Exploring Integrin α5β1 as a Potential Therapeutic Target for Pulmonary Arterial Hypertension: Insights From Comprehensive Multicenter Preclinical Studies.

Background: Pulmonary arterial hypertension (PAH) is characterized by obliterative vascular remodeling of the small pulmonary arteries (PAs) and progressive increase in pulmonary vascular resistance leading to right ventricular failure. Although several drugs are approved for the treatment of PAH, mortality rates remain high. Accumulating evidence supports a pathological function of integrins in vessel remodeling, which are gaining renewed interest as drug targets.

Synthesis and physico-chemical investigation of thiolated dextran derivative: Design and application of a redox-responsive drug delivery system.

In the present investigation, redox-responsive-based dextran carriers were developed for the controlled release of hydrophobic molecules via a reducing agent naturally present in cells, namely glutathione. In this sense, dextran was modified with a thiol derivative. The roles of the hydrophilic segments in the molecular self-organisation of polysaccharide derivatives into nanoparticles were investigated by varying the average dextran molar mass.

A Student-Informed Guide for Success on the OB/GYN Clerkship.

The obstetrics and gynecology (OB/GYN) clerkship is a uniquely enriching and challenging rotation for medical students. Available literature prepares students for medicine and surgery clerkships, but few guides identify and discuss the unique characteristics of OB/GYN that impact student learning and performance during the clerkship. Here, we aim to highlight the specific clinical learning environments, emotionally sensitive experiences, and technical performance expectations that students should anticipate and be prepared for in the OB/GYN clerkship.

Plasma pTau181 and amyloid markers predict conversion to dementia in idiopathic REM sleep behaviour disorder.

Blood-based biomarkers for Alzheimer's disease (AD) pathology have been intensively investigated as markers for AD-related neurodegeneration. Comorbid AD pathology is common in dementia with Lewy bodies (DLB). Accordingly, we hypothesized that plasma biomarkers associated with AD pathology might be useful to predict DLB in a cohort of idiopathic/isolated REM sleep behavior disorder (iRBD), an incipient synucleinopathy.

Trophic magnification rates of eighteen trace elements in freshwater food webs.

Trace elements play diverse roles in animal physiology ranging from essential micronutrients to potent toxicants. Despite animals accumulating many trace elements through their diets, relationships between trophic positions and biological concentrations of most trace elements remain poorly described. We report trophic transfer rates of Al, As, Ba, Cd, Co, Cu, Fe, Hg, Mn, Ni, Pb, Se, Sr, Ti, Tl, U, V, and Zn from 31 freshwaters located in distinct biogeographic regions.

Infertility care and physician trainees: a survey on elective fertility preservation.

Purpose: Female physicians experience a higher rate of infertility than the general population, are more likely to delay childbearing in training and use assisted reproductive technologies. Little is known about how physician trainees use infertility services or perceive an employer-sponsored fertility preservation benefit. This study assessed physician trainee knowledge of and experiences with infertility and gauged interest in an employer-sponsored fertility preservation benefit.

ATP citrate lyase drives vascular remodeling in systemic and pulmonary vascular diseases through metabolic and epigenetic changes.

ATP citrate lyase (ACLY), a crucial enzyme in de novo lipid synthesis and histone acetylation, plays a key role in regulating vascular smooth muscle cell (VSMC) proliferation and survival. We found that human coronary and pulmonary artery tissues had up-regulated ACLY expression during vascular remodeling in coronary artery disease and pulmonary arterial hypertension. Pharmacological and genetic inhibition of ACLY in human primary cultured VSMCs isolated from the coronary arteries of patients with coronary artery diseases and from the distal pulmonary arteries of patients with pulmonary arterial hypertension resulted in reduced cellular proliferation and migration and increased susceptibility to apoptosis.

Systems Immunology Approaches to Understanding Immune Responses in Acute Infection of Yellow Fever Patients.

In the 2018 yellow fever (YF) outbreak in Brazil, we generated new transcriptomic data and combined it with clinical and immunological data to decode the pathogenesis of YF. Analyzing 79 patients, we found distinct gene expression patterns between acute YF, other viral infections, and the milder YF-17D vaccine infection. We identified a critical role for low-density, immature neutrophils in severe outcomes, marked by the downregulation of genes essential for neutrophil migration and maturation, such as PADI4, CSF3R, and ICAM1, in deceased patients.

Social media as health educator: An assessment of the understandability and accuracy of tiktok content about contraception.

Background: Contraception knowledge and attitudes are largely formed from conversations within one's social network. More recently, this network has expanded to include social media. As the fastest growing social media platform, we aimed to assess popular contraception videos on TikTok for content understandability, actionability and accuracy.

Risk of Incident Cancer in Patients with Inflammatory Bowel Disease with Prior Breast Cancer: A Multicenter Cohort Study.

Background & Aims: Breast cancer is the most common malignancy observed in patients with inflammatory bowel diseases (IBD). The aim of our study was to evaluate incident cancer rate (recurrence or new-onset cancer) in a cohort of patients with IBD with a history of breast cancer according to the subsequent IBD treatment provided.

Methods: A multicenter retrospective study included consecutive patients with IBD with prior breast cancer.

Perioperative adjuvant therapy with short course of dupilumab with ESS for recurrent CRSwNP.

Background: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is associated with a high rate of disease recurrence following endoscopic sinus surgery (ESS). Type 2 disease is associated with a higher incidence of recurrence and is believed to impact disease resolution via interference with epithelial healing and pathogen immunity. We wished to verify if perioperative control of Type 2 inflammation with an anti-IL4/IL13 targeting monoclonal antibody and during the resolution period following surgery leads to better control of the disease long term.

Exploring the Nicotine-Parkinson's disease link - Insights from the UK Biobank.

Introduction: Evidence suggests an inverse correlation between smoking and Parkinson's disease (PD), yet the mechanisms remain unclear. This study examines the changing risk relationship between smoking and PD diagnosis using alcohol consumption, another reward-driven behavior, as a comparative measure.

Methods: A nested case-control study was conducted using the UK Biobank (UKBB) database.

Financial toxicity in early-phase cancer clinical trial participants.

Background: Little is known about financial toxicity in early-phase clinical trial (EP-CT) participants. This study sought to describe financial toxicity in EP-CT participants and assess associations with patient characteristics and patient-reported outcomes (PROs).

Methods: Prospectively enrolled EP-CT participants from were followed from April 2021 through January 2023.

DivIVA controls the dynamics of septum splitting and cell elongation in .

Bacterial shape and division rely on the dynamics of cell wall assembly, which involves regulated synthesis and cleavage of the peptidoglycan. In ovococci, these processes are coordinated within an annular mid-cell region with nanometric dimensions. More precisely, the cross-wall synthesized by the divisome is split to generate a lateral wall, whose expansion is insured by the insertion of the so-called peripheral peptidoglycan by the elongasome.

IGLON5 Frequency in Idiopathic REM Sleep Behavior Disorder: A Multicenter Study.

Background And Objectives: Idiopathic/isolated REM sleep behavior disorder (iRBD) has been strongly linked to neurodegenerative synucleinopathies such as Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. However, there have been increasing reports of RBD as a presenting feature of serious and treatable autoimmune syndromes, particularly IGLON5. This study's objective was to investigate the frequency of autoantibodies in a large cohort of participants with iRBD.

Missing Values in Longitudinal Proteome Dynamics Studies: Making a Case for Data Multiple Imputation.

Temporal proteomics data sets are often confounded by the challenges of missing values. These missing data points, in a time-series context, can lead to fluctuations in measurements or the omission of critical events, thus hindering the ability to fully comprehend the underlying biomedical processes. We introduce a Data Multiple Imputation (DMI) pipeline designed to address this challenge in temporal data set turnover rate quantifications, enabling robust downstream analysis to gain novel discoveries.

Recombinant Protein Production from Stable CHO Cell Pools.

The continuous improvement of expression platforms is necessary to respond to the increasing demand for recombinant proteins that are required to carry out structural or functional studies as well as for their characterization as biotherapeutics. While transient gene expression (TGE) in mammalian cells constitutes a rapid and well-established approach, non-clonal stably transfected cells, or "pools," represent another option, which is especially attractive when recurring productions of the same protein are required. From a culture volume of just a few liters, stable pools can provide hundreds of milligrams to gram quantities of high-quality secreted recombinant proteins.

A pre-vaccination immune metabolic interplay determines the protective antibody response to a dengue virus vaccine.

Protective immunity to dengue virus (DENV) requires antibody response to all four serotypes. Systems vaccinology identifies a multi-OMICs pre-vaccination signature and mechanisms predictive of broad antibody responses after immunization with a tetravalent live attenuated DENV vaccine candidate (Butantan-DV/TV003). Anti-inflammatory pathways, including TGF-β signaling expressed by CD68 monocytes, and the metabolites phosphatidylcholine (PC) and phosphatidylethanolamine (PE) positively correlate with broadly neutralizing antibody responses against DENV.

Time Toxicity Experienced by Early-Phase Cancer Clinical Trial Participants.

Purpose: Early-phase clinical trials (EP-CTs) are designed to determine optimal dosing, tolerability, and preliminary activity of novel cancer therapeutics. Little is known about the time that patients spend interacting with the health care system (eg, time toxicity) while participating in these studies.

Methods: We retrospectively reviewed the electronic health records of consecutive patients enrolled in EP-CTs from 2017 to 2019 to obtain baseline characteristics and number of health care-associated days, defined as all inpatient and outpatient visits while on trial.

Exploring Integrin α5β1 as a Potential Therapeutic Target for Pulmonary Arterial Hypertension: Insights from Comprehensive Multicenter Preclinical Studies.

Unlabelled: Pulmonary arterial hypertension (PAH) is characterized by obliterative vascular remodeling of the small pulmonary arteries (PA) and progressive increase in pulmonary vascular resistance (PVR) leading to right ventricular (RV) failure. Although several drugs are approved for the treatment of PAH, mortality remains high. Accumulating evidence supports a pathological function of integrins in vessel remodeling, which are gaining renewed interest as drug targets.