bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic mutational analysis of pediatric acute lymphoblastic leukemia from a single center in China using exon sequencing
Authors: Zhang Honghong , Wang Hongsheng , Qian Xiaowen , Gao Shuai , Xia Jieqi , Liu Junwen , Cheng Yanqin , Man Jie , Zhai Xiaowen 
Published: March 2020

Abstract
Background
Acute lymphoblastic leukemia (ALL), the most common childhood malignancy, is characterized by recurring structural chromosomal alterations and genetic alterations, whose detection is critical in diagnosis, risk stratification and prognostication. However, the genetic mechanisms that give rise to ALL remain poorly understood.

Methods
Using next-generation sequencing (NGS) in matched germline and tumor samples from 140 pediatric Chinese patients with ALL, we landscaped the gene mutations and estimated the mutation frequencies in this disease.

Results
Our results showed that the top driver oncogenes having a mutation prevalence over 5% in childhood ALL included KRAS (8.76%), NRAS (6.4%), FLT3 (5.7%) and KMT2D (5.0%). While the most frequently mutated genes were KRAS, NRAS and FLT3 in B cell ALL (B-ALL), the most common mutations were enriched in NOTCH1 (23.1%), FBXW7 (23.1%) and PHF6 (11.5%) in T cell ALL (T-ALL). These mutant genes are involved in key molecular processes, including the Ras pathway, the Notch pathway, epigenetic modification, and cell-cycle regulation. Strikingly, more than 50% of mutations occurred in the high-hyperdiploid (HeH) ALL existed in Ras pathway, especially FLT3 (20%). We also found that the epigenetic regulator gene KMT2D, which is frequently mutated in ALL, may be involved in driving leukemia transformation, as evidenced by an in vitro functional assay.

Conclusion
Overall, this study provides further insights into the genetic basis of ALL and shows that Ras mutations are predominant in childhood ALL, especially in the high-hyperdiploid subtype in our research.
Identification of lncRNA–miRNA–mRNA regulatory network associated with primary open angle glaucoma
Authors: Zhou Minwen , Lu Bing , Tan Wei , Fu Mingshui 
Published: March 2020

Abstract
Background
Primary open angle glaucoma (POAG) is a multifactorial disorder characterized by a progressive permanent degeneration of retinal ganglion cell (RGCs) death. An increasing number of studies have suggested that long noncoding RNAs (lncRNAs) have the ability to regulate gene expression; however, thus far, the mechanisms and functions of lncRNAs in the development of POAG are still unclear.

Methods
Using the data from Gene Expression Omnibus (GEO), differentially expressed lncRNAs and differentially expressed mRNAs between POAG patients and controls were identified. Then, the lncRNA–miRNA–mRNA competing endogenous RNA (ceRNA) network was constructed, and the key lncRNAs in POAG were identified. A Gene Ontology (GO) analysis and a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to assess the enriched biological functions of mRNA in the ceRNA network.

Results
During this study, a POAG-related ceRNA network with 37 miRNA nodes, 248 lncRNA nodes, 178 mRNA nodes, and 1985 edges was constructed. In addition, four lncRNAs (DNAJC27-AS1, AF121898, OIP5-AS1, and SNX29P2) were established as hub RNAs in this ceRNA network. The functional assay showed that 18 GO terms and 17 pathways were enriched.

Conclusion
This study provides novel insights into the lncRNA-related ceRNA network in POAG, and the four lncRNAs were identified in the development of POAG.
Computerized adaptive testing to screen children for emotional and behavioral problems by preventive child healthcare
Authors: Theunissen Meinou H. C. , de Wolff Marianne S. , Deurloo Jacqueline A. , Vogels Anton G. C. , Reijneveld Sijmen A. 
Published: March 2020

Abstract
Background
Questionnaires to detect emotional and behavioral problems (EBP) in Preventive Child Healthcare (PCH) should be short which potentially affects validity and reliability. Simulation studies have shown that Computerized Adaptive Testing (CAT) could overcome these weaknesses. We studied the applicability (using the measures participation rate, satisfaction, and efficiency) and the validity of CAT in routine PCH practice.

Methods
We analyzed data on 461 children aged 10–11 years (response 41%), who were assessed during routine well-child examinations by PCH professionals. Before the visit, parents completed the CAT and the Child Behavior Checklist (CBCL). Satisfaction was measured by parent- and PCH professional-report. Efficiency of the CAT procedure was measured as number of items needed to assess whether a child has serious problems or not. Its validity was assessed using the CBCL as the criterion.

Results
Parents and PCH professionals rated the CAT on average as good. The procedure required at average 16 items to assess whether a child has serious problems or not. Agreement of scores on the CAT scales with corresponding CBCL scales was high (range of Spearman correlations 0.59–0.72). Area Under Curves (AUC) were high (range: 0.95–0.97) for the Psycat total, externalizing, and hyperactivity scales using corresponding CBCL scale scores as criterion. For the Psycat internalizing scale the AUC was somewhat lower but still high (0.86).

Conclusions
CAT is a valid procedure for the identification of emotional and behavioral problems in children aged 10–11 years. It may support the efficient and accurate identification of children with overall, and potentially also specific, emotional and behavioral problems in routine PCH.
HESPER web - development and reliability evaluation of a web-based version of the humanitarian emergency settings perceived needs scale
Authors: Hugelius K. , Semrau M. , Holmefur M. 
Published: March 2020

Abstract
Background
The Humanitarian Emergency Settings Perceived Needs Scale (HESPER) assesses a wide range of physical, psychological and social perceived needs across 26 questions, and can be used in humanitarian emergencies and disasters for needs assessment or research studies. The original HESPER collects data through individual interviews. Today, a large number of people have access to the internet, including in humanitarian emergencies and disasters. Therefore, this paper aimed to report the development, reliability evaluation and feasibility evaluation of the HESPER Web.

Methods
First, the original HESPER was developed into a web based survey. Thereafter, alternate forms reliability between the HESPER and HESPER Web, and test-retest reliability for the HESPER Web, was evaluated using a study sample of 85 asylum seekers in Sweden in total.

Results
The alternate forms reliability evaluation showed that the HESPER Web was a reliable instrument to assess perceived needs. Intraclass correlation coefficient (ICC) for total number of serious needs was 0.96 (CI 0.93–09.98, p < 0.001). Cohen’s κ was used to analyse the alternate forms reliability between the HESPER and HESPER Web item per item; the correspondence between HESPER and HESPER Web varied between 0.54 and 1.0 for the 26 questions. There was a strong nominal association in first priority need between the HESPER and HESPER Web (Cramer’s V 0.845, p < 0.001). In the test-retest reliability evaluation of HESPER Web, ICC was 0.98 (CI 0.97–0.99, p < 0.001), and Cohen’s κ varied between 0.53 and 1.0. There was a strong nominal association in first priority need between test and re-test (Cramer’s V 0.93, p < 0.001). The HESPER Web was experienced as easy and safe to use and was found less time consuming than the original HESPER interview, according to the study participants.

Conclusion
The HESPER Web is a reliable and usable instrument to assess perceived needs. It can reduce a number of practical challenges both for needs assessment in disasters or humanitarian emergencies as well as in research.
The time spent sitting does not always mean a low level of physical activity
Authors: Matusiak-Wieczorek Ewelina , Lipert Anna , Kochan Ewa , Jegier Anna 
Published: March 2020

AbstractBackgroundThe problem of spending most of the day in a sitting position concerns all people, regardless of their age. Unfortunately, this trend is more and more often observed among young people.The aim of the study was to assess self-reported physical activity and time spent sitting among students of different fields of health related faculty.MethodsThe study group included 216 students (22.3 ± 1.8 years of age) of the Medical University of Lodz: physiotherapy students (n = 101), pharmacy students (n = 73), and dietetics students (n = 42). The time spent sitting and physical activity level were assessed based on the International Physical Activity Questionnaire-long version.ResultsThe time spent sitting among health related faculty students was on average more than 46 h a week (2781.8 ± 1238.5 MET-minutes/week). Regarding all the students the pharmacy students spent most time sitting (3086.0 ± 1032.1 MET-minutes/week), while the dietetics students spent the least (2215.7 ± 1230.1 MET-minutes/week). Taking into account the physical activity level almost 65% of all the students were in a high category (mainly physiotherapy students). Only 1.4% of all the surveyed students were classified as the low physical activity category. Statistical analysis showed no significant differences (P = 0.6880) between the time spent sitting and level of physical activity among all students.ConclusionsStudents of medical universities spend too much hours on sitting, mostly 5–8 h a day. Despite this, they undertake various activities due to which their level of physical activity is moderate or even high. Therefore, it cannot be unequivocally stated that there is a relationship between the time spent sitting and physical activity level.
Google trend analysis of climatic zone based Indian severe seasonal sensitive population
Authors: Patel Jai Chand , Khurana Pankaj , Sharma Yogendra Kumar , Kumar Bhuvnesh , Sugadev Ragumani 
Published: March 2020

Abstract
Background
Our earlier Google Trend (GT) Analytics study reported that the worldwide human population severely subject to four seasonal (sensitive) comorbid lifestyle diseases (SCLD) such as asthma, obesity, hypertension and fibrosis. The human population subject to seasonal variability in these four diseases activity referred as “severe seasonal sensitive population”. In India, the estimated burden of these four seasonal diseases is more than 350 million as on the year 2018. It is a growing crisis for India with a projected disease burden of 500 million in the year 2025. This study was aimed to decipher the genuine SCLD seasonal trends in the entire Indian population using GT and validate these trends in Indian climatic zones.

Methods
GT is used to study the temporal trends in web search using weekly Relative Search Volume (RSV) for the period 2004 to 2017. The relative search volume (RSV) of the four-severe seasonal comorbid diseases namely Asthma, Hypertension, Obesity and Fibrosis were collected with and without obesity as the reference. The RSV were collected using the GT selection options as (i) Whole India (ii) Jammu and Kashmir (Cold zone) (iii) Rajasthan (Hot and Dry zone) (iii) West Bengal (Hot and Humid zone) and (iv) Uttar Pradesh state (Composite zone). The time series analysis was carried out to find seasonal patterns, comorbidity, trends and periodicity in the entire India and four of its states (zones).

Results
Our analysis of entire India (2004–2017) revealed high significant seasonal patterns and comorbidity in all the four diseases of SCLD. The positive tau values indicated strong positive seasonal trends in the SCLD throughout the period (Table). The auto correlation analysis revealed that these diseases were subjected to 3, 4 and 6 months period seasonal variations. Similar seasonal patterns and trends were also observed in all the four Indian temperature zones. Overall study indicated that SCLD seasonal search patterns and trends are highly conserved in India even in drastic Indian climatic zones.

Conclusions
The clinical outcome arise out of these observations could be of immense significance in handling the major chronic life style diseases asthma, hypertension, obesity and fibrosis. The possible strong comorbid relationship among asthma, hypertension, obesity and fibrosis may be useful to segregate Indian seasonal sensitive population. In disease activity-based chronotherapy, the search interest of segment of the population with access to Internet may be used as an indicator for public health sectors in the early detection of SCLD from a specific country or a region. As this disease population could be highly subject to the adverse effect of seasons in addition to life style and other environmental factors. Our study necessitates that these Indian populations need special attention from the Indian health care sectors.
The potential role of central obesity in male infertility: body mass index versus waist to hip ratio as they relate to selected semen parameters
Authors: Keszthelyi Márton , Gyarmathy V. Anna , Kaposi András , Kopa Zsolt 
Published: March 2020

Abstract
Background
Little is known about the potential role of central obesity among men. Our first aim was to confirm what is already known from prior research, namely that both BMI and WHR are inversely associated with selected semen parameters. Our second aim was to examine the potential role of central obesity by assessing if there was a difference between BMI and WHR regarding their relationships to these selected semen parameters.

Methods
In this cross-sectional study between January 2011 to January 2018, we analyzed semen samples from 1169 patients who visited an andrology clinic in Budapest for infertility reasons. Variables assessed were: body measurements (height, weight, waist circumference, and hip circumference), and the results of semen analysis (sperm concentration, total sperm count, progressive sperm motility, and normal sperm morphology).

Results
The mean height and weight were 180.6 cm and 87.3 kg, respectively – the mean BMI was 26.8. The mean waist and hip circumferences were 100.9 cm and 94.8 cm, respectively – the mean waist to hip ratio was 0.94. The mean sperm concentration, total sperm count, and percents of progressive motility and normal morphology were 48.7 M/ml, 165 million, 21.2, and 4.8%, respectively. Both BMI and WHR were significant correlates in all semen parameter regression models. When comparing the parameter estimates for BMI with those for WHR for each semen parameter, the parameter estimate for WHR was significantly lower (indicating a stronger negative association) than that for BMI for progressive motility and total sperm count, but not for normal morphology or concentration.

Conclusions
Our study is the first to examine, using a large patient sample, the potential role of central obesity by comparing the difference between BMI and WHR as they relate to selected semen parameters. Our findings indicate a potential role of central obesity for progressive motility and total sperm count, but not for normal morphology and concentration. Despite the limitations and the exploratory nature of this study, we can conclude that our results point to a potential role of central obesity in male infertility, but this finding should be confirmed and further explored in future research.

Trial registration
The trial was retrospectively authorized after the data collection on September 24, 2018. Registration number: SE RKEB: 169/2018.
What hypertensive patients want to know [and from whom] about their disease: a two-year longitudinal study
Authors: Cappelletti Erika R. , Greco Andrea , Maloberti Alessandro , Giannattasio Cristina , Steca Patrizia , D’Addario Marco 
Published: March 2020

Abstract
Background
This study explored both the evolution of the information needs and the perceived relevance of different health information sources in patients with essential hypertension. It also investigated the relationships between information needs and the perceived relevance of information sources with socio-demographic and clinical variables.

Methods
Two hundred and two patients with essential arterial hypertension were enrolled in the study and evaluated at baseline and during three follow-ups at 6, 12 and 24 months after baseline. Patients had a mean age of 54.3 years [range 21–78; SD = 10.4], and 43% were women. Repeated measures ANOVA, Bonferroni post hoc tests, and Cochran’s Q Test were performed to test differences in variables of interest over time.

Results
It was observed a significant reduction in all the domains of information needs related to disease management except for pharmacological treatment and risks and complications. At baseline, patients reported receiving health information primarily from specialists, general practitioners, relatives, and television, but the use of these sources decreased over time, even if the decrease was significant only for relatives. Multiple patterns of relationships were found between information needs and the perceived relevance of sources of information and socio-demographics and clinical variables, both at baseline and over time.

Conclusions
The findings showed a general decrease in both the desire for information and the perceived relevance of different information sources. Hypertensive patients appeared to show little interest in health communication topics as their disease progressed. Understanding patients’ information needs and the perceived relevance of different information sources is the first step in implementing tailored communication strategies that can promote patients’ self-management skills and optimal clinical outcomes.
Could automated machine-learned MRI grading aid epidemiological studies of lumbar spinal stenosis? Validation within the Wakayama spine study
Authors: Ishimoto Yuyu , Jamaludin Amir , Cooper Cyrus , Walker-Bone Karen , Yamada Hiroshi , Hashizume Hiroshi , Oka Hiroyuki , Tanaka Sakae , Yoshimura Noriko , Yoshida Munehito , Urban Jill , Kadir Timor , Fairbank Jeremy 
Published: March 2020

Abstract
Background
MRI scanning has revolutionized the clinical diagnosis of lumbar spinal stenosis (LSS). However, there is currently no consensus as to how best to classify MRI findings which has hampered the development of robust longitudinal epidemiological studies of the condition. We developed and tested an automated system for grading lumbar spine MRI scans for central LSS for use in epidemiological research.

Methods
Using MRI scans from the large population-based cohort study (the Wakayama Spine Study), all graded by a spinal surgeon, we trained an automated system to grade central LSS in four gradings of the bone and soft tissue margins: none, mild, moderate, severe. Subsequently, we tested the automated grading against the independent readings of our observer in a test set to investigate reliability and agreement.

Results
Complete axial views were available for 4855 lumbar intervertebral levels from 971 participants. The machine used 4365 axial views to learn (training set) and graded the remaining 490 axial views (testing set). The agreement rate for gradings was 65.7% (322/490) and the reliability (Lin’s correlation coefficient) was 0.73. In 2.2% of scans (11/490) there was a difference in classification of 2 and in only 0.2% (1/490) was there a difference of 3. When classified into 2 groups as ‘severe’ vs ‘no/mild/moderate’. The agreement rate was 94.1% (461/490) with a kappa of 0.75.

Conclusions
This study showed that an automated system can “learn” to grade central LSS with excellent performance against the reference standard. Thus SpineNet offers potential to grade LSS in large-scale epidemiological studies involving a high volume of MRI spine data with a high level of consistency and objectivity.
Intraoperative intraocular pressure changes during robot-assisted radical prostatectomy: associations with perioperative and clinicopathological factors
Authors: Shirono Yuko , Takizawa Itsuhiro , Kasahara Takashi , Maruyama Ryo , Yamana Kazutoshi , Tanikawa Toshiki , Hara Noboru , Sakaue Yuta , Togano Tetsuya , Nishiyama Tsutomu , Fukuchi Takeo , Tomita Yoshihiko 
Published: March 2020

Abstract
Background
Steep Trendelenburg position (ST) during robot-assisted radical prostatectomy (RARP) poses a risk of increase in intraocular pressure (IOP) in men receiving robot-assisted radical prostatectomy (RARP). The aim of the study was to identify clinicopathological factors associated with increased IOP during RARP.

Methods
We prospectively studied 59 consecutive prostate cancer patients without glaucoma. IOP was measured at 6 predefined time points before, during and after the operation (T1 to T6).

Results
Compared with T1, IOP decreased after beginning of anesthesia(T2) (by − 6.5 mmHg, p < 0.05), and increased 1 h after induction of pneumoperitoneum in the steep Trendelenburg position (ST) (T3) (+ 7.3 mmHg, p < 0.05). IOP continued to increase until the end of ST (T4) (+ 10.2 mmHg, p < 0.05), and declined when the patient was returned to supine position under general anesthesia (T5) (T1: 20.0 and T5: 20.1 mmHg, p above 0.05). The console time affected the elevation of IOP in ST; IOP elevation during ST was more prominent in men with a console time of ≥4 h (n = 39) than in those with a console time of < 4 h (n = 19) (19.8 ± 6.3 and 15.4 ± 5.8 mmHg, respectively, p < 0.05). Of the 59 patients, 29 had a high baseline IOP (20.0 mmHg or higher), and their IOP elevated during ST was also reduced at T5 (T1: 22.6 and T5: 21.7 mmHg, p above 0.05). There were no postoperative ocular complications.

Conclusions
Console time of < 4 h is important to prevent extreme elevation of IOP during RARP. Without long console time, RARP may be safely performed in those with relatively high baseline IOP.
Optimised production of an anti-fungal antibody in Solanaceae hairy roots to develop new formulations against Candida albicans
Authors: Catellani Marcello , Lico Chiara , Cerasi Mauro , Massa Silvia , Bromuro Carla , Torosantucci Antonella , Benvenuto Eugenio , Capodicasa Cristina 
Published: March 2020

Abstract
Background
Infections caused by fungi are often refractory to conventional therapies and urgently require the development of novel options, such as immunotherapy. To produce therapeutic antibodies, a plant-based expression platform is an attractive biotechnological strategy compared to mammalian cell cultures. In addition to whole plants, hairy roots (HR) cultures can be used, representing an expression system easy to build up, with indefinite growth while handled under containment conditions.

Results
In this study the production in HR of a recombinant antibody, proved to be a good candidate for human immunotherapy against fungal infections, is reported. Expression and secretion of this antibody, in an engineered single chain (scFvFc) format, by HR from Nicotiana benthamiana and Solanum lycopersicum have been evaluated with the aim of directly using the deriving extract or culture medium against pathogenic fungi. Although both Solanaceae HR showed good expression levels (up to 68 mg/kg), an optimization of rhizosecretion was only obtained for N. benthamiana HR. A preliminary assessment to explain this result highlighted the fact that not only the presence of proteases, but also the chemical characteristics of the growth medium, can influence antibody yield, with implications on recombinant protein production in HR. Finally, the antifungal activity of scFvFc 2G8 antibody produced in N. benthamiana HR was evaluated in Candida albicans growth inhibition assays, evidencing encouraging results.

Conclusions
Production of this anti-fungal antibody in HR of N. benthamiana and S. lycopersicum elucidated factors affecting pharming in this system and allowed to obtain promising ready-to-use immunotherapeutics against C. albicans.