Randomized phase II study of bevacizumab with weekly anetumab ravtansine or weekly paclitaxel in platinum-resistant/refractory high grade ovarian cancer (NCI trial).

Purpose: Mesothelin (MSLN) is highly expressed in high grade serous/ endometrioid ovarian cancers (HGOC). Anetumab ravtansine (AR) is an antibody drug conjugate directed at MSLN antigen with a tubulin polymerization inhibitor. We assessed safety, activity and pharmacokinetics of the combination AR/bevacizumab (Bev) (ARB) versus weekly paclitaxel (wP)/Bev (PB) in patients with platinum resistant/refractory HGOC (prrHGOC).

CA-125 as a Biomarker in Renal Medullary Carcinoma: Integrated Molecular Profiling, Functional Characterization, and Prospective Clinical Validation.

Purpose: Renal medullary carcinoma (RMC) is a highly aggressive malignancy defined by the loss of the SMARCB1 tumor suppressor. It mainly affects young individuals of African descent with sickle cell trait, and it is resistant to conventional therapies used for other renal cell carcinomas. This study aimed to identify potential biomarkers for early detection and disease monitoring of RMC.

The Landscape of Vascular Endothelial Growth Factor Inhibition in Retinal Diseases.

Ever since the US Food and Drug Administration (FDA) approved the first vascular endothelial growth factor (VEGF) antagonist 2 decades ago, inhibitors of VEGF have revolutionized the treatment of a variety of ocular disorders involving pathologic neovascularization and retinal exudation. In this perspective, we evaluate the current status of anti-VEGF therapies and the real-world challenges encountered with maintaining therapeutic outcomes. Finally, we describe novel VEGF-based and combinatorial approaches that are in clinical development.

Safety of Human USH1C Transgene Expression Following Subretinal Injection in Wild-Type Pigs.

Purpose: This study aimed to evaluate early-phase safety of subretinal application of AAVanc80.CAG.USH1Ca1 (OT_USH_101) in wild-type (WT) pigs, examining the effects of a vehicle control, low dose, and high dose.

Time Is a Tool: Evaluation of a Prolonged Casualty Care Curriculum With a Focus on Temporal Fidelity.

Introduction: In current and anticipated future conflicts, including large-scale combat operations, medical teams are tasked to provide prolonged casualty care (PCC) or extended patient care that occurs when delays in evacuation exceed the team's capabilities. Although the principles of PCC are often taught to military medical providers using simulation, educators rarely dedicate the time to training required to simulate the prolonged nature of these encounters. Therefore, a lack of knowledge exists regarding which aspects of extended care may be lost in an accelerated training scenario.

Rare cancer survivorship research funding at the National Institutes of Health (NIH), 2017 to 2023.

Purpose: Rare cancers are defined as those for which there are less than 15 cases per 100,000 in the population annually. While much progress in detection and treatment has been made over the past decade for many rare cancers, less progress has been made in understanding survivorship needs. The objective of this study was to characterize the National Institutes of Health (NIH) cancer survivorship grant portfolio focused on rare cancers and to identify gaps specific to this area of science.

Adenocarpine, Marmesin, and Lycocernuine from Ficus benjamina as Promising Inhibitors of Aldose Reductase in Diabetes: A Bioinformatics-Guided Approach.

Diabetes affects approximately 422 million people worldwide, leading to 1.5 million deaths annually and causing severe complications such as kidney failure, neuropathy, and cardiovascular disease. Aldose reductase (AR), a key enzyme in the polyol pathway, is an important therapeutic target for managing these complications.

MRI-assessed Dynamic Hyperinflation Induced by Tachypnea in Chronic Obstructive Pulmonary Disease: The SPIROMICS-HF Study.

Purpose To assess the repeatability of real-time cine pulmonary MRI measures of metronome-paced tachypnea (MPT)-induced dynamic hyperinflation and its relationship with chronic obstructive pulmonary disease (COPD) severity. Materials and Methods SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) (ClinicalTrials.gov identifier no.

Navigating Copyright Law and Fair Use in the Age of Digital Education.

Intellectual property laws were not originally designed to address digital classrooms and shared online learning environments, but these concerns are now relevant to many educational institutions. The recent expansion of technology utilization in health professions education presents educators with the challenges to accurately interpret copyright law and implement best practices under the tenets of fair use. Discerning legal and ethical parameters relevant to copyright law will encourage the implementation of best practices in disseminating information and creating appropriate learning activities in the age of digital education.

Resident-led Seminar and Workshop on Airway Management for Physician Assistant Students: Evaluating Efficacy and Memory Retention.

Introduction: Physician assistants (PAs) should understand the implications and risks involved with airway management. Our study aimed to facilitate PA students' familiarity with airway management with instruction from anesthesiology residents. We assessed the students' knowledge of airway management both before and after a seminar to see if knowledge was retained.

Phase formation and phase stability for the homogenous and heterogeneous amorphous metals versus the crystalline phase.

From molecular dynamics (MD) simulations of melt-quenching and thermal aging procedures in pure Ag, Cu, Ag-Cu binary alloys, and Cu-Zr binary alloys, we have identified two distinct amorphous phases for a metastable undercooled liquid: the homogeneous L-phase with low shear rigidity and the heterogenous G-phase with much higher shear rigidity and a heterogeneity length scale Λ. Here, we examine two-phase equilibration studies showing that the G-phase melts to form the L-phase above ~1,000 K, which then transforms to form the crystal (X) phase; however, below the melting point of the G-Phase (~990 K), the X- and G-phases do not transform into each other. We suggest the presence of a G-phase is likely responsible for embrittlement often observed in metallic glasses.

Bone-Induced Her2 Promotes Secondary Metastasis in HR+/Her2- Breast Cancer.

Bone metastases can disseminate to secondary sites and promote breast cancer progression creating additional clinical challenges. The mechanisms contributing to secondary metastasis are barely understood. Here, we evaluate the prediction power of Her2-expressing (Her2E) circulating tumor cells (CTCs) after analyzing over 13,000 CTCs from a cohort of 137 metastatic breast cancer (MBC) patients with initial HR+/Her2- status and employ preclinical models of bone metastasis (BM) to validate the role of Her2E CTCs in multi-organ metastases.

High unmet needs for cervical cancer screening among women living with HIV in six African countries: A population-based study.

Background: Cisgender women living with HIV (WLWH) are disproportionately impacted by cervical cancer. Nevertheless, disparities in uptake and implementation of cervical cancer services persist in sub-Saharan Africa, where population-level estimates of screening coverage remain scarce.

Methods: We pooled data from nationally representative Population-based HIV Impact Assessment (PHIA) surveys conducted in Ethiopia, Malawi, Rwanda, Tanzania, Zambia, and Zimbabwe (2015-2019).

Comparison Between Molecular Dynamics Potentials for Simulation of Graphene-Based Nanomaterials for Biomedical Applications.

Objective: This article provides a substantial review of recent research and comparison on molecular dynamics potentials to determine which are most suitable for simulating the phenomena in graphene-based nanomaterials (GBNs).

Significance: GBNs gain significant attention due to their remarkable properties and potential applications, notably in nanomedicine. However, the physical and chemical characteristics toward macromolecules that justify their nanomedical applications are not yet fully understood.

Single-cell RNA Sequencing Revealed the Immunophenotypic Features of Macrophages in Cardiac Transplants and Uncovered Lgals9 Promoted Their Polarization towards The M2b Subtype.

Macrophages play a crucial role in the immune response during allograft rejection in organ transplantation. Therefore, our study aimed to explore the genomic features of macrophages in mouse heart transplants and use single-cell RNA sequencing to investigate Galectin-9 (Gal-9, Lgals9), a lectin that can mediate the activation and differentiation of immune cells through ligand-receptor interactions, and the effects of its regulation in transplantation. We discovered a new subset of macrophages called "Myoz2+ macrophages", which specifically expressed genes related to myocardial contraction.

Early detection and management of hearing loss to reduce dementia risk in older adults with mild cognitive impairment: findings from the treating auditory impairment and cognition trial (TACT).

Background: Age-related hearing loss and mild cognitive impairment (MCI) independently increase dementia risk. The Ageing and Cognitive Health Evaluation in Elders randomised controlled trial (RCT) found hearing aids reduce cognitive decline in high-risk older adults with poor hearing.

Methods: This pilot RCT in London memory clinics randomised people with MCI (aged ≥55, untreated hearing loss defined as Pure Tone Average 0.

Improving estimation efficiency for survival data analysis by integrating a coarsened time-to-event outcome from an external study.

In the era of big data, increasing availability of data makes combining different data sources to obtain more accurate estimations a popular topic. However, the development of data integration is often hindered by the heterogeneity in data forms across studies. In this paper, we focus on a case in survival analysis where we have primary study data with a continuous time-to-event outcome and complete covariate measurements, while the data from an external study contain an outcome observed at regular intervals, and only a subset of covariates is measured.

Syngeneic natural killer cell therapy activates dendritic and T cells in metastatic lungs and effectively treats low-burden metastases.

Natural killer (NK) cells can control metastasis through cytotoxicity and IFN-γ production independently of T cells in experimental metastasis mouse models. The inverse correlation between NK activity and metastasis incidence supports a critical role for NK cells in human metastatic surveillance. However, autologous NK cell therapy has shown limited benefit in treating patients with metastatic solid tumors.

From Antibacterial Activity to Molecular Mechanism: Case Study of Hexapeptide RWWRWW and Its Analogues.

In recent years, antimicrobial peptides (AMPs) have emerged as a potent weapon against the growing threat of antibiotic resistance. Among AMPs, the ones containing tryptophan (W) and arginine (R) exhibit enhanced antimicrobial properties, benefiting from the unique physicochemical features of the two amino acids. Herein, we designed three hexapeptides, including WR, DWR (D-isomer), and RF, derived from the original sequence, RWWRWW-NH2 (RW).

Coping with cognitive decline in older adults with mild cognitive impairment or mild dementia: a scoping review.

Objectives: This scoping review aims to map out the coping strategies among Persons with Mild Cognitive Impairment (PwMCI) and Persons with Mild Dementia (PwMD), identifying the facilitators and the barriers to the use of the strategies.

Method: We conducted a systematic search of peer-reviewed studies in PubMed, CINAHL, EMBASE, and PsycINFO. Under the guidance of the Coping Circumflex Model, we identified coping strategies and then conducted thematic synthesis.

Topographic Analysis of the Periorbital Region Including Orbicularis Oculi Muscle Based on Ultrasonography Interpretation.

Objective: Ultrasonographic examination is easy, fast, safe, and used in various fields; however, its application to the facial area has been limited. Complex anatomical structures are mixed within thin, soft tissues in the facial region; therefore, understanding their structural characteristics is crucial. This study aimed to use ultrasonography to obtain information on the layered structure and soft tissue thickness of the eye area around the orbicularis oculi muscle and provide guidance for clinical practice.

Neighborhood opportunity and residential instability: associations with mental health in middle childhood.

Background: Neighborhood quality may contribute to child mental health, but families with young children often move, and residential instability has also been tied to adverse mental health. This study's primary goal was to disentangle the effects of neighborhood quality from those of residential instability on mental health in middle childhood.

Methods: 1,946 children from 1,652 families in the Upstate KIDS cohort from New York state, US, were followed prospectively from birth to age 10.

Larger Perfusion Mismatch Volume Is Associated With Longer Hospital Length of Stay in Medium Vessel Occlusion Stroke.

Background And Purpose: Prolonged length of stay (LOS) following a stroke is associated with unfavorable clinical outcomes. Factors predicting LOS in medium vessel occlusion (MeVO), impacting up to 40% of acute ischemic stroke (AIS) cases, remain underexplored. This study aims to investigate the predictors of LOS in AIS-MeVO.

Geographic disparities in physical and mental health comorbidities and socioeconomic status of residence among Medicaid beneficiaries in Utah.

To examine the relationship between socioeconomic deprivation and complex needs, defined as mental and physical comorbidities, we conducted a cross-sectional retrospective cohort analysis of adult Utah Medicaid beneficiaries. Our analysis included Medicaid beneficiaries with geocoded addresses aged ≥18 years in Utah ( = 157,739). We geocoded beneficiary addresses and assigned them to census block groups.