bluuebunny/crossref_metadata_2025_split huggingface dataset:
QuaDMutNetEx: a method for detecting cancer driver genes with low mutation frequency
Authors: Bokhari Yahya , Alhareeri Areej , Arodz Tomasz 
Published: March 2020

Abstract
Background
Cancer is caused by genetic mutations, but not all somatic mutations in human DNA drive the emergence or growth of cancers. While many frequently-mutated cancer driver genes have already been identified and are being utilized for diagnostic, prognostic, or therapeutic purposes, identifying driver genes that harbor mutations occurring with low frequency in human cancers is an ongoing endeavor. Typically, mutations that do not confer growth advantage to tumors – passenger mutations – dominate the mutation landscape of tumor cell genome, making identification of low-frequency driver mutations a challenge. The leading approach for discovering new putative driver genes involves analyzing patterns of mutations in large cohorts of patients and using statistical methods to discriminate driver from passenger mutations.

Results
We propose a novel cancer driver gene detection method, QuaDMutNetEx. QuaDMutNetEx discovers cancer drivers with low mutation frequency by giving preference to genes encoding proteins that are connected in human protein-protein interaction networks, and that at the same time show low deviation from the mutual exclusivity pattern that characterizes driver mutations occurring in the same pathway or functional gene group across a cohort of cancer samples.

Conclusions
Evaluation of QuaDMutNetEx on four different tumor sample datasets show that the proposed method finds biologically-connected sets of low-frequency driver genes, including many genes that are not found if the network connectivity information is not considered. Improved quality and interpretability of the discovered putative driver gene sets compared to existing methods shows that QuaDMutNetEx is a valuable new tool for detecting driver genes. QuaDMutNetEx is available for download from https://github.com/bokhariy/QuaDMutNetExunder the GNU GPLv3 license.
Transcriptomic profiling of Solanum peruvianum LA3858 revealed a Mi-3-mediated hypersensitive response to Meloidogyne incognita
Authors: Du Chong , Jiang Jingbin , Zhang He , Zhao Tingting , Yang Huanhuan , Zhang Dongye , Zhao Zhentong , Xu Xiangyang , Li Jingfu 
Published: March 2020

Abstract
Background
The Mi-1 gene was the first identified and cloned gene that provides resistance to root-knot nematodes (RKNs) in cultivated tomato. However, owing to its temperature sensitivity, this gene does not meet the need for breeding disease-resistant plants that grow under high temperature. In this study, Mi-3 was isolated from the wild species PI 126443 (LA3858) and was shown to display heat-stable resistance to RKNs. However, the mechanism that regulates this resistance remains unknown.

Results
In this study, 4760, 1024 and 137 differentially expressed genes (DEGs) were enriched on the basis of pairwise comparisons (34 °C vs. 25 °C) at 0 (before inoculation), 3 and 6 days post-inoculation (dpi), respectively. A total of 7035 DEGs were identified from line LA3858 in the respective groups under the different soil temperature treatments. At 3 dpi, most DEGs were enriched in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to plant biotic responses, such as “plant-pathogen interaction” and “plant hormone signal transduction”. Significantly enriched DEGs were found to encode key proteins such as R proteins and heat-shock proteins (HSPs). Moreover, other DEGs were found to participate in Ca2+ signal transduction; the production of ROS; DEGs encoding transcription factors (TFs) from the bHLH, TGA, ERF, heat-shock transcription factor (HSF) and WRKY families were highly expressed, which contribute to be involved into the formation of phytohormones, such as salicylic acid (SA), jasmonic acid (JA) and ethylene (ET), the expression of most was upregulated at 3 dpi at the 25 °C soil temperature compared with the 34 °C soil temperature.

Conclusion
Taken together, the results of our study revealed reliable candidate genes from wild materials LA3858, that are related to Mi-3-mediate resistance to Meloidogyne incognita. A large number of vital pathways and DEGs were expressed specifically in accession LA3858 grown at 34 °C and 25 °C soil temperatures at 3 dpi. Upon infection by RKNs, pattern-recognition receptors (PRRs) specifically recognized conserved pathogen-associated molecular patterns (PAMPs) as a result of pathogen-triggered immunity (PTI), and the downstream defensive signal transduction pathway was likely activated through Ca2+ signal channels. The expression of various TFs was induced to synthesize phytohormones and activate R proteins related to resistance, resulting in the development of effector-triggered immunity (ETI). Last, a hypersensitive response in the roots occurred, which was probably induced by the accumulation of ROS.
Genome‑wide integrated analysis demonstrates widespread functions of lncRNAs in mammary gland development and lactation in dairy goats
Authors: Ji Zhibin , Chao Tianle , Liu Zhaohua , Hou Lei , Wang Jin , Wang Aili , Zhou Jie , Xuan Rong , Wang Guizhi , Wang Jianmin 
Published: March 2020

Abstract
Background
The mammary gland is a unique organ for milk synthesis, secretion and storage, and it undergoes cyclical processes of development, differentiation, lactation and degeneration. At different developmental periods, the biological processes governing mammary gland physiology and internal environmental homeostasis depend on a complex network of genes and regulatory factors. Emerging evidence indicates that lncRNAs have arbitrarily critical functions in regulating gene expression in many organisms; however, the systematic characteristics, expression, and regulatory roles of lncRNAs in the mammary gland tissues of dairy goats have not been determined.

Result
In the present study, we profiled long noncoding RNA (lncRNA) expression in the mammary gland tissues of Laoshan dairy goats (Capra hircus) from different lactation periods at the whole-genome level, to identify, characterize and explore the regulatory functions of lncRNAs. A total of 37,249 transcripts were obtained, of which 2381 lncRNAs and 37,249 mRNAs were identified, 22,488 transcripts, including 800 noncoding transcripts and 21,688 coding transcripts, differed significantly (p ≤ 0.01) among the different lactation stages. The results of lncRNA-RNA interaction analysis showed that six known lncRNAs belonging to four families were identified as the precursors of 67 known microRNAs; 1478 and 573 mRNAs were predicted as hypothetical cis-regulation elements and antisense mRNAs, respectively. GO annotation and KEGG analysis indicated that the coexpressed mRNAs were largely enriched in biological processes related to such activities as metabolism, immune activation, and stress,., and most genes were involved in pathways related to such phenomena as inflammation, cancer, signal transduction, and metabolism.

Conclusions
Our results clearly indicated that lncRNAs involved in responses to stimuli, multiorganism processes, development, reproductive processes and growth, are closely related to mammary gland development and lactation.
Characterization of the Gh4CL gene family reveals a role of Gh4CL7 in drought tolerance
Authors: Sun Shi-Chao , Xiong Xian-Peng , Zhang Xiao-Li , Feng Hong-Jie , Zhu Qian-Hao , Sun Jie , Li Yan-Jun 
Published: March 2020

Abstract
Background
The function of 4-coumarate-CoA ligases (4CL) under abiotic stresses has been studied in plants, however, limited is known about the 4CL genes in cotton (G. hirsutum L.) and their roles in response to drought stress.

Results
We performed genome-wide identification of the 4CL genes in G. hirsutum and investigated the expression profiles of the identified genes in various cotton tissues and in response to stress conditions with an aim to identify 4CL gene(s) associated with drought tolerance. We identified 34 putative 4CL genes in G. hirsutum that were clustered into three classes. Genes of the same class usually share a similar gene structure and motif composition. Many cis-elements related to stress and phytohormone responses were found in the promoters of the Gh4CL genes. Of the 34 Gh4CL genes, 26 were induced by at least one abiotic stress and 10 (including Gh4CL7) were up-regulated under the polyethylene glycol (PEG) simulated drought stress conditions. Virus-induced gene silencing (VIGS) in cotton and overexpression (OE) in Arabidopsis thaliana were applied to investigate the biological function of Gh4CL7 in drought tolerance. The Gh4CL7-silencing cotton plants showed more sensitive to drought stress, probably due to decreased relative water content (RWC), chlorophyll content and antioxidative enzyme activity, increased stomatal aperture, and the contents of malondialdehyde (MDA) and hydrogen peroxide (H2O2). Arabidopsis lines overexpressing Gh4CL7, however, were more tolerant to drought treatment, which was associated with improved antioxidative enzyme activity, reduced accumulation of MDA and H2O2 and up-regulated stress-related genes under the drought stress conditions. In addition, compared to their respective controls, the Gh4CL7-silencing cotton plants and the Gh4CL7-overexpressing Arabidopsis lines had a ~ 20% reduction and a ~ 10% increase in lignin content, respectively. The expression levels of genes related to lignin biosynthesis, including PAL, CCoAOMT, COMT, CCR and CAD, were lower in Gh4CL7-silencing plants than in controls. Taken together, these results demonstrated that Gh4CL7 could positively respond to drought stress and therefore might be a candidate gene for improvement of drought tolerance in cotton.

Conclusion
We characterized the 4CL gene family in upland cotton and revealed a role of Gh4CL7 in lignin biosynthesis and drought tolerance.
An evaluation of inverse probability weighting using the propensity score for baseline covariate adjustment in smaller population randomised controlled trials with a continuous outcome
Authors: Raad Hanaya , Cornelius Victoria , Chan Susan , Williamson Elizabeth , Cro Suzie 
Published: March 2020

Abstract
Background
It is important to estimate the treatment effect of interest accurately and precisely within the analysis of randomised controlled trials. One way to increase precision in the estimate and thus improve the power for randomised trials with continuous outcomes is through adjustment for pre-specified prognostic baseline covariates. Typically covariate adjustment is conducted using regression analysis, however recently, Inverse Probability of Treatment Weighting (IPTW) using the propensity score has been proposed as an alternative method. For a continuous outcome it has been shown that the IPTW estimator has the same large sample statistical properties as that obtained via analysis of covariance. However the performance of IPTW has not been explored for smaller population trials (< 100 participants), where precise estimation of the treatment effect has potential for greater impact than in larger samples.

Methods
In this paper we explore the performance of the baseline adjusted treatment effect estimated using IPTW in smaller population trial settings. To do so we present a simulation study including a number of different trial scenarios with sample sizes ranging from 40 to 200 and adjustment for up to 6 covariates. We also re-analyse a paediatric eczema trial that includes 60 children.

Results
In the simulation study the performance of the IPTW variance estimator was sub-optimal with smaller sample sizes. The coverage of 95% CI’s was marginally below 95% for sample sizes < 150 and ≥ 100. For sample sizes < 100 the coverage of 95% CI’s was always significantly below 95% for all covariate settings. The minimum coverage obtained with IPTW was 89% with n = 40. In comparison, regression adjustment always resulted in 95% coverage. The analysis of the eczema trial confirmed discrepancies between the IPTW and regression estimators in a real life small population setting.

Conclusions
The IPTW variance estimator does not perform so well with small samples. Thus we caution against the use of IPTW in small sample settings when the sample size is less than 150 and particularly when sample size < 100.
Length of stay after childbirth in India: a comparative study of public and private health institutions
Authors: Kumar Pradeep , Dhillon Preeti 
Published: March 2020

AbstractBackgroundThis paper discusses length of stay (LOS) following childbirth as an indicator of quality of postnatal care in health institutions. This research aims to describe LOS according to both vaginal and cesarean deliveries in public and private health care institutions in India, and to identify any association of LOS with postnatal care and post-delivery complications.MethodsWe use recently released nationally-representative data from the National Family Health Survey-4 (2015–16) and apply the Cox proportional hazard model to determine the factors associated with LOS at the health facility after childbirth during a five-year period preceding the survey.ResultsOverall, the average LOS after childbirth is 3.4 days; 2.1 days for vaginal deliveries and 8.6 days for cesarean section (CS) deliveries. Strikingly, half of the women are discharged within 48 h. Women who give birth in private hospitals have a more prolonged stay than those who give birth in public health facilities. For vaginal birth in public hospitals, one-fourth of the women are discharged with insufficient LOS as against only 19.2% women in private hospitals. LOS is significantly related to the cost of delivery only in the case of private facilities. Uneducated women belonging to lower wealth quintile households and those living in rural areas stay for a shorter duration for vaginal deliveries but for a longer duration in case of cesarean deliveries. Women who get four or more antenatal check-ups (ANC) done have a longer stay, while those who receive benefits under theJanani Suraksha Yojna(JSY) have a shorter stay. Another key finding is that women who are discharged on the same day report lower levels of postnatal care and a higher proportion of post-delivery complications.ConclusionThe study concludes that early discharge has a negative association with maternal health outcomes, which has important program implications. Therefore, it is essential to maintain an adequate LOS at a facility after childbirth. We recommend that government programs should strengthen the JSY scheme not only to improve delivery care, but also to provide effective postnatal care by promoting sufficient LOS at facilities.
Knowledge, and use of labour pain relief methods and associated factors among obstetric caregivers at public health centers of East Gojjam zone, Amhara region, Ethiopia: a facility based cross- sectional study
Authors: Bishaw Keralem Anteneh , Sendo Endalew Gemechu , Abebe Workinesh Sinshaw 
Published: March 2020

AbstractBackgroundThe study was conducted in public health centers of East Gojjam Zone, Amhara region, Ethiopia.The purpose of this study was to assess knowledge, and use of labour pain relief methods and associated factors among obstetric caregivers in the study setting.MethodsA facility-based cross-sectional study design was conducted from March 1–30, 2018. The study was conducted among three hundred and nine sampled obstetric caregivers. Structured questionnaire was used to collect the data. The data were entered into Epi-data version 4.2 Software for cleaning and exported to SPSS version 23.0 for data analysis. Multivariate logistic regression was carried out for variables with ap-value < 0.25 in bivariate logistic regression to determine significant relationships between the dependent and independent variables. Statistical significance was determined at 95% confidence interval (CI) andp-value below 0.05.ResultThe overall use of labour pain relief methods reported was 34.4%, (30.4% non-pharmacological and 8.4 pharmacological, respectively). More than half of the study participants (54.2%) had adequate knowledge about labour pain relief methods. In multivariate analysis, being a midwifery profession [AOR =2.814, 95% CI = (1.574–5.031)], having positive attitude [AOR = 4.370, 95% CI = (2.523–7.567)], and professionals with a medium level of education [AOR = 3.450, 95% CI = (1.993–5.971)] were factors significantly associated with knowledge of obstetric caregivers about labour pain relief methods. In multivariate analysis, knowledge of obstetric caregivers [AOR = 3.821, 95% CI = (2.091–6.980)], positive attitude of obstetric caregivers [AOR = 2.455, 95% CI = ((1.358–4.436))] and experience of obstetric caregivers [AOR = 2.56, 95% CI = (1.350–4.845) were factors significantly associated with the use of labour pain relief methods.ConclusionIn this study, the overall use of labour pain relief methods by obstetric caregivers was low. Systemic opioid (Pethdine) was reportedly one of the most known pharmacological pain relief methods in this study. Providers’ knowledge, attitude and work experience had shown statistical significance with the use of labour pain relief methods. Task-oriented in- service training is required to fortify obstetric caregivers’ knowledge and attitude towards the use of labour pain relief methods.
Expression and clinical significance of miR-4516 and miR-21-5p in serum of patients with colorectal cancer
Authors: Jin Xi-Han , Lu Sen , Wang Ai-Fen 
Published: March 2020

Abstract
Background
This study sought to detect the expression and clinical significance of miR-4516 and miR-21-5p in serum of patients with colorectal cancer.

Methods
Bioinformatics methods were used to analyze the expression patterns of miR-4516 and miR-21-5p in colorectal cancer. A total of 80 patients with colorectal cancer, 65 patients with benign colorectal tumors and 50 healthy persons were selected. qRT-PCR was performed to detect the expression levels of serum miR-4516 and miR-21-5p before and after operation or postoperative recurrence. The correlation of miR-4516 and miR-21-5p expression levels with the clinical characteristics and prognosis of colorectal cancer was analyzed, and that with the patient’s survival was further examined by Kaplan-Meier analysis.

Results
MiR-4516 was poorly expressed in colorectal cancer in the preoperative group, and miR-21-5p was highly expressed. While in the postoperative group, miR-4516 was up-regulated, and miR-21-5p was down-regulated. The low expression of miR-4516 was shown to be related to TNM staging, invasion degree, lymph node metastasis and distant metastasis of the patients. Whereas the high expression of miR-21-5p was proved to be correlated with TNM staging and lymph node metastasis. Kaplan-Meier survival analysis showed that high expression of miR-4516 or low expression of miR-21-5p could contribute to better overall survival.

Conclusion
Low miR-4516 or high miR-21-5p could be used as an independent risk factor for prognosis of colorectal cancer.
Population-based SEER analysis of survival in colorectal cancer patients with or without resection of lung and liver metastases
Authors: Siebenhüner Alexander R. , Güller Ulrich , Warschkow Rene 
Published: March 2020

Abstract
Background
Approximately one third of all patients with CRC present with, or subsequently develop, colorectal liver metastases (CRLM). The objective of this population-based analysis was to assess the impact of resection of liver only, lung only and liver and lung metastases on survival in patients with metastatic colorectal cancer (mCRC) and resected primary tumor.

Methods
Ten thousand three hundred twenty-five patients diagnosed with mCRC between 2010 and 2015 with resected primary were identified in the Surveillance, Epidemiology and End Results (SEER) database. Overall, (OS) and cancer-specific survival (CSS) were analyzed by Cox regression with multivariable, inverse propensity weight, near far matching and propensity score adjustment.

Results
The majority (79.4%) of patients had only liver metastases, 7.8% only lung metastases and 12.8% metastases of lung and liver. 3-year OS was 44.5 and 27.5% for patients with and without metastasectomy (HR = 0.62, 95% CI: 0.58–0.65, P < 0.001). Metastasectomy uniformly improved CSS in patients with liver metastases (HR = 0.72, 95% CI: 0.67–0.77, P < 0.001) but not in patients with lung metastases (HR = 0.84, 95% CI: 0.62–1.12, P = 0.232) and combined liver and lung metastases (HR = 0.89, 95% CI: 0.75–1.06, P = 0.196) in multivariable analysis. Adjustment by inverse propensity weight, near far matching and propensity score and analysis of OS yielded similar results.

Conclusions
This is the first SEER analysis assessing the impact of metastasectomy in mCRC patients with removed primary tumor on survival. The analysis provides compelling evidence of a statistically significant and clinically relevant increase in OS and CSS for liver resection but not for metastasectomy of lung or both sites.
Ethical arguments concerning human-animal chimera research: a systematic review
Authors: Kwisda Koko , White Lucie , Hübner Dietmar 
Published: March 2020

AbstractBackgroundThe burgeoning field of biomedical research involving the mixture of human and animal materials has attracted significant ethical controversy. Due to the many dimensions of potential ethical conflict involved in this type of research, and the wide variety of research projects under discussion, it is difficult to obtain an overview of the ethical debate. This paper attempts to remedy this by providing a systematic review of ethical reasons in academic publications on human-animal chimera research.MethodsWe conducted a systematic review of the ethical literature concerning human-animal chimeras based on the research question: “What ethical reasons have been given for or against conducting human-animal chimera research, and how have these reasons been treated in the ongoing debate?” Our search extends until the end of the year 2017, including MEDLINE, Embase, PhilPapers and EthxWeb databases, restricted to peer-reviewed journal publications in English. Papers containing ethical reasons were analyzed, and the reasons were coded according to whether they were endorsed, mentioned or rejected.ResultsFour hundred thirty-one articles were retrieved by our search, and 88 were ultimately included and analyzed. Within these articles, we found 464 passages containing reasons for and against conducting human-animal chimera research. We classified these reasons into five categories and, within these, identified 12 broad and 31 narrow reason types.15% of the retrieved passages contained reasons in favor of conducting chimera research (Category P), while 85% of the passages contained reasons against it. The reasons against conducting chimera research fell into four further categories: reasons concerning the creation of a chimera (Category A), its treatment (Category B), reasons referring to metaphysical or social issues resulting from its existence (Category C) and to potential downstream effects of chimera research (Category D). A significant proportion of identified passages (46%) fell under Category C.ConclusionsWe hope that our results, in revealing the conceptual and argumentative structure of the debate and highlighting some its most notable tendencies and prominent positions, will facilitate continued discussion and provide a basis for the development of relevant policy and legislation.