Association between Locoregional Failure and NFE2L2/KEAP1/CUL3 Mutations in NRG/RTOG 9512: A Randomized Trial of Radiation Fractionation in T2N0 Glottic Cancer.

Purpose: NFE2L2/KEAP1/CUL3 mutations have been validated for radiation resistance in cell-based assays and animal models. However, clinical validation of these biomarkers has been challenging due to multimodality treatment regimens. This study aims to investigate the association between NFE2L2/KEAP1/CUL3 mutations and patient outcomes, including local failure (LF), locoregional failures (LRF), disease-free survival (DFS) and overall survival (OS), using samples from a phase III trial in which patients were treated with radiation monotherapy at 2 controlled doses.

Twice-Yearly Lenacapavir for HIV Prevention in Men and Gender-Diverse Persons.

Background: Twice-yearly subcutaneous lenacapavir has been shown to be efficacious for prevention of HIV infection in cisgender women. The efficacy of lenacapavir for preexposure prophylaxis (PrEP) in cisgender men, transgender women, transgender men, and gender-nonbinary persons is unclear.

Methods: In this phase 3, double-blind, randomized, active-controlled trial, we randomly assigned participants in a 2:1 ratio to receive subcutaneous lenacapavir every 26 weeks or daily oral emtricitabine-tenofovir disoproxil fumarate (F/TDF).

Continuous care engagement in clinical practice: perspectives on selected current strategies for people with HIV in the United States.

Introduction: Modern antiretroviral therapy is associated with reduced rates of HIV-related morbidity and mortality. HIV viral suppression and retention in care are critically important outcomes requiring successful continuous patient engagement. However, barriers to such engagement are complex and require innovative solutions.

Orthodontic treatment protocol versus Peer Assessment Rating: Assessing the quality of orthodontic treatment.

Objective: To apply the Peer Assessment Rating (PAR) to cases that have been assessed by the NHS Business Service Authority (NHSBSA) using the orthodontic treatment protocol (OTO), then compare the NHSBSA outcome assessment with weighted (W) and unweighted (U) PAR scores.

Design: Cross-sectional study.

Setting: UK.

Laboratory realization of relativistic pair-plasma beams.

Relativistic electron-positron plasmas are ubiquitous in extreme astrophysical environments such as black-hole and neutron-star magnetospheres, where accretion-powered jets and pulsar winds are expected to be enriched with electron-positron pairs. Their role in the dynamics of such environments is in many cases believed to be fundamental, but their behavior differs significantly from typical electron-ion plasmas due to the matter-antimatter symmetry of the charged components. So far, our experimental inability to produce large yields of positrons in quasi-neutral beams has restricted the understanding of electron-positron pair plasmas to simple numerical and analytical studies, which are rather limited.

Many-Body Majorana Braiding without an Exponential Hilbert Space.

Qubits built out of Majorana zero modes constitute the primary path toward topologically protected quantum computing. Simulating the braiding process of multiple Majorana zero modes corresponds to the quantum dynamics of a superconducting many-body system. It is crucial to study the Majorana dynamics both in the presence of all other quasiparticles and for reasonably large system sizes.

Personality differences in dental professionals: A cross-sectional survey.

Introduction: Despite its influence on occupational performance and team dynamics, there has been little research into the personality of dental professionals. Existing research does not typically use the prevailing five-factor model of personality. We aimed to measure the personality of dental professionals in the United Kingdom and investigate differences among groups.

Scalable radiotherapy data curation infrastructure for deep-learning based autosegmentation of organs-at-risk: A case study in head and neck cancer.

In this era of patient-centered, outcomes-driven and adaptive radiotherapy, deep learning is now being successfully applied to tackle imaging-related workflow bottlenecks such as autosegmentation and dose planning. These applications typically require supervised learning approaches enabled by relatively large, curated radiotherapy datasets which are highly reflective of the contemporary standard of care. However, little has been previously published describing technical infrastructure, recommendations, methods or standards for radiotherapy dataset curation in a holistic fashion.

CAD/CAM nitinol bonded retainer versus a chairside rectangular-chain bonded retainer: A multicentre randomised controlled trial.

Background: Bonded retainers are widely used to maintain the positions of anterior teeth after orthodontic treatment. Various types of bonded retainer exist however, there is a lack of evidence to indicate which type is superior.

Aim: To compare upper and lower CAD/CAM nitinol bonded retainers (Memotain) with upper and lower chairside rectangular-chain bonded retainers (Ortho-FlexTech™), in terms of stability, retainer failures and patient satisfaction.

UK dental students' ability and confidence in applying the Index of Orthodontic Treatment Need and determining appropriate orthodontic referral.

Introduction: The aim was to assess the ability and confidence of UK undergraduate dental students in applying the Index of Orthodontic Treatment Need (IOTN) and determining appropriate orthodontic referral.

Materials And Methods: This was a cross-sectional survey using a case-based online questionnaire. Fourth and fifth year undergraduate dental students were recruited from UK dental schools through their university and social media.

Proactive strategies to optimize engagement of Black, Hispanic/Latinx, transgender, and nonbinary individuals in a trial of a novel agent for HIV pre-exposure prophylaxis (PrEP).

Introduction: Black and Hispanic/Latinx cisgender men who have sex with men (MSM), transgender women, transgender men, and gender nonbinary (TGNB) individuals have been historically underrepresented in HIV pre-exposure prophylaxis (PrEP) clinical trials. There is an urgent need for ongoing engagement with communities that have been the most impacted by HIV and diverse representation in clinical trials. Here we describe strategic approaches undertaken in the PURPOSE 2 trial to optimize engagement of underrepresented individuals.

Barriers to Creating Healthier Home Food Environments: Process Evaluation Results From 2 Home Food Environment Intervention Studies.

Few studies have identified barriers to creating a home environment more supportive of healthy eating. We examined barriers faced by participants in a randomized controlled trial and an adaptation study of the Healthy Homes/Healthy Families intervention, which uses health coaches to support low-income families in creating healthier home food environments. Coaches maintained logs of participant interactions as part of a process evaluation.

An Intercompany Perspective on Compatibility and In-use Stability Studies to Enable Administration Of Biopharmaceutical Drug Products.

In-use stability and compatibility studies are often used in biotherapeutic development to assess stability and compatibility of biologic drugs with diluents and/or administration components at relevant conditions for the target route of administration (commonly intravenous, subcutaneous or intramuscular), to assure that patient safety and product efficacy are maintained during clinical use. To gain an understanding of current industry approaches for in-use stability and compatibility studies, the Formulation Workstream of the BioPhorum Development Group (BPDG), an industry-wide consortium, conducted an inter-company collaboration exercise, which included five bench-marking surveys around in-use stability and compatibility studies of biologic drugs. The results of this industry collaboration provide insights into the practicalities of these studies and how they are being used to support administration of biologics from early clinical programs to marketed products.

Efficacy of standard- vs reduced-dose insulin for treatment of hyperkalemia: A quasi-experiment.

Purpose: Hyperkalemia more commonly affects patients with a glomerular filtration rate of less than 60 mL/min. Using intravenous (IV) insulin to shift potassium intracellularly may cause hypoglycemia, requiring additional treatment or longer hospitalization. Literature on insulin dosing in this context is limited, with one previous study indicating that 5 units of IV insulin might be as effective and result in less hypoglycemia than the standard dose of 10 units of IV insulin.

A Synthetic Peptide CTL Vaccine Targeting Nucleocapsid Confers Protection from SARS-CoV-2 Challenge in Rhesus Macaques.

Background: Persistent transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has given rise to a COVID-19 pandemic. Several vaccines, conceived in 2020, that evoke protective spike antibody responses are being deployed in mass public health vaccination programs. Recent data suggests, however, that as sequence variation in the spike genome accumulates, some vaccines may lose efficacy.

Paired SARS-CoV-2 spike protein mutations observed during ongoing SARS-CoV-2 viral transfer from humans to minks and back to humans.

A mutation analysis of SARS-CoV-2 genomes collected around the world sorted by sequence, date, geographic location, and species has revealed a large number of variants from the initial reference sequence in Wuhan. This analysis also reveals that humans infected with SARS-CoV-2 have infected mink populations in the Netherlands, Denmark, United States, and Canada. In these animals, a small set of mutations in the spike protein receptor binding domain (RBD), often occurring in specific combinations, has transferred back into humans.

Detoxification Enhanced Lifestyle Intervention Targeting Endotoxemia (DELITE) in the Setting of Obesity and Pain: Results of a Pilot Group Intervention.

Background: Obesity is a complex multifactorial disorder affecting a growing proportion of the population. While therapeutic lifestyle change (TLC) is foundational, results of interventional programs are often inconsistent. Factors related to systemic inflammation, toxin load and endotoxemia have been postulated to play a contributory role.

Why do patients with chronic hepatitis C drink alcohol? An examination of pain, depression and drinking motives.

Alcohol consumption in the setting of chronic HCV is associated with accelerated progression towards cirrhosis, increased risk of hepatocellular carcinoma and higher mortality. This analysis contextualizes how sociodemographic factors, chronic pain and depression relate to the motivations of individuals with chronic HCV to consume alcohol. We conducted a secondary analysis of baseline data from the Hep ART trial of behavioural interventions on alcohol use among patients with HCV.

High energy implementation of coil-target scheme for guided re-acceleration of laser-driven protons.

Developing compact ion accelerators using intense lasers is a very active area of research, motivated by a strong applicative potential in science, industry and healthcare. However, proposed applications in medical therapy, as well as in nuclear and particle physics demand a strict control of ion energy, as well as of the angular and spectral distribution of ion beam, beyond the intrinsic limitations of the several acceleration mechanisms explored so far. Here we report on the production of highly collimated ([Formula: see text] half angle divergence), high-charge (10s of pC) and quasi-monoenergetic proton beams up to [Formula: see text] 50 MeV, using a recently developed method based on helical coil targetry.

Observations of pressure anisotropy effects within semi-collisional magnetized plasma bubbles.

Magnetized plasma interactions are ubiquitous in astrophysical and laboratory plasmas. Various physical effects have been shown to be important within colliding plasma flows influenced by opposing magnetic fields, however, experimental verification of the mechanisms within the interaction region has remained elusive. Here we discuss a laser-plasma experiment whereby experimental results verify that Biermann battery generated magnetic fields are advected by Nernst flows and anisotropic pressure effects dominate these flows in a reconnection region.

Germline transmission of donor, maternal and paternal mtDNA in primates.

Study Question: What are the long-term developmental, reproductive and genetic consequences of mitochondrial replacement therapy (MRT) in primates?

Summary Answer: Longitudinal investigation of MRT rhesus macaques (Macaca mulatta) generated with donor mtDNA that is exceedingly distant from the original maternal counterpart suggest that their growth, general health and fertility is unremarkable and similar to controls.

What Is Known Already: Mitochondrial gene mutations contribute to a diverse range of incurable human disorders. MRT via spindle transfer in oocytes was developed and proposed to prevent transmission of pathogenic mtDNA mutations from mothers to children.

Anti-IL-6 Versus Anti-IL-6R Blocking Antibodies to Treat Acute Ebola Infection in BALB/c Mice: Potential Implications for Treating Cytokine Release Syndrome.

Cytokine release syndrome (CRS) is known to be a factor in morbidity and mortality associated with acute viral infections including those caused by filoviruses and coronaviruses. IL-6 has been implicated as a cytokine negatively associated with survival after filovirus and coronavirus infection. However, IL-6 has also been shown to be an important mediator of innate immunity and important for the host response to an acute viral infection.

An Exploratory Study to Understand Factors Associated with Health-related Quality of Life Among Uninsured/Underinsured Patients as Identified by Clinic Providers and Staff.

Since the release of Healthy People 2020, there has been extensive research understanding factors associated with health-related quality of life (HRQoL) among specific populations. Despite this growing body of research, little has been conducted to understand the factors associated with HRQoL among uninsured/underinsured Americans. The purposes of the present study were to assess clinic staff to determine: (1) whether there is a need to examine HRQoL among uninsured/underinsured individuals, (2) whether there is a need for tailored HRQoL-promoting interventions among uninsured/underinsured individuals, and (3) the factors associated with HRQoL among uninsured/underinsured individuals.

An effective CTL peptide vaccine for Ebola Zaire Based on Survivors' CD8+ targeting of a particular nucleocapsid protein epitope with potential implications for COVID-19 vaccine design.

The 2013-2016 West Africa EBOV epidemic was the biggest EBOV outbreak to date. An analysis of virus-specific CD8+ T-cell immunity in 30 survivors showed that 26 of those individuals had a CD8+ response to at least one EBOV protein. The dominant response (25/26 subjects) was specific to the EBOV nucleocapsid protein (NP).