Implantable Cardioverter-Defibrillators and Cardiovascular Resynchronization Therapy with Left Ventricular Assist Devices: A MOMENTUM 3 Trial Analysis.

Background: The benefit of implantable cardioverter-defibrillators (ICD) and cardiovascular resynchronization therapy (CRT-D) in patients supported with a HeartMate 3 left ventricular assist device (LVAD) remains uncertain.

Methods: An analysis of the MOMENTUM 3 randomized clinical trial and the first 1000 patients in the Continued Access Protocol trial. Patients were divided into three groups based on the presence of ICD and/or CRT-D: No device (n=153, 11%), ICD only (n=699, 50.

Embracing the Future of Clinical Trials in Radiotherapy: An NRG Oncology CIRO Technology Retreat Whitepaper on Pioneering Technologies and AI-Driven Solutions.

This white paper examines the potential of pioneering technologies and artificial intelligence (AI)-driven solutions in advancing clinical trials involving radiotherapy. As the field of radiotherapy evolves, the integration of cutting-edge approaches such as radiopharmaceutical dosimetry, FLASH radiotherapy, image-guided radiation therapy (IGRT), and AI promises to improve treatment planning, patient care, and outcomes. Additionally, recent advancements in quantum science, linear energy transfer/relative biological effect (LET/RBE), and the combination of radiotherapy and immunotherapy create new avenues for innovation in clinical trials.

Risk of carcinomas among children and adolescents with birth defects.

Background: Birth defects are associated with childhood cancer, but little is known regarding pediatric carcinomas, a group of especially rare tumors.

Methods: We used Cox proportional hazards regression to estimate the hazard ratio (HR) and 95 % confidence interval (CI) for any carcinoma, as well as thyroid, hepatocellular, and renal carcinoma specifically, up to 18 years of age among children with major, non-syndromic anomalies or chromosomal/genetic syndromes, relative to unaffected children.

Results: Our registry-linkage study included nine states and 21,933,476 children between 1990 and 2018: 641,827 with non-syndromic anomalies, and 49,619 with syndromes.

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.

Periodically poled aluminum scandium nitride bulk acoustic wave resonators and filters for communications in the 6G era.

Bulk Acoustic Wave (BAW) filters find applications in radio frequency (RF) communication systems for Wi-Fi, 3G, 4G, and 5G networks. In the beyond-5G (potential 6G) era, high-frequency bands (>8 GHz) are expected to require resonators with high-quality factor (Q) and electromechanical coupling ( ) to form filters with low insertion loss and high selectivity. However, both the Q and of resonator devices formed in traditional uniform polarization piezoelectric films of aluminum nitride (AlN) and aluminum scandium nitride (AlScN) decrease when scaled beyond 8 GHz.

Recent advances in deep learning and language models for studying the microbiome.

Recent advancements in deep learning, particularly large language models (LLMs), made a significant impact on how researchers study microbiome and metagenomics data. Microbial protein and genomic sequences, like natural languages, form a , enabling the adoption of LLMs to extract useful insights from complex microbial ecologies. In this paper, we review applications of deep learning and language models in analyzing microbiome and metagenomics data.

Mechanosensation of the heart and gut elicits hypometabolism and vigilance in mice.

Interoception broadly refers to awareness of one's internal milieu. Although the importance of the body-to-brain communication that underlies interoception is implicit, the vagal afferent signalling and corresponding brain circuits that shape perception of the viscera are not entirely clear. Here, we use mice to parse neural circuits subserving interoception of the heart and gut.

Response to induction chemotherapy modifies the effect of conventional prognostic factors in high-risk neuroblastoma: A report from the Children's Oncology Group.

Background: Response to induction chemotherapy has been shown to predict outcome in patients with high-risk neuroblastoma (HR-NB), with those achieving a complete response (CR) having superior outcomes.

Methods: We evaluated whether conventional prognostic factors remain prognostic in subsets of patients defined by response to induction. 1244 Patients from four COG high-risk trials were included.

The FBXO45-GEF-H1 axis controls germinal center formation and B-cell lymphomagenesis.

The role of ubiquitin-mediated degradation mechanisms in the pathogenesis of diffuse large B cell (DLBCL) and follicular lymphoma (FL) is not completely understood. We show that conditional deletion of the E3 ubiquitin ligase Fbxo45 in germinal center B-cells results in B-cell lymphomagenesis in homozygous (100%) and heterozygous (48%) mice. Mechanistically, FBXO45 targets the RHO guanine exchange factor ARHGEF2/GEF-H1 for ubiquitin-mediated degradation.

An Expert Consensus Statement for Implementing Cognitive Behavioral Therapy for Nightmares in Adults.

Objectives: Research supports cognitive behavioral therapies for nightmares (CBT-N) in adults. However, the nuances of implementation and unstandardized nomenclature for treatment components has created confusion in the field. To provide clarification, an expert consensus panel convened to review treatment manual components and to develop guidelines for the standardized implementation and terminology of CBT-N.

Resolving tissue complexity by multimodal spatial omics modeling with MISO.

Spatial molecular profiling has provided biomedical researchers valuable opportunities to better understand the relationship between cellular localization and tissue function. Effectively modeling multimodal spatial omics data is crucial for understanding tissue complexity and underlying biology. Furthermore, improvements in spatial resolution have led to the advent of technologies that can generate spatial molecular data with subcellular resolution, requiring the development of computationally efficient methods that can handle the resulting large-scale datasets.

A histochemical approach to activity-based copper sensing reveals cuproplasia-dependent vulnerabilities in cancer.

Copper is an essential nutrient for sustaining vital cellular processes spanning respiration, metabolism, and proliferation. However, loss of copper homeostasis, particularly misregulation of loosely bound copper ions which are defined as the labile copper pool, occurs in major diseases such as cancer, where tumor growth and metastasis have a heightened requirement for this metal. To help decipher the role of copper in the etiology of cancer, we report a histochemical activity-based sensing approach that enables systematic, high-throughput profiling of labile copper status across many cell lines in parallel.

Experimental bilayer zirconia systems after aging: Mechanical, optical, and microstructural characterization.

Objectives: To characterize two experimental zirconia bilayer materials compared to their monolithic controls, before and after hydrothermal aging.

Methods: Commercial zirconia powders were utilized to fabricate two bilayer materials: 3Y-TZP+ 5Y-PSZ (3Y+5Y/BI) and 4Y-PSZ+ 5Y-PSZ (4Y+5Y/BI), alongside control groups 3Y-TZP (3Y/C), 4Y-PSZ (4Y/C), and 5Y-PSZ (5Y/C). Compacted specimens were sintered (1550 °C- 2 h, 3 °C/min), and half of them underwent hydrothermal aging (134 °C-20h, 2.

Hydralazine inhibits cysteamine dioxygenase to treat preeclampsia and senesce glioblastoma.

The vasodilator hydralazine (HYZ) has been used clinically for ~ 70 years and remains on the World Health Organization's List of Essential Medicines as a therapy for preeclampsia. Despite its longstanding use and the concomitant progress toward a general understanding of vasodilation, the target and mechanism of HYZ have remained unknown. We show that HYZ selectively targets 2-aminoethanethiol dioxygenase (ADO) by chelating its metal cofactor and alkylating one of its ligands.

Efficacy, safety, and target engagement of dazukibart, an IFNβ specific monoclonal antibody, in adults with dermatomyositis: a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial.

Background: Dermatomyositis is a chronic autoimmune disease with distinctive cutaneous eruptions and muscle weakness, and the pathophysiology is characterised by type I interferon (IFN) dysregulation. This study aims to assess the efficacy, safety, and target engagement of dazukibart, a potent, selective, humanised IgG1 neutralising monoclonal antibody directed against IFNβ, in adults with moderate-to-severe dermatomyositis.

Methods: This multicentre, double-blind, randomised, placebo-controlled, phase 2 trial was conducted at 25 university-based hospitals and outpatient sites in Germany, Hungary, Poland, Spain, and the USA.

Novel Computational and Artificial Intelligence Models in Cancer Research.

The ICIBM 2023 marked the 11th annual conference of its kind, with the ICIBM recently becoming the official conference of the International Association for Intelligent Biology and Medicine (IAIBM), showcasing cutting-edge advancements at the intersection of computation and biomedical research [...

Multiomics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature.

Human recombination-activating gene (RAG) deficiency can manifest with distinct clinical and immunological phenotypes. By applying a multiomics approach to a large group of -mutated patients, we aimed at characterizing the immunopathology associated with each phenotype. Although defective T and B cell development is common to all phenotypes, patients with hypomorphic variants can generate T and B cells with signatures of immune dysregulation and produce autoantibodies to a broad range of self-antigens, including type I interferons.

Intelligent biology and medicine: Accelerating innovative computational approaches.

In this editorial, we summarize the 2023 International Conference on Intelligent Biology and Medicine (ICIBM 2023) conference which was held on July 16-19, 2023 in Tampa, Florida, USA. We then briefly describe the nine research articles included in this special issue. ICIBM 2023 scientific program included four tutorials and workshops, four keynote lectures, four eminent scholars' presentations, 11 concurrent scientific sessions, and a poster session.

Identification of a Subpopulation of Astrocyte Progenitor Cells in the Neonatal Subventricular Zone: Evidence that Migration is Regulated by Glutamate Signaling.

In mice engineered to express enhanced green fluorescent protein (eGFP) under the control of the entire glutamate transporter 1 (GLT1) gene, eGFP is found in all 'adult' cortical astrocytes. However, when 8.3 kilobases of the human GLT1/EAAT2 promoter is used to control expression of tdTomato (tdT), tdT is only found in a subpopulation of these eGFP-expressing astrocytes.

Functional evaluation and clinical classification of BRCA2 variants.

Germline BRCA2 loss-of function variants, which can be identified through clinical genetic testing, predispose to several cancers. However, variants of uncertain significance limit the clinical utility of test results. Thus, there is a need for functional characterization and clinical classification of all BRCA2 variants to facilitate the clinical management of individuals with these variants.

Eosinophilic Esophagitis-Related Food Impaction: Distinct Demographics, Interventions, and Promising Predictive Models.

Background: Eosinophilic esophagitis (EoE) is an increasingly common cause of food impaction.

Aims: This study aims to provide a nationwide analysis of food impaction in patients with or without EoE diagnosis, concentrating on patient demographics, interventions, outcomes, and development of predictive machine-learning models.

Methods: A retrospective assessment was conducted using Nationwide Emergency Department Sample data from January 1, 2018, to December 31, 2019.

Mortality, Hepatic Decompensation, and Cardiovascular Outcomes in Lean vs. Non-lean MASLD Cirrhosis: A Veterans Affairs Cohort Study.

Background And Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) has a global prevalence of 25%. Studies on incident liver and cardiovascular outcomes in lean (Body mass index: BMI < 25 kg/m, or < 23 kg/m for Asians) vs. non-lean individuals with MASLD have reported mixed results.