Clinical significance and antifungal susceptibility profile of 103 clinical isolates of species complex and obtained from NIH patients.

Reduced susceptibility to antifungals is common among members of genera and , with optimal treatments still not fully defined. antifungal susceptibility results and clinical data do not comprehensively account for the advent of new species identified by molecular phylogenetics. Using Clinical and Laboratory Standards Institute (CLSI) methodology, we tested a total of 103 clinical isolates obtained from patients at the NIH Clinical Center.

Supplemental oxygen for symptomatic relief in people with serious respiratory illness: a systematic review and meta-analysis.

Background: People with serious respiratory illness frequently have a high symptom burden and may be prescribed supplemental oxygen therapy with the aims of reducing the severity of breathlessness and improving health-related quality of life (HRQoL). This systematic review and meta-analysis aimed to assess the effectiveness of oxygen therapy no oxygen on 1) breathlessness, 2) HRQoL and 3) adverse events.

Methods: A comprehensive search was performed in Embase, Medline and the Cochrane Central Register of Controlled Trials for randomised controlled trials published prior to June 2022.

Patient-Reported Barriers to Foregut Cancer Care in the Deep South.

Background: Many patients with foregut cancer do not receive guideline-concordant treatment (GCT). Although social determinants of health (SDOH) have been associated with differences in receipt of GCT, the underlying mechanisms that perpetuate these disparities remain unknown. This mixed-methods study explored barriers to receipt of care among patients with foregut cancer.

Short 5' UTRs serve as a marker for viral mRNA translation inhibition by the IFIT2-IFIT3 antiviral complex.

Recognition of "non-self" nucleic acids, including cytoplasmic dsDNA, dsRNA, or mRNAs lacking proper 5' cap structures, is critical for the innate immune response to viruses. Here, we demonstrate that short 5' untranslated regions (UTRs), a characteristic of many viral mRNAs, can also serve as a molecular pattern for innate immune recognition via the interferon-induced proteins IFIT2 and IFIT3. The IFIT2-IFIT3 heterodimer, formed through an intricate domain swap structure resolved by cryo-EM, mediates viral mRNA 5' end recognition, translation inhibition, and ultimately antiviral activity.

Low Genetic Diversity and Complex Population Structure in Black Piranha (), a Key Amazonian Predator.

The black piranha (), a widely spread species in the rivers of the Amazon basin, plays a vital role as both key predator and important prey. Despite its essential contribution to ecosystem stability, there is a lack of information regarding its genetic diversity and population dynamics in the central Amazon region. As the Amazon continues to undergo environmental changes in the context of growing anthropogenic threats, such knowledge is fundamental for assist in the conservation of this species.

TIGIT inhibitor M6223 as monotherapy or in combination with bintrafusp alfa in patients with advanced solid tumors: a first-in-human, phase 1, dose-escalation trial.

Background: M6223 is an intravenous (IV), Fc-competent, fully human, antagonistic, anti-T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) antibody. Bintrafusp alfa (BA) is a bifunctional fusion protein that simultaneously blocks nonredundant immunosuppressive TGF-β and PD-(L)1 pathways.

Methods: This first-in-human, dose-escalation study in patients with advanced solid tumors (N=58; aged ≥18 years, ECOG PS≤1) evaluated M6223 alone (Part 1A, n=40; M6223 10-2400 mg every 2 weeks, n=32; M6223 2400 mg every 3 weeks, n=8) or with BA (Part 1B, n=18; M6223 300-1600 mg with BA 1200 mg; both every 2 weeks, intravenous).

Pilot-Scale Enzymatic Conversion of Low Stability, High Free Fatty, Squid Oil to an Oxidatively Stable Astaxanthin-Rich Acylglyceride Oil Suitable for Nutritional Applications.

Squid viscera, a byproduct of squid processing, contains oil rich in omega-3 fatty acids (up to 10% by mass) and the antioxidant astaxanthin. However, its high free fatty acid (FFA) content compromises stability. To address this, pilot-scale (200 L) enzymatic re-esterification of squid oil using immobilized lipase (Lipozyme RMIM) was demonstrated, resulting in high acylglyceride yields.

Exploring the complex relationship between psychosocial stress and the gut microbiome: implications for inflammation and immune modulation.

There is growing interest in understanding the complex relationship between psychosocial stress and the human gastrointestinal microbiome (GIM). This review explores the potential physiological pathways connecting these two and how they contribute to a proinflammatory environment that can lead to the development and progression of the disease. Exposure to psychosocial stress triggers the activation of the sympathetic nervous system (SNS) and hypothalamic-pituitary axis (HPA), leading to various physiological responses essential for survival and coping with the stressor.

Clinical improvements after endoscopic lung volume reduction with valves in patients with advanced emphysema and a 6-min walk test ≤140 m at baseline.

Background: Data regarding the effectiveness and safety of endoscopic lung volume reduction with valves (ELVR) in emphysema patients with a very low 6-min walk test (6MWT) are limited. Patients with severe emphysema and very low exercise capacity, as indicated by a 6MWT ≤140 m, are often excluded from clinical studies on ELVR, assuming limited therapeutic benefits and increased complication risk.

Study Designs And Methods: This study utilised data from the Lungenemphysemregister e.

Metabolic bariatric surgery generates substantial, sustained weight loss and health improvement in a real-world setting.

Background: To determine if the positive outcomes from clinical trials regarding the safety and efficacy of metabolic bariatric surgery are reproducible at a national level.

Methods: A longitudinal registry-based observation study with data collected from all persons undergoing metabolic bariatric surgery in Australia from 28 February 2012-31 December 2021 including data from 122,567 index patients who underwent 134,625 completed bariatric procedures.

Main Outcomes And Measures: Defined adverse outcomes at 90-days (unplanned readmission, intensive care admission and re-operation; death), annual change in weight (percent total body weight loss (TBWL)), diabetes treatment and need for re-operation.

One-quarter of freshwater fauna threatened with extinction.

Freshwater ecosystems are highly biodiverse and important for livelihoods and economic development, but are under substantial stress. To date, comprehensive global assessments of extinction risk have not included any speciose groups primarily living in freshwaters. Consequently, data from predominantly terrestrial tetrapods are used to guide environmental policy and conservation prioritization, whereas recent proposals for target setting in freshwaters use abiotic factors.

Assessing Lung Ventilation and Bronchodilator Response in Asthma and Chronic Obstructive Pulmonary Disease with F MRI.

Background Pulmonary function tests are central to diagnosis and monitoring of respiratory diseases but do not provide information on regional lung function heterogeneity. Fluorine 19 (F) MRI of inhaled perfluoropropane permits quantitative and spatially localized assessment of pulmonary ventilation properties without tracer gas hyperpolarization. Purpose To assess regional lung ventilation properties using F MRI of inhaled perfluoropropane in participants with asthma, participants with chronic obstructive pulmonary disease (COPD), and healthy participants, including quantitative evaluation of bronchodilator response in participants with respiratory disease.

Durlobactam in combination with β-lactams to combat .

() presents significant clinical challenges. This study evaluated the synergistic effects of a β-lactam and β-lactamase inhibitor combination against and explored the underlying mechanisms. Synergy was assessed through MIC tests and time-kill studies, and binding affinities of nine β-lactams and BLIs to eight target receptors (L,D-transpeptidases [LDT] 1-5, D,D-carboxypeptidase, penicillin-binding protein [PBP] B, and PBP-lipo) were assessed using mass spectrometry and kinetic studies.

The Impact of Age and Sex on Fasting Plasma Glucose and Glycated Haemoglobin (HbA1c) in the Non-diabetes Population.

Introduction: We previously reported sex differences in the distribution of glycated haemoglobin (HbA1c) for men/women aged < 50 years vs older individuals, with implications for delayed diabetes diagnosis. Here, we explored whether this pattern was also seen in matched fasting plasma glucose (FPG) levels.

Methods: We extracted data on same-day, paired HbA1c and FPG levels from clinical biochemistry laboratory databases from Mersey and West Lancashire Teaching Hospitals NHS Trust (n = 10,153) and Cambridge University Hospitals NHS Foundation Trust (n = 10,022) between Jan 2019 and Dec 2023.

Serum Folate Concentrations in Exclusively Breastfed Preterm Infants Who Received No Supplementary Oral Folic Acid After Discharge: A Prospective Cohort Study.

Adequate folate intake is required in preterm infants for rapid growth and development, but there is little evidence to back recommendations. We aimed to assess folate status in preterm infants at discharge and in early infancy, according to exposure to folate sources, particularly in those exclusively/predominantly breastfed. A prospective, multicenter, observational cohort study was conducted in the UK, involving 45 preterm infants <33 weeks' gestational age (GA) exclusively/predominantly fed human milk when approaching NICU (Neonatal Intensive Care Unit) discharge.

MIBiG 4.0: advancing biosynthetic gene cluster curation through global collaboration.

Specialized or secondary metabolites are small molecules of biological origin, often showing potent biological activities with applications in agriculture, engineering and medicine. Usually, the biosynthesis of these natural products is governed by sets of co-regulated and physically clustered genes known as biosynthetic gene clusters (BGCs). To share information about BGCs in a standardized and machine-readable way, the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard and repository was initiated in 2015.

Coinfection of Leprosy and Chronic Mucocutaneous Candidiasis in a Family with STAT1 Gain-of-Function Mutation.

This report documents the first known cases of lepromatous leprosy in patients with chronic mucocutaneous candidiasis (CMC) linked to a gain-of-function mutation in the STAT1 gene. Two related patients, a mother and daughter, who both suffer from CMC and lepromatous leprosy, carry a heterozygous STAT1 mutation (c.821G>A; p.

Breathing techniques to reduce symptoms in people with serious respiratory illness: a systematic review.

Background: In adults with serious respiratory illness, breathlessness is prevalent and associated with reduced health-related quality of life. The aim of this review was to assess the impact of breathing techniques on breathlessness in adults with serious respiratory illness.

Methods: Electronic databases were searched to identify randomised controlled trials testing breathing techniques (techniques that aim to alter the respiratory pattern, excluding respiratory muscle training) in people with serious respiratory illness.

Behavioral Correlates of Caregiver-Reported Oral Health of Children with Cleft Palate with or without Cleft Lip Ages 14 to 48 Months: An Observational Study.

To identify behaviors associated with poor caregiver-reported oral health in a population of young children with cleft palate with or without cleft lip (CP ± L). Observational cross-sectional study. U.

Lentiviral vector packaging and producer cell lines yield titers equivalent to the industry-standard four-plasmid process.

Lentiviral vector (LVV)-mediated cell and gene therapies have the potential to cure diseases that currently require lifelong intervention. However, the requirement for plasmid transfection hinders large-scale LVV manufacture. Moreover, large-scale plasmid production, testing, and transfection contribute to operational risk and the high cost associated with this therapeutic modality.

Therapeutic potential of cis-targeting bispecific antibodies.

The growing clinical success of bispecific antibodies (bsAbs) has led to rapid interest in leveraging dual targeting in order to generate novel modes of therapeutic action beyond mono-targeting approaches. While bsAbs that bind targets on two different cells (trans-targeting) are showing promise in the clinic, the co-targeting of two proteins on the same cell surface through cis-targeting bsAbs (cis-bsAbs) is an emerging strategy to elicit new functionalities. This includes the ability to induce proximity, enhance binding to a target, increase target/cell selectivity, and/or co-modulate function on the cell surface with the goal of altering, reversing, or eradicating abnormal cellular activity that contributes to disease.

Clinical Utility of Plasma Microbial Cell-Free DNA Sequencing Among Immunocompromised Patients With Pneumonia.

Background: Plasma microbial cell-free DNA (mcfDNA) sequencing can establish the etiology of multiple infectious syndromes by identifying microbial DNA in plasma. However, data are needed to define the clinical scenarios where this tool offers the highest clinical benefit.

Methods: We conducted a prospective multicenter observational study that evaluated the impact of plasma mcfDNA sequencing compared with usual care testing among adults with hematologic malignancies.