bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comprehensive data‐level investigation of cancer diagnosis on imbalanced data
Authors: Gupta Surbhi , Gupta Manoj Kumar 
Published: May 2021

AbstractCancer is one of the leading causes of death in the world. Cancer research is vital as the prognosis of cancer enables clinical applications for patients. In this study, we have proposed the Stacked Ensemble Model (Stacking of bagged and boosted learners) for the automatic disease diagnosis. The experimental results prove the superiority of the proposed method to conventional machine learning techniques. In the empirical study, the performance of eight data handling methods and 14 classification methods is compared to obtain prediction results. The performance of the model has been evaluated on five benchmark datasets. The appreciable Area under the Curve scores achieved by the proposed methodology on Cervical Cancer (0.98), Mesothelioma (0.93), Breast Cancer (0.99), Prostate Cancer (0.97), and Hepatitis‐C Virus (0.998) datasets make this work more significant than the previously published works. The experimental results show that our proposed method is superior to conventional machine learning techniques and the proposed model contributes in the form of an efficient computational model.
SETD2 epidermal deficiency promotes cutaneous wound healing via activation of AKT/mTOR Signalling
Authors: Li Xiaoxue , Liu Changwei , Zhu Yiwen , Rao Hanyu , Liu Min , Gui Liming , Feng Wenxin , Tang Huayuan , Xu Jin , Gao Wei‐Qiang , Li Li 
Published: May 2021

AbstractObjectivesCutaneous wound healing is one of the major medical problems worldwide. Epigenetic modifiers have been identified as important players in skin development, homeostasis and wound repair. SET domain–containing 2 (SETD2) is the only known histone H3K36 tri‐methylase; however, its role in skin wound healing remains unclear.Materials and MethodsTo elucidate the biological role of SETD2 in wound healing, conditional gene targeting was used to generate epidermis‐specific Setd2‐deficient mice. Wound‐healing experiments were performed on the backs of mice, and injured skin tissues were collected and analysed by haematoxylin and eosin (H&E) and immunohistochemical staining. In vitro, CCK8 and scratch wound‐healing assays were performed on Setd2‐knockdown and Setd2‐overexpression human immortalized keratinocyte cell line (HaCaT). In addition, RNA‐seq and H3K36me3 ChIP‐seq analyses were performed to identify the dysregulated genes modulated by SETD2. Finally, the results were validated in functional rescue experiments using AKT and mTOR inhibitors (MK2206 and rapamycin).ResultsEpidermis‐specific Setd2‐deficient mice were successfully established, and SETD2 deficiency resulted in accelerated re‐epithelialization during cutaneous wound healing by promoting keratinocyte proliferation and migration. Furthermore, the loss of SETD2 enhanced the scratch closure and proliferation of keratinocytes in vitro. Mechanistically, the deletion of Setd2 resulted in the activation of AKT/mTOR signalling pathway, while the pharmacological inhibition of AKT and mTOR with MK2206 and rapamycin, respectively, delayed wound closure.ConclusionsOur results showed that SETD2 loss promoted cutaneous wound healing via the activation of AKT/mTOR signalling.
ERK/Drp1‐dependent mitochondrial fission contributes to HMGB1‐induced autophagy in pulmonary arterial hypertension
Authors: Feng Wei , Wang Jian , Yan Xin , Zhang Qianqian , Chai Limin , Wang Qingting , Shi Wenhua , Chen Yuqian , Liu Jin , Qu Zhan , Li Shaojun , Xie Xinming , Li Manxiang 
Published: May 2021

AbstractObjectivesHigh‐mobility group box‐1 (HMGB1) and aberrant mitochondrial fission mediated by excessive activation of GTPase dynamin‐related protein 1 (Drp1) have been found to be elevated in patients with pulmonary arterial hypertension (PAH) and critically implicated in PAH pathogenesis. However, it remains unknown whether Drp1‐mediated mitochondrial fission and which downstream targets of mitochondrial fission mediate HMGB1‐induced pulmonary arterial smooth muscle cells (PASMCs) proliferation and migration leading to vascular remodelling in PAH. This study aims to address these issues.MethodsPrimary cultured PASMCs were obtained from male Sprague‐Dawley (SD) rats. We detected RNA levels by qRT‐PCR, protein levels by Western blotting, cell proliferation by Cell Counting Kit‐8 (CCK‐8) and EdU incorporation assays, migration by wound healing and transwell assays. SD rats were injected with monocrotaline (MCT) to establish PAH. Hemodynamic parameters were measured by closed‐chest right heart catheterization.ResultsHMGB1 increased Drp1 phosphorylation and Drp1‐dependent mitochondrial fragmentation through extracellular signal‐regulated kinases 1/2 (ERK1/2) signalling activation, and subsequently triggered autophagy activation, which further led to bone morphogenetic protein receptor 2 (BMPR2) lysosomal degradation and inhibitor of DNA binding 1 (Id1) downregulation, and eventually promoted PASMCs proliferation/migration. Inhibition of ERK1/2 cascade, knockdown of Drp1 or suppression of autophagy restored HMGB1‐induced reductions of BMPR2 and Id1, and diminished HMGB1‐induced PASMCs proliferation/migration. In addition, pharmacological inhibition of HMGB1 by glycyrrhizin, suppression of mitochondrial fission by Mdivi‐1 or blockage of autophagy by chloroquine prevented PAH development in MCT‐induced rats PAH model.ConclusionsHMGB1 promotes PASMCs proliferation/migration and pulmonary vascular remodelling by activating ERK1/2/Drp1/Autophagy/BMPR2/Id1 axis, suggesting that this cascade might be a potential novel target for management of PAH.
Bettering the devil you know: Can we drive predator adaptation to restore native fauna?
Authors: Manning Adrian D. , Andrewartha Tim A. , Blencowe Anton , Brewer Kyle , Gordon Iain J. , Evans Maldwyn J. 
Published: May 2021

AbstractPredation of threatened fauna by native and introduced predators can drive extinction and prevent population recovery. Most predator management involves exclusion or culling. Evidence suggests that exclusion may have detrimental effects on a prey species' predator awareness. At the same time, culling can cause selection of control‐resistant predators. There is increasing interest in harnessing evolutionary processes to drive adaptation of threatened fauna to cope, but there is limited attention on trying this from the predator direction. We need to shift the survival advantage away from predators that avoid lethal control, and go on to kill, towards those that demonstrate behaviors that reduce impact on threatened fauna. Instead of driving undesirable predator selection, could we select through management actions desirable traits to make them “less lethal” to threatened fauna? We draw on experimental research on predator aversion that suggests there may be an alternative way to mitigate the impacts of predators, while maintaining the learning opportunities of prey species. Using the case study of the invasive red fox in Australia, we propose a conceptual framework within which future research and management could occur to select for these desirable traits in predators and develop practical regimes for predator impact mitigation.
Current status and further potential of lung donation after circulatory death
Authors: Ehrsam Jonas P , Benden Christian , Immer Franz F , Inci Ilhan 
Published: May 2021

AbstractChronic organ shortage remains the most limiting factor in lung transplantation. To overcome this shortage, a minority of centers have started with efforts to reintroduce donation after circulatory death (DCD). This review aims to evaluate the experimental background, the current international clinical experience, and the further potential and challenges of the different DCD categories. Successful strategies have been implemented to reduce the problems of warm ischemic time, thrombosis after circulatory arrest, and difficulties in organ assessment, which come with DCD donation. From the currently reported results, controlled‐DCD lungs are an effective and safe method with good mid‐term and even long‐term survival outcomes comparable to donation after brain death (DBD). Primary graft dysfunction and onset of chronic allograft dysfunction seem also comparable. Thus, controlled‐DCD lungs should be ceased to be treated as marginal and instead be promoted as an equivalent alternative to DBD. A wide implementation of controlled‐DCD‐lung donation would significantly decrease the mortality on the waiting list. Therefore, further efforts in establishment of legislation and logistics are crucial. With regard to uncontrolled DCD, more data are needed analyzing long‐term outcomes. To help with the detailed assessment and improvement of uncontrolled or otherwise questionable grafts after retrieval, ex‐vivo lung perfusion is promising.
Heart transplantation from donors with left ventricular ejection fraction under forty percent
Authors: Poptsov Vitalii , Khatutskiy Valery , Skokova Anastasiia , Krasivskyi Ihor , Sabashnikov Anton , Merkle‐Storms Julia , Spirina Ekaterina 
Published: May 2021

AbstractBackgroundHeart transplantation (HTx) remains the treatment of choice for patients with end‐stage advanced heart failure. In 2016, the Shumakov National Medical Research Center commenced performing HTx from donors with abnormal left ventricular systolic function (LVEF < 40%). The aim of this study was to evaluate early and late outcomes of recipients after HTx from donors with abnormal LV systolic function.MethodsFour hundred eighty seven patients underwent HTx in our institution from January 2016 to December 2018. 27 (5.5%) patients were transplanted using cardiac allografts from donors with LVEF <40%.ResultsA total of 47 donors with LVEF <40% were evaluated for potential donation. Most heart donors revealed a left ventricular ejection fraction ranging between 30% and 40%. Twenty‐five recipients required urgent HTx. Four recipients presented with early allograft dysfunction. All surviving recipients demonstrated early (85.2%) or delayed (14.8%) recovery of systolic function (LVEF > 60%).ConclusionThe use of dysfunctional donor hearts with impaired LV systolic function may be a realistic approach for expanding the donor pool. However, organs from such donors should be used for recipient cohorts requiring an urgent HTx, particularly for those with pretransplant mechanical circulatory support allowing for hemodynamic support in cases of early graft dysfunction in the post‐transplant period.
National assessments of species vulnerability to climate change strongly depend on selected data sources
Authors: Scherrer Daniel , Esperon‐Rodriguez Manuel , Beaumont Linda J. , Barradas Víctor L. , Guisan Antoine 
Published: May 2021

AbstractAimCorrelative species distribution models (SDMs) are among the most frequently used tools for conservation planning under climate and land use changes. Conservation‐focused climate change studies are often conducted on a national or local level and can use different sources of occurrence records (e.g., local databases, national biodiversity monitoring) collated at different geographic extents. However, little is known about how these restrictions in geographic space (i.e., Wallacean shortfall) can lead to restrictions in environmental space (i.e., Hutchinsonian shortfall) and accordingly affect conclusions about a species’ vulnerability to climate change.LocationAmericas with a focus on Mexico.MethodsWe present an example study constructing SDMs for three Mexican tree species (Alnus acuminata,Liquidambar styracifluaandQuercus xalapensis) using datasets collated at a global (Americas), national (Mexico) and local (cloud forests of eastern Mexico) level to demonstrate the potential effects of a Wallacean shortfall on the estimation of the environmental niche—and thus on a Hutchinsonian shortfall—its projection in space and time and, consequently, on species’ potential vulnerability to climate change.ResultsThe consequence of using the three datasets was species‐specific and strongly depended on the extent to which the Wallacean shortfall affected estimations of environmental niches (i.e., Hutchinsonian shortfall). Where restrictions in geographic space lead to an underestimation of the environmental niche, vulnerability to climate change was estimated to be substantially higher. Additionally, the restrictions in geographic space may increase the likelihood of issues with non‐analogue climates, increasing model uncertainty.Main conclusionWe recommend assessing the extent to which a species’ entire realized environmental niche is captured within the target conservation area, and increasing the geographic extent, if needed, to account for environments and occurrences reflecting potential future conditions. This way, the risk of underestimating the climatic potential of the species (i.e., Hutchinsonian shortfall), as well as the errors induced by extrapolation into “locally novel” climates, can be minimized.
The top 10 research priorities in diabetes and pregnancy according to women, support networks and healthcare professionals
Authors: Ayman Göher , Strachan James A. , McLennan Niamh , Malouf Reem , Lowe‐Zinola Jack , Magdi Fida , Roberts Nia , Alderdice Fiona , Berneantu Iuliana , Breslin Niki , Byrne Caroline , Carnell Sonya , Churchill David , Grisoni Jeannie , Hirst Jane E. , Morris Anna , Murphy Helen R. , O’Brien Jane , Schmutz Caroline , Shah Kamini , Singal Ankita S. , Strachan Mark W. J. , Cowan Katherine , Knight Marian 
Published: May 2021

AbstractAimsTo undertake a Priority Setting Partnership (PSP) to establish priorities for future research in diabetes and pregnancy, according to women with experience of pregnancy, and planning pregnancy, with any type of diabetes, their support networks and healthcare professionals.MethodsThe PSP used established James Lind Alliance (JLA) methodology working with women and their support networks and healthcare professionals UK‐wide. Unanswered questions about the time before, during or after pregnancy with any type of diabetes were identified using an online survey and broad‐level literature search. A second survey identified a shortlist of questions for final prioritisation at an online consensus development workshop.ResultsThere were 466 responses (32% healthcare professionals) to the initial survey, with 1161 questions, which were aggregated into 60 unanswered questions. There were 614 responses (20% healthcare professionals) to the second survey and 18 questions shortlisted for ranking at the workshop. The top 10 questions were: diabetes technology, the best test for diabetes during pregnancy, diet and lifestyle interventions for diabetes management during pregnancy, emotional and well‐being needs of women with diabetes pre‐ to post‐pregnancy, safe full‐term birth, post‐natal care and support needs of women, diagnosis and management late in pregnancy, prevention of other types of diabetes in women with gestational diabetes, women's labour and birth experiences and choices and improving planning pregnancy.ConclusionsThese research priorities provide guidance for research funders and researchers to target research in diabetes and pregnancy that will achieve greatest value and impact.
Bridging the gap: A new integrated early intervention service for young people with complex mental health issues
Authors: White Caitlin , Nash Louise , Karageorge Aspasia , van der Pol Renae , Hunt Glenn E. , Hamilton Blake , Isobel Sophie 
Published: May 2021

AbstractAimTwo integrated headspace Early Intervention Teams (hEITs) were established in 2017 to bridge gaps between headspace, the national primary care youth mental health programme in Australia, and the state funded secondary and tertiary mental health services. This study aims to describe functioning and outcomes of patients referred to hEIT over a 6‐month period.MethodsA retrospective file audit was conducted for all patients accepted into the service over a 6‐month period in 2018. Measures of distress, functioning and client satisfaction were collected and analysed. Exemplar vignettes were created to construct hypothetical examples and illustrate research findings.ResultsAt admission, the three most common presentations were depression/anxiety, trauma and stress related, and psychotic disorders. During their time in the service, young people displayed a statistically significant improvement in functioning, reduction in self‐harm in those 18 years and under, and a trend to reduction in distress scores. hEIT delivered a broad range of services covering social, occupational, educational, medical and mental health care, and the service was experienced positively by the patient cohort.ConclusionshEIT appears to meet the needs of young people requiring greater care than primary care services can deliver. The integrated, wrap‐around care coordination facilitates treatments across social, educational and health domains. Further exploration of young people who disengage from care, improved outcome data reporting and economic evaluation are indicated.
Relationship between plasma rabbit anti‐thymocyte globulin concentration and immunosuppressive therapy response in patients with severe aplastic anemia
Authors: Narita Atsushi , Muramatsu Hideki , Ichikawa Daisuke , Hamada Motoharu , Nishikawa Eri , Suzuki Kyogo , Kawashima Nozomu , Okuno Yusuke , Nishio Nobuhiro , Hama Asahito , Yamazaki Hirohito , Nakao Shinji , Kojima Seiji , Takahashi Yoshiyuki 
Published: May 2021

AbstractObjectivesPatients with acquired aplastic anemia (AA) without HLA‐matched sibling donors or aged >40 years receive immunosuppressive therapy (IST) with anti‐thymocyte globulin (ATG). We investigated the relationship between plasma rabbit ATG (r‐ATG) concentration and IST response.MethodsFrom May 2012 to October 2017, 81 patients with severe AA who required initial IST were included. A 1:1 block randomization was employed for 2.5 and 3.5 mg/kg doses of r‐ATG.ResultsNo significant difference in response rates was observed between the 2.5 and 3.5 mg/kg groups (63% vs. 58%, P = .894). Median r‐ATG concentrations on days 14 and 28 after IST were 15.2 (0.0‐97.7) and 1.8 (0.0‐74.9 µg/mL), respectively. According to r‐ATG concentration, response rates were significantly higher in the group with higher r‐ATG concentration than in those with lower r‐ATG concentration (day 14, 88% vs. 52%; P = .006 and day 28, 79% vs. 46%; P = .005). In multivariate analysis, higher r‐ATG concentrations at day 28 were independent predictors of favorable response to IST at 6 months (odds ratio, 0.29; 95% confidence interval, 0.09‐0.93; P = .037).ConclusionsThe present data indicate that higher r‐ATG concentration at day 28 resulted in improved IST response.
Guillain–Barré syndrome in Eastern China: A study of 595 patients
Authors: Song Yan , Zhang Yong , Yuki Nobuhiro , Wakerley Benjamin R. , Liu Chen , Song Jin , Wang Min , Feng Xungang , Hao Yanlei , Wang Yuzhong 
Published: May 2021

AbstractBackground and purposeThis study aimed to investigate geographical differences in the clinical features of Guillain–Barré syndrome (GBS) between patients from our region in Eastern China and patients from other areas.MethodsA total of 595 patients fulfilling the diagnostic criteria ​for GBS or its variants were included from two large hospitals located in Eastern China. Data collection included demographics, antecedent events, clinical presentation and signs, electrophysiological subtypes, treatment, complications during hospitalization, clinical severity at nadir, and outcome at 12 months, and these data were compared to data from a study conducted in Southern China and the Europe/Americas section of the International GBS Outcome Study.ResultsThe median (interquartile range) age of patients was 50 (36–61) years, the ratio of men to women was 1.2, and 49% of patients had antecedent events. Patients in our region of Eastern China had pure motor predominant GBS (158/340, 46%) and 30% (103/340) had complications during hospitalization. Patients aged over 60 years had a lower frequency of antecedent infections and single, axonal subtypes, but higher disability scores at entry, nadir, and 12 months. When compared with the Europe/Americas data, our patients had a lower frequency of antecedent infection (46% vs. 63%), cranial nerve involvement (43% vs. 49%), sensory deficits (45% vs. 69%), pain (19% vs. 57%) and mechanical ventilation (11% vs. 17%), but a higher frequency of axonal subtype (35% vs. 6%). There was a higher frequency of patients with antecedent gastroenteritis (16% vs. 8%), mechanical ventilation (11% vs. 8%) and axonal subtypes (35% vs. 19%) in our region in Eastern China than in Southern China.ConclusionsPatients with GBS in Eastern China showed significant clinical heterogeneity and differences when compared to other geographic areas.
Increased branched‐chain amino acids at baseline and hours before a spontaneous seizure in the human epileptic brain
Authors: Ong Caroline , Damisah Eyiyemisi C. , Gruenbaum Shaun E. , Dhaher Roni , Deng Yanhong , Sandhu Mani Ratnesh S. , Zaveri Hitten P. , Spencer Dennis D. , Eid Tore 
Published: May 2021

AbstractThe objective of this study was to monitor the extracellular brain chemistry dynamics at baseline and in relation to spontaneous seizures in human patients with refractory epilepsy. Thirty patients with drug‐resistant focal epilepsy underwent intracranial electroencephalography and concurrent brain microdialysis for up to 8 continuous days. Extracellular brain glutamate, glutamine, and the branched‐chain amino acids (BCAAs) valine, leucine, and isoleucine were quantified in the dialysis samples by liquid chromatography–tandem mass spectrometry. Extracellular BCAAs and glutamate were chronically elevated at baseline by approximately 1.5–3‐fold in brain regions of seizure onset and propagation versus regions not involved by seizures. Moreover, isoleucine increased significantly above baseline as early as 3 h before a spontaneous seizure. BCAAs play important roles in glutamatergic neurotransmission, mitochondrial function, neurodegeneration, and mammalian target of rapamycin signaling. Because all of these processes have been implicated in epilepsy, the results suggest a novel role of BCAAs in the pathogenesis of spontaneous seizures.
Shaping cultural participation through social media
Authors: Arnaboldi Michela , Diaz Lema Melisa L 
Published: May 2021

AbstractThe public sector has embraced a user‐orientation paradigm, which has expanded through the open and democratic medium of social media. Although the potential of this digital technology and its visible outcomes have been analyzed in previous studies, there is virtually nothing on the complexity behind its implementation. This paper uses a case study involving three Italian museums to explore how social media strategy is shaped and enacted through their day‐to‐day business and activity. Museums are an ideal field for this kind of research because of the central role played by cultural participation and social media's critical function in pursuing new audiences. The study reveals a deep change to practice, touching praxes and practitioner skills, and modifying strategies planned around the user's approach, in the duality between authoritative and democratic voices. The findings disclose an emergent heterogeneity that is mapped along social media practices and the various associations linked to the praxes, opening the way for future studies concerned with the link between a user's (traditional) physical experience on social media and the level of democracy in user engagement.