bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence Of Glycemic Variability And Factors Associated With The Glycemic Arrays Among End-Stage Kidney Disease Patients On Chronic Haemodialysis.
Authors: Khan Abdul Hanif Khan Yusof , Zakaria Nor Fadhlina , Abidin Muhammad Adil Zainal , Kamaruddin Nor Azmi
Published: September 2020

Introduction: Glycaemic variability (GV) confers a significantly higher risk of diabetic-related complications, especially cardiovascular. Despite extensive research in this area, data on end-stage-kidney-disease (ESKD) patients on chronic haemodialysis are scarce. This study aims to determine the magnitude of GV among ESKD (diabetic vs non-diabetic) patients and its associated factors on haemodialysis days (HDD) and non-haemodialysis days (NHDD).Methods: We recruited 150 patients on haemodialysis, 93 patients with diabetic (DM-ESKD), and 57 with non-diabetic (NDM-ESKD). The GV indices (standard deviation [SD] and percentage co-efficient variant [%CV]) were obtained from 11-point and 7-point self-monitoring blood glucose (SMBG) profiles on HDD and NHDD. The GV indices and its associated factors of both DM-ESKD and NDM-ESKD were analysed to compare HDD vs. NHDD.Results: Mean blood glucose on HDD was 9.33 [SD 2.7, %CV 30.6%] mmol/L in DM-ESKD compared to 6.07 [SD 0.85, %CV 21.3%] mmol/L in NDM-ESKD (p =<0.01). The DM-ESKD group experienced significantly higher GV indices compared to NDM-ESKD on both HDD and NHDD, particularly in the subgroup with HbA1c 8-10% (p= <0.01). Presence of diabetes, older age, hyperlipidaemia, HbA1c, ferritin levels, and albumin were identified as factors associated with GV.Conclusion: DM-ESKD patients have high GV, especially on HDD, therefore increasing their risk of developing future complications. We identified high HbA1c, older age group, presence of hyperlipidaemia, ferritin levels, and albumin as factors associated with GV. Since these groups of patients are vulnerable to CVD mortality, urgent attention is needed to rectify it.
Thoughts on Higher Medical Education Under Major Public Health Emergencies: Thinking Ahead After COVID-19 Outbreak —— A Descriptive study
Authors: Lin Wei , Chen Yan , Shi Songchang , Liang Jixing , Huang Huibin , Li Liantao , Cai Liangchun , Zong Liyao , Wang Nengying , Wen Junping , Chen Gang
Published: September 2020

Background: The spread of coronavirus disease 2019 (COVID-19) has posed great threat to the global population’s health and nearly every medical school throughout the world suspended classes as a precaution against the virus. This study is aimed at exploring a more advanced online teaching and learning pattern for medical school in the future especially during a Public Health Emergency of International Concern (PHEIC) and to evaluate the efficacy of the teaching methods in improving students’ professionalism, knowledge and learning skills including problem analyzing and solving, teamwork skills, self-directed learning, as well as adaptability and acceptance to the courses. Methods: Fifty fourth-year medical students receiving the “5+3” pattern courses regarding internal medicine were enrolled in the study. A five-point Likert scale questionnaire that contains 20 items was used to compare the effect between online TBL via 5G network (hereinafter referred as blended teaching model) and home-based online learning which is not based on TBL via other prevalent forms of wireless internet connection(hereinafter referred as traditional online teaching model). It evaluated the network environment and indices of students’ competencies we put forward based on six core competenciesResults: According to the descriptive statistical analysis of the first part of the questionnaire (question 1-16), the average score of adaptability and acceptance of the courses is 2.60 less than 3, indicating that students are more adapted to traditional online teaching model; the average score of the rest of the questions is greater than 3, indicating that blended teaching model is superior to traditional online teaching model. The number of male students who are inclined to blended teaching model is 0.13 times as much as that of female students (95%CI:0.028~0.602, p=0.009).Conclusion: Online TBL via 5G network is a more advanced online teaching and learning pattern for medical school and may be a more suitable method during PHEIC in the future.
Characterization of polyvinyl alcohol-borax/agarose (PVA-B/AG) double network hydrogel utilized for the cleaning of works of art
Authors: Al-Emam Ehab Awad , Soenen Hilde , Caen Joost , Janssens Koen
Published: September 2020

Since cleaning of artworks may cause undesirable physicochemical alterations and is a nonreversible procedure, it is mandatory to adopt the proper cleaning procedure. Such a procedure should remove undesired materials whilst preserving the original surface. In this regard, numerous gels have been developed and exploited for the cleaning of various artwork surfaces. Lately, agarose (AG) and polyvinyl alcohol-borax (PVA-B) hydrogels have been widely employed as cleaning tools by conservators. Both hydrogels show some limitations in specific cleaning practices. In this work, we investigated the influence of including increased levels of agarose into PVA-B systems. For this reason, we performed a detailed characterization on the double network (DN) hydrogel including the chemical structure, the liquid phase retention, the rheological behavior, and the self-healing behavior of various PVA-B/AG double network hydrogels. These new hydrogels revealed better properties than PVA-B hydrogels and obviated their limitations. The inclusion of AG into PVA-B systems enhanced the liquid retention capacity, shape-stability, and mechanical strength of the blend. Furthermore, AG minimized the expelling/syneresis issue that occurs when loading PVA-B systems with low polarity solvents or chelating agents. The resultant double network hydrogel exhibits relevant self-healing properties. The PVA-B/AG double network is a new and useful cleaning tool that can be added to the conservators’ tool-kit. It is ideal for cleaning procedures dealing with porous and complex structured surfaces, vertical surfaces and for long time applications.
Partnering with Patients to Get Better Outcomes with Chimeric Antigen Receptor T-cell Therapy: Towards Engagement of Patients in Early Phase Trials  
Authors: Foster Madison , Fergusson Dean , Hawrysh Terry , Presseau Justin , Kekre Natasha , Schwartz Stuart , Castillo Gisell , Asad Sarah , Fox Grace , Atkins Harold , Thavorn Kednapa , Montroy Joshua , Holt Robert , Monfaredi Zarah , Lalu Manoj
Published: September 2020

Aim: Though patient engagement in clinical research is growing, recent reports suggest few clinical trials report on such activities. To address this gap, we describe our approach to patient engagement in the development of a clinical trial protocol for a new immunotherapy for blood cancer (chimeric antigen receptor T-cell therapy, CAR-T cell therapy). Methods: Our team developed a clinical trial protocol by working with patient partners from inception. Two patient partners with lived blood cancer experience were identified through referrals from our team’s professional network and patient organization contacts. Our patient partners were onboarded to the team and engaged in several studies conducted to develop the clinical trial protocol, including a systematic review of the existing literature on the therapy, patient interviews and a survey to obtain perspectives on barriers and enablers to participating in the trial, an early economic analysis, and a retrospective cohort study. Results: Engaging patient partners enhanced our research in ways that would not have otherwise occurred. By selecting patient important outcomes for data collection, our partners helped flag that quality of life and health utility measures have not been reported in previous CAR-T cell therapy trials for blood cancer. Our partners also co-developed a non-technical summary of the systematic review that summarized results in an accessible manner. Our patient partners reviewed interview and survey questions, to improve the language and appropriateness; provided recruitment suggestions; and provided a patient perspective on the results, thereby confirming the importance of findings. Input was also obtained on costs for the early economic analysis. Our patient partners identified costs that may be a burden to both patients and caregivers during a trial and helped to confirm that the overall structure of the economic model reflected the patient care pathway. Our patient partners also shared their diagnosis and treatment stories, which helped to provide the research team with insight into this experience.Conclusions: Contributions by our patient partners were invaluable to each component study, as well as the overall development of the trial protocol. We plan to use this approach in the future, to meaningfully engage patients in the development of other clinical trials; we also hope that by reporting our methods this will help other research teams to do the same. Trial Registration: Affiliated with the development of NCT03765177
Definitive-intent uniform megavoltage fractioned radiotherapy protocol for presumed canine intracranial gliomas: retrospective analysis of survival and prognostic factors in 38 cases (2013-2019).
Authors: DEBREUQUE MAUD , DE FORNEL Pauline , DAVID INGRID , DELISLE FRANCOISE , DUCERVEAU MARIE-NOELLE , DEVAUCHELLE PATRICK , THIBAUD JEAN-LAURENT
Published: September 2020

Background: Radiotherapy (RT) is currently considered the treatment of choice for presumed canine intracranial gliomas. However, variable therapeutic responses are described, due to heterogeneous populations and different radiation methods or protocols. Only one study dedicated to intracranial suspected glioma highlighted prognostic criteria. Determination or confirmation of specific clinical and imaging prognostic factors may guide the therapeutic management of these tumours. The objectives were to provide data on long-term clinical outcome (including quality of life, QoL) and to determine specific prognostic factors associated with survival time. We report a single-institution retrospective study, including all dogs with suspected symptomatic primary solitary intracranial glioma, treated with a complete uniform fractionated megavoltage radiation protocol of 15x3Gy over 5 weeks, between January 2013 and February 2019. Thirty-eight client-owned dogs were included. Medical records were retrospectively evaluated for median overall survival time (MST), clinical and imaging responses. Prognostic factors on survival were researched in terms of signalment, clinical presentation, tumour imaging characteristics and response following RT. Finally, the RT’s impact on the dogs’ clinical signs and Qol were evaluated by the owners. Results: The disease-specific MST was 698 days (95% CI: 598-1135). Survival at 1 and 2 years were respectively 74.2±7.4% and 49.0±9.8%. Initial clinical signs were related to survival, as well as tumour characteristics such as cystic-pattern, mass effect and Tumour/Brain volume ratio. No significant adverse effect or radiotoxicity was observed.Conclusions: RT appears as a safe and effective treatment for canine intracranial gliomas, allowing long-term tumour control, improvement of life’s quality and management of associated clinical signs. The initial clinical signs and MRI characteristics (Tumour/Brain volume ratio, cyst-like lesion and mass effect) may help predict the prognosis.
Diminished adherence of Biomphalaria glabrata embryonic cell line to sporocysts of Schistosoma mansoni following programmed knockout of the allograft inflammatory factor
Authors: Coelho Fernanda Sales , Rodpai Rutchanee , Miller Andre , Karinshak Shannon E , Mann Victoria H , Carvalho Omar dos Santos , Cladeira Roberta Lima , Mourao Marina de Moraes , Brindley Paul J , Ittiprasert Wannaporn
Published: September 2020

Background: Larval development in an intermediate host gastropod snail of the genus Biomphalaria is an obligatory component of the life cycle of Schistosoma mansoni. Understanding of the mechanism(s) of host defense may hasten the development of tools that block transmission of schistosomiasis. The allograft inflammatory factor 1, AIF, which is evolutionarily conserved and expressed in phagocytes, is a marker of macrophage activation in both mammals and invertebrates. AIF enhances cell proliferation and migration. The embryonic cell line, termed Bge, from Biomphalaria glabrata is a versatile resource for investigation of the snail-schistosome relationship since Bge exhibits a hemocyte-like phenotype. Hemocytes perform central roles in innate and cellular immunity in gastropods and in some cases can kill the parasite. However, the Bge cells do not kill the parasite in vitro.Methods: Bge cells were transfected by electroporation with plasmid pCas-BgAIFx4, encoding the Cas9 nuclease and a guide RNA specific for exon 4 of the B. glabrata AIF (BgAIF) gene. Transcript levels for Cas9 and for BgAIF were monitored by quantitative reverse-transcription-PCR and, in parallel, adhesion of gene-edited Bge cells during co-culture with of schistosome sporocysts was assessed.Results: Gene knockout manipulation induced gene-disrupting indels, frequently 1-2 bp insertions and/or 8-30 bp deletions, at the programmed target site; a range from 9 to 17% of the copies of the BgAIF gene in the Bge population of cells were mutated. Transcript levels for BgAIF were reduced by up to 73% (49.5±20.2% S.D, P ≤ 0.05, n =12). Adherence by BgAIF gene-edited (ΔBgAIF) Bge to sporocysts diminished in comparison to wild type cells, although cell morphology did not change. Specifically, as scored by a semi-quantitative cell adherence index (CAI), fewer ΔBgAIF than control wild type cells adhered to sporocysts; control CAI, 2.66±0.10, ΔBgAIF, 2.30±0.22 (P ≤ 0.01).Conclusion: The findings supported the hypothesis that BgAIF plays a role in the adherence of B. glabrata hemocytes to sporocysts during schistosome infection in vitro. This demonstration of the activity of programmed gene editing will enable functional genomics approaches using CRISPR/Cas9 to investigate additional components of the snail-schistosome host-parasite relationship.
Toll-like receptor 5-mediated signaling enhances liver regeneration in mice
Authors: Zhang Wen , Wang Lei , Sun Xue-Hua , Liu Xian , Xiao Yang , Zhang Jie , Wang Ting , Chen Hui , Zhan Yi-Qun , Yu Miao , Ge Chang-Hui , Li Chang-Yan , Ren Guang-Ming , Yin Rong-Hua , Yang Xiao-Ming
Published: September 2020

BackgroundToll-like receptor 5 (TLR5)-mediated pathways play critical roles in regulating hepatic immune response and show hepatoprotective effect in mouse models of hepatic diseases. However, the role of TLR5 in experimental models of liver regeneration has not been reported. This study aims to investigate the role of TLR5 in partial hepatectomy (PHx)-induced liver regeneration.MethodsWe performed 2/3 PHx in wild-type (WT) mice, TLR5 knockout mice, or TLR5 agonist CBLB502 treated mice as a model of liver regeneration. Bacterial flagellin content was measured by ELISA, and hepatic TLR5 expression was determined by quantitative PCR analyses and flow cytometry. To study the effects of TLR5 on hepatocyte proliferation, bromodeoxyuridine (BrdU) incorporation and proliferating cell nuclear antigen (PCNA) expression were analyzed by immunohistochemistry (IHC) staining. The effects of TLR5 during the priming phase of liver regeneration was examined by quantitative PCR analyses of immediate early gene mRNA levels, and western blot analysis of hepatic NF-κB and STAT3 activation. Cytokines and growth factors production after PHx were detected using real-time PCR analyses and cytometric bead array (CBA) assays. Oil Red O staining and hepatic lipid concentrations were analyzed to examine the effect of TLR5 on hepatic lipid accumulation after PHx.ResultsThe bacterial flagellin content in serum and liver was increased and the hepatic TLR5 expression was significantly up-regulated in WT mice upon PHx. TLR5-deficient mice exhibited reduced numbers of BrdU- and PCNA-positive cells, suppressed immediate early gene expression, and decreased cytokines and growth factors production. Moreover, PHx-induced hepatic NF-κB and STAT3 activation was inhibited in Tlr5−/− mice compared with WT mice. Consistently, the administration of CBLB502 significantly promoted PHx-mediated hepatocyte proliferation correlated with enhanced production of proinflammatory cytokines and the recruitment of macrophages and neutrophils in the liver. Besides, Tlr5−/− mice displayed significantly decreased hepatic lipid concentrations and Oil Red O positive areas compared to control mice after PHx.ConclusionWe reveal that TLR5 activation contributes to the initial events of liver regeneration after PHx. Our findings demonstrate that TLR5 signaling positively regulates liver regeneration and suggest a potential application of TLR5 agonist in promoting liver regeneration.
Prognostic value of bedside lung ultrasound score in patients with COVID-19
Authors: Ji Li , Cao Chunyan , Gao Ying , Zhang Wen , Xie Yuji , Duan Yilian , Kong Shuangshuang , You Manjie , Ma Rong , Jiang Lili , Liu Jie , Sun Zhenxing , Zhang Ziming , Wang Jing , Yang Yali , Lv Qing , Zhang Li , Li Yuman , Zhang Jinxiang , Xie Mingxing
Published: September 2020

BackgroundBedside lung ultrasound (LUS) has emerged as a useful and noninvasive tool to detect lung involvement and monitor changes in patients with coronavirus disease 2019 (COVID-19). However, the clinical significance of the LUS score in patients with COVID-19 remains unknown. We aimed to investigate the prognostic value of the LUS score in patients with COVID-19.MethodsThe LUS protocol consisted of 12 scanning zones and was performed in 280 consecutive patients with COVID-19. The LUS score based on B-lines, lung consolidation and pleural line abnormalities was evaluated.ResultsPatients in the highest LUS score group were more likely to have a lower lymphocyte percentage (LYM%); higher levels of D-dimer, C-reactive protein, hypersensitive troponin I and creatine kinase muscle-brain; more invasive mechanical ventilation therapy; higher incidence of ARDS; and higher mortality than patients in the lowest LUS score group. After a median follow-up of 14 days [IQR, 10-20 days], 37 patients developed ARDS, and 13 died. Patients with adverse outcomes presented a higher rate of bilateral involvement; more involved zones and B-lines, pleural line abnormalities and consolidation; and a higher LUS score than event-free survivors. The Cox models adding the LUS score as a continuous variable ( hazard ratio [HR] : 1.05, 95% confidence intervals [CI]: 1.02～1.08; P < 0.001; Akaike Information Criterion [AIC] =272; C-index = 0.903) or as a categorical variable (HR: 10.76, 95% CI: 2.75～42.05; P = 0.001; AIC =272; C-index = 0.902) were found to predict poor outcomes more accurately than the basic model ( AIC =286; C-index = 0. 866). An LUS score cut-off >12 predicted adverse outcomes with a specificity and sensitivity of 90.5% and 91.9%, respectively.ConclusionsThe LUS score is a powerful predictor of adverse outcomes in patients with COVID-19 and is important for risk stratification in COVID-19 patients.
The lack of an association between Body Image Satisfaction and Self-Esteem in high school students in Eastern Croatia: A cross-sectional study
Authors: Bosnic Zvonimir , Miletic Maja , Volaric Nikola , Holik Dubravka , Volaric Mile , Majnaric Ljiljana Trtica
Published: September 2020

Introduction: The research objectives are to examine the degree of satisfaction of students in two high schools in Eastern Croatia, regarding their physical appearance and self-esteem based on their gender and type of school - Grammar school or Vocational school. Furthermore, it aims to determine the correlation between degree of satisfaction regarding physical appearance and self-esteem and examines the differences in socio-economic status among the students of the two schools.Methods: The study is designed as a cross-sectional research performed in the Secondary Health and Veterinary School and Grammar School in Vinkovci. The study includes 278 participants. The data were collected in three ways. First, by using a survey on socio-economic status of the participants. Second, a modified test consisting of fourteen questions was used to examine the level of body image satisfaction. Third, a test consisting of ten questions was used to examine the level of self-esteem.Results: Median age of participants is 18 years. The research established a linear correlation between the body image satisfaction and gender of the students in both schools. An association between level of body image satisfaction and self-esteem was not established.Conclusion: To conclude with, adolescents in this region of Croatia are not overly concerned about their physical appearance despite relatively decreased self-esteem. A lack of association between reduced self-esteem and self-assessment of appearance may also be a consequence of later sexual maturation and tradional development which promote the traditional values of family, youth life and marriage
Prevalence of readily detected amyloid blood clots in ‘unclotted’ Type 2 Diabetes Mellitus and COVID-19 plasma
Authors: Pretorius Etheresia , Venter Chantelle , Laubscher Gert Jacobus , Lourens Petrus Johannes , Steenkamp Janami , Kell Douglas B
Published: September 2020

Background
Type 2 Diabetes Mellitus (T2DM) is a well-known comorbidity to COVID-19 and coagulopathies are a common accompaniment to both T2DM and COVID-19. In addition, patients with COVID-19 are known to develop micro-clots within the lungs. The rapid detection of COVID-19 uses genotypic testing for the presence of SARS-Cov-2 virus in nasopharyngeal swabs, but it can have a poor sensitivity. A rapid, host-based physiological test that indicated clotting severity and the extent of clotting pathologies in the individual who was infected or not would be highly desirable.
Methods
We show here that microclots can be detected in the native plasma of COVID-19, as well as T2DM patients, without the addition of any clotting agent, and in particular that such clots are amyloid in nature as judged by a standard fluorogenic stain.
Results
In COVID-19 plasma these microclots are significantly increased when compared to the levels in T2DM.
Conclusions
This fluorogenic test may provide a rapid and convenient test with 100% sensitivity (P < 0.0001), and is consistent with the recognition that the early detection and prevention of such clotting can have an important role in therapy.
Behavioral changes before lockdown and decreased retail and recreation mobility during lockdown contributed most to controlling COVID-19 in Western countries
Authors: Deforche Koen , Vercauteren Jurgen , Müller Viktor , Vandamme Anne-Mieke
Published: September 2020

BackgroundThe COVID-19 pandemic has prompted a lockdown in many countries to control the exponential spread of the SARS-CoV-2 virus, hereby reducing the time-varying basic reproduction number ( R t ) to below one. Governments are looking for evidence to balance the demand of their citizens to ease some of the restriction, against the fear of a second peak in infections. More details on the specific circumstances that promote exponential spread (i.e. R t > 1) are needed.MethodsIncidence data of cases and deaths from the first wave of infections for 35 Western countries (32 European, plus Israel, USA and Canada) were analyzed using epidemiological compartment models in a Bayesian framework. Mobility data was used to estimate the timing of changes associated with a lockdown, and was correlated with estimated reductions of R t .ResultsAcross all countries, the initial median estimate for R t was 3.6 (95% IQR 2.4 – 5.2), and it was reduced to 0.78 (95% IQR 0.58 – 1.01) during lockdown. 48% (18% – 65%) of the reduction occurred already in the week before lockdown, with lockdown itself causing the remaining drop in transmission. A lower R t during lockdown was independently associated with an increased time spent at home (0.21 per 10% more time, p < 0.007), and decreased mobility related to retail and recreation (0.07 per 10% less mobility, p < 0.008).ConclusionsIn a Western population unaware of the risk, SARS-CoV-2 can be highly contagious with a reproduction number R 0 > 5. Our results are consistent with evidence that recreational activities (including restaurant and bar visits) enable super-spreading events. Exiting from lockdown therefore requires continued physical distancing and tight control on this kind of activities.
Denoising Large-Scale Biological Data Using Network Filters
Authors: Kavran Andrew J , Clauset Aaron
Published: September 2020

Background: Large-scale biological data sets, e.g., transcriptomic, proteomic, or ecological, are often contaminated by noise, which can impede accurate inferences about underlying processes. Such measurement noise can arise from endogenous biological factors like cell cycle and life history variation, and from exogenous technical factors like sample preparation and instrument variation. Results: We describe a general method for automatically reducing noise in large-scale biological data sets. This method uses an interaction network to identify groups of correlated or anti-correlated measurements that can be combined or “filtered” to better recover an underlying biological signal. Similar to the process of denoising an image, a single network filter may be applied to an entire system, or the system may be first decomposed into distinct modules and a different filter applied to each. Applied to synthetic data with known network structure and signal, network filters accurately reduce noise across a wide range of noise levels and structures. Applied to a machine learning task of predicting changes in human protein expression in healthy and cancerous tissues, network filtering prior to training increases accuracy up to 58% compared to using unfiltered data. Conclusions: Network filters are a general way to denoise biological data and can account for both correlation and anti-correlation between different measurements. Furthermore, we find that partitioning a network prior to filtering can significantly reduce errors in networks with heterogenous data and correlation patterns, andthis approach outperforms existing diffusion based methods. Our results on proteomics data indicate the broad potential utility of network filters to applications in systems biology.
Non-alcoholic fatty liver disease, diastolic dysfunction, and impaired myocardial glucose uptake in patients with type 2 diabetes
Authors: Lee Minyoung , Kim Kwang Joon , Chung Tae Ha , Bae Jaehyun , Lee Yong-ho , Lee Byung-Wan , Cha Bong-Soo , Yun Mijin , Kang Eun Seok
Published: September 2020

Background

Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in patients with type 2 diabetes and is associated with cardiovascular risk. We investigated whether the degree of NAFLD was associated with myocardial dysfunction related to impaired myocardial glucose uptake in patients with type 2 diabetes.
Methods

In total, 131 patients with type 2 diabetes from a tertiary care hospital were included. Myocardial glucose uptake was assessed using [18F]-fluorodeoxyglucose-positron emission tomography. Hepatic steatosis and fibrosis were determined using transient liver elastography. Echocardiography was performed to evaluate cardiac structure and function.
Results

Patients with NAFLD revealed cardiac diastolic dysfunction with higher left ventricular filling pressure (E/e’ ratio) and left atrial volume index (LAVI) than patients without NAFLD (all p < 0.05). Hepatic steatosis correlated with E/e’ ratio and LAVI, and hepatic fibrosis also correlated with E/e’ ratio (all p < 0.05). In linear regression analyses, a higher degree of hepatic steatosis (r2 = 0.409; p = 0.041) and a higher degree of fibrosis (r2 = 0.423; p = 0.009) were independent determinants for a higher E/e’ ratio even after adjusting for confounding factors. Decreased myocardial glucose uptake was associated with a higher degree of steatosis (p for trend = 0.084) and fibrosis (p for trend = 0.012). In addition, decreased myocardial glucose uptake was an independent determinant factor for a higher E/e’ ratio (r2 = 0.409; p = 0.04).
Conclusions

Hepatic steatosis and fibrosis are significantly associated with diastolic heart dysfunction in patients with type 2 diabetes coupled with impaired myocardial glucose uptake.
National Early Warning Score 2 (NEWS2) and 3-level Triage Scale as Risk Predictors in Frail Older Adults in the Emergency Department
Authors: Kemp Kirsi , Alakare Janne , Harjola Veli-Pekka , Strandberg Timo , Tolonen Jukka , Lehtonen Lasse , Castren Maaret
Published: September 2020

BackgroundThe aim of the emergency department (ED) triage is to recognize critically ill patients and to allocate resources. No strong evidence for accuracy of the current triage instruments, especially for the older adults, exists. We evaluated the National Early Warning Score 2 (NEWS2) and a 3-level triage assessment as risk predictors for frail older adults visiting the ED.MethodsThis prospective, observational study was performed in a Finnish ED. The data were collected in a six-month period and included were ≥75-year-old residents with Clinical Frailty Scale score of at least four. We analyzed the predictive values of NEWS2 and the three-level triage scale for 30-day mortality, hospital admission, high dependency unit (HDU) and intensive care unit (ICU) admissions, a count of 72-hour and 30-day revisits, and ED length-of-stay (LOS). Results A total of 1711 ED visits were included. Median for age, CFS, LOS and NEWS2 were 85 years, 6 points, 6.2 hours and 1 point, respectively. 30-day mortality was 96/1711. At triage, 69, 356 and 1278 of patients were assessed as red, yellow and green, respectively. There were 1103 admissions, of them 31 to an HDU facility, none to ICU.With NEWS2 and triage score, AUCs for 30-day mortality prediction were 0.70 (0.64-0.76) and 0.62 (0.56-0.68); for hospital admission prediction 0.62 (0.60-0.65) and 0.55 (0.52-0.56), and for HDU admission 0.72 (0.61-0.83) and 0.80 (0.70-0.90), respectively.The NEWS2 divided into risk groups of low, medium and high did not predict the ED LOS (p=0.095). There was a difference in ED LOS between the red/yellow and as red/green patient groups (p<0.001) but not between the yellow/green groups (p=0.59).There were 48 and 351 revisits within 72 hours and 30 days, respectively. With NEWS2 AUCs for 72-hour and 30-day revisit prediction were 0.48 (95% CI 0.40-0.56) and 0.47 (0.44-0.51), respectively; with triage score 0.48 (0.40-0.56) and 0.49 (0.46-0.52), respectively. ConclusionsThe NEWS2 and a local 3-level triage scale are statistically significant in predicting 30-day mortality, and HDU admission but not ED LOS or revisit rates for frail older adults. NEWS2 also seems to predict hospital admission
Phage JS02, A Putative Temperate Phage, A Novel Biofilm-Degrading Agent for Staphylococcus Aureus
Authors: Zhang Lili , Ding Huiyan , Shahin Khashayar , Soleimani-Delfan Abbas , Wang Heye , He Tao , Sun Lichang , Wei Ruicheng , Wang Ran
Published: September 2020

Background: Staphylococcus aureus is a biofilm-producing organism that is frequently isolated from various environments worldwide. Because of the natural resistance of S. aureus biofilm to antibiotics, bacteriophages are considered as a promising alternative for its removal. Results: The bacteriophage vB_SauS_JS02 was isolated from livestock wastewater and showed activity against multidrug-resistant (MDR) S. aureus. The phage vB_SauS_JS02 was morphologically classified as Siphoviridae; it had a broad host range (45 out of 81 strains, 55.6%) and high burst size (52 plaque-forming unit (PFU)/infected cell) and could survive in a pH range of 4 to 11 and a temperature range of 40 ºC to 50 ºC. Bioinformatics analysis showed that the phage genome contained a long double-stranded linear DNA genome of 46,435 base pairs with a G＋C content of 33.1% and had 66 putative open reading frames (ORFs). The predicted protein products of the ORFs were clustered functionally into five groups as follows: replication/regulation, DNA packaging, structure/morphogenesis, lysis, and lysogeny. The phage vB_SauS_JS02 was a temperate phage with a higher inhibiting and degrading activity against planktonic cells (~86% reduction) and S. aureus biofilm (∼68% reduction in biofilm formation). Moreover, the removal activity of the phage vB_SauS_JS02 against both planktonic cells and S. aureus biofilms was even better than that of the antibiotic (ceftazidime). Conclusion: In summary, the present study introduced the phage vB_SauS_JS02 as a potential biocontrol agent against biofilm-producing S. aureus.
Linagliptin, a xanthine-based dipeptidyl peptidase-4 inhibitor, ameliorates experimental autoimmune myocarditis by suppressing cathepsin-G activity
Authors: Shiheido-Watanabe Yuka , Maejima Yasuhiro , Nakagama Shun , Tamura Natsuko , Kasama Takeshi , Sasano Tetsuo
Published: September 2020

Background

There is a compelling need for establishing effective therapy for autoimmune myocarditis which primarily manifest as chest pain, heart failure or sudden death. Although our group have previously shown that dipeptidyl peptidase-4 (DPP-4) aggravates experimental autoimmune myocarditis (EAM), the detailed underlying mechanism remains to be unelucidated.
Methods

The effects of linagliptin, a xanthine-based dipeptidyl peptidase-4 inhibitor, on cardiac function were investigated by treating mouse EAM models and elucidated the role of DPP-4 on EAM using proteomic approaches.
Results

Immunohistochemical analyses demonstrated that the number of Th17 cells expressing high level of DPP-4 infiltrated to EAM myocardium was significantly attenuated by linagliptin treatment. MS/MS-based analyses demonstrated that DPP-4 binds to cathepsin-G in EAM hearts. DPP-4 also protects cathepsin-G activity by inhibiting the activity of SerpinA3N, a protease inhibitor that catalyzes cathepsin-G. The activity of cathepsin-G and the level of Angiotensin II were markedly elevated in EAM myocardium; this effect was reversed by linagliptin treatment. Furthermore, we found that linagliptin suppresses oxidative stress in EAM hearts.
Conclusions

DPP-4 physically interacts with cathepsin-G, which, in turn, suppresses SerpinA3N; this promotes angiotensin II accumulation in EAM hearts. Thus, DPP-4 derived from Th17 cells could aggravate cardiac dysfunction during EAM.
Emergency Department Use by Patients With End-stage Renal Disease in the United States
Authors: Wang Ningyuan , Pei Jiao , Fan Hui , Ali Yaseen , Zhao Jian , Zhang Xingyu
Published: September 2020

Background: We sought to describe the national characteristics of ED visits by patients with end-stage renal disease (ESRD) in the United States in order to improve the emergency treatment and screening of ESRD patients. Methods: We analyzed data from 2014-2016 ED visits provided by the National Hospital Ambulatory Medical Care Survey. We sampled adult (age ≥ 18 years) ED patients with ESRD. By proportion or means of weighted sample variables, we quantified annual ED visits by patients with ESRD. We investigated demographics, ED resource utilization, clinical characteristics, and disposition of patients with ESRD vs. those without ESRD. Logistic regression models were used to estimate the association between these characteristics and ESRD ED visits. Results: Approximately 722,692 (7.78%) out of 92,899,685 annual ED visits were ESRD patients. ED patients with ESRD were mostly non-Hispanic whites (51.5%) and males were more likely to be ESRD patients than females (aOR: 1.48; 95% CI: 1.47–1.48). ED patients with ESRD were more likely to be admitted to the hospital (aOR: 2.22; 95% CI: 2.21–2.22) and intensive care unit (ICU) (aOR: 1.53; 95% CI: 1.52–1.54) than patients without ESRD. ED patients with ESRD were more likely to receive blood tests, get medical imaging tests.Conclusion: We described the unique demographic, socioeconomic, and clinical characteristics of ED patients with ESRD, using the most comprehensive, nationally representative study to date. These patients’ higher hospital and ICU admission rates indicate that patients with ESRD require a higher level of emergency care.
A Randomized, Placebo-controlled, Double-blind Study on the Effects of SZL on Patients With Mild to Moderate Depressive Disorder With Comparison to Fluoxetine
Authors: hu yuan , wang yichen , chen chao , yang wenshan , zhu weiyu , liu ping
Published: September 2020

Objective: Kaixinsan (KXS) decoction, as an ancient’s herbal formula, has been demonstrated to be active in various animal models resembling human depression with multi-target effects. This very first study evaluated the efficacy and tolerability of Shen Zhi Ling (SZL) tables (KXS preparation), compared with fluoxetine (FLX, positive comparator), in patients with mild to moderate depressive disorder.Methods: In this randomized double-blind parallel-group study, 156 patients with mild to moderate depression without taken any antidepressants in the past 6 months or 4 straight weeks were randomized to receive either 3.2g/d SZL plus 20mg/d FLX placebo (SZL group) or 20mg/d FLX plus 3.2g/d SZL placebo (FLX group), for 8 weeks. Their clinical presentations and some metabolic indexes were assessed during the 8 weeks visiting period.Results: Patients in SZL group showed a statistically significant improvement after 8 weeks of treatment in HAMD-17 score (18.79±2.09 to 4.43±4.71, p<0.001) and self-rating depression scale (SDS) score (58.49±8.89 to 39.84±12.09, p<0.001), but not in N-back total respond time (1145.55±608.26 to 1128.47±387.49, p>0.05). In addition, no significant difference at 8 weeks of treatment was found between SZL and FLX groups in SDS score (39.84±12.09 vs. 36.63±12.44) and N-back respond time (1128.47±387.49 vs. 1089.43±352.08) as well as reduction of HAMD-17 score (14.79±4.88 vs. 15.24±4.29) (p>0.05 for all). However, the serum APOB, APOC3 and ALB levels and HDL-C/LDL-C ratio decreased significantly in patients after SZL treatment, while only APOB/APOA1 ratio decreased significantly in FLX group. Other metabolic indexes did not alter significantly after treated with SZL or FLX.Conclusion: The efficacy and safety profile of SZL are comparable to that of fluoxetine in patients with mild to moderate depression. The beneficial effect of SZL is probably associated with improvement of lipid metabolic balance.
The Monocyte Chemotactic Protein 1 as a Potential Indicator for SARS-CoV-2 Infected Mild COVID-19 Patients 
Authors: xi xueyan , Guo Yang , Zhu Min , Wei Yuhui , Li Gang , Du Boyu , Wang Yunfu
Published: September 2020

Background: The level of chemokine was markedly elevated in severe COVID-19 patients. But the role of chemokine in mild COVID-19 patients has not yet established. However, most of the COVID-19 patients in Shiyan City, China had mild cases. Methods: In this study, the level of chemokine in the serum for COVID-19 patients in Shiyan City was detected by ELISA. The expression of receptor of chemokine and other signal molecular was detected by real-time PCR. Results: We first demonstrated that COVID-19 patients are characterized by higher levels of chemokine. In particular, monocyte chemotactic protein 1 (MCP-1) has shown higher expression in patients with mild cases of COVID-19. The receptor of MCP-1, CCR2 was then found higher expression in the same mild COVID-19 patients. Finally, the higher expression of MCP-1 in mild COVID-19 patients is correlated with the inhibition of IFN signaling. Conclusion: These findings add to our understanding of the immune-pathologic mechanisms of SARS-CoV-2 infection, and provide potential therapeutic targets and strategies. MCP-1 may be an effective indicator in mild patients, and early use of interferon has a good antiviral therapeutic effect.
Effect modification of the association between plasma glucose and diabetic kidney disease by hypersensitive C-reactive protein in patients with diabetes mellitus
Authors: Yao Zhi , li kuibao , Li Chuang , Fu Yuan
Published: September 2020

Background

Prior studies showed activation inflammatory biomarkers, e.g., hypersensitive C-reactive protein (hs-CRP), were associated with diabetic kidney disease (DKD) susceptibility; inflammatory gene expression profiles in the diabetic mice might be critical features determining susceptibility of DKD. The aim of this investigation was to explore effect modification of hs-CRP on the association between hyperglycemia and DKD in type 2 diabetes mellitus (T2DM).
Methods

We consecutively collected 812 patients with T2DM in a cross-sectional study. Multivariable logistic regression models was used to estimate odd ratios and 95% confidence intervals of plasma glucose for DKD, with adjustment for the potential confounders. Interaction between plasma glucose and hs-CRP was tested by likelihood ratio tests.
Results

The median age of the participants was 54 years (interquartile: 46–63), 58% were male and 26.2% experienced DKD. There seemed to be a nonlinear effect modification on the association between fast plasma glucose (FPG) and DKD by hs-CRP (P for linear interaction = 0.052). For participants with hs-CRP value lower than 3 mg/L, there no existed an interaction effect (P interaction = 0.3). In contrast, a significant interaction effect was noted among individuals with hs-CRP value higher than 3 mg/L (P interaction = 0.003).The marginal effect, i.e., log (odds), of FPG on DKD linearly rose with hs-CRP level increasing among these subjects. In terms of effect modification on the relationship between 2-hour plasma glucose (2 h-PG) and DKD by hs-CRP, it appeared to be linear. The higher the hs-CRP value, the stronger the strength of their associations. Johnson-Neyman plot showed when hs-CRP level was lower than 2.4 mg/L the marginal effect of 2 h-PG on DKD was nonsignificant (boundary of 95% confidence interval included zero) and it became significant as hs-CRP level higher than 2.4 mg/L (boundary of 95% confidence interval excluded zero) .
Conclusions

The associations of 2 h-PG as well as FPG with DKD were modified by hs-CRP in individuals with T2DM. It appeared when hs-CRP level was higher than 3 mg/L in these patients, the association strength of both FPG and 2 h-PG with DKD linearly rose with hs-CRP level increasing. A prospective study is warranted to confirm this finding.
Pattern of Locoregional Recurrence After Radical Surgery in Patients With Esophageal Squamous Cell Carcinoma and The Design of Target Volume of Postoperative Prophylactic Radiotherapy
Authors: Qiu Xiangnan , Jing Shenghua , Jiang Changchen , Shen Zetian , Zhu XiXu , Li Aomei , Yao Yuanhu , Wang Zhen
Published: September 2020

Objective The study was undertaken to evaluate preferred sites for locoregional recurrence after radical surgery for patients with esophageal squamous cell carcinoma (ESCC) and to confirm the target volume of postoperative prophylactic radiotherapy.Methods 139 patients with locoregional recurrent ESCC after radical esophagectomy without postoperative radiotherapy were registered in this study. The sites of locoregional recurrence for these patients were collected and influence factors of locoregional recurrence were analyzed.Results The 1, 2, and 3-year progression-free survival rates were 48.2%, 18.0% and 8.6%, respectively. Mediastinum lymph node (LN) recurrence (74.2%) was the most frequent site of recurrence, following the anastomotic site (28.1%), supraclavicular LN (19.4%) and abdominal LN (15.1%) (P=0.000). The upper mediastinum (72.7%) was one of the most common recurrence occurred in mediastinal LN. Compared with upper and middle segment of ESCC, lower segment had the highest recurrence rate of upper abdominal LN (P=0.001). The predictive factors of anastomotic recurrence were the stage of pT3 or pT4, presence of nerve or vessel invasion, removed LN NO.≤ 17, presence of invasion or adhesion and without postoperative adjuvant chemotherapy. In addition, the risk factors of abdominal LN recurrence in patients with middle segment ESCC included the stage of pT3 or pT4, smoking history and without postoperative adjuvant chemotherapy.Conclusion For thoracic ESCC, supraclavicular, upper mediastinum, subcarinal LNs and anastomosis should be incorporated within target volume of postoperative prophylactic radiotherapy. Regarding to lower segment ESCC, target volume should include upper abdominal LNs. And it need cautious evaluated about upper abdominal LNs when presence of clinicopathologic factor in middle segment ESCC.
Long Non-coding RNA NONSUST006715.1 Suppresses Japanese Encephalitis Virus Proliferation in PK-15 Cells
Authors: Zhou Xiaolong , Yuan Qiongyu , Zhang Chen , Dai Zhenglie , Du Chengtao , Wang Han , Li Xiangchen , Yang Songbai , Zhao Ayong
Published: September 2020

Background: Japanese encephalitis virus is a mosquito-borne neurotropic flavivirus that causes acute viral encephalitis in humans. Pigs are crucial amplifier host of JEV. Recently, long non-coding RNAs have received increasing attention for their antiviral function. Methods: LncRNA-NONSUST006715.1 was overexpression or knockdown using western blotting and reverse-transcription polymerase chain reaction (RT-PCR) to detect the effect of lncRNA on JEV proliferation. CCR1 was found to regulate the expression of lncRNA-NONSUST006715.1 by inhibitors screen. Transcription factor SP1 was overexpression or knockdown using RT-PCR to detect the influence of SP1 on the expression of lncRNA. In addition, the enrichments of transcription factor SP1 on the promoter of lncRNA-NONSUST006715.1 were analyzed by Chromatin immunoprecipitation.Results: In this study, we demonstrated a new function of lncRNA-NONSUST006715.1, the inhibition of JEV proliferation in PK-15 cells. We found that C-C chemokine receptor type 1 inhibited the expression of lncRNA-NONSUST006715.1 via the transcription factor SP1. Knockdown of CCR1 could upregulated the expression of SP1 and lncRNA-NONSUST006715.1, resulting in resistance to JEV proliferation. Conclusions: These findings illustrate the importance of lncRNAs in virus proliferation, and reveal how this virus regulates lncRNAs in host cells to promote its proliferation.
Emergence of Unusual Rotavirus G9p[4] and G8p[8] Strains During Post Vaccination Surveillance in Argentina, 2017-2018 
Authors: Degiuseppe Juan I , Stupka Juan A
Published: September 2020

Background. In 2015, Argentina included RotarixTM monovalent vaccine for universal administration and it showed a sharp decline in all-cause and rotavirus-confirmed cases as well as an immediate predominance of the G2P[4] genotype. The aim of this study was to analyze the impact of rotavirus vaccination on disease burden and genotype distribution in our country following its introduction. Methods. Prevalence and seasonality of laboratory-confirmed rotavirus cases data were assessed. Analyses of circulating genotypes were performed by conventional binary characterization (G and P typing). Phylogenetic study of VP7 gene was performed from emergent unusual strains. Results. During 2017-2018, 1183 rotavirus cases (13.2%) were detected and prevalence was uniform among different age subgroups. Weekly distribution showed a raise of confirmed cases around late July and early August. In 2017 the most frequently detected genotypes were G2P[4] and G3P[8]. However, in 2018 G12P[8] genotype increased and it was detected at a high rate. Noteworthy, the detection of uncommon G9P[4] and G8P[8] strains (bearing DS-1-like genetic backbones) was observed at moderate rates. Conclusions. Following four years of this strategy, the prevalence of rotavirus remained low in children under 5 years of age with a shift of the seasonal peak in early spring. The emergence of uncommon genotypes was due to introduction of new strains rather than to reassortment of local strains. Continuous monitoring of rotavirus burden of disease and genotype distribution provides useful evidence to evaluate existing immunization strategies and to contribute in the development of new vaccines as well.