ALLG APML5: Bioavailability and safety of oral arsenic trioxide assessed during consolidation therapy for APL.

The prognosis for patients with acute promyelocytic leukemia (APL) has improved dramatically since the introduction of all-trans retinoic acid (ATRA) and intravenous arsenic trioxide (ATO). However, ATO administration requires daily infusions over several months, representing an onerous burden for hospitals and patients. We evaluated the bioavailability of a novel encapsulated oral ATO formulation in APL patients in first complete remission during standard-of-care consolidation.

Assessing the performance of AI chatbots in answering patients' common questions about low back pain.

Objectives: The aim of this study was to assess the accuracy and readability of the answers generated by large language model (LLM)-chatbots to common patient questions about low back pain (LBP).

Methods: This cross-sectional study analysed responses to 30 LBP-related questions, covering self-management, risk factors and treatment. The questions were developed by experienced clinicians and researchers and were piloted with a group of consumer representatives with lived experience of LBP.

Patients' Experiences With Opioid Tapering in Noncancer Pain: A Systematic Review and Meta-synthesis.

Tapering opioids is an effective strategy to reduce the risks associated with long-term opioid therapy. However, patients' experience with tapering can influence the success of this treatment. Understanding patients' experiences with opioid tapering will allow for patient-centered approaches to be adopted to tailor interventions to achieve safe and successful taper outcomes.

Could metabolic imaging and artificial intelligence provide a novel path to non-invasive aneuploidy assessments? A certain clinical need.

Pre-implantation genetic testing for aneuploidy (PGT-A) via embryo biopsy helps in embryo selection by assessing embryo ploidy. However, clinical practice needs to consider the invasive nature of embryo biopsy, potential mosaicism, and inaccurate representation of the entire embryo. This creates a significant clinical need for improved diagnostic practices that do not harm embryos or raise treatment costs.

Pollutant accumulation characteristics of substrates and mechanism of microbial action in different ecological ditches.

Ecological ditches serve as one of the important measures for the concentrated infiltration of stormwater in the construction process of sponge cities. Prolonged concentrated infiltration of stormwater can lead to the accumulation of pollutants and pollution risks in the substrate of ecological ditches. In this study, two different substrate ecological ditches were constructed, namely, a combined substrate ecological ditch with zeolite + ceramsite (EA), and a biological substrate ecological ditch (EB).

Predicting Carbonic Anhydrase Binding Affinity: Insights from QM Cluster Models.

A systematic series of QM cluster models has been developed to predict the trend in the carbonic anhydrase binding affinity of a structurally diverse dataset of ligands. Reference DLPNO-CCSD(T)/CBS binding energies were generated for a cluster model and used to evaluate the performance of contemporary density functional theory methods, including Grimme's "3c" DFT composite methods (rSCAN-3c and ωB97X-3c). It is demonstrated that when validated QM methods are used, the predictive power of the cluster models improves systematically with the size of the cluster models.

The Value and Importance of a Professional Ethical Code for Medicines Development: IFAPP International Ethics Framework.

Pharmaceutical medicine professionals have to face many ethical problems during the entire life span of new medicines extending from animal studies to broad clinical practice. The primary aim of the general ethical principles governing research conducted in humans is to diminish the physical and psychological burdens of the participants in human drug studies but overlooks many additional social and ethical problems faced by medicine developers. These arise mainly at the interface connecting the profit-oriented pharmaceutical industry and the healthcare-centered medical profession cooperating in medicines development.

Larsucosterol for the Treatment of Alcohol-Associated Hepatitis.

Background: Larsucosterol is a DNA methyltransferase inhibitor in development for alcohol-associated hepatitis (AH), a disease for which there is no approved therapy.

Methods: In this phase 2b trial, patients with severe AH were randomly assigned 1:1:1 to receive 30 mg or 90 mg of larsucosterol or placebo; a second dose was administered after 72 hours if the patient remained hospitalized. All patients received supportive care as determined by investigators.

Comparison of different microbiome analysis pipelines to validate their reproducibility of gastric mucosal microbiome composition.

Microbiome analysis has become a crucial tool for basic and translational research due to its potential for translation into clinical practice. However, there is ongoing controversy regarding the comparability of different bioinformatic analysis platforms and a lack of recognized standards, which might have an impact on the translational potential of results. This study investigates how the performance of different microbiome analysis platforms impacts the final results of mucosal microbiome signatures.

Agency in young people's unsafe abortion trajectories in Papua New Guinea.

Unsafe abortion is a preventable contributor to maternal morbidity and mortality, particularly for young unmarried women in low resource settings. In Papua New Guinea, abortion is legally restricted and highly stigmatised, limiting access to safe abortion and post-abortion care, resulting in unsafe abortion. This paper explores young people's lived experiences and agency in relation to unsafe abortion.

Categorising reported errors and incidents from morbidity and mortality meetings (M&Ms) in a small animal multi-specialty veterinary teaching hospital.

Background: Errors in veterinary clinical settings can lead to patient harm. Morbidity and mortality meetings (M&Ms) are forums to discuss errors and incidents that can lead or have led to adverse outcomes, potential harm or unsafe conditions, with the purpose of improving patient safety in future. Despite growing implementation of M&Ms in veterinary medicine, their effectiveness in improving future patient safety may be constrained by the need for absolute confidentiality during meetings.

A Community-Led Approach to Understanding How Service Providers Can Support 'Ageing well' for Older Aboriginal People in Australia.

Supporting older people to age well is a global policy priority, however the development and implementation of strategies to support ageing well for older Aboriginal people must be determined by the communities affected. This is necessary in colonial contexts, where socio-political structures impinge on Aboriginal rights and mainstream policy and practice creates and maintains health and social inequities. This article reports on research conducted in partnership with the Dharriwaa Elders Group, an Aboriginal Community Controlled Organisation.

Vaccinating Adolescents With Intellectual and Developmental Disability at School: An Opportunity to Promote Supported Decision Making.

Internationally, vaccination rates among adolescents with intellectual and developmental disability (IDD) are lower than those of the general population. Little research has addressed this issue. This study investigates the experiences of vaccinating adolescents with IDD in special education settings in Australia, with a focus on student engagement.

Overweight yet Undernourished: A Common Juxtaposition in the Specialist Diabetes Foot Service.

Aims: To describe the nutritional status of people with diabetes-related foot complications and explore the association between nutrition and ulceration healing.

Methods: This retrospective cohort study included attendees of a diabetes foot service who completed a dietary questionnaire. Diet was compared to guideline recommendations and biochemical measures were recorded.

Subventricular Accumulation of Cu in the Aging Mouse Brain Does Not Associate with Anticipated Increases in Markers of Oxidative Stress.

Natural aging is associated with mild memory loss and cognitive decline, and age is the greatest risk factor for neurodegenerative diseases, such as Alzheimer's disease. There is substantial evidence that oxidative stress is a major contributor to both natural aging and neurodegenerative disease, and coincidently, levels of redox active metals such as Fe and Cu are known to be elevated later in life. Recently, a pronounced age-related increase in Cu content has been reported to occur in mice and rats around a vital regulatory brain region, the subventricular zone of lateral ventricles.

Generalized Stomatal Optimization of Evolutionary Fitness Proxies for Predicting Plant Gas Exchange Under Drought, Heatwaves, and Elevated CO.

Stomata control plant water loss and photosynthetic carbon gain. Developing more generalized and accurate stomatal models is essential for earth system models and predicting responses under novel environmental conditions associated with global change. Plant optimality theories offer one promising approach, but most such theories assume that stomatal conductance maximizes photosynthetic net carbon assimilation subject to some cost or constraint of water.

Identifying silver ore sources for the earliest coins of Athens.

Unlabelled: This study addresses longstanding questions concerning the ore sources used in the first series of coins of ancient Athens known as the (c.540-c.500 BCE) by combining comprehensive numismatic data on 22 coins (16 new and 6 legacy analyses) with lead isotope and surface elemental measurements (MC-ICP-MS and XRF).

Effect of Bacille Calmette-Guérin vaccination on immune responses to SARS-CoV-2 and COVID-19 vaccination.

Objectives: Bacille Calmette-Guérin (BCG) vaccination has off-target effects on disease risk for unrelated infections and immune responses to vaccines. This study aimed to determine the immunomodulatory effects of BCG vaccination on immune responses to vaccines against SARS-CoV-2.

Methods: Blood samples, from a subset of 275 SARS-CoV-2-naïve healthcare workers randomised to BCG vaccination (BCG group) or no BCG vaccination (Control group) in the BRACE trial, were collected before and 28 days after the primary course (two doses) of ChAdOx1-S (Oxford-AstraZeneca) or BNT162b2 (Pfizer-BioNTech) vaccination.

Epidemiology of pulmonary alveolar proteinosis: a descriptive study using a Japanese national administrative claims database.

https://bit.ly/3Z7uBkg.

Ultrasound measurement of perirenal adipose tissue indicates cardiovascular disease, but standardisation is needed: A systematic review.

Introduction: In both highly industrialised and developing countries, obesity is reaching epidemic proportions and increasingly becoming a critical indicator of general morbidity, cardiovascular disease (CVD) and renal dysfunction. A promising trend in detection and management of obesity is the measurement of perirenal adipose tissue (PRAT), increasingly recognised as a metabolically active endocrine organ in itself. Its measurement by ultrasound is used increasingly to indicate visceral obesity and its clinical management.

Insights into the genetics of body size in the Bull Terrier.

The Bull Terrier (Miniature) and Bull Terrier are two varieties of a dog breed historically divided by size. We identify variety-associated chromosomal regions identified using stratified genome-wide association analysis of 69 Bull Terriers (Miniature) and 33 Bull Terriers. Next, we assess the significance of possible functional variants for body size using height (N = 1458) and weight (N = 1282) of Dog10K individuals with breed-representative metrics available.

GABA Receptor Modulation of Membrane Excitability in Human Pluripotent Stem Cell-Derived Sensory Neurons by Baclofen and α-Conotoxin Vc1.1.

GABA receptor (GABAR) activation is known to alleviate pain by reducing neuronal excitability, primarily through inhibition of high voltage-activated (HVA) calcium (Ca2.2) channels and potentiating G protein-coupled inwardly rectifying potassium (GIRK) channels. Although the analgesic properties of small molecules and peptides have been primarily tested on isolated murine dorsal root ganglion (DRG) neurons, emerging strategies to develop, study, and characterise human pluripotent stem cell (hPSC)-derived sensory neurons present a promising alternative.