RGS1 Modulates Autophagic and Metabolic Programs and Is a Critical Mediator of Human Regulatory T Cell Function.

Regulatory T cells (Tregs) are critical mediators of immune tolerance and play a diametric role in cancer and autoimmunity. Tumor-infiltrating Tregs are often associated with poor prognosis in solid tumors because their enrichment in the tumor microenvironment contributes to immunosuppression. Conversely, dysregulation in the Treg compartment can disrupt self-tolerance, leading to autoimmunity.

Mpox Cases Among Cisgender Women and Pregnant Persons - United States, May 11-November 7, 2022.

Monkeypox (mpox) cases in the 2022 outbreak have primarily occurred among adult gay, bisexual, and other men who have sex with men (MSM); however, other populations have also been affected (1). To date, data on mpox in cisgender women and pregnant persons have been limited. Understanding transmission in these populations is critical for mpox prevention.

BND-22, a first-in-class humanized ILT2-blocking antibody, promotes antitumor immunity and tumor regression.

Background: Cancer immunotherapy has revolutionized cancer treatment. However, considering the limited success of immunotherapy to only some cancer types and patient cohorts, there is an unmet need for developing new treatments that will result in higher response rates in patients with cancer. Immunoglobulin-like transcript 2 (ILT2), a LILRB family member, is an inhibitory receptor expressed on a variety of immune cells including T cells, natural killer (NK) cells and different myeloid cells.

Quantification of Gut Microbiota Dysbiosis-Related Organic Acids in Human Urine Using LC-MS/MS.

Urine organic acid contains water-soluble metabolites and/or metabolites—derived from sugars, amino acids, lipids, vitamins, and drugs—which can reveal a human’s physiological condition. These urine organic acids—hippuric acid, benzoic acid, phenylacetic acid, phenylpropionic acid, 4-hydroxybenzoic acid, 4-hydroxyphenyl acetic acid, 3-hydroxyphenylpropionic acid, 3,4-dihydroxyphenyl propionic acid, and 3-indoleacetic acid—were the eligible candidates for the dysbiosis of gut microbiota. The aim of this proposal was to develop and to validate a liquid chromatography−tandem mass spectrometry (LC-MS/MS) bioanalysis method for the nine organic acids in human urine.

Evidence of the need for modified well-stirred model in vitro to in vivo extrapolation.

In vitro to in vivo extrapolation (IVIVE), an approach for hepatic clearance (CL) prediction used worldwide, remains controversial due to systematic underprediction. Among the various probable factors, the original assumption of the hepatic mathematical model (i.e.

A substructure-based screening approach to uncover N-nitrosamines in drug substances.

Drug substances are at risk of contamination with N-nitrosamines (NAs), well-known carcinogenic agents, during synthesis processes and/or long-term storage. Therefore, in this study, we developed an efficient data-based screening approach to systemically assess marketed products and investigated its scalability for benefiting both regulatory agencies and pharmaceutical industries. A substructure-based screening method employing DataWarrior, an open-source software, was established to evaluate the risks of NA impurities in drug substances.

Change in unemployment by social vulnerability among United States counties with rapid increases in COVID-19 incidence-July 1-October 31, 2020.

Objective: During the COVID-19 pandemic, the unemployment rate in the United States peaked at 14.8% in April 2020. We examined patterns in unemployment following this peak in counties with rapid increases in COVID-19 incidence.

Evolution of Cryoglobulinemia in Direct-Acting Antiviral-Treated Asian Hepatitis C Patients With Sustained Virological Responses: A 4-Year Prospective Cohort Study.

Background: How cryoglobulinemia evolves after sustained virological response (SVR) following direct-acting antiviral (DAA) treatment in Asian hepatitis C virus (HCV)-infected patients remains elusive.

Methods: A prospective cohort study was conducted in 422 Taiwanese patients (358 completed DAA therapy and 353 experienced SVRs). Serum cryoglobulins were surveyed at baseline and every 3-6 months posttherapy.

Microwave- and Ultrasound-Assisted Extraction of Cucurbitane-Type Triterpenoids from L. Cultivars and Their Antiproliferative Effect on SAS Human Oral Cancer Cells.

Cucurbitane-type triterpenoids are a major class of bioactive compounds present in bitter melon. In the present study, six different cultivars of bitter melon were extracted by using microwave- or ultrasound-assisted techniques to identify the prominent method that can extract the majority of cucurbitane-type triterpenoids. A UHPLC-MS/MS (ultra-high-performance liquid chromatography tandem mass spectrometry) system was used for the identification and quantification of ten cucurbitane-type triterpenoids.

Ethnobotanical Survey on Bitter Tea in Taiwan.

In Taiwan, herbal tea is considered a traditional medicine and has been consumed for hundreds of years. In contrast to regular tea, herbal teas are prepared using plants other than the regular tea plant, Camellia sinensis (L.) Kuntze.

A trispecific antibody targeting HER2 and T cells inhibits breast cancer growth via CD4 cells.

Effective antitumour immunity depends on the orchestration of potent T cell responses against malignancies. Regression of human cancers has been induced by immune checkpoint inhibitors, T cell engagers or chimeric antigen receptor T cell therapies. Although CD8 T cells function as key effectors of these responses, the role of CD4 T cells beyond their helper function has not been defined.

Decoupled Glucose and Lipid Metabolic Recovery after Viral Clearance in Direct-Acting Antiviral-Treated HCV Patients: A 3-Year Prospective Cohort Study.

Background/aim: The recovery pattern of hepatitis C virus (HCV)-associated metabolic alteration after sustained virological response (SVR) following direct-acting antivirals (DAAs) remains elusive.

Methods: A prospective cohort study of chronic HCV-infected (CHC) patients (n = 415) receiving DAAs (n = 365) was conducted. Metabolic profiles were examined in SVR patients (n = 360) every 3-6 months after therapy and compared with those of sex- and age-matched controls (n = 470).

A comparison of machine learning classifiers for pediatric epilepsy using resting-state functional MRI latency data.

Epilepsy affects 1 in 150 children under the age of 10 and is the most common chronic pediatric neurological condition; poor seizure control can irreversibly disrupt normal brain development. The present study compared the ability of different machine learning algorithms trained with resting-state functional MRI (rfMRI) latency data to detect epilepsy. Preoperative rfMRI and anatomical MRI scans were obtained for 63 patients with epilepsy and 259 healthy controls.

Critical role of triglycerides for adiponectin levels in hepatitis C: a joint study of human and HCV core transgenic mice.

Background: Both hepatitis C virus (HCV) infection and adiponectin are critically involved in metabolism. The reversal and associations of altering adiponectin levels after sustained virological responses (SVRs) following direct-acting antivirals (DAA) in HCV-infected patients remained elusive.

Methods: A joint study was conducted in a prospective cohort of 427 HCV-infected patients and a line of HCV core transgenic mice.

Precisely adjusting the hepatic clearance of highly extracted drugs using the modified well-stirred model.

Hepatic clearance has been widely studied for over 50 yr. Many models have been developed using either theoretical or empirical tests to predict drug metabolism. The well-stirred, parallel-tube, and dispersion metabolic models have been extensively discussed.

Use of urinary hippuric acid and o-/p-/m-methyl hippuric acid to evaluate surgical smoke exposure in operating room healthcare personnel.

Toluene and xylene are common components of surgical smoke, whereas hippuric acid (HA) and methylhippuric acid (MHA) are the products of toluene and xylene metabolism in humans, respectively. HA and MHA can be used as indicators to evaluate the exposure hazards of toluene and xylene. In this study, we used liquid chromatography tandem mass spectrometry (LC-MS/MS) to simultaneously analyze the HA, o-/m-/p-MHA, and creatinine contents in the urine of healthcare personnel.

Gallic Acid Ameliorated Impaired Lipid Homeostasis in a Mouse Model of High-Fat Diet-and Streptozotocin-Induced NAFLD and Diabetes through Improvement of -oxidation and Ketogenesis.

Gallic acid (GA) is a simple polyphenol found in food and traditional Chinese medicine. Here, we determined the effects of GA administration in a combined mouse model of high-fat diet (HFD)-induced obesity and low-dose streptozotocin (STZ)-induced hyperglycemia, which mimics the concurrent non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes pathological condition. By combining the results of physiological assessments, pathological examinations, metabolomic studies of blood, urine, liver, and muscle, and measurements of gene expression, we attempted to elucidate the efficacy of GA and the underlying mechanism of action of GA in hyperglycemic and dyslipidemic mice.

Convolutional Neural Networks for Pediatric Refractory Epilepsy Classification Using Resting-State Functional Magnetic Resonance Imaging.

Objective: This study aims to evaluate the performance of convolutional neural networks (CNNs) trained with resting-state functional magnetic resonance imaging (rfMRI) latency data in the classification of patients with pediatric epilepsy from healthy controls.

Methods: Preoperative rfMRI and anatomic magnetic resonance imaging scans were obtained from 63 pediatric patients with refractory epilepsy and 259 pediatric healthy controls. Latency maps of the temporal difference between rfMRI and the global mean signal were calculated using voxel-wise cross-covariance.

Health Center Testing for SARS-CoV-2 During the COVID-19 Pandemic - United States, June 5-October 2, 2020.

Long-standing social inequities and health disparities have resulted in increased risk for coronavirus disease 2019 (COVID-19) infection, severe illness, and death among racial and ethnic minority populations. The Health Resources and Services Administration (HRSA) Health Center Program supports nearly 1,400 health centers that provide comprehensive primary health care* to approximately 30 million patients in 13,000 service sites across the United States. In 2019, 63% of HRSA health center patients who reported race and ethnicity identified as members of racial ethnic minority populations (1).