bluuebunny/crossref_metadata_2025 huggingface dataset:
Nitric oxide down-regulates voltage-gated Na+ channel in cardiomyocytes via transcriptional S-nitrosylation signaling pathway
Authors: Wang Pu , Wei Mengyan , Zhu Xiufang , Liu Yangong , Yoshimura Kenshi , Zheng Mingqi , Liu Gang , Kume Shinichiro , Morishima Masaki , Kurokawa Tatsuki , Ono Katsushige
Published: February 2021

Nitric oxide (NO) is produced from endothelial cells and cardiomyocytes composing the myocardium and benefits cardiac function through both vascular-dependent and -independent effects. This study was purposed to investigate the possible adverse effect of NO focusing on the voltage-gated Na+ channel in cardiomyocytes. We carried out patch-clamp experiments on rat neonatal cardiomyocytes demonstrating that NOC-18, an NO donor, significantly reduced Na+ channel current in a dose-dependent manner by a long-term application for 24 h, accompanied by a reduction of Nav1.5-mRNA and the protein, and an increase of a transcription factor forkhead box protein O1 (FOXO1) in the nucleus. The effect of NOC-18 on the Na+ channel was blocked by an inhibitor of thiol oxidation N-ethylmaleimide or a disulfide reducing agent disulfide 1,4-Dithioerythritol, suggesting that NO is a negative regulator of the voltage-gated Na+ channel through thiols in regulatory protein(s) for the channel transcription.
Estimating HIV pre-exposure prophylaxis (PrEP) use and analysis of HIV PrEP needs among men who have sex with men in Germany
Authors: Marcus Ulrich , Schmidt Daniel , Schink Susanne Barbara , Koppe Uwe
Published: February 2021

Data on PrEP use in Germany is not collected systematically. We aim to estimate the number of PrEP users among men having sex with men (MSM) and describe PrEP use in Germany from 2017 through 2020. Moreover, we analyse whether PrEP needs expressed in 2017 could have been met by the expansion of PrEP until 2020.
We estimated the number of PrEP users using drug prescription data, information on on-demand/intermittent PrEP use from online surveys, and number of online profiles indicating PrEP use, based on varying assumptions about the proportion of on-demand/intermittent and daily PrEP users and on the average number of PrEP pills used. Factors associated with intention to use PrEP were identified by a multivariable logistic regression analysis among respondents to an online survey. We estimated the number of MSM in need for PrEP in 2017 based on four groups defined among the survey respondents, combining respondents intending to use PrEP and respondents indicating substantial sexual risks. We used data and assumptions on self-selection biases to estimate a range for the absolute size of these groups among gay men in Germany.
Depending on assumptions, we estimated a total of 15,600 to 21,600 PrEP users in Germany by the end of June 2020, which corresponds to between 40 and 55% of men with the intention to use PrEP in 2017. Distributions of PrEP users from different data sources and PrEP prescriptions by federal state in Germany were highly correlated, except for major deviations for Berlin with a higher proportion of prescriptions in Berlin compared to the proportion of survey participants using PrEP. A correlation between the regional distribution of intention to use PrEP in 11/2017 and actual PrEP use by 06/2020 suggested an unequal regional distribution of unsatisfied needs. The number of men with unmet PrEP needs ranged between 27,500 and 93,000 in 06/2020.
PrEP use in Germany has increased considerably between 10/2017 and 06/2020, but large regional inequalities persist. Results suggested that PrEP is not fully accessible and that there is a need to expand services and encourage demand.
Clinical Feeding Evaluation and Videofluoroscopy: An Integrative Approach to Feeding Management in Children With Suspected Aspiration
Authors: Stafler Patrick , Akel Khaled , Eshel Yuliana , Shimoni Adi , Grozovsky Sylvia , Mei-Zahav Meir , Levine Hagit , Gendler Yulia , Blau Hannah , Prais Dario
Published: February 2021

BackgroundVideo fluoroscopy swallow studies (VFSS) are considered gold standard for the diagnosis of aspiration in children but require resources and radiation compared to clinical feeding evaluation (CFE). We evaluated their added value for diagnosis, feeding management and clinical status.MethodsA retrospective single-center cohort study of children aged 0-18 years, referred for VFSS at a tertiary pediatric hospital. Results 113 children, median age (range) 2.2 years (0.1-17.9) successfully completed VFSS. Forty-six (41%) had oropharyngeal aspiration, 9 (8%) overt alone and 37 (33%) including silent aspirations. Underlying medical conditions included clinically suspected aspiration lung disease (ALD), 87 (77%); neurologic disease, 73 (64%); gastrointestinal disease, 73 (64%) and congenital heart disease, 42 (37%), not mutually exclusive. Those with ALD or cerebral palsy were more likely to have aspiration by VFSS, OR 3.2 and 9.8 respectively. Sensitivity and specificity of CFE for VFSS diagnosis of aspiration were 71% and 84% respectively. Feeding recommendations after VFSS differed significantly from those based on prior CFE, p<0.001: The rate of exclusively orally fed children increased from 65% to 79%, p=0.006 and exclusively enterally fed children from 10% to 14%; p=0.005. During the following year, there were significantly less antibiotic courses, as well as total and respiratory admissions. Conclusions In this population of children with a high prevalence of clinically suspected ALD, VFSS refined diagnosis and altered feeding management compared to CFE, with subsequent clinical improvement.
Estimation of the serial interval of COVID-19 in Ireland using contact tracing data
Authors: McAloon Conor G. , Wall Patrick , Griffin John , Casey Miriam , Barber Ann , Codd Mary , Gormley Eamonn , Butler Francis , Messam Locksley L. McV , Walsh Cathal , Teljeur Conor , Smyth Breda , Nolan Philip , Green Martin J. , O’Grady Luke , Culhane Kieran , Buckley Claire , Carroll Ciara , Doyle Sarah , Martin Jennifer , More Simon J .
Published: February 2021

BackgroundThe serial interval is the period of time between the onset of symptoms in an infector and an infectee and is an important parameter which can impact on the estimation of the reproduction number. Whilst several parameters influencing infection transmission are expected to be consistent across populations, the serial interval can vary across and within populations over time. Therefore, local estimates are preferable for use in epidemiological models developed at a regional level. We used data collected as part of the national contact tracing process in Ireland to estimate the serial interval of SARS-CoV-2 infection in the Irish population, and to estimate the proportion of transmission events that occurred prior to the onset of symptoms.ResultsAfter data cleaning, the final dataset consisted of 471 infected close contacts from 471 primary cases. The mean serial interval was 4.0 (95% confidence intervals 3.75, 4.31) days, whilst the 25th, 50th and 75th percentiles were 2, 4 and 6 days respectively. We found that intervals were lower when the primary or secondary case were in the older age cohort (greater than 64 years). Simulating from an incubation period distribution from international literature, we estimated that 67% of transmission events had greater than 50% probability of occurring prior to the onset of symptoms in the infector.ConclusionsWhilst our analysis was based on a large sample size, data were collected for the primary purpose of interrupting transmission chains. Similar to other studies estimating the serial interval, our analysis is restricted to transmission pairs where the infector is known with some degree of certainty. Such pairs may represent more intense contacts with infected individuals than might occur in the overall population. It is therefore possible that our analysis is biased towards shorter serial intervals than the overall population.
Mg-doped and chemo-thermally treated ZnO nanoflowers for ethanol sensing
Authors: Maity Santanu , Sahu P.P , Thomas Tiju
Published: February 2021

ZnO nanostructures are promising for a wide range of applications, including gas sensors. Ethanol sensing using ZnO remains unexplored though. In this paper, we report ethanol-sensing using un-doped ZnO nano flowers and Mg doped ZnO nano flowers. These are grown using a rather simple chemo-thermal process, making this a plausibly scalable technology. To study the structural and morphological properties of undoped ZnO and Mg doped ZnO nanoflowers, Raman spectroscopy, Fourier Transform Infrared Spectroscopy (FTIR), x-ray diffraction and Field Emission Scanning Electron Microscopy (FESEM) are carried out. Ethanol sensing properties of undoped ZnO and Mg doped ZnO nanoflower devices are investigated toward different ethanol concentration (concentration range of 1–600 ppm at 100°C–200°C). Our findings show that 15% Mg doped ZnO nano flower is better than ZnO nano flower for ethanol gas-sensing applications.
Antenatal care visits of child-bearing mothers having a child five years preceding in the survey and associated factors in Benchi-Sheko Zone, Southwestern Ethiopia:Cross-sectional study
Authors: Gelaw Assaye Belay , Andargie Solomon Abebaw , Terefe Abiyot Negsh
Published: February 2021

Background: Antenatal care (ANC) is the service given by the caregiver for pregnant women to make safe the health of both pregnant women and babies during the pregnancy period. The objective of the current study was to persuade high-quality public health service and plan the mothers and their households expressively and mentally for being motherhood by ever-increasing antenatal care visits from health institutions.Methods: Community-based cross-sectional study design was applied. Cross-sectional survey design mainly used for the collection of information on the Utilization of Antenatal Care Visit of Women During Pregnancy and its Related Factors in Bench-Sheko Zone, South Nation Nationalities Peoples of Region, Southwestern Ethiopia: Cross-sectional study. The study populations are all populations who are living in the study area, South Nation Nationalities peoples of Region, Southwestern Ethiopia.Results: Evidence tells us, one hundred twenty-nine (16.9%) of pregnant women were not visited by the caregiver during pregnancy. Around eighty-three percent of pregnant women were visited in health institutions at least once prior in the five years in the survey. The Poisson regression model was preferred to fit the data. As the output indicated in analysis, the odds ratio of women whose husband education status is illiterate is equal to exp(-0.272)=0.76(95% CI:-0.507,-0.038) (other variables are adjusted), it indicates that the women whose husband education status is 0.76 less likely to ANC visit than women whose husband education status is higher and above. Conclusions: The remark conclusion that the source of information, religion, educational status, birth order, knowledge of danger signs for pregnancy, and service satisfaction were significant at the alpha level of significance on the ANC visit of Women during pregnancy.
MHC Haplotyping of SARS-CoV-2 patients: HLA subtypes are not associated with the presence and severity of Covid-19 in the Israeli population
Authors: Shachar Shay Ben , Barda Noam , Manor Sigal , Israeli Sapir , Dagan Noa , Carmi Shai , Balicer Ran , Zisser Bracha , Louzoun Yoram
Published: February 2021

HLA haplotypes were found to be associated with increased risk for viral infections or disease severity in various diseases, including SARS. Several genetic variants are associated with Covid-19 severity. However, no clear association between HLA and Covid-19 incidence or severity has been reported. We conducted a large scale HLA analysis of Israeli individuals who tested positive for SARS-CoV-2 infection by PCR. Overall, 72,912 individuals with known HLA haplotypes were included in the study, of whom 6,413 (8.8%) were found to have SARS-CoV-2 by PCR. a Total of 20,937 subjects were of Ashkenazi origin (at least 2/4 grandparents). One hundred eighty-one patients (2.8% of the infected) were hospitalized due to the disease. None of the 66 most common HLA loci (within the five HLA subgroups; A, B, C, DQB1, DRB1) was found to be associated with SARS-CoV-2 infection or hospitalization. Similarly, no association was detected in the Ashkenazi Jewish subset. Moreover, no association was found between heterozygosity in any of the HLA loci and either infection or hospitalization.We conclude that HLA haplotypes are not a major risk/protecting factor among the Israeli population for SARS-CoV-2 infection or severity.
APG(Acceleration Plethysmography) Correlate with Moods in Nursing Workers with Fatigue after Work
Authors: Ishizuka Miki , katsuda Shin-ichiro , Hazama Akihiro
Published: February 2021

Fatigue or stress in the workplace is a serious problem. The profession of nursing, in particular, is physically and mentally stressful, which often leads to job retrenchment, and shortage of workers. Solving this problem requires a deeper understanding of the fatigue and stress caused by work, and there is a need to consider countermeasures. Purpose: The purpose of this study is to assess the correlation between the psychological and physiological fatigue of healthy nurses during normal work, and to measure nursing stress and fatigue more conveniently. Method: We examined healthy nurses’ physiology (Acceleration Plethysmography: APG and Blood Pressure: BP) and psychology (Visual Analogue Scale: VAS and Mood Inventory Scale: MIS) before and after a normal workday. Results: We observed that after a normal days’ work, the nurses’ autonomic activity, high-frequency component power (HF), low-frequency component power/high-component power ratio (LF/HF ratio), and total power (LF་HF) increased significantly. Psychologically, VAS increased significantly, while the MIS Refreshing Mood decreased remarkably. The HF value correlated significantly with VAS and the MIS Refreshing Mood. The MIS Refreshing Mood correlates significantly with increased sympathetic and autonomic nervous function. Thus, an MIS test may alternative for physiological tests to detect fatigue more quickly and easily. Conclusion: These findings may help nurses and other workers reduce fatigue, cope with stress, and prevent illness. We hope this study will contribute towards addressing the issues related to workers’ mental health in the workplace.
Down-regulation of EGFL8 regulates migration, invasion and apoptosis of hepatocellular carcinoma through activating Notch signaling pathway
Authors: Wu Fan , Zhang Fang-Yong , Tan Guo-Qian , Chen Wei-Jia , Huang Biao , Yan Lun , Zhang Hao-Lu , Chen Shi , Jiao Yang , Wang Bai-Lin
Published: February 2021

Background: Our previous studies have reported the down-regulation of EGFL8 correlates to the development and prognosis of colorectal and gastric cancer. The present study is carried out to explore the expression pattern and role of EGFL8 in hepatocellular carcinoma (HCC).Methods and materials: EGFL8 expression in 102 cases of HCC tissues matched with adjacent non-tumorous liver tissues and three liver cancer cell lines with different metastatic capacity was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot. Moreover, the clinicopathological features and prognosis of HCC patients were separately correlated with expression levels of EGFL8. Subsequently, the gain‑and loss‑of‑function experiments were carried out to investigate the biological function of EGFL8 in HCC. We also used N-[N-(3,5-Difluorophenacetyl-L-alanyl)]-(S)-phenylglycine t-butyl ester (DAPT), an inhibitor for Notch signaling pathway, in these experiments to verify the involvement of Notch signaling pathway in the effects of EGFL8. Additionally, a mouse model was established to investigate the effect of EGFL8 on metastasis of HCC cells. The expression of Notch signaling pathway in HCC cells and xenograft mouse tumors were detected by Western blot and immunohistochemistory.Results: The expression of EGFL8 was significantly decreased in HCC tissues and EGFL8 down-regulation correlated to multiple nodules, vein invasion, high TNM stage and poor prognosis of HCC. Interestingly, the expression levels of EGFL8 in three liver cancer cell lines were negatively associated with their metastatic capacity. In vitro and in vivo experiments indicated that EGFL8 obviously suppressed metastasis and invasion of HCC cells but slightly promoted apoptosis. Meanwhile, the expression of Notch signaling pathway was obviously suppressed in EGFL8 overexpressed HCCLM3 cells and xenograft mouse tumors generated from these cells but markedly elevated in EGFL8 depleted Hep3B cells. Furthermore, the up-regulated expression of Notch signaling pathway and effects induced by EGFL8 knockdown in Hep3B cells could be counteracted by DAPT treatment. Conclusion: The down-regulation of EGFL8 was correlated to progression and poor prognosis of HCC and regulates HCC cell migration, invasion and apoptosis through activating the Notch signaling pathway, suggesting EGFL8 as a novel therapeutic target and a potential prognostic marker for HCC.
Production and characterization of the maximum liquid product obtained from co-pyrolysis of sugarcane bagasse and thermocol waste
Authors: Mohapatra Sowhm Swain , Singh Raghubansh Kumar
Published: February 2021

The current study explores co-pyrolysis of sugarcane bagasse, and thermocol waste in a semi-batch reactor to evaluate the influence of temperature, and blending ratio on yield of products, and reaction time, and thereby characterize the maximum liquid product. The properties of liquid product (bio-oil), and the solid product (bio-char) obtained from thermal sugarcane bagasse, and co-pyrolysis sugarcane bagasse: thermocol waste bio-oil were investigated for physicochemical characterizations. The compositional analysis result of the co-pyrolysis liquid product established the presence of several aromatic compounds. The co-pyrolysis liquid product manifested a higher calorific value, carbon, and hydrogen content as compared to sugarcane bagasse thermal pyrolysis bio-oil. The co-pyrolysis liquid product can be used as a liquid fuel in internal combustion engines, as well as a precursor for value-added chemicals. The properties of bio-char suggested it can be used as a solid fuel, as well as an adsorbent.
Monitoring Settlements Growth and Development in Algiers City Eastern Area
Authors: Bellout Azzeddine , Vaz Eric , Damásio Bruno
Published: February 2021

Monitoring change detection in urban land use/land use is essential as it pertains to one of the main environmental change drivers, leading to urban pressures impacting cultivated areas. Algiers' eastern area is one of the critical areas of Algiers' state, and it is affected by the growth and development of the composing residential areas. This research aims to analyze the current issues, including aspects of land use, residential patterns, residential development directions, and characteristics of the communities in residential growth areas. We used Landsat 8 Operational Land Imager (OLI) and Thermal Infrared Sensor (TIRS) data as the primary data source, and maps and statistical data as the secondary. The annual growth of urban land has been studied over the past six years in Algiers' eastern area. Descriptive statistics and spatial analysis allowed assessing the data further. Results indicate that there has been a 100% expansion of the residential regions during the decade from 2014 to 2020. Population in the expansion areas increased by 2%. Future studies should understand the impact of rapid urban lands on social, economic, and environmental sustainability. It will also close the gap between currently available data sources, especially regarding the lack of reliable data and environmental and urban planning for Algiers' municipality. This aids directly in developing experimental models to predict future changes of land with great statistical confidence.
Microplastic fibers influence Ag toxicity and bioaccumulation in Eisenia andrei but not in Enchytraeus crypticus
Authors: Tourinho Paula S , Loureiro Susana , Talluri VSSL Prasad , Dolar Andraž , Verweij Rudo , Chvojka Jiří , Michalcová Alena , Kočí Vladimír , Gestel Cornelis A.M. van
Published: February 2021

Microplastic fibers (MF) are released from synthetic textiles during washing and end up in the wastewater. Similarly, silver nanoparticles (AgNP), incorporated in textiles as antimicrobial agents, are released in washing machines, also reaching the wastewater treatment plants. Therefore, both MF and AgNP co-exist in the environment, and enter the soil compartment mainly via the application of biosolids. Yet, the combined effect of MF and AgNP has not been studied. Here, we assessed the effects of polyester MF (0.01% DW) on the toxicity of AgNP (32, 100, 320, 1000, 3200 mg Ag/kg) and AgNO3 (12.8, 32, 80, 200, 500 mg Ag/kg) to the earthworm Eisenia andrei and the enchytraeid Enchytraeus crypticus. The exposure to MF caused a decrease in the number of juveniles and changed the biochemical composition of earthworms. Moreover, the presence of MF increased the toxicity of AgNP to earthworm reproduction (EC50 = 165 mg Ag/kg) when compared to AgNP exposure alone (EC50 = 450 mg Ag/kg), but did not alter the toxicity of AgNO3 (EC50 = 40 mg Ag/kg). For enchytraeids, no significant difference in Ag toxicity could be detected when MF was added to the soil for both AgNP and AgNO3. Overall, Ag bioaccumulation was not affected by MF, with the exception of a decrease in earthworm body concentration at the highest Ag soil concentration (3200 mg Ag/kg). Our results suggest that the presence of MF in the soil compartment may be a cause of concern, and that the joint exposure to Ag may be deleterious depending on the Ag form, organism and endpoint. The present work provides the first evidence that a realistic MF concentration in soil lowers AgNP concentration necessary to provoke reproductive impairment in earthworms. The influence of MF on risk assessment of AgNP should be considered.
Impact of Daikenchuto (TU-100) on The Early Postoperative Period in Duodenal-Jejunal Bypass
Authors: Okikawa Shohei , Kashihara Hideya , Morine Yuji , Shimada Mitsuo , Yoshikawa Kozo , Higashijima Jun , Tokunaga Takuya , Nishi Masaaki , Takasu Chie , Nishiyama Mitsue , Zushi Makoto
Published: February 2021

Introduction: We investigated the effect of Daikenchuto (TU-100) on the early postoperative period in duodenal-jejunal bypass (DJB).Methods: Study 1: The effect of TU-100 on diabetic rats was investigated. Rats were sacrificed after receiving TU-100 for one week. Study 2: The effect of TU-100 on DJB was investigated. Rats in the DJB and TU-100 treated DJB groups were sacrificed 24 hours postoperation to evaluate blood glucose, cytokine expression, and gut microbiome.Results: Study 1: TU-100 did not affect glucose or body weight. TU-100 suppressed intestinal inflammation and modified the gut microbiome. Specifically, Bifidobacterium and Blautia were increased, and Turicibacter were decreased in this group. Study 2: Both DJB and TU-100 treated DJB rats showed lower blood glucose at 24 hours postoperation than at preoperation. Cytokine expression in the liver and small intestine of the TU-100 treated DJB group was significantly lower than that of the DJB group. The gut microbiome composition in TU-100 treated DJB rats was altered. In particular, Bifidobacterium and Blautia were increased in this group.Conclusion: DJB suppressed blood glucose during the early postoperative period. TU-100 may enhance the anti-diabetic effect of metabolic surgery by changing the gut microbiome and suppressing inflammation in the early postoperative period.
Recurrent Brain Metastases: The Role of Resection of in the Era of Molecular Medicine
Authors: Hessler Nadine , Jünger Stephanie T , Meissner Anna-Katharina , kocher Martin , Goldbrunner Roland H , Grau Stefan Josef
Published: February 2021

Purpose

To evaluate the efficacy of surgical resection for pretreated, recurrent brain metastases (BM) in the era of molecular oncologic medicine.
Patients and Methods:

In a retrospective single center study, patients were analyzed who had undergone surgical resection of recurrent BM between 2007 and 2019. Intracranial event-free survival (EFS) and overall survival (OS) were evaluated by Kaplan-Maier and Cox regression analysis.
Results

In total, 107 patients with different primary tumor entities and individual previous treatment for BM were included. Primary tumors comprised non-small cell lung cancer (NSCLC) (37.4%), breast cancer (19.6%), melanoma (13.1%), gastro-intestinal cancer (10.3%) and other, rare entities (19.6%). The number of previous treatments of BM ranged from one to four; these comprised: resection only, focal or whole brain radiotherapy, brachytherapy and radiosurgery. BM-related symptoms were present in 73.8% of the patients. Median pre-operative Karnofsky Performance Score (KPS) was 70% (range 40–100) which was improved to 80% (range 0-100) after surgery. The complication rate was 26.2% and two patients died during the perioperative period. Postoperative local radio-oncologic and/or systemic therapy regimens were applied in 67 (62.6%) patients. Median postoperative EFS and OS were 7.1 (95%CI 5.8–8.2) and 11.1 (95%CI 8.4–13.6) months, respectively. The clinical status (postoperative KPS ≥ 70 (HR 0.27 95%CI 0.16–0.46; p < 0.001) remained the only independent factor for survival in multivariate analysis.
Conclusion

Surgical resection of recurrent BM may improve the clinical status and thus OS, but is associated with a high complication rate; thus, careful patient selection is crucial.
Haploidentical Hematopoietic Stem Cell Transplantation for Malignant Infantile Osteopetrosis and Intermediate Osteopetrosis:A Retrospective Analysis of a Single-Center
Authors: Zhu Guanghua , Wei Ang , Wang Bin , Yang Jun , Yan Yan , Wang Kai , Jia Chenguang , Luo Yanhui , Li Sidan , Zhou Xuan , Wang Tianyou , Zheng Huyong , Qin Maoquan
Published: February 2021

ObjectiveTo evaluate the clinical efficacy of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) for treatment of malignant infantile osteopetrosis (MIOP) and intermediate osteopetrosis.MethodsChildren with MIOP and IOP who underwent haplo-HSCT in Beijing Children’s Hospital, Capital Medical University, from January 2010 to May 2018 were retrospectively analyzed. Data relating to the clinical manifestations, engraftment, and prognosis of the children were extracted from medical records. ResultsTwenty-seven patients, including 18 males and 9 females, with an onset age of 12 (0.04-72) months, were enrolled in this study. The median time from diagnosis to transplantation was 4 (1-23) months. All patients received haplo-HSCT with myeloablative conditioning regimen (including fludarabine, busulfan, and cyclophosphamide). The graft versus host disease (GVHD) prophylaxis was based on anti-human T lymphocyte porcine immunoglobulin /anti-human thymus globulin, methotrexate, and mycophenolate mofetil. The median observation time was 55.2 (0.3-126.2) months. By the end of follow-up, twenty patients survived and seven patients died. The five years overall survival rate was 73.9%. Acute GVHD degree I-II was observed in 20 patients, degree III in 1 patient and without degree IV. Chronic GVHD was observed in 11 patients (40.7%). It was controlled by anti-GVHD therapy.Conclusion﻿Haplo-HSCT was effective for MIOP and IOP, with high survival rate and significantly improved of clinical symptoms. For the patients with vision impairment before HSCT, the improvement was slow after transplantation. The incidence of GVHD was high but mild, and could be effectively controlled after appropriate treatment. These data provided that haplo-HSCT was feasible in the treatment of MIOP and IOP.
Humidifier Disinfectant, Sodium Dichloroisocyanurate (NaDCC): Assessment of Respiratory Effects to Protect Workers’ Health
Authors: Seo Dong Seok , Jo JiMin
Published: February 2021

Background: Biocides are used to control and remove all harmful organisms. In South Korea, they are used in humidifier disinfectants and have been found to cause lung disease in users. Hence, efforts have been focused on studying the toxicity of biocides in workers who handle them. The purpose of this study was to evaluate the effects of inhalation exposure to sodium dichloroisocyanurate (NaDCC) to protect the health of workers handling NaDCC.Methods: F344 rats were exposed to 0.8-, 4-, and 20-mg/m3 of NaDCC for 6 h a day, 5 days a week for 14 days; the post-exposure recovery period was 14 days.Results: In the 20-mg/m3-exposure group, we observed a decrease in food intake in females, a weight loss in males, and a decrease in partially active thromboplastin time in males and females 2 weeks after exposure. We noted a decrease in white blood cells in males in the 4- and 20-mg/m3-exposed groups. Both males and animals in the 20-mg/m3 group and males in the 4-mg/m3 group showed irritation in the larynx related to test substance exposure. However, these findings were not observed in the recovery group.Conclusion: The main target organs affected by repeated 2-week inhalation exposure to NaDCC were the nasal cavity and larynx in the upper respiratory tract. The No Observed Adverse Effect Level (NOAEL) was considered to be 0.8 mg/m3 because the effects related to exposure of NaDCC were observed even at of 4 mg/m3. In addition, these effects were found to be reversible.
The Construction and Analysis of a Novel Four-Long Non-Coding RNA Signature Predicting Survival of Breast Cancer Patients
Authors: Qin Chengdong , Feng Weiliang , Yu Xingfei , Liang Chenlu , Ding Yuqin , Xuan Haojun , Hu Jiejie , Hongjian Yang , Yu Yang
Published: February 2021

Background

As the critical regulators for tumorigenesis and progression, long-noncoding RNAs (lncRNAs) are becoming novel prognostic biomarkers for tumor patients. By the levels of lncRNAs expression, the patients with breast carcinoma may be divided into subgroups with different risk scores. Nevertheless, there is limited evidence to evaluate the role of lncRNAs in the prognosis of breast carcinoma. The present study aimed to construct lncRNA signatures for prognostic analysis and assist clinicians in choosing optimal therapies.
Methods

Abnormal expression profiles of breast cancer-associated lncRNAs were analyzed based on the TCGA datasets. Univariate and multivariate Cox regression analysis was used to build a prognostic risk signature according to the lncRNAs expression. The prognostic ability of this signature was verified in various subgroups. Functional enrichment analysis was employed to reveal the potential roles of these predictive lncRNAs in cancer-related biological processes and pathways.
Results

Compared with normal breast tissues, the differential analysis demonstrated that 286 lncRNAs were abnormally expressed in breast carcinoma. A four-lncRNA signature (RP1-193H18.2, AL022341.3, WDR86-AS1, LINC00511) was found to be closely related to the prognosis of breast carcinoma. The four-lncRNA signature could also qualify the magnitude of treatment benefits for different breast cancer subtypes. Additionally, it was an independent risk factor out of other clinicopathological parameters based on the multivariate Cox analysis. We also uncovered that the four predictive lncRNAs are involved in multiple cellular progression and pathways of breast cancer.
Conclusions

The four-lncRNA signature could be an essential reference for prognostic prediction and making therapeutic strategies.
Synchronous Brain Metastases as a Poor Prognosis Factor in Clear Cell Renal Carcinoma: A Strong Argument for Systematic Brain Screening
Authors: Ruste Valentine , Sunyach Marie-Pierre , Tanguy Ronan , Jouanneau Emmanuel , Schiffler Camille , Carbonnaux Mélodie , Moriceau Guillaume , Neidhardt Eve-Marie , Boyle Helen , Robin Sophie , Négrier Sylvie , Fléchon Aude
Published: February 2021

PurposeBrain metastases (BM) usually represent a poor prognostic factor in solid tumors. About 10% of patients with renal cancer (RCC) will present BM. Local therapies such as stereotactic radiotherapy (SRT), whole brain radiotherapy (WBRT), and surgery are used to achieve brain control. We compared survival between patients with synchronous BM (SynBM group) and metachronous BM (MetaBM group). MethodsIt is a retrospective study of patients with clear cell renal cell carcinoma (ccRCC) and BM treated with TKI between 2005 and 2019 at the Centre Léon Bérard in Lyon. We collected prognostic factors: The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk score, the TNM stage, the histological subtypes and the Fuhrman grade. Overall survival (OS) was defined from diagnosis of metastatic ccRCC to death. Brain progression-free survival (B-PFS) was defined from focal brain therapy to brain progression or death.Results99 patients were analyzed, 44 in the SynBM group and 55 in the MetaBM group. OS in the MetaBM group was 49.4 months versus 19.6 months in the SynBM group, p=0.0002. The median time from diagnosis of metastasic disease to apparition of BM in the MetaBM group was 22.9 months (4.3; 125.7). SRT was used for 101 lesions (66.4%), WBRT for 25 patients (16.4%), surgery for 21 lesions (13.8%), surgery followed by radiation for 5 lesions (3.3%). B-PFS for all patients was 7 months (IC95% [5.0-10.5]). Conclusions﻿Survival of patients with synchronous BM is inferior to that of patients with metachronous BM. Outcome is poor in both cases after diagnosis of BM. Brain screening should be encouraged at time of diagnosis of metastatis in ccRCC.
Evaluating the Effect of Statins on Prognosis in Patients Undergoing Liver Transplantation for Hepatocellular Carcinoma
Authors: Lee Hae Lim , Lee Sung Won , Jang Jeong Won , Bae Si Hyun , Choi Jong Young , Han Nam Ik , Yoon Seung Kew , Choi Ho Joong , Na Gun Hyung , You Young Kyoung , Park Il Young , Kim Dong Goo
Published: February 2021

IntroductionThe anti-cancer effect of statins is drawing attention. However, it is unclear whether statin use reduces the risk of hepatocellular carcinoma (HCC) recurrence in patients who undergo liver transplantation (LT) for HCC.MethodsConsecutive patients who underwent LT for HCC between 1995 and 2019 were enrolled. The effect of statins were compared between statin non-user and statin user groups. The primary endpoint was HCC recurrence. All-cause and HCC-related mortality were also evaluated. We also performed multivariable-stratified and sensitivity analyses for HCC recurrence. ResultsA total of 430 patients was enrolled, among whom 323 (75.1%) were statin non-users and 107 (24.9%) were statin users. During a median of 64.9 months (IQR, 26.1–122.6) of follow-up, 79 patients (18.4%) had HCC recurrence and 111 (25.8%) died. Among those who died, 53 (47.7%) were identified as HCC-related mortalities. Statin use was associated with a significantly lower risk of HCC recurrence (adjusted HR = 0.26, 95% CI, 0.11–0.60; P = 0.002) compared to that in statin non-users. Statin users also had significantly lower all-cause and HCC-related mortality than did statin non-users (P < 0.001 & P = 0.040, respectively). There was a dose-dependent relationship between statin use and HCC recurrence. The anti-cancer effect of statins on HCC recurrence was consistently significant across multivariable-stratified and sensitivity analyses. ConclusionsStatin use significantly reduced the risk of HCC recurrence and improved the survival of patients who underwent LT for HCC.
Cartilage Increases Swimming Efficiency of Underwater Robots
Authors: Yurugi Masaki , Nagai Toshiaki , Shintake Jun , Ikemoto Yusuke
Published: February 2021

Underwater robots are useful for exploring valuable resources and marine life. Traditional underwater robots use screw propellers, which may be harmful to marine life. In contrast, robots that incorporate the swimming principles, morphologies, and softness of aquatic animals are expected to be more adaptable to the surrounding environment. Rajiform is one of the swimming forms observed in nature, which swims by generating the traveling waves on flat large pectoral fins. From an anatomical point of view, Rajiform fins consist of cartilages encapsulated in soft tissue, thereby realizing anisotropic stiffness. We hypothesized that such anisotropy is responsible for the generation of traveling waves that enable a highly efficient swimming. We validate our hypothesis through the development of a stingray robot made of silicone-based cartilages and soft tissue. For comparison, we fabricate a robot without cartilages, as well as the one combining soft tissue and cartilage materials. The fabricated robots are tested to clarify their stiffness and swimming performance. The results show that inclusion of cartilages in the robot fins increases the swimming efficiency. It is suggested that arrangement and distribution of soft and hard areas inside the body structure is a key factor to realize high-performance soft underwater robots.
Strain patterns in normal anterior talofibular and calcaneofibular ligaments and after anatomical reconstruction using gracilis tendon grafts: A cadaver study
Authors: Takao Masato , Lowe Danielle , Ozeki Satoru , Oliva Xavier M , Inokuchi Ryota , Yamazaki Takayuki , Takeuchi Yoshitaka , Kubo Maya , Matsui Kentaro , Katakura Mai , Glazebrook Mark
Published: February 2021

BackgroundInversion sprains of the lateral ankle ligaments often result in symptomatic lateral ankle instability, and some patients need lateral reconstruction surgeries to reduce pain, improve function, and prevent subsequent injuries. Although anatomically reconstructed ligaments should behave in a biomechanically normal manner, previous studies have not measured the strain patterns of the anterior talofibular (ATFL) and calcaneofibular ligaments (CFL) after anatomical reconstruction. This study aimed to measure the strain patterns of normal and reconstructed ATFL and CFLs using a miniaturization ligament performance probe (MLPP) system.MethodsThe MLPP was sutured into the ligamentous bands of the ATFLs and CTLs of three fresh-frozen, lower extremity, cadaveric specimens. Each ankle was manually moved from 15° dorsiflexion to 30° plantar flexion, and a 1.2-N m force was applied to the ankle and subtalar joint complex.ResultsThe normal and reconstructed ATFLs exhibited maximal strain (100) during supination in three-dimensional motion. Although the normal ATFLs were not strained during pronation, the reconstructed ATFLs demonstrated relative strain values of 16–36. During axial motion, the normal ATFLs began to gradually tense at 0° plantarflexion, with the strain increasing, as the plantarflexion angle increased, to a maximal value (100) at 30° plantarflexion; the reconstructed ATFLs showed similar strain patterns. The normal CFLs exhibited maximum strain (100) during plantarflexion-abduction and relative strain measurements of 30–52 during dorsiflexion in three-dimensional motion. The reconstructed CFLs exhibited the most strain during dorsiflexion-adduction and demonstrated relative strain measurements of 29–62 during plantarflexion-abduction. During axial motion, the normal CFLs began to gradually tense at 20° plantarflexion and 5° dorsiflexion.ConclusionOur results showed that the strain patterns of reconstructed ATFLs and CFLs are not exactly the same as those in the normal ligaments.
Field investigation and analysis of rockburst and spalling in a deep hard-rock mine
Authors: Peng Xiao , Guoyan Zhao , Huanxin Liu
Published: February 2021

In order to investigate the ground pressure disasters in deep hard-rock mines, field investigation and theoretical analysis were carried out in a deep hard-rock mine. It is found that the degree and number of ground pressure disasters in the mine have increased significantly with depth. When the maximum tangential stress between 0.4-0.6 times the uniaxial compressive strength of surrounding rock, surrounding rock is prone to local spalling. When maximum tangential stress is greater than 0.6 times uniaxial compressive strength, serious failure is easy to occur, such as rockbursts and large-area collapses. After excavation, the rebound strain and displacement of surrounding rock increases linearly with buried depth, and the strain energy released of surrounding rock increases rapidly with the second power of buried depth. The rapidly increasing strain energy is main reason why deep ground pressure disasters in the mine are becoming more and more serious. In terms of surrounding rock support, energy-absorbing materials such as energy-absorbing bolts can well absorb strain energy released by surrounding rock. The energy-absorbing bolts are used for design of roadway support in the mine.
Integrated Study on Pulse Diagnosis of TCM and Cardiology by Analyzing the Distribution Characteristics of Atherosclerosis Parameters at Six Positions of Cunkou
Authors: Tang Qingfeng , Chen Yankun , Ye Peihan , Liu Qi , Xie Mengzhou , Wang Nanyue , Chen Meiling , Su Benyue , Liu Kui , Pan Zhigeng , Qu Haoyu
Published: February 2021

The authors have requested that this preprint be removed from Research Square.
Investigating Novel and Conventional Biomarkers for Post-resuscitation Prognosis: The Role of Cytokeratin-18, Neuron-specific Enolase, and Lactate
Authors: Csiszar Beata , Nemeth Almos , Marton Zsolt , Riba Janos , Csecsei Peter , Molnar Tihamer , Halmosi Robert , Deres Laszlo , Koszegi Tamas , Sandor Barbara , Toth Kalman , Kenyeres Peter
Published: February 2021

Introduction: We investigated the associations of cell death-related release of cytokeratin-18 (CK-18) and its caspase-cleaved form (CCCK-18) with outcomes, clinical parameters, and neuron-specific enolase (NSE) among cardiac arrest (CA) victims.Methods: We determined CK-18, CCCK-18, and NSE plasma concentrations within 6, at 24, and 72 post-CA hours of 54 successfully resuscitated patients. Baseline characteristics, laboratory, vital parameters, prognostic scores were recorded. The follow-up was 30 days.Results: Neither the absolute values of CK-18, CCCK-18, CCCK-18/CK-18 ratio, or NSE, nor their kinetics showed significant difference according to survival and neurological outcome. CK-18 decreased in good renal function in contrast to renal failure. Lactate levels were increased in non-survivors and poor neurological outcomes. In receiver operator characteristic (ROC) analyses lactate was comparable with prognostic scores in predicting 30-day mortality and neurological outcome. The ROC curve of initial lactate indicated a cut-off as 4.90 mmol/L to predict 30-day mortality (specificity=80%; sensitivity=74%) and 6.00 mmol/L (specificity=80%; sensitivity=84%) for poor neurological outcome.Conclusion: This study was the first to investigate the post-resuscitation prognostic value of CK-18 and CCCK-18 with NSE. Although we could not prove their prognostic value, we confirmed the role of initial lactate in predicting mortality and neurological outcome in unselected resuscitated patients.
Extent of Cardiac Damage and Mortality in Patients Undergoing Transcatheter Aortic Valve Implantation
Authors: Avvedimento Marisa , Franzone Anna , Leone Attilio , Piccolo Raffaele , Castiello Domenico Simone , Mariani Andrea , Ilardi Federica , Esposito Roberta , Iapicca Cristina , Angellotti Domenico , Scalamogna Maria , Santoro Ciro , Cirillo Plinio , Esposito Giovanni
Published: February 2021

PurposeWe sought to assess the prognostic role of the extent of cardiac damage among real-world patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI).MethodsA staging classification was applied to 262 patients from the EffecTAVI Registry at baseline and re-assessed within 30-day after TAVI. All-cause mortality at 1-year was the primary endpoint of the study. Cerebrovascular accident, myocardial infarction, permanent pacemaker implantation, endocarditis and re-hospitalization for all caused were included as secondary endpoints. ResultsAt baseline, 23 (8.7%) patients were in Stage 0/1 (no cardiac damage/left ventricular damage), 106 (40.4%) in Stage 2 (left atrial or mitral valve damage), 59 (22.5%) in Stage 3 (pulmonary vasculature or tricuspid valve damage) and 74 (28.3%) in Stage 4 (right ventricular damage). At 30-day after TAVI, a lower prevalence of advanced stages of cardiac damage than baseline, mainly driven by a significant improvement in left ventricular diastolic parameters and right ventricular function, was reported. At 1-year, a stepwise increase in mortality rates was observed according to staging at baseline: 4.3% in Stage 0/1, 6.6% in Stage 2, 18.6% in Stage 3 and 21.6% in Stage 4 (p= 0.08). No differences were found in secondary endpoints. ConclusionsAlthough TAVI might be associated with an amelioration of the left ventricular diastolic and right ventricular function, patients with a greater extent of cardiac damage at baseline are at higher risk of mortality at 1-year after the procedure.
Electronic prescribing systems as tools to improve patient care: A learning health systems approach to increase guideline concordant prescribing for venous thromboembolism prevention.
Authors: Gallier Suzy , Topham Alexander , Nightingale Peter , Garrick Mark , Woolhouse Ian , Berry Michael. A. , Pankhurst Tanya , Sapey Elizabeth , Ball Simon
Published: February 2021

BackgroundVenous thromboembolism (VTE) causes significant mortality and morbidity in hospitalised patients. Risk factors for VTE are well known and there are validated risk assessment tools to support the use of prophylactic therapies. In England, reporting the percentage of patients with a completed VTE risk assessment is mandated, but this does not include whether that risk assessment resulted in appropriate prescribing. Full guideline compliance, defined as an assessment which led to an appropriate action - here prescribing prophylactic low molecular weight heparin where indicated, is rarely reported. Education, audit and feedback enhance guideline compliance but electronic prescribing systems(EPS) can mandate guideline-compliant actions. We hypothesised that a systems-based EPS intervention (prescribing rules which mandate approval or rejection of a proposed prescription of prophylactic low molecular weight heparin based on the mandated VTE assessment) would increase full VTE guideline compliance more than interventions which focused on targeting individuals. MethodsAll admitted patients within University Hospitals Birmingham NHS Foundation Trust were included for analysis between 2011-2020. The proportion of patients who received a fully compliant risk assessment and action was assessed over time. Interventions included teaching sessions and face-to-face feedback based on measured performance (an individual approach) and mandatory risk assessment and prescribing rules into an EPS (a systems approach).RESULTSData from all 235,005 admissions and all 5503 prescribers were included in the analysis. Risk assessments were completed in >90-95% of patients at all times, but full guideline compliance was lower (70% at the start of this study). Face-to-face feedback improved full VTE guideline compliance from 70% to 77% (p=<0.001). Changes to the EPS to mandate assessment with prescribing rules increased full VTE compliance to 95% (p=<0.001). Further amendments to the EPS system to reduce erroneous VTE assessments slightly reduced full compliance to 92% (p<0.001), but this was then maintained including during changes to the low molecular weight heparin used for VTE prophylaxis. DISCUSSION/ ConclusionAn EPS-systems approach was more effective in improving sustained guideline-compliant VTE prevention over time. Non-compliance remained at 8 – 5% despite this mandated system. Further research is needed to assess the potential reasons for this.