bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radical orchidectomy for suspected testicular cancer: Is preoperative staging computed tomography justified?
Authors: Berridge Christopher T , Stanley Sophie , Rajesh Arumugam , Griffiths TR Leyshon 
Published: December 2020

The standard of care for men with a suspected malignant testicular tumour and normal contralateral testis is radical orchidectomy, testicular tumour markers and computed tomography scan staging. If the definitive orchidectomy histopathology is benign, young men are potentially exposed to unnecessary radiation. We sought to establish the rate of benign pathology returned from radical orchidectomy at our local urology multidisciplinary team (MDT) and if there were any preoperative factors suggestive of benign lesions. We included patients discussed at our local MDT meeting regarding testicular tumours with histology following radical orchidectomy between 1 January 2016 and 31 December 2018. A total of 113 patients were included, with benign histology following radical orchidectomy in seven (6.2%) patients. The benign histology included one adenomatoid tumour, and the remainder showed features of either infarction or inflammation. Metastases were detected on staging imaging in 21% of patients. Of these, 64% had normal preoperative tumour markers. Neither tumour size nor number of preoperative ultrasounds correlated with a risk of benign histology. One patient had chemotherapy prior to orchidectomy. It was reassuring that just 6.2% of patients had benign histology with no significant factors predictive of benign histology. This supports pre-orchidectomy staging imaging and the current MDT pathway for suspected testicular cancers. Level of evidence: Level 2C.
The Predictive Value of Full-length Practice Exams for the New MCAT Exam for Premedical Students
Authors: Chen Wei , Corridon Peter R. 
Published: December 2020

Objective: To investigate whether full-length practice exams could predict performance in the new MCAT exam in a pilot group. Methods: A dataset of the first group of students who enrolled in the premedical post-baccalaureate program, established at Khalifa University of Science and Technology in the 2018-2019 academic year, were used. Nineteen students from the group were subsequently admitted to the newly launched Doctor of Medicine Program at KU in the 2019 fall semester. Results: Performance in the full-length practice exams may significantly predict the MCAT score (β = 0.74, t = 6.50, P = 0.000), independent of English proficiency. Conclusion: These results are the first to provide direct empirical evidence supporting that doing full-length practice exams before the MCAT test day is a good strategy for preparation. Given the size of the cohort and the amount of time the program has been in existence, further studies are thus required to support this initial result.
Genome-wide detection of short tandem repeat expansions by long-read sequencing
Authors: Liu Qian , Tong Yao , Wang Kai 
Published: December 2020

Abstract
Background
Short tandem repeat (STR), or “microsatellite”, is a tract of DNA in which a specific motif (typically < 10 base pairs) is repeated multiple times. STRs are abundant throughout the human genome, and specific repeat expansions may be associated with human diseases. Long-read sequencing coupled with bioinformatics tools enables the estimation of repeat counts for STRs. However, with the exception of a few well-known disease-relevant STRs, normal ranges of repeat counts for most STRs in human populations are not well known, preventing the prioritization of STRs that may be associated with human diseases.

Results
In this study, we extend a computational tool RepeatHMM to infer normal ranges of 432,604 STRs using 21 long-read sequencing datasets on human genomes, and build a genomic-scale database called RepeatHMM-DB with normal repeat ranges for these STRs. Evaluation on 13 well-known repeats show that the inferred repeat ranges provide good estimation to repeat ranges reported in literature from population-scale studies. This database, together with a repeat expansion estimation tool such as RepeatHMM, enables genomic-scale scanning of repeat regions in newly sequenced genomes to identify disease-relevant repeat expansions. As a case study of using RepeatHMM-DB, we evaluate the CAG repeats of ATXN3 for 20 patients with spinocerebellar ataxia type 3 (SCA3) and 5 unaffected individuals, and correctly classify each individual.

Conclusions
In summary, RepeatHMM-DB can facilitate prioritization and identification of disease-relevant STRs from whole-genome long-read sequencing data on patients with undiagnosed diseases. RepeatHMM-DB is incorporated into RepeatHMM and is available at https://github.com/WGLab/RepeatHMM.
Integrative analysis of histopathological images and chromatin accessibility data for estrogen receptor-positive breast cancer
Authors: Xu Siwen , Lu Zixiao , Shao Wei , Yu Christina Y. , Reiter Jill L. , Feng Qianjin , Feng Weixing , Huang Kun , Liu Yunlong 
Published: December 2020

AbstractBackgroundExisting studies have demonstrated that the integrative analysis of histopathological images and genomic data can be used to better understand the onset and progression of many diseases, as well as identify new diagnostic and prognostic biomarkers. However, since the development of pathological phenotypes are influenced by a variety of complex biological processes, complete understanding of the underlying gene regulatory mechanisms for the cell and tissue morphology is still a challenge. In this study, we explored the relationship between the chromatin accessibility changes and the epithelial tissue proportion in histopathological images of estrogen receptor (ER) positive breast cancer.MethodsAn established whole slide image processing pipeline based on deep learning was used to perform global segmentation of epithelial and stromal tissues. We then used canonical correlation analysis to detect the epithelial tissue proportion-associated regulatory regions. By integrating ATAC-seq data with matched RNA-seq data, we found the potential target genes that associated with these regulatory regions. Then we used these genes to perform the following pathway and survival analysis.ResultsUsing canonical correlation analysis, we detected 436 potential regulatory regions that exhibited significant correlation between quantitative chromatin accessibility changes and the epithelial tissue proportion in tumors from 54 patients (FDR < 0.05). We then found that these 436 regulatory regions were associated with 74 potential target genes. After functional enrichment analysis, we observed that these potential target genes were enriched in cancer-associated pathways. We further demonstrated that using the gene expression signals and the epithelial tissue proportion extracted from this integration framework could stratify patient prognoses more accurately, outperforming predictions based on only omics or image features.ConclusionThis integrative analysis is a useful strategy for identifying potential regulatory regions in the human genome that are associated with tumor tissue quantification. This study will enable efficient prioritization of genomic regulatory regions identified by ATAC-seq data for further studies to validate their causal regulatory function. Ultimately, identifying epithelial tissue proportion-associated regulatory regions will further our understanding of the underlying molecular mechanisms of disease and inform the development of potential therapeutic targets.
Network-based drug sensitivity prediction
Authors: Ahmed Khandakar Tanvir , Park Sunho , Jiang Qibing , Yeu Yunku , Hwang TaeHyun , Zhang Wei 
Published: December 2020

AbstractBackgroundDrug sensitivity prediction and drug responsive biomarker selection on high-throughput genomic data is a critical step in drug discovery. Many computational methods have been developed to serve this purpose including several deep neural network models. However, the modular relations among genomic features have been largely ignored in these methods. To overcome this limitation, the role of the gene co-expression network on drug sensitivity prediction is investigated in this study.MethodsIn this paper, we first introduce a network-based method to identify representative features for drug response prediction by using the gene co-expression network. Then, two graph-based neural network models are proposed and both models integrate gene network information directly into neural network for outcome prediction. Next, we present a large-scale comparative study among the proposed network-based methods, canonical prediction algorithms (i.e., Elastic Net, Random Forest, Partial Least Squares Regression, and Support Vector Regression), and deep neural network models for drug sensitivity prediction. All the source code and processed datasets in this study are available athttps://github.com/compbiolabucf/drug-sensitivity-prediction.ResultsIn the comparison of different feature selection methods and prediction methods on a non-small cell lung cancer (NSCLC) cell line RNA-seq gene expression dataset with 50 different drug treatments, we found that (1) the network-based feature selection method improves the prediction performance compared to Pearson correlation coefficients; (2) Random Forest outperforms all the other canonical prediction algorithms and deep neural network models; (3) the proposed graph-based neural network models show better prediction performance compared to deep neural network model; (4) the prediction performance is drug dependent and it may relate to the drug’s mechanism of action.ConclusionsNetwork-based feature selection method and prediction models improve the performance of the drug response prediction. The relations between the genomic features are more robust and stable compared to the correlation between each individual genomic feature and the drug response in high dimension and low sample size genomic datasets.
Antipsychotic and antidepressant prescribing for 704 297 children and young people with and without intellectual disabilities: record linkage study
Authors: Henderson Angela , Kinnear Deborah , Fleming Michael , Stanley Bethany , Greenlaw Nicola , Young-Southward Genevieve , Pell Jill P. , Cooper Sally-Ann 
Published: December 2020

BackgroundPsychotropics are overprescribed for adults with intellectual disabilities; there are few studies in children and young people.AimsTo investigate antipsychotic and antidepressant prescribing in children and young people with and without intellectual disabilities, and prescribing trends.MethodScotland's annual Pupil Census, which identifies pupils with and without intellectual disabilities, was record-linked to the Prescribing Information System. Antidepressant and antipsychotic data were extracted. Logistic regression was used to analyse prescribing between 2010 and 2013.ResultsOf the 704 297 pupils, 16 142 (2.29%) had a record of intellectual disabilities. Antipsychotic and antidepressant use increased over time, and was higher in older pupils; antipsychotic use was higher in boys, and antidepressant use was higher in girls. Overall, antipsychotics were prescribed to 281 (1.74%) pupils with intellectual disabilities and 802 (0.12%) without (adjusted odds ratio 16.85, 95% CI 15.29–18.56). The higher use among those with intellectual disabilities fell each year (adjusted odds ratio 20.19 in 2010 v. 14.24 in 2013). Overall, 191 (1.18%) pupils with intellectual disabilities and 4561 (0.66%) without were prescribed antidepressants (adjusted odds ratio 2.28, 95% CI 2.03–2.56). The difference decreased each year (adjusted odds ratio 3.10 in 2010 v. 2.02 in 2013).ConclusionsSignificantly more pupils with intellectual disabilities are prescribed antipsychotics and antidepressants than are other pupils. Prescribing overall increased over time, but less so for pupils with intellectual disabilities; either they are not receiving the same treatment advances as other pupils, or possible overprescribing in the past is changing. More longitudinal data are required.
Dietary Intake Regulates White Adipose Tissues Angiogenesis via Liver Fibroblast Growth Factor 21 in Male Mice
Authors: Hua Lun , Li Jing , Feng Bin , Jiang Dandan , Jiang Xuemei , Luo Ting , Che Lianqiang , Xu Shengyu , Lin Yan , Fang Zhengfeng , Wu De , Zhuo Yong 
Published: December 2020

Abstract
Obesity and related metabolic disorders have become epidemic diseases. Intermittent fasting has been shown to promote adipose tissue angiogenesis and have an anti-obesity feature; however, the mechanisms of how intermittent fasting modulates adipose tissues angiogenesis are poorly understood. We investigated the effect of fasting on vascular endothelial growth factor (VEGF) levels in white adipose tissues (WAT) and the function of fibroblast growth factor 21 (FGF21) in 1-time fasting and long-term intermittent fasting-induced VEGF expression. In the current study, fasting induced a selective and drastic elevation of VEGF levels in WAT, which did not occur in interscapular brown adipose tissue and liver. The fasting-induced Vegfa expression occurred predominantly in mature adipocytes, but not in the stromal vascular fraction in epididymal WAT and inguinal WAT (iWAT). Furthermore, a single bolus of recombinant mouse FGF21 injection increased VEGF levels in WAT. Long-term intermittent fasting for 16 weeks increased WAT angiogenesis, iWAT browning, and improved insulin resistance and inflammation, but the effect was blunted in FGF21 liver-specific knockout mice. In summary, these data suggest that FGF21 is a potent regulator of VEGF levels in WAT. The interorgan FGF21 signaling-induced WAT angiogenesis by VEGF could be a potential new therapeutic target in combination with obesity-related metabolic disorders.
Conceiving of the End of the World: Christian Doctrine and Nahua Perspectives in the Sermonary of Juan Bautista Viseo
Authors: Schmidt Stephanie 
Published: December 2020

AbstractThis article considers questions of authorship in Juan Bautista Viseo’s “Second Sermon for Advent” about “frightful, and terrible signs” of Judgment Day. Although Bautista acknowledges important contributions by Nahua scholars in the production of his Nahuatl-language sermonary, he does not plainly recognize them as coauthors. However, the text itself registers indigenous perspectives. This sermon describes several natural phenomena, such as eclipses, comets, floods, windstorms, and earthquakes, as signs of the Apocalypse. For Nahuas, these phenomena similarly foretold disaster or correlated to storied calamities of ages past. Therefore, the sermon refutes ancestral teachings on celestial signs and age-ending cataclysms, distinguishing so-called lies from doctrinal truth. Yet other passages take a heterodox step in the opposite direction, reinforcing connections between Christian and native thought on world time and portents of doom, or citing figurative “signs” of ancestral tradition that speak to the theme of divine judgment. Such passages, this article demonstrates, suggest Nahua co-authorship.
Multi locus sequence typing of clinical Burkholderia pseudomallei isolates from Malaysia
Authors: Arushothy Revathy , Amran Fairuz , Samsuddin Nazirah , Ahmad Norazah , Nathan Sheila 
Published: December 2020

Background
Melioidosis is a neglected tropical disease with rising global public health and clinical importance. Melioidosis is endemic in Southeast Asia and Northern Australia and is of increasing concern in Malaysia. Despite a number of reported studies from Malaysia, these reports are limited to certain parts of the country and do not provide a cohesive link between epidemiology of melioidosis cases and the nation-wide distribution of the causative agent Burkholderia pseudomallei.

Methodology/principle findings
Here we report on the distribution of B. pseudomallei sequence types (STs) in Malaysia and how the STs are related to STs globally. We obtained 84 culture-confirmed B. pseudomallei from confirmed septicaemic melioidosis patients from all over Malaysia. Prior to performing Multi Locus Sequence Typing, the isolates were subjected to antimicrobial susceptibility testing and detection of the YLF/BTFC genes and BimA allele. Up to 90.5% of the isolates were sensitive to all antimicrobials tested while resistance was observed for antimicrobials typically administered during the eradication stage of treatment. YLF gene cluster and bimABp allele variant were detected in all the isolates. The epidemiological distribution patterns of the Malaysian B. pseudomallei isolates were analysed in silico using phylogenetic tools and compared to Southeast Asian and world-wide isolates. Genotyping of the 84 Malaysian B. pseudomallei isolates revealed 29 different STs of which 6 (7.1%) were novel. ST50 was identified as the group founder followed by subgroup founders ST376, ST211 and ST84. A low-level diversity is noted for the B. pseudomallei isolates described in this study while phylogenetic analysis associated the Malaysian STs to Southeast Asian isolates especially isolates from Thailand. Further analysis also showed a strong association that implicates agriculture and domestication activities as high-risk routes of infection.

Conclusions/significance
In conclusion, MLST analysis of B. pseudomallei clinical isolates from all states in Malaysia revealed low diversity and a close association to Southeast Asian isolates.
Factors affecting the implementation of evidence-based Progressive Tinnitus Management in Department of Veterans Affairs Medical Centers
Authors: Zaugg Tara L. , Thielman Emily J. , Carlson Kathleen F. , Tuepker Anaïs , Elnitsky Christine , Drummond Karen L. , Schmidt Caroline J. , Newell Summer , Kaelin Christine , Choma Christie , Henry James A. 
Published: December 2020

Purpose
Progressive Tinnitus Management (PTM) is an evidence-based interdisciplinary stepped-care approach to improving quality of life for patients with tinnitus. PTM was endorsed by Department of Veterans Affairs (VA) Audiology leadership in 2009. Factors affecting implementation of PTM are unknown. We conducted a study to: 1) estimate levels of PTM program implementation in VA Audiology and Mental Health clinics across the country; and 2) identify barriers and facilitators to PTM implementation based on the experiences of VA audiologists and mental health providers.

Method
We conducted an anonymous, web-based survey targeting Audiology and Mental Health leaders at 144 major VA facilities. Quantitative analyses summarized respondents’ facility characteristics and levels of program implementation (full PTM, partial PTM, or no PTM). Qualitative analyses identified themes in factors influencing the implementation of PTM across VA sites.

Results
Surveys from 87 audiologists and 66 mental health clinicians revealed that few facilities offered full PTM; the majority offered partial or no PTM. Inductive analysis of the open-ended survey responses identified seven factors influencing implementation of PTM: 1) available resources, 2) service collaboration, 3) prioritization, 4) Veterans’ preferences and needs, 5) clinician training, 6) awareness of (evidence-based) options, and 7) perceptions of scope of practice.

Conclusion
Results suggest wide variation in services provided, a need for greater engagement of mental health providers in tinnitus care, and an interest among both audiologists and mental health providers in receiving tinnitus-related training. Future research should address barriers to PTM implementation, including methods to: 1) improve understanding among mental health providers of their potential role in tinnitus management; 2) enhance coordination of tinnitus-related care between health care disciplines; and 3) collect empirical data on Veterans’ need for and interest in PTM, including delivery by telehealth modalities.
Explaining socioeconomic inequalities in self-reported health outcomes: The mediating role of perceived life stress, financial self-reliance, psychological capital, and time perspective orientations
Authors: Schelleman-Offermans Karen , Massar Karlijn 
Published: December 2020

Objective
The main aim of the current study was to investigate what role perceived life stress, psychological capital (PsyCap), financial self-reliance and time perspective orientations play in explaining socioeconomic health inequalities, specifically self-perceived health and self-reported physical health conditions.

Methods
Individuals (total n = 600) aged 16+ years from a general Dutch population sample (LISS panel) completed an online questionnaire measuring three different SEP indicators (highest achieved educational level, personal monthly disposable income and being in paid employment), perceived life stress, PsyCap, financial self-reliance, time perspective, self-perceived health, and self-reported physical health conditions. Structural equation modelling using a cross-sectional design was used to test the mediation paths from SEP indicators to self-perceived health and self-reported physical health conditions through perceived life stress, PsyCap, financial self-reliance and time perspective orientations.

Results
Highest achieved educational level and being in paid employment showed to play a role in the social stratification within self-reported and self-perceived health outcomes, whereas this was not found for personal monthly disposable income. The association between a lower highest achieved educational level and lower self-perceived health was mediated by lower PsyCap and higher perceived life stress levels. The association between a lower highest achieved educational level and higher levels of self-reported physical health conditions was mediated by less financial self-reliance and higher perceived life stress levels. Although no mediating role was found for time perspective orientations in the association between the measured SEP indicators and health outcomes, negative time perspective orientations were associated with either self-perceived health or self-reported physical health conditions.

Conclusions
reserves (PsyCap and financial self-reliance) and perceived life stress seem to play a larger role in explaining the health gradient in achieved educational level than time perspective orientations. Prevention efforts trying to reduce the SEP-health gradient should focus on a) increasing reserves and lowering perceived life stress levels for individuals with a low achieved educational level, and b) reducing unemployment and narrowing opportunity gaps in education for people with a low SEP.