bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment and Outcomes of Primary Urethral Cancer
Authors: yang shujun , Wang Shun , Zheng Duo , Ma Gui , Ying Yongsheng , Li Weiping , Shang Panfeng
Published: July 2021

Objective: To evaluate the clinical data, pathological types, treatment methods, and long-term outcome of 17 cases on Primary Urethral Cancer (PUC).Patients and Methods: We did a retrospective review of 17 patients diagnosed with PUC from January 2011 to December 2020 at four hospitals in Gansu Province.We stratified the patient concerning to their age, gender, histological type, stage, treatment modality and final follow-up, among which those at an early stage were defined as Tis-T2N0M0, while those at an advanced stage as T3-4. Then we analyzed the stratified samples based on clinical stage, treatment method, and outcome.Results: The majority of the 17 patients were female (F: M=13:4), And the number of cases at an early stage is roughly the same as those at an advanced stage (9:8). The most common histologic types were squamous cell carcinoma (35.3%) and urothelial carcinoma (35.3%), while adenocarcinoma (11.8%), malignant melanoma (11.8%), and small cell carcinoma (6.9%) accounted for a relatively small proportion. Surgery was a primary treatment modality for early cases, While for advanced cases, multimodal treatment was preferred.Conclusion: Survival rates are significantly lower in rare tumors than common tumors; besides, patients with early-stage PUC show better outcomes thanks to the single-mode therapy, whereas patients with advanced cancers need the most advanced multimode treatment to benefit patients as much as possible. However, due to the rarity of this malignancy, multi-agency experience provides the best evidence available.
The Seasonality, Steroid and the Lower Ratio of Neutrophil to Lymphocyte Associated With Listeriosis in Japan
Authors: Watanabe Yusuke , Nakamura Itaru , Miura Yuri , Watanabe Hidehiro
Published: July 2021

Background: Although listeriosis is a foodborne infection with a high mortality rate, studies of listeriosis from Asia are limited. We aimed to compare the characteristics of listeriosis and non-listeriosis (defined as bacteremia without Listeria monocytegenes infection) in Japan.Methods: We conducted a case–control study of adults with listeriosis or with bacteremia without L. monocytegenes infection from January 1, 2010, to December 31, 2019, at Tokyo Medical University Hospital in Japan. We recorded the incidence of admissions and the clinical characteristics, including age and sex; underlying disease; clinical symptoms; onset month; whether listeriosis was community-associated or health care–associated; medicine; blood count; biochemical findings; antibiotics use; admission to the intensive care unit; and outcome.Results: A total of 12 patients were included in the case group and 28 patients were included in the control group. Most cases of listeriosis were present in patients of an advanced age, with underlying disease, and/or on immunosuppressant therapy. Two patients died within 30 days and one developed a brain abscess. Listeriosis onset was associated with the warm season (90.9% vs. 53.8%; P = 0.033), steroid use (54.5% vs. 19.2%; P = 0.042), and a lower ratio of neutrophils to lymphocytes (9.46 vs. 18.44; P = 0.015).Conclusion: The incidence of listeriosis in this study was similar to that in other Asian countries and the 30-day mortality rate was 18.2%. We observed that listeriosis onset was associated with the warm season, steroid use, and a lower ratio of neutrophils to lymphocytes.
HULTIG-C: NLP Corpus and Services in the Cloud
Authors: Pais Sebastião , Cordeiro João , Jamil Muhammad
Published: July 2021

Nowadays, the use of language corpora for many purposes has increased significantly. General corpora exist for numerous languages, but research often needs more specialized corpora. The Web's rapid growth has significantly improved access to thousands of online documents, highly specialized texts and comparable texts on the same subject covering several languages in electronic form. However, research has continued to concentrate on corpus annotation instead of corpus creation tools. Consequently, many researchers create their own corpora, independently solve problems, and generate project-specific systems. The corpus construction is used for many NLP applications, including machine translation, information retrieval, and question-answering. This paper presents a new NLP Corpus and Services in the Cloud called HULTIG-C. HULTIG-C is characterized by various languages that include unique annotations such as keywords set, sentences set, named entity recognition set, and multiword set. Moreover, a framework incorporates the main components for license detection, language identification, boilerplate removal and document deduplication to process the HULTIG-C. Furthermore, this paper presents some potential issues related to constructing multilingual corpora from the Web.
Quantum-Chemical Study on the Relative Stability of Sildenafil Tautomers
Authors: Oziminski Wojciech Piotr , Wiśniewski Igor
Published: July 2021

The tautomeric equilibrium of Sildenafil molecule was theoretically studied using B3LYP and M06-2X Density Functional Theory (DFT) methods in connection with aug-cc-pVDZ correlation consistent basis set. Calculations were performed for gas phase and water solution conditions modelled by Polarizable Continuum Model (PCM). Three tautomeric forms are possible. Two keto forms: A – where the tautomeric proton in more distant from carbonyl group, B – where it is closer, and one enol form denoted C. Both DFT methods qualitatively give similar tautomer stability order: B>A>C. The B tautomer is dominant in gas phase and water environment, whereas the C tautomer is too high in energy to be present in the tautomeric mixture. Regarding the A tautomer, it is not present in the gas phase but is present in small amounts in water solution. According to B3LYP/ aug-cc-pVDZ the relative Gibbs free energies for A and C relative to B, are 10.05 kcal/mol and 11.91 kcal/mol for gas phase and 5.49 kcal/mol and 12.49 kcal/mol for water solution. According to M06-2X/aug-cc-pVDZ the relative Gibbs free energies for A and C are 9.12 kcal/mol and 10.60 kcal/mol for gas phase and 4.27 kcal/mol and 10.23 kcal/mol for water solution. Therefore, for in vivo conditions we expect that the B tautomer is dominant and there may exist small amounts of the A tautomer. The C enol tautomer is not present at all. This picture is very different from the parent tautomeric system: 4-hydroxypyrimidine/4-pyrimidinone where the C enol tautomer is less stable than keto B only by about 1 kcal/mol in the gas phase and the A keto tautomer is the least stable and not present in the tautomeric mixture. In order to understand these differences we performed additional calculations for series of parent molecules starting from 4-hydroxypyrimidine/4-pyrimidinone, going through two in-between model molecules and ending at Sildenafil molecule. We found that the most important reasons of C form destabilization are: dearomatization of the 6-membered ring caused by the fusion with pyrazole ring, lack of strong intramolecular hydrogen bond in C form of Sildenafill and presence of destabilizing steric interaction of oxygen and nitrogen atoms of two 6-memberd rings in this tautomer.
Decline in Iran’s River Flows
Authors: Maghrebi Mohsen , Noori Roohollah , Darougheh Farzaneh , Razmgir Rahman , Farnoush Hossein , Taherpour Hamid , Moghadam Seyed Mohammad Reza Alavai , Araghi Alireza , Haghighi Ali Torabi , Kløve Bjørn
Published: July 2021

This study examined changes in Iran’s river flows by applying regression and analysis of variance methods to long-term ground-truth data. Evaluations were performed for the country’s data-rich rivers, covering almost 97% of all rivers and including more than 35 years of measurements. The results showed that about 56% of Iran’s rivers have experienced a negative trend in mean annual flow that is approximately 2.5 times greater than that reported for world’s rivers, leading to a shift from perennial to intermittent for about 20% of rivers in Iran’s sub-basins. This reflects surface freshwater shortages in Iran caused by natural and, more importantly, anthropogenic disturbances. It may even indicate the development of new hydrological regimes which can have significant implications for future surface water storage in Iran. This research improves understanding of changes in Iran’s river flows and provides beneficial information for sustainable water resources management in the country.
Circulating microRNA-122 in HCV Cirrhotic Patients with High Frequency of Genotype 3
Authors: Ullah Amin , Yu Xiaojie , Odenthal Margarete , Meemboor Sonja , Ahmad Bashir , Rehman Irshad ur , Ahmad Jamshaid , Ali Qurban , Nadeem Tariq
Published: July 2021

MicroRNA-122 (miR-122) is a liver abundant microRNA that is released upon liver injury. In the present study, we investigated the circulating miR-122 profiles in a Pakistani patients´ cohort with HCV chronic liver disease that was mainly based on HCV genotype 3 infections.From 222 patients with chronic HCV liver disease, classified as mild, moderate, or gross, serum samples were collected. Cell-free RNA was isolated and used for miR-122 quantification by qPCR. More than 60% of 222 patients were infected with HCV genotype 3. ALT values and HCV viral load showed no correlation with the HCV genotype. Circulating miR-122 levels were significantly upregulated in patients with cirrhosis. Notably, HCV patients with mild cirrhosis showed the most marked increase in serum miR-122 levels (p=0.0001). Furthermore, we proved a positive correlation (r=0.46) of miR-122 with the ALT values in patients with mild cirrhosis. Importantly, the increased miR-122 profiles of serum samples obtained from patients with mild, moderate, and gross cirrhosis did not depend on the HCV genotype. Importantly, our findings confirm that serum miR-122 levels are significantly upregulated in the HCV cirrhotic patients serving in particular as a biomarker for the non-advanced stages of cirrhosis, independently of the HCV genotype.
Ranking the explanatory power of factors associated with worldwide new Covid-19 cases
Authors: Moustakas Aristides
Published: July 2021

Disease spread is a complex phenomenon requiring an interdisciplinary approach. Covid-19 exhibited a global spatial spread in a very short time frame resulting in a global pandemic. Data of new Covid-19 cases per million were analysed worldwide at the spatial scale of a country and time replicated from the end of December 2019 to late May 2020. Data driven analysis of epidemiological, economic, public health, and governmental intervention variables was performed in order to select the optimal variables in explaining new Covid-19 cases across all countries in time. Sequentially, hierarchical variance partitioning of the optimal variables was performed in order to quantify the independent contribution of each variable in the total variance of new Covid-19 cases per million. Results indicated that from the variables available new tests per thousand explained the vast majority of the total variance in new cases (51.6%) followed by the governmental stringency index (15.2%). Availability of hospital beds per 100k inhabitants explained 9% extreme poverty explained 8.8%, hand washing facilities 5.3%, the fraction of the population aged 65 or older explained 3.9%, and other disease prevalence (cardiovascular diseases plus diabetes) explained 2.9%. The percentage of smokers within the population explained 2.6% of the total variance, while population density explained 0.6%.
Study of The Diversity of 16S–23S rDNA Internal Transcribed Spacer (ITS) Typing of Escherichia Coli Strains Isolated From Various Biotopes in Tunisia
Authors: Badi Souhir , Ammeri Rim , Abbassi Mohamed , Snousssi Mejdi , Cremosini Paola , Luini Mario , Castiglioni Bianca , Hassen Abdennaceur
Published: July 2021

We investigated the 16 S-23S rRNA intergenic spacer region (ISR)-PCR and the phylogenetic PCR analyzes of 150 Escherichia coli isolates as tools to explore their diversity, according to their sampling origins, and their relative dominance in these sampling sources. So, these genetic markers are used to explore phylogenetic and genetic relationships of these 150 E. coli isolates recovered from different environmental sources (water, food, animal, human and vegetables). These isolates are tested for their biochemical pattern and later genotyped through the 16S–23S rRNA intergenic spacer PCR amplification and their polymorphism investigation of PCR-amplified 16S-23S rDNA ITS. The main results of the pattern band profile revealed one to 4 DNA fragments. Distributing 150 E. coli isolates according to their ITS and by using RS-PCR, revealed 4 genotypes and 4 subtypes. The DNA fragment size ranged from 450 to 550 bp. DNA band patterns analysis revealed considerable genetic diversity in interspecies. Thus, the 450 and 550 bp size of the common bands in all E. coli isolates are highly diversified. Genotype I appeared as the most frequent with 77.3% (116 isolates), genotype II with 12% (18 isolates); genotype III with 9.7% (14 isolates), and the IV rarely occurred with 4% (2 isolates). Distributing the E. coli phylogroups showed 84 isolates (56%) of group A, 35 isolates (23.3%) of group B1, 28 isolates (18.7%) of group B2 and only 3 isolates (2%) of group D.
Clinical Characteristics, Serum Uric Acid and Bullosis Diabeticorum Outcomes in Patients With Diabetes Mellitus
Authors: Cai Yulan , Zhang Shili , Cao Ying , Gao Fang , Zou Mengchen
Published: July 2021

Background: Bullosis diabeticorum (BD) is a spontaneous, non-inflammatory vesicular disease of diabetes, with the observed risk of infection, including diabetic skin ulcers, osteomyelitis and even leading to amputation. However, the exact cause of BD is not well understood. So the aim of this study is to explore the high-risk factors of BD for preventing its occurrence.Methods: A retrospective study was conducted, including baseline characteristics, laboratory data, and bullosis diabeticorum outcomes of 602 patients with bullosis diabeticorum. Besides, 904 diabetic patients without bullosis diabeticorum in the same period were randomly selected as the control group. The indicators of the two groups were compared. Multivariable logistic regression analysis was performed to investigate which indicator was most associated with bullosis diabeticorum outcomes.Results: SCr[145.00(69.00-195.00) μmol/L, n = 602 vs. 81.00(27.40-35.60) μmol/L, n= 904, p=0.032], BUA [674.00(372.50-758.50) µmol/L, n = 602 vs. 318.50(241.75-415.25) µmol/L, n= 904, p = 0.003] and Cys-C[1.96(1.10-2.95) mg/L, n = 602 vs. 1.49(1.10-1.62) mg/L, n = 904, p=0.004] was significantly higher in BD-positive patients than that in BD-negative patients, whereas eGFR [67.38(45.33-87.53) ml/min, n = 602 vs. 75.86(56.80-95.69) ml/min, n = 904, p=0.038] of patients with BD was significantly lower than that of patients without BD. Multiple logistic regression analysis showed that BUA, but not SCr, Cys-C and eGFR, was independently and significantly associated in a positive manner with BD (odds ratio: 8.569, 95% confidence interval: 1.136-55.250, p=0.004).Conclusion: We found a positive and independent association of BUA with BD, which provides a great clinical predictive factor for BD and helps to prevent the appearance of diabetic foot.
Predictors of Mortality among TB-HIV Co-Infected Children Attending Anti-Retroviral Therapy Clinics of Selected Public Hospitals in Southern, Ethiopia: Retrospective Cohort Study
Authors: Gemechu Jifare , Gebremichael Bereket , Tesfaye Tewodros , Seyum Alula , Erkalo Desta
Published: July 2021

Background: Co-infection of tuberculosis and HIV has a significant impact on public health. TB is the most common opportunistic infection and the leading cause of death in HIV-positive children worldwide. But there is paucity of studies concerning the predictors of mortality among TB-HIV co-infected children. This study aimed to determine the predictors of mortality among TB-HIV co-infected children attending ART clinics of public hospitals in Southern Nation, Nationalities and Peoples Region (SNNPR), Ethiopia. Methods: A hospital-based retrospective cohort study design was used among 284 TB-HIV co-infected children attending ART clinics at selected public hospitals in SNNPR, Ethiopia, from January 2009 to December 2019. Then, medical records of children who were TB/HIV co-infected and on ART were reviewed using a structured data extraction tool. Data were entered using Epidata 4.6 and analyzed using SPSS version 23. The Kaplan Meier survival curve along with log rank tests was used to estimate and compare survival time. Bivariable and multivariable analyses were conducted to identify predictors of mortality among TB/HIV co-infected children. Adjusted Hazard Ratio with p value < 0.05 and 95 % confidence interval was considered statistically significant.Result: A total of 284 TB/HIV co-infected children were included in the study. Among these, 35 (12.3%) of them died during the study period. The overall mortality rate was 2.78 (95%CI= 1.98-3.99) per 100 child years of observation. The predictors of mortality were anemia (AHR=3.6; 95%CI: 1.39-9.31), fair or poor ART drug adherence (AHR=2.9; 95%CI=1.15-7.43), extra pulmonary TB (AHR=3.9; 95%CI: 1.34-11.45) and TB drug resistance (AHR=5.7; 95%CI: 2.07-15.96). Conclusion: Mortality rate of TB/HIV co-infected children in selected public hospitals in SNNPR, Ethiopia was documented as 2.78 per child years of observation as a result of this study. Moreover, Anemia, drug resistant tuberculosis, extra pulmonary TB and poor adherence to ART drugs were identified as the predictors of mortality among these children.
Modular-Level Alterations of Single-Subject Gray Matter Networks in Schizophrenia
Authors: Xiang Jie , Ma Yunxiao , Wang Gongshu , Li Dandan , Wang Tong , Wang Bin , Yan TianYi
Published: July 2021

Schizophrenia is often regarded as a psychiatric disorder caused by disrupted connections in the brain. Evidence suggests that the gray matter of schizophrenia patients is damaged in a modular pattern. Recently, abnormal topological organization was observed in the gray matter networks of patients with schizophrenia. However, the modular-level alteration of gray matter networks in schizophrenia remains unclear. In this study, single-subject gray matter networks were constructed for a total of 217 subjects (116 patients with schizophrenia and 101 controls). We analyzed the topological characteristics of the brain network and the strengths of connections between and within modules. Compared with the outcomes in the control group, the global efficiency and participation coefficient values of the single-subject gray matter networks in schizophrenic patients were significantly reduced. The nodal participation coefficient of the regions involving the FPN, DMN and SCN were significantly decreased in subjects with schizophrenia. The intermodule connections between the FPN and VIS and between the DMN and SCN, in the FPN were significantly reduced in the patient group. In the FPN, the intramodule nodal connection strength of the left orbital inferior frontal gyrus and right inferior parietal gyrus was significantly decreased in schizophrenia patients. Reduced intermodule nodal connection strength between the FPN and VIS was associated with the severity of schizophrenia symptoms. These findings suggest that abnormal intramodule and intermodule connections in the structural brain network may a biomarker of schizophrenia symptoms.
Prognostic Value of Neutrophil-to-Lymphocyte Ratio in Patients With Sepsis
Authors: Liao Xinyu , Li Fuxing , Wang Fuke , Wang Guoliang , Zheng Yaxing , Zhong Ruiying , He Lu
Published: July 2021

Objective: We attempt to evaluate the role of neutrophil-to-lymphocyte ratio (NLR) in predicting 28-day mortality in patients with sepsis to investigate its prognostic value.Method: Relevant clinical and laboratory data of 91 healthy controls, 87 non-septic patients admitted to intensive care unit (ICU) and 127 septic patients on admission were collected, and septic patients were divided into survival (n=79) and death groups (n=48) according to their prognoses. NLR levels among different groups were compared and analyzed for associations with C-reactive protein (CRP), procalcitonin (PCT) and SOFA score. Univariate logistic regression analysis was used to assess the prognostic value of the NLR in patients with sepsis. Result: The NLR level was significantly higher in the septic patients compared to the case controls and healthy individuals (P < 0.05), and was much higher in septic patients who died (P < 0.05). ROC analysis indicated that the NLR had the best prognostic value for sepsis, with an AUC of 0.77 (95% CI: 0.69-0.84). Univariate logistic regression analysis suggested that NLR >8.25 was an independent risk factor for sepsis (odds ratio [OR] 6.39, P = 0.001). Correlation analysis suggested that the NLR was positively correlated with CRP, PCT and SOFA score.Conclusion: Peripheral serum NLR appeares to have a predictive value for 28-day mortality in patients with sepsis.
Diagnostic Accuracy and Appropriate Cut Off Value of Risk of Malignancy Index in Preoperative Discrimination Between Malignant and Benign Ovarian Tumors: Prospective Cross-sectional Study
Authors: Dabi bezza Kedida , Disasa Fanta Asefa , Olika Ayantu Kebede
Published: July 2021

BackgroundRisk of malignancy index (RMI) is scoring system which was introduced to differentiate between benign and malignant ovarian tumor. It incorporates CA-125, ultrasound score and menopausal status for prediction of ovarian malignancies in preoperative period. There is no universal screening method to discriminate between benign and malignant adnexal masses yet. So, this study was conducted to determine the diagnostic accuracy of RMI and determine best cut off value for RMI.MethodsProspective cross-sectional study was carried out among women with ovarian mass admitted to Gynecology ward and operated from September 1, 2019 to June 30, 2020.Data analysis was carried out using SPSS version 26. CA-125 level, menopausal status and ultrasound score were used to calculate RMI. Finally, RMI score was compared to histopathology result used as gold standard.ResultsNinity nine patients were enrolled in this study. Prevalence of benign ovarian tumors were 61.6% (61/99) and that of malignant ovarian tumors were 38.4% (38/99). The mean age for benign tumors was 30±9yrs and the mean age for malignant tumors was 50.6±10.8yrs. Among benign tumors, serous cystadenoma was the most common (36%), followed by dermoid cyst (32.9%), mucinous cyst adenoma (14.8%). The most common malignant ovarian tumor was serous cyst adenocarcinoma (63.2%), followed by mucinous cystadenocarcinoma (23.8%) and dysgerminoma (5.3%). Overall, using RMI score cut off value 220 has good sensitivity (84.2%), specificity (77%), PPV (69.5%), NPV (88.7%) and diagnostic accuracy (79.8%) for discriminating between benign and malignant ovarian tumors.ConclusionFrom this study there were high proportion of women with RMI>=220 in malignant ovarian tumors group. The study shows that there is significant role of RMI in prediction of ovarian malignancy thus helping in deciding which patients need referral to a center where gynecologic oncologists are available. It is good practice to use it in developing countries including our country because of its simplicity, safety and applicability in initial evaluations of patients with adnexal mass.
Risk Factors for Pelvic Lymph Node Metastasis and Recurrence in Patients Undergoing Radical Hysterectomy for Cervical Cancer
Authors: Wang Xinmei , Zhang Hongyuan , Xu Juan , Qu Pengpeng
Published: July 2021

Background: Radical hysterectomy and bilateral pelvic lymphadenectomy are standard treatments for early-stage cervical cancer. Pelvic lymph node metastasis (PLNM) is one of the critical factors affecting the postoperative prognosis of patients. Therefore, the identification of preoperative risk factors for PLNM will minimize its occurrence and improve prognosis. The purpose of this study was to investigate the risk factors for PLNM and its recurrence in patients undergoing radical hysterectomy for cervical cancer.Methods: Medical records of 245 patients who underwent radical hysterectomy and bilateral pelvic lymphadenectomy as primary treatment for the International Federation of Gynaecology and Obstetrics (FIGO) stage IA-IIA cervical cancer between January 2010 and December 2015 at our hospital were reviewed. Age, FIGO stage, preoperative hemoglobin level, depth of stromal invasion, lymphovascular space invasion (LVSI), human papillomavirus(HPV) infection, parametrial infiltration, tumor diameter, number of lymphadenectomies, and pathological type were retrospectively analyzed. All patients were followed up for 5–10 years.Results: Among the 245 patients, 185 (75.51%) had no PLNM, whereas 60 (24.49%) had PLNM. Preoperative hemoglobin level, FIGO stage, LVSI, parametrial infiltration, and tumor diameter differed significantly between the two groups (P<0.05). Multivariate analysis revealed preoperative hemoglobin <110 g/L, FIGO stage II, LVSI, parametrial infiltration, and tumor diameter ≥4 cm as significant risk factors for PLNM and recurrence of cervical cancer after surgery (P<0.05). PLNM was identified as the independent risk factor for recurrence in patients with cervical cancer after surgery (P<0.05).Conclusions: PLNM is an important prognostic indicator for the clinical treatment of cervical cancer. Patients at a high risk of recurrence, especially PLNM patients, should be followed up closely after surgery to ensure the timely detection of recurrence and treatment.
Fate of Antibiotic Resistance Genes in Abandoned Swine Feedlots in China: Seasonal Variation
Authors: Li Na , Chen Jianguo , Liu Chong , Li Binxu , Zhu Changxiong , Li Hongna
Published: July 2021

Background: Environmental hygiene concerns are needed to be settled before the reuse of abandoned swine feedlot sites. However, few researchers have focused on the fate of antibiotic resistance genes (ARGs) in soil microbiota around abandoned swine feedlots. In this study, we examined the seasonal alterations of ARGs and bacterial community composition in soil using quantitative PCR and high-throughput sequencing of 16S rRNA gene. Results: The seasonal variation patterns were different for different ARG subtypes and soil sampling sites. The bacterial community composition at the genus level generally showed no significant alteration from winter to summer. Moreover, the co-occurrence network suggested that the bacterial genera host range of ARGs was broader in the summer than in the winter. Conclusion: This study offers further data on ARG transfer risk in soil, emphasizing the necessity of continuous concern before reuse of abandoned feedlots.
Net Zero 2050 As An Eu Priroty – Modeling a System for Efficient Investment in Eco Innovation for Climate Change Mitigation
Authors: Jesic Jelena , Okanovic Andrea , Panic Andrea Andrejevic
Published: July 2021

Background: Study background is based on the fact that the EU recovery plan envisages investing 30% of the huge budget in climate change, with the goal of zero gas emission by 2050. This ambitious plan will require (for now indefinitely) investment in research and innovation. The main objective of the study is to check and analyze the existing and propose a new model of effective investment in eco-innovation, on the basis of which a contribution to effective long-term investment policy, climate change impact and mitigation of consequences will be given. Methods:. The basic methodological tools for solution of the problems discussed in this study were correlation analysis, regression analysis and pared sample t-test. All calculations were performed in the statistical software SPSS 20. Time series data of the selected indicators were obtained from the European Innovation Scoreboard 2020. Database used to collect the data for EU member countries and selected third countries for the conducted analysis is the European Innovation Scoreboard 2020. To avoid sample selection bias, we considered all of the available data for all member countries and selected third countries in European Innovation Scoreboard 2020 for period 2012 to 2019.Results: Results of the study are showing the path which developing countries should direct their inevitable and increasing eco-innovation investments, taking into account the arguments of structural differences in financing R&D. According to European Eco-innovation Scoreboard the best eco-innovation performers are Luxembourg, Denmark, Finland, Sweden and Austria. While countries catching up with eco-innovations are Lithuania, Greece, Estonia, Malta, Croatia, Slovakia, Poland, Romania, Cyprus, Hungary, Bulgaria. Conclusions: Study conclusions are summarized as proposal of appropriate approach of R&D financing model to developing countries with a greater share of eco-innovation and self-sustainable R&D financing for climate preserving products. This study is important as it provides the new evidence on financing R&D investments in leading and developing countries according to Innovation Scoreboards.
Discovery of Endophytic Strains With Excellent Antagonism to Colletotrichum Scovillei in Sweet Pepper and Study on Their Biological Functions
Authors: Wei Lijuan , Yang Chengde , Cui Lingxiao , Jin Mengjun , Osei Richard
Published: July 2021

Anthracnose caused by Colletotrichum spp. is a well-known disease that causes severe losses in pepper production which is used as a spice for thousands of households in many parts of China. With the biological control properties of endophytic strains have been developed and used have been of great importance in the prevention and control of anthracnose and environmental protection. Therefore, to control the pathogen Colletotrichum scovillei more safely, 58 endophytic strains were isolated from pepper leaves in this experiment. Plate resistance method was used to screen the antagonistic strains of C. scovillei, and it was found that the inhibition rate of 25 antagonistic strains against C. scovillei was greater than 60%, and the inhibitory rates of L1-7 and L3-5 against it were 79% and 80%, respectively. They were identified as Bacillus amyloliquefaciens and Bacillus velezensis by culture and morphological identification, combined with 16S rDNA and gyrB gene sequence analysis. The two antagonistic endophytic bacteria also had the ability to fix nitrogen and secrete IAA, and all had high salt tolerance. Controlled pot experiments in the laboratory showed that L1-7 and L3-5 had a good control effect against C. scovillei, with the control efficiency reaching 80.64% and 73.39%, respectively. Thus, B. amyloliquefaciens (L1-7) and B. velezensis (L3-5) could be useful as biological control agents to protect peppers from anthracnose disease caused by C. scovillei. The results of this test provide a basis for the development of pepper endophytic bacterial resources, and also bacterial resources for the biological control of C. scovillei.
Smad3 Regulates Smooth Muscle Cell Fate and Governs Adverse Remodeling and Calcification of Atherosclerotic Plaque
Authors: Cheng Paul , Wirka Robert , Kim Juyong , Nguyen Trieu , Kundu Ramendra , Zhao Quanyi , Sharma Disha , Pedroza Albert , Nagao Manabu , Iyer Dharini , Fischbein Michael , Quertermous Thomas
Published: July 2021

Atherosclerotic plaques consist mostly of smooth muscle cells (SMC), and genes that influence SMC biology can modulate coronary artery disease (CAD) risk. Allelic variation at 15q22.33 has been identified by genome-wide association studies to modify the risk of CAD, and is associated with expression of SMAD3 in SMC, but the mechanism by which this gene modifies CAD risk remains poorly understood. SMC-specific deletion of Smad3 in a murine atherosclerosis model resulted in greater plaque burden, more positive remodeling, and increased vascular calcification. Single-cell transcriptomic analyses revealed that loss of Smad3 altered SMC transition cell state toward two fates: a novel SMC phenotype that governs both vascular remodeling and recruitment of inflammatory cells, as well as a chondromyocyte fate. The remodeling population was marked by uniquely high Mmp3 and Cxcl12 expression, and its appearance correlated with higher risk plaque features such as increased positive remodeling and macrophage content. Further, investigation of transcriptional mechanisms by which Smad3 alters SMC cell fate revealed novel roles for Hox and Sox transcription factors whose direct interaction with Smad3 regulate an extensive transcriptional program balancing remodeling and vascular extracellular matrix with significant implications for atherosclerotic and Mendelian aortic aneurysmal diseases. Together, these data suggest that Smad3 expression in SMC inhibits the emergence of specific SMC phenotypic transition cells that mediate adverse plaque features, including positive remodeling, monocyte recruitment, and vascular calcification.
Non-high-density Lipoprotein Cholesterol May Predict the Cardio-cerebrovascular Risk in Patients on Maintenance Hemodialysis
Authors: Luo Denggui , Luo Yueming , Zou Yanhong , Xu Yuanzhao , Fu Bo , Yang Dong , Yang Jun , Xu Cai , Ling Shuyi , Li Shunmin , Qi Airong
Published: July 2021

BackgroundNon-high-density lipoprotein cholesterol (non-HDL-C) may be an independent risk factor for cardio-cerebrovascular disease (CVD); however, the cutoff level in patients on maintenance hemodialysis (MHD) is unknown. MethodsWe performed a multicenter retrospective study of MHD patients treated at 10 dialysis centers in Guangdong Province from July 1, 2016, to April 1, 2017. We collected laboratory test data and recorded CVD complications and outcomes. ResultsA total of 1,288 patients were enrolled; the non-HDL-C interquartile range was 2.76 (2.24–3.45) mmol/L. Over a median follow-up time of 23 months, 142 patients developed CVD. The non-HDL-C level was a principal risk factor for such events (P < 0.05; area under the curve 0.822, 95% confidence interval 0.800–0.842). The maximum Youden index was 0.549 and the best cutoff > 3.39 mmol/L. ConclusionHigher baseline non-HDL-C levels are associated with an increased risk of CVD in MHD patients. Thus, non-HDL-C effectively predicts CVD.
Increasing SOC sequestration and closing N cycle during post-agricultural restoration in karst region, Southwest China
Authors: Liu Man , Han Guilin , Zhang Qian
Published: July 2021

Purpose

Post-agricultural restoration affects soil organic carbon (SOC) sequestration and ecosystem nitrogen (N) cycle. However, the control mechanism of SOC sequestration and alteration of ecosystem N status following post-agricultural restoration are not well understood in karst regions.
Methods

Croplands, abandoned croplands, and native vegetation forests were selected to represent three stages following post-agricultural restoration using a space for time substitution approach in a karst critical zone in Guizhou province, Southwest China. The variations of soil aggregate associated SOC and relationships between soil Ca and SOC were analyzed to identify SOC sequestration potential. Foliar δ15N composition and soil to plant 15N enrichment factor (EF = δ15Nlitter − δ15Nsoil) were analyzed to determine ecosystem N status.
Results

Macro-aggregate proportions and their SOC concentrations significantly increased following post-agricultural restoration. Soil Ca concentrations non-linearly increased with increasing SOC concentrations of bulk soils and aggregates. Foliar δ15N values and EF values significantly decreased following post-agricultural restoration, mainly attributed to the increasing plant uptake of 15N-depleted inorganic N, which was produced from soil organic nitrogen (SON) mineralization and nitrification. During post-agricultural restoration, the increasing plant biomass and slow SON mineralization led to more inorganic N uptake and less N loss, i.e., a more closed N cycle.
Conclusion

Soil aggregates and Ca play important roles in promoting SOC sequestration, and ecosystem N cycles are towards closed during post-agricultural restoration in the karst ecosystem.
Validity of Resting Strain/strain Rate in Prediction of Myocardial Viability
Authors: Hanafy Amr , Ibrahim Soliman Ghareb , Mansour Hossam Eldein Mohamed Mohamed , Soliman Aml Mohamed , Salama Mohamed Kamal
Published: July 2021

PurposeTo evaluate the validity of the resting strain/strain rate measurements in predicting myocardial viability taking delayed enhancement cardiac magnetic resonance imaging as the gold standard. Methods: A cohort of 60 patients at three months followed up after acute myocardial infarction were recruited for this study. Resting echocardiography with offline analysis of deformation indices and gadolinium contrast enhanced cardiac magnetic resonance imaging were applied for all patients. ResultsFor the final assessment, 268 segments with significant resting wall motion abnormalities were presented. Resting longitudinal strain was significantly (p<0.05) higher in viable, compared with non-viable segments in all the studied individual myocardial segments (apical inferior, mid antro-lateral, mid-inferolateral, mid infero-septum, and all other segments). Likewise, resting longitudinal strain rate was significantly (p<0.05) higher in viable, compared with non-viable segments in almost all studied individual myocardial segments apart from apical inferior, mid inferolateral and basal antro-septum (p=0.245, p=0.098, p=0.097 respectively). ConclusionResting Strain and Resting Strain rate could be used as accurate predictors of myocardia viability following acute myocardial infarction.
Mesenchymal Stem Cell Secretome Ameliorates Hyperalgesia in a Post-operative Pain Model
Authors: Maoudis Chrysostomos Constantine , McKinnirey Flyn , Vesey Graham , Blaber Sinead , Hutchinson Mark
Published: July 2021

BackgroundThe treatment and management of post-operative pain remain a significant challenge. There is a significant unmet need that requires novel therapeutics. The aim of this study was to investigate the effects of the mesenchymal stem cell secretome (MSC-S) in a rat incisional post-operative pain model. MethodsA post-operative pain model in rats was used to assess the human adipose-derived MSC-S therapeutic benefits. Male Sprague Dawley (SD) rats (n=40) underwent surgery whereby a 1 cm longitudinal incision was made over the plantar surface of the right hind paw where the plantaris muscle was incised longitudinally. The incision was closed with two stitches. At 1-hour post-surgery, test and control articles were administered topically for 15 minutes to the incision site. Von Frey and hotplate testing were conducted to assess mechanical and thermal pain responses, respectively. Statistical analysis of thermal and mechanical withdrawal thresholds was undertaken using an ordinary 2-way analysis of variance (ANOVA) utilising uncorrected Fishers LSD test with individual variances computed for each comparison.ResultsA statistically significant increase in thermal nociceptive threshold (analgesia) was observed in the high dose MSC-S group when compared to vehicle at 1.5 hours (p<0.0001) and 3 hours post-surgery (p<0.0001). High dose MSC-S had a more potent analgesic effect than low dose MSC-S. A statistically higher analgesic effect was observed in the high dose MSC-S group compared to morphine at the 3 hours post-surgery hot plate assessment (p<0.002). Morphine (10mg/kg) administration resulted in a significant increase in hot plate withdrawal threshold compared to vehicle at 1.5 hours (p<0.0001) and 3hours (p<0.008) post-surgery. Animals that received morphine displayed significantly less allodynia than vehicle control animals at 1.5 hours post-surgery (p<0.0001).ConclusionsThe present study demonstrated that the MSC-S topically administered in a rat post-operative pain model significantly improved thermal nociceptive thresholds. The MSC-S has potential as a non-opioid based therapy for the treatment of acute post-operative pain.
Comparison of Accuracy of Intraocular Lens Power calculation for Eyes with an Axial Length Greater Than 29.0 mm
Authors: Guo Chengyao , Yin Shengjie , Qiu Kunliang , Zhang Mingzhi
Published: July 2021

PurposeTo evaluate and compare the accuracy of six different formulas (EVO 2.0, Kane, SRK/T, Barrett Universal II, Haigis and Olsen) in intraocular lens (IOL) power calculation for extremely long eyes.MethodsRetrospective case-series. 73 eyes with axial length (AL) ≥ 29.0 mm and 920H IOL implantation were included. Prediction errors (PE) were calculated and compared between different formulas. Multiple regression analysis was performed to investigate factors associated with the PE.ResultsThe Kane formula had mean prediction error close to zero (-0.01 D, P = 0.841), whereas the EVO 2.0, SRK/T, Barrett Universal II, Haigis and Olsen formulas produced hyperopic outcomes (all P < 0.001). The median absolute error produced by the EVO 2.0, Kane, Barrett Universal II and Olsen formulas showed no significant difference (0.33 D, 0.30 D, 0.29 D, 0.34 D, respectively, pairwise comparison P > 0.05), but was significantly lower than that of the SRK/T and Haigis formulas (0.85 D, 0.80 D, respectively, pairwise comparison P＜ 0.001). The accuracy of the SRK/T formula in extremely myopic eyes was affected by the AL, suggesting that a longer AL was always associated with a hyperopic surprise and a shorter AL was always associated with a myopic surprise, whereas the accuracy of other formulas was less affected by the AL.Conclusions﻿For cataract patients with axial length greater than 29.0 mm, the accuracy of the EVO 2.0, Kane, Barrett Universal II and Olsen formulas is comparable and significantly better than that of the SRK/T and Haigis formulas.
Dasabuvir Suppresses Esophageal Squamous Cell Carcinoma Growth As a Novel ROCK1 Inhibitor
Authors: Liu Xinning , Jiang Yanan , Zhou Hao , Li Mingzhu , Bao Zhuo , Wang Zitong , Zhang Chenyang , Xie Zhenliang , Zhao Jimin , Dong Zigang , Guo Zhiping , Liu Kangdong
Published: July 2021

Background: Esophageal squamous cell carcinoma (ESCC) is a high recurrence rate of upper-digestive cancer with a low 5-year survival rate. Therefore, there is an urgent need for effective chemopreventive drugs that can extend the survival rate of patients. Through screening of FDA-approved drugs, dasabuvir was found to suppress ESCC proliferation. Methods: Cell number count assay was used to screen for drugs with inhibitory effect on ESCC cells and detect the inhibitory effect of dasabuvir on proliferation of ESCC cells KYSE150 and KYE450. Phosphoproteomics and proteomics were used to investigate the mechanism of dasabuvir inhibiting ESCC. In vitro kinase assay was used to verify the inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) activation by ROCK1 by dasabuvir. The PDX model was used to test the inhibitory effect of dasabuvir on ESCC in vivo.Results: In this study, we found that dasabuvir is a novel inhibitor of Rho-associated protein kinase 1 (ROCK1). Dasabuvir inhibited the growth of the KYSE150 and KYSE450 ESCC cell lines in a time and dose-dependent manner and arrested cell cycle at the G0/G1 phase. The antitumor activity was validated in vivo using a patient-derived xenograft tumor model in mice. Dasabuvir inhibited the activation of ERK1/2 by ROCK1 and downregulated cyclin-dependent kinase 4 (CDK4) and cyclin D1 expression. Conclusions: These results provide the first evidence that dasabuvir serves as a ROCK1 inhibitor, suppresses ESCC growth in vivo and in vitro, and arrests the cell cycle through the ROCK1/ERK signaling pathway.
Response to first line chemotherapy regimen is associated with efficacy of Immune Checkpoint Blockade Therapies in Patients with Metastatic Urothelial Carcinoma
Authors: Tural Deniz , Selçukbiricik Fatih , Ölmez Ömer Fatih , Sümbül Ahmet Taner , Erman Mustafa , Coşkun Hasan Şenol , Artaç Mehmet , Kılıçkap Saadettin
Published: July 2021

Background
Atezolizumab (ATZ) has demonstrated antitumor activity in the previous studies in patients with metastatic platinum-resistant urothelial carcinoma. However, the response rate of ATZ was modest. Therefore, finding biologic or clinical biomarkers that could help to select patients who respond to the immune checkpoint blockade remains important.
Patients and Methods
In this study, we present the retrospective analysis of 105 patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy. Data of patients were obtained from patient files and hospital records. The association between response to first-line chemotherapy and ATZ was using Fisher’s exact test. Median follow-up was calculated using the reverse Kaplan-Meier method. OS was estimated by using the Kaplan-Meier method.
Results
The median follow-up time was 23.5 months. Forty (74.1%) of patients who experienced clinical benefit after firs-line chemotherapy also had clinical benefit after atezolizumab, while only 14 (25.9%) of patients with initial PD after first-line chemotherapy subsequently experience clinical benefit with ATZ (p = 0.001). The median OS on ATZ of 14.8 and 3.4 months for patients with clinical benefit and progressive disease in response to first-line chemotherapy, respectively (p = 0.001). Three of the adverse prognostic factors according to the Bellmunt criteria were independent factors of short survival: liver metastases (Hazard Ratio [HR] = 1.9; p = 0.04), ECOG PS ≥ 1 (HR = 2.7; p = 0.001), and Hemoglobin level below 10 mg/dl (HR = 2.8; p < 0.001). In addition, patients with clinical benefit from first-line chemotherapy (HR = 0.39; p < 0.001) maintained a significant association with OS in multivariate analysis.
Conclusions
Our study demonstrated that clinical benefit from first-line chemotherapy was independent prognostic factors on OS in patients' use of ATZ as second-line treatment in metastatic bladder cancer. Furthermore, these findings are important for stratification factors for future immunotherapy study design in patients with bladder cancer who have progressed after first-line chemotherapy
Surface Roughness Effect on Fatigue Strength of Aluminum Alloy Using Revised Stress Field Intensity Approach
Authors: Zhao Bingfeng , Song Jiaxin , Xie Liyang , Hu Zhiyong , Chen Jianpeng
Published: July 2021

The fatigue strength of component is known to highly depend on its surface quality and it is very necessary to develop a reliable appropriate mathematical model for fatigue strength assessment considering the effect of surface roughness. In this paper, different underlying physical mechanisms of roughness effect at different regions of specimen were studied by the fatigue test of 7N01 aluminium alloy. For quantitative analysis of the surface roughness effect, a revised stress field intensity approach for fatigue strength assessment of micro-size notch was proposed as the theoretical support. In the new model, a new form of weight function was built to adapt the characteristics of micro-size notch. In addition, the effect of the field radius is weakened fundamentally on solution of the stress field intensity and the difficulty of fatigue failure region definition in traditional method is overcome correspondingly in the proposed model, which makes the calculated field strength accurate and objective. Finally, to demonstrate the validity of the revised approach quantitatively, specimens with notches in conventional size have been subjected to stress field intensity calculation. The results show that the revised approach has a satisfactory accuracy compared with the other two traditional approaches from the perspective of quantitative analysis.