bluuebunny/crossref_metadata_2025_split huggingface dataset:
Size matters: Large copy number losses in Hirschsprung disease patients reveal genes involved in enteric nervous system development
Authors: Kuil Laura E. , MacKenzie Katherine C. , Tang Clara S. , Windster Jonathan D. , Le Thuy Linh , Karim Anwarul , de Graaf Bianca M. , van der Helm Robert , van Bever Yolande , Sloots Cornelius E. J. , Meeussen Conny , Tibboel Dick , de Klein Annelies , Wijnen René M. H. , Amiel Jeanne , Lyonnet Stanislas , Garcia-Barcelo Maria-Mercè , Tam Paul K. H. , Alves Maria M. , Brooks Alice S. , Hofstra Robert M. W. , Brosens Erwin 
Published: August 2021

Hirschsprung disease (HSCR) is a complex genetic disease characterized by absence of ganglia in the intestine. HSCR etiology can be explained by a unique combination of genetic alterations: rare coding variants, predisposing haplotypes and Copy Number Variation (CNV). Approximately 18% of patients have additional anatomical malformations or neurological symptoms (HSCR-AAM). Pinpointing the responsible culprits within a CNV is challenging as often many genes are affected. Therefore, we selected candidate genes based on gene enrichment strategies using mouse enteric nervous system transcriptomes and constraint metrics. Next, we used a zebrafish model to investigate whether loss of these genes affects enteric neuron development in vivo.
This study included three groups of patients, two groups without coding variants in disease associated genes: HSCR-AAM and HSCR patients without associated anomalies (HSCR-isolated). The third group consisted of all HSCR patients in which a confirmed pathogenic rare coding variant was identified. We compared these patient groups to unaffected controls. Predisposing haplotypes were determined, confirming that every HSCR subgroup had increased contributions of predisposing haplotypes, but their contribution was highest in isolated HSCR patients without RET coding variants. CNV profiling proved that specifically HSCR-AAM patients had larger Copy Number (CN) losses. Gene enrichment strategies using mouse enteric nervous system transcriptomes and constraint metrics were used to determine plausible candidate genes located within CN losses. Validation in zebrafish using CRISPR/Cas9 targeting confirmed the contribution of UFD1L, TBX2, SLC8A1, and MAPK8 to ENS development. In addition, we revealed epistasis between reduced Ret and Gnl1 expression and between reduced Ret and Tubb5 expression in vivo. Rare large CN losses—often de novo—contribute to HSCR in HSCR-AAM patients. We proved the involvement of six genes in enteric nervous system development and Hirschsprung disease.
Model-based small area estimation methods and precise district-level HIV prevalence estimates in Uganda
Authors: Ouma Joseph , Jeffery Caroline , Awor Colletar Anna , Muruta Allan , Musinguzi Joshua , Wanyenze Rhoda K. , Biraro Sam , Levin Jonathan , Valadez Joseph J. 
Published: August 2021

Background
Model-based small area estimation methods can help generate parameter estimates at the district level, where planned population survey sample sizes are not large enough to support direct estimates of HIV prevalence with adequate precision. We computed district-level HIV prevalence estimates and their 95% confidence intervals for districts in Uganda.

Methods
Our analysis used direct survey and model-based estimation methods, including Fay-Herriot (area-level) and Battese-Harter-Fuller (unit-level) small area models. We used regression analysis to assess for consistency in estimating HIV prevalence. We use a ratio analysis of the mean square error and the coefficient of variation of the estimates to evaluate precision. The models were applied to Uganda Population-Based HIV Impact Assessment 2016/2017 data with auxiliary information from the 2016 Lot Quality Assurance Sampling survey and antenatal care data from district health information system datasets for unit-level and area-level models, respectively.

Results
Estimates from the model-based and the direct survey methods were similar. However, direct survey estimates were unstable compared with the model-based estimates. Area-level model estimates were more stable than unit-level model estimates. The correlation between unit-level and direct survey estimates was (β1 = 0.66, r2 = 0.862), and correlation between area-level model and direct survey estimates was (β1 = 0.44, r2 = 0.698). The error associated with the estimates decreased by 37.5% and 33.1% for the unit-level and area-level models, respectively, compared to the direct survey estimates.

Conclusions
Although the unit-level model estimates were less precise than the area-level model estimates, they were highly correlated with the direct survey estimates and had less standard error associated with estimates than the area-level model. Unit-level models provide more accurate and reliable data to support local decision-making when unit-level auxiliary information is available.
Screening and identification of key biomarkers of papillary renal cell carcinoma by bioinformatic analysis
Authors: Xu Yingying , Kong Deyang , Li Zhongtang , Qian Lingling , Li Junchao , Zou Chunbo 
Published: August 2021

Background
Papillary renal cell carcinoma (PRCC) is the most common type of renal cell carcinoma after clear cell renal cell carcinoma (ccRCC). Its pathological classification is controversial, and its molecular mechanism is poorly understood. Therefore, the identification of key genes and their biological pathways is of great significance to elucidate the molecular mechanisms of PRCC occurrence and progression.

Methods
The PRCC-related datasets GSE7023, GSE48352 and GSE15641 were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified, and gene ontology (GO) term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed. Cytoscape and STRING were used to construct the protein-protein interaction network (PPI) and perform module analysis to identify hub genes and key pathways. A heatmap of hub genes was constructed using the UCSC cancer genomics browser. Overall survival and recurrence-free survival of patients stratified by the expression levels of hub genes were analysed using Kaplan-Meier Plotter. The online database UALCAN was applied to analyse gene expression based on tissue type, stage, subtype and race.

Results
A total of 214 DEGs, specifically, 205 downregulated genes and 9 upregulated genes, were identified. The DEGs were mainly enriched in angiogenesis, kidney development, oxidation-reduction process, metabolic pathways, etc. The 17 hub genes identified were mainly enriched in the biological processes of angiogenesis, cell adhesion, platelet degranulation, and leukocyte transendothelial migration. Survival analysis showed that EGF, KDR, CXCL12, REN, PECAM1, CDH5, THY1, WT1, PLAU and DCN might be related to the carcinogenesis, metastasis or recurrence of PRCC. UALCAN analysis showed that low expression of PECAM1 and PLAU in PRCC tissues was related to stage, subtype and race.

Conclusions
The DEGs and hub genes identified in the present study provide insight into the specific molecular mechanisms of PRCC occurrence and development and may be potential molecular markers and therapeutic targets for the accurate classification and efficient diagnosis and treatment of PRCC.
The recently found Map of the World (Kunyutu 坤輿圖): a philological survey
Authors: de Morsier-Fritz Claudia 
Published: August 2021

Abstract
This paper is a first presentation of a Chinese Map of the World or Kunyutu 坤輿圖 discovered in a Federal library in Berne in 2017. It focusses on the rendering of the 7000 characters contained within the map. The translation of the complete 112 text blocks on the map will be provided in a second paper, whilst Indices I and II of this paper render the 1025 toponyms. The text blocks contain information on the customs and products of a given place, as well as describing other curiosities associated with it. These texts are compared with other maps and texts, in particular with The Complete World Map (Kunyu quantu 坤輿全圖) and The Explanations to the World Map (Kunyutu shuo 坤輿圖說) of 1674 by Verbiest. The re-translation of the text blocks helps to identify certain anachronisms and inaccuracies although the map purports to reflect the political situation in the years 1700–1729. This reveals the extent to which the text blocks draw on previous sources. Moreover, the rendering of the toponyms detects some inconsistencies in orthography and these interferences offer valuable pointers to the source and target languages. These various pieces of evidence suggest that the map was made much later by a copyist and is not only a cartographic composite of earlier maps, but also a fusion of Northern and Southern Mandarin. The translations presumably from French, Portuguese and Spanish sources in Southern Mandarin – the language of the officials (guanhua 官話) of the late Ming – as well as a variety of Southern Chinese dialects point to the underlying influence of a Jesuit tradition.
The BACH project protocol: an international multicentre total Bile Acid Comparison and Harmonisation project and sub-study of the TURRIFIC randomised trial
Authors: Markus Corey , Coat Suzette , Marschall Hanns-Ulrich , Williamson Catherine , Dixon Peter , Fuller Maria , Matthews Susan , Rankin Wayne , Metz Michael , Hague William M. 
Published: August 2021

Abstract

Objectives
Multicentre international trials relying on diagnoses derived from biochemical results may overlook the importance of assay standardisation from the participating laboratories. Here we describe a study protocol aimed at harmonising results from total bile acid determinations within the context of an international randomised controlled Trial of two treatments, URsodeoxycholic acid and RIFampicin, for women with severe early onset Intrahepatic Cholestasis of pregnancy (TURRIFIC), referred to as the Bile Acid Comparison and Harmonisation (BACH) study, with the aims of reducing inter-laboratory heterogeneity in total bile acid assays.

Methods
We have simulated laboratory data to determine the feasibility of total bile acid recalibration using a reference set of patient samples with a consensus value approach and subsequently used regression-based techniques to transform the data.

Results
From these simulations, we have demonstrated that mathematical recalibration of total bile acid results is plausible, with a high probability of successfully harmonising results across participating laboratories.

Conclusions
Standardisation of bile acid results facilitates the commutability of laboratory results and collation for statistical analysis. It may provide the momentum for broader application of the described techniques in the setting of large-scale multinational clinical trials dependent on results from non-standardised assays.
Hickam’s dictum, Occam’s razor, and Crabtree’s bludgeon: a case of renal failure and a clavicular mass
Authors: Blaser Simone , Schaye Verity , Hwang John , Cocks Patrick , Kudlowitz David 
Published: August 2021

Abstract

Objectives
Our discussant’s thoughtful consideration of the patient’s case allows for review of three maxims of medicine: Occam’s razor (the simplest diagnosis is the most likely to be correct), Hickam’s dictum (multiple disease entities are more likely than one), and Crabtree’s bludgeon (the tendency to make data fit to an explanation we hold dear).

Case presentation
A 66-year-old woman with a history of hypertension presented to our hospital one day after arrival to the United States from Guinea with chronic daily vomiting, unintentional weight loss and progressive shoulder pain. Her labs are notable for renal failure, nephrotic range proteinuria and normocytic anemia while her shoulder X-ray shows osseous resorption in the lateral right clavicle. Multiple myeloma became the team’s working diagnosis; however, a subsequent shoulder biopsy was consistent with follicular thyroid carcinoma. Imaging suggested the patient’s renal failure was more likely a result of a chronic, unrelated process.

Conclusions
It is tempting to bludgeon diagnostic possibilities into Occam’s razor. Presumption that a patient’s signs and symptoms are connected by one disease process often puts us at a cognitive advantage. However, atypical presentations, multiple disease processes, and unique populations often lend themselves more to Hickam’s dictum than to Occam’s razor. Diagnostic aids include performing a metacognitive checklist, engaging analytic thinking, and acknowledging the imperfections of these axioms.
Potential role of melatonin in prevention and treatment of leukaemia
Authors: Ng Ming Guan , Ng Khuen Yen , Koh Rhun Yian , Chye Soi Moi 
Published: August 2021

Abstract
Leukaemia is a haematological malignancy originated from the bone marrow. Studies have shown that shift work could disrupt the melatonin secretion and eventually increase leukaemia incidence risk. Melatonin, a pineal hormone, has shown promising oncostatic properties on a wide range of cancers, including leukaemia. We first reviewed the relationship between shift work and the incidence rate of leukaemia and then discussed the role of melatonin receptors (MT1 and MT2) and their functions in leukaemia. Moreover, the connection between inflammation and leukaemia, and melatonin-induced anti-leukaemia mechanisms including anti-proliferation, apoptosis induction and immunomodulation are comprehensively discussed. Apart from that, the synergistic effects of melatonin with other anticancer compounds are also included. In short, this review article has compiled the evidence of anti-leukaemia properties displayed by melatonin and discuss its potential to act as adjunct for anti-leukaemia treatment. This review may serve as a reference for future studies or experimental research to explore the possibility of melatonin serving as a novel therapeutic agent for leukaemia.
An online COVID-19 self-assessment framework supported by IoMT technology
Authors: Nsaif Mohammed Kamal , Mahdi Bilal Adil , Bahar Al-Mayouf Yusor Rafid , Mahdi Omar Adil , Aljaaf Ahmed J. , Khan Suleman 
Published: August 2021

AbstractAs COVID-19 pandemic continued to propagate, millions of lives are currently at risk especially elderly, people with chronic conditions and pregnant women. Iraq is one of the countries affected by the COVID-19 pandemic. Currently, in Iraq, there is a need for a self-assessment tool to be available in hand for people with COVID-19 concerns. Such a tool would guide people, after an automated assessment, to the right decision such as seeking medical advice, self-isolate, or testing for COVID-19. This study proposes an online COVID-19 self-assessment tool supported by the internet of medical things (IoMT) technology as a means to fight this pandemic and mitigate the burden on our nation’s healthcare system. Advances in IoMT technology allow us to connect all medical tools, medical databases, and devices via the internet in one collaborative network, which conveys real-time data integration and analysis. Our IoMT framework-driven COVID-19 self-assessment tool will capture signs and symptoms through multiple probing questions, storing the data to our COVID-19 patient database, then analyze the data to determine whether a person needs to be tested for COVID-19 or other actions may require to be taken. Further to this, collected data can be integrated and analyzed collaboratively for developing a national health policy and help to manage healthcare resources more efficiently. The IoMT framework-driven online COVID-19 self-assessment tool has a big potential to prevent our healthcare system from being overwhelmed using real-time data collection, COVID-19 databases, analysis, and management of people with COVID-19 concerns, plus providing proper guidance and course of action.
On a nonlinear system of Riemann-Liouville fractional differential equations with semi-coupled integro-multipoint boundary conditions
Authors: Alsaedi Ahmed , Ahmad Bashir , Alghamdi Badrah , Ntouyas Sotiris K. 
Published: August 2021

Abstract
We study a nonlinear system of Riemann-Liouville fractional differential equations equipped with nonseparated semi-coupled integro-multipoint boundary conditions. We make use of the tools of the fixed-point theory to obtain the desired results, which are well-supported with numerical examples.
Measurement and simulation validation of numerical model parameters of fresh concrete
Authors: Zhang Ke , Yu Wenda , Li Dong , Zou Defang , Zhang Shiying 
Published: August 2021

Abstract
In the numerical simulation of the macroscopic flow of the concrete, it can optimize the performance indicators of the screw conveyor and improve the uniformity of the material to be discharged in the batch production. The discrete element method is effective. The accuracy of physical parameters of this method is a key issue for the reliability of the simulation results of concrete. In this study, we measured the parameters describing the interaction between gravel, mortar, as well as between these two materials and the wall (steel). The experimentally determined parameters include the particle density, size, shape, coefficient of restitution, coefficients of static, and rolling friction. The cohesion coefficient of mortar particles for batch time was obtained by comparing the spread diameter and flow time in V-funnel experiments and simulation. After these calibration steps, the DEM parameters were validated by comparison of the mass flow rate and driving power by the batch production of screw conveying in simulations and experiments. The calculated results are proved to be close to the experimental data, which demonstrates that the measured DEM parameters are of sufficient accuracy to be used in the simulation of concrete flow performance (mass flow rate, energy consumption) in the screw conveyors.
Between Resistance and Repatriarchalization. Women’s Activism in the Bay of Kotor in the 1990s
Authors: Dabižinović Ervina 
Published: August 2021

Abstract
The author offers an account of women’s activism in the Bay of Kotor in the 1990s, thereby filling a gap in the academic literature on antiwar and peace activism in Montenegro during the Yugoslav wars. Although the Bay of Kotor saw regular antiwar and peace initiatives organized and led by women, these were unregistered grassroots activities. They went largely unnoticed by the media, which effectively erased them from the view of Montenegrin citizens and hid them from domestic and international historians and social scientists. The author compares the work of two non-governmental organizations, the ANIMA Centre for Women’s and Peace Education in Kotor, and RIZA–Bijela. She explores how the two organizations understood the place and role of women in the processes that took place in Montenegro in the 1990s. She assesses the similarities and differences of their respective approaches, and the effects of their work.
Optical coherent tomography in the diagnosis of inflammatory and ischemic optical neuropathies (clinical cases)
Authors: Moyseyenko Nataliya 
Published: August 2021

Optic neuropathy is a group of diseases of the optic nerve. Using diagnostic techniques such as ophthalmoscopy and perimetry diagnosis are insufficient, as the found abnormalities are not specific for either inflammation or ischemia. Establishing the predominant factor in the pathogenesis of neuropathy is crucial in determining the method of treatment.
The aim of the study: to investigate the features of optic nerve damage using optical coherent tomography (OCT) in optic neuropathy in the acute period.
Materials and methods: two patients with visual impairment were examined.
Result. Patient G. had concomitant rheumatoid arthritis with unregulated Methotrexate therapy. OCT revealed edema of the nerve fibre layer convinced of the predominance of inflammatory neuropathy (atypical neuritis). Pulse therapy with corticosteroids was prescribed, which gave a positive functional effect.
A patient O. with pneumonia on the background of Covid-19 with a history of OST showed a decrease in the thickness of the layer of nerve fibres in the lower segment, and in the angio mode – drusen of the optic disc.
Conclusions. Thus, the use of OCT for the diagnosis of optic neuropathies in the acute period showed that under conditions of inflammatory lesions is more characteristic of edema and an increase in the thickness of the layer of nerve fibres. In ischemic neuropathy, on the contrary, a decrease in the thickness of nerve fibres is more characteristic, which correlates in location with the localization of scotoma in the field of view.
Therefore, the use of OCT of the optic nerve will help in understanding the pathogenesis of forms of optic neuropathy. This will help in the choice of treatment tactics
Features of formation of motivation for online learning of students of pedagogical specialties
Authors: Shrol Tetiana , Poliukhovych Nataliia 
Published: August 2021

The concept of "motivation" and modern theories of learning motivation are theoretically substantiated and described: expectancy-value theory, attribution theory, social-cognitive theory, goal orientation theory, self-determination theory. Teaching strategies and pedagogical conditions that motivate students to educational and cognitive activities in the online environment, taking into account the theory of self-determination, are determined. In particular, in order to succeed in mastering something new, a student must feel competent (acquire the appropriate skills to perform practical tasks), related (feel belonging and attachment to groups or individuals), autonomous (feel that he/she controls his/her behavior and is responsible for its goals, capable of self-learning).
The pedagogical conditions for the formation of positive motivation and involvement of students in learning online are substantiated and determined, namely: giving a student the opportunity to be an accomplice in the learning process; structuring educational materials in accordance with learning objectives; promoting student initiative and creativity, ensuring group activities and a multidimensional assessment system.
The key to fulfilling the pedagogical conditions is the teacher's motivation to implement online learning at the level of the course author, mentor and tutor for higher education students. External and internal factors of motivation of teachers for introduction of elements of distance (online) and mixed (alternation of online and offline) training by teachers in the educational process of establishments of higher education are defined.
Experimentally confirmed: positive impact on the motivation of the implemented online learning strategies and pedagogical conditions; revealed a significant direct relationship between the student's ability to self-development and self-learning and his/her motivation for online learning