A Brief History of Human Challenge Studies (1900-2021) Emphasising the Virology, Regulatory and Ethical Requirements, Raison D'etre, Ethnography, Selection of Volunteers and Unit Design.

Venetian quarantine 400 years ago was an important public health measure. Since 1900 this has been refined to include "challenge" or deliberate infection with pathogens be they viruses, bacteria, or parasites. Our focus is virology and ranges from the early experiments in Cuba with Yellow Fever Virus to the most widespread pathogen of our current times, COVID-19.

A Cell Trappable Methyl Rhodol-Based Fluorescent Probe for Hydrogen Sulfide Detection.

Hydrogen sulfide is a biologically important molecule and developing chemical tools that enable further investigations into the functions of H S is essential. Fluorescent turn-on H S probes have been developed for use in cellulo and in vivo, but the membrane permeability of these probes can lead to probe leakage and signal attenuation over time. Here we report a cell trappable fluorescent probe for H S, CT-MeRhoAz, which is based on a methylrhodolazide scaffold derivatized with an acetoxymethyl ester group.

Observation of B (2S)K and B (2S)K decays.

Using a data sample of proton-proton collisions collected by the CMS experiment at the LHC in 2017 and 2018 with an integrated luminosity of , the and decays are observed with significances exceeding 5 standard deviations. The resulting branching fraction ratios, measured for the first time, correspond to and , where the last uncertainty in the first ratio is related to the uncertainty in the ratio of production cross sections of and mesons, .

Prognostic factors for patients with anal cancer treated with conformal radiotherapy-a systematic review.

Aims: Anal cancer is primarily treated using concurrent chemoradiotherapy (CRT), with conformal techniques such as intensity modulated radiotherapy (IMRT) and volumetric arc therapy (VMAT) now being the standard techniques utilised across the world. Despite this, there is still very limited consensus on prognostic factors for outcome following conformal CRT. This systematic review aims to evaluate the existing literature to identify prognostic factors for a variety of oncological outcomes in anal cancer, focusing on patients treated with curative intent using contemporary conformal radiotherapy techniques.

Special Issue "Innovative Techniques and Approaches in the Control and Prevention of Rabies Virus".

Rabies is an ancient lethal scourge that has plagued humankind for centuries [...

Stabilization of swine faecal samples influences taxonomic and functional results in microbiome analyses.

Studies on the microbiome of different species are on the rise, due to a growing interest in animal health and the safety of food products of animal origin. A challenge with studying animals' microbiomes is to find methods that obtain a good representation of the microbial community of interest. Good unbiased sampling protocols are the basis for a solid experimental design, but may need to be done in environments where sample preservation could be difficult.

The experience of structural burden for culturally and linguistically diverse family carers of people living with dementia in Australia.

Evidence suggests that family carers of culturally and linguistically diverse (CALD) people living with dementia experience higher stress and unmet need than the general Australian population. These disparities are often framed as the result of CALD communities failing to seek formal support. Challenging this, we draw on the concept of 'structural burden' to explore how the complexity of health and aged systems contribute to the burden that CALD carers experience.

Mifepristone and Misoprostol for Undesired Pregnancy of Unknown Location.

Objective: To compare immediate initiation with delayed initiation of medication abortion among patients with an undesired pregnancy of unknown location.

Methods: This retrospective cohort study used electronic medical record data from the Planned Parenthood League of Massachusetts (2014-2019) for patients who requested medication abortion with a last menstrual period (LMP) of 42 days or less and pregnancy of unknown location (no gestational sac) on initial ultrasonogram. Clinicians could initiate medication abortion with mifepristone followed by misoprostol while simultaneously excluding ectopic pregnancy with serial serum human chorionic gonadotropin (hCG) testing (same-day-start group) or establish a diagnosis with serial hCG tests and repeat ultrasonogram before initiating treatment (delay-for-diagnosis group).

Clinical prediction models for diagnosis of COVID-19 among adult patients: a validation and agreement study.

Background: Since the beginning of the pandemic, hospitals have been constantly overcrowded, with several observed waves of infected cases and hospitalisations. To avoid as much as possible this situation, efficient tools to facilitate the diagnosis of COVID-19 are needed.

Objective: To evaluate and compare prediction models to diagnose COVID-19 identified in a systematic review published recently using performance indicators such as discrimination and calibration measures.

Age of Acquisition Modulates Alpha Power During Bilingual Speech Comprehension in Noise.

Research on bilingualism has grown exponentially in recent years. However, the comprehension of speech in noise, given the ubiquity of both bilingualism and noisy environments, has seen only limited focus. Electroencephalogram (EEG) studies in monolinguals show an increase in alpha power when listening to speech in noise, which, in the theoretical context where alpha power indexes attentional control, is thought to reflect an increase in attentional demands.

A mixed methods study of provider factors in buprenorphine treatment retention.

Background: Low retention is a persistent challenge in the delivery of buprenorphine treatment for opioid use disorder (OUD). The goal of this study was to identify provider factors that could drive differences in treatment retention while accounting for the contribution of patient characteristics to retention.

Methods: We developed a novel a mixed-methods approach to explore provider factors that could drive retention while accounting for patient characteristics.

Supratentorial ependymoma, zinc finger translocation-associated fusion positive, with extensive synaptophysin immunoreactivity arising from malignant transformation of clear cell ependymoma: A case report.

Background: We describe a case of a supratentorial ependymoma, zinc finger translocation-associated () fusion positive with extensive synaptophysin immunoreactivity arising from malignant transformation of an ependymoma with clear cell features in a patient with long-term follow-up.

Case Description: A 55-year-old woman presented with seizures and ataxia 15 years after an initial resection of a clear cell ependymoma, Grade 2. Imaging demonstrated an enhancing right paracentral mass and the patient underwent biopsy and resection.

Clinical and neuroradiologic characteristics in varicella zoster virus reactivation with central nervous system involvement.

Objective: To investigate the clinical and magnetic resonance imaging (MRI) characteristics of patients with varicella zoster virus (VZV) reactivation involving the cranial nerves and central nervous system (CNS).

Methods: This is a retrospective, multi-center case-series of 37 patients with VZV infection affecting the cranial nerves and CNS.

Results: The median age was 71 years [IQR 51.

A Phase II trial of Higher RadiOtherapy Dose In The Eradication of early rectal cancer (APHRODITE): protocol for a multicentre, open-label randomised controlled trial.

Introduction: The standard of care for patients with localised rectal cancer is radical surgery, often combined with preoperative neoadjuvant (chemo)radiotherapy. While oncologically effective, this treatment strategy is associated with operative mortality risks, significant morbidity and stoma formation. An alternative approach is chemoradiotherapy to try to achieve a sustained clinical complete response (cCR).

Search for low-mass dilepton resonances in Higgs boson decays to four-lepton final states in proton-proton collisions at .

A search for low-mass dilepton resonances in Higgs boson decays is conducted in the four-lepton final state. The decay is assumed to proceed via a pair of beyond the standard model particles, or one such particle and a boson. The search uses proton-proton collision data collected with the CMS detector at the CERN LHC, corresponding to an integrated luminosity of 137 , at a center-of-mass energy .

Translational PK-PD for targeted protein degradation.

Targeted protein degradation has emerged from the chemical biology toolbox as one of the most exciting areas for novel therapeutic development across the pharmaceutical industry. The ability to induce the degradation, and not just inhibition, of target proteins of interest (POIs) with high potency and selectivity is a particularly attractive property for a protein degrader therapeutic. However, the physicochemical properties and mechanism of action for protein degraders can lead to unique pharmacokinetic (PK) and pharmacodynamic (PD) properties relative to traditional small molecule drugs, requiring a shift in perspective for translational pharmacology.

Rapid design and implementation of a virtual pain management programme due to COVID-19: a quality improvement initiative.

Background: The COVID-19 pandemic interrupted the delivery of face-to-face pain services including pain management programmes in the United Kingdom with considerable negative impact on patients with chronic musculoskeletal pain. We aimed to develop and implement a remotely delivered pain management programme (PMP) using video-conferencing technology that contains all the core components of a full programme: the 'virtual PMP' (vPMP). By reporting on the process of this development, we endeavour to help address the paucity of literature on the development of remote pain management programmes.

Using Z Boson Events to Study Parton-Medium Interactions in Pb-Pb Collisions.

The spectra measurements of charged hadrons produced in the shower of a parton originating in the same hard scattering with a leptonically decaying Z boson are reported in lead-lead nuclei (Pb-Pb) and proton-proton (pp) collisions at a nucleon-nucleon center-of-mass energy of 5.02 TeV. Both Pb-Pb and pp data sets are recorded by the CMS experiment at the LHC and correspond to an integrated luminosity of 1.

Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge in young adults.

Since its emergence in 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused hundreds of millions of cases and continues to circulate globally. To establish a novel SARS-CoV-2 human challenge model that enables controlled investigation of pathogenesis, correlates of protection and efficacy testing of forthcoming interventions, 36 volunteers aged 18-29 years without evidence of previous infection or vaccination were inoculated with 10 TCID of a wild-type virus (SARS-CoV-2/human/GBR/484861/2020) intranasally in an open-label, non-randomized study (ClinicalTrials.gov identifier NCT04865237 ; funder, UK Vaccine Taskforce).

Perceptions of COVID-19 Mitigation Strategies between Rural and Non-Rural Adults in the US: How Public Health Nurses Can Fill the Gap.

The purpose of this study was to capture the perceptions of COVID-19 mitigations' efficacy of rural and non-rural participants, using the health belief model (HBM), as well as to describe where public health nursing may be able to fill behavior gaps in rural communities. Rural and non-rural participants completed electronic surveys. Surveys collected demographic information and perceptions of various mitigation strategies' effectiveness.

Rapidly progressive crescentic diabetic nephropathy: two case reports.

Crescents are not a well recognised feature of diabetic nephropathy. We present two cases of patients presenting with a rapid decline in renal function and subacute onset of nephrotic syndrome. Glomerulonephritis screening was negative, and renal biopsy revealed non-necrotising cellular crescents and typical features of late-stage diabetic nephropathy.

COVID-19 and the adaptive evolution of genetic counseling.

Emerging diseases such as the Coronavirus Disease (COVID-19) have exposed severe weaknesses in the United States and global health. Healthcare systems have struggled and are still severely challenged and strained by this pandemic. It is clear that additional resources are needed to support healthcare providers in managing this and future pandemics.

Postoperative Myocardial Injury and Outcomes in Liver and Kidney Transplant Patients.

Background/purpose: Myocardial injury after noncardiac surgery (MINS) is associated with major adverse cardiac events (MACE), but its significance post-liver and post-kidney transplantation is not well-defined.

Methods/materials: We retrospectively studied consecutive patients undergoing single-organ liver or kidney transplantation at a large tertiary transplant center. Liver and kidney transplant patients with troponins drawn within 30 days of transplantation were included.

Search for strongly interacting massive particles generating trackless jets in proton-proton collisions at .

A search for dark matter in the form of strongly interacting massive particles (SIMPs) using the CMS detector at the LHC is presented. The SIMPs would be produced in pairs that manifest themselves as pairs of jets without tracks. The energy fraction of jets carried by charged particles is used as a key discriminator to suppress efficiently the large multijet background, and the remaining background is estimated directly from data.