Biochemical, structural, and cellular characterization of S-but-3-yn-2-ylglycine as a mechanism-based covalent inactivator of the flavoenzyme proline dehydrogenase.

The mitochondrial flavoenzymes proline dehydrogenase (PRODH) and hydroxyproline dehydrogenase (PRODH2) catalyze the first steps of proline and hydroxyproline catabolism, respectively. The enzymes are targets for chemical probe development because of their roles in cancer cell metabolism (PRODH) and primary hyperoxaluria (PRODH2). Mechanism-based inactivators of PRODH target the FAD by covalently modifying the N5 atom, with N-propargylglycine (NPPG) being the current best-in-class of this type of probe.

Effect of formulation composition on trastuzumab stability.

For monoclonal antibody drug products as for other biologics, while the innovator drug products first becomes commercially available, they are often followed by one or more biosimilar products. These biosimilars often differ from the innovator product, as well as from each other, in their formulation composition. However, the impact of the formulation composition on the stability of the active pharmaceutical ingredient subjected to different 'stresses' is still not understood.

A Comparison of Endoscopic and Surgical Gastrojejunostomy in Patients with Malignant Gastric Outlet Obstruction: A National Cohort Analysis (2016-2020).

Background And Aims: Malignant gastric outlet obstruction (MGOO) is an unfortunate complication of advanced upper gastrointestinal malignancies. Historically, surgical gastrojejunostomy has been the procedure of choice to achieve enteral bypass. Recently, endoscopic techniques have gained popularity in the management of MGOO.

Role of institutional and state policies in management of pregnancies of unknown location: a 2024 online survey of Ryan Programs in the United States.

Objective: To assess the perceived impact of state and institutional policies on managing pregnancies of unknown location (PUL) at U.S. Ryan residency programs.

CDC WONDER: Trends in diabetes mellitus mortality in the United States from 1968 to 2021.

This study analyzes U.S. diabetes mortality trends from 1968 to 2019 using CDC WONDER data.

Utilization of smartphone technology and wearable technology following TKA.

Introduction: The widespread adoption of smartphones and wearable technology has introduced innovative approaches in healthcare, particularly in postoperative rehabilitation. These technologies hold significant promise for improving recovery following lower extremity arthroplasty, especially total knee arthroplasty (TKA). Despite growing interest, the evidence on their effectiveness and long-term impact remains variable.

Impact of Second Internal Thoracic Artery on Long-term Survival After Coronary Bypass Surgery.

Background: The survival advantages of bilateral internal thoracic artery (BITA) grafts in coronary artery bypass surgery (CABG) remain unclear. Therefore, this study aims to systematically evaluate the time-dependent influence of BITA on long-term survival in elective CABG patients presenting with stable multi-vessel coronary artery disease.

Methods: Data from 3,693 patients undergoing isolated CABG with single internal thoracic artery (SITA) or BITA, with or without additional vein grafts, between 2002 and 2012 were retrospectively analyzed.

Selective pressure of various levels of erythromycin on the development of antibiotic resistance.

This study evaluated microbial fitness under selective pressure of various erythromycin concentrations and the development of resistance genes in Escherichia coli (E. coli) and Enterococcus faecalis (E. faecalis).

In vitro comparative analysis of metabolic capabilities and inhibitory profiles of selected CYP2D6 alleles on tramadol metabolism.

Tramadol, the 41st most prescribed drug in the United States in 2021 is a prodrug activated by CYP2D6, which is highly polymorphic. Previous studies showed enzyme-inhibitor affinity varied between different CYP2D6 allelic variants with dextromethorphan and atomoxetine metabolism. However, no study has compared tramadol metabolism in different CYP2D6 alleles with different CYP2D6 inhibitors.

The Extended Mind in Young Children: Cost-Dependent Trade-Off Between External and Internal Memory.

Most work on working memory development has children remember a set of items as well as they can. However, this approach sidesteps the , the integration of external information with memory. Indeed, adults prefer to use external resources (e.

Pitfalls and practical suggestions for using local field potential recordings in DBS clinical practice and research.

Local field potential (LFP) recordings using chronically implanted sensing-enabled stimulators are a powerful tool for indexing symptom presence and severity in neurological and neuropsychiatric disorders, and for enhancing our neurophysiological understanding of brain processes. LFPs have gained interest as input signals for closed-loop deep brain stimulation (DBS) and can be used to inform DBS parameter selection. LFP recordings using chronically implanted sensing-enabled stimulators have various implementational challenges.

First-in-human experience performing high-resolution cortical mapping using a novel microelectrode array containing 1,024 electrodes.

Localization of function within the brain and central nervous system is an essential aspect of clinical neuroscience. Classical descriptions of functional neuroanatomy provide a foundation for understanding the functional significance of identifiable anatomic structures. However, individuals exhibit substantial variation, particularly in the presence of disorders that alter tissue structure or impact function.

Disentangling effects of the COVID-19 pandemic and Black Lives Matter protests on implicit anti-Black bias.

Terror Management Theory (TMT) holds that mortal threats bolster people's desire to support their worldviews, which may contribute to increased outgroup bias. In 2020, two events likely increased mortality salience and death anxiety: COVID-19 and the Black Lives Matter (BLM) protests that followed George Floyd's murder. We used Project Implicit data to investigate their impact on implicit anti-Black bias, controlling for demographic variables.

Psychosocial interventions for children and adolescents with adverse childhood experiences: A systematic review and meta-analysis.

Backgrounds: Exposure to adverse childhood experiences (ACEs) is associated with adverse neurobiological, developmental, cognitive, behavioral, psychological, and social consequences among children and adolescents. Psychosocial interventions hold promise for mitigating the negative impacts of ACEs, but there is a lack of updated and comprehensive evidence summarizing their effects qualitatively and quantitatively.

Aims: We performed a systematic review and meta-analysis of existing evidence on the effectiveness of psychosocial interventions on children's outcomes, including internalizing and externalizing problems.

Stimulant-involved overdose deaths: Constructing dynamic hypotheses.

The overdose epidemic in the United States is evolving, with a rise in stimulant (cocaine and/or methamphetamine)-only and opioid and stimulant-involved overdose deaths for reasons that remain unclear. We conducted interviews and group model building workshops in Massachusetts and South Dakota. Building on these data and extant research, we identified six dynamic hypotheses, explaining changes in stimulant-involved overdose trends, visualized using causal loop diagrams.

Leveraging Artificial Intelligence to Develop a Decision-Support Tool for Visual Symptom Assessment of Grapevine Leafroll and Red Blotch Diseases.

The timely detection of viral pathogens in vineyards is a critical aspect of management. Diagnostic methods can be labor-intensive and may require specialized training or facilities. The emergence of artificial intelligence (AI) has the potential to provide innovative solutions for disease detection but requires a significant volume of high-quality data as input.

Crop rotation effects on the population density of soybean soilborne pathogens under no-till cropping system.

Soilborne diseases are persistent problems in soybean production. Long-term crop rotation can contribute to soilborne disease management. However, the response of soilborne pathogens to crop rotation is inconsistent, and rotation efficacy is highly variable.

Evaluating oomycete pathogen and community responses to chemical- and Slow Sand Filtration-based water treatment strategies to enable water recycling in nursery production systems.

While recycling irrigation water can reduce water use constraints and costs in nurseries, adoption is hindered by the associated risk of recirculating and spreading waterborne pathogens. To enable regional water re-use, this study assessed oomycete re-circulation risks and recycled water treatment efficacy at organismal and community scales. In culture-based analysis of recycled pond water at two Mid-Atlantic nurseries across three years, diverse oomycetes (12+ species) were detected using culture-based analysis, with Phytopythium helicoides as the dominant species; MiSeq analysis detected eight of these species, plus 24 additional taxa.

Construction of tetrahedral mesh phantom for Chinese women of childbearing age.

Although the Boundary Representation (BREP) method creates detailed surface phantoms of Chinese women of childbearing age, these phantoms cannot be directly used in Monte Carlo simulations. They must first be converted into voxel phantoms, a process that may diminish some of the inherent advantages of the surface phantoms. Therefore, the aim of this study is to construct a tetrahedral mesh (TM) phantom of Chinese women of childbearing age based on the BREP phantom, incorporating micron-level structural refinements to certain organ tissues while maintaining the original model's structure.

Investigation on the Heating Effects of Intra-Tumoral Injectable Magnetic hydrogels (IT-MG) for Cancer Hyperthermia.

Capacitive-based radiofrequency (Rf) radiation at 27 MHz offers a non-invasive approach for inducing hyperthermia, making it a promising technique for thermal cancer therapy applications. To achieve focused and site-specific hyperthermia, external material is required that efficiently convert Rf radiation into localized heat. Nanomaterials capable of absorbing Rf energy and convert into heat for targeted ablation are of critical importance.

Biomechanical and Functional Features of the Carrier Erythrocytes Prolonging Circulation Time of Biotherapeutic Targeted to Glycophorin A.

Red blood cells (RBCs) serve as natural transporters and can be modified to enhance the pharmacokinetics and pharmacodynamics of a protein cargo. Affinity targeting of Factor IX (FIX) to the RBC membrane is a promising approach to improve the (pro)enzyme's pharmacokinetics. For RBC targeting, purified human FIX was conjugated to the anti-mouse glycophorin A monoclonal antibody Ter119.

Bioconjugation of Synthetic Peptides onto Universal Chimeric Antigen Receptor T Cells for Targeted Cancer Immunotherapies.

The recent development of modular universal chimeric antigen receptor (CAR) T-cell platforms that use bifunctional adaptor intermediates to redirect engineered T-cell effector function has greatly expanded the capabilities of adoptive T-cell therapy, enabling safer and more comprehensive cancer treatment. However, universal CAR receptor systems rely on unstable transient recognition of tag-coupled intermediates for T-cell activation, and the array of targeting intermediates has been limited to antibodies and small molecules. Addressing these shortcomings, we engineered universal CAR T-cell receptors that can be covalently modified with synthetic biomaterials by accelerated SpyCatcher003-SpyTag003 chemistry for cancer-cell targeting.

Perspectives on Swedish Regulations for Online Record Access Among Adolescents With Serious Health Issues and Their Parents: Mixed Methods Study.

Background: With the increasing implementation of patient online record access (ORA), various approaches to access to minors' electronic health records have been adopted globally. In Sweden, the current regulatory framework restricts ORA for minors and their guardians when the minor is aged between 13 and 15 years. Families of adolescents with complex health care needs often desire health information to manage their child's care and involve them in their care.

Methods to Adjust for Confounding in Test-Negative Design COVID-19 Effectiveness Studies: Simulation Study.

Background: Real-world COVID-19 vaccine effectiveness (VE) studies are investigating exposures of increasing complexity accounting for time since vaccination. These studies require methods that adjust for the confounding that arises when morbidities and demographics are associated with vaccination and the risk of outcome events. Methods based on propensity scores (PS) are well-suited to this when the exposure is dichotomous, but present challenges when the exposure is multinomial.

Digital Gaming and Subsequent Health and Well-Being Among Older Adults: Longitudinal Outcome-Wide Analysis.

Background: Digital gaming has become increasingly popular among older adults, potentially offering cognitive, social, and physical benefits. However, its broader impact on health and well-being, particularly in real-world settings, remains unclear.

Objective: This study aimed to evaluate the multidimensional effects of digital gaming on health and well-being among older adults, using data from the Japan Gerontological Evaluation Study conducted in Matsudo City, Chiba, Japan.