Cancer-specific innate and adaptive immune rewiring drives resistance to PD-1 blockade in classic Hodgkin lymphoma.

Hodgkin Reed-Sternberg (HRS) cells of classic Hodgkin lymphoma (cHL), like many solid tumors, elicit ineffective immune responses. However, patients with cHL are highly responsive to PD-1 blockade, which largely depends on HRS cell-specific retention of MHC class II and implicates CD4 T cells and additional MHC class I-independent immune effectors. Here, we utilize single-cell RNA sequencing and spatial analysis to define shared circulating and microenvironmental features of the immune response to PD-1 blockade in cHL.

Territory Sizes and Patterns of Habitat Use by Forest Birds Over Five Decades: Ideal Free or Ideal Despotic?

Relations among territoriality, abundance and habitat suitability are fundamental to the ecology of many animal populations. Theory suggests two classes of possible responses to increasing abundance in territorial species: (1) the ideal free distribution (IFD), which predicts smaller territory sizes and decreased fitness as individuals adaptively pack into suitable habitats, and (2) the ideal despotic distribution (IDD), which predicts stable territory sizes and fitness in preferred habitats for dominant individuals and increased use of marginal habitats, reduced fitness and changes in territory sizes for subordinate individuals. We analysed the territory sizes and locations of seven migratory songbird species occupying a 10-ha plot in the Hubbard Brook Experimental Forest, New Hampshire, USA over a 52-year period.

Estimation of Ligand Binding Free Energy Using Multi-eGO.

The computational study of ligand binding to a target protein provides mechanistic insight into the molecular determinants of this process and can improve the success rate of drug design. All-atom molecular dynamics (MD) simulations can be used to evaluate the binding free energy, typically by thermodynamic integration, and to probe binding mechanisms, including the description of protein conformational dynamics. The advantages of MD come at a high computational cost, which limits its use.

Regulations of activities and protection levels in marine protected areas of the European Union: A dataset compiled from multiple data sources.

The dataset gathers available regulations of human activities and protection levels of Marine Protected Areas (MPAs) of the European Union (EU). The MPA list and polygons were extracted from the MPA database of the European Environment Agency (EEA) and completed with available zoning systems (all were filtered for their marine area reported under the Marine Strategy Framework Directive). Fully-overlapping MPAs were merged.

Distinct regulation of Tau Monomer and aggregate uptake and intracellular accumulation in human neurons.

Background: The prion-like spreading of Tau pathology is the leading cause of disease progression in various tauopathies. A critical step in propagating pathologic Tau in the brain is the transport from the extracellular environment and accumulation inside naïve neurons. Current research indicates that human neurons internalize both the physiological extracellular Tau (eTau) monomers and the pathological eTau aggregates.

Anticoagulation therapy for the prevention of subclinical leaflet thrombosis after transcatheter aortic valve replacement: A comprehensive literature review and future directions.

Leaflet thrombosis after transcatheter aortic valve replacement (TAVR) presents a significant challenge, leading to adverse clinical outcomes. Subclinical leaflet thrombosis (SLT) is increasingly recognized, and there is a growing concern about its role in clinical events and hemodynamic valve deterioration. Current recommendations for prophylactic anticoagulation or antiplatelet therapy following TAVR are primarily based on expert consensus rather than definitive evidence from randomized trials, resulting in a variety of antithrombotic strategies in clinical practice.

The impact of functional correlations on task information coding.

State-dependent neural correlations can be understood from a neural coding framework. Noise correlations-trial-to-trial or moment-to-moment covariability-can be interpreted only if the underlying signal correlation-similarity of task selectivity between pairs of neural units-is known. Despite many investigations in local spiking circuits, it remains unclear how this coding framework applies to large-scale brain networks.

Biopsy Quotas: Ethical Implications of Financial Incentives and Penalties on Dermatologic Care Providers.

The evolution of healthcare payment models has profoundly influenced clinical practices and physician decision-making. While fee-for-service (FFS) models incentivize procedural volume, systems based on Relative Value Units (RVUs) have introduced standardized metrics to compensate physicians based on care complexity and workload. As corporations increasingly own healthcare, financial incentives such as RVUs and procedural quotas raise ethical concerns.

A novel concept of an acoustic ultrasound wearable for early detection of implant failure.

Mechanical failure of medical implants, especially in orthopedic poses a significant burden to the patients and healthcare system. The majority of the implant failures are diagnosed at very late stages and are of mechanical causes. This makes the diagnosis and screening of implant failure very challenging.

A descriptive examination of rurality in the Environmental influences on Child Health Outcomes Cohort: Implications, illustrations, and future directions.

Purpose: The Environmental influences on Child Health Outcomes (ECHO) Cohort has enrolled over 60,000 children to examine how early environmental factors (broadly defined) are associated with key child health outcomes. The ECHO Cohort may be well-positioned to contribute to our understanding of rural environments and contexts, which has implications for rural health disparities research. The present study examined the outcome of child obesity to not only illustrate the suitability of ECHO Cohort data for these purposes but also determine how various definitions of rural and urban populations impact the presentation of findings and their interpretation.

Shared Decision-Making in Total Hip and Knee Arthroplasty: Understanding Surgeon and Patient Perspectives Regarding When It Is Time for Surgery.

Background: Although total hip and total knee arthroplasty are highly successful operations, the decision of whether and when to undergo surgery is highly subjective and discretionary, and specific guidelines regarding readiness for surgery remain elusive. The nature of these decisions underscores the importance of shared decision-making, which is founded on the concept that patients substantially contribute to determining their own readiness for surgery. The OPTION survey was developed as a conversation aid to facilitate shared decision-making in the context of total joint arthroplasty.

Shape of the Doppler Sonographic Systolic Blood Flow Profile of the Pulmonary Artery of Healthy Racing Pigeons and the Influence of Anesthesia.

There is scant information available about the blood flow of the pulmonary artery in avian cardiology. In human medicine, the shape of the Doppler sonographic blood flow profile of the pulmonary artery can be used to access the pressure conditions of the right heart. With this background, this study focused on the examination of the acceleration and deceleration phase of the pulsed-wave Doppler flow profile of the pulmonary artery of healthy racing pigeons.

Electrochemical Method for the Design of New Possible Gadolinium-Based Contrast Agents.

Magnetic resonance imaging (MRI) is a technique that employs strong magnetic fields and radio frequencies to generate detailed images of the body's interior. In oncology patients, gadolinium-based contrast agents (GBCAs) are frequently administered to enhance the visualization of tumors. Those contrast agents are gadolinium chelates, characterized by high stability that prevents the release of the toxic gadolinium ion into the body.

The Reproducibility and Reliability of Insulin Sensitivity and Secretion Indices in Children and Adolescents.

Context: Insulin sensitivity and secretion indices can be useful tools in understanding insulin homeostasis in children at risk for diabetes. There have been few studies examining the reproducibility of these measures in pediatrics.

Objective: To determine whether fasting or oral glucose tolerance test (OGTT)-derived insulin measures would be more reproducible and whether there would be differences based on weight, sex, race, and pubertal status.

Proactive Management of Lactation in the Birth Hospital to Ensure Long-Term Milk Production and Sustainable Breastfeeding.

Individuals who are at risk of not achieving a full milk supply are often overlooked in scientific literature. There is available guidance to help establish an adequate milk supply for healthy individuals experiencing a physiologic labor and birth, and there are robust recommendations for the lactating parents of small, sick, and preterm newborns to ensure that these newborns can receive human milk. Missing from the literature are clinical practice guidelines that address the preexisting health, pregnancy, birth, or newborn-related risk factors for suboptimal lactation.

Pathology Findings and In-Life Correlates in the Nonclinical Development of Adeno-Associated Virus (AAV)-Based Retinal Gene Therapies.

Adeno-associated virus (AAV)-based vectors are the most frequently used platform for retinal gene therapy. Initially explored for the treatment of loss-of-function mutations underpinning many inherited retinal diseases, AAV-based ocular gene therapies are increasingly used to transduce endogenous cells to produce therapeutic proteins, thus producing site-specific biofactories. Relatively invasive ocular routes of administration (ROA) mean prominent procedure-related in-life, and histopathological findings may be observed with some regularity.

WATCH: A Workflow to Assess Treatment Effect Heterogeneity in Drug Development for Clinical Trial Sponsors.

This article proposes a Workflow for Assessing Treatment effeCt Heterogeneity (WATCH) in clinical drug development targeted at clinical trial sponsors. WATCH is designed to address the challenges of investigating treatment effect heterogeneity (TEH) in randomized clinical trials, where sample size and multiplicity limit the reliability of findings. The proposed workflow includes four steps: analysis planning, initial data analysis and analysis dataset creation, TEH exploration, and multidisciplinary assessment.

Bacterial growth temperature as a horizontally acquired polygenic trait.

Evolutionary events leading to organismal preference for a specific growth temperature, as well as genes whose products are needed for a proper function at that temperature, are poorly understood. Using 64 bacteria from phylum Thermotogota as a model system, we examined how optimal growth temperature changed throughout Thermotogota history. We inferred that Thermotogota's last common ancestor was a thermophile and that some Thermotogota evolved the mesophilic and hyperthermophilic lifestyles secondarily.

Patterns of initial treatment and subsequent care escalation among medicare beneficiaries with neck pain: a retrospective cohort study.

Purpose: To compare long-term care escalation encounters among three care patterns for new episodes of neck pain among Medicare beneficiaries.

Methods: We examined Medicare claims spanning a four-year period for beneficiaries with new episodes of neck pain beginning in 2019. All patients were continuously enrolled under Medicare parts A, B, and D and aged 65-99 years.

Neural correlates of audiovisual integration in schizophrenia - an ERP study.

Introduction: Multisensory integration (MSI) enhances perception by combining information from different sensory modalities. In schizophrenia, individuals often exhibit impaired audiovisual processing, resulting in broader temporal binding windows (TBWs) which appear to be associated with symptom severity. Since the underlying mechanisms of these aberrations are not yet fully understood, the present study aims to investigate multisensory processing in schizophrenia in more detail.

Emerging cancer therapies: targeting physiological networks and cellular bioelectrical differences with non-thermal systemic electromagnetic fields in the human body - a comprehensive review.

A steadily increasing number of publications support the concept of physiological networks, and how cellular bioelectrical properties drive cell proliferation and cell synchronization. All cells, especially cancer cells, are known to possess characteristic electrical properties critical for physiological behavior, with major differences between normal and cancer cell counterparts. This opportunity can be explored as a novel treatment modality in Oncology.

Mechanistic Insight into the Formation and Deposition of Conductive, Layered Metal-Organic Framework Nanocrystals.

This paper describes the use of the layered conductive metal-organic framework (MOF) (nickel)-(hexahydroxytriphenylene) [Ni(HHTP)] as a model system for understanding the process of self-assembly within this class of materials. We confirm and quantify experimentally the role of the oxidant in the synthetic process. Monitoring the deposition of Ni(HHTP) with infrared spectroscopy revealed that MOF formation is characterized by an initial induction period, followed by linear growth with respect to time.

Comparative assessment of the transduction efficiency and safety associated with the delivery of AAV9-GFP vector via lumbar puncture to cynomolgus macaques with and without anti-AAV9 pre-existing antibodies.

Administration of AAV-based gene therapies into the intra-cerebrospinal fluid (CSF) compartments via routes such as lumbar puncture (LP) has been implemented as an alternative to intravenous dosing to target the CNS regions. This route enables lower doses, decreases systemic toxicity, and circumvents intravascular pre-existing anti-AAV antibodies. In this study, AAV9-GFP vectors were administered via LP to juvenile cynomolgus macaques with and without pre-existing serum anti-AAV9 antibodies at a 5.