bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can a nation-wide e-cohort of ADHD and ASD in childhood be established using Welsh routinely available datasets?
Authors: Langley Kate , Del Pozo-Banos Marcos , Daalsgard Søren , Paranjothy Shantini , Riglin Lucy , John Ann , Thapar Anita 
Published: August 2023

ObjectivesWe investigated the feasibility and validity of establishing a nationwide e-cohort of individuals with a diagnosis of attention deficit hyperactivity disorder (ADHD) and/or autism spectrum disorder (ASD) for future longitudinal research.DesignIndividuals with a childhood diagnosis of ADHD/ASD as recorded on routinely available healthcare datasets were compared with matched controls and a sample of directly assessed individuals with ADHD.SettingThis study used data from the Welsh Secure Anonymised Information Linkage Databank in Wales, UK. Routinely collected data from primary care, emergency department and hospital admissions were linked at person level.ParticipantsAll individuals in Wales, UK born between 1 January 1991 and 31 December 2000. Individuals with a recorded diagnosis of ADHD and/or ASD by age 18 years were identified using International Classification of Diseases, 10th Revision and National Health Service (NHS) READ codes and matched to 3 controls each and 154 individuals with ADHD recruited from an established research study.Outcome measuresRecorded service use for anxiety and depression, alcohol and drug use and self-harm including emergency department use in young adulthood (age 16–25 years).Results7726 individuals had a recorded diagnosis of ADHD (80% male) and 5001 of ASD (79% male); 1.4% and 0.9% of the population, respectively. Cox’s regression analyses showed ADHD was associated with increased risks of anxiety/depression (HR: 2.36, 95% CI: 2.20 to 2.53), self-harm (HR: 5.70, 95% CI: 5.07 to 6.40), alcohol (HR: 3.95, 95% CI: 3.42 to 4.56), drug use (HR: 5.88, 95% CI: 5.08 to 6.80) and emergency department service use (HR: 1.36, 95% CI: 1.31 to 1.41). Those with ASD were at increased risk of anxiety/depression (HR: 2.11, 95% CI: 1.91 to 2.34), self-harm (HR: 2.93, 95% CI: 2.45 to 3.50) and drug use (HR: 2.21, 95% CI: 1.66 to 2.95) but not alcohol use. The ADHD e-cohort were similar to the directly assessed cohort.ConclusionsOur identification strategy demonstrated the feasibility of establishing a large e-cohort of those with ADHD/ASD with expected patterns of poorer early adult outcomes, demonstrating a valid method of identifying large samples for future longitudinal studies without selective attrition.
Carbon footprint of industry-sponsored late-stage clinical trials
Authors: Mackillop Neil , Shah Jayesh , Collins Michael , Costelloe Thomas , Öhman Daniel 
Published: August 2023

ObjectivesTo quantify the carbon footprint from a sample of pharma industry sponsored phase III trials. To develop an approach that can readily be applied to future trials by AstraZeneca and other trial sponsors.DesignLife cycle assessment including all the sources of carbon emissions associated with a completed, an ongoing and a planned clinical trial. The methodology followed the guidance on appraising the sustainability of Care Pathways, developed by the UK National Health Service in collaboration with parties across the healthcare system.SettingThree multicentre late phase trials. One completed heart failure trial, one ongoing oncology trial and one asthma trial with the addition of devices to be representative of current practice.ParticipantsThe three trials had a total number of 7412 participants.Main outcome measuresTotal carbon emissions from each trial, the drivers of those emissions and the emissions per patient.ResultsThe total carbon footprint for the cardiovascular trial was calculated as 2498 tonnes carbon dioxide equivalents (CO2e), the first 3 years of the oncology trial resulted in 1632 tonnes CO2e and the respiratory trial 1437 tonnes CO2e.ConclusionsWe have shown that it is feasible to perform a retrospective life cycle assessment to appraise the carbon footprint of large clinical trials and confirmed that phase III trials result in significant emissions. Having identified all the drivers of emissions and their magnitude, we are well placed to develop a plan for achieving net-zero carbon clinical trials. Now it is possible to expand the use of life cycle assessment to planned studies so that scientific aims can be achieved with a minimum of carbon emissions. We encourage other trialists to apply the same methodology as a necessary first step in reducing the carbon footprint of clinical trials.
Effect of aqueous olanexidine versus alcohol-based chlorhexidine for surgical skin antisepsis on incidence of surgical site infections in gastrointestinal surgery: multicentre randomised controlled clinical trial (OEDO trial) protocol
Authors: Takeuchi Masashi , Obara Hideaki , Furube Tasuku , Kawakubo Hirofumi , Kitago Minoru , Okabayashi Koji , Aoyama Junya , Amemiya Ryusuke , Fujisaki Hiroto , Sano Junichi , Goto Rei , Sato Yasunori , Kitagawa Yuko 
Published: August 2023

IntroductionSurgical site infections (SSIs) are among the most common nosocomial infections in surgery patients. Two types of preparations, povidone-iodine and chlorhexidine-alcohol, are commonly used in preoperative antiseptic procedures worldwide. However, there are inconsistencies among international guideline recommendations concerning skin antiseptics. This trial aimed to evaluate the superiority of olanexidine, which reduced SSI rates more than povidone-iodine in our previous randomised trial, over chlorhexidine-alcohol in clean-contaminated surgery.Methods and analysisThis multicentre randomised controlled clinical trial will compare two antiseptics (1.5% olanexidine and 1.0% chlorhexidine-alcohol) to prevent SSI in clean-contaminated gastrointestinal surgeries with surgical wounds. On providing consent, patients aged <18 years will be included. The primary outcome will be the postoperative 30-day overall SSI rate, while the secondary outcomes will be the postoperative 30-day superficial incisional SSI rate, deep incisional SSI rate, organ/space SSI rate, positive bacterial wound culture rate, cultured bacterial strains, rates of intervention-related toxicity and allergic events (eg, erythema, pruritus, dermatitis and other symptoms of allergy around the region disinfected by the antiseptic during surgery), rate of reoperations due to SSI, medical economic effect indicators (based on health insurance claims) and hospital duration. The Mantel-Haenszel method will be used to estimate the adjusted risk ratio and its 95% CI for the primary analysis, which will compare the treatment effects.Ethics and disseminationThe protocol was approved by the Institutional Review Board of Keio University School of Medicine and subsequently by the board of each participating site. Participant recruitment began in January 2023. The final results will be published in medical journals after international peer review.Trial registration numberUMIN000049712.
TP53gain-of-function mutation modulates the immunosuppressive microenvironment in non-HPV-associated oral squamous cell carcinoma
Authors: Shi Yewen , Ren Xiaoyong , Cao Shaolong , Chen Xi , Yuan Bo , Brasil da Costa Fabio Henrique , Rodriguez Rosario Alanis E , Corona Arnoldo , Michikawa Chieko , Veeramachaneni Ratna , Osman Abdullah A , Xie Tongxin , Wang Wenyi , Sikora Andrew G , Myers Jeffrey N , Rangel Roberto 
Published: August 2023

BackgroundTP53, the most mutated gene in solid cancers, has a profound impact on most hallmarks of cancer. SomaticTP53mutations occur in high frequencies in head and neck cancers, including oral squamous cell carcinoma (OSCC). Our study aims to understand the role ofTP53gain-of-function mutation in modulating the tumor immune microenvironment (TIME) in OSCC.MethodsShort hairpin RNA knockdown of mutantp53R172Hin syngeneic oral tumors demonstrated changes in tumor growth between immunocompetent and immunodeficient mice. HTG EdgeSeq targeted messenger RNA sequencing was used to analyze cytokine and immune cell markers in tumors with inactivated mutantp53R172H. Flow cytometry and multiplex immunofluorescence (mIF) confirmed the role of mutantp53R172Hin the TIME. The gene expression of patients with OSCC was analyzed by CIBERSORT and mIF was used to validate the immune landscape at the protein level.ResultsMutantp53R172Hcontributes to a cytokine transcriptome network that inhibits the infiltration of cytotoxic CD8+T cells and promotes intratumoral recruitment of regulatory T cells and M2 macrophages. Moreover,p53R172Halso regulates the spatial distribution of immunocyte populations, and their distribution between central and peripheral intratumoral locations. Interestingly,p53R172H-mutated tumors are infiltrated with CD8+and CD4+T cells expressing programmed cell death protein 1, and these tumors responded to immune checkpoint inhibitor and stimulator of interferon gene 1 agonist therapy. CIBERSORT analysis of human OSCC samples revealed associations between immune cell populations and theTP53R175Hmutation, which paralleled the findings from our syngeneic mouse tumor model.ConclusionsThese findings demonstrate that syngeneic tumors bearing theTP53R172Hgain-of-function mutation modulate the TIME to evade tumor immunity, leading to tumor progression and decreased survival.
Intratumoral T-cell and B-cell receptor architecture associates with distinct immune tumor microenvironment features and clinical outcomes of anti-PD-1/L1 immunotherapy
Authors: Schina Aimilia , Sztupinszki Zsofia , Marie Svane Inge , Szallasi Zoltan , Jönsson Göran , Donia Marco 
Published: August 2023

BackgroundEffective cooperation between B-cells and T-cells within the tumor microenvironment may lead to the regression of established tumors. B-cells and T-cells can recognize tumor antigens with exquisite specificity via their receptor complexes. Nevertheless, whether a diverse intratumoral B-cells and T-cell receptor (BCR, TCR) repertoire affects the tumor immune microenvironment (TIME) and clinical outcomes in patients treated with immunotherapy is unclear.MethodsWe extracted information on BCR and TCR repertoire diversity from large clinical datasets and measured the association between immune receptor diversity features, the TIME, and clinical outcomes of patients treated with anti-PD-1/PD-L1 immunotherapy.ResultsIn multiple tumor types, an increasingly diverse TCR repertoire was strongly associated with a highly activated TIME, while BCR diversity was more associated with antibody responses but not with the overall B-cell infiltration nor with measures related to intratumoral CD8+T cell activity. Neither TCR nor BCR diversity was independent prognostic biomarkers of survival across multiple cancer types. However, both TCR and BCR diversity improved the performance of predictive models combined with established biomarkers of response to immunotherapy.ConclusionOverall, these data indicate a currently unexplored immunological role of intratumoral B-cells associated with BCR diversity and antibody responses but independent of classical anticancer T-cells intratumoral activities.
Well performance in relation to design, construction and wellfield operation: a case study from the fossil Ram Sandstone aquifer in southern Jordan
Authors: Charalambous Andreas N. , Burnet Bertrand R. 
Published: August 2023

The Dubaydib wellfield in southern Jordan comprises 55 wells that are up to 600 m in depth, and exploits the fossil Ram Sandstone aquifer. It has an average output of 100 million cubic metres per year (Mm
3
a
−1
) and well yields of 51–80 l s
−1
. Drilling fluid has affected well performance with lowest specific capacities of 1.56 l s
−1
m
−1
in bentonite-drilled wells, highest (5.46 l s
−1
m
−1
) in water-drilled open hole constructions and in the middle range (3.07 l s
−1
m
−1
) in polymer drilled wells. Well loss coefficients and skin effect values confirm these results. The productivity of wells drilled using bentonite-based drilling fluids has not improved during production, indicating that the damage has been irreversible. Well efficiency evaluations have been found to be sensitive to the method of calculation and not to provide a reliable measure of productivity. During the course of wellfield operation (2013–21) specific capacities declined from an all-well average of 3.78 l s
−1
m
−1
down to 3.13 l s
−1
m
−1
(or
c.
17% reduction). The decline reflects the deepening of groundwater levels as a result of aquifer response rather than well deterioration. As groundwater extraction is from storage, specific capacities will continue to fall, with tentative estimates suggesting values down to 2.56 l s
−1
m
−1
after 25 years and 2.16 l s
−1
m
−1
after 50 years.
Introduction to SP519 – volcanic islands: from hazard assessment to risk mitigation
Authors: Griffiths James S. , Law Richard D. 
Published: August 2023

Abstract
The Cities and Volcanoes Commission of the International Association of Volcanology and Chemistry of the Earth's Interior encourage the exchange of experiences on volcanic islands to identify best practice in hazard assessment, monitoring techniques and risk mitigation strategies. This volume is a contribution to these aims and this introduction provides some background on the nature of hazards on volcanic islands and a brief review of the nine papers in the book.
The Possible Mediatory Role of Inflammatory Markers on the Association of Dietary Insulin Index and Insulin Load with Metabolic Syndrome in Women with Overweight and Obesity: A Cross-Sectional Study
Authors: Darzi Melika , Shiraseb Farideh , da Silva Alessandra , Bressan Josefina , Clark Cain C. T. , Mahmoodi Sara , Mirzaei Khadijeh 
Published: August 2023

Background. Metabolic syndrome (MetS) is associated with increased inflammation. Diet plays an important role in the prevention and management of MetS, while some dietary factors can also increase or decrease markers of systemic inflammation. In this study, we aimed to determine the mediated association of inflammatory markers induced by dietary insulin index (DII) and dietary insulin load (DIL) with MetS and its components. Methods. This cross-sectional study was conducted with 219 women aged 18–28 years. Dietary intake was assessed by a 147-item food frequency questionnaire (FFQ). DII and DIL were calculated using the standard formula. The guidelines of the National Cholesterol Education Program’s Adult Treatment Panel III were used to define MetS. Biochemical parameters and anthropometric and blood pressure measures were evaluated by standard protocols. Results. After the adjustment for potential confounders, a marginally significant association was found between DII and MetS (OR = 2.11; 95% CI = 0.93–4.82;

P

= 0.06). However, we did not find a significant association between DIL and MetS. Furthermore, DII was significantly associated with waist circumference (WC) (OR = 1.67; 95% CI = 1.09– 4.03;

P

= 0.03) and marginally associated with triglyceride (TG) (OR = 1.10; 95% CI = 0.92–2.33;

P

= 0.07) and systolic blood pressure/diastolic blood pressure (SBP/DBP) (OR = 1.84; 95% CI = 0.85–3.99;

P

= 0.07). Moreover, there was a significant association between DIL and SBP/DBP (OR = 1.74; 95% CI = 1.54–5.61;

P

= 0.04). Also, we found that MCP-1 may have a mediatory role in the association between DII and DIL with MetS and several components of MetS. Hs-CRP did not have mediatory role in the association between DII and MetS. However, hs-CRP had a mediatory role in several MetS components. Furthermore, hs-CRP may have a mediatory role in the association of DIL with MetS and with some of its components. Conclusions. A higher DII score may increase the odds of MetS and its components. DIL was not significantly associated with the odds of MetS, but the association of DIL and SBP/DBP was significant. MCP-1 may have a mediatory role in associations between DII and DIL with MetS. In addition, hs-CRP may have a mediatory role in the association between DIL and MetS.
Predicted Heart Mass: A Tale of 2 Ventricles
Authors: Ródenas-Alesina Eduard , Foroutan Farid , Fan Chun-Po , Stehlik Josef , Bartlett Ina , Tremblay-Gravel Maxime , Aleksova Natasha , Rao Vivek , Miller Robert J.H. , Khush Kiran K. , Ross Heather J. , Moayedi Yasbanoo 
Published: August 2023

BACKGROUND:
Total predicted heart mass (PHM) is the recommended metric to assess donor-recipient size matching in patients undergoing heart transplantation. Separately measuring right ventricular (RV) and left ventricular (LV) PHM may improve risk prediction of 1-year graft failure.

METHODS:
Adult heart transplant recipients from the UNOS database from 2000 to 2018 were included in the study. LV and RV PHM were modeled as restricted cubic splines. The association with 1-year graft failure was determined using adjusted Cox regression. The risk reclassification of using both LV and RV PHM versus total PHM was assessed using the net reclassification index.

RESULTS:

A total of 34 976 recipients were included. We observed a
U
-shaped association between total PHM and 1-year graft failure, such that risk increased for hearts undersized by >15% and those oversized by more than 27%. Graft failure incrementally increased when LV PHM was undersized by more than 5% and when RV was oversized by >20%. There was 1.5-fold greater risk of graft failure for an LV undersized by >26% or an RV oversized by more than 40%. Using LV and RV PHM risk-assessment separately led to a net reclassification index=8.5% ([95% CI, 5.3%–11.7%], nonevent net reclassification index=9.1%, event net reclassification index=−0.6%).

CONCLUSIONS:
The association between donor-recipient PHM match and the risk of graft failure after heart transplantation can be further understood as risk attributable to LV undersizing and RV oversizing. Assessing LV and RV PHM separately instead of total PHM could further refine the methods used to match donors and recipients for heart transplantation, minimize the risk of 1-year graft failure, and increase the use of donor organs.
Age-related variability in network engagement during music listening
Authors: Faber Sarah E. M. , Belden Alexander G. , Loui Psyche , McIntosh Randy 
Published: August 2023

Abstract
Listening to music is an enjoyable behaviour that engages multiple networks of brain regions. As such, the act of music listening may offer a way to interrogate network activity, and to examine the reconfigurations of brain networks that have been observed in healthy aging. The present study is an exploratory examination of brain network dynamics during music listening in healthy older and younger adults. Network measures were extracted and analyzed together with behavioural data using a combination of hidden Markov modelling and partial least squares. We found age- and preference-related differences in fMRI data collected during music listening in healthy younger and older adults. Both age groups showed higher occupancy (the proportion of time a network was active) in a temporal-mesolimbic network while listening to self-selected music. Activity in this network was strongly positively correlated with liking and familiarity ratings in younger adults, but less so in older adults. Additionally, older adults showed a higher degree of correlation between liking and familiarity ratings consistent with past behavioural work on age-related dedifferentiation. We conclude that, while older adults do show network and behaviour patterns consistent with dedifferentiation, activity in the temporal-mesolimbic network is relatively robust to dedifferentiation. These findings may help explain how music listening remains meaningful and rewarding in old age.
Assimilation of Additional Radiosonde Observation Helps Improve the Prediction of Typhoon-Related Rainfall in the Pearl River Delta
Authors: Chen Jianqiao , Han Bo , Yang Qinghua , Luo Hao , Xian Zhipeng , Zhang Yunfei , Li Xing , Zhang Xiaobo 
Published: August 2023

Abstract
Typhoons frequently hit the Pearl River Delta (PRD), threatening the region’s dense population and assets. Typhoon precipitation forecasting in this region is challenging, in part because of the complex hydrometeorological effects over the coast and the scarcity of upstream marine meteorological observations. Typhoon Mun was formed in the South China Sea on 2 July 2019, and it brought heavy rainfall to the PRD when its center moved to the Beibu Gulf. During Typhoon Mun, an additional sounding was conducted offshore in the PRD every 12 h to assess the incremental impact on the skill of precipitation forecasting. A precipitation prediction based on the Weather Research and Forecasting (WRF) Model underestimated the 12-h accumulated precipitation over the PRD by 87%, with the Final Analysis (FNL) data from the National Centers for Environmental Prediction in the United States as initial fields. To address this issue, we implemented a solution by reconstructing the initial field through the assimilation of the additional radiosonde observations using the WRF three-dimensional variational (3D-Var) method. The prediction with the new initial fields reduced the rainfall underestimation by 24%. A difference analysis indicates that the planetary boundary layer scheme used in FNL underestimates the low-level temperature and humidity, especially after the rainfall peak. In contrast, assimilation gives a more realistic lower-tropospheric structure, significantly enhancing the moisture flux convergence around 925 hPa and divergence around 700 hPa around the PRD. Sensitivity experiments show that assimilating atmospheric thermal (i.e., temperature and humidity) profiles is more helpful than dynamic (wind) profiles in improving the rainfall prediction of the typhoon.

Significance Statement
The impact of typhoon-related precipitation in the Pearl River Delta (PRD) is significant. Improving the numerical forecast precision in this region poses challenges, partly due to the influences of land–sea thermal and topographic factors near the boundary layer, as well as the scarcity of upstream observational data. This study proposes a practical method to improve typhoon-related precipitation prediction from a case study of Typhoon Mun. By assimilating additional sounding observations, we obtain a more realistic structure of the lower atmosphere, better spatial patterns of water vapor fluxes, and, ultimately, better precipitation forecasts. The results of our study suggest that a more advanced observing system of vertical atmospheric structure, especially the thermal one, over the South China Sea is important for improving typhoon predictions.