bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and Characterization of Verticillium Nonalfalfae-responsive Micrornas in the Roots of Resistant and Susceptible Hop Cultivars
Authors: Kunej Urban , Jakše Jernej , Radišek Sebastjan , Štajner Nataša
Published: December 2020

BackgroundMicro RNAs are 21- to 24-nucleotide-long, non-coding RNA molecules that regulate gene expression at the post-transcriptional level. They can modulate various biochemical and physiological processes, including plant response and resistance to fungal pathogens, by regulating the expression of numerous genes. Hops are grown for use in the brewing industry and have recently attracted the attention of the pharmaceutical industry. Severe Verticillium wilt disease caused by the phytopathogenic fungus Verticillium nonalfalfae is the main factor in yield loss in many crops, including hops (Humulus lupulus L.). ResultsIn our study, we identified miRNAs in hops and their expression patterns in the roots of susceptible and resistant hop cultivars in the early stages of infection with the fungus V. nonalfalfae. In total 56 known and 43 novel miRNAs were predicted. In response to infection with V. nonalfalfae, we found five known and two novel miRNAs that are differentially expressed in the susceptible cultivar and six known miRNAs in the resistant cultivar. Differentially expressed miRNAs target 49 transcripts and their gene ontology enrichment analysis showed that the susceptible cultivar responds by modulating the processes of protein localization and pigment synthesis, whereas the resistant cultivar responds by modulating transcription factors and hormone signalling.ConclusionThe results of our study suggest that the susceptible and the resistant cultivar respond differently at the miRNA level to infection with V. nonalfalfae and that miRNAs may contribute to the successful defence of the resistant cultivar.
Functioning Assessment Short Test (FAST): Validity and Reliability in Adults With Autism Spectrum Disorder
Authors: Gustemps Laura Gisbert , Marín Jorge Lugo , Ramos Imanol Setien , Martín Gemma Español , Vieta Eduard , Bonnín Caterina Mar , Quiroga Josep Antoni Ramos
Published: December 2020

Background: The assessment of functional impairment is crucial both for the diagnosis and the therapeutic approach to autism spectrum disorder (ASD). The purpose of the present study was to evaluate whether the FAST is a reliable and valid tool to assess functional impairment in adults with Level 1 ASD and to study the differences in psychosocial functioning between younger and older adults with ASD.Methods: A case–control study was carried out in a sample of 150 participants, 71 adults with Level 1 ASD, and 79 adults without psychiatric history records.Results: Results showed good psychometric properties in terms of validity and reliability. Cronbach’s alpha for the total scale was .91 and the area under the curve was .98. The study also showed that adults with ASD present different profiles of functional impairment depending on their age: while younger patients present greater impairment in autonomy, older patients show more difficulties in interpersonal relationships Conclusions: Our results support the use of the FAST in the evaluation of adaptive functioning in adults with Level 1 ASD.
Interleukin-1 Beta Regulates Lysophosphatidic Acid-accelerated Skin Wound Healing
Authors: Ge Delong , Mou Xiaoxiao , Liu Liying , Li Yanwei , Jiang Hui , Xie Jinjing , Guan Qingyan , Dai Gong , Yang Xiao , Gao Yuanyuan , Yang Xiaoyun
Published: December 2020

Background: Interleukin 1 beta (IL-1β) is considered to be a mediator of infectious, inflammatory and autoimmune diseases, and the kinetics of its production is relevant to understanding the pathogenesis of these diseases. Lysophosphatidic acid (LPA), the structurally simplest bioactive phospholipid, is necessary for homeostasis in various physiological and pathophysiological processes and plays a pivotal role in wound healing. Skin trauma can not only weaken the barrier function, but also cause pain and infection. Chronic wounds are characterized by impaired healing and uncontrolled inflammation that damages the protection of the immune system. The aim of this study is to investigate whether inflammatory factor IL-1β has an effect on LPA in the wound healing model. Results: In this study, the kinetics of IL-1β gene expression was studied in vivo and in vitro with a wound healing model by quantitative real-time polymerase chain reaction (qRT-PCR) through LPA treatment. As a result, we found that LPA up-regulated inflammatory factor IL-1β in HaCaT cell and skin wound healing. The pro-inflammatory cytokines IL-1β mRNA had higher expression in LPA-treated mice group 3 days after the treatment. In vitro, after the treatment with LPA (20 μM) for 6, 12, and 24 hours, IL-1β mRNA expression increased by 61.16%, 129.39%, and 117.07%, respectively. Conclusion: These results strongly suggest that IL-1β may regulate LPA-accelerated skin wound healing. IL-1β has significant efficacy, and our observations are of interest to the development of drugs targeting LPA in skin therapy.
Global, regional, and national prevalence of diabetes mellitus in patients with pulmonary tuberculosis: a systematic review and meta-analysis
Authors: Li Minmin , Chen Tao , Hua Zhongqiu , Yan Hong , Wang Duolao , Li Zhaoqing , Kang Yijun , Zhu Ni , Li Chao
Published: December 2020

Background：Both TB and DM are major global public health problem. We estimated the global, regional, and national prevalence of diabetes mellitus in population with pulmonary tuberculosis.Methods：We assessed observational studies of diabetes mellitus in people with pulmonary tuberculosis, using PubMed and Embase electronic bibliographic databases in English language, to identify articles published until August 31, 2018. We included original research that reported the prevalence of diabetes mellitus in pulmonary tuberculosis or had enough data to compute these estimates. Studies were excluded if they did not provide primary data or were case studies and reviews. 2 authors independent extraction of articles and collected detailed information using predefined questionnaire. The country-specific random-effects meta-analyses for countries with two or more available studies and a fractional response regression model to predict individual studies prevalence of diabetes mellitus in pulmonary tuberculosis for countries with one or no study. The study is registered with PROSPERO, registration number CRD42018101989.Results. We identified 18042 studies, and 127 were retained for data extraction across 46 countries. The global prevalence of diabetes mellitus in patients with pulmonary tuberculosis were estimated to be 12.07% (95%CI: 10.43-14.85). The prevalence was 13.38% (95%CI: 11.16-16.05) in region of Americas, 13.34% (95%CI: 12.82-14.61) in European region, 12.68% (95%CI: 9.15-16.37) in South-East Asia, 12.56% (95%CI: 11.79-22.70) in Western Pacific region, 10.95% (95%CI: 9.04-17.83) in Eastern Mediterranean region and 7.54% (95%CI: 6.51-8.77) in African region. The country with the highest estimated prevalence was Mauritius (39.65%, 95%CI: 4.22-90.74).Conclusion: Pulmonary tuberculosis combined diabetes mellitus is still prevalent.
The Common European Mosquitoes Culex Pipiens and Aedes Albopictus Are Unable to Transmit SARS-CoV-2, After a Natural-mimicking Challenge With Infected Blood
Authors: Fortuna Claudia , Montarsi Fabrizio , Severini Francesco , Marsili Giulia , Toma Luciano , Amendola Antonello , Bertola Michela , Michelutti Alice , Ravagnan Silvia , Capelli Gioia , Rezza Giovanni , Luca Marco Di
Published: December 2020

BackgroundOn March 11 2020, the World Health Organization (WHO) declared COVID-19 outbreak a pandemic. As the mosquito season progressed, the understandable concern that such insects could transmit the virus began to spread. In response to this request, the vector competence for SARS-CoV-2 of Culex pipiens and Aedes albopictus, the two most common species of vector mosquitoes in Europe, was investigated. Due to the peculiar feeding behaviour, the role of Aedes albopictus in a potential mechanical transmission of the virus was also evaluated. MethodsFor the vector competence study, mosquitoes were allowed to take up an infectious blood meal. Mosquitoes were collected and analysed at 0, 3, 7 and 10 days post-feeding. For the mechanical transmission test Ae. albopictus females were allowed to feed for a short time on a feeder containing infectious blood and then on a feeder containing virus-free blood. Mosquitoes and blood were tested for viral presence.ResultsCx. pipiens and Ae. albopictus tested resulted not competent for SARS-CoV-2 and Ae. albopictus was unable to mechanically transmit the virus. Conclusions﻿This study shows that the most common species of vector mosquitoes in Europe don’t transmit SARS-CoV-2 and, for the first time, that Ae. albopictus is unable to mechanically transmit the virus by feeding from a positive host to a healthy host.
Molecular Detection of Tick-Borne Pathogens in Ticks Collected From Hainan Island, China
Authors: Lu Miao , Tang Guangpeng , Bai Xiaosong , Qin Xincheng , Guo Wenping , Li Kun
Published: December 2020

BackgroundKinds of pathogens such as viruses, bacteria and protozoa are transmitted by ticks as vectors, and they have deeply impact on human and animal health worldwide. MethodsTo better understand the genetic diversity of bacteria and protozoans carried by ticks in Chengmai county of Hainan province, China, 285 adult hard ticks belonging to two species (Rhipicephalus sanguineus: 183, 64.21% and R. microplus: 102, 35.79%) from dogs, cattle, and goats were colleted. Rickettsiales bacteria, Coxiellaceae bacteria, Babesiidae, and Hepatozoidae were identified in these ticks by amplifying the 18S rRNA, 16S rRNA (rrs), citrate synthase (gltA), and heat shock protein (groEL) genes. ResultsOur data revealed the presence of four recognized species and two Candidatus spp. of Anaplasmataceae and Coxiellaceae in locality. ConclusionsIn sum, these data reveal an extensive diversity of Anaplasmataceae bacteria, Coxiellaceae bacteria, Babesiidae, and Hepatozoidae in ticks from Chengmai county, highlighting the need to understand the tick-borne pathogen infection in local animals and humans.
Surgery in Congenital Lung Malformations: The Evolution From Thoracotomy to Minimally Invasive Surgery, 10-year Experience in a Single Center
Authors: Ceylan Kenan Can , Batıhan Güntuğ , ÜÇVET Ahmet , Gürsoy Soner
Published: December 2020

BackgroundCongenital lung malformation is an umbrella term and consist of various kind of parenchymal and mediastinal pathologies. Surgical intervention is often necessary for diagnosis and treatment for these pathologies. We aimed to review our experience in surgical treatment for congenital lung disease and present the role of minimally invasive surgery. Methods From January 2009 to May 2019, a total of 94 patients fitted the criteria for inclusion in this retrospective study. We investigated the clinical results obtained retrospectively.Results There were no significant differences between pathological subtypes in the postoperative length of hospital stay and drainage duration. There wasn't a significant difference between VATS and thoracotomy group in perioperative complicationsConclusions Congenital lung malformations consist of a heterogeneous group of diseases and video-assisted thoracoscopic surgery should be considered as the first choice in the surgical treatment of these patients.
Radical treatment of severe open fractures of extremities by orthoplastic surgery: a 10-year retrospective study
Authors: Yang Zhao , Xu Chao , Zhu Yong-Gang , Li Jun , Wu Zi-Xiang , Zou Ji-Wei , Xue Bao-Bao , Miao Dan-Min , Shang Lei , Zhao Guang-Yue
Published: December 2020

Orthoplastic treatment based on the collaboration of orthopedic and plastic surgeons in an “orthoplastic” central unit has been recommended by the British Association of Plastic Reconstructive and Aesthetic Surgery. However, this approach is not used worldwide especially in most developing countries. Based on the aggressive orthoplastic management, orthoplastic experience with Chinese characteristics has been carried out in last 10 years. The clinical data of 41 consecutive patients with severe open fracture (Gustilo IIIb or IIIc) of the limb, who underwent successful surgical debridement, fixation, and soft tissue reconstruction in one stage between January 2008 and April 2019, were retrospectively reviewed. Postoperative indicators, including infection rate and union time, were acquired by a regular follow-up and analyzed. The mean (±SD) age of the patients was 38±16 years. The soft tissue cover was achieved within 72 h. The overall rate of infection was 14.6% (6/41). Sex and the Mangled Extremity Severity Score were associated with infection. The median union time of 40 patients (one amputation) was 32 weeks. The overall rate of infection exhibited a lower tendency in this study. These results indicated that the single-stage radical orthoplastic treatment was an effective and reliable option for reconstructing severe open fractures.
Hydrochemistry of sediment pore water in the Bratsk reservoir (Baikal region, Russia)
Authors: Poletaeva Vera , Tirskikh Elvira , Pastukhov Mikhail
Published: December 2020

This study was aimed at identifying the processes responsible for the major ion composition of pore water from the bottom sediments of the Bratsk water reservoir, which is a part of the largest freshwater Baikal-Angara water system. The pore water ionic composition varies both along the sediment depth profile and across the water area. In pore water, the difference between the highest and lowest values is remarkably large: 5.1 times for K+, 13 times for Mg2+, 16 times for HCO3-, 20 times for Ca2+, 23 times for Na+, 80 times for SO42-, 105 times for Cl-. Such a variability suggests that the dominant factors, influencing pore water chemistry, depend on the location. At the first stages of the sedimentation process, the chemistry of the pore water in the Bratsk reservoir is dependent on HCO3-Ca of the overlying water. Later on, due to the interaction with the sedimentary terrigenous material, they changed to SO4, SO4-HCO3, HCO3-SO4, HCO3-Cl-SO4-water types with exchangeable cations, mainly Ca. Some of pore waters may have a complex genesis associated with subaqueous groundwater discharge. The change in the redox potential observed in the pore water is the indicator of early-diagenetic transformations taking place in bottom sediments.
Association of Sex with the Global Burden of Age-related Macular Degeneration
Authors: Wu Jing , Zhou Jiayue , Tang Xiajing , Yu Xiaoning , Shentu Xingchao
Published: December 2020

Background: Age-related macular degeneration (AMD) is the third leading cause of blindness and affects approximately 196 million people. This study aims to explore the association of sex with the global burden of AMD by year, age, and socioeconomic status using disability-adjusted life-years (DALYs).Methods: Global, national sex-specific DALY numbers, crude DALY rates, and age-standardized DALY rates caused by AMD, by year and age, were extracted from the Global Burden of Disease Study 2017. The human development index (HDI) in 2017 was extracted as an indicator of national socioeconomic status from the Human Development Report 2018 (HDR 2018). Pearson correlation and linear regression analyses were conducted to investigate the association between socioeconomic status and sex inequality of AMD.Results: Differences in the sex-specific global burden of AMD have persisted since 1990 to 2017. Female individuals had higher burden than male individuals of the same age in 2017, and the differences gradually increased after 55 years and maximized at 80 years or older with 105.41 DALYs rates in female vs 81.00 DALYs rates in male. The paired Wilcoxon signed rank test indicated that female had higher age-standardized DALY rates than male had (Z = -6.520, P < 0.001) and countries with lower HDI values had higher age-standardized DALY rates among both sexes. DALY rate ratio and sex differences in age-standardized DALY rates were positively associated with HDI in both Pearson correlation analyses and linear regression analyses of AMD. (P < 0.05).Conclusions: Although global blindness and vision impairment health care is progressing, sex inequality in AMD burden remained persistent since the past few decades. These findings might raise more public attention to the gender differences in global AMD burden and the association between the sex-related global burden and socioeconomic status.
A Case Report of Isolated Pigmentosus Atrophic Lichen Planus on the Supramaxillary Area: A New Variant ？
Authors: Liu Ningyuan , Zhao Ruiheng , Su Danni , Zhang Xiaoyan
Published: December 2020

Background: Lichen planus pigmentosus (LPP) and atrophic lichen planus (ALP) are two rare subtypes of Lichen Planus（LP）, the former is characterized by epidermal atrophy and the latter by over pigmentation. LP with both of the above manifestations has few reports and there is a lack of treatment experience. Case presentation: We herein reported a 22-year old girl with a complaint of a sharply edged brown plaque on the supramaxillary area with pain and itchy for 6 months. The skin biopsy sample from the forehead revealed thinning of epidermal ridges, liquefaction degeneration of basal cells, loss of cuticular process, lichenoid lymphocytic infiltration and incontinence of pigment as well as numerous melanophages. It was diagnosed as atrophic Lichen planus pigmentosus (ALPP), and the plaque was completely cleared after 10 months of Alternating topical corticosteroids or calcineurin inhibitors. Discussion and Conclusions: ALPP might be an independent variant of LP or LPP that causes significant epidermal atrophy in the degenerative phase. This case revealed the special type of LP and provided a clinical reference for the treatment.
Effect of Add-on Hydroxychloroquine Therapy on Serum Proinflammatory Factor Levels in Patients with Systemic Lupus Erythematosus With or Without Lupus Nephritis
Authors: Wakiya Risa , Ueeda Kiyo , Nakashima Shusaku , Shimada Hiromi , Kameda Tomohiro , Mansour Mai Mahmoud Fahmy , Kato Mikiya , Sugihara Koichi , Ushio Yusuke , Kadowaki Norimitsu , Dobashi Hiroaki
Published: December 2020

Background: We investigated the effects of add-on hydroxychloroquine (HCQ) therapy on the expression of proinflammatory cytokines and other factors in systemic lupus erythematosus (SLE) patients with low disease activity.Methods: Patients who had low disease activity of at least 3 months duration were included. Patients with a history of lupus nephritis (LN+) must have been in remission for at least 3 months prior to enrollment. Serum levels of interferon interferon-α, S100A8, S100A9, tumor necrosis factor(TNF) -α, interleukin(IL)-2, IL-6, IL-8, vascular endothelial growth factor (VEGF)-A, Monocyte Chemotactic Protein-1, macrophage inflammatory protein-1α, IL-1β, Interleukin 1 receptor antagonist(IL-1ra), and Granulocyte Colony Stimulating Factor were measured immediately before and 3 months after treatment with oral HCQ treatment.Results: Of the 42 patients enrolled in the study (4 males, 38 females, mean age ± standard deviation age 41.4±13.3 years), 19 patients had a history of lupus nephritis but were currently in remission (LN+), and the remaining 23 patients had no history of LN (LN−). Serum levels of IL-1ra, S100A8, and S100A9 at baseline were significantly higher in the LN+ group compared with the LN− group (p=0.0092, p=0.012, and p=0.0043, respectively). In the full cohort, HCQ treatment led to significantly reduced serum levels of TNF-α, IL-6, VEGF-A, IL-1ra, IL-2, S100A8, and S100A9, and to decreased, albeit not significantly, levels of IL-8 and MIP-1α. The HCQ-induced changes in serum IL-8, IL-1ra, S100A8, and S100A9 levels were greater for patients in the LN+ group than those in the LN−group (p=0.0039, p=0.0011, p=0.0201, and p=0.0092, respectively). Conclusion: Add-on HCQ treatment decreased several proinflammatory cytokines levels in SLE patients with low disease activity, especially those with LN. The ability of HCQ to reduce IL-8 levels in patients with a history of LN suggests that HCQ treatment may improve the prognosis of LN.
Tactile Cortical Responses and Association with Tactile Sensitivity in Young Children on the Autism Spectrum
Authors: Espenhahn Svenja , Godfrey Kate J. , Kaur Sakshi , Ross Maia , McMorris Carly , Cortese Filomeno , Wright Charlene , Murias Kara , Dewey Deborah , Protzner Andrea B. , McCrimmon Adam , Bray Signe , Harris Ashley D.
Published: December 2020

Background: Unusual responses to sensory stimuli are frequently reported in individuals on the autism spectrum (AS). Despite the early emergence of sensory features (<age 3) and their potential impact on development and quality of life, little is known about the neural mechanisms underlying sensory sensitivities in early childhood autism. Methods: Here, we used electroencephalography (EEG) to investigate tactile cortical processing in young children aged 3-6 years with autism and in neurotypical (NT) children. Scalp EEG was recorded from 33 children with autism, including those with low cognitive and/or verbal abilities, and 45 age- and sex-matched NT children during passive tactile fingertip stimulation. We compared properties of early and later somatosensory-evoked potentials (SEPs) and their adaptation with repetitive stimulation between autistic and NT children and assessed whether these neural measures are linked to “real-world” parent-reported behavioral tactile sensitivity.Results: As expected, we found elevated behavioral tactile sensitivity in children on the autism spectrum. Our findings indicated no differences in amplitude or latency of early and mid-latency somatosensory-evoked potentials (P50, N80, P100), nor adaptation between autistic and NT children. However, latency of later processing of tactile information (N140) differed between young children with and without autism, suggesting faster processing speed in young autistic children. Further, correlational analyses and exploratory analyses using tactile phenotype as a grouping variable found that enhanced early neural responses were associated with greater behavioral tactile sensitivity in autism. Limitations: The relatively small sample size and the inclusion of a broad range of autistic children (e.g., with low cognitive and/or verbal abilities) may have limited our power to detect subtle group differences and associations. Hence, replications are needed to verify these results.Conclusions: Our findings suggest that electrophysiological somatosensory cortex processing measures may be indices of “real-world” tactile sensitivity in early childhood autism. Together, these findings advance our understanding of the neurophysiological mechanisms underlying tactile sensitivity in early childhood autism and, in the clinical context, may have therapeutic implications.
Electrochemistry: Electrochemical cell, thermodynamic and
kinetic aspects
Authors: Dan Dan
Published: December 2020

The field of electrochemistry can be defined as the set of physical and chemical phenomena involved by the passage of an electric current in an ionic conductor. These phenomena involve the use of electrodes characterized by at least one interface common to two conductors of different nature. They manifest themselves in various ways in electrochemical reactors made up of two electronic conductors or electrodes separated by an ionic conductive medium. After having defined the main phenomena involved in the flow of current, the article presents the thermodynamic and kinetic aspects of electrochemistry (electrochemical cell). The main industrial applications of electrochemistry are briefly presented.
The Importance of Choosing the Right Strategy to Treat Small Cell Carcinoma of the Cervix: A Comparative Analysis of Treatments
Authors: Kawamura Mariko , Koide Yutaro , Murai Taro , Ishihara Shunichi , Takase Yuuki , Murao Takayuki , Okazaki Dai , Yamaguchi Takahiro , Uchiyama Kaoru , Itoh Yoshiyuki , Kodaira Takeshi , Shibamoto Yuta , Mizuno Mika , Kikkawa Fumitaka , Naganawa Shinji
Published: December 2020

Background: Standard treatments for small cell carcinoma of the cervix (SCCC) is unclear. We aimed to estimate the optimal treatment strategy for SCCC. Methods: This was a multicentre retrospective study. Medical records of patients with pathologically proven SCCC treated between 2003 and 2016 were retrospectively analyzed. Overall survival (OS) was plotted using the Kaplan-Meier method. The log-rank test and cox regression model were used to assess the differences in survival due to the stage, treatment strategy, and chemotherapy regimen. Results: Seventy-seven patients were evaluated. Their median age was 47 (range: 24-83) years. The number of patients with stage I, II, III, and IV, as defined according to the Union for International Cancer Control (UICC), was 28, 9, 24, and 16, respectively. Of 64 patients who had undergone chemotherapy, 43 received a small cell carcinoma regimen and 21 received a non-small cell carcinoma regimen as their first-line chemotherapy regimen. The 5-year OS for all patients was 51%. The 5-year OS rates for the patients with UICC stage I, II, III, and IV were 61%, 76%, 54%, and 18%, respectively. The 5-year OS rates for patients who underwent treatments with a small cell carcinoma and non-small cell carcinoma regimen were 62% and 15% (p<0.001), respectively. This trend was observed in all UICC stages, except in stage I. Multivariate analysis showed that presence of metastasis was a significant prognostic factor in all the patients. Application of surgery was not a significant prognostic factor in multivariate analysis. The 5-year OS was similar in the concurrent chemoradiotherapy (CCRT) and surgery group if CCRT with small cell carcinoma regimen was selected. Conclusion: The role of chemotherapy in stage I SCCC is unclear; however, if chemotherapy is applicable, SCCC patients should be treated with a chemotherapy regimen used for localized small cell carcinoma.
Anaplastic Thyroid Cancer: Recent Trend Toward Improved Survival
Authors: Huang Chi , Ji Jiuying , Qian Tao , Fei Zongqi , Ma Binge , Zeng Xiangtai , wang Jianhua
Published: December 2020

Background: Anaplastic thyroid carcinoma is a rare malignant tumor of the thyroid. In this study, we summarize the survival changes of Anaplastic thyroid carcinoma in recent years. Methods: Patients with Anaplastic thyroid carcinoma were selected from The Surveillance, Epidemiology, and End Results database (1973-2015). Survival rates were calculated and survival trends were compared among different stage, different years, under surgery and under radiotherapy or not.Results: A total of 1293 patients were enrolled in the study. The 5-year overall survival (OS) for Stage IVA, B and C were 26.6%, 11.7% and 2.5%, respectively. The 5-year cancer-specific survival (CSS) for the same respective stage were 43.5%, 22.3% and 4.9%. After year 1995, the CSS was further improvement (χ2=13.608, P=0.003 for log-rank test) and there was obvious improvement in survival for patients at stage IVB and stage IVC (stage IVB: χ2=12.987, P=0.005, stage IVC: χ2=21.992, P<0.001 for log-rank test). The surgery survival benefit was only observed in Stage IVB (OS: χ2=43.887, P<0.001, CSS: χ2=27.301, P<0.001 for log-rank test) and C (OS: χ2=16.399, P<0.001, CSS: χ2=12.521, P<0.001 for log-rank test). The radiotherapy OS benefit was observed in all different stage(stage IVA: χ2=7.346, P=0.007 for log-rank test, stage IVB: χ2=37.491, P<0.001 for log-rank test，stage IVC: χ2=23.208, P<0.001 for log-rank test) and the CSS benefit was observed in Stage IVB (χ2=18.717, P<0.001 for log-rank test) and C (χ2=12.615, P<0.001 for log-rank test). The median OS of patients with stage IV A receiving surgery, radiotherapy alone and the combination of the two is 4, 5 and 33 months (95% CI: 0.411-7.589, 0.000-10.500, 16.290-49.710, respectively). For Stage IVA patients, compared with the patients received surgery alone, the survival benefit was observed in patients who received surgery and radiotherapy combined (OS: χ2=6.454, P=0.011 for log-rank test). Conclusion: The 5-year cancer-specific survival for Anaplastic thyroid carcinoma was improved in recent years since 1990s. Patients with local metastasis or distant metastasis could benefit from surgery and radiotherapy. For Stage IVA patients, surgery or radiotherapy alone did not improve the cancer-specific survival. Combination of surgery and radiotherapy should get survival benefit.
Low-carbohydrate Dietary Pattern on Glycemic Outcomes Trial (ADEPT) among Individuals with Elevated Hemoglobin A1c: Study Protocol for a Randomized Controlled Trial
Authors: Dorans Kirsten S. , Bazzano Lydia A. , Qi Lu , He Hua , Appel Lawrence J. , Samet Jonathan M. , Chen Jing , Mills Katherine T. , Nguyen Bernadette T. , O'Brien Matthew J. , Uwaifo Gabriel I. , He Jiang
Published: December 2020

• Background: Type 2 diabetes mellitus (T2DM) is a major cause of morbidity and mortality globally. Strong evidence supports the importance of diet and other lifestyle factors in preventing T2DM. Among individuals with T2DM, low-carbohydrate diets lead to decreases in hemoglobin A1c (HbA1c). However, research on the effects of low-carbohydrate diets on glycemic outcomes among individuals not currently on glucose-lowering medications who have elevated HbA1c is limited.• Methods: The objective of this randomized controlled trial is to study the effect of a healthy low-carbohydrate diet achieved through behavioral intervention and key food supplementation compared with usual diet on HbA1c and other metabolic risk factors among individuals with HbA1c from 6.0 to 6.9% who are not on glucose-lowering medications. In this parallel trial, 150 participants will be randomized to the intervention or control group for 6 months. The healthy low-carbohydrate diet target is <40 grams of net carbohydrates during the first 3 months and <40 to 60 net grams for months 3 to 6. This diet is characterized by abundant unsaturated fat and protein, high-fiber foods such as non-starchy vegetables and nuts, and minimal refined carbohydrates. The primary outcome is the difference in HbA1c change from baseline to 6 months in the intervention compared with usual diet group. Secondary outcomes include differences between groups in 6-month changes in fasting glucose, systolic blood pressure, total-to high-density lipoprotein cholesterol ratio, and body weight. Exploratory outcomes include differences in 6-month changes in fasting insulin, homeostasis model assessment of insulin resistance, diastolic blood pressure, waist circumference, and 10-year cardiovascular disease risk. An intention-to-treat analysis will be used. • Discussion: We expect that the results from this study will lead to new approaches for developing and implementing dietary approaches (other than the most commonly used reduced fat diet) that will substantially reduce risk of cardiometabolic disease among adults with or at high risk of T2DM. The study intervention involves behavioural counselling and promotes consumption of dietary components thought to reduce risk of cardiometabolic disease and has expected applicability in clinical practice.• Trial registration: Clinicaltrials.gov registry: https://clinicaltrials.gov/ct2/show/NCT03675360. Registered on September 18, 2018 (prior to enrolment of the first participant).
Inhibiting BDNF/TrkB receptor improves resiniferatoxin-induced postherpetic neuralgia through decreasing ASIC3 signaling in dorsal root ganglia
Authors: Wei Xiang , Wang Lina , Hua Jie , Jin Xiao-hong , Ji Fuhai , Peng Ke , Zhou Bin , Yang Jianping , Meng Xiaowen
Published: December 2020

Background Postherpetic neuralgia (PHN) is a devastating complication after varicella-zoster virus infection. Brain-derived neurotrophic factor (BDNF) has been shown to participate in the pathogenesis of PHN. Tropomyosin receptor kinase B (TrkB), an endogenous high-affinity receptor of BDNF is abundantly expressed in primary sensory neurons. Acid-sensitive ion channel 3 (ASIC3) is involved in chronic neuropathic pain, but its relation with BDNF/TrkB during PHN is unclear. This study aimed to investigate whether BDNF/TrkB contributes to PHN through regulating ASIC3 signaling in dorsal root ganglia (DRGs). Methods Resiniferatoxin (RTX) was used to induce rat PHN models. Mechanical allodynia was assessed by measuring the paw withdrawal thresholds (PWTs). Thermal hyperalgesia was determined by measuring the paw withdrawal latencies (PWLs). We evaluated the effects of TrkB/ASIC3 signaling inhibition on the behavioral test, neuronal excitability and inflammatory response in rat models of PHN. ASIC3 short hairpin RNA (shRNA) transfection was used to investigate the effect of exogenous BDNF on inflammatory response in cultured PC-12 cells. Results RTX resulted in significant mechanical allodynia, upregulated the protein expression of BDNF, TrkB, ASIC3, TRAF6, nNOS and c-Fos, and increased neuronal excitability in DRGs. Inhibition of ASIC3 reversed the above-mentioned effects of RTX, except for BDNF and TrkB protein expression. In addition, inhibition of TrkB blocked RTX-induced mechanical allodynia, activation of ASIC3 signaling and hyperexcitability of neurons. RTX-induced activation of BDNF was found in both neurons and satellite glia cells in DRGs. Furthermore, exogenous BDNF activated ASIC3 signaling, increased NO level and enhanced IL-6, IL-1β, TNF-α level in PC-12 cells, which was blocked by shRNA-ASIC3 transfection. Conclusion These findings demonstrate that inhibiting BDNF/TrkB reduced inflammation, decreased neuronal hyperexcitability and improved mechanical allodynia through regulating ASIC3 signaling pathway in DRGs, which may provide a novel therapeutic target for patients with PHN.
HDAC6 Inhibitors Sensitize Claudin-high Breast Cancer Cells to Cysteine Depletion via Activation of PKCγ Signaling
Authors: Alothaim Tahiyat , Charbonneau Morgan , Tang Xiaohu
Published: December 2020

IntroductionTriple-negative breast cancer (TNBC) is a highly malignant breast cancer type with poor prognosis and lacks effective therapy. TNBC is not responsive to targeted therapy for hormone receptors and often exhibit resistance to current chemotherapeutic agents. Targeting tumor metabolism is an emergent strategy to treat cancer. Therefore, identification of tumor metabolic deregulations and development of effective targeted therapies are urgently needed.MethodsWe performed the epigenetic compound library screening in claudin-high breast tumor cells and identified therapeutical sensitizers to overcome the drug resistance of targeted cysteine-dependence therapy. Gene expression profiling were generated to analyze signaling pathways induced by the combined tubacin and cysteine deprivation treatment. Specific inhibitors, shRNA, and CRISPR/Cas9 gene editing approaches were used to target cellular proteins HDAC6 and PKCγ and examine their roles in cell death. Cell viability, RT-qPCR, and Western blotting assays were performed in cysteine-independent tumor cells to examine the anticancer effects of combined tubacin and cysteine deprivation treatment. ResultsWe found that TNBC has differential death responses to cysteine deprivation and the cysteine-dependence of TNBC corelates with the expression levels of claudin genes in addition to the classical EMT markers. To overcome drug resistance in claudin-high/cysteine-independent breast tumor cells, HDAC6 inhibitors were identified by the epigenetic compound library screening as potent sensitizers that synergize with cysteine deprivation to eradicate cysteine-independent tumor cells. Unexpectedly, HDAC6 knockout did not recapitulate the HDAC6 inhibitors-mediated synthetic lethality, indicating that HDAC6 is not the actual target of HDAC6 inhibitors in this context. Transcriptomic profiling revealed that HDAC6 inhibitors synergizes with cysteine depletion to trigger a profound gene transcriptional program. Notably, a zinc-related gene response was observed to accompany with a prominent increase of labile zinc in cells during cell death. We further showed that activation of PKCγ signaling is required to interfere cellular zinc homeostasis and drive HDAC6 inhibitors-mediated cell death.ConclusionOur study demonstrated that HDAC6 inhibitors function as potent sensitizers to overcome the resistance of cysteine deprivation in claudin-high breast tumor cells. Identification of such sensitizers would make the targeted cysteine-dependence therapy applicable in various subtypes of breast cancer.
High BRCA1 Gene Expression Increases the Risk of Early Onset Distant Metastasis in ER+ Breast Cancers
Authors: Chang Hui-Ju , Yang Ueng-Cheng , Lai Mei-Yu , Chen Chen-Hsin , Fann Yang-Cheng
Published: December 2020

BackgroundMore than 30% of ER+ breast cancer patients developed distant metastasis after adjuvant tamoxifen therapy. It has been shown that decreased BRCA1 protein function confers anti-estrogen “resistance.” Since the functional status of BRCA1 protein auto-regulates its own gene expression, BRCA1 transcript level should possibly be used to assess its active protein levels. Thus, it is interesting to explore the potential links between BRCA1 gene expression status and the prognosis of ER+ breast tumors.MethodsEarly-staged ER+ Breast cancer microarray samples were selected from the NCBI Gene Expression Omnibus (GEO) database. The aggressiveness of these tumors was evaluated based on molecular subtypes or patients’ distant metastasis-free survival (DMFS) time found in associated GEO datasets. In survival analysis, the optimal threshold to define high and low transcript levels was assessed by the logistic-accelerated failure time mixture regression model in a pooled data set, which simultaneously envisages the lifetime risk of distant metastasis and the distribution of the DMFS time from the surgery of a patient susceptible to distant metastasis. ResultsOn the basis of molecular subtyping, the relatively aggressive Luminal B tumor cells expressed significantly more BRCA1 transcripts than the less aggressive Luminal A tumor cells. This observation was supported by DMFS time analysis. When the upper 10% of the high BRCA1 expression patients was compared with the rest of the patients, the result was quite drastic. In patients susceptible to distant metastasis, the median onset time of distant metastasis for high BRCA1 expression group (2.2 years) was about one-fifth of the BRCA1 low expression group (10.5 years).Conclusions﻿High BRCA1 transcript level does not increase the incidence of distant metastasis, but increases the risk of early onset distant metastasis in ER+ breast cancers. As new therapeutic drugs have been developed for tumors with BRCA function loss, our findings suggest that BRCA1 gene expression test not only is useful for predicting patients’ outcome but also can be used in treatment decision.
Dynamic Analysis and Parametric Optimization of Telescopic Tubular Mast Applied on Solar Sail
Authors: Ji Chen-Yang , Liu Jin-Guo , Wu Chen-Chen , Zhao Peng-Yuan , Chen Ke-Li
Published: December 2020

The Telescopic Tubular Mast (TTM) has excellent performance and is widely used in aerospace. Reasonable parameter design and optimization can shorten development
cycle and improve performance for TTM. This paper designed a TTM driven by the bistable carbon reeled composite boom. The equivalent model of the TTM is established and simulated, which can be used as ex-tending structure for the solar sail. The work flow of the solar sail with the TTM is introduced. The natural frequency of the equivalent model and the segmented model is solved respectively using ABAQUS. The TTM under six different load conditions is analyzed. The influence of different factors on the vibration characteristics of the TTM is analyzed and the sensitivity analysis is carried out. Parameters including stiffness, natural frequency, mass and extension ratio are optimized using the multi-objective genetic optimization algorithm. According to the optimization results, the prototype was processed, and the experiment was completed with the equivalent load of solar sail. It provides a reference for the parametric design of the TTM.
Clinical Profiles of Osteoporotic Vertebral Compression Fractures: A Secondary Data Analysis of 358 Patients from a Prospective Clinical Study
Authors: Jin Huaijian , Ma Xiaoyuan , Liu Mingyong , Wang Zhong , Zhao Jianhua , Liu Peng
Published: December 2020

Background: For back pain patients with spine dysfunction, clinical profiles are crucial for clinicians to establish the diagnostic and therapeutic decision-making. The objectives of this study were (1) to outline the incident clinical findings and familiarize physicians with the clinical profiles of osteoporotic vertebral fractures (OVFs) and (2) to characterize patients with radiating pain (RP), spinal palpation tenderness (SPT), or axial spinal percussion pain (ASPP). Methods: This is a secondary data analysis of 358 patients from a prospective clinical study (November 1, 2016, to September 30, 2018) with particular focus on the incident RP, SPT, and ASPP. Predictive analyses for the incident RP, SPT and ASPP were done along the clinical profiles in 358 patients (284 females).Results: The cohort patients who complained of spinal movement-related pain performed a limited amplitude of movements with the purpose of avoiding the onset of back pain in daily life. Of the patients who had OVFs, 76 (21.2%) patients had RP, 197 (55.0%) patients had SPT, and 83 (23.2%) patients had ASPP. On multiple regression analysis, only patients with VFs located in T1–T9 or those who had a -2.5 ≤ T-score < -3.5 showed significantly higher incidences of RP, SPT, and ASPP (p < 0.05).Conclusion: Dynamic back pain and backache avoidance behavior are the typical clinical presentations of patients with OVFs. RP, SPT, and ASPP are nondeterministic incidents, indicating that avoidance is necessary with respect to cognitive bias in clinical practice.
miRNA-6087 Delivered by Exosomes Derived from Human Bone Marrow Mesenchymal Stem Cells, Inhibition of miR-6087 in Exosomes can Significantly Inhibit the Proliferation, Invasion and Migration of Tumor Cells.
Authors: Yang Xiaowei , Zhou Yibiao , Lai Qi , Huang Sheng , Liu Xuqiang , Hu Bolin , Dai Min , Zhang Bin
Published: December 2020

Background: Mesenchymal stem cells (hBMSCs) function in most of tumor microenvironment，including osteosarcoma,and interact with proximal cells. Here, in view of exosomes derived from hBMSCs, we studied the miRNA secreted from hBMSCs in the growth of human U2OS cells. Methods: hBMSCs were cultured in α-DMEM containing fetal bovine serum. After 48 hours, the cell culture supernatants containing the exosomes were harvested and exosome purification was performed by PEG-based vesicle enrichment. Osteosarcoma (U2OS) cells were treated with exosomes derived from hBMSCs enriched with or without miR-6087. Cell viability was measured by the scratch migration assay, Transwell invasion assay, and CCK-8 test. The expression of HSP70/ALIX and miR-6087 in exosomes was determined by western blotting and RT-PCR, respectively. Results: hBMSC-derived exosomes were found to play a key role in the U2OS cell growth. Inhibition of miR-6087 in exosomes can significantly inhibit the proliferation and invasion of tumor cells.Conclusion: This was the first time that we demonstrated that exosomes derived from hBMSCs have the power to suppress the growth of U2OS cells by downregulating miRNA-6087. Our research shows a new possibility for the way in which hBMSCs take part in tumor progression.
Designing a Sustainable Biofuel Supply Chain by Considering Carbon Policies: A Case Study in Iran
Authors: Zarrinpoor Naeme , Khani Aida
Published: December 2020

Background: Population growth and increasing the utilization of fossil fuels have increased carbon emissions and the global warming phenomenon with detrimental impacts on the human life and the environment. Therefore, finding a sustainable substitution for fossil fuels becomes a great challenge for all societies from all over the world. Renewable energies such as biofuels are the appropriate alternative to decrease environmental concerns.Methods: This study develops a multi-objective multi-period multi-echelon biofuel supply chain (BSC) from switch grass regarding economic, environmental and social aspects of the sustainability. For considering the environmental aspect, four carbon policies are taken into account; namely the carbon cap, the carbon tax, the carbon trade and the carbon offset. The fuzzy interactive programming method is implemented to solve the multi-objective model and the fuzzy best-worst method (FMWM) is applied for weighting social objective components.Results: To illustrate the applicability of the model, an actual case study in Iran is considered. It is revealed that different solutions are obtained for the location of switch grass resources, preprocessing centers, and bio-refineries under different carbon policies. Numerical results also demonstrate that biofuel production and transportation activities have a great share in carbon emissions and BSC costs. Applying the carbon cap policy in the proposed case study decreases the carbon emission over 14% in comparison to the basic situation. Moreover, implementing the carbon trade policy increases the total BSC profit about 11% in comparison to the basic situation. The carbon offset policy plays a significant role in improving social considerations compared with other policies. Overall, since three aspects of sustainability have appropriate values under the carbon trade policy, it can be concluded that this policy is the most appropriate policy.Conclusions: The proposed model can aid policy makers and governments to optimize the profitability of the BSC, the carbon emission reduction, and the social consideration, simultaneously.
Distinct symptoms and underlying comorbidities with latitude and longitude in COVID-19: A systematic review and meta-analysis
Authors: Tian Yong , Wu Qian , Li Honwei , Wu Qi , Xie Yi , Li Li , Chen Huaiyong
Published: December 2020

The coronavirus disease 2019 (COVID-19) pandemic is straining global health resources and the prevalence of severe disease appears to vary across countries. In accordance with PRISMA guidelines, we performed a systematic review and meta-analysis of clinical features and underlying medical conditions of COVID-19. Eighty-seven studies, involving 1,434,931 COVID-19 patients from the Americas, Asia, Europe, and Oceania, were included. Geographically, the rate of severity was highest in Asia (95% confidence interval [CI] 0.23‒0.30). The rates of comorbidities of COVID-19 patients in the Americas were significantly higher than those in Asia. Most Asian patients had fever (95%CI 0.70‒0.81), and most Oceanian patients had cough (95%CI 0.68‒0.70) as their prevalent symptom. Dyspnea was common in the Americas (95%CI 0.33‒0.64), Europe (95%CI 0.29‒0.64), and high latitude regions (95%CI 0.53‒0.82). European patients exhibited significantly high rates of loss of smell and taste (95%CI 0.60-0.97). In low-latitude regions, cancer (95%CI 14.50‒4.89) had the strongest correlation with illness severity. Comorbid diseases and clinical manifestations of severe COVID-19 patients vary substantially between latitudes and longitudes. Region-specific care should be considered to treat and improve the prognosis of COVID-19 patients.