Low agreement and frequent invalid controls in two SARS-CoV-2 T-cell assays in people with compromised immune function.

T-cell response plays an important role in SARS-CoV-2 immunogenicity. For people living with HIV (PWH) and solid organ transplant (SOT) recipients there is limited evidence on the reliability of commercially available T-cell tests. We assessed 173 blood samples from 81 participants (62 samples from 35 PWH; 111 samples from 46 SOT recipients [lung and kidney]) with two commercial SARS-CoV-2 Interferon-γ (IFN-γ) release assays (IGRA; SARS-CoV-2 IGRA by Euroimmun, and IGRA SARS-CoV-2 by Roche).

Initial Multicenter Experience With a Novel Self-Expanding TAVR System in Patients With Aortic Valve Stenosis.

Background: As transcatheter aortic valve replacement is performed increasingly in younger, low-risk patients, the need for commissural alignment and coronary access has increased. Design elements of the JenaValve Trilogy (JVT) transcatheter heart valve (THV) ensure both.

Objectives: This study sought to evaluate the outcome of patients with aortic stenosis (AS) treated with this novel transfemoral, self-expanding THV.

Progressive natural killer cell dysfunction in advanced-stage clear-cell renal cell carcinoma and association with clinical outcomes.

Background: Natural killer (NK) cells are important contributors to antitumor immunity in clear-cell renal cell carcinoma (ccRCC). However, their phenotype, function, and association with clinical outcomes in ccRCC remain poorly understood.

Materials And Methods: We analyzed single-cell RNA sequencing data from 13 primary tumors, 1 localized tumor extension, and 1 metastasis from ccRCC patients at different clinical stages.

Dereplication of Natural Product Antifungals via Liquid Chromatography-Tandem Mass Spectrometry and Chemical Genomics.

Recently expanded reports of multidrug-resistant fungal infections underscore the need to develop new and more efficient methods for antifungal drug discovery. A ubiquitous problem in natural product drug discovery campaigns is the rediscovery of known compounds or their relatives; accordingly, we have integrated Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) for structural dereplication and Yeast Chemical Genomics for bioprocess evaluation into a screening platform to identify such compounds early in the screening process. We identified 450 fractions inhibiting and the resistant strains of and among more than 40,000 natural product fractions.

Reproducibility and Reliability of Intraoral Scanners for Evaluating Peri-Implant Tissues and Implant-Supported Prostheses: A Cross-Sectional Study.

Objective: To assess the reproducibility and reliability of the pink (PES) and white esthetic scores (WES) using digital images and the intra- and inter-examiner agreement among different clinical backgrounds and assessment methods.

Material And Methods: Standardized intraoral images were obtained from adult subjects with an implant-supported single-tooth fixed dental prosthesis located in the maxillary esthetic zone using a digital camera and a true-color intraoral scanner. According to the PES and WES criteria, the images were evaluated by 20 calibrated evaluators, 5 prosthodontists, 5 periodontists, 5 undergraduates, and 5 oral surgeons.

Immunogenomic determinants of exceptional response to immune checkpoint inhibition in renal cell carcinoma.

Immune checkpoint inhibitors can lead to 'exceptional', durable responses in a subset of persons. However, the molecular basis of exceptional response (ER) to immunotherapy in metastatic clear cell renal cell carcinoma (mccRCC) has not been well characterized. Here we analyzed pretherapy genomic and transcriptomic data in treatment-naive persons with mccRCC treated with standard-of-care immunotherapies: (1) combination of programmed cell death protein and ligand 1 (PD1/PDL1) and cytotoxic T lymphocyte-associated protein 4 inhibitors (IO/IO) or (2) combination of PD1/PDL1 and vascular endothelial growth factor (VEGF) receptor inhibitors (IO/VEGF).

Impact of Higher Cell-Free DNA Yields on Liquid Biopsy Testing in Glioblastoma Patients.

Background: Minimally invasive molecular profiling using cell-free DNA (cfDNA) is increasingly important to the management of cancer patients; however, low sensitivity remains a major limitation, particularly for brain tumor patients. Transiently attenuating cfDNA clearance from the body-thereby, allowing more cfDNA to be sampled-has been proposed to improve the performance of liquid biopsy diagnostics. However, there is a paucity of clinical data on the effect of higher cfDNA recovery.

Diagnostic Laboratory Stewardship in a Growing Integrated Delivery Network.

Background: Many organizations institute laboratory diagnostic stewardship (DS) programs to improve the utilization of laboratory resources.

Methods: In this paper, we describe the road to implementing laboratory DS in a large, not-for-profit integrated delivery network located in the western United States.

Results: Program structure, projects, challenges, and future opportunities are discussed, providing tactics and opportunities that facilities can employ to maximize their initial foray into the DS landscape.

Femoral or Radial Secondary Access in TAVR: A Subanalysis From the Multicenter PULSE Registry.

Background: Transradial secondary access (TR-SA) may serve as an alternative to the traditional femoral secondary access (TF-SA) for pigtail placement in transcatheter aortic valve replacement (TAVR).

Objectives: The aim of this study was to assess the incidence of secondary access-related vascular complications after TR-SA or TF-SA in TAVR.

Methods: The PULSE (Plug or sUture based vascuLar cloSurE after TAVR) registry retrospectively evaluated data of 10,120 patients who underwent transfemoral TAVR at 10 heart centers from 2016 to 2021.

Stone selection by wild chimpanzees shares patterns with Oldowan hominins.

The use of broad tool repertoires to increase dietary flexibility through extractive foraging behaviors is shared by humans and their closest living relatives (chimpanzees, Pan troglodytes). However, comparisons between tool use in ancient human ancestors (hominins) and chimpanzees are limited by differences in their toolkits. One feature shared by primate and hominin toolkits is rock selection based on physical properties of the stones and the targets of foraging behaviors.

Mechanochemical synthesis and transformation of the polymorphic double carbonates fairchildite and buetschliite, (KCa(CO)): an X-ray powder diffraction study.

This study presents the mechanochemical synthesis of the two KCa(CO) polymorphs, fairchildite and buetschliite, from CaCO and KCO using a shaker mill. Unlike previous methods requiring high temperatures and prolonged heating, fairchildite, a high-temperature polymorph, is formed initially in all experiments, adhering to Ostwald's rule of stages. Notably, the transformation to the stable buetschliite phase can be achieved by varying milling parameters, particularly frequency and moisture content.

PALS1-dependent modulations of mRNA profiles in MDCK II cells grown in non-confluent monolayers and three-dimensional cysts.

In epithelia, apicobasal cell polarization is closely linked to cell-cell contact formation, both controlled by the conserved Crumbs (CRB) complex, which includes the transmembrane protein Crumbs (CRB3a) and adapter proteins PALS1, PATJ, and LIN7c. In MDCK II cells, a model for cell polarization, depletion of PALS1 - which binds to all CRB components - leads to defective cell polarization and improper distribution of tight junction proteins, resulting in severe epithelial barrier defects in 3D cyst models. This study investigated whether this phenotype is associated with transcriptional changes by analyzing wildtype (WT) and PALS1 knockout (KO) MDCK II cell lines grown under non-confluent conditions and in 3D cyst cultures.

Structural Insights into the Iodothyronine Deiodinase 2 Catalytic Core and Deiodinase Catalysis and Dimerization.

Iodothyronine deiodinases (Dio) are selenocysteine-containing membrane enzymes that activate and inactivate the thyroid hormones (TH) through reductive iodide eliminations. The three deiodinase isoforms are homodimers sharing highly conserved amino acid sequences, but they differ in their regioselectivities for the deiodination reaction and regulatory features. We have now solved a crystal structure of the mouse deiodinase 2 (Dio2) catalytic domain.

Booster-free anti-retroviral therapy for persons living with HIV and multidrug resistance (B-Free): protocol for a multicentre, multistage, randomised, controlled, non-inferiority trial.

Introduction: Anti-retroviral therapy (ART) simplification strategies are needed for treatment-experienced people with HIV (PWH) and multidrug-resistant viruses. These individuals are commonly treated with boosted ART regimens and are thereby at risk for harmful drug-drug interactions (DDI). In this trial, we aim to assess the efficacy of the combination doravirine, dolutegravir and lamivudine (DOR/DTG/3TC) among people with a history of virological failure who receive boosted ART.

HIV-1 low-level viremia predicts viral failure in participants on antiretroviral therapy in the Swiss HIV Cohort Study.

Background: Most individuals on combination antiretroviral therapy (ART) have HIV plasma viral loads below the limit of detection. However, episodes of low-level viremia (LLV) are observed in subsets of individuals, risk factors and clinical significance of which remain debated.

Methods: We included participants enrolled in the Swiss HIV Cohort Study, starting ART between July 1999 and April 2023, with HIV RNA <200 copies/ml six months post ART initiation.

Decoy-resistant IL-18 reshapes the tumor microenvironment and enhances rejection by anti-CTLA-4 in renal cell carcinoma.

The cytokine IL-18 has immunostimulatory effects but is negatively regulated by a secreted binding protein, IL-18BP, that limits IL-18's anticancer efficacy. A decoy-resistant form of IL-18 (DR-18) that avoids sequestration by IL-18BP while maintaining its immunostimulatory potential has recently been developed. Here, we investigated the therapeutic potential of DR-18 in renal cell carcinoma (RCC).

Transcriptional profile of infection in people living with HIV.

In people with HIV-1 (PWH), (MTB) infection poses a significant threat. While active tuberculosis (TB) accelerates immunodeficiency, the interaction between MTB and HIV-1 during asymptomatic phases remains unclear. Analysis of peripheral blood mononuclear cells (PBMC) transcriptomic profiles in PWH, with and without controlled viral loads, revealed distinct clustering in MTB-infected individuals.

Decreased lipidated ApoE-receptor interactions confer protection against pathogenicity of ApoE and its lipid cargoes in lysosomes.

While apolipoprotein E (APOE) is the strongest genetic modifier for late-onset Alzheimer's disease (LOAD), the molecular mechanisms underlying isoform-dependent risk and the relevance of ApoE-associated lipids remain elusive. Here, we report that impaired low-density lipoprotein (LDL) receptor (LDLR) binding of lipidated ApoE2 (lipApoE2) avoids LDLR recycling defects observed with lipApoE3/E4 and decreases the uptake of cholesteryl esters (CEs), which are lipids linked to neurodegeneration. In human neurons, the addition of ApoE carrying polyunsaturated fatty acids (PUFAs)-CE revealed an allelic series (ApoE4 > ApoE3 > ApoE2) associated with lipofuscinosis, an age-related lysosomal pathology resulting from lipid peroxidation.

Efficacy and Safety of Dolutegravir Plus Emtricitabine vs Combined Antiretroviral Therapy for the Maintenance of HIV Suppression: Results Through Week 144 of the SIMPL'HIV Trial.

The SIMPL'HIV study investigated whether switching to dolutegravir (DTG) + emtricitabine (FTC) was noninferior to continuing combined antiretroviral therapy for maintaining HIV-1 suppression at 144 weeks. The study demonstrated that viral suppression, CD4 gains, adverse events, quality of life, and patient satisfaction were comparable between groups, confirming DTG + FTC's safety and efficacy for long-term management of HIV-1 infection.

Physical Activity and Pregnancy Norms Among Daasanach Semi-Nomadic Pastoralist Women in Northern Kenya.

Objectives: In subsistence populations, high physical activity is typically maintained throughout pregnancy. Market integration shifts activity patterns to resemble industrialized populations, with more time allocated to sedentary behavior. Daasanach semi-nomadic pastoralists living in northern Kenya face lifestyle heterogeneity due to the emergence of a market center.

The effect of air pollution on hospitalizations with Parkinson's disease among medicare beneficiaries nationwide.

We examined the effect of annual exposure to fine particulate matter (PM), nitrogen dioxide (NO), and ozone (O), on the rate of first hospitalization with a PD-related diagnosis (hospitalization with PD) among Medicare Fee-for-Service beneficiaries (2001-2016). Machine learning-derived annual air pollution concentrations were linked to residential ZIP codes. For each exposure, we fitted four models: 1) traditional outcome stratification, 2) marginal structural, 3) doubly robust, and 4) generalized propensity score matching Poisson regression models, adjusted for sociodemographic and meteorological confounders and long-term trends.