Fragmenstein: predicting protein-ligand structures of compounds derived from known crystallographic fragment hits using a strict conserved-binding-based methodology.

Current strategies centred on either merging or linking initial hits from fragment-based drug design (FBDD) crystallographic screens generally do not fully leaverage 3D structural information. We show that an algorithmic approach (Fragmenstein) that 'stitches' the ligand atoms from this structural information together can provide more accurate and reliable predictions for protein-ligand complex conformation than general methods such as pharmacophore-constrained docking. This approach works under the assumption of conserved binding: when a larger molecule is designed containing the initial fragment hit, the common substructure between the two will adopt the same binding mode.

An exploratory analysis of differences in serum protein expression by sex in patients with systemic sclerosis associated interstitial lung disease.

Background: Systemic sclerosis (SSc) is a rare connective tissue disease, frequently affecting the skin, lungs, and pulmonary vasculature. Approximately 30-50% of SSc patients develop interstitial lung disease (SSc-ILD), with 30-35% of related deaths attributed to it. Even though men are less likely to develop systemic sclerosis, they have a higher incidence of SSc-ILD than women, and they tend to develop it at a younger age with a higher mortality rate.

Factors associated with tuberculosis treatment initiation among bacteriologically negative individuals evaluated for tuberculosis: An individual patient data meta-analysis.

Background: Globally, over one-third of pulmonary tuberculosis (TB) disease diagnoses are made based on clinical criteria after a negative bacteriological test result. There is limited information on the factors that determine clinicians' decisions to initiate TB treatment when initial bacteriological test results are negative.

Methods And Findings: We performed a systematic review and individual patient data meta-analysis using studies conducted between January 2010 and December 2022 (PROSPERO: CRD42022287613).

Preliminary Development and Validation of Automated Nociception Recognition Using Computer Vision in Perioperative Patients.

Background: Effective pain recognition and treatment in perioperative environments reduce length of stay and decrease risk of delirium and chronic pain. We sought to develop and validate preliminary computer vision-based approaches for nociception detection in hospitalized patients.

Methods: Prospective observational cohort study using red-green-blue camera detection of perioperative patients.

Cognitive and Affective Responses to the U.S. FDA E-Cigarette Addiction Warning and Advertisements among Young Adults in California: Product Design, Imagery, and Use.

The current study tested contextual features (product design, imagery, and use) of e-cigarette advertisements on responses to the mandated U.S. FDA addiction text warning.

Long RP Tachycardia and Short RP Tachycardia: Is the Nodoventricular Pathway a Culprit or an Innocent Bystander?

We encountered a single case in which a transition between orthodromic reciprocating tachycardia with a concealed nodoventricular pathway and atrioventricular nodal reentrant tachycardia with a bystander nodoventricular pathway was observed.

Implementing Mutational Epidemiology on a Global Scale: Lessons from Mutographs.

The Mutographs Cancer Grand Challenge team aimed to discover unknown causes of cancer through mutational epidemiology, an alliance of cancer epidemiology and somatic genomics. By generating whole-genome sequences from thousands of cancers and normal tissues from more than 30 countries on five continents, it discovered unsuspected mutagenic exposures affecting millions of people, raised the possibility that some carcinogens act by altering forces of selection in tissue microenvironments rather than by mutagenesis, and demonstrated changes to the direction of somatic evolution in normal cells of the human body in response to exogenous exposures and noncancer diseases. See related article by Bressan et al.

Insurance gaps at age-19 and age-26 health insurance eligibility thresholds by childhood-onset condition severity, Colorado 2014-2018.

Objective: To characterize health insurance gap patterns related to age-19 Medicaid and age-26 commercial age-eligibility cutoffs.

Study Setting And Design: This descriptive analysis spans 2014-2018, after Affordable Care Act implementation, but before COVID-19 emergency provisions. We defined insurance gaps as ≥3 consecutive months without observed enrollment, preceded and followed by ≥1 month of enrollment and stratified results by insurance source and clinical severity (e.

Concomitant Waldenström Macroglobulinemia/Lymphoplasmacytic Lymphoma and Non-Immunoglobulin M Plasma Cell Neoplasm.

Context.—: The co-occurrence of plasma cell neoplasm (PCN) and lymphoplasmacytic lymphoma (LPL) is rare, and their clonal relationship remains unclear.

Objective.

Characteristics and recovery trends of severe TBI patients with a favorable functional outcome at 6-month follow-up.

Traumatic Brain Injury (TBI) is a devastating cause of death and disability. Outcomes following TBI have been extensively studied; however, less attention has been given to identifying characteristics of individuals who have a favorable outcome following severe TBI. We conducted a retrospective analysis of a database containing information on TBI patients admitted to a level 1 trauma center between 2015 and 2021.

Expert opinion on Centiloid thresholds suitable for initiating anti-amyloid therapy. Summary of discussion at the 2024 spring Alzheimer's Association Research Roundtable.

A 24-30 Centiloid (CL) threshold was collectively considered by a group of global dementia experts as a practical and implementable cut-off for anti-amyloid therapy intervention, in Alzheimer's disease patients who have been diagnosed at the mild cognitive impairment or mild dementia stage of their disease. Though additional validation is needed, knowledge of this threshold would be valuable to those involved in diagnosing and treating patients in the new AD care pathways, as well as entry into clinical trials. Therapy monitoring to determine future treatment response and assess amyloid clearance can be accomplished with amyloid PET with some technical details still to be elucidated.

Comparison of Clinical and Radiological Outcomes of Three-Column Lumbar Osteotomies with and without Interbody Cages for Adult Spinal Deformity.

Background Context: Correcting sagittal malalignment in adult spinal deformity (ASD) is a challenging task, often requiring complex surgical interventions like pedicle subtraction osteotomies (PSOs). Different types of three-column osteotomies (3COs), including Schwab 3, Schwab 4, Schwab 4 with interbody cages, and the "sandwich" technique, aim to optimize alignment and fusion outcomes. The role of interbody cages in enhancing fusion and segmental correction remains unclear.

Associations of prenatal maternal psychosocial stress and depression with neurodevelopmental outcomes in 7.5-month-old infants in the ECHO.CA.IL prospective birth cohorts.

Background: Exposure to maternal stress and depression during pregnancy can have a marked impact on birth outcomes and child development, escalating the likelihood of preterm birth, lower birth weight, and various domains of physical and neurodevelopment.

Methods: The joint ECHO.CA.

Psychotic-Spectrum Disorders With Comorbid Anxiety are Predisposing Factors for Parkinson's Disease in a Case-Control Study.

Background: Multiple studies have demonstrated associations between psychiatric conditions and Parkinson's disease (PD) development; fewer have examined psychotic-spectrum disorders and PD development.

Objective: The objective was to assess the prevalence of psychotic-spectrum disorders with and without depression and anxiety preceding a PD diagnosis.

Methods: In this retrospective, case-control study of adults > 60 years of age, cases were identified by PD diagnosis and controls were identified in a 3:1 ratio by ambulatory encounter from 2015 to 2020.

Unsupervised deep learning of electrocardiograms enables scalable human disease profiling.

The 12-lead electrocardiogram (ECG) is inexpensive and widely available. Whether conditions across the human disease landscape can be detected using the ECG is unclear. We developed a deep learning denoising autoencoder and systematically evaluated associations between ECG encodings and ~1,600 Phecode-based diseases in three datasets separate from model development, and meta-analyzed the results.

Nicotine levels in flavoured hookah (waterpipe) tobacco products: discrepancies between labelled and measured levels.

Background: Hookah tobacco smoking is prevalent among youth and young adults. While health warning labels play a critical role in communicating the health risks of tobacco product use to consumers, compliance with US Federal Regulation's nicotine warning requirements on hookah tobacco packaging is low. Some labelling suggests that consumers are exposed to 'only 0.

Clinical Outcomes With Immune Checkpoint Inhibitors in Patients With FGFR2/3, MTAP or ERBB2 Genomic Alterations in Advanced Urothelial Carcinoma.

Background: FGFR2/3, MTAP and ERBB2 genomic alterations have treatment targets in advanced urothelial carcinoma (aUC). These alterations may affect tumor microenvironment and outcomes with immune checkpoint inhibitors (ICIs) in aUC.

Patients And Methods: We identified patients with available genomic data in our multi-institution cohort of patients with aUC treated with ICI.

A Primer on Carceral Health for Clinicians: Care Delivery, Regulatory Oversight, Legal and Ethical Considerations, and Clinician Responsibilities.

The United States has one of the highest incarceration rates in the world, with approximately 1.7 million individuals detained in jails or federal or state prisons. Chronic medical conditions are more prevalent among adults in custody than among their nonincarcerated counterparts, resulting in needs that often surpass the on-site medical treatment capabilities of carceral facilities.

Host-microbe multiomic profiling identifies distinct COVID-19 immune dysregulation in solid organ transplant recipients.

Coronavirus disease 2019 (COVID-19) poses significant risks for solid organ transplant recipients, who have atypical but poorly characterized immune responses to infection. We aim to understand the host immunologic and microbial features of COVID-19 in transplant recipients by leveraging a prospective multicenter cohort of 86 transplant recipients age- and sex-matched with 172 non-transplant controls. We find that transplant recipients have higher nasal SARS-CoV-2 viral abundance and impaired viral clearance, and lower anti-spike IgG levels.

Safety, bactericidal activity, and pharmacokinetics of the antituberculosis drug candidate BTZ-043 in South Africa (PanACEA-BTZ-043-02): an open-label, dose-expansion, randomised, controlled, phase 1b/2a trial.

Background: The broad use of bedaquiline and pretomanid as the mainstay of new regimens to combat tuberculosis is a risk due to increasing bedaquiline resistance. We aimed to assess the safety, bactericidal activity, and pharmacokinetics of BTZ-043, a first-in-class DprE1 inhibitor with strong bactericidal activity in murine models.

Methods: This open-label, dose-expansion, randomised, controlled, phase 1b/2a trial was conducted in two specialised tuberculosis sites in Cape Town, South Africa.

Effect of telehealth yoga on loneliness and social isolation among rural older adults: a randomized controlled trial.

Objectives: Loneliness and social isolation are associated with a range of deleterious health outcomes. Yoga is a mind-body physical activity that is used in health care settings and increasingly in a telehealth group format. This trial aimed to determine the effect of a brief course of telehealth yoga on loneliness among rural older adults.