bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combination chemoradiotherapy with temozolomide, vincristine, and interferon-β might improve outcomes regardless of O6-methyl-guanine-DNA-methyltransferase (MGMT) promoter methylation status in newly glioblastoma
Authors: Asano Kenichiro , Fumoto Toshio , Matsuzaka Masashi , Hasegawa Seiko , Suzuki Naoya , Akasaka Kenichi , Katayama Kosuke , Kamataki Akihisa , Kurose Akira , Ohkuma Hiroki 
Published: July 2021

Abstract
Background
This investigator-initiated, open-label, single-arm, single-institute study was conducted to investigate the effectiveness of induction combination chemoradiotherapy and long-term maintenance therapy with temozolomide (TMZ) plus interferon (IFN)-β for glioblastoma.

Methods
The initial induction combination chemoradiotherapy comprised radiotherapy plus TMZ plus vincristine plus IFN-β. Maintenance chemotherapy comprised monthly TMZ, continued for 24–50 cycles, plus weekly IFN-β continued for as long as possible. The primary endpoint was 2-year overall survival (2y-OS). The study protocol was to be considered valid if the expected 2y-OS was over 38% and the lower limit of the 95% confidence interval (CI) was no less than 31.7% compared with historical controls, using Kaplan-Meier methods. Secondary endpoints were median progression-free survival (mPFS), median OS (mOS), 5-year OS rate (5y-OS), and mPFS and mOS classified according to MGMT promoter methylation status.

Results
Forty-seven patients were analyzed. The 2y-OS was 40.7% (95%CI, 27.5–55.4%). The mPFS and mOS were 11.0 months and 18.0 months, respectively, and 5y-OS was 20.3% (95%CI, 10.9–34.6%). The mPFS in groups with and without MGMT promoter methylation in the tumor was 10.0 months and 11.0 months (p = 0.59), respectively, and mOS was 24.0 months and 18.0 months (p = 0.88), respectively. The frequency of grade 3/4 neutropenia was 19.1%.

Conclusions
The 2y-OS with induction multidrug combination chemoradiotherapy and long-term maintenance therapy comprising TMZ plus IFN-β tended to exceed that of historical controls, but the lower limit of the 95%CI was below 31.7%. Although the number of cases was small, this protocol may rule out MGMT promoter methylation status as a prognostic factor.

Trial registration
University Hospital Medical Information Network (number UMIN000040599).
Cancer cell line microarray as a novel screening method for identification of radioresistance biomarkers in head and neck squamous cell carcinoma
Authors: Routila Johannes , Suvila Karri , Grénman Reidar , Leivo Ilmo , Westermarck Jukka , Ventelä Sami 
Published: July 2021

Abstract
Background
Currently, no clinically useful biomarkers for radioresistance are available in head and neck squamous cell carcinoma (HNSCC). This study assesses the usefulness of Cell Line Microarray (CMA) method to enhance immunohistochemical screening of potential immunohistochemical biomarkers for radioresistance in HNSCC cell lines.

Methods
Twenty-nine HNSCC cell lines were cultured, cell pellets formalin-fixed, paraffin-embedded, and arrayed. Radioresistance features of the cell lines were combined to immunohistochemical stains for p53, NDFIP1, EGFR, stem cell marker Oct4, and PP2A inhibitor CIP2A.

Results
Expression of p53, EGFR or CIP2A did not indicate intrinsic radioresistance in vitro. Stem cell marker Oct4 nuclear positivity and NDFIP1 nuclear positivity was correlated with increased intrinsic radioresistance.

Conclusion
The usefulness of CMA in analysis of HNSCC cell lines and discovery of biomarkers is demonstrated. CMA is very well adapted to both testing of antibodies in a large panel of cell lines as well as correlating staining results with other cell line characteristics. In addition, CMA-based antibody screening proved an efficient and relatively simple method to identify potential radioresistance biomarkers in HNSCC.
Perceptions, emotional reactions and needs of adolescent psychiatric inpatients during the COVID-19 pandemic: a qualitative analysis of in-depth interviews
Authors: Giannakopoulos George , Mylona Savvina , Zisimopoulou Anastasia , Belivanaki Maria , Charitaki Stella , Kolaitis Gerasimos 
Published: July 2021

Abstract
Background
The new coronavirus pandemic (COVID-19) has been accompanied by severe psychological pressure on the entire population. However, little is known about how this pandemic could affect the more vulnerable population with severe mental illness.

Aims
To explore adolescent psychiatric inpatients’ perceptions, emotional reactions and needs during the first wave of the COVID-19 pandemic.

Methods
Individual in-depth interviews were conducted with nine psychiatric inpatients aged 12–17 years. Through open-ended questions, interviewers initiated five themes: (a) knowledge about coronavirus pandemic, (b) changes in everyday routine due to the pandemic, (c) adolescents’ feelings about the pandemic, (d) adolescents’ positive thoughts and behaviors, and (e) how the social environment can help adolescents deal with the pandemic-related situation. A thematic analysis was conducted using line-by-line open coding.

Results
Regarding their knowledge of the impact of the current pandemic, almost all adolescents focused on information about the nature of coronavirus and on existing crisis management practices. Almost all patients identified predominantly negative changes due to the quarantine state, including restrictions on both social life and personal freedom as well as excessive contact with family members during home isolation. As far as their emotions were concerned, adolescents did acknowledge anxiety about self-harm and harming their loved ones as well as mood swings within the family nucleus; anxiety was also manifested about the unknown and the management of the pandemic in other countries. Avoidance of thought rumination about the coronavirus and its consequences, positive thinking and looking towards the future were reported as constructive strategies for coping with challenging emotions. Additionally, a sense of belongingness seems to have been playing a pivotal role in the adolescents coping strategies. Trust in the authorities and the community was another quite noteworthy point that emerged during the interviews. Lastly, our findings indicated adolescents’ benefit from receiving balanced health messaging coupled with balanced thinking within their social and family environment.

Conclusions
Enhanced comprehension of possible mediating psychological pathways is needed to help clinicians, researchers, and decision-makers to avert the deterioration of mental disorders and overall functioning, as well as additional stress-related disorders.
Mental health and wellbeing coordinators in primary schools to support student mental health: protocol for a quasi-experimental cluster study
Authors: Darling S. , Dawson G. , Quach J. , Smith R. , Perkins A. , Connolly A. , Smith A. , Moore C. L. , Ride J. , Oberklaid F. 
Published: July 2021

Abstract
Background
Half of mental health disorders begin before the age of 14, highlighting the importance of prevention and early-intervention in childhood. Schools have been identified globally by policymakers as a platform to support good child mental health; however, the majority of the research is focused on secondary schools, with primary schools receiving very little attention by comparison. The limited available evidence on mental health initiatives in primary schools is hindered by a lack of rigorous evaluation. This quasi-experimental cluster study aims to examine the implementation and effectiveness of a Mental Health and Wellbeing Co-ordinator role designed to build mental health capacity within primary schools.

Methods
This is a primary (ages 5–12) school-based cluster quasi-experimental study in Victoria, Australia. Before baseline data collection, 16 schools selected by the state education department will be allocated to intervention, and another 16 matched schools will continue as ‘Business as Usual’. In intervention schools, a mental health and well-being coordinator will be recruited and trained, and three additional school staff will also be selected to receive components of the mental health training. Surveys will be completed by consenting staff (at 2-, 5-, 10- and 17-months post allocation) and by consenting parents/carers (at 3-, 10- and 17-months post allocation) in both intervention and business as usual schools. The primary objective is to assess the change in teacher’s confidence to support student mental health and wellbeing using the School Mental Health Self-Efficacy Teacher Survey. Secondary objectives are to assess the indirect impact on systemic factors (level of support, prioritisation of child mental health), parent and teachers’ mental health literacy (stigma, knowledge), care access (school engagement with community-based services), and student mental health outcomes. Implementation outcomes (feasibility, acceptability, and fidelity) and costs will also be evaluated.

Discussion
The current study will examine the implementation and effectiveness of having a trained Mental Health and Wellbeing Coordinator within primary schools. If the intervention increases teachers’ confidence to support student mental health and wellbeing and builds the capacity of primary schools it will improve student mental health provision and inform large-scale mental health service reform.

Trial registration
The trial was retrospectively registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) on July 6, 2021. The registration number is ACTRN12621000873820.
Preprints in times of COVID19: the time is ripe for agreeing on terminology and good practices
Authors: Ravinetto Raffaella , Caillet Céline , Zaman Muhammad H. , Singh Jerome Amir , Guerin Philippe J. , Ahmad Aasim , Durán Carlos E. , Jesani Amar , Palmero Ana , Merson Laura , Horby Peter W. , Bottieau E. , Hoffmann Tammy , Newton Paul N. 
Published: July 2021

AbstractOver recent years, the research community has been increasingly using preprint servers to share manuscripts that are not yet peer-reviewed. Even if it enables quick dissemination of research findings, this practice raises several challenges in publication ethics and integrity. In particular, preprints have become an important source of information for stakeholders interested in COVID19 research developments, including traditional media, social media, and policy makers. Despite caveats about their nature, many users can still confuse pre-prints with peer-reviewed manuscripts. If unconfirmed but already widely shared first-draft results later prove wrong or misinterpreted, it can be very difficult to “unlearn” what we thought was true. Complexity further increases if unconfirmed findings have been used to inform guidelines. To help achieve a balance between early access to research findings and its negative consequences, we formulated five recommendations: (a) consensus should be sought on a term clearer than ‘pre-print’, such as ‘Unrefereed manuscript’, “Manuscript awaiting peer review” or ‘’Non-reviewed manuscript”; (b) Caveats about unrefereed manuscripts should be prominent on their first page, and each page should include a red watermark stating ‘Caution—Not Peer Reviewed’; (c) pre-print authors should certify that their manuscript will be submitted to a peer-review journal, and should regularly update the manuscript status; (d) high level consultations should be convened, to formulate clear principles and policies for the publication and dissemination of non-peer reviewed research results; (e) in the longer term, an international initiative to certify servers that comply with good practices could be envisaged.
Psychometric properties of the ethical conflict in nursing questionnaire critical care version among Chinese nurses: a cross-sectional study
Authors: Liu Yuanfei , Cui Nianqi , Zhang Yuping , Wang Xiyi , Zhang Hui , Chen Dandan , Sun Shunxia , Jin Jingfen 
Published: July 2021

AbstractBackgroundEthical conflicts are common in the critical care setting, and have compromised job satisfaction and nursing care quality. Using reliable and valid instruments to measure the ethical conflict is essential. This study aimed to translate the Ethical Conflict in Nursing Questionnaire — Critical Care Version into Chinese and determine the reliability and validity in the population of Chinese nurses.MethodsResearchers obtained permission and followed the translation-backward method to develop the Chinese version of the Ethical Conflict in Nursing Questionnaire — Critical Care Version (ECNQ-CCV-C). Relevant psychometric properties were selected according to the Consensus-based standards for the selection of health status measurement instruments checklist. Critical care nurses were recruited from two tertiary public hospitals in Hangzhou, Zhejiang Province, and Kunming, Yunnan Province. Of the 264 nurses we approached, 248 gave their consent and completed the study.ResultsThe ECNQ-CCV-C achieved Cronbach’s alphas 0.902 and McDonald’s omega coefficient 0.903. The test-retest reliability was satisfactory within a 2-week interval (intraclass correlation coefficient = 0.757). A unidimensional structure of the ECNQ-CCV-C was determined. Confirmatory factor analysis supported acceptable structure validity. Concurrent validity was confirmed by a moderate relation with a measure for hospital ethical climate (r = − 0.33,p < 0.01). The model structure was invariant across different gender groups, with no floor/ceiling effect.ConclusionsThe ECNQ-CCV-C demonstrated acceptable reliability and validity among Chinese nurses and had great clinical utility in critical care nursing.
Rabbit haemorrhagic disease virus Lagovirus europaeus/GI.1d strain: genome sequencing, in vivo virus replication kinetics, and viral dose effect
Authors: Droillard Clément , Lemaitre Evelyne , Amelot Michel , Blanchard Yannick , Keita Alassane , Eterradossi Nicolas , Le Gall-Reculé Ghislaine 
Published: July 2021

Abstract
Background
Rabbit haemorrhagic disease virus Lagovirus europaeus/GI.1d variant (GI.1d/RHDV) was identified in 1990 in France, and until the emergence of the new genotype GI.2, it was the main variant circulating in the country. The early stages of RHDV infection have been described in a few studies of rabbits experimentally infected with earlier strains, but no information was given on the minimum infective dose. We report the genomic and phenotypic characterisation of a GI.1d/RHDV strain collected in 2000 in France (GI.1d/00–21).

Results
We performed in vivo assays in rabbits to study virus replication kinetics in several tissues at the early stage of infection, and to estimate the minimum infective dose. Four tested doses, negligible (10− 1 viral genome copies), low (104), high (107) and very high (1011) were quantified using a method combining density gradient centrifugation of the viral particles and an RT-qPCR technique developed to quantify genomic RNA (gRNA). The GI.1d/00–21 genome showed the same genomic organisation as other lagoviruses; however, a substitution in the 5′ untranslated region and a change in the potential p23/2C-like helicase cleavage site were observed. We showed that the liver of one of the two rabbits inoculated via the oral route was infected at 16 h post-infection and all tissues at 39 h post-infection. GI.1d/00–21 induced classical RHD signs (depression) and lesions (haemorrhage and splenomegaly). Although infective dose estimation should be interpreted with caution, the minimum infective dose that infected an inoculated rabbit was lower or equal to 104 gRNA copies, whereas between 104 and 107 gRNA copies were required to also induce mortality.

Conclusions
These results provide a better understanding of GI.1d/RHDV infection in rabbits. The genome analysis showed a newly observed mutation in the 5′ untranslated region of a lagovirus, whose role remains unknown. The phenotypic analysis showed that the pathogenicity of GI.1d/00–21 and the replication kinetics in infected organs were close to those reported for the original GI.1 strains, and could not alone explain the observed selective advantage of the GI.1d strains. Determining the minimum dose of viral particles required to cause mortality in rabbits is an important input for in vivo studies.
Rare hereditary nonspherocytic hemolytic anemia caused by a novel homozygous mutation, c.301C > A, (Q101K), in the AK1 gene in an Indian family
Authors: Dongerdiye Rashmi , Sampagar Abhilasha , Devendra Rati , Warang Prashant , Kedar Prabhakar 
Published: July 2021

Abstract
Background
Adenylate kinase (AK) deficiency is a rare red cell enzymopathy associated with moderate to severe congenital nonspherocytic hemolytic anemia, along with mental and psychomotor retardation (in exceptional cases). Only ten mutations have been detected in the AK1 gene to date. In this study, we aimed to diagnose the unexplained issue of haemolytic anaemia and offer antenatal screening to the family.

Methods
Genomic DNA was isolated from whole blood by a standard protocol. Targeted next-generation sequencing (t-NGS) was performed to identify pathogenic variants in the patient and control samples. A chronic villus sample was collected at 11 weeks of gestation from the mother, and molecular testing was performed. Genetic confirmation was concluded by Sanger DNA sequencing. Bioinformatics tools predicted the pathogenicity of the variant.

Results
t-NGS revealed a homozygous variant (c.301C > A, p. Gln101Lys) in the AK1 gene in the patient and heterozygosity in the fetus and parental samples. The prediction tools SIFT, Polyphen2, Provean, PMUT, Mutation taster, and Mutation Assessor, confirmed the damaging effect of the variant on the AK1 protein structure

Conclusion
We have presented a novel mutation in the AK1 gene (p. Gln101Lys) associated with adenylate kinase deficiency. It is the first prenatal diagnosis of AK deficiency in India, where heterogeneity is exceptionally high.
Expression and prognostic significance of CBX2 in colorectal cancer: database mining for CBX family members in malignancies and vitro analyses
Authors: Zhou He , Xiong Yongfu , Liu Zuoliang , Hou Songlin , Zhou Tong 
Published: July 2021

Abstract
Background
The Chromobox (CBX) domain protein family, a core component of polycomb repressive complexes 1, is involved in transcriptional repression, cell differentiation, and program development by binding to methylated histone tails. Each CBX family member plays a distinct role in various biological processes through their own specific chromatin domains, due to differences in conserved sequences of the CBX proteins. It has been demonstrated that colorectal cancer (CRC) is a multiple-step biological evolutionary process, whereas the roles of the CBX family in CRC remain largely unclear.

Methods
In the present study, the expression and prognostic significance of the CBX family in CRC were systematically analyzed through a series of online databases, including Cancer Cell Line Encyclopedia (CCLE), Oncomine, Human Protein Atlas (HPA), and Gene Expression Profiling Interactive Analysis (GEPIA). For in vitro verification, we performed cell cloning, flow cytometry and transwell experiments to verify the proliferation and invasion ability of CRC cells after knocking down CBX2.

Results
Most CBX proteins were found to be highly expressed in CRC, but only the elevated expression of CBX2 could be associated with poor prognosis in patients with CRC. Further examination of the role of CBX2 in CRC was performed through several in vitro experiments. CBX2 was overexpressed in CRC cell lines via the CCLE database and the results were verified by RT-qPCR. Moreover, the knockdown of CBX2 significantly suppressed CRC cell proliferation and invasion. Furthermore, the downregulation of CBX2 was found to promote CRC cell apoptosis.

Conclusions
Based on these findings, CBX2 may function as an oncogene and potential prognostic biomarker. Thus, the association between the abnormal expression of CBX2 and the initiation of CRC deserves further exploration.
Classification of microcalcification clusters in digital breast tomosynthesis using ensemble convolutional neural network
Authors: Xiao Bingbing , Sun Haotian , Meng You , Peng Yunsong , Yang Xiaodong , Chen Shuangqing , Yan Zhuangzhi , Zheng Jian 
Published: July 2021

Abstract
Background
The classification of benign and malignant microcalcification clusters (MCs) is an important task for computer-aided diagnosis (CAD) of digital breast tomosynthesis (DBT) images. Influenced by imaging method, DBT has the characteristic of anisotropic resolution, in which the resolution of intra-slice and inter-slice is quite different. In addition, the sharpness of MCs in different slices of DBT is quite different, among which the clearest slice is called focus slice. These characteristics limit the performance of CAD algorithms based on standard 3D convolution neural network (CNN).

Methods
To make full use of the characteristics of the DBT, we proposed a new ensemble CNN, which consists of the 2D ResNet34 and the anisotropic 3D ResNet to extract the 2D focus slice features and 3D contextual features of MCs, respectively. Moreover, the anisotropic 3D convolution is used to build 3D ResNet to avoid the influence of DBT anisotropy.

Results
The proposed method was evaluated on 495 MCs in DBT images of 275 patients, which are collected from our collaborative hospital. The area under the curve (AUC) of receiver operating characteristic (ROC) and accuracy of classifying benign and malignant MCs using decision-level ensemble strategy were 0.8837 and 82.00%, which were significantly higher than the experimental results of 2D ResNet34 (AUC: 0.8264, ACC: 76.00%) and anisotropic 3D ResNet (AUC: 0.8455, ACC: 76.00%). Compared with the results of 3D features classification in the radiomics, the AUC of the deep learning method with decision-level ensemble strategy was improved by 0.0435, and the F1 score was improved from 79.37 to 85.71%. More importantly, the sensitivity increased from 78.13 to 84.38%, and the specificity increased from 66.67 to 77.78%, which effectively reduced the false positives of diagnosis

Conclusion
The results fully prove that the ensemble CNN can effectively integrate 2D features and 3D features, improve the classification performance of benign and malignant MCs in DBT, and reduce the false positives.