Evolutionary and Structural Insights into the RNA Polymerase I A34 Protein Family: A Focus on Intrinsic Disorder and Phase Separation.

Background: Eukaryotic RNA polymerase I consists of 12 or 11 core subunits and three dissociable subunits, Rrn3, A34, and A49. The A34 and A49 subunits exist as a heterodimer. In silico analysis of the A34 family of transcription factors demonstrates a commonly shared domain structure despite a lack of sequence conservation, as well as N-terminal and C-terminal disordered regions.

Understanding the Impact of Obesity on Liver Transplant Outcomes: A Comprehensive Analysis.

Background: The purpose of this investigation is to assess how effective it is to exclude individuals from the liver transplant (LT) using the body mass index (BMI) as a criterion.

Methods And Materials: A retrospective longitudinal analysis of patients with liver transplant outcomes from January 2001 to May 2020 was conducted using the United Network for Organ Sharing (UNOS) database.

Results: A total of 118,486 LT cases included in the study.

A Call for a Neoadjuvant Kidney Cancer Consortium: Lessons Learned from Other Cancer Types.

Neoadjuvant systemic treatment strategies have improved outcomes in several solid tumour types. This success has not yet been replicated in renal cell carcinoma (RCC). A consensus and international collaboration are urgently needed for the development of adaptive perioperative immunotherapy strategies for patients with RCC at high risk of recurrence.

Prevalence of Autoimmune Diseases in Patients Treated With Immune Checkpoint Inhibitors: An Epidemiological Study Using A Global Network of Health Care Organizations.

Objective: Evaluate prevalence of new onset autoimmune conditions (ACs) after commencement of immune checkpoint inhibitors (ICIs).

Methods: This retrospective observational study was done using TriNetX. Patients with neoplasm for which ICIs were approved were stratified into two groups based on ICI use.

The Role of WDR77 in Cancer: More Than a PRMT5 Interactor.

WD repeat domain 77 protein (WDR77), a WD-40 domain-containing protein, is a crucial regulator of cellular pathways in cancer progression. While much of the past research on WDR77 has focused on its interaction with PRMT5 in histone methylation, WDR77's regulatory functions extend beyond this pathway, influencing diverse mechanisms such as mRNA translation, chromatin assembly, cell cycle regulation, and apoptosis. WDR77 is a key regulator of cell cycle progression, regulating the transition from the G1 phase.

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.

Aminocholestane and Aminoandrostane Inhibitors of the SH2 Domain-Containing Inositol 5'-Phosphatase (SHIP).

The SH2-containing inositol phosphatase (SHIP) has become an actively researched therapeutic target for a number of disorders, including Alzheimer's Disease, Graft-vs-Host disease, obesity and cancer. Analogs of the aminosteroid SHIP inhibitor 3a-aminocholestane (3AC) have been synthesized and tested. Analogs with improved water solubility have been identified.

Psychiatric, Neurological, and Somatic Comorbidities in Intermittent Explosive Disorder.

Importance: Intermittent explosive disorder (IED) is an understudied psychiatric condition marked by impulsive aggression and poorly regulated emotional control, often resulting in interpersonal and societal consequences. Better understanding of comorbidities can improve screening, diagnosis, and treatment.

Objective: To investigate the prevalence of IED and its associations with psychiatric, neurological, and somatic disorders.

Impact of cell plasticity on prostate tumor heterogeneity and therapeutic response.

Epithelial-mesenchymal transition (EMT) is a dynamic process of lineage plasticity in which epithelial cancer cells acquire mesenchymal traits, enabling them to metastasize to distant organs. This review explores the current understanding of how lineage plasticity and phenotypic reprogramming drive prostate cancer progression to lethal stages, contribute to therapeutic resistance, and highlight strategies to overcome the EMT phenotype within the prostate tumor microenvironment (TME). Emerging evidence reveals that prostate tumor cells can undergo lineage switching, adopting alternative growth pathways in response to anti-androgen therapies and taxane-based chemotherapy.

The Impact of Learning Curve on Robotic Living Donor Nephrectomy Outcomes: Retrospective Analysis.

Background: We aimed to investigate the outcome of patients after RDN at different time points.

Methods: We studied the outcomes of 77 living robotic living donor nephrectomies (RDN). Donors were separated into three groups: learning curve period (LCP), stabilisation period (SP), and teaching period (TP).

Assessment and Reporting of Extraintestinal Manifestations and Fatigue in Phase 3 Inflammatory Bowel Disease Clinical Trials.

Background: Extraintestinal Manifestations (EIMs) of Inflammatory Bowel Disease (IBD) are frequently experienced by patients and may lead to severe symptoms and fatigue. However, the reporting patterns of these outcomes in IBD randomized controlled trials (RCTs) is not clear.

Methods: We searched placebo controlled phase 3 RCTs of advanced therapies in IBD and assessed the frequency and means of reporting EIM and fatigue data in these studies.

Reviewing manuscripts for scientific journals: recommendations for early career scientists.

Publication of articles in international scientific journals has been one of the main strategies for the communication of scientific findings and ideas. Prepublication peer review is a fundamental aspect of the publishing process in indexed scientific journals and, associated with the large growth in journals and articles, there has been a recent challenge in having adequate peer reviewers for international journals. In this article, we provide a short overview of the publishing process, give recommendations to early career researchers about writing peer reviews of adequate quality, and discuss some possibilities for the future.

Neurons Are Not All the Same: Diversity in Neuronal Populations and Their Intrinsic Responses to Spinal Cord Injury.

Functional recovery following spinal cord injury will require the regeneration and repair of damaged neuronal pathways. It is well known that the tissue response to injury involves inflammation and the formation of a glial scar at the lesion site, which significantly impairs the capacity for neuronal regeneration and functional recovery. There are initial attempts by both supraspinal and intraspinal neurons to regenerate damaged axons, often influenced by the neighboring tissue pathology.

The impact of mental health disorders on outcomes following total ankle arthroplasty: A systematic review.

Background: The purpose of this systematic review was to evaluate the impact of mental health disorders (MHDs) on the clinical and functional outcomes following total ankle arthroplasty (TAA) for the treatment of end-stage ankle arthritis.

Methods: A systematic review of the EMBASE, MEDLINE, and Cochrane Library databases was conducted in April 2024 following PRISMA guidelines. Data collected included patient demographics, clinical outcomes, complications, and failures.

V-ATPase Disassembly at the Yeast Lysosome-Like Vacuole Is a Phenotypic Driver of Lysosome Dysfunction in Replicative Aging.

Declines in lysosomal acidification and function with aging are observed in organisms ranging from yeast to humans. V-ATPases play a central role in organelle acidification, and V-ATPase activity is regulated by reversible disassembly in many different settings. Using the yeast Saccharomyces cerevisiae as a replicative aging model, we demonstrate that V-ATPases disassemble into their V and V subcomplexes in aging cells, with release of V subunit C (Vma5) from the lysosome-like vacuole into the cytosol.

Meconium Influences Pulmonary Short-Chain Fatty Acid Concentration in Porcine Meconium Aspiration Model.

Introduction: The factors influencing meconium aspiration syndrome (MAS) severity remain poorly understood. In a piglet model of MAS, we hypothesized the respiratory microbiome would reflect the bacterial signature of meconium with short-chain fatty acid (SCFA) accumulation as a byproduct of bacterial fermentation.

Methods: Cesarean section at approximately 115-day term was performed on two sows.

Best Interests and Decisions to Withdraw Life-Sustaining Treatment from a Conscious, Incapacitated Patient.

Conscious but incapacitated patients need protection from both undertreatment and overtreatment, for they are exceptionally vulnerable, and dependent on others to act in their interests. In the United States, the law prioritizes autonomy over best interests in decision making. Yet U.

Identification of Behavioral, Clinical, and Psychological Antecedents of Acute Stimulant Poisoning: Development and Implementation of a Mixed Methods Psychological Autopsy Study.

Background: Despite increasing fatal stimulant poisoning in the United States, little is understood about the mechanism of death. The psychological autopsy (PA) has long been used to distinguish the manner of death in equivocal cases, including opioid overdose, but has not been used to explicitly explore stimulant mortality.

Objective: We aimed to develop and implement a large PA study to identify antecedents of fatal stimulant poisoning, seeking to maximize data gathering and ethical interactions during the collateral interviews.

Mechanistic implications of the Mediterranean diet in patients with newly diagnosed Crohn's disease- multi-omic results from a prospective cohort.

Background: To decipher the mechanisms underlying the protective role of the Mediterranean diet (MED) in Crohn's disease (CD), we explored the implications of adherence to MED on CD course, inflammatory markers, microbial and metabolite composition.

Methods: Patients with newly diagnosed CD were recruited and followed prospectively. MED adherence was assessed by repeated food frequency questionnaires (FFQ), using a predefined IBDMED score, alongside validated MED adherence screeners.