Association of serum chloride levels with all-cause mortality among patients in surgical intensive care units: a retrospective analysis of the MIMIC-IV database.

This study explores the association between serum chloride concentrations and all-cause mortality among patients in the Surgical Intensive Care Unit (SICU). Employing a retrospective cohort design, the study utilized data extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, specifically focusing on individuals admitted to the surgical/trauma ICUs. This dataset encompassed demographic profiles, laboratory findings, historical medical data, vital statistics, and variables pertinent to prognosis.

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.

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).

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.

Localized In Vivo Prodrug Activation Using Radionuclides.

Radionuclides used for imaging and therapy can show high molecular specificity in the body with appropriate targeting ligands. We hypothesized that local energy delivered by molecularly targeted radionuclides could chemically activate prodrugs at disease sites while avoiding activation in off-target sites of toxicity. As proof of principle, we tested whether this strategy of radionuclide-induced drug engagement for release (RAiDER) could locally deliver combined radiation and chemotherapy to maximize tumor cytotoxicity while minimizing off-target exposure to activated chemotherapy.

Fast EEG/MEG BEM-Based Forward Problem Solution for High-Resolution Head Models.

A fast BEM (boundary element method) based approach is developed to solve an EEG/MEG forward problem for a modern high-resolution head model. The method utilizes a charge-based BEM accelerated by the fast multipole method (BEM-FMM) with an adaptive mesh pre-refinement method (called b-refinement) close to the singular dipole source(s). No costly matrix-filling or direct solution steps typical for the standard BEM are required; the method generates on-skin voltages as well as MEG magnetic fields for high-resolution head models within 90 seconds after initial model assembly using a regular workstation.

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.

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.

Neural regulation of pain anticipation is associated with mindful behavior change in patients with anxiety or depression: A pilot study.

Behavior change often requires overcoming discomfort or difficult emotions. Emotional dysregulation associated with anxiety or depression may prevent behavior change initiation among people managing chronic illness. Mindfulness training may catalyze chronic disease self-management by reducing experiential avoidance of aversive experiences that act as barriers to change initiation.

Comparative Analysis of Intracranial Response Assessment Criteria in Patients With Melanoma Brain Metastases Treated With Combination Nivolumab + Ipilimumab in CheckMate 204.

Purpose: In CheckMate 204, nivolumab + ipilimumab showed high intracranial (IC) objective response rates (icORRs) in patients with melanoma brain metastases (MBMs). Using icORR as a surrogate for overall survival (OS) has prompted use of alternate response criteria. To set the stage for harmonized MBM trials, the aim of this exploratory analysis was to determine icORR using several response criteria and examine correlations of response with survival.

Exploratory analysis of gait mechanics in farmers.

Farmers may be at a higher risk of developing hip osteoarthritis (OA) due to the high demands of their occupation. To the authors' knowledge, the gait patterns of farmers that may be associated with hip joint degeneration have yet to be analyzed. Therefore, this study compares gait mechanics between farmers and non-farmers (controls).

The American Clinical Neurophysiology Society Guideline on Indications for Continuous Electroencephalography Monitoring in Neonates.

Purpose: Continuous EEG (cEEG) monitoring is increasingly used in the management of neonates with seizures. There remains debate on what clinically relevant information can be gained from cEEG in neonates with suspected seizures, at high risk for seizures, or with definite seizures, as well as the use of cEEG for prognosis in a variety of conditions. In this guideline, we address these questions using American Clinical Neurophysiology Society structured methodology for clinical guideline development.

Renal Tubule-Specific Angiotensinogen Deletion Attenuates SGLT2 Expression and Ameliorates Diabetic Kidney Disease in Murine Models of Type 1 Diabetes.

The role of the intrarenal renin-angiotensin system (iRAS) in diabetic kidney disease (DKD) progression remains unclear. In this study, we generated mice with renal tubule-specific deletion of angiotensinogen (Agt; RT-Agt-/-) in both Akita and streptozotocin (STZ)-induced mouse model of diabetes. Both Akita RT-Agt-/- and STZ-RT-Agt-/- mice exhibited significant attenuation of glomerular hyperfiltration, urinary albumin/creatinine ratio, glomerulomegaly and tubular injury.

The Age-Old Question in Nipple-Sparing Mastectomy: Is Older Age a Contraindication?

Background: Nipple-sparing mastectomy (NSM) is infrequently performed in older women, at least in part owing to concerns regarding age-related complications. We describe postoperative outcomes of NSM in older women and risk factors for complications, with the goal of informing patient selection and decision-making.

Patients And Methods: Cases of NSM with immediate implant-based reconstruction were identified from an institutional database (2009-2019).

Basic Science and Pathogenesis.

Background: Genome-wide association studies (GWAS) in Alzheimer's disease (AD) leveraging endophenotypes beyond case/control diagnosis, such as brain amyloid β pathology, have shown promise in identifying novel variants and understanding their potential functional impact. In this study, we leverage two brain amyloid β pathology measurement modalities, PET imaging and neuropathology, to address sample size limitations and to discover novel genetic drivers of disease.

Method: We conducted a meta-analysis on an amyloid PET imaging GWAS (N = 7,036, 35% amyloid positive, 53.

Basic Science and Pathogenesis.

Background: Women are disproportionately affected by Alzheimer's disease (AD) and exhibit greater AD neuropathology than men. Women possess two X chromosomes, with one randomly silenced across each cell for dosage compensation. X chromosome inactivation (XCI) is not complete, and XCI-escaping genes provide a promising avenue of discovery for biological pathways driving sex-specific AD risk.

Basic Science and Pathogenesis.

Background: A significant proportion of individuals preserve cognitive function despite meeting neuropathological criteria for Alzheimer's disease (AD) at autopsy, known as cognitive resilience. We aimed to define the molecular and cellular signatures of cognitive resilience against AD.

Method: We integrated multi-modal data from the Religious Order Study and Memory and Aging Project (ROSMAP), including bulk (n = 631) and multi-regional single nucleus (n = 48) RNA sequencing.

Basic Science and Pathogenesis.

Background: Some individuals can tolerate the presence of Alzheimer disease neuropathologic changes (ADNC) (e.g., plaques and tangles) without developing dementia.

Basic Science and Pathogenesis.

Background: Cerebral small vessel disease (CSVD), which includes cerebral amyloid angiopathy (CAA) and arteriolosclerosis, often co-occurs with Alzheimer's disease (AD) pathology. The medial temporal lobe (MTL) is susceptible to hosting multiple AD pathologies, such as neurofibrillary tangles (NFTs), amyloid-β plaques, phospho-Tar-DNA-Binding-Protein-43 (pTDP-43), as well as CSVD. Whether a causal relationship between these pathologies exists remains largely unknown, but one potential linking mechanism is the dysfunction of perivascular clearance.

Basic Science and Pathogenesis.

Background: In cerebral amyloid angiopathy, amyloid beta accumulates within the walls of blood vessels and contributes to impaired vascular integrity and function. In this work, we observe that tau protein similarly builds up along blood vessels in Alzheimer's disease brain.

Method: We obtained frozen inferior temporal cortex from the Massachusetts Alzheimer's Disease Research Center from n = 7 neuropathological confirmed Alzheimer's disease donors and n = 6 normal aging controls.

Basic Science and Pathogenesis.

Background: Angiotensin-converting enzyme (ACE) is a validated risk locus for developing late-onset Alzheimer's disease (LOAD). ACE1 controls blood pressure through the renin-angiotensin system (RAS), but it is also present and acts locally in the brain. Hypertension is associated with an increased risk for developing AD, and people taking select RAS-targeting therapeutics have reduced incidence of AD.