bluuebunny/crossref_metadata_2025_split huggingface dataset:
Establishment and Drug Screening of Patient-Derived Extrahepatic Biliary Tract Carcinoma Organoids
Authors: Wang Zhiwei , Guo Yinghao , Jin Yun , Zhang Xiaoxiao , Geng Hao , Xie Guangyuan , Ye Dan , Yu Yuanquan , Liu Daren , Zhou Donger , Li Baizhou , Luo Yan , Peng Shuyou , Li Jiang-Tao 
Published: June 2021

Abstract
Background: Patient-derived organoids (PDO) have been proposed as a novel in vitro method of drug screening for different types of cancer. However, to date, extrahepatic biliary tract carcinoma (eBTC) PDOs have not yet been fully established. Methods: We collected six samples of gallbladder carcinoma (GBC) and one sample of extrahepatic cholangiocarcinoma (eCCA) from seven patients in order to attempt to establish eBTC PDOs for drug screening. Eventually, we successfully established five GBC PDOs and one eCCA PDO. Histological staining was used to compare the structural features of original tissues and cancer PDOs. Then, whole exome sequencing (WES) was used to analysed the genetic profiles of original tissues and cancer PDOs. Drug screening, including gemcitabine, 5-fluorouracil, cisplatin, paclitaxel, infigratinib, and ivosidenib, was measured and verified by some cases. Results: Different PDOs were found to have different growth rates during in vitro culture. Hematoxylin and eosin staining demonstrated that the structures of most cancer PDOs are able to retain the original structures of adenocarcinoma. Immunohistological staining and periodic acid-schiff staining were then discovered that marker expression in cancer PDOs were similar to those of the original specimens. Genetic profiles of the four original specimens, as well as paired cancer PDOs, were measured using whole exome sequencing. Three of the four PDOs exhibited a high degree of similarity, compared to the original specimens, except GBC2 PDO, which only had a concordance of 74% in the proportion of single nucleotide polymorphisms in the coding sequence. In general, gemcitabine was found to be the most efficient drug for treatments of the eBTCs, as it showed moderate or significant inhibitory impact on the growth of cancers. Results from the drug screening can be verified by three clinical cases, to a certain extent. Conclusions: Our study successfully established a series of eBTC PDOs, which helped fill in gaps in the field of eBTC PDOs. Additional measures should be explored to improve the growth rate of PDOs, and to preserve their immune microenvironment.
Histone Methylation Modification Patterns and Relevant M-RiskScore in Acute Myeloid Leukemia
Authors: Rong Dade , Chen Xiaomin , Liu Daiyuan , Ni Xiangna , Mo Zhuomao , Tong Xiuzhen , Wang Haihe 
Published: June 2021

Abstract
Background: Acute myeloid leukemia (AML) is a type of heterogeneous disease with varied prognosis, but current classification methods for AML do not play an ideal role in guiding the therapy. Emerging studies shown alteration of histone methylation is closely related to leukemogenesis. This study aimed at identifying the molecular subtypes associated with histone methylation and establishing a relevant score to predict treatment respond and prognosis in AML.Methods: Gene expression data and clinical characteristics of patients with AML were obtained from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database. Molecular subtypes were identified by consensus clustering based on the expression of 24 histone methylation modification regulators (HMMRs). The clinical and biological features of each pattern were investigated by unsupervised clustering, survival, principle component (PCA), somatic mutations, gene set variation (GSVA), tumor mutation burden (TMB) and immune cell infiltration analyses. Different expression analysis and lasso regression analysis was conducted to establish the scoring system that was explored in the role of prognosis by using receivers operating curve (ROC) analysis and univariate/multivariate Cox regression analyses. Moreover, correlation analysis was performed to investigate the value of scoring system in chemotherapeutic prediction. Finally, an independent GSE dataset was used as a reference to validate the established clustering system.Results: Two distinct histone methylation modification patterns had been identified that exhibit remarkable differences in several clinical and biological characteristics, including HMMRs’ expression, AML-M0 distribution, mutations of NPM1, survival, tumor mutation burden, somatic mutations, pathways activation and immune cell infiltration. Besides, based on the clustering, we established the scoring system, M-RiskScore. Integrated analysis demonstrated that M-RiskScore-low patients displayed a prominent survival advantage and a better respond to decitabine treatment, while the opposite site was reported to M-RiskScore-high patients but they could benefit more from IA regimen therapy.Conclusion: Our results demonstrate that detection of HMMRs’ expression is potentially useful to AML therapy decisions, and targeting histone methylation would be a more promising strategy for either AML-M0 or NPM1 mutant patients. M-RiskScore is a hopeful independent poor prognostic biomarker and be able to benefits the treatment decisions in AML.
Estimating the Risk of Malignancy in Adnexal Masses: Validation of the ADNEX Model in the Hands of Non-expert Ultrasonographers in a Gynecological Oncology Center in China
Authors: He Ping , Wang Jingjing , Duan Wei , Song Chao , Yang Yu , Wu Qingqing 
Published: June 2021

Abstract
Background:

The diagnosis of adnexal masses depends more on ultrasonography. This study aim to validate the diagnostic accuracy of the International Ovarian Tumor Analysis (IOTA) ADNEX model in the preoperative diagnosis of adnexal masses in the hands of non-expert ultrasonographers in a gynecological oncology center in China.
Methods:

This was a single oncology center, retrospective diagnostic accuracy study from 620 patients. All patients underwent surgery and the histopathological diagnosis was used as reference standard. The masses were divided into five types according to the ADNEX model: benign ovarian tumor, borderline ovarian tumor (BOT), Stage-I ovarian cancer (OC), Stages-II-IV OC and ovarian metastasis. Receiver-operating characteristics (ROC) curve analysis was used to evaluate the ability of the ADNEX model to classify tumors into different histological types with and without Cancer antigen 125 (CA 125) results.
Results:

Of the 620 women, 402 (64.8%) had a benign ovarian tumor and, 218 (35.2%) had a malignant ovarian tumor, including 86 (13.9%) with BOT, 75 (12.1%) with Stage-I OC, 53 (8.5%) with Stages-II-IV OC and 4 (0.6%) with ovarian metastasis. The AUC of the model to differentiate between benign and malignant adnexal masses was 0.97 (95% CI, 0.96–0.98). Performance was excellent for the discrimination between benign vs Stage II-IV OC, benign vs ovarian metastasis with AUCs of 0.99 (95% CI, 0.99-1.00) and 0.99 (95% CI, 0.98-1.00), respectively. Performance of the model was less effective at distinguishing between BOT and Stage I OC and between BOT and ovarian metastasis, with AUC of 0.54 (95% CI, 0.45–0.64) and 0.66 (95% CI, 0.56–0.77), respectively. When including CA125 in the model, performance in discriminating between Stages II–IV OC with stage I OC and ovarian metastasis were improved (AUC increased from 0.88 to 0.94, P = 0.01; 0.86 to 0.97, p = 0.01, respectively).
Conclusions:

The IOTA ADNEX model has excellent performance in differentiating benign and malignant adnexal masses in the hands of non-expert ultrasonographers with limited experienced in China. Between classification different subtypes of ovarian cancers, the model has difficulty to differentiate BOT from stage I OC, BOT from ovarian metastases.
Real-world Evidence Data on the Monoclonal Antibody Erenumab in Migraine Prevention: Perspectives of Treating Physicians in Germany
Authors: Straube Andreas , Stude Philipp , Gaul Charly , Schuh Katrin , Koch Mirja Annika 
Published: June 2021

Abstract
Background Erenumab, the first-in-class fully human monoclonal antibody targeting the calcitonin gene-related peptide receptor, was shown to be efficacious and safe for the prophylactic treatment of migraine in adults in randomized clinical trials. Large-scale, real-world evidence in multi-centre settings is still needed to confirm these results. Erenumab patient profiles outside clinical trials and physicians’ treatment patterns, as well as data from patients treated in Germany, a severely impacted population, are not published yet. MethodsTELESCOPE was a multi-centre survey gathering real-world data from 45 German headache centres between July 2019 and December 2019. The project consisted of two parts. In the first part, treating physicians shared their experiences on current erenumab treatment with regard to patient profiles, treatment patterns and treatment responses. In the second part, a retrospective chart review was conducted of 542 migraine patients treated with erenumab for at least three months. Treatment responses focused on various aspects of patients’ quality of life. ResultsThe analysis of 542 patients’ charts revealed that three-month treatment with erenumab significantly reduced monthly headaches, migraine and acute medication days. Furthermore, headache intensity and frequency were reduced in over 75 % and accompanying aura in 35 % of patients. The clinical global impression scale revealed a general improvement in 91 % of patients. According to the treating physicians’ professional judgement, 83 % of patients responded to erenumab and 80 % were satisfied with the treatment. Physicians evaluated restricted quality of life, the number of monthly migraine days and previous, prophylactic treatments as the main components of the current patient profile for monoclonal antibody recipients. Based on the assessment of physicians, erenumab reduced migraine symptoms in 65 % and increased quality of life in more than 75 % of their patients. ConclusionsTELESCOPE confirms positive treatment responses with erenumab shown in clinical trials in a real-world multi-centre setting. The results show consistently positive experiences of physicians utilizing erenumab in clinical practice and underline that therapy with this monoclonal antibody is effective in migraine patients, particular in those, who have failed several prophylactic therapies.
Rescue of Two Recombinant Canine Distemper Viruses That Separately Express Dabie Bandavirus Gn and Gc in Vitro
Authors: Liu Fuxiao , Lin Jiahui , Wang Qianqian , Shan Hu 
Published: June 2021

Abstract
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne zoonosis with a high mortality rate in humans. Additionally, dogs are frequently reported to be infected with this disease. There has been no commercially available vaccine for humans and animals as yet. The SFTS is caused by Dabie bandavirus (DBV), formerly known as SFTS virus. The DBV is now classified into the genus Bandavirus in the family Phenuiviridae. DBV Gn and Gc can induce specific immune responses in vivo. In this study, we used reverse genetics to construct two recombinant canine distemper viruses (rCDV), rCDV-Gn and -Gc, which could express Dabie bandavirus Gn and Gc in vitro, respectively. Two foreign sequences, Gn and Gc open reading frames, were genetically stable during twenty serial viral passages in cells. Growth curve of the rCDV-Gc basically coincided with that of a wild-type CDV, but showed a significant difference from that of the rCDV-Gn. The rCDV-Gn and -Gc were derived from a common parental CDV, the virulence-attenuating QN strain. Therefore, if proven to be efficient in resisting both canine distemper and SFTS in dogs, either or both recombinant CDVs would be potential vaccine candidates.
Chemical Constituents and Antibacterial Activity of Essential Oils of Needles of Pinus Sylvestris (Scots Pine) from South West Nigeria
Authors: Oyewole Kehinde A. , Oyedara Omotayo O. , Awojide Shola H. , Olawade Mary O. , Adetunji Charles O. 
Published: June 2021

Abstract
Pinus sylvestris (Scots pine) is a coniferous plant that possesses different biological properties such as antiseptic, antioxidant, antifungal, and anti-inflammatory. This study investigated the chemical constituents and in vitro antibacterial activities of essential oil (EO) of Pinus sylvestris (Scots pine) against thirteen bacterial species using Gas chromatography/mass spectrophotometry (GC/MS) and standard agar well diffusion assay. The EO exhibited excellent antibacterial activity inhibiting all the bacterial isolates tested with the diameter zone of inhibitions (Zi) ranging from 8–24 mm. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) ranged between 0.025mg/ml and 25.000mg/ml. The highest antibacterial activity was recorded against Micrococcus luteus NCIB 196 and Klebsiella pneumonia NCIB 418 (Zi = 24 mm), while the lowest activity was recorded against Proteus vulgaris (Zi = 8 mm). The GC/MS analysis revealed the presence of 30 chemical compounds, of which seven possess antibacterial properties. These include three oxygenated monoterpenes (α-terpineol, borneol, and fenchol), two sesquiterpenes (caryophyllene and δ-cadinene), one saturated fatty acid (palmitic acid) and monounsaturated fatty acid (oleic acids). Therefore, the results suggest the potential of P. sylvestris as an antimicrobial agent for incorporation in the treatment of pathogens.
4D Structural Root Architecture Modeling From Digital Twins By X-Ray Computed Tomography
Authors: Herrero Monica , Meline Valerian , Iyer-Pascuzzi Anjali S. , Souza Augusto M. , Tuinstra Mitchell R. , Yang Yang 
Published: June 2021

Abstract
BackgroundBreakthrough imaging technologies are a potential solution to address the plant phenotyping bottleneck regarding marker-assisted breeding and genetic mapping. X-Ray CT (computed tomography) technology is able to acquire the digital twin of root system architecture (RSA) but computational methods to quantify RSA traits and analyze their changes over time are limited. RSA traits extremely affect agricultural productivity. We develop a spatial-temporal root architectural modeling method based on 4D data from X-ray CT. This novel approach is optimized for high-throughput phenotyping considering the cost-effective time to process the data and the accuracy and robustness of the results. Significant root architectural traits, including root elongation rate, number, length, growth angle, height, diameter, branching map, and volume of axial and lateral roots are extracted from the model based on the digital twin. Our pipeline is divided into two major steps: (i) first, we compute the curve-skeleton based on a constrained Laplacian smoothing algorithm. This skeletal structure determines the registration of the roots over time; (ii) subsequently, the RSA is robustly modeled by a cylindrical fitting. The experiment was carried out at the Ag Alumni Seed Phenotyping Facility (AAPF) from Purdue University in West Lafayette (IN, USA). ResultsRoots from three samples of tomato plants at two different times and three samples of corn plants at three different times were scanned. Regarding the first step, the PCA analysis of the skeleton is able to accurately and robustly register temporal roots. From the second step, the volume from the cylindrical model was compared against the root digital twin, reaching a coefficient of determination (R2) of 0.84 and a P < 0.001. ConclusionsThe results confirm the feasibility of the proposed methodology, providing scalability to a comprehensive analysis to high throughput root phenotyping.
COVID-19 Potential To Infect 4.44% Indian Population
Authors: Patel Jayendrakumar , Parikh Shalin , Patel Rakesh , Patel Shwetaben , Patel Ronak , Patel Payalben , Patel Ankita 
Published: June 2021

Abstract
Background: Quantitative characterisation of any contagious diseases could help in making effective strategy to prevent further spreading of the disease. Despite the rapid research in prevention of spreading COVID-19, yet there is no quantitatively information about spatiotemporal epidemiology and epidemic intensity of COVID-19. Therefore, we aimed to quantitatively characterize spatiotemporal epidemiology and epidemic intensity of COVID-19 in Indian geography by determine it’s infectability rate, efficacy rate, transmission rate and likelihood of total populations to be infected with COVID-19 in India.Method: Novel statistical model was designed to quantitatively characterize spatiotemporal epidemiology and epidemic intensity of COVID-19. A Retrospective Cohort study was carried out online and offline in Indian geography using a COVID-19 transmission questionnaires sheet that comprises five mandatory questions. The collected offline as well as online data was then entered into a Microsoft excel sheet to obtain primary data and secondary data required for the mathematical model to calculate quantitative data of spatiotemporal epidemiology and epidemic intensity of COVID-19 in India geography.Result and Discussion: Total 539 responses were analysed in the current study out of 557 received responses between April-2021 to May-2021. Average reproductive number of secondary cases was found 0.77. Infectability rate of COIVD-19 patient was found 38.11% while healthy person has 21.08% risk of becoming infected if they expose to the Primary case. J-Index and H-Index were found 55.32% and 4.44%, respectively, indicating that COVID-19 disease outbreaks as severe epidemic disease in India and has potential to infect ~4.44% Indian population.Conclusion: Higher infectability rate (38.11%) of COIVD-19 patient and higher efficacy rate (21.08%) of healthy individual to be infected with COVID-19 outbreak it a severe epidemic in India. COVID-19 potential to infect about 4.44% Indian population, at present, COVID-19 already infected ~2.13% Indian population, which is about 50% of the anticipated population to be infected i.e., 4.44%.
Triglyceride-Glucose Index Mediates the Effect of General and Central Obesity on Cardiovascular Disease: A Prospective Cohort Study
Authors: Wang Anxin , Tian Xue , Zuo Yingting , Chen Shuohua , Meng Xia , Chen Pan , Wu Shouling , Wang Yongjun 
Published: June 2021

Abstract
Background: The mechanisms linking obesity to cardiovascular disease (CVD) are still not clearly defined. Individuals who are overweight or obese often develop insulin resistance, mediation of the association between obesity and CVD through the triglyceride-glucose (TyG) index (a simple surrogate of insulin resistance) seems plausible and has not been investigated. This study aimed to evaluate whether and to what extend the effect of general and central obesity is mediated by the TyG index.Methods: A total of 94,136 participants without CVD at baseline were recruited from the Kailuan study. The TyG index was calculated as ln [fasting triglyceride (mg/dL)×fasting glucose (mg/dL)/2]. Mediation analysis using a newly proposed 2-stage regression method for survival data was to explore the mediating effects of the TyG index on the association between obesity and CVD.Results: During a median follow-up of 13.01 years, we identified 7,327 cases of CVD. Mediation analyses showed that 45.60% of the total association (hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.18-1.31) between overweight and CVD was mediated through the TyG index (HR [indirect association], 1.10; 95% CI, 1.08-1.11), and the proportion mediated was 38.30% for general obesity. For central obesity, analysis by waist circumference, waist/hip, and waist/height categories yielded an attenuated proportion mediated of 33.76%, 37.10%, and 33.10% for obesity, taken normal weight as reference. Similar results were observed for stroke and myocardial infarction.Conclusions: This study found that the association between obesity and CVD was mediated by the TyG index, suggesting proper control of insulin resistance can be effective to significantly reduce the effects of general and central obesity on CVD.
On The Formulation of Bianchi Identity from Action Principle
Authors: Debnath Shiladittya 
Published: June 2021

Abstract
In this letter, we investigate the basic property of the Hilbert-Einstein action principle and its infinitesimal variation under suitable transformation of the metric tensor. We find that for the variation in action to be invariant, it must be a scalar so as to obey the principle of general covariance. From this invariant action principle, we eventually derive the Bianchi identity (where, both the 1st and 2nd forms are been dissolved) by using the Lie derivative and Palatini identity. Finally, from our derived Bianchi identity, splitting it into its components and performing cyclic summation over all the indices, we eventually can derive the covariant derivative of the Riemann curvature tensor. This very formulation was first introduced by S Weinberg in case of a collision less plasma and gravitating system. We derive the Bianchi identity from the action principle via this approach; and hence the name ‘Weinberg formulation of Bianchi identity’.
Impact of Inflammation on Atrial Fibrillation in patients with Metabolic Syndrome
Authors: Jani Ylber , Haxhirexha Kastriot , Baftiu Nehat , Pocesta Bekim , Rexhepi Atila , Xhunga Sotiraq , Serani Artur , Ferati Fatmir , Lala Dali , Zeqiri Agim , Kamberi Ahmet 
Published: June 2021

Abstract
BACKGROUND: Inflammation have been involved in the pathogenesis of both metabolic syndrome(MS) and atrial fibrillation(AF). The magnitude of elevations in plasma C-reactive protein(CRP) a marker of inflammation, is probably related to atrial structural remodeling and impaired atrial function.In patient with MS,limited data exist regarding impact of plasma levels of inflammatory markers,such as C-reactive protein on the: type of AF and atrial structural and functional remodeling. OBJECTIVE: We set to analyze the impact of degree of systemic inflammation (assessed acrording to CRP levels),on the type of AF,atrial functional and structural remodeling in patients with MS.METHODS: We conducted an multicenter observational cross-sectional study. Recruited were 425 consecutive participants,with MS and AF(paroxysmal, persistent and permanent AF),who attended outpatient visits at 7 general cardiology Health Care Clinics, during 1 calendar year,stratified according CRP-levels:(211 participans with level of CRP ≥3mg/l, and 214, with level of CRP <3mg/l). RESULTS: Permanent type of AF, was more common in participans with CRP-levels ≥3mg/l(54.6% vs.20.5%,p= 0.000),whereas parhoxysmal AF, was more common in participans with CRP-levels of <3 mg/l (9.9% vs.52.3%,p=0.000).Patients who had CRP levels above the cut-off of 3 mg/l,had increased dimension of left atrium{(LA),(4.2±0.3 vs. 3.7±0.2,p=0.000)},higher prevalence of enlargement of LA {defined as left atrial volum index(LAVI) ≥29ml/m2(84.1% vs.48.5%,p=0.002)} and inverse relationship of LA function(defined as left atrial emptying fraction(LAEF <45%, (30.8±3.4 vs.41.9±2.6, p=0.00). There was observed significant association of CRP levels above the cut-off of 3 mg/l and: frequence of persistent AF(OR=8.824,95% CI 1.689-46.100), permanent AF(OR=13.955, 95%CI 2.676 -72.780),increased LA dimension (OR=3.817,95% CI 0.989 -1.544), and decreased LA function.{(expressed by: LAVI >29ml/m2OR=4.014, 95% CI 2.620-6.152),LAEF <45%(OR=3.323,95%CI 2.062 -5.351) and LAVI>29 + LAEF-reduced (OR=3.354,95% CI 1.693 - 6.646)}.CONCLUSIONS: In patients with Metabolic Syndrome,degree of systemic inflammation have significant impact on clinical presentation of Atrial Fibrillation,atrial functional and structural remodeling .