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.

Long-term safety of lentiviral or gammaretroviral gene-modified T cell therapies.

Long-term risks of gene therapy are not fully understood. In this study, we evaluated safety outcomes in 783 patients over more than 2,200 total patient-years of observation from 38 T cell therapy trials. The trials employed integrating gammaretroviral or lentiviral vectors to deliver engineered receptors to target HIV-1 infection or cancer.

Racism and Postpartum Blood Pressure in a Multiethnic Prospective Cohort.

Background: Postpartum hypertension is a key factor in racial-ethnic inequities in maternal mortality. Emerging evidence suggests that experiences of racism, both structural and interpersonal, may contribute to disparities. We examined associations between gendered racial microaggressions (GRMs) during obstetric care with postpartum blood pressure (BP).

Enhanced D614G and Omicron Variants Antibody Persistence in Infants at 2 Months of Age Following Maternal mRNA Booster Vaccination During Pregnancy or Postpartum.

Background: Following maternal COVID-19 vaccination, the persistence of antibodies in sera and breast milk for mothers and infants is not well characterized. We sought to describe the persistence of antibodies through 2 months after delivery in maternal and infant serum and breast milk following maternal COVID-19 mRNA vaccination and to examine differences by receipt of booster dose during pregnancy or postpartum.

Methods: This is a prospective cohort study with enrollment from July 2021 to January 2022 at 9 US academic sites.

How to Use Imaging: Complex Cases of Atherosclerosis, Myocardial Inflammation, and Cardiomyopathy in Cardio-Oncology.

It is well understood that cancer therapies including chemotherapy, tyrosine kinase inhibitors, immune checkpoint inhibitors, and radiation can increase the risk of cardiovascular disease in patients with cancer. This can manifest as a multitude of pathologies including left ventricular dysfunction, myocarditis, cardiomyopathy, accelerated atherosclerosis, and coronary vasospasm. Multimodal cardiac imaging plays a critical role in diagnosing such pathologies by relying on noninvasive tools including echocardiograms, cardiac magnetic resonance imaging, positron emission tomography, single-photon emission computed tomography, and coronary computed tomography angiography.

Nuclear speckles regulate functional programs in cancer.

Nuclear speckles are dynamic nuclear bodies characterized by high concentrations of factors involved in RNA production. Although the contents of speckles suggest multifaceted roles in gene regulation, their biological functions are unclear. Here we investigate speckle variation in human cancer, finding two main signatures.

Yes, We Can! Ensuring That our Graduating Resident's Procedural Skills Meet the Needs of Their Patients.

Objectives: There is a burgeoning discrepancy between the procedural competency of graduating diagnostic radiology residents and the needs of our patient population. The causes of this mismatch and opportunities for improvement are explored by the APDR Procedural Competency of Graduating DR Residents Task Force.

Materials And Methods: The APDR convened a task force consisting of diverse broad stakeholder viewpoints, drawing from organized radiology, academic and private practices.

Role of Altmetric Attention Scores in Evaluating the Influence of Spine Surgery Research.

Study Design: Retrospective cohort.

Objective: To analyze the annual trends in the most prevalent topics, journals, and geographic regions of the top 100 spine surgery articles, as determined by altmetric attention scores (AASs). We also describe the relationship between AAS and traditional article metrics.

Operationalizing the New Global Definition of ARDS: A Retrospective Cohort Study From South Africa.

Background: A proposed new global definition of ARDS seeks to update the Berlin definition and account for nonintubated ARDS and ARDS diagnoses in resource-variable settings.

Research Question: How do ARDS epidemiologic characteristics change with operationalizing the new global definition of ARDS in a resource-limited setting?

Study Design And Methods: We performed a real-use retrospective cohort study among adult patients meeting criteria for the Berlin definition of ARDS or the global definition of ARDS at ICU admission in two public hospitals in the KwaZulu-Natal Department of Health, South Africa, from January 2017 through June 2022.

Results: Among 5,760 adults (aged ≥ 18 years) admitted to the ICU, 2,027 patients (35.

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.

The QIBA Profile for Dynamic Susceptibility Contrast MRI Quantitative Imaging Biomarkers for Assessing Gliomas.

The dynamic susceptibility contrast (DSC) MRI measures of relative cerebral blood volume (rCBV) play a central role in monitoring therapeutic response and disease progression in patients with gliomas. Previous investigations have demonstrated promise of using rCBV in classifying tumor grade, elucidating tumor viability after therapy, and differentiating pseudoprogression and pseudoresponse. However, the quantification and reproducibility of rCBV measurements across patients, devices, and software remain a critical barrier to routine or clinical trial use of longitudinal DSC MRI in patients with gliomas.

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.

The dynamics of hematopoiesis over the human lifespan.

Over a lifetime, hematopoietic stem cells (HSCs) adjust their lineage output to support age-aligned physiology. In model organisms, stereotypic waves of hematopoiesis have been observed corresponding to defined age-biased HSC hallmarks. However, how the properties of hematopoietic stem and progenitor cells change over the human lifespan remains unclear.

Integrating Out-of-Pocket Costs Into Shared Decision-Making for Heart Failure With Reduced Ejection Fraction: A Stepped-Wedge Trial (POCKET-COST-HF).

Background: Guideline-directed medical therapy for heart failure (HF) with reduced ejection fraction can entail high out-of-pocket (OOP) costs, prompting concerns about financial toxicity and access. OOP costs are generally unavailable during encounters. This trial assessed the impact of providing patient-specific OOP costs to patients and clinicians.

Post-COVID Pandemic Radiology Resident Readout Best Practices: An Institutional Needs Assessment and Initial Guidelines.

Rationale And Objectives: Radiology resident readout practices were adapted during the COVID pandemic, with several institutions transitioning to virtual and asynchronous readouts. Some pandemic-era practices persist today, with unclear effects on resident education. We developed institutional Readout Best Practices and assessed implementation.

Interleukin-15-armoured GPC3 CAR T cells for patients with solid cancers.

Interleukin-15 (IL-15) promotes the survival of T lymphocytes and enhances the antitumour properties of chimeric antigen receptor (CAR) T cells in preclinical models of solid neoplasms in which CAR T cells have limited efficacy. Glypican-3 (GPC3) is expressed in a group of solid cancers, and here we report the evaluation in humans of the effects of IL-15 co-expression on GPC3-expressing CAR T cells (hereafter GPC3 CAR T cells). Cohort 1 patients ( NCT02905188 and NCT02932956 ) received GPC3 CAR T cells, which were safe but produced no objective antitumour responses and reached peak expansion at 2 weeks.

Use of Basket Trials to Solve Sleep Problems in Patients with Rare Diseases.

The need for sleep is universal, and the ability to meet this need impacts the quality of life for patients, families, and caregivers. Although substantial progress has been made in treating rare diseases, many patients have unmet medical sleep needs, and current regulatory policy makes it prohibitively difficult to address those needs medically. This opinion reviews the rare disease experience with sleep disorders and explores potential solutions.

S100A1ct: A Synthetic Peptide Derived From S100A1 Protein Improves Cardiac Performance and Survival in Preclinical Heart Failure Models.

Background: The EF-hand Ca sensor protein S100A1 has been identified as a molecular regulator and enhancer of cardiac performance. The ability of S100A1 to recognize and modulate the activity of targets such as SERCA2a (sarcoplasmic reticulum Ca ATPase) and RyR2 (ryanodine receptor 2) in cardiomyocytes has mostly been ascribed to its hydrophobic C-terminal α-helix (residues 75-94). We hypothesized that a synthetic peptide consisting of residues 75 through 94 of S100A1 and an N-terminal solubilization tag (S100A1ct) could mimic the performance-enhancing effects of S100A1 and may be suitable as a peptide therapeutic to improve the function of diseased hearts.

Evaluating Social Determinants of Health-Based Alternatives to Race-Based Cognitive Normative Models.

Background And Objectives: Race and ethnicity are proxy measures of sociocultural factors that influence cognitive test performance. Our objective was to compare different regression-based cognitive normative models adjusting for demographics and different combinations of easily accessible/commonly used social determinants of health (SDoH) factors, which may help describe cognitive performance variability historically captured by ethnoracial differences.

Methods: We performed cross-sectional analyses on data from Black and White participants without mild cognitive impairment/dementia in the Atherosclerosis Risk in Communities Study who attended visit 5 in 2011-2013.

Association of achieving clinical disease control criteria and patient-reported outcomes in bimekizumab-treated patients with active psoriatic arthritis: results from two phase III studies.

Background: Psoriatic arthritis (PsA) is a chronic inflammatory disease that causes pain and fatigue, reduces physical function, and negatively impacts health-related quality of life (HRQoL). In the phase III BE OPTIMAL and BE COMPLETE studies, bimekizumab demonstrated clinical efficacy and meaningful improvements in patient-reported outcome (PRO) measures in biologic disease-modifying antirheumatic drug (bDMARD)-naïve patients, and those who had prior inadequate response/intolerance to tumor necrosis factor inhibitors (TNFi-IR).

Objectives: To examine the association between achieving increasingly stringent clinical disease control criteria and improvements in PRO measures in patients with active PsA receiving bimekizumab.

State of the art of mobile health technologies use in clinical arrhythmia care.

The rapid growth in consumer-facing mobile and sensor technologies has created tremendous opportunities for patient-driven personalized health management. The diagnosis and management of cardiac arrhythmias are particularly well suited to benefit from these easily accessible consumer health technologies. In particular, smartphone-based and wrist-worn wearable electrocardiogram (ECG) and photoplethysmography (PPG) technology can facilitate relatively inexpensive, long-term rhythm monitoring.

GABA Type A receptors expressed in triple negative breast cancer cells mediate chloride ion flux.

Triple negative breast cancer (TNBC) is known for its heterogeneous nature and aggressive onset, limited unresponsiveness to hormone therapies and immunotherapy as well as high likelihood of metastasis and recurrence. Since no targeted standard treatment options are available for TNBC, novel and effective therapeutic targets are urgently needed. Ion channels have emerged as possible novel therapeutic candidates for cancer therapy.

Recombinant Erwinia asparaginase (JZP458) in ALL/LBL: complete follow-up of the Children's Oncology Group AALL1931 study.

Children's Oncology Group study AALL1931 investigated the efficacy and safety of recombinant Erwinia asparaginase (JZP458) in patients with acute lymphoblastic leukemia/lymphoblastic lymphoma and hypersensitivity reactions/silent inactivation to Escherichia coli-derived asparaginases. Each pegylated Escherichia coli asparaginase dose remaining in a patient's treatment plan was replaced by intramuscular (IM) or IV JZP458 (6 doses) administered Monday/Wednesday/Friday (MWF). Three IM cohorts (1a [25 mg/m2 MWF], n = 33; 1b [37.