Polysomnographic titration of non-invasive ventilation in motor neurone disease (3TLA): study protocol for a randomised controlled trial.

Background: Non-invasive ventilation (NIV) uses positive pressure to assist people with respiratory muscle weakness or severe respiratory compromise to breathe. Most people use this treatment during sleep when breathing is most susceptible to instability. The benefits of using NIV in motor neurone disease (MND) are well-established.

mRNA export factors store nascent transcripts within nuclear speckles as an adaptive response to transient global inhibition of transcription.

Several transcription inhibitors have been developed as cancer therapies. However, they show modest clinical activity, highlighting that our understanding of the cellular response to transcriptional inhibition remains incomplete. Here we report that potent inhibitors of transcription not only impact mRNA output but also markedly impair mRNA transcript localization and nuclear export.

Detection of Real-Time Changes in Direction of COVID-19 Transmission Using National- and State-Level Epidemic Trends Based on R Estimates - United States Overall and New Mexico, April-October 2024.

Public health practitioners rely on timely surveillance data for planning and decision-making; however, surveillance data are often subject to delays. Epidemic trend categories, based on time-varying effective reproductive number (R) estimates that use nowcasting methods, can mitigate reporting lags in surveillance data and detect changes in community transmission before reporting is completed. CDC analyzed the performance of epidemic trend categories for COVID-19 during summer 2024 in the United States and at the state level in New Mexico.

Chemical tools to expand the ligandable proteome: Diversity-oriented synthesis-based photoreactive stereoprobes.

Chemical proteomics enables the global analysis of small molecule-protein interactions in native biological systems and has emerged as a versatile approach for ligand discovery. The range of small molecules explored by chemical proteomics has, however, remained limited. Here, we describe a diversity-oriented synthesis (DOS)-inspired library of stereochemically defined compounds bearing diazirine and alkyne units for UV light-induced covalent modification and click chemistry enrichment of interacting proteins, respectively.

Outcomes of emergency colorectal surgery within a non-colorectal split site service-a retrospective cohort study.

Background: Emergency colorectal surgery carries a high risk of morbidity and mortality. Subspecialisation and split-site geographically distinct services may lead to critically unwell patients presenting to a non-colorectal specialist centre requiring urgent on-site intervention.

Aims: This study aims to determine outcomes of this high-risk patient cohort.

Insomnia treatment effects on negative emotionality among veterans in treatment for alcohol use disorder.

Background: Insomnia symptoms are pervasive and persistent in alcohol use disorder (AUD), though little is known about the mechanisms that underlie this association. We previously found that cognitive behavioral therapy for insomnia (CBT-I) reduced alcohol-related problems among veterans by improving insomnia severity (NCT03806491). In this planned secondary analysis of the same clinical trial data, we tested negative emotionality as one potential mechanism to explain this effect.

Early Warning Scores With and Without Artificial Intelligence.

Importance: Early warning decision support tools to identify clinical deterioration in the hospital are widely used, but there is little information on their comparative performance.

Objective: To compare 3 proprietary artificial intelligence (AI) early warning scores and 3 publicly available simple aggregated weighted scores.

Design, Setting, And Participants: This retrospective cohort study was performed at 7 hospitals in the Yale New Haven Health System.

Development and Validation of a Machine Learning Model for Early Detection of Untreated Infection.

Background: Early diagnostic uncertainty for infection causes delays in antibiotic administration in infected patients and unnecessary antibiotic administration in noninfected patients.

Objective: To develop a machine learning model for the early detection of untreated infection (eDENTIFI), with the presence of infection determined by clinician chart review.

Derivation Cohort: Three thousand three hundred fifty-seven adult patients hospitalized between 2006 and 2018 at two health systems in Illinois, United States.

Causes, Diagnostic Testing, and Treatments Related to Clinical Deterioration Events Among High-Risk Ward Patients.

Importance: Timely intervention for clinically deteriorating ward patients requires that care teams accurately diagnose and treat their underlying medical conditions. However, the most common diagnoses leading to deterioration and the relevant therapies provided are poorly characterized.

Objectives: We aimed to determine the diagnoses responsible for clinical deterioration, the relevant diagnostic tests ordered, and the treatments administered among high-risk ward patients using manual chart review.

Feeling in control in sexual situations: Day-level associations with alcohol use and alcohol protective behavioral strategies.

Background: Feeling in control in a sexual situation may vary as a function of contextual factors, such as whether alcohol is used prior to a sexual experience. Alcohol protective behavioral strategies (PBS) reduce adverse alcohol-related outcomes and may promote greater sense of control in sexual situations. It was hypothesized that, at the day level, (1) greater alcohol use would be associated with lower likelihood of feeling in control in sexual situations, (2) more PBS would be associated with a greater likelihood of feeling in control, and (3) more PBS would weaken the negative association between alcohol use and sexual control.

Robotic-assisted laparoscopic excision of a rare primary seminal vesicle leiomyoma.

A primary seminal vesicle leiomyoma (PSVL) is a rare male genitourinary tract tumor. No previous reports have utilized a robotic-assisted laparoscopic posterior approach (RALPA) for surgical management. A 76-year-old man was incidentally found to have a 5cm lobulated mass posterior to the bladder in an abdominal/pelvic computed tomography scan.

Limited proteolysis of neutrophil granule proteins by the bacterial protease RgpB depletes neutrophil antimicrobial capacity.

Neutrophils are highly abundant in the gingival tissues where they play an essential role in immune homeostasis by preventing microbial invasion. Here, we show that the oral periodontal pathogen Porphyromonas gingivalis utilizes its cysteine proteases (gingipains) to disengage phagosomal antimicrobial capacity. Arginine gingipains are a sub-family of trypsin-like proteases produced by P.

Alcohol Feedback, Reflection, and Morning Evaluation (A-FRAME): Refining and testing feasibility and acceptability of a smartphone-delivered alcohol intervention for heavy-drinking young adults.

Background: Young adults drink heavily and experience negative alcohol consequences. To capitalize on mornings after drinking as an optimal time to intervene, we developed a novel, theory-based personalized feedback intervention (PFI) called Alcohol Feedback, Reflection, and Morning Evaluation (A-FRAME), to reduce heavy drinking. An initial prototype was refined via feedback from college students who drink heavily.

A Common Longitudinal Intensive Care Unit data Format (CLIF) to enable multi-institutional federated critical illness research.

Background: Critical illness, or acute organ failure requiring life support, threatens over five million American lives annually. Electronic health record (EHR) data are a source of granular information that could generate crucial insights into the nature and optimal treatment of critical illness. However, data management, security, and standardization are barriers to large-scale critical illness EHR studies.

An exploratory analysis of drinking motives and alcohol-related problems among Hispanic college students.

The increase in college enrollment for Hispanic college students warrants increased attention to their health and wellness. Given that a common threat to health and well-being in college students is alcohol use and that Hispanic college students are at elevated risk for alcohol-related problems, it is essential to investigate factors that might lead to heightened alcohol-related problems among this population. The present study is a secondary data analysis of an NIAAA-funded study investigating brief interventions for alcohol use among 583 heavy-drinking college students.

Massachusetts Medicaid ACO Program May Have Improved Care Use And Quality For Pregnant And Postpartum Enrollees.

Value-based care models, such as Medicaid accountable care organizations (ACOs), have the potential to improve access to and quality of care for pregnant and postpartum Medicaid enrollees. We leveraged a natural experiment in Massachusetts to evaluate the effects of Medicaid ACOs on quality-of-care-sensitive measures and care use across the prenatal, delivery, and postpartum periods. Using all-payer claims data on Medicaid-covered live deliveries in Massachusetts, we used a difference-in-differences approach to compare measures before (the first quarter of 2016 through the fourth quarter of 2017) and after (the third quarter of 2018 through the fourth quarter of 2020) Medicaid ACO implementation among ACO and non-ACO patients.

Digoxin and exercise effects on skeletal muscle Na,K-ATPase isoform gene expression in healthy humans.

In muscle, digoxin inhibits Na,K-ATPase (NKA) whereas acute exercise can increase NKA gene expression, consistent with training-induced increased NKA content. We investigated whether oral digoxin increased NKA isoform mRNA expression (qPCR) in muscle at rest, during and post-exercise in 10 healthy adults, who received digoxin (DIG, 0.25 mg per day) or placebo (CON) for 14 days, in a randomised, double-blind and cross-over design.

Development and Validation of a Machine Learning COVID-19 Veteran (COVet) Deterioration Risk Score.

Background And Objective: To develop the COVid Veteran (COVet) score for clinical deterioration in Veterans hospitalized with COVID-19 and further validate this model in both Veteran and non-Veteran samples. No such score has been derived and validated while incorporating a Veteran sample.

Derivation Cohort: Adults (age ≥ 18 yr) hospitalized outside the ICU with a diagnosis of COVID-19 for model development to the Veterans Health Administration (VHA) (n = 80 hospitals).

Small-molecule probe for IBD risk variant GPR65 I231L alters cytokine signaling networks through positive allosteric modulation.

The proton-sensing heterotrimeric guanine nucleotide-binding protein-coupled receptor GPR65 is expressed in immune cells and regulates tissue homeostasis in response to decreased extracellular pH, which occurs in the context of inflammation and tumorigenesis. Genome-wide association studies linked to several autoimmune and inflammatory diseases such as multiple sclerosis and inflammatory bowel disease (IBD). The loss-of-function GPR65 I231L IBD risk variant alters cellular metabolism, impairs protective tissue functions, and increases proinflammatory cytokine production.

Foals of mares vaccinated for Hendra virus have a suboptimal response to HeV vaccination.

Hendra virus (HeV) is lethal to horses and a zoonotic threat to humans in Australia, causing severe neurological and/or respiratory disease with high mortality. An equine vaccine has been available since 2012. Foals acquire antibodies from their dams by ingesting colostrum after parturition, therefore it is assumed that foals of mares vaccinated against HeV will have passive HeV antibodies circulating during the first several months of life until they are actively vaccinated.

Provision of Behavioral Health Services at Community Health Centers and Hospital Emergency Department Visits.

Background: Numerous US patients seek the hospital emergency department (ED) for behavioral health care. Community Health Centers (CHCs) offer a potential channel for redirecting many to a more patient-centered, lower cost setting.

Objective: The aim of this study was to identify unique market areas serviced by CHCs and to examine whether CHCs are effective in offsetting behavioral health ED visits.

Sildenafil Versus Placebo for Early Pulmonary Vascular Disease in Scleroderma (SEPVADIS): protocol for a randomized controlled trial.

Background: Pulmonary hypertension (PH) is a leading cause of death in patients with systemic sclerosis (SSc). An important component of SSc patient management is early detection and treatment of PH. Recently the threshold for the diagnosis of PH has been lowered to a mean pulmonary artery pressure (mPAP) threshold of > 20 mmHg on right heart catheterization (RHC).

Development and external validation of deep learning clinical prediction models using variable-length time series data.

Objectives: To compare and externally validate popular deep learning model architectures and data transformation methods for variable-length time series data in 3 clinical tasks (clinical deterioration, severe acute kidney injury [AKI], and suspected infection).

Materials And Methods: This multicenter retrospective study included admissions at 2 medical centers that spanned 2007-2022. Distinct datasets were created for each clinical task, with 1 site used for training and the other for testing.