bluuebunny/crossref_metadata_2025 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

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.
Complete Genome Sequences of the Type Strains Rouxiella badensis DSM 100043 and R. chamberiensis DSM 28324, Resolved Using Nanopore Long-Read Sequencing
Authors: Paul Saina , Anderson Peter J. , Maynard Gregg J. , Dyall-Smith Mike , Kudinha Timothy
Published: June 2023

The complete genome sequences of
Rouxiella badensis
DSM 100043
T
and
Rouxiella chamberiensis
DSM 28324
T
were determined using Oxford Nanopore long-read sequencing and the Flye assembler. The former contains a circular chromosome of 4,964,479 bp and a circular plasmid of 116,582 bp; the latter contains a circular chromosome of 4,639,296 bp.
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

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.
Risk and Outcome of Infective Endocarditis in Streptococcal Bloodstream Infections according to Streptococcal Species
Authors: Seo Hyeonji , Hyun Junho , Kim Haein , Park Sunghee , Chung Hyemin , Bae Seongman , Jung Jiwon , Kim Min Jae , Kim Sung-Han , Lee Sang-Oh , Choi Sang-Ho , Kim Yang Soo , Chong Yong Pil
Published: June 2023

Our study of risk of infective endocarditis in patients with streptococcal bloodstream infection demonstrated that
Streptococcus sanguinis
,
S. mutans
, and
S. gallolyticus
were significantly associated with higher risk of infective endocarditis. However, when we evaluated the performance of echocardiography in patients with streptococcal bloodstream infection, patients with
S. mutans
and
S. gordonii
bloodstream infection had a tendency of low performance in echocardiography.
Complete transection of the descending colon following blunt abdominal trauma
Authors: Jambor Maxwell , Irwin Matthew , Kirkland Olivia , Seton Rebecca
Published: June 2023

We present the case of a man in his 30s who was crushed between two vehicles sustaining blunt trauma to his lower limbs and torso. The patient was in shock on arrival to the emergency department, and immediate resuscitation was given with massive transfusion protocol activation. Once the patient’s haemodynamic status was stabilised, a CT scan revealed a complete colon transection. The patient was taken to the operating theatre where a midline laparotomy was performed, and the transected descending colon was managed with a segmental resection and handsewn anastomosis. The patient followed an unremarkable postoperative course, with bowels opening on day 8 postoperatively. Colon injuries are rare following blunt abdominal trauma, and a delay in diagnosis may lead to increased morbidity and mortality. As such, a low threshold for surgical intervention is recommended.
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

Objectives

To (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.

Design

Three surveys: two on a probability-based household panel (NORC’s AmeriSpeak) and one on Facebook.

Setting

The 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.

Participants

All participants were aged 18+ and living in the USA.

Outcome measures

In 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.

Results

Only 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.

Conclusions

Psychobehavioural 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

Introduction

Artificial 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 analysis

This 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 dissemination

The 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

Introduction

Acute 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 analysis

This 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 dissemination

This 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 number

ChiCTR1900027763.
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

Objective

To 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.

Design

Observational, longitudinal, repeated measures study.

Settings

Six healthcare centres (one emergency department and five urgent care centres) in the city of Concepción, Chile during 2018 and 2019.

Participants

This 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 measures

Absolute 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.

Results

Percentage 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).

Conclusions

The 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

Introduction

As 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 analysis

A 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 dissemination

Ethical 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 number

NCT05022407.
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

Objective

Sedentary 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.

Design

A 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 sources

PubMed, Embase and MEDLINE databases were searched up to 28 February 2023, supplemented by grey literature searches.

Eligibility criteria for selecting studies

Observational human studies evaluating the association between sedentary behaviour and endometrial cancer.

Data extraction and synthesis

Two 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.

Results

Sixteen 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.

Conclusions

Higher 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

Objective

We 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, participants

This 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 measures

The 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.

Results

During 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.

Conclusions

The 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

Introduction

In 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 analysis

This 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 dissemination

Ethics 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.
Multicentre, interventional, single-arm study protocol of telemonitored circadian rhythms and patient-reported outcomes for improving mFOLFIRINOX safety in patients with pancreatic cancer (MultiDom, NCT04263948)
Authors: Bouchahda Mohamed , Ulusakarya Ayhan , Thirot-Bidault Anne , Attari Amal , Bossevot Rachel , Tuligenga Richard , Hammel Pascal , Adam René , Levi Francis
Published: June 2023

Introduction

Circadian clocks regulate cellular proliferation and drug effects. Tolerability and/or efficacy of anticancer therapies have been improved by their administration according to circadian rhythms, while being predicted by circadian robustness. The combination of leucovorin, fluorouracil, irinotecan and oxaliplatin (mFOLFIRINOX) is a standard treatment for pancreatic ductal adenocarcinoma (PDAC), that generates grades 3–4 adverse events in the majority of patients and an estimated 15%–30% emergency admission rate. The MultiDom study evaluates whether mFOLFIRINOX safety can be improved using a novel circadian-based telemonitoring-telecare platform in patients at home. The detection of early warning signals of clinical toxicities could guide their early management, possibly preventing emergency hospital admissions.

Methods and analysis

This multicentre, interventional, prospective, longitudinal, single-arm study hypothesises that the mFOLFIRINOX-related emergency admission rate will be 5% (95% CI 1.7% to 13.7%), among 67 patients with advanced PDAC. Study participation is 7 weeks for each patient, including a reference week before chemotherapy onset and 6 weeks afterwards. Accelerometry and body temperature are measured q1-min using a continuously worn telecommunicating chest surface sensor, daily body weight is self-measured with a telecommunicating balance and 23 electronic patient-reported outcomes (e-PROs) are self-rated using a tablet. Hidden Markov model, spectral analyses and other algorithms automatically compute physical activity, sleep, temperature, body weight change, e-PRO severity and 12 circadian sleep/activity parameters, including the dichotomy index I<O (% activity ‘in-bed’ below median activity ‘out-of-bed’), once to four times daily. Health professionals access visual displays of near-real time parameter dynamics and receive automatic alerts, with trackable digital follow-up.

Ethics and dissemination

The study has been approved by the National Agency for Medication and Health Product Safety (ANSM) and Ethics Committee West V (2 July 2019; third amendment, 14 June 2022). The data will be disseminated at conferences and in peer-reviewed journals and will support large-scale randomised evaluation.

Trial registration numbers

NCT04263948and ID RCB-2019-A00566-51.
Efficacy of alcohol reduction interventions among people with HIV as evaluated by self-report and a phosphatidylethanol (PEth) outcome: protocol for a systematic review and individual participant data meta-analysis
Authors: Kane Jeremy C , Allen Isabel , Fatch Robin , Scheffler Aaron , Emenyonu Nneka , Puryear Sarah B , Chirayil Priya , So-Armah Kaku , Kahler Christopher W , Magidson Jessica F , Conroy Amy A , Edelman E Jennifer , Woolf-King Sarah , Parry Charles , Kiene Susan M , Chamie Gabriel , Adong Julian , Go Vivian F , Cook Robert L , Muyindike Winnie , Morojele Neo , Blokhina Elena , Krupitsky Evgeny , Fiellin David A , Hahn Judith A
Published: June 2023

Introduction

Unhealthy alcohol use is associated with a range of adverse outcomes among people with HIV (PWH). Testing the efficacy and promoting the availability of effective interventions to address unhealthy alcohol use among PWH is thus a priority. Alcohol use outcomes in intervention studies are often measured by self-report alone, which can lead to spurious results due to information biases (eg, social desirability). Measuring alcohol outcomes objectively through biomarkers, such as phosphatidylethanol (PEth), in addition to self-report has potential to improve the validity of intervention studies. This protocol outlines the methods for a systematic review and individual participant data meta-analysis that will estimate the efficacy of interventions to reduce alcohol use as measured by a combined categorical self-report/PEth variable among PWH and compare these estimates to those generated when alcohol is measured by self-report or PEth alone.

Methods and analysis

We will include randomised controlled trials that: (A) tested an alcohol intervention (behavioural and/or pharmacological), (B) enrolled participants 15 years or older with HIV; (C) included both PEth and self-report measurements, (D) completed data collection by 31 August 2023. We will contact principal investigators of eligible studies to inquire about their willingness to contribute data. The primary outcome variable will be a combined self-report/PEth alcohol categorical variable. Secondary outcomes will include PEth alone, self-report alone and HIV viral suppression. We will use a two-step meta-analysis and random effects modelling to estimate pooled treatment effects; I2will be calculated to evaluate heterogeneity. Secondary and sensitivity analyses will explore treatment effects in adjusted models and within subgroups. Funnel plots will be used to explore publication bias.

Ethics and dissemination

The study will be conducted with deidentified data from completed randomised controlled trials and will be considered exempt from additional ethical approval. Results will be disseminated through peer-reviewed publications and international scientific meetings.

PROSPERO registration number

CRD42022373640.
Emergency cerclage using double-level versus single-level suture in the management of cervical insufficiency (Cervical Occlusion double-level Stitch Application,COSA): study protocol for a multicentre, non-blinded, randomised controlled trial
Authors: Kosińska Kaczyńska Katarzyna , Rebizant Beata , Bednarek Katarzyna , Dabrowski Filip Andrzej , Kajdy Anna , Muzyka-Placzyńska Katarzyna , Filipecka-Tyczka Dagmara , Uzar Piotr , Kwiatkowski Sebastian , Torbe Andrzej , Grzesiak Mariusz , Kaczmarek Piotr , Żyła Monika , Brawura-Biskupski-Samaha Robert
Published: June 2023

Introduction

Cervical insufficiency accounts for 15% of recurrent pregnancy losses between 16 and 28 weeks of gestation. The aim of the study is to verify the effectiveness of emergency double-level cerclage with vaginal progesterone in cervical insufficiency treatment in terms of the prevention of preterm delivery before 34 weeks of gestation.

Methods and analysis

This trial is a multicentre, non-blinded, randomised study with 1:1 allocation ratio. The study is conducted at tertiary perinatal care departments in Poland. It will include patients with cervical insufficiency with the fetal membranes visible in the open cervical canal or protruding into the vagina between 16+0 and 23+6 weeks of pregnancy. They will be randomised into two arms: emergency single-level cerclage with vaginal progesterone or double-level cerclage with vaginal progesterone. All will be administered antibiotics and indomethacin. The primary outcome is the rate of deliveries below 34+0 weeks of gestation, while secondary outcomes include gestational age at delivery, neonatal outcomes, maternal outcomes according to the Core Outcome Set for Evaluation of Interventions to Prevent Preterm Birth and cerclage procedure complications. The planned number of participants according to the power analysis is 78.

Ethics and dissemination

The study protocol was written in accordance with the Standard Protocol Items: Recommendations for Interventional Trials statement. It was created according to the requirements of the Declaration of Helsinki for Medical Research involving Human Subject. Ethical approval was obtained from the Ethics Committee of the Centre of Postgraduate Medical Education (no. 1/2022). The study protocol was approved and published by ClinicalTrials.gov (posted on 24 February 2022). All participants gave a written informed consent. After completion of the study its results will be published in a peer-reviewed English language journal.

Trial registration

NCT05268640.
Effect of plant milk consumption on childhood growth: protocol for a systematic review
Authors: Soczynska Izabela , da Costa Bruno R , O'Connor Deborah L , Jenkins David J A , Birken Catherine S , Keown-Stoneman Charles D G , D'Hollander Curtis , Calleja Sabine , Maguire Jonathon L
Published: June 2023

Introduction

There has been considerable debate about whether plant milks can support the nutritional requirements of growing children. The proposed systematic review aims to assess the evidence on the relationship between plant milk consumption and growth and nutritional status in childhood.

Methods and analysis

Ovid MEDLINE ALL (1946–present), Ovid EMBASE Classic (1947–present), CINAHL Complete (Cumulative Index to Nursing and Allied Health Literature), Scopus, the Cochrane Library and grey literature will be searched comprehensively (from 2000 to present; English language) to find studies that describe the association between plant milk consumption and growth or nutrition in children 1–18 years of age. Two reviewers will identify eligible articles, extract data and assess the risk of bias in individual studies. If a meta-analyses is not conducted, the evidence will be synthesised narratively and the overall certainty of evidence will be rated using the Grading of Recommendations Assessment, Development and Evaluation approach.

Ethics and dissemination

Ethical approval is not required for this study since no data will be collected. Results of the systematic review will be published in a peer-reviewed journal. Findings from this study may be useful in informing future evidence-based recommendations about plant milk consumption in children.

PROSPERO registration number

CRD42022367269.
Novel risk score for acute upper gastrointestinal bleeding in elderly patients: a single-centre retrospective study
Authors: Li Yajie , Lu Qin , Song Mingyang , Wu Kexuan , Ou Xilong
Published: June 2023

Objectives

Acute upper gastrointestinal bleeding (UGIB) is a common reason for emergency hospital admission. Identifying low-risk patients suitable for outpatient management is a clinical and research priority. This study aimed to develop a simple risk score to identify elderly patients with UGIB for whom hospital admission is not required.

Design

This was a single-centre retrospective study.

Setting

This study was conducted at Zhongda Hospital affiliated with Southeast University in China.

Participants

Patients from January 2015 to December 2020 for the derivation cohort and from January 2021 to June 2022 for the validation cohort were enrolled in this study. A total of 822 patients (derivation cohort=606 and validation cohorts=216) were included in this study. Patients aged ≥65 years with coffee-grounds vomiting, melena or/and haematemesis were included in the analysis. Patients admitted but had UGIB or transferred between hospitals were excluded.

Methods

Baseline demographic characteristics and clinical parameters were recorded at the first visit. Data were collected from electronic records and databases. Multivariable logistic regression modelling was performed to identify predictors of safe discharge.

Results

304/606 (50.2%) and 132/216 (61.1%) patients were not safely discharged in the derivation and validation cohorts, respectively. A clinical risk score of five variables was entered into UGIB risk stratification: Charlson Comorbidity Index >2, systolic blood pressure <100 mm Hg, haemoglobin <100 g/L, blood urea nitrogen ≥6.5 mmol/L, albumin <30 g/L. The optimal cut-off value was ≥1, the sensitivity was 97.37% and the specificity was 19.21% for predicting the inability to discharge safely. The area under the receiver operating characteristic curve was 0.806.

Conclusions

A novel clinical risk score with good discriminative performance was developed to identify elderly patients with UGIB who were suitable for safe outpatient management. This score can reduce unnecessary hospitalisations.
Efficacy of autologous plateletpheresis in adult aortic surgery: study protocol for a randomised controlled trial
Authors: Gao Jie , Jia Jinna , Gao Xurong , Ji Hongwen
Published: June 2023

Introduction

Perioperative coagulopathy is common in patients undergoing aortic surgery, increasing the risk of excessive blood loss and subsequent allogeneic transfusion. Blood conservation has become a vital part of cardiovascular surgery, but measures to protect platelets from destruction by cardiopulmonary bypass (CPB) are still lacking. Autologous platelet concentrate (APC) may have potential benefits for intraoperative blood preservation, but its efficacy has not been studied extensively. This study aims to evaluate the efficacy of APC as a blood conservation technique to reduce blood transfusion in adult aortic surgery.

Methods and analysis

This is a prospective, single-centre, single-blind randomised controlled trial. A total of 344 adult patients undergoing aortic surgery with CPB will be enrolled and randomised to either the APC group or the control group with a 1:1 randomisation ratio. Patients in the APC group will receive autologous plateletpheresis before heparinisation, while those in the control group will not. The primary outcome is the perioperative packed red blood cell (pRBC) transfusion rate. Secondary endpoints include the volume of perioperative pRBC transfusion; drainage volume within 72 hours post-surgery; postoperative coagulation and platelet function; and the incidence of adverse events. Data will be analysed according to the intention-to-treat principle.

Ethics and dissemination

This study was approved by the institutional review board of Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (no. 2022-1806). All procedures included in this study will be performed in adherence to the Helsinki Declaration. The results of the trial will be published in an international peer-reviewed journal.

Trial registration number

Chinese Clinical Trial Register (ChiCTR2200065834).
Learning from experience: a qualitative study of surgeons’ perspectives on reporting and dealing with serious adverse events
Authors: Øyri Sina Furnes , Søreide Kjetil , Søreide Eldar , Tjomsland Ole
Published: June 2023

Introduction

In surgery, serious adverse events have effects on the patient journey, the patient outcome and may constitute a burden to the surgeon involved. This study aims to investigate facilitators and barriers to transparency around, reporting of and learning from serious adverse events among surgeons.

Methods

Based on a qualitative study design, we recruited 15 surgeons (4 females and 11 males) with 4 different surgical subspecialties from four Norwegian university hospitals. The participants underwent individual semistructured interviews and data were analysed according to principles of inductive qualitative content analysis.

Results and discussion

We identified four overarching themes. All surgeons reported having experienced serious adverse events, describing these as part of ‘the nature of surgery’. Most surgeons reported that established strategies failed to combine facilitation of learning with taking care of the involved surgeons. Transparency about serious adverse events was by some felt as an extra burden, fearing that openness on technical-related errors could affect their future career negatively. Positive implications of transparency were linked with factors such as minimising the surgeon’s feeling of personal burden with positive impact on individual and collective learning. A lack of facilitation of individual and structural transparency factors could entail ‘collateral damage’. Our participants suggested that both the younger generation of surgeons in general, and the increasing number of women in surgical professions, might contribute to ‘maturing’ the culture of transparency.

Conclusion and implications

This study suggests that transparency associated with serious adverse events is hampered by concerns at both personal and professional levels among surgeons. These results emphasise the importance of improved systemic learning and the need for structural changes; it is crucial to increase the focus on education and training curriculums and offer advice on coping strategies and establish arenas for safe discussions after serious adverse events.
Young persons and healthcare professionals experience of virtual gastroenterology consultations: a multicentre survey conducted during the COVID-19 pandemic
Authors: Hubbard Rhona , Brooks Alenka , Arebi Naila , El-Khouly Sara , Kiparissi Fevronia , Mozdiak Ella , Muhammed Rafeeq , Smith Philip J , Zarate-Lopez Natalia , Garrick Victoria , Greenan-Barrett James , Baker Sarah , Bradbury Keith , DelNero Nicholas , Narula Priya
Published: June 2023

Objective

To explore Young Persons (YP) and healthcare professionals (HCP) experiences of virtual consultations (VC) and establish whether developmentally appropriate healthcare can be delivered virtually.

Method

YP and HCP questionnaire surveys were designed and piloted. Electronic questionnaire links were sent by post, email or text message January–April 2021 to YP aged 13–25 years old, with predefined chronic gastrointestinal conditions, attending a gastroenterology/hepatology VC. HCP undertaking VC were invited to complete staff questionnaire. Results were anonymous and collated using Excel version 2302.

Results

Five UK hospital trusts participated, with 35 HCP responses. Of the 100 YP completing the survey 66% were female and 34% male aged between 13 years and 25 years (median: 18 years). 13% were new appointments and 87% follow ups, 29% were by video, 69% by phone and 2% gave no response. 80% of HCP spoke to YP directly but not privately (69%). 87% of YP and 88% HCP found VC useful. 83% of YP want VC again, although 20% preferred face to face. 43% of HCP required improved phone/internet connection. 77% of YP required hospital appointments for tests following VC.

Conclusions

Overall respondents were satisfied with VC, finding them useful, convenient and time saving. Successful VC rely on appropriate patient selection and availability of reliable technology. Patient preference is key which may alter with time.
Vaccinating against cancer: getting to prime time
Authors: Chang Ryan , Gulley James L , Fong Lawrence
Published: June 2023

Immunotherapies, such as immune checkpoint inhibitors, cellular therapies, and T-cell engagers, have fundamentally changed our approach to treating cancer. However, successes with cancer vaccines have been more difficult to realize. While vaccines against specific viruses have been widely adopted to prevent the development of cancer, only two vaccines can improve survival in advanced disease: sipuleucel-T and talimogene laherparepvec. These represent the two approaches that have the most traction: vaccinating against cognate antigen and priming responses using tumors in situ. Here, we review the challenges and opportunities researchers face in developing therapeutic vaccines for cancer.
Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of gastrointestinal cancer
Authors: Kelly Ronan J , Bever Katherine , Chao Joseph , Ciombor Kristen K , Eng Cathy , Fakih Marwan , Goyal Lipika , Hubbard Joleen , Iyer Renuka , Kemberling Holly T , Krishnamurthi Smitha , Ku Geoffrey , Mordecai Mindy Mintz , Morris Van K , Paulson Andrew Scott , Peterson Valerie , Shah Manish A , Le Dung T
Published: June 2023

Gastrointestinal (GI) cancers, including esophageal, gastroesophageal junction, gastric, duodenal and distal small bowel, biliary tract, pancreatic, colon, rectal, and anal cancer, comprise a heterogeneous group of malignancies that impose a significant global burden. Immunotherapy has transformed the treatment landscape for several GI cancers, offering some patients durable responses and prolonged survival. Specifically, immune checkpoint inhibitors (ICIs) directed against programmed cell death protein 1 (PD-1), either as monotherapies or in combination regimens, have gained tissue site-specific regulatory approvals for the treatment of metastatic disease and in the resectable setting. Indications for ICIs in GI cancer, however, have differing biomarker and histology requirements depending on the anatomic site of origin. Furthermore, ICIs are associated with unique toxicity profiles compared with other systemic treatments that have long been the mainstay for GI cancer, such as chemotherapy. With the goal of improving patient care by providing guidance to the oncology community, the Society for Immunotherapy of Cancer (SITC) convened a panel of experts to develop this clinical practice guideline on immunotherapy for the treatment of GI cancer. Drawing from published data and clinical experience, the expert panel developed evidence- and consensus-based recommendations for healthcare professionals using ICIs to treat GI cancers, with topics including biomarker testing, therapy selection, and patient education and quality of life considerations, among others.