Plasma phosphorylated tau217 strongly associates with memory deficits in the Alzheimer's disease spectrum.

Plasma phosphorylated tau biomarkers open unprecedented opportunities for identifying carriers of Alzheimer's disease pathophysiology in early disease stages using minimally invasive techniques. Plasma p-tau biomarkers are believed to reflect tau phosphorylation and secretion. However, it remains unclear to what extent the magnitude of plasma p-tau abnormalities reflects neuronal network disturbance in the form of cognitive impairment.

Job-exposure matrix (JEM) validity on crystalline silica among systemic sclerosis patients.

Background: Systemic sclerosis (SSc) is the connective tissue disease with the highest individual mortality. Crystalline silica is known to be an occupational risk factor for SSc. To assess past crystalline silica exposure, we aimed to study the validity of a job exposure matrix (JEM) to assess occupational exposure to crystalline silica compared to specific occupational interviews in two populations of SSc patients.

Impact of Online Interactive Decision Tools on Women's Decision-Making Regarding Breast Cancer Screening: Systematic Review and Meta-Analysis.

Background: The online nature of decision aids (DAs) and related e-tools supporting women's decision-making regarding breast cancer screening (BCS) through mammography may facilitate broader access, making them a valuable addition to BCS programs.

Objective: This systematic review and meta-analysis aims to evaluate the scientific evidence on the impacts of these e-tools and to provide a comprehensive assessment of the factors associated with their increased utility and efficacy.

Methods: We followed the 2020 PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and conducted a search of MEDLINE, PsycINFO, Embase, CINAHL, and Web of Science databases from August 2010 to April 2023.

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).

Acute encephalopathy without hyperammonemia has a different presentation than overt hepatic encephalopathy and displays similarly severe prognosis.

Background And Aims: In cirrhosis, some patients display acute encephalopathy without hyperammonemia (NonHep E) which is not considered as overt hepatic encephalopathy (OHE). We aimed to assess the prevalence and characteristics of NonHep E and OHE in cirrhotic patients displaying acute encephalopathy, assess their respective prognosis and compare it to other causes of acute decompensation (AD) with/without hyperammonemia.

Approach And Results: We conducted a retrolective analysis from a prospective cohort of patients hospitalized for AD.

First-Line Mobocertinib Versus Platinum-Based Chemotherapy in Patients With Exon 20 Insertion-Positive Metastatic Non-Small Cell Lung Cancer in the Phase III EXCLAIM-2 Trial.

Purpose: Mobocertinib is an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that targets exon 20 insertion (ex20ins) mutations in non-small cell lung cancer (NSCLC). This open-label, phase III trial (EXCLAIM-2: ClinicalTrials.gov identifier: NCT04129502) compared mobocertinib versus platinum-based chemotherapy as first-line treatment of ex20ins+ advanced/metastatic NSCLC.

Development and Functions of MAIT Cells.

Mucosal-associated invariant T (MAIT) cells are evolutionarily conserved T cells that recognize microbial metabolites. They are abundant in humans and conserved during mammalian evolution, which suggests that they have important nonredundant functions. In this article, we discuss the evolutionary conservation of MAIT cells and describe their original developmental process.

Fatuamide A, a Hybrid PKS/NRPS Metallophore from a sp. Marine Cyanobacterium Collected in American Samoa.

A structurally novel metabolite, fatuamide A (), was discovered from a laboratory cultured strain of the marine cyanobacterium sp., collected from Faga'itua Bay, American Samoa. A bioassay-guided approach using NCI-H460 human lung cancer cells directed the isolation of fatuamide A, which was obtained from the most cytotoxic fraction.

MELANOMAS, SARCOMAS, AND RENAL METASTASES IN THE LIVER: HOW TO TREAT?

Liver metastases from melanomas, sarcomas, and renal tumors are less frequent. Treatment and prognosis will depend on whether they are isolated or multiple, size and location, the presence or absence of extrahepatic neoplastic disease, age, stage of the initial disease, initial treatments instituted, time of evolution, and clinical condition of the patient. Recently, a high number of oncological therapies including monotherapy or in combination, neoadjuvants or adjuvants, and immuno-oncological treatments have been developed and tested, increasing disease-free time and survival.

Statistical analysis plan for hemodynamic phenotype-based, capillary refill time-targeted resuscitation in early septic shock: the ANDROMEDA-SHOCK-2 randomized clinical trial.

Background: ANDROMEDA-SHOCK 2 is an international, multicenter, randomized controlled trial comparing hemodynamic phenotype-based, capillary refill time-targeted resuscitation in early septic shock to standard care resuscitation to test the hypothesis that the former is associated with lower morbidity and mortality in terms of hierarchal analysis of outcomes.

Objective: To report the statistical plan for the ANDROMEDA--SHOCK 2 randomized clinical trial.

Methods: We briefly describe the trial design, patients, methods of randomization, interventions, outcomes, and sample size.

Working Memory Deficits in School-Age Children With Cochlear Implants Are Primarily Explained by Deficits in the Processing of Auditory and Lexical Information.

Purpose: Prelingual deaf children with cochlear implants show lower digit span test scores compared to normal-hearing peers, suggesting a working memory impairment. To pinpoint more precisely the subprocesses responsible for this impairment, we designed a sequence reproduction task with varying length (two to six stimuli), modality (auditory or visual), and compressibility (sequences with more or less regular patterns). Results on 22 school-age children with cochlear implants and 21 normal-hearing children revealed a deficit of children with cochlear implants only in the auditory modality.

Tree age affects key fine root morphological traits but does not interfere strongly with (ecto-)mycorrhizal traits.

Background And Aims: It is assumed that trees should adapt their above and belowground organs as they age. However, most studies to date have quantified these trait adjustments in homogeneous forest stands, confounding the effect of stand aging on soil properties and the intrinsic response of trees to aging.

Methods: Here, we examined 11 morphological, architectural, anatomical and mycorrhizal fine root traits of each of the first five orders for 66 Pinus koraiensis individuals of 16 to 285 years old in northeast China, while accounting for soil characteristics (pH and total C, N and P concentrations).

Early-onset sleep alterations found in patients with amyotrophic lateral sclerosis are ameliorated by orexin antagonist in mouse models.

Sleep alterations have been described in several neurodegenerative diseases yet are currently poorly characterized in amyotrophic lateral sclerosis (ALS). This study investigates sleep macroarchitecture and related hypothalamic signaling disruptions in ALS. Using polysomnography, we found that both patients with ALS as well as asymptomatic and mutation carriers exhibited increased wakefulness and reduced non-rapid eye movement sleep.

Unraveling Ofloxacin Behavior in Aqueous Environments: Molecular Dynamics of Colloidal Formation and Surface Adsorption Mechanisms.

Ofloxacin, a commonly prescribed antibiotic, raises serious environmental concerns due to its persistence in aquatic systems. This study offers new insights into the environmental behavior of ofloxacin and its interactions with carbon-based adsorbents with the aim of enhancing our understanding of its removal mechanisms via adsorption processes. Using a comprehensive computational approach, we analyzed the speciation, pK values, and solubility of ofloxacin across various pH conditions, accounting for all four microspecies, including the often-overlooked neutral form.

European ILD registry algorithm for self-assessment in interstitial lung diseases (eurILDreg ASA-ILD).

Background And Aims: Predicting progression and prognosis in Interstitial Lung Diseases (ILD), especially Idiopathic Pulmonary Fibrosis (IPF) and Progressive Pulmonary Fibrosis (PPF), remains a challenge. Integrating patient-centered measurements is essential for earlier and safer detection of disease progression. Home monitoring through e-health technologies, such as spirometry and oximetry connected to smartphone applications, holds promise for early detection of ILD progression or acute exacerbations, enabling timely therapeutic interventions.

HIV-1 resistance mutations and genetic diversity among children failing antiretroviral treatment in five healthcare facilities in Benin, West Africa.

Background: Antiretroviral treatment increases the risk of accumulation of resistance mutations that negatively impact the possibilities of future treatment. This study aimed to present the frequency of HIV-1 antiretroviral resistance mutations and the genetic diversity among children with virological failure in five pediatric care facilities in Benin.

Methods: A cross-sectional study was carried out from November 20, 2020, to November 30, 2022, in children under 15 years of age who failed ongoing antiretroviral treatment at five facilities care in Benin (VL > 3log10 on two consecutive realizations three months apart).

A simple tool to evaluate the effectiveness of HIV care for settings with gaps in data availability (ESTIHIV).

Many HIV clinics with poor IT-infrastructure are unable to report data on individuals in care with HIV, on antiretroviral treatment (ART) and virologically suppressed (VS), with the aim of monitoring the HIV Continuum of Care to estimate efficacy of HIV treatment programmes. We developed an estimation-tool, ESTIHIV, and determined the minimal data required for a random sample, to produce representative estimates, with a specified level of precision, of people with HIV on ART and VS. For proof of concept, 8852 HIV positive persons from seven clinics in seven different countries, with a follow-up visit during 2017, were included.

Replication-Poison Treatment in BRCA1-Deficient Breast Cancer Causes MRE11 Over-Resection that Induces Single-Stranded DNA Accumulation and Mitotic Catastrophe.

BRCA1 deficiency is observed in approximately 25% of triple-negative breast cancer (TNBC). BRCA1, a key player of homologous recombination (HR) repair, is also involved in stalled DNA replication fork protection and repair. Here, we investigated the sensitivity of BRCA1-deficient TNBC models to the frequently used replication chain terminator gemcitabine, which does not directly induce DNA breaks.

Computational Methods for Modeling Lipid-Mediated Active Pharmaceutical Ingredient Delivery.

Lipid-mediated delivery of active pharmaceutical ingredients (API) opened new possibilities in advanced therapies. By encapsulating an API into a lipid nanocarrier (LNC), one can safely deliver APIs not soluble in water, those with otherwise strong adverse effects, or very fragile ones such as nucleic acids. However, for the rational design of LNCs, a detailed understanding of the composition-structure-function relationships is missing.

Metabolically stable apelin analogs: development and functional role in water balance and cardiovascular function.

Apelin, a (neuro) vasoactive peptide, plays a prominent role in controlling water balance and cardiovascular functions. Apelin and its receptor co-localize with vasopressin in magnocellular vasopressinergic neurons. Apelin receptors (Apelin-Rs) are also expressed in the collecting ducts of the kidney, where vasopressin type 2 receptors are also present.

Amphiphilic Poly(β-Myrcene--Acrylic Acid) Copolymers Synthesized by Nitroxide-Mediated Copolymerization as Stabilizers of Terpene-Based Waterborne Latex.

Terpene-based amphiphilic copolymers have been designed as biobased stabilizers for waterborne latex synthesized by miniemulsion or emulsion polymerization of 1,3-diene terpene monomers. The pH-responsive P(AA--My) amphiphilic copolymers were synthesized by nitroxide-mediated radical copolymerization of β-myrcene (My) and acrylic acid (AA) with reactivity ratios of = 0.24 ± 0.

Default Bulk Ordering and Text Messaging to Enhance Outreach for Lipid Screening: A Randomized Clinical Trial.

Importance: A comprehensive lipid panel is recommended by guidelines to evaluate atherosclerotic cardiovascular disease risk, but uptake is low.

Objective: To evaluate whether direct outreach including bulk orders with and without text messaging increases lipid screening rates.

Design, Setting, And Participants: Pragmatic randomized clinical trial conducted from June 6, 2023, to September 6, 2023, at 2 primary care practices at an academic health system among patients aged 20 to 75 years with at least 1 primary care visit in the past 3 years who were overdue for lipid screening.

Stochastic Density Functional Theory for Ions in a Polar Solvent.

In recent years, the theoretical description of electrical noise and fluctuation-induced effects in electrolytes has gained renewed interest, enabled by stochastic field theories like stochastic density functional theory (SDFT). Such models, however, treat solvents implicitly, ignoring their generally polar nature. In the present study, starting from microscopic principles, we derive a fully explicit SDFT theory that applies to ions in a polar solvent.