bluuebunny/crossref_metadata_2025 huggingface dataset:
Warm-Up in Triathlon: Do Triathletes Follow the Scientific Guidelines?
Authors: Quagliarotti Claudio , Villanova Simone , Marciano Alessio , López-Belmonte Óscar , Caporali Cristiano , Bottoni Alessandro , Lepers Romuald , Piacentini Maria Francesca
Published: October 2024

Purpose: Warming up before competition is universally recognized as an effective way to enhance performance. However, only a few articles have directly investigated different warm-up strategies adopted by triathletes and suggested by coaches. The Olympic-distance triathlon is an endurance competition characterized, at least for the elite, by a fast start with a strong correlation to the final position in the race. Thus, executing a proper warm-up protocol would be beneficial in optimizing performance. The present study aimed to provide an overview of the warm-up protocol adopted/suggested by national-caliber triathletes/coaches before an Olympic-distance triathlon race. Methods: Online surveys were created and shared between national- and international-caliber Italian, French, and Spanish triathletes and coaches. Information about the rationale, structure, and specific exercises adopted/suggested during personal warm-up protocols was collected. Thereafter, triathletes were grouped according to the discipline sequence reported. Results: Seventy-nine triathletes and nineteen coaches completed the survey. The cycle–run–swim was the most reported discipline sequence adopted, with a total time of 90.0 (25.0) minutes, against the 62.5 (25.0) minutes suggested by coaches. Conditioning exercises were performed by only 31.6% of triathletes 20 to 10 minutes before the race start. Conclusions: Triathletes who took part in this survey adopted very long protocols with the specific intention of including all disciplines. These results highlight the need to raise awareness in triathletes and coaches on the correct warm-up procedures and to stimulate researchers to design studies that directly investigate the effects of different warm-up protocols before competitions.
Striving for Global Consensus: A Systematic Review of Social Return on Investment Applied to Physical Activity and Sport
Authors: Nieto Inés , Mayo Xián , Davies Larissa , Reece Lindsey , Strafford Ben , Jimenez Alfonso
Published: October 2024

Background: Physical activity and sport (PAS) have been related to health and social benefits, but their monetary value remains unclear. This systematic review on the social return on investment of PAS aimed to find what are the social outcomes measured in previous PAS literature and how are these measured and valued. Methods: A systematic search was conducted on WoS, PubMed, and EconLit. Articles in English, measuring the social value of any type of PAS in monetary terms and utilizing a social return on investment framework, were included. Risk of bias was evaluated using the Drummond checklist. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Results: Fifty-five documents (2010–2022), from all continents except America, were included; only 8 were published in peer-reviewed journals, whereas 47 were reports. Most studies evaluated the benefits of specific programs, and 6 measured the engagement in PAS at the population level based on national or community surveys. The social outcomes identified were health (94.5%), crime (50.9%), education (83.6%), subjective well-being (89.1%), social capital (60%), and other (3.6%–23.6%). The valuation methods included willingness to pay, well-being valuation, the cost of an activity that could result in the same outcome, and cost databases associating outcomes with a monetary value. Conclusions: This study updates a previous review and widens the scope by answering the question of how social outcomes are measured and valued in previous PAS literature. Given the heterogeneity found in the application of the method, this review will inform a Delphi study to reach a Global Consensus Statement on the measurement of social value and PAS.
VGLL3 modulates chemosensitivity through promoting DNA double-strand break repair
Authors: Wu Wei , Fan Zhenzhen , Fu Hui , Ma Xiaolu , Wang Dongzhou , Liu Hongmei , Zhang Chuanchao , Zheng Hui , Yang Yeran , Wu Honglin , Miao Xiuxiu , An Ruiyuan , Gong Yifei , Tang Tie-Shan , Guo Caixia
Published: October 2024

Transcription cofactor vestigial-like 3 (VGLL3), as a master regulator of female-biased autoimmunity, also functions in tumor development, while the underlying mechanisms remain largely elusive. Here, we report that VGLL3 plays an important role in DNA damage response (DDR). VGLL3 can be recruited to damage sites in a PARylation-dependent manner. VGLL3 depletion impairs the accumulation of RNF8 and RAD51 at sites of DNA damage, leading to reduced homologous recombination efficiency and increased cellular sensitivity to chemotherapeutic drugs. Mechanistically, VGLL3 can prevent CtIP from KLHL15-mediated ubiquitination and degradation through competitive binding with KLHL15 and, meanwhile, stabilize MDC1 by limiting TRIP12-MDC1 but promoting USP7-MDC1 associations for optimal RNF8 signaling initiation. Consistently, VGLL3 depletion delays tumor development and sensitizes the xenografts to etoposide treatment. Overall, our results reveal an unexpected role of VGLL3 in DDR, which is distinct from its transcriptional cofactor function and not conserved among VGLL family members.
Bring me the head of
Arthropleura
Authors: Lamsdell James C.
Published: October 2024

After 170 years of searching, scientists finally know what the head of the largest known arthropod
Arthropleura
looked like, unlocking the key to its affinities.
Alicyclobacillus suci
produces more guaiacol in media and has duplicate copies of
vdcC
compared to closely related
Alicyclobacillus acidoterrestris
Authors: Roth Katerina , Rana Yadwinder Singh , Worobo Randy , Snyder Abigail B.
Published: October 2024

Some species of the genus
Alicyclobacillus
cause spoilage in juices and other beverages due to the production of guaiacol, a phenolic compound, and off-aroma. However, little is known about the genomic determinants of guaiacol production across the genus. In this study, we found that several of the genes significantly enriched in guaiacol-producing
Alicyclobacillus
spp. are associated with oxidative stress response, including
vdcC
, a phenolic acid decarboxylase putatively responsible for guaiacol synthesis. The food industry recognizes
Alicyclobacillus acidoterrestris
as the primary guaiacol-producing species found in beverages, though that species was recently split into two closely related yet genetically distinct species,
Alicyclobacillus suci
and
A. acidoterrestris
. We found that strains of
A. suci
(63.0 ± 14.2 ppm) produced significantly (
P
< 0.01) more guaiacol on average in media than did strains of
A. acidoterrestris
(25.2 ± 7.0 ppm). Additionally,
A. suci
and
Alicyclobacillus fastidiosus
genomes each had duplicate copies of
vdcC
, while only a single copy of
vdcC
was found in the genomes of
A. acidoterrestris, Alicyclobacillus acidiphilus,
and
Alicyclobacillus herbarius
. Although the food industry has not historically differentiated between
A. suci
and
A. acidoterrestris,
it may be increasingly important to target the species with greater spoilage potential. Therefore, we also demonstrated that sequencing a single locus, such as the full-length 16S region or
rpoB,
is sufficient to differentiate between
A. acidoterrestris
and
A. suci
.

IMPORTANCE

Microbial spoilage increases food waste. To address that challenge, it is critical to recognize and control those microbial groups with the greatest spoilage potential. Non-specific targeting of broad microbial groups (e.g., the genus of
Alicyclobacillus
) in which only some members cause food spoilage results in untenable, overly broad interventions. Much of the food industry does not differentiate between guaiacol-producing and non-guaiacol-producing
Alicyclobacillus
species. This is overly broad because
Alicyclobacillus
spp. which cannot produce guaiacol can be present in beverages without causing spoilage. Furthermore, no distinction is made between
Alicyclobacillus suci
and
Alicyclobacillus acidoterrestris
because
A. suci
is newly split from
A. acidoterrestris
and most of the food industry still considers them to be the same. However, these findings indicate that
A. suci
may have greater spoilage potential than
A. acidoterrestris
due to differences in their genomic determinants for guaiacol production.
Investigating oral microbiome dynamics in chronic kidney disease and post-transplantation in continuous culture
Authors: Campbell Paul M. , Willmott Thomas , Summers Angela , Knight Christopher G. , Humphreys Gavin J. , Konkel Joanne E. , Augustine Titus , McBain Andrew J.
Published: October 2024

The oral microbiome is influenced by environmental factors in chronic kidney disease and following kidney transplantation affecting microbial composition, which may have implications for health and recovery. A major driver of oral microbiome perturbation is the accumulation of urea in saliva. We have modelled increased salivary urea concentrations associated with CKD and subsequent reductions that may occur post-transplantation. Oral microbiota were established in constant-depth film fermenters by inoculation with saliva. Duplicate validation runs were maintained with artificial saliva with baseline urea concentrations (0.205 mg/mL) for 21 days. Triplicate treatment runs were then done with baseline urea for 10 days (healthy phase) before urea was increased for 10 days to reflect CKD concentrations (0.92 mg/mL) (CKD phase). This was followed by reversion to baseline urea concentrations (post-transplant phase). Biofilms in primary validation runs reached dynamic stability within 5 days according to viable counting. DNA sequence data indicated minimal taxonomic variation over time and between low and high urea treatments despite background noise indicating changes in bacteria belonging to the family Gemellaceae and the genera TG5 and
Leptotrichia
. Significant differences in alpha and beta diversity occurred between low and high urea states but not following reversion to a low urea environment. Increased abundance of the TG5 was detected in late model phases, despite apparent count stability, and independent of changes in urea concentrations.

IMPORTANCE

This study investigates dynamic changes in the oral microbiome associated with changes in salivary urea concentration, an important factor in chronic kidney disease (CKD). The
in vitro
system modeled increased urea concentrations and subsequent reductions post-transplantation. The study provides insight into the oral microbial shifts during different simulated clinical phases. Understanding these dynamics is crucial for advancing our comprehension of CKD-associated oral microbiome variations and their potential impact on patient well-being and recovery.
Alkali-carbonate melts in the cratonic mantle evidenced by a wehrlite xenolith from the Majuagaa kimberlite, West Greenland
Authors: Kiseeva Ekaterina S. , Kamenetsky Vadim S. , Chayka Ivan F. , Maas Roland , Nielsen Troels F.D.
Published: October 2024

Carbonate melts are critically important for the deep carbon cycle, mantle melting, redox reactions, and transport of highly incompatible elements. The presence of carbonate melts in the cratonic mantle has been inferred from experimental studies, metasomatic transformations, and melt/fluid inclusions in xenoliths, kimberlites, and diamonds. However, the exact composition of such melts is difficult to determine due to their ephemeral nature and highly reactive properties. Once formed, they migrate away from the source and react with silicate mantle minerals, especially orthopyroxene, causing mantle metasomatism. Wehrlite is one of the products of interaction between the carbonate melt and peridotitic mantle and hence is an excellent candidate for locating in situ carbonate melts. Here, we report petrological, geochemical, and melt inclusion data for a garnet wehrlite xenolith in the Majuagaa kimberlite dike, West Greenland. The xenolith, which last equilibrated with the mantle at 4.5 GPa and 1000 °C, contains abundant melt pools composed of dolomite, calcite, serpentine, spinel, apatite, and phlogopite. Although the original magmatic mineralogy was largely destroyed by low-temperature alteration, remnants of the crystallized carbonatitic melt are preserved as primary melt inclusions in the liquidus Ti-Mg-Fe spinel. These melt inclusions, composed of carbonates, alkali carbonates, periclase/brucite, and minor halides, K-sulfide, apatite, and phlogopite, are the first direct evidence for in situ alkali-carbonate melt in the deep cratonic mantle. Compositionally, they are very similar to primary Na-dolomite melt found in experiments and in fluid inclusions within diamonds.
Sediment supply variation control on Lower Eocene delta sequences (Tremp Basin, Spain)
Authors: Vaucher Romain , Musajo Claire , Spangenberg Jorge E. , Poyatos-Moré Miquel , Zeeden Christian , Puigdefàbregas Cai , Prieur Marine , Castelltort Sébastien , Adatte Thierry
Published: October 2024

Sediment supply variations are often overlooked when interpreting depositional sequences, with most studies instead emphasizing changes in accommodation space. Here, we investigated a temporally well-constrained shallow-marine succession in the Tremp Basin to test the control of sediment supply variations on the development of deltaic sequences during the early Eocene. We analyzed the paleoenvironmental record (sedimentary facies and δ13Corg values) of the Morillo Limestone and the Castigaleu Formation (52.2–50.6 Ma). The first progradation of the deltaic system is marked by the abrupt appearance of thick delta-front sandstones and associated with the first negative carbon isotopic excursions (CIEs) in the measured δ13Corg record. Subsequent phases of progradation align with subsequent negative CIEs. Conversely, positive CIEs correspond to finer-grained, more-distal prodelta deposits. A series of hyperthermal events occurred during the deposition, globally identified as negative CIEs on δ13Ccarb reference curves, which we tentatively correlate with our δ13Corg data. We therefore suggest that during deposition of this Lower Eocene shallow-marine succession, the primary trigger behind sequence generation was the high-frequency climate-induced variation in sediment supply, specifically the hyperthermal events, rather than changes in accommodation. This linkage underscores the complex interactions between climate dynamics and sedimentary responses that shape the stratigraphic architecture of shallow-marine settings.
Colour-Electric and Colour-Magnetic Confinement
Authors: Agasian N. O. , Khaidukov Z. V. , Lukashov M. S. , Simonov Yu. A.
Published: October 2024

The basic properties of the confinement mechanism in QCD—the temperature dependence of the spatial and temporal string tensions ($${{\sigma }_{{\text{s}}}}(T)$$ and $${{\sigma }_{{\text{E}}}}(T)$$)—are studied in the framework of the Field Correlator Method (FCM). It is shown that both functions are connected respectively to the spatial and temporal parts of the vacuum gluon energy $${{\epsilon }_{{\text{s}}}}$$ and $${{\epsilon }_{{\text{E}}}}$$ which define their equal values at $$T = 0$$. However at $$T > 0$$ the spatial part is growing with T while the temporal part is destroyed by the hadronic pressure at $$T = {{T}_{{\text{c}}}}$$ (the deconfinement). Both properties are derived within the same method and are in a good agreement with the corresponding lattice data.
Disparities in availability of new cancer drugs worldwide: 1990-2022
Authors: Li Meng , Ka DukHee , Chen Qiushi
Published: October 2024

Introduction

Despite progress in the development of new cancer drugs, concerns about equity of access remain. This study aimed to examine the availability and timeliness of availability of new cancer drugs around the globe over the past three decades and their associations with country characteristics.

Methods

From a pharmaceutical intelligence database we identified new cancer drugs launched between 1990 and 2022. We calculated the number of new drugs launched in each country and the delay in launches. Using a multivariable linear regression and a Cox regression model with shared frailty, we examined the associations of the country’s Gross National Income (GNI) per capita, cancer incidence, number of physicians per population, and Gini index with the number of new cancer drug launches and launch delay in a country, respectively.

Results

A total of 568 cancer drugs were launched for the first time globally between 1990 and 2022. Among these, 35% had been launched in only one country by 2022, 22% in 2–5 countries, 15% in 6–10 countries, and 28% in more than 10 countries. The number of new cancer drugs launched in a country in this period ranged from 0 to 345. The average delays from the first global launch to the second, third, fourth, and fifth launch were 18.0 months, 24.3 months, 32.5 months, and 39.4 months, respectively. Our multivariate models showed that higher GNI per capita and cancer incidence in a country were associated with more launches and shorter delays.

Conclusion

This research reveals significant disparities in the availability and timeliness of availability of new cancer drugs across countries. These disparities are likely to have contributed to the poor cancer outcomes observed in many countries.
Is cardiovascular risk profiling from UK Biobank retinal images using explicit deep learning estimates of traditional risk factors equivalent to actual risk measurements? A prospective cohort study design
Authors: Qian Yiming , Li Liangzhi , Nakashima Yuta , Nagahara Hajime , Nishida Kohji , Kawasaki Ryo
Published: October 2024

Objective

Despite extensive exploration of potential biomarkers of cardiovascular diseases (CVDs) derived from retinal images, it remains unclear how retinal images contribute to CVD risk profiling and how the results can inform lifestyle modifications. Therefore, we aimed to determine the performance of cardiovascular risk prediction model from retinal images via explicitly estimating 10 traditional CVD risk factors and compared with the model based on actual risk measurements.

Design

A prospective cohort study design.

Setting

The UK Biobank (UKBB), a prospective cohort study, following the health conditions including CVD outcomes of adults recruited between 2006 and 2010.

Participants

A subset of data from the UKBB which contains 52 297 entries with retinal images and 5-year cumulative incidence of major adverse cardiovascular events (MACE) was used. Our dataset is split into 3:1:1 as training set (n=31 403), validation set (n=10 420) and testing set (n=10 474). We developed a deep learning (DL) model to predict 5-year MACE using a two-stage DL neural network.

Primary and secondary outcome measures

We computed accuracy, area under the receiver operating characteristic curve (AUC) and compared variations in the risk prediction models combining CVD risk factors and retinal images.

Results

The first-stage DL model demonstrated that the 10 CVD risk factors can be estimated from a given retinal image with an accuracy ranging between 65.2% and 89.8% (overall AUC of 0.738 with 95% CI: 0.710 to 0.766). In MACE prediction, our model outperformed the traditional score-based models, with 8.2% higher AUC than Systematic COronary Risk Evaluation (SCORE), 3.5% for SCORE 2 and 7.1% for the Framingham Risk Score (with p value<0.05 for all three comparisons).

Conclusions

Our algorithm estimates the 5-year risk of MACE based on retinal images, while explicitly presenting which risk factors should be checked and intervened. This two-stage approach provides human interpretable information between stages, which helps clinicians gain insights into the screening process copiloting with the DL model.
Influence of a structured, 1-year-long dietary intervention regarding body composition and cardiovascular risk (ARCTIC) in coeliac disease: a protocol of a multicentre randomised controlled trial
Authors: Vereczkei Zsófia , Szakács Zsolt , Peresztegi Míra Zsófia , Lemes Klára , Hagymási Krisztina , Dakó Sarolta , Dakó Eszter , Lada Szilvia , Faluhelyi Nándor , Szekeres Gábor , Pásztor Gyula , Farkas Nelli , Pár Gabriella , Mezősi Emese , Bajor Judit
Published: October 2024

Introduction

Coeliac disease (CD) affects 1% of the population worldwide. The only available evidence-based treatment is a strict gluten-free diet (GFD), which can readily lead to weight gain and unfavourable metabolic changes (eg, dyslipidaemia, fatty liver disease and insulin resistance) if followed without adequate dietary control. That can lead to increased cardiovascular risk (CV). We planned a randomised controlled trial to test the effect of a group-based, structured, 1-year, advanced dietary education, per the proposal of a Mediterranean diet vs standard of care, regarding the most relevant CV risk factors (eg, metabolic parameters and body composition) in CD patients.

Methods and analysis

Randomisation will occur after the baseline dietary education and interview in a 1:1 allocation ratio. Outcomes include anthropometric parameters (body composition analysis including weight, Body Mass Index, fat mass, per cent body fat, skeletal muscle mass, visceral fat area and total body water) and CV risk-related metabolic parameters (eg, lipid profile, homocysteine, fasting glucose, haemoglobin A1c, Homeostatic Model Assessment Index, metabolic hormones, waist circumference, blood pressure, liver function tests, liver steatosis rate and diet composition). In this study, we aim to draw attention to a new aspect regarding managing CD: dietary education can lead to a better quality of the GFD, thereby reducing the risk of potential metabolic and CV complications.

Ethics and dissemination

The study was approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (27521-5/2022/EÜIG). Findings will be disseminated at research conferences and in peer-reviewed journals.

Trial registration number

NCT05530070
Physician perspectives on statin continuation and discontinuation in older adults in primary cardiovascular prevention: a qualitative methods study
Authors: Marti Andreas , Zbinden Samuel , Brunner Laureline , Rodondi Nicolas , Schneider Claudio , Aubert Carole Elodie
Published: October 2024

Objectives

In the context of limited evidence on statin use in primary cardiovascular prevention in older adults, we assessed physician perspectives on decision-making about statin continuation or discontinuation in this population.

Design

Qualitative descriptive approach including four focus groups. Inductive and deductive thematic analysis.

Setting and participants

18 physicians including two neurologists, three cardiologists, seven hospital internists and six primary care providers (PCPs) recruited at a hospital and primary care practices in the area of Bern in Switzerland.

Results

Concerning knowledge about statins in older adults, physicians reported defining if a patient is treated for primary or secondary prevention as challenging and that lack of evidence makes the decision to continue or discontinue the statin difficult. In terms of beliefs, fear of a possible rebound effect after statin discontinuation was reported. Regarding decision-making, physicians mentioned that statin discontinuation or continuation should be a shared decision between the patient and the physician. Concerning the professional role, environmental context and resources, the PCP office was identified as the ideal setting to discuss discontinuation, as all necessary information is available and PCPs have a longer relationship with the patients, thus facilitating a shared decision. Discontinuation of a chronic medication was perceived as difficult in general. Furthermore, PCPs noticed a possible negative impact on patient–physician relationship as some patients felt not being worth it, given up or undertreated if the statin was discontinued.

Conclusions

This study highlights the challenges of statin continuation and discontinuation in older patients and the crucial role of PCPs in situations with unclear evidence for a medication, where shared decision-making between physicians and patients is important. More evidence forming the background for a decision aid would be helpful.
Reasons for encounter in video contacts at a Danish out-of-hours primary care service: a questionnaire study
Authors: Nebsbjerg Mette Amalie , Bomholt Katrine Bjørnshave , Vestergaard Claus Høstrup , Christensen Morten Bondo , Huibers Linda
Published: October 2024

Objective

To investigate reasons for encounter in telephone triage contacts to an out-of-hours primary care service for which general practitioners (GPs) use video consultations (video contact), overall and stratified for patient age and time of day.

Design

A cross-sectional questionnaire study among GPs doing telephone triage in an out-of-hours primary care service. The questionnaire was integrated into the electronic patient registration system, popping up after every third video contact. This setup automatically linked patient register data, including age and sex, with the questionnaire data.

Setting

The study was conducted from 5 September 2022 to 21 December 2022 at the out-of-hours primary care service in the Central Denmark Region.

Participants

649 volunteer GPs who answered 2452 questionnaires.

Main outcome measures

Reasons for encounter in video contacts registered with codes from International Classification of Primary Care (ICPC) coding system, V.2 (ICPC-2).

Results

GPs doing telephone triage in out-of-hours primary care used video contacts for a broad range of ICPC-2 codes within few ICPC-2 chapters. 83% of all reasons for encounter were due to symptoms in chapters S ‘Skin’ (34.5%), R ‘Respiratory’ (21.8%), A ‘General and unspecified’ (14.7%) and L ‘Musculoskeletal’ (12.0%) in the ICPC-2 classification system. Video contacts concerning skin and musculoskeletal symptoms were more frequent among older children and adults compared with young children. Respiratory symptoms and general and unspecified symptoms dominated by fever were more frequent among video contacts for young children compared with older children and adults.

Conclusion

Our study suggests a focused use of video contacts in an out-of-hours primary care setting; the majority of registered ICPC-2 codes were within few ICPC-2 chapters.
Assessing the safety and pharmacokinetics of casirivimab and imdevimab (CAS+IMD) in a cohort of pregnant outpatients with COVID-19: results from an adaptive, multicentre, randomised, double-blind, phase 1/2/3 study
Authors: Norton Thomas D , Thakur Mazhar , Ganguly Samit , Ali Shazia , Chao Jesse , Waldron Alpana , Xiao Jing , Patel Yogesh , Turner Kenneth C , Davis John D , Irvin Susan C , Pan Cynthia , Atmodjo-Watkins Dominique , Hooper Andrea T , Hamilton Jennifer D , Subramaniam Danise , Bocchini Joseph A , Kowal Bari , DiCioccio A. Thomas , Bhore Rafia , Geba Gregory P , Cox Edward , Braunstein Ned , Dakin Paula , Herman Gary A
Published: October 2024

Objective

Pregnant women with COVID-19 are at elevated risk for severe outcomes, but clinical data on management of these patients are limited. Monoclonal antibodies, such as casirivimab plus imdevimab (CAS+IMD), have proven effective in treating non-pregnant adults with COVID-19, prompting further evaluation in pregnant women.

Methods

A phase 3 portion of an adaptive, multicentre, randomised, double-blind, placebo-controlled trial evaluated the safety, clinical outcomes, pharmacokinetics and immunogenicity of CAS+IMD (1200 mg or 2400 mg) in the treatment of pregnant outpatients with COVID-19 (NCT04425629). Participants were enrolled between December 2020 and November 2021, prior to the emergence of Omicron-lineage variants against which CAS+IMD is not active. Safety was evaluated in randomised participants who received study drug (n=80); clinical outcomes were evaluated in all randomised participants (n=82). Only two pregnant participants received placebo, limiting conclusions regarding treatment effect. Infants born to pregnant participants were followed for developmental outcomes ≤1 year of age.

Results

In pregnant participants, CAS+IMD was well tolerated, with no grade ≥2 hypersensitivity or infusion-related reactions reported. There were no participant deaths, and only one COVID-19–related medically attended visit. Although two pregnancies (3%) reported issues in the fetus/neonate, they were confounded by maternal history or considered to be due to an alternate aetiology. No adverse developmental outcomes in infants ≤1 year of age were considered related to in utero exposure to the study drug. CAS+IMD 1200 mg and 2400 mg rapidly and similarly reduced viral loads, with a dose-proportional increase in concentrations of CAS+IMD in serum. Pharmacokinetics were consistent with that reported in the general population. Immunogenicity incidence was low.

Conclusion

CAS+IMD treatment of pregnant outpatients with COVID-19 showed similar safety, clinical outcomes and pharmacokinetic profiles to that observed in non-pregnant adults. There was no evidence of an impact on developmental outcomes in infants ≤1 year of age.

Trial registration number

NCT04425629.
Hybrid versus catheter ablation for Hypertrophic CardioMyopathy with Atrial Fibrillation (HCM-AF): study protocol for a randomised controlled trial
Authors: Tang Yajie , Li Le , Chen Sipeng , Xue Yumei , Guo Huiming , Song Lei , Tang Min , Yao Yan , Zheng Zhe
Published: October 2024

Introduction

Atrial fibrillation (AF) is an independent predictor of adverse outcomes in patients with hypertrophic cardiomyopathy (HCM). Although catheter ablation is highly recommended for general AF populations, it is less effective in maintaining sinus rhythm in patients with HCM associated with AF. Hybrid ablation, combining a cosmetic approach with a lower rate of AF relapse, lacks comparative studies to verify its efficacy against CA in HCM. This study aims to assess the rhythm control effectiveness of hybrid versus CA in non-obstructive HCM (non-oHCM) patients with AF.

Methods/analysis

This prospective, multicentre, randomised trial involves a blinded assessment of outcomes in non-oHCM patients with non-paroxysmal AF. Sixty-six candidates from three centres will be randomised 1:1 to either hybrid or CA, including isthmus addressed lesion sets. Participants will be stratified by left atrial (LA) size (LA diameter ≤50 mm or >50 mm). Follow-ups at the 3rd, 6th and 12th months will evaluate the primary endpoint of freedom from documented atrial tachycardia lasting over 30 s within 12 months post-procedure without antiarrhythmic drugs, along with secondary endpoints of all-cause mortality, cardiovascular-related mortality, cerebral stroke, peripheral vascular embolism, heart failure-related rehospitalisation, all-cause rehospitalisation and quality of life assessments.

Ethics and disseminationapproval

The central ethics committee at Fuwai Hospital has approved the Hypertrophic CardioMyopathy with Atrial Fibrillation trial (approval number: 2022-1736). Results will be disseminated through publications in peer-reviewed journals and presentations at conferences.

Trial registration number

NCT05610215.
Investigation of factors associated with delayed initiation of breastfeeding in Papua New Guinea: a cross-sectional study
Authors: Maviso McKenzie , Pulsan Francis , Vallely Lisa M
Published: October 2024

Background

Breastfeeding within the first hour of birth is critical for newborn survival. However, in Papua New Guinea (PNG), about 40% of newborns are not breastfed within the first hour of birth. This study aimed to determine the prevalence and factors associated with delayed initiation of breastfeeding in PNG.

Methods

This study used secondary data from the 2016–2018 PNG Demographic and Health Survey, a nationally representative cross-sectional study. A total weighted sample of 4748 women aged 15–49 were included. Complex samples analysis was performed to determine the direction of association between the independent variables and delayed initiation of breastfeeding.

Results

About a quarter (24.6%) of women delayed initiation of breastfeeding. Women with an unplanned pregnancy (adjusted OR (AOR) 1.32; 95% CI 1.03 to 1.68), those who had a caesarean section (AOR 3.16; 95% CI 1.39 to 7.17), those who did not initiate newborn skin-to-skin contact immediately after birth (AOR 1.83; 95% CI 1.41 to 2.38) and those who watched television (AOR 1.39; 95% CI 1.11 to 1.75), and were from the Momase region (AOR 1.31; 95% CI 1.00 to 1.93) had higher odds of delayed breastfeeding initiation. Conversely, the odds of delayed initiation of breastfeeding was lower among women who read a newspaper or magazine (AOR 0.76; 95% CI 0.61 to 0.95), were from the Southern (AOR 0.81; 95% CI 0.56 to 1.15) and Highlands (AOR 0.86; 95% CI 0.58 to 1.29) regions, and gave birth at home or in the village (AOR 0.69; 95% CI 0.49 to 0.96).

Conclusion

One in four women in this study delayed initiation of breastfeeding until after 1 hour after birth. Interventions to promote optimal breastfeeding require a multi-sectoral approach, as well as bolstering health workers’ capacity to encourage and support early initiation of breastfeeding during the antenatal and early postnatal periods.
Survey of the endoscopy workforce’s perception of sustainability
Authors: Poo Stephanie Xiu Wern , Kader Rawen , Shakweh Eathar , Kronsten Victoria T , Baddeley Robin ,   Gastroenterology London Investigative Network for Trainees Study Group (GLINT), Siddhi Sandeep , Hayee Bu'Hussain
Published: October 2024

Objective

The National Health Service is a significant contributor to greenhouse gas emissions, with endoscopy ranking as the third highest contributor of waste in healthcare. We aimed to ascertain the endoscopy workforce attitudes towards sustainable practices, barriers to change and potential solutions towards achieving a more sustainable endoscopy practice.

Methods

A prospective cross-sectional online survey was distributed to endoscopy staff through the Joint Advisory Group on Gastrointestinal Endoscopy, the British Society of Gastroenterology (BSG), the Green Endoscopy Centre for Sustainable Healthcare Network and trainee research networks. The survey used a 5-point Likert scale to include:

(1) perceived importance of sustainability in endoscopy, (2) factors contributing to waste generation in endoscopy, (3) barriers to sustainability in endoscopy and (4) strategies for sustainable change

Results

Of 202 participants, 83% were highly concerned about climate change and 71% recognised the significant carbon footprint generation within endoscopy. Lack of environmental consideration (77%), personal protective equipment and decontamination (76%), and packaging of single-use items (74%) were considered the most significant factors impacting waste generation in endoscopy. Participants ranked poor access to recyclable equipment (55%), poor awareness (52%) and poor attitudes (47%) as the main barriers to sustainable change. Concerningly, only a third would inform others if they noticed the wasting of resources.

An overwhelming majority agreed with the BSG prioritising sustainability highly (84%), with 88.6% supporting policy and guideline development on sustainable endoscopy practice.

Conclusion

We identified a strong consensus supporting the BSG’s prioritisation of activities relating to sustainability and climate change, with endoscopy being a key area of focus for improvement.
Neuroimaging studies in major depressive disorder with suicidal ideation or behaviour among Chinese patients: implications for neural mechanisms and imaging signatures
Authors: Su Yun-Ai , Ye Chong , Xin Qin , Si Tianmei
Published: October 2024

Major depressive disorder (MDD) with suicidal ideation or behaviour (MDSI) is associated with an increased risk of future suicide. The timely identification of suicide risk in patients with MDD and the subsequent implementation of interventions are crucially important to reduce their suffering and save lives. However, the early diagnosis of MDSI remains challenging across the world, as no objective diagnostic method is currently available. In China, the challenge is greater due to the social stigma associated with mental health problems, leading many patients to avoid reporting their suicidal ideation. Additionally, the neural mechanisms underlying MDSI are still unclear, which may hamper the development of effective interventions. We thus conducted this narrative review to summarise the existing neuroimaging studies of MDSI in Chinese patients, including those involving structural magnetic resonance imaging (MRI), functional MRI, neuronal electrophysiological source imaging of the brain dynamics with electroencephalography and magnetoencephalography. By synthesising the current research efforts in neuroimaging studies of Chinese patients with MDSI, we identified potential objective neuroimaging biomarkers, which may aid in the early identification of patients with MDSI who are at high suicide-related risk. Our findings also offer insights into the complex neural mechanisms underlying MDSI and suggest promising therapeutic targets. Furthermore, we propose future directions to discover novel imaging signatures, improve patient care, as well as help psychiatrists and clinical investigators plan their future research.
Proactive assessment of patient reported outcomes in ovarian cancer studies: a systematic review and call for action in future studies
Authors: Madariaga Ainhoa , Sánchez-Bayona Rodrigo , Kasherman Lawrence , Estrada-Lorenzo Jose Manuel , Manso Luis , Tolosa Pablo , Alva Manuel , Lema Laura , González-Deza Cristina , Ciruelos Eva , Valcarcel David , Lheureux Stephanie , Oza Amit M
Published: October 2024

Objective

This systematic review aims to evaluate the proactive or real-time assessment of patient reported outcomes in studies involving patients with ovarian cancer undergoing systemic therapy.

Methods

PubMed, Embase, and Cochrane databases were searched (from database inception until February 2022), and prospective ovarian cancer studies (experimental or observational) that incorporated patient reported outcomes, including quality of life, were included. The primary objective was to assess the ratio of studies incorporating real-time use of patient reported outcomes among those studies performing patient reported outcomes. A secondary objective was to describe the patient reported outcome reporting. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 checklist was followed. Descriptive statistics were used.

Results

3071 articles were screened, with 117 included in the final analysis. Studies were published between 1990 and 2022, and consisted of 35 735 patients (median 140 patients per study; interquartile range 58–415). Median time from patient enrollment initiation to study publication was 7 years (range 1–15). Most studies were experimental/clinical trials (n=93, 79%) followed by observational (n=23, 20%). Therapeutic strategies were assessed in 98% (91/93) of experimental studies, most frequently chemotherapy (n=53, 58%), followed by antiangiogenics or poly-ADP ribose polymerase (PARP) inhibitors (n=8, 9%, each). Patient reported outcomes were the primary endpoint in 7.5% (7/93) and 83% (19/23) of experimental and observational studies, respectively. The ratio of real-time patient reported outcomes assessment/evaluation was 0.9% (1/117).

Conclusions

Completion of patient reported outcome questionnaires involves time and effort for patients with ovarian cancer. Responses to these questionnaires were only assessed in real time in <1% of analyzed studies. Efforts should be made to incorporate proactive assessment of patient reported outcomes to optimize patient care and safety.
Novel H-2Db-restricted CD8 epitope derived from mouse MAGE-type antigen P1A mediates antitumor immunity in C57BL/6 mice
Authors: McAuliffe James , Panetti Silvia , Steffke Emily , Wicki Amanda , Pereira-Almeida Vinnycius , Noblecourt Laurine , Hu Yushu , Guo Shi Yu William , Lesenfants Julie , Ramirez-Valdez Ramiro Andrei , Chandrasekar Vineethkrishna , Ahmad Maryam , Stroobant Vincent , Vigneron Nathalie , Van den Eynde Benoit J , Leung Carol Sze Ki
Published: October 2024

Background

Melanoma antigen gene (MAGE)-type antigens are promising targets for cancer immunotherapy as they are expressed in cancer cells but not in normal tissues, except for male germline cells. The mouse P1A antigen shares this MAGE-type expression pattern and has been used as a target antigen in preclinical tumor models aiming to induce antitumor CD8+T-cell responses. However, so far only one MHC I-restricted P1A epitope has been identified. It is presented by H-2Ldin mice of the H-2dgenetic background such as DBA/2 and BALB/c. Given the availability of multiple genetically altered strains of mice in the C57BL/6 background, it would be useful to define P1A T-cell epitopes presented by the H-2bhaplotype, to facilitate more refined mechanistic studies.

Methods

We employed a heterologous prime-boost vaccination strategy based on a chimpanzee adenovirus (ChAdOx1) and a modified vaccinia Ankara (MVA) encoding P1A, to induce P1A-specific T-cell responses in C57BL/6 mice. Vaccine-induced responses were measured by intracellular cytokine staining and multiparameter flow cytometry. We mapped the immunogenic CD8 epitope and cloned the cognate T-cell receptor (TCR), which we used for adoptive cell therapy.

Results

ChAdOx1/MVA-P1A vaccination induces a strong P1A-specific CD8+T-cell response in C57BL/6 mice. This response is directed against a single 9-amino acid peptide with sequence FAVVTTSFL, corresponding to P1A amino acids 43–51. It is presented by H-2Db. P1A vaccination, especially with ChAdOx1 administered intramuscularly and MVA delivered intravenously, protected mice against P1A-expressing EL4 (EL4.P1A) tumor cell challenge. We identified and cloned four TCRs that are specific for the H-2Db-restricted P1A43-51peptide. T cells transduced with these TCRs recognized EL4.P1A but not MC38.P1A and B16F10.P1A tumor cells, likely due to differences in the proteasome subtypes present in these cells. Adoptive transfer of these T cells in mice bearing EL4.P1A tumors reduced tumor growth and increased survival.

Conclusions

We identified the first CD8+T-cell epitope of the MAGE-type P1A tumor antigen presented in the H-2bbackground. This opens new perspectives for mechanistic studies dissecting MAGE-type specific antitumor immunity, making use of the wealth of genetically altered mouse strains available in the C57BL/6 background. This should facilitate the advancement of specific cancer immunotherapies.
Neurointerventional surveys between 2000 and 2023: a systematic review
Authors: Bosshart Salome Lou , Stebner Alexander , Weyland Charlotte Sabine , Radu Răzvan Alexandru , Ospel Johanna Maria
Published: October 2024

Background

Surveys are increasingly used in neurointervention to gauge physicians’ and patients’ attitudes, practice patterns, and ‘real-world’ treatment strategies, particularly in conditions for which few, or no evidence-based, recommendations exist. While survey-based studies can provide valuable insights into real-world problems and management strategies, there is an inherent risk of bias.

Objective

To assess key themes, sample characteristics, response metrics, and report frequencies of quality indicators of neurointerventional surveys.

Methods

A systematic review compliant with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was performed. The PubMed database was searched for neurointerventional surveys published between 2000 and 2023. Survey topics, design, respondent characteristics, and survey quality criteria suggested by the Consensus-Based Checklist for Reporting of Survey Studies (CROSS) were assessed and described using descriptive statistics. Response rates and numbers of participants were further assessed for their dependence on sample characteristics and survey methodologies.

Results

A total of 122 surveys were included in this analysis. The number of surveys published each year increased steeply between 2000 (n=1) and 2023 (n=14). The most common survey topics were stroke (51/122, 41.8%) and aneurysm treatment (49/122, 40.2%). The median response rate was 58.5% (IQR=30.4–86.3), with a median number of respondents of 79 (IQR=50–201). Sixty-eight of 122 (55.7%) surveys published the questionnaire used for data collection. Only a subset of studies reported response rates (n=89, 73%), data collection time period (n=91, 74.6%), and strategies to prevent duplicate responses (n=57, 46.7%).

Conclusion

Surveys are increasingly used by neurointerventional researchers, particularly to assess real-world practice patterns in endovascular stroke and aneurysm treatment. Adapting best-practice guidelines like the CROSS checklist might improve homogeneity and quality in neurointerventional survey research.
HIV epidemic among key populations in Nigeria: results of the integrated biological and behavioural surveillance survey (IBBSS), 2020–2021
Authors: Emmanuel Faran , Ejeckam Chukwuebuka Chukwukadibia , Green Kalada , Adesina Adediran Adesola , Aliyu Gambo , Ashefor Gregory , Aguolu Rose , Isac Shajy , Blanchard James
Published: October 2024

Introduction

Nigeria has the fastest-growing HIV epidemic in West and Central Africa and key populations (KPs) bear a higher burden of HIV. This integrated biological and behavioural surveillance survey was conducted among female sex workers (FSW), men who have sex with men (MSM), people who inject drugs (PWID) and transgender (TG) populations to understand the changing dynamics of HIV to improve HIV prevention efforts in Nigeria.

Methods

Using a cross-sectional design, data were collected between October and November 2020 in 12 states, from randomly selected KP members using multistage probability sampling. Behavioural data were collected using a structured questionnaire followed by three rapid HIV tests. The study was approved by ethical review boards in Nigeria and Canada and all ethical considerations including maintaining the privacy and confidentiality of all study subjects were followed.

Results

A total number of 17 975 KP members were interviewed, with a response rate of over 98.0%. A weighted HIV prevalence of 28.8% (95% CI 27.4% to 30.2%), 25.0% (95% CI 23.7% to 26.3%), 15.5% (95% CI 14.3% to 16.4%) and 10.9% (95% CI 9.9% to 11.8%) was found among TGs, MSMs, FSWs and PWIDs respectively. A high number of sex partners and consistent condom use were low for all types of KPs, especially with regular partners. Both MSM and TGs reported high rates of unprotected receptive anal intercourse ranging between 71.2% and 85.0%. Nearly 60.0% of PWID shared their used syringe with another PWID. Overall, 90.2% FSWs, 77.2% MSM, 81.9% TGs and 84.3% PWID were ever tested for HIV.

Conclusion

This study highlights the progressing trends of HIV prevalence among all KPs in Nigeria. A focused prevention approach is needed to control the emerging epidemic among KPs who constitute the epicentre of the HIV epidemic in Nigeria.