Anti-correlation of LacI association and dissociation rates observed in living cells.

The rate at which transcription factors (TFs) bind their cognate sites has long been assumed to be limited by diffusion, and thus independent of binding site sequence. Here, we systematically test this assumption using cell-to-cell variability in gene expression as a window into the in vivo association and dissociation kinetics of the model transcription factor LacI. Using a stochastic model of the relationship between gene expression variability and binding kinetics, we performed single-cell gene expression measurements to infer association and dissociation rates for a set of 35 different LacI binding sites.

How do hospitals exert market power? Evidence from health systems and commercial health plan prices.

Consolidation of independent hospitals and physician practices into integrated health systems has reshaped the delivery of health care. While the literature suggests that provider consolidation raises prices, few studies have examined the interplay of health systems and insurers in relation to prices. Using negotiated price data that commercial insurers recently released under the Transparency in Coverage Final Rule, we examined the association between hospital concentration under health systems and prices for outpatient procedures in local health care markets with different levels of insurer concentration.

Artificial intelligence models using F-wave responses predict amyotrophic lateral sclerosis.

Nerve conduction F-wave studies contain critical information about subclinical motor dysfunction which may be used to diagnose patients with amyotrophic lateral sclerosis (ALS). However, F-wave responses are highly variable in morphology, making waveform interpretation challenging. Artificial Intelligence techniques can extract time-frequency features to provide new insights into ALS diagnosis and prognosis.

Child sleep problems mediate prospective associations between fathers' parenting stress and child blood glucose levels.

The present study examined the role of first-time fathers' parenting stress during infancy in relation to children's mean blood glucose via glycated hemoglobin (HbA1c) levels during middle childhood while also exploring the mediating role of child sleep problems in this association. A total of 306 fathers self-reported on parenting stress when their children were 10 months old (49% of girls). Fathers also reported on child sleep problems when their children were 24 months old.

Long-term outcomes of patients who received extracorporeal cardiopulmonary resuscitation (ECPR) following in-hospital cardiac arrest: Analysis of EXCEL registry data.

Objective: To describe the six-month functional outcomes of patients who received extracorporeal cardiopulmonary resuscitation (ECPR) following in-hospital cardiac arrest (IHCA) in Australia.

Design: Secondary analysis of EXCEL registry data.

Setting: EXCEL is a high-quality, prospective, binational registry including adult patients who receive extracorporeal membrane oxygenation (ECMO) in Australia and New Zealand.

Wastewater-based analysis of antimicrobial resistance at UK airports: Evaluating the potential opportunities and challenges.

With 40 million annual passenger flights, airports are key hubs for microbial communities from diverse geographic origins to converge, mix, and distribute. Wastewater derived from airports and aircraft represent both a potential route for the global dispersion of antimicrobial resistant (AMR) organisms and an under-utilised resource for strengthening global AMR surveillance. This study investigates the abundance and diversity of antimicrobial resistance genes (ARGs) in wastewater samples collected from airport terminals (n = 132), aircraft (n = 25), and a connected wastewater treatment plant (n = 11) at three international airports in the UK (London Heathrow, Edinburgh and Bristol).

Can fast wall shear stress computation predict adverse cardiac events in patients with intermediate non-flow limiting stenoses?

Background And Aims: Coronary angiography-derived wall shear stress (WSS) may enable identification of vulnerable plaques and patients. A new recently introduced software allows seamless three-dimensional quantitative coronary angiography (3D-QCA) reconstruction and WSS computation within a single user-friendly platform carrying promise for clinical applications. This study examines for the first time the efficacy of this software in detecting vulnerable lesions in patients with intermediate non-flow limiting stenoses.

The partisanship of mayors has no detectable effect on police spending, police employment, crime, or arrests.

In this paper, we examine whether mayors' partisan affiliations lead to differences in crime and policing. We use a large new dataset on mayoral elections and three different modern causal inference research designs (a regression discontinuity design centered around close elections and two robust difference-in-differences methods) to determine the causal effect of mayoral partisanship on crime, arrests, and racial differences in arrest patterns in medium and large US cities. We find no evidence that mayoral partisanship affects police employment or expenditures, police force or leadership demographics, overall crime rates, or numbers of arrests.

A scoping review of the reporting quality of reviews of commercially and publicly available mobile health apps.

Objectives: There is no guidance to support the reporting of systematic reviews of mobile health (mhealth) apps (app reviews), so authors attempt to use/modify the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). There is a need for reporting guidance, building on PRISMA where appropriate, tailored to app reviews. The objectives were to describe the reporting quality of published mHealth app reviews, identify the need for, and develop potential candidate items for a reporting guideline.

Improvement in Temple Hollowing with VYC-20L Hyaluronic Acid Filler: A Multicenter, Randomized Controlled Trial of Safety and Effectiveness.

Background: Temple hollowing is characterized by the reduction of volume in the temporal fossa, which can result in a skeletonized look and contribute to an aged appearance. This study aimed to evaluate the safety and effectiveness of the VYC-20L injectable gel for improvement of temple hollowing.

Methods: Adults with minimal, moderate, or severe temple hollows were randomized 2:1 to receive VYC-20L or no treatment.

Clinical criteria for limbic-predominant age-related TDP-43 encephalopathy.

Limbic predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is highly prevalent in late life and a common co-pathology with Alzheimer's disease neuropathologic change (ADNC). LATE-NC is a slowly progressive, amnestic clinical syndrome. Alternatively, when present with ADNC, LATE-NC is associated with a more rapid course.

Longitudinal FDG-PET Metabolic Change Along the Lewy Body Continuum.

Importance: Although 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a well-established cross-sectional biomarker of brain metabolism in dementia with Lewy bodies (DLB), the longitudinal change in FDG-PET has not been characterized.

Objective: To investigate longitudinal FDG-PET in prodromal DLB and DLB, including a subsample with autopsy data, and report estimated sample sizes for a hypothetical clinical trial in DLB.

Design, Setting, And Participants: Longitudinal case-control study with mean (SD) follow-up of 3.

Comparative genomic analysis of Fusarium oxysporum f. sp. lycopersici reveals telomeric duplications of a lineage-specific region carrying SIX8 and PSL1 and genome-wide expansion of Foxy transposable elements.

Fusarium oxysporum f. sp. lycopersici (Fol), the causal agent of tomato wilt disease, is a soil-borne, vascular-colonizing fungal pathogen that severely impacts tomato production in most growing regions worldwide.

A novel interleukin-10 antibody graft to treat inflammatory bowel disease.

Inflammatory bowel disease (IBD) consists of chronic conditions that severely impact a patient's health and quality of life. Interleukin-10 (IL-10), a potent anti-inflammatory cytokine has strong genetic links to IBD susceptibility and has shown strong efficacy in IBD rodent models, suggesting it has great therapeutic potential. However, when tested in clinical trials for IBD, recombinant human IL-10 (rhIL-10) showed weak and inconsistent efficacy due to its short half-life and pro-inflammatory properties that counteract the anti-inflammatory efficacy.

Metagenomics unveils the role of hospitals and wastewater treatment plants on the environmental burden of antibiotic resistance genes and opportunistic pathogens.

Antimicrobial resistance (AMR) is a global health challenge, with hospitals and wastewater treatment plants (WWTPs) serving as significant pathways for the dissemination of antibiotic resistance genes (ARGs). This study investigates the potential of wastewater-based epidemiology (WBE) as an early warning system for assessing the burden of AMR at the population level. In this comprehensive year-long study, effluent was collected weekly from three large hospitals, and treated and untreated wastewater were collected monthly from three associated community WWTPs.

The Society of Thoracic Surgeons (STS) Clinical Practice Guideline on Surgical Management of Oligometastatic Non-small Cell Lung Cancer.

Background: The use of local consolidative therapy (LCT) in patients with oligometastatic non-small cell lung cancer (NSCLC) is rapidly evolving, with a preponderance of data supporting the benefits of such therapeutic approaches incorporating pulmonary resection for appropriately selected candidates. However, practices vary widely institutionally and regionally, and evidence-based guidelines are lacking.

Methods: The Society of Thoracic Surgeons assembled a panel of thoracic surgical oncologists to evaluate and synthesize the available evidence regarding the role of pulmonary resection as LCT.

Sixty-five draft genome sequences of and from table egg layer chickens.

We present the draft genomic sequences of 65 isolates of spp. (38 and 27 ) isolated from table egg-layer chickens, which are not generally associated with human transmission. Up to this time, there are no publicly available genomic sequences of isolated from laying hens.

A PAS-targeting hERG1 activator reduces arrhythmic events in Jervell and Lange-Nielsen syndrome patient-derived hiPSC-CMs.

The hERG1 potassium channel conducts the cardiac repolarizing current, IKr. hERG1 has emerged as a therapeutic target for cardiac diseases marked by prolonged actional potential duration (APD). Unfortunately, many hERG1 activators display off-target and proarrhythmic effects that limit their therapeutic potential.

Clinicopathologic and genomic features associated with brain metastasis after resection of lung adenocarcinoma.

Objective: To identify clinicopathologic and genomic features associated with brain metastasis after resection of lung adenocarcinoma (LUAD) and to evaluate survival after brain metastasis.

Methods: Patients who underwent complete resection of stage I-IIIA LUAD between 2011 and 2020 were included. A subset of patients had broad-based panel next-generation sequencing performed on their tumors.

Sex differences in mitochondrial free-carnitine levels in subjects at-risk and with Alzheimer's disease in two independent study cohorts.

A major challenge in the development of more effective therapeutic strategies for Alzheimer's disease (AD) is the identification of molecular mechanisms linked to specific pathophysiological features of the disease. Importantly AD has a two-fold higher incidence in women than men and a protracted prodromal phase characterized by amnestic mild-cognitive impairment (aMCI) suggesting that biological processes occurring early can initiate vulnerability to AD. Here, we used a sample of 125 subjects from two independent study cohorts to determine the levels in plasma (the most accessible specimen) of two essential mitochondrial markers acetyl-L-carnitine (LAC) and its derivative free-carnitine motivated by a mechanistic model in rodents in which targeting mitochondrial metabolism of LAC leads to the amelioration of cognitive function and boosts epigenetic mechanisms of gene expression.

Remote Symptom Monitoring in Thoracic Surgery Patients After Discharge.

Objective: Evaluate an electronic platform for remote symptom monitoring to enhance postdischarge care in thoracic surgery using patient reporting of symptoms.

Summary Background Data: Owing to the increased use of enhanced recovery after surgery protocols, patients are spending a larger portion of their postoperative course at home. For patients undergoing complex operations, this represents an opportunity for early identification of abnormal symptoms at home before deterioration.

YAP regulates periosteal expansion in fracture repair.

Bone fracture repair initiates by periosteal expansion. The periosteum is typically quiescent, but upon fracture, periosteal cells proliferate and contribute to bone fracture repair. The expansion of the periosteum is regulated by gene transcription; however, the molecular mechanisms behind periosteal expansion are unclear.

Biglycan-driven risk stratification in ZFTA-RELA fusion supratentorial ependymomas through transcriptome profiling.

Recent genomic studies have allowed the subdivision of intracranial ependymomas into molecularly distinct groups with highly specific clinical features and outcomes. The majority of supratentorial ependymomas (ST-EPN) harbor ZFTA-RELA fusions which were designated, in general, as an intermediate risk tumor variant. However, molecular prognosticators within ST-EPN ZFTA-RELA have not been determined yet.

Proton Accumulation Modulated Surface Potential in Proton Conducting Ceramics Revealed by Near-Ambient Pressure X-ray Photoelectron Spectroscopy.

Proton conducting electrochemical cells (PCECs) are efficient and clean intermediate-temperature energy conversion devices. The proton concentration across the PCECs is often nonuniform, and characterizing the distribution of proton concentration can help to locate the position of rate-limiting reactions. However, the determination of the local proton concentration under operating conditions remains challenging.