Myricetin exposure reduces PC differentiation in vitro in primary human B cells.

Background: The process of B cell activation and plasma cell (PC) formation involves morphological, transcriptional, and metabolic changes in the B cell. Blocking or reducing PC differentiation is one approach to treat autoimmune diseases that are characterized by the presence of pathogenic autoantibodies. Recent studies have suggested the potential of myricetin, a natural flavonoid with anti-inflammatory and antioxidant properties, to block or reduce PC differentiation.

Lymphatic vessel network injury reduces local tumor control despite preservation of the tumor-draining lymph node.

The lymphatic system plays complex, often contradictory, roles in many cancers, including melanoma; these roles include contributions to tumor cell metastasis and immunosuppression in the tumor microenvironment as well as generation of antitumor immunity. Advancing our understanding of lymphatic vessel involvement in regulating tumor growth and immune response may provide new therapeutic targets or treatment plans to enhance the efficacy of existing therapies. We utilized a syngeneic murine melanoma model in which we surgically disrupted the lymphatic vessel network draining from the tumor to the tumor-draining lymph node (TDLN) while leaving the TDLN intact.

Noisy-channel language comprehension in aphasia: A Bayesian mixture modeling approach.

Individuals with "agrammatic" receptive aphasia have long been known to rely on semantic plausibility rather than syntactic cues when interpreting sentences. In contrast to early interpretations of this pattern as indicative of a deficit in syntactic knowledge, a recent proposal views agrammatic comprehension as a case of "noisy-channel" language processing with an increased expectation of noise in the input relative to healthy adults. Here, we investigate the nature of the noise model in aphasia and whether it is adapted to the statistics of the environment.

Readmissions and Mortality After "Before Medically Advised" Hospital Discharges Among Medicare Beneficiaries with Opioid Use Disorder.

Background: "Before medically advised" (BMA) discharges are rising among hospitalized people with opioid use disorder (OUD) and associated with worse outcomes. However, little is known about BMA discharge among the growing share of U.S.

Use of Antihyperglycemic Medications Among US People with Limited English Proficiency.

Background: Language barriers can impact pharmaceutical disease management leading to potential health disparities among limited English proficiency (LEP) people with diabetes mellitus (DM) in the United States (US).

Objective: To assess the use of antihyperglycemic medications and estimate their impact on glycemic control by LEP status.

Design: Cross-sectional design.

Sex-specific transcriptomic profiling reveals key players in bone loss associated with Alzheimer's disease.

Alzheimer's disease (AD), a progressive neurodegenerative disorder, is frequently associated with musculoskeletal complications, including sarcopenia and osteoporosis, which substantially impair patient quality of life. Despite these clinical observations, the molecular mechanisms linking AD to bone loss remain insufficiently explored. In this study, we examined the femoral bone microarchitecture and transcriptomic profiles of APP/PS1 transgenic mouse models of AD to elucidate the disease's impact on bone pathology and identify potential gene candidates associated with bone deterioration.

Nedosiran in pediatric patients with PH1 and relatively preserved kidney function, a phase 2 study (PHYOX8).

Background: Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disorder with dysregulated glyoxylate metabolism in the liver. Oxalate over-production leads to renal stones, progressive kidney damage and renal failure, with potentially life-threatening systemic oxalosis. Nedosiran is a synthetic RNA interference therapy, designed to reduce hepatic lactate dehydrogenase (LDH) to decrease oxalate burden in PH.

Intestinal neutrophil extracellular traps promote gut barrier damage exacerbating endotoxaemia, systemic inflammation and progression of diabetic retinopathy in type 2 diabetes.

Aims/hypothesis: Within the small intestine, neutrophils play an integral role in preventing bacterial infection. Upon interaction with bacteria or bacteria-derived antigens, neutrophils initiate a multi-staged response of which the terminal stage is NETosis, formation of protease-decorated nuclear DNA into extracellular traps. NETosis has a great propensity to elicit ocular damage and has been associated with diabetic retinopathy and diabetic macular oedema (DME) progression.

Structural basis for human NKCC1 inhibition by loop diuretic drugs.

Na-K-Cl cotransporters functions as an anion importers, regulating trans-epithelial chloride secretion, cell volume, and renal salt reabsorption. Loop diuretics, including furosemide, bumetanide, and torsemide, antagonize both NKCC1 and NKCC2, and are first-line medicines for the treatment of edema and hypertension. NKCC1 activation by the molecular crowding sensing WNK kinases is critical if cells are to combat shrinkage during hypertonic stress; however, how phosphorylation accelerates NKCC1 ion transport remains unclear.

Infertility and risk of ovarian cancer in the women's health initiative.

Purpose: There is a consistent relationship with greater ovulation frequency and increased risk of ovarian cancer. However, prior research on infertility, which may be associated with ovulation frequency through multiple mechanisms, and ovarian cancer has yielded conflicting results, possibly due to prior research conflating fertility treatment with infertility and restricting follow-up to premenopausal cases. Our objective was to determine the association between infertility and risk of postmenopausal ovarian cancer, overall and by histotype, in a population that had not received treatment with IVF.

Description of STRIVE-ON Study Protocol: Safety and Tolerability of GTX-104 (Nimodipine Injection for IV Infusion) Compared with Oral Nimodipine in Patients Hospitalized for Aneurysmal Subarachnoid Hemorrhage (aSAH): A Prospective, Randomized, Phase III Trial (STRIVE-ON).

Oral nimodipine is the only drug approved in North America for patients with aneurysmal subarachnoid hemorrhage (aSAH). However, bioavailability is variable and frequently poor, leading to fluctuations in peak plasma concentrations that cause dose-limiting hypotension. Furthermore, administration is problematic in patients who cannot swallow.

Who drives weight stigma? A multinational exploration of clustering characteristics behind weight bias against preconception, pregnant, and postpartum women.

Background: Weight bias is a global health challenge and community members are endorsed as the most common source of weight bias. The nature of weight biases specifically against preconception, pregnant, and postpartum (PPP) women from the perspective of community members is not known, especially in terms of cross-cultural trends. We investigated the magnitude of explicit and implicit weight bias and profiles of characteristics associated with harbouring weight bias.

Mutant p53 regulates a distinct gene set by a mode of genome occupancy that is shared with wild type.

To directly examine the interplay between mutant p53 or Mdm2 and wild type p53 in gene occupancy and expression, an integrated RNA-seq and ChIP-seq analysis was performed in vivo using isogenically matched mouse strains. Response to radiation was used as an endpoint to place findings in a biologically relevant context. Unexpectedly, mutant p53 and Mdm2 only inhibit a subset of wild type p53-mediated gene expression.

Association of oxidative balance score with the risk of all-cause and CVD mortality in younger US adults with diabetes.

Oxidative balance score (OBS) is a composite measures that assess the balance between pro-oxidant and antioxidant factors in an individual's diet and lifestyle, with higher scores indicating greater antioxidant exposure. Despite its potential significance, there is a limited body of research exploring the relationship between OBS and all-cause and cardiovascular disease (CVD) mortality specifically in younger patients with diabetes. We aimed to investigate the possible relationship between OBS and all-cause and CVD mortality in younger patients with diabetes.

Leveraging synthetic data to improve regional sea level predictions.

The rapid increase in sea levels driven by climate change presents serious risks to coastal communities around the globe. Traditional prediction models frequently concentrate on developed regions with extensive tide gauge networks, leaving a significant gap in data and forecasts for developing countries where the tide gauges are sparse. This study presents a novel deep learning approach that combines TimesGAN with ConvLSTM to enhance regional sea level predictions using the more widely available satellite altimetry data.

Argonaute2 modulates megakaryocyte development and sex-specific control of platelet protein expression and reactivity.

Platelets are enriched in miRNAs and harbor Ago2 as the principal RNA silencing Argonaute. However, roles in thrombopoiesis and platelet function remain poorly understood. We generated megakaryocyte/platelet-specific Ago2-deleted (Ago2 KO) mice and assessed proteomic and functional effects.

Large language models improve the identification of emergency department visits for symptomatic kidney stones.

Recent advancements of large language models (LLMs) like generative pre-trained transformer 4 (GPT-4) have generated significant interest among the scientific community. Yet, the potential of these models to be utilized in clinical settings remains largely unexplored. In this study, we investigated the abilities of multiple LLMs and traditional machine learning models to analyze emergency department (ED) reports and determine if the corresponding visits were due to symptomatic kidney stones.

Association between ethylene oxide exposure and cognitive function in older adults from NHANES data.

Ethylene Oxide (EO), a volatile organic compound, has garnered considerable attention for its potential impact on human health. Yet, the ramifications of EO exposure on the cognitive functionality of the elderly remain unclear. The aim of this study is to determine whether EO exposure in the elderly correlates with cognitive function.

SARS-CoV-2 S-protein expression drives syncytia formation in endothelial cells.

SARS-CoV-2 is a viral infection, best studied in the context of epithelial cell infection. Epithelial cells, when infected with SARS-CoV-2 express the viral S-protein, which causes host cells to fuse together into large multi-nucleated cells known as syncytia. Because SARS-CoV-2 infections also frequently present with cardiovascular phenotypes, we sought to understand if S-protein expression would also result in syncytia formation in endothelial cells.

Deepening water scarcity in breadbasket nations.

Water is crucial for meeting sustainability targets, but its unsustainable use threatens human wellbeing and the environment. Past assessments of water scarcity (i.e.

Greater residential greenness is associated with reduced epigenetic aging in adults.

Potential pathways linking urban green spaces to improved health include relaxation, stress alleviation, and improved immune system functioning. Epigenetic age acceleration (EAA) is a composite biomarker of biological aging based on DNA methylation measurements; it is predictive of morbidity and mortality. This cross-sectional study of 116 adult residents of a metropolitan area in central North Carolina investigated associations between exposure to residential green spaces and EAA using four previously developed epigenetic age formulas.

Polygenic burden of short tandem repeat expansions promotes risk for Alzheimer's disease.

Studies of the genetics of Alzheimer's disease (AD) have largely focused on single nucleotide variants and short insertions/deletions. However, most of the disease heritability has yet to be uncovered, suggesting that there is substantial genetic risk conferred by other forms of genetic variation. There are over one million short tandem repeats (STRs) in the genome, and their link to AD risk has not been assessed.

Morphological and functional decline of the SNc in a model of progressive parkinsonism.

The motor symptoms of Parkinson's Disease are attributed to the degeneration of dopamine neurons in the substantia nigra pars compacta (SNc). Previous work in the MCI-Park mouse model has suggested that the loss of somatodendritic dopamine transmission predicts the development of motor deficits. In the current study, brain slices from MCI-Park mice were used to investigate dopamine signaling in the SNc prior to and through the onset of movement deficits.

Plant interactions associated with a directional shift in the richness range size relationship during the Glacial-Holocene transition in the Arctic.

A nearly ubiquitous negative relationship between taxonomic richness and mean range-size (average area of taxa) is observed across space. However, the complexity of the mechanism limits its applicability for conservation or range prediction. We explore whether the relationship holds over time, and whether plant speciation, environmental heterogeneity, or plant interactions are major factors of the relationship within northeast Siberia and Alaska.

One state's journey with a reflective supervision professional development series: Development, implementation, and adaptation.

Reflective supervision (RS) has been viewed as best practice and is therefore incorporated-and often mandated-as a key feature of many relationship-based infant and early childhood serving programs. To promote the implementation of high-quality RS for infant and early childhood professionals, it is critical that a focus is placed on how infant and early childhood professionals are trained to build RS capacities. To this end, we describe Rhode Island, United States's journey developing, implementing, and iteratively adapting an RS professional development series.