TP53 Wild-type, HPV-independent Anal Growth/(intra)Epithelial Lesion (ANGEL): a Potential Precursor of Anal Squamous Cell Carcinoma.

Human papillomavirus (HPV) underpins approximately 90% of squamous cell carcinomas (SCC) of the anus and perianal region. These tumors usually arise in association with precursor lesions such anal intraepithelial neoplasia/ high-grade squamous intraepithelial lesion (AIN 3/ HSIL), whereas a small subset of HPV-negative cancers may harbor mutations in TP53. Recently, vulvar lesions termed differentiated exophytic vulvar intraepithelial lesion/vulvar acanthosis with altered differentiated (DEVIL/VAAD) have been recognized as HPV-independent, TP53 wild-type precursors for vulvar carcinoma; however, analogous anal lesions have not been described.

Unique considerations in the assessment and management of traumatic brain injury in older adults.

The age-specific incidence of traumatic brain injury in older adults is rising in high-income countries, mainly due to an increase in the incidence of falls. The severity of traumatic brain injury in older adults can be underestimated because of a delay in the development of mass effect and symptoms of intracranial haemorrhage. Management and rehabilitation in older adults must consider comorbidities and frailty, the treatment of pre-existing disorders, the reduced potential for recovery, the likelihood of cognitive decline, and the avoidance of future falls.

Pharmacokinetic Evaluation of Neutral Sphinghomyelinase2 (nSMase2) Inhibitor Prodrugs in Mice and Dogs.

: Extracellular vesicles (EVs) can carry pathological cargo, contributing to disease progression. The enzyme neutral sphingomyelinase 2 (nSMase2) plays a critical role in EV biogenesis, making it a promising therapeutic target. Our lab previously identified a potent and selective inhibitor of nSMase2, named DPTIP (IC = 30 nM).

Contextual cues facilitate dynamic value encoding in the mesolimbic dopamine system.

Adaptive behavior in a dynamic environmental context often requires rapid revaluation of stimuli that deviates from well-learned associations. The divergence between stable value-encoding and appropriate behavioral output remains a critical component of theories of dopamine's function in learning, motivation, and motor control. Yet, how dopamine neurons are involved in the revaluation of cues when the world changes, to alter our behavior, remains unclear.

Cerebellar Volume Measures Differentiate Multiple Sclerosis Fallers from Non-Fallers.

Introduction: The cerebellum is a common lesion site in persons with multiple sclerosis (PwMS). Physiologic and anatomic studies have identified a topographic organization of the cerebellum including functionally distinct motor and cognitive areas. In this study, a recent parcellation algorithm was applied to a sample of PwMS and healthy controls to examine the relationships among specific cerebellar regions, fall status, and common clinical measures of motor and cognitive functions.

Lung injury in myocardial infarction-associated cardiogenic shock supported by venoarterial extracorporeal membrane oxygenation: a scoping review.

Background: Acute lung injury and acute respiratory failure are frequent complications of cardiogenic shock and are associated with increased morbidity and mortality. Even with increased use of temporary mechanical circulatory support, such as venoarterial extracorporeal membrane oxygenation (VA-ECMO), acute lung injury related to cardiogenic shock continues to have a determinantal effect on patient outcomes.

Objectives: To summarize potential mechanisms of acute lung injury described in patients with cardiogenic shock supported by VA-ECMO and determine current knowledge gaps.

Computational Nuclear Oncology Toward Precision Radiopharmaceutical Therapies: Ethical, Regulatory, and Socioeconomic Dimensions of Theranostic Digital Twins.

Computational nuclear oncology for precision radiopharmaceutical therapy (RPT) is a new frontier for theranostic treatment personalization. A key strategy relies on the possibility to incorporate clinical, biomarker, image-based, and dosimetric information in theranostic digital twins (TDTs) of patients to move beyond a one-size-fits-all approach. The TDT framework enables treatment optimization by real-time monitoring of the real-world system, simulation of different treatment scenarios, and prediction of resulting treatment outcomes, as well as facilitating collaboration and knowledge sharing among health care professionals adopting a harmonized TDT.

Does exercise demonstrate a dose-dependent benefit with cognition in Parkinson's disease?

Background: Exercise confers motor benefits in Parkinson's disease (PD) and may even have disease modifying effects. While the impact of exercise on motor symptoms and quality of life is well-studied in PD, its relationship with cognitive performance warrants further attention.

Methods: In people with PD, self-reported exercise information was quantified using the Rapid Assessment of Physical Activity (RAPA).

SARS-CoV-2 IgG antibodies in COVID-19 convalescent plasma and conventional plasma units.

Background: The Association for the Advancement of Blood and Biotherapies guidelines recommend the use of high-titer COVID-19 convalescent plasma (CCP) for patients with SARS-CoV-2 at high risk of disease progression, including those who are immunocompromised. We hypothesized that conventional plasma units have comparable neutralizing antibody levels to CCP.

Study Design And Methods: Conventional plasma and CCP units were obtained from blood suppliers.

The prediction value of serum anion gap for short-term mortality in pulmonary hypertension patients with sepsis: a retrospective cohort study.

Background: The relationship between anion gap (AG) and short-term mortality of pulmonary hypertension (PH) patients with sepsis in the intensive care unit (ICU) remains unclear.

Methods: This study involved a retrospective analysis of incident PH patients with sepsis first admitted to the ICU in the MIMIC IV database (2008 to 2019). Short-term outcomes include in-hospital mortality and 28-day mortality.

Medical Students' Observations of High Value and Potentially Wasteful Care Behaviors Modeled During Clinical Rotations.

Background: Medical student exposure to role-modeling of high-value care (HVC) behaviors may shape professional identity formation and future HVC practices.

Objective: To investigate the frequency and characteristics of HVC role-modeling witnessed by medical students during core clinical rotations.

Design: Cross-sectional survey study.

Hepatitis C Treatment in Kentucky Medicaid Recipients with Concurrent Opioid Use Disorder: A Cross-Sectional Study.

Background: Hepatitis C virus (HCV) infections and injection drug use have concurrently increased in the last decade. Evidence supports simultaneously treating chronic HCV and opioid use disorder (OUD) with medication. Kentucky is a hard-hit state for both conditions that has undertaken policy and practice efforts to increase access to both types of medications.

Punctuational evolution is pervasive in distal site metastatic colonization.

The evolution of metastasis, the spread of cancer to distal sites within the body, represents a lethal stage of cancer progression. Yet, the evolutionary dynamics that shape the emergence of metastatic disease remain unresolved. Here, using single-cell lineage tracing data in combination with phylogenetic statistical methods, we show that the evolutionary trajectory of metastatic disease is littered with bursts of rapid molecular change as new cellular subpopulations appear, a pattern known as punctuational evolution.

Barriers to Adherence with Clinic Visits in Patients with Uveitis.

Purpose: To assess the patient barriers to adherence with appointment follow-up in patients with ocular inflammatory disorders across the United States.

Methods: This was a multicenter study of adult and pediatric patients at the Wilmer Eye Institute, University of Texas at Austin, University of Wisconsin-Madison, University of Minnesota, Minneapolis Veterans Administration Hospital, and Washington University of St. Louis.

Using Community Engagement to Create a Telecoaching Intervention to Improve Self-Management in Adolescents and Young Adults With Cystic Fibrosis: Qualitative Study.

Background: Adolescents and young adults (AYA) with cystic fibrosis (CF) are at risk for deviating from their daily treatment regimen due to significant time burden, complicated daily therapies, and life stressors. Developing patient-centric, effective, engaging, and practical behavioral interventions is vital to help sustain therapeutically meaningful self-management.

Objective: This study aimed to devise and refine a patient-centered telecoaching intervention to foster self-management in AYA with CF using a combination of intervention development approaches, including an evidence- and theory-based approach (ie, applying existing theories and research evidence for behavior change) and a target population-centered approach (ie, intervention refinement based on the perspectives and actions of those individuals who will use it).

Moderate-to-Vigorous Physical Activity at any Dose Reduces All-Cause Dementia Risk Regardless of Frailty Status.

Objectives: Reaching the moderate-to-vigorous physical activity (MVPA) recommendations of 150 min/wk is difficult for older adults, particularly among those living with frailty and its associated risk of dementia. We examined the dose-response relationship between MVPA and dementia risk among at-risk persons living with and without frailty enrolled in the UK Biobank study.

Design: Survival analysis within a prospective cohort study.

Merits of the social return on investment methodology for assessing the value of palliative care programmes.

Despite the widely accepted benefits of palliative care for individuals with serious illnesses and their families, the utilisation of this approach remains low. Although an increased use of palliative care services can increase the value of health-care spending by providing comprehensive wraparound services to support care, the economic evidence required to implement, promote, and engage in palliative care models on a wide scale eludes the affected individuals, health-care providers, payers, and policy makers. This gap in evidence is partly owing to the methodological limitations of standard value-assessment frameworks, which do not capture important societal dimensions of the value generated by palliative care.

Association between interhospital transfer status and outcomes following nontraumatic subdural hemorrhage.

Background: Patients with nontraumatic subdural hemorrhage often require immediate surgical intervention that may not be available at community hospitals and are therefore transferred to tertiary care centers. This study aims to evaluate the effects of interhospital transfer (IHT) on postoperative complications and outcomes following ntSDH.

Methods: The National Surgical Quality Improvement Program (NSQIP) database was queried for patients treated for ntSDH from January 2014 to January 2020.

Cerebral blood volume index in the era of thrombectomy-treated large and medium vessel ischemic strokes.

The cerebral blood volume index (CBV index) is a perfusion-based marker of collateral status. Several real-world data analyses from observational stroke cohorts have established relationships between this parameter and a range of favorable and unfavorable stroke outcomes. In this review, an overview is provided of the CBV index, within the context of thrombectomy-treated large vessel and medium vessel occlusion ischemic strokes.