Sparse Bernoulli mixture modeling with negative-unlabeled data: an approach to identify and characterize long COVID.

SARS-CoV-2-infected individuals have reported a diverse collection of persistent and often debilitating symptoms commonly referred to as long COVID or post-acute sequelae of SARS-CoV-2 (PASC). Identifying PASC and its subphenotypes is challenging because available data are "negative-unlabeled" as uninfected individuals must be PASC negative, but those with prior infection have unknown PASC status. Moreover, feature selection among many potentially informative characteristics can facilitate reaching a concise and easily interpretable PASC definition.

IL-15 complex enhances agonistic anti-CD40 + anti-PDL1 by correcting the T-bet to Tox ratio in CD8+ T cells infiltrating pancreatic ductal adenocarcinoma.

Agonistic anti-CD40 with anti-PD-1 can elicit objective responses in a small number of patients with pancreatic ductal adenocarcinoma (PDA). Better understanding of their individual effects on the PDA tumor microenvironment will help inform new strategies to further improve outcomes. Herein, we map tumor-specific CD8+ T-cell differentiation following agonistic anti-CD40 and/or anti-PDL1 in PDA.

Corneal Keratocytes, Fibroblasts, and Myofibroblasts Exhibit Distinct Transcriptional Profiles In Vitro.

Purpose: After stromal injury to the cornea, the release of growth factors and pro-inflammatory cytokines promotes the activation of quiescent keratocytes into a migratory fibroblast and/or fibrotic myofibroblast phenotype. Persistence of the myofibroblast phenotype can lead to corneal fibrosis and scarring, which are leading causes of blindness worldwide. This study aims to establish comprehensive transcriptional profiles for cultured corneal keratocytes, fibroblasts, and myofibroblasts to gain insights into the mechanisms through which these phenotypic changes occur.

A Novel Model for Cornea Power Shift in Eyes Wearing Orthokeratology Lenses With Different Back Optic Zone Diameters for Myopia Control.

Purpose: The purpose of this study was to quantify the corneal power changes after wearing orthokeratology lenses of different back optic zone diameters (BOZDs) and to propose a novel 4-parameter model capable of revealing the associations between each parameter and axial length growth (ALG).

Methods: A prospective self-controlled study was conducted between June 2022 and December 2023. One eye in each subject (N = 33) was randomly assigned to wear a lens with a BOZD of either 5 mm (5 oz) or 6 mm (6 oz).

Estimation and Hypothesis Testing of Strain-Specific Vaccine Efficacy With Missing Strain Types With Application to a COVID-19 Vaccine Trial.

Based on data from a randomized, controlled vaccine efficacy trial, this article develops statistical methods for assessing vaccine efficacy (VE) to prevent COVID-19 infections by a discrete set of genetic strains of SARS-CoV-2. Strain-specific VE adjusting for possibly time-varying covariates is estimated using augmented inverse probability weighting to address missing viral genotypes under a competing risks model that allows separate baseline hazards for different risk groups. Hypothesis tests are developed to assess whether the vaccine provides at least a specified level of VE against some viral genotypes and whether VE varies across genotypes.

Airborne particulate matter exposure in male sugarcane workers at risk for chronic kidney disease in Guatemala.

Background: There is an international epidemic of chronic kidney disease of unknown cause (CKDu) in agricultural working populations. Particulate air pollution is a likely contributing factor in populations at risk for CKDu, but there is little personal breathing zone data for these workers.

Methods: We collected 1 to 3 personal breathing zone particulate matter <5 microns (PM5) gravimetric measurements in 143 male sugarcane harvesters over 2 seasons and concurrent ambient samples using personal sampling pumps and cyclone inlets as a sampling train.

Characterization of Three Resistance-Breaking Isolates of Sugarcane Mosaic Virus from Rwanda and Implications for Maize Lethal Necrosis.

Maize lethal necrosis (MLN) is a devastating disease of maize caused by synergy between two viruses: maize chlorotic mottle virus (MCMV) and a potyvirus, often sugarcane mosaic virus (SCMV). Throughout the 2010s, severe MLN outbreaks occurred in East Africa including Kenya, Rwanda, and Ethiopia. Previous studies have shown extensive sequence diversity among SCMV isolates collected from this region.

Pressure-Induced Phase Transitions in Bismutotantalite (BiTaO): Insights from Single-Crystal Diffraction and Raman Spectroscopy.

In situ high-pressure single-crystal X-ray diffraction and Raman spectroscopy analyses were performed on a natural bismutotantalite with an α-BiTaO structure. The results indicate that α-BiTaO transforms into an orthorhombic phase (HP γ-BiTaO), likely through an intermediate orthorhombic phase (HP β-BiTaO). The transition pressures are 11.

Novel Non-Destructive Detection Methods for in Northern Red Oak and Chestnut.

Oak wilt, caused by the fungal pathogen , spreads via root grafts and insect vectors, threating oaks ( spp.) and chestnuts ( spp.) in the United States.

KLF family members control expression of genes required for tissue macrophage identities.

Tissue-resident macrophages adopt distinct gene expression profiles and exhibit functional specialization based on their tissue of residence. Recent studies have begun to define the signals and transcription factors that induce these identities. Here we describe an unexpected and specific role for the broadly expressed transcription factor Krüppel-like factor 2 (KLF2) in the development of embryonically derived large cavity macrophages (LCMs) in the serous cavities.

Iridium Nanocrystals Enriched with Defects and Atomic Steps to Enhance Oxygen Evolution Reaction Performance.

The presence of defects can significantly improve catalytic activity and stability, as they influence the binding of the reactants, intermediates, and products to the catalyst. Controlling defects in the structures of nanocrystal catalysts is synthetically challenging. In this study, we demonstrate the ability to control the growth of Ir nanocrystals, enabling the tuning of both structural and surface defects.

Biological Regulation Studied and with Modified Proteins.

ConspectusProteins and peptides occur ubiquitously in organisms and play key functional roles, as structural elements and catalysts. Their major natural source is ribosomal synthesis, which produces polypeptides from 20 amino acid building blocks. Peptides containing noncanonical amino acids have long been prepared by chemical synthesis, which has provided a wealth of physiologically active compounds.

Leukemogenic Kras mutation reprograms multipotent progenitors to facilitate its spread through the hematopoietic system.

Leukemia-driving mutations are thought to arise in hematopoietic stem cells (HSC), yet the natural history of their spread is poorly understood. We genetically induced mutations within endogenous murine HSC and traced them in unmanipulated animals. In contrast to mutations associated with clonal hematopoiesis (such as Tet2 deletion), the leukemogenic KrasG12D mutation dramatically accelerated HSC contribution to all hematopoietic lineages.

Unraveling the impact of congenital deafness on individual brain organization.

Research on brain plasticity, particularly in the context of deafness, consistently emphasizes the reorganization of the auditory cortex. But to what extent do all individuals with deafness show the same level of reorganization? To address this question, we examined the individual differences in functional connectivity (FC) from the deprived auditory cortex. Our findings demonstrate remarkable differentiation between individuals deriving from the absence of shared auditory experiences, resulting in heightened FC variability among deaf individuals, compared to more consistent FC in the hearing group.

Update on Cancer Screening Recommendations for Individuals with Li-Fraumeni Syndrome.

Li-Fraumeni syndrome (LFS) is an autosomal dominant cancer predisposition condition characterized by a high lifetime risk for a wide spectrum of malignancies associated with germline pathogenic/likely pathogenic (P/LP) variants in the TP53 tumor suppressor gene. Secondary malignant neoplasms are particularly common. Early cancer detection through surveillance enables early intervention and leads to improved clinical outcomes with reduced tumor-related mortality and treatment-related morbidity.

The Legalome: Microbiology, Omics and Criminal Justice.

Advances in neuromicrobiology and related omics technologies have reinforced the idea that unseen microbes play critical roles in human cognition and behaviour. Included in this research is evidence indicating that gut microbes, through direct and indirect pathways, can influence aggression, anger, irritability and antisocial behaviour. Moreover, gut microbes can manufacture chemicals that are known to compromise cognition.

Volumetric, Microfluidic Plasmonic RT-PCR.

Decentralized molecular detection of pathogens remains an important goal for public health. Although polymerase chain reaction (PCR) remains the gold-standard molecular detection method, thermocycling using Peltier heaters presents challenges in decentralized settings. Recent work has demonstrated plasmonic PCR, where nanomaterials on a surface or nanoparticles in solution heat upon stimulation by light, as a promising method for rapid thermocycling.

Macroscopically Self-Aligned and Chiralized Carbon Nanotubes: From Filtration to Innovation.

Because of their natural 1D structure combined with intricate chiral variations, carbon nanotubes (CNTs) exhibit various exceptional physical properties, such as ultrahigh thermal conductivity and diameter-dependent electrical behavior, ranging from semiconducting to metallic. While CNTs excel individually at the nanoscale, their 1D and chiral nature can be lost on a macroscopic scale when they are randomly assembled. Therefore, the alignment and organization of CNTs in macroscopic structures is crucial for harnessing their full potential.

Antitumor efficacy of intermittent low-dose erlotinib plus sulindac via MHC upregulation and remodeling of the immune cell niche.

A previously reported clinical trial in familial adenomatous polyposis (FAP) patients treated with erlotinib plus sulindac (ERL + SUL) highlighted immune response/interferon-γ signaling as a key pathway. In this study, we combine intermittent low-dose ERL ± SUL treatment in the polyposis in rat colon (Pirc) model with mechanistic studies on tumor-associated immune modulation. At clinically relevant doses, short-term (16 weeks) and long-term (46 weeks) ERL ± SUL administration results in near-complete tumor suppression in Pirc colon and duodenum (p < 0.

Deep Learning Estimation of Small Airways Disease from Inspiratory Chest CT: Clinical Validation, Repeatability, and Associations with Adverse Clinical Outcomes in COPD.

Rationale: Quantifying functional small airways disease (fSAD) requires additional expiratory computed tomography (CT) scan, limiting clinical applicability. Artificial intelligence (AI) could enable fSAD quantification from chest CT scan at total lung capacity (TLC) alone (fSAD).

Objectives: To evaluate an AI model for estimating fSAD, compare it with dual-volume parametric response mapping fSAD (fSAD), and assess its clinical associations and repeatability in chronic obstructive pulmonary disease (COPD).

Preserving the Biologically Coherent Generic Concept of , 'Plant Destroyer'.

is a long-established, well known and globally important genus of plant pathogens. Phylogenetic evidence has shown that the biologically distinct, obligate biotrophic downy mildews evolved from at least twice. Since, cladistically, this renders 'paraphyletic', it has been proposed that evolutionary clades be split into multiple genera (Runge et al.

Diagnosis and Treatment of Gestational Diabetes Mellitus: A National Survey of Physician Practices.

We aimed to identify changes in United States practice patterns in gestational diabetes mellitus (GDM) diagnosis and treatment following publication of the 2008 Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study that supported transition toward a 2-hour oral glucose tolerance test. A total of 1,030 U.S.

Tryptophan and Its Metabolite Serotonin Impact Metabolic and Mental Disorders via the Brain-Gut-Microbiome Axis: A Focus on Sex Differences.

The crisis of metabolic and mental disorders continues to escalate worldwide. A growing body of research highlights the influence of tryptophan and its metabolites, such as serotonin, beyond their traditional roles in neural signaling. Serotonin acts as a key neurotransmitter within the brain-gut-microbiome axis, a critical bidirectional communication network affecting both metabolism and behavior.

Metaboloepigenetics: Role in the Regulation of Flow-Mediated Endothelial (Dys)Function and Atherosclerosis.

Endothelial dysfunction is the main initiating factor in atherosclerosis. Through mechanotransduction, shear stress regulates endothelial cell function in both homeostatic and diseased states. Accumulating evidence reveals that epigenetic changes play critical roles in the etiology of cardiovascular diseases, including atherosclerosis.