Overexpression of PLCG2 and TMEM38A inhibit tumor progression in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma is a prevalent urological malignancy, imposing substantial burdens on both patients and society. In our study, we used bioinformatics methods to select four putative target genes associated with EMT and prognosis and developed a nomogram model which could accurately predicting 5-year patient survival rates. We further analyzed proteome and single-cell data and selected PLCG2 and TMEM38A for the following experiments.

Predictors, patterns, and correlates of moderate-severe psychological distress among New York City College Students during Waves 2-4 of COVID-19.

The COVID-19 pandemic may have exacerbated mental health conditions by introducing and/or modifying stressors, particularly in university populations. We examined longitudinal patterns, time-varying predictors, and contemporaneous correlates of moderate-severe psychological distress (MS-PD) among college students. During 2020-2021, participants completed self-administered questionnaires quarterly (T1 = 562, T2 = 334, T3 = 221, and T4 = 169).

Joint association of objective and subjective aging with premature mortality.

Objective and subjective aging indicators reflect diverse biological and psychosocial processes, yet their combined association with premature mortality remains underexplored. This study aimed to investigate the association between a multidomain framework of aging indicators and premature mortality, addressing gaps in understanding cumulative effects. We included 369,741 UK Biobank participants initially free of cardiovascular disease (CVD) and cancer, followed until December 31, 2022.

Ultra high density imaging arrays in diffuse optical tomography for human brain mapping improve image quality and decoding performance.

Functional magnetic resonance imaging (fMRI) has dramatically advanced non-invasive human brain mapping and decoding. Functional near-infrared spectroscopy (fNIRS) and high-density diffuse optical tomography (HD-DOT) non-invasively measure blood oxygen fluctuations related to brain activity, like fMRI, at the brain surface, using more-lightweight equipment that circumvents ergonomic and logistical limitations of fMRI. HD-DOT grids have smaller inter-optode spacing (~ 13 mm) than sparse fNIRS (~ 30 mm) and therefore provide higher image quality, with spatial resolution ~ 1/2 that of fMRI, when using the several source-detector distances (13-40 mm) afforded by the HD-DOT grid.

Evaluating physician concordance in interpretation of tracheobronchomalacia diagnosis and phenotyping using dynamic expiratory chest computed tomography.

Tracheobronchomalacia (TBM) presents diagnostic challenges due to its nonspecific symptoms and variability in diagnostic methods. This study evaluates physician concordance in TBM diagnosis and phenotyping using chest computed tomography (CT) scans with dynamic expiratory views. We conducted a retrospective cross-sectional study at Mayo Clinic Rochester, analyzing 150 patients with dynamic expiratory CT scans.

Poor fixation stability does not account for motion perception deficits in amblyopia.

People with amblyopia show deficits in global motion perception, especially at slow speeds. These observers are also known to have unstable fixation when viewing stationary fixation targets, relative to healthy controls. It is possible that poor fixation stability during motion viewing interferes with the fidelity of the input to motion-sensitive neurons in visual cortex.

Fluid flow impacts endothelial-monocyte interactions in a model of vascular inflammatory fibrosis.

The aberrant vascular response associated with tendon injury results in circulating immune cell infiltration and a chronic inflammatory feedback loop leading to poor healing outcomes. Studying this dysregulated tendon repair response in human pathophysiology has been historically challenging due to the reliance on animal models. To address this, our group developed the human tendon-on-a-chip (hToC) to model cellular interactions in the injured tendon microenvironment; however, this model lacked the key element of physiological flow in the vascular compartment.

Multidimensional library for the improved identification of per- and polyfluoroalkyl substances (PFAS).

As the occurrence of human diseases and conditions increase, questions continue to arise about their linkages to chemical exposure, especially for per-and polyfluoroalkyl substances (PFAS). Currently, many chemicals of concern have limited experimental information available for their use in analytical assessments. Here, we aim to increase this knowledge by providing the scientific community with multidimensional characteristics for 175 PFAS and their resulting 281 ion types.

Fecal microbiota transplantation to prevent acute graft-versus-host disease: pre-planned interim analysis of donor effect.

Gut microbiota disruptions after allogeneic hematopoietic cell transplantation (alloHCT) are associated with increased risk of acute graft-versus-host disease (aGVHD). We designed a randomized, double-blind placebo-controlled trial to test whether healthy-donor fecal microbiota transplantation (FMT) early after alloHCT reduces the incidence of severe aGVHD. Here, we report the results from the single-arm run-in phase which identified the best of 3 stool donors for the randomized phase.

On the pursuit of reproducibility: the importance of large sample sizes in psychoimmunology.

Peripheral inflammatory markers (PIMs), such as C-reactive protein (CRP) or white blood cell count (WBC), have been associated with depression severity in meta-analyses and large cohort studies. However, in typically-sized psychoimmunology studies (N < 200) that explore associations between PIMs and neurobiological/psychosocial constructs related to depression and studies that examine less-studied PIMs (e.g.

CHD6 has poly(ADP-ribose)- and DNA-binding domains and regulates PARP1/2-trapping inhibitor sensitivity via abasic site repair.

To tolerate oxidative stress, cells enable DNA repair responses often sensitive to poly(ADP-ribose) (PAR) polymerase 1 and 2 (PARP1/2) inhibition-an intervention effective against cancers lacking BRCA1/2. Here, we demonstrate that mutating the CHD6 chromatin remodeler sensitizes cells to PARP1/2 inhibitors in a manner distinct from BRCA1, and that CHD6 recruitment to DNA damage requires cooperation between PAR- and DNA-binding domains essential for nucleosome sliding activity. CHD6 displays direct PAR-binding, interacts with PARP-1 and other PAR-associated proteins, and combined DNA- and PAR-binding loss eliminates CHD6 relocalization to DNA damage.

High-resolution fleezers reveal duplex opening and stepwise assembly by an oligomer of the DEAD-box helicase Ded1p.

DEAD-box RNA-dependent ATPases are ubiquitous in all domains of life where they bind and remodel RNA and RNA-protein complexes. DEAD-box ATPases with helicase activity unwind RNA duplexes by local opening of helical regions without directional movement through the duplexes and some of these enzymes, including Ded1p from Saccharomyces cerevisiae, oligomerize to effectively unwind RNA duplexes. Whether and how DEAD-box helicases coordinate oligomerization and unwinding is not known and it is unclear how many base pairs are actively opened.

Genetic variation in IL-4 activated tissue resident macrophages determines strain-specific synergistic responses to LPS epigenetically.

How macrophages in the tissue environment integrate multiple stimuli depends on the genetic background of the host, but this is still poorly understood. We investigate IL-4 activation of male C57BL/6 and BALB/c strain specific in vivo tissue-resident macrophages (TRMs) from the peritoneal cavity. C57BL/6 TRMs are more transcriptionally responsive to IL-4 stimulation, with induced genes associated with more super enhancers, induced enhancers, and topologically associating domains (TAD) boundaries.

The 40S ribosomal subunit recycling complex modulates mitochondrial dynamics and endoplasmic reticulum - mitochondria tethering at mitochondrial fission/fusion hotspots.

The 40S ribosomal subunit recycling pathway is an integral link in the cellular quality control network, occurring after translational errors have been corrected by the ribosome-associated quality control (RQC) machinery. Despite our understanding of its role, the impact of translation quality control on cellular metabolism remains poorly understood. Here, we reveal a conserved role of the 40S ribosomal subunit recycling (USP10-G3BP1) complex in regulating mitochondrial dynamics and function.

Anthracyclines disaggregate and restore mutant p63 function: a potential therapeutic approach for AEC syndrome.

Ankyloblepharon-Ectodermal Defects-Cleft Lip/Palate (AEC) syndrome is a rare genetic disorder caused by mutations in the TP63 gene, which encodes a transcription factor essential for epidermal gene expression. A key feature of AEC syndrome is chronic skin erosion, for which no effective treatment currently exists. Our previous studies demonstrated that mutations associated with AEC syndrome lead to p63 protein misfolding and aggregation, exerting a dominant-negative effect.

Evaluation of an indirect Na1.7 inhibitor as adjunctive analgesic in burn-related neuropathic pain in a cat.

Burn-related neuropathic pain (BRNP) can arise following burn-induced nerve damage, affects approximately 6% of burned human patients and can result in chronic pain. Although widely studied in humans, data on BRNP or its treatment in animals is lacking. A 4-year-old domestic shorthair cat was presented with an infected, non-healing wound suspected to be a caustic burn.

Ethnicity predicts long-term depressive symptom patterns in older adults with type 2 diabetes.

Objectives: Depression is a chronic disorder that significantly affects functional decline in older adults, especially those with type 2 diabetes (T2D). Ethnic groups may experience different depression risks and severities, yet the effect of ethnicity on depression trajectories and specific dimensions in older adults with T2D remains largely unexamined. We examined the longitudinal associations of ethnicity with depression and its specific dimensions over time in older Ashkenazi and non-Ashkenazi Jews with T2D.

Microbiota and immune dynamics in rheumatoid arthritis: Mechanisms and therapeutic potential.

Rheumatoid arthritis (RA) is a complex autoimmune disease with growing evidence implicating the microbiota as a critical contributor to its pathogenesis. This review explores the multifaceted roles of microbial dysbiosis in RA, emphasizing its impact on immune cell modulation, autoantibody production, gut barrier integrity, and joint inflammation. Animal models reveal how genetic predisposition and environmental factors interact with specific microbial taxa to influence disease susceptibility.

Protocol for a systematic review and individual participant data meta-analysis for risk factors for lung cancer in individuals with lung nodules identified by low-dose CT screening.

Background: Worldwide, lung cancer (LC) is the second most frequent cancer and the leading cause of cancer related mortality. Low-dose CT (LDCT) screening reduced LC mortality by 20-24% in randomised trials of high-risk populations. A significant proportion of those screened have nodules detected that are found to be benign.

Adherence to tuberculosis (TB) treatment in high compared to low TB burden countries: study protocol for a systematic review and meta-analysis with a qualitative meta-synthesis of themes.

Introduction: Non-adherence to tuberculosis (TB) treatment poses a significant challenge to effective TB management globally and is a major contributor to the emergence of multidrug-resistant TB. Although adherence to TB treatment has been widely studied, a comprehensive evaluation of the comparative levels of adherence in high- versus low-TB burden settings remains lacking. The objective of this systematic review and meta-analysis is to assess the levels of adherence to TB treatment in high-TB burden countries compared to low-burden countries.

The Role of Imaging in Pulmonary Vascular Disease: The Clinician's Perspective.

Pulmonary vascular diseases, particularly when accompanied by pulmonary hypertension, are complex disorders often requiring multimodal imaging for diagnosis and monitoring. Echocardiography is the primary screening tool for pulmonary hypertension, while cardiac MR imaging (CMR) is used for more detailed characterization and risk stratification in right ventricular failure. Chest computed tomography (CT) is used to detect vascular anomalies and parenchymal lung diseases.

Role of Cardiovascular MR Imaging and MR Angiography in Patients with Pulmonary Vascular Disease.

Cardiac MR imaging and pulmonary MR angiography (MRA) are important clinical tools for the assessment of pulmonary vascular diseases. There are evolving noncontrast and contrast-enhanced techniques to evaluate pulmonary vasculature. Pulmonary MRA is a feasible imaging alternative to CTA in pulmonary embolism detection.