Bioinformatic and biochemical analysis uncovers novel activity in the 2-ER subfamily of OYEs.

Members of the old yellow enzyme (OYE) family utilize a flavin mononucleotide cofactor to catalyze the asymmetric reduction of activated alkenes. The 2-enoate reductase (2-ER) subfamily are of particular industrial relevance as they can reduce α/β alkenes near electron-withdrawing groups. While the broader OYE family is being extensively explored for biocatalytic applications, oxygen sensitivity and poor expression yields associated with the presence of an Fe/S cluster in 2-ERs have hampered their characterization.

Optimizing care for gastric cancer with overt bleeding: Is systemic therapy a valid option?

Gastric cancer (GC) and gastroesophageal junction cancer (GEJC) represent a significant burden globally, with complications such as overt bleeding (OB) further exacerbating patient outcomes. A recent study by Yao evaluated the effectiveness and safety of systematic treatment in GC/GEJC patients presenting with OB. Using propensity score matching, the study balanced the comparison groups to investigate overall survival and treatment-related adverse events.

Rate estimation and trend analysis of new HIV infections among the international migrant population in Chile from 2013 to 2022.

Background: International migrants are central to HIV research, but comparative data on their infection rates versus resident populations, including in Chile, are scarce. This study compares HIV incidence rates between international migrants and Chileans.

Methods: A longitudinal study was conducted.

The PIKASO trial (Preventing Injured Knees from Osteoarthritis: Severity Outcomes): Rationale and design features for a randomized controlled trial.

Objective: Given the high burden and increasing prevalence of post-traumatic osteoarthritis (PTOA), identifying clinically beneficial strategies to prevent or delay its onset could improve the quality of life of those at high risk of developing the disease.

Methods: Preventing Injured Knees from OsteoArthritis: Severity Outcomes (PIKASO) is a multicenter blinded, parallel, two-arm randomized controlled trial of 512 individuals aged 18-45 years undergoing anterior cruciate ligament reconstruction (ACLR). This study is designed to evaluate the efficacy of a 12-month intervention of oral metformin vs.

Sleep duration, sleep disturbances and skeletal muscle mass change over time: A population-based longitudinal analysis in Peru.

Background: The skeletal muscle has mainly a structural function and plays a role in human's metabolism. Besides, the association between sleep quality and muscle mass, in the form of sarcopenia, has been reported. This study aimed to assess whether changes of skeletal muscle mass (SMM) over time are associated with baseline sleep duration and disturbances in a resource-constrained adult Peruvian population.

Therapeutic use of music listening in patients undergoing invasive coronary procedures: A meta-analysis.

Background: Listening to music has been shown to reduce pain and anxiety before, during, and after invasive coronary procedures.

Aim: To perform a systematic review and meta-analysis to explore the effect of therapeutic use of music on both, perioperative and postoperative outcomes of invasive coronary procedures.

Methods: An exhaustive literature search of 3 electronic databases (MEDLINE, Scopus, Cochrane CENTRAL) was conducted from inception until 10 December 2023.

Dancing towards speech improvement: Repurposing dance for motor speech deficits in neurodegenerative diseases.

Dance or rhythmic movement-based training has demonstrated significant efficacy in addressing a range of motor and cognitive deficits associated with neurodegenerative diseases like Parkinson's and Alzheimer's diseases. Leveraging both human and non-human animal behavioral and neurobiological evidence, I hypothesize a possible untapped role of dance training in mitigating impairments in the motor control of speech, a complex sensorimotor behavior affected in these conditions. Here, this hypothesis is supported by an in-depth examination of motor speech deficits in Parkinson's and Alzheimer's diseases, at a behavioral, physiological, and neural level.

Intergenerational impacts of racial discrimination on child executive functioning problems.

The proposed study sought to investigate whether maternal experiences of racial discrimination and gendered racial stress are associated with offspring executive functioning. Total 266 Black mother-child pairs in the United States were assessed from pregnancy through child age of 4 years. We hypothesized that children whose mothers reported higher rates of perceived gendered racial stress during pregnancy and racial discrimination throughout their lifetime would have lower scores on executive functioning assessments.

Understanding the opioid syndemic in North Carolina: A novel approach to modeling and identifying factors.

The opioid epidemic is a significant public health challenge in North Carolina, but limited data restrict our understanding of its complexity. Examining trends and relationships among different outcomes believed to reflect opioid misuse provides an alternative perspective to understand the opioid epidemic. We use a Bayesian dynamic spatial factor model to capture the interrelated dynamics within six different county-level outcomes, such as illicit opioid overdose deaths, emergency department visits related to drug overdose, treatment counts for opioid use disorder, patients receiving prescriptions for buprenorphine, and newly diagnosed cases of acute and chronic hepatitis C virus and human immunodeficiency virus.

Noninvasive in vivo imaging of macrophages: understanding tumor microenvironments and delivery of therapeutics.

Macrophages are pivotal in the body's defense and response to inflammation. They are present in significant numbers and are widely implicated in various diseases, including cancer. While molecular and histological techniques have advanced our understanding of macrophage biology, their precise function within the cancerous microenvironments remains underexplored.

Machine learning approach for noninvasive intracranial pressure estimation using pulsatile cranial expansion waveforms.

Noninvasive methods for intracranial pressure (ICP) monitoring have emerged, but none has successfully replaced invasive techniques. This observational study developed and tested a machine learning (ML) model to estimate ICP using waveforms from a cranial extensometer device (brain4care [B4C] System). The model explored multiple waveform parameters to optimize mean ICP estimation.

Volume-Outcome Relationship of Norwood Procedures: Insights from the National Pediatric Cardiology - Quality Improvement Collaborative Database.

Background: Prior investigations of the center-specific case volume on outcomes in hypoplastic left heart syndrome have conflicting results. This study utilized the National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC) registry to investigate the center volume-outcome relationship in patients following the Norwood procedure with consideration of pre-operative high-risk features.

Methods: Between 2016 and 2023, centers were categorized by Norwood procedure volume into low (≤ 5 cases/year), medium (6 to 10 cases/year), and high-volume centers (> 10 cases/year).

The Society of Thoracic Surgeons National Intermacs Database Risk Model for Durable Left Ventricular Assist Device Implantation.

Background: Statistical risk models for durable left ventricular assist device (LVAD) implantation inform candidate selection, quality improvement, and evaluation of provider performance. We developed a 90-day mortality risk model utilizing The Society of Thoracic Surgeons National Intermacs Database (STS Intermacs).

Methods: STS Intermacs was queried for primary durable LVAD implants from 1/ 2019 - 9/2023.

Oxidative Gaseous Air Pollutant Exposure Interacts with PNPLA3-I148M Genotype to Influence Liver Fat Fraction and Multi-Omics Profiles in Young Adults.

PNPLA3-I148M genotype is the strongest predictive single-nucleotide polymorphism for liver fat. We examine whether PNPLA3-I148M modifies associations between oxidative gaseous air pollutant exposure (O) with i) liver fat and ii) multi-omics profiles of miRNAs and metabolites linked to liver fat. Participants were 69 young adults (17-22 years) from the Meta-AIR cohort.

HIV co-infection is associated with increased HLA-DR expression by Mycobacterium tuberculosis-specific CD4 T cells in people with latent tuberculosis infection.

Infection with HIV is associated with dysregulated CD4 T cell responses to Mycobacterium tuberculosis (Mtb) and increased risk of developing tuberculosis. Mtb-specific CD4 T cells in people with HIV have diminished Th1 cytokine production capacity, thus we utilized a flow cytometry-based assay to measure CD40L expression by Mtb-specific CD4 T cells in a cytokine-independent manner. We evaluated the frequency and phenotype of Mtb-specific CD4 responses in Kenyan adults with latent Mtb infection and found that the majority of Mtb-specific CD4 T cells expressed CD40L in the absence of IFN-γ, regardless of HIV infection status.

ISCT MSC committee statement on the US FDA approval of allogenic bone-marrow mesenchymal stromal cells.

The December 2024 US Food and Drug Administration (FDA) approval of Mesoblast's Ryoncil (remestemcel-L-rknd)-allogeneic bone marrow mesenchymal stromal cell (MSC(M)) therapy-in pediatric acute steroid-refractory graft-versus-host-disease finally ended a long-lasting drought on approved MSC clinical products in the United States. While other jurisdictions-including Europe, Japan, India, and South Korea-have marketed autologous or allogeneic MSC products, the United States has lagged in its approval. The sponsor's significant efforts and investments, working closely with the FDA addressing concerns regarding clinical efficacy and consistent MSC potency through an iterative process that spanned several years, was rewarded with this landmark approval.

Global metabolomic alterations associated with endocrine-disrupting chemicals among pregnant individuals and newborns.

Background: Gestational exposure to non-persistent endocrine-disrupting chemicals (EDCs) may be associated with adverse pregnancy outcomes. While many EDCs affect the endocrine system, their effects on endocrine-related metabolic pathways remain unclear. This study aims to explore the global metabolome changes associated with EDC biomarkers at delivery.

Implementation of An Advance Care Planning Intervention in Dialysis Clinics.

Rationale & Objective: Sharing Patient's Illness Representations to Increase Trust (SPIRIT) is an evidence-based advance care planning intervention targeting dialysis patients and their surrogate decision-makers. To address SPIRIT's implementation potential, we report on a process evaluation in our recently completed five-state cluster-randomized trial.

Study Design: A descriptive study of implementation within a randomized clinical trial.

Placental PFAS concentrations are associated with perturbations of placental DNA methylation.

The placenta is crucial for fetal development, is affected by PFAS toxicity, and evidence is accumulating that gestational PFAS perturb the epigenetic activity of the placenta. Gestational PFAS exposure can adversely affect offspring, yet individual and cumulative impacts of PFAS on the placental epigenome remain underexplored. Here, we conducted an epigenome-wide association study (EWAS) to examine the relationships between placental PFAS levels and DNA methylation in a cohort of mother-infant dyads in Arkansas (N=151).

Structural and functional analysis of SAM-dependent N-methyltransferases involved in ovoselenol and ovothiol biosynthesis.

Thio/selenoimidazole Nπ-methyltransferases are an emerging family of enzymes catalyzing the final step in the production of the S/Se-containing histidine-derived antioxidants ovothiol and ovoselenol. These enzymes, prevalent in prokaryotes, show minimal sequence similarity to other methyltransferases, and the structural determinants of their reactivities remain poorly understood. Herein, we report ligand-bound crystal structures of OvsM from the ovoselenol pathway as well as a member of a previously unknown clade of standalone ovothiol-biosynthetic Nπ-methyltransferases, which we have designated OvoM.