Distribution-based sub-population selection (DSPS): A method for in-silico reproduction of clinical trials outcomes.

Diabetes presents a significant challenge to healthcare due to the short- and long-term complications associated with poor blood sugar control. Computer simulation platforms have emerged as promising tools for advancing diabetes therapy by simulating patient responses to treatments in a virtual environment. The University of Virginia Virtual Lab (UVLab) is a new simulation platform engineered to mimic the metabolic behavior of individuals with type 2 diabetes (T2D) using a mathematical model of glucose homeostasis in T2D and a large population of 6062 virtual subjects.

Insight into copper coordination in O reduction by water-soluble cytochrome oxidase models.

Iron-copper complexes have been extensively studied in the search for efficient cytochrome oxidase models. Whereas most dinuclear materials usually focus on fine-tuning the coordination of heme-Fe, this work shows that the coordination of copper in cytochrome oxidase models should be carefully taken into consideration. A β-cyclodextrin dimer was built around a bipyridine linker and combined with Fe-tetraphenylsulfonatoporphyrinate (FeTPPS) to generate a self-assembled hydrosoluble cytochrome oxidase model.

Advancing canopy-level entomological surveillance to monitor vector-borne and zoonotic disease dynamics.

Faced with the increased frequency of zoonotic spillover in recent decades, emerging vector-borne diseases from nonhuman primates pose a significant threat to global public health. Understanding transmission dynamics driven by arthropod vectors between wildlife populations is critical for surveillance, modeling, and mitigation. Elevated canopy-level sampling is a valuable approach for elucidating vector behavior and sylvatic transmission.

Nrf2 mediates mitochondrial and NADPH oxidase-derived ROS during mild heat stress at 40 °C.

Hyperthermia is an adjuvant to chemotherapy and radiotherapy and sensitizes tumors to these treatments. However, repeated heat treatments result in acquisition of heat resistance (thermotolerance) in tumors. Thermotolerance is an adaptive survival response that appears to be mediated by upregulated cellular defenses.

Chimeras Derived from a P2Y Receptor Antagonist and UDP-Sugar Agonists for Potential Treatment of Inflammation.

Tethered glycoconjugates of a naphthalene- and piperidine-containing antagonist of the P2Y receptor (PPTN) were synthesized, and their nM receptor binding affinity was determined using a fluorescent tracer in hP2YR-expressing whole CHO cells. The rationale for preparing mono- and disaccharide conjugates of the antagonists was to explore the receptor binding site, which we know recognizes a glucose moiety on the native agonist (UDP-glucose), as well as enhance aqueous solubility and pharmacokinetics, including kidney excretion to potentially counteract sterile inflammation. Glycoconjugates with varied linker length, including PEG chains, were compared in hP2YR binding, suggesting that an optimal affinity (IC, nM) in the piperidine series was achieved for triazolyl -linked glucose conjugates having one (, MRS4872, 3.

Heterozygous variant as a novel genetic cause of telomere biology disorders.

Premature telomere shortening or telomere instability is associated with a group of rare and heterogeneous diseases collectively known as telomere biology disorders (TBDs). Here we identified two unrelated individuals with clinical manifestations of TBDs and short telomeres associated with the identical monoallelic variant c.767A>G; Y256C in Although the replication protein A2 (RPA2) mutant did not affect ssDNA binding and G-quadruplex-unfolding properties of RPA, the mutation reduced the affinity of RPA2 with the ubiquitin ligase RFWD3 and reduced RPA ubiquitination.

Outcomes of transcatheter aortic valve implantation for native aortic valve regurgitation.

Background: Large datasets of transcatheter aortic valve implantation (TAVI) for pure aortic valve regurgitation (PAVR) are scarce.

Aims: We aimed to report procedural safety and long-term clinical events (CE) in a contemporary cohort of PAVR patients treated with new-generation devices (NGD).

Methods: Patients with grade III/IV PAVR enrolled in the FRANCE-TAVI Registry were selected.

Detection of Tumor-Associated Autoantibodies in the Sera of Pancreatic Cancer Patients Using Engineered MUC1 Glycopeptide Nanoparticle Probes.

Pancreatic cancer is one of the deadliest cancers worldwide, mainly due to late diagnosis. Therefore, there is an urgent need for novel diagnostic approaches to identify the disease as early as possible. We have developed a diagnostic assay for pancreatic cancer based on the detection of naturally occurring tumor associated autoantibodies against Mucin-1 (MUC1) using engineered glycopeptides on nanoparticle probes.

Development and Validation of a Novel Placental DNA Methylation Biomarker of Maternal Smoking during Pregnancy in the ECHO Program.

Background: Maternal cigarette smoking during pregnancy (MSDP) is associated with numerous adverse health outcomes in infants and children with potential lifelong consequences. Negative effects of MSDP on placental DNA methylation (DNAm), placental structure, and function are well established.

Objective: Our aim was to develop biomarkers of MSDP using DNAm measured in placentas (), collected as part of the Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function double-blind, placebo-controlled randomized clinical trial conducted between 2012 and 2016.

The stand-alone regulator RofA exhibits characteristics of a PRD-containing virulence regulator.

[group A streptococcus (GAS)] is a human pathogen capable of infecting diverse tissues. To successfully infect these sites, GAS must detect available nutrients and adapt accordingly. The phosphoenolpyruvate transferase system (PTS) mediates carbohydrate uptake and metabolic gene regulation to adapt to the nutritional environment.

Site-Selective Radical Aromatic C-H Functionalization of Alloxazine and Flavin through Ground-State Single Electron Transfer.

Flavins and their alloxazine isomers are key chemical scaffolds for bioinspired electron transfer strategies. Their properties can be fine-tuned by functional groups, which must be introduced at an early stage of the synthesis as their aromatic ring is inert towards post-functionalization. We show that the introduction of a remote metal-binding redox site on alloxazine and flavin activates their aromatic ring towards direct C-H functionalization.

Neurocognition and its predictors in a linguistically and culturally diverse cohort of people with HIV.

: HIV/AIDS disproportionately affects Black and Latino people in the United States, yet there is a lack of research on predictors of neurocognitive outcomes in these groups. We examined neurocognitive performance and its key predictors across White, Black, and Latino people with HIV (PWH). : Participants included 586 PWH of White, Black, and Latino (English- and Spanish-speaking) background.

Nutritional and Morphofunctional Assessment of Post-ICU Patients with COVID-19 at Hospital Discharge: NutriEcoMuscle Study.

This paper presents baseline results from the NutriEcoMuscle study, a multicenter observational study conducted in Spain which focused on changes in nutritional status, body composition, and functionality in post-intensive care unit (ICU) COVID-19 patients following a nutritional intervention. Assessments at hospital discharge included Subjective Global Assessment (SGA), Global Leadership Initiative on Malnutrition (GLIM) criteria, the Barthel index, handgrip strength (HGS) and the Timed Up-and-Go test, bioelectrical impedance analysis (BIA), and nutritional ultrasound (US). The study involved 96 patients (71.

Increased Risk of Gestational Hypertension by Periconceptional Exposure to Ambient Air Pollution and Effect Modification by Prenatal Depression.

Background: Air pollution has been associated with gestational hypertension (GH) and preeclampsia, but susceptible windows of exposure and potential vulnerability by comorbidities, such as prenatal depression, remain unclear.

Methods: We ascertained GH and preeclampsia cases in a prospective pregnancy cohort in Los Angeles, CA. Daily levels of ambient particulate matters (with a diameter of ≤10 μm [PM] or ≤2.

Short-term exposure to high pCO leads to decreased branchial cytochrome C oxidase activity in the presence of octopamine in a decapod.

In a recent mechanistic study, octopamine was shown to promote proton transport over the branchial epithelium in green crabs, Carcinus maenas. Here, we follow up on this finding by investigating the involvement of octopamine in an environmental and physiological context that challenges acid-base homeostasis, the response to short-term high pCO exposure (400 Pa) in a brackish water environment. We show that hyperregulating green crabs experienced a respiratory acidosis as early as 6 h of exposure to hypercapnia, with a rise in hemolymph pCO accompanied by a simultaneous drop of hemolymph pH.

The science of micronutrients in clinical practice - Report on the ESPEN symposium.

Background & Aims: The European Society for Clinical Nutrition and Metabolism published its first clinical guidelines for use of micronutrients (MNs) in 2022. A two-day web symposium was organized in November 2022 discussing how to apply the guidelines in clinical practice. The present paper reports the main findings of this symposium.

Integration of a Safety Module to Prevent Rebound Hypoglycemia in Closed-Loop Artificial Pancreas Systems.

Background: With automated insulin delivery (AID) systems becoming widely adopted in the management of type 1 diabetes, we have seen an increase in occurrences of rebound hypoglycemia or generated hypoglycemia induced by the controller's response to rapid glucose rises following rescue carbohydrates. Furthermore, as AID systems aim to enable complete automation of prandial control, algorithms are designed to react even more strongly to glycemic rises. This work introduces a rebound hypoglycemia prevention layer (HypoSafe) that can be easily integrated into any AID system.

Integrated vector genomes may contribute to long-term expression in primate liver after AAV administration.

The development of liver-based adeno-associated virus (AAV) gene therapies is facing concerns about limited efficiency and durability of transgene expression. We evaluated nonhuman primates following intravenous dosing of AAV8 and AAVrh10 vectors for over 2 years to better define the mechanism(s) of transduction that affect performance. High transduction of non-immunogenic transgenes was achieved, although expression declined over the first 90 days to reach a lower but stable steady state.

Prevalent and Disseminated Recombinant and Wild-Type Adeno-Associated Virus Integration in Macaques and Humans.

Integration of naturally occurring adeno-associated viruses (AAV; wild-type AAV [wtAAV]) and those used in gene therapy (recombinant AAV [rAAV]) into host genomic DNA has been documented for over two decades. Results from mouse and dog studies have raised concerns of insertional mutagenesis and clonal expansion following AAV exposure, particularly in the context of gene therapy. This study aimed to characterize the genomic location, abundance, and expansion of wtAAV and rAAV integrations in macaque and human genomes.

Sublethal perfluorooctanoic acid and perfluorooctanesulfonic acid delay larval development and population growth but do not alter egg hatching.

Perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) are polyfluoroalkyl substances (PFAS) used as surface coatings in manufacturing. Exposure to PFAS was shown to be correlated with infertility, low birth weight, and delayed aspects of pubertal development in mammals. Despite many correlational studies, there have been few direct investigations examining the link between PFAS exposure and early animal development.

Therapy Settings Associated with Optimal Outcomes for t:slim X2 with Control-IQ Technology in Real-World Clinical Care.

To determine insulin dosing parameters that are associated with and predict optimal outcomes for people using t:slim X2 with Control-IQ technology (CIQ). Retrospective deidentified data from CIQ users were analyzed to determine the effect of Correction Factor, Carbohydrate-to-Insulin (C:I) Ratio, and basal rate settings (standardized by total daily insulin [TDI]) on glycemic control. We performed an associative analysis followed by linear regressions to determine the relative importance of the settings and confounding variables (e.