Strengthening serological studies: the need for greater geographical diversity, biobanking, and data-accessibility.

Serological studies uniquely strengthen infectious disease surveillance, expanding prevalence estimates to encompass asymptomatic infections, and revealing the otherwise inapparent landscape of immunity, including who is and is not susceptible to infection. They are thus a powerful complement to often incomplete epidemiological and public health measures (administrative measures of vaccination coverage, incidence estimates, etc.).

Finerenone and new-onset diabetes in heart failure: a prespecified analysis of the FINEARTS-HF trial.

Background: Data on the effect of mineralocorticoid receptor antagonist therapy on HbA levels and new-onset diabetes are conflicting. We aimed to examine the effect of oral finerenone, compared with placebo, on incident diabetes in the Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients with Heart Failure (FINEARTS-HF) trial.

Methods: In this randomised, double-blind, placebo-controlled trial, 6001 participants with heart failure with New York Heart Association functional class II-IV, left ventricular ejection fraction 40% or higher, evidence of structural heart disease, and elevated N-terminal pro-B-type natriuretic peptide levels were randomly assigned to finerenone or placebo, administered orally.

Modeling non-genetic adaptation in tumor cells.

Treatment resistance poses a significant challenge in the care of cancer patients. Hirsch et al. applied computational and genomic approaches, examining gene expression dynamics from a mouse model of melanoma at single-cell resolution to reveal that semi-heritable non-genetic alterations in tumor cell populations confer adaptive resistance to treatment.

Environmental contaminants assessment for frequently harvested migratory waterfowl in the Northeast Atlantic flyway.

Waterfowl serve as indicators of ecosystem health and represent a pathway of contaminant exposure for hunters who consume them. In the northeast Atlantic Flyway, data on baseline contaminant loads in waterfowl are lacking. We assessed five species of commonly harvested (and consumed) waterfowl for mercury, polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans, polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), and per- and polyfluoroalkyl substances (PFAS).

The (in)dependence of single-cell data inferences on model constructs.

Recent developments in single-cell analysis have revolutionized basic research and have garnered the attention of the forensic domain. Though single-cell analysis is not new to forensics, the ways in which these data can be generated and interpreted are. Modern interpretation strategies report likelihood ratios that rely on a model of the world that is a simplification of it.

Opposing roles of p38α-mediated phosphorylation and PRMT1-mediated arginine methylation in driving TDP-43 proteinopathy.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder typically characterized by insoluble inclusions of hyperphosphorylated TDP-43. The mechanisms underlying toxic TDP-43 accumulation are not understood. Persistent activation of p38 mitogen-activated protein kinase (MAPK) is implicated in ALS.

Probing the functional constraints of influenza A virus NEP by deep mutational scanning.

The influenza A virus nuclear export protein (NEP) is a multifunctional protein that is essential for the viral life cycle and has very high sequence conservation. However, since the open reading frame of NEP largely overlaps with that of another influenza viral protein, non-structural protein 1, it is difficult to infer the functional constraints of NEP based on sequence conservation analysis. In addition, the N-terminal of NEP is structurally disordered, which further complicates the understanding of its function.

Open-label, phase Ia study of STING agonist BI 1703880 plus ezabenlimab for patients with advanced solid tumors.

BI 1703880, a novel STimulator of INterferon Genes (STING) agonist, has demonstrated preclinical antitumor activity. As STING activation can upregulate programmed death ligand 1 and human leukocyte antigen in tumor cells, a combination of BI 1703880 and an anti-programmed cell death protein 1-antibody, such as ezabenlimab, may improve efficacy. This first-in-human phase Ia study (NCT05471856) is evaluating BI 1703880 plus ezabenlimab in patients with advanced solid tumors.

Electroconvulsive therapy in the treatment of catatonia in a patient with Budd Chiari syndrome: a case report.

Catatonia may manifest as an independent entity or as a feature of a neuropsychiatric or medical illness. While electroconvulsive therapy (ECT) is the gold standard treatment for catatonia, it is typically administered if the patient's symptoms fail to respond to benzodiazepines. We describe the case of a 22-year-old male with Budd Chiari induced cirrhosis and no prior psychiatric history, who presented with symptoms of psychosis and hepatic encephalopathy, was treated in the ICU for multi-factorial delirium, developed symptoms of catatonia that failed to respond to lorazepam, ultimately requiring ECT with a favorable response.

Olaparib as treatment for platinum-sensitive relapsed ovarian cancer by BRCA mutation and homologous recombination deficiency: Phase 2 LIGHT study final overall survival analysis.

Background: LIGHT (oLaparib In HRD-Grouped Tumor types; NCT02983799) prospectively evaluated olaparib treatment in patients with platinum-sensitive relapsed ovarian cancer (PSROC) assigned to cohorts by known BRCA mutation (BRCAm) and homologous recombination deficiency (HRD) status: germline BRCAm (gBRCAm), somatic BRCAm (sBRCAm), HRD-positive non-BRCAm, and HRD-negative. At the primary analysis, olaparib treatment demonstrated activity across all cohorts, with greatest efficacy in terms of objective response rate and progression-free survival observed in the g/sBRCAm cohorts. The authors report final overall survival (OS).

Coexisting Calcific Aortic Stenosis and Transthyretin Cardiac Amyloidosis: Real-World Evaluation of Clinical Characteristics and Outcomes.

Background: The coexistence of transthyretin cardiac amyloidosis (ATTR-CA) and aortic stenosis (AS) is increasingly recognized, but the clinical consequences are unclear. We aimed to characterize clinical outcomes in AS plus ATTR-CA compared with only AS or ATTR-CA.

Methods And Results: In a retrospective cohort study, patients with AS only, ATTR-CA only, or AS plus ATTR-CA were identified using all-payer claims data (2015-2021).

A Phase 1 Randomized Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Escalating Oral Doses of Dordaviprone and the Effects of Food on the Bioavailability of Dordaviprone in Healthy Adult Subjects.

Dordaviprone (ONC201) is a novel, small molecule imipridone with antitumor effects in glioma patients. This study evaluated the pharmacokinetics and safety of dordaviprone following single escalating doses (Part A), as a capsule content mixed with applesauce or Gatorade (sports drink) [Part B1]), and with or without food [Part B2]. The most common treatment-emergent adverse events pooled across study parts (Parts A, B1, and B2) were headache, dizziness, and headache, respectively; all were mild.

Lessons learned from 5 years of pegvaliase in US clinics: A case series.

Objective: To provide insights and strategies for pegvaliase management in challenging cases with phenylketonuria (PKU) based on the first 5 years of experience with pegvaliase in real-world clinical practice.

Methods: Twelve PKU experts gathered during a one-day, in-person meeting to discuss clinical cases illustrating important lessons from their experiences treating patients with pegvaliase in real-world clinical practice. Challenges with pegvaliase experienced prior to and during treatment and corresponding strategies to overcome them were discussed.

A conceptual model for advanced/metastatic gastric or gastroesophageal junction cancer: a review of qualitative studies and results from patient interviews.

Background: Despite approvals of new first-line immunotherapies for advanced/metastatic gastric cancer/gastroesophageal junction cancer (aGC/GEJC), patients' median survival is around 14 months and their health-related quality of life (HRQoL) is affected by disease-related symptoms and treatment-related side effects. Using a targeted literature review (TLR) and patient interviews, this study identified disease- and treatment-related concepts that are important to patients with aGC/GEJC and their HRQoL.

Methods: A TLR was conducted to identify primary qualitative studies from 2018 to 2021 on patients' experiences with aGC/GEJC.

Resolving tissue complexity by multimodal spatial omics modeling with MISO.

Spatial molecular profiling has provided biomedical researchers valuable opportunities to better understand the relationship between cellular localization and tissue function. Effectively modeling multimodal spatial omics data is crucial for understanding tissue complexity and underlying biology. Furthermore, improvements in spatial resolution have led to the advent of technologies that can generate spatial molecular data with subcellular resolution, requiring the development of computationally efficient methods that can handle the resulting large-scale datasets.

Daratumumab plus lenalidomide/dexamethasone in untreated multiple myeloma: analysis of key subgroups of the MAIA study.

In the MAIA study (median follow-up, 56.2 months), daratumumab plus lenalidomide and dexamethasone (D-Rd) significantly improved progression-free survival (PFS) and overall survival versus lenalidomide and dexamethasone (Rd) alone in transplant-ineligible newly diagnosed multiple myeloma (NDMM). In this post hoc analysis of clinically important subgroups in MAIA (median follow-up, 64.

Ancient DNA reveals reproductive barrier despite shared Avar-period culture.

After a long-distance migration, Avars with Eastern Asian ancestry arrived in Eastern Central Europe in 567 to 568 CE and encountered groups with very different European ancestry. We used ancient genome-wide data of 722 individuals and fine-grained interdisciplinary analysis of large seventh- to eighth-century CE neighbouring cemeteries south of Vienna (Austria) to address the centuries-long impact of this encounter. We found that even 200 years after immigration, the ancestry at one site (Leobersdorf) remained dominantly East Asian-like, whereas the other site (Mödling) shows local, European-like ancestry.

Antibacterial and antioxidant potentials, detection of host origin compounds, and metabolic profiling of endophytic Bacillus spp. isolated from Rauvolfia serpentina (L.) Benth. ex Kurz.

The research highlights the importance of exploring endophytic microbiomes of medicinal plants to uncover their potential for secondary metabolite production and their role in the biosynthesis of host-derived compounds. This study was aimed to isolate leaf endophytic bacteria of Rauvolfia serpentina, investigate their antibacterial, antioxidant potentials and detect host-origin compound reserpine using Reverse Phase High-Performance Liquid Chromatography (RPHPLC). Untargeted analysis via Ultra High-Performance Liquid Chromatography-High-Resolution Mass Spectrometry (UHPLC-HRMS/MS) was conducted for profiling main phytochemicals in the leaves and to explore potential bioactive compounds in bacterial extracts.

Machine learning analysis of cervical balance in early-onset scoliosis post-growing rod surgery: a case-control study.

We aimed to analyze the cervical sagittal alignment change following the growing rod treatment in early-onset scoliosis (EOS) and identify the risk factors of sagittal cervical imbalance after growing-rod surgery of machine learning. EOS patients from our centre between 2007 and 2019 were retrospectively reviewed. Radiographic parameters include the cervical lordosis (CL), T1 slope, C2-C7 sagittal vertical axis (C2-7 SVA), primary curve Cobb angle, thoracic kyphosis (TK), C7-S1 sagittal vertical axis (C7-S1 SVA) and proximal junctional angle (PJA) were evaluated preoperatively, postoperatively and at the final follow-up.

Auditory decision-making deficits after permanent noise-induced hearing loss.

Loud noise exposure is one of the leading causes of permanent hearing loss. Individuals with noise-induced hearing loss (NIHL) suffer from speech comprehension deficits and experience impairments to cognitive functions such as attention and decision-making. Here, we investigate the specific underlying cognitive processes during auditory perceptual decision-making that are impacted by NIHL.

Association between abatacept exposure levels and infection occurrence in patients with rheumatoid arthritis: post hoc analysis of the AVERT-2 study.

Objective: To determine if higher serum exposure during subcutaneous (SC) abatacept treatment was associated with an increased infection risk in adult patients with early rheumatoid arthritis (RA).

Methods: Data from AVERT-2 (Assessing Very Early Rheumatoid arthritis Treatment-2, NCT02504268), a randomized, placebo-controlled study in anticitrullinated protein antibody- positive patients with early RA, were analyzed. A post hoc population pharmacokinetic (PPK) analysis was performed.