bluuebunny/crossref_metadata_2025_split huggingface dataset:
A rank-based marker selection method for high throughput scRNA-seq data
Authors: Vargo Alexander H. S. , Gilbert Anna C. 
Published: October 2020

Abstract
Background
High throughput microfluidic protocols in single cell RNA sequencing (scRNA-seq) collect mRNA counts from up to one million individual cells in a single experiment; this enables high resolution studies of rare cell types and cell development pathways. Determining small sets of genetic markers that can identify specific cell populations is thus one of the major objectives of computational analysis of mRNA counts data. Many tools have been developed for marker selection on single cell data; most of them, however, are based on complex statistical models and handle the multi-class case in an ad-hoc manner.

Results
We introduce RankCorr, a fast method with strong mathematical underpinnings that performs multi-class marker selection in an informed manner. RankCorr proceeds by ranking the mRNA counts data before linearly separating the ranked data using a small number of genes. The step of ranking is intuitively natural for scRNA-seq data and provides a non-parametric method for analyzing count data. In addition, we present several performance measures for evaluating the quality of a set of markers when there is no known ground truth. Using these metrics, we compare the performance of RankCorr to a variety of other marker selection methods on an assortment of experimental and synthetic data sets that range in size from several thousand to one million cells.

Conclusions
According to the metrics introduced in this work, RankCorr is consistently one of most optimal marker selection methods on scRNA-seq data. Most methods show similar overall performance, however; thus, the speed of the algorithm is the most important consideration for large data sets (and comparing the markers selected by several methods can be fruitful). RankCorr is fast enough to easily handle the largest data sets and, as such, it is a useful tool to add into computational pipelines when dealing with high throughput scRNA-seq data. RankCorr software is available for download at https://github.com/ahsv/RankCorrwith extensive documentation.
A new esophageal gland transcriptome reveals signatures of large scale de novo effector birth in the root lesion nematode Pratylenchus penetrans
Authors: Vieira Paulo , Shao Jonathan , Vijayapalani Paramasivan , Maier Thomas R. , Pellegrin Clement , Eves-van den Akker Sebastian , Baum Thomas J. , Nemchinov Lev G. 
Published: October 2020

Abstract
Background
The root lesion nematode Pratylenchus penetrans is a migratory plant-parasitic nematode responsible for economically important losses in a wide number of crops. Despite the importance of P. penetrans, the molecular mechanisms employed by this nematode to promote virulence remain largely unknown.

Results
Here we generated a new and comprehensive esophageal glands-specific transcriptome library for P. penetrans. In-depth analysis of this transcriptome enabled a robust identification of a catalogue of 30 new candidate effector genes, which were experimentally validated in the esophageal glands by in situ hybridization. We further validated the expression of a multifaceted network of candidate effectors during the interaction with different plants. To advance our understanding of the “effectorome” of P. penetrans, we adopted a phylogenetic approach and compared the expanded effector repertoire of P. penetrans to the genome/transcriptome of other nematode species with similar or contrasting parasitism strategies. Our data allowed us to infer plausible evolutionary histories that shaped the effector repertoire of P. penetrans, as well as other close and distant plant-parasitic nematodes. Two remarkable trends were apparent: 1) large scale effector birth in the Pratylenchidae in general and P. penetrans in particular, and 2) large scale effector death in sedentary (endo) plant-parasitic nematodes.

Conclusions
Our study doubles the number of validated Pratylenchus penetrans effectors reported in the literature. The dramatic effector gene gain in P. penetrans could be related to the remarkable ability of this nematode to parasitize a large number of plants. Our data provide valuable insights into nematode parasitism and contribute towards basic understating of the adaptation of P. penetrans and other root lesion nematodes to specific host plants.
Identification, expression, and artificial selection of silkworm epigenetic modification enzymes
Authors: Gao Rui , Li Chun-Lin , Tong Xiao-Ling , Han Min-Jin , Lu Kun-Peng , Liang Shu-Bo , Hu Hai , Luan Yue , Zhang Bi-Li , Liu Yan-Yu , Dai Fang-Yin 
Published: October 2020

AbstractBackgroundUnderstanding the genetic basis of phenotype variations during domestication and breeding is of great interest. Epigenetics and epigenetic modification enzymes (EMEs) may play a role in phenotypic variations; however, no comprehensive study has been performed to date. Domesticated silkworm(Bombyx mori)may be utilized as a model in determining how EMEs influence domestication traits.ResultsWe identified 44EMEsin the genome of silkworm (Bombyx mori) using homology searching. Phylogenetic analysis showed that genes in a subfamily among different animals were well clustered, and the expression pattern ofEMEsis constant amongBombyx mori,Drosophila melanogaster, andMus musculus. These are most highly expressed in brain, early embryo, and internal genitalia. By gene-related selective sweeping, we identified fiveBmEMEsunder artificial selection during the domestication and breeding of silkworm. Among these selected genes,BmSuv4–20 and BmDNMT2harbor selective mutations in their upstream regions that alter transcription factor-binding sites. Furthermore, these two genes are expressed higher in the testis and ovary of domesticated silkworm compared to wild silkworms, and correlations between their expression pattern and meiosis of the sperm and ova were observed.ConclusionsThe domestication of silkworm has induced artificial selection on epigenetic modification markers that may have led to phenotypic changes during domestication. We present a novel perspective to understand the genetic basis underlying animal domestication and breeding.
Drought-hardening improves drought tolerance in Nicotiana tabacum at physiological, biochemical, and molecular levels
Authors: Khan Rayyan , Ma Xinghua , Shah Shahen , Wu Xiaoying , Shaheen Aaqib , Xiao Lixia , Wu Yuanhua , Wang Shusheng 
Published: October 2020

Abstract
Background
Drought stress is the most harmful one among other abiotic stresses with negative impacts on crop growth and development. Drought-hardening is a feasible and widely used method in tobacco seedlings cultivation. It has gained extensive interests due to its role in improving drought tolerance. This research aimed to investigate the role of drought-hardening and to unravel the multiple mechanisms underlying tobacco drought tolerance and adaptation.

Results
This study was designed in which various drought-hardening treatments (CK (no drought-hardening), T1 (drought-hardening for 24 h), T2 (drought-hardening for 48 h), and T3 (drought-hardening for 72 h)) were applied to two tobacco varieties namely HongHuaDaJinYuan (H) and Yun Yan-100 (Y). The findings presented a complete framework of drought-hardening effect at physiological, biochemical, and gene expression levels of the two tobacco varieties under drought stress. The results showed that T2 and T3 significantly reduced the growth of the two varieties under drought stress. Similarly, among the various drought-hardening treatments, T3 improved both the enzymatic (POD, CAT, APX) and non-enzymatic (AsA) defense systems along with the elevated levels of proline and soluble sugar to mitigate the negative effects of oxidative damage and bringing osmoregulation in tobacco plants. Finally, the various drought-hardening treatments (T1, T2, and T3) showed differential regulation of genes expressed in the two varieties, while, particularly T3 drought-hardening treatment-induced drought tolerance via the expression of various stress-responsive genes by triggering the biosynthesis pathways of proline (P5CS1), polyamines (ADC2), ABA-dependent (SnRK2, AREB1), and independent pathways (DREB2B), and antioxidant defense-related genes (CAT, APX1, GR2) in response to drought stress.

Conclusions
Drought-hardening made significant contributions to drought tolerance and adaptation in two tobacco variety seedlings by reducing its growth and, on the other hand, by activating various defense mechanisms at biochemical and molecular levels. The findings of the study pointed out that drought-hardening is a fruitful strategy for conferring drought tolerance and adaptations in tobacco. It will be served as a useful method in the future to understand the drought tolerance and adaptation mechanisms of other plant species.

Graphical abstract
Drought-hardening improved drought tolerance and adaptation of the two tobacco varieties. T1 indicates drought-hardening for 24 h, T2 indicates drought-hardening for 48 h, T3 indicates drought-hardening for 72 h
Metabolomics analysis reveals Embden Meyerhof Parnas pathway activation and flavonoids accumulation during dormancy transition in tree peony
Authors: Zhang Tao , Yuan Yanchao , Zhan Yu , Cao Xinzhe , Liu Chunying , Zhang Yuxi , Gai Shupeng 
Published: October 2020

AbstractBackgroundBud dormancy is a sophisticated strategy which plants evolve to survive in tough environments. Endodormancy is a key obstacle for anti-season culture of tree peony, and sufficient chilling exposure is an effective method to promote dormancy release in perennial plants including tree peony. However, the mechanism of dormancy release is still poorly understood, and there are few systematic studies on the metabolomics during chilling induced dormancy transition.ResultsThe tree peony buds were treated with artificial chilling, and the metabolmics analysis was employed at five time points after 0–4 °C treatment for 0, 7, 14, 21 and 28 d, respectively. A total of 535 metabolites were obtained and devided into 11 groups including flavonoids, amino acid and its derivatives, lipids, organic acids and its derivates, nucleotide and its derivates, alkaloids, hydroxycinnamoyl derivatives, carbohydrates and alcohols, phytohormones, coumarins and vitamins. Totally, 118 differential metabolites (VIP ≥ 1,P < 0.05) during chilling treatment process were detected, and their KEGG pathways involved in several metabolic pathways related to dormancy. Sucrose was the most abundant carbohydrate in peony bud. Starch was degradation and Embden Meyerhof Parnas (EMP) activity were increased during the dormancy release process, according to the variations of sugar contents, related enzyme activities and key genes expression. Flavonoids synthesis and accumulation were also promoted by prolonged chilling. Moreover, the variations of phytohormones (salicylic acid, jasmonic acid, abscisic acid, and indole-3-acetic acid) indicated they played different roles in dormancy transition.ConclusionOur study suggested that starch degradation, EMP activation, and flavonoids accumulation were crucial and associated with bud dormancy transition in tree peony.
Changes in abscisic acid metabolism in relation to the maturation of grapevine (Vitis vinifera L., cv. Mencía) somatic embryos
Authors: Acanda Yosvanis , Martínez Óscar , Prado María Jesús , González María Victoria , Rey Manuel 
Published: October 2020

Abstract

Background
Somatic embryogenesis in grapevines is a complex process that depends on many physiological and genetic factors. One of its main limitations is the process of precocious germination of the somatic embryos in differentiation medium. This process lowers plant conversion rates from the somatic embryos, and it is probably caused by a low endogenous abscisic acid (ABA) content.

Results
Precocious germination of the somatic embryos was successfully avoided by culturing grapevine cv. Mencía embryogenic aggregates over a semipermeable membrane extended on top of the differentiation medium. The weekly analysis of the endogenous ABA and ABA-glucosyl ester (ABA-GE) contents in the aggregates showed their rapid accumulation. The expression profiles of 9-cis-epoxycarotenoid dioxygenase (VvNCED1), 8′-hydroxylase (VvHyd2), UDP-glucosyltransferase (VvUGT) and β-glucosidase (VvBG2) genes in grapevine revealed that the occurrence of a first accumulation peak of endogenous ABA in the second week of culture over the semipermeable membrane was mainly dependent on the expression of the VvNCED1 gene. A second increase in the endogenous ABA content was observed in the fourth week of culture. At this point in the culture, our results suggest that of those genes involved in ABA accumulation, one (VvNCED1) was repressed, while another (VvBG2) was activated. Similarly, of those genes related to a reduction in ABA levels, one (VvUGT) was repressed while another (VvHyd2) was activated. The relative expression level of the VvNCED1 gene in embryogenic aggregates cultured under the same conditions and treated with exogenous ABA revealed the significant downregulation of this gene.

Conclusions
Our results demonstrated the involvement of ABA metabolism in the control of the maturation of grapevine somatic embryos cultured over a semipermeable membrane and two important control points for their endogenous ABA levels. Thus, subtle differences in the expression of the antagonistic genes that control ABA synthesis and degradation could be responsible for the final level of ABA during the maturation of grapevine somatic embryos in vitro. In addition, the treatment of somatic embryos with exogenous ABA suggested the feedback-based control of the expression of the VvNCED1 gene by ABA during the maturation of grapevine somatic embryos.
Impact of statin intake on malignant hyperthermia: an in vitro and in vivo swine study
Authors: Gonzalez Asensio , Iles Tinen L. , Iaizzo Paul A. , Bandschapp Oliver 
Published: October 2020

Abstract
Background
Statin intake is associated with muscular side effects, among which the unmasking of latent myopathies and of malignant hyperthermia (MH) susceptibility have been reported. These findings, together with experimental data in small animals, prompt speculation that statin therapy may compromise the performance of skeletal muscle during diagnostic in vitro contracture tests (IVCT). In addition, statins might reduce triggering thresholds in susceptible individuals (MHS), or exacerbate MH progression. We sought to obtain empirical data to address these questions.

Methods
We compared the responses of 3 different muscles from untreated or simvastatin treated MHS and non-susceptible (MHN) pigs. MHS animals were also invasively monitored for signs of impending MH during sevoflurane anesthesia.

Results
Muscles from statin treated MHS pigs responded with enhanced in vitro contractures to halothane, while responses to caffeine were unaltered by the treatment. Neither agent elicited contractures in muscles from statin treated MHN pigs. In vivo, end- tide pCO2, hemodynamic evolution, plasma pH, potassium and lactate concentrations consistently pointed to mild acceleration of MH development in statin-treated pigs, whereas masseter spasm and rigor faded compared to untreated MHS animals.

Conclusions
The diagnostic sensitivity and specificity of the IVCT remains unchanged by a short-term simvastatin treatment in MHS swine. Evidence of modest enhancement in cardiovascular and metabolic signs of MH, as well as masked pathognomonic muscle rigor observed under simvastatin therapy suggest a potentially misleading influence on the clinical presentation of MH. The findings deserve further study to include other statins and therapeutic regimes.
Validation of myocardial infarction diagnosis in patients with congenital heart disease in Sweden
Authors: Fedchenko Maria , Mandalenakis Zacharias , Hultsberg-Olsson Görel , Dellborg Helena , Eriksson Peter , Dellborg Mikael 
Published: October 2020

Abstract
Background
The population of adults with congenital heart disease (CHD) is growing, and increasingly more patients with CHD reach older ages. Patients with CHD are at an increased risk of myocardial infarction (MI) with increased age. Diagnosing MI in patients with CHD can be challenging in clinical practice owing to a high prevalence of aberrant electrocardiograms, ventricular hypertrophy, and heart failure, among other factors. The National Swedish Patient Register (NPR) is widely used in epidemiological studies; however, MI diagnoses specifically in patients with CHD have never been validated in the NPR.

Methods
We contacted hospitals and medical archive services to request medical records for 249 patients, born during 1970–2012, with both CHD and MI diagnoses and who were randomly selected from the NPR by the Swedish National Board of Health and Welfare. Follow-up was until 2015. We performed a medical chart review to validate the MI diagnoses; we also validated CHD diagnoses to ensure that only patients with confirmed CHD diagnoses were included in the MI validation process.

Results
We received medical records for 96.4% (n = 238/249) of patients for validation of CHD diagnoses. In total, 74.8% (n = 178/238) had a confirmed CHD diagnosis; of these, 70.2% (n = 167) had a fully correct CHD diagnosis in the NPR; a further 4.6% (n = 11) had a CHD diagnosis, but it was misclassified. MI diagnoses were validated in 167 (93.8%) patients with confirmed CHD. Of the patients with confirmed CHD, 88.0% (n = 147/167) had correct MI diagnoses. Patients with non-complex CHD diagnoses had more correct MI diagnoses than patients with complex CHD (91.0%, n = 131 compared with 69.6%, n = 16). The main cause for incorrect MI diagnoses was typographical error, contributing to 50.0% of the incorrect diagnoses.

Conclusions
The validity of MI diagnoses in patients with confirmed CHD in the NPR is high, with nearly 9 of 10 MI diagnoses being correct (88.0%). MI in patients with CHD can safely be studied using the NPR.
Predictive approaches to heterogeneous treatment effects: a scoping review
Authors: Rekkas Alexandros , Paulus Jessica K. , Raman Gowri , Wong John B. , Steyerberg Ewout W. , Rijnbeek Peter R. , Kent David M. , van Klaveren David 
Published: October 2020

Abstract
Background
Recent evidence suggests that there is often substantial variation in the benefits and harms across a trial population. We aimed to identify regression modeling approaches that assess heterogeneity of treatment effect within a randomized clinical trial.

Methods
We performed a literature review using a broad search strategy, complemented by suggestions of a technical expert panel.

Results
The approaches are classified into 3 categories: 1) Risk-based methods (11 papers) use only prognostic factors to define patient subgroups, relying on the mathematical dependency of the absolute risk difference on baseline risk; 2) Treatment effect modeling methods (9 papers) use both prognostic factors and treatment effect modifiers to explore characteristics that interact with the effects of therapy on a relative scale. These methods couple data-driven subgroup identification with approaches to prevent overfitting, such as penalization or use of separate data sets for subgroup identification and effect estimation. 3) Optimal treatment regime methods (12 papers) focus primarily on treatment effect modifiers to classify the trial population into those who benefit from treatment and those who do not. Finally, we also identified papers which describe model evaluation methods (4 papers).

Conclusions
Three classes of approaches were identified to assess heterogeneity of treatment effect. Methodological research, including both simulations and empirical evaluations, is required to compare the available methods in different settings and to derive well-informed guidance for their application in RCT analysis.
Determining factors in the retention of physicians in rural and underdeveloped areas: a systematic review
Authors: Mohammadiaghdam Nasrin , Doshmangir Leila , Babaie Javad , Khabiri Roghayeh , Ponnet Koen 
Published: October 2020

Abstract
Background
Imbalance in distribution of Health Care Workers (HCWs) in a country is a global challenge. Almost all of the rural and underdeveloped areas are struggling with the shortage of HCWs, especially physicians. Therefore, this study aimed to identify factors governing the retention of physicians in rural and underdeveloped areas.

Methods
International databases including Scopus, PubMed, Web of Science, Proquest, and Embase were searched using Mesh terms in order to find peer-reviewed journal articles addressing physicians’ retention factors in rural and underdeveloped areas. The records were screened, and any duplicate results were removed. The quality of the studies was assessed according to the Critical Appraisal Skills Program developed for different types of studies. Then, through content analysis, the related factors were identified from finally selected papers, coded, and categorized.

Results
The initial search resulted in 2312 relevant articles. On the basis of specific selection criteria, 35 full-text articles were finally reviewed.. The major affecting factors in physicians’ retention in rural and underdeveloped regions were classified into the following six categories: 1) financial; 2) career and professional; 3) working conditions; 4) personal; 5) cultural; and 6) living conditions factors.

Conclusion
There is a complex interplay of factors governing physicians’ retention in rural and underdeveloped areas. If health organizations are concerned with physicians’ retention in deprived areas, they should take into account these main factors. Moreover, they should develop policies and strategies to attract and retain physicians in rural and underdeveloped areas.
Effect of poor glycemic control in cognitive performance in the elderly with type 2 diabetes mellitus: The Mexican Health and Aging Study
Authors: Mimenza-Alvarado Alberto J. , Jiménez-Castillo Gilberto A. , Yeverino-Castro Sara G. , Barragán-Berlanga Abel J. , Pérez-Zepeda Mario U. , Ávila-Funes J. Alberto , Aguilar-Navarro Sara G. 
Published: October 2020

Abstract
Background
Cognitive impairment is twice more frequent in elderly with type 2 diabetes mellitus (DM). This study was conducted to determine the association between glycemic control and cognitive performance among community-dwelling elderly persons in Mexico.

Methods
Cross-sectional study conducted in individuals aged 60 years or elderly participating in the 2012 Mexican Health and Aging Study. Type 2 DM participants were classified in 3 groups according to their glycated hemoglobin levels (HbA1c): < 7% (intensive control), 7–7.9% (standard control) or ≥ 8% (poor control), and cognitive performance: low (CCCE ≤44 points), intermediate (44.1–59.52 points), or high (≥59.53 points). Multinomial logistic regression models were constructed to determine this association.

Results
Two hundred sixteen community-dwelling adults aged 60 and older with type 2 diabetes were selected. Subjects in the low cognitive performance group were older (69.7 ± 6.6 vs 65.86 ± 5.18 years, p < .001) and had a lower educational level (2.5 ± 2.6 vs 7.44 ± 4.15 years, p < .000) when compared to the high cognitive performance participants. HbA1c ≥ 8% was associated with having low (Odds Ratio (OR) 3.17, 95% CI 1.17–8.60, p = .024), and intermediate (OR 3.23, 95% CI 1.27–8.20, p = .014) cognitive performance; this trend was not found for HbA1c 7.0–7.9% group.
The multinomial regression analysis showed that the presence of HbA1c ≥ 8% (poor glycemic control) was associated with low (OR 3.17, 95% CI = 1.17–8.60, p = .024), and intermediate (OR 3.23, 95% CI = 1.27–8.20, p = .014) cognitive performance. After adjusting for confounding variables.

Conclusions
Glycemic control with a HbA1c ≥ 8% was associated with worse cognitive performance.