bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechano-calcium and mechano-electric feedbacks in the human cardiomyocyte analyzed in a mathematical model
Authors: Balakina-Vikulova Nathalie A. , Panfilov Alexander , Solovyova Olga , Katsnelson Leonid B. 
Published: February 2020

AbstractExperiments on animal hearts (rat, rabbit, guinea pig, etc.) have demonstrated that mechano-calcium feedback (MCF) and mechano-electric feedback (MEF) are very important for myocardial self-regulation because they adjust the cardiomyocyte contractile function to various mechanical loads and to mechanical interactions between heterogeneous myocardial segments in the ventricle walls. In in vitro experiments on these animals, MCF and MEF manifested themselves in several basic classical phenomena (e.g., load dependence, length dependence of isometric twitches, etc.), and in the respective responses of calcium transients and action potentials. However, it is extremely difficult to study simultaneously the electrical, calcium, and mechanical activities of the human heart muscle in vitro. Mathematical modeling is a useful tool for exploring these phenomena. We have developed a novel model to describe electromechanical coupling and mechano-electric feedbacks in the human cardiomyocyte. It combines the ‘ten Tusscher–Panfilov’ electrophysiological model of the human cardiomyocyte with our module of myocardium mechanical activity taken from the ‘Ekaterinburg–Oxford’ model and adjusted to human data. Using it, we simulated isometric and afterloaded twitches and effects of MCF and MEF on excitation–contraction coupling. MCF and MEF were found to affect significantly the duration of the calcium transient and action potential in the human cardiomyocyte model in response to both smaller afterloads as compared to bigger ones and various mechanical interventions applied during isometric and afterloaded twitches.
Tracking intratumoral heterogeneity in glioblastoma via regularized classification of single-cell RNA-Seq data
Authors: Lopes Marta B. , Vinga Susana 
Published: February 2020

AbstractBackgroundUnderstanding cellular and molecular heterogeneity in glioblastoma (GBM), the most common and aggressive primary brain malignancy, is a crucial step towards the development of effective therapies. Besides the inter-patient variability, the presence of multiple cell populations within tumors calls for the need to develop modeling strategies able to extract the molecular signatures driving tumor evolution and treatment failure. With the advances in single-cell RNA Sequencing (scRNA-Seq), tumors can now be dissected at the cell level, unveiling information from their life history to their clinical implications.ResultsWe propose a classification setting based on GBM scRNA-Seq data, through sparse logistic regression, where different cell populations (neoplastic and normal cells) are taken as classes. The goal is to identify gene features discriminating between the classes, but also those shared by different neoplastic clones. The latter will be approached via the network-based regularizer to identify gene signatures shared by neoplastic cells from the tumor core and infiltrating neoplastic cells originated from the tumor periphery, as putative disease biomarkers to target multiple neoplastic clones. Our analysis is supported by the literature through the identification of several known molecular players in GBM. Moreover, the relevance of the selected genes was confirmed by their significance in the survival outcomes in bulk GBM RNA-Seq data, as well as their association with several Gene Ontology (GO) biological process terms.ConclusionsWe presented a methodology intended to identify genes discriminating between GBM clones, but also those playing a similar role in different GBM neoplastic clones (including migrating cells), therefore potential targets for therapy research. Our results contribute to a deeper understanding on the genetic features behind GBM, by disclosing novel therapeutic directions accounting for GBM heterogeneity.
IPCO: Inference of Pathways from Co-variance analysis
Authors: Das Mrinmoy , Ghosh Tarini Shankar , Jeffery Ian B. 
Published: February 2020

AbstractBackgroundKey aspects of microbiome research are the accurate identification of taxa and the profiling of their functionality. Amplicon profiling based on the 16S ribosomal DNA sequence is a ubiquitous technique to identify and profile the abundance of the various taxa. However, it does not provide information on their encoded functionality. Predictive tools that can accurately extrapolate the functional information of a microbiome based on taxonomic profile composition are essential. At present, the applicability of these tools is limited due to requirement of reference genomes from known species. We present IPCO (Inference of Pathways from Co-variance analysis), a new method of inferring functionality for 16S-based microbiome profiles independent of reference genomes. IPCO utilises the biological co-variance observed between paired taxonomic and functional profiles and co-varies it with the queried dataset.ResultsIPCO outperforms other established methods both in terms of sample and feature profile prediction. Validation results confirmed that IPCO can replicate observed biological associations between shotgun and metabolite profiles. Comparative analysis of predicted functionality profiles with other popular 16S-based functional prediction tools showed significantly lower performances with predicted functionality showing little to no correlation with paired shotgun features across samples.ConclusionsIPCO can infer functionality from 16S datasets and significantly outperforms existing tools. IPCO is implemented in R and available fromhttps://github.com/IPCO-Rlibrary/IPCO.
A multiplex PCR assay for rapid identification of major tospovirus vectors reported in India
Authors: Jangra Sumit , Mittal Anubha , Dhall Heena , Jain Rakesh Kumar , Ghosh Amalendu 
Published: February 2020

Abstract
Background
To date, four thrips vectors have been reported to transmit five different tospoviruses in India. Their identification at an early stage is crucial in formulating appropriate pest management strategies. Since morphometric key-based thrips identification based on the adult stage is time-consuming, there is a need to develop diagnostic tools which are rapid, accurate, and independent of developmental stages. Here, we report a multiplex PCR assay to identify four major thrips vectors viz. Thrips palmi, T. tabaci, Scirtothrips dorsalis, and Frankliniella schultzei present in India.

Results
Cytochrome oxidase subunit III and internal transcribed spacer region 2 were utilized to design species-specific primers. Of 38 pairs of primers tested, primer pairs AG35F-AG36R, AG47F-AG48R, AG87F-AG88R, and AG79F-AG80R amplified 568 bp, 713 bp, 388 bp, and 200 bp products from the DNA templates of T. palmi, S. dorsalis, T. tabaci, and F. schultzei, respectively at same PCR conditions. The specificity of the primer pairs was validated with a large number of known specimens and no cross-reactivity was observed with other thrips species. The multiplex PCR assay with a cocktail of all the four primer pairs detected four thrips vectors efficiently and could discriminate all of them concurrently in a single reaction.

Conclusion
The multiplex PCR reported in this study could identify the major thrips vectors reported in India. The assay will be useful in ascertaining distribution profile of major thrips vectors, disease epidemiology, screening large samples, and quarantine.
Transcriptional reprogramming strategies and miRNA-mediated regulation networks of Taxus media induced into callus cells from tissues
Authors: Chen Ying , Zhang Meng , Jin Xiaofei , Tao Haoran , Wang Yamin , Peng Bo , Fu Chunhua , Yu Longjiang 
Published: February 2020

Abstract
Background
Taxus cells are a potential sustainable and environment-friendly source of taxol, but they have low survival ratios and slow grow rates. Despite these limitations, Taxus callus cells induced through 6 months of culture contain more taxol than their parent tissues. In this work, we utilized 6-month-old Taxus media calli to investigate their regulatory mechanisms of taxol biosynthesis by applying multiomics technologies. Our results provide insights into the adaptation strategies of T. media by transcriptional reprogramming when induced into calli from parent tissues.

Results
Seven out of 12 known taxol, most of flavonoid and phenylpropanoid biosynthesis genes were significantly upregulated in callus cells relative to that in the parent tissue, thus indicating that secondary metabolism is significantly strengthened. The expression of genes involved in pathways metabolizing biological materials, such as amino acids and sugars, also dramatically increased because all nutrients are supplied from the medium. The expression level of 94.1% genes involved in photosynthesis significantly decreased. These results reveal that callus cells undergo transcriptional reprogramming and transition into heterotrophs. Interestingly, common defense and immune activities, such as “plant–pathogen interaction” and salicylic acid- and jasmonic acid-signaling transduction, were repressed in calli. Thus, it’s an intelligent adaption strategy to use secondary metabolites as a cost-effective defense system. MiRNA- and degradome-sequencing results showed the involvement of a precise regulatory network in the miRNA-mediated transcriptional reprogramming of calli. MiRNAs act as direct regulators to enhance the metabolism of biological substances and repress defense activities. Given that only 17 genes of secondary metabolite biosynthesis were effectively regulated, miRNAs are likely to play intermediate roles in the biosynthesis of secondary metabolites by regulating transcriptional factors (TFs), such as ERF, WRKY, and SPL.

Conclusion
Our results suggest that increasing the biosynthesis of taxol and other secondary metabolites is an active regulatory measure of calli to adapt to heterotrophic culture, and this alteration mainly involved direct and indirect miRNA-induced transcriptional reprogramming. These results expand our understanding of the relationships among the metabolism of biological substances, the biosynthesis of secondary metabolites, and defense systems. They also provide a series of candidate miRNAs and transcription factors for taxol biosynthesis.
Effect of availability of HIV self-testing on HIV testing frequency among men who have sex with men attending university in China (UniTest): protocol of a stepped-wedge randomized controlled trial
Authors: Fan Song , Liu Zhongquan , Luo Zhenzhou , Yu Maohe , Ouyang Lin , Gong Hui , Ding Yi , Li Peiyang , Yuan Tanwei , Zhou Yepeng , Wu Guohui , Zou Huachun 
Published: February 2020

Abstract
Background
HIV testing plays a central role in the combat against HIV. We aimed to determine if the availability of HIV self-testing (HIVST) would increase the frequency of testing among men who have sex with men (MSM) attending university in China.

Methods
A stepped wedge randomized controlled trial will be conducted in 4 provinces in China: Chongqing, Guangdong, Shandong, and Tianjin. Eligibility assessment will include (1) male, aged 16 years or older, (2) university student (technical diploma and undergraduate students), (3) MSM (sexual behaviors including mutual masturbation, oral sex, and anal sex), (4) HIV negative, and (5) willing to provide informed consent.
Participants will be randomly allocated to HIV self-testing intervention with free HIVST kits in every 30 days according to the intervention waiting lists with a computer-generated randomized sequence. All participants will complete a self-administrated online questionnaire onsite at baseline and 12-month follow-up and complete an online questionnaire at 4- and 8-month.
The primary outcome is the effect of HIVST on HIV testing frequency. Secondary outcomes include the change in sexual behaviors and HIV incidence.

Discussion
No previous study had measured the effect of social media based HIVST intervention on the change in HIV testing behaviors, sexual behaviors and incident HIV infection among MSM attending university in China. Findings from this study will provide evidence for further interventional practice promotions and prevention strategies scale-up, including HIV testing, pre-exposure prophylaxis (PrEP) or post-exposure prophylaxis (PEP), and sexual partner serosorting.

Trial registration
Chinese Clinical Trial Registry: ChiCTR1900020645. Registered 11 January 2019.
Predictive model for bacterial late-onset neonatal sepsis in a tertiary care hospital in Thailand
Authors: Husada Dominicus , Chanthavanich Pornthep , Chotigeat Uraiwan , Sunttarattiwong Piyarat , Sirivichayakul Chukiat , Pengsaa Krisana , Chokejindachai Watcharee , Kaewkungwal Jaranit 
Published: February 2020

AbstractBackgroundEarly diagnosis of neonatal sepsis is essential to prevent severe complications and avoid unnecessary use of antibiotics. The mortality of neonatal sepsis is over 18%in many countries. This study aimed to develop a predictive model for the diagnosis of bacterial late-onset neonatal sepsis.MethodsA case-control study was conducted at Queen Sirikit National Institute of Child Health, Bangkok, Thailand. Data were derived from the medical records of 52 sepsis cases and 156 non-sepsis controls. Only proven bacterial neonatal sepsis cases were included in the sepsis group. The non-sepsis group consisted of neonates without any infection. Potential predictors consisted of risk factors, clinical conditions, laboratory data, and treatment modalities. The model was developed based on multiple logistic regression analysis.ResultsThe incidence of late proven neonatal sepsis was 1.46%. The model had 6 significant variables: poor feeding, abnormal heart rate (outside the range 100–180 x/min), abnormal temperature (outside the range 36o-37.9 °C), abnormal oxygen saturation, abnormal leucocytes (according to Manroe’s criteria by age), and abnormal pH (outside the range 7.27–7.45). The area below the Receiver Operating Characteristics (ROC) curve was 95.5%. The score had a sensitivity of 88.5% and specificity of 90.4%.ConclusionA predictive model and a scoring system were developed for proven bacterial late-onset neonatal sepsis. This simpler tool is expected to somewhat replace microbiological culture, especially in resource-limited settings.
BSCN: bidirectional symmetric cascade network for retinal vessel segmentation
Authors: Guo Yanfei , Peng Yanjun 
Published: February 2020

Abstract
Background
Retinal blood vessel segmentation has an important guiding significance for the analysis and diagnosis of cardiovascular diseases such as hypertension and diabetes. But the traditional manual method of retinal blood vessel segmentation is not only time-consuming and laborious but also cannot guarantee the accuracy and efficiency of diagnosis. Therefore, it is especially significant to create a computer-aided method of automatic and accurate retinal vessel segmentation.

Methods
In order to extract the blood vessels’ contours of different diameters to realize fine segmentation of retinal vessels, we propose a Bidirectional Symmetric Cascade Network (BSCN) where each layer is supervised by vessel contour labels of specific diameter scale instead of using one general ground truth to train different network layers. In addition, to increase the multi-scale feature representation of retinal blood vessels, we propose the Dense Dilated Convolution Module (DDCM), which extracts retinal vessel features of different diameters by adjusting the dilation rate in the dilated convolution branches and generates two blood vessel contour prediction results by two directions respectively. All dense dilated convolution module outputs are fused to obtain the final vessel segmentation results.

Results
We experimented the three datasets of DRIVE, STARE, HRF and CHASE_DB1, and the proposed method reaches accuracy of 0.9846/0.9872/0.9856/0.9889 and AUC of 0.9874/0.9941/0.9882/0.9874 on DRIVE, STARE, HRF and CHASE_DB1.

Conclusions
The experimental results show that compared with the state-of-art methods, the proposed method has strong robustness, it not only avoids the adverse interference of the lesion background but also detects the tiny blood vessels at the intersection accurately.
A phase-II/III randomized controlled trial of adjuvant radiotherapy or concurrent chemoradiotherapy after surgery versus surgery alone in patients with stage-IIB/III esophageal squamous cell carcinoma
Authors: Ni Wenjie , Yu Shufei , Zhang Wencheng , Xiao Zefen , Zhou Zongmei , Chen Dongfu , Feng Qinfu , Liang Jun , Lv Jima , Gao Shugeng , Mao Yousheng , Xue Qi , Sun Kelin , Liu Xiangyang , Fang Dekang , Li Jian , Wang Dali 
Published: February 2020

Abstract
Background
Preoperative chemoradiotherapy (CRT) followed by surgery is the most common approach for patients with resectable esophageal cancer. Nevertheless, considerable numbers of esophageal-cancer patients undergo surgery as the first treatment. The benefit of neoadjuvant therapy might only be for patients with a pathologic complete response, so stratified research is necessary. Postoperative treatments have important roles because of the poor survival rates of patients with stage-IIB/III disease treated with resection alone. Five-year survival of patients with stage-IIB/III thoracic esophageal squamous cell carcinoma (TESCC) after surgery is 20.0–28.4%, and locoregional lymph-node metastases are the main cause of failure. Several retrospective studies have shown that postoperative radiotherapy (PORT) and postoperative chemoradiotherapy (POCRT) after radical esophagectomy for esophageal carcinoma with positive lymph-node metastases and stage-III disease can decrease locoregional recurrence and increase overall survival (OS). Using intensity-modulated RT, PORT reduces locoregional recurrence further. However, the rate of distant metastases increases to 30.7%. Hence, chemotherapy may be vital for these patients. Therefore, a prospective randomized controlled trial (RCT) is needed to evaluate the value of PORT and concurrent POCRT in comparison with surgery alone (SA) for esophageal cancer.

Method
This will be a phase-II/III RCT. The patients with pathologic stage-IIB/III esophageal squamous cell carcinoma will receive concurrent POCRT or PORT after radical esophagectomy compared with those who have SA. A total of 120 patients in each group will be recruited. POCRT patients will be 50.4 Gy concurrent with paclitaxel (135–150 mg/m2) plus cisplatin or nedaplatin (50–75 mg/m2) treatment every 28 days. Two cycles will be required for concurrent chemotherapy. The prescription dose will be 54 Gy for PORT. The primary endpoint will be disease-free survival (DFS). The secondary endpoint will be OS. Other pre-specified outcome measures will be the proportion of patients who complete treatment, toxicity, and out-of-field regional recurrence rate between PORT and POCRT.

Discussion
This prospective RCT will provide high-level evidence for postoperative adjuvant treatment of pathologic stage-IIB/III esophageal squamous cell carcinoma.

Trial registration
clinicaltrials.gov (NCT02279134). Registered on October 26, 2014.
Diacron reactive oxygen metabolites and biological antioxidant potential tests for patients with age-related macular degeneration
Authors: Matsuura Toshiyuki , Kaneko Hiroki , Takayama Kei , Shibata Rei , Kataoka Keiko , Ito Seina , Tsunekawa Taichi , Shimizu Hideyuki , Suzumura Ayana , Namba Rina , Ito Yasuki , Murohara Toyoaki , Terasaki Hiroko 
Published: February 2020

Abstract
Background
Previously, we showed that serum malondialdehyde (MDA) was significantly higher in patients with neovascular age-related macular degeneration (nAMD) than in those without AMD. The Diacron reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP) tests are known markers of oxidative stress. The aim of this study was to use d-ROMs and BAP tests to evaluate changes in systemic oxidative stress in patients with nAMD.

Methods
Blood serum samples were collected from 34 patients with nAMD (mean age: 76.5 ± 7.7 years; 22 men) and 20 control subjects (mean age: 62.9 ± 14.0 years; 10 men), and d-ROMs and BAP tests were examined.

Results
In men, the mean level of d-ROMs for the nAMD patients was significantly higher than that for the controls (312.0 ± 52.4 vs. 275.1 ± 45.5 U.CARR, respectively; P < .05). There was a significant correlation between d-ROM level and CNV lesion area in the male nAMD group (r = .42, P = .05). There were no significant differences in mean BAP test results between the nAMD patients and controls for either sex (men: 2241 ± 549 vs. 2136 ± 246 μmol/L; women: 2263 ± 292 vs. 2335 ± 161 μmol/L).

Conclusion
The d-ROMs test may provide a useful indicator of nAMD in men but not in women.
Dynamics of toxigenic Clostridium perfringens colonisation in a cohort of prematurely born neonatal infants
Authors: Shaw Alexander G. , Cornwell Emma , Sim Kathleen , Thrower Hannah , Scott Hannah , Brown Joseph C. S. , Dixon Ronald A. , Kroll J. Simon 
Published: February 2020

Abstract
Background
Clostridium perfringens forms part of the human gut microbiota and has been associated with life-threatening necrotising enterocolitis (NEC) in premature infants. Whether specific toxigenic strains are responsible is unknown, as is the extent of diversity of strains in healthy premature babies. We investigated the C. perfringens carrier status of premature infants in the neonatal intensive care unit, factors influence this status, and the toxic potential of the strains.

Methods
C. perfringens was isolated by culture from faecal samples from 333 infants and their toxin gene profiles analysed by PCR. A survival analysis was used to identify factors affecting probability of carriage. Competitive growth experiments were used to explore the results of the survival analysis.

Results
29.4% of infants were colonized with C. perfringens before they left hospital. Three factors were inversely associated with probability of carriage: increased duration of maternal milk feeds, CPAP oxygen treatment and antibiotic treatment. C. perfringens grew poorly in breast milk and was significantly outperformed by Bifidobacterium infantis, whether grown together or separately. Toxin gene screening revealed that infants carried isolates positive for collagenase, perfringolysin O, beta 2, beta, becA/B, netB and enterotoxin toxin genes, yet none were observed to be associated with the development of NEC.

Conclusions
Approximately a third of preterm infants are colonised 3 weeks after birth with toxin gene-carrying C. perfringens. We speculate that increased maternal breast milk, oxygen and antibiotic treatment creates an environment in the gut hostile to growth of C. perfringens. Whilst potentially toxigenic C. perfringens isolates were frequent, no toxin type was associated with NEC.

Trial registration
clinicaltrials.govNCT01102738, registered 13th April 2010.