Immunogenomic determinants of exceptional response to immune checkpoint inhibition in renal cell carcinoma.

Immune checkpoint inhibitors can lead to 'exceptional', durable responses in a subset of persons. However, the molecular basis of exceptional response (ER) to immunotherapy in metastatic clear cell renal cell carcinoma (mccRCC) has not been well characterized. Here we analyzed pretherapy genomic and transcriptomic data in treatment-naive persons with mccRCC treated with standard-of-care immunotherapies: (1) combination of programmed cell death protein and ligand 1 (PD1/PDL1) and cytotoxic T lymphocyte-associated protein 4 inhibitors (IO/IO) or (2) combination of PD1/PDL1 and vascular endothelial growth factor (VEGF) receptor inhibitors (IO/VEGF).

Parenting and Family Concerns of Couples Navigating Advanced Breast Cancer: Exploring Discussions Around Parenting Challenges and Targets for Intervention.

Background: Parents with advanced cancer and their partners are more likely to experience psychological distress than their counterparts without minor children. Greater relationship functioning may support parents in distress.

Aims: The current study seeks to explore couples' cancer-related parenting communication behaviors, perception and their associations with psychological and relational wellbeing.

Anti-CTLA-4 generates greater memory response than anti-PD-1 via TCF-1.

The effects of T cell differentiation arising from immune checkpoint inhibition targeting cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) on the immunological memory response remain unclear. Our investigation into the effects of anti-CTLA-4 and anti-PD-1 on memory T cell formation in mice reveals that memory T cells generated by anti-CTLA-4 exhibit greater expansion, cytokine production, and antitumor activity than those from anti-PD-1. Notably, anti-CTLA-4 preserves more T cell factor-1 (TCF-1)+ T cells during priming, while anti-PD-1 leads to more thymocyte selection-associated high mobility group box (TOX)+ T cells.

Expert Rater Agreement for Symptoms and Diagnosis of Bipolar Disorder in Youth.

The diagnosis of bipolar disorder (BD) in young children has been a topic of debate, in part owing to varied interpretation of manic-like symptoms. We examined how expert academic clinicians participating in the pediatric bipolar biobank varied in their interpretation and application of Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria and diagnoses. Study co-investigators reviewed 12 standardized narratives and for each marked a visual analog scale with their confidence in the presence of manic episodes and criteria.

Endovascular interventions in cancer patients with compromise of the mediastinal vasculature: a review.

The mediastinal vasculature can be affected by various etiologies in cancer patients. Both direct and indirect sequela of cancer may result in life-threatening clinical presentations. Tumor growth may cause vessel narrowing and decreased blood flow from either extrinsic mass effect, invasion into the vascular wall, or tumor thrombus within the lumen.

The TRIPOD-LLM reporting guideline for studies using large language models.

Large language models (LLMs) are rapidly being adopted in healthcare, necessitating standardized reporting guidelines. We present transparent reporting of a multivariable model for individual prognosis or diagnosis (TRIPOD)-LLM, an extension of the TRIPOD + artificial intelligence statement, addressing the unique challenges of LLMs in biomedical applications. TRIPOD-LLM provides a comprehensive checklist of 19 main items and 50 subitems, covering key aspects from title to discussion.

Diuretic Potentiation Strategies in Acute Heart Failure.

Several trials have evaluated diuretic-based strategies to improve symptoms and outcomes in patients with acute heart failure (AHF). The authors sought to summarize the effect of different combination strategies on symptoms, physical signs, physiological variables, and outcomes in patients with AHF. Twelve trials were identified that assessed the addition of thiazide diuretics, sodium-glucose cotransporter 2 inhibitors, mineralocorticoid receptor antagonists, vasopressin receptor antagonists, carbonic anhydrase inhibitors, or loop diuretic intensification to conventional therapy for AHF.

Underrepresented in Medicine Mentorship Program: Perceived Benefits and Lessons Learned.

Background And Objectives: Faculty members who are underrepresented in medicine (URM) may benefit from mentorship that is designed specifically to meet their unique needs and is focused on improving their career pathways in academic medicine. The Underrepresented in Medicine Mentorship Program (URM-MP) is an academic society-based mentorship program that pairs early career URM faculty with mid- to late-career faculty specifically trained to address URM issues.

Methods: During the first 3 years of the program, mentors received web-based training on addressing oppression and marginalization of URM faculty in academic medicine.

Impact of Functional Training on Injuries After Anterior Cruciate Ligament Reconstruction for Return-to-Duty Status in U.S. Naval Academy Midshipmen: A Retrospective Analysis.

Introduction: Acute anterior cruciate ligament (ACL) injuries can be disabling because of prolonged rehabilitation process following surgical reconstructions. Rates of ACL injuries among military service members are close to 10 times greater than the general civilian population, likely because of the operation tempo and the unique physical requirements. Studies debated functional testing requirements for return to sports, but no study investigated the impact of functional training and re-injury rates following ACL reconstruction and their association with functional testing outcomes and time to return to full duty in United States Naval Academy (USNA) Midshipmen.

Clinical, laboratory, and orbital imaging features of giant cell arteritis in comparison to non-arteritic anterior ischemic optic neuropath: a single center case series.

Background: Giant cell arteritis (GCA) is the most common vasculitis in patients older than 50 years and is considered a "do not miss" diagnosis. However, it remains a diagnostic challenge given overlapping clinical syndromes such as non-arteritic anterior ischemic optic neuropathy (NAION) and poorly explored imaging findings.

Materials And Methods: In this retrospective study between the time period of January 2013 and December 2021, a total of 13 consecutive patients with a pathological diagnosis of GCA and 8 patients with clinical diagnosis of NAION were isolated.

Associations Between Socioeconomic, Spatial and Educational Factors and Midlife Periodontal Disease Risk: Evidence From 'High School and Beyond'.

Background: Periodontal disease (PD) is a prevalent, preventable and treatable oral infection associated with substantial morbidity globally. There is little information from population-representative cohort studies about the sociodemographic, educational and other early life factors that stratify PD risk.

Methods: We used data from the U.

Traditional online and live-streaming dual-channel strategies and pricing policies.

This study examines the pricing policies and the dual-channel strategies in a two-tier supply chain where a manufacturer distributes products through a retailer and considers the opening of a traditional direct online channel or a live-streaming sales channel The manufacturer has three sales modes, i.e., traditional retail channel only, opening a traditional direct online channel and opening a live-streaming direct sales channel, to consider.

Standardizing the reporting of cholangiocarcinoma: the society of abdominal radiology disease focused panel on cholangiocarinoma lexicon.

In March 2023, the Society of Abdominal Radiology (SAR) Disease Focused Panel (DFP) on Cholangiocarcinoma (CCA) was formed. One of its initial tasks was for creation of a lexicon specific for CCA to complement the terms related to the Liver Imaging Reporting and Data System (LI-RADS) category M. A committee was formed and vetted 15 unique terms for CCA.

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.

Diabetes Mellitus Is Not a Risk Factor for Difficult Intubation Among Critically Ill Adults: A Secondary Analysis of Multicenter Trials.

Objectives: Diabetes mellitus has been associated with greater difficulty of tracheal intubation in the operating room. This relationship has not been examined for tracheal intubation of critically ill adults. We examined whether diabetes mellitus was independently associated with the time from induction of anesthesia to intubation of the trachea among critically ill adults.

Perseverance of Optimal Realignment is Associated With Improved Cost-utility in Adult Cervical Deformity Surgery.

Background: Early-term complications may not predict long-term success after adult cervical deformity (ACD) correction.

Objective: Evaluate whether optimal realignment results in similar rates of perioperative complications but achieves longer-term cost-utility.

Study Design: Retrospective cohort study.

Harvi Cardiovascular Modeling Accurately Predicts Hemodynamic Improvements Produced by a New Direct Cardiac Compression Device.

Despite advancements in mechanical circulatory support (MCS) technology, persistent critical complications related to blood contact remain unresolved. To provide a safer alternative therapy, CorInnova is developing a non-blood contacting direct cardiac compression (DCC) device for MCS. To support product development toward clinical trials, a simulation platform has been developed to predict clinical outcomes under patient-specific conditions, guiding patient selection for clinical trials.

Learning from Hindsight: Examining Autonomic, Inflammatory, and Endocrine Stress Biomarkers and Mental Health in Healthy Terrorism Survivors Many Years Later.

Introduction: Terrorism and trauma survivors often experience changes in biomarkers of autonomic, inflammatory and hypothalamic-pituitary-adrenal (HPA) axis assessed at various times. Research suggests interactions of these systems in chronic stress.

Study Objective: This unprecedented retrospective study explores long-term stress biomarkers in three systems in terrorism survivors.

Paid Domestic Work and Depressive Symptoms in Mexico: Results of a National Health Survey.

Paid domestic work (PDW) is an important source of employment for the global female workforce. It is frequently performed under precarious working conditions and occupational risks that are often associated with depressive symptoms (DSs). Although 10% (2.

Neuronal cell type specific roles for Nprl2 in neurodevelopmental disorder-relevant behaviors.

Loss of function in the subunits of the GTPase-activating protein (GAP) activity toward Rags-1 (GATOR1) complex, an amino-acid sensitive negative regulator of the mechanistic target of rapamycin complex 1 (mTORC1), is implicated in both genetic familial epilepsies and Neurodevelopmental Disorders (NDDs) (Baldassari et al., 2018). Previous studies have found seizure phenotypes and increased activity resulting from conditional deletion of GATOR1 function from forebrain excitatory neurons (Yuskaitis et al.

Structures of ATP-binding cassette transporter ABCC1 reveal the molecular basis of cyclic dinucleotide cGAMP export.

Cyclic nucleotide GMP-AMP (cGAMP) plays a critical role in mediating the innate immune response through the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway. Recent studies showed that ATP-binding cassette subfamily C member 1 (ABCC1) is a cGAMP exporter. The exported cGAMP can be imported into uninfected cells to stimulate a STING-mediated innate immune response.

A taxonomy of the factors contributing to the overtreatment of cancer patients at the end of life. What is the problem? Why does it happen? How can it be addressed?

Many patients with cancer approaching the end of life (EOL) continue to receive treatments that are unlikely to provide meaningful clinical benefit, potentially causing more harm than good. This is called overtreatment at the EOL. Overtreatment harms patients by causing side-effects, increasing health care costs, delaying important discussions about and preparation for EOL care, and occasionally accelerating death.

A precision oncology-focused deep learning framework for personalized selection of cancer therapy.

Precision oncology matches tumors to targeted therapies based on the presence of actionable molecular alterations. However, most tumors lack actionable alterations, restricting treatment options to cytotoxic chemotherapies for which few data-driven prioritization strategies currently exist. Here, we report an integrated computational/experimental treatment selection approach applicable for both chemotherapies and targeted agents irrespective of actionable alterations.

Once daily Bromelain-based enzymatic debridement of venous leg ulcers versus gel vehicle (placebo) and non-surgical standard of care: a three-arm multicenter, double blinded, randomized controlled study.

Background: Debridement is considered the first step in treatment of chronic wounds, however, current enzymatic and autolytic debridement agents are slow or ineffective. Previous studies have shown positive initial results with EscharEx® (EX-02 formulation), a Bromelain-based enzymatic debridement agent in development for chronic wounds. The main objective of this study was to assess its efficacy in debriding venous leg ulcers (VLU), compared to gel vehicle (GV) as a placebo control and to non-surgical standard of care (NSSOC).