Phosphorylation-dependent WRN-RPA interaction promotes recovery of stalled forks at secondary DNA structure.

The WRN protein is vital for managing perturbed replication forks. Replication Protein A strongly enhances WRN helicase activity in specific in vitro assays. However, the in vivo significance of RPA binding to WRN has largely remained unexplored.

Short-term evolutionary implications of an introgressed size-determining supergene in a vulnerable population.

The Thorny Skate (Amblyraja radiata) is a vulnerable species displaying a discrete size-polymorphism in the northwest Atlantic Ocean (NWA). We conducted whole genome sequencing of samples collected across its range. Genetic diversity was similar at all sampled sites, but we discovered a ~ 31 megabase bi-allelic supergene associated with the size polymorphism, with the larger size allele having introgressed in the last ~160,000 years B.

Utilizing TP53 hotspot mutations as effective predictors of gemcitabine treatment outcome in non-small-cell lung cancer.

TP53 mutations are recognized to correlate with a worse prognosis in individuals with non-small cell lung cancer (NSCLC). There exists an immediate necessity to pinpoint selective treatment for patients carrying TP53 mutations. Potential drugs were identified by comparing drug sensitivity differences, represented by the half-maximal inhibitory concentration (IC50), between TP53 mutant and wild-type NSCLC cell lines using database analysis.

The transcriptional response of cortical neurons to concussion reveals divergent fates after injury.

Traumatic brain injury (TBI) is a risk factor for neurodegeneration, however little is known about how this kind of injury alters neuron subtypes. In this study, we follow neuronal populations over time after a single mild TBI (mTBI) to assess long ranging consequences of injury at the level of single, transcriptionally defined neuronal classes. We find that the stress-responsive Activating Transcription Factor 3 (ATF3) defines a population of cortical neurons after mTBI.

Splicing accuracy varies across human introns, tissues, age and disease.

Alternative splicing impacts most multi-exonic human genes. Inaccuracies during this process may have an important role in ageing and disease. Here, we investigate splicing accuracy using RNA-sequencing data from >14k control samples and 40 human body sites, focusing on split reads partially mapping to known transcripts in annotation.

Integrating representation learning, permutation, and optimization to detect lineage-related gene expression patterns.

Recent barcoding technologies allow reconstructing lineage trees while capturing paired single-cell RNA-sequencing (scRNA-seq) data. Such datasets provide opportunities to compare gene expression memory maintenance through lineage branching and pinpoint critical genes in these processes. Here we develop Permutation, Optimization, and Representation learning based single Cell gene Expression and Lineage ANalysis (PORCELAN) to identify lineage-informative genes or subtrees where lineage and expression are tightly coupled.

Current Practices and Evidence of Aspirin Usage in Microvascular Surgery: A Systematic Review and Meta-Analysis.

Background: Acetylsalicylic acid (ASA) has been used in reconstructive microsurgery since the inception of the field. However, when compared to placebo groups, its efficacy is not confirmed. In our study, we hypothesize that the utility of ASA postoperatively in microvascular surgery is not associated with improved outcomes.

The politicization of influenza: partisan changes in flu vaccination before and after COVID-19.

Background: Democrats are more likely to be vaccinated for COVID-19 than Republicans. It is unknown if political polarization surrounding the COVID-19 vaccine has affected flu vaccine uptake. The purpose of this study is to examine the partisan differences in annual flu vaccine uptake before and after the COVID-19 pandemic.

Evidence-Based Surgical Guidelines for Treating Children With Rhabdomyosarcoma.

Background: Surgery remains the cornerstone of treatment for rhabdomyosarcoma (RMS) in children. However, there is considerable variation in surgical management practices worldwide, highlighting the need for standardized Clinical Practice Guidelines (CPG).

Methods: The CPG development involved assembling a multidisciplinary group, prioritizing 10 key topic areas, conducting evidence searches, and synthesizing findings.

From circuits to lifespan: translating mouse and human timelines with neuroimaging based tractography.

Animal models are commonly used to investigate developmental processes and disease risk, but humans and model systems (e.g., mice) differ substantially in the pace of development and aging.

Characterizing olfactory brain responses in young infants.

Odor perception plays a critical role in early human development, but the underlying neural mechanisms are not fully understood. To investigate these, we presented appetitive and aversive odors to infants of both sexes at one month of age while recording functional magnetic resonance imaging (fMRI) and nasal airflow data. Infants slept during odor presentation to allow MRI scanning.

Tobacco product flavour policies in the USA.

Objectives: Characterise US residents' exposure to restrictions on sales of flavoured electronic nicotine delivery system (ENDS), cigars and menthol cigarettes across states and time, and assess correlations between these policies.

Methods: From 2022 to 2024, we compiled flavour policy locations from advocacy groups and online searches, located corresponding legal texts and reviewed these to identify policy details, including effective dates. Using census data, we calculated the proportion of state residents covered by each policy quarterly from 2009 to 2024 and estimated correlations between them and cigarette taxes.

Addressing residual and recurrent aneurysms post-Woven EndoBridge device embolization: a systematic review and meta-analysis.

Background: Early literature on the Woven EndoBridge (WEB) device reported 80-90% adequate aneurysm occlusion but low complete occlusion (40-55%). It is uncertain whether residual or recurrent aneurysms require re-treatment to prevent future rupture.

Objective: To systematically review the literature to meta-analyze occlusion and complication rates after re-treatment of these aneurysms.

Characteristics of injury deaths among homeless and non-homeless US veterans (2017-2021).

Objective: The objective of this study is to assess whether experiencing homelessness may be associated with future risk of injury death and characterise these injury deaths by homelessness status among veterans who received healthcare through the US Department of Veterans Affairs (VA).

Methods: A retrospective cohort study was conducted among 6 128 921 veterans (399 125 homeless and 5 729 796 non-homeless) who received VA healthcare between 2017 and 2020 and were followed until 2021 using linked data from VA's Corporate Data Warehouse, Homeless Operations Management System and the VA/Department of Defense Joint Mortality Data Repository. Injury death rates were estimated by homelessness status with 95% CIs using the exact Poisson method.

Positive affect amplifies integration within episodic memories in the laboratory and the real world.

Emotional events hold a privileged place in our memories, differing in accuracy and structure from memories for neutral experiences. Although much work has focused on the pronounced differences in memory for negative experiences, there is growing evidence that positive events may lead to more holistic, or integrated, memories. However, it is unclear whether these affect-driven changes in memory structure, which have been found in highly controlled laboratory environments, extend to real-world episodic memories.

Strengthening advanced therapy for sickle cell disease in Africa: experience from sickle cell disease centre in Dar es Salaam, Tanzania.

Despite progress in healthcare services for individuals living with sickle cell disease (SCD) in Africa, substantial gaps remain in advanced treatments for SCD. To help address this burden, Tanzania has established one of the largest single-centre SCD programmes in the world and developed an advanced therapy programme for SCD focused on patient engagement and advocacy, clinical activities involving exchange blood transfusion (ExBT) and haematopoietic stem cell transplant (HSCT), gene therapy (GT) preparedness, and enabling partnerships. This report describes the programme's genesis, structure and progress achieved.

Unique presentation of cavernous sinus thrombosis in a paediatric patient.

A paediatric patient presented with periorbital oedema and fever. Initially, there was low suspicion for cavernous sinus thrombosis and orbital cellulitis due to the presence of full extraocular movements. However, given worsening bilateral periorbital oedema, lethargy and sepsis, neuroimaging was performed demonstrating inflammation and enhancement of the leptomeninges and left cavernous sinus, and raising concern for cavernous sinus thrombosis in the setting of orbital cellulitis.

Vancomycin-induced acute generalised exanthematous pustulosis.

Antibiotics have been well documented to result in several dermatological adverse reactions. Many of these adverse reactions are rashes that are difficult to distinguish. We present a case of a female patient in her 30s with acute generalised exanthematous pustulosis following vancomycin treatment for left breast cellulitis.

Polymicrobial empyema in a patient with lung adenocarcinomacontaining .

A man in his 60s with advanced COPD and lung adenocarcinoma presented with sepsis and acute hypoxaemic respiratory failure. Imaging revealed bilateral pleural effusions, and he was found to have a polymicrobial empyema which included Despite appropriate treatment, he continued to deteriorate and ultimately died of sepsis. species, typically benign constituents of the oral microbiota, rarely can instigate pleuropulmonary infections, especially in immunocompromised individuals.

Evaluating the Impact of an Educational Intervention on Nursing Labor Support Practices and Cesarean Birth Rates.

Over 30% of births in the United States occur via cesarean section despite increased risks to the birthing person and neonate. Evidence-based nursing practice related to fetal monitoring, patient positioning, and management of the second stage of labor can decrease the incidence of cesarean birth. The objective is to decrease the cesarean birth rate by 3% in a Midwestern suburban hospital.

A Quality Improvement Initiative to Improve First-Case On-Time Starts for Elective Surgeries.

Surgical delays can lead to patient dissatisfaction and negatively affect hospital revenue. Maximizing operating room (OR) efficiencies is a high priority. A common metric for OR efficiency is first-case on-time start (FCOTS).

Motivational Interviewing to Address Vaccine Hesitancy in a Rural Population.

Individuals experience vaccination hesitancy for many reasons. However, not receiving vaccinations leaves individuals at increased risk for vaccine-preventable illnesses. Individuals in rural areas are more likely to experience vaccine hesitancy.

Intensive care unit acquired weakness and physical rehabilitation in the ICU.

Approximately half of critically ill adults experience intensive care unit acquired weakness (ICUAW). Patients who develop ICUAW may have negative outcomes, including longer duration of mechanical ventilation, greater length of stay, and worse mobility, physical functioning, quality of life, and mortality. Early physical rehabilitation interventions have potential for improving ICUAW; however, randomized trials show inconsistent findings on the efficacy of these interventions.

Effect of SARS-CoV2 Infection on Endovascular Thrombectomy Outcomes - Data from the Florida Stroke Registry.

Background And Purpose: Endovascular thrombectomy outcomes are impacted by changes in stroke systems of care. During the pandemic, SARS-CoV2 positive status had major implications on hospital arrival and treatment models of non-COVID related hospital admissions. Using the Florida Stroke Registry, we compared the rates of in-hospital death and discharge outcomes of patients treated with endovascular thrombectomy who tested positive for SARS-CoV2 infection during their hospitalization.

microbiota model recapitulates and predicts individualised sensitivity to dietary emulsifier.

Background: Non-absorbed dietary emulsifiers, including carboxymethylcellulose (CMC), directly disturb intestinal microbiota, thereby promoting chronic intestinal inflammation in mice. A randomised controlled-feeding study (Functional Research on Emulsifiers in Humans, FRESH) found that CMC also detrimentally impacts intestinal microbiota in some, but not all, healthy individuals.

Objectives: This study aimed to establish an approach for predicting an individual's sensitivity to dietary emulsifiers via their baseline microbiota.