Smart Imitator: Learning from Imperfect Clinical Decisions.

Objectives: This study introduces Smart Imitator (SI), a 2-phase reinforcement learning (RL) solution enhancing personalized treatment policies in healthcare, addressing challenges from imperfect clinician data and complex environments.

Materials And Methods: Smart Imitator's first phase uses adversarial cooperative imitation learning with a novel sample selection schema to categorize clinician policies from optimal to nonoptimal. The second phase creates a parameterized reward function to guide the learning of superior treatment policies through RL.

Treatment of very high risk membranous nephropathy complicated by pulmonary embolism with glucocorticoids and rituximab: Case report.

Rationale: We report the efficacy of combination prednisolone and intravenous (IV) rituximab as an immunosuppressive regimen for a young male presenting with extensive venous thromboembolism including a submassive pulmonary embolism secondary to life-threatening nephrotic syndrome from very high risk anti-phospholipase-A2 receptor (PLA2R) positive membranous nephropathy. Initial treatment was with mechanical thrombectomy and anticoagulation. Thereafter, oral prednisolone was initiated to induce remission, during a period of uninterrupted anticoagulation.

Sequential Targeting Chondroitin Sulfate-Bilirubin Nanomedicine Attenuates Osteoarthritis via Reprogramming Lipid Metabolism in M1 Macrophages.

The infiltration and excessive polarization of M1 macrophages contribute to the induction and persistence of low-grade inflammation in joint-related degenerative diseases such as osteoarthritis (OA). The lipid metabolism dysregulation promotes M1 macrophage polarization by coordinating the compensatory pathways of the inflammatory and oxidative stress responses. Here, a self-assembling, licofelone-loaded nanoparticle (termed LCF-CSBN), comprising chondroitin sulfate and bilirubin joined by an ethylenediamine linker, is developed to selectively reprogram lipid metabolism in macrophage activation.

Whole-genome phylogenetic analysis of complex from clinical respiratory samples.

Unlabelled: The complex (MAC) is a common causative agent causing nontuberculous mycobacterial (NTM) pulmonary disease worldwide. Whole-genome sequencing was performed on a total of 203 retrospective MAC isolates from respiratory specimens. Phylogenomic analysis identified eight subspecies and species.

Remission of persistent hypertension and hypokalaemia following redo adrenalectomy for primary aldosteronism - case report.

We report on a case of a 67-year-old male who was referred to our care with persistent aldosteronism post adrenalectomy. Biochemical failure after surgery is rare after surgery for primary aldosteronism (PA). Persistent hypokalaemia and raised aldosteronism is an indication of treatment failure after surgery.

[The mediational role of cognitive function on occupational outcomes in persons with major depressive and bipolar disorder].

Background: Improving functioning in adults with major depressive disorder (MDD) and bipolar disorder (BD) is a priority therapeutic objective.

Methods: This retrospective post hoc secondary analysis evaluated 108 patients with MDD or BD receiving the antidepressants vortioxetine, ketamine, or infliximab. The analysis aimed to determine if changes in objective or subjective cognitive function mediated the relationship between depression symptom severity and workplace outcomes.

Factors Associated With Mental Health Literacy, Depression, and Anxiety Amongst Indonesian Adolescents.

Aims: This study aims to identify factors associated with mental health literacy (mental health knowledge and attitudes towards mental health and help-seeking behaviours), depression and anxiety amongst adolescents, and test the hypothesised model by examining the interrelationships between these outcomes.

Design: Cross-sectional descriptive quantitative research.

Methods: Using convenient sampling, 615 adolescents from four public schools completed online questionnaires measuring mental health literacy, depression, and anxiety.

Formation of I+III supercomplex rescues respiratory chain defects.

Mitochondrial electron transport chain (ETC) complexes partition between free complexes and quaternary assemblies known as supercomplexes (SCs). However, the physiological requirement for SCs and the mechanisms regulating their formation remain controversial. Here, we show that genetic perturbations in mammalian ETC complex III (CIII) biogenesis stimulate the formation of a specialized extra-large SC (SC-XL) with a structure of I+III, resolved at 3.

Right Ventricular Injury Definition and Management in Veno-Venous Extracorporeal Membrane Oxygenation.

Right ventricular injury (RVI) in respiratory failure receiving veno-venous extracorporeal membrane oxygenation (VV ECMO) is associated with significant mortality. A scoping review is necessary to map the current literature and guide future research regarding the definition and management of RVI in patients receiving VV ECMO. We searched for relevant publications on RVI in patients receiving VV ECMO in Medline, EMBASE, and Web of Science.

Outcomes of Endoscopic versus Microscopic Ossicular Chain Reconstruction-A Systematic Review and Meta-analysis.

Objective: The efficacy of the transcanal endoscopic approach in tympanoplasty, cholesteatoma removal, and stapedotomy is detailed. This study reviews evidence on the feasibility of endoscopic ossiculoplasty as a suitable alternative to traditional microscopic ossiculoplasty.

Data Sources: PubMed, Embase, and Cochrane Library were searched from inception to 19 June 2024 for articles comparing endoscopic and microscopic ossicular chain reconstruction.

Heritable polygenic editing: the next frontier in genomic medicine?

Polygenic genome editing in human embryos and germ cells is predicted to become feasible in the next three decades. Several recent books and academic papers have outlined the ethical concerns raised by germline genome editing and the opportunities that it may present. To date, no attempts have been made to predict the consequences of altering specific variants associated with polygenic diseases.

Prevalence and risk factors of myopic macular degeneration: the Aier-SERI high myopia adult cohort.

Purpose: To assess the prevalence and risk factors of myopic macular degeneration (MMD) in young and middle-aged individuals with high myopia in Changsha, central China.

Methods: A total of 445 adults with high myopia (worse than or equal to -5.0 D) were examined between 2021 and 2023.

Coordination of Focal Adhesion Nanoarchitecture and Dynamics in Mechanosensing for Cardiomyoblast Differentiation.

Focal adhesions (FAs) are force-bearing multiprotein complexes, whose nanoscale organization and signaling are essential for cell growth and differentiation. However, the specific organization of FA components to exert spatiotemporal activation of FA proteins for force sensing and transduction remains unclear. In this study, we unveil the intricacies of FA protein nanoarchitecture and that its dynamics are coordinated by a molecular scaffold protein, BNIP-2, to initiate downstream signal transduction for cardiomyoblast differentiation.

Mortality of gastrointestinal cancers attributable to smoking, alcohol, and metabolic risk factors, and its association with socioeconomic development status 2000-2021: GI Cancer Mortality and Risk Factors.

Objective: Gastrointestinal (GI) cancers account for one-third of global cancer mortality, with nearly half being preventable. This study updates the global burden of GI cancers attributed to major risk factors: smoking, alcohol, and metabolic disturbances.

Methods: We utilized data from the Global Burden of Disease Study 2021 to examine trends in death and age-standardized death rates related to GI cancers caused by smoking, alcohol, high body mass index (BMI), and high fasting blood glucose (FBG) from 2000 to 2021.

Body Composition in Adults Born at Very Low Birthweight-A Sibling Study.

Background: Individuals born preterm at very low birthweight (VLBW, < 1500 g) tend to attain a smaller adult body size compared with term-born peers but less is known regarding specific body composition characteristics.

Objectives: We aimed to assess whether adults born at VLBW have less beneficial body composition characteristics, potentially mediating the association between VLBW birth and cardiometabolic disease. Sibling controls were used to account for the potential influence of shared genetic and/or lifestyle factors.

Identification and monitoring of cell heterogeneity from plasmid recombination during limonene production.

Detecting alterations in plasmid structures is often performed using conventional molecular biology. However, these methods are laborious and time-consuming for studying the conditions inducing these mutations, which prevent real-time access to cell heterogeneity during bioproduction. In this work, we propose combining both flow cytometry and fluorescence-activated cell sorting, integrated with mechanistic modelling to study conditions that lead to plasmid recombination using a limonene-producing microbial system as a case study.

Aqueous Proteomic and Metabolomic Profiles in Low-Energy vs High-Energy Femtosecond Laser-Assisted Cataract Surgery.

Purpose: To investigate the aqueous proteomics and metabolomics in low-energy and high-energy femtosecond laser-assisted cataract surgery (FLACS).

Methods: In this prospective observational study, 72 patients were randomized to 3 groups: low-energy FLACS, high-energy FLACS, and conventional phacoemulsification (controls). Aqueous was collected after femtosecond laser treatment or at the beginning of surgery (controls).

Spatially Resolved Tumor Ecosystems and Cell States in Gastric Adenocarcinoma Progression and Evolution.

Gastric cancer (GC) is a major cause of global cancer mortality with high levels of heterogeneity. To explore geospatial interactions in tumor ecosystems, we integrated 2,138 spatial transcriptomic regions-of-interest (ROIs) with 152,423 single-cell expression profiles across 226 GC samples from 121 patients. We observed pervasive expression-based intratumor heterogeneity, recapitulating tumor progression through spatially localized and functionally ordered subgroups associated with specific immune microenvironments, checkpoint profiles, and genetic drivers such as SOX9.

Sociobiology meets oncology: unraveling altruistic cooperation in cancer cells and its implications.

Altruism, an act of benefiting others at a cost to the self, challenges our understanding of evolution. This Perspective delves into the importance of altruism in cancer cells and its implications for therapy. Against the backdrop of existing knowledge on various social organisms found in nature, we explore the mechanisms underlying the manifestation of altruism within breast tumors, revealing a complex interplay of seemingly counteracting cancer signaling pathways and processes that orchestrate the delicate balance between cost and benefit underlying altruistic cooperation.

Increased MASH-associated liver cancer in younger demographics.

Background: The incidence of cancer and the prevalence of metabolic disease and metabolic dysfunction-associated steatotic liver disease is increasing in young adults. However, updated global data on metabolic dysfunction-associated steatohepatitis (MASH)-associated primary liver cancer (PLC) in young adults remains scarce.

Methods: This study analyzed data from the Global Burden of Disease study between 2000 and 2021 to assess the age-standardized incidence, mortality, and disability-adjusted life years rates from MASH-associated PLC in young adults (15-49 y).

Antiscience, Vaccine Hesitancy, and Pandemic Responses: Highlights from the Asia Pacific Summit on Infectious Diseases and Immunization.

The recent resurgence of mpox highlights the urgent need for rethinking vaccination strategies globally, underscored by the painful memories of past public health crises where delayed responses and inequitable vaccine distribution exacerbated the spread of infectious diseases. The inaugural APIC-ADVA Asia Pacific Summit on Infectious Diseases and Immunization, themed "Vaccination for All: Access, Confidence and Equity (ACE)", was held in Singapore from 31 October to 1 November 2023 in an attempt to present best practices and hard-won insights from battling COVID-19 and other pandemics in the Asia-Pacific region. This summit was co-convened by the Asia-Pacific Immunization Coalition (APIC) and Asia Dengue Voice and Action (ADVA).

Development and Pragmatic Randomized Controlled Trial of Healthy Ketogenic Diet Versus Energy-Restricted Diet on Weight Loss in Adults with Obesity.

: The ketogenic diet (KD) is widely used for weight management by reducing appetite, enhancing fat oxidation, and facilitating weight loss. However, the high content of total and saturated fats in a conventional KD may elevate low-density lipoprotein (LDL)-cholesterol levels, a known risk factor for cardiovascular diseases, highlighting the need for healthier alternatives. This study aimed to investigate the effect of a newly developed Healthy Ketogenic Diet (HKD) versus an Energy-Restricted Diet (ERD) on weight loss and metabolic outcomes among adults with obesity.

A Comparison of Three Automated Nucleic Acid Extraction Systems for Human Stool Samples.

Automated nucleic acid extractors are useful instruments for the high-throughput processing of bio-samples and are expected to improve research throughput in addition to decreased inter-sample variability inherent to manual processing. We evaluated three commercial nucleic acid extractors Bioer GenePure Pro (Bioer Technology, Hangzhou, China), Maxwell RSC 16 (Promega Corporation, Madison, WI, USA), and KingFisher Apex (ThermoFisher Scientific, Waltham, MA, USA) based on their DNA yield, DNA purity, and 16S rRNA gene amplicon results using both human fecal samples and a mock community (ZymoBIOMICS Microbial Community Standard (Zymo Research Corp., Irvine, CA, USA)).

Loss of Glutathione-S-Transferase Theta 2 (GSTT2) Modulates the Tumor Microenvironment and Response to BCG Immunotherapy in a Murine Orthotopic Model of Bladder Cancer.

Loss of the glutathione-S-transferases Theta 2 (Gstt2) expression is associated with an improved response to intravesical , Bacillus Calmette-Guérin (BCG) immunotherapy for non-muscle-invasive bladder cancer (NMIBC) patients who receive fewer BCG instillations. To delineate the cause, Gstt2 knockout (KO) and wildtype (WT) C57Bl/6J mice were implanted with tumors before treatment with BCG or saline. RNA was analyzed via single-cell RNA sequencing (scRNA-seq) and real-time polymerase chain reaction (RT-PCR).