Evaluating generalizability of oncology trial results to real-world patients using machine learning-based trial emulations.

Randomized controlled trials (RCTs) evaluating anti-cancer agents often lack generalizability to real-world oncology patients. Although restrictive eligibility criteria contribute to this issue, the role of selection bias related to prognostic risk remains unclear. In this study, we developed TrialTranslator, a framework designed to systematically evaluate the generalizability of RCTs for oncology therapies.

Large floods drive changes in cause-specific mortality in the United States.

Flooding greatly endangers public health and is an urgent concern as rapid population growth in flood-prone regions and more extreme weather events will increase the number of people at risk. However, an exhaustive analysis of mortality following floods has not been conducted. Here we used 35.

Examination of hierarchical form perception in African grey parrots (Psittacus erithacus).

The perception of objects is a challenging task that requires recognizing visual elements and integrating them into a whole. While human vision prioritizes attention to the overall configuration, data from other species suggests this bias towards global form perception is not universal. Studies with pigeons indicate preferential attention to local details when both local and global information may be diagnostic, but studies with other bird species are more limited.

The Impact of Addiction Consultation and Medication for Opioid or Alcohol Use Disorder on Hospital Readmission.

Background: Patients with substance use disorder (SUD) are frequently hospitalized and readmitted. Hospitalization is an opportunity for treatment initiation, including medications for alcohol (MAUD) and opioid use disorder (MOUD). Addiction consult teams are one model for increasing hospital-based SUD treatment.

Refining breast cancer genetic risk and biology through multi-ancestry fine-mapping analyses of 192 risk regions.

Genome-wide association studies have identified approximately 200 genetic risk loci for breast cancer, but the causal variants and target genes are mostly unknown. We sought to fine-map all known breast cancer risk loci using genome-wide association study data from 172,737 female breast cancer cases and 242,009 controls of African, Asian and European ancestry. We identified 332 independent association signals for breast cancer risk, including 131 signals not reported previously, and for 50 of them, we narrowed the credible causal variants down to a single variant.

Blood DNA virome associates with autoimmune diseases and COVID-19.

Aberrant immune responses to viral pathogens contribute to pathogenesis, but our understanding of pathological immune responses caused by viruses within the human virome, especially at a population scale, remains limited. We analyzed whole-genome sequencing datasets of 6,321 Japanese individuals, including patients with autoimmune diseases (psoriasis vulgaris, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), pulmonary alveolar proteinosis (PAP) or multiple sclerosis) and coronavirus disease 2019 (COVID-19), or healthy controls. We systematically quantified two constituents of the blood DNA virome, endogenous HHV-6 (eHHV-6) and anellovirus.

ZIC1 is a context-dependent medulloblastoma driver in the rhombic lip.

Transcription factors are frequent cancer driver genes, exhibiting noted specificity based on the precise cell of origin. We demonstrate that ZIC1 exhibits loss-of-function (LOF) somatic events in group 4 (G4) medulloblastoma through recurrent point mutations, subchromosomal deletions and mono-allelic epigenetic repression (60% of G4 medulloblastoma). In contrast, highly similar SHH medulloblastoma exhibits distinct and diametrically opposed gain-of-function mutations and copy number gains (20% of SHH medulloblastoma).

The Complex Relationship Between Cannabis Use and Mental Health: Considering the Influence of Cannabis Use Patterns and Individual Factors.

The relationship between cannabis use and mental health is complex, as studies often report seemingly contradictory findings regarding whether cannabis use results in more positive or negative treatment outcomes. With an increasing number of individuals using cannabis for both recreational (i.e.

A review of deep learning for brain tumor analysis in MRI.

Recent progress in deep learning (DL) is producing a new generation of tools across numerous clinical applications. Within the analysis of brain tumors in magnetic resonance imaging, DL finds applications in tumor segmentation, quantification, and classification. It facilitates objective and reproducible measurements crucial for diagnosis, treatment planning, and disease monitoring.

Deeper response predicts better outcomes in high-risk-smoldering-myeloma: results of the I-PRISM phase II clinical trial.

Early therapeutic intervention in high-risk smoldering multiple myeloma (HR-SMM) has shown benefits, however, no studies have assessed whether biochemical progression or response depth predicts long-term outcomes. The single-arm I-PRISM phase II trial (NCT02916771) evaluated ixazomib, lenalidomide, and dexamethasone in 55 patients with HR-SMM. The primary endpoint, median progression-free survival (PFS), was not reached (NR) (95% CI: 57.

Outcomes of venous sinus stenosis stenting in patients with pulsatile tinnitus and sigmoid sinus wall anomalies.

Background: Transverse sinus stenosis (TSS) and sigmoid sinus wall anomalies (SSWAs) are the most common causes of pulsatile tinnitus (PT). While these conditions may co-occur, they usually require different management approaches. This study aims to evaluate whether TSS stenting alone, without targeted treatment of SSWAs, is sufficient to resolve PT in patients presenting with PT, TSS, and SSWAs.

Comparative analysis of injuries related to self-harm, assault, and intimate partner violence: insights from U.S. Emergency Departments (2005-2021).

Background: Emergency departments are on the front lines of non-fatal self-harm injury (SHI). This study identifies patterns in patients presenting to emergency departments with SHI compared with patients presenting with assault and intimate partner violence.

Methods: Using the National Electronic Injury Surveillance System All Injury Program database, we analyzed SHI cases in the emergency department from 2005 to 2021 and examined demographic characteristics, injury mechanism and anatomic location, emergency department disposition and temporal patterns relative to cases involving assault and intimate partner violence.

Participant perspectives related to individual chemical exposure report-back approaches in three environmental health studies.

Returning results to participants of environmental exposure studies has become more common in recent years. Despite evidence of benefits for study participants, there are challenges in communicating results to people with limited resources or capacity to mitigate chemical exposures. We interviewed N=54 participants and compared exposure report-back conducted in 2010-2013 across three susceptible study populations: 1) low-income pregnant individuals in the Chemicals in Our Bodies (CIOB) study; 2) the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) cohort; and 3) early childhood educators (ECE).

Classification of non-TCGA cancer samples to TCGA molecular subtypes using compact feature sets.

Molecular subtypes, such as defined by The Cancer Genome Atlas (TCGA), delineate a cancer's underlying biology, bringing hope to inform a patient's prognosis and treatment plan. However, most approaches used in the discovery of subtypes are not suitable for assigning subtype labels to new cancer specimens from other studies or clinical trials. Here, we address this barrier by applying five different machine learning approaches to multi-omic data from 8,791 TCGA tumor samples comprising 106 subtypes from 26 different cancer cohorts to build models based upon small numbers of features that can classify new samples into previously defined TCGA molecular subtypes-a step toward molecular subtype application in the clinic.

Development of an FKBP12-recruiting chemical-induced proximity DNA-encoded library and its application to discover an autophagy potentiator.

Chemical inducers of proximity (CIPs) are molecules that recruit one protein to another and introduce new functionalities toward modulating protein states and activities. While CIP-mediated recruitment of E3 ligases is widely exploited for the development of degraders, other therapeutic modalities remain underexplored. We describe a non-degrader CIP-DNA-encoded library (CIP-DEL) that recruits FKBP12 to target proteins using non-traditional acyclic structures, with an emphasis on introducing stereochemically diverse and rigid connectors to attach the combinatorial library.

CIROZ is dispensable in ancestral vertebrates but essential for left-right patterning in humans.

Four genes-DAND5, PKD1L1, MMP21, and CIROP-form a genetic module that has specifically evolved in vertebrate species that harbor motile cilia in their left-right organizer (LRO). We find here that CIROZ (previously known as C1orf127) is also specifically expressed in the LRO of mice, frogs, and fish, where it encodes a protein with a signal peptide followed by 3 zona pellucida N domains, consistent with extracellular localization. We report 16 individuals from 10 families with bi-allelic CIROZ inactivation variants, which cause heterotaxy with congenital heart defects.

Characteristics Associated With Early Ileocolonic Resection in Pediatric Crohn's Disease.

Introduction: Pediatric-onset Crohn's disease (CD) has a more severe phenotype than adult-onset, and nearly one-third of pediatric CD patients will require surgical therapy. There is limited data on patient/disease characteristics that are associated with earlier surgical management.

Methods: All pediatric CD patients (<22 yrs) who underwent ileocolectomy from 2005 to 2021 were included.

Chaperone-mediated insertion of mitochondrial import receptor TOM70 protects against diet-induced obesity.

Outer mitochondrial membrane (OMM) proteins communicate with the cytosol and other organelles, including the endoplasmic reticulum. This communication is important in thermogenic adipocytes to increase the energy expenditure that controls body temperature and weight. However, the regulatory mechanisms of OMM protein insertion are poorly understood.

Complement classical and alternative pathway activation contributes to diabetic kidney disease progression: a glomerular proteomics on kidney biopsies.

Increasing evidence points toward an essential role for complement activation in the pathogenesis of diabetic kidney disease (DKD). However, the precise molecular mechanisms remain unclear, and the pathway predominantly contributing to complement activation in DKD is of particular interest. In this study, the glomerular proteome, especially the profiles of the complement proteins, was analyzed in kidney biopsies from 40 DKD patients and 10 normal controls using laser microdissection-assisted liquid chromatography-tandem mass spectrometry (LMD-LC-MS/MS).