Comparison of RT-qPCR With Branched DNA to Quantify a Lipid Nanoparticle-Encapsulated mRNA Therapeutic in Serum and Liver Tissue Samples From Nonclinical PK Studies.

While the branched DNA (bDNA) assay is an established bioanalytical method for measurement of lipid nanoparticle (LNP)-encapsulated messenger RNA (mRNA) pharmacokinetic parameters, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) has been considered as an alternative platform. RT-qPCR and bDNA platforms were compared for sensitivity, specificity, correlation, and overall assay performance using serum and tissue samples from 2 nonclinical mouse studies of a therapeutic mRNA candidate, LNP-PAH-mRNA, which encodes for human phenylalanine hydroxylase enzyme. Pharmacokinetic parameter noncompartmental analysis was completed using Phoenix WinNonlin.

Phthalate esters in water and sediment of Asunle stream of Obafemi Awolowo University, Ile-Ife, Nigeria: Distribution and human health risks.

This study determined the concentrations and seasonal variations of phthalate esters (PAEs) in water and sediment samples of the receiving stream within the vicinity of the Obafemi Awolowo University, Ile-Ife dumpsite. The objective of this study was to evaluate the pollution status of the study area by determining the levels of PAEs in water and sediment samples. This assessment aimed to understand the presence and extent of phthalate ester pollution in the study area.

Precision Psychobiotics for Gut-Brain Axis Health: Advancing the Discovery Pipelines to Deliver Mechanistic Pathways and Proven Health Efficacy.

Advancing microbiome-gut-brain axis science requires systematic, rational and translational approaches to bridge the critical knowledge gaps currently preventing full exploitation of the gut microbiome as a tractable therapeutic target for gastrointestinal, mental and brain health. Current research is still marked by many open questions that undermine widespread application to humans. For example, the lack of mechanistic understanding of probiotic effects means it remains unclear why even apparently closely related strains exhibit different effects in vivo.

Effect of hearing experience on preschool-aged children's eye gaze to a talker during spoken language processing.

Speechreading-gathering speech information from talkers' faces-supports speech perception when speech acoustics are degraded. Benefitting from speechreading, however, requires listeners to visually fixate talkers during face-to-face interactions. The purpose of this study is to test the hypothesis that preschool-aged children allocate their eye gaze to a talker when speech acoustics are degraded.

ADAMTS4-Specific MR Peptide Probe for the Assessment of Atherosclerotic Plaque Burden in a Mouse Model.

Introduction: Atherosclerosis is the underlying cause of multiple cardiovascular pathologies. The present-day clinical imaging modalities do not offer sufficient information on plaque composition or rupture risk. A disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) is a strongly upregulated proteoglycan-cleaving enzyme that is specific to cardiovascular diseases, inter alia, atherosclerosis.

Comprehensive analysis of targetable mutations and tumor microenvironment in urachal cancer.

Urachal cancer, a rare malignancy, generally presents in the clinical setting with advanced stages of disease. Systemic treatment with chemotherapy is generally utilized in this setting. However, there remains a paucity of data on the effectiveness of immune checkpoint inhibitors or targeted therapies for urachal cancer.

Components of the Endosome-Lysosome Vesicular Machinery as Drivers of the Metastatic Cascade in Prostate Cancer.

Prostate cancer remains a significant global health concern, with over 1.4 million new cases diagnosed and more than 330,000 deaths each year. The primary clinical challenge that contributes to poor patient outcomes involves the failure to accurately predict and treat at the onset of metastasis, which remains an incurable stage of the disease.

Effect of Creatine Monohydrate Supplementation on Macro- and Microvascular Endothelial Function in Older Adults: A Pilot Study.

A pilot study was conducted to investigate the effect of four weeks of creatine monohydrate (CrM) on vascular endothelial function in older adults. In a double-blind, randomized crossover trial, twelve sedentary, healthy older adults were allocated to either the CrM or placebo (PL) group for four weeks, at a dose of 4 × 5 g/day for 5 days, followed by 1 × 5 g/day for 23 days. Macrovascular function (flow-mediated dilation [FMD%], normalized FMD%, brachial-ankle pulse wave velocity [baPWV], pulse wave analysis [PWA]), microvascular function (microvascular reperfusion rate [% StO/sec]), and biomarkers of vascular function (tetrahydrobiopterin [BH], malondialdehyde [MDA], oxidized low-density lipoprotein [oxLDL], glucose, lipids) were assessed pre- and post-supplementation with a four-week washout period.

Assessment of Hypercoagulability in Splanchnic Vein Thrombosis by Measurement of the Hemostasis Enzymes Thrombin and Activated Protein C.

Splanchnic vein thrombosis (SVT), which is particularly prevalent in myeloproliferative neoplasms (MPNs), has a multifactorial pathomechanism involving the anticoagulant protein C (PC) pathway. To better characterize the hypercoagulable state in SVT we assessed its key enzymes thrombin and activated PC (APC). The study population included 73 patients with SVT, thereof 36 MPN+, confirmed by bone marrow biopsy, 37 MPN-, and 30 healthy controls.

Lactams Exhibit Potent Antifungal Activity Against Monospecies and Multispecies Interkingdom Biofilms on a Novel Hydrogel Skin Model.

Infections of intact and damaged skin barriers and keratin are frequently associated with complex biofilm communities containing bacteria and fungi, yet there are limited options for successful management. This study intended to focus on the utility of some novel proprietary lactam molecules, quorum sensing (QS)-derived halogenated furanones, which act to block the QS pathway, against key fungal pathogens of the skin (Candida albicans, Malassezia furfur and Microsporum gypseum). Moreover, we aimed to assess how these actives performed against complex interkingdom biofilms in a clinically relevant model.

Analysis of time to regulatory approval in an exception from informed consent trial in trauma patients.

Background: The interactive media-based approach to community consultation and public disclosure (CC/PD), a key step when conducting exception from informed consent (EFIC) clinical trials, is intended to be completed in 4 months. This analysis characterizes the process, from initiation of CC/PD activities to institutional review board approval, to better understand the barriers and how these can be mitigated.

Methods: This is a retrospective post hoc analysis of data collected as part of the CC/PD campaigns conducted for a large trial involving up to 90 trauma centers in the United States.

Analysis of the NMR Parameters Shielding and Spin-Spin Coupling Constants of Glycine Conformers.

In this study, we worked at the CCSD/aug-cc-pVTZ level to obtain the conformers of glycine in its neutral and zwitterionic forms in the gas and water phases. We then computed the NMR properties (spin-spin coupling constants and nuclear magnetic shieldings) at the SOPPA/aug-cc-pVTZ-J level. We attempt to elucidate the apparent discrepancy arising from two previous works by Valverde et al.

Impact of Heart Transplant Allocation Changes on Waitlist Mortality and Clinical Practice in Pediatric and Adult Patients With Congenital Heart Disease and Cardiomyopathy.

Background: The United Network of Organ Sharing made changes to the priority for allocation of hearts for transplantation (HT) in 2016 for pediatric patients and 2018 for adult patients. Although recent work has evaluated the impact of the revised allocation systems on mechanical circulatory support practices and waitlist outcomes, there are limited data that focus more specifically on the impact of the allocation changes on patients with congenital heart disease (CHD) or cardiomyopathy and how these relationships might differ in pediatric and adult patients.

Methods: The United Network of Organ Sharing database was queried for pediatric (<18 years of age) and adult (18-50 years of age) patients with a CHD or cardiomyopathy diagnosis listed for HT.

Remotely delivered weight management for people with long COVID and overweight: the randomized wait-list-controlled ReDIRECT trial.

Long COVID (LC) is a complex multisymptom condition with no known disease-modifying treatments. This wait-list-controlled open-label trial tested whether a remotely delivered structured weight management program could improve respective LC symptoms in people living with overweight. Adults with LC (symptoms >12 weeks) and body mass index >27 kg m (>25 kg m for South Asians) were randomized (n = 234, 1:1) to control (n = 116, usual care) or the remotely delivered structured weight management (n = 118, total diet replacement (850 kcal per day) for 12 weeks, followed by food reintroduction and weight loss maintenance support) via minimization and randomization (80:20) to balance dominant LC symptom, sex, age, ethnicity and postcode-based index of multiple deprivation between groups.

Scaling convolutional neural networks achieves expert level seizure detection in neonatal EEG.

Neonatal seizures require urgent treatment, but often go undetected without expert EEG monitoring. We have developed and validated a seizure detection model using retrospective EEG data from 332 neonates. A convolutional neural network was trained and tested on over 50,000 hours (n = 202) of annotated single-channel EEG containing 12,402 seizure events.

Intracerebroventricular B7-H3-targeting CAR T cells for diffuse intrinsic pontine glioma: a phase 1 trial.

Diffuse intrinsic pontine glioma (DIPG) is a fatal central nervous system (CNS) tumor that confers a median survival of 11 months. As B7-H3 is expressed on pediatric CNS tumors, we conducted BrainChild-03, a single-center, dose-escalation phase 1 clinical trial of repetitive intracerebroventricular (ICV) dosing of B7-H3-targeting chimeric antigen receptor T cells (B7-H3 CAR T cells) for children with recurrent or refractory CNS tumors and DIPG. Here we report results from Arm C, restricted to patients with DIPG.

[Multimorbid patients in visceral surgery-Upper gastrointestinal tract].

The treatment of multimorbid patients in oncological surgery of the upper gastrointestinal tract requires a differentiated consideration of every single risk factor in order to provide a holistic assessment. This article focuses on pre-existing diseases that are particularly relevant for elective esophageal and gastric surgery and have practical clinical consequences. In this way a differtiation is made between metabolic, vascular, cardiopulmonary and organ-specific risks.

Safety of Adjunctive Intraarterial Tenecteplase Following Mechanical Thrombectomy: The ALLY Pilot Trial.

Background: Recent studies suggest that the use of adjunctive intraarterial alteplase after mechanical thrombectomy (MT) may improve outcomes; however, there are limited data on the use of intraarterial tenecteplase, a newer-generation lytic, in this acute ischemic stroke patient population. Here, we evaluate the use of intraarterial tenecteplase in the ALLY pilot study (Adjunctive Intraarterial Tenecteplase Following Mechanical Thrombectomy).

Methods: ALLY was a prospective, single-center, nonrandomized pilot study assessing the feasibility and safety of intraarterial tenecteplase up to 4.

A Global Collaborative Comparison of SARS-CoV-2 Antigenicity Across 15 Laboratories.

Setting up a global SARS-CoV-2 surveillance system requires an understanding of how virus isolation and propagation practices, use of animal or human sera, and different neutralisation assay platforms influence assessment of SARS-CoV-2 antigenicity. In this study, with the contribution of 15 independent laboratories across all WHO regions, we carried out a controlled analysis of neutralisation assay platforms using the first WHO International Standard for antibodies to SARS-CoV-2 variants of concern (source: NIBSC). Live virus isolates (source: WHO BioHub or individual labs) or spike plasmids (individual labs) for pseudovirus production were used to perform neutralisation assays using the same serum panels.

Weight-neutral early time-restricted eating improves glycemic variation and time in range without changes in inflammatory markers.

Early time-restricted eating (eTRE) is a dietary strategy that restricts caloric intake to the first 6-8 h of the day and can effect metabolic benefits independent of weight loss. However, the extent of these benefits is unknown. We conducted a randomized crossover feeding study to investigate the weight-independent effects of eTRE on glycemic variation, multiple time-in-range metrics, and levels of inflammatory markers.

Adoptive T cell therapy targeting an inducible and broadly shared product of aberrant mRNA translation.

Prolonged exposure to interferon-gamma (IFNγ) and the associated increased expression of the enzyme indoleamine 2,3-dioxygenase 1 (IDO1) create an intracellular shortage of tryptophan in the cancer cells, which stimulates ribosomal frameshifting and tryptophan to phenylalanine (W>F) codon reassignments during protein synthesis. Here, we investigated whether such neoepitopes can be useful targets of adoptive T cell therapy. Immunopeptidomic analyses uncovered hundreds of W>F neoepitopes mainly presented by the HLA-A24:02 allele.

A risk-based approach can guide safe cell line development and cell banking for scaled-up cultivated meat production.

For commercial viability, cultivated meats require scientifically informed approaches to identify and manage hazards and risks. Here we discuss food safety in the rapidly developing field of cultivated meat as it shifts from lab-based to commercial scales. We focus on what science-informed risk mitigation processes can be implemented from neighbouring fields.