor (ER)-specific first primary breast cancer exists due to deleterious germline variants in moderate- to high-penetrance breast cancer susceptibility genes, but it is unknown if these associations occur in ER-specific CBC.

Objective: To determine the association of deleterious germline variants in breast cancer susceptibility genes with ER-specific CBC development and whether ER status of the first primary breast cancer modifies these associations.

Design, Setting, And Participants: This case-control study included CBC cases and matched unilateral breast cancer controls from The Women's Environment, Cancer, and Radiation Epidemiology (WECARE) Study, a population-based case-control study.

Pain Coping Skills Training for Patients Receiving Hemodialysis: The HOPE Consortium Randomized Clinical Trial.

Importance: Chronic pain is common among individuals with dialysis-dependent kidney failure.

Objective: To evaluate the effectiveness of pain coping skills training (PCST), a cognitive behavioral intervention, on pain interference.

Design, Setting, And Participants: This multicenter randomized clinical trial of PCST vs usual care was conducted across 16 academic centers and 103 outpatient dialysis facilities in the US.