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.

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.

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.

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.

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.

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.

Synergizing CRISPR-Cas9 with Advanced Artificial Intelligence and Machine Learning for Precision Drug Delivery: Technological Nexus and Regulatory Insights.

The evolution of genetic exploration tools, from laborious methods like radiationinduced mutations to the transformative CRISPR-Cas9 system, has fundamentally reshaped genetic research and gene editing capabilities. This journey, initiated by foundational techniques such as ZFNs and TALENs and culminating in the groundbreaking work of Doudna and Charpentier in 2012, has ushered in an era of precise DNA alteration and profound insights into gene functions. The CRISPR/Cas9 system uses the Cas9 enzyme and guides RNA (gRNA) to precisely target and cleave DNA, with subsequent repair via error-prone NHEJ or precise HDR, enabling versatile gene editing.

Enablers and inhibitors of nursing and midwifery leadership in Pacific Island collectivist cultures.

Aim: To identify and explore inhibitors and enablers of nursing and midwifery leadership in the Pacific; to develop context-specific recommendations for policy and practice.

Background: Many Pacific Island countries experience poor health outcomes and are vulnerable to climate-related health emergencies. Nursing and midwifery leadership is essential to improve regional health outcomes through influencing policy decisions, strengthening health systems and ensuring optimal health workforce utilisation.

Australian Registered Nurse's' Awareness of Key Issues, Ambivalence and Education Related to the Health of People With Intellectual Disability and/or Autism.

Background: Health outcomes of people with Autism Spectrum Disorder and/or Intellectual Disability are poor. Yet there is a paucity of nurse education and preparation to care for people with Autism Spectrum Disorder and Intellectual Disability.

Method: A cross sectional survey of Australian Registered Nurses related to their educational experience, awareness of the national disability support scheme and the concept of making reasonable adjustments.

Can responsible leaders transmute sustainability & OCBE among manufacturers in developing economy? A mediated moderated approach for organizational sustainability.

This study examined the link among environmentally conscious organizational citizenship behavior (OCBE) and responsible leadership among 167 management-level workers in manufacturing plants of arts industry in a developing economy. The study explored the impact of responsible leadership on OCBE, both directly and indirectly through colleague exchange. It also explored the role of a green organizational environment, employee goal orientation, and supervisory support in regulating the link between coworker exchange and OCBE.

A psychometric appraisal of a revised preparedness for medication administration questionnaire in final-year undergraduate nursing students: a secondary analysis.

Background: Students must be prepared for the transference of medication administration (pharmacology knowledge and clinical skills) to clinical practice. The Preparedness for Medication Oral Administration questionnaire has been used in several studies and demonstrated strong internal reliability and consistency. The questionnaire has been revised to align with updated medication competencies.

Correlations between postmortem quantitative MRI parameters and demyelination, axonal loss and gliosis in multiple sclerosis: A systematic review and meta-analysis.

Magnetic resonance imaging (MRI) is frequently used to monitor disease progression in multiple sclerosis (MS). This study aims to systematically evaluate the correlation between MRI measures and histopathological changes, including demyelination, axonal loss, and gliosis, in the central nervous system of MS patients. We systematically reviewed post-mortem histological studies evaluating myelin density, axonal loss, and gliosis using quantitative imaging in MS.

Fear of cancer recurrence in long-term colorectal cancer survivors: a nationwide cross-sectional study.

Purpose: Knowledge about fear of cancer recurrence (FCR) among recurrence-free long-term colorectal cancer survivors (CRCS) is limited. This national cross-sectional study aimed to (1) assess the prevalence and correlates of FCR among CRCS; (2) investigate associations between colorectal cancer-specific symptoms and FCR; and (3) identify predictors of interest in engaging in FCR treatment.

Methods: We identified 9638 living Danish CRCS, age above 18 years, diagnosed between 2014 and 2018 through the Danish Clinical Registries.

An Exploration of the Interplay Between Caffeine and Antidepressants Through the Lens of Pharmacokinetics and Pharmacodynamics.

Caffeine consumption is regarded as a widespread phenomenon, and its usage has continued to increase. In addition, the growing usage of antidepressants worldwide and increase in mental health disorders were shown in recent statistical analyses conducted by the World Health Organisation. The coadministration of caffeine and antidepressants remains a concern due to potential interactions that can alter a patient's response to therapy.

Machine learning meta-analysis identifies individual characteristics moderating cognitive intervention efficacy for anxiety and depression symptoms.

Cognitive training is a promising intervention for psychological distress; however, its effectiveness has yielded inconsistent outcomes across studies. This research is a pre-registered individual-level meta-analysis to identify factors contributing to cognitive training efficacy for anxiety and depression symptoms. Machine learning methods, alongside traditional statistical approaches, were employed to analyze 22 datasets with 1544 participants who underwent working memory training, attention bias modification, interpretation bias modification, or inhibitory control training.

International myeloma working group immunotherapy committee recommendation on sequencing immunotherapy for treatment of multiple myeloma.

T-cell redirecting therapy (TCRT), specifically chimeric antigen receptor T-cell therapy (CAR T-cells) and bispecific T-cell engagers (TCEs) represent a remarkable advance in the treatment of multiple myeloma (MM). There are several products available around the world and several more in development targeting primarily B-cell maturation antigen (BCMA) and G protein-coupled receptor class C group 5 member D (GRPC5D). The relatively rapid availability of multiple immunotherapies brings the necessity to understand how a certain agent may affect the safety and efficacy of a subsequent immunotherapy so MM physicians and patients can aim at optimal sequential use of these therapies.

A High Fat, High Sugar Diet Exacerbates Persistent Post-Surgical Pain and Modifies the Brain-Microbiota-Gut Axis in Adolescent Rats.

Persistent post-surgical pain (PPSP) occurs in a proportion of patients following surgical interventions. Research suggests that specific microbiome components are important for brain development and function, with recent studies demonstrating that chronic pain results in changes to the microbiome. Consumption of a high fat, high sugar (HFHS) diet can drastically alter composition of the microbiome and is a modifiable risk factor for many neuroinflammatory conditions.

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.

Interactive segmentation for accurately isolating metastatic lesions from low-resolution, large-size bone scintigrams.

Bone is a common site for the metastasis of malignant tumors, and Single Photon Emission Computed Tomography (SPECT) is widely used to detect these metastases. Accurate delineation of metastatic bone lesions in SPECT images is essential for developing treatment plans. However, current clinical practices rely on manual delineation by physicians, which is prone to variability and subjective interpretation.

TractGraphFormer: Anatomically informed hybrid graph CNN-transformer network for interpretable sex and age prediction from diffusion MRI tractography.

The relationship between brain connections and non-imaging phenotypes is increasingly studied using deep neural networks. However, the local and global properties of the brain's white matter networks are often overlooked in convolutional network design. We introduce TractGraphFormer, a hybrid Graph CNN-Transformer deep learning framework tailored for diffusion MRI tractography.