Applications of genome sequencing as a single platform for clinical constitutional genetic testing.

The number of human disease genes has dramatically increased over the past decade, largely fueled by ongoing advances in sequencing technologies. In parallel, the number of available clinical genetic tests has also increased, including the utilization of exome sequencing for undiagnosed diseases. Although most clinical sequencing tests have been centered on enrichment-based multigene panels and exome sequencing, the continued improvements in performance and throughput of genome sequencing suggest that this technology is emerging as a potential platform for routine clinical genetic testing.

Prioritizing post-COVID-19 health research in sub-Saharan Africa: A modified Delphi study for future pandemic.

Background: The COVID-19 pandemic exposed weaknesses in healthcare systems and disparities in healthcare access across sub-Saharan Africa (SSA). The insights of frontline healthcare professionals (HCPs), and healthcare researchers involved with the response to COVID in SSA are crucial to ensuring that health systems are optimally prepared for the next pandemic threat. Nonetheless, there is limited consensus as to what are the clinical and public health research priorities necessary to ensure that SSA is optimally prepared and responsive to future pandemics.

How do hospitals exert market power? Evidence from health systems and commercial health plan prices.

Consolidation of independent hospitals and physician practices into integrated health systems has reshaped the delivery of health care. While the literature suggests that provider consolidation raises prices, few studies have examined the interplay of health systems and insurers in relation to prices. Using negotiated price data that commercial insurers recently released under the Transparency in Coverage Final Rule, we examined the association between hospital concentration under health systems and prices for outpatient procedures in local health care markets with different levels of insurer concentration.

Coding intensity variation in Medicare Advantage.

Enrollment in Medicare Advantage (MA) plans rose to over 50% of eligible Medicare patients in 2023. Payments to MA plans incorporate risk scores that are largely based on patient diagnoses from the prior year, which incentivizes MA plans to code diagnoses more intensively. We estimated coding inflation rates for individual MA contracts using a method that allows for differential selection into contracts based on patient health.

Services and payments associated with the medicare new technology add-on payment program.

In 2001, the Centers for Medicare and Medicaid Services established the New Technology Add-On Payment (NTAP) program to incentivize access to costly new technologies for Medicare beneficiaries. These technologies, authorized by the Food and Drug Administration (FDA), must demonstrate "substantial clinical improvement" when compared to existing technologies. However, in FY2021, the FDA introduced two expedited authorization pathways, allowing technologies with either designation to bypass the "substantial clinical improvement" criterion.

Association of Rate of Functional Recovery With Therapy Time and Content Among Adults With Acquired Brain Injuries in Inpatient Rehabilitation.

Objective: To examine associations among the time and content of rehabilitation treatment with self-care and mobility functional gain rate for adults with acquired brain injury.

Design: Retrospective cohort study using electronic health record and administrative billing data.

Setting: Inpatient rehabilitation unit at a large, academic medical center.

Defects Calculation and Accelerated Interfacial Charge Transfer in a Photoactive MOF-Based Heterojunction.

Photocatalytic hydrogen production is currently considered a clean and sustainable route to meet the energy and environmental issues. Among, heterojunction photocatalysts have been developed to improve their photocatalytic efficiency. Defect engineering of heterojunction photocatalysts is attractive due to it can perform as electron trap and change the band structure to optimize the interfacial separation rate of photogenerated electron-hole pairs.

DAA-PASS: A Prospective Evaluation of HCC Recurrence After Direct Acting Antiviral Therapy.

Direct-acting antiviral (DAA) therapy is associated with a significant reduction in hepatocellular carcinoma (HCC) incidence among patients with cirrhosis, but data are conflicting about the risk of recurrence following DAA therapy. DAA-PASS was a prospective, pragmatic, observational study designed to estimate the risk of HCC recurrence associated with DAA therapy exposure during routine clinical care. Eligible patients were DAA treatment naive with Barcelona Clinic Liver Cancer (BCLC) stage A.

Understanding Cancer Treatment Decision Making Among Cancer Survivors: Weighing Cancer Recurrence Versus Cardiotoxicity.

Background: Nearly 20% of US cancer survivors develop cardiovascular disease (CVD) from cardiotoxic cancer treatments. Patients and providers may consider alternative treatments to lower cardiotoxicity risk, but these may be less effective at preventing relapse/recurrence, presenting a difficult tradeoff.

Aims: This study explored survivors' cancer treatment decision-making when weighing this tradeoff.

"Cofactors" for Natural Products.

Cofactors are non-protein entities necessary for proteins to operate. They provide "functional groups" beyond those of the 20 canonical amino acids and enable proteins to carry out more diverse functions. Such a viewpoint is rarely mentioned, if at all, when it comes to natural products and is the theme of this Concept.

Clinical Relevance of 'Cap' and 'Track' Development after Recent Small Subcortical Infarct.

Objective: After a recent small subcortical infarct (RSSI), some patients develop perilesional or remote hyperintensities ('caps/tracks') to the index infarct on T2/FLAIR MRI. However, their clinical relevance remains unclear. We investigated the clinicoradiological correlates of 'caps/tracks', and their impact on long-term outcomes following RSSI.

It's all downstream from here: RTK/Raf/MEK/ERK pathway resistance mechanisms in glioblastoma.

Background: The receptor tyrosine kinase (RTK)/Ras/Raf/MEK/ERK signaling pathway is one of the most tumorigenic pathways in cancer, with its hyperactivation strongly linked to the aggressive nature of glioblastoma (GBM). Although extensive research has focused on developing therapeutics targeting this pathway, clinical success remains elusive due to the emergence of resistance mechanisms.

Objective: This review investigates how inhibition of the RTK/Ras/Raf/MEK/ERK pathway alters transcription factors, contributing to acquired resistance mechanisms in GBM.

Ambiguity in robotic surgical instruction: lessons from remote and in-person simulation.

The rise of robotic surgery has been accompanied by numerous educational challenges as surgeons and trainees learn skills unique to the robotic platform. Remote instruction is a solution to provide surgeons ongoing education when in-person teaching is not feasible. However, surgical instruction faces challenges from unclear communication.

Indication of air pollution based on the comparison of mercury and other elements in the faeces of marmots from the Western Carpathians and the Dzungarian Alatau.

The Dzungarian Alatau in Central Asia and the Western Carpathians in Central Europe are exposed to anthropogenic sources of pollution that are impacting high-altitude mountain systems through long-range transport of emissions. Based on analyses of the autumn faeces of two species of marmots (Marmota baibacina from the alpine habitats of Zhongar Alatau National Park, Marmota marmota latirostris from the alpine habitats of the Western Tatras), we determined the environmental load of mercury and other chemical elements. Our results show significantly higher levels of total mercury amounts (p < 0.

A comparative study of human amniotic membrane, tilapia skin collagen, and Centella asiatica derived gel to treat burn wound in rat model.

In the quest for an ideal wound healing material, human amniotic membrane (AM), tilapia skin collagen (TSC), and Centella asiatica (CA) have been studied separately for their healing potential. In this study, we formulated AM, TSC, and CA gel and studied their competency and wound healing efficacy in vivo. Gel was formulated using AM, TSC, CA, Carbopol 934, acrylic acid, glycerine, and triethanolamine and physicochemical properties e.

Impact of Park Redesign and Renovation on Children's Health-Related Quality of Life.

Despite increasing interest in the role of parks on children's health, there has been little empirical research on the impact of park interventions. We used a quasi-experimental pre-post study design with matched controls to evaluate the effects of park redesign and renovation on children's health-related quality of life (QoL) in underserved neighborhoods in New York City, with predominantly Hispanic and Black populations. Utilizing longitudinal data from the Physical Activity and Redesigned Community Spaces (PARCS) Study, we examined the parent-reported health-related QoL of 201 children aged 3-11 years living within a 0.

Biopesticide transplant dips and foliar acaricide applications for control of cyclamen mite (Phytonemus pallidus) in strawberry.

Cyclamen mite (Phytonemus pallidus) causes injury to new growth of strawberry plants and is difficult to control because it is protected by folded leaves and plant crowns. Since cyclamen mite is easily transferred from strawberry nurseries to fruiting fields, dipping transplants in biopesticides may reduce initial populations. However, cyclamen mite numbers at 1 and 3 months-after-planting, and yield and cyclamen mite injury to fruit in the following season did not differ among transplants immersed for 30 s in Captiva® Prime, EcoTrol® EC, Landscape Oil, SuffOil-X® or Kopa Insecticidal Soap or the untreated control.

RNA Interference Approaches to Study Epidermal Cell Adhesion.

In this chapter, we provide a method for silencing target genes in epidermal cells via RNA interference. Specifically, we describe a protocol for transfection-mediated delivery of small interfering RNA oligonucleotides (siRNA). Functional assays are indispensable to characterize the biological consequences of gene knockdowns, and we also provide a method to analyze alterations in cell adhesion properties, consequent to knockdown of genes involved in this process.

Differential Relations Between Parenting and Emotion Regulation in Children with ASD Across Dyadic and Independent Contexts.

Many children with ASD exhibit difficulties with emotion regulation that greatly impair functioning. Certain intrinsic correlates of dysregulation have been identified in this population, but the search for potential environmental influences has been less fruitful. The current study examined several aspects of parenting as correlates of observed regulation in Autistic children, as measured in both parent-child and independent regulatory contexts.

Obstructive sleep apnea in bariatric surgery patients: a population-based study.

Purpose: A high proportion of obstructive sleep apnea (OSA) remains undiagnosed. The main objectives of this study were to measure the prevalence of diagnosed OSA and determine OSA predictors in patients who underwent bariatric surgery, who are predominantly female and pre-menopausal and represent an understudied population in OSA literature.

Methods: This was a cross-sectional population-based study using the Ontario Bariatric Registry (OBR) from 2010 to 2016, linked to ICES databases which include health administrative data on all encounters within a single public-payer system.

Cardiomyocyte-specific long noncoding RNA Trdn-as induces mitochondrial calcium overload by promoting the mA modification of calsequestrin 2 in diabetic cardiomyopathy.

Diabetic cardiomyopathy (DCM) is a medical condition characterized by cardiac remodeling and dysfunction in individuals with diabetes mellitus. Sarcoplasmic reticulum (SR) and mitochondrial Ca overload in cardiomyocytes have been recognized as biological hallmarks in DCM; however, the specific factors underlying these abnormalities remain largely unknown. In this study, we aimed to investigate the role of a cardiac-specific long noncoding RNA, D830005E20Rik (Trdn-as), in DCM.

Personalized neuron-specific enolase level based on EEG pattern for prediction of poor outcome after cardiac arrest.

Background: After cardiac arrest (CA), the European recommendations suggest to use a neuron-specific enolase (NSE) level > 60 µg/L at 48-72 h to predict poor outcome. However, the prognostic performance of NSE can vary depending on electroencephalogram (EEG). The objective was to determine whether the NSE threshold which predicts poor outcome varies according to EEG patterns and the effect of electrographic seizures on NSE level.

Treatment of Venous Thromboembolism with Edoxaban over 18 Months: Results from ETNA-VTE Europe.

Background:  The benefits and risks of extending anticoagulant treatment beyond the first 3 to 6 months in patients with venous thromboembolism (VTE) in clinical practice are not well understood.

Methods:  ETNA-VTE Europe is a prospective, noninterventional, post-authorization study in unselected patients with VTE treated with edoxaban in eight European countries for up to 18 months. Recurrent VTE, major bleeding, and all-cause death were the primary study outcomes.

Humanized Candida and NanoBiT Assays Expedite Discovery of Bdf1 Bromodomain Inhibitors With Antifungal Potential.

The fungal Bromodomain and Extra-Terminal (BET) protein Bdf1 is a potential antifungal target against invasive fungal infections. However, the need to selectively inhibit both Bdf1 bromodomains (BDs) over human orthologs and the lack of molecular tools to assess on-target antifungal efficacy hamper efforts to develop Bdf1 BD inhibitors as antifungal therapeutics. This study reports a phenyltriazine compound that inhibits both Bdf1 BDs from the human fungal pathogen Candida glabrata with selectivity over the orthologous BDs from the human BET protein Brd4.