An Open-Label Phase II Trial of Pembrolizumab, an Immune Checkpoint Inhibitor Alone or in Combination With Oral Azacitidine as Second-Line Therapy for Advanced Head and Neck Squamous Cell Cancers.

Background And Aims: Sensitivity to immune checkpoint inhibitor (ICI) therapy depends in part on the genetic and epigenetic makeup of cancer cells, and CD8 T-lymphocytes that mediate immune responses. Epigenetics are heritable reversible changes in gene expression that occur without any changes in the nuclear DNA sequence or DNA copy number.

Primary Objective: i.

Practical Steps to Design Brucellosis Preventive Interventions: An Intervention Mapping Approach.

Background And Aims: Common diseases between humans and animals are one of the health problems of countries, which requires targeted intervention. The intervention mapping model provides guidance for choosing the most appropriate methods and applications. Since one of the most important challenges in the endemic areas of Iran is the control of brucellosis.

Exploring the Epidemiological Characteristics and Survival Analysis Among Prostate Cancer Patients Under 50: A Seer-Based Population Study.

Background And Aims: Even though aging is a known risk factor for prostate cancer incidence and mortality, there has been an increase in incidence among young men since the late 1980s with notably lower survival rates than those among older men. However, there is insufficient knowledge about recent trends in the incidence and survival of this disease.

Methods: We analyzed prostatic cancer incidence trends in men under 50 from 1975 to 2020 using Surveillance, Epidemiology, and End Results (SEER) 8 registries data.

Developing and validating a scale to measure perceived barriers to prosthodontics treatments among partially edentulous patients.

Background: People experiencing tooth loss need dental prostheses to preserve the integrity of their oral structures and replace the missing teeth. Patient-related outcome measures (PROMs) for perceived barriers to prosthodontics treatment are scarce in the literature.

Aims: The aim of this study was to develop a comprehensive scale to identify and measure barriers to prosthodontic treatment as perceived by partially edentulous patients.

After-hours, Severity, and Distance are Associated with Non-VHA Emergency Department Use for Older Veterans: Insights from a Regional Health Information Exchange.

Background: Older adults treated in emergency departments (EDs) are at higher risk for adverse outcomes. Using multiple facilities can worsen this issue through service duplication and poor care transitions. Veterans with dual insurance coverage can access both Veterans Health Administration (VHA) and non-VHA EDs.

Relationship between pregnant women's combined exposure to heavy metals and their offspring's congenital heart defects in Lanzhou, China.

Background: Previous research has demonstrated that exposure to individual heavy metals elevates the incidence rate of congenital heart defects (CHDs). However, there is a paucity of data concerning the relationship between combined exposure to multiple heavy metals and the occurrence of CHDs. This study seeks to investigate the association between combined heavy metal exposure in pregnant women and the incidence of CHDs in their offspring in Lanzhou, China.

Computational identification of novel natural inhibitors against triple mutant DNA gyrase A in fluoroquinolone-resistant Typhimurium.

The rising resistance to fluoroquinolones in Typhimurium poses a significant global health challenge. This computational research addresses the pressing need for new therapeutic drugs by utilizing various computational tools to identify potential natural compounds that can inhibit the triple mutant DNA gyrase subunit A enzyme, which is crucial in fluoroquinolone resistance. Initially, the three-dimensional structure of the wild-type DNA gyrase A protein was modeled using homology modeling, and followed by mutagenesis to create the clinically relevant triple mutant (SER83PHE, ASP87GLY, ALA119SER) DNA gyrase A protein structure.

Assessing the Value of Further Investment in R&D Using Mixed Methods: A Case Study of Biosensor-Integrated Arteriovenous Grafts.

This study illustrates the utility of a mixed-methods approach in assessing the value of an example novel technology-biosensor-integrated self-reporting arteriovenous grafts (smart AVGs). Currently in preclinical development, the device will detect arteriovenous graft stenosis (surveillance-only use case) and treat stenosis (interventional use case). The approach to value assessment adopted in this study was multifaceted, with one stage informing the next and comprised a stakeholder engagement with clinical experts to explore the device's clinical value, a cost-utility analysis (CUA) from a US Medicare perspective to estimate pricing headroom, and an investment model estimating risk-adjusted net present value analysis (rNPVs) to determine commercial viability.

Disentangling protein metabolic costs in human cells and tissues.

While more data are becoming available on gene activity at different levels of biological organization, our understanding of the underlying biology remains incomplete. Here, we introduce a metabolic efficiency framework that considers highly expressed proteins (HEPs), their length, and biosynthetic costs in terms of the amino acids (AAs) they contain to address the observed balance of expression costs in cells, tissues, and cancer transformation. Notably, the combined set of HEPs in either cells or tissues shows an abundance of large and costly proteins, yet tissues compensate this with short HEPs comprised of economical AAs, indicating a stronger tendency toward mitigating costs.

Targeted barcoding of variable antibody domains and individual transcriptomes of the human B-cell repertoire using Link-Seq.

Here, we present Link-Seq, a highly efficient droplet microfluidic method for combined sequencing of antibody-encoding genes and the transcriptome of individual B cells at large scale. The method is based on 3' barcoding of the transcriptome and subsequent single-molecule PCR in droplets, which freely shift the barcode along specific gene regions, such as the antibody heavy- and light-chain genes. Using the immune repertoire of COVID-19 patients and healthy donors as a model system, we obtain up to 91.

Primordial black holes and their gravitational-wave signatures.

In the recent years, primordial black holes (PBHs) have emerged as one of the most interesting and hotly debated topics in cosmology. Among other possibilities, PBHs could explain both some of the signals from binary black hole mergers observed in gravitational-wave detectors and an important component of the dark matter in the Universe. Significant progress has been achieved both on the theory side and from the point of view of observations, including new models and more accurate calculations of PBH formation, evolution, clustering, merger rates, as well as new astrophysical and cosmological probes.

Amphotericin B tissue penetration and pharmacokinetics in healthy and -infected rats: insights from microdialysis and population modeling.

Introduction: This study evaluated the relationship between total plasma and free kidney concentrations of amphotericin B (AmB) in healthy and -infected Wistar rats using microdialysis and has the potential to significantly impact future research in this field and promote the development of antifungal drugs. The findings of this study, which show that plasma levels are a good predictor for AmB kidney concentrations and can be used to optimize its dosing regimen, underscore the importance of this research.

Methods: Microdialysis probe recovery rates were determined by dialysis and retrodialysis , as well as by retrodialysis .

Assembly of ceria-Nrf2 nanoparticles as macrophage-targeting ROS scavengers protects against myocardial infarction.

Myocardial infarction (MI) is a leading cause of morbidity and mortality worldwide, and mitigating oxidative stress is crucial in managing MI. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a critical role in combating oxidative stress and facilitating cardiac remodeling post-MI. Here, we engineered Cerium oxide (CeO) nanoparticle-guided assemblies of ceria/Nrf2 nanocomposites to deliver Nrf2 plasmids.

Survival analysis of a 16-year cohort of follicular lymphoma patients receiving systemic treatment in Brazil.

Introduction: Follicular lymphoma (FL) is a common type of non-Hodgkin lymphoma that is incurable but often follows an indolent course. While survival is improving thanks to advances in diagnosis, supportive care, and new therapies, understanding outcomes and their impact on overall survival is still limited. There are few studies on FL in Brazil, so this study aims to evaluate the patient's profile, morbidity and mortality treated by the Brazilian national health service (SUS) and evaluate risk factors associated with treatment failure.

Prognostic factors for disease progression of central high-grade conventional osteosarcoma of the appendicular skeleton: Single-centre experience within South Africa with minimum 3-year follow-up.

Background: Disease progression (DP) of osteosarcomas, albeit with aggressive treatments, hinders improving survival. The DP patterns are unique in low- and middle-income countries like South Africa. We determine the prognostic factors associated with disease progression (DP) of the appendicular skeleton's central high-grade conventional osteosarcoma (COS).

A novel machine learning based framework for developing composite digital biomarkers of disease progression.

Background: Current methods of measuring disease progression of neurodegenerative disorders, including Parkinson's disease (PD), largely rely on composite clinical rating scales, which are prone to subjective biases and lack the sensitivity to detect progression signals in a timely manner. Digital health technology (DHT)-derived measures offer potential solutions to provide objective, precise, and sensitive measures that address these limitations. However, the complexity of DHT datasets and the potential to derive numerous digital features that were not previously possible to measure pose challenges, including in selection of the most important digital features and construction of composite digital biomarkers.

Pulse approach: a physics-guided machine learning model for thermal analysis in laser-based powder bed fusion of metals.

Fast and accurate representation of heat transfer in laser powder-bed fusion of metals (PBF-LB/M) is essential for thermo-mechanical analyses. As an example, it benefits the detection of thermal hotspots at the design stage. While traditional physics-based numerical approaches such as the finite element (FE) method are applicable to a wide variety of problems, they are computationally too expensive for PBF-LB/M due to the space- and time-discretization requirements.

Development of a Prandtl-Ishlinskii hysteresis model for a large capacity magnetorheological fluid damper.

Magnetorheological (MR) fluid (MRF) dampers, serving as fail-safe semi-active devices, exhibit nonlinear hysteresis characteristics, emphasizing the necessity for accurate modeling to formulate effective control strategies in smart systems. This paper introduces a novel stop operator-based Prandtl-Ishlinskii (PI) model, featuring a reduced parameter set (seven), designed to estimate the nonlinear hysteresis properties of a large-scale bypass MRF damper with variable stiffness capabilities under varying applied current. With only seven parameters, the model realizes current, displacement, and rate dependencies.

Factors Influencing Adolescents' Knowledge, Practices, and Attitudes Towards Oral Health in the Rupa-Rupa District, Peru.

Aim: This study aimed to identify factors associated with adolescents' knowledge, practices, and attitudes (KPA-OH) regarding oral health in the Rupa-Rupa district, a high jungle region of Peru.

Materials And Methods: An analytical study was conducted with a sample of 408 adolescents (aged 13-17 years) from seven public schools in the Rupa-Rupa district (elevation: 649 meters above sea level). The sample was stratified by sex, age, and school.

Impact of the COVID-19 Pandemic on Oral Health Perception, Hygiene Behaviors, and Oral Health-Related Quality of Life in Myanmar.

Background And Aims: The COVID-19 pandemic has significantly impacted various aspects of daily life, including oral health. However, limited research has explored the effects of the pandemic on oral health perceptions, hygiene behaviors, and their subsequent influence on oral health-related quality of life (OHRQoL) in underserved settings. This study aims to assess changes in oral health perceptions and behaviors during the pandemic and their impact on OHRQoL in Myanmar.

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Unlabelled: The present work investigates the impact of pressure (; 300-600 MPa) and holding time (; 5-20 min) on the quality attributes and microbial stability of jackfruit shreds. The results revealed that the and had significantly affected physico-chemcial and bioactive composition of the jackfruit shreds. Higher levels of and increased the firmness of the shreds.

Contagious acquisition of antimicrobial resistance is critical for explaining emergence in western Canadian feedlots-insights from an agent-based modelling tool.

Introduction: Antimicrobial resistance (AMR) is a growing threat to the efficacy of antimicrobials in humans and animals, including those used to control bovine respiratory disease (BRD) in high-risk calves entering western Canadian feedlots. Successful mitigation strategies require an improved understanding of the epidemiology of AMR. Specifically, the relative contributions of antimicrobial use (AMU) and contagious transmission to AMR emergence in animal populations are unknown.

Improving auditory attention decoding by classifying intracranial responses to glimpsed and masked acoustic events.

Listeners with hearing loss have trouble following a conversation in multitalker environments. While modern hearing aids can generally amplify speech, these devices are unable to tune into a target speaker without first knowing to which speaker a user aims to attend. Brain-controlled hearing aids have been proposed using auditory attention decoding (AAD) methods, but current methods use the same model to compare the speech stimulus and neural response, regardless of the dynamic overlap between talkers which is known to influence neural encoding.

Temporal variations in and predictive values of ABG results prior to in-hospital cardiac arrest.

In-hospital cardiac arrest (IHCA) has been understudied relative to out-of-hospital cardiac arrest. Further, studies of IHCA have mainly focused on a limited number of pre-arrest patient characteristics (e.g.