Integrative proteogenomic analysis identifies COL6A3-derived endotrophin as a mediator of the effect of obesity on coronary artery disease.

Obesity strongly increases the risk of cardiometabolic diseases, yet the underlying mediators of this relationship are not fully understood. Given that obesity strongly influences circulating protein levels, we investigated proteins mediating the effects of obesity on coronary artery disease, stroke and type 2 diabetes. By integrating two-step proteome-wide Mendelian randomization, colocalization, epigenomics and single-cell RNA sequencing, we identified five mediators and prioritized collagen type VI α3 (COL6A3).

Dual anti-CTLA-4 and anti-PD-1 blockade in metastatic basal cell carcinoma.

We report the basal cell cancer (BCC) cohort of the SWOG/NCI 1609 Dual Anti-CTLA-4 & Anti-PD-1 blockade in Rare Tumors (DART), a phase II prospective, multicenter basket trial of nivolumab and ipilimumab. The primary endpoint was objective response rate (ORR) (RECIST v1.1).

Mobility of South America's transcontinental drainage divide and shrinkage of the Paraná river basin linked to lithologic and geodynamic controls.

The South American Transcontinental Drainage Divide (TDD) is roughly oriented NE-SW from its Atlantic termination in SE Brazil to its NW termination in the limits between the southwestern edges of the Amazon Craton and the Andean Foreland. Based on a weak spatial coincidence with 90 - 70 Ma igneous intrusions, the origin and stability of the TDD have been attributed to intraplate magmatic activity. Using geomorphic analysis of drainage divides, we infer an overall southward migration of the TDD, even in areas with constrained uplift associated with intrusions.

"I'm living in a 'no' world now…"- A qualitative study of the widespread impact of living with chronic breathlessness, and experiences of identification and assessment of this symptom in an older, frail community-based population.

Chronic breathlessness is a debilitating symptom with detrimental impact on individuals and carers. However, little is known about the experiences of community-dwelling, frail, older adults living with chronic breathlessness. To explore, (i) the psychological impact of living with chronic breathlessness, (older frail adult patients, carers) and (ii) how patients, carers, and clinicians experience identification and assessment of chronic breathlessness in the primary care setting.

Unraveling complexity and leveraging opportunities in uncommon breast cancer subtypes.

Special histologic subtypes of breast cancer (BC) exhibit unique phenotypes and molecular profiles with diagnostic and therapeutic implications, often differing in behavior and clinical trajectory from common BC forms. Novel methodologies, such as artificial intelligence may improve classification. Genetic predisposition plays roles in a subset of cases.

Understanding the Impact of Obesity on Liver Transplant Outcomes: A Comprehensive Analysis.

Background: The purpose of this investigation is to assess how effective it is to exclude individuals from the liver transplant (LT) using the body mass index (BMI) as a criterion.

Methods And Materials: A retrospective longitudinal analysis of patients with liver transplant outcomes from January 2001 to May 2020 was conducted using the United Network for Organ Sharing (UNOS) database.

Results: A total of 118,486 LT cases included in the study.

Practice Advisory for Postoperative Pain Management of Cardiac Surgical Patients: A Report by Society of Cardiovascular Anesthesiologists.

Moderate to severe pain after cardiac surgery is relatively common, which increases the risk of postoperative cardiopulmonary complications and delays hospital discharge. Opioids have been useful agents for postoperative pain control after cardiac surgery, but are associated with serious adverse effects. As a result, multimodal analgesia has been adopted widely to decrease reliance on opioids for treating postoperative pain, reduce opioid-related adverse effects, and promote early recovery.

A Call for a Neoadjuvant Kidney Cancer Consortium: Lessons Learned from Other Cancer Types.

Neoadjuvant systemic treatment strategies have improved outcomes in several solid tumour types. This success has not yet been replicated in renal cell carcinoma (RCC). A consensus and international collaboration are urgently needed for the development of adaptive perioperative immunotherapy strategies for patients with RCC at high risk of recurrence.

Critical Perspectives on Global Health Policy, Diagnostic Access and Practice Gaps towards a Tuberculosis Free India.

Tuberculosis (TB) poses a significant public health challenge in India. According to the World Health Organization (WHO), India tops the list of 30 countries responsible for 87% of global TB cases in 2023. Recent data indicates that India's TB incidence rate was 195 cases per 100,000 population in 2023, accounting for approximately 26% of global TB cases.

Histoplasmosis in a Solid Organ Transplant Patient in a Non-Endemic Region in New York City.

Objective: To present the case of a solid organ transplant recipient with Histoplasmosis in New York City.

Case Report: We present a 39-year-old female liver transplant recipient, who experienced a two-week history of progressive shortness of breath and dyspnea on exertion that interfered with all activities of daily living. Physical examination by the team revealed the patient had a WBC of 11.

Epidemiology of gender dysphoria and gender incongruence in children and young people attending primary care practices in England: retrospective cohort study.

Objective: To examine trends in diagnosis of gender dysphoria and related conditions in children and young people attending primary care practices in England.

Design: Longitudinal analysis of electronic primary care records from the Clinical Practice Research Datalink (CPRD) Aurum database linked to hospital and Index of Multiple Deprivation data.

Setting: Primary care practices in England between 2011 and 2021.

Real-world treatment patterns and clinical characteristics in patients with moderate-to-severe systemic lupus erythematosus: an analysis of the SLE Prospective Observational Cohort Study (SPOCS).

Objectives: Systemic lupus erythematosus (SLE) is a disease with heterogeneous treatment patterns largely based on organ involvement and disease severity. The SLE Prospective Observational Cohort Study (SPOCS) collected data worldwide over 3 years from patients with moderate-to-severe SLE. We report real-world patterns of medication use in patients enrolled in SPOCS.

Clinical outcomes of patients with unsuccessful mechanical thrombectomy versus best medical management of medium vessel occlusion stroke in the middle cerebral artery territory.

Background: Current randomized controlled trials are investigating the efficacy and safety of mechanical thrombectomy (MT) in patients with medium vessel occlusion (MeVO) stroke. Whether best medical management (MM) is more efficient than unsuccessful vessel recanalization during MT remains unknown.

Methods: This was a retrospective cohort study using data from 37 academic centers across North America, Asia, and Europe between September 2017 and July 2021.

Mechanical thrombectomy in elderly stroke patients with low ASPECTS: insights from STAR.

Background: The elderly population (≥80 years) were underrepresented in recent trials of endovascular thrombectomy (EVT) for anterior circulation large vessel occlusion acute ischemic stroke (LVO-AIS) with low Alberta Stroke Program Early CT Score (ASPECTS) (≤5).

Methods: This study analyzed data from a prospectively maintained database of 37 thrombectomy centers. The primary cohort of the study comprised patients with LVO-AIS aged ≥80 who underwent EVT with ASPECTS≤5 from 2013 to 2023.

Elucidating the Origins of High Capacity in Iron-Based Conversion Materials: Benefit of Complementary Advanced Characterization toward Mechanistic Understanding.

ConspectusLithium-ion batteries are recognized as an important electrochemical energy storage technology due to their superior volumetric and gravimetric energy densities. Graphite is widely used as the negative electrode, and its adoption enabled much of the modern portable electronics technology landscape. However, developing markets, such as electric vehicles and grid-scale storage, have increased demands, including higher energy content and a diverse materials supply chain.

A proposed screening strategy for evaluating the genotoxicity potential of botanicals and botanical extracts.

Botanicals have long been used to promote health and treat diseases, but the safety of many currently marketed botanicals has not been adequately evaluated. Given the chemical complexity of botanicals, which often contain numerous unknown constituents, and their widespread use, comprehensive toxicity assessments are needed. The Botanical Safety Consortium was established to address this challenge.

Frailty Predicts Failure to Rescue following Malignant Brain Tumor Resection: A NSQIP Analysis of 14,721 Patients (2012- 2020).

Purpose: Failure to rescue (FTR) is defined as mortality within 30 days following a major complication. While FTR has been studied in various brain tumor resections, its predictors in malignant brain tumor resection (mBTR) remain unexplored. This study aims to identify FTR predictors in mBTR resection patients using a frailty-driven model.

Association of Alcohol Use Disorder and Perioperative Complications and Adverse Events After Spinal Fusion Surgery During the In-hospital Period: An Analysis of the National Inpatient Sample (NIS) Database.

Objective: Alcohol use disorder carries major effects shown to limit social support, increase recovery times, and lead to a higher incidence of surgical complications. This retrospective cohort study investigated the influence of AUD on perioperative outcomes and adverse events after spinal fusions in the largest sample size to date and spanning 11 years.

Methods: Data for adult (>18 years old) patients who underwent a spinal fusion as their primary surgery were identified from the Nationwide Inpatient Sample (NIS) database for the years 2009-2020.

Implantable Cardioverter-Defibrillators and Cardiovascular Resynchronization Therapy with Left Ventricular Assist Devices: A MOMENTUM 3 Trial Analysis.

Background: The benefit of implantable cardioverter-defibrillators (ICD) and cardiovascular resynchronization therapy (CRT-D) in patients supported with a HeartMate 3 left ventricular assist device (LVAD) remains uncertain.

Methods: An analysis of the MOMENTUM 3 randomized clinical trial and the first 1000 patients in the Continued Access Protocol trial. Patients were divided into three groups based on the presence of ICD and/or CRT-D: No device (n=153, 11%), ICD only (n=699, 50.

The Efficacy and Safety of Cardiac Myosin Inhibitors Versus Placebo in Patients with Symptomatic Obstructive Hypertrophic Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials.

Introduction: Obstructive hypertrophic cardiomyopathy (oHCM) is a genetic disorder characterized by myocardial hypertrophy, which can obstruct left ventricular outflow. Cardiac myosin inhibitors (CMIs) have emerged as a novel therapeutic agent targeting cardiac muscle hypercontractility.

Objective: To compare the efficacy and safety of CMIs mavacamten and aficamten vs.

Critical Review of Guidelines for Type B Aortic Dissection.

The management of type B aortic dissection is one of the most challenging and debated topics in contemporary cardiovascular surgery practice. Patients with acute or chronic dissection-related complications, face high morbidity and mortality if not treated promptly. For most patients requiring intervention, thoracic endovascular aortic repair (TEVAR) is considered the gold standard.

Consensus statement on the treatment of proximal humerus fractures: a Delphi approach by the Neer Circle of the American Shoulder and Elbow Surgeons.

Background: The treatment of patients who suffer a proximal humeral fracture (PHF) remains controversial. The purpose of this study was to find consensus among experts using a validated iterative process in the treatment of patients after a PHF.

Methods: The Neer Circle is an organization of shoulder experts recognized for their service to the American Shoulder and Elbow Surgeons.

The effect of distraction and feedback on prefrontal cortex activity and balance in middle-aged adults: A functional near-infrared spectroscopy pilot study.

Maintaining balance while simultaneously performing other tasks is common during everyday activities. However, this dual-tasking (DT) divides attention and increases cognitive demand, which can be detrimental to stability in older adults. It is unknown if the focus of attention influences how a dual-task affects balance and whether this is detectable in middle-aged adults.

A low-cost transhumeral prosthesis operated via an ML-assisted EEG-head gesture control system.

Objective Key challenges in upper limb prosthetics include a lack of effective control systems, the often invasive surgical requirements of brain-controlled limbs, and prohibitive costs. As a result, disuse rates remain high despite potential for increased quality of life. To address these concerns, this project developed a low cost, noninvasive transhumeral neuroprosthesis-operated via a combination of electroencephalography (EEG) signals and head gestures.