bluuebunny/crossref_metadata_2025_split huggingface dataset:
MONTAGE: a new tool for high-throughput detection of mosaic copy number variation
Authors: Glessner Joseph T. , Chang Xiao , Liu Yichuan , Li Jin , Khan Munir , Wei Zhi , Sleiman Patrick M. A. , Hakonarson Hakon 
Published: February 2021

Abstract
Background
Not all cells in a given individual are identical in their genomic makeup. Mosaicism describes such a phenomenon where a mixture of genotypic states in certain genomic segments exists within the same individual. Mosaicism is a prevalent and impactful class of non-integer state copy number variation (CNV). Mosaicism implies that certain cell types or subset of cells contain a CNV in a segment of the genome while other cells in the same individual do not. Several studies have investigated the impact of mosaicism in single patients or small cohorts but no comprehensive scan of mosaic CNVs has been undertaken to accurately detect such variants and interpret their impact on human health and disease.

Results
We developed a tool called Montage to improve the accuracy of detection of mosaic copy number variants in a high throughput fashion. Montage directly interfaces with ParseCNV2 algorithm to establish disease phenotype genome-wide association and determine which genomic ranges had more or less than expected frequency of mosaic events. We screened for mosaic events in over 350,000 samples using 1% allele frequency as the detection limit. Additionally, we uncovered disease associations of multiple phenotypes with mosaic CNVs at several genomic loci. We additionally investigated the allele imbalance observations genome-wide to define non-diploid and non-integer copy number states.

Conclusions
Our novel algorithm presents an efficient tool with fast computational runtime and high levels of accuracy of mosaic CNV detection. A curated mosaic CNV callset of 3716 events in 2269 samples is presented with comparability to previous reports and disease phenotype associations. The new algorithm can be freely accessed via: https://github.com/CAG-CNV/MONTAGE.
Ascorbic acid modulation by ABI4 transcriptional repression of VTC2 in the salt tolerance of Arabidopsis
Authors: Kakan Xiamusiya , Yu Yanwen , Li Shenghui , Li Xiaoying , Huang Rongfeng , Wang Juan 
Published: February 2021

Abstract
Background
Abscisic acid (ABA) plays an important role in plant abiotic stress responses, and ABA INSENSITIVE 4 (ABI4) is a pivotal transcription factor in the ABA signaling pathway. In Arabidopsis, ABI4 negatively regulates salt tolerance; however, the mechanism through which ABI4 regulates plant salt tolerance is poorly understood. Our previous study showed that ABI4 directly binds to the promoter of the VITAMIN C DEFECTIVE 2 (VTC2) gene, inhibiting the transcription of VTC2 and ascorbic acid (AsA) biosynthesis.

Results
In the present study, we found that treatment with exogenous AsA could alleviate salt stress sensitivity of ABI4-overexpressing transgenic plants. The decreased AsA content and increased reactive oxygen species (ROS) levels in ABI4-overexpressing seedlings under salt treatment indicated that AsA-promoted ROS scavenging was related to ABI4-mediated salt tolerance. Gene expression analysis showed that ABI4 was induced at the early stage of salt stress, giving rise to reduced VTC2 expression. Accordingly, the abundance of the VTC2 protein decreased under the same salt stress conditions, and was absent in the ABI4 loss-of-function mutants, suggesting that the transcriptional inhibition of ABI4 on VTC2 resulted in the attenuation of VTC2 function. In addition, other encoding genes in the AsA biosynthesis and recycling pathways showed different responses to salt stress, demonstrating that AsA homeostasis is complicated under salinity stress.

Conclusions
This study elucidates the negative modulation of ABI4 in salt stress tolerance through the regulation of AsA biosynthesis and ROS accumulation in plants.
Binocular integration and stereopsis in children with television torticollis
Authors: Yang Cheng , Huang Wanshu , Cui Ying , Zhang Guanrong , Wang Dongmei , Xie Wenjuan , Wiederhold Mark , Wiederhold Brenda , Chu Hang , Yan Li , Zeng Jin 
Published: February 2021

Abstract
Background
To observe the characteristics of binocular integration and stereopsis in children with television torticollis.

Methods
A retrospective study was carried out, where data were collected from 25 children with television torticollis as the disease group after refractive error correction and 25 normal children as the control group. A virtual reality system was used to assess and analyze the characteristics of binocular integration by a contrast balance test and binocular stereopsis.

Results
The 25 children in the disease group included 17 males and 8 females with an average age of 7.5 ± 1.9 years old and an average binocular spherical equivalent of − 0.35 ± 1.46D. The 25 children in the control group were also 17 males and 8 females with an average age of 7.3 ± 2.2 years old and the average binocular spherical equivalent of − 0.48 ± 0.93D. No significant differences were found in the horizontal bar contrast balance test between the 2 groups at near and far distances. Near-distance vertical bar contrast balance test was normal in 23 subjects and suppressed in 2 subjects in the control group, while it was normal in 13 subjects and suppressed in 12 subjects in the disease group, which showed a statistically significant difference (P = 0.002). Far distance vertical bar contrast balance test was normal in 24 subjects and suppressed in 1 subject in the control group, normal in 7 subjects and suppressed in 18 subjects in the disease group, showing a statistically significant difference (P = 0.000). All subjects in the 2 groups showed 100〞 as near distance stereoacuity. At far distance, the mean stereoacuity was 176.00〞 ± 92.56〞 in the control group, and 352.00〞 ± 270.99〞 in the disease group, with a statistically significant difference (P = 0.011).

Conclusion
By using virtual reality technology, defects in binocular visual function were found in children whose television torticollis persisted after regular refractive error correction. Television torticollis may be associated with the deficit of binocular integration for vertical bars and far distance stereopsis.
The impact of COVID-19 pandemic outbreak on education and mental health of Chinese children aged 7–15 years: an online survey
Authors: Ma Zhongren , Idris Sakinah , Zhang Yinxia , Zewen Liu , Wali Amaad , Ji Yunpeng , Pan Qiuwei , Baloch Zulqarnain 
Published: February 2021

Abstract
Background
The emerging of psychological problems triggered by COVID-19 particularly in children have been extensively highlighted and emphasized, but original research in this respect is still lagging behind. Therefore, we designed this study to evaluate the impact of COVID-19 pandemic on mental health and the effectiveness and attitudes towards online education among Chinese children aged 7–15 years.

Methods
A detailed questionnaire, comprising of 62 questions was designed and parents or caretakers of 7 to 15 years old children were invited to participate via WeChat, a multi-purpose messaging, social media and mobile payment app, which is widely used by the Chinese population. A total of 668 parents across different regions of China were included.

Results
During COVID-19 pandemic, 20.7 and 7.2% children report experiencing post-traumatic stress disorder (PTSD) and depressive symptoms due to the COVID-19 pandemic. PTSD and SMFQ-P scores are significantly higher in middle school and boarding school students compared to primary and day school students. Multiple logistic regression analysis revealed that school system and province of origin are factors significantly associated with developing PSTD symptoms. 44.3% respondents feel online education is effective in gaining knowledge and improving practical and communications skills. 78.0% believe the online education system is efficient. Overall 79.8% respondents are satisfied and children can adapt to this new education system. During the COVID-19 pandemic, we found 1 in five children have PTSD and 1 in 14 children have depressive symptoms.

Conclusion
In summary, COVID-19 epidemic has caused PTSD and depression symptoms among Chinese children aged 7 to 15 years. In general, a large proportion of respondents are satisfied with online education, but still a substantial proportion of students are not comfortable with this new form of learning. Authorities should optimize online education systems and implement effective interventions to cope with the psychological effects of COVID-19 on children, as it is affecting the global population and remains uncertain when it will end.
Diagnosis and surgical treatment of primary isolated aggressive lumbar myeloid sarcoma: a rare case report and review of the literatures
Authors: Bai Cheng-Rui , Li Xiang , Wang Jing-Shi , Li Jin-Jun , Liu Ning , Fei Qi , Li Dong , Yang Yong 
Published: February 2021

Abstract
Background
Myeloid sarcoma is a rare, extramedullary, solid tumor derived from immature myeloid cell precursors. It is most frequently accompanied by acute myelogenous leukemia, though infrequently found in non-acute myelogenous leukemia patients. The tumor may involve any part of the body, but the lumbar spine is seldom involved. The present case study aims to understand the diagnosis and surgical treatment of a rare primary isolated myeloid sarcoma of the lumbar spine causing aggressive spinal cord compression in a non-acute myelogenous leukemia patient.

Case presentation
A 29-year-old man complained of an aggressive radiating pain to the lower extremities and moderate dysuria with a Visual Analogue Scale score that gradually increased from 3 to 8. Lumbar enhanced magnetic resonance imaging and computed tomography revealed a lumbar canal lesion at lumbar spine L2 to L4 with spinal cord compression. A whole body bone scan with fused single photon emission computed tomography/computed tomography demonstrated abnormal 99mTc-methylene diphosphonate accumulation in the L3 lamina and spinous process. No evidence of infection or hematology disease was observed in laboratory tests.
Due to rapid progression of the symptoms and lack of a clear diagnosis, decompression surgery was performed immediately. During the operation, an approximately 6.0 × 2.5 × 1.2 cm monolithic, fusiform, soft mass in the epidural space and associated lesion tissues were completely resected. The radiating pain was relieved immediately and the dysuria disappeared within 1 week. Intraoperative pathological frozen section analysis revealed a hematopoietic malignant tumor and postoperative immunohistochemistry examination confirmed the diagnosis of myeloid sarcoma.

Conclusions
The primary isolated aggressive lumbar myeloid sarcoma is rarely seen, the specific symptoms and related medical history are unclear. Surgery and hematological treatment are effective for understanding and recognizing this rare tumor.
Paradigms about the COVID-19 pandemic: knowledge, attitudes and practices from medical students
Authors: Lincango-Naranjo Eddy , Espinoza-Suarez Nataly , Solis-Pazmino Paola , Vinueza-Moreano Paul , Rodriguez-Villafuerte Santiago , Lincango-Naranjo Jose , Barberis-Barcia Giuseppe , Ruiz-Sosa Carlos , Rojas-Velasco Giovanni , Gravholt Derek , Golembiewski Elizabeth , Soto-Becerra Percy , Khan Maryam , Ortiz-Prado Esteban 
Published: February 2021

Abstract
Background
As the disease caused by the novel coronavirus has spread globally, there has been significant economic instability in the healthcare systems. This reality was especially accentuated in Ecuador where, the shortage of healthcare workers combined with cultural and macroeconomic factors has led Ecuador to face the most aggressive outbreak in Latin America. In this context, the participation of final-year medical students on the front line is indispensable. Appropriate training on COVID-19 is an urgent requirement that universities and health systems must guarantee. We aimed to describe the knowledge, attitudes, and practices of Ecuadorian final-year medical students that could potentially guide the design of better medical education curricula regarding COVID-19.

Methods
This was a cross-sectional 33-item online survey conducted between April 6 to April 2020 assessing the knowledge, attitudes, and practices toward the diagnosis, treatment, prevention, and prognosis toward COVID-19 in Ecuadorian final-year medical students. It was sent by email, Facebook, and WhatsApp.

Results
A total of 309 students responded to the survey. Out of which 88% of students scored high (≥ 70% correct) for knowledge of the disease. The majority of students were pessimistic about possible government actions, which is reflected in the negative attitude towards the control of COVID-19 and volunteering during the outbreak in Ecuador (77%, and 58% of the students, respectively). Moreover, 91% of students said they did not have adequate protective equipment. The latter finding was significantly associated with negative attitudes.

Conclusions
Although a large number of students displayed negative attitudes, the non-depreciable percentage of students who were willing to volunteer and the coexisting high level of knowledge displayed by students, suggests that Ecuador has a capable upcoming workforce that could benefit from an opportunity to strengthen, improve and advance their training in preparation for COVID-19. Not having personal protective equipment was significantly associated to negative attitudes. Providing the necessary tools and creating a national curriculum may be one of the most effective ways to ensure all students are trained, whilst simultaneously focusing on the students’ most pressing concerns. With this additional training, negative attitudes will improve and students will be better qualified.
Linking clinotypes to phenotypes and genotypes from laboratory test results in comprehensive physical exams
Authors: Nguyen Thanh , Zhang Tongbin , Fox Geoffrey , Zeng Sisi , Cao Ni , Pan Chuandi , Chen Jake Y. 
Published: February 2021

Abstract
Background
In this work, we aimed to demonstrate how to utilize the lab test results and other clinical information to support precision medicine research and clinical decisions on complex diseases, with the support of electronic medical record facilities. We defined “clinotypes” as clinical information that could be observed and measured objectively using biomedical instruments. From well-known ‘omic’ problem definitions, we defined problems using clinotype information, including stratifying patients—identifying interested sub cohorts for future studies, mining significant associations between clinotypes and specific phenotypes-diseases, and discovering potential linkages between clinotype and genomic information. We solved these problems by integrating public omic databases and applying advanced machine learning and visual analytic techniques on two-year health exam records from a large population of healthy southern Chinese individuals (size n = 91,354). When developing the solution, we carefully addressed the missing information, imbalance and non-uniformed data annotation issues.

Results
We organized the techniques and solutions to address the problems and issues above into CPA framework (Clinotype Prediction and Association-finding). At the data preprocessing step, we handled the missing value issue with predicted accuracy of 0.760. We curated 12,635 clinotype-gene associations. We found 147 Associations between 147 chronic diseases-phenotype and clinotypes, which improved the disease predictive performance to AUC (average) of 0.967. We mined 182 significant clinotype-clinotype associations among 69 clinotypes.

Conclusions
Our results showed strong potential connectivity between the omics information and the clinical lab test information. The results further emphasized the needs to utilize and integrate the clinical information, especially the lab test results, in future PheWas and omic studies. Furthermore, it showed that the clinotype information could initiate an alternative research direction and serve as an independent field of data to support the well-known ‘phenome’ and ‘genome’ researches.
Chromatin architecture reveals cell type-specific target genes for kidney disease risk variants
Authors: Duan Aiping , Wang Hong , Zhu Yan , Wang Qi , Zhang Jing , Hou Qing , Xing Yuexian , Shi Jinsong , Hou Jinhua , Qin Zhaohui , Chen Zhaohong , Liu Zhihong , Yang Jingping 
Published: February 2021

AbstractBackgroundCell type-specific transcriptional programming results from the combinatorial interplay between the repertoire of active regulatory elements. Disease-associated variants disrupt such programming, leading to altered expression of downstream regulated genes and the onset of pathological states. However, due to the non-linear regulatory properties of non-coding elements such as enhancers, which can activate transcription at long distances and in a non-directional way, the identification of causal variants and their target genes remains challenging. Here, we provide a multi-omics analysis to identify regulatory elements associated with functional kidney disease variants, and downstream regulated genes.ResultsIn order to understand the genetic risk of kidney diseases, we generated a comprehensive dataset of the chromatin landscape of human kidney tubule cells, including transcription-centered 3D chromatin organization, histone modifications distribution and transcriptome with HiChIP, ChIP-seq and RNA-seq. We identified genome-wide functional elements and thousands of interactions between the distal elements and target genes. The results revealed that risk variants for renal tumor and chronic kidney disease were enriched in kidney tubule cells. We further pinpointed the target genes for the variants and validated two target genes by CRISPR/Cas9 genome editing techniques in zebrafish, demonstrating that SLC34A1 and MTX1 were indispensable genes to maintain kidney function.ConclusionsOur results provide a valuable multi-omics resource on the chromatin landscape of human kidney tubule cells and establish a bioinformatic pipeline in dissecting functions of kidney disease-associated variants based on cell type-specific epigenome.
Long non‐coding RNA VPS9D1-AS1 facilitates cell proliferation, migration and stemness in hepatocellular carcinoma
Authors: Fa Xinxin , Song Ping , Fu Yu , Deng Yu , Liu Kai 
Published: February 2021

Abstract
Background
Hepatocellular carcinoma (HCC) is a common cancer leading to high morbidity and mortality in worldwide. Previous studies revealed that SEC61 translocon alpha 1 subunit1 (SEC61A) can act as an oncogene in colon adenocarcinoma. However, the functions and molecular mechanism associated with HCC progression remain to be explored. This study aimed at exploring the role of SEC61A1 in HCC progression.

Methods
EdU assay and colony formation assay were applied to assess cell proliferation. The migratory ability of transfected HCC cells was evaluated by transwell migration assay. Sphere formation assay was used to detect the stemneess of HCC cells. Bioinformatics analysis tools and mechanism experiments were used to predict and analyze the potential molecular mechanism associated with the upregulation of SEC61A1 in HCC cells.

Results
Up-regulated SEC61A1 facilitated cell proliferation, migration and stemness in HCC cells. MiR-491-5p negatively regulated SEC61A1 and inhibited HCC cell proliferation and migration by targeting SEC61A1. VPS9D1 antisense RNA 1 (VPS9D1-AS1) could up-regulate SEC61A1 through sponging miR-491-5p. Early growth response 1 (EGR1) was identified as the upstream transcriptional activator for both SEC61A1 and VPS9D1-AS1.

Conclusions
Our study unveiled a novel molecular pathway facilitating HCC cell proliferation, migration and stemness, which may shed new insight into HCC treatment.
Disparity in physician-patient communication by ethnicity: evidence from Bangladesh
Authors: Zakaria Muhammad , Karim Rezaul , Rahman Murshida , Cheng Feng , Xu Junfang 
Published: February 2021

Abstract
Background
Physician-patient communication behavior (PPCB) is the primary process by which medical decision-making occurs and health outcome depends. Physician-patient communication differences may partly from the ethnic disparities. To examine this problem, this study aims to explore whether physician-patient communication differs by ethnicity during primary care medical consultations.

Methods
The study was conducted among the Bengali and ethnic minority patients (N = 850) who visited a physician for medical consultations. Data were collected using a structured post-consultation questionnaire. T-test was conducted to compare the communication between the Bengali and ethnic minority patients. Multiple linear regression analyses were performed to identify the factors associated with favorable communication behavior from the physicians.

Results
Bengali patients received more supportive communication behaviors from the Bengali doctors than that of ethnic minority patients including physicians’ cheerful greetings, encouraging patients to express health problems and asking questions, listening carefully, responding to questions and concerns, explaining to patients about medical examination procedures, medication, probable side effects, discussing treatment options, involved the patients in decisions, and spending adequate time. Results of linear regression showed that respondents’ level of education, internet use, knowledge about the health issue, having a pre-organized plan about the content of medical consultation, information seeking about the health problem, visiting female doctors, and a quiet ambience of the doctor’s room are significantly associated with a better PPCB score for the Bengali patients. In contrast, age, being the resident of an urban area, perception of affecting a minor health problem, having a pre-organized plan about the content of medical consultation, patients’ involvement in physicians’ decision-making about the treatment, and talking time resulted in better physician-patient communication for the ethnic minority patients.

Conclusion
This study suggests that reducing disparity in the socio-economic status of the ethnic minority groups through development programs and educating healthcare providers on how to use patient-centered communication skills to engage with their patients is one solution to improve equity in the delivery of healthcare and ensure than patients are receiving high-quality treatment, no matter their race or ethnicity.