bluuebunny/crossref_metadata_2025_split huggingface dataset:
HAP-FAST: a feasibility study incorporating qualitative, mechanistic and costing sub-studies alongside a randomised pilot trial comparing chest x-ray to low-dose CT scan and empirical antibiotics to antibiotics guided by the BIOFIRE® FILM ARRAY® pneumoniapluspanel in adults with suspected non-ventilator-associated hospital-acquired pneumonia
Authors: Shafiqa Natalia , Aston Stephen , Howard Alex , Turtle Lance , Abrams Simon , Young Bridget , Sherratt Frances , Alvarez Nishio Anica , Willshaw Stephanie , Jones Ashley P , Wootton Dan G 
Published: July 2024

IntroductionNon-ventilator-associated hospital-acquired pneumonia (nv-HAP) is the most common healthcare-associated infection (HCAI), is associated with high mortality and morbidity and places a major burden on healthcare systems. Diagnosis currently relies on chest x-rays to confirm pneumonia and sputum cultures to determine the microbiological cause. This approach leads to over-diagnosis of pneumonia, rarely identifies a causative pathogen and perpetuates unnecessary and imprecise antibiotic use. The HAP-FAST study aims to evaluate the feasibility of a randomised trial to evaluate the clinical impact of low-dose, non-contrast-enhanced thoracic CT scans and rapid molecular sputum analysis using the BIOFIRE® FILMARRAY® pneumoniapluspanel (FAPP) for patients suspected with nv-HAP.Methods and analysisThe HAP-FAST feasibility study consists of a pilot randomised trial, a qualitative study, a costing analysis and exploratory analyses of clinical samples to investigate the immune-pathophysiology of HAP. Participants are identified and recruited from four acute hospitals in the Northwest of the UK. Using a Research Without Prior Consent model, the pilot trial will recruit 220 adult participants, with or without mental capacity, and with suspected HAP. HAP-FAST is a non-blinded, sequential, multiple assignment, randomised trial with two possible stages of randomisation: first, chest x-ray (CXR) or CT; second, if treated as nv-HAP, FAPP or standard microbiological processing alone (no FAPP). Pathogen-specific antibiotic guidance will be provided for FAPP results. Randomisation uses a web-based platform and followed up for 90 days. The feasibility of a future trial will be determined by assessing trial processes, outcome measures and patient and staff experiences.Ethics and disseminationThis study has undergone combined review by the UK NHS Research Ethics Committee and Health Research Authority. Results will be disseminated via peer-reviewed journals, via the funders’ website and through a range of media to engage the public.Trial registration numberNCT05483309.
Impact of isotype on the mechanism of action of agonist anti-OX40 antibodies in cancer: implications for therapeutic combinations
Authors: Willoughby Jane E , Dou Lang , Bhattacharya Sabyasachi , Jackson Heather , Seestaller-Wehr Laura , Kilian David , Bover Laura , Voo Kui S , Cox Kerry L , Murray Tom , John Mel , Shi Hong , Bojczuk Paul , Jing Junping , Niederer Heather , Shepherd Andrew J , Hook Laura , Hopley Stephanie , Inzhelevskaya Tatyana , Penfold Chris A , Mockridge C Ian , English Vikki , Brett Sara J , Srinivasan Roopa , Hopson Christopher , Smothers James , Hoos Axel , Paul Elaine , Martin Stephen L , Morley Peter J , Yanamandra Niranjan , Cragg Mark S 
Published: July 2024

BackgroundOX40 has been widely studied as a target for immunotherapy with agonist antibodies taken forward into clinical trials for cancer where they are yet to show substantial efficacy. Here, we investigated potential mechanisms of action of anti-mouse (m) OX40 and anti-human (h) OX40 antibodies, including a clinically relevant monoclonal antibody (mAb) (GSK3174998) and evaluated how isotype can alter those mechanisms with the aim to develop improved antibodies for use in rational combination treatments for cancer.MethodsAnti-mOX40 and anti-hOX40 mAbs were evaluated in a number of in vivo models, including an OT-I adoptive transfer immunization model in hOX40 knock-in (KI) mice and syngeneic tumor models. The impact of FcγR engagement was evaluated in hOX40 KI mice deficient for Fc gamma receptors (FcγR). Additionally, combination studies using anti-mouse programmed cell death protein-1 (mPD-1) were assessed. In vitro experiments using peripheral blood mononuclear cells (PBMCs) examining possible anti-hOX40 mAb mechanisms of action were also performed.ResultsIsotype variants of the clinically relevant mAb GSK3174998 showed immunomodulatory effects that differed in mechanism; mIgG1 mediated direct T-cell agonism while mIgG2a acted indirectly, likely through depletion of regulatory T cells (Tregs) via activating FcγRs. In both the OT-I and EG.7-OVA models, hIgG1 was the most effective human isotype, capable of acting both directly and through Treg depletion. The anti-hOX40 hIgG1 synergized with anti-mPD-1 to improve therapeutic outcomes in the EG.7-OVA model. Finally, in vitro assays with human peripheral blood mononuclear cells (hPBMCs), anti-hOX40 hIgG1 also showed the potential for T-cell stimulation and Treg depletion.ConclusionsThese findings underline the importance of understanding the role of isotype in the mechanism of action of therapeutic mAbs. As an hIgG1, the anti-hOX40 mAb can elicit multiple mechanisms of action that could aid or hinder therapeutic outcomes, dependent on the microenvironment. This should be considered when designing potential combinatorial partners and their FcγR requirements to achieve maximal benefit and improvement of patient outcomes.
Predictors of a relapsing course in myelin oligodendrocyte glycoprotein antibody-associated disease
Authors: Virupakshaiah Akash , Schoeps Vinicius A , Race Jonathan , Waltz Michael , Sharayah Siefaddeen , Nasr Zahra , Moseley Carson E , Zamvil Scott S , Gaudioso Cristina , Schuette Allison , Casper Theron Charles , Rose John , Flanagan Eoin P , Rodriguez Moses , Tillema Jan-Mendelt , Chitnis Tanuja , Gorman Mark P , Graves Jennifer S , Benson Leslie A , Rensel Mary , Abrams Aaron , Krupp Lauren , Lotze Timothy E , Aaen Gregory , Wheeler Yolanda , Schreiner Teri , Waldman Amy , Chong Janet , Mar Soe , Waubant Emmanuelle 
Published: July 2024

BackgroundMyelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently described demyelinating disorder, and children represent about 50% of all cases. Almost half of the patients experience relapses, but very few studies have evaluated predictors of relapse risk, challenging clinical management. The study aimed to identify predictors at MOGAD onset that are associated with a relapsing course.MethodsProspectively collected data from paediatric patients with MOGAD seen by the US Network of Paediatric MS Centres were leveraged. Univariable and adjusted multivariable models were used to predict recurrent disease.ResultsWe identified 326 MOGAD cases (mean age at first event 8.9 years [SD 4.3], 57% female, 77% white and 74% non-Hispanic) and 46% relapsed during a mean follow-up of 3.9 years (SD 4.1). In the adjusted multivariable model, female sex (HR 1.66, 95% CI 1.17 to 2.36, p=0.004) and Hispanic/Latino ethnicity (HR 1.77, 95% CI 1.19 to 2.64, p=0.005) were associated with a higher risk of relapsing MOGAD. Maintenance treatment initiated before a second event with rituximab (HR 0.25, 95% CI 0.07 to 0.92, p=0.037) or intravenous immunoglobulin (IVIG) (HR 0.35, 95% CI 0.14 to 0.88, p=0.026) was associated with lower risk of a second event in multivariable analyses. Conversely, maintenance steroids were associated with a higher estimated relapse risk (HR 1.76, 95% CI 0.90 to 3.45, p=0.097).ConclusionSex and ethnicity are associated with relapsing MOGAD. Use of rituximab or IVIG therapy shortly after onset is associated with a lower risk of the second event. Preventive treatment after a first event could be considered for those with a higher relapse risk.
Validation of self-reported male circumcision status and genital ulcer disease among Ugandan men
Authors: Galiwango Ronald Moses , Kigozi Godfrey , Feng Xinyi , Reynolds Steven , Quinn Thomas , Kiboneka Stephen Dalton , Mpagazi Josephine , Kereba John Baptist , Nakayijja Annet , Ssekubugu Robert , Chang Larry , Kagayi Joseph , Tobian Aaron , Grabowski Mary K 
Published: July 2024

Objective
Voluntary medical male circumcision (MC) is a critical tool in combination HIV prevention programmes in Africa. Self-reported MC (SrMC) status is used in HIV epidemiological surveys to assess MC coverage but is subject to response bias with limited validation. This study evaluated the utility of SrMC status as a marker of MC as well as self-reported genital lesions for genital ulcer disease (GUD) among Ugandan men.

Methods
Male participants aged 18–49 years in the cross-sectional Sexually Transmitted Infection Prevalence study, conducted between May and October 2019, responded to a questionnaire capturing SrMC status and current genital ulcer symptoms followed by clinical assessment to verify MC and presence of GUD.
Sensitivity, specificity, positive predictive value, negative predictive value and corresponding CIs (95% CI) for SrMC status and GUD were estimated.

Results
There were 853 male participants, of whom 470 (55.1%) self-reported being circumcised and 23 (2.7%) self-reported GUD (SrGUD). MC was clinically confirmed in 50.2% (n=428) of participants with sensitivity of SrMC status at 99% (95% CI: 98% to 100%) and specificity 89% (95% CI: 86% to 92%). Specificity of SrMC was lowest among persons living with HIV and viremic (>1000 copies/mL) at 72% (95% CI: 46% to 90%). 18 participants had clinically confirmed GUD, but only 12 SrGUD symptoms, corresponding to a sensitivity and specificity of 67% (95% CI: 41% to 87%) and 99% (95% CI: 98% to 99%), respectively.

Conclusions
SrMC status is a robust proxy for clinically confirmed MC status and may reliably be used to assess MC coverage in this setting. Conversely, GUD symptoms were under-reported, which may impact effective syndromic management of sexually transmitted infections and warrants further examination.
Quality, acceptability and usability of self-sampling kits used by non-healthcare professionals for STI diagnosis in Spain: a single-blind study
Authors: Gómez-Castellá Javier , Cobos Briz Marta , Nuño Néstor , Diaz Asuncion , Bru-Gorraiz Francisco Javier , Martín-Gorgojo Alejandro , Almonacid-Garrido Maria Concepción , Mir Anna , Muñoz Mario , Del Amo Julia 
Published: July 2024

Objectives
Sexually transmitted infections (STIs) have markedly increased over the last decade in Spain, calling for prevention and control innovative approaches. While there is evidence indicating the effectiveness of self-sampling for STI diagnosis, no kits for this purpose have been authorised in Spain.

Methods

A prospective single-blind cross-sectional study carried out between November and December 2022 in an STI clinic in Madrid, Spain, to determine the validity, feasibility and acceptability of self-sampling kits used by non-healthcare professionals from vagina, pharynx, rectum and urethra to diagnose
Chlamydia trachomatis
(CT) and
Neisseria gonorrhoeae
(NG). Self-samples were compared with samples collected by healthcare professional (HC samples) and analysed by PCR. Frequency of CT and NG diagnosis by sample type was compared using McNemar’s test for paired data. Sensitivity and specificity of self-samples for CT and NG diagnosis were also calculated.

Results
306 self-samples from 51 participants were analysed. 80% were men with median age of 33 (IQR: 28–38) years. Self-samples and HC samples showed no significant statistical differences in CT and NG diagnosis. Self-samples had a sensitivity of 81% for CT and 93% for NG, with a specificity of 97% for CT and 95% for NG. More than 90% of participants had no difficulty understanding the kit instructions and 71% expressed high levels of satisfaction with the self-sampling kit.

Conclusion
Self-sampling kits for CT and NG diagnosis can be safely and effectively used by non-healthcare professionals in Spain. National strategies for STI prevention and control should prioritise self-sampling strategies.
Driving voltage frequency and electrode material effects on electromagnetic radiation of the surface dielectric barrier discharge in the air
Authors: Pekárek Stanislav 
Published: July 2024

AbstractThe electrical discharges are, among others, accompanied by the emission of electromagnetic waves of various frequencies. We studied this emission for the surface dielectric barrier discharge in the air. We used the discharge with one strip-driven electrode and a sinusoidal driving voltage of frequencies 5 and 10 kHz. From the spectra of emitted waves in the frequency band up to 3 GHz, we found that this type of discharge emits the radiation of frequencies below 500 MHz. In this frequency band, we focused on the effect of the driving voltage frequency and driven electrode material on the spectra of these waves. It was found that emitted radiation is distributed in several packages of frequencies, and an increase in the driving voltage frequency or voltage increases the power level of emitted radiation. Compared with the radiation spectrum of the discharge with an aluminium-driven electrode in the spectrum of the discharge with the copper-driven electrode, new peaks of various power levels and the shift of certain radiation frequencies to lower values appear. To understand the underlying mechanism of the discharge electromagnetic waves emission, we focused on the correlation between the electric component of emitted EMWs and the discharge electrical parameters as a function of time and discharge voltage.
Graphical abstract
Do Precipitation and Temperature Influence Perceptions of Urban Cleanliness?
Authors: Mazon Jordi , Pino David , López Daniel 
Published: July 2024

Abstract
This study explores the correlation between weather and the perception of urban cleanliness across the 47 largest cities in Spain. Utilizing survey data conducted by the national Consumers and Users Organization (OCU) in 2015, 2019, and 2023 to assess cleanliness perceptions, we analyze potential associations with precipitation and temperature recorded by weather stations of the Spanish Meteorological Agency. Additionally, we consider computed values of the De Martonne aridity index. The OCU data reveal regional disparities in perceived cleanliness quality. Higher cleanliness scores are obtained in cities located in the northern and north-central regions of Spain, characterized by humid and superhumid climates according to the De Martonne index. Conversely, lower cleanliness ratings are given to cities in the southern and eastern regions of Spain, where a Mediterranean climate and lower aridity index values prevail. In conducting a statistical analysis on the perception of cleanliness and variables related to precipitation and temperature, the results of the chi-square and linear correlation tests found no strong statistical correlation, although a tendency is observed. Cities with higher annual precipitation and lower values of average annual temperature tend to receive better cleanliness ratings, while drier and warmer cities exhibit the worst values of perceived urban cleanliness. Furthermore, our findings indicate that the Gompertz model effectively captures a strong statistical correlation in the relationship between cleanliness perception and the De Martonne index: As aridity increases, cleanliness perception decreases. These results are relevant for the development of future cleaning methods and systems, particularly in light of the climate change scenarios that are anticipated in the Mediterranean region due to warmer and drier conditions and, consequently, an increase in aridity.
Blood transcriptomic signatures for symptomatic tuberculosis in an African multicohort study
Authors: Muwanga Vanessa Mwebaza , Mendelsohn Simon C. , Leukes Vinzeigh , Stanley Kim , Mbandi Stanley Kimbung , Erasmus Mzwandile , Flinn Marika , Fisher Tarryn-Lee , Raphela Rodney , Bilek Nicole , Malherbe Stephanus T. , Tromp Gerard , Van Der Spuy Gian , Walzl Gerhard , Chegou Novel N. , Scriba Thomas J. 
Published: July 2024

BackgroundMultiple host blood transcriptional signatures have been developed as non-sputum triage tests for tuberculosis (TB). We aimed to compare the diagnostic performance of 20 blood transcriptomic TB signatures for differentiating between symptomatic patients who have TBversusother respiratory diseases (ORD).MethodsAs part of a nested case–control study, individuals presenting with respiratory symptoms at primary healthcare clinics in Ethiopia, Malawi, Namibia, Uganda, South Africa and The Gambia were enrolled. TB was diagnosed based on clinical, microbiological and radiological findings. Transcriptomic signatures were measured in whole blood using microfluidic real-time quantitative PCR. Diagnostic performance was benchmarked against the World Health Organization Target Product Profile (TPP) for a non-sputum TB triage test.ResultsAmong 579 participants, 158 had definite, microbiologically confirmed TB, 32 had probable TB, while 389 participants had ORD. Nine signatures differentiated between ORD and TB with equivalent performance (Satproedprai7: area under the curve 0.83 (95% CI 0.79–0.87); Jacobsen3: 0.83 (95% CI 0.79–0.86); Suliman2: 0.82 (95% CI 0.78–0.86); Roe1: 0.82 (95% CI 0.78–0.86); Kaforou22: 0.82 (95% CI 0.78–0.86); Sambarey10: 0.81 (95% CI 0.77–0.85); Duffy9: 0.81 (95% CI 0.76–0.86); Gliddon3: 0.8 (95% CI 0.75–0.85); Suliman4 0.79 (95% CI 0.75–0.84)). Benchmarked against a 90% sensitivity, these signatures achieved specificities between 44% (95% CI 38–49%) and 54% (95% CI 49–59%), not meeting the TPP criteria. Signature scores significantly varied by HIV status and country. In country-specific analyses, several signatures, such as Satproedprai7 and Penn-Nicholson6, met the minimal TPP criteria for a triage test in Ethiopia, Malawi and South Africa.ConclusionNo signatures met the TPP criteria in a pooled analysis of all countries, but several signatures met the minimum criteria for a non-sputum TB triage test in some countries.
Effectiveness of ICS/LABA and LAMA/LABA in COPD due to biomass
Authors: Ramírez-Venegas Alejandra , Montiel-Lopez Francisco , Robles-Hernández Robinson E. , Celli Bartolome R. , Sansores Raúl H. , Cassou-Martínez Maricruz , Lara-Albisua José L. Pérez , González-González Claudia , Mayar-Maya María E. , Hernández-Morales Aloisa P. , Hernández-Zenteno Rafael J. , Falfán-Valencia Ramcés , Thirión-Romero Ireri , Pérez-Bautista Oliver , Pérez-Padilla Rogelio 
Published: July 2024

BackgroundCOPD due to biomass exposure (COPD-B) is highly prevalent in low- and middle-income countries, and there are no clinical trials designed to evaluate the effectiveness of the treatments currently recommended for patients with COPD due to cigarette smoking (COPD-C). The purpose of the study was to compare the efficacy of fluticasone furoate/vilanterol (FF/V) 100/25 μg and umeclidinium/vilanterol (UMEC/VI) 62.5/25 μg on the rate of exacerbations, the time to first exacerbation, on dyspnoea, health-related quality of life (HRQL), forced expiratory volume in 1 s (FEV1) and inspiratory capacity (IC) during a period of 6 months in patients with COPD-B and COPD-C, at a third level referral centre in Mexico City.MethodsA pilot, single-centre, open-label, parallel-group study included 132 patients with a history of at least two exacerbations. They were randomised to receive one of four treatment groups: 33 COPD-B patients received FF/VI 100/25 μg, 31 COPD-B patients received UMEC/VI 62.5/25 μg, 34 COPD-C patients received FF/V and 34 COPD-C patients received UMEC/VI.ResultsThere were no differences in exacerbation rates between patients receiving FF/VI or UMEC/VI in either the COPD-B (0.07 (95% CI 0.03–0.13), 0.06 (95% CI 0.03–0.12)) or COPD-C group (0.06 (95% CI 0.04–0.11), 0.08 (95% CI 0.05–0.13)), nor in the time of first exacerbation, nor FEV1and IC. All groups showed improvement in dyspnoea and HRQL, independently of medication used.ConclusionsAmong patients with COPD-B and COPD-C with a history of exacerbation, FF/VI was equally effective as UMEC/VI in preventing exacerbations and improving dyspnoea and HRQL.
Hypoxaemic load in sleep apnoea is associated with acute changes in T-wave amplitude
Authors: Sillanmäki Saara , Ebrahimian Serajeddin , Hietakoste Salla , Hernando David , Bailon Raquel , Leppänen Timo , Kainulainen Samu 
Published: July 2024

AimsObstructive sleep apnoea (OSA) imposes significant stress on the cardiovascular system and the heart. While long-term cardiac effects are understood, the immediate impact of hypoxaemia on the heart's electrophysiology lacks understanding. Our study aims to explore desaturation severity on cardiovascular repolarisation.MethodsWe retrospectively analysed ECGs from full diagnostic polysomnographies from 492 patients with suspected OSA. The analyses were conducted before, during and after 9137 nocturnal apnoea- or hypopnoea-related desaturations. The mean andsdof T-wave amplitude change from the baseline level to the level during and after desaturations (ΔTamp_meanand ΔTamp_SD) were calculated. To investigate the modulatory effects of desaturation severity, the data were divided into subgroups based on the desaturation duration (Tdes; 10 s≤Tdes<20 s, 20 s≤Tdes<30 s, 30 s≤Tdes<45 s and Tdes≥45 s) and magnitude of blood oxygen saturation drop (change in peripheral oxygen saturation (ΔSpO2); 3%≤ΔSpO2<4.5%, 4.5%≤ΔSpO2<6%, 6%≤ΔSpO2<7.5% and ΔSpO2≥7.5%) for men and women.ResultsDesaturations caused significant (p<0.01) changes in ΔTamp_meanduring and after desaturations. In men, the median ΔTamp_meanduring and after deep (ΔSpO2≥7.5%) desaturations were 21 µV and 24 µV, respectively. In women, the median ΔTamp_meanin deep desaturations was 15 µV during and 21 µV after desaturations. Similarly, the ΔTamp_SDincreased during and after deep desaturations. In regression analysis, the desaturation depth was an independent predictor for ventricular repolarisation instability.ConclusionWe found an association between the severity of nocturnal desaturations and cardiac repolarisation instability. These findings hold particular importance, as repolarisation instability has been linked with cardiovascular morbidity and could potentially serve as a trigger for arrhythmias and sudden cardiac death.