bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of single-dose oral secnidazole for the treatment of trichomoniasis in women co-infected with trichomoniasis and bacterial vaginosis: a post hoc subgroup analysis of phase 3 clinical trial data
Authors: Muzny Christina A , Van Gerwen Olivia T , Kaufman Gregory , Chavoustie Steven 
Published: February 2024

ObjectivesBacterial vaginosis (BV) and trichomoniasis are the most common causes of vaginitis. Both infections are associated with increased risk of acquisition and transmission of HIV and other sexually transmitted infections as well as adverse reproductive health outcomes. Co-infection is common, with rates ranging from 60% to 80%. We evaluated the efficacy of single-dose oral secnidazole 2 g for the treatment of trichomoniasis in a subgroup of women co-infected with BV and trichomoniasis.DesignPost hoc analysis of data from a phase 3 randomised, double-blind, placebo-controlled, delayed-treatment study.Setting10 centres in the USA.ParticipantsSubgroup of women (aged ≥12 years) with a confirmed diagnosis ofTrichomonas vaginalisand co-infection with BV clinically diagnosed using Amsel’s criteria.InterventionSingle dose of secnidazole 2 g or placebo.Outcome measuresThe primary efficacy outcome was the microbiological cure (negative culture forT. vaginalis) at the test of cure (TOC) visit 6–12 days after dosing in the modified intent-to-treat population (mITT). At TOC, participants received the opposite treatment.ResultsOf the 131T.vaginalis-infected participants in the mITT, 79 (60.3%) met ≥3 Amsel’s criteria for BV at enrolment. Microbiological cure rates for trichomoniasis at TOC among this subgroup of women were 97.7% (42/43) for secnidazole and 0% (0/36) for placebo.ConclusionSingle-dose oral secnidazole 2 g was highly efficacious in curing trichomoniasis in women co-infected with BV. Appropriate and effective treatment options for co-infection are essential for reducing transmission and reinfection. Secnidazole is the only single-dose medication approved by the Food and Drug Administration for the treatment of BV in women and trichomoniasis in women and men.Trial registration numberClinicalTrials.gov,NCT03935217; post-results.
Prognosis of patients with long COVID symptoms: a protocol for a longitudinal cohort study at a primary care referred outpatient clinic in Helsinki, Finland
Authors: Virrantaus Hélène , Liira Helena , Posharina Tatiana , Sulg Aleksandra , Mäntylä Teemu , Kanerva Mari , Laakso Sini , Sainio Markku , Malmivaara Antti , Vuokko Aki , Varonen Mikko , Venäläinen Mikko , Arokoski Jari 
Published: February 2024

IntroductionAfter COVID-19, many continue to experience persistent debilitating symptoms, that is, long COVID. Its most prevalent symptoms are chest pain, difficulties with breathing, painful muscles, ageusia or anosmia, tingling extremities and general tiredness. This paper describes the protocol of the Long COVID Cohort Study to assess the prognosis and prognostic determinants of patients with long COVID by implementing patient-reported outcome measures (PROMs), patient-reported experience measures (PREMs) and clinical examinations during a 1-year follow-up.Methods and analysisThis is a prospective, single-site cohort study consisting of administering questionnaires and clinical examinations to adult patients referred to the Clinic for Long-Term Effects of COVID-19 at Helsinki University Hospital (Hospital district of Helsinki and Uusimaa). The referrals are from all healthcare units within HUS and other hospital districts during years 2021–2023. All admitted patients have had laboratory-confirmed COVID-19. The targeted study sample size is 500 participants. The questionnaires are administered at 0, 3, 6 and 12 months. The main outcome variables are the changes in self-reported functional abilities and quality of life. In addition, we will evaluate functional abilities at baseline using neurocognitive evaluation, a 6MWT and a measurement of hand grip strength. The Long COVID Cohort Study will form a quality register for the clinic and characterise the first systematic collection of PROMs, PREMs, questionnaire and clinical examinations related to long COVID in Finland. The Study belongs to a study consortium Long COVID—HORIZON-HLTH-2021-DISEASE-04 that aims to reveal the biomechanisms of long COVID.Ethics and disseminationThis study has been approved by the Helsinki University Hospital research ethics committee board, ID HUS/1493/2021 on 6 March 2021. All study participants sign written informed consent for participation. The study findings will be reported for publication in peer-reviewed journals.Trial registration numberNCT05699512; Pre-results.
Mediterranean diet and time-restricted eating as a cardiac rehabilitation approach for patients with coronary heart disease and pre-diabetes: the DIABEPIC-1 protocol of a feasibility trial
Authors: Iglesies-Grau Josep , Dionne Valérie , Latour Élise , Gayda Mathieu , Besnier Florent , Gagnon Daniel , Debray Amélie , Gagnon Christine , Pelletier Véronique , Nigam Anil , L’Allier Philippe L , Juneau Martin , Bouabdallaoui Nadia , Bherer Louis 
Published: February 2024

IntroductionDespite proven programmes, implementing lifestyle interventions for pre-diabetes and type 2 diabetes is challenging. Cardiac rehabilitation, provide a valuable opportunity to promote the adoption of healthy lifestyle behaviours for patients with atherosclerotic cardiovascular disease (ASCVD). However, only a limited number of studies have explored the potential for reversing the underlying causes of ASCVD in this setting.ObjectivesThe DIABEPIC1 study is an ongoing single-arm lifestyle clinical trial to assess the feasibility of an upgraded 6-month intensive cardiac rehabilitation programme combining an innovative diet assignment with exercise training to reverse newly onset pre-diabetes (glycated haemoglobin 5.7%–6.4%) to normal glucose concentrations in patients with coronary heart disease.Methods and analysis36 patients referred from the Montreal Heart Institute for cardiac rehabilitation, aged ≥40 years with a recent diagnosis of pre-diabetes in the last 6 months, will be offered to participate in the upgraded programme. Interventions will include four sessions of nutritional counselling on ultra-processed foods intake reduction and a moderate-carbohydrate (<40%) ad libitum Mediterranean diet coupled with 36 1-hour sessions of supervised exercise training (continuous and interval aerobic training, and resistance training) and educational intervention. Phase 2 will continue the same interventions adding 8:16 hour time-restricting eating (TRE) at least 5 days per week. During this second phase, exercise training will be performed with autonomy.The primary objectiveswill be to evaluate the recruitment rate, the completion rates at 3 and 6 months, and the compliance of participants.The secondary objectiveswill be to assess the proportion of prediabetic participants in remission of pre-diabetes at the programme’s end and to characterise the factors associated with remission.Ethics and disseminationThe DIABEPIC1 feasibility study is approved by the Research Ethics Board of the Montreal Heart Institute (Project Number ICM 2022-3005). Written informed consent will be obtained from each participant prior to inclusion. Results will be available through research articles and conferences.ConclusionsThe DIABEPIC1 trial will examine the feasibility and effectiveness of an enhanced cardiac rehabilitation programme combining exercise training with an ultra-processed food reduction intervention, a Mediterranean diet, and TRE counselling to remit pre-diabetes to normal glucose concentrations.Trial registration numberNCT05459987.
Shaping care home COVID-19 testing policy: a protocol for a pragmatic cluster randomised controlled trial of asymptomatic testing compared with standard care in care home staff (VIVALDI-CT)
Authors: Adams Natalie , Stirrup Oliver , Blackstone James , Krutikov Maria , Cassell Jackie A , Cadar Dorina , Henderson Catherine , Knapp Martin , Goscé Lara , Leiser Ruth , Regan Martyn , Cullen-Stephenson Iona , Fenner Robert , Verma Arpana , Gordon Adam , Hopkins Susan , Copas Andrew , Freemantle Nick , Flowers Paul , Shallcross Laura 
Published: February 2024

IntroductionCare home residents have experienced significant morbidity, mortality and disruption following outbreaks of SARS-CoV-2. Regular SARS-CoV-2 testing of care home staff was introduced to reduce transmission of infection, but it is unclear whether this remains beneficial. This trial aims to investigate whether use of regular asymptomatic staff testing, alongside funding to reimburse sick pay for those who test positive and meet costs of employing agency staff, is a feasible and effective strategy to reduce COVID-19 impact in care homes.Methods and analysisThe VIVALDI-Clinical Trial is a multicentre, open-label, cluster randomised controlled, phase III/IV superiority trial in up to 280 residential and/or nursing homes in England providing care to adults aged >65 years. All regular and agency staff will be enrolled, excepting those who opt out. Homes will be randomised to the intervention arm (twice weekly asymptomatic staff testing for SARS-CoV-2) or the control arm (current national testing guidance). Staff who test positive for SARS-CoV-2 will self-isolate and receive sick pay. Care providers will be reimbursed for costs associated with employing temporary staff to backfill for absence arising directly from the trial.The trial will be delivered by a multidisciplinary research team through a series of five work packages.The primary outcome is the incidence of COVID-19-related hospital admissions in residents. Secondary outcomes include the number and duration of outbreaks and home closures. Health economic and modelling analyses will investigate the cost-effectiveness and cost consequences of the testing intervention. A process evaluation using qualitative interviews will be conducted to understand intervention roll out and identify areas for optimisation to inform future intervention scale-up, should the testing approach prove effective and cost-effective. Stakeholder engagement will be undertaken to enable the sector to plan for results and their implications and to coproduce recommendations on the use of testing for policy-makers.Ethics and disseminationThe study has been approved by the London—Bromley Research Ethics Committee (reference number 22/LO/0846) and the Health Research Authority (22/CAG/0165). The results of the trial will be disseminated regardless of the direction of effect. The publication of the results will comply with a trial-specific publication policy and will include submission to open access journals. A lay summary of the results will also be produced to disseminate the results to participants.Trial registration numberISRCTN13296529.
Protocol for the challenge non-typhoidalSalmonella(CHANTS) study: a first-in-human, in-patient, double-blind, randomised, safety and dose-escalation controlled human infection model in the UK
Authors: Smith Christopher , Smith Emma , Rydlova Anna , Varro Robert , Hinton Jay C D , Gordon Melita A , Choy Robert K M , Liu Xinxue , Pollard Andrew J , Chiu Christopher , Cooke Graham S , Gibani Malick M 
Published: February 2024

IntroductionInvasive non-typhoidalSalmonella(iNTS) serovars are a major cause of community-acquired bloodstream infections in sub-Saharan Africa (SSA). In this setting,Salmonella entericaserovar Typhimurium accounts for two-thirds of infections and is associated with an estimated case fatality rate of 15%–20%. Several iNTS vaccine candidates are in early-stage assessment which—if found effective—would provide a valuable public health tool to reduce iNTS disease burden. The CHANTS study aims to develop a first-in-humanSalmonellaTyphimurium controlled human infection model, which can act as a platform for future vaccine evaluation, in addition to providing novel insights into iNTS disease pathogenesis.Methods and analysisThis double-blind, safety and dose-escalation study will randomise 40–80 healthy UK participants aged 18–50 to receive oral challenge with one of two strains ofS. Typhimurium belonging to the ST19 (strain 4/74) or ST313 (strain D23580) lineages. 4/74 is a global strain often associated with diarrhoeal illness predominantly in high-income settings, while D23580 is an archetypal strain representing invasive disease-causing isolates found in SSA. The primary objective is to determine the minimum infectious dose (colony-forming unit) required for 60%–75% of participants to develop clinical or microbiological features of systemic salmonellosis. Secondary endpoints are to describe and compare the clinical, microbiological and immunological responses following challenge. Dose escalation or de-escalation will be undertaken by continual-reassessment methodology and limited within prespecified safety thresholds. Exploratory objectives are to describe mechanisms of iNTS virulence, identify putative immune correlates of protection and describe host–pathogen interactions in response to infection.Ethics and disseminationEthical approval has been obtained from the NHS Health Research Authority (London—Fulham Research Ethics Committee 21/PR/0051; IRAS Project ID 301659). The study findings will be disseminated in international peer-reviewed journals and presented at national/international stakeholder meetings. Study outcome summaries will be provided to both funders and participants.Trial registration numberNCT05870150
Genital tract infections, the vaginal microbiome and gestational age at birth among pregnant women in South Africa: a cohort study protocol
Authors: Gigi Ranjana M S , Mdingi Mandisa M , Jung Hyunsul , Claassen-Weitz Shantelle , Bütikofer Lukas , Klausner Jeffrey D , Muzny Christina A , Taylor Christopher M , van de Wijgert Janneke H H M , Peters Remco P H , Low Nicola 
Published: February 2024

IntroductionPreterm birth complications are the most common cause of death in children under 5 years. The presence of multiple microorganisms and genital tract inflammation could be the common mechanism driving early onset of labour. South Africa has high levels of preterm birth, genital tract infections and HIV infection among pregnant women. We plan to investigate associations between the presence of multiple lower genital tract microorganisms in pregnancy and gestational age at birth.Methods and analysisThis cohort study enrols around 600 pregnant women at one public healthcare facility in East London, South Africa. Eligible women are ≥18 years and at <27 weeks of gestation, confirmed by ultrasound. At enrolment and 30–34 weeks of pregnancy, participants receive on-site tests forChlamydia trachomatisandNeisseria gonorrhoeae, with treatment if test results are positive. At these visits, additional vaginal specimens are taken for: PCR detection and quantification ofTrichomonas vaginalis,Candidaspp.,Mycoplasma genitalium, M. hominis,Ureaplasma urealyticumandU. parvum; microscopy and Nugent scoring; and for 16S ribosomal RNA gene sequencing and quantification. Pregnancy outcomes are collected from a postnatal visit and birth registers. The primary outcome is gestational age at birth. Statistical analyses will explore associations between specific microorganisms and gestational age at birth. To explore the association with the quantity of microorganisms, we will construct an index of microorganism load and use mixed-effects regression models and classification and regression tree analysis to examine which combinations of microorganisms contribute to earlier gestational age at birth.Ethics and disseminationThis protocol has approvals from the University of Cape Town Research Ethics Committee and the Canton of Bern Ethics Committee. Results from this study will be uploaded to preprint servers, submitted to open access peer-reviewed journals and presented at regional and international conferences.Trial registration numberNCT06131749; Pre-results.
Protective effect of height on long-term survival of resectable lung cancer: a new feature of the lung cancer paradox
Authors: Daffré Elisa , Porcher Raphaël , Iannelli Antonio , Prieto Mathilde , Brouchet Laurent , Falcoz Pierre Emmanuel , Le Pimpec Barthes Françoise , Pages Pierre Benoit , Thomas Pascal Alexandre , Dahan Marcel , Alifano Marco 
Published: February 2024

IntroductionUnlike most malignancies, higher body mass index (BMI) is associated with a reduced risk of lung cancer and improved prognosis after surgery. However, it remains controversial whether height, one of determinants of BMI, is associated with survival independently of BMI and other confounders.MethodsWe extracted data on all consecutive patients with resectable non-small cell lung cancer included in Epithor, the French Society of Thoracic and Cardiovascular Surgery database, over a 16-year period. Height was analysed as a continuous variable, and then categorised into four or three categories, according to sex-specific quantiles. Cox proportional hazards regression was used to estimate the association of height with survival, adjusted for age, tobacco consumption, forced expiratory volume in one second (FEV1), WHO performance status (WHO PS), American Society of Anesthesiologists (ASA) score, extent of resection, histological type, stage of disease and centre as a random effect, as well as BMI in a further analysis.ResultsThe study included 61 379 patients. Higher height was significantly associated with better long-term survival after adjustment for other variables (adjusted HR 0.97 per 10 cm higher height, 95% CI 0.95 to 0.99); additional adjustment for BMI resulted in an identical HR. The prognostic impact of height was further confirmed by stratifying by age, ASA class, WHO PS and histological type. When stratifying by BMI class, there was no evidence of a differential association (p=0.93). When stratifying by stage of disease, the prognostic significance of height was maintained for all stages except IIIB-IV.ConclusionsOur study shows that height is an independent prognostic factor of resectable lung cancer.
CIRCUS: an autonomous control system for antimatter, atomic and quantum physics experiments
Authors: Volponi M. , Huck S. , Caravita R. , Zielinski J. , Kornakov G. , Kasprowicz G. , Nowicka D. , Rauschendorfer T. , Rienäcker B. , Prelz F. , Auzins M. , Bergmann B. , Burian P. , Brusa R. S. , Camper A. , Castelli F. , Ciuryło R. , Consolati G. , Doser M. , Glöggler L. T. , Graczykowski Ł. , Grosbart M. , Guatieri F. , Gusakova N. , Gustafsson F. , Haider S. , Janik M. , Khatri G. , Kłosowski Ł. , Krumins V. , Lappo L. , Linek A. , Malamant J. , Mariazzi S. , Penasa L. , Petracek V. , Piwiński M. , Pospisil S. , Povolo L. , Rangwala S. , Rawat B. S. , Rodin V. , Røhne O. M. , Sandaker H. , Smolyanskiy P. , Sowiński T. , Tefelski D. , Vafeiadis T. , Welsch C. P. , Wolz T. , Zawada M. , Zurlo N. 
Published: February 2024

AbstractA powerful and robust control system is a crucial, often neglected, pillar of any modern, complex physics experiment that requires the management of a multitude of different devices and their precise time synchronisation. The AEḡIS collaboration presents CIRCUS, a novel, autonomous control system optimised for time-critical experiments such as those at CERN’s Antiproton Decelerator and, more broadly, in atomic and quantum physics research. Its setup is based on Sinara/ARTIQ and TALOS, integrating the ALPACA analysis pipeline, the last two developed entirely in AEḡIS. It is suitable for strict synchronicity requirements and repeatable, automated operation of experiments, culminating in autonomous parameter optimisation via feedback from real-time data analysis. CIRCUS has been successfully deployed and tested in AEḡIS; being experiment-agnostic and released open-source, other experiments can leverage its capabilities.
Cleenex: Support for User Involvement during an Iterative Data Cleaning Process
Authors: Pereira João L. M. , Fonseca Manuel J. , Lopes Antónia , Galhardas Helena 
Published: February 2024

The existence of large amounts of data increases the probability of occurring data quality problems. A data cleaning process that corrects these problems is usually an iterative process, because it may need to be re-executed and refined to produce high-quality data. Moreover, due to the specificity of some data quality problems and the limitation of data cleaning programs to cover all problems, often a user has to be involved during the program executions by manually repairing data. However, there is no data cleaning framework that appropriately supports this involvement in such an iterative process, a form of human-in-the-loop, to clean structured data. Moreover, data preparation tools that somehow involve the user in data cleaning processes have not been evaluated with real users to assess their effort.
Therefore, we propose Cleenex, a data cleaning framework with support for user involvement during an iterative data cleaning process, and conduct two data cleaning experimental evaluations: an assessment of the Cleenex components that support the user when manually repairing data with a simulated user; and a comparison, in terms of user involvement, of data preparation tools with real users.
Results show that Cleenex components reduce the user effort when manually cleaning data during a data cleaning process, for example, the number of tuples visualized is reduced in 99%. Moreover, when performing data cleaning tasks with Cleenex, real users need less time/effort (e.g., half the clicks) and, based on questionnaires, prefer it to the other tools used for comparison, OpenRefine and Pentaho Data Integration.
Human ASXL1-Mutant Hematopoiesis Is Driven by a Truncated Protein Associated with Aberrant Deubiquitination of H2AK119
Authors: Köhnke Thomas , Nuno Kevin A. , Alder Catherine C. , Gars Eric J. , Phan Paul , Fan Amy C. , Majeti Ravindra 
Published: February 2024

Abstract

Mutations in additional sex combs like 1 (ASXL1) confer poor prognosis both in myeloid malignancies and in premalignant clonal hematopoiesis (CH). However, the mechanisms by which these mutations contribute to disease initiation remain unresolved, and mutation-specific targeting has remained elusive. To address this, we developed a human disease model that recapitulates the disease trajectory from ASXL1-mutant CH to lethal myeloid malignancy. We demonstrate that mutations in ASXL1 lead to the expression of a functional, truncated protein and determine that truncated ASXL1 leads to global redistribution of the repressive chromatin mark H2AK119Ub, increased transposase-accessible chromatin, and activation of both myeloid and stem cell gene-expression programs. Finally, we demonstrate that H2AK119Ub levels are tied to truncated ASXL1 expression levels and leverage this observation to demonstrate that inhibition of the PRC1 complex might be an ASXL1-mutant–specific therapeutic vulnerability in both premalignant CH and myeloid malignancy.

Significance:
Mutant ASXL1 is a common driver of CH and myeloid malignancy. Using primary human HSPCs, we determine that truncated ASXL1 leads to redistribution of H2AK119Ub and may affect therapeutic vulnerability to PRC1 inhibition.
Entities, Uncertainties, and Behavioral Indicators of Consciousness
Authors: Johnson L. Syd M 
Published: February 2024

Abstract
Two problems related to the identification of consciousness are the distribution problem—or how and among which entities consciousness is distributed in the world—and the moral status problem—or which species, entities, and individuals have moral status. The use of inferences from neurobiological and behavioral evidence, and their confounds, for identifying consciousness in nontypically functioning humans, nonhuman animals, and artificial intelligence is considered in light of significant scientific uncertainty and ethical biases, with implications for both problems. Methodological, epistemic, and ethical consensus are needed for responsible consciousness science under epistemic and ethical uncertainty. Consideration of inductive risk is proposed as a potential tool for managing both epistemic and ethical risks in consciousness science.