bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cohort profile of BIGPROMISE: a perioperative biobank of a high-risk surgical population
Authors: Noordzij Peter G , Ruven Henk JT , Reniers Ted , Idema Rene N , Thio Maaike SY , Cremer Olaf L , Hollema Nynke , Smit Kyra N , Vernooij Lisette M , Dijkstra Ineke M , Rettig Thijs CD 
Published: June 2024

PurposePostoperative complications increase mortality, disability and costs. Advanced understanding of the risk factors for postoperative complications is needed to improve surgical outcomes. This paper discusses the rationale and profile of the BIGPROMISE (biomarkers to guide perioperative management and improve outcome in high-risk surgery) cohort, that aims to investigate risk factors, pathophysiology and outcomes related to postoperative complications.ParticipantsAdult patients undergoing major surgery in two tertiary teaching hospitals. Clinical data and blood samples are collected before surgery, at the end of surgery and on the first, second and third postoperative day. At each time point a panel of cardiovascular, inflammatory, renal, haematological and metabolic biomarkers is assessed. Aliquots of plasma, serum and whole blood of each time point are frozen and stored. Data on severe complications are prospectively collected during 30 days after surgery. Functional status is assessed before surgery and after 120 days using the WHO Disability Assessment Schedule (WHODAS) 2.0. Mortality is followed up until 2 years after surgery.Findings to dateThe first patient was enrolled on 8 October 2021. Currently (1 January 2024) 3086 patients were screened for eligibility, of whom 1750 (57%) provided informed consent for study participation. Median age was 66 years (60; 73), 28% were female, and 68% of all patients were American Society of Anaesthesiologists (ASA) physical status class 3. Most common types of major surgery were cardiac (49%) and gastro-intestinal procedures (26%). The overall incidence of 30-day severe postoperative complications was 16%.Future plansBy the end of the recruitment phase, expected in 2026, approximately 3000 patients with major surgery will have been enrolled. This cohort allows us to investigate the role of pathophysiological perioperative processes in the cause of postoperative complications, and to discover and develop new biomarkers to improve risk stratification for adverse postoperative outcomes.Trial registration numberNCT05199025.
Efficacy and safety of tirofiban in patients with acute branch atheromatous disease-related stroke (BRANT): a protocol for a randomised controlled trial
Authors: Li Shengde , Zhang Dingding , Sha Yuhui , Zhu Yicheng , Zhou Lixin , Peng Bin , Ni Jun 
Published: June 2024

IntroductionBranch atheromatous disease (BAD)-related stroke is increasingly becoming a clinical entity and prone to early neurological deterioration (END) and poor prognosis. There are no effective regimens to reduce the disability caused by BAD-related stroke in acute phase. Recent studies have indicated the efficacy of tirofiban in acute ischaemic stroke; however, its efficacy has not been validated in patients with BAD-related stroke. Thus, we aim to test whether intravenous tirofiban initiated within 48 hours after the onset would improve the functional outcome in patients with acute BAD-related stroke, in comparison with the standard antiplatelet therapy based on the current guideline.Methods and analysisBRANT is a multicentre, randomised, open-label, blinded endpoint, parallel-controlled, phase III trial conducted in 21 hospitals in China. Participants aged 18–75 years with acute BAD-related stroke within 48 hours after the stroke onset are randomised in a 1:1 ratio to the tirofiban or control group. The treatment period is 48 hours in both groups. The primary outcome is the excellent functional outcome (modified Rankin Scale Score: 0–1) at 90 days. The secondary outcomes include END, major bleeding, stroke, death, functional status, serious adverse events and change in bleeding-related markers. Assuming the rates of the primary outcome to be 74% in the tirofiban group and 62% in the control group, a total of 516 participants are needed for 0.8 power (two-sided 0.05 alpha).Ethics and disseminationBRANT study has been approved by the Ethics Committee of the Peking Union Medical College Hospital (I-23PJ1242). Written informed consent is required for all the patients before enrolment. The results of the study will be published in a peer-reviewed journal.Trial registration numberClinicalTrials.gov (NCT06037889).
Understanding the association between family planning and fertility reduction in Southeast Asia: a scoping review
Authors: Rizkianti Anissa , Kistiana Sari , Fajarningtiyas Desy Nuri , Hutasoit Evalina Franciska , Baskoro Andhika Ajie , Maryani Herti , Titisari Anastasia Septya , Sari Diah Puspita , Naibaho Margareth Maya P , Melissa Melissa , Muthmainnah Muthmainnah 
Published: June 2024

ObjectivesWe aimed to explore and understand the extent and type of evidence on fertility reduction and its association with family planning (FP) in Southeast Asia.DesignScoping review, following the methodological principles developed by Arksey and O’Malley and Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines for reporting.Data sourceWe searched PubMed/MEDLINE, ProQuest, EBSCO, Scopus, Web of Science, Google Scholar and reference lists of relevant articles between 1 January 2012 and 31 December 2022. Only open-access articles in English were considered.Study selectionFor inclusion, observational studies were selected for eligibility based on the original articles investigating the uptake of FP on women aged 15–49 years and its association with fertility decline in Southeast Asian (SEA) countries.Data extraction and analysisTwo reviewers screened the records independently for eligibility and extracted all data. The specific details of the studies, including data on the authors, year of publication, setting, study design, aims/objectives of the study, specific intervention, outcomes and main findings, were reported.ResultsWe retrieved 615 articles and retained 12 articles included in the analysis. Of these, 11 were quantitative studies and 1 was qualitative study. The frequently reported strategy of FP was the use of contraception. FP not only allows women to control their birth by spacing and limiting their pregnancies but also delay their first childbirth by using contraceptive methods.ConclusionOur review suggests that the FP programmes aiming at reducing fertility should have a specific focus on improving the uptake and continuation of FP services.
Neoadjuvant toripalimab combined with axitinib in patients with locally advanced clear cell renal cell carcinoma: a single-arm, phase II trial
Authors: Huang Jiwei , Wang Yueming , Xu Fan , Wang Zaoyu , Wu Guangyu , Kong Wen , Cheoklong NG , Tricard Thibault , Wu Xiaorong , Zhai Wei , Zhang Wei , Zhang Jiyang , Zhang Ding , Chen Shuyin , Lian Yuqing , Chen Yonghui , Zhang Jin , Huang Yiran , Xue Wei 
Published: June 2024

BackgroundA combination of axitinib and immune checkpoint inhibitors (ICIs) demonstrated promising efficacy in the treatment of advanced renal cell carcinoma (RCC). This study aims to prospectively evaluate the safety, efficacy, and biomarkers of neoadjuvant toripalimab plus axitinib in non-metastatic clear cell RCC.MethodsThis is a single-institution, single-arm phase II clinical trial. Patients with non-metastatic biopsy-proven clear cell RCC (T2-T3N0-1M0) are enrolled. Patients will receive axitinib 5 mg twice daily combined with toripalimab 240 mg every 3 weeks (three cycles) for up to 12 weeks. Patients then will receive partial (PN) or radical nephrectomy (RN) after neoadjuvant therapy. The primary endpoint is objective response rate (ORR). Secondary endpoints include disease-free survival, safety, and perioperative complication rate. Predictive biomarkers are involved in exploratory analysis.ResultsA total of 20 patients were enrolled in the study, with 19 of them undergoing surgery. One patient declined surgery. The primary endpoint ORR was 45%. The posterior distribution of πORR had a mean of 0.44 (95% credible intervals: 0.24–0.64), meeting the predefined primary endpoint with an ORR of 32%. Tumor shrinkage was observed in 95% of patients prior to nephrectomy. Furthermore, four patients achieved a pathological complete response. Grade ≥3 adverse events occurred in 25% of patients, including hypertension, hyperglycemia, glutamic pyruvic transaminase/glutamic oxaloacetic transaminase (ALT/AST) increase, and proteinuria. Postoperatively, one grade 4a and eight grade 1–2 complications were noted. In comparison to patients with stable disease, responders exhibited significant differences in immune factors such as Arginase 1(ARG1), Melanoma antigen (MAGEs), Dendritic Cell (DC), TNF Superfamily Member 13 (TNFSF13), Apelin Receptor (APLNR), and C-C Motif Chemokine Ligand 3 Like 1 (CCL3-L1). The limitation of this trial was the small sample size.ConclusionNeoadjuvant toripalimab combined with axitinib shows encouraging activity and acceptable toxicity in locally advanced clear cell RCC and warrants further study.Trial registration numberclinicaltrials.gov,NCT04118855.
Value of SLE-DAS in assessing disease activity in patients with systemic lupus erythematosus: a single-centre retrospective study
Authors: Ma Jinlu , Zhang Lin , Yan Mengxue , Liu Zhichun , Xue Leixi 
Published: June 2024

ObjectivesThis study aimed to evaluate the clinical value of the Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS) for assessing disease activity in patients with SLE.MethodsClinical data were collected from patients with SLE who were admitted at the Second Affiliated Hospital of Soochow University from January 2009 to December 2022. The glucocorticoid dose grading was used as the gold standard for disease activity assessment in SLE. The SLE-DAS value was calculated, and the SLE disease activity status was graded based on the SLE-DAS value. Another scoring criterion, the SLE Disease Activity Index 2000 (SLEDAI 2000), served as a control. Spearman correlation analysis was used to calculate the correlation between the scoring criteria and other variables.ResultsThe analysis included 396 patients with SLE. A strong correlation was found between SLE-DAS and SLEDAI 2000 (ρ=0.709, 95% CI 0.648 to 0.766, p<0.001), with median SLE-DAS and SLEDAI 2000 scores of 15.32 (7.90 to 24.45) and 13 (8 to 19), respectively. Compared with the SLEDAI 2000 value, the SLE-DAS value correlated better with glucocorticoid dose grading (ρ=0.434 vs 0.518), gammaglobulin use (ρ=0.170 vs 0.318) and immunosuppressant use (ρ=0.122 vs 0.221). A moderate correlation based on disease activity grading was found between SLE-DAS and glucocorticoid dose grading (ρ=0.441), whereas a mild correlation was observed between SLEDAI 2000 and glucocorticoid dose grading (ρ=0.325). Additionally, SLE-DAS revealed a positive correlation with severe thrombocytopenia, cardiac involvement and pulmonary involvement but not SLEDAI 2000.ConclusionCompared with SLEDAI 2000, SLE-DAS may provide a more accurate disease activity assessment in patients with SLE, especially those with severe thrombocytopenia and cardiopulmonary involvement.
Two-year clinical follow-up enhances the diagnosis of early-stage hip osteoarthritis: data from check cohort
Authors: Runhaar Jos , Özbulut Ömer , Kloppenburg Margreet , Boers Maarten , Bijlsma Johannes W J , Bierma-Zeinstra Sita 
Published: June 2024

ObjectiveTo provide a set of diagnostic criteria for early-stage hip osteoarthritis (OA) in primary care, using signs and symptoms monitored over 2 years in individuals with hip pain and/or stiffness. Additionally, the study aimed to see whether these factors were additive to factors based on baseline signs and symptoms only.MethodsData of the 543 persons with 735 symptomatic hips were collected from the prospective Cohort Hip and Cohort Knee cohort study. Using data from 5 to 10 years of follow-up, 24 experts (13 general practitioners, 11 secondary care physicians (6 rheumatologists and 5 orthopaedic surgeons)) inspected individuals’ medical data on the presence of clinically relevant hip OA. Their diagnoses are used as reference standards. Backward selection method was used to provide models using the factors from baseline to 2 years of follow-up. Additionally, new models were combined with previously published models, using same selection method. Area under the curve (AUC) was calculated after each removal of factors in the final combined models.ResultsRadiographic factors and high-sensitive C reactive protein did not end up in any model with change factors only. AUC value (SD) of the final obtained model of change factors was 0.70 (0.01). Adding newly defined factors to previously published models significantly (p<0.0001) increased the AUC value to 0.75 (0.01).ConclusionFinal diagnostic criteria, consisting only of the factors obtained through history taking and physical examination, were able to detect early-stage hip OA associated with clinically relevant hip OA 5–10 years later, with ‘moderate’ precision.
Left atrial appendage closure in patients with atrial fibrillation and acute ischaemic stroke despite anticoagulation
Authors: Abramovitz Fouks Avia , Yaghi Shadi , Selim Magdy H , Gökçal Elif , Das Alvin S , Rotschild Ofer , Silverman Scott B , Singhal Aneesh B , Kapur Sunil , Greenberg Steven M , Gurol Mahmut Edip 
Published: June 2024

BackgroundThe occurrence of acute ischaemic stroke (AIS) while using oral anticoagulants (OAC) is an increasingly recognised problem among nonvalvular atrial fibrillation (NVAF) patients. We aimed to elucidate the potential role of left atrial appendage closure (LAAC) for stroke prevention in patients with AIS despite OAC use (AIS-despite-OAC).MethodsWe retrospectively collected baseline and follow-up data from consecutive NVAF patients who had AIS-despite-OAC and subsequently underwent endovascular LAAC, between January 2015 and October 2021. The primary outcome measure was the occurrence of AIS after LAAC, and the safety outcome was symptomatic intracerebral haemorrhage (ICH).Results29 patients had LAAC specifically because of AIS-despite-OAC. The mean age at the time of the procedure was 73.4±8.7, 13 were female (44.82%). The mean CHA2DS2-VASc score was 5.96±1.32, with an expected AIS risk of 8.44 per 100 patient-years. 14 patients (48%) had two or more past AIS-despite-OAC. After LAAC, 27 patients (93.10%) were discharged on OAC which was discontinued in 17 (58.62%) after transoesophageal echocardiogram at 6 weeks. Over a mean of 1.75±1.0 years follow-up after LAAC, one patient had an AIS (incidence rate (IR) 1.97 per 100 patient-years). One patient with severe cerebral microangiopathy had a small ICH while on direct OAC and antiplatelet 647 days after LAAC.ConclusionsLAAC in AIS-despite-OAC patients demonstrated a low annual AIS recurrence rate in our cohort (1.97%) compared with the expected IR based on their CHA2DS2-VASc scores (8.44%) and to recent large series of AIS-despite-OAC patients treated with OAC/aspirin only (5.3%–8.9%). These hypothesis-generating findings support randomised trials of LAAC in AIS-despite-OAC patients.
Dual Antiplatelet Therapy After Embolic Stroke of Undetermined Source: A Subgroup Analysis of the CHANCE-2 Trial
Authors: Xie Xuewei , Jing Jing , Meng Xia , Johnston S. Claiborne , Bath Philip M. , Li Zixiao , Zhao Xingquan , Wang Yilong , Xu Qin , Wang Anxin , Jiang Yong , Li Hao , Wang Yongjun ,   for the CHANCE-2 Investigators
Published: June 2024

BACKGROUND:
The atherosclerotic sources of embolism are a significant contributor to embolic stroke of undetermined source (ESUS). However, there is limited evidence for the efficacy of intensive dual antiplatelet therapy for ESUS. We conducted an investigation to determine whether gene-directed dual antiplatelet therapy could reduce the risk of recurrent stroke in patients with ESUS.

METHODS:

CHANCE-2 (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events-II) was an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled trial that objectively compared ticagrelor plus aspirin and clopidogrel plus aspirin in patients with minor stroke or transient ischemic attack who carried
CYP2C19
loss-of-function alleles in China. All study participants were classified into ESUS and non-ESUS groups for the prespecified exploratory analysis. Cox proportional hazards models were used to assess the interaction of the state of ESUS with the effects of dual antiplatelet therapy with ticagrelor-aspirin versus clopidogrel-aspirin, adjusting for sociodemographic and clinical factors.

RESULTS:

The subgroup analysis comprised 5796 participants (90.4% of the total 6412 participants) in the CHANCE-2 trial, with a median age of 64.9 years (range, 57.0–71.4 years), of whom 1964 (33.9%) were female. These participants underwent diffusion-weighted imaging as part of the study protocol. After systematic evaluation, 15.2% of patients (881/5796) were deemed to have ESUS. The incidence of stroke recurrence in patients with ESUS was found to be 5.6% in the ticagrelor-aspirin group and 9.2% in the clopidogrel-aspirin group (hazard ratio, 0.57 [95% CI, 0.33–0.99];
P
=0.04). In patients without ESUS, the respective incidence rates were 5.6% and 7.5% (hazard ratio, 0.72 [95% CI, 0.58–0.90];
P
<0.01). The
P
value was 0.56 for the treatment × ESUS status interaction effect.

CONCLUSIONS:

In this prespecified exploratory analysis, ticagrelor with aspirin was superior to clopidogrel with aspirin for preventing stroke at 90 days in patients with acute ischemic stroke or transient ischemic attack who carried
CYP2C19
loss-of-function alleles and were classified as ESUS.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT04078737.
Nimodipine Protects Vascular and Cognitive Function in an Animal Model of Cerebral Small Vessel Disease
Authors: Yang Zhiyuan , Lange Frédéric , Xia Yiqing , Chertavian Casey , Cabolis Katerina , Sajic Marija , Werring David J. , Tachtsidis Ilias , Smith Kenneth J. 
Published: June 2024

BACKGROUND:
Cerebral small vessel disease is a common cause of vascular cognitive impairment and dementia. There is an urgent need for preventative treatments for vascular cognitive impairment and dementia, and reducing vascular dysfunction may provide a therapeutic route. Here, we investigate whether the chronic administration of nimodipine, a central nervous system-selective dihydropyridine calcium channel blocking agent, protects vascular, metabolic, and cognitive function in an animal model of cerebral small vessel disease, the spontaneously hypertensive stroke-prone rat.

METHODS:
Male spontaneously hypertensive stroke-prone rats were randomly allocated to receive either a placebo (n=24) or nimodipine (n=24) diet between 3 and 6 months of age. Animals were examined daily for any neurological deficits, and vascular function was assessed in terms of neurovascular and neurometabolic coupling at 3 and 6 months of age, and cerebrovascular reactivity at 6 months of age. Cognitive function was evaluated using the novel object recognition test at 6 months of age.

RESULTS:

Six untreated control animals were terminated prematurely due to strokes, including one due to seizure, but no treated animals experienced strokes and so had a higher survival (
P
=0.0088). Vascular function was significantly impaired with disease progression, but nimodipine treatment partially preserved neurovascular coupling and neurometabolic coupling, indicated by larger (
P
<0.001) and more prompt responses (
P
<0.01), and less habituation upon repeated stimulation (
P
<0.01). Also, animals treated with nimodipine showed greater cerebrovascular reactivity, indicated by larger dilation of arterioles (
P
=0.015) and an increase in blood flow velocity (
P
=0.001). This protection of vascular and metabolic function achieved by nimodipine treatment was associated with better cognitive function (
P
<0.001) in the treated animals.

CONCLUSIONS:
Chronic treatment with nimodipine protects from strokes, and vascular and cognitive deficits in spontaneously hypertensive stroke-prone rat. Nimodipine may provide an effective preventive treatment for stroke and cognitive decline in cerebral small vessel disease.
Future Changes in Day-to-Day Precipitation Variability in Europe
Authors: Lhotka Ondřej , Plavcová Eva , Beranová Romana 
Published: June 2024

Abstract
We analyzed regional patterns of day-to-day precipitation variability across Europe and assessed their future changes using Coordinated Regional Climate Downscaling Experiment (CORDEX) regional climate models. A discrete Markov chain process was employed to calculate transition probabilities from wet and dry states, and the precipitation variability was quantified using the proposed variability index (IVAR, the sum of wet-to-dry and dry-to-wet transitions divided by the total number of transitions). The IVAR is, in general, lowest in southern Europe and gradually increases northward in the observed data. Performance of the regional climate models is season dependent: They capture IVAR reasonably well in summer, but higher simulated variability was found for the winter season. The IVAR trends computed for the 2006–95 period suggest decreasing day-to-day precipitation variability over southern Europe, especially in summer under the high-concentration RCP8.5 pathway. By contrast, increased variability is projected in northern Europe. Between these two regions, future IVAR trends are less clear because they strongly depend on the selection of driving global model, hinting of an uncertain future hydroclimate in the central European region.

Significance Statement
In a warming world, water availability will play a key role in ecosystem productivity. Although future changes in rainfall amounts have been studied extensively, much less attention has been given to changes in their temporal distribution and variability. Because grouping wet or dry days into sequences vitally contributes to characterizing floods or droughts, we aimed to study future changes in these tendencies. We found that although future changes in wet or dry days grouping tendencies are mostly driven solely by change in their frequency, climate models do not agree on the change in the frequency of wet days over large parts of continental Europe. This leaves major uncertainties in a future European hydroclimate and implications for impact modeling.