Genomic prediction using low-coverage portable Nanopore sequencing.

Most traits in livestock, crops and humans are polygenic, that is, a large number of loci contribute to genetic variation. Effects at these loci lie along a continuum ranging from common low-effect to rare high-effect variants that cumulatively contribute to the overall phenotype. Statistical methods to calculate the effect of these loci have been developed and can be used to predict phenotypes in new individuals.

Blood-brain barrier-restricted translocation of from cortical capillaries.

The cellular barriers of the central nervous system proficiently protect the brain parenchyma from infectious insults. Yet, the single-celled parasite commonly causes latent cerebral infection in humans and other vertebrates. Here, we addressed the role of the cerebral vasculature in the passage of to the brain parenchyma.

An Epigenetic Aging Clock for Cattle Using Portable Sequencing Technology.

Extensively grazed cattle are often mustered only once a year. Therefore, birthdates are typically unknown or inaccurate. Birthdates would be useful for deriving important traits (growth rate; calving interval), breed registrations, and making management decisions.

Combination of ONC201 and TLY012 induces selective, synergistic apoptosis in vitro and significantly delays PDAC xenograft growth in vivo.

The five-year survival rate for pancreatic ductal adenocarcinoma (PDAC) has remained a dismal 9% for approximately 40 years with an urgent need for novel therapeutic interventions. ONC201 is the founding member of the imipridone class, comprised of orally bioavailable small molecules that have shown efficacy in multiple tumor types both in animal models and in Phase I/II clinical trials. ONC201 is a potent inducer of the tumor necrosis factor related apoptosis inducing ligand (TRAIL) pathway.

Regional Anesthesia Use in Pediatric Burn Surgery: A Descriptive Retrospective Series.

Pediatric burns are a common and often devastating injury. Treatment, reconstruction, and rehabilitation are painful experiences. For some, the experience triggers post-traumatic stress disorder and/or a chronic pain syndrome.

Unsupervised Learning for Automated Detection of Coronary Artery Disease Subgroups.

Background The promise of precision population health includes the ability to use robust patient data to tailor prevention and care to specific groups. Advanced analytics may allow for automated detection of clinically informative subgroups that account for clinical, genetic, and environmental variability. This study sought to evaluate whether unsupervised machine learning approaches could interpret heterogeneous and missing clinical data to discover clinically important coronary artery disease subgroups.

Keepers of the House: A documentary.

Background: Our documentary, Keepers of the House, highlights ways that hospital housekeepers, typically unnoticed care team members, provide emotional support for patients and their families. This film addresses a gap in education by emphasizing the importance of valuing and reflecting on the unique lived experiences of others.

Approach: We created this documentary to expose students to the experiences and perceptions of hospital housekeepers.

Osseosurface electronics-thin, wireless, battery-free and multimodal musculoskeletal biointerfaces.

Bioelectronic interfaces have been extensively investigated in recent years and advances in technology derived from these tools, such as soft and ultrathin sensors, now offer the opportunity to interface with parts of the body that were largely unexplored due to the lack of suitable tools. The musculoskeletal system is an understudied area where these new technologies can result in advanced capabilities. Bones as a sensor and stimulation location offer tremendous advantages for chronic biointerfaces because devices can be permanently bonded and provide stable optical, electromagnetic, and mechanical impedance over the course of years.

Improved Treatment Effect of Triamcinolone Acetonide Extended-Release in Patients with Concordant Baseline Pain Scores on the Average Daily Pain and Western Ontario and McMaster Universities Osteoarthritis Index Pain Scales.

Introduction: A phase 3 randomized controlled study comparing triamcinolone acetonide extended-release (TA-ER) to conventional TA crystalline suspension (TAcs) reported variable efficacy results. Enrollment criteria may have contributed to this discrepancy, as moderate-to-severe average daily pain (ADP) was required at baseline, whereas no limitations were placed on Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC-A) pain severity. We conducted a post hoc sensitivity analysis to compare treatment effects in patients reporting moderate-to-severe osteoarthritis (OA) pain on both scales.

Technical note: overcoming host contamination in bovine vaginal metagenomic samples with nanopore adaptive sequencing.

Animal metagenomic studies, in which host-associated microbiomes are profiled, are an increasingly important contribution to our understanding of the physiological functions, health and susceptibility to diseases of livestock. One of the major challenges in these studies is host DNA contamination, which limits the sequencing capacity for metagenomic content and reduces the accuracy of metagenomic profiling. This is the first study comparing the effectiveness of different sequencing methods for profiling bovine vaginal metagenomic samples.

Optimizing Outcomes With the 1550/1927 nm Dual Wavelength Non-Ablative Fractional Laser: Experienced User Recommendations.

Background: Fractional laser treatment was introduced in 2004 as a non-invasive technique to treat sun-damaged and aging skin. Since then, numerous ablative and non-ablative photothermolysis technologies and devices have been introduced, increasing the options for clinicians and patients but also increasing the complexity regarding which system to use and the techniques to optimize outcomes. No two devices are the same and the user-manuals preset dosimetry does not address many clinical situations, which can create confusion for new and inexperienced users.

Intrarectal Xyloglucan Administration Reduces Disease Severity in the Dextran Sodium Sulfate Model of Mouse Colitis.

Background: The pathophysiology of inflammatory bowel diseases remains poorly understood and treatment remains suboptimal for many patients. We hypothesize that the inflammatory milieu secondarily prolongs the injury and attenuates healing. We propose primary or adjuvant therapy with biocompatible adhesives to restore a barrier to protect submucosal structures, particularly stem cells.

Accessing targeted therapies for cancer: self and collective advocacy alongside and beyond mainstream cancer charities.

As precision oncology has evolved, patients and their families have become more involved in efforts to access these treatments via fundraising and campaigning that take place outside of the larger cancer charities. In this paper, we explore the solidarities, networks, and emotional work of the UK-based access advocates, drawing on the stories of nine advocates, which included interviews and content analyses of their social media posts and coverage of their case in news, commentary, and fundraising websites. We consider the emotional and knowledge work of building networks that spanned consumerist and activist agendas, forged individual and collective goals, and orientations toward the public, private, and third sectors as part of securing support and access.

A linkage disequilibrium-based approach to position unmapped SNPs in crop species.

Background: High-density SNP arrays are now available for a wide range of crop species. Despite the development of many tools for generating genetic maps, the genome position of many SNPs from these arrays is unknown. Here we propose a linkage disequilibrium (LD)-based algorithm to allocate unassigned SNPs to chromosome regions from sparse genetic maps.

Digital Health Integration With Neuromodulation Therapies: The Future of Patient-Centric Innovation in Neuromodulation.

Digital health can drive patient-centric innovation in neuromodulation by leveraging current tools to identify response predictors and digital biomarkers. Iterative technological evolution has led us to an ideal point to integrate digital health with neuromodulation. Here, we provide an overview of the digital health building-blocks, the status of advanced neuromodulation technologies, and future applications for neuromodulation with digital health integration.

Effects of climate and land use changes on water quantity and quality of coastal watersheds of Narragansett Bay.

Land use is rapidly changing in coastal watersheds, with implications on eutrophication of coastal watersheds. The long-term consequences of climate change on these impacts are critical to watershed management. With coastal watersheds facing frequent hypoxic events and cultural eutrophication, the coupled influence of land use and climate change can lead to policies under nonstationarity assumptions.

Using Machine Learning to Predict Patterns of Employment and Day Program Participation.

In this article, we demonstrate the potential of machine learning approaches as inductive analytic tools for expanding our current evidence base for policy making and practice that affects people with intellectual and developmental disabilities (IDD). Using data from the National Core Indicators In-Person Survey (NCI-IPS), a nationally validated annual survey of more than 20,000 nationally representative people with IDD, we fit a series of classification tree and random forest models to predict individuals' employment status and day activity participation as a function of their responses to all other items on the 2017-2018 NCI-IPS. The most accurate model, a random forest classifier, predicted employment outcomes of adults with IDD with an accuracy of 89 percent on the testing sample, and 80 percent on the holdout sample.

Antitumorigenic effect of combination treatment with ONC201 and TRAIL in endometrial cancer and .

ONC201 demonstrated promising activity in patients with advanced endometrial cancer in a Phase I clinical trial. ONC201 activates the integrated stress response (ISR) and upregulates TRAIL and its receptor DR5. We hypothesized ONC201 upregulation of DR5 could sensitize tumors to TRAIL and combination of ONC201 and TRAIL would lead to enhanced cell death in endometrial cancer models.

Anti-cancer efficacy including Rb-deficient tumors and VHL-independent HIF1α proteasomal destabilization by dual targeting of CDK1 or CDK4/6 and HSP90.

A prevalent characteristic of solid tumors is intra-tumoral hypoxia. Hypoxia-inducible factor 1α (HIF1α) predominantly mediates the adaptive response to O oscillation and is linked to multiple malignant hallmarks. Here we describe a strategy to robustly target HIF1α by dual inhibition of CDK(s) and heat shock protein 90 (HSP90).

Piloting a New Curriculum: Guided At-Home Pediatric Regional Anesthesia Education Using a Portable Ultrasound.

Ultrasound-guided regional anesthesia is the standard of care for most regional blocks in pediatric anesthesiology.Training programs must educate physicians to perform regional blocks safely and efficiently. Hands-on learning with simulation and live models is the gold standard.

Treatment outcome with a selective RET tyrosine kinase inhibitor selpercatinib in children with multiple endocrine neoplasia type 2 and advanced medullary thyroid carcinoma.

Background: Medullary thyroid carcinoma (MTC) in the context of multiple endocrine neoplasia type 2 (MEN2) is caused by mutations in the RET proto-oncogene. Therefore, in children with MEN2 and advanced MTC, the RET tyrosine kinase (TK) pathway is a target for treatment with selpercatinib, a selective RET TK inhibitor.

Patients And Methods: A retrospective review of the clinical, genetic, biochemical (calcitonin and carcinoembryonic antigen [CEA]) and imaging data of six medically untreated children with MEN2 and recurrent and or progressive MTC.

Study of a 532/1064 Fractional Picosecond Laser for Facial Rejuvenation.

Background And Objectives: Picosecond (ps) fractional lasers create small wounds, presumably by laser-induced optical breakdown. We studied a ps fractional laser in the treatment of wrinkles and mottled pigment.

Materials And Methods: This was a single center, prospective, open-label clinical trial.

The overlap of frailty and malnutrition in older hospitalised patients: An observational study.

Background And Objectives: Frailty and malnutrition are geriatric syndromes with common risk-factors. Limited studies have investigated these two conditions simultaneously in hospitalised patients. This study investigated the overlap of frailty and malnutrition in older hospitalised patients.