Evolution of promoter-proximal pausing enabled a new layer of transcription control.

Promoter-proximal pausing of RNA polymerase II (Pol II) is a key regulatory step during transcription. Despite the central role of pausing in gene regulation, we do not understand the evolutionary processes that led to the emergence of Pol II pausing or its transition to a rate-limiting step actively controlled by transcription factors. Here we analyzed transcription in species across the tree of life.

Specific vegetable types are associated with lower long-term risk for late-life dementia: the Perth Longitudinal Study of Aging Women.

This study examined the relationship between total vegetable intake, including specific vegetable types with long-term late-life dementia (LLD) risk in older Australian women. 1206 community-dwelling older women aged ≥70 years were included. Consumption of total vegetable intake and vegetable types (yellow/orange/red [YOR], cruciferous, allium, green leafy vegetables [GLV], and legumes) were estimated using a validated food frequency questionnaire at baseline (1998).

Fetal alcohol spectrum disorder (FASD) and the criminal justice system: A guide for legal professionals.

Fetal Alcohol Spectrum Disorder (FASD) is a lifelong disorder caused by prenatal alcohol exposure (PAE) and is one of the most common causes of brain damage and developmental disability. FASD has been characterized by an array of symptoms that negatively affects cognitive, social, and adaptive functioning. Individuals living with FASD, relative to the general population, are more likely to become entangled in the legal system due to challenges associated with the disorder.

Exploring the impact of work experience on the detection of specific cancers across different breast density levels on screening mammograms.

Purpose: This study explores the attributes of true positive and false positive rates in screening mammogram test sets assessed by breast screening radiologists in order to identify the combined impact of prior images, breast density and lesion features with experience factors linked to diagnostic performance.

Methods: 869 radiologists' first-time readings across nine mammogram BREAST test sets with 361 normal and 179 cancer mammograms were collected between 2014 and 2023. Participants viewed digital mammograms on diagnostic monitors and localized abnormal lesions.

Patient-Reported Outcomes Among Adults With Congenital Heart Disease in the Congenital Heart Initiative Registry.

Importance: In the US, there are more than 1.5 million adults living with congenital heart disease (CHD). The Congenital Heart Initiative (CHI) is a digital, online, patient-empowered registry that was created to advance multicenter research and improve clinical care by gathering patient-reported outcomes (PROs) in adults with CHD.

Total Synthesis and Structural Reassignment of the Antitubercular Natural Product Evybactin.

The escalating threat posed by antibiotic resistance is a global concern and underscores the need for new antibiotics. In this context, the recent discovery of evybactin, a nonribosomal depsipeptide antibiotic that selectively and potently inhibits the growth of M. tuberculosis, is particularly noteworthy.

Proximity within adolescent peer networks predicts neural similarity during affective experience.

Individuals befriend others who are similar to them. One important source of similarity in relationships is similarity in felt emotion. In the present study, we used novel methods to assess whether greater similarity in the multivoxel brain representation of affective stimuli was associated with adolescents' proximity within real-world school-based social networks.

Discovery of BAY 2666605, a Molecular Glue for PDE3A and SLFN12.

A subset of phosphodiesterase 3 (PDE3) inhibitors kills cancer cells that express both PDE3A and SLFN12 by inducing a protein-protein interaction between the two, triggering SLFN12 tRNase activity. Following discovery of the prototypical tool compound, , an improved compound, , was discovered to be potent in cells and active in several tumor models . More analogs were prepared and tested with the goal of increasing metabolic stability and decreasing PDE3 inhibition while maintaining the cellular activity of .

Speech motor impairment in ALS is associated with multiregional cortical thinning beyond primary motor cortex.

Introduction: Cortical thinning is well-documented in individuals with amyotrophic lateral sclerosis (ALS), yet its association with speech deterioration remains understudied. This study characterizes anatomical changes in the brain within the context of speech impairment patterns in individuals with ALS, providing insight into the disease's multiregional spread and biology.

Methods: To evaluate patterns of cortical thickness in speakers with ALS with and without functional speech changes compared to healthy controls (HCs) using whole-brain and region of interest (ROI) analyses.

Transvenous extraction of conduction system and lumenless pacing leads.

Introduction: Conduction system pacing (CSP), often accomplished with lumenless pacing leads, is increasingly employed to achieve physiologic ventricular activation. There are limited data on the extraction of these leads. The objective of this study was to describe the safety and efficacy of extraction of CSP pacing leads and compare outcomes with extraction of non-CSP lumenless leads.

A Machine Learning Model Based on Global Mammographic Radiomic Features Can Predict Which Normal Mammographic Cases Radiology Trainees Find Most Difficult.

This study aims to investigate whether global mammographic radiomic features (GMRFs) can distinguish hardest- from easiest-to-interpret normal cases for radiology trainees (RTs). Data from 137 RTs were analysed, with each interpreting seven educational self-assessment test sets comprising 60 cases (40 normal and 20 cancer). The study only examined normal cases.

Unveiling Sex Differences in Pediatric Burns Through the World Health Organization (WHO) Global Burn Registry.

Introduction: Pediatric burns present a significant global health challenge, particularly in low- and middle-income countries (LMICs). Despite this burden, few studies have explored global sex-based differences in pediatric burns. This study aims to describe pediatric burn incidence, burn care facilities' capacities, and burn outcomes with a focus on sex, comparing LMICs to HICs.

Relative muscular effort in the older adults during the sit-to-stand task: Monitoring neuromuscular reserve and movement limitations.

Background: Due to lower maximum strength, older adults purportedly need to exert greater muscular effort to stand up from a chair. This study investigated joint-specific muscular effort during a sit-to-stand by calculating relative-muscular-effort and investigating differences between healthy older and young adults.

Methods: Fifteen older (age: 69.

Applying co-production principles in research: reflections from young people and academics.

Co-production, a form of collaborative working, is guided by principles including valuing all participants, building on individual strengths, blurring distinctions between roles, delivering benefits for all participants, building support networks and supporting people to deliver work themselves. This article explores how co-production is understood by young people and researchers and how co-production principles can be applied within a research context. We identify challenges of implementing existing co-production frameworks in research and key areas to consider for future work.

Mapping vulnerability to climate-related hazards to inform local authority action in adaptation: A feasibility study.

Background: Local authorities have a crucial role in building community resilience to the health effects of a changing climate. Support in achieving local action can be provided through improving available public health intelligence to inform decision making. We aimed to co-develop with a local authority a tool mapping vulnerability to climate related hazards.

"So You Made a Mistake" - The Path Forward Through Surgical Pathology Errors by Extreme Ownership and a Focus on the Patient.

Our goal for medicine is to make zero mistakes, yet the reality is that mistakes are an unfortunate part of medical practice. And when it comes to surgical pathology, it is a special case where the diagnostic "bottom line" is provided starkly and directly for all to see in the final diagnosis of the pathology report. When this diagnosis is wrong, particularly when it has serious adverse consequences for the patient, the resulting physical, mental, and emotional effects on patient, provider, pathologist, and health care system can be extremely serious.

Voluntary assisted dying: impacts on health professionals.

Objective The introduction and implementation of voluntary assisted dying (VAD) legislation represents a major shift in Australian health policy. Given potential repercussions for health professionals, understanding how they are being affected by this legislation is important to guide future policy and legislative changes. This study aims to explore the perspectives and experiences of Australian health professionals on VAD and compare impacts on those working under different state legislation in Victoria and WA.

Coherent growth of high-Miller-index facets enhances perovskite solar cells.

Obtaining micron-thick perovskite films of high quality is key to realizing efficient and stable positive (p)-intrinsic (i)-negative (n) perovskite solar cells, but it remains a challenge. Here we report an effective method for producing high-quality, micron-thick formamidinium-based perovskite films by forming coherent grain boundaries, in which high-Miller-index-oriented grains grow on the low-Miller-index-oriented grains in a stabilized atmosphere. The resulting micron-thick perovskite films, with enhanced grain boundaries and grains, showed stable material properties and outstanding optoelectronic performances.