bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental investigation on long-term behavior of prestressed concrete beams under coupled effect of sustained load and corrosion
Authors: Yang Jun , Guo Tong , Li Aiqun
Published: May 2020

Prestressed concrete beams are widely used in construction, while they may be attacked by the corrosion medium during the service. Past research works show that coupled effect of high stress and corrosion can significantly deteriorate the performance of prestressed concrete structures. This article presents an experimental investigation on long-term behavior of prestressed concrete beams under the coupled effect of sustained load and corrosion. During the accelerated corrosion process, six prestressed concrete beams were subjected to different levels of sustained loads, and time-dependent prestress loss and concrete stains were recorded and analyzed. It is observed that the local corrosion (i.e. pitting corrosion) of the steel strands was significantly affected by the sustained load level, and the coupled effect led to more serious damage on the beams than individual sustained load or corrosion. Bending loads were finally applied to investigate the influence of corrosion on flexural capacities of these beams. It was found that the flexural capacities and failure mode of the beams were significantly influenced by corrosion. Meanwhile, the corrosion has more significant effect on tension strength of strands rather than bond strength.
Real-time GNSS precise positioning: RTKLIB for ROS
Authors: Ferreira António , Matias Bruno , Almeida José , Silva Eduardo
Published: May 2020

The global navigation satellite system (GNSS) constitutes an effective and affordable solution to the outdoor positioning problem. When combined with precise positioning techniques, such as the real time kinematic (RTK), centimeter-level positioning accuracy becomes a reality. Such performance is suitable for a whole new range of demanding applications, including high-accuracy field robotics operations. The RTKRCV, part of the RTKLIB package, is one of the most popular open-source solutions for real-time GNSS precise positioning. Yet the lack of integration with the robot operating system (ROS), constitutes a limitation on its adoption by the robotics community. This article addresses this limitation, reporting a new implementation which brings the RTKRCV capabilities into ROS. New features, including ROS publishing and control over a ROS service, were introduced seamlessly, to ensure full compatibility with all original options. Additionally, a new observation synchronization scheme improves solution consistency, particularly relevant for the moving-baseline positioning mode. Real application examples are presented to demonstrate the advantages of our rtkrcv_ros package. For community benefit, the software was released as an open-source package.
Cytotoxic Triterpenes From Trametes orientalis
Authors: Xiao Kun-Min , Wang Jun-Ming , Zhou Ling-Yun , Guo Lei , Tan Da-Cong , Yan Qi , Hua Yan
Published: May 2020

One new triterpene, 24-ene-2′-methyl carboxy acetylquercinicate, and 3 known compounds were isolated from the ethyl acetate extract of the fruiting bodies of Trametes orientalis (Yasuda) Imazeki. Their structures were elucidated by means of extensive spectroscopic analysis and compared with data reported in the literature. Furthermore, they were evaluated for their cytotoxicity against 5 human cancer cell lines in vitro. Compound 4 showed significant cytotoxicity, especially to the leukemic HL-60 cell line (IC50 = 1.77 ± 0.07 μM), while compounds 1-3 showed significant cytotoxicity to SMMC-7721 (hepatoma cell line).
Psychedelic treatment of functional neurological disorder: a systematic review
Authors: Butler Matthew , Seynaeve Mathieu , Nicholson Timothy R. , Pick Susannah , Kanaan Richard A. , Lees Andrew , Young Allan H. , Rucker James
Published: May 2020

Functional neurological disorder (FND), formerly known as conversion disorder, causes a high burden of disability and distress, and is amongst the most commonly encountered conditions in neurology clinics and neuropsychiatric services, yet the therapeutic evidence base is somewhat limited. There has been recent interest in the therapeutic potential of psychedelics such as psilocybin and lysergic acid diethylamide (LSD), and in recent studies psychedelics have shown promise in treating a range of neuropsychiatric conditions. Modification of neural circuits associated with self-representation is thought to underlie some of this effect, and as some contemporary theories of FND focus on aberrant somatic self-representation, psychedelics may therefore represent an unexplored treatment option for FND. We systematically reviewed studies involving the use of psychedelics in FND. Nine studies published between 1954 and 1967, with a total of 26 patients, were identified. Due to restriction of licencing of psychedelic drugs since this period, no modern studies were identified. In most cases, patients received a course of psychotherapy with variable adjunctive administration of psychedelics (in a combination known as ‘psycholytic therapy’), with protocols varying between studies. Of those treated, 69% ( n = 18) were found to have made at least some recovery on heterogeneous and subjective clinician-rated criteria. Adverse events were mostly mild and transient; however, at least one patient terminated the study due to distressing effects. All included studies were of low quality, often lacking control groups and valid outcome measures. Although no conclusions on efficacy may be drawn from these data, further research may help to determine whether psychedelics offer a feasible, safe and effective treatment for FND.
Ketamine as an antidepressant: overview of its mechanisms of action and potential predictive biomarkers
Authors: Matveychuk Dmitriy , Thomas Rejish K. , Swainson Jennifer , Khullar Atul , MacKay Mary-Anne , Baker Glen B. , Dursun Serdar M.
Published: May 2020

Ketamine, a drug introduced in the 1960s as an anesthetic agent and still used for that purpose, has garnered marked interest over the past two decades as an emerging treatment for major depressive disorder. With increasing evidence of its efficacy in treatment-resistant depression and its potential anti-suicidal action, a great deal of investigation has been conducted on elucidating ketamine’s effects on the brain. Of particular interest and therapeutic potential is the ability of ketamine to exert rapid antidepressant properties as early as several hours after administration. This is in stark contrast to the delayed effects observed with traditional antidepressants, often requiring several weeks of therapy for a clinical response. Furthermore, ketamine appears to have a unique mechanism of action involving glutamate modulation via actions at the N-methyl-D-aspartate (NMDA) and [Formula: see text]-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, as well as downstream activation of brain-derived neurotrophic factor (BDNF) and mechanistic target of rapamycin (mTOR) signaling pathways to potentiate synaptic plasticity. This paper provides a brief overview of ketamine with regard to pharmacology/pharmacokinetics, toxicology, the current state of clinical trials on depression, postulated antidepressant mechanisms and potential biomarkers (biochemical, inflammatory, metabolic, neuroimaging sleep-related and cognitive) for predicting response to and/or monitoring of therapeutic outcome with ketamine.
In vivo three-dimensional scapular kinematic alterations after reverse total shoulder arthroplasty
Authors: Kim Eugene , Jang Taedong , Park Hee Jin , Ikemoto Sumika , Murase Tsuyoshi , Sugamoto Kazuomi , Hong Seok Woo
Published: May 2020

Background:

In vivo three-dimensional (3D) kinematics of the scapula after reverse total shoulder arthroplasty (rTSA) have been sparsely investigated. The aim of this study was to analyze static and dynamic kinematic alterations of the scapula after rTSA in vivo with the use of computer-aided 3D reconstruction program.

Methods:

A total of 15 patients with cuff tear arthropathy treated by rTSA participated. Scapulae with rTSA and the contralateral scapulae were evaluated with computed tomography scan data in 0° and 120° forward flexion positions of the glenohumeral joint. To examine static scapular kinematic alterations, the angular position and distance from the thorax were evaluated in the shoulder neutral position. 3D rotational and translational movements of the scapula in relation to the thorax were also measured during arm elevation to evaluate dynamic scapular kinematic alterations.

Results:

Scapulae with rTSA were more anteriorly tilted in the sagittal plane and more internally rotated in the axial plane than were the contralateral scapulae. However, no significant differences were observed in the upward rotated position in the coronal plane or in the distance from the thorax in any plane between the scapulae with rTSA and the contralateral scapulae. In dynamic analyses, upward rotational movement in the coronal plane, external rotation in the axial plane, and posterior tilting in the sagittal plane showed significant differences between the scapulae with rTSA and the contralateral scapulae during elevation. In contrast, translational movements in coordination revealed no statistical differences between the two scapular groups except for lateral translation.

Conclusion:

Data from the 3D reconstruction program showed that rTSA might result in static positional changes and dynamic movement alterations.

Level of Evidence:

Therapeutic, IV
Efficacy of Ultrasonography in the Diagnosis of Peritoneal Catheter Obstruction in Children: A Case Series
Authors: Tamura Hiroshi , Nakazato Hitoshi , Kuraoka Shohei
Published: May 2020

Catheter obstruction is a serious complication associated with peritoneal dialysis (PD). Diagnostic imaging techniques play a role in the management of patients undergoing PD, mainly in detecting potential catheter-related complications. Imaging can help in the treatment decision process. Visualizing the obstruction and understanding the etiology are crucial for accurate management of patients and in determining therapeutic strategies. Although a PD catheter obstruction can be diagnosed using magnetic resonance imaging (MRI), ultrasonography (US) has been reported to be equally effective. The effectiveness of US and MRI in detecting PD catheter obstructions was compared in four pediatric patients. These cases demonstrate that US was more useful in visualizing PD obstruction compared with MRI. US can be repeated more conveniently and is noninvasive, especially in children. US can be considered an effective tool for diagnosing PD catheter obstruction in children.
Effects of germline DHFR and FPGS variants on methotrexate metabolism and relapse of leukemia
Authors: Tulstrup Morten , Moriyama Takaya , Jiang Chuang , Grosjean Marie , Nersting Jacob , Abrahamsson Jonas , Grell Kathrine , Hjalgrim Lisa Lyngsie , Jónsson Ólafur Gísli , Kanerva Jukka , Lund Bendik , Nielsen Stine Nygaard , Nielsen Rikke Linnemann , Overgaard Ulrik , Quist-Paulsen Petter , Pruunsild Kaie , Vaitkeviciene Goda , Wolthers Benjamin Ole , Zhang Hui , Gupta Ramneek , Yang Jun J. , Schmiegelow Kjeld
Published: May 2020

Methotrexate (MTX) during maintenance therapy is essential for curing acute lymphoblastic leukemia (ALL), but dosing strategies aiming at adequate treatment intensity are challenged by interindividual differences in drug disposition. To evaluate genetic factors associated with MTX metabolism, we performed a genome-wide association study in 447 ALL cases from the Nordic Society for Pediatric Haematology and Oncology ALL2008 study, validating results in an independent set of 196 patients. The intergenic single-nucleotide polymorphism rs1382539, located in a regulatory element of DHFR, was associated with increased levels of short-chain MTX polyglutamates (P = 1.1 × 10−8) related to suppression of enhancer activity, whereas rs35789560 in FPGS (p.R466C, P = 5.6 × 10−9) was associated with decreased levels of long-chain MTX polyglutamates through reduced catalytic activity. Furthermore, the FPGS variant was linked with increased relapse risk (P = .044). These findings show a genetic basis for interpatient variability in MTX response and could be used to improve future dosing algorithms.
The conditional survival analysis of relapsed DLBCL after autologous transplant: a subgroup analysis of LY.12 and CORAL
Authors: Assouline Sarit , Li Shen , Gisselbrecht Christian , Fogarty Patrick , Hay Annette , van den Neste Eric , Shepherd Lois E. , Schmitz Norbert , Baetz Tara , Keating Armand , Robinson Sue , Seftel Matthew , Stelitano Caterina , Djurfeldt Marina S. , Meyer Ralph , Chen Bingshu E. , Crump Michael
Published: May 2020

The conditional survival of patients after frontline therapy for diffuse large B-cell lymphoma (DLBCL) approaches that of the general population once patients have survived disease free for 2 years. We sought to determine the conditional survival of patients among patients with relapsed de novo DLBCL successfully undergoing an autologous stem-cell transplant (ASCT) after first relapse. A total of 478 patients with de novo DLBCL, relapsed after 1 treatment from the Collaborative Trial in Relapsed Aggressive Lymphoma (CORAL) and LY.12, were included. Patients were followed prospectively after ASCT for a median of 5.3 and 8.2 years, respectively. Individual patient data were analyzed for event-free survival (EFS) and overall survival. Standardized mortality ratios (SMRs) were estimated using French and Canadian life tables. The EFS estimates declined with each year of follow-up after ASCT and were 50.1% (95% confidence interval [CI]: 43.7% to 56.3%) and 43.4% (95% CI: 36.7% to 49.9%) at 5 years in CORAL and LY.12, respectively. The rate of death stabilized once patients achieved at least 4 years of EFS. Compared with the age- and sex-matched population, the SMR was significantly higher until 5 years after ASCT, when values were no longer statistically significant. Patients undergoing ASCT for relapsed DLBCL continue to have a higher rate of death at least until they have survived event free for 5 years. These observations can help to determine endpoints for future clinical trials in this population and for patient counseling. This trial was registered at www.clinicaltrials.gov as #NCT00078949.
Development of an anti-human complement C6 monoclonal antibody that inhibits the assembly of membrane attack complexes
Authors: Lin Kimberly , Zhang Lingjun , Kong Michael , Yang Maojing , Chen Yinghua , Poptic Earl , Hoffner Melanie , Xu Jijun , Tam Connie , Lin Feng
Published: May 2020

Membrane attack complexes (MACs; C5b-9) assembled after complement activation can directly injure self-tissues, leading to various diseases. Eculizumab, a monoclonal antibody (mAb) against complement component C5, is being used in the clinic to treat diseases in which MAC-mediated tissue damage is a primary cause. However, C5 is not a selective target for MAC assembly inhibition, and some patients respond incompletely or not at all to the eculizumab treatment. Therefore, C6, the next essential component in the terminal pathway of complement activation, may be an alternative target for the selective inhibition of MAC formation. Surprisingly, few reports describe a functional blockade of C6 using a specific mAb. Here, we report the development of an anti-human C6 mAb (clone 1C9) that recognizes C6 both in free circulation and within C5b6 complexes. This mAb blocked C7 binding to C5b6 complexes and consequently inhibited MAC formation and protected affected paroxysmal nocturnal hemoglobinuria patient red blood cells from MAC-mediated damage in vitro. In addition, this mAb cross-reacts with rhesus monkey but not mouse complement C6. Finally, 1C9 significantly reduced human complement–mediated intravascular hemolysis in vivo in a mouse model. These results suggest that the anti-C6 mAb holds promise as a new therapeutic agent that selectively targets MAC for many complement-mediated pathological conditions.
Assessment methods in respiratory medicine training in Europe: current status and future needs
Authors: Primhak Robert
Published: May 2020

There is a perceived need for harmonisation of training standards in medicine across Europe. Assessment methodology is a fundamental part of this harmonisation. Assessment may be: summative, measuring competency at the end of training, usually in a pass/fail mode; or formative, assessing strengths and weaknesses during training with a view to optimising performance. A survey of experienced respiratory medicine trainers in Europe was undertaken to discover the formative and summative assessment methods being used, and to explore the use of workplace-based assessments (WBAs). Structured interviews were sought with experienced trainers in adult and paediatric respiratory medicine. 35 trainers from 22 (71%) out of 31 countries were interviewed.

The number of types of summative assessments required at the end of training varied from 0 to 4 including clinical (25%), written (44%) and oral (47%) examinations. Four respondents required a research thesis as a proof of clinical competence.

WBA was not commonly used. Only 14% of respondents reported using a formal case-based discussion, 20% used a form of multisource feedback and 25% described some form of formal assessment of procedural skills. However, 77% of all respondents expressed a wish to have access to case-based discussion and 72% wanted to have a facility for multisource feedback. The majority also wanted training in the use of these tools. Almost half of the respondents had received no formal training in educational supervision and 80% of all respondents expressed a wish to receive such training.

The findings suggest that there is no adequate process of ensuring uniform standards for specialist accreditation in Europe, and demonstrate a need and desire among trainers for more WBA tools and training in their use to be made available.
Transcriptome analysis of neural progenitor cells derived from Lowe syndrome induced pluripotent stem cells: identification of candidate genes for the neurodevelopmental and eye manifestations
Authors: Liu Hequn , Barnes Jesse , Pedrosa Erika , Herman Nathaniel S. , Salas Franklin , Wang Ping , Zheng Deyou , Lachman Herbert M.
Published: May 2020

Background

Lowe syndrome (LS) is caused by loss-of-function mutations in the X-linked gene OCRL, which codes for an inositol polyphosphate 5-phosphatase that plays a key role in endosome recycling, clathrin-coated pit formation, and actin polymerization. It is characterized by congenital cataracts, intellectual and developmental disability, and renal proximal tubular dysfunction. Patients are also at high risk for developing glaucoma and seizures. We recently developed induced pluripotent stem cell (iPSC) lines from three patients with LS who have hypomorphic variants affecting the 3′ end of the gene, and their neurotypical brothers to serve as controls.

Methods

In this study, we used RNA sequencing (RNA-seq) to obtain transcriptome profiles in LS and control neural progenitor cells (NPCs).

Results

In a comparison of the patient and control NPCs (n = 3), we found 16 differentially expressed genes (DEGs) at the multiple test adjusted p value (padj) < 0.1, with nine at padj < 0.05. Using nominal p value < 0.05, 319 DEGs were detected. The relatively small number of DEGs could be due to the fact that OCRL is not a transcription factor per se, although it could have secondary effects on gene expression through several different mechanisms. Although the number of DEGs passing multiple test correction was small, those that were found are quite consistent with some of the known molecular effects of OCRL protein, and the clinical manifestations of LS. Furthermore, using gene set enrichment analysis (GSEA), we found that genes increased expression in the patient NPCs showed enrichments of several gene ontology (GO) terms (false discovery rate < 0.25): telencephalon development, pallium development, NPC proliferation, and cortex development, which are consistent with a condition characterized by intellectual disabilities and psychiatric manifestations. In addition, a significant enrichment among the nominal DEGs for genes implicated in autism spectrum disorder (ASD) was found (e.g., AFF2, DNER, DPP6, DPP10, RELN, CACNA1C), as well as several that are strong candidate genes for the development of eye problems found in LS, including glaucoma. The most notable example is EFEMP1, a well-known candidate gene for glaucoma and other eye pathologies.

Conclusion

Overall, the RNA-seq findings present several candidate genes that could help explain the underlying basis for the neurodevelopmental and eye problems seen in boys with LS.
Male infant patient with a mesenteric cyst in the greater and lesser omenta: a case report
Authors: del Pilar Pereira-Ospina Rocio , Montoya-Sanchez Laura Catherine , Abella-Morales Diana María , Pinzón-Salamanca Javier Yesid , Suescún-Vargas José Miguel , Rueda-Martínez Sergio
Published: May 2020

Background

Mesenteric cysts are intra-abdominal masses of congenital origin, which most frequently occur in children, with an incidence of approximately 1 case per 20,000 pediatric admissions. Its progression can be asymptomatic, and its diagnosis can be incidental. However, it usually occurs with symptoms such as nausea, vomiting, constipation, sensation of a mass, and/or diarrhea. The diagnostic imaging method of choice is abdominal ultrasound.

Case presentation

Below, we present the case of a previously healthy 1-year-old male patient with nonspecific symptoms, who was referred to a tertiary hospital. The presence of a mesenteric cyst was detected at the end of the diagnostic approach.

Conclusion

It is important to know these pathologies even though they are infrequent, because although they are benign masses by definition, they can lead to complications such as intestinal torsion, intestinal obstruction, and even peritonitis.
Cluster correlation based method for lncRNA-disease association prediction
Authors: Yuan Qianqian , Guo Xingli , Ren Yang , Wen Xiao , Gao Lin
Published: May 2020

Background

In recent years, increasing evidences have indicated that long non-coding RNAs (lncRNAs) are deeply involved in a wide range of human biological pathways. The mutations and disorders of lncRNAs are closely associated with many human diseases. Therefore, it is of great importance to predict potential associations between lncRNAs and complex diseases for the diagnosis and cure of complex diseases. However, the functional mechanisms of the majority of lncRNAs are still remain unclear. As a result, it remains a great challenge to predict potential associations between lncRNAs and diseases.

Results

Here, we proposed a new method to predict potential lncRNA-disease associations. First, we constructed a bipartite network based on known associations between diseases and lncRNAs/protein coding genes. Then the cluster association scores were calculated to evaluate the strength of the inner relationships between disease clusters and gene clusters. Finally, the gene-disease association scores are defined based on disease-gene cluster association scores and used to measure the strength for potential gene-disease associations.

Conclusions

Leave-One Out Cross Validation (LOOCV) and 5-fold cross validation tests were implemented to evaluate the performance of our method. As a result, our method achieved reliable performance in the LOOCV (AUCs of 0.8169 and 0.8410 based on Yang’s dataset and Lnc2cancer 2.0 database, respectively), and 5-fold cross validation (AUCs of 0.7573 and 0.8198 based on Yang’s dataset and Lnc2cancer 2.0 database, respectively), which were significantly higher than the other three comparative methods. Furthermore, our method is simple and efficient. Only the known gene-disease associations are exploited in a graph manner and further new gene-disease associations can be easily incorporated in our model. The results for melanoma and ovarian cancer have been verified by other researches. The case studies indicated that our method can provide informative clues for further investigation.
methCancer-gen: a DNA methylome dataset generator for user-specified cancer type based on conditional variational autoencoder
Authors: Choi Joungmin , Chae Heejoon
Published: May 2020

Background

Recently, DNA methylation has drawn great attention due to its strong correlation with abnormal gene activities and informative representation of the cancer status. As a number of studies focus on DNA methylation signatures in cancer, demand for utilizing publicly available methylome dataset has been increased. To satisfy this, large-scale projects were launched to discover biological insights into cancer, providing a collection of the dataset. However, public cancer data, especially for certain cancer types, is still limited to be used in research. Several simulation tools for producing epigenetic dataset have been introduced in order to alleviate the issue, still, to date, generation for user-specified cancer type dataset has not been proposed.

Results

In this paper, we present methCancer-gen, a tool for generating DNA methylome dataset considering type for cancer. Employing conditional variational autoencoder, a neural network-based generative model, it estimates the conditional distribution with latent variables and data, and generates samples for specified cancer type.

Conclusions

To evaluate the simulation performance of methCancer-gen for the user-specified cancer type, our proposed model was compared to a benchmark method and it could successfully reproduce cancer type-wise data with high accuracy helping to alleviate the lack of condition-specific data issue. methCancer-gen is publicly available at https://github.com/cbi-bioinfo/methCancer-gen.
Multi-task learning sparse group lasso: a method for quantifying antigenicity of influenza A(H1N1) virus using mutations and variations in glycosylation of Hemagglutinin
Authors: Li Lei , Chang Deborah , Han Lei , Zhang Xiaojian , Zaia Joseph , Wan Xiu-Feng
Published: May 2020

Background

In addition to causing the pandemic influenza outbreaks of 1918 and 2009, subtype H1N1 influenza A viruses (IAVs) have caused seasonal epidemics since 1977. Antigenic property of influenza viruses are determined by both protein sequence andN-linked glycosylation of influenza glycoproteins, especially hemagglutinin (HA). The currently available computational methods are only considered features in protein sequence but notN-linked glycosylation.

Results

A multi-task learning sparse group least absolute shrinkage and selection operator (LASSO) (MTL-SGL) regression method was developed and applied to derive two types of predominant features including protein sequence andN-linked glycosylation in hemagglutinin (HA) affecting variations in serologic data for human and swine H1N1 IAVs. Results suggested that mutations and changes inN-linked glycosylation sites are associated with the rise of antigenic variants of H1N1 IAVs. Furthermore, the implicated mutations are predominantly located at five reported antibody-binding sites, and within or close to the HA receptor binding site. All of the threeN-linked glycosylation sites (i.e. sequons NCSV at HA 54, NHTV at HA 125, and NLSK at HA 160) identified by MTL-SGL to determine antigenic changes were experimentally validated in the H1N1 antigenic variants using mass spectrometry analyses. Compared with conventional sparse learning methods, MTL-SGL achieved a lower prediction error and higher accuracy, indicating that grouped features and MTL in the MTL-SGL method are not only able to handle serologic data generated from multiple reagents, supplies, and protocols, but also perform better in genetic sequence-based antigenic quantification.

Conclusions

In summary, the results of this study suggest that mutations and variations inN-glycosylation in HA caused antigenic variations in H1N1 IAVs and that the sequence-based antigenicity predictive model will be useful in understanding antigenic evolution of IAVs.
The seasonal development dynamics of the yak hair cycle transcriptome
Authors: Bao Pengjia , Luo Jiayu , Liu Yanbin , Chu Min , Ren Qingmiao , Guo Xian , Tang Bolin , Ding Xuezhi , Qiu Qiang , Pan Heping , Wang Kun , Yan Ping
Published: May 2020

Background

Mammalian hair play an important role in mammals’ ability to adapt to changing climatic environments. The seasonal circulation of yak hair helps them adapt to high altitude but the regulation mechanisms of the proliferation and differentiation of hair follicles (HFs) cells during development are still unknown. Here, using time series data for transcriptome and hormone contents, we systematically analyzed the mechanism regulating the periodic expression of hair development in the yak and reviewed how different combinations of genetic pathways regulate HFs development and cycling.

Results

This study used high-throughput RNA sequencing to provide a detailed description of global gene expression in 15 samples from five developmental time points during the yak hair cycle. According to clustering analysis, we found that these 15 samples could be significantly grouped into three phases, which represent different developmental periods in the hair cycle. A total of 2316 genes were identified in these three consecutive developmental periods and their expression patterns could be divided into 9 clusters. In the anagen, genes involved in activating hair follicle growth are highly expressed, such as the WNT pathway, FGF pathway, and some genes related to hair follicle differentiation. In the catagen, genes that inhibit differentiation and promote hair follicle cell apoptosis are highly expressed, such as BMP4, and Wise. In the telogen, genes that inhibit hair follicle activity are highly expressed, such as DKK1 and BMP1. Through co-expression analysis, we revealed a number of modular hub genes highly associated with hormones, such as SLF2, BOP1 and DPP8. They may play unique roles in hormonal regulation of events associated with the hair cycle.

Conclusions

Our results revealed the expression pattern and molecular mechanisms of the seasonal hair cycle in the yak. The findings will be valuable in further understanding the alpine adaptation mechanism in the yak, which is important in order to make full use of yak hair resources and promote the economic development of pastoral plateau areas.
Origin, clonal diversity, and evolution of the parthenogenetic lizard Darevskia unisexualis
Authors: Vergun Andrey A. , Girnyk Anastasiya E. , Korchagin Vitaly I. , Semyenova Seraphima K. , Arakelyan Marine S. , Danielyan Felix D. , Murphy Robert W. , Ryskov Alexey P.
Published: May 2020

Background

The hybridization of femaleD. raddeiand maleD. valentinigave rise to the parthenogenetic Caucasian rock lizardDarevskia unisexualis. A previously identified genetic polymorphism in the species consisted of one common and two allozyme clones. Analysis of microsatellites and single nucleotide polymorphisms (SNPs) from the three species yields estimates of clonal diversity and tests the hypothesis of a single origin forD. unisexualis.

Results

Genotyping and sequencing of four microsatellite-containing loci for 109 specimens ofD. unisexualis, 17D. valentini,and 45D. raddei nairensisidentified 12 presumptive clones,including one widespread and 11 rare clones. Most individuals in some localities had a rare clone. Clone-specific alleles inD. unisexualiswere compared with those of the parental species. The results inferred a single hybridization event. Post-formation mutations best explain the less common clones.

Conclusions

Interspecific analyses identify alleles inherited byD. unisexualisfrom its bisexual ancestors.SNP analyses fail to reject the hypothesis of a single interspecific origin ofD. unisexualis,followed by microsatellite mutations in this initial clone. Microsatellites detect higher clonal diversity inD. unisexualiscompared to allozymes and identify the likely origins of clones.Our approach may be applicable to other unisexual species whose origins involve interspecific hybridization.
High-resolution profile of transcriptomes reveals a role of alternative splicing for modulating response to nitrogen in maize
Authors: Wang Yuancong , Xu Jinyan , Ge Min , Ning Lihua , Hu Mengmei , Zhao Han
Published: May 2020

Background

The fluctuation of nitrogen (N) contents profoundly affects the root growth and architecture in maize by altering the expression of thousands of genes. The differentially expressed genes (DEGs) in response to N have been extensively reported. However, information about the effects of N variation on the alternative splicing in genes is limited.

Results

To reveal the effects of N on the transcriptome comprehensively, we studied the N-starved roots of B73 in response to nitrate treatment, using a combination of short-read sequencing (RNA-seq) and long-read sequencing (PacBio-sequencing) techniques. Samples were collected before and 30 min after nitrate supply. RNA-seq analysis revealed that the DEGs in response to N treatment were mainly associated with N metabolism and signal transduction. In addition, we developed a workflow that utilizes the RNA-seq data to improve the quality of long reads, increasing the number of high-quality long reads to about 2.5 times. Using this workflow, we identified thousands of novel isoforms; most of them encoded the known functional domains and were supported by the RNA-seq data. Moreover, we found more than 1000 genes that experienced AS events specifically in the N-treated samples, most of them were not differentially expressed after nitrate supply-these genes mainly related to immunity, molecular modification, and transportation. Notably, we found a transcription factor ZmNLP6, a homolog of AtNLP7-a well-known regulator for N-response and root growth-generates several isoforms varied in capacities of activating downstream targets specifically after nitrate supply. We found that one of its isoforms has an increased ability to activate downstream genes. Overlaying DEGs and DAP-seq results revealed that many putative targets of ZmNLP6 are involved in regulating N metabolism, suggesting the involvement of ZmNLP6 in the N-response.

Conclusions

Our study shows that many genes, including the transcription factor ZmNLP6, are involved in modulating early N-responses in maize through the mechanism of AS rather than altering the transcriptional abundance. Thus, AS plays an important role in maize to adapt N fluctuation.
Genome-wide association study leads to novel genetic insights into resistance to Aspergillus flavus in maize kernels
Authors: Han Guomin , Li Cuiping , Xiang Fangzhi , Zhao Qianqian , Zhao Yang , Cai Ronghao , Cheng Beijiu , Wang Xuewen , Tao Fang
Published: May 2020

Background

Fungus infection in staple grains affects the food storage and threatens food security. TheAspergillus flavusis known to infect multiple grains and produce mycotoxin Aflatoxin B1, which is mutagenic, teratogenic and causes immunosuppression in animals. However, the molecular mechanism of maize resistance toA. flavusis largely unknown.

Results

Here we used corn kernels to investigate resistance genes toA. flavususing genome-wide association study (GWAS) of 313 inbred lines. We characterized the resistance levels of kernels after inoculating withA. flavus. The GWAS with 558,529 SNPs identified four associated loci involving 29 candidate genes that were linked to seed development, resistance or infection, and involved in signal pathways, seed development, germination, dormancy, epigenetic modification, and antimicrobial activity. In addition, a few candidate genes were also associated with several G-protein signaling and phytohormones that might involve in synergistic work conferring different resistance during seed development. Expression of 16 genes out of 29 during kernel development was also associated with resistance levels.

Conclusions

We characterized the resistance levels of 313 maize kernels after inoculating withA. flavus, and found four associated loci and 16 candidate maize genes. The expressed 16 genes involved in kernel structure and kernel composition most likely contribute to mature maize kernels’ resistance toA. flavus, and in particular, in the development of pericarp. The linked candidate genes could be experimentally transformed to validate and manipulate fungal resistance. Thus this result adds value to maize kernels in breeding programs.
Using alcohol consumption diary data from an internet intervention for outcome and predictive modeling: a validation and machine learning study
Authors: Lindner Philip , Johansson Magnus , Gajecki Mikael , Berman Anne H.
Published: May 2020

Background

Alcohol use disorder (AUD) is highly prevalent and presents a large treatment gap. Self-help internet interventions are an attractive approach to lowering thresholds for seeking help and disseminating evidence-based programs at scale. Internet interventions for AUD however suffer from high attrition and since continuous outcome measurements are uncommon, little is known about trajectories and processes. The current study investigates whether data from a non-mandatory alcohol consumption diary, common in internet interventions for AUD, approximates drinks reported at follow-up, and whether data from the first half of the intervention predict treatment success.

Methods

N = 607 participants enrolled in a trial of online self-help for AUD, made an entry in the non-mandatory consumption diary (total of 9117 entries), and completed the follow-up assessment. Using multiple regression and a subset of calendar data overlapping with the follow-up, scaling factors were derived to account for missing entries per participant and week. Generalized estimating equations with an inverse time predictor were then used to calculate point-estimates of drinks per week at follow-up, the confidence intervals of which were compared to that from the measurement at follow-up. Next, calendar data form the first half of the intervention were retained and summary functions used to create 18 predictors for random forest machine learning models, the classification accuracies of which were ultimately estimated using nested cross-validation.

Results

While the raw calendar data substantially underestimated drinks reported at follow-up, the confidence interval of the trajectory-derived point-estimate from the adjusted data overlapped with the confidence interval of drinks reported at follow-up. Machine learning models achieved prediction accuracies of 64% (predicting non-hazardous drinking) and 48% (predicting AUD severity decrease), in both cases with higher sensitivity than specificity.

Conclusions

Data from a non-mandatory alcohol consumption diary, adjusted for missing entries, approximates follow-up data at a group level, suggesting that such data can be used to reveal trajectories and processes during treatment and possibly be used to impute missing follow-up data. At an individual level, however, calendar data from the first half of the intervention did not have high predictive accuracy, presumable due to a high rate of missing data and unclear missing mechanisms.
Reduced mean platelet volume levels predict shorter survival in patients with resectable pancreatic ductal adenocarcinoma and type 2 diabetes
Authors: Yin Ji-bin , Li Na , Cui Ming-ming , Wang Xin , Wang Rui-tao
Published: May 2020

Background

Type 2 diabetes mellitus (T2DM) increased the risk of developing pancreatic cancer. Pancreatic ductal adenocarcinoma (PDAC) is the most common neoplastic disease originating from the pancreas. Increasing evidence indicates that platelets activation plays a prominent role in tumor and T2DM. Mean platelet volume (MPV) is an indicator of activated platelets and is altered in several cancers. The current study aimed to evaluate the prognostic role of MPV in resectable PDAC patients with T2DM.

Methods

Eight hundred and three patients with PDAC were included in this retrospective study. We determined the optimal cutoff value of MPV for 5-year overall survival (OS) using the receiver operating characteristic (ROC) method. The associations between MPV levels and clinical characteristics were analyzed. Kaplan-Meier survival analysis and Cox’s proportional hazard regression model were used to evaluate the prognostic value of MPV for OS.

Results

Compared to the PDAC patients without T2DM, MPV levels were significantly higher in the PDAC patients with T2DM. Moreover, MPV was significantly associated with the differentiation between T2DM and non-T2DM. In addition, Kaplan-Meier analysis found that patients with low MPV levels had a poorer 5-year OS than patients with high MPV levels in diabetic patients. Multivariate analyses revealed that MPV was an independent prognostic factor for OS in patients with T2DM. However, the independent prognostic role of MPV was not observed in patients without T2DM.

Conclusion

MPV independently predicts poor survival in PDAC patients with T2DM. Prospective studies are required to confirm the role of MPV in PDAC.
Production of ERCP training model using a 3D printing technique (with video)
Authors: Kwon Chang-Il , Shin Yeonsun , Hong Jaeok , Im Minje , Kim Guk Bae , Koh Dong Hee , Song Tae Jun , Park Won Suk , Hyun Jong Jin , Jeong Seok
Published: May 2020

Background

ERCP training models are very different in terms of anatomical differences, ethical issues, storage problems, realistic tactile sensation, durability and portability. There is no easy way to select an optimized model for ERCP training. If the ERCP training model could be made as a soft silicone model using 3D printing technique, it would have numerous advantages over the models presented so far. The purpose of this study was to develop an optimized ERCP training model using a 3D printing technique and to try to find ways for implementing various practical techniques.

Methods

All organ parts of this model were fabricated using silicone molding techniques with 3D printing. Especially, various anatomy of the ampulla of Vater and common bile duct (CBD) were creatively designed for different diagnostic and therapeutic procedures. In order to manufacture each of the designed organ parts with silicone, a negative part had to be newly designed to produce the molder. The negative molders were 3D printed and then injection molding was applied to obtain organ parts in silicone material. The eight different types of ampulla and CBD were repeatedly utilized and replaced to the main system as a module-type.

Results

ERCP training silicone model using 3D technique was semi-permanently used to repeat various ERCP procedures. All ERCP procedures using this model could be observed by real-time fluoroscopic examination as well as endoscopic examination simultaneously. Using different ampulla and CBD modules, basic biliary cannulation, difficult cannulation, stone extraction, mechanical lithotripsy, metal stent insertion, plastic stent insertion, and balloon dilation were successfully and repeatedly achieved. Endoscopic sphincterotomy was also performed on a specialized ampulla using a Vienna sausage. After repeat procedures and trainings, all parts of organs including the ampulla and CBD modules were not markedly damaged or deformed.

Conclusions

We made a specialized ERCP training silicon model with 3D printing technique. This model is durable, relatively cheap and easy to make, and thus allows the users to perform various specialized ERCP techniques, which increases its chances of being a good ERCP training model.
Molecular identification and antifungal susceptibility profile of yeast from vulvovaginal candidiasis
Authors: Shi Yu , Zhu Yuxia , Fan Shangrong , Liu Xiaoping , Liang Yiheng , Shan Yingying
Published: May 2020

Background

Accurate identification Candida is important for successful therapy and epidemiology study. The aim of research is to study API 20C yeast identification system identification rate by using molecular identification as gold standard and tested the antifungal susceptibility of Candida from patients with vulvovaginal candidiasis (VVC).

Methods

In total, 3574 yeast isolates were obtained from patients with VVC. API 20C yeast identification, molecular identification and in vitro antifungal susceptibility were performed.

Results

C. albicans was the predominant Candida species [2748 isolates, 76.9%] in VVC. The isolates from vaginal samples represented 22 species based on molecular identification. The API 20C system identifies only 11 of the species encountered during the study period. Based on the API 20C system, 3273 (91.58%) isolates were correctly identified to the species level. The correct identification rate of the API 20C system for rare yeast was 15.29% (26/170 isolates). Antifungal susceptibility was tested in a total of 1844 isolates of Candida from patients with VVC. C. albicans was susceptible to most of the tested antifungals. The MICs of azoles for C. glabrata were higher than those for C. albicans. The MICs of echinocandins for C. parapsilosis were higher than those for C. albicans.

Conclusions

The API 20C yeast identification system can be used to reliably identify the most common Candida species while molecular methods are necessary for the identification of closely related, emerging, and rare yeast species. The results from this study suggest that much of the previous studies on the epidemiology of VVC should be re-thought. C. albicans was susceptible to most of the tested antifungals.
Anopheles gambiae s.l (Diptera: Culicidae) seasonal abundance, abdominal status and parity rates in Metema-Armachiho lowland, Northwest Ethiopia
Authors: Aschale Yibeltal , Ayehu Animen , Worku Ligabaw , Addisu Ayenew , Zeleke Ayalew Jejaw , Bayih Abebe Genetu , Lemma Wossenseged
Published: May 2020

Background

Malaria is a life threating vector borne disease caused by different Plasmodium parasites. Metema and Armachiho are two of the top five malaria endemic areas among the districts of Amhara region in Ethiopia. Transmission pattern is seasonal and migrant laborers who visit these areas for employment in mechanized agriculture are highly affected. The aim of this study was to investigate seasonal abundance, abdominal status and parity rate of An.gambiae s.l in Metema-Armachiho lowlands, Northwest Ethiopia.

Method

A 1 year longitudinal entomological study was conducted in Metema-Armachiho lowlands from June 2016–May 2017. Mosquitoes were collected using CDC-light traps in indoor and outdoor sites for four consecutive days in each month. A total of eight standard battery operated CDC-light traps were used to collect mosquitoes. Female mosquitoes were classed as unfed, fed or gravid under a dissecting microscope. The ovaries of all unfed An.gambiae s.l mosquitoes were examined for evidence of parity. Data were entered and analyzed using SPSS-20 software. Chi-square test was applied to show significant difference between variables. P-value< 0.05 was taken as statistically significant.

Results

Of the total 1253 mosquitoes collected, 713 (552 female, 161 male) were culex and 540 (501 female, 39 male) were An.gambiae s.l. About 50.9% were collected in June–August 2016, 21.7% in September–November 2016, 12.0% in December 2016–February 2017 and 15.4% in March to May 2017. Of the total, 57.2 and 42.8% of the An.gambiae s.l were collected from indoor and outdoor sites respectively. Of the total females collected, 76.8% were unfed; of which 69.4% were parous. Significantly higher number of female An.gambiae s.l were collected in indoor and there was significant difference in abdominal status of An.gambiae s.l mosquitoes collected in different season (P < 0.05).

Conclusions

Highest number of An.gambiae s.l was observed from June–August followed by September–November. The parity rate of An.gambiae s.l was high and there was significant difference in abdominal status of An.gambiae s.l collected in different season.