bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of fetal unmodified and 5-hydroxymethylated CG sites in maternal cell-free DNA for non-invasive prenatal testing
Authors: Gordevičius Juozas , Narmontė Milda , Gibas Povilas , Kvederavičiūtė Kotryna , Tomkutė Vita , Paluoja Priit , Krjutškov Kaarel , Salumets Andres , Kriukienė Edita 
Published: October 2020

Abstract
Background
Massively parallel sequencing of maternal cell-free DNA (cfDNA) is widely used to test fetal genetic abnormalities in non-invasive prenatal testing (NIPT). However, sequencing-based approaches are still of high cost. Building upon previous knowledge that placenta, the main source of fetal circulating DNA, is hypomethylated in comparison to maternal tissue counterparts of cfDNA, we propose that targeting either unmodified or 5-hydroxymethylated CG sites specifically enriches fetal genetic material and reduces numbers of required analytical sequencing reads thereby decreasing cost of a test.

Methods
We employed uTOPseq and hmTOP-seq approaches which combine covalent derivatization of unmodified or hydroxymethylated CG sites, respectively, with next generation sequencing, or quantitative real-time PCR.

Results
We detected increased 5-hydroxymethylcytosine (5hmC) levels in fetal chorionic villi (CV) tissue samples as compared with peripheral blood. Using our previously developed uTOP-seq and hmTOP-seq approaches we obtained whole-genome uCG and 5hmCG maps of 10 CV tissue and 38 cfDNA samples in total. Our results indicated that, in contrast to conventional whole genome sequencing, such epigenomic analysis highly specifically enriches fetal DNA fragments from maternal cfDNA. While both our approaches yielded 100% accuracy in detecting Down syndrome in fetuses, hmTOP-seq maintained such accuracy at ultra-low sequencing depths using only one million reads. We identified 2164 and 1589 placenta-specific differentially modified and 5-hydroxymethylated regions, respectively, in chromosome 21, as well as 3490 and 2002 Down syndrome-specific differentially modified and 5-hydroxymethylated regions, respectively, that can be used as biomarkers for identification of Down syndrome or other epigenetic diseases of a fetus.

Conclusions
uTOP-seq and hmTOP-seq approaches provide a cost-efficient and sensitive epigenetic analysis of fetal abnormalities in maternal cfDNA. The results demonstrated that T21 fetuses contain a perturbed epigenome and also indicated that fetal cfDNA might originate from fetal tissues other than placental chorionic villi. Robust covalent derivatization followed by targeted analysis of fetal DNA by sequencing or qPCR presents an attractive strategy that could help achieve superior sensitivity and specificity in prenatal diagnostics.
Leveraging locus-specific epigenetic heterogeneity to improve the performance of blood-based DNA methylation biomarkers
Authors: Miller Brendan F. , Pisanic II Thomas R. , Margolin Gennady , Petrykowska Hanna M. , Athamanolap Pornpat , Goncearenco Alexander , Osei-Tutu Akosua , Annunziata Christina M. , Wang Tza-Huei , Elnitski Laura 
Published: October 2020

Abstract
Background
Variation in intercellular methylation patterns can complicate the use of methylation biomarkers for clinical diagnostic applications such as blood-based cancer testing. Here, we describe development and validation of a methylation density binary classification method called EpiClass (available for download at https://github.com/Elnitskilab/EpiClass) that can be used to predict and optimize the performance of methylation biomarkers, particularly in challenging, heterogeneous samples such as liquid biopsies. This approach is based upon leveraging statistical differences in single-molecule sample methylation density distributions to identify ideal thresholds for sample classification.

Results
We developed and tested the classifier using reduced representation bisulfite sequencing (RRBS) data derived from ovarian carcinoma tissue DNA and controls. We used these data to perform in silico simulations using methylation density profiles from individual epiallelic copies of ZNF154, a genomic locus known to be recurrently methylated in numerous cancer types. From these profiles, we predicted the performance of the classifier in liquid biopsies for the detection of epithelial ovarian carcinomas (EOC). In silico analysis indicated that EpiClass could be leveraged to better identify cancer-positive liquid biopsy samples by implementing precise thresholds with respect to methylation density profiles derived from circulating cell-free DNA (cfDNA) analysis. These predictions were confirmed experimentally using DREAMing to perform digital methylation density analysis on a cohort of low volume (1-ml) plasma samples obtained from 26 EOC-positive and 41 cancer-free women. EpiClass performance was then validated in an independent cohort of 24 plasma specimens, derived from a longitudinal study of 8 EOC-positive women, and 12 plasma specimens derived from 12 healthy women, respectively, attaining a sensitivity/specificity of 91.7%/100.0%. Direct comparison of CA-125 measurements with EpiClass demonstrated that EpiClass was able to better identify EOC-positive women than standard CA-125 assessment. Finally, we used independent whole genome bisulfite sequencing (WGBS) datasets to demonstrate that EpiClass can also identify other cancer types as well or better than alternative methylation-based classifiers.

Conclusions
Our results indicate that assessment of intramolecular methylation density distributions calculated from cfDNA facilitates the use of methylation biomarkers for diagnostic applications. Furthermore, we demonstrated that EpiClass analysis of ZNF154 methylation was able to outperform CA-125 in the detection of etiologically diverse ovarian carcinomas, indicating broad utility of ZNF154 for use as a biomarker of ovarian cancer.
Time course of altered DNA methylation evoked by critical illness and by early administration of parenteral nutrition in the paediatric ICU
Authors: Verlinden Ines , Güiza Fabian , Derese Inge , Wouters Pieter J. , Joosten Koen , Verbruggen Sascha C. , Van den Berghe Greet , Vanhorebeek Ilse 
Published: October 2020

Abstract
Background
A genome-wide study identified de novo DNA methylation alterations in leukocytes of children at paediatric intensive care unit (PICU) discharge, offering a biological basis for their impaired long-term development. Early parenteral nutrition (early-PN) in PICU, compared with omitting PN in the first week (late-PN), explained differential methylation of 23% of the affected CpG-sites. We documented the time course of altered DNA methylation in PICU and the impact hereon of early nutritional management.

Results
We selected 36 early-PN and 36 late-PN matched patients, and 42 matched healthy children. We quantified DNA methylation on days 3, 5 and 7 for the 147 CpG-sites of which methylation was normal upon PICU admission in this subset and altered by critical illness at PICU discharge. Methylation in patients differed from healthy children for 64.6% of the 147 CpG-sites on day 3, for 72.8% on day 5 and for 90.5% on day 7 as revealed by ANOVA at each time point. Within-patients methylation time course analyses for each CpG-site identified different patterns based on paired t test p value and direction of change. Rapid demethylation from admission to day 3 occurred for 76.2% of the CpG-sites, of which 67.9% remained equally demethylated or partially remethylated and 32.1% further demethylated beyond day 3. From admission to day 3, 19.7% of the CpG-sites became hypermethylated, of which, beyond day 3, 34.5% remained equally hypermethylated or partially demethylated again and 65.5% further hypermethylated. For 4.1% of the CpG-sites, changes only appeared beyond day 3. Finally, for the CpG-sites affected by early-PN on the last PICU day, earlier changes in DNA methylation were compared for early-PN and late-PN patients, revealing that 38.9% were already differentially methylated by day 3, another 25.0% by day 5 and another 13.9% by day 7.

Conclusions
Critical illness- and early-PN-induced changes in DNA methylation occurred mainly within 3 days. Most abnormalities were at least partially maintained or got worse with longer time in PICU. Interventions targeting aberrant DNA methylation changes should be initiated early.
Design and analysis of e-commerce and modern logistics for regional economic integration in wireless networks
Authors: Tang Xiaodong , Wang Gangyi 
Published: October 2020

AbstractThe rapid development of e-commerce has greatly promoted the development of modern logistics. The application level of e-commerce and the application status of modern logistics largely determine the development of a regional economic structure. Under such circumstances, it is particularly important to comprehensively strengthen the research on the impact of e-commerce and modern logistics on the network regional economy. China is as one of the most active regions over the world. Therefore, in this paper, we take the network regional economic as the research object. Firstly, we obtain relevant regional logistics nodes and e-commerce information through wireless networks. Secondly, based on information acquisition, we propose an empirical analysis of the development status of the logistics industry and e-commerce, and we also explain their contributions to regional economic growth. Finally, this paper proposes countermeasures to further increase the contribution of logistics and e-commerce to economic growth. This will provide a reference for building a regionally coordinated logistics-e-commerce system and realizing regional economic integration.
A robotic end-effector with rolling up mechanism for pick-and-release of a cotton sheet
Authors: Abe Taiki , Kawasaki Yuichi , Yamazaki Kimitoshi 
Published: October 2020

AbstractIn this paper we introduce a novel robotic end-effector for pick-and-release of a sheet of cotton cloth. One of the main operations in a factory for sewing cloth products is to pick up cloth parts, provide them to a sewing machine, and sew them together. Fabric products are assembled by performing this work in various processes. Each work starts with a lot of cloth parts stacked near a sewing machine. In the case of underwear, thin cotton cloth is the target of manipulation, but such cloth parts tend to stick to each other, and a certain skill or technical acuity is required for picking up. Therefore, this work is basically done manually in the present. The purpose of this study is to automate such manipulation, so we devise an end-effector that picks up only the top one of stacked cotton sheets. The proposed end-effector has a mechanism that is a cylindrical brush attached with a remover cloth on its surface. The cylindrical brush is grounded on a cotton sheet, and then is rotated to roll up only the cotton sheet. This mechanism makes it possible to release the sheet by rotating the brush in the reverse. We constructed hardware with this function and attached it to the tip of a robotic manipulator. In addition, we performed system integration so that the initial position of rolling up a cotton sheet could be automatically determined from images taken by a camera. We also conducted evaluation experiments.
Comparative study between intranasal dexmedetomidine and intranasal ketamine as a premedication for anxiolysis and sedation before pediatric general anesthesia
Authors: Elshafeey Ahmed Elsayed Ahmed Mohamed , Youssef Gehan Fouad Kamel , Elsalam Ehab Hamed Abd , Saleh Mohamed , Mahrose Ramy 
Published: October 2020

Abstract
Background
This study compared dexmedetomidine versus ketamine as regard sedation and anxiolysis produced by giving them through intranasal route to pediatric patients undergoing adenotonsillectomy. This study was double-blinded randomized comparative prospective interventional clinical study done in Ain Shams University Hospital (El Demerdash Hospital) on 76 pediatric patients who underwent adenotonsillectomy, and they were randomly allocated equally into two main groups; group D received 2 μg/kg intranasal dexmedetomidine and group K received 5 μg/Kg intranasal ketamine 30 min before the operation, and the aim of this study was to compare the efficacy of intranasal dexmedetomidine versus intranasal ketamine for anxiolysis and sedation to alleviate stress, agitation, and anxiety in children before general anesthesia and for promoting good level of sedation for them.

Results
Results of this study as regards sedation level that was assessed by modified Ramsay sedation score showed that there was statistically significant difference between both groups at 10, 20, and 30 min from intranasal application of the drug (P value < 0.05), the median (IQR) of sedation score at 10, 20, and 30 min preoperative in group D was (2 (2 – 2)), (3 (3 – 4)), (4 (4 – 5)) compared to (2 (2 – 3)), (3 (2 – 3)), (4 (3 – 4)) in group K respectively which revealed that there was better and effective sedation in group D more than in group K, this difference was statistically significant but clinically insignificant as both drugs produced an acceptable level of sedation and decreased the level of anxiety in children.

Conclusion
Both drugs produce effective and favorable sedation level with superiority to dexmedetomidine in sedation scores and time of onset of sedation, and also there was little decrease in heart rate and mean arterial pressure which is favorable during such surgeries; also, there was accepted level of cannulation and parental separation scores, and the parents were highly satisfied with the procedure and were grateful for us due to alleviating stress and anxiety from them and from their children.
Pharmacovigilance and incidence of adverse drug reactions in hospitalized pediatric patients: a mini systematic review
Authors: Khan Zakir , Muhammad Khayal , Karatas Yusuf , Bilen Cagri , Khan Farman Ullah , Khan Faiz Ullah 
Published: October 2020

AbstractBackgroundPharmacovigilance is an identifying and responding process against an adverse drug reaction (ADRs) problem encountered in the drug administration. ADRs are among the common reasons for morbidity and fatality in pediatrics throughout the globe.Main bodyA systemic review of the previous 10 years (2010–2019) published studies were taken into consideration to describe observational studies on ADRs and to determine the incidence and characteristics of ADRs in pediatrics. Electronic relevant literature was searched in PMC, PubMed, Google Scholar, and OvidSP databases using MESH heading and text words. The titles, text, and abstracts were checked for patients below 18 years of age, nature of ADRs, observational studies (prospective or retrospective), and maximum information was recorded to count their frequency. The studies which discussed specific or particular drug exposures were not selected in this review. Of the 36,689 titles retrieved, 27 studies were selected for full-text review. Ten observational studies were added in the final review. Observational studies on pediatric were carried out in seven distinct nations. The predominant study design within observational methodological studies was prospective (n= 5, 50%). The overall average occurrence of ADRs incidence was 9.52%. ADRs reporting in male patients (54.6%) were more than females (45.4%). The severe types of ADRs were reported in four studies. Anti-microbials were the most common class of drugs related to ADRs.ConclusionThis systematic review reveals that ADRs in pediatrics are serious public health problems. Periodic drug surveillance studies are mandatory for the safe and appropriate usage of medicines in pediatrics.
Radical External-Beam Radiotherapy in Combination With Intracavitary Brachytherapy for Localized Carcinoma of the Cervix in Sri Lanka: Is Treatment Delayed Treatment Denied?
Authors: Joseph Nuradh , Jayalath Hasanthi , Balawardena Jayantha , Skandarajah Thurairajah , Perera Kanthi , Gunasekera Dehan , Weerasinghe Sujeeva , Hoskin Peter , Choudhury Ananya 
Published: October 2020

PURPOSE Radical external-beam radiotherapy (EBRT) followed by intracavitary brachytherapy is standard of care for patients with localized carcinoma of the cervix unsuitable for radical surgery. However, outcome data are scarce in resource-limited settings. We conducted a retrospective analysis of survival in a cohort of patients treated with this strategy in Sri Lanka. PATIENTS AND METHODS All patients with localized cervical cancer treated with primary EBRT and intracavitary brachytherapy from 2014 to 2015 were included in the study. Primary end point was disease-free survival (DFS), defined as time to local or systemic recurrence or death. Univariable analysis was performed to determine the prognostic significance of the following variables: age, stage, use of concurrent chemotherapy, EBRT dose, brachytherapy dose, and time to completion of treatment (dichotomized at 60 days). Factors significant on univariable analysis were included in a multivariable model. RESULTS A total of 113 patients with available data were included in the analysis. Mean age was 58 years (range, 35-85 years), and most patients (n = 103 of 113) presented with stage ≥ IIB disease. Median time to delivery of brachytherapy from commencement of EBRT was 110 days (range, 34-215 days), with only 12 (11%) of 113 patients completing treatment within 60 days. Median follow-up was 28 months (range, 5-60 months), and 2-year DFS was 63.7% (95% CI, 55.4% to 73.2%). Treatment delay was the only significant factor associated with inferior DFS on univariable analysis (log-rank P = .03), and therefore, multivariable analysis was not performed. CONCLUSION There are significant delays in receiving intracavitary brachytherapy after completing EBRT for cervical cancer in Sri Lanka, which is associated with inferior DFS. Increasing brachytherapy resources is an urgent priority to improve outcomes of patients with cervical cancer.
Elevated Plasma Branched-Chain Amino Acid Levels Correlate With Type 2 Diabetes–Related Metabolic Disturbances
Authors: Vanweert Froukje , de Ligt Marlies , Hoeks Joris , Hesselink Matthijs K C , Schrauwen Patrick , Phielix Esther 
Published: October 2020

Abstract

Context
Patients with type 2 diabetes mellitus (T2DM) have elevated plasma branched-chain amino acid (BCAA) levels. The underlying cause, however, is not known. Low mitochondrial oxidation of BCAA levels could contribute to higher plasma BCAA levels.

Objective
We aimed to investigate ex vivo muscle mitochondrial oxidative capacity and in vivo BCAA oxidation measured by whole-body leucine oxidation rates in patients with T2DM, first-degree relatives (FDRs), and control participants (CONs) with overweight or obesity.

Design and Setting
An observational, community-based study was conducted.

Participants
Fifteen patients with T2DM, 13 FDR, and 17 CONs were included (age, 40-70 years; body mass index, 27-35 kg/m2).

Main Outcome Measures
High-resolution respirometry was used to examine ex vivo mitochondrial oxidative capacity in permeabilized muscle fibers. A subgroup of 5 T2DM patients and 5 CONs underwent hyperinsulinemic-euglycemic clamps combined with 1-13C leucine-infusion to determine whole-body leucine oxidation.

Results
Total BCAA levels were higher in patients with T2DM compared to CONs, but not in FDRs, and correlated negatively with muscle mitochondrial oxidative capacity (r = –0.44, P &lt; .001). Consistently, whole-body leucine oxidation rate was lower in patients with T2DM vs CON under basal conditions (0.202 ± 0.049 vs 0.275 ± 0.043 μmol kg–1 min–1, P &lt; .05) and tended to be lower during high insulin infusion (0.326 ± 0.024 vs 0.382 ± 0.013 μmol kg–1 min–1, P = .075).

Conclusions
In patients with T2DM, a compromised whole-body leucine oxidation rate supports our hypothesis that higher plasma BCAA levels may originate at least partly from a low mitochondrial oxidative capacity.
External Financing and Customer Capital: A Financial Theory of Markups
Authors: Dou Winston Wei , Ji Yan 
Published: October 2020

We develop a continuous-time industry equilibrium model of monopolistic competition to understand how product markups are determined in the presence of external financing costs and customer capital. Firms optimally set markups to balance the tradeoff between profiting from their existing customer base and developing their future customer base. We characterize how the equilibrium markups are determined by the interaction between the marginal value of corporate liquidity and the marginal value of customer base. Firms’ markups are more responsive to changes in their marginal value of corporate liquidity when the marginal value of customer base is higher. Moreover, the model predicts that greater product market threats lead to more conservative financial policies, which is supported by the data. This paper was accepted by Gustavo Manso, finance.
Minimum ten-year follow-up of a randomized trial comparing acetabular component fixation of two porous in-growth surfaces using radiosteriometric analysis
Authors: Rahman Luthfur , Ibrahim Mazin S. , Somerville Lyndsay , Teeter Matthew G. , Naudie Douglas D. , McCalden Richard W. 
Published: October 2020

Aims To compare the in vivo long-term fixation achieved by two acetabular components with different porous ingrowth surfaces using radiostereometric analysis (RSA). Methods This was a minimum ten-year follow-up of a prospective randomized trial of 62 hips with two different porous ingrowth acetabular components. RSA exams had previously been acquired through two years of follow-up. Patients returned for RSA examination at a minimum of ten years. In addition, radiological appearance of these acetabular components was analyzed, and patient-reported outcome measures (PROMs) obtained. Results In all, 15 hips were available at ten years. There was no statistically significant difference in PROMS between the two groups; PROMs were improved at ten years compared to preoperative scores. Conventional radiological assessment revealed well-fixed components. There was minimal movement for both porous surfaces in translation (X, Y, Z, 3D translation in mm (median and interquartile range (IQR)), StikTite (Smith and Nephew, Memphis, Tennessee, USA): 0.03 (1.08), 0.12 (0.7), 0.003 (2.3), 0.37 (0.30), and Roughcoat (Smith and Nephew): -0.6 (0.59),–0.1 (0.49), 0.1 (1.12), 0.48 (0.38)), and rotation (X, Y, Z rotation in degrees (median and IQR), (Stiktite: -0.4 (3), 0.28 (2), -0.2 (1), and Roughcoat: - 0.4 (1),–0.1 (1), 0.2 (2)). There was no statistically significant difference between the two cohorts (p-value for X, Y, Z, 3D translation - 0.54, 0.46, 0.87, 0.55 and for X, Y, Z rotation - 0.41, 0.23, 0.23 respectively) at ten years. There was significant correlation between two years and ten years 3D translation for all components ( r = 0.81(p =< 0.001)). Conclusion Both porous ingrowth surfaces demonstrated excellent fixation on plain radiographs and with RSA at ten years. Short-term RSA data are good predictors for long-term migration data.
Admittance analysis of broadband omnidirectional near-perfect absorber in epsilon-near-zero mode
Authors: Liao Wei-Bo , Lee Cheng-Chung , Chang Ya-Chen , Cho Wen-Hao , Chen Hung-Pin , Kuo Chien-Cheng 
Published: October 2020

In this paper, we propose a broadband omnidirectional near-perfect absorber that transforms light energy into heat. In contrast to previous research on structural metamaterials, this study focuses on light absorption in the epsilon-near-zero (ENZ) layers without any structural patterns. Chromium (Cr) thin films were applied as ENZ layers. Using the admittance method, we found the proper thicknesses of

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layers to match the incident medium and achieve perfect absorption. Also, the absorber is angular insensitive up to 60°. The temperature of the absorber increases from room temperature to 42°C, which is 4°C higher than the uncoated substrate at 38°C, after exposure to sunlight for 20 min.