bluuebunny/crossref_metadata_2025_split huggingface dataset:
Theoretical characterisation of strand cross-correlation in ChIP-seq
Authors: Anzawa Hayato , Yamagata Hitoshi , Kinoshita Kengo 
Published: September 2020

Abstract
Background
Strand cross-correlation profiles are used for both peak calling pre-analysis and quality control (QC) in chromatin immunoprecipitation followed by sequencing (ChIP-seq) analysis. Despite its potential for robust and accurate assessments of signal-to-noise ratio (S/N) because of its peak calling independence, it remains unclear what aspects of quality such strand cross-correlation profiles actually measure.

Results
We introduced a simple model to simulate the mapped read-density of ChIP-seq and then derived the theoretical maximum and minimum of cross-correlation coefficients between strands. The results suggest that the maximum coefficient of typical ChIP-seq samples is directly proportional to the number of total mapped reads and the square of the ratio of signal reads, and inversely proportional to the number of peaks and the length of read-enriched regions. Simulation analysis supported our results and evaluation using 790 ChIP-seq data obtained from the public database demonstrated high consistency between calculated cross-correlation coefficients and estimated coefficients based on the theoretical relations and peak calling results. In addition, we found that the mappability-bias-correction improved sensitivity, enabling differentiation of maximum coefficients from the noise level. Based on these insights, we proposed virtual S/N (VSN), a novel peak call-free metric for S/N assessment. We also developed PyMaSC, a tool to calculate strand cross-correlation and VSN efficiently. VSN achieved most consistent S/N estimation for various ChIP targets and sequencing read depths. Furthermore, we demonstrated that a combination of VSN and pre-existing peak calling results enable the estimation of the numbers of detectable peaks for posterior experiments and assess peak calling results.

Conclusions
We present the first theoretical insights into the strand cross-correlation, and the results reveal the potential and the limitations of strand cross-correlation analysis. Our quality assessment framework using VSN provides peak call-independent QC and will help in the evaluation of peak call analysis in ChIP-seq experiments.
Intermittent hypoxia reduces infarct size in rats with acute myocardial infarction: a systematic review and meta-analysis
Authors: Hu Ke , Deng Wei , Yang Jing , Wei Yu , Wen Chaolin , Li Xingsheng , Chen Qingwei , Ke Dazhi , Li Guiqiong 
Published: September 2020

AbstractBackgroundTo determine whether intermittent hypoxia (IH) can reduce the infarct size (IS) after acute myocardial infarction (AMI) in rats.MethodsArticles were identified in PubMed, EMBASE and the Web of Science and were included if they evaluated the effect of IH on the changes in the infarcted area after AMI in rats.ResultsA preliminary search identified 3633 articles and 29 data sets from 23 articles (12 in vivo, 16 in vitro). The IS decreased after AMI in IH rats both in vitro (SMD -1.46, 95% CI [− 2.37, − 0.55]; I2 = 85.6%,P = 0.000) and in vivo (SMD -1.43, 95% CI [− 2.05, − 0.82], I2 = 73.6%,P = 0.000). Sensitivity analysis indicated that IH had a strong protective effect against myocardial infarction, and the hypoxia concentration was significantly correlated with the change in IS after AMI.ConclusionIH can reduce IS after AMI in rats. This effect of IH may be related to the dose of hypoxia, and the oxygen concentration may be one of the most important influencing factors.
A multicenter prospective phase III clinical randomized study of simultaneous integrated boost intensity-modulated radiotherapy with or without concurrent chemotherapy in patients with esophageal cancer: 3JECROG P-02 study protocol
Authors: Gao Lin-rui , Wang Xin , Han Weiming , Deng Wei , Li Chen , Wang Xiaomin , Zhao Yidian , Ni Wenjie , Chang Xiao , Zhou Zongmei , Deng Lei , Wang Wenqing , Liu Wenyang , Liang Jun , Zhang Tao , Bi Nan , Wang Jianyang , Zhai Yirui , Feng Qinfu , Lv Jima , Li Ling , Xiao Zefen 
Published: September 2020

Abstract
Background
Since the development of three-dimensional conformal radiotherapy and intensity-modulated radiotherapy (IMRT), no prospective study has investigated whether concurrent chemoradiotherapy (SIB-IMRT with 60 Gy) remains superior to radiotherapy (SIB-IMRT) alone for unresectable esophageal cancer (EC). Furthermore, the optimal therapeutic regimen for patients who cannot tolerate concurrent chemoradiotherapy is unclear. We recently completed a phase I/II radiation dose-escalation trial using simultaneous integrated boost (SIB), elective nodal irradiation, and concurrent chemotherapy for unresectable EC. We now intend to conduct a prospective, phase III, randomized study of SIB-IMRT with or without concurrent chemotherapy. We aim to find a safe, practical, and effective therapeutic regimen to replace the conventional segmentation (1.8–2.0 Gy) treatment mode (radiotherapy ± chemotherapy) for unresectable EC.

Methods
This two-arm, open, randomized, multicenter, phase III trial will recruit esophageal squamous cell carcinoma patients (stage IIA–IVB [UICC 2002]; IVB only with metastasis to the supraclavicular or celiac lymph nodes). In all, 164 patients will be randomized using a 1:1 allocation ratio, and stratified by study site and disease stage, especially the extent of lymph node metastasis. Patients in the SIB arm will receive definitive SIB radiotherapy (95% planning target volume/planning gross tumor volume, 50.4 Gy/59.92 Gy/28 f, equivalent dose in 2-Gy fractions = 60.62 Gy). Patients in the SIB + concurrent chemotherapy arm will receive definitive SIB radiotherapy with weekly paclitaxel and a platinum-based drug (5–6 weeks). Four cycles of consolidated chemoradiotherapy will also be recommended. The primary objective is to compare the 1-year, 2-year, and 3-year overall survival of the SIB + chemotherapy group and SIB groups. Secondary objectives include progression-free survival, local recurrence-free rate, completion rate, and adverse events. Detailed radiotherapy protocol and quality-assurance procedures have been incorporated into this trial.

Discussion
In unresectable, locally advanced EC, a safe and effective total radiotherapy dose and reasonable segmentation doses are required for the clinical application of SIB-IMRT + two-drug chemotherapy. Whether this protocol will replace the standard treatment regimen will be prospectively investigated. The effects of SIB-IMRT in patients with poor physical condition who cannot tolerate definitive chemoradiotherapy will also be investigated.

Trial registration
clinicaltrials.gov (NCT03308552, November 1, 2017).
Somatic mutation detection efficiency in EGFR: a comparison between high resolution melting analysis and Sanger sequencing
Authors: Joy Reenu Anne , Thelakkattusserry Sukrishna Kamalasanan , Vikkath Narendranath , Bhaskaran Renjitha , Krishnan Sajitha , Vasudevan Damodaran , Ariyannur Prasanth S. 
Published: September 2020

Abstract
Background
High resolution melting curve analysis is a cost-effective rapid screening method for detection of somatic gene mutation. The performance characteristics of this technique has been explored previously, however, analytical parameters such as limit of detection of mutant allele fraction and total concentration of DNA, have not been addressed. The current study focuses on comparing the mutation detection efficiency of High-Resolution Melt Analysis (HRM) with Sanger Sequencing in somatic mutations of the EGFR gene in non-small cell lung cancer.

Methods
The minor allele fraction of somatic mutations was titrated against total DNA concentration using Sanger sequencing and HRM to determine the limit of detection. The mutant and wildtype allele fractions were validated by multiplex allele-specific real-time PCR. Somatic mutation detection efficiency, for exons 19 & 21 of the EGFR gene, was compared in 116 formalin fixed paraffin embedded tumor tissues, after screening 275 tumor tissues by Sanger sequencing.

Results
The limit of detection of minor allele fraction of exon 19 mutation was 1% with sequencing, and 0.25% with HRM, whereas for exon 21 mutation, 0.25% MAF was detected using both methods. Multiplex allele-specific real-time PCR revealed that the wildtype DNA did not impede the amplification of mutant allele in mixed DNA assays. All mutation positive samples detected by Sanger sequencing, were also detected by HRM. About 28% cases in exon 19 and 40% in exon 21, detected as mutated in HRM, were not detected by sequencing. Overall, sensitivity and specificity of HRM were found to be 100 and 67% respectively, and the negative predictive value was 100%, while positive predictive value was 80%.

Conclusion
The comparative series study suggests that HRM is a modest initial screening test for somatic mutation detection of EGFR, which must further be confirmed by Sanger sequencing. With the modification of annealing temperature of initial PCR, the limit of detection of Sanger sequencing can be improved.
Combined and interaction effect of chlamydia pneumoniae infection and smoking on lung cancer: a case-control study in Southeast China
Authors: Xu Xin , Liu Zhiqiang , Xiong Weimin , Qiu Minglian , Kang Shuling , Xu Qiuping , Cai Lin , He Fei 
Published: September 2020

AbstractBackgroundThis case-control study investigated the role ofChlamydia pneumoniae(Cpn) infection in the pathogenesis of lung cancer and the combined and interaction effect of Cpn infection, smoking, and various environmental factors.MethodsThe study comprised 449 lung cancer patients and 512 age- and sex-matched healthy controls. All participants provided a 5 ml fasting peripheral venous blood sample for testing Cpn-specific IgG and IgA by using micro-immunofluorescence. Besides analyzing the associations between Cpn and lung cancer, combined effect analysis, logistic regression, and the Excel table made by Andersson were used to analyze the combined and interaction effects of Cpn and environmental factors on lung cancer.ResultsCompared to those with no evidence of serum Cpn IgA or Cpn IgG, those with both Cpn IgG+ and IgA+ had 2.00 times the risk (95% CI: 1.34–3.00) of developing lung cancer. Cpn IgG+ or IgA+ was associated with a significantly increased risk of lung cancer among smokers; the adjusted odds ratio (OR) was 1.79 (95% CI: 1.10–2.91) and 2.27 (95% CI: 1.38–3.72), respectively. Those exposed to passive smoking with Cpn IgG+ or IgA+ also showed an increased risk of lung cancer; the adjusted OR was 1.82 (95% CI: 1.20–2.77) or 1.87 (95% CI: 1.22–2.87), respectively. Similar results were also observed among alcohol drinkers. Multiplicative and additive interactions were not observed between Cpn infection and environmental factors. The combined effects of Cpn IgG+ or IgA+ with smoking, passive smoking, and family history of cancer on lung cancer were determined.ConclusionCpn infection is potentially associated with primary lung cancer in the Chinese Han population and has combined effects with smoking, passive smoking, and family history of cancer.
Hypoketotic hypoglycemia in citrin deficiency: a case report
Authors: Wada Yoichi , Arai-Ichinoi Natsuko , Kikuchi Atsuo , Sakamoto Osamu , Kure Shigeo 
Published: September 2020

Abstract
Background
Citrin deficiency (CD) is a recessive metabolic disease caused by biallelic pathogenic variants in SLC25A13. Although previous studies have reported ketosis in CD, it was observed at the time of euglycemia or mild hypoglycemia. Blood ketone levels concomitant with symptomatic or severe hypoglycemia in CD have not been a topic of focus despite its importance in identifying the etiology of hypoglycemia and assessing the ability of fatty acid utilization. Herein, we describe a patient with CD who had repeated episodes of hypoglycemia with insufficient ketosis.

Case presentation
A 1-year-old boy with repetitive hypoglycemia was referred to us to investigate its etiology. The fasting load for 13 h led to hypoketotic hypoglycemia, indicating the possibility of partial β-oxidation dysfunction. A genetic test led to the diagnosis of CD. The hypoglycemic episodes disappeared after switching to a medium-chain triglyceride-containing formula.

Conclusions
This case report suggests that symptomatic or severe hypoglycemia in patients with CD could be associated with relatively low levels of ketone bodies, implying that β-oxidation in these patients might possibly be partially disrupted. When encountering a patient with hypoglycemia, clinicians should check blood ketone levels and bear in mind the possibility of CD because excessive intravenous administration of glucose can cause decompensated symptoms in patients with CD as opposed to other disorders presenting with hypoketotic hypoglycemia, such as fatty acid oxidation disorders. Further studies in a large-scale cohort are warranted to confirm our speculation.
Testing a physical education-delivered autonomy supportive intervention to promote leisure-time physical activity in lower secondary school students: the PETALS trial
Authors: Schneider Jekaterina , Polet Juho , Hassandra Mary , Lintunen Taru , Laukkanen Arto , Hankonen Nelli , Hirvensalo Mirja , Tammelin Tuija H. , Törmäkangas Timo , Hagger Martin S. 
Published: September 2020

Abstract
Background
Inadequate physical activity in young people is associated with several physical and mental health concerns. Physical education (PE) is a potentially viable existing network for promoting physical activity in this population. However, little research has been conducted on whether PE teachers can influence students’ engagement in leisure-time physical activity. The present study therefore examined the efficacy of an intervention aimed at increasing PE teachers’ autonomy support on students’ leisure-time physical activity (the PETALS trial). The intervention was guided by the trans-contextual model (TCM) explaining the processes by which PE teachers’ provision of autonomy support during PE promotes students’ motivation and engagement in physical activity in their leisure time.

Methods
The study adopted a cluster-randomized, waitlist control intervention design with randomization by school. Participants were PE teachers (N = 29, 44.83%female; M age = 42.83, SD = 9.53 yrs) and their lower secondary school students (N = 502, 43.82%female; M age = 14.52, SD = 0.71 yrs). We measured TCM constructs, including perceived autonomy support, autonomous motivation in PE and leisure time, beliefs and intentions towards leisure-time physical activity, and physical activity behavior at baseline, post-intervention, and at one-, three-, and six-months. Study hypotheses were tested through a series of ANOVAs and structural equation models using post-intervention and one-month follow-up data.

Results
We found no changes in TCM constructs or physical activity behavior in either group at post-intervention or at 1 month. Path analyses supported two propositions of the TCM as change variables: perceived autonomy support had a significant effect on autonomous motivation in PE and autonomous motivation in PE had a significant effect on autonomous motivation in leisure time. Although we found a direct effect of autonomous motivation in leisure time on physical activity, we did not find support for the third premise of the TCM that autonomous motivation in leisure time indirectly affects physical activity through beliefs and intentions.

Conclusions
Current findings did not support the efficacy of the PETALS intervention at changing physical activity behavior and TCM constructs. More research is required to determine whether the TCM predictive validity is supported when other model variables are manipulated through experimental and intervention studies.

Trial registration
ISRCTN, ISRCTN39374060. Registered 19 July 2018. Prospectively registered.
Predictors of Poor Postoperative Outcomes in Pediatric Surgery Patients in Rural Ghana
Authors: Peiffer Sarah , Ssentongo Anna E. , Keeney Laura , Amponsah-Manu Forster , Yeboako Richard , Ofosu-Akromah Richard , Arkorful Temitope Ebenezer , Agyemang Eric , Tsai Anthony , Oh John , Ssentongo Paddy 
Published: September 2020

AbstractBackground/PurposePerioperative complications cause significant pediatric morbidity and mortality in low- and lower middle -income countries. This study investigates factors associated with prolonged length of stay, 90-day readmission and in-hospital mortality among pediatric patients at Eastern Regional Hospital (ERH) in Ghana.MethodsThis is a retrospective review of perioperative morbidity and mortality in children < 18 years at ERH in Koforidua, Ghana. All pediatric surgeries performed between January 2015 and December 2017 were included in this study. Univariate analysis was performed using Pearson’s chi-square tests or Fisher’s exact tests. Variables that were significant on univariate analysis were included in multivariable logistic regression models adjusted for age and gender.ResultsWe analyzed 468 patients < 18 years of age with a median length of stay (LOS) of 3 days. The 90-day readmission and in-hospital mortality rates were 138 and 17 per 1000 patients, respectively. The most common procedures were herniorrhaphy (19 %) and appendectomy (15 %). Gastrointestinal surgery, surgical trauma, surgical infection and lack of insurance were significantly associated with prolonged LOS. Young age and female gender were significantly associated with in-hospital mortality. Malaria was significantly associated with 90-day readmission.ConclusionsMalaria infection is a significant risk factor for readmission, which should be investigated and treated in pediatric surgical patients in rural Ghana. Ensuring that all patients have insurance may result in shorter hospital stays. Provision of laparoscopic equipment may reduce hospital stays for patients undergoing gastrointestinal surgery. Expansion of the surgical work force, particularly pediatric surgeons, could improve perioperative survival in the very young population.Level of EvidenceRetrospective comparative study.
Weight gain in patients with severe atopic dermatitis treated with dupilumab: a cohort study
Authors: Johansson Emma Kristin , Ivert Lina Ulrika , Bradley Baltzar , Lundqvist Maria , Bradley Maria 
Published: September 2020

AbstractBackgroundDupilumab, targeting the interleukin-4α receptor and inhibiting the action of interleukin-4 and interleukin-13, was recently approved for treatment of moderate to severe atopic dermatitis. There is limited data on long-term effects and safety among patients with severe atopic dermatitis treated with dupilumab. Weight gain was observed among patients treated with dupilumab in our clinic. The aim was to describe weight change in a cohort study of patients with severe atopic dermatitis treated with dupilumab from baseline to follow-up after 12 months, and to analyze if weight change was associated with effect of treatment, reported appetite, and/or disturbed night sleep due to itching.MethodsAll patients with atopic dermatitis receiving systemic treatment at the Unit of Dermatology, Karolinska University Hospital, have been registered and monitored consecutively since January 2017. This cohort constituted all patients who started treatment on dupilumab or methotrexate between 10 January 2017 and 30 June 2019 with at least 6 months of follow-up within the study period. The following variables were monitored at start of and during treatment: Eczema Severity Score Index, Patient-Oriented Eczema Measure, visual analogue scale for pruritus 10 cm, Montgomery-Åsberg Depression Rating Scale, Dermatology Life Quality Index, and weight. Data analyses were performed using two-sample Wilcoxon-Mann-Whitney rank-sum test, or the Wilcoxon matched-pairs sign-rank test with ap-value < 0.05 considered as statistically significant.ResultsPatients treated with dupilumab (n = 12) gained weight (mean 6.1 kg, range [0.1–18.0],p = 0.002) after 1 year on treatment. The majority of patients showed a good response to treatment with dupilumab (n = 11); at follow-up at 6, 9, or 12 months, they reached EASI-90 (n = 6), EASI-75 (n = 4), or EASI-50 (n = 1). There was no significant association between weight gain and treatment response, reported appetite, or disturbed night-sleep due to itch. Patients treated with methotrexate showed no significant weight change (n = 8).ConclusionsTo our knowledge, this is the first report on a possible association between weight gain and dupilumab treatment; the extent of the association is yet to be seen, as is the mechanism behind this finding.
Variability of residents’ ratings of faculty’s teaching performance measured by five- and seven-point response scales
Authors: Debets Maarten P. M. , Scheepers Renée A. , Boerebach Benjamin C. M. , Arah Onyebuchi A. , Lombarts Kiki M. J. M. H. 
Published: September 2020

Abstract
Background
Medical faculty’s teaching performance is often measured using residents’ feedback, collected by questionnaires. Researchers extensively studied the psychometric qualities of resulting ratings. However, these studies rarely consider the number of response categories and its consequences for residents’ ratings of faculty’s teaching performance. We compared the variability of residents’ ratings measured by five- and seven-point response scales.

Methods
This retrospective study used teaching performance data from Dutch anaesthesiology residency training programs. Questionnaires with five- and seven-point response scales from the extensively studied System for Evaluation of Teaching Qualities (SETQ) collected the ratings. We inspected ratings’ variability by comparing standard deviations, interquartile ranges, and frequency (percentage) distributions. Relevant statistical tests were used to test differences in frequency distributions and teaching performance scores.

Results
We examined 3379 residents’ ratings and 480 aggregated faculty scores. Residents used the additional response categories provided by the seven-point scale – especially those differentiating between positive performances. Residents’ ratings and aggregated faculty scores showed a more even distribution on the seven-point scale compared to the five-point scale. Also, the seven-point scale showed a smaller ceiling effect. After rescaling, the mean scores and (most) standard deviations of ratings from both scales were comparable.

Conclusions
Ratings from the seven-point scale were more evenly distributed and could potentially yield more nuanced, specific and user-friendly feedback. Still, both scales measured (almost) similar teaching performance outcomes. In teaching performance practice, residents and faculty members should discuss whether response scales fit their preferences and goals.