bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chimeric antigen receptor T-cell therapy targeting a MAGE A4 peptide and HLA-A*02:01 complex for unresectable advanced or recurrent solid cancer: protocol for a multi-institutional phase 1 clinical trial
Authors: Okumura Satoshi , Ishihara Mikiya , Kiyota Naomi , Yakushijin Kimikazu , Takada Kohichi , Kobayashi Shinichiro , Ikeda Hiroaki , Endo Makoto , Kato Koji , Kitano Shigehisa , Matsumine Akihiko , Nagata Yasuhiro , Kageyama Shinichi , Shiraishi Taizo , Yamada Tomomi , Horibe Keizo , Takesako Kazuto , Miwa Hiroshi , Watanabe Takashi , Miyahara Yoshihiro , Shiku Hiroshi 
Published: November 2022

IntroductionAdoptive cell transfer of genetically engineered T cells is a promising treatment for malignancies; however, there are few ideal cancer antigens expressed on the cell surface, and the development of chimeric antigen receptor T cells (CAR-T cells) for solid tumour treatment has been slow. CAR-T cells, which recognise major histocompatibility complex and peptide complexes presented on the cell surface, can be used to target not only cell surface antigens but also intracellular antigens. We have developed a CAR-T-cell product that recognises the complex of HLA-A*02:01 and an epitope of the MAGE-A4 antigen equipped with a novel signalling domain of human GITR (investigational product code: MU-MA402C) based on preclinical studies.Methods and analysisThis is a dose-escalation, multi-institutional, phase 1 study to evaluate the tolerability and safety of MU-MA402C for patients with MAGE A4-positive and HLA-A*02:01-positive unresectable advanced or recurrent solid cancer. Two dose cohorts are planned: cohort 1, MU-MA402C 2×108/person; cohort 2, MU-MA402C 2×109/person. Prior to CAR-T-cell infusion, cyclophosphamide (CPA) and fludarabine (FLU) will be administered as preconditioning chemotherapy. Three evaluable subjects per cohort, for a total of 6 subjects (maximum of 12 subjects), will be recruited for this clinical trial. The primary endpoints are safety and tolerability. The severity of each adverse event will be evaluated in accordance with Common Terminology Criteria for Adverse Events V.5.0. The secondary endpoint is efficacy. Antitumour response will be evaluated according to Response Evaluation Criteria in Solid Tumours V.1.1.Ethics and disseminationThis clinical trial will be conducted in accordance with the current version of Good Clinical Practice. The protocol was approved by the Clinical Research Ethics Review Committee of Mie University Hospital (approval number F-2021-017). The trial results will be published in peer-reviewed journals and/or disseminated through international conferences.Trial registration numberjRCT2043210077.
Study on Hamstring Re-injury Prevention (SHARP): protocol for an international multicentre, randomised controlled trial
Authors: Zein Muhammad Ikhwan , Reurink Gustaaf , Verhagen Evert , Kerkhoffs Gino M M J , van der Horst Nick , Goedhart Edwin , Anggunadi Angelica , Knapstad Anders , Andersen Thor Einar , Ishøi Lasse , Hølmich Per , Tol Johannes L 
Published: November 2022

IntroductionPrevious studies showed that the Nordic hamstring exercise (NHE) effectively prevents primary hamstring injury. However, no study investigated the secondary preventing effect of the NHE on hamstring reinjury. The primary purpose of this study is to investigate the effectiveness of the NHE for preventing hamstring reinjury after return to play (RTP) following a hamstring injury in football players. The secondary purpose is to determine the effect of the NHE on sprint and jump performance.Methods and analysisThis is an international multicentre, prospective, parallel-group randomised controlled trial study. Subjects include male or female football players aged 18–40 years and within 1 week of RTP following a hamstring injury will be randomised into Nordics or a control group. Subjects in both groups continue their regular football training, but the Nordics group will perform an additional NHE programme. An online questionnaire will be sent to the subjects in both groups once per week within the first 10 weeks, then continued at months 6, 9 and 12. In a (performance) substudy, we will evaluate the effect of the NHE on sprint and vertical jump performance at three time points (at the beginning of the study, after 10 weeks and 12 months of follow-up).The primary outcomes are the incidence of hamstring reinjury within 2 and 12 months. The secondary outcomes are sprint and jump performance, adherence to the programme, duration of reinjury and reinjury burden.Ethics and disseminationThis study is approved by the medical ethics committee of Amsterdam University Medical Center (UMC) in the Netherlands (METC 2021_117), Faculty of Medicine Universitas Gadjah Mada in Indonesia (KE/FK/1248/EC/2021), Norwegian School of Sport Sciences in Norway (number 216–2 70 122) and Denmark (ethical submission in process). The study’s findings will be disseminated in scientific peer-reviewed journals and presented at international conferences.Trial registration numberNL9711.
Learning from stakeholders to inform good practice guidance on consent to research in intensive care units: a mixed-methods study
Authors: Paddock Katie , Woolfall Kerry , Kearney Anna , Pattison Natalie , Frith Lucy , Gamble Carrol , Welters Ingeborg , Trinder John , Young Bridget 
Published: November 2022

ObjectivesObtaining informed consent from patients in intensive care units (ICUs) prior to enrolment in a study is practically and ethically complex. Decisions about the participation of critically ill patients in research often involve substitute decision makers (SDMs), such as a patient’s relatives or doctors. We explored the perspectives of different stakeholder groups towards these consent procedures.Design and methodsMixed-methods study comprising surveys completed by ICU patients, their relatives and healthcare practitioners in 14 English ICUs, followed by qualitative interviews with a subset of survey participants. Empirical bioethics informed the analysis and synthesis of the data. Survey data were analysed using descriptive statistics of Likert responses, and analysis of interview data was informed by thematic reflective approaches.ResultsAnalysis included 1409 survey responses (ICU patients n=333, relatives n=488, healthcare practitioners n=588) and 60 interviews (ICU patients n=13, relatives n=30, healthcare practitioners n=17). Most agreed with relatives acting as SDMs based on the perception that relatives often know the patient well enough to reflect their views. While the practice of doctors serving as SDMs was supported by most survey respondents, a quarter (25%) disagreed. Views were more positive at interview and shifted markedly depending on particularities of the study. Participants also wanted reassurance that patient care was prioritised over research recruitment. Findings lend support for adaptations to consent procedures, including collaborative decision-making to correct misunderstandings of the implications of research for that patient. This empirical evidence is used to develop good practice guidance that is to be published separately.ConclusionsParticipants largely supported existing consent procedures, but their perspectives on these consent procedures depended on their perceptions of what the research involved and the safeguards in place. Findings point to the importance of explaining clearly what safeguards are in place to protect the patient.
Colombian ocular inflammatory diseases epidemiology study (COIDES): prevalence, incidence and sociodemographic characterisation of Scleritis in Colombia, 2015–2020
Authors: Cifuentes-González Carlos , Rojas-Carabali William , Mejia-Salgado Germán , Pineda-Sierra Juan Sebastián , Muñoz-Vargas Paula Tatiana , Boada-Robayo Laura , Cruz Danna Lesley , de-la-Torre Alejandra 
Published: November 2022

ObjectiveTo describe the epidemiological and demographic characteristics of scleritis in Colombia.Methods and analysisPopulation-based study using the national database from the Colombian Ministry of Health, using the International Classification of Diseases-10 code for Scleritis (H150) to estimate the prevalence and incidence from 2015 to 2019. Additionally, we evaluated the impact of the COVID-19 pandemic lockdown on the epidemiology of the disease during 2020, using the Gaussian Random Markov Field model (conditional autoregressive; CAR model). Finally, a standardised morbidity rate map was made to assess the geographic distribution of scleritis in the country.ResultsThe 5-year average prevalence and incidence of scleritis in Colombia were 0.6 (95% CI 0.59 to 0.6) and 0.65 (95% CI 0.64 to 0.64) cases per 100 000 inhabitants, respectively. We found 1429 registers of scleritis throughout the country between 2015 and 2019. Women represented 64.3%. The age groups with most cases were between 40 and 69 years in both sexes. However, women between 30 and 39 years and men between 20 and 29 years presented the highest number of new cases. In 2020, the pandemic reduced approximately 0.23 points the incidence of scleritis. Bogotá, Valle del Cauca and Antioquia had most of the cases, the latter two with an increased risk over time.ConclusionColombia has a lower incidence of scleritis than the reported in other latitudes, with a pattern of presentation at younger ages. Furthermore, the lockdown derived from the CODIV-19 pandemic affected the follow-up and diagnosis of patients with scleritis. This is the first epidemiological description of scleritis in a developing country and South America.
Scaling and spreading the electronic capture of patient-reported outcomes using a national surgical quality improvement programme: a feasibility study protocol
Authors: Melucci Alexa D , Liu Jason B , Brajcich Brian C , Collins Courtney E , Kazaure Hadiza S , Ko Clifford Y , Pusic Andrea L , Temple Larissa K 
Published: November 2022

IntroductionPatient-reported outcomes (PROs) are important for research, patient care and quality assessment; however, large-scale collection among the US surgical patient population has been limited. A structured implementation and dissemination programme focused on electronic PRO collection could improve the use of PROs data to improve surgical care. This study aims to (1) evaluate the feasibility of PRO collection among a larger volume of surgical patients through the stepwise implementation of PRO collection processes in a sample of American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) hospitals; (2) identify best practices and barriers to PRO collection through qualitative study of participating hospitals and patients; and (3) evaluate the utility of PROs at detecting differences in the quality of care among surgical patients.Methods and analysisACS NSQIP-participating hospitals are being recruited, and patients at participating hospitals who undergo elective surgical procedures receive invitations via e-mail or short message service ‘text’message to complete PROs after surgery. Validated PRO measures which evaluate physical and mental health-related quality of life, pain, fatigue, physical function and shared decision-making were selected. The scalability of PRO collection will be assessed by site enrolment, patient accrual and response rates. Qualitative interviews and focus groups will be performed with patients and hospital personnel to identify best practices and barriers to successful enrolment and PRO collection. Multivariable hierarchical regression models will be used to evaluate the distinctness of PROs from clinical outcomes captured in ACS NSQIP and the ability of PROs to detect differences in hospital performance.Ethics and disseminationThis study was reviewed by the Advarra Institutional Review Board (IRB) and deemed to be exempt from IRB oversight. Findings will be disseminated through peer-reviewed manuscripts, reports and presentations.
Vascular Reactivity Index and PELOD-2 as a mortality predictor in paediatric septic shock: a single-centre retrospective study
Authors: Yuniar Irene , Setianingsih Utami Kurniawati , Pardede Sudung O , Kadim Muzal , Iskandar Adhi Teguh Perma , Prawira Yogi 
Published: November 2022

BackgroundThe mortality rate for children with septic shock is stil quite high in low-income and middle-income countries (31.7%). One of the most widely used scoring systems to assess mortality in sepsis or septic shock is Paediatric Logistic Organ Dysfunction 2 (PELOD-2). However, it requires various laboratory evaluations. A non-invasive, fast and easy method is needed to assess the mortality of children with septic shock at an early stage. Therefore, this study aims to evaluate the ability of Vascular Reactivity Index (VRI) compared with PELOD-2 score as a predictor of mortality in children with septic shock based on vascular response to vasoactive agents.MethodsA retrospective cohort study was conducted using data from children aged 1 month to 18 years with septic shock treated in the ER and paediatric intensive care unit (PICU) of the tertiary hospital from 2017 to 2021. The serial haemodynamic data were analysed including Systemic Vascular Resistant Index (SVRI) and the cardiac index from ultrasound cardiac output monitoring device was recorded in the first and sixth hours after the diagnosis of septic shock. The VRI was determined by dividing SVRI/Vasoactive Inotropic Score (ie, accumulated doses of dopamine, dobutamine, epinephrine, milrinone, vasopressin and norepinephrine). The receiver operating curve was used to calculate the area under the curve (AUC), sensitivity and specificity of each cut-off point.ResultsA total of 68 subjects fulfilled the inclusion and exclusion criteria, the median age was 54 months with a range of 2–204 months and the mortality rate was 47%. The majority of the patients who died were found in the high cardiac index and low SVRI group (17.6%). Moreover, the optimum cut-off point of VRI was obtained to predict mortality in septic shock of 32.1, with 87.5% sensitivity and 88.9% specificity. The AUC for predicting death using VRI was 95% (95% CI 90% to 100%, p<0.001) and PELOD-2 92.6% (95% CI 96.4% to 98.8%, p<0.001).ConclusionThe VRI <32.1 may potentially be used to predict mortality in children with septic shock and its predictive ability is as good as PELOD-2. The assessment of VRI is faster and easier than PELOD-2.
Building Blocks for the Long-acting and Permanent Contraceptives Coordinated Registry Network
Authors: Baird Courtney E , Guiahi Maryam , Chudnoff Scott , Loyo-Berrios Nilsa , Garcia Stephanie , Jung Mary , Gressler Laura Elisabeth , Mao Jialin , Hodshon Beth , Sedrakyan Art , Andrews Sharon , Colden Kelly , Roberts Jason , Anderson Abby , Sewell Catherine , Marinac-Dabic Danica 
Published: November 2022

ObjectivesA multistakeholder expert group under the Women’s Health Technology Coordinated Registry Network (WHT-CRN) was organized to develop the foundation for national infrastructure capturing the performance of long-acting and permanent contraceptives. The group, consisting of representatives from professional societies, the US Food and Drug Administration, academia, industry and the patient community, was assembled to discuss the role and feasibility of the CRN and to identify the core data elements needed to assess contraceptive medical product technologies.DesignWe applied a Delphi survey method approach to achieve consensus on a core minimum data set for the future CRN. A series of surveys were sent to the panel and answered by each expert anonymously and individually. Results from the surveys were collected, collated and analyzed by a study design team from Weill Cornell Medicine. After the first survey, questions for subsequent surveys were based on the analysis process and conference call discussions with group members. This process was repeated two times over a 6-month time period until consensus was achieved.ResultsTwenty-three experts participated in the Delphi process. Participation rates in the first and second round of the Delphi survey were 83% and 100%, respectively. The working group reached final consensus on 121 core data elements capturing reproductive/gynecological history, surgical history, general medical history, encounter information, long-acting/permanent contraceptive index procedures and follow-up, procedures performed in conjunction with the index procedure, product removal, medications, complications related to the long-acting and/or permanent contraceptive procedure, pregnancy and evaluation of safety and effectiveness outcomes.ConclusionsThe WHT-CRN expert group produced a consensus-based core set of data elements that allow the study of current and future contraceptives. These data elements influence patient and provider decisions about treatments and include important outcomes related to safety and effectiveness of these medical devices, which may benefit other women’s health stakeholders.
Health-related quality of life, patient-centred communication and self-efficacy in ovarian cancer: a mediation analysis
Authors: Pozzar Rachel A , Xiong Niya , Mazzola Emanuele , Wright Alexi A , Goff Barbara A , Tulsky James A , Hammer Marilyn J , Berry Donna L 
Published: November 2022

ObjectiveTo assess the role of self-efficacy as a mediator of the association between patient-centred communication (PCC) and health-related quality of life (HRQoL) in a sample of participants with ovarian cancer.MethodsEnglish-speaking adults with ovarian cancer completed a cross-sectional survey. We assessed self-efficacy with the Self-Efficacy for Managing Chronic Disease scale, PCC with the Patient-Centred Communication in Cancer Care-36, and HRQoL with the Functional Assessment of Cancer Therapy-General. We used the PROCESS macro to calculate regression coefficients for the total effect of PCC on HRQoL and direct effect of PCC on HRQoL. We calculated a 95% CI for the indirect effect of PCC on HRQoL using 10 000 bootstrapped samples.ResultsThe total effect of PCC on HRQoL (9.47, 95% CI 6.21 to 12.74) was greater than the direct effect of PCC on HRQoL (3.47, 95% CI 0.73 to 6.21). The indirect effect of PCC on HRQoL was 6.00 (95% CI 3.56 to 8.95). Self-efficacy explained approximately 63.4% of the association between PCC and HRQoL.ConclusionsSelf-efficacy partially mediated the association between PCC and HRQoL. Self-efficacy is a potential target for communication interventions that aim to improve HRQoL. Research to validate this finding in the setting of a randomised trial is warranted.
Illegal Experimental Tobacco Marketplace II: effects of vaping product bans — findings from the 2020 International Tobacco Control Project
Authors: Freitas-Lemos Roberta , Stein Jeffrey S , Tegge Allison N , Kaplan Brent A , Heckman Bryan W , McNeill Ann , Cummings K Michael , Fong Geoffrey T , Bickel Warren K 
Published: November 2022

SignificanceRestrictive e-cigarette policies may increase purchases from illegal sources. The Illegal Experimental Tobacco Marketplace (IETM) allows examination of how restrictions impact illegal purchases. We investigated (1) the effect of a vaping ban, total flavour vaping ban and partial flavour vaping ban on the probability of purchasing illegal vaping products among different regulatory environments (USA, Canada and England) and tobacco user types (cigarette smokers, dual users and e-cigarette users); and (2) the relation between ban endorsement and illegal purchases.MethodsParticipants (N=459) from the International Tobacco Control Survey rated their support of bans and chose to purchase from a hypothetical legal experimental tobacco marketplace or IETM under control and the three ban conditions.ResultsIn total, 25% of cigarette smokers, 67% of dual users and 79% of e-cigarette users made IETM purchases. Cross-country comparisons depicted dual users from Canada (OR: 19.8), and e-cigarette users from the USA (OR: 12.9) exhibited higher illegal purchases odds than the same user type in England. Within-country comparisons showed e-cigarette and dual users are more likely to purchase from the IETM than cigarette smokers in the most restrictive condition, with the largest effects in e-cigarette users (England—OR: 1722.6, USA—OR: 22725.3, Canada—OR: 6125.0). Increased opposition towards partial or total flavour ban was associated with increased IETM purchasing in the corresponding condition.ConclusionsVaping restrictions may shift users’ preference to the illegal marketplace in a regulatory environment. Evidence of the IETM generalisability in a geographically dispersed sample enhances its utility in tobacco regulatory science.
Guide to key Bowland Shale Formation outcrop localities in the Craven and Edale basins
Authors: Waters Colin N. , Haslam Richard B. , Emmings Joseph F. , Riley Nick J. 
Published: November 2022

Abstract
This is a guide to the key exposures of the Bowland Shale Formation present within the Craven and Edale basins of England, providing contrasting settings from respectively the northern and southern parts of the Craven Group extent. It provides a description of the evolution of the deposition of the hemipelagic mudstone-dominated components of the Craven Group during the Visean to early Namurian (Mississippian to early Pennsylvanian). It explains the significance of the chosen localities in understanding the development of the Bowland Shale Formation and gives details on the sections visible at the time of compilation, providing useful guidance for field visits.
Projecting Future Energy Production from Operating Wind Farms in North America. Part I: Dynamical Downscaling
Authors: Pryor S. C. , Coburn J. J. , Barthelmie R. J. , Shepherd T. J. 
Published: November 2022

Abstract
New simulations at 12-km grid spacing with the Weather and Research Forecasting (WRF) Model nested in the MPI Earth System Model (ESM) are used to quantify possible changes in wind power generation potential as a result of global warming. Annual capacity factors (CF; measures of electrical power production) computed by applying a power curve to hourly wind speeds at wind turbine hub height from this simulation are also used to illustrate the pitfalls in seeking to infer changes in wind power generation directly from low-spatial-resolution and time-averaged ESM output. WRF-derived CF are evaluated using observed daily CF from operating wind farms. The spatial correlation coefficient between modeled and observed mean CF is 0.65, and the root-mean-square error is 5.4 percentage points. Output from the MPI-WRF Model chain also captures some of the seasonal variability and the probability distribution of daily CF at operating wind farms. Projections of mean annual CF (CFA) indicate no change to 2050 in the southern Great Plains and Northeast. Interannual variability of CFA increases in the Midwest, and CFA declines by up to 2 percentage points in the northern Great Plains. The probability of wind droughts (extended periods with anomalously low production) and wind bonus periods (high production) remains unchanged over most of the eastern United States. The probability of wind bonus periods exhibits some evidence of higher values over the Midwest in the 2040s, whereas the converse is true over the northern Great Plains.

Significance Statement
Wind energy is playing an increasingly important role in low-carbon-emission electricity generation. It is a “weather dependent” renewable energy source, and thus changes in the global atmosphere may cause changes in regional wind power production (PP) potential. We use PP data from operating wind farms to demonstrate that regional simulations exhibit skill in capturing actual power production. Projections to the middle of this century indicate that over most of North America east of the Rocky Mountains annual expected PP is largely unchanged, as is the probability of extended periods of anomalously high or low production. Any small declines in annual PP are of much smaller magnitude than changes due to technological innovation over the last two decades.