bluuebunny/crossref_metadata_2025 huggingface dataset:
Spreading of Tau Protein Does Not Depend on Aggregation Propensity
Authors: Rodrigues Sara , Anglada-Huguet Marta , Hochgräfe Katja , Kaniyappan Senthilvelrajan , Wegmann Susanne , Mandelkow Eva-Maria
Published: March 2021

Background: The stereotypical progression of Tau pathology during Alzheimer disease has been attributed to trans-neuronal spreading of misfolded Tau proteins, followed by prion-like templated aggregation of Tau. The nature of Tau and the cellular mechanisms of Tau spreading are still under debate. We hypothesized that Tau's propensity for aggregation would correlate with its ability to spread across synapses and propagate pathology.Methods: To study the progressive propagation of Tau proteins in brain regions relevant for Alzheimer disease, we used mice expressing near-physiological levels of full-length human Tau protein carrying pro-aggregant (TauΔK280, TauΔK) or anti-aggregant (TauΔK280-PP, TauΔK-PP) mutations in the entorhinal cortex (EC). To enhance Tau expression in the EC, we performed EC injections of adeno-associated virus (AAV) particles encoding TauΔK or TauΔK-PP. The brains of injected and non-injected EC/TauΔK and EC/TauΔK-PP mice were studied by immunohistological and biochemical techniques to detect Tau propagation to dentate gyrus (DG) neurons and Tau-induced pathological changes.Results: Pro- and anti-aggregant mice had comparable low transgene expression (~0.2-times endogenous mouse Tau). They accumulated human Tau at similar rates and only in expressing EC neurons, including their axonal projections of the perforant path and presynaptic terminals in the molecular layer of the DG. Pro-aggregant EC/TauΔK mice showed misfolded Tau and synaptic protein alterations in EC neurons, not observed in anti-aggregant EC/TauΔK-PP mice. Additional AAV-mediated expression of TauΔK or TauΔK-PP in EC/TauΔK or EC/TauΔK-PP mice, resp., increased the human Tau expression to ~0.65-times endogenous mouse Tau, with comparable spreading of TauΔK and TauΔK-PP throughout the EC. There was a low level of transcellular propagation of Tau protein, without pathological phosphorylation or misfolding, as judged by diagnostic antibodies. Additionally, TauΔK but not TauΔK-PP expression induced hippocampal astrogliosis.Conclusions: Low levels of pro- or anti-aggregant full-length Tau show equivalent distributions in EC neurons, independent of their aggregation propensity. Increasing the expression via AAV induce local Tau misfolding in the EC neurons, synaptotoxicity, and astrogliosis, and lead to a low level of detectable trans-neuronal spreading of Tau. This depends on its concentration in the EC, but, contrary to expectations, does not depend on Tau's aggregation propensity/misfolding, and does not lead to templated misfolding in recipient neurons.
Multi-electrode endovascular denervation at a new site of celiac artery for glycemic control in patients with type 2 diabetes mellitus: a promisingly primary result
Authors: Pan Tao , Wei Qiong , Wang Zhi , Zhang Qi , Qian Yue , Li Rui , Liu De-Chen , Wang Yao , Sun Zi-Lin , Li Ling , Teng Gao-Jun
Published: March 2021

Background: Although renal denervation (RDN) may theoretically be effective on type 2 diabetes mellitus (T2DM), most clinical data failed to demonstrate such a concept. We investigated the safety and primary effects of catheter-based endovascular denervation (EDN) at new sites of the celiac artery (CA), and the abdominal aorta around CA using a novel multi-electrode device on glycemic control in T2DM patients. Methods: With a novel six-electrode catheter system, EDN was conducted in T2DM patients at new sites of CA and aorta between CA and superior mesenteric artery (SMA) in purpose of targeting on the postganglionic efferent nerves innervating the liver, islet, and other metabolic organs. The major inclusion criteria were T2DM patients diagnosed over 5 years, with hemoglobin A1c (HbA1c) over 7.5%. The primary outcomes were evaluated by the safety, HbA1c, homeostasis-model assessment of insulin resistance (HOMA-IR), fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (2hPG), and oral glucose tolerance test (OGTT) based 3-hour C-peptide test. The antidiabetic medication, lifestyle, physical condition, blood pressure (BP), plasma norepinephrine, angiotensin II, liver biochemistry, and plasma lipids were also recorded.Results: A total of 11 patients were included for analysis. The technical success was 100% and no severe treatment-related adverse events or major complications were observed. Both HbA1c and HOMA-IR significantly reduced at 6 months (9.9 vs. 8.0, P = 0.005; 13.3 vs. 6.0, P = 0.016, respectively). Decreases of FPG and 2hPG were observed (15.4 vs.10.1 mmol/L, P < 0.001; 17.9 vs. 11.4 mmol/L, P = 0.001, respectively). OGTT based C-peptide test indicated improved beta-cell function ([AUC] 0.23 vs. 0.28 pmol/mL, P =0.046). A reduction of daily insulin injection (P = 0.02) and improvement of liver function (ALT, P = 0.014; GGT, P = 0.021) were also observed without changes in lifestyle, physical conditions, and other metabolic measurements.Conclusions: The 6-month analysis of this trial showed that EDN at new sites of CA and the abdominal aorta around celiac artery using the novel six-electrode catheter system elicits a clinically significant improvement in glycemic control and insulin resistance in patients with T2DM, with good tolerability. Trial Registration Number NCT 04086043, dated 11/9/2019.
Validation of the German version of the Needs Assessment Tool: Progressive Disease – Heart Failure
Authors: Gonzalez-Jaramillo Valentina , Guyer Jelena , Luethi Nora , Sobanski Piotr , Zbinden Rut , Rodriguez Eveline , Hunziker Lukas , Eychmüller Steffen , Maessen Maud
Published: March 2021

BackgroundThe Needs Assessment Tool: Progressive Disease-Heart Failure (NAT: PD-HF) is a tool created to assess the needs of people living with heart failure and their informal caregivers to assist delivering care in a more comprehensive way that addresses actual needs that are unmet, and to improve quality of life. In this study we aimed to 1) Translate the tool into German and culturally adapt it. 2) Assess internal consistency, inter-rater reliability, and test-retest reliability of the German NAT: PD-HF. 3) Evaluate whether and how patients and health care personnel understand the tool and its utility. 4) Assess the tool’s face validity, applicability, relevance, and acceptability among health care personnel.MethodsSingle-center validation study. The tool was translated from English into German using a forward–backward translation. To assess internal consistency, we used Cronbach´s alpha. To assess inter-rater reliability and test-retest reliability, we used Cohen´s kappa, and to assess validity we used face validity. ResultsThe translated tool showed good internal consistency. Raters were in substantial agreement on a majority of the questions, and agreement was almost perfect for all the questions in the test-retest analysis. Face validity was rated high by health care personnel.ConclusionThe German NAT: PD-HF is a reliable, valid, and internally consistent tool that is well accepted by both patients and health care personnel. However, it is important to keep in mind that effective use of the tool requires training of health care personnel.
Olfactory impairment in patients with primary Sjogren’s syndrome and its correlation with organ involvement and immunological abnormalities
Authors: Xu Xue , Geng Lin-yu , Chen Chen , Kong Wen-tao , Wen Bao-jie , Kong Wei , Chen Si-wen , Sun Ling-yun , Zhang Huayong , Jun Liang
Published: March 2021

Objective Patients with autoimmune diseases often present with olfactory impairment. The aim of the study was to assess the olfactory functions of patients with primary Sjögren’s syndrome, and to correlate these findings with their disease activity.Methods Fifty-two patients with primary SS and 52 sex- and age- matched healthy control subjects were included. All of them underwent clinical and laboratory examination. Olfactory functions were evaluated using olfactory function assessment by computerized testing including the three stages of smell: threshold, identification and memory of the different odors. Results All the olfactory scores (olfactory threshold, identification and memory) in patients with pSS were significantly decreased than the control group (all P<0.01). Patients had higher proportion of anosmia (13.5% vs 0%) and hyposmia (19.2% vs 11.5%) than controls (χ2 =10.526, P <0.01). Multivariable regression analysis revealed that ESSDAI and the symptoms of dryness, fatigue and limb pain had negative influence on olfactory function (adjusted R2=0.381, 0.387, 0.513 and 0.614, respectively). ESSPRI showed significantly negative association with olfactory threshold, identification, memory and total scores. Olfactory identification and memory scores were decreased in pSS patients with thyroid dysfunction or hypocomplementemia (P<0.05). Smell threshold scores were decreased in pSS patients with anti-SSA antibody or anti-nuclear antibody compared with those without those autoantibodies (P<0.01). Conclusion Our findings indicate that olfactory functions are impaired in pSS patients. There was close correlation between olfactory dysfunction with disease severity and immunological abnormalities. Immune and systemic inflammation dysregulation might play a role in the mechanism of this defect.
Synchronous Pancreatic Acinar Cell Adenocarcinoma and Gastric Adenocarcinoma: a Case Report and Literature Review
Authors: Fang Tian , Liang Tingting , Wang Yizhuo , Wang Chang
Published: March 2021

Background: Multiple primary malignant tumors are two or more malignancies in an individual without any relationship between the neoplasms. In recent years, increasing number of cases have been reported. However, Synchronous double primary gastric cancer and pancreatic acinar cell carcinoma are relatively rare to be reported. Further, most pancreatic tumors are consistent with pancreatic ductal adenocarcinomas, and other histologies are rare. We present the first case of synchronous pancreatic acinar cell adenocarcinoma and gastric adenocarcinoma.Case presentation: A 69-year-old man came to our department with a history of vomiting, epigastric pain, and weight loss. Imaging revealed space-occupying lesions in the stomach and the tail of the pancreas, respectively. The patient underwent laparoscopic radical gastrectomy and pancreatectomy simultaneously. The pathologies of surgical specimens were completely different: the resected gastric specimen was a moderate to poorly differentiated adenocarcinoma, whereas the pancreatic tumor was consistent with acinar cell carcinoma. The patient was treated with six cycles of oxaliplatin and S-1 chemotherapy. As of March 2021, the patient was healthy without any recurrence or metastasis. After reviewing lots of literatures on simultaneous pancreatic and gastric cancers at home and abroad, we discuss the clinical characteristics of these rare synchronous double cancers. Most of the cases had undergone surgery and adjuvant chemotherapy, and all of the cases were pathologically confirmed by postoperative specimen. Conclusions: Synchronous pancreatic acinar cell and gastric adenocarcinoma can occur and should be considered when tumors are found in these organs.
Optimizing Pre Liming pH for Efficient Juice Clarification Process in Sri Lankan Sugar Factories
Authors: Sewwandi Natasha , Ariyawansha Sandya , Kumara Buddhika Sampath , Maralanda Aloka
Published: March 2021

This study was conducted treating with Milk of Lime to reach different pH levels (T1- with Initial pH, T2, T3 and T4 with 6.5, 7.5 and 8.5 of pH respectively) to determine the optimum pre-liming pH which could result in best cane juice clarification in Sri Lankan sugar industries. The experiment design used was RCBD with five replicates. ANOVA followed by Duncan’s Multiple Range Test (DNMRT) were used to identify significant mean differences. Regression analyses were carried out to model the variation of turbidity, mud volume and CaO with change of juice pH. Quadratic model (R 2 = 99.2%, p <0.001) best fitted to explain the effect of pH on turbidity of juice. Effect of pH on deposited mud volume and CaO were explained by cubic models with R 2 = 99.4% (p <0.001) and R 2 = 93.9%, (p <0.001) respectively.Among tested treatments, pH 7.5 is selected as the best for turbidity improvement of the clarified juice while pH 8.5 is the second best. However pH 8.5 (370 ml) was able to deposited significantly high mud volume than pH 7.5 (270 ml). Further, the amount of residual Ca2+ ions in the clarified juice at pH 7.5 (2715 ppm) is clearly lower than the amount of Ca2+ ions remaining in the clarified juice at pH 8.5 (2945 ppm). It is expected to obtain high turbidity and higher mud volume with low sugar inversion at optimum pH. Therefore the results suggest optimum pH range lie around pH 7.5 to 8.5. Conducting similar experiment by using mixed juice extracted from sugar factory mills with pH range around 7.0 to 8.4 at 0.2 increments is suggested to validate the optimum pH.
Structural and optical properties of co-doped ZnO (V, Dy) nanoparticles synthesized by sol-gel
Authors: Al-Harbi F.F. , ghoul Jaber EL
Published: March 2021

In the present work, sol–gel process was used for the synthesisof Zn0.99-xV0.01DyxO (x = 0.00, 0.04 and 0.08). We studied the impact of doping on the physical properties of the synthesized nanoparticles. In our synthetic approach, under an esterification reaction the release of water was carried out slowly, this step was followed by drying beyond the critical point of ethanol then by calcination in air at 500°C for 2 hours. The structural and morphological studies show the presence of wurtzite structure with an average crystallite size of about 30 nm. In addition, no secondary phase was detected, which shows that the doping elements reacted with the matrix. The reflectance measurements show that by increasing the doping concentration the energy of the band gap energy decreases. Photoluminescence (PL) indicates the presence of two emission bands situated at at around 481 nm and 577 nm linked to doping with Dy.
Liquefaction potential mapping of Newtown, Kolkata, India using Deterministic and Reliability analysis
Authors: Sett Srijani , Chattopadhyay Kalyan Kumar
Published: March 2021

Liquefaction is a phenomenon where the effective stress of the soil gets reduced to zero and the soil losses its shear strength completely. Such occurrence is common during an earthquake and hence the need for evaluating the liquefaction potential of soil arises. The region of Newtown-Rajarhat is undergoing a massive industrial and residential growth and as the area has layers of sand and silt mixed with clay and organic matter, it is essential to determine its liquefaction potential. In this study, the deterministic methods proposed by Youd et al. (2001) and Boulanger and Idriss (2014) were utilized to evaluate the liquefaction potential of the region using 102 borehole data for earthquake magnitudes of 6 and 7. However it was observed that both methods gave different results for the same input parameters. The parameter uncertainties were identified and a reliability analysis was performed to represent the liquefaction potential in terms of reliability index and probability of liquefaction. The First-Order-Second-Moment (FOSM) method was utilized here and contour maps were prepared for depths of 7m and 13m for both the earthquake magnitudes. It was concluded that the study area is vulnerable to liquefaction at a depth of 13m in the regions of Newtown, Rajarhat and Sector V.
PAK1 Inhibition Slows Growth and Partially Promotes Differentiation of AMKL Cells
Authors: fu chunling , wang chunqing , hu xueting , qi kunming , wang shujin , gao yong , yang qiong , ju wen , zeng lingyu , Crispino John D , wen qiang jeremy , xu kailin
Published: March 2021

The authors have requested that this preprint be removed from Research Square.
Credit Spread Disparity Between Japanese Domestic Bonds and Foreign Bonds
Authors: SHIIYAMA Ikuko
Published: March 2021

This article is an empirical study of credit spread disparity between Japanese domestic bonds and foreign bonds on primary issuance. There exist differences between credit spreads issued in domestic market and that of foreign market, despite that the credit risk of these bonds are considered the same. We explore this issue and find that the disparity can be explained by the sensitivity to risk-free rate and leverage. In other words, foreign investors put more premium on the credit risk which is driven by risk-free rate factor and leverage factor.
De Novo Biosynthesis of C-Arabinosylated Flavones by Utilization of Indica Rice C-Glycosyltransferases
Authors: Chen Zhuo , Sun Yuwei , Wang Guangyi , Zhang Ying , Zhang Qian , Zhang Yulian , Li Jianhua , Wang Yong
Published: March 2021

Flavone C-arabinosides/xylosides are plant-originated glycoconjugates with various bioactivities. However, the potential utility of these molecules is hindered by their low abundance in nature. Engineering biosynthesis pathway in heterologous bacterial chassis provides a sustainable source of these C-glycosides. We previously reported bifunctional C-glucosyl/C-arabinosyltransferases in Oryza sativa japonica and O. sativa indica, which influence the C-glycoside spectrum in different rice varieties. In this study, we proved the C-arabinosyltransferring activity of rice C-glycosyltransferases (CGTs) on the mono-C-glucoside substrate nothofagin, followed by taking advantage of specific CGTs and introducing heterologous UDP-pentose supply, to realize the production of eight different C-arabinosides/xylosides in recombinant E. coli. Fed-batch fermentation and precursor supplement maximized the titer of rice-originated C-arabinosides to 20~110 mg/L in an E. coli chassis. The optimized final titer of schaftoside and apigenin di-C-arabinoside reached 19.87 and 113.16 mg/L respectively. We demonstrate here the success of de novo bio-production of C-arabinosylated and C-xylosylated flavones by heterologous pathway reconstitution. These results lay a foundation for further optimal manufacture of complex flavonoid compounds in microbial cell factories.
Endoscopy-Assisted Versus Open Tissue Expander Placement in Plastic and Reconstructive Surgery: A Meta-Analysis
Authors: Dong Chen , Dong Liwei , Yu Zhou , Ma Xianjie
Published: March 2021

Background

Tissue expansion can solve the problem of tissue deficiency in plastic and reconstructive surgery, but it is a lengthy process with many possible complications. This meta-analysis aimed to determine whether endoscopy-assisted expander placement could decrease complications and shorten treatment time.
Methods

A literature search was performed in eight databases from their inception dates up to November 22, 2020, to identify clinical studies on endoscopy-assisted and/or open tissue expander placement in plastic and reconstructive surgery. Risk difference (RD) and weighted mean difference (WMD), along with the 95% confidence intervals (95% CI), were calculated to compare the pooled results.
Results

Seven studies met the inclusion criteria. Of the 759 patients, 194 received endoscopy-assisted expander placement and 565 patients received open expander placement. Overall complication rate was significantly lower in the endoscopy-assisted group than in the open expander group (pooled RD − 0.28, 95% CI, − 0.38 to − 0.18, p < 0.001). Subgroup analysis showed significantly lower incidence rates for haemotoma, infection, and dehiscence, but not for extrusion and deflation. The endoscopy-assisted group also had significantly shorter surgery time (WMD, − 13.97 min; 95% CI, − 15.85 to − 12.08 minutes, p < 0.001), hospital stay (WMD, − 16.88 hours; 95% CI, − 24.36 to − 9.40 hours, p < 0.001), and time to full expansion (WMD, − 27.54 days; 95% CI, − 38.85 to − 16.24 days, p < 0.001).
Conclusions

Endoscopy-assisted expander placement may help lower the risk of complications such as haemotoma, infection, and dehiscence, and also reduce surgery time, hospital stay, and time to full expansion. (PROSPERO: CRD42021226116)
Bacterial contamination of the surgical mask and forehead in aerosol-producing conservative-preventive dental treatment
Authors: Gund Madline , Boros Gabor , Hannig Matthias , Thieme-Ruffing Sigrid , Gärtner Barbara , Rohrer Tilman , Simon Arne , Rupf Stefan
Published: March 2021

Background

Microbial contamination of dental professionals’ facial protective equipment and skin from aerosols and droplets generated during dental treatment has not been studied in all aspects so far. Our aim was therefore to investigate and compare treatment-related bacterial contamination of the forehead skin and surgical mask of dental practitioners.
Methods

We analyzed samples from 67 consecutive aerosol-producing conservative-preventive dental treatments. Sterile nylon swabs were used to collect samples from the forehead skin before and after performing treatment. Contact samples were obtained from the used surgical face masks. Samples were cultivated on agar under aerobic and anaerobic conditions. Bacteria were classified by MALDI-TOF mass spectrometry. The frequency of detection of obligate and facultative oral bacteria, as well as an increase in bacterial abundance, were examined (bacterial scoring: 0: no growth on agar; 1: <102 colonies; 2: >102 colonies; 3: dense bacterial growth).
Results

Bacteria were detected in 95% of the skin swabs and 76% of mask samples. Median bacterial scores were 2 for the forehead skin samples before and after treatment, and 1 for samples obtained from masks. Obligate and facultative oral bacteria were more frequent (6% and 30%) in samples from forehead skin after treatment. Samples taken from the forehead skin after treatment showed increased scores for these bacteria (28%). Five percent of samples were positive for methicillin-sensitive Staphylococcus aureus (MSSA). Obligate anaerobes were present in 3% of samples.
Conclusions

Although exposed during treatment, the forehead skin was significantly less contaminated with obligate oral bacteria than expected based on the surgical face mask findings. Forehead skin samples showed an increase in bacteria in the after treatment, which can be attributed to aerosol-producing procedures. We hypothesize that the forehead’s physiological skin flora may offer some protection against contamination with other microorganisms.
Filling the Matrix: An ANOVA-Based Method to Emulate Regional Climate Model Simulations for Equally-Weighted Properties of Ensembles of Opportunity
Authors: Christensen Ole Bøssing , Kjellström Erik
Published: March 2021

Collections of large ensembles of regional climate model (RCM) downscaled climate data for particular regions and scenarios can be organized in a usually incomplete matrix consisting of GCM (global climate model) x RCM combinations. When simple ensemble averages are calculated, each GCM will effectively be weighted by the number of times it has been downscaled. In order to facilitate more equal and less random weighting among downscaled GCM results, we present a method to emulate the missing combinations in such a matrix, enabling equal weighting among participating GCMs and hence among regional consequences of large-scale climate change simulated by each GCM. This method is based on a traditional Analysis of Variance (ANOVA) approach. The method is applied and studied for fields of seasonal average temperature, precipitation and surface wind and for the 10-year return value of daily precipitation and of 10-m wind speed for a completely filled matrix consisting of 5 GCMs and 4 RCMs. We quantify the skill of the two averaging methods for different numbers of missing simulations and show that ensembles where lacking members have been emulated by the ANOVA technique are better at representing the full ensemble than corresponding simple ensemble averages, particularly in cases where only a few model combinations are absent. The technique breaks down when the number of missing simulations reaches the sum of the numbers of GCMs and RCMs.
The Role and Molecular Mechanism of SLC34A2 in Stemness Maintenance of CD44+CD166+ Lung Cancer Stem Cells (LCSCs) with AT-II cells’ characteristics
Authors: Yang Yan , Pu Qiang , Liao Hu , Yuan Yue , Hu Xueting , Luo Xinmei , Jiang Qianqian , Su Xiaolan , Zhu Wen
Published: March 2021

Background

Evidence showed some non-small cell lung cancers (NSCLCs) had the type II alveolar epithelium cells’(AT-II cells) characteristics, and AT-II cells were a kind of original stem cells of NSCLCs. But how AT-II cells malignantly transformed into NSCLCs was unclear. Recent evidence indicated SLC34A2 was critical in the development of AT-II cells, and SLC34A2 might be a new gene in the initiation of NSCLCs. However, whether SLC34A2 participated in the malignant transformation of AT-II cells remained unknown. The exact role and mechanism of SLC34A2 in the initiation of NSCLCs needed to be further investigated.
Methods

The expression of Napi-IIb (encoded by SLC34A2) in the NSCLC cells was compared with that in AT-II cells using immunohistochemistry (IHC). Also coexpression of CD44 and CD166 was detected in these NSCLCs tissues by IHC. Then the CD44+CD166+ cells were sorted from lung tumor spheres by FACS. They were assessed by sphere, proliferation and tumorgenicity assay. Besides, their expression of surfactants C(SP-C) was stained by IHC. Next, the role and mechanism of SLC34A2 in CD44+CD166+ lung cancer stem cells were explored by siRNA-mediated SLC34A2 knockdown, related pathway pharmacological inhibition or activation. In vitro findings were furtherly validated in vivo and NSCLCs samples.
Results

The expression of SLC34A2 was downregulated in NSCLCs cells compared with AT-II cells in clinic samples. Then the CD44+CD166+ population was identified as CD44+CD166+ lung cancer stem cells (LCSCs). And LCSCs showed abundant expression of SP-C, the hallmark of AT-II cells. Higher expression of SLC34A2 was found in LCSCs compared to their origin NSCLC cells. Additionally, the expression of SLC34A2 was decreased after LCSCs were differentiated, and the morphology of the differentiated cells from LCSCs was similar to their origin NSCLC cells. Knockdown SLC34A2 made declined abilities of self-renewal, drug-resistance, migration and invasion in vitro as well as tumorigenicity in vivo in LCSCs. And SLC34A2 could maintain stemness of LCSCs via PI3K/AKT/STAT3/Sox2 axis. Besides, the connection between SLC34A2 maintaining stemness of lung cancer stem cells and PI3K/AKT/STAT3/Sox2 axis was also validated in vivo and in clinic samples.
Conclusions

For the first time, we illustrated the expression of SLC34A2 was downregulated in NSCLCs cells compared with AT-II cells. We discovered the downregulated expression of SLC34A2 performed a vital role in the malignant transformation of AT-II cells into NSCLCs. And SLC34A2 could maintain stemness of CD44+CD166+ lung cancer stem cells, which were with AT-II cell’s characteristic, via PI3K/AKT/STAT3/Sox2 axis. It had important significance in the revelation of a new mechanism for the initiation of NSCLCs.
Lower serum bilirubin is a risk factor for cardiovascular mortality in maintenance hemodialysis patients: a retrospective cohort study
Authors: Chen Yu , Zhao Peilei , Fan Weifeng , Li Hongmei , Zhong Xiaojing , Niu Jianying
Published: March 2021

Background: Although recent studies showed serum bilirubin, an endogenous antioxidant, is protective against cardiovascular diseases, cancer, and diabetic complications, less information is available its association with cardiovascular mortality in hemodialysis patients. This study aimed to investigate the relationship between serum bilirubin and the cardiovascular mortality in maintenance hemodialysis patients.Methods: This retrospective study included 284 chronic hemodialysis patients who started hemodialysis between January 01, 2003, and May 30, 2019. The endpoint was cardiovascular death and all-cause death. A Cox proportional hazards model was used to evaluate the risk factors for cardiovascular death in the maintenance hemodialysis. The cardiovascular mortality was evaluated by Kaplan-Meier analysis.Results: Up to 2019, the median follow-up time was 53 months. In Kaplan–Meier analysis curves, the risk of cardiovascular death in the patients with serum indirect bilirubin (IBIL) levels＜3.0 μmol/L was significantly higher than those with serum IBIL levels≥3.0 μmol/L(p =0.045). In multivariate Cox regression analysis, the risk of cardiovascular mortality in patients with serum IBIL levels ≥3.0 μmol/L was 0.556 times the risk in patients with serum IBIL levels＜3.0 μmol/L (Hazard ratio=0.556, 95% confidence interval 0.334~0.926, p =0.024). However, there was no significant association between serum IBIL and all-cause mortality (p =0.269). Conclusions: Our findings suggest that low serum IBIL level is independently associated with high risk of cardiovascular death in maintenance hemodialysis patients.
A dual electro-optical biosensor based on Chlamydomonas reinhardtii immobilised on paper-based nanomodified screen-printed electrodes for herbicide monitoring
Authors: Antonacci Amina , Attaallah Raouia , Arduini Fabiana , Amine Aziz , Giardi Maria Teresa , Scognamiglio Viviana
Published: March 2021

The indiscriminate use of herbicides in agriculture contributes to soil and water pollution, with important endangering consequences on the ecosystems. Among the available analytical systems, algal biosensors have demonstrated to be valid tools thanks to their high sensitivity, cost-effectiveness, and eco-design. Herein, we report the development of a dual electro-optical biosensor for herbicide monitoring, based on Chlamydomonas reinhardtii whole cells immobilised on paper-based screen-printed electrodes modified with carbon black nanomaterials. To this aim, a systematic study was performed for the selection and characterisation of a collection among 28 different genetic variants of the alga with difference response behaviour towards diverse herbicide classes. Thus, CC125 strain was exploited as case study for the study of the analytical parameters. The biosensor was tested in standard solutions and real samples, providing high sensitivity (detection limit in the pico/nanomolar), high repeatability (RSD of 5% with n = 100), long lasting working (10 h) and storage stability (3 weeks), any interference in the presence of heavy metals and insecticides, and low matrix effect in drinking water and moderate effect in surface one.
AI-assisted quantitative lung CT evaluation following umbilical cord mesenchymal stem cell treatment in severe COVID-19 patients
Authors: Zhou Huang , Lu Ji-zhen , Huang Dao-yi , Wu Xiao-dong , Luo Zhi-bing , Gao Shao-yong , He Long , Shi Yan , Zheng Liang , Jiang Er-peng , Jia Wen-wen , Qiang Li , Chu Shu-guang , Liu Zhong-min
Published: March 2021

BackgroundThe COVID-19 has high transmission and mortality. Previous studies support the efficacy and safety of mesenchymal stem cells (MSCs) in the treatment of lung injury. In this study, We aimed to evaluate the CT changes of lung lesions in severe COVID-19 patients treated with umbilical cord mesenchymal stem cells (UC-MSCs) by using AI-assisted quantification method.Methods46 patients with severe COVID-19 from March 5 to April 1, 2020 were selected by single-blind, non-randomized controlled clinical study and divided into three groups: 11 cases in UC-MSCs treatment group 1 (MSC-1, with cells infusion once), 26 cases in UC-MSCs treatment group 2 (MSC-2, with cells infusion twice or three times), and 9 cases in control group with routine treatment. Repeated measure ANOVA was used to compare the effects of treatment factors on chest CT parameters of COVID-19 patients between control and experimental groups, and pairwise comparison using LSD test.FindingsThe differences between the percentage of GGO in total lung or the percentage of total lung infection volume on day 0 and that in day 60 as well as in day 90 were statistically significant among the three groups. The P values were 0.034 and 0.018 respectively. Pairwise comparison results showed that the percentage difference of the whole lung GGO and total lung infection volume in MSC-1 group was smaller than that in control group and MSC-2 group respectively, but there was no statistical difference between control group and MSC-2 group. The distribution characteristics and other CT parameters post-proceeded by AI software were not significantly different among the three groups. There were no serious adverse events related to stem cell infusion in all treated patients.InterpretationUC-MSC infusion is safe for the treatment of severe COVID-19 patients. The absorption of lung lesions at 60 days and 90 days after UC-MSC infusion once was more obvious than that in the control group. AI quantification of lung lesions is more suitable for comparative studies before and after treatment.
The Modification of Newton's Gravitational Law and its Application in the Study of Dark Matter and Black Hole
Authors: Wang Jian'an
Published: March 2021

In this paper, Newton's gravitational formula is modified by the principle of spatial energy field superposition, and the problem of "missing mass " of galaxies is analyzed by this modified gravitational formula. It is concluded that the velocity of stars in the galaxy is too fast because the energy field intensity of the inner space of the galaxy or space-time curvature of the galaxy is seriously underestimated, and there is no dark matter and supermassive black hole in the galaxy.
Development and Testing of a Novel Universal Transdermal Drug Delivery Platform to Reduce Medication Nonadherence
Authors: Ramesh Gautam , Zamat Ali , Vadlamudi Srujan , Liu Neiman , Akuthota Praveen
Published: March 2021

Medication nonadherence results in avoidable symptom exacerbations and hospitalization, causing thousands of deaths and billions of dollars in healthcare costs annually. Although pharmacological therapies are present for chronic diseases, lengthy and complicated medication regimens often have high rates of nonadherence. Transdermal drug delivery is a potential method of reducing medication nonadherence as it allows for long-course medication regimens to be simplified to a one-time epidermal patch. We have engineered a transdermal drug delivery system on a customizable platform to longitudinally deliver a wide variety of soluble small-molecule drugs. As a proof of concept, we have chosen to administer long-course corticosteroids for chronic inflammatory disease via epidermal patch. The transdermal drug delivery system has an integrated tapering mechanism to avoid end-of-course steroid dependence and can incorporate other small-molecule medications required for cases of polypharmacy. To date, there have been no successful attempts to develop long-term steroid patches for systemic delivery which can be attributed to issues with patch adhesion and skin irritation over extended periods of time. We have analyzed such challenges and have designed a proof of concept system to overcome these obstacles in order to provide patients with a simple, inexpensive, and effective solution to complicated and long-term treatment regimens.
Device-to-device and mobile user communication with queuing in NOMA-based network
Authors: Balyan Vipin , Gupta Dhiraj
Published: March 2021

In this paper, device-to-device (D2D) pairs use the uplink resource of a mobile user. The transmission is done using a non-orthogonal multiple access (NOMA) technology. The D2D pairs are placed in a queue with maximum threshold time. The channel is allocated to D2D pairs using the TDMA scheme with the first in first out (FIFO) principle. Considering the slots of time division multiple access (TDMA) and channel state, the channel is shared by one D2D pair with the mobile user. The signal to interference (SIC) is employed for D2D pair or mobile user based on NOMA. A hybrid of TDMA and NOMA is used in which time and bit allocation are judiciously adopted. The results are simulated for four different scenarios of power and rate requirements with reduced latency and interference.
ASGARİ ADALET KAVRAMLAŞTIRMASI ÜZERİNE: ADALETİN ASGARİ İLKELERİ
Authors: AKTAŞ Sururi
Published: March 2021

Bu makale çalışmasında, Hans Kelsen gibi hukuki pozitivistler tarafından sübjektif ahlaki bir değer yargısı olması ve belirsizlikler taşıması gerekçesiyle hukuk kavramının dışında tutulmak istenilen adalet değerinin, kolayca reddedilemeyen oldukça yüksek bir belirlilik alanına sahip olduğu ortaya konmaya çalışılmıştır. Asgari adalet ilkelerinin oluşturduğu bu belirlilik alanı “asgari adalet kavramı” olarak tanımlanmıştır. Asgari adalet kavramlaştırmasının olanaklığı, yöntem olarak ılımlı hukuki pozitivizmi savunan H.L.A Hart’ın hukuk kuralının belirlilik ve belirsizliğine ilişkin yaptığı analiz, yine Hart’ın “doğal hukukun asgari içeriği” tanımlaması, doğal hukukçu Lon L. Fuller’ın ahlakla ilgili yaptığı analiz ve David Schmidtz’in periyodik cetvel benzetmesiyle desteklenmiştir. Bir asgari adalet kavramının inşa edilmesi ve bu yönde bir hassasiyet meydana getirilmesinin, pozitif hukuka bir değer ölçüsü oluşturması bakımından önemli olduğunun altı çizilmiştir. Çalışmada “asgari adalet kavramı”nı oluşturduğu düşünülen bazı ilkeler genel hatlarıyla açıklanmaya çalışılmıştır. Ayrıca asgari adalet kavramı içinde yer verilen adalet ilkelerinin sayı bakımından mutlak olmadığı, yenilerinin eklenebileceği ve dolayısıyla ucu açık bir öneri niteliğinde olduğu vurgulanmıştır. Sonuç bölümünde asgari adalet kavramını oluşturan adalet ilkelerinin nitelikleri ve pozitif hukuk bakımından taşıdığı önem ortaya konmaya çalışılmıştır.
Macroeconomic factors that influence the bank loans rate in international and Ukrainian practice
Authors: Ivakhnenkov Sergiy , Hlushchenko Svitlana , Sverenko Kamilla
Published: March 2021

The goal of the paper is to disclose the links between the dynamics of macroeconomic indicators and the level of bank loan rates based on international and Ukrainian practice. On the basis of the previous analysis, the paper also aims to identify the key trends in the formation of loan prices in the long run and identify problematic issues related to bank loan rates. The main characteristics of bank lending rates in Ukraine are: a) their high rates; b) sharp changes in the weighted average bank loan rates from year to year; c) higher loan rates for households compared to the cost of bank loans for businesses; d) higher bank loan rates for short- and medium-term loans versus long-term ones; e) lower rates on loans in foreign currency compared to the loans in hryvnia; and f) high share of non-performing loans to households and businesses in bank portfolios. In the context of world and Ukrainian practice, the paper demonstrates the reverse effect between macroeconomic indicators such as GDP per capita, the ratio of loans to GDP, the ease of doing business index and bank loan rates. The article also demonstrates a direct relationship between the dynamics of inflation rate in the country, the dynamics of non-performing bank loans and their rates.
Assessment of public welfare in Ukraine in the context of the COVID-19 pandemic and economy digitalization
Authors: Kozlovskyi Serhii , Petrunenko Iaroslav , Baidala Viktoriia , Myronchuk Viktoriia , Kulinich Tetiana
Published: March 2021

With the emergence of the global COVID-19 pandemic in 2019, a process of transformation of the modern economic system took place, which requires new approaches to assessing economic processes. One of such processes is the assessment of public welfare. The purpose of this study is to develop an approach to assessing the level of public welfare of the population of Ukraine in the context of the COVID-19 pandemic and economy digitalization. To solve this problem, the methods of artificial intelligence, in particular the method of fuzzy sets theory, which allows using the incomplete information and making high-quality forecast calculations, are used. The factors influencing the level of public welfare during the COVID-19 pandemic have been identified. These are the following factors: gross domestic product, poverty rate, welfare index, human development index, subsistence level, and indicators that characterize the COVID-19 pandemic (i.e. the total number of COVID-19 cases, the total number of deaths from COVID-19, and the total number of vaccinations from COVID-19 in Ukraine). Using fuzzy sets theory, an economic-mathematical model for assessing the level of public welfare in the context of the COVID-19 pandemic in Ukraine was built. Two-dimensional dependences of the level of public welfare of Ukraine in the context of the COVID-19 pandemic on indicators such as gross domestic product, subsistence level, and the total number of cases of COVID-19 in Ukraine were obtained. The results of the study established that the level of public welfare in the context of the COVID-19 pandemic on the 0-100 scale is predicted to be as follows points: 2021 – 17, 2022 – 23, 2023 – 27, 2024 – 19, 2025 – 35 and will not meet international standards.
Anti-Inflammatory Meroterpenoids of Cordia glazioviana (Boraginaceae)
Authors: Silva Ana Karine , Pinto Francisco , Canuto Kirley , Braz‑Filho Raimundo , Silva Rose Anny , Santos Flávia , Monteiro Norberto , Silveira Edilberto , Pessoa Otília
Published: March 2021

The phytochemical reinvestigation from the heartwood of the extracts of Cordia glazioviana led to the isolation of four still undescribed hydroquinones derivatives designated as cordiaquinol D (1), cordiaquinol E (2), (10R)-10,11-dihydrofuran-1,4-dihydroxy-globiferin (3) and 2-[(1’E,6’E)-3’,8’‑dihydroxy-3’,7’-dimethylocta-1’,6’-dienyl]-benzene-1,4-diol (4), along with the naphthoquinone 6-[(2’R)-2’-hydroxy-3’,6’-dihydro-2H-pyran-5’-yl]-2‑methoxy- 7‑methylnaphthalene-1,4-dione (5). Additionally, six previously known compounds were also isolated: rel-1,4-dihydroxy-8α,11α;9α,11α-diepoxy-2-methoxy-8aβ-methyl- 5,6,7,8,8a,9,10,10a‑octahydro-10-antracenone (6), didehydroconicol (7), 1β,6β-dihydroxy-7-epieudesm-3-ene (8), 1β,6β-dihydroxy-7-epi-eudesm-4(15)-ene (9), 10,11-dihydroxybisabolol (10), and hamanasal-A (11). The structures of the new compounds were assigned by high-resolution mass spectrometry (HRMS) and nuclear magnetic resonance (NMR) analyses. The relative stereochemistry of 3, 4, and 5 was improved by quantum mechanical calculations. Eight, out of the eleven isolated compounds (2-9), were tested through cellular viability and lipopolysaccharide (LPS)-induced inflammation assays against RAW 264.7 macrophage-like cells. Compounds 3-5 exhibited a stronger effect on LPS-induced NO production (half-maximal inhibitory concentration (IC50) 50.34, 105.83, and 66.73 μM, respectively).
Alternative Financing of Small and Medium Businesses: Experience of Foreign Countries
Authors: Pin'koveckaya Yuliya
Published: March 2021

Small and medium enterprises play an important role in modern national economies. However, many of these enterprises experience difficulties in attracting the necessary investments for operation and further development. Personal finances are usually not enough to solve all problems, especially in crisis conditions. Bank loans are not available for most small and medium businesses because of small fixed assets, poor credit history, and incomplete reporting. As foreign experience shows, alternative forms and methods of obtaining the necessary funds can be an effective way to increase the financing of such enterprises. This review article examines the experience gained in recent years in using alternative financing. This experience is relevant for the current domestic entrepreneurship. Factoring, order financing, warehouse receipts, leasing, trade credit, and crowdfunding proved to be the main alternative financing tools. For each of these financial instruments, the article gives brief characteristics, advantages and disadvantages, requirements for regulatory support, and related types of activities. The research results can help entrepreneurs who have difficulties in financing their production and sale, especially beginners. The results obtained can be used by government authorities to form a policy to improve access of business structures to working capital and investment in Russia and its regions.
Effect of Geographic Information Technologies on Regional Economy
Authors: Rada Artem , Gavrilenko Irina , Kolesnik Alina
Published: March 2021

This study featured the geographic information system of the Kemerovo region (Kuzbass). The research objective was to determine the economic benefits of using various analytical layers of GIS Kuzbass. The authors reviewed the theoretical foundations of geographic information systems, as well as defined the main directions and advantages of their application. The paper introduces a detailed description of GIS Kuzbass and its effect on the local economy. The study involved descriptive, analytical, and comparative methods. Geographic information systems use multifactor information, which is constantly updated and systematized, thus making it possible to manage the territory quite effectively. GIS Kuzbass proved to be extremely effective. First, it can increase budget revenues of urban districts by increasing tax revenues from objects identified by the system. Second, it can increase budgets by obtaining fines for offenses detected by GIS Kuzbass.
Developing the Occupational Mobility of Youth: Tendencies in Social Practices
Authors: Efremova Evgeniya
Published: March 2021

The new social reality increased public interest in the issues of occupational mobility of the youth. The research objective was to determine the tendencies of social practices in this sphere. The author analyzed and generalized scientific publications on the problems of occupational mobility of young population and the related labor market. The paper introduces various interpretations of the concept of "social practices" and systematizes them. The author identified four trends in the social practices: 1) an increase in the flexibility of social practices, 2) an expansion of channels of professional mobility, 3) the development of the Internet industry, and 4) a change in the attitude of young people to employment. The research results can improve the management of the occupational mobility of young people in modern society, as well as provide targeted management impact on social facilities by revealing their resources and potential. By taking into account modern trends in social practices of occupational mobility of young population, organizations can ensure professional growth and competitiveness of young employees in the labor market.
Curbing the Unemployment in Modern Conditions: State Response
Authors: Abdulmanapov Salihbek , Medzhidov Zaur
Published: March 2021

Socio-economic stability, good living standards, and low unemployment are the key aspects of the state development strategy in modern economic conditions. They have a direct impact on the national competitiveness and security. The current pandemic and global economic crisis made it important to curb the growing unemployment and protect the unemployed population. The study featured the global labor market with its structural and economic relations, trends and patterns. The research objective was to identify the potential problems of unemployment growth and provide recommendations for their localization and leveling. The authors analyzed the forecasts made by Russian and international experts about the state of the global labor market during the pandemic, assessed its features and main trends, studied the consequences of the COVID-19 pandemic on the unemployment rate, and systematized measures of social support for unemployed population in different countries. The paper introduces some measures that can prevent the growth of global unemployment.