Single-cell analyses reveal that monocyte gene expression profiles influence HIV-1 reservoir size in acutely treated cohorts.

Elimination of latent HIV-1 is a major goal of AIDS research but the host factors determining the size of these reservoirs are poorly understood. Here, we investigated whether differences in host gene expression modulate the size of the HIV-1 reservoir during suppressive ART. Peripheral blood mononuclear cells (PBMC) from fourteen individuals initiating ART during acute infection who demonstrated effective viral suppression but varying magnitude of total HIV-1 DNA were characterized by single-cell RNA sequencing (scRNA-seq).

Synthesis, Biological Evaluation, and Mechanistic Insights of Rubrolide Analogues as Antitumor Agents.

Marine natural products and their analogues have as of now been acknowledged as an important source of bioactive molecules for the treatment of cancer. Rubrolides, a unique group of -butenolides derived from marine microorganisms, have shown strong cytotoxic activity against various tumor cells. In this study, we synthesized and characterized 21 rubrolide analogues (including 16 new compounds) and investigated their antitumor activities in order to screen more active molecules and elucidate their mechanism of action.

Mortality in septic patients treated with short-acting betablockers: a comprehensive meta-analysis of randomized controlled trials.

Background: Treatment with short-acting betablockers in septic patients remains controversial. Two recent large multicenter trials have provided additional evidence on this therapeutic approach. We thus performed a meta-analysis, including the most recent data, to evaluate the potential impacts of treatment with short-acting betablockers on mortality in adult septic patients.

Changing expectations toward end-of-life communication: An experimental investigation.

Objectives: To investigate the effect of a) a brief video intervention and b) end-of-life (EOL) conversations with relatives on EOL communication expectations.

Methods: 272 participants from the general population were randomly assigned to three different video conditions (Intervention group: Persons reporting positive EOL conversation experiences +imagination task, Control group 1: Video unrelated to EOL topics, Control group 2: Persons reporting different attitudes toward EOL conversations +imagination task). Primary outcome was negative expectations.

Impact of personalized response-directed surgery and adjuvant therapy on survival after neoadjuvant immunotherapy in stage III melanoma: Comparison of 3-year data from PRADO and OpACIN-neo.

Background: Pathologic response following neoadjuvant immune checkpoint blockade (ICB) in stage III melanoma serves as a surrogate marker for long-term outcomes. This may support more personalized, response-directed treatment strategies.

Methods: The OpACIN-neo and PRADO trials were phase 2 studies evaluating neoadjuvant treatment with ipilimumab and nivolumab in stage III melanoma.

Season-dependent variation in the contents of glucosinolates and S-methyl-l-cysteine sulfoxide and their hydrolysis in Brassica oleracea.

Brassica vegetables contain glucosinolates and S-methyl-l-cysteine sulfoxide, which can be enzymatically hydrolyzed to form bioactive compounds. Glucosinolate hydrolysis can result in formation of health-promoting isothiocyanates, however, often less desirable nitriles and epithionitriles are formed due to presence of specifier proteins. Also, S-methyl-l-cysteine sulfoxide yields beneficial volatile organosulfur compounds (VOSC), such as S-methyl methanethiosulfinate.

Ravulizumab and Efgartigimod in Myasthenia Gravis: A Real-World Study.

Background And Objectives: Biologics that target pathogenic antibodies (Abs) and their effector functions such as the complement inhibitor ravulizumab and the neonatal Fc receptor agonist efgartigimod have recently been approved for the treatment of acetylcholine receptor (AChR)-Ab-positive myasthenia gravis (MG), but comparative studies are lacking.

Methods: In a prospective, exploratory real-world study, we assessed clinical efficacy, safety, and biological effects of ravulizumab and efgartigimod treatment initiation. Myasthenia Gravis-Activities of Daily Living and Quantitative Myasthenia Gravis scores were used as clinical endpoints.

Benefits of Clinical Decision Support Systems for the Management of Noncommunicable Chronic Diseases: Targeted Literature Review.

Background: Clinical decision support systems (CDSSs) are designed to assist in health care delivery by supporting medical practice with clinical knowledge, patient information, and other relevant types of health information. CDSSs are integral parts of health care technologies assisting in disease management, including diagnosis, treatment, and monitoring. While electronic medical records (EMRs) serve as data repositories, CDSSs are used to assist clinicians in providing personalized, context-specific recommendations derived by comparing individual patient data to evidence-based guidelines.

Development of bombesin-tubulysin conjugates using multicomponent chemistry to functionalize both the payload and the homing peptide.

Peptide-drug conjugates (PDCs) have recently gained significant attention for the targeted delivery of anticancer therapeutics, mainly due to their cost-effective and chemically defined production and lower antigenicity compared to ADCs, among other benefits. In this study, we designed and synthesized novel PDCs by conjugating new thiol-functionalized tubulysin analogs (tubugis) to bombesin, a peptide ligand with a relevant role in cancer research. Two tubulysin analogs bearing ready-for-conjugation thiol groups were prepared by an on-resin multicomponent peptide synthesis strategy and subsequently tested for their stand-alone anti-proliferative activity against human cancer cells, which resulted in IC values in the nanomolar range.

Vitamin D Is Associated with Lipid Metabolism: A Sex- and Age-Dependent Analysis of a Large Outpatient Cohort.

Vitamin D is a fat-soluble steroid that influences cardiovascular health by affecting lipid metabolism. Since dyslipidemia is a key risk factor for cardiovascular disease (CVD), our study aimed to explore the relationship between vitamin D levels and lipid parameters, considering the effects of age and gender. : In this cross-sectional study of 47,778 outpatients, we analyzed correlations between two forms of vitamin D-25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)D)-and lipid parameters, including low-density lipoprotein (LDL), high-density lipoprotein (HDL), and total cholesterol (TC).

Harmonizing Dietary Exposure of Adult and Older Individuals: A Methodological Work of the Collaborative PROMED-COG Pooled Cohorts Study.

The PROtein-enriched MEDiterranean diet to combat undernutrition and promote healthy neuroCOGnitive ageing in older adults (PROMED-COG) is a European project that investigates the role of nutritional status on neurocognitive ageing. This methodological paper describes the harmonization process of dietary data from four Italian observational studies (Pro.V.

Dose-Reduced FLA-IDA in Combination with Venetoclax Is an Effective and Safe Salvage Therapy in Relapsed and Refractory Acute Myeloid Leukemia (R/R AML).

Despite the development of targeted therapies in first-line AML, complete remissions (CR) cannot be achieved in 30-40%, and relapse rates remain high. In R/R AML the intensive treatment regimen of fludarabine, cytarabine, idarubicin combined with venetoclax (FLA-VIDA) showed improved remission rates compared to FLA-IDA. In this retrospective single-center analysis, we investigated the efficacy and safety of dose-reduced FLA-IDA with and without venetoclax to minimize the risk of infectious complications and excessive myelosuppression; Methods: Between 2011 and 2023, 89 R/R AML patients were treated with dose-reduced FLA-IDA (fludarabine 30 mg/m day 1-4, cytarabine 2000 mg/m day 1-4, idarubicin 10 mg/m day 1 + 4).

New-to-nature CO-dependent acetyl-CoA assimilation enabled by an engineered B-dependent acyl-CoA mutase.

Acetyl-CoA is a key metabolic intermediate and the product of various natural and synthetic one-carbon (C1) assimilation pathways. While an efficient conversion of acetyl-CoA into other central metabolites, such as pyruvate, is imperative for high biomass yields, available aerobic pathways typically release previously fixed carbon in the form of CO. To overcome this loss of carbon, we develop a new-to-nature pathway, the Lcm module, in this study.

A snapshot of biomanufacturing and the need for enabling research infrastructure.

Biomanufacturing is crucial for the bioeconomy, with growing investment and attention from industries and governments. Over recent decades numerous biotech companies have been founded, and policies have increasingly prioritised sustainable production methods. However, translation of biotechnological innovations into industrial applications remains challenging, requiring interdisciplinary research infrastructures (RIs) to address gaps in bioprocess development, scalability, and competitiveness.

Prolonged Venous Transit on Perfusion Imaging is Associated with Longer Lengths of Stay in Acute Large Vessel Occlusions.

Background And Purpose: Prolonged venous transit (PVT+) is a marker of venous outflow; it is defined as the presence or absence of time-to-maximum ≥10 seconds timing in either the superior sagittal sinus or torcula. This novel perfusion imaging-based metric has been associated with higher odds of mortality and lower odds of functional recovery. This study aims to assess the relationship between PVT on admission perfusion imaging and length of hospital stay in large vessel occlusion strokes successfully reperfused with mechanical thrombectomy.

Within-host dynamics of antiviral treatment with remdesivir for SARS-CoV-2 infection.

The effectiveness of antiviral treatment with remdesivir against COVID-19 has been investigated in clinical trials suggesting earlier recovery. However, this effect seems to be rather modest. In this study, we tracked the clinical course of SARS-CoV-2 infections in 369 COVID-19 individuals across a spectrum of illness severities, including both untreated individuals and individuals who received antiviral treatment with remdesivir.

Design of a Duplex-to-Complex Structure-Switching Approach for the Homogeneous Determination of Marine Biotoxins in Water.

In this report, we describe a fluorescent assay for the detection of six marine toxins in water. The mechanism of detection is based on a duplex-to-complex structure-switching approach. The six aptamers specific to the targeted cyanotoxins were conjugated to a fluorescent dye, carboxyfluorescein (FAM).

Moiré Lattice of Twisted Bilayer Graphene as Template for Non-Covalent Functionalization.

We present a novel approach to achieve spatial variations in the degree of non-covalent functionalization of twisted bilayer graphene (tBLG). The tBLG with twist angles varying between ~5° and 7° was non-covalently functionalized with 1,4,5,8,9,11-hexaazatriphenylenehexacarbonitrile (HATCN) molecules. Our results show a correlation between the degree of functionalization and the twist angle of tBLG.

Increased Disability Progression in rs10191329 Carriers with Multiple Sclerosis Is Preceded by Neurofilament Light Chain Elevations.

Objective: We examined the impact of the rs10191329 genetic risk variant on neuroaxonal damage as measured by serum neurofilament light chain (sNfL) levels, and disability progression in people with multiple sclerosis (pwMS).

Methods: In a cohort of pwMS (n = 740), 658 participants were prospectively monitored every 2 years for less than a decade while 82 of 740 pwMS were monitored retrospectively for up to 40 years. We investigated associations between rs10191329 variants and clinical outcome, including Expanded Disability Status Scale (EDSS), disability accrual (defined by EDSS-increase of at least 1.

High-density sampling reveals volume growth in human tumours.

In growing cell populations such as tumours, mutations can serve as markers that allow tracking the past evolution from current samples. The genomic analyses of bulk samples and samples from multiple regions have shed light on the evolutionary forces acting on tumours. However, little is known empirically on the spatio-temporal dynamics of tumour evolution.

The impact of an integrated alcohol policy: The example of Lithuania.

Introduction: Although integrated alcohol policies, characterised by being consistent, structurally connected and interdependent, are considered to be best practices, very few evaluations of such policies exist. We evaluated the impact of two phases of integrated alcohol policies implemented in Lithuania in 2008/2009 and 2017/2018 on adult (15+ years of age) alcohol per capita consumption.

Methods: Alcohol per capita consumption was the main outcome, based on national data from Statistics Lithuania.