Multi-omics characterization of improved cognitive functions in Parkinson's disease patients after the combined metabolic activator treatment: a randomized, double-blinded, placebo-controlled phase II trial.

Parkinson's disease is primarily marked by mitochondrial dysfunction and metabolic abnormalities. We recently reported that the combined metabolic activators improved the immunohistochemical parameters and behavioural functions in Parkinson's disease and Alzheimer's disease animal models and the cognitive functions in Alzheimer's disease patients. These metabolic activators serve as the precursors of nicotinamide adenine dinucleotide and glutathione, and they can be used to activate mitochondrial metabolism and eventually treat mitochondrial dysfunction.

End-to-end deep-learning model for the detection of coronary artery stenosis on coronary CT images.

Purpose: We examined whether end-to-end deep-learning models could detect moderate (≥50%) or severe (≥70%) stenosis in the left anterior descending artery (LAD), right coronary artery (RCA) or left circumflex artery (LCX) in iodine contrast-enhanced ECG-gated coronary CT angiography (CCTA) scans.

Methods: From a database of 6293 CCTA scans, we used pre-existing curved multiplanar reformations (CMR) images of the LAD, RCA and LCX arteries to create end-to-end deep-learning models for the detection of moderate or severe stenoses. We preprocessed the images by exploiting domain knowledge and employed a transfer learning approach using EfficientNet, ResNet, DenseNet and Inception-ResNet, with a class-weighted strategy optimised through cross-validation.

Infection in Teen With Acute Myeloid Leukemia Receiving Echinocandin Prophylaxis.

We report a case of a 15-year-old with refractory and relapsed AML and profound prolonged neutropenia who developed a disseminated invasive infection while on echinocandin prophylaxis for invasive fungal disease. Azole antifungal therapies, which are often used as prophylaxis, were initially avoided due to concerns for CYP drug interactions. Treatment with a combination of liposomal amphotericin B, voriconazole, and adjuvant granulocyte transfusions was successful as he awaited neutrophil recovery.

Developing and Evaluating SEE-Diabetes: A Patient-Centered Educational Decision Support System for Diabetes Care.

Objectives: This feasibility study evaluated the effectiveness of Support-Engage-Empower-Diabetes (SEE-Diabetes), a patient-centered educational tool designed to promote shared decision-making of diabetes management in older adults. We aimed to assess SEE-Diabetes's ability to facilitate patient engagement and collaborative goal setting, as measured by the Observational Patient Involvement (OPTION) scale and Shared Decision-Making Questionnaire (SDM-Q-Doc). We hypothesized that these instruments would effectively differentiate between healthcare providers who actively leveraged SEE-Diabetes to guide patient-centric conversations and set goals compared to those who did not.

Targeting CD38 with monoclonal antibodies disrupts key survival pathways in paediatric Burkitt's lymphoma malignant B cells.

Objectives: Paediatric Burkitt's lymphoma (pBL) is the most common childhood non-Hodgkin B-cell lymphoma. Despite the encouraging survival rates for most children, treating cases with relapse/resistance to current therapies remains challenging. CD38 is a transmembrane protein highly expressed in pBL.

Multi-omics analysis reveals the key factors involved in the severity of the Alzheimer's disease.

Alzheimer's disease (AD) is a debilitating neurodegenerative disorder with a global impact, yet its pathogenesis remains poorly understood. While age, metabolic abnormalities, and accumulation of neurotoxic substances are potential risk factors for AD, their effects are confounded by other factors. To address this challenge, we first utilized multi-omics data from 87 well phenotyped AD patients and generated plasma proteomics and metabolomics data, as well as gut and saliva metagenomics data to investigate the molecular-level alterations accounting the host-microbiome interactions.

Quantifying Triglyceride-Rich Lipoprotein Atherogenicity, Associations With Inflammation, and Implications for Risk Assessment Using Non-HDL Cholesterol.

Background: Triglyceride-rich lipoproteins and remnants (TRL/remnants) have a causal, but not yet quantified, relationship with coronary heart disease (CHD): myocardial infarction plus revascularization.

Objectives: The authors sought to estimate TRL/remnant per-particle atherogenicity, investigate causal relationships with inflammation, and determine whether differences in the atherogenicity of TRL/remnants and low-density lipoprotein (LDL) impact the causal association of non-high-density lipoprotein cholesterol (non-HDL-C) with CHD.

Methods: Single nucleotide polymorphisms (SNPs) (N = 1,357) identified by genome-wide association in the UK Biobank were ranked into 10 clusters according to the effect on TRL/remnant-C vs LDL-C.

Complete genome sequence of type strain KR-87: a rare biofilm-producing representative of the genus .

Here, we present a complete genome of KR-87, a biofilm-producing mesophile from the Arizonan Sonoran Desert. The sequence, assembled using Oxford Nanopore Technologies' long-read sequencing platform, predicts a genome size of 4.78 Mbp, with 6 replicons, 4,361 protein-coding genes, and a G+C content of 69.

Examining the relationship between proposed anti-LGBTQ+ legislation and LGBTQ+ college student mental health: findings from the Healthy Minds Study, 2021-2022.

This study aimed to investigate the association between proposed anti-LGBTQ+ legislation and depressive symptoms among LGBTQ+ college students. Participants ( = 72,135) included LGBTQ+ college students ( = 21,466) from over 530 colleges and universities, including technical and community institutions, across the United States who took part in the Healthy Minds Study (HMS). Data on proposed anti-LGBTQ+ legislation introduced in 2021-2022 were collected from all 50 US states, categorized, and analyzed.

Extracellular vesicles transport RNA between cells: Unraveling their dual role in diagnostics and therapeutics.

Modern methods of molecular diagnostics and therapy have revolutionized the field of medicine in recent years by providing more precise and effective tools for detecting and treating diseases. This progress includes a growing exploration of the body's secreted vesicles, known as extracellular vesicles (EVs), for both diagnostic and therapeutic purposes. EVs are a heterogeneous population of lipid bilayer vesicles secreted by almost every cell type studied so far.

Serial Diffusion Tensor Imaging and Rate of Ventricular Blood Clearance in Patients with Intraventricular Hemorrhage.

Background: We developed a noninvasive biomarker to quantify the rate of ventricular blood clearance in patients with intracerebral hemorrhage and extension to the ventricles-intraventricular hemorrhage.

Methods: We performed magnetic resonance imaging in 26 patients at 1, 14, 28, and 42 days of onset and measured their hematoma volume (HV), ventricular blood volume (VBV), and two diffusion metrics: fractional anisotropy (FA), and mean diffusivity (MD). The ipasilesional ventricular cerebral spinal fluid's FA and MD were associated with VBV and stroke severity scores (National Institute of Health Stroke Scale [NIHSS]).

Discovery of Cell-Permeable Allosteric Inhibitors of Liver Pyruvate Kinase: Design and Synthesis of Sulfone-Based Urolithins.

Metabolic dysfunction-associated fatty liver disease (MAFLD) presents a significant global health challenge, characterized by the accumulation of liver fat and impacting a considerable portion of the worldwide population. Despite its widespread occurrence, effective treatments for MAFLD are limited. The liver-specific isoform of pyruvate kinase (PKL) has been identified as a promising target for developing MAFLD therapies.

Aging AdipoR2-deficient mice are hyperactive with enlarged brains excessively rich in saturated fatty acids.

To investigate how the fatty acid composition of brain phospholipids influences brain-specific processes, we leveraged the AdipoR2 (adiponectin receptor 2) knockout mouse model in which the brain is enlarged, and cellular membranes are excessively rich in saturated fatty acids. Lipidomics analysis of brains at 2, 7, and 18 months of age showed that phosphatidylcholines, which make up about two-thirds of all cerebrum membrane lipids, contain a gross excess of saturated fatty acids in AdipoR2 knockout mice, and that this is mostly attributed to an excess palmitic acid (C16:0) at the expense of oleic acid (C18:1), consistent with a defect in fatty acid desaturation and elongation in the mutant. Specifically, there was a ~12% increase in the overall saturated fatty acid content within phosphatidylcholines and a ~30% increase in phosphatidylcholines containing two palmitic acids.

Design and synthesis of novel JNK inhibitors targeting liver pyruvate kinase for the treatment of non-alcoholic fatty liver disease and hepatocellular carcinoma.

Non-alcoholic fatty liver disease (NAFLD) comprises a broad range of liver disease including hepatocellular carcinoma (HCC) with is no FDA-approved drug. Liver pyruvate kinase (PKL) is a major regulator of metabolic flux and ATP generation in liver presenting a potential target for the treatment of NAFLD. Based on our recent finding of JNK-5A's effectiveness in inhibiting PKLR expression through a drug repositioning pipeline, this study aims to improve its efficacy further.

Claims data analysis of provider-to-provider tele-mentoring program impact on opioid prescribing in Missouri.

Objective: The objective of this study was to assess opioid prescribing patterns of primary care providers (PCPs) participating in a virtual tele-mentoring program for patients with chronic pain as compared to nonparticipants.

Design: We utilized Missouri Medicaid claims from 2013 to 2021 to compare opioid prescription dosages and daily supply of opioids prescribed by PCPs. Participants and nonparticipants were matched using propensity score matching.

Combined Metabolic Activators with Different NAD+ Precursors Improve Metabolic Functions in the Animal Models of Neurodegenerative Diseases.

Background: Mitochondrial dysfunction and metabolic abnormalities are acknowledged as significant factors in the onset of neurodegenerative disorders such as Parkinson's disease (PD) and Alzheimer's disease (AD). Our research has demonstrated that the use of combined metabolic activators (CMA) may alleviate metabolic dysfunctions and stimulate mitochondrial metabolism. Therefore, the use of CMA could potentially be an effective therapeutic strategy to slow down or halt the progression of PD and AD.

Adipocyte PI3K links adipostasis with baseline insulin secretion at fasting through an adipoincretin effect.

Insulin-PI3K signaling controls insulin secretion. Understanding this feedback mechanism is crucial for comprehending how insulin functions. However, the role of adipocyte insulin-PI3K signaling in controlling insulin secretion in vivo remains unclear.