bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decreased Estimated Glomerular Filtration Rate and Proteinuria and Long-Term Outcomes After Ischemic Stroke: A Longitudinal Observational Cohort Study
Authors: Ueki Kana , Matsuo Ryu , Kuwashiro Takahiro , Irie Fumi , Wakisaka Yoshinobu , Ago Tetsuro , Kamouchi Masahiro , Kitazono Takanari , Ishitsuka Takao , Ibayashi Setsuro , Kusuda Kenji , Fujii Kenichiro , Nagao Tetsuhiko , Okada Yasushi , Yasaka Masahiro , Ooboshi Hiroaki , Irie Katsumi , Omae Tsuyoshi , Toyoda Kazunori , Nakane Hiroshi , Sugimori Hiroshi , Arakawa Shuji , Fukuda Kenji , Kitayama Jiro , Fujimoto Shigeru , Arihiro Shoji , Kuroda Junya , Fukushima Yoshihisa , Nakamura Kuniyuki , Kiyohara Takuya , Hata Jun , Kumai Yasuhiro 
Published: April 2023

Background:
It remains unclear how chronic kidney disease and its underlying pathological conditions, kidney dysfunction, and kidney damage, are associated with cardiovascular outcomes. This study aimed to determine whether kidney dysfunction (ie, decreased estimated glomerular filtration rate), kidney damage (ie, proteinuria), or both are associated with the long-term outcomes after ischemic stroke.

Methods:

A total of 12 576 patients (mean age, 73.0±12.6 years; 41.3% women) with ischemic stroke who were registered in a hospital-based multicenter registry, Fukuoka Stroke Registry, between June 2007 and September 2019, were prospectively followed up after stroke onset. Kidney function was assessed by estimated glomerular filtration rate and categorized into G1: ≥60 mL/(min·1.73 m
2
), G2: 45–59 mL/(min·1.73 m
2
), and G3: <45 mL/(min·1.73 m
2
). Kidney damage was evaluated by proteinuria using a urine dipstick test and classified into P1: −, P2: ±/1+, and P3: ≥2+. Hazard ratios and 95% CI for events of interest were estimated by a Cox proportional hazards model. Long-term outcomes included recurrence of stroke and all-cause death.

Results:
During the median follow-up of 4.3 years (interquartile range, 2.1–7.3 years), 2481 patients had recurrent stroke (48.0/1000 patient-years) and 4032 patients died (67.3/1000 patient-years). Chronic kidney disease was independently associated with increased risks of stroke recurrence and all-cause death even after adjustment for multiple confounding factors, including traditional cardiovascular risk factors. Both estimated glomerular filtration rate and proteinuria were independently associated with increased risks of stroke recurrence (multivariable-adjusted hazard ratio [95% CI], G3: 1.22 [1.09–1.37] versus G1, P3: 1.25 [1.07–1.46] versus P1) and death (G3: 1.45 [1.33–1.57] versus G1, P3: 1.62 [1.45–1.81] versus P1). In subgroup analyses, effect modifications were found in the association of proteinuria with death by age and stroke subtype.

Conclusions:
Kidney dysfunction and kidney damage were independently, but differently, associated with increased risks of recurrent stroke and all-cause death.
Augmented Reality in Physics Education: Students with Intellectual Disabilities Inquire the Structure of Matter
Authors: Iatraki Georgia , Mikropoulos Tassos A. 
Published: April 2023

Abstract
Immersive technologies support educational activities and provide motivating contexts which are increasingly implemented in special education settings. Augmented Reality (AR) seems to improve the level of engagement in teaching and learning processes for all students, including students with Intellectual Disabilities (ID). However, there is a lack of research that investigates AR learning environments where students with ID can be involved in inquiry-based activities and acquire academic content linked to real situations. The purpose of this study was to implement a single-subject design and evaluate the effects of an AR system on students’ performance on the microscopic level of the structure of matter and especially the phase-states of water. A functional relationship was found between students’ correct responses during probe sessions and the AR inquiry-based intervention. In addition, a social validity assessment indicated that the AR glasses helped students with ID to acquire physics concepts, as well as inquiry skills in a vivid experience. The students also reported satisfaction from using the AR glasses. Suggestions for future research include the design of AR-based interventions for other science concepts for students with ID as well as other special educational needs.
Further Applications of Social Cognition to Göbekli Tepe
Authors: Henley Tracy B. , Reysen Stephen 
Published: April 2023

Abstract
Göbekli Tepe is an archaeological site that has challenged much prior thought on human history with respect to our Neolithic revolution from animistic, egalitarian, hunter-gatherers to settled, socially stratified, and religious peoples. In the present paper we review the structures and possible purposes of Göbekli Tepe, summarize past considerations of the connection between psychological concepts and matters found thereat, and then introduce social identity theory as an apt theoretical perspective from which to best understand the peoples who constructed and utilized the site. Throughout we show that social-cognitive processes and concepts have merit in interpreting the advent and utility of Göbekli Tepe, suggesting then a greater use for psychology within the framework of cognitive archaeology.
The Battle of Ideas under LOSC Dispute Settlement Procedures
Authors: Song Ke 
Published: April 2023

Abstract
Dispute settlement procedures under the United Nations Convention on the Law of the Sea (LOSC) can be a great laboratory for observing judicial processes of exploring and testing the acceptability of multiple solutions to issues of interpretation through a battle of ideas among LOSC adjudicators. The analysis observes that LOSC tribunals tend towards two jurisprudential patterns when battling their ideas: (1) the International Tribunal for the Law of the Sea (ITLOS) takes an implicit approach of deviating from previous case law of other LOSC tribunals; and (2) Annex VII arbitral tribunals have been quite straightforward when facing a diverging interpretative discourse. This article explains the institutional dynamics underpinning these two jurisprudential patterns. Calibrating judicial reasoning of the ITLOS is proposed, which would hopefully stimulate a vibrant battle of ideas facilitating coherent development of international law.
The International Laws of War: Linguistic Analysis from the Perspectives of Register, Corpus and Grammatical Patterning
Authors: Lukin Annabelle , Marrugo Alexandra García 
Published: April 2023

Abstract
All texts, including all legal texts, are constructed in language. All legal constructs and discriminations are an effect of language. As such, linguistics and text analysis should be considered a necessary adjunct to legal studies and, in particular, to critical legal studies. While the disciplines of linguistics and law are increasingly interacting, there is a paucity of linguistic analysis in the field of the international laws of war. This paper seeks to open doors to collaboration, by viewing the texts of the international laws of war from three linguistic perspectives: as a ‘register’, as a ‘corpus’, and in terms of their lexicogrammatical patterning. In terms of register, the international laws of war herald a new form of textual practice, the function and effects of which are subject to debate. As a corpus, some dominant lexical habits of these texts are explored and interpreted for their ideological implications and reactances. Finally, an examination of covert lexicogrammatical meanings in this register, via a small extract from Article 8 of the Rome Statute, illuminates the contradictory meanings that these texts navigate. These three perspectives offer a preliminary glimpse into the value of linguistic analysis for critical perspectives on the international laws of war.
Pharmacogenetics testing (DPYD and UGT1A1) for fluoropyrimidine and irinotecan in routine clinical care: Perspectives of medical oncologists and oncology pharmacists
Authors: Glewis Sarah , Lingaratnam Senthil , Krishnasamy Mei , H Martin Jennifer , Tie Jeanne , Alexander Marliese , Michael Michael 
Published: April 2023

Background Despite robust evidence and international guidelines, to support routine pharmacogenetic (PGx) testing, integration in practice has been limited. This study explored clinicians’ views and experiences of pre-treatment DPYD and UGT1A1 gene testing and barriers to and enablers of routine clinical implementation. Methods A study-specific 17-question survey was emailed (01 February–12 April 2022) to clinicians from the Medical Oncology Group of Australia (MOGA), the Clinical Oncology Society of Australia (COSA) and International Society of Oncology Pharmacy Practitioners (ISOPP). Data were analysed and reported using descriptive statistics. Results Responses were collected from 156 clinicians (78% medical oncologists, 22% pharmacists). Median response rate of 8% (ranged from 6% to 24%) across all organisations. Only 21% routinely test for DPYD and 1% for UGT1A1. For patients undergoing curative/palliative intent treatments, clinicians reported intent to implement genotype-guided dosing by reducing FP dose for DPYD intermediate metabolisers (79%/94%), avoiding FP for DPYD poor metabolisers (68%/90%), and reducing irinotecan dose for UGT1A1 poor metabolisers (84%, palliative setting only). Barriers to implementation included: lack of financial reimbursements (82%) and perceived lengthy test turnaround time (76%). Most Clinicians identified a dedicated program coordinator, i.e., PGx pharmacist (74%) and availability of resources for education/training (74%) as enablers to implementation. Conclusion PGx testing is not routinely practised despite robust evidence for its impact on clinical decision making in curative and palliative settings. Research data, education and implementation studies may overcome clinicians’ hesitancy to follow guidelines, especially for curative intent treatments, and may overcome other identified barriers to routine clinical implementation.
Realignment Surgery for Failed Osteochondral Autologous Transplantation in Osteochondral Lesions of the Talus Associated With Malalignment
Authors: Kim Jaeyoung , Rajan Lavan , Gagne Oliver , Kim Ji-Beom , Lee Woo-Chun 
Published: April 2023

Background While osteochondral autologous transplantation (OAT) offers favorable results in most patients with osteochondral lesions of the talus (OLT), some patients continue to experience persistent pain following the procedure. Information regarding the etiology of this pain and outcomes of revision surgery are limited. This study aimed to report results of revision surgery with realignment procedures in patients with failed OAT who demonstrated concomitant malalignment at the distal tibia or hindfoot. Methods Eight patients (8 ankles), who had been experiencing persistent pain for more than 1 year following OAT, underwent realignment procedures during revision surgery. All patients underwent primary OAT for the treatment of medial OLTs. Patients were divided into 2 groups based on the main location of deformity: the supramalleolar realignment group (SRG, 5 ankles) and the hindfoot realignment group (HRG, 3 ankles). No direct procedure was performed on the osteochondral lesion at the time of revision surgery. Ankle and hindfoot alignment were evaluated using 6 parameters in weightbearing radiographs. Computed tomography (CT) was used to assess for medial gutter narrowing, spur formation, and cyst volume around transplanted osteochondral plug preoperatively and postoperatively. Clinical outcomes were assessed using Foot Function Index and Visual Analogue Scale. Results All patients had medial gutter narrowing or spur formation, which are early signs of ankle arthritis. The SRG had varus distal tibial alignment with a median medial distal tibial angle of 85.7 degrees (interquartile range [IQR], 3.2). The HRG had valgus hindfoot alignment and a lower medial longitudinal arch with a median hindfoot moment arm of 8.4 mm (IQR, 6.1) and a median Meary’s angle of 11.8 degrees (IQR, 1.4). Spontaneous restoration of the osteochondral lesion was observed after realignment surgery, with cyst volume decreasing from 0.2592 to 0.0873 cm3 (P < .05). Clinical scores improved in all patients. Conclusion The current study demonstrates the effectiveness of realignment surgery in a selected patient group who experienced persistent pain and showed radiographic evidence of malalignment after primary OAT. Our study provides evidence supporting the use of realignment procedures in these cases, with results indicating improved patient-reported outcomes and spontaneous restoration of osteochondral lesions. Levels of Evidence: Level IV: Case series
Wnt7a deficit is associated with dysfunctional angiogenesis in pulmonary arterial hypertension
Authors: Chakraborty Ananya , Nathan Abinaya , Orcholski Mark , Agarwal Stuti , Shamskhou Elya A. , Auer Natasha , Mitra Ankita , Guardado Eleana Stephanie , Swaminathan Gowri , Condon David F. , Yu Joyce , McCarra Matthew , Juul Nicholas H. , Mallory Alden , Guzman-Hernandez Roberto A. , Yuan Ke , Rojas Vanesa , Crossno Joseph T. , Yung Lai-Ming , Yu Paul B. , Spencer Thomas , Winn Robert A. , Frump Andrea , Karoor Vijaya , Lahm Tim , Hedlin Haley , Fineman Jeffrey R. , Lafyatis Robert , Knutsen Carsten N.F. , Alvira Cristina M. , Cornfield David N. , de Jesus Perez Vinicio A. 
Published: April 2023

Introduction:Pulmonary arterial hypertension (PAH) is characterised by loss of microvessels. The Wnt pathways control pulmonary angiogenesis but their role in PAH is incompletely understood. We hypothesised that Wnt activation in pulmonary microvascular endothelial cells (PMVECs) is required for pulmonary angiogenesis, and its loss contributes to PAH.Methods:Lung tissue and PMVECs from healthy and PAH patients were screened for Wnt production. Global and endothelial-specificWnt7a−/–mice were generated and exposed to chronic hypoxia and Sugen-hypoxia (SuHx).Results:Healthy PMVECs demonstrated >6-fold Wnt7a expression during angiogenesis that was absent in PAH PMVECs and lungs. Wnt7a expression correlated with the formation of tip cells, a migratory endothelial phenotype critical for angiogenesis. PAH PMVECs demonstrated reduced vascular endothelial growth factor (VEGF)-induced tip cell formation as evidenced by reduced filopodia formation and motility, which was partially rescued by recombinant Wnt7a. We discovered that Wnt7a promotes VEGF signalling by facilitating Y1175 tyrosine phosphorylation in vascular endothelial growth factor receptor 2 (VEGFR2) through receptor tyrosine kinase-like orphan receptor 2 (ROR2), a Wnt-specific receptor. We found that ROR2 knockdown mimics Wnt7a insufficiency and prevents recovery of tip cell formation with Wnt7a stimulation. While there was no difference between wild-type and endothelial-specificWnt7a−/–mice under either chronic hypoxia or SuHx, globalWnt7a+/–mice in hypoxia demonstrated higher pulmonary pressures and severe right ventricular and lung vascular remodelling. Similar to PAH,Wnt7a+/–PMVECs exhibited an insufficient angiogenic response to VEGF-A that improved with Wnt7a.Conclusions:Wnt7a promotes VEGF signalling in lung PMVECs and its loss is associated with an insufficient VEGF-A angiogenic response. We propose that Wnt7a deficiency contributes to progressive small vessel loss in PAH.
Characteristics of severe asthma patients on biologics: a real-life European registry study
Authors: Principe Stefania , Richards Levi B. , Hashimoto Simone , Kroes Johannes Anthon , Van Bragt Job J.M.H. , Vijverberg Susanne J. , Sont Jacob K. , Scichilone Nicola , Bieksiene Kristina , Ten Brinke Anneke , Csoma Zsuzsanna , Dahlén Barbro , Gemicioglu Bilun , Grisle Ineta , Kuna Piotr , Lazic Zorica , Mihaltan Florin , Popović-Grle Sanja , Škrgat Sabina , Marcon Alessandro , Caminati Marco , Djukanovic Ratko , Porsbjerg Celeste , Maitland Van Der Zee Anke-Hilse 
Published: April 2023

BackgroundThe use of anti-interleukin-5 (IL5) for severe asthma is based on criteria from randomised controlled trials (RCTs), but in real-life patients might not fulfil the eligibility criteria but may benefit from biologics. We aimed to characterise patients starting anti-IL5(R) in Europe and evaluate the discrepancies between initiation of anti-IL5(R) in real life and in RCTs.Materials and methodsWe performed a cross-sectional analysis with data from the severe asthma patients at the start of anti-IL5(R) in the Severe Heterogeneous Asthma Research collaboration Patient-centred (SHARP Central) registry. We compared the baseline characteristics of the patients starting anti-IL5(R) from 11 European countries within SHARP with the baseline characteristics of the severe asthma patients from 10 RCTs (four for mepolizumab, three for benralizumab and three for reslizumab). Patients were evaluated following eligibility criteria from the RCTs of anti-IL5 therapies.ResultsPatients starting anti-IL5(R) in Europe (n=1231) differed in terms of smoking history, clinical characteristics and medication use. The characteristics of severe asthma patients in the SHARP registry differed from the characteristics of patients in RCTs. Only 327 (26.56%) patients fulfilled eligibility criteria of all the RCTs; 24 patients were eligible for mepolizumab, 100 for benralizumab and 52 reslizumab. The main characteristics of ineligibility were: ≥10 pack-years, respiratory diseases other than asthma, Asthma Control Questionnaire score ≤1.5 and low-dose inhaled corticosteroids.ConclusionA large proportion of patients in the SHARP registry would not have been eligible for anti-IL5(R) treatment in RCTs, demonstrating the importance of real-life cohorts in describing the efficacy of biologics in a broader population of patients with severe asthma.
Diffuse alveolar haemorrhage in children: an international multicentre study
Authors: Ring Astrid Madsen , Schwerk Nicolaus , Kiper Nural , Aslan Ayse Tana , Aurora Paul , Ayats Roser , Azevedo Ines , Bandeira Teresa , Carlens Julia , Castillo-Corullon Silvia , Cobanoglu Nazan , Elnazir Basil , Emiralioğlu Nagehan , Eyuboglu Tugba Sismanlar , Fayon Michael , Gursoy Tugba Ramaslı , Hogg Claire , Kötz Karsten , Karadag Bülent , Látalová Vendula , Krenke Katarzyna , Lange Joanna , Manali Effrosyni D. , Osona Borja , Papiris Spyros , Proesmans Marijke , Reix Philippe , Roditis Lea , Rubak Sune , Rumman Nisreen , Snijders Deborah , Stehling Florian , Weiss Laurence , Yalcın Ebru , Zirek Fazilcan , Bush Andrew , Clement Annick , Griese Matthias , Buchvald Frederik Fouirnaies , Nathan Nadia , Nielsen Kim Gjerum 
Published: April 2023

BackgroundPaediatric diffuse alveolar haemorrhage (DAH) is a rare heterogeneous condition with limited knowledge on clinical presentation, treatment and outcome.MethodsA retrospective, descriptive multicentre follow-up study initiated from the European network for translational research in children's and adult interstitial lung disease (Cost Action CA16125) and chILD-EU CRC (the European Research Collaboration for Children's Interstitial Lung Disease). Inclusion criteria were DAH of any cause diagnosed before the age of 18 years.ResultsData of 124 patients from 26 centres (15 counties) were submitted, of whom 117 patients fulfilled the inclusion criteria. Diagnoses were idiopathic pulmonary haemosiderosis (n=35), DAH associated with autoimmune features (n=20), systemic and collagen disorders (n=18), immuno-allergic conditions (n=10), other childhood interstitial lung diseases (chILD) (n=5), autoinflammatory diseases (n=3), DAH secondary to other conditions (n=21) and nonspecified DAH (n=5). Median (IQR) age at onset was 5 (2.0–12.9) years. Most frequent clinical presentations were anaemia (87%), haemoptysis (42%), dyspnoea (35%) and cough (32%). Respiratory symptoms were absent in 23%. The most frequent medical treatment was systemic corticosteroids (93%), hydroxychloroquine (35%) and azathioprine (27%). Overall mortality was 13%. Long-term data demonstrated persistent abnormal radiology and a limited improvement in lung function.ConclusionsPaediatric DAH is highly heterogeneous regarding underlying causes and clinical presentation. The high mortality rate and number of patients with ongoing treatment years after onset of disease underline that DAH is a severe and often chronic condition. This large international study paves the way for further prospective clinical trials that will in the long term allow evidence-based treatment and follow-up recommendations to be determined.
Genomic adaptation to extreme climate conditions in beef cattle as a consequence of cross-breeding program
Authors: Tian Rugang , Asadollahpour Nanaie Hojjat , Wang Xiao , Dalai Baolige , Zhao Meng , Wang Feng , Li Hui , Yang Ding , Zhang Hao , Li Yuan , Wang Tingyue , Luan Tu , Wu Jianghong 
Published: April 2023

Abstract
Background
Understanding the evolutionary forces related to climate changes that have been shaped genetic variation within species has long been a fundamental pursuit in biology. In this study, we generated whole-genome sequence (WGS) data from 65 cross-bred and 45 Mongolian cattle. Together with 62 whole-genome sequences from world-wide cattle populations, we estimated the genetic diversity and population genetic structure of cattle populations. In addition, we performed comparative population genomics analyses to explore the genetic basis underlying variation in the adaptation to cold climate and immune response in cross-bred cattle located in the cold region of China. To elucidate genomic signatures that underlie adaptation to cold climate, we performed three statistical measurements, fixation index (FST), log2 nucleotide diversity (θπ ratio) and cross population composite likelihood ratio (XP-CLR), and further investigated the results to identify genomic regions under selection for cold adaptation and immune response-related traits.

Results
By generating WGS data, we investigated the population genetic structure and phylogenetic relationship of studied cattle populations. The results revealed clustering of cattle groups in agreement with their geographic distribution. We detected noticeable genetic diversity between indigenous cattle ecotypes and commercial populations. Analysis of population structure demonstrated evidence of shared genetic ancestry between studied cross-bred population and both Red-Angus and Mongolian breeds. Among all studied cattle populations, the highest and lowest levels of linkage disequilibrium (LD) per Kb were detected in Holstein and Rashoki populations (ranged from ~ 0.54 to 0.73, respectively). Our search for potential genomic regions under selection in cross-bred cattle revealed several candidate genes related with immune response and cold shock protein on multiple chromosomes. We identified some adaptive introgression genes with greater than expected contributions from Mongolian ancestry into Molgolian x Red Angus composites such as TRPM8, NMUR1, PRKAA2, SMTNL2 and OXR1 that are involved in energy metabolism and metabolic homeostasis. In addition, we detected some candidate genes probably associated with immune response-related traits.

Conclusion
The study identified candidate genes involved in responses to cold adaptation and immune response in cross-bred cattle, including new genes or gene pathways putatively involved in these adaptations. The identification of these genes may clarify the molecular basis underlying adaptation to extreme environmental climate and as such they might be used in cattle breeding programs to select more efficient breeds for cold climate regions.