multimutants enable efficient identification of SPI-2 effector protein function in gut inflammation and systemic colonization.

enterica spp. rely on translocation of effector proteins through the SPI-2 encoded type III secretion system (T3SS) to achieve pathogenesis. More than 30 effectors contribute to manipulation of host cells through diverse mechanisms, but interdependency or redundancy between effectors complicates the discovery of effector phenotypes using single mutant strains.

Early Palliative Care Following Aborted Cancer Surgery: Results of a Prospective Feasibility Trial.

Background: Although resection is generally necessary for curative-intent treatment of most solid organ cancers, surgery is occasionally aborted due to intraoperative findings. Following aborted cancer surgery, patients have unique care needs that specialized palliative care (PC) providers may be best equipped to manage. We hypothesized that early ambulatory PC referral following aborted cancer surgery would be feasible and acceptable.

Biomechanical modeling combined with pressure-volume loop analysis to aid surgical planning in patients with complex congenital heart disease.

Patients with congenitally corrected transposition of the great arteries (ccTGA) can be treated with a double switch operation (DSO) to restore the normal anatomical connection of the left ventricle (LV) to the systemic circulation and the right ventricle (RV) to the pulmonary circulation. The subpulmonary LV progressively deconditions over time due to its connection to the low pressure pulmonary circulation and needs to be retrained using a surgical pulmonary artery band (PAB) for 6-12 months prior to the DSO. The subsequent clinical follow-up, consisting of invasive cardiac pressure and non-invasive imaging data, evaluates LV preparedness for the DSO.

Genetic analysis of psychosis Biotypes: shared Ancestry-adjusted polygenic risk and unique genomic associations.

The Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) created psychosis Biotypes based on neurobiological measurements in a multi-ancestry sample. These Biotypes cut across DSM diagnoses of schizophrenia, schizoaffective disorder, and bipolar disorder with psychosis. Two recently developed post hoc ancestry adjustment methods of Polygenic Risk Scores (PRSs) generate Ancestry-Adjusted PRSs (AAPRSs), which allow for PRS analysis of multi-ancestry samples.

The Association between Obesity and Efficacy of Psoriasis Therapies: An Expert Consensus Panel.

Background: Psoriasis is a chronic inflammatory skin disease often associated with obesity. Psoriasis therapies may be less effective in obese patients. The purpose of this expert consensus panel is to evaluate the relationship between obesity and efficacy of psoriasis therapies, thereby optimizing patient care.

Stroke-bleeding risk score pairings within individuals in the outcomes registry for better informed treatment of atrial fibrillation (ORBIT-AF) registry.

Background: Decisions about stroke prevention strategies in atrial fibrillation (AF) typically balance thromboembolism reduction against increased bleeding from oral anticoagulation therapy (OAC). When determining eligibility for OAC, guidelines recommend calculation of thromboembolic event rates using a validated score such as CHA2DS2-VASc. In contrast, routine calculation of bleeding scores is not recommended, in part because many patient factors associated with an increased risk of bleeding are associated with an even larger increased risk of ischemic stroke.

Intraoperative Molecular Imaging With Pafolacianine: Histologic Characteristics of Identified Nodules.

Background: With increased early detection efforts, surgery for early-stage lung cancer is expected to rise. Pafolacianine is the first FDA approved targeted optical imaging agent indicated as an adjunct for intraoperative identification of malignant and nonmalignant pulmonary lesions in adult patients with known or suspected cancer in the lung.

Methods: This is a retrospective review of the malignant and nonmalignant lesions identified by pafolacianine with intraoperative molecular imaging (IMI) in the multi-center Phase 2 and Phase 3 ELUCIDATE clinical trials.

Trends in Cardiovascular Disease-Related Mortality in Texas.

Background: Cardiovascular disease (CVD) is associated with high mortality in the United States, but the burden of CVD mortality is unevenly distributed between demographic and geographic subgroups, with poor characterization of state-specific trends. In this study, the disparities in CVD-related mortality trends in Texas and the United States from 1999 to 2019 were assessed.

Methods: Trends in CVD-related mortality were evaluated through analysis of the Multiple Causes of Death Files from the National Center for Health Statistics.

Blood biomarker discovery for autism spectrum disorder: A proteomic analysis.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and social interaction and restricted, repetitive patterns of behavior, interests, or activities. Given the lack of specific pharmacological therapy for ASD and the clinical heterogeneity of the disorder, current biomarker research efforts are geared mainly toward identifying markers for determining ASD risk or for assisting with a diagnosis. A wide range of putative biological markers for ASD are currently being investigated.

Analysis of Phosphatidylinositol Transfer at ER-PM Contact Sites in Receptor-Stimulated Live Cells.

Phosphatidylinositol (PI) is an inositol-containing phospholipid synthesized in the endoplasmic reticulum (ER). PI is a precursor lipid for PI 4,5-bisphosphate (PI(4,5)P) in the plasma membrane (PM) important for Ca signaling in response to extracellular stimuli. Thus, ER-to-PM PI transfer becomes essential for cells to maintain PI(4,5)P homeostasis during receptor stimulation.

Pleuropulmonary blastoma and DICER1-related tumor predisposition: from clinicopathologic observations to clinical trial.

Purpose Of Review: Pleuropulmonary blastoma (PPB) is a rare primary lung neoplasm of infancy and childhood. The purpose of this review is to highlight recent developments in our understanding of PPB and research strategies to facilitate future rare cancer research.

Recent Findings: The International PPB/DICER1 Registry has recently assembled the largest-ever cohorts of type I and Ir PPB and type II and III PPB.

A literature review of artificial intelligence (AI) for medical image segmentation: from AI and explainable AI to trustworthy AI.

Background And Objective: Medical image segmentation is a vital aspect of medical image processing, allowing healthcare professionals to conduct precise and comprehensive lesion analyses. Traditional segmentation methods are often labor intensive and influenced by the subjectivity of individual physicians. The advent of artificial intelligence (AI) has transformed this field by reducing the workload of physicians, and improving the accuracy and efficiency of disease diagnosis.

Ghost Sign on Diffusion-Weighted Imaging Generated Apparent Diffusion Coefficient Map: Additional MRI Diagnostic Marker for Extremity Osteomyelitis.

 The aim of this study was to determine the sensitivity and specificity and inter-reader reliability of previously known "ghost sign" and "penumbra sign" on T1-weighted (T1W) imaging and "ghost sign" on apparent diffusion coefficient (ADC) map in osteomyelitis (OM) of the extremities.  In this cross-sectional retrospective study, two fellowship-trained musculoskeletal readers blinded to final diagnosis of OM versus no OM were asked to report the penumbra sign and ghost sign on T1W images and ghost sign on ADC map, as well as diagnosis of OM. Cohen's kappa was used.

Heme promotes venetoclax resistance in multiple myeloma through MEK-ERK signaling and purine biosynthesis.

We previously demonstrated that reduced intrinsic electron transport chain (ETC) activity predicts and promotes sensitivity to the BCL-2 antagonist, venetoclax (Ven) in multiple myeloma (MM). Heme, an iron-containing prosthetic group, and metabolite is fundamental to maintaining ETC activity. Interrogation of the CD2 subgroup of MM from the CoMMpass trial (NCT01454297), which can be used as a proxy for Ven-sensitive MM (VS MM), shows reduced expression of the conserved heme biosynthesis pathway gene signature.

Race/ethnicity, sex, and age differences in pediatric SCAT-5 concussion symptoms.

Objective: To examine sociodemographic differences in concussion symptom reporting, among young children by race/ethnicity, sex, and age at initial presentation to guide potential interventions for children from different backgrounds.

Method: Participants were elementary-age children (ages 5 to 12 years;  = 392) who sustained a concussion within 30 days of specialty concussion clinic visit. Independent variables were self-defined race/ethnic group, participants' sex, and age.

Material economic hardship is associated with adverse 1-year outcomes after pediatric liver transplantation: Prospective cohort results from the multi-center SOCIAL-Tx study.

Pediatric liver transplant outcomes exhibit disparities, necessitating identification of modifiable risk factors to develop targeted interventions. We characterized associations between household material economic hardship (e.g.

Acute MeCP2 loss in adult mice reveals transcriptional and chromatin changes that precede neurological dysfunction and inform pathogenesis.

Mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene cause Rett syndrome, a severe childhood neurological disorder. MeCP2 is a well-established transcriptional repressor, yet upon its loss, hundreds of genes are dysregulated in both directions. To understand what drives such dysregulation, we deleted Mecp2 in adult mice, circumventing developmental contributions and secondary pathogenesis.

Cost-Effectiveness of a Biomarker-Based Screening Strategy for Hepatocellular Carcinoma in Patients with Cirrhosis.

Introduction: Given suboptimal performance of ultrasound-based surveillance for early hepatocellular carcinoma (HCC) detection in patients with cirrhosis, there is interest in alternative surveillance strategies, including blood-based biomarkers. We aimed to evaluate the cost-effectiveness of biomarker-based surveillance in patients with cirrhosis.

Methods: We constructed a decision-analytic model to compare ultrasound/alpha-fetoprotein (AFP) and biomarker-based surveillance strategies in 1,000,000 simulated patients with compensated cirrhosis.

The Effects of Syphilis Infection on Total Knee Arthroplasty Outcomes: A Retrospective Cohort Study.

This study investigated the impact of recent syphilis infection on postoperative outcomes following total knee arthroplasty (TKA). We hypothesized that patients with a documented history of syphilis infection would experience a higher rate of postoperative complications compared to those without such a history. We conducted a retrospective cohort analysis using a national insurance claims database.

Molecular Pathway and Immune Profile Analysis of IPMN-Derived Versus PanIN-Derived Pancreatic Ductal Adenocarcinomas.

Intraductal papillary mucinous neoplasms (IPMN) are commonly detected pancreatic cysts that may transform into pancreatic ductal adenocarcinoma (PDAC). Predicting which IPMNs will progress to PDAC remains a clinical challenge. Moreover, identifying those clinically evident IPMNs for which a surveillance approach is best is a dire clinical need.

Sirtuins as Key Regulators in Pancreatic Cancer: Insights into Signaling Mechanisms and Therapeutic Implications.

Pancreatic ductal adenocarcinoma (PDAC) stands as one of the most lethal cancers, marked by rapid progression, pronounced chemoresistance, and a complex network of genetic and epigenetic dysregulation. Within this challenging context, sirtuins, NAD-dependent deacetylases, have emerged as pivotal modulators of key cellular processes that drive pancreatic cancer progression. Each sirtuin contributes uniquely to PDAC pathogenesis.

Immune aging and infectious diseases.

The rise in global life expectancy has led to an increase in the older population, presenting significant challenges in managing infectious diseases. Aging affects the innate and adaptive immune systems, resulting in chronic low-grade inflammation (inflammaging) and immune function decline (immunosenescence). These changes would impair defense mechanisms, increase susceptibility to infections and reduce vaccine efficacy in older adults.

Modeling healthcare demands and long-term costs following pediatric traumatic brain injury.

Introduction: Traumatic brain injury (TBI) is a leading cause of death and disability in children, but data on the longitudinal healthcare and financial needs of pediatric patients is limited in scope and duration. We sought to describe and predict these metrics following acute inpatient treatment for TBI.

Methods: Children surviving their initial inpatient treatment for TBI were identified from Optum's deidentified Clinformatics® Data Mart Database (2007-2018).