bluuebunny/crossref_metadata_2025_split huggingface dataset:
Seismic evidence of an extremely thin crust along a 70 Ma slow-spreading crustal segment in the equatorial Atlantic Ocean
Authors: Dhabaria Nirmit , Singh Satish C. 
Published: October 2024

Abstract
The oceanic crust at slow-spreading ridges is formed by a combination of magmatic and tectonic processes. Seismic tomographic studies, commonly used to determine crustal structures, indicate that mature slow-spreading crust has an average thickness of 6.1 ± 0.9 km, with a lower to upper crustal thickness ratio of 2.3. However, tomographic methods are based on high-frequency approximations and can only provide information about large-scale crustal structures. Using seismic full-waveform inversion applied to ocean bottom seismometer data, we report the presence of nearly uniform and extremely thin crust (4 ± 0.2 km) with a lower to upper crustal thickness ratio of 0.74 along an ~100 km, 70 Ma crustal segment formed at the slow-spreading Mid-Atlantic Ridge in the equatorial Atlantic Ocean. This thin crust is underlain by a Moho transition zone that is 1 ± 0.5 km thick, resulting in a combined crustal and Moho transition zone thickness of 5 ± 0.6 km. The crustal thinning is primarily due to the thinning of the lower crust, suggesting that a significant part of the crust is formed by lava flows and dike intrusions. The presence of an extremely thin crust indicates a decrease in mantle temperature by at least 50 °C, suggesting a vast extent of the upper mantle thermal minimum in the equatorial Atlantic Ocean, and the absence of influence of the mantle from the Siera Leone mantle plume 70 m.y. ago.
Ocean oxygenation and ecological restructuring caused by the late Paleozoic evolution of land plants
Authors: Stacey Jack , Wallace Malcolm W. , Hood Ashleigh v.S. , Shuster Alice M. , Corlett Hilary , Reed Christopher P. , Moynihan Conor 
Published: October 2024

Abstract
The dramatic increase in ocean-atmosphere oxygen levels during the Devonian and Mississippian is increasingly linked to the diversification of land plants, yet the timing and extent of this event remain uncertain. This study uses the redox-sensitive rare earth element cerium (cerium anomaly—Ce/Ce*) to investigate ocean redox conditions during the deposition of globally distributed Paleozoic carbonate strata. Our Paleozoic Ce/Ce* record suggests that Cambrian, Ordovician, and Silurian oceans had relatively low O2 levels (mean Ce/Ce* = 0.86 ± 0.10, 0.91 ± 0.14, and 0.91 ± 0.10 [±1σ], respectively). In contrast, short-lived ocean oxygenation events, possibly related to the diversification of small land plants, likely occurred throughout the Early and Middle Devonian (mean Ce/Ce* = 0.80 ± 0.07 and 0.58 ± 0.14, respectively). “Modern” Ce/Ce* values (&lt;0.36) first occurred during the Late Devonian, suggesting that the main phase of Devonian and Mississippian oceanic oxygenation was related to the evolution of large vascular plants and the first forests. Despite this, the significant variability of Ce/Ce* values during this time suggests that shallow marine settings were susceptible to redox instability, possibly caused by upwelling of anoxic deep waters. This redox instability potentially provides evidence of a mechanism for contemporaneous mass extinction and metazoan reef collapse events. Development of strongly oxic conditions during the Late Devonian may have resulted in the demise of many Paleozoic-type organisms, facilitated the radiation of the modern evolutionary fauna, and established the modern oxygenated ocean-atmosphere system.
Investing in health workers: a retrospective cost analysis of a cohort of return-of-service bursary recipients in Southern Africa
Authors: Mabunda Sikhumbuzo A , Durbach Andrea , Chitha Wezile W , Phiri Hawor , Phalane Mahlane , Nomatshila Sibusiso C , Joshi Rohina , Angell Blake 
Published: October 2024

BackgroundReturn-of-service (RoS) schemes are investment strategies that governments use to increase the pool of health professionals through the issuing of bursaries and scholarships to health sciences students in return for service after graduation. Despite using these schemes for many years, Eswatini, South Africa, Botswana and Lesotho have not assessed the costs and return on investment of these schemes. This study aimed to assess the costs and relative rates of contract defaulting in these four Southern African countries.MethodsA retrospective cohort study was carried out by reviewing databases of RoS beneficiaries for selected health sciences programmes who were funded between 2000 and 2010. Costs of the schemes were assessed by country, degree type and whether bursary holders completed their required service or defaulted on their public service obligations.ResultsOf the 5616 beneficiaries who studied between 1995 and 2019 in the four countries, 1225 (21.8%) beneficiaries from 2/9 South African provinces and Eswatini were presented in the final analysis. Only Eswatini had data on debt recovery or financial repayments. Beneficiaries were mostly medical students and slightly biased towards males. Medical students benefited from 56.7% and 81.3% of the disbursement in Eswatini (~US$2 million) and South Africa (~US$57 million), respectively. Each South African medical student studying in Cuba cost more than five times the rate of medical students who studied in South Africa. Of the total expenditure, 47.7% and 39.3% of the total disbursement is spent on individuals who default the RoS scheme in South Africa and Eswatini, respectively.ConclusionsRoS schemes in these countries have loss of return on investment due to poor monitoring. The schemes are costly, ineffective and have never been evaluated. There are poor mechanisms for identifying beneficiaries who exit their contracts prematurely and inadequate debt recovery processes.
Predicting mucosal inflammation in IBD patients using patient-reported symptom scores and a faecal calprotectin home test: protocol for a multicentre prospective validation study
Authors: Janssen Laura , van Linschoten Reinier Cornelis Anthonius , West Rachel Louise , Gilissen Lennard P L , Romberg-Camps Mariëlle , Brandts Lloyd , Mujagic Zlatan , Römkens Tessa EH , Pierik M 
Published: October 2024

IntroductionCrohn’s disease and ulcerative colitis are chronic inflammatory bowel diseases (IBD) with a relapsing-remitting nature. With adequate non-invasive prediction of mucosal inflammation, endoscopies can be prevented and treatment optimised earlier for better disease control. We aim to validate and recalibrate commonly used patient-reported symptom scores combined with a faecal calprotectin (FC) home test as non-invasive diagnostic tool for remote monitoring of IBD, both in daily practice and in a strict trial setting. Endoscopy will be used as the gold standard.Methods and analysisIn this multicentre prospective validation study, adult IBD patients are asked to fill out questionnaires regarding disease activity (Monitor IBD At Home, mobile Health Index, Manitoba IBD Index, IBD control and patient-HBI/patient-Simple Clinical Colitis Activity Index), perform a FC home test and collect a stool sample for routine laboratory FC measurement, before the start of the bowel preparation for the ileocolonoscopy. Endoscopic disease activity will be scored according to the simplified endoscopic score for Crohn’s disease (CD) for CD patients or Ulcerative Colitis Endoscopic Index for Severity and Mayo Endoscopic Subscore for ulcerative colitis patients. The main study outcome is the diagnostic test accuracy of the various patient-reported scores to assess mucosal inflammation in combination with a FC home test.Ethics and disseminationThis study is approved by the Medical Research Ethics Committee of azM/UM in Maastricht dated 03 March 2021 (METC 20–085) and is monitored by the Clinical Trial Centre Maastricht according to Good Clinical Practice guidelines. Written informed consent will be obtained from all patients. Study results will be published in international peer-reviewed medical journals.Trial registration numberNCT05886322
Exploring willingness to use adverse drug reaction reporting systems: a multicentre qualitative study in China based on the technology acceptance model and task-technology fit integration approach
Authors: Xia Xudong , Yang Xue , Du Jiayi , Cheng Weigao , Chen Xiaobo , Zhang Wan , Yin Zhao 
Published: October 2024

BackgroundAdverse drug reaction (ADR) reporting systems are critical for monitoring and managing drug safety. However, various factors influence the willingness to use these systems. This study aimed to investigate the willingness to use ADR reporting systems through an integrated model of the Technology Acceptance Model (TAM) and Task-Technology Fit (TTF) theory, conducting a multicentre qualitative study from the user’s perspective.MethodsThis study used qualitative research methods, including in-depth interviews with clinicians, nurses, pharmacists and administrators who reported ADRs through the National Adverse Drug Reaction Monitoring System (NADRMS) and the China Hospital Pharmacovigilance System (CHPS). The interviews were audio-recorded, transcribed verbatim and analysed using QDA Miner software for data management and thematic analysis.ResultsEighteen healthcare workers from five healthcare organisations participated in the study. They found the ease of use and usefulness of the current NADRMS and CHPS to be acceptable. The essential technical requirements identified included accuracy, standardisation, timeliness and confidentiality. However, challenges such as inaccurate information capture, unstable interfacing with medical record systems, low reporting efficiency and lack of data sharing were highlighted. Overall, front-line healthcare workers exhibited a generally negative attitude towards using NADRMS and CHPS, driven more by necessity than preference. Factors influencing their willingness to use these systems included ease of use, practicality, risk perception and social impact, with varying attitudes and requirements observed between user groups.ConclusionThis study provides practical recommendations that can be readily implemented to enhance the effectiveness and sustainability of ADR reporting systems. While front-line users in China acknowledged the systems’ ease of use and usefulness, they also noted significant gaps in technological adaptation. They expressed the need for improvements in data openness and sharing, accessibility and system intelligence.
Process evaluation of a cluster randomised implementation trial examining strategies to increase early access to exercise for people with knee osteoarthritis: protocol
Authors: Orsatti Amy , Bowden Jocelyn L , Naylor Justine M , Boland Robert , Pardey Margery , Descallar Joseph , Mills Kathryn 
Published: October 2024

IntroductionFirst steps for knee osteoarthritis (OA) is a cluster randomised implementation trial examining the effect of an educational reminder message included in knee X-ray reports on the proportion of people subsequently referred to exercise professionals for their knee OA. Evaluating the processes supporting the completion of the study and the efficacy of the reminder message is essential to interpreting the outcomes of the study and aiding translation into practice.Methods and analysisWe will conduct a concurrent process evaluation throughout the current study using a previously published framework for examining cluster randomised trials. This framework divides processes into those occurring at the cluster level and those at the target population level. For the current study, the cluster level is within radiology clinics. The target population is people with newly diagnosed radiologically evident, structural knee OA. A mixed methods design, incorporating survey data, administrative records, field notes and semi-structured interviews with representatives from radiology clinics and people with knee OA, will evaluate these processes. The focus of the evaluation will be recruitment and response processes of the radiology clinics and delivery and response processes for the people with knee OA. We will also describe the context and explore how the nudge theory of behavioural change influences the outcome of the study.Ethics and disseminationThe study protocol, inclusive of the process evaluation, was approved by Macquarie University Human Research Ethics Committee (#520221190343842). Findings will be disseminated through national and international conferences, national industry stakeholders and patient advocacy groups to reach all levels of healthcare. Staff at radiology clinics and people with knee OA involved in interviews provide written, informed consent to participate in the process evaluation. Specific findings will be incorporated into training modules aimed at radiology clinics and will be developed by our industry partners.Trial registrationProspectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12622001414707p). Registration occurred in December 2022
Segmentation and multiparametric evaluation of corneal whorl-like nerves for in vivo confocal microscopy images in dry eye disease
Authors: Yu Kang , Chen Yupei , Feng Ziqing , Wang Gengyuan , Deng Yuqing , Li Jiaxiong , Ling Lirong , Xu Ruiwen , Xiao Peng , Yuan Jin 
Published: October 2024

ObjectiveTo establish an automated corneal nerve analysis system for corneal in vivo confocal microscopy (IVCM) images from both the whorl-like corneal nerves in the inferior whorl (IW) region and the straight ones in the central cornea and to characterise the geometric features of cornea nerves in dry eye disease (DED).Methods and analysisAn encoder–decoder-based semi-supervised method was proposed for corneal nerve segmentation. This model’s performance was compared with the ground truth provided by experienced clinicians, using Dice similarity coefficient (DSC), mean intersection over union (mIoU), accuracy (Acc), sensitivity (Sen) and specificity (Spe). The corneal nerve total length (CNFL), tortuosity (CNTor), fractal dimension (CNDf) and number of branching points (CNBP) were used for further analysis in an independent DED dataset including 50 patients with DED and 30 healthy controls.ResultsThe model achieved 95.72% Acc, 97.88% Spe, 80.61% Sen, 75.26% DSC, 77.57% mIoU and an area under the curve value of 0.98. For clinical evaluation, the CNFL, CNBP and CNDffor whorl-like and straight nerves showed a significant decrease in DED patients compared with healthy controls (p<0.05). Additionally, significantly elevated CNTor was detected in the IW in DED patients (p<0.05). The CNTor for straight corneal nerves, however, showed no significant alteration in DED patients (p>0.05).ConclusionThe proposed method segments both whorl-like and straight corneal nerves in IVCM images with high accuracy and offered parameters to objectively quantify DED-induced corneal nerve injury. The IW is an effective region to detect alterations of multiple geometric indices in DED patients.
GOG-3097/ENGOT-ov81/GTG-UK/RAMP 301: a phase 3, randomized trial evaluating avutometinib plus defactinib compared with investigator’s choice of treatment in patients with recurrent low grade serous ovarian cancer
Authors: Grisham Rachel , Monk Bradley J , Van Nieuwenhuysen Els , Moore Kathleen Nadine , Fabbro Michel , O’Malley David M , Oaknin Ana , Thaker Premal , Oza Amit M , Colombo Nicoletta , Gershenson David , Aghajanian Carol A , Choi Chel Hun , Lee Yeh Chen , Mirza Mansoor Raza , Coleman Robert L , Cobb Lauren , Harter Philipp , Lustgarten Stephanie , Youssoufian Hagop , Banerjee Susana 
Published: October 2024

BackgroundThere are no approved treatments specifically for low grade serous ovarian cancer; current standard of care treatment options are limited in efficacy and tolerability. The combination of avutometinib with defactinib has demonstrated efficacy and a consistent safety profile in two clinical trials in recurrent low grade serous ovarian cancer, and a lower discontinuation rate due to adverse events compared with historical rates for standard of care.Primary ObjectiveTo compare the progression free survival of the combination of avutometinib with defactinib versus investigator’s choice of treatment in patients with recurrent low grade serous ovarian cancer.Study HypothesisCombination treatment with avutometinib–defactinib will significantly improve progression free survival compared with investigator’s choice of treatment in patients with recurrent low grade serous ovarian cancer.Trial DesignGOG-3097/ENGOT-ov81/GTG-UK/RAMP 301 is a phase 3, randomized, international, open label study designed to compare avutometinib with defactinib versus investigator’s choice of treatment in patients with recurrent low grade serous ovarian cancer who have progressed on a previous platinum based therapy. On confirmation of disease progression using a blinded independent central review, patients on the investigator’s choice of treatment arm may cross over to the avutometinib–defactinib arm.Major Inclusion/Exclusion CriteriaPatients must have recurrent low grade serous ovarian cancer (KRASmutant or wild-type) and have documented progression (radiographic or clinical) or recurrence of low grade serous ovarian cancer after at least one platinum based chemotherapy regimen. Unlimited additional previous lines of therapy are allowed, including previous MEK/RAF inhibitor. Patients will be excluded if they have co-existing high grade ovarian cancer or had previous treatment with avutometinib, defactinib, or any other FAK inhibitor.Primary EndpointProgression free survival according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, blinded-independent central review.Sample SizeApproximately 270 patients will be randomized in a 1:1 fashion to either the combination avutometinib with defactinib arm (n~135) or the investigator’s choice of treatment arm (n~135).Estimated Dates for Completing Accrual and Presenting ResultsThe estimated primary completion date of RAMP 301 is 2028, and the estimated study completion date is 2031.Trial RegistrationClinicalTrials.govNCT06072781
Methyl-donor supplementation in women with systemic lupus erythematosus with different nutritional status: the protocol for a randomised, double-blind, placebo-controlled trial
Authors: da Mota Jhulia C N L , Carvalho Lucas M , Ribeiro Amanda A , Souza Leticia L , Borba Eduardo F , Roschel Hamilton , Gualano Bruno , Nicoletti Carolina F 
Published: October 2024

Introduction

DNA hypomethylation in patients with systemic lupus erythematosus (SLE) has been recently documented in the literature. Low levels of DNA methylation have been observed globally and in genes associated with immune and inflammatory pathways in SLE’s CD4+T lymphocytes. Given that certain micronutrients can either donate methyl groups within one-carbon metabolism pathways or serve as cofactors for enzymes involved in the DNA methylation process, this randomised, double-blind, placebo-controlled trial aims to investigate whether a 3-month supplementation of folic acid and vitamin B
12
will modulate the DNA methylation profile in subcutaneous adipose tissue (primary outcome) of women with SLE and normal weight or excess body weight. As secondary objectives, we will assess gene expression, telomere length and phenotypic characteristics (ie, clinical parameters, body weight and composition, abdominal circumference, food intake and disordered eating attitude, physical activity, lipid profile, serum concentrations of leptin, adiponectin, and cytokines).

Methods and analysis

Patients will be classified according to their nutritional status by body mass index in normal weight or excess body weight. Subsequently, patients in each group will be randomly assigned to either a placebo or an intervention group (folic acid (400 mcg) and vitamin B
12
(2000 mcg) supplementation). Endpoint evaluations will be conducted using both intention-to-treat and per-protocol analyses. This study has the potential to design new personalised nutritional approaches as adjunctive therapy for patients with SLE.

Ethics and dissemination
This study has been reviewed and approved by the Ethical Committee from Clinical Hospital of the School of Medicine of the University of Sao Paulo, Brazil (CAAE.: 47317521.8.0000.0068).

Trial registration number

NCT05097365
(first version).
Contemporary characteristics, outcomes and novel risk score for Takotsubo cardiomyopathy: a national inpatient sample analysis
Authors: Agrawal Ankit , Bhagat Umesh , Yesilyaprak Abdullah , Bayat Aqieda , Sawhney Aanchal , Arockiam Aro Daniela , Haroun Elio , Faulx Michael , Desai Milind Y , Jaber Wael , Menon Venu , Griffin Brian , Wang Tom Kai Ming 
Published: October 2024

BackgroundTakotsubo cardiomyopathy (TC) is an established differential diagnosis of myocardial infarction with non-obstructive coronaries with significant interest but limited data on prognostication. We reviewed the characteristics and in-hospital outcomes and developed a novel risk score for TC.MethodsUsing the National Inpatient Sample data from 2016 to 2020, we identified adult patients (≥18 years) with acute coronary syndrome (ACS) and TC. We divided the cohort into ACS with and without TC and retrieved baseline data. Multivariable regression analysis was conducted to identify factors associated with TC diagnosis and adverse outcomes, leading to the development of a risk-scoring system.ResultsAmong 7 219 004 adult ACS admissions, 78 214 (1.0%) were diagnosed with TC, with a mean age of 68.2 years, 64 526 (82.5%) being female and 5475 (7.0%, compared with 8.4% for other ACS) in-hospital mortality events. Factors significantly associated with TC were female sex (OR 6.78 (95% CI 6.47 to 7.09), p<0.001) and chronic heart failure (OR 1.60 (95% CI 1.54 to 1.66), p<0.001). A novel risk score was developed, including the following parameters: male sex, age >70 years, non-white race, hypertension, hyperlipidemia, history of coronary artery bypass grafting, history of percutaneous coronary intervention, cardiac arrhythmias, renal failure, cardiogenic shock and vasopressor use. The area under curves for in-hospital mortality was 0.716 in the derivation and 0.725 in the validation cohorts.ConclusionsTC remains a high-risk diagnosis in a minority of ACS cases, with mortality rates similar to other ACS causes. Our novel risk score offers a valuable tool for risk stratification in patients with TC, but external validation is needed to confirm its utility.