Analytical Quality Evaluation of the Tox21 Compound Library.

The analytical quality of compounds subjected to high-throughput screening (HTS) impacts accurate interpretation of assay results, with poor quality samples potentially leading to false negatives or positives. The Tox21 "10K" library consists of over 8900 unique compounds, spanning a diverse landscape of environmental and pharmaceutical chemicals, posing opportunities and challenges for analytical quality control (QC) determinations. Tox21 sample plates stored in DMSO at ambient conditions for 0 (T0) and/or 4 months (T4), totaling more than 13K unique sample identifiers (Tox21 IDs), were subjected to various analyses, including liquid and gas chromatography mass spectrometry (LC-MS, GC-MS) and nuclear magnetic resonance (NMR).

Dihydropyrimidine enzyme activity and its effect on chemotherapy toxicity: importance of genetic testing.

Purpose: Patients with partial or complete DPD deficiency have decreased capacity to degrade fluorouracil and are at risk of developing toxicity, which can be even life-threatening.

Case: A 43-year-old man with moderately differentiated rectal adenocarcinoma on capecitabine presented to the emergency department with complaints of nausea, vomiting, diarrhea, weakness, and lower abdominal pain for several days. Laboratory findings include grade 4 neutropenia (ANC 10) and thrombocytopenia (platelets 36,000).

Assessing Program Culture in Virtual Fellowship Interviews: Insights From Pulmonary and Critical Care Fellows.

Background: Virtual interviewing for fellowship training programs has been widely adopted since the COVID-19 pandemic. However, whether fellowship candidates can adequately evaluate training program culture through virtual interviews is unclear.

Objective: Our aim was to explore how pulmonary and critical care fellows ascertained program culture during virtual and in-person fellowship program recruitment interviews, with the overall goal of improving our virtual recruiting interview processes.

Association of endovascular thrombectomy volume and outcomes in acute ischemic stroke: A National Inpatient Sample Study.

Background: Previous studies suggest a positive relationship between higher hospital endovascular thrombectomy (EVT) volume and improved outcomes. We investigated this association using the National Inpatient Sample (NIS) database from 2016 to 2020.

Methods: A cross-sectional analysis of the NIS examined the relationship between hospital EVT volume and outcomes.

Proteomic analysis reveals dysregulation of peripheral blood neutrophils in patients with Multiple Sclerosis.

Introduction: Multiple Sclerosis (MS) is a complex auto-inflammatory disease affecting the brain and spinal cord, which results in axonal de-myelination and symptoms including fatigue, pain, and difficulties with vision and mobility. The involvement of the immune system in the pathology of MS is well established, particularly the adaptive T cell response, and there has been a particular focus on the IL-17-producing subset of Th17 cells and their role in driving disease. However, the importance of innate immune cells has not been so well characterised.

Ex-vivo lung perfusion: National trends and post-transplant outcomes.

Background: Ex-vivo lung perfusion (EVLP) has potential to expand donor lung utilization, evaluate allograft viability, and mitigate ischemia-reperfusion injury. However, trends in EVLP use and recipient outcomes are unknown on a national scale. We examined trends in EVLP use and recipient outcomes in the United States.

Intimate partner violence help-seeking norms: scale reliability and cross-sectional multilevel associations with intimate partner violence among youth in Nairobi, Kenya.

Objectives: Intimate partner violence (IPV) threatens women's health and safety. Support services can mitigate the impact, yet few survivors seek services in part due to social norms that discourage use. Little agreement exists on how to measure norms and attitudes related to IPV help-seeking.

In vivo itaconate tracing reveals degradation pathway and turnover kinetics.

Itaconate is an immunomodulatory metabolite that alters mitochondrial metabolism and immune cell function. This organic acid is endogenously synthesized via tricarboxylic acid (TCA) metabolism downstream of TLR signaling. Itaconate-based treatment strategies are being explored to mitigate numerous inflammatory conditions.

Tibial-based Posterolateral Corner Reconstruction Following Proximal Fibula Resection Restores Knee Stability: A Case Report.

Introduction: Fibular- and tibiofibular-based reconstructions are the gold standard treatment for posterolateral corner (PLC) injuries of the knee. This is the first report describing a wholly tibial-based PLC reconstruction.

Case Report: A 50-year-old female presented with knee instability following proximal fibular resection for a benign tumor, associated with chronic anterior cruciate ligament (ACL) deficiency from a previous injury.

Factors Contributing to Opioid Overprescribing at Surgical Discharge.

Introduction: Opioids remain the gold standard for treating acute pain, whereas overprescribing occurs regularly in the postoperative setting with little clinical guidance. The objective of this study is to examine whether the length of surgery is an independent risk factor for opioid overprescribing at discharge.

Methods: We conducted a retrospective case-control study to determine if there is an association between the length of surgery and overprescribed opioids.

Analyses of the Gene in Triple Negative Breast Cancer: Evidence of Regulation of the Gene and Identification of a Specific Exon Overexpressed in Tumor Cell Lines.

Previous data show that the knockdown of the gene in the MDA-MB-231 cell line leads to the downregulation of gene expression. In addition, and genes are co-expressed and dysregulated in some of the same triple negative breast cancer patient samples. We propose that the co-expression of the two genes is attributed to the MYBL1 transcription factor regulation of the gene.

Percutaneous Thrombovegectomy as an Alternative to Surgery for Tricuspid Valve Endocarditis.

Background: Undergoing an urgent valve surgical procedure to treat patients with tricuspid valve endocarditis carries a high risk of operative morbidity and mortality. Use of a percutaneous vacuum-assisted system to treat tricuspid valve endocarditis is an alternative to surgical procedures.

Methods: This study retrospectively analyzed data from 187 transcatheter vacuum-assisted aspiration procedures performed in 177 patients with tricuspid valve vegetations at 3 different centers between 2017 and April 2022.

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Bile acid synthesis impedes tumor-specific T cell responses during liver cancer.

The metabolic landscape of cancer greatly influences antitumor immunity, yet it remains unclear how organ-specific metabolites in the tumor microenvironment influence immunosurveillance. We found that accumulation of primary conjugated and secondary bile acids (BAs) are metabolic features of human hepatocellular carcinoma and experimental liver cancer models. Inhibiting conjugated BA synthesis in hepatocytes through deletion of the BA-conjugating enzyme bile acid-CoA:amino acid -acyltransferase (BAAT) enhanced tumor-specific T cell responses, reduced tumor growth, and sensitized tumors to anti-programmed cell death protein 1 (anti-PD-1) immunotherapy.

CAGI6 ID panel challenge: assessment of phenotype and variant predictions in 415 children with neurodevelopmental disorders (NDDs).

The Genetics of Neurodevelopmental Disorders Lab in Padua provided a new intellectual disability (ID) Panel challenge for computational methods to predict patient phenotypes and their causal variants in the context of the Critical Assessment of the Genome Interpretation, 6th edition (CAGI6). Eight research teams submitted a total of 30 models to predict phenotypes based on the sequences of 74 genes (VCF format) in 415 pediatric patients affected by Neurodevelopmental Disorders (NDDs). NDDs are clinically and genetically heterogeneous conditions, with onset in infant age.

Predicting purification process fit of monoclonal antibodies using machine learning.

In early-stage development of therapeutic monoclonal antibodies, assessment of the viability and ease of their purification typically requires extensive experimentation. However, the work required for upstream protein expression and downstream purification development often conflicts with timeline pressures and material constraints, limiting the number of molecules and process conditions that can reasonably be assessed. Recently, high-throughput batch-binding screen data along with improved molecular descriptors have enabled development of robust quantitative structure-property relationship (QSPR) models that predict monoclonal antibody chromatographic binding behavior from the amino acid sequence.

The prevalence of HIV pre-exposure prophylaxis (HIV-PrEP) use and HIV-PrEP-to-need ratio in nine Canadian provinces, 2018-2021.

Background: Measuring trends in HIV pre-exposure prophylaxis (HIV-PrEP) uptake is important to inform planning for prevention programs and policies. The HIV-PrEP-to-need ratio (PnR) is a construct used by public health organizations to explore disparities in the provision of HIV-PrEP across geographic areas and demographic categories (e.g.

Hippocampal neuronal activity is aligned with action plans.

Neurons in the hippocampus are correlated with different variables, including space, time, sensory cues, rewards and actions, in which the extent of tuning depends on ongoing task demands. However, it remains uncertain whether such diverse tuning corresponds to distinct functions within the hippocampal network or whether a more generic computation can account for these observations. Here, to disentangle the contribution of externally driven cues versus internal computation, we developed a task in mice in which space, auditory tones, rewards and context were juxtaposed with changing relevance.

Helminth infection induces innate immune priming in plasmacytoid dendritic cells.

Heligmosomoides polygyrus co-infection is reported to have protective antiviral effects against pulmonary viral infections. To investigate a potential underlying mechanism, we infected C57BL/6 mice with H. polygyrus larvae for two weeks.

Immunophenotyping of Synovial Tissue in Adolescents Undergoing ACL Reconstruction: What Is the Role of Synovial Inflammation in Arthrofibrosis?

Background: Loss of motion and arthrofibrosis after anterior cruciate ligament (ACL) reconstruction (ACLR) can be devastating complications for athletes. The cellular and molecular pathogenesis of arthrofibrosis is poorly understood, limiting prevention and treatment options. Synovial inflammation may contribute to post-ACLR arthrofibrosis.

Developing Chemical Signatures for Categories of Household Consumer Products Using Suspect Screening Analysis.

Consumer products are a major source of chemicals that may pose a health risk. It is important to understand what chemicals are in these products to evaluate risk and assess new products for uncommon ingredients. Suspect screening analysis (SSA) using two-dimensional gas chromatography-high-resolution-time-of-flight/mass spectrometry (GCxGC-HR-TOF/MS) was applied to 92 consumer products from 5 categories.

Predicted Potential for Aquatic Exposure Effects of Per- and Polyfluorinated Alkyl Substances (PFAS) in Pennsylvania's Statewide Network of Streams.

Per- and polyfluoroalkyl substances (PFAS) are contaminants that can lead to adverse health effects in aquatic organisms, including reproductive toxicity and developmental abnormalities. To assess the ecological health risk of PFAS in Pennsylvania stream surface water, we conducted a comprehensive analysis that included both measured and predicted estimates. The potential combined exposure effects of 14 individual PFAS to aquatic biota were estimated using the sum of exposure-activity ratios (ΣEARs) in 280 streams.

Exposure to Environmental Chemicals and Infertility Among US Reproductive-Aged Women.

Environmental chemical exposure has been rising over the past few decades but its impact on fertility remains uncertain. We assessed exposures to 23 common chemicals across a range of sociodemographic characteristics and their relationship with self-reported infertility. The analytic sample was non-pregnant women aged 18-49 years without a history of hysterectomy or oophorectomy (n = 2579) from the National Health and Nutrition Examination Survey (2013-2016).