bluuebunny/crossref_metadata_2025_split huggingface dataset:
ElTetrado: a tool for identification and classification of tetrads and quadruplexes
Authors: Zok Tomasz , Popenda Mariusz , Szachniuk Marta 
Published: January 2020

Abstract
Background
Quadruplexes are specific structure motifs occurring, e.g., in telomeres and transcriptional regulatory regions. Recent discoveries confirmed their importance in biomedicine and led to an intensified examination of their properties. So far, the study of these motifs has focused mainly on the sequence and the tertiary structure, and concerned canonical structures only. Whereas, more and more non-canonical quadruplex motifs are being discovered.

Results
Here, we present ElTetrado, a software that identifies quadruplexes (composed of guanine- and other nucleobase-containing tetrads) in nucleic acid structures and classifies them according to the recently introduced ONZ taxonomy. The categorization is based on the secondary structure topology of quadruplexes and their component tetrads. It supports the analysis of canonical and non-canonical motifs. Besides the class recognition, ElTetrado prepares a dot-bracket and graphical representations of the secondary structure, which reflect the specificity of the quadruplex’s structure topology. It is implemented as a freely available, standalone application, available at https://github.com/tzok/eltetrado.

Conclusions
The proposed software tool allows to identify and classify tetrads and quadruplexes based on the topology of their secondary structures. It complements existing approaches focusing on the sequence and 3D structure.
Basal hsp70 expression levels do not explain adaptive variation of the warm- and cold-climate O3 + 4 + 7 and OST gene arrangements of Drosophila subobscura
Authors: Puig Giribets Marta , Santos Mauro , García Guerreiro María Pilar 
Published: January 2020

AbstractBackgroundDrosophila subobscuraexhibits a rich inversion polymorphism, with some adaptive inversions showing repeatable spatiotemporal patterns in frequencies related to temperature. Previous studies reported increased basal HSP70 protein levels in homokaryotypic strains for a warm-climate arrangement compared to a cold-climate one. These findings do not match the similarhsp70genomic organization between arrangements, where gene expression levels are expected to be similar. In order to test this hypothesis and understand the molecular basis forhsp70expression, we compared basalhsp70mRNA levels in males and females, and analysed the 5′ and 3′ regulatory regions ofhsp70genes in warm- and cold-climate isochromosomal O3 + 4 + 7and OSTlines ofD. subobscura.ResultsWe observed comparable mRNA levels between the two arrangements and a sex-biasedhsp70gene expression. The number of heat-shock elements (HSEs) and GAGA sites on the promoters were identical amongst the OSTand O3 + 4 + 7lines analysed. This is also true for 3′ AU-rich elements where most A and B copies ofhsp70have, respectively, two and one element in both arrangements. Beyond the regulatory elements, the only notable difference between both arrangements is the presence in 3′ UTR of a 14 bp additional fragment after the stop codon in thehsp70A copy in five O3 + 4 + 7lines, which was not found in any of the six OSTlines.ConclusionsThe equivalenthsp70mRNA amounts in OSTand O3 + 4 + 7arrangements provide the first evidence of a parallelism between gene expression and genetic organization inD. subobscuralines having these arrangements. This is reinforced by the lack of important differential features in the number and structure of regulatory elements between both arrangements, despite the genetic differentiation observed when the complete 5′ and 3′ regulatory regions were considered. Therefore, the basal levels ofhsp70mRNA cannot account, in principle, for the adaptive variation of the two arrangements studied. Consequently, further studies are necessary to understand the intricate molecular mechanisms ofhsp70gene regulation inD. subobscura.
Identification of functional regulatory elements in the human genome using pooled CRISPR screens
Authors: Borys Samantha M. , Younger Scott T. 
Published: January 2020

Abstract
Background
Genome-scale pooled CRISPR screens are powerful tools for identifying genetic dependencies across varied cellular processes. The vast majority of CRISPR screens reported to date have focused exclusively on the perturbation of protein-coding gene function. However, protein-coding genes comprise < 2% of the sequence space in the human genome leaving a substantial portion of the genome uninterrogated. Noncoding regions of the genome harbor important regulatory elements (e.g. promoters, enhancers, silencers) that influence cellular processes but high-throughput methods for evaluating their essentiality have yet to be established.

Results
Here, we describe a CRISPR-based screening approach that facilitates the functional profiling of thousands of noncoding regulatory elements in parallel. We selected the tumor suppressor p53 as a model system and designed a pooled CRISPR library targeting thousands of p53 binding sites throughout the genome. Following transduction into dCas9-KRAB-expressing cells we identified several regulatory elements that influence cell proliferation. Moreover, we uncovered multiple elements that are required for the p53-mediated DNA damage response. Surprisingly, many of these elements are located deep within intergenic regions of the genome that have no prior functional annotations.

Conclusions
This work diversifies the applications for pooled CRISPR screens and provides a framework for future functional studies focused on noncoding regulatory elements.
Comparative chloroplast genomics of the genus Taxodium
Authors: Duan Hao , Guo Jinbo , Xuan Lei , Wang Ziyang , Li Mingzhi , Yin Yunlong , Yang Ying 
Published: January 2020

Abstract
Background
Chloroplast (cp) genome information would facilitate the development and utilization of Taxodium resources. However, cp genome characteristics of Taxodium were poorly understood.

Results
We determined the complete cp genome sequences of T. distichum, T. mucronatum, and T. ascendens. The cp genomes are 131,947 bp to 132,613 bp in length, encode 120 genes with the same order, and lack typical inverted repeat (IR) regions. The longest small IR, a 282 bp trnQ-containing IR, were involved in the formation of isomers. Comparative analysis of the 3 cp genomes showed that 91.57% of the indels resulted in the periodic variation of tandem repeat (TR) motifs and 72.46% single nucleotide polymorphisms (SNPs) located closely to TRs, suggesting a relationship between TRs and mutational dynamics. Eleven hypervariable regions were identified as candidates for DNA barcode development. Hypothetical cp open reading frame 1(Ycf1) was the only one gene that has an indel in coding DNA sequence, and the indel is composed of a long TR. When extended to cupressophytes, ycf1 genes have undergone a universal insertion of TRs accompanied by extreme length expansion. Meanwhile, ycf1 also located in rearrangement endpoints of cupressophyte cp genomes. All these characteristics highlight the important role of repeats in the evolution of cp genomes.

Conclusions
This study added new evidence for the role of repeats in the dynamics mechanism of cp genome mutation and rearrangement. Moreover, the information of TRs and hypervariable regions would provide reliable molecular resources for future research focusing on the infrageneric taxa identification, phylogenetic resolution, population structure and biodiversity for the genus Taxodium and Cupressophytes.
Genome-wide association study reveals that different pathways contribute to grain quality variation in sorghum (Sorghum bicolor)
Authors: Kimani Wilson , Zhang Li-Min , Wu Xiao-Yuan , Hao Huai-Qing , Jing Hai-Chun 
Published: January 2020

AbstractBackgroundIn sorghum (Sorghum bicolor), one paramount breeding objective is to increase grain quality. The nutritional quality and end use value of sorghum grains are primarily influenced by the proportions of tannins, starch and proteins, but the genetic basis of these grain quality traits remains largely unknown. This study aimed to dissect the natural variation of sorghum grain quality traits and identify the underpinning genetic loci by genome-wide association study.ResultsLevels of starch, tannins and 17 amino acids were quantified in 196 diverse sorghum inbred lines, and 44 traits based on known metabolic pathways and biochemical interactions amongst the 17 amino acids calculated. A Genome-wide association study (GWAS) with 3,512,517 SNPs from re-sequencing data identified 14, 15 and 711 significant SNPs which represented 14, 14, 492 genetic loci associated with levels of tannins, starch and amino acids in sorghum grains, respectively. Amongst these significant SNPs, two SNPs were associated with tannin content on chromosome 4 and colocalized with three previously identified loci forTannin1, and orthologs ofZm1andTT16genes. One SNP associated with starch content colocalized with sucrose phosphate synthase gene. Furthermore, homologues ofopaque1andopaque2genes associated with amino acid content were identified. Using the KEGG pathway database, six and three candidate genes of tannins and starch were mapped into 12 and 3 metabolism pathways, respectively. Thirty-four candidate genes were mapped into 16 biosynthetic and catabolic pathways of amino acids. We finally reconstructed the biosynthetic pathways for aspartate and branched-chain amino acids based on 15 candidate genes identified in this study.ConclusionPromising candidate genes associated with grain quality traits have been identified in the present study. Some of them colocalized with previously identified genetic regions, but novel candidate genes involved in various metabolic pathways which influence grain quality traits have been dissected. Our study acts as an entry point for further validation studies to elucidate the complex mechanisms controlling grain quality traits such as tannins, starch and amino acids in sorghum.
Characterization of wheat homeodomain-leucine zipper family genes and functional analysis of TaHDZ5-6A in drought tolerance in transgenic Arabidopsis
Authors: Li Shumin , Chen Nan , Li Fangfang , Mei Fangming , Wang Zhongxue , Cheng Xinxiu , Kang Zhensheng , Mao Hude 
Published: January 2020

AbstractBackgroundMany studies inArabidopsisand rice have demonstrated that HD-Zip transcription factors play important roles in plant development and responses to abiotic stresses. Although common wheat (Triticum aestivumL.) is one of the most widely cultivated and consumed food crops in the world, the function of the HD-Zip proteins in wheat is still largely unknown.ResultsTo explore the potential biological functions ofHD-Zipgenes in wheat, we performed a bioinformatics and gene expression analysis of the HD-Zip family. We identified 113 HD-Zip members from wheat and classified them into four subfamilies (I-IV) based on phylogenic analysis against proteins fromArabidopsis, rice, and maize. MostHD-Zipgenes are represented by two to three homeoalleles in wheat, which are named asTaHDZX_ZA,TaHDZX_ZB, orTaHDZX_ZD, where X denotes the gene number and Z the wheat chromosome on which it is located.TaHDZsin the same subfamily have similar protein motifs and intron/exon structures. The expression profiles ofTaHDZgenes were analysed in different tissues, at different stages of vegetative growth, during seed development, and under drought stress. We found that mostTaHDZgenes, especially those in subfamilies I and II, were induced by drought stress, suggesting the potential importance of subfamily I and IITaHDZmembers in the responses to abiotic stress. Compared with wild-type (WT) plants, transgenicArabidopsisplants overexpressingTaHDZ5-6Adisplayed enhanced drought tolerance, lower water loss rates, higher survival rates, and higher proline content under drought conditions. Additionally, the transcriptome analysis identified a number of differentially expressed genes between35S::TaHDZ5-6Atransgenic and wild-type plants, many of which are involved in stress response.ConclusionsOur results will facilitate further functional analysis of wheatHD-Zipgenes, and also indicate thatTaHDZ5-6Amay participate in regulating the plant response to drought stress. Our experiments show thatTaHDZ5-6Aholds great potential for genetic improvement of abiotic stress tolerance in crops.
A randomized controlled trial evaluating the impact of selective axillary nerve block after arthroscopic subacromial decompression
Authors: Rothe Christian , Lund Jørgen , Jenstrup Morten Troels , Steen-Hansen Christian , Lundstrøm Lars Hyldborg , Andreasen Asger Mølgaard , Lange Kai Henrik Wiborg 
Published: January 2020

Abstract
Background
The sensory innervation of the shoulder is complex and there are variations in the branching patterns of the sensory fibres. Articular branches from the axillary nerve to the subacromial bursa are described in more than 50% of investigated shoulders but the isolated contribution of sensory input from the axillary nerve has never been investigated clinically.
We hypothesized that a selective block of the axillary nerve would reduce morphine consumption and pain after arthroscopic subacromial decompression.

Methods
We included 60 patients in a randomized, blinded, placebo-controlled study. Patients were randomized to a preoperative selective ultrasound-guided axillary nerve block with 20 mL ropivacaine (7.5 mg/mL) or 20 mL saline. Primary outcome was intravenous morphine consumption 0–4 h postoperatively. Secondary outcome was postoperative pain evaluated by a visual analogue scale (VAS) score (0–100).

Results
We analysed data from 50 patients and found no significant difference in 0–4 h postoperative morphine consumption between the two groups (ropivacaine 14 mg, placebo 18 mg (P = 0.12)). There was a reduction in postoperative pain: VAS 0–4 h (area under the curve) (ropivacaine 135, placebo 182 (P = 0.03)), VAS after 8 h (ropivacaine 9, placebo 20 (P = 0.01)) and VAS after 24 h (ropivacaine 7, placebo 18 (P = 0.04)). Eight out of 19 patients with a successful selective axillary nerve block needed an interscalene brachial plexus escape block.

Conclusions
Selective block of the axillary nerve has some pain relieving effect, but in this setting the effect was unpredictable, variable and far from sufficient in a large proportion of the patients.

Trial registration
ClinicalTrials.gov (NCT01463865). Registered: November 1, 2011.
Selenium, copper, zinc and hypertension: an analysis of the National Health and Nutrition Examination Survey (2011–2016)
Authors: Bastola Mrigendra M. , Locatis Craig , Maisiak Richard , Fontelo Paul 
Published: January 2020

Abstract
Background
Hypertension is a major cardiovascular illness worldwide with many underlying causes. The role of trace elements selenium, copper, and zinc in hypertension is uncertain. The objective of this study was to evaluate the role of these trace elements in hypertension.

Method
Data from 6683 National Health and Nutrition Examination Survey (NHANES) participants from 2011 to 2016 were analyzed using Statistical Analytical System (SAS, version 9.4) software for the role of trace elements in hypertension in age range 8 to 80 years, irrespective of the antihypertensive medication taken. Recent American Heart Association guidelines and pediatric practice guidelines for hypertension were used.

Results
Findings showed a significant positive association between serum selenium levels and hypertension but not serum zinc and copper. At optimal levels for transport and distribution, serum selenium levels of 120 μg/L or higher (reference level 70–150 μg/L) were significantly associated with hypertension (OR = 1.46, 95% CI = 1.29–1.66) after adjusting for confounding factors. At serum selenium level greater than 150 μg/L, the association with hypertension strengthened (OR = 1.69, 95% CI = 1.32–2.17).

Conclusion
A positive association was found between serum selenium and hypertension, irrespective of age or anti-hypertensive medications intake. These findings also suggest that the reference levels of serum levels in healthy individuals may need to be re-determined, if supported by additional studies. If validated, patients with hypertension may also need to be cautioned about selenium intake.
Regional differences in reasons for consultation and general practitioners’ spectrum of services in northern Germany – results of a cross-sectional observational study
Authors: Schäfer Ingmar , Hansen Heike , Ruppel Thomas , Lühmann Dagmar , Wagner Hans-Otto , Kazek Agata , Scherer Martin 
Published: January 2020

Abstract
Background
Among other factors, the patients’ consultation reasons and GPs’ spectrum of services determine the process and outcome of the medical treatment. So far, however, there has been little information on differences in reasons for consultation and GPs’ services between urban and rural areas. Our study’s goal was thus to investigate these factors in relation to the regional location of GPs’ practices.

Methods
We conducted a cross-sectional observational study based on standardised GP interviews in a quota sampling design. All counties and independent cities within a radius of 120 km around Hamburg were divided into three regional categories (urban area, environs, rural area) and stratified proportionally to the population size. Differences in the number of reasons for consultation and services were analysed by multivariate linear regressions in mixed models adjusted for random effects on the levels of the German federal states and administrative districts. Differences in individual consultation reasons and services were identified by logistic regression via stepwise forward and backward selection.

Results
Primary care practices in 34 of the 37 selected administrative districts (91.9%) were represented in the dataset. In total, 211 GPs were personally interviewed. On average, GPs saw 344 patients per month with a slightly higher number of patients in rural areas. They reported 59.1 ± 15.4 different reasons for consultation and 30.3 ± 3.9 different services. There was no statistically significant regional variation in the number of different consultation reasons, but there was a broader service spectrum by rural GPs (ß = − 1.42; 95% confidence interval − 2.75/− 0.08; p = 0.038) which was statistically explained by a higher level of medical training. Additionally, there were differences in the frequency of individual consultation reasons and services between rural and urban areas.

Conclusion
GPs in rural areas performed more frequently services usually provided by medical specialists in urban areas. This might be caused by a low availability of specialists in rural areas. The association between medical training and service spectrum might imply that GPs compensate the specific needs of their patients by completing advanced medical training before or after setting up a medical practice.

Trial registration
The study was registered in ClinicalTrials.gov (NCT02558322).
Prevention and management of diarrhea associated with naldemedine among patients receiving opioids: a retrospective cohort study
Authors: Takagi Yusuke , Osawa Gakuji , Kato Yoriko , Ikezawa Eri , Kobayashi Chika , Aruga Etsuko 
Published: January 2020

Abstract
Background
Naldemedine, a novel peripherally-acting mu-opioid receptor antagonist, has improved opioid-induced constipation in randomized controlled trials. The most frequent adverse event of naldemedine is diarrhea, which can cause abdominal pain and often leads to treatment discontinuation. We aimed to identify risk factors and appropriate management strategies for key adverse events including diarrhea associated with naldemedine, since those have not been extensively studied.

Methods
We conducted a multi-center retrospective cohort study. Eligible patients had cancer, had undergone palliative care at participating centers, had been prescribed regular opioids, and had taken at least one dose of naldemedine between June 2017 and March 2018. The primary endpoint was the incidence of diarrhea according to baseline characteristics. Secondary endpoints included the duration of naldemedine administration, daily defecation counts before and after starting naldemedine, duration and severity of diarrhea as an adverse event of naldemedine, other adverse events, and the incidence of constipation within 7 days after recovery from diarrhea. We defined patients who started naldemedine within three days of starting a regularly prescribed opioid as the early group, and the remainder as the late group.

Results
Among 103 patients who received naldemedine, 98 fulfilled the eligibility criteria. The median age was 68 years and 48% of the patients were female. Median performance status was 3, and the median oral intake was 50%. The median duration of naldemedine administration and overall survival were 25 and 64 days, respectively. The incidence of diarrhea in the early group (n = 26) was significantly lower than in the late group (n = 72) (3.9% vs. 22.2%, p = 0.02). Daily defecation counts increased after late (median 0.43 to 0.88, p < 0.001), but remained stable after early naldemedine administration (median 1.00 to 1.00, p = 0.34). Constipation after the diarrhea was resolved was common (53%), especially among patients who stopped naldemedine (78%). The diarrhea was improved within three days in 92% of patients who stopped other laxatives.

Conclusions
The early administration of naldemedine is beneficial because it reduces adverse events including diarrhea. Diarrhea caused by naldemedine can be effectively managed by stopping other laxatives while continuing naldemedine.
Safety of endoscopic procedures with monopolar versus bipolar instruments in an ex vivo porcine model
Authors: Shinmura Kensuke , Ikematsu Hiroaki , Kojima Motohiro , Nakamura Hiroshi , Osera Shozo , Yoda Yusuke , Hori Keisuke , Oono Yasuhiro , Ochiai Atsushi , Yano Tomonori 
Published: January 2020

Abstract
Background
Monopolar instruments are generally used in colorectal endoscopic mucosal resection (EMR). Bipolar instruments have previously been reported to be as safe as monopolar instruments. We sought to compare the safety of the monopolar and bipolar snare and hemostatic forceps in an animal model.

Methods
We created 5-mm, 10-mm, and 15-mm target lesions on an ex vivo porcine rectum. Two lesions of each size were resected via monopolar polypectomy (M-P), monopolar EMR (M-E), bipolar polypectomy (B-P), and bipolar EMR (B-E). We performed a pathological evaluation of the conditions of perforation and the effects of burning on the tissues. In addition, we burned the muscularis propria covered with submucosal layer using monopolar and bipolar hemostatic forceps and performed pathological evaluations.

Results
Polypectomy and EMR were performed in a total of 24 target lesions. A perforation was found on histology in one case of M-P and one case of M-E after removing target lesions of 15 mm in diameter. There were no perforations during endoscopic resection using the bipolar snare. The thermal denaturation in B-P did not reach the muscularis propria layer regardless of the size of the target lesion. Although thermal damage after using monopolar hemostatic forceps was extensive, thermal denaturation was only seen on the surface of the submucosal layer when bipolar hemostatic forceps were used.

Conclusions
Bipolar instruments cause less damage to the tissue than monopolar instruments. Our results also suggest that bipolar instruments may be safer than monopolar instruments in endoscopic procedures for colorectal lesions.