bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of the
Escherichia coli
ubiquinone-synthesizing UbiUVT pathway in adaptation to changing respiratory conditions
Authors: Arias-Cartin Rodrigo , Kazemzadeh Ferizhendi Katayoun , Séchet Emmanuel , Pelosi Ludovic , Loeuillet Corinne , Pierrel Fabien , Barras Frédéric , Bouveret Emmanuelle 
Published: June 2023

ABSTRACT

Isoprenoid quinones are essential for cellular physiology. They act as electron and proton shuttles in respiratory chains and various biological processes.
Escherichia coli
and many α-, β-, and γ-proteobacteria possess two types of isoprenoid quinones: ubiquinone (UQ) is mainly used under aerobiosis, while demethylmenaquinones (DMK) are mostly used under anaerobiosis. Yet, we recently established the existence of an anaerobic O
2
-independent UQ biosynthesis pathway controlled by
ubiT
,
ubiU
, and
ubiV
genes. Here, we characterize the regulation of
ubiTUV
genes in
E. coli
. We show that the three genes are transcribed as two divergent operons that are both under the control of the O
2
-sensing Fnr transcriptional regulator. Phenotypic analyses using a
menA
mutant devoid of DMK revealed that UbiUV-dependent UQ synthesis is essential for nitrate respiration and uracil biosynthesis under anaerobiosis, while it contributes, though modestly, to bacterial multiplication in the mouse gut. Moreover, we showed by genetic study and
18
O
2
labeling that UbiUV contributes to the hydroxylation of ubiquinone precursors through a unique O
2
-independent process. Last, we report the crucial role of
ubiT
in allowing
E. coli
to shift efficiently from anaerobic to aerobic conditions. Overall, this study uncovers a new facet of the strategy used by
E. coli
to adjust its metabolism on changing O
2
levels and respiratory conditions. This work links respiratory mechanisms to phenotypic adaptation, a major driver in the capacity of
E. coli
to multiply in gut microbiota and of facultative anaerobic pathogens to multiply in their host.

IMPORTANCE

Enterobacteria multiplication in the gastrointestinal tract is linked to microaerobic respiration and associated with various inflammatory bowel diseases. Our study focuses on the biosynthesis of ubiquinone, a key player in respiratory chains, under anaerobiosis. The importance of this study stems from the fact that UQ usage was for long considered to be restricted to aerobic conditions. Here we investigated the molecular mechanism allowing UQ synthesis in the absence of O
2
and searched for the anaerobic processes that UQ is fueling in such conditions. We found that UQ biosynthesis involves anaerobic hydroxylases, that is, enzymes able to insert an O atom in the absence of O
2
. We also found that anaerobically synthesized UQ can be used for respiration on nitrate and the synthesis of pyrimidine. Our findings are likely to be applicable to most facultative anaerobes, which count many pathogens (
Salmonella
,
Shigella
, and
Vibrio
) and will help in unraveling microbiota dynamics.
Physiological and genomic evidence of cysteine degradation and aerobic hydrogen sulfide production in freshwater bacteria
Authors: Tran Patricia Q. , Bachand Samantha C. , Hotvedt Jacob C. , Kieft Kristopher , McDaniel Elizabeth A. , McMahon Katherine D. , Anantharaman Karthik 
Published: June 2023

ABSTRACT

The sulfur-containing amino acid cysteine is abundant in the environment, including in freshwater lakes. Biological cysteine degradation can result in hydrogen sulfide (H
2
S), a toxic and ecologically relevant compound that is a central player in biogeochemical cycling in aquatic environments. Here, we investigated the ecological significance of cysteine in oxic freshwater, using isolated cultures, controlled experiments, and multiomics. We screened bacterial isolates enriched from natural lake water for their ability to produce H
2
S when provided cysteine. We identified 29 isolates (Bacteroidota, Proteobacteria, and Actinobacteria) that produced H
2
S. To understand the genomic and genetic basis for cysteine degradation and H
2
S production, we further characterized three isolates using whole-genome sequencing (using a combination of short-read and long-read sequencing) and tracked cysteine and H
2
S levels over their growth ranges:
Stenotrophomonas maltophilia
(Gammaproteobacteria),
S. bentonitica
(Gammaproteobacteria), and
Chryseobacterium piscium
(Bacteroidota). Cysteine decreased and H
2
S increased, and all three genomes had genes involved in cysteine degradation. Finally, to assess the presence of these organisms and genes in the environment, we surveyed a 5-year time series of metagenomic data from the same isolation source (Lake Mendota, Madison, WI, USA) and identified their presence throughout the time series. Overall, our study shows that diverse isolated bacterial strains can use cysteine and produce H
2
S under oxic conditions, and we show evidence using metagenomic data that this process may occur more broadly in natural freshwater lakes. Future considerations of sulfur cycling and biogeochemistry in oxic environments should account for H
2
S production from the degradation of organosulfur compounds.

IMPORTANCE

Hydrogen sulfide (H
2
S), a naturally occurring gas with both biological and abiotic origins, can be toxic to living organisms. In aquatic environments, H
2
S production typically originates from anoxic (lacking oxygen) environments, such as sediments, or the bottom layers of thermally stratified lakes. However, the degradation of sulfur-containing amino acids such as cysteine, which all cells and life forms rely on, can be a source of ammonia and H
2
S in the environment. Unlike other approaches for biological H
2
S production such as dissimilatory sulfate reduction, cysteine degradation can occur in the presence of oxygen. Yet, little is known about how cysteine degradation influences sulfur availability and cycling in freshwater lakes. In our study, we identified diverse bacteria from a freshwater lake that can produce H
2
S in the presence of O
2
. Our study highlights the ecological importance of oxic H
2
S production in natural ecosystems and necessitates a change in our outlook on sulfur biogeochemistry.
How do psychobehavioural variables shed light on heterogeneity in COVID-19 vaccine acceptance? Evidence from United States general population surveys on a probability panel and social media
Authors: Charles Grace K , Braunstein Sofia P , Barker Jessica L , Fung Henry , Coome Lindsay , Kumar Rohan , Huang Vincent S , Kemp Hannah , Grant Eli , Bernard Drew , Barefoot Darren , Sgaier Sema K 
Published: June 2023

ObjectivesTo (1) understand what behaviours, beliefs, demographics and structural factors predict US adults’ intention to get a COVID-19 vaccination, (2) identify segments of the population (‘personas’) who share similar factors predicting vaccination intention, (3) create a ‘typing tool’ to predict which persona people belong to and (4) track changes in the distribution of personas over time and across the USA.DesignThree surveys: two on a probability-based household panel (NORC’s AmeriSpeak) and one on Facebook.SettingThe first two surveys were conducted in January 2021 and March 2021 when the COVID-19 vaccine had just been made available in the USA. The Facebook survey ran from May 2021 to February 2022.ParticipantsAll participants were aged 18+ and living in the USA.Outcome measuresIn our predictive model, the outcome variable was self-reported vaccination intention (0–10 scale). In our typing tool model, the outcome variable was the five personas identified by our clustering algorithm.ResultsOnly 1% of variation in vaccination intention was explained by demographics, with about 70% explained by psychobehavioural factors. We identified five personas with distinct psychobehavioural profiles: COVID Sceptics (believe at least two COVID-19 conspiracy theories), System Distrusters (believe people of their race/ethnicity do not receive fair healthcare treatment), Cost Anxious (concerns about time and finances), Watchful (prefer to wait and see) and Enthusiasts (want to get vaccinated as soon as possible). The distribution of personas varies at the state level. Over time, we saw an increase in the proportion of personas who are less willing to get vaccinated.ConclusionsPsychobehavioural segmentation allows us to identifywhypeople are unvaccinated, not justwhois unvaccinated. It can help practitioners tailor the right intervention to the right person at the right time to optimally influence behaviour.
CONFIDENT-trial protocol: a pragmatic template for clinical implementation of artificial intelligence assistance in pathology
Authors: Flach Rachel N , Stathonikos Nikolas , Nguyen Tri Q , Ter Hoeve Natalie D , van Diest Paul J , van Dooijeweert Carmen 
Published: June 2023

IntroductionArtificial intelligence (AI) has been on the rise in the field of pathology. Despite promising results in retrospective studies, and several CE-IVD certified algorithms on the market, prospective clinical implementation studies of AI have yet to be performed, to the best of our knowledge. In this trial, we will explore the benefits of an AI-assisted pathology workflow, while maintaining diagnostic safety standards.Methods and analysisThis is a Standard Protocol Items: Recommendations for Interventional Trials–Artificial Intelligence compliant single-centre, controlled clinical trial, in a fully digital academic pathology laboratory. We will prospectively include prostate cancer patients who undergo prostate needle biopsies (CONFIDENT-P) and breast cancer patients who undergo a sentinel node procedure (CONFIDENT-B) in the University Medical Centre Utrecht. For both the CONFIDENT-B and CONFIDENT-P trials, the specific pathology specimens will be pseudo-randomised to be assessed by a pathologist with or without AI assistance in a pragmatic (bi-)weekly sequential design. In the intervention group, pathologists will assess whole slide images (WSI) of the standard hematoxylin and eosin (H&E)-stained sections assisted by the output of the algorithm. In the control group, pathologists will assess H&E WSI according to the current clinical workflow. If no tumour cells are identified or when the pathologist is in doubt, immunohistochemistry (IHC) staining will be performed. At least 80 patients in the CONFIDENT-P and 180 patients in the CONFIDENT-B trial will need to be enrolled to detect superiority, allocated as 1:1. Primary endpoint for both trials is the number of saved resources of IHC staining procedures for detecting tumour cells, since this will clarify tangible cost savings that will support the business case for AI.Ethics and disseminationThe ethics committee (MREC NedMec) waived the need of official ethical approval, since participants are not subjected to procedures nor are they required to follow rules. Results of both trials (CONFIDENT-B and CONFIDENT-P) will be published in scientific peer-reviewed journals.
Anzhen Risk Evaluation System for Acute Aortic Syndrome (AZSCORE-AAS): protocol for a multicentre prospective cohort study in northern China
Authors: Wang Han-Zhang , Chen Su-Wei , Zhong Yong-Liang , Ge Yi-Peng , Qiao Zhi-Yu , Li Cheng-Nan , Guo Ru-Tao , Zhang Zhe , Qiao Chen-Hui , Zhu Jun-Ming 
Published: June 2023

IntroductionAcute aortic syndrome (AAS) is a group of acute and critical conditions, including acute aortic dissection (AAD), acute intramural haematoma and penetrating aortic ulcer. High mortality and morbidity rates result in a poor patient prognosis. Prompt diagnoses and timely interventions are paramount for saving patients’ lives. In recent years, risk models for AAD have been established worldwide; however, a risk evaluation system for AAS is still lacking in China. Therefore, this study aims to develop an early warning and risk scoring system in combination with the novel potential biomarker soluble ST2 (sST2) for AAS.Methods and analysisThis multicentre, prospective, observational study will recruit patients diagnosed with AAS at three tertiary referral centres from 1 January 2020 to 31 December 2023. We will analyse the discrepancies in sST2 levels in patients with different AAS types and explore the accuracy of sST2 in distinguishing between them. We will also incorporate potential risk factors and sST2 into a logistic regression model to establish a logistic risk scoring system for predicting postoperative death and prolonged intensive care unit stay in patients with AAS.Ethics and disseminationThis study was registered on the Chinese Clinical Trial Registry website (http://www. chictr. org. cn/). Ethical approval was obtained from the human research ethics committees of Beijing Anzhen Hospital (KS2019016). The ethics review board of each participating hospital agreed to participate. The final risk prediction model will be published in an appropriate journal and disseminated as a mobile application for clinical use. Approval and anonymised data will be shared.Trial registration numberChiCTR1900027763.
Tear gas exposure and its association with respiratory emergencies in infants and older adults during the social uprising of 2019 in Chile: an observational, longitudinal, repeated measures study
Authors: Huerta Patricia Alejandra , Cifuentes Manuel , González Marcelo , Ugarte-Avilés Tamara 
Published: June 2023

ObjectiveTo evaluate if extensive use of tear gas during the Chilean social uprising of 2019 was associated with a higher frequency of respiratory emergencies and bronchial diseases in a residential vulnerable population.DesignObservational, longitudinal, repeated measures study.SettingsSix healthcare centres (one emergency department and five urgent care centres) in the city of Concepción, Chile during 2018 and 2019.ParticipantsThis study was conducted on daily respiratory emergencies and diagnosis. Daily frequency of urgency and emergency visits are administrative data, publicly available and previously de-identified.Primary and secondary outcome measuresAbsolute and relative frequency of daily respiratory emergencies in infants and older adults. A secondary outcome was the relative frequency of bronchial diseases (International Classification of Diseases 10th Revision, ICD-10: J20–J21; J40–J46) in both age groups. We finally measured the rate ratio (RR) of bronchial diseases above the daily grand mean, since the number of visits with these diagnoses in several days was zero. Tear gas exposure was assessed as the uprising period. Models were adjusted by weather and air pollution information.ResultsPercentage of respiratory emergencies during the uprising rose by 1.34 percentage points (95% CI 1.26 to 1.43) in infants and 1.44 percentage points (95% CI 1.34 to 1.55) in older adults. In infants, the emergency department experienced a larger increment in respiratory emergencies (6.89 percentage points; 95% CI 1.58 to 2.28) than the urgent care centres (1.67 percentage points; 95% CI 1.46 to 1.90). The RR of bronchial diseases above the daily grand mean during the uprising period was 1.34 in infants (95% CI 1.15 to 1.56) and 1.50 in older adults (95% CI 1.28 to 1.75).ConclusionsThe massive use of tear gas increases the frequency and probability of respiratory emergencies and particularly bronchial diseases in the vulnerable population; we recommend revising public policy to restrict its use.
Measuring the burden of SARS-CoV-2 infection among persons living with HIV and healthcare workers and its impact on service delivery in Mozambique: protocol of a prospective cohort study
Authors: De Schacht Caroline , Nhacule Edna , Belo Celso , Young Peter W , Bhatt Nilesh , Júnior Faustino , Pimentel De Gusmão Eduarda , Muquingue Humberto , Muteerwa Ana , Bila Dulce , Ouenzar Mohammed A , Madede Tavares , Cumbane Reginalda , Amorim Gustavo , Viegas Edna 
Published: June 2023

IntroductionAs COVID-19 continues to spread globally and within Mozambique, its impact among immunosuppressed persons, specifically persons living with HIV (PLHIV), and on the health system is unknown in the country. The ‘COVid and hIV’ (COVIV) study aims to investigate: (1) the seroprevalence and seroincidence of SARS-CoV-2 among PLHIV and healthcare workers providing HIV services; (2) knowledge, attitudes, practices and perceptions regarding SARS-CoV-2 infection; (3) the pandemic’s impact on HIV care continuum outcomes and (4) facility level compliance with national COVID-19 guidelines.Methods and analysisA multimethod study will be conducted in a maximum of 11 health facilities across Mozambique, comprising four components: (1) a cohort study among PLHIV and healthcare workers providing HIV services to determine the seroprevalence and seroincidence of SARS-CoV-2, (2) a structured survey to assess knowledge, attitudes, perceptions and practices regarding COVID-19 disease, (3) analysis of aggregated patient data to evaluate retention in HIV services among PLHIV, (4) an assessment of facility implementation of infection prevention and control measures.Ethics and disseminationEthical approval was obtained from the National Health Bioethics Committee, and institutional review boards of implementing partners. Study findings will be discussed with local and national health authorities and key stakeholders and will be disseminated in clinical and scientific forums.Trial registration numberNCT05022407.
Association between domain-specific sedentary behaviour and endometrial cancer: a systematic review and meta-analysis
Authors: Yuan Lei , Ni Jingyi , Lu Wen , Yan Qin , Wan Xiaoping , Li Zhen 
Published: June 2023

ObjectiveSedentary behaviour is associated with increased cancer risk. We aim to assess the associations of domain-specific and total sedentary behaviour with risk of endometrial cancer, with additional attention paid to potential differences in adjustment strategy for obesity and physical activity.DesignA systematic review and meta-analysis was conducted in accordance with the guidelines of Preferred Reporting Items for Systematic Reviews (PRISMA) and Meta-Analyses and the Meta-analysis of Observational Studies in Epidemiology (MOOSE).Data sourcesPubMed, Embase and MEDLINE databases were searched up to 28 February 2023, supplemented by grey literature searches.Eligibility criteria for selecting studiesObservational human studies evaluating the association between sedentary behaviour and endometrial cancer.Data extraction and synthesisTwo reviewers extracted data and conducted the quality assessment based on Newcastle-Ottawa Scale (NOS) independently. We used a random-effects model with inverse variance approach to pool the estimates. The extent of heterogeneity was quantified with theI2statistics.ResultsSixteen studies were included in the systematic review. Fourteen studies involving 882 686 participants were included in the meta-analysis. The pooled relative risks (RRs) for high versus low level of overall sedentary behaviour was 1.28 (95% CI: 1.14 to 1.43;I2=34.8%). The increased risk regarding specific domains was 1.22 (95% CI: 1.09 to 1.37; I2=13.4%, n=10) for occupational domain, 1.34 (95% CI: 0.98 to 1.83; I2=53.7%, n=6) for leisure-time domain and 1.55 (95% CI: 1.27 to 1.89; I2=0.0%, n=2) for total sedentary behaviour. Larger pooled RRs were observed among studies with adjustment for physical activity and studies without adjustment for body mass index.ConclusionsHigher levels of sedentary behaviour, total and occupational sedentary behaviour in particular, increase the risk of endometrial cancer. Future studies are needed to verify domain-specific associations based on objective quantification of sedentary behaviour, as well as the interaction of physical activity, adiposity and sedentary time on endometrial cancer.
Comparison of novel oncology drugs that received dual approval from the US accelerated approval and EU conditional marketing authorisation pathways, 2006–2021: a cross-sectional study
Authors: Xie Jinping , Li Jinlian , Liu Yue , Wang Haoyang , Wang Yifei , Yang Yifan , Chen Yi , Jiang Rong , Shao Rong 
Published: June 2023

ObjectiveWe aimed to provide insight into differences in drug review decisions made by the US Food and Drug Administration’s (FDA) accelerated approval (AA) pathway and the European Medicines Agency’s (EMA) conditional marketing authorisation (CMA) pathway, and to add to the current knowledge base of drug approval processes.Design, setting, participantsThis cross-sectional study thoroughly examines novel oncology drugs with dual approval through FDA AA and EMA CMA between 2006 and 2021. Statistical analysis was performed from June to July 2022.Primary and secondary outcome measuresThe study examined the regulatory differences between regions for dually approved novel oncology drugs, including approval decisions, pivotal efficacy clinical trials, speed of review and postmarketing obligations.ResultsDuring this time period, there was a difference in the use of the FDA AA and the EMA CMA (FDA: EMA: 41.2%: 70.0%, p<0.05). Of the 25 drugs approved by both the FDA AA and the EMA CMA, 22 (88.0%) of the regulatory decisions were based on the same pivotal clinical trials. But there were more differences in the requirements for postmarketing obligations, with the EMA’s postmarketing obligations focusing on the efficacy and safety of the drug (EMA: FDA: 63.0%: 27.0%, p＜0.05) and the FDA’s postmarketing obligations focusing more on the efficacy (FDA: EMA: 73.0%: 23.9%, p＜0.05). In addition, both the USA and EU had some postmarketing obligations completed beyond the schedule (30.4% and 19.2% in the USA and EU, respectively), with the longest delays lasting 3.7 years (0.2–3.7 years) and 3.3 years (0.04–3.3 years) in the USA and EU, respectively.ConclusionsThe FDA and EMA have different orientations and benefit–risk balance considerations in the use of AA or CMA. It is also the case that the shortcomings in the design and implementation of postmarketing studies have made it a challenge to obtain the evidence needed to confirm a drug’s benefits.
Eye-tracking in adult depression: protocol for a systematic review and meta-analysis
Authors: Noyes Blake , Biorac Aleks , Vazquez Gustavo , Khalid-Khan Sarosh , Munoz Douglas , Booij Linda 
Published: June 2023

IntroductionIn recent years, eye-tracking has been proposed as a promising tool to identify potential biomarkers for mental disorders, including major depression. We will conduct an updated systematic review and meta-analysis on eye-tracking research in adults with major depressive disorder or other clinically diagnosed depressive disorders.Methods and analysisThis protocol follows all reporting items in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol extension. We will conduct a systematic search of PubMed, PsycINFO, Google Scholar and EMBASE for sources published up until March 2023. Abstract and full-text review will be completed independently by two reviewers. Non-randomised studies using eye movement tasks in individuals with a depressive disorder versus controls will be included. Eye movement tasks of interest include, but are not limited to, saccade, smooth pursuit, fixation, free-viewing, attentional disengagement, visual search and attentional blink tasks. Results will be categorised by eye movement task. Risk of bias will be assessed using the National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies and confidence in cumulative evidence will be assessed using Grading of Recommendations, Assessment, Development and Evaluation criteria.Ethics and disseminationEthics approval is not required due to the nature of the proposed analysis. Results will be disseminated through a journal article, conference presentations and/or dissertations.