bluuebunny/crossref_metadata_2025 huggingface dataset:
Intestinal protozoan infections and environment conditions among rural schoolchildren in Western Brazilian Amazon
Authors: Balbino Layane Ferreira , Filho Alberto Alves , Farias Beatrice Émeli Silva , Costa Geórgia Veloso , Sinhorin Gustavo Henrique , Silva Lidyane Liadja Souza , Marques Rubens de Cássio Reis , Jucá Francimar Leão , Brilhante Andreia Fernandes , Melchior Leonardo Augusto Kohara
Published: September 2020

Objective

This study sought to analyse the occurrence of intestinal parasites in schoolchildren from rural areas in Rio Branco, State of Acre, Western Brazilian Amazon.
Results

The proportion of children tested positive for intestinal parasites in this study was 91.48%, of which all of them had protozoan infections. About 65.96% of the students were characterised by a polyparasitism state. Among the parasites found, Endolimax nana, Blastocystis sp., and Giardia duodenalis were the most prevalent in the positive samples. The proportions observed between sociodemographic and environment conditions data and positive diagnosis did not show significant statistical.
Evaluation of The Relationship of Nasal Septum Deviation With Pharyngeal Airway and Cervico-Craniofacial Measurements on Cephalometric Analysis
Authors: Sadry Sanaz , Ok Ufuk , Özdaş Didem Öner
Published: September 2020

The authors have requested that this preprint be removed from Research Square.
Hexanol Biosynthesis From Syngas by Clostridium Carboxidivorans P7 - Investigation of Product Toxicity, Temperature Dependence and in Situ Extraction 
Authors: Kottenhahn Patrick , Philipps Gabriele , Jennewein Stefan
Published: September 2020

BackgroundClostridium carboxidivorans P7 converts synthesis gas (also called syngas, a mixture of CO, CO2 and H2) directly into industrially relevant alcohols (hexanol, butanol and ethanol) and their corresponding acids (caproate, butyrate and acetate). The product titers and ratios are highly dependent on fermentation parameters and the compositions of syngas as well as the growth medium. Hexanol titers produced by C. carboxidivorans P7 have recently been improved by optimizing these conditions, but little is known about the toxicity of hexanol towards Clostridium species. We hypothesized that the hexanol titers currently produced by C. carboxidivorans P7 are limited by product toxicity. ResultsWe tested our hypothesis by analyzing IC50 values for hexanol at 30 °C and 37 °C, which we determined as 17.5 ± 1.6 mM and 11.8 mM ± 0.6 mM, respectively, indicating a major influence of growth temperature on hexanol sensitivity. We found that 20 mM hexanol was acutely toxic to C. carboxidivorans P7 at 30 °C and growth was already completely inhibited in the presence of 15 mM hexanol at 37 °C. Membrane fatty acid analysis showed that the cell membrane composition of C. carboxidivorans adapted strongly to the higher growth temperature but surprisingly did not change significantly when grown in the presence of 10 mM hexanol. To avoid product toxicity during hexanol production we added oleyl alcohol as an extraction solvent. At 30 °C, addition of the solvent increased total hexanol titers nearly 2.5-fold from 10.5 to 23.9 mM. However hexanol titers decreased from 7.0 to 5.6 mM in the presence of oleyl alcohol at 37 °C. At 30 °C, the extraction phase contained large amounts of hexanol (448 ± 130 mM) and butanol (102 ± 20 mM). Values were lower at 37 °C with 101 ± 27 mM hexanol and 50 ± 6 mM butanol. Growth was not inhibited by oleyl alcohol. Biomass remained high in the presence of oleyl alcohol at 30 °C, but rapidly decreased in the absence of the solvent. At 37 °C biomass decreased even in the presence of oleyl alcohol. We tested corn oil and sunflower seed oil as potentially cheaper and more sustainable extraction solvents. While oleyl alcohol displayed the highest extraction efficiency for hexanol, total hexanol titers were similar with all solvents tested. ConclusionsBoth, product toxicity and growth temperature were identified as limiting factors during the conversion of syngas to hexanol by C. carboxidivorans P7. At 30 °C the addition of a biocompatible solvent led to detoxification and a significant increase in hexanol titers, 80% higher than highest previously reported titers. These findings help to mediate the limitation of product toxicity in hexanol production from syngas for the development of more efficient process designs and production strains.
Hypoxia-regulated expression of CD44 and osteopontin can change the phenotype of glioma stem-like cells from highly invasive to less invasive/proliferative tumors in glioblastoma
Authors: Nishikawa Masahiro , Inoue Akihiro , Ohnishi Takanori , Yano Hajime , Ozaki Saya , Kanemura Yonehiro , Matsumoto Shirabe , Suehiro Satoshi , Ohtsuka Yoshihiro , Kohno Shohei , Ohue Shiro , Shigekawa Seiji , Watanabe Hideaki , Kitazawa Riko , Tanaka Junya , Kunieda Takeharu
Published: September 2020

Background

The poor prognosis of glioblastoma multiforme (GBM) is primarily due to highly invasive and highly migratory glioma stem-like cells (GSCs) in tumors. Upon GBM recurrence or progression, the highly invasive phenotype of GSCs changes to a less-motile, proliferative phenotype, thus generating tumor mass. Elucidating the molecular mechanism underlying this phenotypic transition could lead to the identification of effective molecular targets for treating GBM.
Methods

We examined mRNA expression of hypoxia-inducible factor (HIF)-1α, HIF-2α, CD44, and osteopontin in GBM tissues and investigated the effect of hypoxia (1% O2: severe or 5% O2: moderate) on expression of these molecules using two lines of cultured GSCs. We also analyzed the effect of osteopontin on the invasiveness, migration, and proliferation of GSCs under hypoxic conditions. In addition, the effect of CD44 knockdown on tumor growth and survival were investigated in vitro and in vivo using a mouse xenograft model.
Results

Severe hypoxia upregulates CD44 expression via activation of HIF-1α, inducing GSCs to assume a highly invasive phenotype. In contrast, moderate hypoxia upregulates osteopontin expression via activation of HIF-2α. Osteopontin in turn binds to CD44, simultaneously inhibiting CD44-promoted GSC migration and invasion and stimulating GSC proliferation, resulting in GSCs assuming a less-invasive, highly proliferative phenotype. CD44 knockdown significantly inhibited GSC migration and invasion both in vitro and in vivo. However, although CD44 knockdown did not affect tumor growth in vitro, mouse brain tumors generated from GSCs with CD44 knockdown exhibited diminished invasiveness, and the mice survived significantly longer than control mice. In contrast, siRNA-mediated silencing of the osteopontin gene led to decreased GSC proliferation, but the osteopontin-mediated inhibition of high GSC migratory behavior and invasiveness was diminished.
Conclusion

The highly invasive phenotype of GSCs can be reversed by switching from severe to moderate hypoxia, leading to less-invasive and proliferative tumors. CD44 and osteopontin, which are expressed in a mutually exclusive manner under severe or moderate hypoxia, play a central role in regulating GSC invasion and proliferation by inducing a phenotypic transition, suggesting that these molecules could be effective targets for treating both primary and recurrent GBM.
Intrinsic coupling between spatially-separated surface Fermi-arcs in Weyl orbit quantum Hall states
Authors: Nishihaya Shinichi , Uchida Masaki , Nakazawa Yusuke , Kriener Markus , Taguchi Yasujiro , Kawasaki Masashi
Published: September 2020

Topological semimetals hosting bulk Weyl points and surface Fermi-arc states are expected to realize unconventional Weyl orbits, which interconnect two surface Fermi-arc states on opposite sample surfaces under magnetic fields. While the presence of Weyl orbits has been proposed to play a vital role in recent observation of quantum Hall effect even in three-dimensional topological semimetals, actual spatial distribution of the quantized surface transport has been experimentally elusive. Here, we demonstrate intrinsic coupling between two spatially-separated surface states in the Weyl orbits by measuring a dual-gate device of a Dirac semimetal film. Independent scans of top- and back-gate voltages reveal concomitant modulation of doubly-degenerate quantum Hall states, which is not possible in conventional surface orbits as in topological insulators. Our results evidencing the unique spatial distribution of Weyl orbits provide new opportunities for controlling the novel quantized transport by various means such as external fields and interface engineering.
Proton capture strategy for enhancing electrochemical CO2 reduction on atomically dispersed metal-nitrogen active sites
Authors: Wang Xinyue , Sang Xiahan , Dong Chung-Li , Yao Siyu , Shuai Ling , Lu Jianguo , Yang Bin , Li Zhongjian , Lei Lecheng , Qiu Ming , Dai Liming , Hou Yang
Published: September 2020

Electrocatalysts play a key role in accelerating the sluggish electrochemical CO2 reduction (ECR) involving multi-electron and proton transfer. Herein, we develop a proton capture strategy via accelerating the water dissociation reaction catalyzed by transition metal nanoparticles (NPs) adjacent to atomically dispersed Ni-Nx active sites (Ni@NiNCM) to accelerate the proton transfer to the latter for boosting the intermediate protonation step, and hence the whole ECR process. For the first time, the accelerated protonation process is amply demonstrated experimentally. Aberration-corrected scanning transmission electron microscopy and synchrotron radiation X-ray absorption spectroscopy, together with DFT calculations, revealed that the Ni NPs accelerated the adsorbed H (Had) generation and transfer to the adjacent Ni-Nx sites for boosting the intermediate protonation and the overall ECR processes. This proton capture strategy is highly general, which can be extended to the design and preparation of various high-performance catalysts for diverse electrochemical reactions even beyond ECR.
Blood-brain barrier permeability is regulated by matrix metalloproteinase-3 via the ERK signaling pathway
Authors: Zhang Qin , Zheng Mei , Betancourt Cristian E , Liu Lifeng , Sitikov Albert , Sladojevic Nikola , Zhao Qiong , Zhang John H , Liao James K , Wu Rongxue
Published: September 2020

Background

The blood–brain barrier (BBB) regulates the exchange of molecules between the brain and peripheral blood and is composed primarily of microvascular endothelial cells (BMVECs), which form the lining of cerebral blood vessels and are linked via tight junctions (TJs). The BBB is regulated by components of the extracellular matrix (ECM), and matrix metalloproteinase 3 (MMP3) remodels the basal lamina of the ECM, which forms part of the BBB. Thus, we investigated whether MMP3 modulates BBB permeability.
Methods

Experiments included in-vivo assessments of isoflurane anesthesia and dye extravasation from brain in wild-type (WT) and MMP3-deficient (MMP3-KO) mice, as well as in-vitro assessments of the integrity of monolayers of WT and MMP3-KO BMVECs (via measurements of transendothelial electrical resistance [TEER] and transwell assays in a co-culture of BMVECs with astrocytes and the expression of junction proteins.
Results

Compared to assessments in WT mice, measurements of isoflurane usage and anesthesia induction time were higher in MMP3-KO mice and lower in WT mice that had been treated with MMP3 (WT + MMP3), while anesthesia emergence times were shorter in MMP3-KO mice and longer in WT + MMP3 mice than in WT mice. Extravasation of systemically administered dyes was also lower in MMP3-KO mouse brains, and higher in WT + MMP3 mouse brains, than in the brains of WT mice, and the results from both TEER and transwell assays indicated that MMP3 deficiency (or inhibition) increased, while MMP3 upregulation reduced, barrier integrity in either BMVEC monolayers or the co-culture. MMP3 deficiency also increased the abundance of TJ and VE-cadherin proteins in BMVECs, and the protein abundance declined when MMP3 activity was upregulated in BMVECs, but not when the cells were treated with an inhibitor of extracellular signal related kinase (ERK).
Conclusion

MMP3 increases BBB permeability by upregulating the ERK signaling pathway, which subsequently reduces TJ and VE-cadherin proteins abundance in BMVECs. Collectively, these observations suggest that MMP3 could be therapeutically targeted to manipulate BBB permeability and treat neurological disease.
Predictors for Outcomes related to upper Extremity Musculoskeletal Disorders in a healthy Working Population: a methodological Approach
Authors: Lotter Oliver , Lieb Tobias , Molsner Jochen , Breul Viktor
Published: September 2020

BackgroundTo investigate the association between different clinical endpoints and the presence of upper extremity work-related musculoskeletal disorders (WMSDs) in a healthy working population. Furthermore, the influence of socio-demographic, work-related and individual predictors on different endpoints was examined.MethodsTwo self-completion questionnaires were administered to 70 workers and employees. In addition, a standardized physical examination and an industry test were performed in this cross-sectional study. Correlations between WMSDs and clinical endpoints were analysed with the Spearman method. Depending on the type of dependent endpoint, linear or logistic multivariate regression models were used to study the strength of associations with a pre-defined set of potential influencing factors.ResultsThe prevalence of WMSDs was 56% (39/70). Correlations between WMSDs and the DASH score / pain under strain (VAS) were by far the strongest ones. Independent predictors could not be identified as risk factors for WMSDs, but there was some correlation between these factors.ConclusionsThe DASH score, used in the primary analysis of the study data, remains a close candidate for best surrogate endpoint for WMSD detection. The VAS has to be examined for this role in further research. Our analysis should help to improve the methodological quality of future occupational health studies through improved standards.Trial registrationThis study was registered at ClinicalTrials.org with the identifier NCT03014128, on January 9, 2017.
Key Technologies and Equipment for Contaminated Surface/Groundwater Environment in the Rural River Network Area of China: Integrated Remediation
Authors: Wang Han , Wang Tianbei , Xue Gang , Zhao Jiang , Ma Weiwu , Qian Yajie , Wu Min , Zhang Zhuoran , Guo Jingsong , Wang Yayi
Published: September 2020

In eastern China, the rural river network area (RRNA) is an anthropic active area characterized by its rapid economic development and high gross national product. However, the water environmental pollution in these areas is increasingly severe, which has greatly hindered its sustainable development. Especially, the frequent interactions between surface/groundwater (SW-GW) have intensified the pollution migration and transformation in RRNA. Therefore, an integrated remediation in rural river network area project (IR-RRNA) has been launched, funded by the Ministry of Science and Technology of the People’s Republic of China, to realize the integrated remediation of SW/GW and soil in RRNA. The IR-RRNA (2019–2022) will apply the related interdisciplinary and methodological knowledge to elucidate the transportation and transformation of pollutants in water and soil during SW-GW interaction, and develop key remediation technologies of surface water, groundwater, and soil suitable for the RRNA. By this way, we attempt to realize the remediation technologies integration for surface/groundwater and soil in RRNA and implementing application demonstration. Meanwhile, a technical guideline will be compiled for the integrated remediation suitable for the RRNA. This project is conducive to addressing the urgent environmental problems of RRNA, and promoting the rural economic revitalization and ecological environment optimization.
Early Myopia Onset, Predicted by First Spectacle Use, is A Risk Factor for High Myopia in Adulthood: A Retrospective Study
Authors: Chiang Wei-Yu , Chen Yun-Wen , Liu Yu-Peng , Liu Yung-Hsun , Wu Pei-Chang
Published: September 2020

Background: To investigate the risk factors for high myopia in adulthood, especially as it relates to the age of first spectacle wearing.Methods: A retrospective study enrolled adults aged between 20 and 45 years being invited to complete a questionnaire about age, sex, current refractive error, high myopia in parents, age at first spectacle use, refractive power of the first spectacles, and life habits at different educational stages. The association between these factors and high myopia were then evaluated and analyzed.Results: In total, 331 participants were enrolled. Their average refractive error was -4.03 diopters, and high myopia was noted in 27.5% of the study population. Only 3.3% of participants had fathers with high myopia, while 6.0% had mothers with high myopia. The participants received their first spectacles at a mean age of 13.35 years, with a mean refractive error of -1.63 diopters.The significant risk factors for developing high myopia in adult life were earlier age at first spectacle use (p < 0.001), higher refractive power of first spectacles (p < 0.001), mother with high myopia (p = 0.015), and after-school class attendance in senior high school (p = 0.018). Those who wore their first spectacles at < 9 years of age were more predisposed to high myopia than those who did so at ≧ 13 years, with an odds ratio of 24.891, while the odds ratio for those aged between 10 and 12 years was 5.294.Conclusions: The present study shows that earlier age at first spectacle use, higher myopic refraction of first spectacles, mothers with high myopia, and after-school class attendance in senior high school are predictive factors for high myopia in adulthood. The most important predictive factor is earlier age at first spectacle use, which emphasizes earlier myopia control is a protective factor for high myopia in adulthood.
Assessment of Implant Surface Changes due to instrumentation with different tips for ultrasonic-driven debridement
Authors: Sahrmann Philipp , Winkler Sophie , Gubler Andrea , Attin Thomas
Published: September 2020

Background
To assess the changes of implant surfaces of different roughness after instrumentation with ultrasonic-driven scaler tips of different materials.
Methods
Experiments were performed on two moderately rough surfaces (I – Inicell® and II – SLA®), one surface without pre-treatment (III) and one smooth machined surface (IV). Scaler tips made of steel (A), PEEK (B), titanium (C), carbon (D) and resin (E) were used for instrumentation with a standardized pressure of 100 g for ten seconds and under continuous automatic motion. Each combination of scaler tip and implant surface was performed three times on 8 titanium discs. After instrumentation roughness was assessed by profilometry. Morphological changes were assessed by scanning electron microscopy, and element distribution on the utmost surface by energy dispersive X-ray spectroscopy.
Results
The surface roughness of discs I and II were significantly reduced by instrumentation with all tips except E. For disc III and IV roughness was enhanced by tip A and C and, only for IV, by tip D. Instrumentation with tips B, D and E left extensive residuals on surface I, II and III. The element analysis of these deposits proved consistent with the elemental composition of the respective tip materials.
Conclusion
Instrumentation by ultrasonic-driven tips changes implant surfaces of different roughness significantly. The least change of implant surfaces might result from resin or carbon tips on machined surfaces.
Prognostic Value of Non-alcoholic Fatty Liver Disease in Predicting Cardiovascular Events in Diabetes Mellitus Patients: A Prospective Cohort Study
Authors: Ichikawa Keishi , Miyoshi Toru , Osawa Kazuhiro , Miki Takashi , Toda Hironobu , Ejiri Kentaro , Yoshida Masashi , Nakamura Kazufumi , Morita Hiroshi , Ito Hiroshi
Published: September 2020

Background: Risk stratification of cardiovascular events in patients with type 2 diabetes mellitus (T2DM) has not been established. coronary artery calcium score (CACS) and non-alcoholic fatty liver disease (NAFLD) are independently associated with cardiovascular events in T2DM patients. This study examined the incremental prognostic value of NAFLD assessed by non-enhanced computed tomography (CT) in addition to CACS and Framingham risk score (FRS) on cardiovascular events in T2DM patients.Methods: This prospective pilot study included 529 T2DM outpatients without history of cardiovascular disease who underwent CACS measurement due to suspected coronary artery disease. NAFLD was defined on CT images as a hepatic: spleen attenuation ratio <1.0. cardiovascular events were defined as cardiovascular death, nonfatal myocardial infarction, late coronary revascularization, nonfatal stroke, or hospitalization for heart failure.Results: Of 529 patients (61% men, mean age 65 years), NAFLD was identified in 143 (27%). During the median 4.4 years of follow-up, 44 cardiovascular events were documented. In multivariate Cox regression analysis, the presence of NAFLD, CACS and FRS were associated with cardiovascular events with hazard ratios of 5.45 (95% confidential interval [CI]: 2.84–10.45; p<0.001), 1.56 (95% CI: 1.32–1.85; p<0.001), and 1.23 (95% CI: 1.08–1.39; p=0.001), respectively. The global chi-square score for predicting cardiovascular events significantly increased from 27.0 to 49.7 by adding NAFLD to CACS and FRS (p<0.001). The addition of NAFLD to a model including CACS and FRS significantly increased the C-statistic from 0.71 to 0.80 (p=0.005). The net reclassification achieved by adding CACS and FRS was 0.551 (p<0.001). Conclusions: NAFLD assessed by CT, in addition to CACS and FRS, could be useful in assessing T2DM patients at higher risk of cardiovascular events.
In-Hospital Mortality After Blood Purification With and Without Acrylonitrile-Co-Methallyl Sulfonate Surface-Treated Membrane for Pneumonia-Associated Sepsis: A Retrospective Cohort Study
Authors: Hayashi Kentaro , Sasabuchi Yusuke , Matsui Hiroki , Nakajima Mikio , Ohbe Hiroyuki , Fushimi Kiyohide , Ono Kazuyuki , Yasunaga Hideo
Published: September 2020

Background: Cytokine removal therapy is one of the available therapies for sepsis. Acrylonitrile-co-methallyl sulfonate surface-treated (AN69ST, sepXiris®) membrane has cytokine adsorption capacity and has been widely used for treating sepsis in Japan. The aim of this study was to compare the effects of continuous renal replacement therapy (CRRT) with AN69ST membrane and conventional CRRT for patients with pneumonia-associated sepsis.Methods: We conducted a retrospective cohort study using the Diagnosis Procedure Combination database, a nationwide inpatient database in Japan. We identified adult patients who were hospitalized due to pneumonia and received CRRT within 2 days of admission from September 2014 to March 2017. We included patients who received CRRT with AN69ST membrane within 2 days of admission in the treatment group (AN69ST group); those who received CRRT with other membranes within 2 days of admission were included in the control group (non-AN69ST group). Propensity score matching was used to compare in-hospital mortality between the two groups.Results: Eligible patients (n=2,393) were categorized into the AN69ST group (n=631) or the non-AN69ST group (n=1,762). The overall in-hospital mortality rate in pneumonia patients treated with CRRT was 38.9%. Propensity score matching created a matched cohort of 545 pairs of patients. The in-hospital mortality rate was significantly lower in the AN69ST group than in the non-AN69ST group (35.8 vs. 41.8%, p=0.046).Conclusion: Our data suggest that CRRT with the AN69ST membrane was associated with a significantly lower in-hospital mortality than CRRT with standard membranes among patients with pneumonia-associated sepsis.
Psychometric Properties of the “Lasher and Faulkender Anxiety about Aging Scale” among Iranian older people
Authors: Pakpour Amir , Namjoo Shamsedin , Sabahiazar Khadijeh , Jafarabadi Mohammad Asghari , Chattu Vijay Kumar r , Allahverdipour Hamid
Published: September 2020

BackgroundAssessing anxiety in the elderly and the factors affecting this phenomenon will help the health care providers to provide appropriate and effective support and health care services for older adults. The aim of the present study was to assess the psychometric properties of the Aging Scale (AAS) among Persian speaking older adults.Method:A sample of 703 community-dwelling older adults was recruited for the study. A 'forward-backward' translation procedure was conducted to develop the Iranian version of the AAS. Confirmatory factor analysis (CFA) and Rasch model were then used for construct validity, and GHQ-12 and MSPSS were utilized for assessing concurrent validity of the AAS.ResultThe study participants included 416 (59.2%) men and 287 (40.8%) women with an average age of 69.4 years (SD D 8.11). Cronbach’s alpha for Fear of Old People, Psychological Concerns, Physical Appearance, Fear of Losses and the overall score was 0.881, 0.705, 0.748, 0.768 and 0.77, respectively. Applying CFA, it was found that the four original factors model was the best solution with 0.55 of the total variance. The result of the CFA indicated that this four-factor model had a good fit to the data. The results were then confirmed by Rasch analysis. Moreover, the AAS was significantly correlated with MSPSS (r=-0.395, p < 0.001) and GHQ_12 (r = 0.238, p < 0.001).ConclusionThe Persian version of the AAS was found to be valid and reliable for measuring anxiety of ageing among Persian speaking elderly populations.
Multi-Biomarker Panel Prediction Model for Diagnosis of Pancreatic Cancer: a retrospective and multi-center cohort study
Authors: Lee Doo-Ho , Yoon Woongchang , Lee Areum , Han Youngmin , Byun Yoonhyeong , Kang Jae Seung , Kim Hongbeom , Kwon Wooil , Suh Young-Ah , Choi Yonghwan , Namkung Junghyun , Han Sangjo , Yi Sung Gon , Heo Jin Seok , Han In Woong , Park Joon Oh , Park Joo Kyung , Kim Song Cheol , Jun Eunsung , Kang Chang Moo , Lee Woo Jin , Lee Hyeon Kook , Lee Huisong , Lee Seungyeoun , Jeong Seung-Yong , Lee Kyu Eun , Han Wonshik , Park Taesung , Jang Jin-Young
Published: September 2020

Background

Early diagnosis is paramount in increasing the survival rate of pancreatic ductal adenocarcinoma (PDAC). However, effective early diagnostic tools are lacking at present. The current study aimed to develop a prediction model using a multi-marker panel (LRG1, TTR, and CA19-9) as a diagnostic screening tool for PDAC.
Methods

A large multi-center cohort of 1,991 samples were collected from January 2011 to September 2019, of which 609 are normal (NL), 145 are other cancer (OC; colorectal, thyroid, and breast cancer), 314 are pancreatic benign disease (PB), and 923 are PDAC. The automated multi-biomarker Enzyme-Linked Immunosorbent Assay kit was developed using three potential biomarkers, LRG1, TTR, and CA 19 − 9. Using a logistic regression (LR) model trained on training data set, the predicted values for PDACs were obtained, and the result was classified into one of the three risk groups: low, intermediate, and high. The five covariates used to create the model were sex, age, and biomarkers TTR, CA 19 − 9, and LRG1.
Results

Participants were categorized into four groups as NL (n = 609, 30.6%), OC (n = 145, 7.3%), PB (n = 314, 15.7%), and PDAC (n = 923, 46.4%). The NL, OC, and PB groups were clubbed into the non-PDAC group (n = 1068, 53.6%). The positive and negative predictive value, sensitivity, and specificity were 94.12, 90.40, 93.81, and 90.86, respectively.
Conclusions

This study demonstrates a significant diagnostic performance of the multi-marker panel in distinguishing PDAC from normal and benign pancreatic disease states, as well as patients with other cancers. The study indicates that the introduced multi-marker panel prediction model for PDAC diagnosis can help guide medical decisions for patients, including patients with early stage PDAC or with normal levels of CA 19 − 9.
The Risk of Bias in Iranian Randomized Controlled Trials Included in Cochrane Reviews
Authors: Kabir Ali , Sofi-Mahmudi Ahmad , Behnagh Arman Karimi , Eidkhani Vahid , Baradaran Hamid Reza , Kabiri Payam , Haghdoost Ali Akbar , Mesgarpour Bita
Published: September 2020

Background: Among interventional studies, randomized controlled trials (RCTs) provide the most conclusive evidence. However, RCTs can be susceptible to the risk of bias (RoB). Systematic reviews can be performed to appraise the RoB in the included articles using evaluative tools. This study aimed to describe the main characteristics and focus on the ROB of RCTs conducted in Iran and included in Cochrane Reviews (CRs).Methods: We searched "Iran" by selecting the "Search All Text" and "Review" fields in the Cochrane Database of Systematic Reviews within Ovid. CRs that included the RCTs conducted in Iran were retrieved. A trial was selected only if it was included in CRs, described as a controlled clinical trial, involved human subjects and its RoB was assessed by CR authors. The trials were characterized by investigating the relevant articles and the table "Characteristics of included studies" in each CR. The RoB was investigated by collecting the judgments of the review authors made based on tables of RoB assessment in the CRs.Results: Out of 1166 Iranian RCTs included by 571 CRs, a low RoB was found in 44.9% for random sequence generation, 20.8% for allocation concealment, 32.3% for blinding of participants/personnel, 36.5% for blinding of outcome assessors, 56.3% for incomplete outcome data, 41.3% for selective outcome reporting and 53.8% for other sources of bias.Conclusion: The RoB in Iranian RCTs was found to be mostly high or unclear. It is therefore recommended that the methodological quality of RCTs be seriously addressed in Iran.
Maternal mortality rate in Bao'an district, Shenzhen, China, 1999-2018
Authors: zhu yuanfang , Luo Yali , Wang Wei , Wang Liling , Cheng Yuli , Li Jianmei , Chen Xu
Published: September 2020

Background

China had achieved impressive success in reducing maternal mortality rate (MMR), while substantial heterogeneity still existed, and reports from Shenzhen region remained a blank. This study aiming to use all available data sources to evaluate the MMR from 1999 to 2018 in Bao’an district, Shenzhen, China.
Methods

Data on maternal deaths and key health-service-related indicators were obtained from registration forms and Shenzhen Maternal and Child Health Management System. The levels and trends of MMR, profiles and leading causes of death, as well as results from the maternal mortality review committee were analyzed.
Results

The MMR in Bao’an district declined from 95.31 per 100,000 live births in 1999 to zero in 2018, with an annualized rate of decline of 12.03% per year. A significant declining trend of MMR was observed over 5-year intervals (from 82.61 to 5.22 per 100,000 live births). MMR was higher among migrant population, women aged ≥ 35 years or those who given birth outside the hospital. The first three causes of maternal death included hemorrhage (27.69%), amniotic fluid embolism (22.31%) and internal medical disease complications (15.38%). Nearly ninety percent (86.78%) of maternal deaths were determined to be preventable.
Conclusions

Bao’an district had experienced a fast decline in MMR for a two-decade period, its experience in lowering MMR could provide a guideline for other regions to focus on those who needed particular attention and take targeted interventions to reduce maternal deaths.
Comparison of various behavioral intervention approaches for tobacco cessation- A protocol for a systematic review and network meta-analysis
Authors: Dhawan Priyanka , Goel Sonu , Aggarwal Ashutosh , Ghosh Abhishek , Vijayvergiya Rajesh , Khurana Dheeraj , Verma Roshan , Medhi Bikash
Published: September 2020

Background﻿Despite substantial progress in tobacco control in the last two decades, there is limited literature on the most effective tobacco cessation behavioral intervention. This network meta-analysis will compare various behavior change intervention for tobacco cessation and attempt to rank them to identify the best approach for cessation.MethodologyThe network meta-analysis will include randomized controlled trials on behavior change for tobacco cessation. The PICOS framework will be used while selecting the studies from various established scientific databases viz. Pubmed, Scopus, Embase, and other sources including Clinicaltrial.gov. The primary outcome for this review will be sustained or point prevalence tobacco abstinence at 6 months or 12 months. To graphically depict and document the studies Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines along with PRISMA Network Meta-Analysis extension statement will be used.ConclusionThe network meta-analysis will provide the rankings of behavior change interventions thus determining the most and least effective modality for tobacco cessation. The information obtained will be an important guide for policymakers, implementors, and researchers to choose the priority cessation intervention.RegistrationProtocol of this review and network meta-analysis was registered in PROSPERO: International prospective register of systematic reviews (registration number: CRD42020145768).
Long non-coding RNA LINC00152 regulates cell proliferation and migration by epigenetically repressing LRIG1 expression in cholangiocarcinoma
Authors: Wang Ni , Yu Yang , Xu Boming , Zhang Chunmei , Liu Jie , Dong Liyang , He Xuezhi , Miao Lin , Li Quanpeng
Published: September 2020

Background: Recently, long non-coding RNAs (lncRNAs) have been verified to have significant regulatory roles in multiple human cancer processes. Long non-coding RNA LINC00152, located on chromosome 2p11.2, was identified as an oncogenic lncRNA in various cancers. However, the biological function and molecular mechanism of LINC00152 in cholangiocarcinoma (CCA) are still unknown.Methods: Bioinformatic analysis was performed to determine LINC00152 expression levels in the CCA and normal tissues by using raw microarray data downloaded from Gene Expression Omnibus (GSE76297) and The Cancer Genome Atlas (TCGA). Quantitative reverse transcription PCR (qRT-PCR) was used to validate LINC00152 expression in the CCA tissues compared with that in the paired normal tissues. CCK8, colony formation, Edu assays, transwell assays, flow cytometry, and in vivo tumor formation assays were performed to investigate the biological function of LINC00152 on CCA cell phenotypes. RNA-seq was carried out to identify the downstream target gene which was further examined by qRT-PCR, western bolt and rescue experiments. RNA immunoprecipitation (RIP) and Chromatin immunoprecipitation (ChIP) assays were performed to reveal the factors involved in the mechanism of LINC00152 functions in CCA.Results: LINC00152 is significantly upregulated in cholangiocarcinoma. LINC00152 regulated the proliferation and migration of cholangiocarcinoma cells both in vitro and in vivo. RNA-seq revealed that LINC00152 knockdown preferentially affected genes linked with cell proliferation, cell differentiation and cell adhesion. Furthermore, mechanistic investigation validated that LINC00152 could bind EZH2 and modulate the histone methylation of promoter of leucine rich repeats and immunoglobulin like domains 1 (LRIG1), thereby affecting cholangiocarcinoma cells growth and migration.Conclusion: Taken together, these results demonstrated the significant roles of LINC00152 in cholangiocarcinoma and suggested a new diagnostic and therapeutic direction of cholangiocarcinoma.
Clinical and Para Clinical Findings in Children with Progressive Familial Intrahepatic Cholestasis in Iran; A Referral Center Report
Authors: Zarenezhad Mohammad , Dehghani Seyed Mohsen , Ejtehadi Fardad , Fattahi Mohammad Reza , Kaboodkhani Reza , Tabei Seyyed Mohammad Bagher , Doroudchi Alireza , Forouzesh Mehdi
Published: September 2020

BackgroundProgressive Familial Intrahepatic Cholestasis (PFIC) is a heterogeneous group of disorders with various clinical and para-clinical manifestations. We report clinical and para-clinical findings in children with progressive familial intrahepatic cholestasis in Southern Iran.MethodsMedical records of 102 patients aged ≤18 years old diagnosed with PFIC who referred to our referral center were evaluated from 2008 to 2012. Baseline and clinical characteristics, outcomes and survival of these patients were recorded. ResultsThe study included 61 boys and 41 girls. Most common complaints were jaundice in 53 (51.96 %), pruritus and jaundice in 15 (14.70 %) and jaundice+elevated liver enzymes in 11 (10.78%) children. Main clinical findings in children were jaundice (51.96%), ascites (28.43%), pruritus (19.60%), fever (16.66%) and encephalopathy (14.70%). Inhomogeneous echogenicity (31.37%), splenomegaly (26.47%), hepatomegaly (17.64%), cirrhosis (9.80%) and ascites (6.86%) were the most common sonography findings among children with PFIC, respectively. Histopathologic evaluation showed cirrhosis (34.31%), followed by fibrosis (18.62%), cholestasis (10.78%), inflammation of liver tissue (4.90%), nodule formation (2.94%), and destruction of lobular and vascular architecture (1.96%). Liver transplantation, medical therapy and biliary diversion had been performed for 67%, 13% and 11% of the patients, respectively. Mean (SD) PELD and MELD scores among children with PFIC were 7.14±14.63 and 15.75±7.21, respectively. Three month mortality rate for PFIC patients with end stage liver disease was 13.1%.ConclusionInhere we reported invaluable clinicopathological findings among a large series of patients with PFIC.
Design and Validation of a Questionnaire to Measure the Acceptance of Telemedicine by Healthcare Professionals in Germany
Authors: Verfürth Martina
Published: September 2020

Background: Telemedicine allows healthcare professionals to manage patient treatments remotely and to benefit from the interaction of telemedicine centers. Even though telemedicine responds to the current burdens in healthcare systems, these complex infrastructures depend on technology, financing, organization, policy, legislation, and, not least, on their corresponding acceptance by the user. Little is known in this context about the drivers for this acceptance by healthcare professionals giving treatment. Germany, with the highest healthcare spending in the world, is particularly lagging here. As there is less focus on guidance for building acceptance constructs, and, in particular, little research on the acceptance of interactive telemedicine by healthcare professionals in Germany, the objective was the collection of the relevant factors influencing German healthcare professionals in the implementation of telemedicine service programs (TSSs). Acceptance constructs were built and operationalized in a questionnaire, taking into consideration the gold standard technology acceptance model of Davis.Methods: A literature review was conducted to identify the acceptance factors that had already been detected and frequently confirmed. These factors were evaluated according to the coverage of the interactive infrastructures with telemedicine centers and how accurately they fitted Germany. The identified factors were adapted, and missing factors were designed, via an idea collection for items. The reliability of the developed constructs was tested using a field test to check the constructs using item revision analysis.Results: Frequently supported external variables, taken from 17 filtered studies covering the technical, organizational, social, legal, and individual context, were identified. However, the review showed that there was less focus on the German setting and the interactive aspect, so the market-related variables were adapted and new constructs of “trust in the telemedicine center” and “relationship to patient” were added. Ten variables were proven to have a reliability, measured with Cronbach’s Alpha, of more than 0.7.Conclusion: This paper enhances the already existing technology acceptance studies in healthcare by covering German specifications and the interactive character of TSSs. A corresponding questionnaire has been developed ready for future research.
Construction of a Six Immune-Related lncRNAs Signature to Predict Outcome, Immune Cell Infiltration and Immunotherapy Response in Patients with Hepatocellular Carcinoma
Authors: Zhou Pengcheng , Wei Jiang , Yuhua Lu , Lei Wang , Yewei Zhang
Published: September 2020

Background: Hepatocellular carcinoma (HCC) is one of the most lethal malignant tumors worldwide with poor prognosis. Growing evidence has demonstrated that immune-related long non-coding RNAs (lncRNAs) are relevant to tumor microenvironment (TME) and can help to assess the effects of immunotherapy and evaluate prognosis. This study aimed to identify an immune-related lncRNA signature for the prospective assessment of immunotherapy and prognosis in HCC. Methods: HCC RNA-seq data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) project database. Firstly, we used ESTIMATE to evaluate the tumor microenvironment (TME). Then, cox regression analysis was used to construct a prognostic signature and the risk score. Univariate Cox regression, multivariate Cox regression, principal components analysis (PCA), the receiver operating characteristic (ROC) curve and stratification analyses were applied to conﬁrm. Gene set enrichment analysis (GSEA) analysis was employed to explore the biological processes and pathways. Besides, CIBERSORT was used to estimate the abundance of tumor-inﬁltrating immune cells (TIICs). Furthermore, the relationship between the immune-related lncRNA signature and immune checkpoint genes was investigated. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) assays were used to demonstrated the expression of the six lncRNAs. Results:.We identified a six immune-related lncRNAs (MSC-AS1, AC145207.5, SNHG3, AL365203.2, AL031985.3, NRAV) with the ability to stratify patients into high-risk and low-risk groups with significantly different survival. Univariate Cox regression, multivariate Cox regression, ROC and stratification analyses conﬁrmed that the six immune-related lncRNA signature was a novel independent prognostic factor in HCC patients. The high-risk group and low-risk group illustrated different distributions in PCA. GSEA suggested that the six immune-related lncRNA signature is involved in the immune-related biological processes and pathways. Besides, the six immune-related lncRNA signature was associated with the infiltration of immune cells. Furthermore, the six immune-related lncRNA signature was associated with the expression of critical immune genes and could predict the clinical response of immunotherapy. Finally, qRT-PCR demonstrated that the six lncRNAs were signiﬁcantly differentially expressed in HCC cell lines and normal hepatic cell line. Conclusions: In summary, we identified a six immune-related lncRNA signature with the ability to predict outcome, immune cell infiltration and immunotherapy response in patients with hepatocellular carcinoma.
Combining Renal Cell Arrest and Damage Biomarkers to Predict Progressive AKI in Patient with Sepsis
Authors: Tao Xiaolei , Chen Chunbo , Luo Weihong , Zhou Jing , Tian Jianwei , yang xiaobing , Hou Fan Fan
Published: September 2020

Background: Sepsis is the most common trigger for AKI and up to 40% of mild or moderate septic AKI would progress to more severe AKI, which is associated with significantly increased risk for death and later CKD/ESRD. Early identifying high risk patients for AKI progression is a major challenge in patients with septic AKI. This study aims to evaluated the utility of combining renal cell arrest and damage biomarkers for predicting the progression of AKI in patient with sepsis. Methods: This is a prospective, multicenter cohort study which enrolled adult patients with sepsis and initially developed stage 1 or 2 AKI from January 2014 to March 2018. AKI was diagnosed and staged according to 2012 KDIGO-AKI guidelines. Renal cell arrest biomarkers (urinary TIMP2*IGFBP7, u[TIMP-2]*[IGFBP7]) and renal damage biomarkers (urinary KIM-1[uKIM-1] and urinary IL-18 [uIL-18]) were measured at time of AKI clinical diagnosis, and the utility of biomarkers for predicting septic AKI progression alone or in combination were evaluated. The primary outcome was AKI progression defined as worsening of AKI stage. The second outcome was AKI progression with subsequent death during hospitalization. Results: Among 433 screened patients, 149 patients with sepsis and stage 1 or 2 AKI were included, in which 63 patients developed progressive AKI and 49 patients subsequently died during hospitalization. u[TIMP-2]*[IGFBP7], uKIM-1 and uIL-18 independently predicted the progression of septic AKI in which u[TIMP-2]*[IGFBP7] showed the greatest AUC (0.745; 95%CI, 0.667-0.823) as compared to uKIM-1 (AUC 0.719; 95%CI 0.638-0.800) and uIL-18 (AUC 0.619; 95%CI 0.525-0.731). Combination of u[TIMP-2]*[IGFBP7] with uKIM-1 improved the performance of predicting septic AKI progression with AUC of 0.752. u[TIMP-2]*[IGFBP7], alone or combined with uKIM-1/uIL-18, improved the risk reclassification over the clinical risk factor model alone both for the primary and secondary outcomes, as evidenced by significant category-free net reclassification index. Conclusion: Combination of renal cell arrest and damage biomarkers enhanced the prediction of AKI progression in patients with sepsis and improved risk reclassification over the clinical risk factors.
Association Between Body Mass Index and Severe Infection in Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis: A Retrospective Cohort in Japan
Authors: Sugiyama Hirokazu , Yamaguchi Makoto , Katsuno Takayuki , Nobata Hironobu , Iwagaitsu Shiho , Kinashi Hiroshi , Banno Shogo , Ishimoto Takuji , Ito Yasuhiko
Published: September 2020

Background: Although previous studies have evaluated risk factors for the incidence of severe infection in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV), the relationship between body mass index (BMI) and severe infection in AAV has not been elucidated. We hypothesized that elderly AAV patients with a low BMI would be at a higher risk of infection. To evaluate this hypothesis, we investigated the association between underweight at AAV diagnosis and subsequent severe infection in elderly AAV patients.Methods: This single-center retrospective cohort study included 98 consecutive elderly AAV patients treated at the Aichi Medical University Hospital in Japan between 2004 and 2018. The relationships between BMI at diagnosis and subsequent first severe infection were assessed using multivariate Cox proportional hazards models.Results: During the entire follow-up period (median, 22 months; interquartile range, 7‒52 months), 32 (32.7%) patients developed at least one severe infection. Low BMI (< 18.5 kg/m2 compared with normal BMI [18.5‒23.0 kg/m2], adjusted hazard ratio [HR] = 2.70, 95% confidence interval [CI]: 1.18–6.17; P = 0.018) and use of methylprednisolone pulse therapy (adjusted HR = 3.09, 95% CI: 1.37–6.99; P = 0.007) were the significant predictors of severe infection. Furthermore, an interaction effect between unintentional body weight loss (> 10%) within 6 months before diagnosis and low BMI was observed (P < 0.001).Conclusions: Low BMI was associated with a higher risk of severe infection in elderly AAV patients, suggesting that careful management may be required to prevent the development of infection in patients with a low BMI. Further studies are needed to elucidate the optimal treatment strategy for these patients.