Cognition in patients with mild autonomous cortisol secretion at baseline and post-adrenalectomy.

Objectives: The impact of mild autonomous cortisol secretion (MACS) on cognition is incompletely characterized. We aimed to assess cognition in patients with MACS, identify factors associated with lower cognition, and determine the impact of adrenalectomy on cognition.

Methods: We conducted a cross-sectional study (4/2019 to 10/2022) and a longitudinal cohort study (10/2021 to 9/2023) of adults with MACS and referent subjects.

Very long-term outcomes of robotic mesh sacrocolpopexy for pelvic organ prolapse repair.

To assess the very long-term functional outcomes and complications of robot-assisted sacrocolpopexy (RASC) at our institution where this robotic technology for pelvic organ prolapse (POP) repair has been available since 2006. A retrospective review of a cohort of women who underwent a RASC was performed by an investigator not involved in the clinical care of these patients. Women with no electronic medical record follow-up in the last 2 years were contacted by telephone.

Choice of Link Functions for Generalized Linear Mixed Models in Meta-Analyses of Proportions.

Two-step approaches for synthesizing proportions in a meta-analysis require first transforming the proportions to a scale where their distribution across studies can be approximated by a normal distribution. Commonly used transformations include the log, logit, arcsine, and Freeman-Tukey double-arcsine transformations. Alternatively, a generalized linear mixed model (GLMM) can be fit directly on the data using the exact binomial likelihood.

Effective remediation for advanced practice providers with lowest patient experience: The power of relational resources.

Objectives: Healthcare providers with low patient experience scores may provide suboptimal care and experience burnout. Communication skills training (CST) can be effective, but remedial programs may be poorly received. We aimed to create a program to support advanced practice providers (APPs) with lowest patient experience ratings.

Impact of racial, ethnic, and socioeconomic disparities on presentation and survival of HCC: A multicenter study.

Background: Racial and ethnic disparities have been reported for HCC prognosis, although few studies fully account for clinically important factors and social determinants of health, including neighborhood socioeconomic status.

Methods: We conducted a retrospective multicenter cohort study of patients newly diagnosed with HCC from January 2010 through August 2018 at 4 large health systems in the United States. We used multivariable logistic regression and cause-specific Cox proportional hazard models to identify factors associated with early-stage HCC presentation and overall survival.

Imaging Findings and Management Strategies for Liver Masses in Children with Predisposition Disorders: A Review by the Pediatric LI-RADS Group.

Liver masses in children with underlying systemic disease or a predisposing syndrome can be benign or malignant, ranging from focal fat to hepatocellular carcinoma (HCC). Knowledge of the underlying condition, the pathophysiologic effect on the liver, and the development of liver disease and specific liver lesions allows radiologists to guide imaging with regard to modality and frequency and give recommendations for biopsy when appropriate. In some predisposition disorders, such as Beckwith Wiedemann spectrum, familial adenomatous polyposis syndrome, and tuberous sclerosis complex, established guidelines for imaging screening exist.

Effect of Ketorolac Administration on the Rate of Nonunion of Operatively Treated Pediatric Long-Bone Fractures: A Matched Cohort Analysis.

Background: Nonunion is a rare yet serious complication in pediatric fracture healing that can lead to patient morbidity and economic burden. The administration of nonsteroidal anti-inflammatory drugs (NSAIDs) has been associated with an increased risk of fracture nonunion in adults, but data are lacking in the pediatric population. This study examines the relationship between postoperative ketorolac administration and nonunion in operatively managed pediatric long-bone fractures.

Testing the Antigenic Potential of Transmembrane Proteins To Develop a Thermostable Tuberculosis MOF-Liposomal Vaccine.

Tuberculosis is one of the deadliest infectious diseases and continues to be a major health risk in many parts of the world. Even today, the century-old Bacillus Calmette-Guerin (BCG) vaccine is the only formulation on the market and is ineffective for several sections of the global population responsible for transmission. In the search for antigens that can mount a robust immune response, we have reported the recombinant expression and purification of two novel membrane proteins, the Cation transporter protein V (CtpV) and the Mycobacterial copper transporter B (MctB) present on the membrane surface of .

Unveiling non-coding variants: synergising RNA sequencing and DNA sequencing for enhanced molecular diagnosis.

Background: Pathogenic variants in the gene are associated with dystrophinopathy including Duchenne and Becker muscular dystrophy (DMD/BMD). Targeted gene, gene panels, exomes and genome sequencing have advanced genetic diagnostics, yet some cases remain elusive.

Methods: We performed total RNA sequencing (RNAseq) on muscle biopsy from 13 male patients with a clinical diagnosis of DMD/BMD.

Association between Obstructive Sleep Apnea and Age-related Macular Degeneration Development and Progression.

Objective: To evaluate the risk of age-related macular degeneration (AMD) development and progression in individuals with diagnosed obstructive sleep apnea (OSA).

Design: Retrospective cohort study.

Subjects: Before propensity score matching (PSM), 60 652 and 1 173 723 individuals with OSA or not, respectively, were included in the study.

SRC kinase drives multidrug resistance induced by KRAS-G12C inhibition.

Direct targeting of the -mutant protein using covalent inhibitors (G12Ci) acts on human non-small cell lung cancer (NSCLC). However, drug resistance is an emerging concern in this approach. Here, we show that MRTX849, a covalent inhibitor targeting the mutation, leads to the reactivation of the mitogen-activated protein kinase signaling pathway in MRTX849-resistant NSCLC and pancreatic ductal adenocarcinoma.

Prospective clinical performance of CoVarScan in identifying SARS-CoV-2 Omicron subvariants.

The purpose of this work was to evaluate the performance of CoVarScan, a multiplex fragment analysis approach, in identifying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of the Omicron lineage rapidly and accurately. The ability to identify variants with high fidelity and low turnaround time is important both epidemiologically and clinically for pandemic monitoring and therapeutic monoclonal antibody (mAb) selection. Currently, the gold-standard test for this task is whole-genome sequencing (WGS), which is prohibitively expensive and/or inaccessible due to equipment requirements for many laboratories.

High resistance barrier and prophylactic protection in preclinical models of SARS-CoV-2 with two siRNA combination.

RNA interference is a natural antiviral mechanism that could be harnessed to combat SARS-CoV-2 infection by targeting and destroying the viral RNA. We identified potent lipophilic small interfering RNA (siRNA) conjugates targeting highly conserved regions of SARS-CoV-2 outside of the spike-encoding region capable of achieving ≥3-log viral reduction. Serial passaging studies demonstrated that a two-siRNA combination prevented development of resistance compared to a single siRNA approach.

Gain of function NOTCH3 variants cause familial partial lipodystrophy due to activation of senescence pathways.

Despite elucidation of the molecular genetic basis of several lipodystrophy syndromes, molecular defects in some ultra-rare subtypes of familial lipodystrophies remain unidentified. We analyzed whole exome sequencing (WES) data of four affected and two unaffected females from an undiagnosed autosomal dominant familial partial lipodystrophy (FPL) pedigree and identified only one novel heterozygous variant, p.Ala1603Tyr in NOTCH3 meeting the filtering criteria.

Serum levels of total bile acids are associated with an increased risk of HCC in patients with cirrhosis.

Background: Previous studies have reported higher circulating bile acid levels in patients with HCC compared to healthy controls. However, the association between prediagnostic bile acid levels and HCC risk among patients with cirrhosis is unclear.

Methods: We measured total BA (TBA) concentration in serum samples collected from a prospective cohort of patients with cirrhosis who were followed until the development of HCC, death, or last study date.

PET/MRI evaluation of hepatobiliary tumors.

Positron-emission tomography magnetic resonance imaging (PET/MRI) has emerged as a powerful hybrid molecular imaging technique in clinical practice, overcoming initial technical challenges to provide comprehensive anatomic and metabolic information. This advanced modality combines the superior soft tissue contrast of MRI with the metabolic insights of PET, offering advantages in hepatobiliary imaging, including improved detection of small liver metastases and reduced radiation exposure. The evolution of PET/MRI technology has been marked by significant advancements, such as the development of MRI-compatible PET detectors and sophisticated motion compensation techniques.

Blinatumomab in Standard-Risk B-Cell Acute Lymphoblastic Leukemia in Children.

Background: B-cell acute lymphoblastic leukemia (B-cell ALL) is the most common childhood cancer. Despite a high overall cure rate, relapsed B-cell ALL remains a leading cause of cancer-related death among children. The addition of the bispecific T-cell engager molecule blinatumomab (an anti-CD19 and anti-CD3 single-chain molecule) to therapy for newly diagnosed standard-risk (as defined by the National Cancer Institute) B-cell ALL in children may improve outcomes.

Heterogeneity of aerobic fitness changes with exercise training in progressive multiple sclerosis: Secondary, exploratory analysis of data from the CogEx trial.

Background: There is heterogeneity of aerobic fitness (VO) changes with a standardized exercise training stimulus in the general population (i.e. some participants demonstrate improvements, others no change, and some a reduction in VO).

Perceived Barriers and Facilitators of Behavioral-Health Modality Change Adoption During the COVID-19 Pandemic: A Systematic Review.

Introduction: During the Coronavirus Disease 2019 pandemic, there was a surge in demand for mental health services worldwide, presenting challenges for healthcare institutions as they navigated changes in policy and safety regulations. In the United States, this resulted in many behavioral health modality changes to remain in compliance with the Center for Disease Control guidelines. A growing body of literature has documented these, yet few explored barriers and facilitators affecting the adoption of these modality delivery changes.

Targeting hardship: poverty as a modifiable risk factor in childhood leukemia and lymphoma treatment.

Racial, ethnic, and socioeconomic survival disparities have been well-demonstrated across population-based and clinical trial datasets in pediatric hematologic malignancies. To date, these analyses have relied on trial-collected data such as race, ethnicity, insurance, and zip code. These exposures serve as proxies for factors such as structural racism, genetic ancestry, and adverse social determinants of health (SDOH).

How to think about acute leukemia of ambiguous lineage.

Classification of acute leukemia involves assigning lineage by resemblance of blasts to normal progenitor cells. This approach provides descriptive information that is useful for disease monitoring, provides clues to pathogenesis, and can help to select effective chemotherapeutic regimens. Acute leukemias of ambiguous lineage (ALAL) are those leukemias that either fail to show evidence of myeloid, B-lymphoid, or T-lymphoid lineage commitment or show evidence of commitment to more than 1 lineage, including mixed-phenotype acute leukemia (MPAL).