bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression and function of transmembrane 4 superfamily proteins in digestive system cancers
Authors: Qi Yaoyue , Li Hui , Lv Jing , Qi Weiwei , Shen Liwei , Liu Shihai , Ding Aiping , Wang Gongjun , Sun Libin , Qiu Wensheng
Published: June 2020

Background Although the medical level is constantly improving, cancer is still a major disease that threatens human health, and very effective treatments have not been found. In recent years, studies have found that four-transmembrane superfamily proteins are involved in multiple stages of tumorigenesis and development, but their expression and function in tumors have not been systematically studied.Methods We used the Oncomine database to analyze the mRNA expression levels of TSPAN family in various cancers. Then differentially expressed genes were screened out and verified by liver cancer, colorectal cancer, and gastric cancer cells by q-PCR and Western blot analysis. CCK8 and EDU analysis are used to detect cell proliferation, Cell wound scrape assay and Cell invasion assay are used to analyze cell invasion and metastasis. Nude tumor formation test used to verify the tumor suppressive effect of TSPAN7 in vivo.Results Differential analysis of 33 TSPAN proteins revealed that a total of 11 proteins showed differential expression in 10% of independent analyses, namely TSPAN1, TSPAN3, TSPAN5, TSPAN6, TSPAN7, TSPAN8, TSPAN13, TSPAN25, TSPAN26, TSPAN29, TSPAN30 . TSPAN7 is the only four-transmembrane protein with reduced expression in three types of digestive tract tumors, so we chose TSPAN7 to be selected for cellular and molecular level verification. We found that compared with normal cells, the expression of TSPAN7 in liver cancer cells was significantly reduced, while the expression of gastric and colon cancer was not significantly different from that of normal cells. In addition, we also found that the high expression of Tspan7 not only inhibited the proliferation of HCC-LM3 cells, but also inhibited its invasion and metastasis.Conclusions Our study evaluated the expression and function of the TSPANs family in digestive cancers and explored TSPAN7 in hepatoma cells in detail. We found some members of the TSPAN family show significant expression differences between cancer and normal tissues, of which TSPAN7 may be a potential biomarker for liver cancer.
Mortality of severely injured patients after ICU discharge: An underestimated problem?
Authors: Hamsen Uwe , Drotleff Niklas , Lefering Rolf , Gerstmeyer Julius , Schildhauer Thomas Armin , Waydhas Christian
Published: June 2020

Background Most trauma patients admitted to the hospital alive and die later on, decease during the initial care in the emergency department or the intensive care unit (ICU). However, a number of patients pass away after having been discharged from the ICU during the initial hospital stay. On first sight these cases could be seen as “failure to rescue” of potentially salvageable patients. A low rate of such patients might be a potential indicator of quality for trauma care on ICUs and surgical wards.Methods Retrospective analysis of the TraumaRegister DGU® with data from 2015-2017. Patients that died during the initial ICU stay were compared to those who were discharged from the initial ICU stay for at least 24 hours but died later on.Results A total of 82,313 trauma patients were included in the TraumaRegister DGU®. In total, 6,576 patients (8.0%) died during their hospital stay. Out of those, 5,481 were admitted to the ICU alive and 972 patients (17.7%) were discharged from ICU and died later on. Those were older (mean age: 77 vs. 68 years), less severely injured (mean ISS: 23.1 vs. 30.0 points) and had a longer mean ICU length of stay (10 vs. 6 days). A limitation of life-sustaining therapy due to a documented living will was present in 46.1% of all patients who died during their initial ICU stay and in 59.9% of patients who died after discharge from their initial ICU stay.Conclusions 17.7% of all non-surviving severely injured trauma patients died within the hospital after discharge from their initial ICU treatment. Their death can partially be explained by a limitation of therapy due to a living will. In conclusion, the rate of such late deaths may represent patients that died of potentially avoidable or treatable complications.
Inferring Grasp Intentions from Arm Trajectories via Deep Learning to Enable Functional Movement in Quadriplegia Revised Title Determining Grasp Selection from Arm Trajectories via Deep Learning to Enable Functional Hand Movement in Tetraplegia
Authors: Bhagat Nikunj , King Kevin , Ramdeo Richard , Stein Adam , Bouton Chad
Published: June 2020

Background: Cervical spinal cord injury severely affects grasping ability of its survivors. Fortunately, many individuals with tetraplegia retain residual arm movements that allow them to reach for objects. We propose a wearable technology that utilizes arm movement trajectory information and deep learning methods to determine grasp selection. Furthermore, we combined this approach with neuromuscular stimulation to determine if self-driven functional hand movement could be enabled in spinal cord injury participants.Methods: Two cervical SCI participants performed arbitrary and natural reaching movements toward target objects in three-dimensional space, which were recorded using an inertial sensor worn on their wrist. Time series classifiers were trained to recognize the trajectories using either a Dynamic Time Warping (DTW) algorithm or a Long Short-Term Memory (LSTM) recurrent neural network. As an initial proof-of-concept, we demonstrate real-time classification of the arbitrary movements using DTW only (due to its implementation simplicity), which when used in combination with a high density neuromuscular stimulation sleeve with textile electrodes, enabled participants to perform functional grasping.Results: Participants were able to consistently perform arbitrary two-dimensional and three-dimensional arm movements which could be classified with high accuracy. Furthermore, it was found that natural reaching trajectories for two different target objects (requiring two different grasp types) were distinct and also discriminable with high accuracy. In offline comparisons, LSTM (mean accuracies 99%) performed significantly better than DTW (mean accuracies 86% and 83%) for both arbitrary and natural reaching movements, respectively. Type I and II errors occurred more frequently for DTW (up to 60% and 15%, respectively), whereas it stayed under 5% for LSTM. Also, DTW achieved online accuracy of 79%. Conclusions: We demonstrate the feasibility of utilizing arm trajectory information to determine grasp selection using a wearable inertial sensor along with DTW and deep learning methods. Importantly, this technology can be successfully used to control neuromuscular stimulation and restore functional independence to individuals living with paralysis.
The profile of hematinic deficiencies in patients with oral lichen planus: a case-control study
Authors: Bao Zhe-xuan , Yang Xiao-wen , Shi Jing , Wang Yufeng
Published: June 2020

Background: Oral lichen planus (OLP) is a relatively common mucocutaneous disorder, its causative factors and pathogenesis are not fully understood. The existing studies on the association between hematinic deficiencies and OLP are limited and inconsistent. The aim of this study was to assess the hematinic deficiencies in a cohort of OLP patients and evaluate the correlation between hematinic deficiencies and OLP. Methods: 236 OLP patients and 226 age-and gender-matched healthy controls were enrolled in this study. The levels of hemoglobin (Hb), serum folate, vitamin B12 and ferritin were measured and compared between OLP patients and healthy controls. REU (reticular/hyperkeratotic, erosive/erythematous, ulcerative) scoring system was adopted and compared between the OLP patients with and without hematinic deficiencies. The correlation between hematinic deficiencies and OLP was analyzed. Results: The frequencies of serum ferritin and vitamin B12 deficiency in OLP patients were both significantly higher than those of the healthy controls. According to gender and age, the profiles of hematinic deficiencies in OLP patients were significantly different. As for REU score, no significant difference existed between OLP patients with and without hematinic deficiencies. Both serum ferritin deficiency and serum vitamin B12 deficiency were significantly correlated with OLP. Conclusions The present study suggested a significant association between hematinic deficiencies and OLP. Iron, folate, and vitamin B12 levels in OLP patients should be monitored routinely. Further studies are warranted to explore the interactions between OLP and hematinic deficiencies.
Signs and symptoms do not predict, but may help rule out acute Q fever in favour of other respiratory tract infections, and reduce antibiotics overuse in primary care
Authors: Hackert Volker Heinz , Dukers-Muijrers Nicole H.T.M. , Hoebe Christian J.P.A.
Published: June 2020

Background: From early 2009, the Dutch region of South Limburg experienced a massive outbreak of Q fever, overlapping with the influenza A(H1N1)pdm09 pandemic during the second half of the year and affecting approximately 2.9% of a 300,000 population. Acute Q fever shares clinical features with other respiratory conditions. Most symptomatic acute infections are characterized by mild symptoms, or an isolated febrile syndrome. Pneumonia was present in a majority of hospitalized patients during the Dutch 2007-2010 Q fever epidemic. Early empiric doxycycline, guided by signs and symptoms and patient history, should not be delayed awaiting laboratory confirmation, as it may shorten disease and prevent progression to focalized persistent Q fever. We assessed signs’ and symptoms’ association with acute Q fever to guide early empiric treatment in primary care patients. Methods: In response to the outbreak, regional primary care and hospital-based specialty physicians tested a total of 1218 subjects for Q fever. Testing activity was bimodal, a first “wave” lasting from March to December 2009, followed by a second “wave” which lasted into 2010 and coincided with peak pandemic influenza activity. We approached all 253 notified acute Q fever cases and a random sample of 457 Q fever negative individuals for signs and symptoms of disease. Using data from 140/229(61.1%) Q fever positive and 194/391(49.6%) Q fever negative respondents from wave 1, we built symptom-based models predictive of Q-fever outcome, validated against subsets of data from wave 1 and wave 2. Results: Our models had poor to moderate AUC scores (0.68% to 0.72%), with low positive (4.6-8.3%), but high negative predictive values (91.7-99.5%). Male sex, fever, and pneumonia were strong positive predictors, while cough was a strong negative predictor of acute Q fever in these models. Conclusion: Whereas signs and symptoms of disease do not appear to predict acute Q fever, they may help rule it out in favour of other respiratory conditions, prompting a delayed or non-prescribing approach instead of early empiric doxycycline in primary care patients with non-severe presentations. Signs and symptoms thus may help reduce the overuse of antibiotics in primary care during and following outbreaks of Q fever.
Kidney ventrally rotation technique in retroperitoneal robot-assisted partial nephrectomy for posterior hilar tumor: technical feasibility and preliminary results
Authors: Yin Xiaotao , Jiang Sinan , Shao Zhiqiang , Lu Yongliang , Guo Jiangxiang , Xiao Yi , Zhu Xiaoying , Yu Hualiang , Ma Han , Yang Yu , Gao Jiangping
Published: June 2020

Purpose: The retroperitoneal robotic assisted partial nephrectomy (RAPN) is suitable for tumors locating on the posterior side of the kidney. However, the posterior hilar tumor poses additional surgical challenge due to the special location and poor tumor exposure. We developed a novel kidney ventrally rotation technique to overcome this difficulty during retroperitoneal RAPN, and evaluated its efficacy in a retrospective case-control comparative .Methods: From March 2016 to April 2019, a total of 39 patients with posterior renal hilar tumor underwent retroperitoneal RAPN. The kidney ventrally rotation technique, which improved the tumor exposure by opening the peritoneum and rotating the kidney ventrally, was applied in 24 cases and the conventional RAPN was performed in the other 15 cases (control group). Perioperative data was analyzed to evaluate the efficacy of the kidney ventrally rotation technique.Results: In kidney rotation group, the 24 patients underwent RAPN successfully without converting to open surgery or radical nephrectomy. The warm ischemia time was 17.4 ± 6.6 min, which was significantly shorter than 24.5 ± 8.3 min in control group. The mean operation time (80 ± 24 min) and estimated blood loss (104 ± 65 ml) were not different from control group. No sever complications occurred, and no positive surgical margin was found in all the malignant cases. After 14 months follow-up, no recurrence or metastasis occurred in all cases.Conclusion: Kidney ventrally rotation technique is safe and feasible for improving the exposure of posterior renal hilar tumor during retroperitoneal RAPN. It could be regarded as an efficient option for the management of posterior hilar tumor.
Short Wave Enhances Mesenchymal Stem Cell Recruitment through Hypoxia-Inducible Factor-1 Signaling in Fracture Healing
Authors: Ye Dongmei , Chen Chen , Wang Qiwen , Zhang Qi , Li Sha , Liu Hongwei
Published: June 2020

Background: As a type of high-frequency electrotherapy, a Short-Wave can promote the fracture healing process; yet, its underlying therapeutic mechanisms still remain unclear.Purpose: To observe the effect of Short-Wave therapy on mesenchymal stem cell (MSC) homing and relative mechanisms associated with fracture healing. Materials and Methods: The effect of Short-Wave therapy in relation to fracture healing was examined in 40 SD rats. Stabilized femur fractures were established by intramedullary fixation; radiography was used to analyze the morphology and micro-architecture of the callus. Additionally, fluorescence assays were used to analyze the MSC migration after treatment in 20 nude mice with a femoral fracture. For in vitro study, osteoblast simulated fracture site was first irradiated by the Short-Wave; siRNA targeting HIF-1 was used to investigate the role of HIF-1. Osteoblast culture medium was then collected as chemotaxis content of MSC, and the migration of MSC was evaluated using wound healing assay and trans-well chamber test. The expression of HIF-1 and its related factors were quantified by q RT-PCR, ELISA, and Western blot.Results: Our in vivo experiment indicated that Short-Wave therapy could promote MSC migration, increase local and serum HIF-1 and SDF-1 levels, induce changes in callus formation, and improve callus microarchitecture and mechanical properties, thus speeding up the healing process of the fracture site. Moreover, the in vitro results further indicated that Short-Waves therapy upregulated HIF-1 and SDF-1 expression in osteoblast and in the medium, as well as the expression of CXCR-4, β-catenin, F-actin and phosphorylation levels of FAK in MSC. On the other hand, the inhibition of HIF-1α was significantly restrained by the inhibition of HIF-1α in osteoblast, and it partially inhibited the migration of MSC.Conclusions: These results suggested that Short-Wave therapy could increase HIF-1 in callus, which is one of the crucial mechanisms of chemotaxis MSC homing in fracture healing.
The psychometric properties of the Persian Menopause Rating Scale
Authors: Jahangiry Leila , Parviz Robabeh , Mirghafourvand Mojgan , Khazaee-Pool Maryam , Ponnet Koen
Published: June 2020

Background: To measure the severity of menopausal complaints and determine the pattern of menopausal symptoms, a valid and reliable instrument is needed in women’s healthcare. The Menopause Rating Scale (MRS) is one of the best-known tools in response to the lack of standardized scales. The purpose of this study was to examine the psychometric properties of the MRS in an Iranian example. Methods: Participants were randomly selected from women referred to healthcare centers in Miandoab, West Azerbaijan, Iran. A total of 330 questionnaires were completed (response rate of 96.9%). Two samples were considered for analysis in the validation process. An exploratory factor analysis (EFA) was conducted on the first sample (n1 =165), and a confirmatory factor analysis (CFA) was done using a second study sample (n2 = 165). The psychometric properties process was concluded with assessment of internal consistency and test-retest reliability. Results: The EFA with Principal Component Analysis extracted three factors explaining 75.47% cumulative variance. The CFA confirmed a three-factor structure of the 11-items MRS. All fit indices proved to be satisfactory. The relative chi-square (χ2/df) was 3.686 (p < .001). The Root Mean Square Error of Approximation (RMSEA) of the model was .04 (90% CI = .105 – .150). All comparative indices of the model, including the Comparative Fit Index, Normed Fit Index, and Relative Fit Index, were more than .80 (.90, .87, and .80, respectively). For the overall scale, Cronbach’s alpha was .931, whereas the alpha for the subscales ranged from 0.705-0.950. The intraclass correlation was .91 (95% CI = .89-.93), p < 0.001. Conclusion: The results of the study indicate that the Persian model of the MRS is a valid and reliable scale. As a screening tool, the Persian MRS could be used to identify the pattern of symptoms among menopausal, premenopausal, and postmenopausal women to care for and educate them on how to identify and treat the symptoms.
Platelet count as a biomarker for monitoring treatment response and disease recurrence in recurrent epithelial ovarian cancer
Authors: Hu Qinghong , Hada Abha , HAN Liping
Published: June 2020

Objectives: We sought to determine the impact of pretreatment plasma platelet levels, dimerized plasmin fragment (D-dimer) and fibrinogen in recurrent epithelial ovarian cancer (EOC) and the impact of platelet levels on SKOV3 cell lines growth and responsiveness to chemotherapy.Methods: Under approval of ethical committee, we identified 104 women with recurrent EOC who underwent treatment between January 2010 and February 2015. Reviewing clinical, laboratory, and pathologic records from this retrospective cohort, we analyzed the correlation between pretreatment plasma D-dimer, fibrinogen, platelet levels and clinicopathological parameters, progression free survival (PFS)and overall survival (OS). Inco-culture experiments human ovarian cancer SKOV3 cell lines were used to test the effect of platelet levels on tumor growth and responsiveness to docetaxel.Results: Of the 104 recurrent EOC, thrombocytosis at diagnosis and the decrease of platelet count by less than 25% after primary therapy were associated with worse median progression free survival (P=0.003;P=0.021) and median overall survival (P = 0.009;P=0.009).Mean platelet levels declined at the end of primary therapy(P<0.001) and rose at recurrence(P=0.007) .In multivariate analysis, elevated platelet levels at primary therapy and the decrease of platelet count less than 25% after primary therapy were unfavorable prognostic factor for PFS( P=0.022; P=0.015) and OS(P=0.013;P=0.007)in recurrent EOC, but elevated plasma D-dimer and fibrinogen were not. In SKOV-3 ovarian cancer cell lines, suitable concentration platelet co-culture protected against apoptosis (P< 0.05).Conclusions: Platelet count during treatment could be used as a biomarker used for monitoring the disease recurrence and predicting treatment response. And platelet with suitable concentration co-culture protected against apoptosis in SKOV3 cell line, which may explain clinical observations.
Predictors of poor outcome in cervical spondylotic myelopathy patients underwent anterior hybrid approach: focusing on change of local kyphosis
Authors: Cheng XingJian , Jin Lin , Wang Xin , Zhang Wen , Shen Yong
Published: June 2020

Object: This study was a retrospective multivariable analysis for risk factors of poor outcome in patients underwent anterior hybrid approach, and discussed the causes of worsening of postoperative local alignment.Methods: A total of 86 patients with progressive spinal cord compression and local kyphosis underwent an anterior hybrid approach (ACDF+ACCF), between June 2011 and June 2017. We evaluated clinical outcome by the Japanese Orthopaedic Association (JOA) score and recovery rate. Patients were divided into two groups according to worsening and improving of postoperative local alignment. Multivariate logistic regression analysis and receiver operating characteristic (ROC) curve were applied to the evaluation of risk factors. Mann–Whitney U-test, Independent t-test and Chi-squared test was performed for the comparison of local kyphosis between postoperative and last follow-up.Results: There were twenty patients who had a recovery rate of less than 50%. Advance age, longer duration of symptoms, bigger T1 slope angle and lower change of local kyphosis angle was significantly associated with a poor clinical outcome by multivariate logistic regression analysis. The ROC curve showed that the cutoff values of change of local angle between preoperative and last follow-up was 10.2 angle. The cause of worsening of postoperative local alignment had T1 slope, C2-7 sagittal vertical axis (SVA), adjacent segment degeneration (ASD), and implant subsidence.Conclusions: The change of local kyphosis was a predictor of clinical outcome after the hybrid approach. Furthermore, postoperative ASD, implant subsidence, T1 slope and C2-7 Cobb were associated with recurrence of postoperative cervical kyphosis.
Transcriptomic analysis of flower opening response to relatively low temperatures in Osmanthus fragrans
Authors: Fu Jianxin , Zhang Chao , Liu Yucheng , Pang Tianhong , Dong Bin , Gao Xiaoyue , Zhu Yimin , Zhao Hongbo
Published: June 2020

Background: Sweet osmanthus ( Osmanthus fragrans Lour.) is one of the top ten traditional ornamental flowers in China. The flowering time of once-flowering cultivars in O . fragrans is greatly affected by the relatively low temperature, but there are few reports on its molecular mechanism to date. A hypothesis had been raised that genes related with flower opening might be up-regulated in response to relatively low temperature in O . fragrans . Thus, our work was aimed to explore the underlying molecular mechanism of flower opening regulated by relatively low temperature in O . fragrans . Results: The cell size of adaxial and abaxial petal epidermal cells and ultrastructural morphology of petal cells at different developmental stages were observed. The cell size of adaxial and abaxial petal epidermal cells increased gradually with the process of flower opening. Then the transcriptomic sequencing was employed to analyze the differentially expressed genes (DEGs) under different number of days’ treatments with relatively low temperatures (19°C) or 23°C. Analysis of DEGs in Gene Ontology analysis showed that “metabolic process”, “cellular process”, “binding”, “catalytic activity”, “cell”, “cell part”, “membrane”, “membrane part”, “single-organism process”, and “organelle” were highly enriched. In KEGG analysis, “metabolic pathways”, “biosynthesis of secondary metabolites”, “plant-pathogen interaction”, “starch and sucrose metabolism”, and “plant hormone signal transduction” were the top five pathways containing the greatest number of DEGs. The DEGs involved in cell wall metabolism, phytohormone signal transduction pathways, and eight kinds of transcription factors were analyzed in depth. Conclusions: Several unigenes involved in cell wall metabolism, phytohormone signal transduction pathway, and transcription factors with highly variable expression levels between different temperature treatments may be involved in petal cell expansion during flower opening process in response to the relatively low temperature. These results could improve our understanding of the molecular mechanism of relatively-low-temperature-regulated flower opening of O. fragrans , provide practical information for the prediction and regulation of flowering time in O . fragrans , and ultimately pave the way for genetic modification in O . fragrans .
Patterns of recurrence in adenocarcinoma of the esophagogastric junction: a retrospective study
Authors: xu haitao , Zhang Lianguo , Miao Jing , Liu Shuai , Liu Hongjian , Jia Teng , Zhang Qingguang
Published: June 2020

Background: The prognosis of adenocarcinoma of the esophagogastric junction (AEG) is poor. Understanding the postoperative recurrence pattern of AEG is helpful to verify the effectiveness of treatment and optimize subsequent treatment, so as to improve prognosis.Methods: This single centre,retrospective study included patients with stage III AEG who underwent surgical treatment between January 2009 and December 2016. According to the different postoperative treatment arm, patients were divided into surgery and surgery plus chemotherapy groups. Recurrence-free survival was used as the outcome to compare the recurrence site and pattern between the groups. Results: In total, enrolled 306 patients, 123 in the surgery group and 183 in the surgery plus chemotherapy group.During follow-up (median 17.1 months) of 24 months after surgery, 62.0% of patients had tumor recurrence. The overall recurrence rates in the surgery and surgery plus chemotherapy group were 86.9% and 77.0%, respectively. The recurrence patterns of both groups were mainly distant metastasis. Postoperative chemotherapy reduced the incidence of hematogenous dissemination from 51.2% to 42.0%. Multivariate Cox analysis showed that pN stage increased the risk of recurrence,while surgery plus chemotherapy reduced the risk. Conclusions: Patients with AEG have a risk of hematogenous dissemination after surgery. Postoperative treatment arm and pN stage were independent risk factors in patients with AEG.Surgery plus chemotherapy can improve RFS and reduce distant metastasis, but they do not have a beneficial role in controlling local recurrence.
Identification of novel genes associated with dysregulation of B cells in patients with primary Sjögren's syndrome
Authors: Inamo Jun , Suzuki Katsuya , Takeshita Masaru , Kassai Yoshiaki , Takiguchi Maiko , Kurisu Rina , Okuzono Yuumi , Tasaki Shinya , Yoshimura Akihiko , Takeuchi Tsutomu
Published: June 2020

Background. The aim of this study was to identify the molecular mechanism of dysregulation of B cell subpopulations of primary Sjögren's syndrome (pSS) at the transcriptome level. Methods. We enrolled patients with pSS (n=6) and healthy controls (HC) (n=6) in the discovery cohort using microarray and pSS (n=14) and HC (n=12) in the validation cohort using quantitative PCR (qPCR). Peripheral B cells acquired from these subjects were separated by cell sorting into four subsets: CD38-IgD+ (Bm1), CD38+IgD+ (naïve B cells), CD38highIgD+ (pre-germinal centre B cells) and CD38±IgD- (memory B cells). We performed differentially expressed genes (DEGs) analysis and weighted gene co-expression network analysis (WGCNA).Results. Expression of the long non-coding RNA LINC00487 was significantly upregulated in all B cell subsets, as was that of HLA and interferon (IFN) signature genes. Moreover, the normalized intensity value of LINC00487 significantly correlated with the disease activity score of all pSS B cell subsets. Studies of human B cell lines revealed that the expression of LINC00487 was strongly induced by IFNα. WGCNA revealed six gene clusters associated with the B cell subpopulation of pSS. Further, SOX4 was identified as an inter-module hub gene.Conclusion. Our transcriptome analysis revealed key genes involved in the dysregulation of B cell subpopulations associated with pSS.
Bioinformatics analysis and characterization of a secretory cystatin from Thelohanellus kitauei
Authors: Zhang Fengli , Yang Yalin , Gao Chenchen , Yao Yuanyuan , Xia Rui , Hu Juan , Ran Chao , Zhang Zhen , Zhou Zhigang
Published: June 2020

Thelohanellus kitauei , is a group of obligate parasitic Myxozoans, which causes intestinal giant-cystic disease of common carp ( Cyprinus carpio) and has resulted in significant economic losses in carp farms. Cystatin secreted by parasites can regulate the immune response of host to facilitate parasite’s survival. In this study, the secretory TK-cystatin gene, encoding a protein of 120 amino acid residues (13.65 kDa), was cloned from T. kitauei genome. Phylogenetic analysis showed that TK-cystatin gene is closely related to the cystatin-A from Hydra vulgaris . Multiple sequence alignment revealed that TK-cystatin had three conserved motifs: N-terminal G 19 G 20 , Q 73 VVAG 77 , and C-terminal L 102 P 103 . Molecular docking between TK-cystatin and three cysteine proteases showed a lower binding energy (-13 kal/mol) with cathepsin L whereas a higher binding energy (-8.6 kal/mol) with cathepsin B. TK-cystatin gene was expressed in Escherichia coli . Activity assays revealed that TK-cystatin has stronger inhibitory activity on endopeptidases (papain and cathepsin L) and weaker inhibitory activity on exopeptidase (cathepsin B). TK-cystatin was stable under the condition of acidity or alkalinity or below 57 °C. This study laid a foundation for the design and development of the anti-TK-cystatin vaccine in carp culture in the future.
Guidance concerning chiropractic practice in response to COVID-19 in the U.S.: A summary of state regulators' web-based information
Authors: Neff Shawn M , Roecker Christopher B , Okamoto Casey S , Holguin Samuel L , Napuli Jason G , Mattox Ross , Hinkeldey Nathan A , Paris David J
Published: June 2020

Introduction: The COVID-19 pandemic led to unprecedented changes, as many state and local governments enacted stay-at-home orders and non-essential businesses were closed. State chiropractic licensing boards play an important role in protecting the public via regulation of licensure and provision of guidance regarding standards of practice, especially during times of change or uncertainty. Objective: The purpose of this study was to summarize the guidance provided in each of the 50 United States, related to chiropractic practice during the COVID-19 pandemic.Methods: A review of the public facing websites of governors and state chiropractic licensing boards was conducted in the United States. Data were collected regarding the official guidance provided by each state’s chiropractic licensing board as well as the issuance of stay-at-home orders and designations of essential personnel by state governors. Descriptive statistics were used to report the findings from this project. Results: Each of the 50 state governor’s websites and individual state chiropractic licensing board’s websites were surveyed. Stay-at-home or shelter-in-place orders were issued in 86% of all states. Chiropractors were classified as essential providers in 54% of states, non-essential in one state (2%), and no guidance was provided in the remaining 44% of all states. Fourteen states (28%) recommended restricting visits to only urgent cases and the remaining states (72%) provided no guidance. Twenty-seven states (54%) provided information regarding protecting against infectious disease and the remaining states (46%) provided no guidance. Twenty-two states (44%) provided recommendations regarding chiropractic telehealth and the remaining states (56%) provided no guidance. Seventeen states (34%) altered license renewal requirements and eight states (16%) issued warnings against advertising misleading or false information regarding spinal manipulation and protection from COVID-19.Conclusion: State guidance during the COVID-19 pandemic was heterogenous, widely variability in accessibility, and often no guidance was provided by state chiropractic licensing boards. Some state chiropractic licensing boards chose to assemble guidance for licensees into a single location, which we identified as a best practice for future situations where changes in chiropractic practice must be quickly communicated.
E Health and Electronic Health Record: The Italian experience in the European Context
Authors: Marino Alfonso , Pariso Paolo , Landriani Loris
Published: June 2020

Background In the reform context as declared by the Italian Government Law, related to National Health Service, the country are implementing the Information and Communication Technology such as eHealth and Electronic Health Record (EHR). This study aims at evaluating the degree of diffusion and adoption of the Electronic Health Records in southern Italy.Methods Starting from Italian Regional Inpatient Dataset, that collects data from the hospitals, the study considered several strategic variables in order to assess, within main hospitals of six provincial capitals of southern Italy (Napoli, Bari, Reggio Calabria, Potenza, Palermo, Cagliari), the implementation status of Electronic Health Records. These variables set up Hospital Organizational Indicator and by using SPSS a univariate regression analysis has been developed to obtain descriptive statistics.Results The results provide a preliminary forecast at the Electronic Health Records’ use and suggests that, in their actual implementation, Electronic Health Records have not begun to reach targets and have a smaller impact than expected on hospital organization.Conclusions The study shows how the EHR is in close correlation with E Health policies and how it can affect such policies as well. The nature of the Italian E Health and applied to the Electronic Health Record showed dated and unsolved bottlenecks within southern Italy, highlighting on the one hand a digital divide between the provision of digital services and the patients and, the on the other hand, a weakness linked to the structure of the organizations based only on rules and procedures and not outcomes and results.
Silencing of KNTC1 inhibits hepatocellular carcinoma cells progression via suppressing PI3K/Akt pathway
Authors: Tong Hui , Xie Junjie , Liu Xiaohui , Peng Chenghong , Shen Baiyong , Zhu Zhecheng
Published: June 2020

Background: Kinetochore associated 1 (KNTC1) encodes a kinetochore component in Rod‐Zwilch‐ZW10 (RZZ) complex which is essential for the segregation of sister chromatids during mitosis and participates in the spindle checkpoint. Recent research demonstrated that kinetochore proteins may be potential biomarkers and may contribute to the development of human malignancies. Here, we sought to identify the biological significances of KNTC1 in hepatocellular carcinoma (HCC).Methods: KNTC1 expression was studied in HCC tissues by immunohistochemistry. Lentivirus delivered short hairpin RNA (shRNA) was performed to generate KNTC1 knockdown HCC cell lines. The effects of KNTC1 on HCC cells proliferation, migration, apoptosis and tumor formation was analyzed by MTT assay, colony formation assay, wound‐healing assay, transwell migration assay, annexin V assay in vitro and in nude mouse models in vivo.Results: Our immunohistochemistry experiment showed that KNTC1 was highly expressed in HCC tissues and correlated with terrible prognosis, indicating that KNTC1 acts a pivotal role in HCC development. Furthermore, shRNA KNTC1 (Lv‐shKNTC1) was applied to infect BEL‐7404 and SK‐HEP‐1 to identify roles of KNTC1 on HCC. Lv‐shKNTC1 cells showed reduced proliferation ability, increased apoptosis and decreased migration ability. In vivo experiments suggested that xenografts grow significantly slower upon the silencing of KNTC1. Mechanistically, the protein levels of PIK3CA, p‐Akt, CCND1, CDK6 are all down‐regulated in Lv‐KNTC1 SK‐HEP‐1 cells. Therefore, KNTC1 may affect the biological activity of HCC cells through PI3K/Akt signaling pathway.Conclusions: In summary, the key finding of this report highlighted the significance of KNTC1 in tumor regression of HCC, demonstrating KNTC1 as an innovative target for adjuvant treatment of HCC.
Effect of the Electrode Array-Retina Gap Distance on Visual Function in Patients with the Argus II Retinal Prosthesis
Authors: Naidu Abhishek , Ghani Nimra , Yazdanie Mohammad Saad , Chaudhary Khurram
Published: June 2020

Background
Post-implantation visual outcomes in patients with the Argus II Retinal Prosthesis is dependent on a multitude of factors including the positioning of the electrode array on the retina. The purpose of this study is to determine whether the average electrode array-retina gap distance correlates with objective visual function outcomes and sensitivity detection thresholds in patients implanted with the Argus II Retinal Prosthesis.
Methods
5 patients with implantation of the Argus II Retinal Prosthesis were enrolled in this single-institution retrospective study. Patient demographics were collected from medical records. Visual function data (Square Localization [SL] and Direction of Motion [DOM]) and Optical Coherence Tomography (Cirrus HD-OCT) images were extracted retrospectively from the Argus II Retinal Prosthesis Post-Approval study. Visual function tests were performed with the device OFF and ON at each study visit. Electrode array-retina gap distances were measured at each of the array’s 60 electrodes using the Cirrus HD-OCT software in both the nasotemporal and superoinferior planes. Data was obtained at baseline, and post-operative month 1, month 3, month 6, and year 1. Sensitivity detection thresholds were obtained at the initial programming visit and each reprogramming session.
Results
1 of 5 patients had a significant average improvement in the SL visual function test and 0 of 5 had a significant average improvement in the DOM visual when the device was ON compared to OFF (p < 0.05). Electrode array-retina gap distance did not show a significant correlation with changes in SL visual function (r = 0.20; p = > 0.05) or DOM visual function (r = -0.18; p = > 0.05). In addition, electrode array-retina gap distance did not show a significant correlation with sensitivity detection threshold (r = -0.01; p = 0.98).
Conclusion
Our results demonstrate that the average electrode array-retina gap distance does not correlate with changes in objective visual acuity function or sensitivity detection thresholds in a cohort of patients implanted with the Argus II Retinal Prosthesis. Therefore, complete apposition between the electrode array and retina may not always be necessary to achieve optimal visual outcomes.
Systematic Profiling of Survival-Associated Alternative Splicing Events in Adrenocortical Carcinoma
Authors: Fang Xia , Wan Qin , Long Yang , Teng Fangyuan , Tan Xiaozhen , Guo Man , Jiang Zongzhe , xu yong
Published: June 2020

Background: Aberrant alternative splicing (AS) is involved in many oncogenic processes and systematic analysis of survival-associated aberrant AS events has been reported in many cancers. This study aims to systematic profiling the AS signature in Adrenocortical carcinoma (ACC).Methods: Data of ACC were downloaded from TCGA and TCGA SpliceSeq. Clinical information and AS events data were integrated with the same TCGA ID. Then, we performed univariate Cox analysis to identify survival-related AS events. Lasso regression and multivariate Cox analysis were used to establish prognostic model. In addition, several bioinformatics analyses were conducted to identify pathways enriched by genes of survival-associated AS events and construct splicing-factor-regulated network.Results: A total of 77 patients with complete clinical information and PSI values of AS events were included in the present study. We detected 3781 AS events in 2366 genes were associated with overall survival of ACC patients. All the predictive models showed efficiency in distinguishing good and poor outcomes of ACC patients. All the AUCs of predictive models were greater than 0.7. Functional analysis genes with survival-associated AS events suggested that the POLR2H, TCEB2, PSMA1, PSMD11 and SKP2 ranked at the core. The splicing-factor-regulated network revealed the potential regulatory mechanisms of AS events in ACC.Conclusions: Our systematic profiling of survival-associated AS events in ACC patients provides novel molecular alternations and contributes to decipher the underlying mechanisms of AS in oncogenesis of ACC.
Sick Leaves Pattern in A Tertiary Healthcare Facility in Saudi Arabia
Authors: Elabd Kossay Abdelhamid Ali , Alkhenizan Abdullah , Aldughaither Abdullah S.
Published: June 2020

BACKGROUND : Frequent sick leaves in any healthcare organization is a critical problem that can undermine the patients' care. METHODS : This is a quantitative cross-sectional study looking at the frequency of sick leaves among employees of a large, tertiary healthcare facility in Riyadh. We randomly selected 474 employees, who were seen in family medicine clinics during one-year period. We collected all the data retrospectively from their electronic medical records. Then we reviewed and analyzed all the data using SPSS software. RESULTS : There was no difference in the sick leaves rate between males and females (P-value 0.8618), but we saw a higher rate among younger employees (40 years old or less) compared to those 41 years or older (p-value <0.0001). We also investigated those who took four sick leaves or more during the period of the study, and we found that most of them were mainly nursing staff (31.71%), hospital assistances (24.39%) and housekeepers (14.63%). The commonest cause for taking sick leave in our study was viral upper respiratory tract infection. Therefore, we studied the effect of influenza vaccine on the frequency of sick leaves and we found that those who took the vaccine were less likely to take a leave because of flu (P-value <0.0001, Odd ratio 0.4067 with 95% CI 0.2739-0.608). CONCLUSION : younger employees, nurses, hospital assistants and housekeepers are more likely to take sick leaves. These findings need to be studied further in the future to help us dealing with the problem of absenteeism. Flu is the leading cause for sick leaves and influenza vaccine seemed to reduce its rate. In this study, we also discussed different methods that can be used by any healthcare organization to reduce absence rate.
Trends in prevalence, mortality and morbidity associated with high systolic blood pressure in Brazil from 1990 to 2017: estimates from the “Global Burden of Disease 2017” (GBD2017) study
Authors: Nascimento Bruno Ramos , Brant Luisa Campos Caldeira , Yadgir Simon , Oliveira Gláucia Maria Moraes , Roth Gregory , Glenn Scott Devon , Mooney Meghan , Naghavi Mohsen , Passos Valéria Maria Azeredo , Duncan Bruce Bartholow , Silva Diego Augusto Santos , Malta Deborah Carvalho , Ribeiro Antonio Luiz Pinho
Published: June 2020

Background
Hypertension remains the leading risk factor for cardiovascular disease (CVD) worldwide, and its impact in Brazil should be assessed in order to better address the issue. We aimed to describe trends in prevalence and burden of disease attributable to high systolic blood pressure (HSBP) among Brazilians ≥ 25 years old according to sex and federal units (FU) using the Global Burden of Disease (GBD) 2017 estimates.
Methods
We used the comparative risk assessment developed for the GBD study to estimate trends in attributable deaths and disability-adjusted life-years (DALY), by sex, and FU for HSBP from 1990 to 2017. This study included 14 HSBP-outcome pairs. HSBP was defined as ≥ 140 mmHg for prevalence estimates and a theoretical minimum risk exposure level (TMREL) of 110–115 mmHg was considered for disease burden. We estimated the portion of deaths and DALYs attributed to HSBP. We also explored the drivers of trends in HSBP burden, as well as the correlation between disease burden and sociodemographic development index (SDI).
Results
In Brazil, the prevalence of HSBP is 18.9% (95% uncertainty intervals [UI] 18.5–19.3%), with an annual 0.4% increase rate, while age-standardized death rates attributable to HSBP decreased from 189.2 (95%UI 168.5-209.2) deaths to 104.8 (95%UI 94.9-114.4) deaths per 100,000 from 1990 to 2017. In spite of that, the total number of deaths attributable to HSBP increased 53.4% and HSBP raised from 3rd to 1st position, as the leading risk factor for deaths during the period. Regarding total DALYs, HSBP raised from 4th in 1990 to 2nd cause in 2017. The main driver of change of HSBP burden is population aging. Across FUs, the reduction in the age-standardized death rates attributable to HSBP correlated with higher SDI.
Conclusions
While HSBP prevalence shows an increasing trend, age-standardized death and DALY rates are decreasing in Brazil, probably as results of successful public policies for CVD secondary prevention and control, but suboptimal control of its determinants. Reduction was more significant in FUs with higher SDI, suggesting that the effect of health policies was heterogeneous. Moreover, HSBP has become the main risk factor for death in Brazil, mainly due to population aging.
CERTL Reduces C16 Ceramide, Amyloid-β Levels and Inflammation in a Model of Alzheimer's Disease
Authors: Crivelli Simone Mwenda , Luo Qian , Stevens Jo , Giovagnoni Caterina , Kruining Daan van , Bode Gerard , Hoedt Sandra den , Hobo Barbara , Scheithauer Anna-Lena , Walter Jochen , Mulder Monique T , Exley Christopher , Mielke Michelle M. , De Vries Helga E , Wouters Kristiaan , Hove Daniel L.A. van den , Berkes Dusan , Ledesma María Dolores , Verhaagen Joost , Losen Mario , Bieberich Erhard , Martinez-Martinez Pilar
Published: June 2020

Background: Deregulation of ceramide and sphingomyelinlevels have been suggested tocontribute tothe pathogenesis of Alzheimer’s disease (AD).Ceramide transfer proteins (CERTs) are ceramide carriers, crucial for ceramide and sphingomyelin balance in cells.Extracellular forms of CERTs co-localize with amyloid-β (Aβ) plaques in AD brains. To date, the significance of these observations for the pathophysiology of AD remains uncertain.Methods: The plasmid expressing CERTL, the long isoform of CERTs, was used to study the interaction of CERTLwith amyloid precursor protein (APP) by co-immunoprecipitation and immunofluorescencein HEK cells.The recombinant CERTL protein wasemployed to study interaction of CERTLwith amyloid-β (Aβ), Aβ aggregation process in presence of CERTL, and the resulting changes inAβ toxicity in neuroblastoma cells. CERTLwas overexpressed in neurons by adeno associatedvirus (AAV) in a familial mouse model of familial AD (5xFAD). Ten weeks after transduction animal were challenged with behavior tests for memory, anxiety and locomotion. At week twelve brains were investigated for sphingolipid levels by mass spectrometry, plaques and neuroinflammation by immunohistochemistry, gene expression and/or immunoassay.Results:Here, we report that CERTL, binds to APP, modifies Aβ aggregation and reduces Aβ neurotoxicity in vitro. Furthermore, we show that intracortical injection of AAV, mediating the expression of CERTL, decreases levels of ceramide d18:1/16:0 and increases sphingomyelin levels in the brain of male transgenic mice, modelling familial AD (5xFAD). CERTLin vivo over-expression hasa mild effect on animal locomotion and decreases Aβ formation and modulates microglia by decreasing their pro-inflammatory phenotype.Conclusion: Our results demonstratea crucial role of CERTL in regulatingceramidelevels in the brain, in amyloid plaque formation and neuroinflammation,thereby opening research avenuesfor therapeutic targets of AD and other neurodegenerative diseases.