Frailty and Mortality Risk Among Dogs with Extreme Longevity: Development and Predictive Validity of a Clinical Frailty Index in the Exceptional Aging in Rottweilers Study.

Frailty refers to a state of increased vulnerability to mortality and other adverse outcomes as a consequence of age-related decline in physiologic reserve and function. Comparative biomedical scientists are relied upon to innovate approaches to enhance understanding of the similarities and differences between humans and other animal species that can impact healthy aging. The research aim of this study was to develop a clinical frailty index (FI) in the Exceptional Aging in Rottweilers Study (EARS) and test its ability to predict all-cause mortality in elderly dogs.

TIGIT and PD-L1 co-blockade promotes clonal expansion of multipotent, non-exhausted antitumor T cells by facilitating co-stimulation.

Blockade of immune checkpoints PD-1 and TIGIT has demonstrated activity in mouse tumor models and human patients with cancer. Although these coinhibitory receptors can restrict signaling in CD8 T cells by regulating their associated co-stimulatory receptors CD28 and CD226, the functional consequences of combining PD-1 and TIGIT blockade remain poorly characterized. In mouse tumor models, we show that combination blockade elicited CD226-driven clonal expansion of tumor antigen-specific CD8 T cells.

Circulating tumor DNA predicts venous thromboembolism in patients with cancers.

Background: Despite rapid advances in liquid biopsy for circulating tumor DNA (ctDNA), its prognostic value for venous thromboembolism (VTE) in patients with cancer is underexplored, particularly in underserved and minoritized populations.

Objectives: To evaluate the role of ctDNA in risk stratification for cancer-associated VTE.

Methods: We analyzed data from 1038 cancer patients who underwent ctDNA measurement for oncologic care at a large safety-net hospital system in the United States.

Comparison of Cranial Cruciate Ligament Rupture Incidence among Parous and Nulliparous Rottweiler Bitches: Evidence from a Lifetime Cohort Study Supporting a Paradigm of Pregnancy-Associated Protection against Subsequent Non-Reproductive Disease Outcomes.

Emerging evidence in women supports the notion that pregnancy may reset disease resistance, thereby providing protection against subsequent adverse health outcomes, but this hypothesis has not been adequately explored in domestic dogs. Cranial cruciate ligament (CCL) rupture is a degenerative orthopedic disease that frequently affects pet dogs, and its risk has been associated with disruption of the reproductive hormone axis. Our research team is conducting a lifetime cohort study of purebred Rottweilers in North America that have lived 30% longer than breed-average.

Cutaneous Squamous Cell Carcinoma of the Head and Neck: Pathological Features and What They Mean for Prognosis and Treatment.

Cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers worldwide, with an incidence that has increased over the past 30 years. Although usually curable with excision, cSCC can become widely metastatic and aggressive with poor outcomes. Whereas the clinical and radiographic extent of any cancer will always guide selection of treatment modality, pathological features of cSCC also play an important role in determining prognosis and, subsequently, the need for further therapy.

Translational PK/PD and the first-in-human dose selection of a PD1/IL15: an engineered recombinant targeted cytokine for cancer immunotherapy.

Introduction: Interleukin 15 (IL-15) is a potential anticancer agent and numerous engineered IL-15 agonists are currently under clinical investigation. Selective targeting of IL-15 to specific lymphocytes may enhance therapeutic effects while helping to minimize toxicities.

Methods: We designed and built a heterodimeric targeted cytokine (TaCk) that consists of an anti-programmed cell death 1 receptor antibody (anti-PD-1) and an engineered IL-15.

Comparison of Patterns and Demographics of Isolated Traumatic Mandibular Fracture Between Incarcerated and General Populations.

Introduction The management of maxillofacial trauma can be challenging in different unique clinical presentations. While maxillofacial fractures vary in location based on the mechanism of injury, the mandibular fracture is noted to be one of the most common facial fractures. The objective of this study was to explore the differences in injury patterns, outcomes, and demographics of isolated traumatic mandibular fractures between incarcerated and general populations.

Diaphragmatic Ultrasound in Children With Asthma Exacerbations.

Objectives: Asthma is a leading cause of pediatric emergency department visits, yet few tools exist to objectively measure asthma severity. Diaphragmatic ultrasound (DUS) is a novel method of assessing respiratory distress; however, data are lacking for children.Our primary aim was to determine if diaphragmatic excursion (DE), diaphragmatic thickening (DT), or diaphragmatic thickening fraction (TF) correlated with asthma severity as determined by the Pediatric Respiratory Assessment Measure (PRAM) score.

A unit process log reduction database for water reuse practitioners.

Pathogen reduction for the purpose of human health protection is a critical function provided by water reuse systems. Pathogen reduction performance potential is dependent on a wide range of design and operational parameters. Poor understanding of pathogen reduction performance has important consequences-under treatment can jeopardize human health, while over treatment can lead to unnecessary costs and environmental impacts.

Assessment of cardiac adverse events following COVID-19 vaccination by speckle tracking echocardiography.

Cardiac discomfort has been reported periodically in COVID-19-vaccinated individuals. Thus, this study aimed to evaluate the role of myocardial strains in the early assessment of the clinical presentations after COVID-19 vaccination. Totally, 121 subjects who received at least one dose of vaccine within 6 weeks underwent laboratory tests, electrocardiogram (ECG), and echocardiogram.

IL-15/IL-15Rα-Fc-Fusion Protein XmAb24306 Potentiates Activity of CD3 Bispecific Antibodies through Enhancing T-Cell Expansion.

An insufficient quantity of functional T cells is a likely factor limiting the clinical activity of T-cell bispecific antibodies, especially in solid tumor indications. We hypothesized that XmAb24306 (efbalropendekin alfa), a lymphoproliferative interleukin (IL)-15/IL-15 receptor α (IL-15Rα) Fc-fusion protein, may potentiate the activity of T-cell dependent (TDB) antibodies. The activation of human peripheral T cells by cevostamab, an anti-FcRH5/CD3 TDB, or anti-HER2/CD3 TDB resulted in the upregulation of the IL-2/15Rβ (CD122) receptor subunit in nearly all CD8+ and majority of CD4+ T cells, suggesting that TDB treatment may sensitize T cells to IL-15.

A cyclic dipeptide for salinity stress alleviation and the trophic flexibility of endophyte provide insights into saltmarsh plant-microbe interactions.

In response to climate change, the nature of endophytes and their applications in sustainable agriculture have attracted the attention of academics and agro-industries. This work focused on the endophytic halophiles of the endangered Taiwanese salt marsh plant, , and evaluated the functions of these isolates through salinity stress alleviation assay using . The endophytic strain BP01R2, which can promote plant growth and salinity tolerance, was further characterized through multi-omics approaches.

Reducing inpatient opioid consumption after caesarean delivery: effects of an opioid stewardship programme and racial impact in a community hospital.

Caesarean section is the most common inpatient surgery in the USA, with more than 1.1 million procedures in 2020. Similar to other surgical procedures, healthcare providers rely on opioids for postoperative pain management.

Efficacy of emicizumab therapy in two adult patients with type 3 von Willebrand disease.

Type 3 von Willebrand disease (T3VWD) is a rare inherited bleeding disorder caused by the absence of von Willebrand factor (VWF). The traditional treatment for T3VWD has been VWF concentrates, but their effectiveness may be limited due to the development of alloantibodies. Emicizumab, a bispecific mAb, has shown promise in treating hemophilia A and is being studied as prophylaxis for T3VWD.

Anti-TIGIT antibody improves PD-L1 blockade through myeloid and T cells.

Tiragolumab, an anti-TIGIT antibody with an active IgG1κ Fc, demonstrated improved outcomes in the phase 2 CITYSCAPE trial (ClinicalTrials.gov: NCT03563716 ) when combined with atezolizumab (anti-PD-L1) versus atezolizumab alone. However, there remains little consensus on the mechanism(s) of response with this combination.

How often should I meditate? A randomized trial examining the role of meditation frequency when total amount of meditation is held constant.

Meditation apps are the most commonly used mental health apps. However, the optimal dosing of app-delivered meditation practice has not been established. We examined whether the distribution of meditation practices across a day impacted outcomes in a distressed population.

Canine Descemet Stripping Endothelial Keratoplasty with a Tissue Insertion Device: Technique and Long-Term Outcome.

. We describe a case of canine Descemet's stripping endothelial keratoplasty (DSEK) using an open-source canine tissue delivery device. .

The correlation between hip alpha angle and acetabular labral tear location and size: A cross-sectional study.

Background: Explore the correlation between hip morphology and labral tear location/size.

Methods: This retrospective study analyzed patients with hip pain who received magnetic resonance (MR) arthrography at our institution, between January 2017 and December 2020. Imaging analysis includes labral tear location and size, and hip morphology measurement with alpha angle, lateral center-edge (CE) angle, anterior CE angle, and femoral neck version.

The Price of Practice Change: Assessing the Cost of Integrating Research Findings Into Clinical Practice.

Background: Clinicians, health care administrators, and implementation scientists know that it takes intentional effort, resources, and implementation strategies to integrate research findings into routine clinical practice. An oft-cited concern for those considering whether and how to implement an evidence-based program is how much it will cost to implement the change. Yet information about the cost of implementation is not often available to health care decision-makers.