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.

An NGS approach for the identification of precise homoeologous recombination sites between A and C genomes in genus.

The introgression of heterologous genomes through interspecific hybridization offers a great opportunity to expand the gene pool of crops, thereby broadening the traits that can be targeted for improvement. The introgression of C genomic regions carrying desirable traits from (AACC) into the diploid (AA) via homoeologous recombination (HR) has been commonly used. However, the precise identification of HR sites remains a significant challenge, limiting the practical application of genome introgression via HR in breeding programs.

Gingival Debulking Surgery for a Child With Severe Aplastic Anemia: A Case Report.

Introduction: Aplastic anemia (AA) is a rare condition that frequently manifests with pancytopenia. Management of severe disease is through either allogenic stem cell transplantation or immunosuppressive therapy with supportive care. Drug-induced gingival overgrowth (DIGO) is a potential complication of a number of medications, including cyclosporine and amlodipine.

The biodiversity of ice-free Antarctica database.

Antarctica is one of Earth's most untouched, inhospitable, and poorly known regions. Although knowledge of its biodiversity has increased over recent decades, a diverse, wide-ranging, and spatially explicit compilation of the biodiversity that inhabits Antarctica's permanently ice-free areas is unavailable. This absence hinders both Antarctic biodiversity research and the integration of Antarctica in global biodiversity-related studies.

Rethinking the residual approach: leveraging statistical learning to operationalize cognitive resilience in Alzheimer's disease.

Cognitive resilience (CR) describes the phenomenon of individuals evading cognitive decline despite prominent Alzheimer's disease neuropathology. Operationalization and measurement of this latent construct is non-trivial as it cannot be directly observed. The residual approach has been widely applied to estimate CR, where the degree of resilience is estimated through a linear model's residuals.

Discourse on measurement.

Measurement literacy is required for strong scientific reasoning, effective experimental design, conceptual and empirical validation of measurement quantities, and the intelligible interpretation of error in theory construction. This discourse examines how issues in measurement are posed and resolved and addresses potential misunderstandings. Examples drawn from across the sciences are used to show that measurement literacy promotes the goals of scientific discourse and provides the necessary foundation for carving out perspectives and carrying out interventions in science.

Obsessive-compulsive symptoms in individuals with a history of eating disorders.

Background: OCD symptoms are well documented in anorexia nervosa (AN) and to a lesser extent in bulimia nervosa (BN), yet remain virtually unstudied in binge-eating disorder (BED).

Methods: In this cross-sectional observational study, 5927 participants with lifetime eating disorders (EDs) (i.e.

Vitamin D Supplementation Is Associated with Inflammation Amelioration and Cognitive Improvement in Decompensated Patients with Cirrhosis.

Decompensated cirrhosis is characterized by systemic inflammation and innate and adaptive immune dysfunction. Hepatic encephalopathy (HE) is a prevalent and debilitating condition characterized by cognitive disturbances in which ammonia and inflammation play a synergistic pathogenic role. Extraskeletal functions of vitamin D include immunomodulation, and its deficiency has been implicated in immune dysfunction and different forms of cognitive impairment.

Unraveling complexity and leveraging opportunities in uncommon breast cancer subtypes.

Special histologic subtypes of breast cancer (BC) exhibit unique phenotypes and molecular profiles with diagnostic and therapeutic implications, often differing in behavior and clinical trajectory from common BC forms. Novel methodologies, such as artificial intelligence may improve classification. Genetic predisposition plays roles in a subset of cases.

The effect of a 14-day Gymnema sylvestre intervention to reduce sugar intake in people self-identifying with a sweet tooth.

Gymnema sylvestre (GS) contains gymnemic acids which can reversibly suppress sweet taste responses. This randomised crossover study aimed to investigate whether supplemental GS use can reduce sugar cravings, sweet food desire and consumption among adults that identify as high sweet food consumers (having a 'sweet tooth'). Participants were told three different mints were trialled to avoid bias.

Sex-Specific Clinical and Genetic Factors Associated With Adverse Outcomes in Hypertrophic Cardiomyopathy.

Background: Females with hypertrophic cardiomyopathy present at a more advanced stage of the disease and have a higher risk of heart failure and death. The factors behind these differences are unclear. We aimed to investigate sex-related differences in clinical and genetic factors affecting adverse outcomes in the Sarcomeric Human Cardiomyopathy Registry.

Pooled safety analysis and management of sotorasib-related adverse events in KRAS G12C-mutated advanced non-small cell lung cancer.

Introduction: We describe the safety of sotorasib monotherapy in patients with KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC) and discuss practical recommendations for managing key risks.

Methods: Incidence rates of treatment-related adverse events (TRAEs) were pooled from 4 clinical trials: CodeBreaK 100 (NCT03600883), CodeBreaK 101 (NCT04185883), CodeBreaK 105 (NCT04380753), and CodeBreaK 200 (NCT04303780) and graded according to CTCAE v5.0.

Long-term safety and efficacy of ritlecitinib in adults and adolescents with alopecia areata and at least 25% scalp hair loss: Results from the ALLEGRO-LT phase 3, open-label study.

Background: ALLEGRO-LT is an ongoing, long-term, open-label, multicentre, phase 3 study of ritlecitinib in adults and adolescents with alopecia areata (AA).

Objectives: To evaluate ritlecitinib safety and efficacy through Month 24 in patients with AA and ≥25% scalp hair loss.

Methods: ALLEGRO-LT enrolled rollover patients who previously received study intervention in either ALLEGRO phase 2a or 2b/3 studies and de novo patients who had not received treatment in either study.

Antimicrobial stewardship: a definition with a One Health perspective.

Antimicrobial stewardship (AMS) is a commonly advocated approach to address antimicrobial resistance. However, AMS is often defined in different ways depending on where it is applied, such that a range of definitions is now in use. These definitions may be functional and well-structured for a given context but are often ill-adapted for collaborative work, creating difficulties for intersectoral communication on AMS and complicating the design, implementation, and evaluation of AMS interventions from a One Health perspective.

Genomics yields biological and phenotypic insights into bipolar disorder.

Bipolar disorder is a leading contributor to the global burden of disease. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.

Human Endogenous Retrovirus K in Astrocytes Is Altered in Parkinson's Disease.

Background: Parkinson's disease (PD) is the most common neurodegenerative movement disease. Human endogenous retroviruses (HERVs) are proviral remnants of ancient retroviral infection of germ cells that now constitute about 8% of the human genome. Under certain disease conditions, HERV genes are activated and partake in the disease process.

The genomes of the most diverse AA genome rice species provide a resource for rice improvement and studies of rice evolution and domestication.

Rice (Oryza sativa) is a staple food crop globally, with origins in wild progenitors within the AA genome group of Oryza species. Oryza rufipogon and Oryza meridionalis are native to tropical Asia and Northern Australia and offer unique genetic reservoirs. Here we explored the relationships of the genomes of these wild rice species with the domesticated rice genome.

Psychotropic Polypharmacy in Dementia: A Retrospective Analysis for People with Neuropsychiatric Symptoms Referred to an Australian Dementia Support Service.

Background And Objectives: Despite their limited benefits and serious adverse effects, psychotropics remain frequently prescribed for neuropsychiatric symptoms (NPS) of dementia. Psychotropic polypharmacy, the use of two or more concomitant psychotropic medications, is therefore not recommended for people with dementia. The objectives of this study were to investigate the prevalence of psychotropic polypharmacy in Australians living with dementia whose caregivers sought external NPS support from Dementia Support Australia (DSA; the national provider of NPS support) and the association of psychotropic polypharmacy with their demographics and NPS characteristics.

Study protocol: multi-centre, randomised controlled clinical trial exploring stromal targeting in locally advanced pancreatic cancer; STARPAC2.

Background: Pancreatic cancer (PDAC: pancreatic ductal adenocarcinoma, the commonest form), a lethal disease, is best treated with surgical excision but is feasible in less than a fifth of patients. Around a third of patients presentlocally advanced, inoperable, non-metastatic (laPDAC), whose stadrd of care is palliative chemotherapy; a small minority are down-sized sufficiently to enable surgical excision. We propose a phase II clinical trial to test whether a combination of standard chemotherapy (gemcitabine & nab-Paclitaxel: GEM-NABP) and repurposing All Trans Retinoic Acid (ATRA) to target the stroma may extend progression-free survival and enable successful surgical resection for patients with laPDAC, since data from phase IB clinical trial demonstrate safety of GEM-NABP-ATRA combination to patients with advanced PDAC with potential therapeutic benefit.

A first-in-human study of JNJ-70218902, a bispecific T-cell-redirecting antibody against TMEFF2 in metastatic castration-resistant prostate cancer.

Background: Metastatic castration-resistant prostate cancer (mCRPC) has a poor prognosis, necessitating the investigation of novel treatments and targets. This study evaluated JNJ-70218902 (JNJ-902), a T-cell redirector targeting transmembrane protein with epidermal growth factor-like and 2 follistatin-like domains 2 (TMEFF2) and cluster of differentiation 3, in mCRPC.

Patients And Methods: Patients who had measurable/evaluable mCRPC after at least one novel androgen receptor-targeted therapy or chemotherapy were eligible.

Unraveling Various Stacking Modes and Local Structures in Poly(triazine imide) Materials via Low-Dose Electron Microscopy.

Poly(triazine imide) (PTI) materials, a class of layered graphitic carbon nitrides, have garnered significant attention for their unique electronic, thermal, and catalytic properties. These properties can be adjusted through postsynthesis treatments. However, the influence of these treatments on the layer stacking modes and local structures within PTI remains largely unexplored.

Hypoxia impairs decitabine-induced expression of HLA-DR in acute myeloid leukaemia cell lines.

Background: Hypomethylating agents (HMA), such as azacytidine (AZA) and decitabine (DAC), are epigenetic therapies used to treat some patients with acute myeloid leukaemia (AML) and myelodysplastic syndrome. HMAs act in a replication-dependent manner to remove DNA methylation from the genome. However, AML cells targeted by HMA therapy are often quiescent within the bone marrow, where oxygen levels are low.

Quantitative pre-clinical imaging of hypoxia and vascularity using MRI and PET.

During hypoxia, tissues are subjected to an inadequate oxygen supply, disrupting the balance needed to maintain normal function. This deficiency can occur due to reduced oxygen delivery caused by impaired blood flow or a decline in the blood's ability to carry oxygen. In tumors, hypoxia and vascularization play crucial roles, shaping their microenvironments and influencing cancer progression, response to treatment and metastatic potential.

Dysregulation of the Kynurenine Pathway in Relapsing Remitting Multiple Sclerosis and Its Correlations With Progressive Neurodegeneration.

Background And Objectives: Despite the absence of acute lesion activity in multiple sclerosis (MS), chronic neurodegeneration continues to progress, and a potential underlying mechanism could be the kynurenine pathway (KP). Prolonged activation of the KP from chronic inflammation is known to exacerbate the progression of neurodegenerative diseases through the production of neurotoxic metabolites. Among the 8 KP metabolites, six of them, namely kynurenine (KYN), 3-hydroxylkynurenine (3HK), anthranilic acid (AA), kynurenic acid (KYNA), and quinolinic acid (QUIN), have been associated with neurodegeneration.