Oral Regimens for Rifampin-Resistant, Fluoroquinolone-Susceptible Tuberculosis.

Background: For decades, poor treatment options and low-quality evidence plagued care for patients with rifampin-resistant tuberculosis. The advent of new drugs to treat tuberculosis and enhanced funding now permit randomized, controlled trials of shortened-duration, all-oral treatments for rifampin-resistant tuberculosis.

Methods: We conducted a phase 3, multinational, open-label, randomized, controlled noninferiority trial to compare standard therapy for treatment of fluoroquinolone-susceptible, rifampin-resistant tuberculosis with five 9-month oral regimens that included various combinations of bedaquiline (B), delamanid (D), linezolid (L), levofloxacin (Lfx) or moxifloxacin (M), clofazimine (C), and pyrazinamide (Z).

Sphingolipid metabolism orchestrates establishment of the hair follicle stem cell compartment.

Sphingolipids serve as building blocks of membranes to ensure subcellular compartmentalization and facilitate intercellular communication. How cell type-specific lipid compositions are achieved and what is their functional significance in tissue morphogenesis and maintenance has remained unclear. Here, we identify a stem cell-specific role for ceramide synthase 4 (CerS4) in orchestrating fate decisions in skin epidermis.

Exploring the relationship between established HIV risk factors and depressive symptoms amongst young women without HIV in two sites in South Africa.

Purpose: Adolescent girls are at high risk for depression and human immunodeficiency virus (HIV) acquisition. Poor mental health can increase vulnerability to risky sexual behaviours. Therefore, this study aims to determine the prevalence of depressive symptomology and explore the convergence of HIV risk factors with depressive symptoms amongst cis-gender adolescent girls and young women (AGYW) in rural KwaZulu-Natal (KZN) and peri-urban Western Cape (WC) communities in South Africa.

The Impact of Physical Therapy Postprofessional Education Programs on Productivity in a Large Academic Medical Center.

Introduction: Emerging evidence shows positive impact of postprofessional physical therapy education (residency and fellowship) specific to participants; however, outcomes on organizational impact are largely unknown. The purpose of this project was to describe the impact residency and fellowship training has on financial metrics. A secondary purpose of this case study was to describe trends associated with higher productivity.

Prioritizing questions and topics for the development of guidelines and consensus-based recommendations supported by ILAE: A scoping review and proposal of prioritization criteria.

Clinical practice guidelines (CPGs) and consensus-based recommendations (CBRs) require considerable effort, collaboration, and time-all within the constraints of finite resources. Professional societies, such as the International League Against Epilepsy (ILAE), must prioritize what topics and questions to address. Implementing evidence-based care remains a crucial challenge in clinical practice.

Individualizing musical tempo to spontaneous rates maximizes music-induced hypoalgesia.

Music has long been recognized as a noninvasive and cost-effective means of reducing pain. However, the selection of music for pain relief often relies on intuition rather than on a scientific understanding of the impact of basic musical attributes on pain perception. This study examines how a fundamental element of music-tempo-affects its pain-relieving properties.

Multi-omics analysis reveals distinct gene regulatory mechanisms between primary and organoid-derived human hepatocytes.

Hepatic organoid cultures are a powerful model to study liver development and diseases in vitro. However, hepatocyte-like cells differentiated from these organoids remain immature compared to primary human hepatocytes (PHHs), which are the benchmark in the field. Here, we applied integrative single-cell transcriptome and chromatin accessibility analysis to reveal gene regulatory mechanisms underlying these differences.

Refractory Psychosis as a Red Flag for End of Life in Individuals With Dementia With Lewy Bodies: A Case Series and Re-analysis of Prior Qualitative Data.

Objectives: Many individuals with dementia with Lewy bodies (DLB) die of disease-related complications, but predicting the end of life can be challenging. We identified a phenotype associated with approaching end of life.

Methods: We present 4 exemplar cases where individuals with DLB experienced refractory psychosis before death.

Prognostic significance and accuracy of oncologists' estimates of survival time in recurrent ovarian cancer.

Objective: We evaluated the accuracy of oncologists' estimates of expected survival time in recurrent ovarian cancer.

Methods: Oncologists estimated expected survival time at baseline for each patient, who were then followed up for survival time. We hypothesized that oncologists' estimates of expected survival time would be independently significant predictors of survival, unbiased (approximately equal proportions [50%] living longer versus shorter than their expected survival time), or imprecise (<30% within 0.

An evolved, orthogonal ssDNA generator for targeted hypermutation of multiple genomic loci.

Achieving targeted hypermutation of specific genomic sequences without affecting other regions remains a key challenge in continuous evolution. To address this, we evolved a T7 RNA polymerase (RNAP) mutant that synthesizes single-stranded DNA (ssDNA) instead of RNA in vivo, while still exclusively recognizing the T7 promoter. By increasing the error rate of the T7 RNAP mutant, it generates mutated ssDNA that recombines with homologous sequences in the genome, leading to targeted genomic hypermutation.

Telomemore enables single-cell analysis of cell cycle and chromatin condensation.

Single-cell RNA-seq methods can be used to delineate cell types and states at unprecedented resolution but do little to explain why certain genes are expressed. Single-cell ATAC-seq and multiome (ATAC + RNA) have emerged to give a complementary view of the cell state. It is however unclear what additional information can be extracted from ATAC-seq data besides transcription factor binding sites.

Interventions to reduce non-prescription antimicrobial sales in community pharmacies.

Background: Antimicrobial resistance (AMR) is a major global health concern. One of the most important causes of AMR is the excessive and inappropriate use of antimicrobial drugs in healthcare and community settings. Most countries have policies that require antimicrobial drugs to be obtained from a pharmacy by prescription.

Cross-cultural validation of plasma p-tau217 and p-tau181 as precision biomarkers for amyloid PET positivity: An East Asian study in Taiwan and Korea.

Introduction: Plasma phosphorylated tau (p-tau) biomarkers have improved Alzheimer's disease (AD) diagnosis, but data from diverse Asian populations are limited. This study evaluated plasma p-tau217 and p-tau181 levels in Korean and Taiwanese populations.

Methods: All participants (n = 270) underwent amyloid positron emission tomography (PET) and blood tests.

A short screen for lifetime sexual victimization experiences: Expanding research on the Sexual Abuse History Questionnaire (SAHQ) across cultures, genders, and sexual identities.

The Sexual Abuse History Questionnaire (SAHQ), a widely used screening tool for childhood sexual abuse (CSA) and adolescent/adult sexual assault (AASA) experiences, has limited examination of its psychometric properties in diverse populations. Our study assessed the SAHQ's psychometric properties (i.e.

Knowledge and Awareness of Pre-Exposure Prophylaxis Among Men in Sub-Saharan Africa: A Scoping Review Protocol.

Introduction: About 39.9 million people were living with HIV as of 2023, and HIV is more prevalent in sub-Saharan Africa. Pre-exposure prophylaxis (PrEP) is highly effective in HIV prevention.

Heart Failure in Atrial Fibrillation Subtypes in Women and Men in the Tromsø Study.

Background: Atrial fibrillation (AF) and heart failure (HF) often coexist and impact morbidity and mortality. There is limited knowledge on the association of AF subtypes with HF according to sex.

Objectives: The purpose of this study was to explore sex-specific associations between AF subtypes and subsequent HF, identifying HF risk factors in participants with AF, and exploring the combined impact on mortality.

Formulation and validation of mathematical model for co-sputtering conditions to attain stoichiometric CZTS films: Expedience of using all metal sulfide targets.

A soda lime glass substrate is used for fabricating CuZnSnS (CZTS) thin films using copper (II) sulfide (CuS), zinc sulfide (ZnS), and tin sulfide (SnS) targets using an advanced co-sputtering deposition process. Following that, the films are annealed at 470 °C without sulfur (S). An algorithm based on the deposition rate of the previously specified targets set the co-sputtering condition, which maintains a deposition pressure of 5, 10, 15, and 20 mTorr.

SPIRIT-DEFINE explanation and elaboration: recommendations for enhancing quality and impact of early phase dose-finding clinical trials protocols.

Unlabelled: Transparent and accurate reporting in early phase dose-finding (EPDF) clinical trials is crucial for informing subsequent larger trials. The SPIRIT statement, designed for trial protocol content, does not adequately cover the distinctive features of EPDF trials. Recent findings indicate that the protocol contents in past EPDF trials frequently lacked completeness and clarity.

CONSORT-DEFINE explanation and elaboration: recommendations for enhancing reporting quality and impact of early phase dose-finding clinical trials.

Unlabelled: Early phase dose-finding (EPDF) trials are key in the development of novel therapies, with their findings directly informing subsequent clinical development phases and providing valuable insights for reverse translation. Comprehensive and transparent reporting of these studies is critical for their accurate and critical interpretation, which may improve and expedite therapeutic development. However, quality of reporting of design characteristics and results from EPDF trials is often variable and incomplete.

Confronting food insecurity through agricultural interventions: the Farmer FIRST program in India.

Introduction: Nutrition-sensitive agricultural interventions are crucial in addressing malnutrition and promoting food security. The Farmer, Farm, Innovation, Resources, Science, and Technology (FIRST) Program is a national-level agricultural intervention program that was started in 2016 by the Indian Council of Agricultural Research (ICAR). Its primary objective is to transform the lives and livelihoods of Indian farmers, with a focus on income and livelihood security.

Estimation of Urinary Lead and Urinary δ-Aminolevulinic Acid as an Index of Lead Exposure in Urban and Rural Residents of West Bengal, India.

Background: Chronic exposure to low-level environmental lead (Pb) causes several health effects in humans. Its biomonitoring by non-invasive biomarkers is imperative to identify Pb exposure in the occupationally unexposed general public.

Objective: To quantify urinary lead (U-Pb) and urinary δ-Aminolevulinic acid (ALA) in the general population of West Bengal, India, and identify the impact of routine life activities (smoking habit, traveling, and cooking activities) and sociodemographic factors on U-Pb and U-ALA levels.

Quality of care delivery in patients with acute heart failure: insights from the international REPORT-HF registry.

Background: Heart Failure (HF) quality of care (QoC) is associated with clinical outcomes. Therefore, we investigated differences in HF QoC across worldwide regions (with differing national income) and the association of quality indicators with outcomes.

Methods: We examined the quality of care (QoC) in acute heart failure (HF) patients across different regions using quality indicators (QIs) from the European Society of Cardiology (ESC) and the American Heart Association (AHA) to evaluate QoC.

Transforming the tradition of discrete milk yield correction factors: A continuous 1-step DeLorenzo-Wiggans method.

Over the past decades, various methods have been proposed to estimate daily milk yields from partial yields. Many of these methods divide milking interval time into varied classes, assuming that the yield correction factors are constant within classes but vary between classes. The DeLorenzo and Wiggans (D-W) method has been widely used in the United States, typically following a 2-step process.

The promise of community-driven preprints in ecology and evolution.

Publishing preprints is quickly becoming commonplace in ecology and evolutionary biology. Preprints can facilitate the rapid sharing of scientific knowledge establishing precedence and enabling feedback from the research community before peer review. Yet, significant barriers to preprint use exist, including language barriers, a lack of understanding about the benefits of preprints and a lack of diversity in the types of research outputs accepted (e.

Top-Down Strategy Enabling Elastic Wood Nanocarbon Sponges with Wrinkled Multilayer Structure and High Compressive Strength for High-Performance Compressible Supercapacitors.

3D porous carbon electrodes have attracted significant attention for advancing compressible supercapacitors (SCs) in flexible electronics. The micro- and nanoscale architecture critically influences the mechanical and electrochemical performance of these electrodes. However, achieving a balance between high compressive strength, electrochemical stability, and cost-effective sustainable production remains challenging.