bluuebunny/crossref_metadata_2025 huggingface dataset:
Metal Speciation in Sludges: a Tool to Evaluate Risks of Land Application and to Track Heavy Metals Contamination in Sewage Network
Authors: Cherfouh Rabia , Lucas Yves , Derridj Arezki , Merdy Patricia
Published: July 2021

Agricultural spreading of dewatered sewage sludge from wastewater treatment plants is economically profitable but care must be taken to ensure that there is neither degradation of the agronomic quality of the soils nor contamination of them in the long term, particularly by accumulation of heavy metals. To evaluate the variability of the sludge in a given geographical area, we studied the sludge coming from five treatment plants in northern Algeria. We determined parameters that account for the agronomic quality of sludges and total content of Ag, Cd, Co, Cr, Cu, Ni, Pb, Ti and Zn. We evaluated the bioavailability of theses metals by determining their speciation by sequential extraction, each metal being distributed among five fractions: easily exchangeable, acido-soluble, bound to carbonates and partly to Fe-sulphides, bound to Fe- and Mn-oxides, bound to organic matter or sulphides, contained in poorly soluble minerals. We found that all the analysed sludges had satisfactory properties from an agronomic quality point of view. High total Ni content indicated that three sludges were not spreadable under French or Chinese regulations. Metal speciation, however, showed that Ni was contained in very poorly bioavailable fractions, and therefore presented a low risk in the soils concerned. In contrast, the total Cu was below the regulatory limit values, but contained in very bioavailable fractions with a risk of toxic effects by accumulation over less than 10 years. These results showed that regulations must take into account the bioavailability with regard to the characteristics of the soils on which sludge will be spread. Metal speciation in the sludge also made it possible to identify the zone of the sewerage network on which the sources of contamination must be sought and gave indications on the nature of these sources.
Integration of Satellite Image Derived Temperature and Water Depth for Assessing Fish Habitability in Dam Controlled Flood Plain Wetland
Authors: Kundu Sonali , Pal Swades , Talukdar Swapan , Mahato Susanta , Singha Pankaj
Published: July 2021

The present study attempted to investigate the changes in temperature conducive to fish habitability during the summer months in a hydrologically modified wetland following damming over a river. Satellite image-driven temperature and depth data calibrated with field data were used to analyse fish habitability and the presence of thermally optimum habitable zones in some fishes such as Labeo Rohita, Cirrhinus mrigala, Tilapia fish, Small shrimp, and Cat fishes. The study was conducted both at the water's surface and at the optimum depth of survival. It is very obvious from the analysis that a larger part of wetland has become an area that destroyed aquatic habitat during the post-dam period and existing wetlands have suffered significant shallowing of water depth. This has resulted in a shrinking of the thermally optimum area of fish survival in relation to surface water temperature (from 100.09 km2 to 74.24 km2 before the dam to 93.97 km2 to 0 km2 after the dam) and an improvement in the optimum habitable condition in the comfortable depth niche of survival. In the post-dam period, it increased from 75.49 % to 99.765%. Since the damming effect causes a 30.53 to 100% depletion of the optimum depth niche, improving the thermal environment has no effect on fish habitability. More water must be released from dams for restoration. Image-driven depth and temperature data calibrated with field information has been successfully applied in data sparse conditions, and it is further recommended in future work.
Confirmation Value of Western Blotting in Detecting Anti-treponema Pallidum Specific Antibodies With Suspicious Results
Authors: Xu Siqi , Li hongsheng , Wu xiaoyan , Guo jianwei , Zhang jiaoli , Hu xuqi
Published: July 2021

ObjectiveThis study aimed to evaluate the necessity of Western blotting (WB) in samples with inconsistent results in detecting anti-treponema pallidum (TP) antibodies by enzyme-linked immunosorbent assay (ELISA) and Treponema pallidum granule agglutination assay (TPPA). MethodsSpecific anti-TP test results in our clinical laboratory were retrospectively analyzed. The specimens with a positive or a negative result, but with colored ELISA plates, were retested by TPPA. WB was used to confirm the suspicious results between ELISA and TPPA. The chi-square test was used to analyze whether the difference was statistically significant. ResultsA total of 106,757 anti-TP specimens were screened by ELISA from August 2018 to December 2019; 3972 were retested by TPPA, and 3809 were positive by TPPA. ELISA and TPPA showed different results in 163 specimens. Among them, 29 specimens were negative and 134 were positive by ELISA; 76 were negative, 23 were positive, and 64 were “reserve” by TPPA; 93 were negative, 31 were positive, and 39 were suspicious by the WB confirmation test. Compared with WB, the difference in the results of ELISA and TPPA was statistically significant. Conclusions﻿TPPA is an effective retest method for anti-TP antibody detection. If the results of anti-TP antibodies by ELISA and TPPA are inconsistent, it is necessary to use WB for confirmation.
Effects and Comprehensive Evaluation of Different Organic Fertilizer Substitution Ratios on Maize Yield, Soil Organic Carbon Fractions, Nutrients and Heavy Metals
Authors: He Hao , Hou Zhenan , Ru Sibo , Li Junhua
Published: July 2021

Organic fertilizer substitution technology is an effective measure to solve the excessive application of chemical fertilizers in agricultural production. A pot experiment was set up with 5 treatments: no fertilizer (CK) and organic fertilizer substituting 0% (CF), 8% (OF8), 16% (OF16), and 24% (OF24) of chemical N fertilizer to analyze their effects on maize yield, soil organic carbon (SOC) and its fractions, carbon pool management index (CPMI), nutrients and heavy metals to provide a scientific basis for safe fertilizer application to maize. This study found that OF8, OF16, and OF24 all increased the content and proportion of SOC and labile organic C (LOC) fractions, CPMI, most of the middle and trace elements, and heavy metals content and their pollution indices in soil and grain compared to CF. Grain was more vulnerable to pollution compared to soil. There was a strong positive correlation between the content of middle and trace elements, and heavy metal, SOC and its fractions (except LLOC), and organic fertilizer substitution ratio, all with no significant correlation with yield. OF8 and OF16 promoted maize growth with a significant increase yield of 35.65% and 30.28% (P <0.05), respectively. A comprehensive analysis determined the optimum substitution ratio of 8% (OF8), which can reduce chemical fertilizer and increase yield, improve soil fertility, low heavy metal pollution risk, is beneficial to promote sustainable agricultural development.
Expression Patterns of Immune Checkpoints in Breast Cancer Patients
Authors: Qiu Dan , Yan Xianxin , Zhang Guijuan , Xiao Xinqin , Cao Jingyu , Wang Yanqiu , Ma Ruirui , Hong Shouyi , Ma Min
Published: July 2021

Background: immunotherapy with immune checkpoint inhibitors (ICIs) for solid tumors had significantly improved overall survival (OS). Positive response to PD-1/PD-L1 blockades was observed in the treatment of solidtumors. Breast cancer (BC) patients are no exception. However, the efficacy of immunocheckpoint therapy in BC patients remains poor. A particularly important factor is the lack of studies on the expression patterns of immune checkpoints in BC patients. Method: in this study, the microarray dataset GSE10810 was downloaded from the Gene Expression Database Synthesis (GEO) to analyze the differential expression of BC genes and perform GO and KEGG analysis. Then, we explored theprognostic value of ICs for BC patients by analyzing RNA-seq and mutation data from 657 BC patients from theCancer Genome Atlas (TCGA) database. Next, we analyzed the differences in the expression of relevant immune checkpoints between 1085 BC patients and 291 healthy controls (HC) in the Genotype-Tissue Expression (GTEx) database. Finally, we analyzed the expression levels of IFNγ-R, PD-L1, STAT1, IDO and other genes in MCF-10A, MF-10AT, MCF-7, MDA-MB-231 cell lines.Results: It was found that increased expression of PD-1, PD-L1, STAT1, CTLA-4 was associated with poor OS in BC patients. In addition, co-expression of PD-L1 with PD-1, STAT1or CTLA-4 and co-expression of PD-1 with CTLA-4was related to poor OS. We analyzed associations between the proportionate expression of PD-L1 and PD-1, PD-L1 and STAT1, PD-1 and CTLA-4, PD-1 and LAG3, PD-L1 and CTLA-4 in BC patients, there was significance in correlation in both of the BC patients.The expression of STAT1 in BC patients was compared with that of HC, and it was found that STAT1 was highly expressed in BC patients. Conclusions: our results suggest that transcriptome-based co-expression of STAT1 and PD-L1 is a predictor for poor OS in BC patients, which might provide novel insight into designing combinational targeted therapy for BC.
Effect of Evolutionary Adaptation on Metabolic Enzyme Activities of Thermotolerant Strain Kluyveromyces Marxianus NIRE-K1 and NIRE-K3 for Bioethanol Production
Authors: Sharma Nilesh Kumar , Behera Shuvashish , Arora Richa , Kumar Sachin
Published: July 2021

Evolutionary adaptation provides stability to the strains in the challenging environment. As extension of earlier study, the evolved strains Kluyveromyces marxianus NIRE-K1.1 and K. marxianus NIRE-K3.1 were subjected for secondary adaptation on minimal salt (MS) medium with the aim to enhance xylose utilization for ethanol production together with salt tolerance. Both the strains were adapted till saturated improvement in xylose uptake i.e., 54 generations on MS medium containing xylose. Xylose utilization increased from 14.21 to 45.80% and 10.55 to 45.31%, in evolved strains KmNIRE-K1.2 and KmNIRE-K3.2, respectively. Specific xylose reductase activity has also increased 2.04 and 3.36-folds in KmNIRE-K1.2 and KmNIRE-K3.2, respectively. Xylitol dehydrogenase activity was also increased by 2.82 and 1.35-folds in KmNIRE-K1.2 and KmNIRE-K3.2, respectively. Decrease in redox imbalance was observed in evolved strains, and hence there was a reduction in xylitol production during growth and fermentation. Xylose uptake rate increased by 2.53 and 1.5-folds in KmNIRE-K1.2 and KmNIRE-K3.2, respectively with 2.20 and 6.46-folds higher ethanol concentration, and 2.25 and 5.86-folds higher volumetric productivity, respectively. This study has demonstrated the role of evolutionary adaptation for developing robust yeast strains. KmNIRE-K1.2 and KmNIRE-K3.2 have shown enhanced ethanol production, enzyme activities and less by-product formation like xylitol during xylose metabolism.
How Equitable Is Health Spending On Curative Services And Institutional Delivery In Malawi? Evidence From A Quasi-Longitudinal Benefit Incidence Analysis
Authors: Rudasingwa Martin , Yeboah Edmund , Ridde Valéry , Bonnet Emmanuel , De Allegri Manuela , Muula Adamson Sinjani
Published: July 2021

Background: Malawi is one of a handful of countries that had resisted the implementation of user fees, showing a commitment to providing free healthcare to its population even before the concept of Universal Health Coverage (UHC) acquired global popularity. Several evaluations have investigated the effects of key policies, such as the essential health package or performance-based financing, in sustaining and expanding access to quality health services in the country. Understanding the distributional impact of health spending over time due to these policies has received limited attention. Our study fills this knowledge gap by assessing the distributional incidence of public and overall health spending between 2004 and 2016.Methods: We relied on a Benefit Incidence Analysis (BIA) to measure the socioeconomic inequality of public and overall health spending on curative services and institutional delivery across different health facility typologies. We used data from household surveys and National Health Accounts. We used a concentration index (CI) to determine the health benefits accrued by each socioeconomic group. Results: Socioeconomic inequality in both public and overall health spending substantially decreased over time, with higher inequality observed in overall spending, non-public health facilities, curative health services, and at higher levels of care. Between 2004 and 2016, the inequality in public spending on curative services decreased from a CI of 0.037 (SE 0.013) to a CI of 0.004 (SE 0.011). Whiles, it decreased from a CI of 0.084 (SE 0.014) to a CI of 0.068 (SE 0.015) for overall spending in the same period. For institutional delivery, inequality in public and overall spending decreased between 2004 and 2016 from a CI of 0.032 (SE 0.028) to a CI of -0.057 (SE 0.014) and from a CI of 0.036 (SE 0.022) to a CI of 0.028 (SE 0.018), respectively. Conclusion: Through its free healthcare policy, Malawi has reduced socioeconomic inequality in health spending over time, but some challenges still need to be addressed to achieve a truly egalitarian health system. Our findings indicate a need to increase public funding for the health sector to ensure access to care and financial protection.
Initiation of Complementary Feeding Practice And Associated Factors Among Mothers Having Children 6-23 Month of Age, In Meket Woreda, North Wollo Ethiopia, 2020: A Multicenter Community -Based Cross-Sectional Study.
Authors: Feleke Dejen , Tadesse Abebu Yasin , Chanie Ermias Sisay , Wolie Amare Kassaw , Tassew Sheganew Fetene , Wubet Gashaw Mehiret , Demelash Agimasie Tigabu , Dires Tadela , Alemu Eshtie Molla , Azanaw Mekalem Mamuye , Techane Masresha Asmare , Yehualashet Sisay Shewasinad , Lake Eyasu Alem , Demissie Birhanu Wondmieneh , Hailemeskel Habtamu Shimeles , Alemayehu Sintayehu Asenakew
Published: July 2021

Introduction: improving the infant and young child feeding practices in children aged 0-23months is critical. It is necessary to improved infant and young child health, nutrition, and development. Infant and under five mortality rate in Ethiopia are 43/1,000 and 55/1,000 live births respectively. Objective: To assess Initiation of CF practice and associated factors among mothers with children aged 6−23months.Methods: a multicenter Community based cross sectional study was conducted among 416 mother-infant pairs of 6-23 months in Meket Woreda, Northwest Ethiopia from March 20-June 30, 2020. Bivariate and multivariable logistic regeration model was fitted to identify factors associated CF Practice. P-value less than 0.05 considered as significance.Result: Among 416 mothers with children aged 6–23 months, 76.4% mothers started giving CF timely at recommended age of 6 month of child age. Advised About CF during ANC follow up [AOR=0.03; 95%CI: 0.003-0.356], Child delivered place at a health facility [AOR=0.07; 95%CI: 0.0-0.619], mothers take family planning [AOR= 0.049; 95%CI: 0.011-0.23], give additional diet the 1st 6month [AOR = 0.035; 95% CI: 0.009-0.137] and BF makes appearance [AOR = 0.064; 95% CI: 0.003-0.687] were found to be independent predictors of CF practice.Conclusion and Recommendation: About 23.6% of mothers were not initiated CF practice their children at recommended age of 6month. This would have negative implication on the health of infants and young children. Health professionals should focus on advising and counseling mothers on appropriate CF during prenatal, delivery, post natal, and immunization services.
Parthenolide Inhibits Migration and Reverses the EMT Process in Breast Cancer Cells by Suppressing TGFβ and TWIST1
Authors: Sufian Hazera Binte , Santos Julianna Maria , Khan Zeina Shreen , Munir Maliha Tabassum , Zahid MD Khurshidul , Al-Harrasi Ahmed , Gollahon Lauren S. , Hussain Fazle , Rahman Shaikh Mizanoor
Published: July 2021

Breast cancer metastasis is the leading cause of mortality among breast cancer patients. Epithelial to mesenchymal transition (EMT) is a biological process that plays a fundamental role in facilitating breast cancer metastasis. The present study assessed the efficacy of parthenolide (PTL,Tanacetum parthenium) on EMT and its underlying mechanisms in in both lowly metastatic, estrogen-receptor positive, MCF-7 cells and highly metastatic triple-negative MDA-MB-231 cells. Cell viability was determined by MTT (3-(4,5-dimethy lthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay. Apoptosis was analyzed by FITC (fluorescein isothiocyanate) annexin V apoptosis detection kit. The monolayer wound scratch assay was employed to evaluate cancer cell migration. Proteins were separated and identified by Western blotting. Gene expression was analyzed by quantitative real-time PCR. PTL treatment significantly reduced cell viability and migration while inducing apoptosis in both cell lines. Also, PTL treatment reverses the EMT process by decreasing the mesenchymal marker vimentin and increasing the epithelial marker E-cadherin compared to the control treatment. Importantly, PTL downregulates TWIST1 (a transcription factor and regulator of EMT) gene expression concomitant with the reduction of transforming growth factor beta (TGFβ) protein and gene expression in both cell lines. Our findings provide insights into the therapeutic potential of PTL to mitigate EMT and breast cancer metastasis. These promising results demand in vivo studies.
Long Term Dental Effects in Adolescents Who were Treated for Cancer in Childhood
Authors: HALPERSON ELINOR , Matalon Vered , Goldstein Gal , Spilberg Shirly Saieg , Herzog Karin , Fux-Noy Avia , Shmueli Aviv , Ram Diana , Moskovitz Moti
Published: July 2021

Objectives: Survival following childhood cancer has increased considerably. We examined associations of cancer therapy with the presence of Dental Developmental Anomalies (DDA)among childhood cancer survivors.Procedure: 131 children who were diagnosed with malignancies during childhood were included. Permanent teeth were examined clinically and radiographically to identify DDA: hypocalcification or hypoplasia, microdontia, root changes and hypodontia.Results: observed in 56 (46%) of 121 children, in 309 teeth (9%). Hypocalcification or hypoplasia of enamel appeared in 21 (17%) patients. Altered root development appeared in 26 patients and hypodontia affected 13(10%). Dental anomalies were observed in 36(43%) individuals who received chemotherapy and not radiation, in 20 (52.63%) who received radiotherapy, and in 15 (60%)of those who received head & neck radiotherapy. Young age (under 6 years) was associated with a higher number of malformed teeth among patients who received only chemotherapy. Various chemotherapy agents associated similarly with dental anomalies.Conclusions: Antineoplastic treatment that combines chemotherapy and radiotherapy appears to increase the risk of developing DDA. Radiation to the head and neck area particularly increases the risk of DDA. No specific chemotherapy agent was found to be associated more than the others with dental side effects.
Light-Chain Cardiac Amyloidosis: A Case Report and Review of the Literature
Authors: Gong Jing , Li Yang , Dai Qiming , Liu Naifeng
Published: July 2021

Background: Light-chain (AL) cardiac amyloidosis is a rare cardiomyopathy associated with poor prognosis. Due to the advances of imaging technology, cardiac amyloidosis can be now sufficiently diagnosed without myocardial biopsy. Case presentation: This study reports a 69-year-old female who was admitted with chest distress, abdominal distension, anorexia, resistant hypotension, oliguria, and hyponatremia. The patient was confirmed as AL cardiac amyloidosis with the aid of cardiac MR 2 years after symptom onset. The patient received palliative care due to the end stage of the disease. Conclusions: Early diagnosis by cardiac imaging and etiology-oriented treatment are of importance to improve prognosis of AL cardiac amyloidosis.
Real-world Evaluation of Second Line Chemotherapy for Patients With Advanced Non-small Cell Lung Cancer Harboring Preexisting Interstitial Lung Disease
Authors: Igawa Satoshi , Yokoba Masanori , Takakura Akira , Hosotani Shinji , Nakahara Yoshiro , Sato Takashi , Mitsufuji Hisashi , Sasaki Jiichiro , Naoki Katsuhiko
Published: July 2021

Background: The optimal second and subsequent lines of chemotherapy for patients with non-small cell lung cancer (NSCLC) who have preexisting interstitial lung disease (ILD) are unclear. Hence, we examined the clinical efficacy and safety of second-line chemotherapy in such patients, including any exacerbation of preexisting ILD.Methods: The medical records of patients with NSCLC and preexisting ILD who received both first- and second-line chemotherapy were retrospectively reviewed.Results: Twenty-four patients with a median age of 71 years who were treated between April 2013 and March 2021 were included. The response rate after second-line chemotherapy with S-1 (n=13), docetaxel (n=8), pemetrexed (n=2), or docetaxel plus ramucirumab (n=1) was 12.5%, with a median progression-free survival (2nd line PFS) of 3.8 months. The overall survival from a start of first-line chemotherapy (1st line OS) and post-progression survival (PPS) post-first-line chemotherapy were 18.7 and 9.7 months, respectively. Spearman rank correlation and linear regression analyses showed that PPS was strongly correlated with 1st line OS (R = 0.85, P < 0.00001). Importantly, the 2nd line PFS was also significantly correlated with 1st line OS (R = 0.71, P = 0.0001). While second-line chemotherapy-related acute exacerbation of ILD was observed in 7 patients (29.2%), there were no treatment-related fatalities.Conclusions: Second-line chemotherapy has a strong positive impact on the OS of patients with NSCLC who have preexisting ILD. Given the findings of this study, second-line chemotherapy may be valuable in terms of prolonging long-term OS.
Tropical Terrestrial And Epiphytic Ferns Have Different Leaf Stoichiometry With Ecological Implications.
Authors: Sulaiman Syazwan Pengiran , Cicuzza Daniele
Published: July 2021

Terrestrial and epiphytic herbaceous forest species have different ecology and leaf stoichiometry. In tropical regions, a great component of herbaceous forest species is represented by ferns with different lifeforms. However, little is known about the differences in leaf stoichiometry between the lifeforms. We account for the concentrations of leaf elements (N, P, K, Ca and Mg) between terrestrial and epiphyte lifeforms and evolutionary clades. The fern species were sampled from the forest of Brunei Darussalam. Five leaves were collected from 5 individuals from 16 terrestrial and 4 epiphytic ferns. The leaves were then acid-digested and analyzed. Epiphytic species had higher concentration of most of the leaf elements. The N:P ratio showed that the epiphytic species being much more nutrient-limited, relying on stochastic events, compared to the terrestrial species which have a constant availability of soil elements. Epiphytes showed a higher concentration of P, which could be explained by their luxury consumption. Epiphytes accumulate elements in a higher concentration than is needed by their normal metabolic activity. Furthermore, epiphyte species have a significantly higher concentration of Ca which could be interpreted as necessity of coping with severe habitat conditions with schlerophyll leaves. The results bring in more information on the poorly studied stoichiometry of tropical Asian fern species. Important in understanding the eco-physiology of terrestrial and epiphytic ferns and determining which species are sensitive to the different forest management and the effect of climate change. This, is in addition to the associated mechanisms.
Health-Related Quality of Life In T1DM Patients After High-Dose Cholecalciferol Supplementation.
Authors: de Souza Ana Carolina Contente Braga , de Oliveira Maria Clara Neres Iunes , de Lemos Gabriela Nascimento , Silva Emanuele Rocha da , de Souza Ícaro José Araújo , Silva Wanderson Maia da , de Alcântara Angélica Leite , Said Nivin Mazen , de Moraes Lorena Vilhena , Neto João Felício Abrahão , Passos Simone Rodrigues dos , Monteiro Ádria Aline Alves , de Queiroz Natércia Neves Marques , de Melo Franciane Trindade Cunha , Felício Karem Miléo , Silva Lilian de Souza D’Albuquerque , Pinheiro Danielle Dias da Silva , Mourão Neyla Arroyo Lara , Piani Pedro Paulo Freire , Lobato Isabel Jane Campos , Felício João
Published: July 2021

Background: Type 1 Diabetes Mellitus (T1DM) impacts health-related quality of life (HRQoL). Cross-sectional studies suggest that low levels of vitamin D (VD) may impair HRQoL, however, the effect of VD supplementation on quality of life in patients with T1DM has not yet been clarified. The objective of the study was to evaluate the effects of high-dose VD supplementation on HRQoL in patients with T1DM. Methods: We performed a prospective interventional study with 64 patients supplemented with high doses of cholecalciferol (4,000 IU/day for patients with 25-OH-vitamin D [25(OH)D] between 30 and 60 ng/mL, and 10,000 IU/day for those with 25(OH)D below 30 ng/mL) for 12 weeks. HRQoL was assessed with EuroQol instruments (EQ-5D and EQ-VAS). Results: There was an improvement in global EQ-5D index at the end of vitamin D supplementation. Analysing only the EQ-5D domains, we observed particularly an improvement in mobility (1.3 ± 0.6 versus 1.1 ± 0.3, p <0.01). Evaluating possible outcome influencing variables, we detected a reduction in albuminuria at the end of the trial, without changes in BMI, lipids, blood pressure, glycemic control, insulin doses and in peripheral diabetic neuropathy. We also found a correlation between final albuminuria and the dimensions: mobility (r = 0.6; p <0.01), personal care (r = 0.7; p <0.01), pain and discomfort (r = 0.6; p <0.01) and habitual activities (r = 0.6; p <0.01), suggesting an association between albuminuria reduction and the impact of VD supplementation on HRQoL. Conclusion: Our data showed that high doses of cholecalciferol supplementation can improve HRQoL in patients with T1DM, and the reduction of albuminuria seems to be an important factor in this context.Trial registration: ISRCTN, ISRCTN32601947. Registered 3 June 2017 - Retrospectively registered, http://www.isrctn.com/ISRCTN32601947
The Association Between Metabolic Syndrome and Heart Failure in Middle-aged Men and Women : Population-Based Study of 2 Million Individuals
Authors: Kim Tae-Eun , Kim Hyeongsu , Sung JiDong , Kim Duk-Kyung , Lee Myoung-Soon , Han Seong Woo , Kim Hyun-Joong , Kim Sung Hea , Ryu Kyu-Hyung
Published: July 2021

Background: Although the association between metabolic syndrome (MetS) and heart failure (HF) risk is known, large longitudinal studies that can permit causal inferences are limited. In this study, we investigated metabolic status as a risk factor for HF in middle-aged men and women and evaluated sex differences in various risk factors for HF using nationwide real-world data.Methods: Data obtained from the Korean National Health Insurance Service from 2009 to 2016 were analyzed. A total of 2151597 middle-age subjects (1149642 men and 1001955 women) (between 50 and 59 years old) without a history of Cardiovascular or cerebrovascular disease or malignancy were enrolled. Subjects were divided into three groups according to the number of MetS components: 0 (normal), 1–2 (Pre‐MetS) or 3–5 (MetS) based on the National Cholesterol Education Program Adult Treatment Panel III criteria. Cox proportional hazard models were used to estimate the association between MetS and incident HF after adjusting for clinical risk factors.Results: At baseline, MetS existed in 23,77% of men and 10.58% of women. Pre-MetS and MetS increased the risk of HF: the hazard ratio (95% confidence interval) of pre-MetS was 1.508 (1.287-1.767) in men and 1.395 (1.158-1.681) in women; the hazard ratio (95% confidence interval) of MetS was 1.711 (1.433-2.044) in men and 2.144 (1.674-2.747) in women. Current smoking, low hemoglobin level, underweight (BMI<18.5) and high creatinine level as well as acute myocardial infarction were also predictors of HF in both men and women.Conclusions: This study confirmed that pre-MetS and MetS are risk factors for HF in middle-aged men and women. The effect of MetS on the occurrence of HF was stronger in women than in men. Pre-MetS was also a predictor of HF but was associated with a lower risk than MetS.
Association Between Plasma Glycosylated Hemoglobin A1c/high-density Lipoprotein Cholesterol Ratio and Carotid Atherosclerosis: A Real-world Study
Authors: Hu Xiangming , Li Wei , Wang Chenyang , Zhang Haotian , Lu Haoyu , Li Guang , Zhou Yingling , dong haojian
Published: July 2021

Background: Diabetes mellitus (DM) and dyslipidemia are the main risk factors for atherosclerosis. Elevated glycosylated hemoglobin A1c (HbA1c) and reduced high-density lipoprotein cholesterol (HDL-C) are associated with the progression of atherosclerosis. The aim of this study is to explore the relationship between the HbA1c/HDL-C ratio and atherosclerosis evaluated using carotid artery intima-media thickness (cIMT) and carotid artery plaque.Methods: In this retrospective study, we enrolled 1304 patients who had multiple cardiovascular risk factors or symptoms of suspected coronary artery disease. cIMT and carotid artery plaque were measured using ultrasonography. Logistic regression was used to explore the correlation between the HbA1c/HDL-C ratio and cIMT or carotid artery plaque. We used restricted cubic spline curves to assess nonlinear relationships between the HbA1c/HDL-C ratio and cIMT or carotid artery plaque.Results: With increased quartiles of HbA1c/HDL-C, patients had higher cIMT and a greater carotid plaque burden. After adjusting for other relevant clinical covariates, patients with the highest HbA1c/HDL-C ratio (Quartile 4 [Q4]) had a 2.88-times (95% confidence interval [CI]: 2.02–4.10, P<0.001) more abnormal mean cIMT, 3.72-times (95% CI: 2.55–5.44, P<0.001) more abnormal maximum cIMT, and 2.58-times (95% CI: 1.70–3.91, P<0.001) greater carotid artery plaque burden compared with patients who had the lowest HbA1c/HDL-C ratio (Q1). Moreover, the association of HbA1c/HDL-C with atherosclerosis remained significant in a subsample of patients with and without DM.Conclusions: As a novel compound indicator for evaluating blood glucose homeostasis and dyslipidemia, the HbA1c/HDL-C ratio was positively correlated with carotid atherosclerosis evaluated using the mean and maximum cIMT as well as the carotid artery plaque burden.
Structural insights into the gating mechanism of human Cx43/GJA1 gap junction channel
Authors: Woo Jae-Sung , Lee Hyuk-Joon , Cha Hyung Jin , Jeong Hyeongseop , Lee Seu-Na , Lee Chang-Won , Kim Minsoo , Yoo Jejoong
Published: July 2021

Connexin family proteins assemble into hexameric hemichannels in a cell membrane, which dock together between two adjacent membranes to form gap junction intercellular channels (GJIChs). The most ubiquitously expressed connexin Cx43 plays important roles in numerous biological processes. Here we report cryo-EM structures of Cx43 GJIChs at 3.1–3.6 Å resolutions, which show dynamic conformational changes of N-terminal helices (NTHs) caused by pH change or C-terminal truncation. Cx43 GJIChs in a channel-closing condition contain 12 protomers in gate-covering NTH (GCN) conformation, while those in opening conditions have varying compositions of GCNs and pore-lining NTHs (PLNs) resulting in various pore dimensions and electrostatic surface potentials. GCN-to-PLN transition accompanies π-helix formation in the first transmembrane helix (TM1), movement of TM2-4 that creates a side opening to the membrane, and structural stabilization of the cytoplasmic loop. Our study provides structural insights into the intercellular ion/metabolite transfer and the lateral lipid transport through Cx43 GJICh.
Cataract by electrocution. Case report
Authors: Fariña MD. Eliana Duarte , Vera Guillermo Raúl , Arrúa Martin , Gonzalez Luis
Published: July 2021

IntroductionElectrical burns generate a special type of injury. the longer a person is exposed to electricity, the worse the injuries will be. Cataracts resulting from this mechanism are of low frequency. Casewe present a case of a cataract secondary to an electrical accident, whose vision worsened over time, which led him to the service consultation. DiscussionThe formation of cataracts after various types of exposure to electricity has been reported but the exact pathogenesis of electrical cataract is controversial, and several theories have been proposed. ConclusionThis type of accident or events related to electrocution should have a complete routine ophthalmology evaluation, as soon as the patient is stable. Although they turn out to be a minimal cause of frequency, you should think about the possibility of their existence. Generally, these cases, without previous affections is considered to have a good visual prognosis.
Dipeptidyl Peptidase-4 Inhibitors Reduced Long-term Cardiovascular Risk in Japanese Diabetic Patients After Percutaneous Coronary Intervention via Insulin-like Growth Factor-1 Axis: A 10-year Follow-up Study
Authors: Chikata Yuichi , Iwata Hiroshi , Miyosawa Katsutoshi , Koike Takuma , Yasuda Hidetoshi , Funamizu Takehiro , Doi Shinichiro , Endo Hirohisa , Wada Hideki , Naito Ryo , Ogita Manabu , Dohi Tomotaka , Kasai Takatoshi , Isoda Kikuo , Okazaki Shinya , Miyauchi Katsumi , Minamino Tohru
Published: July 2021

Background: Dipeptidyl-peptidase-4 inhibitors (DPP4i) have become one of the most used antidiabetic medications worldwide due to their good safety profiles and tolerability with a low risk of hypoglycemia, however, no large cardiovascular outcome trials (CVOTs) have shown any significant superiority with respect to reducing cardiovascular risk. On the contrary, since observational studies have suggested the effects of DPP4i are enhanced some populations, such as Asians and those who without overweight, their prognostic benefit is still under debate. Therefore, the aim of this study was to assess the prognostic impact of DPP4i in patients with both diabetes and coronary artery disease (CAD) through the insulin-like growth factor-1 (IGF-1) axis, a substrate of DPP4 and it is relevant for the cardiovascular system.Methods: This single-center analysis involved consecutive Japanese diabetic patients who underwent percutaneous coronary intervention (PCI) for the first time between 2008 and 2018 (n=885). Primary and secondary endpoints were set as cardiovascular (CV)-death and the composite of CV-death, non-fatal myocardial infarction and ischemic stroke (3P-MACE). Serum levels of IGF-1 and its main binding protein (IGF- binding protein 3: IGFBP-3) were measured by ELISA.Results: Unadjusted Kaplan-Meier analyses revealed reduced incidences of CV-death and 3P-MACE by DPP4i, which was particularly enhanced in patients who were not overweight (BMI ≤25). Multivariate Cox hazard analyses consistently indicated reduced risks of CV-death by DPP4i at PCI (hazard ratio (HR): 0.39, 95% confidence interval (CI): 0.16–0.82, p=0.01) and 3P-MACE (HR: 0.47, 95% CI: 0.25–0.84, p=0.01), respectively. Moreover, elevated IGF-1 activity indicated by the IGF-1/IGFBP-3 ratio was associated with decreased risks of both endpoints and it was significantly higher in patients with DPP4i (p<0.0001).Conclusion: The findings of the present study indicate that DPP4i improved outcomes in Japanese diabetic patients following PCI, in which the beneficial effects might be mediated by DPP4-IGF-1 axis. Trial registration: This study reports the retrospective analysis of a prospective registry database of patients who underwent PCI at Juntendo University Hospital, Tokyo, Japan (Juntendo Physicians’ Alliance for Clinical Trials, J-PACT), which is publicly registered (University Medical Information Network Japan - Clinical Trials Registry, UMIN-CTR 000035587).
Split luciferase-based assay to detect botulinum neurotoxins using human motor neurons derived from induced pluripotent stem cell.
Authors: Cotter Laurent , Yu Feifan , De Lamotte Juliette Duschene , Dong Min , Krupp Johannes , Nicoleau Camille
Published: July 2021

Botulinum neurotoxins (BoNTs) have been widely used clinically as a muscle relaxant. These toxins target motor neurons and cleave proteins essential for neurotransmitter release like Synaptosomal-associated protein of 25 kDa (SNAP-25). Most in vitro assays for BoNT testing use rodent cells or immortalized cell lines, which showed limitations in accuracy and physiological relevance. Here, we report a cell-based assay for detecting SNAP25-cleaving BoNTs by combining human induced Pluripotent Stem Cells (hiPSC)-derived motor neurons and a luminescent detection system based on split nanoluc luciferase. This assay is convenient, rapid, free-of-specialized antibodies, and can discriminate the potency of different BoNTs, with a detection sensitivity of femtomolar concentrations of toxin and can be used to study the different steps of BoNT intoxication. Abreviations: BoNT, Botulinum neurotoxin, SNAP-25, Synaptosomal-associated protein of 25 kDa, hiPSC, human induced Pluripotent Stem Cells, SNARE, soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor, SV2, synaptic vesicle proteins, MLB, mouse lethality bioassay, LD50, toxin’s dose lethal for half of the animal injected, CB-assay, cell-based assays, FRET, Förster resonance energy transfer, Concanamycin A, EC50, Half maximal effective concentration, MNs, motor neurons.
18nm n-channel and p-channel Dopingless Asymmetrical Junctionless DG-MOSFET: Low Power CMOS Based Digital and Memory Applications
Authors: Mendiratta Namrata , Tripathi Suman Lata
Published: July 2021

In this paper, an 18nm dopingless asymmetrical junctionless (AJ) double gate (DG) MOSFET has been designed for suppressed short channel effects (SCEs) for low power applications. A desired ON and OFF state current ratio with subthreshold performance parameters under limit, is the major focus of the proposed transistor. Different sensitivity parameters of dopingless AJ DG MOSFET such as drain extension, length of gate overlapping and oxide thickness are compared with the AJ DG MOSFET with doped channel region. The ON-state current obtained is 3.80 x 10-6 A/µm with reduced OFF-state leakage current up to 1.37 x 10-17 A/µm. The subthreshold slope (SS) and drain induced barrier lowering (DIBL) of the device obtained are 59.5 mV/decade and 10.5 mV/V respectively. Temperature analysis of proposed device at various temperature such as 250 K, 300 K, 350 K and 400 K shows a small variation in OFF-state current (< 15%). Additionally, a p-channel AJ DG MOSFET along with n-channel AJ DG MOSFET are designed and their performance is evaluated for CMOS inverter circuit and 6T SRAM cell. All the design and analysis has been done with a 2D/3D Visual TCAD device simulator.
Induction of CD73 Prevents Death After Emergency Open Aortic Surgery for a Ruptured Abdominal Aortic Aneurysm – A Randomized, Double-Blind, Placebo-Controlled Study
Authors: Hakovirta Harri , Jalkanen Juho , Saimanen Eija , Kukkonen Tiia , Romsi Pekka , Suominen Velipekka , Vikatmaa Leena , Valtonen Mika , Karvonen Matti , Venermo Maarit
Published: July 2021

Background: Mortality remains high after emergency open surgery for a ruptured abdominal aortic aneurysm (RAAA). The aim of the present study was to assess, if intravenous (IV) Interferon (IFN) beta-1a improve survival after surgery by up-regulating Cluster of differentiation (CD73). Methods: This is a multi-center phase II double-blind, 2:1 randomized, parallel group comparison of the efficacy and safety of IV IFN beta-1a vs. placebo for the prevention of death after open surgery for an infra-renal RAAA. All study patients presented a confirmed infra-renal RAAA, survived the primary emergency surgery and were treated with IFN beta-1a (10μg) or matching placebo for 6 days after surgery. Major exclusion criteria included irreversible hemorrhagic shock, unconsciousness at arrival, chronic renal replacement therapy, diagnosed liver cirrhosis, severe congestive heart failure, advanced malignant disease, primary attempt of endovascular aortic repair (EVAR), and per-operative suprarenal clamping over 30 minutes. Main outcome measure was all-cause mortality at day 30 (D30) from initial emergency aortic reconstruction. Results: Out of 40 randomized patients 38 were included in the outcome analyses (27 active arm and 11 placebo). Treatment groups were comparable by baseline characteristics. D30 all-cause mortality was 22.2% (6/27) in the active arm and 18.2% (2/11) in the placebo arm (OR 1.30; 95% CI, 0.21 – 8.19). The most common adverse event relating to the IFN beta-1a was pyrexia (20.7% in the active arm vs. 9.1% in the placebo arm). High level of serum CD73 associated with survival (P = 0.001) whereas the use of glucocorticoids associated with a poor CD73 response and poor survival in the active arm (P = 0.002).Conclusions: IV IFN beta-1a was well tolerated. Survival after open RAAA surgery associated strongly with up-regulation of serum CD73, but the use of glucocorticoids blocked IFN beta-1a from up-regulating CD73. Trial registration: ClinicalTrials.gov NCT03119701Funding/Support: This study was sponsored by Faron Pharmaceuticals Ltd.
CT Radiomics Nomogram for the Preoperative Prediction of Severe Post-Hepatectomy Liver Failure in Patients with Huge (≥10 cm) Hepatocellular Carcinoma
Authors: Xiang Fei , Liang Xiaoyuan , Yang Lili , Liu Xingyu , Yan Sheng
Published: July 2021

Background To establish a radiomics-based nomogram for predicting severe (grade B or C) post-hepatectomy liver failure (PHLF) in patients with huge (≥10 cm) hepatocellular carcinoma (HCC).Methods 186 patients with huge HCC (n = 131 for training dataset and n = 55 for test dataset) who underwent curative hepatic resection were included. The least absolute shrinkage and selection operator approach was applied to develop the radiomics signature for grade B or C PHLF prediction in the training dataset. A multivariable logistic regression model was used by incorporating radiomics signature and other clinical predictors to establish a radiomics nomogram. A decision tree was created to stratify the risk for severe PHLF.Results The radiomics signature consisting of nine features predicted severe PHLF with an AUC of 0.766 and 0.745 in the training and test datasets, respectively. The radiomics nomogram was generated by integrating the radiomics signature, the extent of resection and model for end-stage liver disease (MELD) score. The nomogram exhibited satisfactory discrimination and calibration, with an AUC of 0.842 and 0.863 in the training and test datasets, respectively. Decision tree split patients into 3 risk classes: low-risk patients with radiomics score < -0.247 and MELD score < 10 or，radiomics score ≥ -0.247 and underwent partial resections; intermediate-risk patients with radiomics score < -0.247 but MELD score ≥10; high-risk patients with radiomics score ≥ -0.247 and underwent extended resections.Conclusions The radiomics nomogram was able to predict severe PHLF in huge HCC patients. Decision tree may be useful in surgical decision-making for huge HCC hepatectomy.
5-methylcytosine profiles in mouse transcriptomes suggest the randomness of m5C formation catalyzed by RNA methyltransferase
Authors: Liu Junfeng
Published: July 2021

5-methylcytosine (m5C) is a type of chemical modification on the nucleotides and is widespread in both DNA and RNA. Although the DNA m5C has been extensively studied over the past years, the distribution and biological function of RNA m5C still remain to be elucidated. Here, I explored the profiles of RNA m5C in four mouse tissues and found that the methylation rates of cytosine were the same with the averages of methylation level at single-nucleotide level. Furthermore, I gave a mathematical formula to describe the observed relationship and analyzed it deeply. The sufficient necessary condition for the given formula suggests that the methylation levels at most m5C sites are the same in four mouse tissues. Therefore, I proposed a hypothesis that the m5C formation catalyzed by RNA methyltransferase is random and with the same probability at most m5C sites, which is the methylation rate of cytosine. My hypothesis can be used to explain the observed profiles of RNA m5C in four mouse tissues and will be benefit to future studies of the distribution and biological function of RNA m5C in mammals.
Long-term Outcomes and Prognostic Factors in Papillary Thyroid Microcarcinoma Patients with Distant Metastases
Authors: Weng Huai-Yu , Yan Ting , Qiu Wang-Wang , Xi Chuang , Hou Li-Ying , Yang Zhi-Li , Qiu Zhong-Ling
Published: July 2021

PurposesDistant metastasis from papillary thyroid microcarcinoma (PTMC) is extremely rare and the long-term outcome and independent prognostic factors remain unclear.The present study aimed to investigate clinicopathological characteristics and evaluate the long-term outcomes and prognostic factors of PTMC patients with distant metastases (DM) who underwent surgery and radioactive iodine (131I) treatment.MethodsWe retrospectively reviewed the medical records of 13,441 patients with thyroid cancer (including 1,697 cases with PTMC) who underwent 131I treatment at our institution between January 2008 and December 2019. PTMC patients with distant metastases with sufficient clinical follow-up data were enrolled in this cohort study. The overall survival (OS) and progression-free survival (PFS) were analyzed by the Kaplan–Meier method and the prognostic factors were assessed by Cox proportional hazards. ResultsThirty-three PTMC patients with DM were enrolled in this study. The median follow-up was 75 months (range: 5–151 months).The 5-year and 10-year OS rates were 96.97% and 81.41%, respectively, and the 5-year and 10-year PFS rates were 90.46% and 69.68%, respectively. Multivariate analysis showed that male sex(P=0.005) , radioactive iodine refractory PTMC (P=0.033) and symptomatic DM (P=0.022) were significantly associated with worse 10-year PFS in PTMC patients with DM. No independent predictor related to poor 10-year OS found in the present study.ConclusionsThe prognosis of PTMC patients becomes worse after the development of DM. Male sex, radioactive iodine refractory PTMC and symptomatic DM were identified as independent factors associated with PFS.
Optimization in the Aqueous Two Phase Extraction of a Toxic Metabolite, Solasodine, From S. Mauritianum and Analysis via UHPLC-qTOF-MS
Authors: Mokgehle Tebogo , Madala Ntakadzeni , Gitari Wilson , Tavengwa Nikita
Published: July 2021

Aqueous two phase extraction (ATPE) was applied in the extraction of an allelochemical, solasodine, from an invasive plant, Solanum mauritianum. Central composite design was performed which included numerical parameters such as time and mass of plant powder. The categorical factors included the type of salt used in aiding extraction such as the chaotrope (NaCl) and kosmotrope (Na2CO3). Fitting the central composite design response surface model to the experimental data generated a quadratic model with a good fit (R2 = 0.925). The linear effect of mass of plant powder was a statistically significant (p < 0.05) parameter for solasodine extraction. The optimized conditions for the extraction of solasodine in the presence of NaCl or Na2CO3 were time: 10 min and mass of plant powder: 1.2 g. Corresponding to these conditions, the maximal mean extraction based on multiple reaction monitoring (MRM) transition of solasodine (m/z 414 → 396) on the UHPLC-qTOF-MS was 233.65 mg kg-1 and 413.50 mg kg-1 for NaCl and Na2CO3, respectively. The greater extraction ability of the kosmotrope was due to the higher negative charge density of the carbonate ion during salting-out. Furthermore, the synergistic effect of mass of plant powder and salting-out was shown to enhance extraction of solasodine compared to the chaotrope. The kosmotrope assisted solasodine ATPE extracts from Solanum mauritianum, can potentially be applied as antipathogenic agents in medicine while simultaneously limiting the allelopathic impact of Solanum mauritianum.