Diffuseness of coronary artery disease impacts on immediate hemodynamic and predicted clinical outcomes.

Diffuse coronary artery disease (CAD) impacts the immediate hemodynamic and clinical outcomes of percutaneous coronary intervention (PCI). We evaluated whether the diffuse pattern of CAD derived from angiographic Quantitative flow ratio (QFR) impacts the immediate hemodynamic outcome post-PCI and the medium term predicted vessel-oriented composite endpoint (VOCE). Paired pre-procedure QFRs were assessed in 503 patients and 1022 vessels in the Multivessel TALENT (MVT) trial.

Disruption of BCAA degradation is a critical characteristic of diabetic cardiomyopathy revealed by integrated transcriptome and metabolome analysis.

In this study, we integrated transcriptomic and metabolomic analyses to achieve a comprehensive understanding of the underlying mechanisms of diabetic cardiomyopathy (DCM) in a diabetic rat model. Functional and molecular characterizations revealed significant cardiac injury, dysfunction, and ventricular remodeling in DCM. A thorough analysis of global changes in genes and metabolites showed that amino acid metabolism, especially the breakdown of branched-chain amino acids (BCAAs) such as valine, leucine, and isoleucine, is highly dysregulated.

Cognitive and Alzheimer's disease biomarker effects of oral nicotinamide riboside (NR) supplementation in older adults with subjective cognitive decline and mild cognitive impairment.

Introduction: Age-associated depletion in nicotinamide adenine dinucleotide (NAD+) concentrations has been implicated in metabolic, cardiovascular, and neurodegenerative disorders. Supplementation with NAD+ precursors, such as nicotinamide riboside (NR), offers a potential therapeutic avenue against neurodegenerative pathologies in aging, Alzheimer's disease, and related dementias. A crossover, double-blind, randomized placebo (PBO) controlled trial was conducted to test the safety and efficacy of 8 weeks' active treatment with NR (1 g/day) on cognition and plasma AD biomarkers in older adults with subjective cognitive decline and mild cognitive impairment.

CD137 agonism enhances anti-PD1 induced activation of expanded CD8 T cell clones in a neoadjuvant pancreatic cancer clinical trial.

Successful pancreatic ductal adenocarcinoma (PDAC) immunotherapy requires therapeutic combinations that induce quality T cells. Tumor microenvironment (TME) analysis following therapeutic interventions can identify response mechanisms, informing design of effective combinations. We provide a reference single-cell dataset from tumor-infiltrating leukocytes (TILs) from a human neoadjuvant clinical trial comparing the granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting allogeneic PDAC vaccine GVAX alone, in combination with anti-PD1 or with both anti-PD1 and CD137 agonist.

Enabling next-generation engineered TCR-T therapies based on high-throughput TCR discovery from diagnostic tumor biopsies.

Adoptive cell therapy with tumor-infiltrating lymphocytes (TIL) can mediate tumor regression, including complete and durable responses, in a range of solid cancers, most notably in melanoma. However, its wider application and efficacy has been restricted by the limited accessibility, proliferative capacity and effector function of tumor-specific TIL. Here, we develop a platform for the efficient identification of tumor-specific TCR genes from diagnostic tumor biopsies, including core-needle biopsies frozen in a non-viable format, to enable engineered T cell therapy.

Association of Pre- and Postinjury Mental Health With Long-term Clinical and Financial Outcomes.

Background: As increased attention is placed on optimizing long-term outcomes of trauma patients by addressing mental health, little is known regarding the interplay of pre- and postinjury mental health on long-term financial and functional outcomes.

Methods: Patients from 19 Level 1 and 2 trauma centers took part in serial surveys 1 to 24 months postdischarge. Preinjury mental health diagnoses were identified using trauma registry data and postinjury mental health symptoms from survey data.

Comparison of optimization algorithms for automated method development of gradient profiles.

Optimization algorithms play an important role in method development workflows for gradient elution liquid chromatography. Their effectiveness has not been evaluated for chromatographic method development using standardized comparisons across factors such as sample complexity, chromatographic response functions (CRFs), gradient complexity, and application type. This study compares six optimization algorithms - Bayesian optimization (BO), differential evolution (DE), a genetic algorithm (GA), covariance-matrix adaptation evolution strategy (CMA-ES), random search, and grid search - for the development of gradient elution LC methods.

Efficacy and Safety of a Mixture of Microencapsulated Sodium Butyrate, Probiotics, and Short Chain Fructooligosaccharides in Patients with Irritable Bowel Syndrome-A Randomized, Double-Blind, Placebo-Controlled Study.

Biotics are increasingly being used in the treatment of irritable bowel syndrome (IBS). This study aimed to assess the efficacy and safety of a mixture of microencapsulated sodium butyrate, probiotics ( DSM 26357, DSM 32418, DSM 32946, DSM 32403, and DSM 32269), and short-chain fructooligosaccharides (scFOSs) in IBS patients. This was a randomized, double-blind, placebo-controlled trial involving 120 adult participants with IBS.

Peptide-Purified Anti-N-methyl-D-aspartate Receptor (NMDAR) Autoantibodies Have Inhibitory Effect on Long-Term Synaptic Plasticity.

Recent studies, typically using patient cerebrospinal fluid (CSF), have suggested that different autoantibodies (Aabs) acting on their respective receptors, may underlie neuropsychiatric disorders. The GluN1 (NR1) subunit of the N-methyl-D-aspartate receptor (NMDAR) has been identified as a target of anti-NMDAR Aabs in a number of central nervous system (CNS) diseases, including encephalitis and autoimmune epilepsy. However, the role or the nature of Aabs responsible for effects on neuronal excitability and synaptic plasticity is yet to be established fully.

P2 Receptor Antagonists Rescue Defective Heme Content in an In Vitro SLC25A38-Associated Congenital Sideroblastic Anemia Cell Model.

Mutations in the SLC25A38 gene are responsible for the second most common form of congenital sideroblastic anemia (CSA), a severe condition for which no effective treatment exists. We developed and characterized a K562 erythroleukemia cell line with markedly reduced expression of the SLC25A38 protein (A38-low cells). This model successfully recapitulated the main features of CSA, including reduced heme content and mitochondrial respiration, increase in mitochondrial iron, ROS levels and sensitivity to oxidative stress.

High-Resolution Free-Breathing Chemical-Shift-Encoded MRI for Characterizing Lymph Nodes in the Upper Abdomen.

Objectives: Accurate lymph node (LN) staging is crucial for managing upper abdominal cancers. Ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging effectively distinguishes healthy and metastatic LNs through fat/water and -weighted imaging. However, respiratory motion artifacts complicate detection of abdominal LNs.

Segmentation aware probabilistic phenotyping of single-cell spatial protein expression data.

Spatial protein expression technologies can map cellular content and organization by simultaneously quantifying the expression of >40 proteins at subcellular resolution within intact tissue sections and cell lines. However, necessary image segmentation to single cells is challenging and error prone, easily confounding the interpretation of cellular phenotypes and cell clusters. To address these limitations, we present STARLING, a probabilistic machine learning model designed to quantify cell populations from spatial protein expression data while accounting for segmentation errors.

National Institute of Neurological Disorders and Stroke Clinical Trials Methodology Course: Summary and Accomplishments 2014-2023.

The Clinical Trials Methodology Course (CTMC), given from 2014 to 2023, was conducted to educate early-career clinical investigators from various backgrounds in neurosciences in the design of clinical trials and to provide mentorship to enhance academic careers and retention plus improve research productivity and the likelihood of successful grant applications. This summary describes the rationale, history, structure, and trainee outcomes of the CTMC. The course used small groups, consisting of 1-2 clinical faculty advisor(s), 1 faculty biostatistician, and 2-4 trainees who met remotely approximately weekly over 12 weeks.

Recording practices of body mass index, overweight and obesity by Dutch general practitioners: an observational study.

Background: Routine body mass index (BMI) recording in electronic health records (EHR) could support general practitioners (GPs) in managing patients with obesity. This study aimed to evaluate recording practices of BMI, overweight, and obesity in adults including subgroup analysis of age, sex, and comorbidities in primary care in the Netherlands.

Methods: An observational study of individuals aged ≥ 18 years and registered between 2007 and 2023, using routine healthcare data from the Extramural LUMC Academic Network (ELAN) in the Netherlands.

Retinal Müller Cell-Released Exosomal MiR-92a-3p Delivers Interleukin-17A Signal by Targeting Notch-1 to Promote Diabetic Retinopathy.

Purpose: Inflammatory processes have been involved in diabetic retinopathy (DR). Interleukin (IL)-17A, a pro-inflammatory cytokine, is associated with DR occurrence and development. However, mechanisms underlying the IL-17A impact on DR need further investigations.

Nano-Armed Limosilactobacillus reuteri for Enhanced Photo-Immunotherapy and Microbiota Tryptophan Metabolism against Colorectal Cancer.

Despite being a groundbreaking approach to treating colorectal cancer (CRC), the efficacy of immunotherapy is significantly compromised by the immunosuppressive tumor microenvironment and dysbiotic intestinal microbiota. Here, leveraging the superior carrying capacity and innate immunity-stimulating property of living bacteria, a nanomedicine-engineered bacterium, LR-S-CD/CpG@LNP, with optical responsiveness, immune-stimulating activity, and the ability to regulate microbiota metabolome is developed. Immunoadjuvant (CpG) and carbon dot (CD) co-loaded plant lipid nanoparticles (CD/CpG@LNPs) are constructed and conjugated to the surface of Limosilactobacillus reuteri (LR) via reactive oxygen species (ROS)-responsive linkers.

Design of an equilibrative nucleoside transporter subtype 1 inhibitor for pain relief.

The current opioid crisis urgently calls for developing non-addictive pain medications. Progress has been slow, highlighting the need to uncover targets with unique mechanisms of action. Extracellular adenosine alleviates pain by activating the adenosine A1 receptor (A1R).

Towards designing improved cancer immunotherapy targets with a peptide-MHC-I presentation model, HLApollo.

Based on the success of cancer immunotherapy, personalized cancer vaccines have emerged as a leading oncology treatment. Antigen presentation on MHC class I (MHC-I) is crucial for the adaptive immune response to cancer cells, necessitating highly predictive computational methods to model this phenomenon. Here, we introduce HLApollo, a transformer-based model for peptide-MHC-I (pMHC-I) presentation prediction, leveraging the language of peptides, MHC, and source proteins.

A phase I, randomized, placebo-controlled trial to evaluate the pharmacokinetics, safety, and tolerability of nirsevimab in healthy Chinese adults.

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection (LRTI) in infants worldwide. Nirsevimab, an extended half-life monoclonal antibody against RSV, is approved in China for the prevention of RSV lower respiratory tract disease in infants; however, global nirsevimab trials did not enroll Chinese infants. To inform the investigation of nirsevimab for the prevention of RSV LRTI in Chinese infants, this Phase I, randomized, placebo-controlled trial evaluated the pharmacokinetics (PK) and safety of nirsevimab in healthy Chinese adults.

Coupling of response biomarkers between tumor and peripheral blood in patients undergoing chemoimmunotherapy.

Platinum-based chemotherapy in combination with anti-PD-L1 antibodies has shown promising results in mesothelioma. However, the immunological mechanisms underlying its efficacy are not well understood and there are no predictive biomarkers to guide treatment decisions. Here, we combine time course RNA sequencing (RNA-seq) of peripheral blood mononuclear cells with pre-treatment tumor transcriptome data from the single-arm, phase 2 DREAM trial (N = 54).

Challenges and opportunities of acquiring cortical recordings for chronic adaptive deep brain stimulation.

Deep brain stimulation (DBS), a proven treatment for movement disorders, also holds promise for the treatment of psychiatric and cognitive conditions. However, for DBS to be clinically effective, it may require DBS technology that can alter or trigger stimulation in response to changes in biomarkers sensed from the patient's brain. A growing body of evidence suggests that such adaptive DBS is feasible, it might achieve clinical effects that are not possible with standard continuous DBS and that some of the best biomarkers are signals from the cerebral cortex.

ROS scavenging and corneal epithelial wound healing by a self-crosslinked tissue-adhesive hydrogel based-on dual-functionalized hyaluronic acid.

Reactive oxygen species (ROS) scavenging is a viable approach to promote corneal epithelium wound healing. This study created a single-component hydrogel (HA Gel) with a novel dual-functionalized hyaluronic acid derivative (HA-GA-PBA) containing gallol and phenylboronic acid (PBA) moieties. Both of these moieties were dual-functional.

Quantification of high molecular weight organic carbon concentrations with LC-OCD and PHMOC for biological stability investigation of drinking water produced from surface water.

The presence of aquatic biopolymeric organic carbon of high (> 10 - 20 kDa) molecular weight (high-MW OC) in drinking water produced from surface water affects its biological stability which may cause regrowth in disinfectant-free distribution. This study compares two analytical methods for determining the concentration of aquatic high-MW OC, namely LC-OCD (liquid chromatography - organic carbon detection) and PHMOC (particulate and colloidal high-molecular weight OC). LC-OCD entails prefiltration of the water sample, chromatographical separation of the relevant biopolymer (BP) OC-fraction, and in-line OC detection.

Combined Anterior Cruciate Ligament and Anterolateral Ligament Reconstruction Shows Superior Graft Remodeling, Maturation, and Stability Compared With Isolated Anterior Cruciate Ligament Reconstruction.

Purpose: To compare graft remodeling, as measured by magnetic resonance imaging (MRI), and clinical outcomes between patients who underwent isolated anterior cruciate ligament reconstruction (ACLR) versus combined anterior cruciate ligament and anterolateral ligament reconstruction (ACLR + ALLR).

Methods: A retrospective review was conducted on patients who underwent primary ACLR with quadruple hamstring grafts between January 2019 and March 2022, with a minimum follow-up period of 2 years. Patients were categorized into 2 groups on the basis of the addition of ALLR with tibialis anterior allografts: an isolated ACLR group and an ACLR + ALLR group.