bluuebunny/crossref_metadata_2025_split huggingface dataset:
ppiGReMLIN: a graph mining based detection of conserved structural arrangements in protein-protein interfaces
Authors: Queiroz Felippe C. , Vargas Adriana M. P. , Oliveira Maria G. A. , Comarela Giovanni V. , Silveira Sabrina A. 
Published: April 2020

Abstract
Background
Protein-protein interactions (PPIs) are fundamental in many biological processes and understanding these interactions is key for a myriad of applications including drug development, peptide design and identification of drug targets. The biological data deluge demands efficient and scalable methods to characterize and understand protein-protein interfaces. In this paper, we present ppiGReMLIN, a graph based strategy to infer interaction patterns in a set of protein-protein complexes. Our method combines an unsupervised learning strategy with frequent subgraph mining in order to detect conserved structural arrangements (patterns) based on the physicochemical properties of atoms on protein interfaces. To assess the ability of ppiGReMLIN to point out relevant conserved substructures on protein-protein interfaces, we compared our results to experimentally determined patterns that are key for protein-protein interactions in 2 datasets of complexes, Serine-protease and BCL-2.

Results
ppiGReMLIN was able to detect, in an automatic fashion, conserved structural arrangements that represent highly conserved interactions at the specificity binding pocket of trypsin and trypsin-like proteins from Serine-protease dataset. Also, for the BCL-2 dataset, our method pointed out conserved arrangements that include critical residue interactions within the conserved motif LXXXXD, pivotal to the binding specificity of BH3 domains of pro-apoptotic BCL-2 proteins towards apoptotic suppressors. Quantitatively, ppiGReMLIN was able to find all of the most relevant residues described in literature for our datasets, showing precision of at least 69% up to 100% and recall of 100%.

Conclusions
ppiGReMLIN was able to find highly conserved structures on the interfaces of protein-protein complexes, with minimum support value of 60%, in datasets of similar proteins. We showed that the patterns automatically detected on protein interfaces by our method are in agreement with interaction patterns described in the literature.
Comparing copy-number profiles under multi-copy amplifications and deletions
Authors: Cordonnier Garance , Lafond Manuel 
Published: April 2020

Abstract
Background
During cancer progression, malignant cells accumulate somatic mutations that can lead to genetic aberrations. In particular, evolutionary events akin to segmental duplications or deletions can alter the copy-number profile (CNP) of a set of genes in a genome. Our aim is to compute the evolutionary distance between two cells for which only CNPs are known. This asks for the minimum number of segmental amplifications and deletions to turn one CNP into another. This was recently formalized into a model where each event is assumed to alter a copy-number by 1 or −1, even though these events can affect large portions of a chromosome.

Results
We propose a general cost framework where an event can modify the copy-number of a gene by larger amounts. We show that any cost scheme that allows segmental deletions of arbitrary length makes computing the distance strongly NP-hard. We then devise a factor 2 approximation algorithm for the problem when copy-numbers are non-zero and provide an implementation called . We evaluate our approach experimentally by reconstructing simulated cancer phylogenies from the pairwise distances inferred by and compare it against two other alternatives, namely the distance and the Euclidean distance.

Conclusions
The experimental results show that our distance yields more accurate phylogenies on average than these alternatives if the given CNPs are error-free, but that the distance is slightly more robust against error in the data. In all cases, our experiments show that either our approach or the approach should preferred over the Euclidean distance.
Whole-genome genotyping and resequencing reveal the association of a deletion in the complex interferon alpha gene cluster with hypothyroidism in dogs
Authors: Bianchi Matteo , Rafati Nima , Karlsson Åsa , Murén Eva , Rubin Carl-Johan , Sundberg Katarina , Andersson Göran , Kämpe Olle , Hedhammar Åke , Lindblad-Toh Kerstin , Rosengren Pielberg Gerli 
Published: April 2020

AbstractBackgroundHypothyroidism is a common complex endocrinopathy that typically has an autoimmune etiology, and it affects both humans and dogs. Genetic and environmental factors are both known to play important roles in the disease development. In this study, we sought to identify the genetic risk factors potentially involved in the susceptibility to the disease in the high-risk Giant Schnauzer dog breed.ResultsBy employing genome-wide association followed by fine-mapping (top variantp-value = 5.7 × 10− 6), integrated with whole-genome resequencing and copy number variation analysis, we detected a ~ 8.9 kbp deletion strongly associated (p-value = 0.0001) with protection against development of hypothyroidism. The deletion is located between two predicted Interferon alpha (IFNA) genes and it may eliminate functional elements potentially involved in the transcriptional regulation of these genes. Remarkably, type I IFNs have been extensively associated to human autoimmune hypothyroidism and general autoimmunity. Nonetheless, the extreme genomic complexity of the associated region on CFA11 warrants further long-read sequencing and annotation efforts in order to ascribe functions to the identified deletion and to characterize the canineIFNAgene cluster in more detail.ConclusionsOur results expand the current knowledge on genetic determinants of canine hypothyroidism by revealing a significant link with the human counterpart disease, potentially translating into better diagnostic tools across species, and may contribute to improved canine breeding strategies.
Coordinated mechanisms of leaves and roots in response to drought stress underlying full-length transcriptome profiling in Vicia sativa L
Authors: Min Xueyang , Lin Xiaoshan , NDAYAMBAZA Boniface , Wang Yanrong , Liu Wenxian 
Published: April 2020

Abstract
Background
Common vetch (Vicia sativa L.) is an important self-pollinating annual forage legume and is of interest for drought prone regions as a protein source to feed livestock and human consumption. However, the development and production of common vetch are negatively affected by drought stress. Plants have evolved common or distinct metabolic pathways between the aboveground and underground in response to drought stress. Little is known regarding the coordinated response of aboveground and underground tissues of common vetch to drought stress.

Results
Our results showed that a total of 30,427 full-length transcripts were identified in 12 samples, with an average length of 2278.89 bp. Global transcriptional profiles of the above 12 samples were then analysed via Illumina-Seq. A total of 3464 and 3062 differentially expressed genes (DEGs) were identified in the leaves and roots, respectively. Gene Ontology (GO) enrichment analyses identified that the dehydrin genes and Δ1-pyrroline-5-carboxylate synthase were induced for the biosynthesis of proline and water conservation. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis results indicated that the DEGs were significantly enriched in hormone signal transduction, starch and sucrose metabolism, and arginine and proline metabolism, and various drought response candidate genes were also identified. Abscisic acid (ABA; the AREB/ABF-SnRK2 pathway) regulates the activity of AMY3 and BAM1 to induce starch degradation in leaves and increase carbon export to roots, which may be associated with the drought stress responses in common vetch. Among the co-induced transcription factors (TFs), AREB/ABF, bHLH, MYB, WRKY, and AP2/ERF had divergent expression patterns and may be key in the crosstalk between leaves and roots during adaption to drought stress. In transgenic yeast, the overexpression of four TFs increased yeast tolerance to osmotic stresses.

Conclusion
The multipronged approach identified in the leaves and roots broadens our understanding of the coordinated mechanisms of drought response in common vetch, and further provides targets to improve drought resistance through genetic engineering.
Ultrahigh-activity immune inducer from Endophytic Fungi induces tobacco resistance to virus by SA pathway and RNA silencing
Authors: Peng Chune , Zhang Ailing , Wang Qingbin , Song Yunzhi , Zhang Min , Ding Xinhua , Li Yang , Geng Quanzheng , Zhu Changxiang 
Published: April 2020

AbstractBackgroundPlant viruses cause severe economic losses in agricultural production. An ultrahigh activity plant immune inducer (i.e., ZhiNengCong, ZNC) was extracted from endophytic fungi, and it could promote plant growth and enhance resistance to bacteria. However, the antiviral function has not been studied. Our study aims to evaluate the antiviral molecular mechanisms of ZNC in tobacco.ResultsHere, we usedPotato X virus(PVX), wild-type tobacco andNahGtransgenic tobacco as materials to study the resistance of ZNC to virus. ZNC exhibited a high activity in enhancing resistance to viruses and showed optimal use concentration at 100–150 ng/mL. ZNC also induced reactive oxygen species accumulation, increased salicylic acid (SA) content by upregulating the expression of phenylalanine ammonia lyase (PAL) gene and activated SA signaling pathway. We generated transcriptome profiles from ZNC-treated seedlings using RNA sequencing. The first GO term in biological process was positive regulation of post-transcriptional gene silencing, and the subsequent results showed that ZNC promoted RNA silencing. ZNC-sprayed wild-type leaves showed decreased infection areas, whereas ZNC failed to induce a protective effect against PVX inNahGleaves.ConclusionAll results indicate that ZNC is an ultrahigh-activity immune inducer, and it could enhance tobacco resistance to PVX at low concentration by positively regulating the RNA silencing via SA pathway. The antiviral mechanism of ZNC was first revealed in this study, and this study provides a new antiviral bioagent.
BioMonitor 2 in-office setting insertion safety and feasibility evaluation with device functionality assessment: results from the prospective cohort BioInsight study
Authors: Awad Khaled , Weiss Raul , Yunus Asim , Bittrick Jon M. , Nekkanti Rajasekhar , Houmsse Mahmoud , Okabe Toshimasa , Adamson Teagan , Miller Crystal , Alawwa Abdul K. 
Published: April 2020

Abstract
Background
Insertable cardiac monitors are utilized for the diagnosis of arrhythmias and traditionally have been inserted within hospitals. Recent code updates allow for reimbursement of office-based insertions; however, there is limited information regarding the resources and processes required to support in-office insertions. We sought to determine the safety and feasibility of in-office insertion of the BioMonitor 2 and better understand in-office procedures, including patient selection, pre-insertion protocols, resource availability, and staff support.

Methods
Patients meeting an indication for a rhythm monitor were prospectively enrolled into this single-arm, non-randomized trial. All patients underwent insertion in an office setting. Two follow-up visits at days 7 and 90 were required. Information on adverse events, device performance, office site preparations, and resource utilization were collected.

Results
Eighty-two patients were enrolled at six sites. Insertion was successful in all 77 patients with an attempt. Oral anticoagulation was stopped in 20.8% of patients and continued through insertion in 23.4%, while prophylactic antibiotics were infrequently utilized (37.7% of study participants). On average, the procedure required a surgeon plus two support staff and 35 min in an office room to complete the 8.4 min insertion procedure. The mean R-wave amplitude was 0.77 mV at insertion and 0.67 mV at 90-days with low noise burden (2.7%). There were no procedure related complications. Two adverse events were reported (event rate 2.7% [95% CI 0.3, 9.5%]).

Conclusions
In-office insertion of the BioMonitor 2 is safe and feasible. Devices performed well with high R-wave amplitudes and low noise burden. These results further support shifting cardiac monitor insertions to office-based locations.

Trial registration
clinicaltrials.gov, NCT02756338. Registered 29 April 2016.
Susceptible gene polymorphism in patients with three-vessel coronary artery disease
Authors: Liu Ru , Song Lei , Jiang Lin , Tang Xiaofang , Xu Lianjun , Gao Zhan , Zhao Xueyan , Xu Jingjing , Gao Runlin , Yuan Jinqing 
Published: April 2020

Abstract
Background
Data of susceptible gene polymorphisms related to progression of coronary atherosclerosis in patients with three-vessel disease (TVD) is limited in China. This case-control study aimed to analyze the differences of variant carrier frequencies between cases and controls, and to explain the possible genetic effects on the progression of TVD.

Methods
A total of 8943 TVD patients were consecutively enrolled. Major adverse cardiac and cerebrovascular events (MACCE) included all-cause death, acute myocardial infarction, repeat revascularization, readmission and stroke. Patients with 1-year MACCE in this cohort were selected as MACCE group. Blood samples from MACCE group and non-CAD control groups were collected, and a deoxyribonucleic acid library was created. A total of 34 tag or hot single nucleotide polymorphisms (SNPs) in six genes including CDKN2B-AS1, ADAMTS7, ABO, ADAMTS13, IL-18, and PECAM1 were analyzed by a SNPscan™ multi-genotyping kit. Carrier frequencies of each SNP were compared between the two groups using dominant, recessive and codominant allele model, respectively. Multivariate logistic regression model was established.

Results
Variant allele frequencies of rs10757274, rs1333042, rs1333049, rs4977574, rs9632884, rs1063192 and rs3217986 on CDKN2B-AS1 gene showed significant differences between the two groups in at least one allele model. Variant allele frequency of rs3217986 was not statistically significant after adjusting for the false discovery rate using Benjamini-Hochberg procedure (Q > 0.05). Variant allele frequencies of rs1333049, rs10757274, rs4977574 on CDKN2B-AS1 gene were significantly higher in MACCE group in all dominant, recessive and codominant models. Rs1055432 on ADAMTS13 and rs8176694 on ABO gene showed threshold significance between the two groups. After multivariable adjustment, G mutant homozygous rs9632884 (GG vs. GC + CC) (OR: 0.24; 95% CI: 0.09–0.65; P = 0.005) on CDKN2B-AS1 gene were independent protective factor of MACCE in recessive model.

Conclusions
In patients with TVD in China, variant alleles on CDKN2B-AS1 gene may form part of the genetic basis of coronary atherosclerosis progression, promoting or suppressing ischemic events.
Physical activity benefits of attending a senior center depend largely on age and gender: a study using GPS and accelerometry data
Authors: Marquet Oriol , Maciejewska Monika , Delclòs-Alió Xavier , Vich Guillem , Schipperijn Jasper , Miralles-Guasch Carme 
Published: April 2020

Abstract
Background
Senior centers offer important opportunities for physical activity and social interaction. Seniors who visit a senior center regularly can gain physical activity from transportation and from specific activities offered within the senior center. However, there is very little knowledge regarding the specific physical activity gains obtained from regular visits to senior centers, and no effort has been made to use device-based measures of physical activity to test the potential physical activity benefits of attending a senior center.

Methods
To fill this gap, the present study examined the physical activity patterns of 227 seniors living in the Barcelona Metropolitan Area in Spain. Using GPS and Accelerometer 7-day tracking data, and GIS measures we assessed the light physical activity and moderate-to-vigorous intensity physical activity (MVPA) benefits of attending the senior center on a weekly and daily basis.

Results
Seniors who attended a senior center at least once a week did not accumulate significantly more daily physical activity (211.6 min; 95% CI 196.6; 226.6) than seniors without any visit 215.9 min; 95% CI 202.7; 229). However, on a day-to-day basis, it was found that visiting a senior center had positive effects in physical activity and was associated with less sedentary time among younger participants in general (− 18.2 daily min 95% CI − 33.2;-3.3 p = 0.016) and among older female participants in particular (− 19.7 daily min 95% CI -21.06;-18.5 p = 0.011).

Conclusions
The benefits of attending senior centers in terms of physical activity should not be viewed as universal, but rather as contingent to the demographics of the user, and the type of activity that the visit is replacing.
Characteristics of Clostridium difficile isolates and the burden of hospital-acquired Clostridium difficile infection in a tertiary teaching hospital in Chongqing, Southwest China
Authors: Dai Wei , Yang Tianxiang , Yan Li , Niu Siqiang , Zhang Chuanming , Sun Jide , Wang Zhu , Xia Yun 
Published: April 2020

Abstract
Background
Clostridium difficile infection (CDI), especially hospital-acquired Clostridium difficile infection (HA-CDI), continues to be a public health problem and has aroused great concern worldwide for years. This study aimed to elucidate the clinical and epidemiological features of HA-CDI and the characteristics of C.difficile isolates in Chongqing, Southwest China.

Methods
A case-control study was performed to identify the clinical incidence and risk factors of HA-CDI. C. difficile isolates were characterised by polymerase chain reaction (PCR) ribotyping, multilocus sequence typing (MLST), toxin gene detection and antimicrobial susceptibility testing.

Results
Of the 175 suspicious patients, a total of 122 patients with antibiotic-associated diarrhea (AAD) were included in the study; among them, 38 had HA-CDI. The incidence of AAD and HA-CDI was 0.58 and 0.18 per 1000 patient admissions, respectively. Chronic renal disease and cephalosporin use were independent risk factors for HA-CDI. Fifty-five strains were assigned into 16 sequence types (STs) and 15 ribotypes (RTs). ST2/RT449 (8, 14.5%) was the predominant genotype. Of the 38 toxigenic isolates, A + B + CDT- isolates accounted for most (34, 89.5%) and 1 A + B + CDT+ isolate emerged. No isolate was resistant to vancomycin, metronidazole or tigecycline, with A-B-CDT- being more resistant than A + B + CDT-.

Conclusions
Different genotypes of C. difficile strains were witnessed in Chongqing, which hinted at the necessary surveillance of HA-CDI. Adequate awareness of patients at high risk of HA-CDI acquisition is advocated and cautious adoption of cephalosporins should be highlighted.
A descriptive epidemiological study of the incidence of newly diagnosed Lyme disease cases in a UK primary care cohort, 1998–2016
Authors: Tulloch John S. P. , Christley Robert M. , Radford Alan D. , Warner Jenny C. , Beadsworth Mike B. J. , Beeching Nick J. , Vivancos Roberto 
Published: April 2020

Abstract
Background
Primary care is likely to see the highest number of Lyme disease patients. Despite this, there is limited published data regarding Lyme disease patients accessing primary care in the UK. We aim to describe trends in the incidence of a new diagnosis, and demographics of patients identified in a primary care electronic health database.

Methods
A descriptive epidemiological study of Lyme disease coded patients in UK primary care. 3725 patients coded for Lyme disease during 1998–2016 were identified within The Health Improvement Network (THIN). Incidence rates and the demographics of cases identified were described. Poisson regression was used to analyse socio-demographic characteristics of the cases.

Results
There was an increase in annual crude incidence rates, peaking in 2015 at 5.47 (95% CI 4.85–6.14) cases per 100,000 population per year. Multivariable analysis showed there were significant differences in the ages of those affected, incidence of a new diagnosis rose as deprivation levels improved, and that there was a higher incidence of cases living in rural areas compared to urban areas. There was no significant difference between sexes for the UK. Cases were significantly more likely to identify with being white compared to the national population.

Conclusions
An increasing incidence of patients newly coded with Lyme disease related Read codes was identified using data from a UK national primary care database. By comparing these incidence figures with national laboratory-confirmed surveillance data, a multiplication factor of 2.35 (95%CI 1.81–2.88) can be calculated in order to estimate the annual number of cases seen in primary care. The significant socio-demographic variables associated with a Lyme disease diagnosis likely reflect a complex interplay of socio-economic issues, which needs to be further explored. Future work is needed to examine the treatment and management of patients within this database.
Factors associated with provision of smoking cessation support to pregnant women – a cross-sectional survey of midwives in New South Wales, Australia
Authors: Passey Megan E. , Longman Jo M. , Adams Catherine , Johnston Jennifer J. , Simms Jessica , Rolfe Margaret 
Published: April 2020

AbstractBackgroundSmoking is the most important preventable cause of adverse pregnancy outcomes, but provision of smoking cessation support (SCS) to pregnant women is poor. We examined the association between midwives’ implementation of SCS (5As – Ask, Advise, Assess, Assist, Arrange follow-up) and reported barriers/enablers to implementation.MethodsOn-line anonymous survey of midwives providing antenatal care in New South Wales (NSW), Australia, assessing provision of the 5As and barriers/enablers to their implementation, using the Theoretical Domains Framework (TDF). Factor analyses identified constructs underlying the 5As; and barriers/enablers. Multivariate general linear models examined relationships between the barrier/enabler factors and the 5As factors.ResultsOf 750 midwives invited, 150 (20%) participated. Respondents more commonly reported Asking and Assessing than Advising, Assisting, or Arranging follow-up (e.g. 77% always Ask smoking status; 17% always Arrange follow-up). Three 5As factors were identified– ‘Helping’, ‘Assessing quitting’ and ‘Assessing dependence’. Responses to barrier/enabler items showed greater knowledge, skills, intentions, and confidence with Assessment than Assisting; endorsement for SCS as a priority and part of midwives’ professional role; and gaps in training and organisational support for SCS. Nine barrier/enabler factors were identified. Of these, the factors of ‘Capability’(knowledge, skills, confidence); ‘Work Environment’ (service has resources, capacity, champions and values SCS) and ‘Personal priority’ (part of role and a priority) predicted ‘Helping’.ConclusionThe TDF enabled systematic identification of barriers to providing SCS, and the multivariate models identified key contributors to poor implementation. Combined with qualitative data, these results have been mapped to intervention components to develop a comprehensive intervention to improve SCS.