bluuebunny/crossref_metadata_2025 huggingface dataset:
The Pharmacokinetics of [18F]UCB-H Revisited in The Healthy Non-Human Primate Brain
Authors: Goutal Sébastien , Guillermier Martine , Becker Guillaume , Gaudin Mylène , Bramoullé Yann , Luxen André , Lemaire Christian , Plenevaux Alain , Salmon Eric , Hantraye Philippe , Barret Olivier , Camp Nadja Van
Published: November 2020

Background Positron Emission Tomography (PET) imaging of the Synaptic Vesicle glycoprotein (SV) 2A is a new tool to quantify synaptic density. [18F]UCB-H was one of the first promising SV2A-ligands to be labelled and used in vivo in rodent and human, while limited information on its pharmacokinetic properties is available in the non-human primate. Here, we aimed to characterize [18F]UCB-H in the non-human cynomolgus primate and to discuss the obtained results in the light of the current state of SV2A PET ligands.Results [18F]UCB-H pharmacokinetic data was optimally fitted with a two-compartment model (2TCM), even though a slow component led to instability for the estimation of k3 and k4, and hence the total volume of distribution. 2TCM with coupled fit K1/k2 across brain regions stabilized the quantification, and confirmed a lower non-displaceable binding potential, BPND (estimated by k3/k4), of [18F]UCB-H compared to the newest SV2A-ligands. However, the non-displaceable distribution volume (VND) and the influx parameter (K1) is similar to what has been reported for other SV2A ligands. These data were reinforced by displacement studies using [19F]UCB-H, demonstrating only 50 % displacement of the total [18F]UCB-H signal at maximal occupancy of SV2A. Conclusions Modeling issues with a 2TCM due to a slow component have previously been reported for other SV2A ligands with low specific binding, or after blocking of specific binding. As all SV2A ligands share chemical structural similarities, we hypothesize that this slow binding component is common for all SV2A ligands, but only hampers quantification when specific binding is low.
Innovative Strategies for Developing Tuberculosis Implementation Research in Sudan
Authors: Elshayeb Ayman Ahmed , Ahmed Nihad Mohammed , Salih Karimeldin Mohammed , Nugoud Osama Abu Zaid , Yagoub Abd Allah Elnayeb , Ali Abdel Karim Sabir
Published: November 2020

Introduction: Sudan, especially Eastern States are very poor areas at great risk of endemic and communicable diseases particularly tuberculosis. The reasons for the spread and transmission of this disease include medical, economical and geographical issues, besides Sudan’s location in the middle of nine countries in East Africa, its boundaries were affected by free movement, high number of conflicts displaced peoples from boarders’ countries, high illiteracy rates, limited financial resources and shortages in medical services. Objectives: This project is conducted to implement a new developed system for eliminating Tuberculosis infections among eastern Sudanese populations focusing on the eradication of multidrug resistant Mycobacterium tuberculosis including novel methods for the targeted delivery of new therapeutic drugs. Methods: Strategies adopted in this work are proposed to increase access includes to communicable and economic factors. Disease Survey and Laboratorial Investigation for Multi Drug Resistant bacterial strains confirmation. Medical Assessment of TB Patients to facilitate improved efficiencies through metric measurement and enable patients’ relationship management. Established a national level policy of treatment, vaccination and prevention. Administering regular evaluation of the disease situation and control.Results: Implementation outcomes includes the conceptual framework for this project were informed by a combination of the general program logic model, the health system framework of the World Health Organization, WHO, the pillars of the Sudan health agenda, and the framework of the Strategic Elimination Plan. It is assumed that the reduction of TB burden at the national level (long-term output or impact) is preceded by improved case-finding and case-holding practices (short-term output). Impact outcome of the project is derived from the observation that tuberculosis is much more common at the boarders than center of Sudan where no adequate clinical services are available. It is conceivable that, although outbreaks may occur periodically, the control of disease might be easier to overcome than direct medication.Conclusion: A major success of the project accomplishment, is the stimulation of the implementation strategy development for elimination and eradication of Tuberculosis in Sudan with a view to bring diagnostic and surveillance issues much higher up according to the implementation research agenda especially for those areas explored with similar national and international research projects, reports and technical initiatives.
Development of HIV drug resistance in a cohort of adults on first-line antiretroviral therapy in Tanzania during the stavudine era
Authors: Sangeda Raphael Z , Gómes Perpétua , Rhee Soo-Yon , Mosha Fausta , Camacho Ricardo J. , Wijngaerden Eric Van , Lyamuya Eligius F. , Vandamme Anne-Mieke
Published: November 2020

As more HIV patients start combination antiretroviral therapy (cART), the emergence of HIV drug resistance (HIVDR) is inevitable. This will have consequences for the transmission of HIVDR, the success of ART, and the nature and trend of the epidemic. We recruited a cohort of 223 patients starting or continuing their first-line cART in Tanzania during the stavudine era in 2010. Patients were then followed up for one year. From those with a viral load test at baseline and follow-up time, 34% were failing virologically at the one-year endpoint. From 41 patients, protease and reverse transcriptase genotyping were successful. Eighteen samples were from therapy-naïve patients and 23 samples were taken under therapy either baseline for patients already under cART at study entry, or follow-up sample. The isolates were mostly subtype A, followed by C and D at 41.5%, 22% and 12.2% of the patients, respectively. No transmitted HIVDR was detected, as scored using the surveillance drug resistance mutations (DRMs) list. However, in 3 of the 18 samples from therapy-naïve patients, the clinical Rega interpretation algorithm scored 44D or 138A as non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance-associated polymorphisms. The most observed nucleoside reverse transcriptase inhibitor (NRTI) mutation was 184V. The mutation was found in 16 patients causing resistance to lamivudine and emtricitabine. Nineteen patients had NNRTI resistance mutations, the most common of which was 103N observed in 8 patients. These high levels of resistance calls for regular drug resistance surveillance in Tanzania to control the emergence and transmission of HIVDR.
Effects of Glucocorticoid Pulse Therapy on Thyroid Function and Thyroid Antibodies in Children with Graves’ Disease
Authors: Hu Yanyan , Man Yulin , Sun Xuemei , Xue Yongzhen
Published: November 2020

Objective The purpose of this study is to observe the effects of glucocorticoid pulse therapy on thyroid function and thyroid antibodies in children with Graves’ disease (GD).Methods Twenty children who were treated by intravenous methylprednisolone pulse therapy (MPT) followed by oral prednisolone administration and antithyroid drugs were included in the pulse group. Twenty children who were treated with antithyroid drugs alone were included in the control group. Serum concentrations of free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TGAb), and thyrotropin receptor antibodies (TRAb) were recorded at baseline and 10 days, 30days, and 60 days after treatment. Results Significant differences in FT3, FT4, TSH, TPOAb, TGAb, and TRAb levels were found in both groups from baseline to follow-up time points (all P<0.05). On the 30th day, the TRAb level in the pulse group was significantly lower than that in the control group (P=0.023). However, the level of TRAb rose on the 60th day. For values of TRAb at baseline, 10 days, and 60 days after treatment, there were no significant differences respectively between the two groups (all P>0.05). No significant differences were observed in FT3, FT4, TSH, TPOAb, and TGAb levels between the two groups (all P>0.05). Conclusion Our results suggest that the effects of intravenous MPT followed by oral prednisolone on TRAb level are temporary in children with GD. It is not helpful to the sustained recovery of thyroid function.
WITHDRAWN: Prevalence, Types and Risk Factors of Congenital Anomalies (A Hospital Based Study)
Authors: Shalaby Amira M. , EL-Gazzar Amira F.
Published: November 2020

Background: Congenital anomalies (CA) are common causes of infant’s and childhood deaths and disability. Objectives: The aim of the study is to determine the prevalence, describe the types and risk factors of congenital anomalies among newborns admitted to Neonatal Intensive Care Unit (NICU) of a Children's Hospital. Study design: It is a prospective observational study(analytic cross sectional study) was performed and screening of the newborn admitted at NICU of a Children's Hospital during the period of 6 months from 1 to 12-2017 to the end of 5-2018. The sample was 346 newborns, 173 cases and 173 control. We collected data using a record checklist and an interviewing questionnaire.Results: There were a significant difference between cases and control concerning gestational age (P=0.001), single or multiple babies (P=0.002), residence (P=0.001), consanguineous marriage (P=0.01) and family history of unfavorable outcome (P=0.001). We also found that the most common type of congenital anomalies was gastrointestinal anomalies 63 cases (36.4%) with tracheoesophageal fistula 17 cases (27%) being the most common GIT anomalies. Then the musculoskeletal anomalies being the second common anomalies 14.5% with diaphragmatic hernia 10 cases being the most common in musculoskeletal anomalies followed by other anomalies (22 multiple +1Conjoined Twins 23 cases (13.3%) followed by circulatory anomalies 22 cases (12.7%), followed by CNS anomalies 18 cases (10%). Conclusion: The prevalence of congenital anomalies was 22.97%. The most common anomalies were gastrointestinal anomalies (GIT), musculoskeletal anomalies, multiple anomalies and circulatory system anomalies. The risk factors were consanguineous marriage, positive family history, urban areas, full-term and singleton pregnancies.
Predictors of Prolonged Mechanical Ventilation After Cardiopulmonary Bypass in Infants with Congenital Heart Disease Less than 3 Months Old
Authors: Wang Ruonan , Yu Di , Zou Liang , Shu Yaqin , Mo Xuming , Peng Wei
Published: November 2020

Objective: To identify the predictors of prolonged mechanical ventilation (PMV) after cardiopulmonary bypass (CPB) in infants with congenital heart disease (CHD) less than 3 months. Methods: From June 2017 to May 2020, a total of 165 infants less than 3 months old with CHD admitted to the Children's Hospital of Nanjing Medical University for CPB were enrolled in this study. The following data were collected including gender, age, weight, Risk Adjustment in Congenital Heart Surgery-1 (RACHS-1) score, preoperative levels of thyroid hormones, CPB time, aortic cross-clamping (ACC) time, mechanical ventilation time, ICU mortality and infection. The PMV was defined as the ventilator assisted time > 72h. PMV prediction was assessed by multivariate binary logistic regression analysis. Results: Compared with non-PMV group, PMV group was younger (44.74 ± 25.27 days vs. 35.44 ± 26.91 days, P= 0.001), and most were newborns (41/93 vs. 10/57, P=0.000), with a higher proportion of RACHS-1 (29/93 vs.6/57, P=0.000) and more cases of infection (47/93 vs. 17/57,P= 0.004).PMV group had significantly lower weight than non-PMV group (3.79 ± 0.83Kg vs. 4.28 ± 1.01Kg, P=0.001). In PMV group, CPB (133.74 ± 89.65 vs. 72.30 ± 44.82, P =0.000) and ACC time (52.02 ± 24.80 vs. 36.98 ± 16.63, P =0.000) were both longer. FT4 and TT4 were higher while FT3, TT3 and TSH were lower in PMV group, but only FT3 (4.99 ± 1.67 vs. 5.29 ± 1.23, P =0.017) and TT3 (1.91 ± 0.59 vs. 1.96 ± 0.49, P =0.050) showed significant differences between PMV group and non-PMV group. Conclusion: Multiple logistic regression analysis showed that weight, infection, FT3 and CPB time were independent predictors of PMV after CPB in infants with CHD.
Infection control Knowledge, Practices, and Perceived barriers towards COVID-19 among physicians in university hospitals, Cairo, Egypt.
Authors: Hussein Rasha Saad , Abdel-Salam Shimaa A. , Mohamed Asmaa F. Gebrel
Published: November 2020

Background: WHO declared COVID-19 a global pandemic on 11th March 2020. Due to the lack of adequate treatment and approved vaccines, proper infection control practices are the only effective tools for prevention and control of COVID-19 infection among the health care facilities. Objectives: This study aimed to assess the infection control knowledge, practices, and perceived barriers towards COVID-19 among physicians working at Ain Shams University hospitals. Methods: Cross-sectional was carried out among a sample of physicians working at Ain Shams university hospitals, Cairo, Egypt, by using an online questionnaire. The design of the questionnaire was based mainly on the WHO guidance for infection prevention and control during health care when novel coronavirus infection is suspected and CDC guidance for COVID-19. Results: A total of 318 physicians with different job titles and specialties participated in this study, results showed average infection control knowledge (the mean correct answer rate was 57.1%+ 15.9%) and practices (infection control practices score was 78.76% + 12.17%) among our studied group. Patients overload and improper design of the working places were perceived as barriers to infection control practices by the majority (90%) of our participants. Conclusion: Our study results showed average infection control knowledge and practices towards COVID-19. There are defects in certain aspects related to infection control knowledge and practices that needed more practical training and properly designed working places to improve it.
Improved Tumor Discrimination and Shortened Administration-to-Imaging Times in Fluorescence Guided Surgery Through Paired-Agent Protocols
Authors: Wang Cheng , Folaron Margaret , Gunn Jason , Hodge Sassan , Chen Eunice , Hoopes P. Jack , Tichauer Kenneth , Samkoe Kimberley
Published: November 2020

Background: The goal of fluorescence guided surgery (FGS) in oncology is to improve the surgical therapeutic index by enhancing contrast between cancerous and healthy tissue. However, optimal discrimination between these tissues is complicated by the non-specific uptake and retention of molecular targeted agents and the heterogeneity of fluorescence signal. Paired-agent imaging (PAI) employs co-administration of an untargeted imaging agent with a molecular targeted agent, providing a normalization factor to minimize nonspecific and heterogeneous signals. The resulting measured binding potential is quantitative and equivalent to in vivo immunohistochemistry of the target protein. This study demonstrates that PAI improves the accuracy of tumor-to-healthy tissue discrimination compared to single agent imaging for in vivo FGS. Methods: PAI using a fluorescent anti-EGFR affibody molecule (ABY-029, eIND 122681) with untargeted IRDye 700DX carboxylate was compared to ABY-029 alone in an oral squamous cell carcinoma xenograft mouse model at 3 hours (n = 30). Results: PAI significantly enhanced tumor discrimination, as compared to ABY-029 alone (diagnostic accuracy - 0.94 vs 0.86, ROC curve AUC - 0.991 vs. 0.925, respectively). Additionally, the AUC of the ROC curve for PAI was stable as patient cohort number was increased from n = 1 to 20, while ABY-029 decreased as n increased, indicating a potential for universal FGS image thresholds to determine surgical margins. In addition, PAI reduced the administration-to-imaging time from 3 hours to 30 minutes and exhibited a statistically stronger correlation to EGFR expression heterogeneity (r = 0.58 compared to r = 0.47, p = 9B10-8). Conclusion: The quantitative receptor delineation of PAI promises to improve the surgical therapeutic index of cancer resection in a clinically relevant timeline.
Development of key quality indicators for appropriate antibiotic use in the Republic of Korea: results of a modified Delphi survey
Authors: Kim Bongyoung , Kim Myung Jin , Park Se Yoon , Moon Song Mi , Song Kyoung-Ho , Kim Tae Hyong , Kim Eu Suk , Kim Hong Bin
Published: November 2020

Background: An effective antibiotic stewardship program relies on the measurement of appropriate antibiotic use, on which there is a lack of consensus. We aimed to develop a set of key quality indicators (QIs) for nationwide point surveillance in the Republic of Korea.Methods: A systematic literature search of PubMed, EMBASE, and Cochrane Library (publications until 20th November 2019) was conducted. Potential key QIs were retrieved from the search and then evaluated by a multidisciplinary expert panel using a RAND-modified Delphi procedure comprising two online surveys and a face-to-face meeting. Results: The 23 potential key QIs identified from 21 studies were submitted to 25 multidisciplinary expert panels, and 17 key QIs were retained, with a high level of agreement (13 QIs for inpatients, 7 for outpatients, and 3 for surgical prophylaxis). After adding up the importance score and applicability, six key QIs [6 QIs (Q 1–6) for inpatients and 3 (Q 1, 2, and 5) for outpatients] were selected: (1) prescribe empirical antibiotic therapy according to guideline, (2) change empirical antibiotics to pathogen-directed therapy, (3) obtain culture samples from suspected infection sites, (4) obtain two blood cultures, (5) adapt antibiotic dosage to renal function, and (6) document antibiotic plan. In surgical prophylaxis, the QI to prescribe antibiotics according to the guideline and initiate antibiotic therapy 1 h before incision was selected.Conclusions: We identified key QIs to measure the appropriateness of antibiotic therapy for the identification of targets for improvement and to evaluate effects of antibiotic stewardship intervention.
MiR-21-3p promotes hepatocellular carcinoma progression through regulating Smad7/Yap1.
Authors: Hong Yinghui , Ye Mingliang , Wang Dan , Wang Chun , Luo Jie , Liu Jialiang , Liu Jing , Zhao Qiu , Chang Ying
Published: November 2020

Background Hepatocellular carcinoma (HCC) remains the global burden due to its high prevalence and mortality. Emerging evidence confirms that microRNAs (miRNAs) play a vital role in cancer initiation and progression. MiRNAs are widely involved in the regulation of signaling pathways by targeting downstream genes. MiR-21-3p as a liver-enriched miRNA has not been fully investigated. Abnormal activation of TGF-β transduction pathway promoted by deletion of Smad7 matters since HCC occurrence. While the relation between miR-21-3p and Smad7 has not yet been confirmed. We aimed to explore the influence of miR-21-3p on HCC initiation and progression by targeting Smad7 and further facilitating the expression of Yap1. Methods MicroRNA (miRNA) microarray analysis was performed for miRNA screening. Dual-luciferase assay was adopted for target verifying. The expressions of miRNA and related genes were quantified by qRT-PCR, western blotting, and immunohistochemical staining. Flow cytometry and transwell assay were used to discover cell apoptosis, invasion and metastasis abilities. Rat models were established to explore the axis's role in hepatocarcinogenesis. Bioinformatics analysis was performed for analyzing clinical significance. Results ­ MiR-21-3p was significantly increased in HCC, indicating a poor overall survival (OS) rate. High miR-21-3p was associated with advanced stages (P=0.029), especially T stages (P=0.026). Low Smad7/high Yap1 was verified in HCCs and rat models. Smad7 was proved to be the direct target of miR-21-3p. MiR-21-3p's effect on tumor malignant phenotypes and promotion of Yap1 could be partly reversed through transfecting Smad7. Overexpressed Yap1 promoted the downstream effector connective tissue growth factor (CTGF). Co-survival analysis indicated that lower miR-21-3p/higher Smad7 (P=0.0494) and lower miR-21-3p/lower Yap1 group (P=0.0379) patients had better OS rates. GSVA analysis of miR-21-3p and Smad7 related gene sets displayed strong relation with TGF-β signaling pathway in HCC. Conclusions MiR-21-3p promotes HCC migration and invasion via directly inhibiting Smad7 and further improving the expression of Yap1.
Obesity as a Predictor for Adverse Outcomes Among COVID-19 Patients: A Meta-Analysis
Authors: Das Pranta , Samad Nandeeta , Seidu Abdul-Aziz , Aboagye Richard Gyan , Tetteh Justice Kanor , Ahinkorah Bright Opoku
Published: November 2020

Background: The 2019 Severe Acute Respiratory Syndrome Coronavirus (COVID-19) is an unexpected pandemic causing mortalities across all ages. However, the severity of its health implications is mostly reported in persons with chronic health conditions with obesity being identified as one of the leading predisposing factors in acquiring the novel virus and developing its adverse complications. This meta-analysis sought to determine the estimated association between obesity and adverse outcomes among COVID-19 patients. Methods: We followed the recommended PRISMA guidelines in executing this study. A systematic literature search was conducted in PubMed, Google Scholar, and ScienceDirect for published literature between December 1, 2019, and October 2, 2020. The data for the study were pooled from studies that contained the search terms "Obesity" AND (COVID-19 or 2019-nCoV or Coronavirus or SARS-CoV-2) AND ("ICU admission" OR "Hospitalization" OR "Disease severity" OR "Invasive mechanical ventilator" OR "Death" OR "Mortality"). All the online searches were supplemented by reference screening of retrieved studies for additional literature. The pooled odds ratio (OR) and confidence intervals (CI) from the retrieved studies were calculated using the random effect model (Inverse-Variance method). Findings: A total of five (5) studies with a combined sample size of 335,192 patients were included in the meta-analysis. The pooled OR from the final analysis showed that patients who are severely obese were more likely to experience adverse outcome (death or ICU admission or needing IMV or hospitalization) compared to the normal patients [OR = 2.81, 95% CI = 2.33 – 3.40, I2 = 29%].Conclusion: Severe obesity is a risk factor in developing adverse outcomes among COVID-19 patients. The finding of the study signifies promotive, preventive, and curative attention to be accorded patients diagnosed with severe obesity and COVID-19.
Changing Paradigms in the Initial Treatment of Ectopic Pregnancy at a University Hospital in Brazil
Authors: Tavares Bárbara Virginia Gonçalves , Delfino Letícia Sathler , Ignarro Isabella Silvestre , Baccaro Luiz
Published: November 2020

Background: to evaluate the use of different treatment options for ectopic pregnancy and the frequency of severe complications in a university hospital. Methods: observational study with women with ectopic pregnancy admitted at UNICAMP Women´s Hospital, Brazil, between 01/01/2000 and 12/31/2017. The outcome variables were the type of treatment (first choice) and the presence of severe complications. Independent variables were clinical and sociodemographic data. Statistical analysis was carried out by the Cochran–Armitage test, chi-square test, Mann–Whitney test and multiple Cox regression. Results: 673 women were included in the study. The mean age was 29.0 years (±6.1) and the mean gestational age was 7.7 (±2.5). The frequency of surgical treatment decreased significantly over time (z=-4.69; p<0.001). Conversely, there was a significant increase in the frequency of clinical treatment (z=4.73; p<0.001). Seventy-one women (10.5%) developed some type of severe complication. In the final statistical model, the prevalence of severe complications was higher in women who were diagnosed with a ruptured ectopic pregnancy at admission (PR=2.97; 95%CI: 1.61–5.46), did not present with vaginal bleeding (PR=2.45; 95%CI: 1.41–4.25), had never undergone laparotomy/laparoscopy (PR=6.69; 95%CI: 1.62–27.53), had a non-tubal ectopic pregnancy (PR=4.61; 95%CI: 1.98–10.74), and do not smoke (PR=2.41; 95%CI: 1.08–5.36). Conclusion: there was a change in the first treatment option for cases of ectopic pregnancy in the hospital during the period of analysis. Factors inherent to a disease that is more difficult to treat are related to a higher frequency of severe complications.
A Novel MSC-Based Immune Induction Strategy in ABO-Incompatible Liver Transplantation: A Phase I/II Randomized, Open-Labeled, Controlled Trial
Authors: Zhang Yingcai , Zhang Jiebin , Yi Huimin , Zheng Jun , Cai Jianye , Chen Wenjie , Lu Tongyu , Chen Liang , Du Cong , Liu Jianrong , Yao Jia , Zhao Hui , Wang Guoying , Fu Binsheng , Zhang Tong , Zhang Jian , Wang Genshu , Li Hua , Xiang Andy Peng , Chen Guihua , Yi Shuhong , Zhang Qi , Yang Yang
Published: November 2020

Background: ABO-incompatible liver transplantation (ABO-i LT) has become a rescue therapeutic option for severe hepatic failure patients. Although the use of rituximab greatly reduces the morbidity of antibody-mediated rejection (AMR), severe adverse effects, such as infection and biliary complications still seriously threatening the survival of the transplant recipients. The aim of this study is to evaluate the safety and feasibility of using mesenchymal stem cells (MSCs) to replace rituximab in ABO-i LT. Methods: 22 severe hepatic failure patients undergoing ABO-i LT were enrolled and randomly divided into two groups, including the MSC group and Rituximab group. The safety of the application of MSCs and the incidence of allograft rejection, including antibody-mediated rejection (AMR) and acute cellular rejection (ACR) were evaluated in both groups at 2-year follow-up period as primary endpoints. Recipients and graft survivals and other postoperative complications were compared as secondary endpoints. Results: No severe adverse effects occurred in the MSC group related to the MSC infusion. MSCs treatment obtained comparable, if not better, results to rituximab for decreasing the incidence of acute rejection, especially AMR (9.1% vs 27.3%). Inspiringly, compared to the Rituximab group, biliary complications (0% vs 45.5%) and infection (9.1% vs 81.8%), were significantly decreased in MSCs group. In addition, there were no significant difference in 2-year graft and recipient survivals in the two groups (81.8% vs 72.7%). Conclusions: Our data shows that MSCs transfusion is comparable to rituximab treatment for AMR prophylaxis following ABO-i LT. Additionally, the results indicate that MSC is more beneficial to the prevention of infection and biliary complications, which may be introduced as a novel immunosuppressive approach for ABO-i LT. Trial registration: Trial registration: chictr.org.cn, ChiCTR2000037732. Registered 31 August 2020- Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=57074.
Monocyte Distribution Widths for Early Sepsis Detection in Emergency Department and Comparison with C-reactive Protein and Procalcitonin
Authors: woo Ala , Oh Dong-Kyu , Park Chan Jung , Hong Sang-Bum
Published: November 2020

Background: Monocyte undergo morphological changes in response to infection. Monocyte distribution width (MDW) reflects the morphological changes and increase in septic conditions. Currently, it has been suggested that MDW can act as an early biomarker of sepsis, but there are few reports on the comparison with conventional biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT).Methods: Patients who visited the emergency department (ED) were screened and enrolled prospectively. Tests for complete blood count, MDW, CRP, and PCT were done. Diagnostic performance for sepsis was tested in terms of area under the curve (AUC) of receiver operating characteristic (ROC) curves, sensitivity, and specificity.Results: In total, 665 patients were screened, and 549 patients with validated laboratory test results were included for the analysis. The patients were categorized into three groups according to Sepsis-3 criteria: non-infection, infection, and sepsis. MDW was the highest in the sepsis group (median [Q1-Q3] 24.0 [20.8-27.8]). AUC [95%CI] for MDW, CRP, PCT, and white blood cells for sepsis were 0.71[0.67-0.75], 0.75[0.71-0.78], 0.76[0.72-0.79], and 0.61[0.57-0.65], respectively. With the optimal cut-off value from the cohort, the sensitivity was 85.6% with MDW (cut-off 19.8), 69.7% with CRP (4.0), and 76.6% with PCT (0.05). Combination of quick sequential organ failure score (qSOFA) with MDW and WBC improved the AUC (0.78[CI 0.74-0.82]) to a greater extent compared to qSOFA alone (0.67[CI 0.62-0.72]).Conclusions: MDW reflected comparable diagnostic performance with conventional diagnostic markers, implying that MDW could be an alternative biomarker and that the combination with qSOFA improves the diagnostic performance for early sepsis.
Clearance of Inflammatory Cytokines in Patients with Septic Acute Kidney Injury During Renal Replacement Therapy Using the EMiC2 Filter (Clic-AKI Study)
Authors: Lumlertgul Nuttha , Hall Anna , Camporota Luigi , Crichton Siobhan , Ostermann Marlies
Published: November 2020

BackgroundThe Ultraflux EMiC2 membrane is a high cutoff hemofilter (45 kiloDalton). Little is known regarding its efficacy in eliminating medium-sized cytokines in sepsis. This study aimed to explore the effects of continuous veno-venous hemodialysis (CVVHD) using the EMiC2 filter on cytokine clearance.MethodsThis was a prospective observational study conducted in critically ill patients with sepsis and acute kidney injury requiring kidney replacement therapy. We measured concentrations of 12 cytokines [Interleukin (IL) IL-1β, IL-1α, IL-2, IL-4, IL-6, IL-8, IL-10, interferon (IFN)-ƴ, tumor necrosis factor (TNF)-α, vascular endothelial growth factor (VEGF), monocyte chemoattractant protein (MCP)-1, epidermal growth factor (EGF)] in plasma at baseline (T0) and pre- and post-dialyzer at 1, 6, 24, and 48 hours after CVVHD initiation and in the effluent fluid at corresponding time points. Outcomes were the effluent and adsorptive clearance rates, sieving coefficients (SCs), mass balances, and changes in serial serum concentrations.ResultsTwelve patients were included in the final analysis. All cytokines except EGF concentrations declined over 48 hours (p<0.001). Apart from IL-4, IL-8 and MCP-1, the SCs of the cytokines were <0.6. The effluent clearance rates were variable and ranged from negligible values for IL-2, IFN-ƴ, IL-1α, IL-1β, and EGF, to 19.0 ml/min for TNF-α. Negative or minimal adsorption was observed. The effluent and adsorptive clearance rates remained steady over time. The percentage of cytokine removal was low for most cytokines throughout the 48-hour period. ConclusionEMiC2-CVVHD achieved modest removal of most cytokines by diffusion and demonstrated small to no adsorptive capacity despite a decline in plasma cytokine concentrations. This suggests that changes in plasma cytokine concentrations may not be solely influenced by extracorporeal removal.Trial registrationNCT03231748, registered on 27th July 2017
Neutral Polysaccharide from Panax notoginseng enhanced cyclophosphamide antitumor efficacy in hepatoma H22‑bearing mice
Authors: Liu Yanhong , Qin Huayan , Zhong Yuanyuan , Li Shuang , Wang Huajing , Wang Hong , Chen Liling , Tang Xiang , Li Yalin , Qian Zhongyi , Li Huaiyu , Zhang Lei , Chen Tong
Published: November 2020

Background: Our previous studies demonstrated that the administration of crude Polysaccharide from Panax notoginseng (CPPN) can effectively prolong the lifespan of tumor-bearing mice via boosting the host immune system as well as weak cytotoxicity against hepatocellular carcinoma (HCC). In the present study, Neutral Polysaccharide (NPPN) were further purified from crude polysaccharide isolated from panax notoginseng. The effects of NPPN on the immune function and hematopoietic function of mice with low immunity and myelosuppression induced by cyclophosphamide (CTX) were investigated. The effect of NPPN combined with CTX on the tumor inhibition rate of the H22 tumor-bearing mice and the impact of NPPN on the proliferation of H22 liver cancer cells in vitro were investigated.Methods: CPPN was obtained by water extraction and alcohol precipitation method, and further purified by DEAE Sepharose Fast Flow ion exchange resin column. NPPN was added to the immunosuppressed with myelosuppression mice induced by CTX. Thymus index, spleen index, lymphocyte proliferation stimulation index by adding of concanavalin A, determination of serum hemolysin, NK cell activity assay, mice carbon clearance experiment, blood count tests were detected. The tumor inhibition rate of the H22 tumor-bearing mice treated with NPPN combined with CTX was recorded.Results: NPPN and 4 kinds of acid polysaccharide from Panax notoginseng (APPN) were successfully isolated from the CPPN by DEAE Sepharose Fast Flow ion exchange resin column. NPPN inhibited the growth of H22 cells and significantly increase the tumor inhibition rate of the H22 tumor-bearing mice combined with CTX. The elevation of the cellular and humoral immunity levels as well as a variety of blood count tests indicators of immunosuppressive with myelosuppression mice may contribute to the antitumor activity of NPPN.Conclusion: NPPN has a potential antitumor activity for the treatment of liver cancer combined with cyclophosphamide.
Physiological and molecular characterization of active fungi in pesticides contaminated soils for degradation of glyphosate
Authors: Njoku Kelechi L. , Eludini Peter O. , Adesuyi Adeola A. , Ude Emea O. , Oyelami Ayodeji O.
Published: November 2020

Understanding the physiological and molecular characteristics of naturally occurring fungi in glyphosate pesticide-contaminated environment is crucial to managing its contamination. The study was aimed at isolating and characterizing soil fungi for their physiological roles towards glyphosate degradation. Pure cultures of fungi were isolated from soil contaminated with glyphosate at farms in Lagos, Nigeria. The cultures were grown on minimal salt agar media amended with glyphosate. The best isolates exhibiting good tolerance to the glyphosate were characterized using molecular techniques. The BLAST search indicated that the fungi belong to four Aspergillus species (Aspergillus flavus strain JN-YG-3-5, Aspergillus niger strain APBSDSF96, Aspergillus fumigatus strain FJAT-31052 and Aspergillus flavus strain APBSWTPF130, Trichoderma gamsii and Penicillium simplicissimum. The biodegradation study of the glyphosate by the selected fungi species showed the presence of Aminomethylphosphonic Acid (AMPA) except for Aspergillus fumigatus strain FJAT-31052. Annotation analysis of the partial gene sequence showed that the strains possess protein coding gene clusters for glyphosate utilization and other physiological activities. The GhostKOALA output confirmed that CYP2W1 gene (Cytochrome P450, fungi type) was present in Aspergillus fumigatus strain FJAT-31052 which was absent in the genome of other fungi. The physiological and molecular characteristics of Aspergillus fumigatus strain FJAT-31052 clearly show that this fungus is a useful organism for managing contamination by glyphosate pesticide.
Changes in the characteristics of dental emergencies under the influence of SARS-CoV-2 pandemic: A retrospective study
Authors: Wu Kan , Li Chunjie , Yang Zheng , Yang Shangchun , Yang Wenbin , Hua Chengge
Published: November 2020

Background Further understanding of the distribution and changing characteristics of dental diseases is of great significance for all dental emergency centers for strengthening the medical staff’s treatment abilities and effective use of emergency resources in the face of public health emergencies involving highly infectious respiratory diseases.Methods The medical records of 4158 cases of dental emergency patients from 2019 to 2020 were retrospectively analyzed, with patients divided into the pre-SARS-COV-2 group and the SARS-COV-2 group, according to the date of their admission to the dental emergency center. The dental emergency patients’ demographic data, date and time, diagnoses, and treatment approaches were compared before and during the SARS-COV-2 pandemic.Results During the SARS-COV-2 pandemic, the number of dental emergency visits increased by 29.7%. The peak of the number of patients at weekends and at night is not obvious compared with the pre-SARS-COV-2 group. During the pandemic, males (n=286, 58.1%) were more likely to visit dental emergency centers for trauma than females (n=206, 41.9%) (P<0.05); females (n=242, 60.8%) were more likely to visit dental emergency centers for acute gingivitis and acute pericoronitis than males (n=156, 39.2%) (P<0.05). A major change in diagnosis was related to acute pulpitis (K04.0) and acute apical periodontitis (K04.4), which increased by 9.2%; acute gingivitis (K05.0) and acute pericoronitis (K05.2) increased by 3.5%; open wound of the lip and oral cavity (S01.5) decreased by 17.9%; other conditions (non-emergency diseases) increased by 6.8%, compared with the pre-SARS-COV-2 period. Among the treatment modalities, during the pre-SARS-COV-2 period, 304 patients (17.7%) received a prescription for antibiotics and analgesics, and 1485 (86.5%) received a prescription for local treatment. During the SARS-COV-2 period, 958 (39.2%) received a prescription for antibiotics and analgesics, and 1636 (67.0%) received a prescription for local treatment.Conclusion SARS-COV-2 pandemic led to changes in the characteristics of dental emergency patients. Trauma, acute pulpitis, and acute periodontitis are the leading reasons patients refer to dental emergency centers. Dental emergency centers should optimize treatment procedures, optimize the staff, and reasonably allocate materials according to the changes to improve the on-site treatment capacity and provide adequate dental emergency care.
Changing trends of birth weight with maternal age: a cross-sectional study in Xi'an city of Northwestern China
Authors: Wang Shanshan , Yang Liren , Shang Li , Yang Wenfang , Qi Cuifang , Huang Liyan , Xie Guilan , Wang Ruiqi , Chung Mei Chun
Published: November 2020

Background: Most studies have shown that maternal age is associated with birth weight. However, the specific relationship between each additional year of maternal age and birth weight remains unclear. The study aimed to analyze the specific association between maternal age and birth weight. Methods: Raw data for all live births from 2015 to 2018 were obtained from the Medical Birth Registry of Xi’an, China. A total of 490143 mother-child pairs with full-term singleton live births and the maternal age ranging from 20 to 40 years old were included in our study. Birth weight, gestational age, neonatal birth date, maternal birth date, residence and ethnicity were collected. Generalized additive model and two-piece wise linear regression model were used to analyze the specific relationships between maternal age and birth weight, risk of low birth weight, and risk of macrosomia. Results: The relationships between maternal age and birth weight, risk of low birth weight, and risk of macrosomia were nonlinear. Birth weight increased 16.204 g per year when maternal age was less than 24 years old (95%CI: 14.323, 18.086), and increased 12.051g per year when maternal age ranged from 24 to 34 years old (95%CI: 11.609, 12.493), then decreased 0.824g per year (95% CI: -3.112, 1.464). The risk of low birth weight decreased with the increase of maternal age until 36 years old (OR= 0.917, 95%CI: 0.903, 0.932 when maternal age was younger than 27 years old; OR= 0.965, 95%CI: 0.955, 0.976 when maternal age ranged from 27 to 36 years old), then increased when maternal age was older than 36 years old (OR=1.133, 95%CI: 1.026, 1.250). The risk of macrosomia increased with the increase of maternal age (OR=1.102, 95%CI: 1.075, 1.129 when maternal age was younger than 24 years old; OR=1.065, 95%CI: 1.060, 1.071 when maternal age ranged from 24 to 33 years old; OR=1.029, 95%CI: 1.012, 1.046 when maternal age was older than 33 years old). Conclusions: For women of childbearing age (20-40 years old), the threshold of maternal age on low birth weight was 36 years old, and the risk of macrosomia increased with the increase of maternal age.
LncRNA LINC00240 suppresses invasion and migration in non-small cell lung cancer by sponging miR-7-5p
Authors: Ku gwan woo , Kang Yujin , Yu Seong-Lan , Park Joonghoon , Park Sejin , Jeong In Beom , Kang Min Woong , Son Ji Woong , Kang Jaeku
Published: November 2020

Background: lncRNAs have important roles in regulating cancer biology. Accumulating evidence has established a link between the dysregulation of lncRNAs and microRNA in cancer progression. In previous studies, miR-7-5p has been found to be significantly down-regulated in mesenchymal-like lung cancer cell lines and directly regulated EGFR. In this work, we investigated the lncRNA partner of miR-7-5p in the progression of lung cancer.Methods: We investigated the expression of miR-7-5p and the lncRNA after transfection with an miR-7-5p mimics using a microarray. The microarray results were validated using quantitative real time-polymerase Chain Reaction (qRT-PCR). The regulatory effects of lncRNA on miR-7-5p and its target were evaluated by changes in the expression of miR-7-5p after transfection with siRNAs for lncRNA and the synthesis of full-length lncRNA. The effect of miR-7-5p on lncRNA and the miRNA target was evaluated after transfection with miRNA mimic and inhibitor. The role of lncRNA in cancer progression was determined using invasion and migration assays. The level of lncRNA and EGFR in lung cancer and normal lung tissue was analyzed using TCGA data.Results: We found that LINC00240 was downregulated in lung cancer cell line after miR-7-5p transfection with an miR-7-5p mimic. Further investigations revealed that the knockdown of LINC00240 induced the overexpression of miR-7-5p. The overexpression of miR-7-5p diminished cancer invasion and migration. The EGFR expression was down regulated after siRNA treatment for LINC00240. Silencing LINC00240 suppressed the invasion and migration of lung cancer cells, whereas LINC00240 overexpression exerted the opposite effect. The lower expression of LINC00240 in squamous lung cancer was analyzed using TCGA data.Conclusions: Taken together, LINC00240 acted as a sponge for miR-7-5p and induced the overexpression of EGFR. LINC00240 may represent a potential target for the treatment of lung cancer.
Multidisciplinary Approach to Enhancing Provider Well-Being in a Metropolitan Medical Group in the United States
Authors: Shields Lisa Barbara , Jennings James T. , Honaker Joshua T.
Published: November 2020

Background: Physician burnout refers to depersonalization, emotional exhaustion, and a sense of lower personal accomplishment. Affecting approximately 50% of physicians in the United States, physician burnout negatively impacts both the physician and patient. Over a 3-year-period, this prospective study evaluated the multidisciplinary approach to decreasing provider burnout and improving provider well-being in our metropolitan community. Methods: A multidisciplinary Well-Being Task Force was established at our Institution in 2017 to assess the myriad factors that may play a role in provider burnout and offer solutions to mitigate the stressors that may lead to decreased provider well-being. Four multifaceted strategies were implemented: (1) provider engagement & growth; (2) workflow/office efficiencies; (3) relationship building; and (4) communication. Providers at our Institution took the Mayo Clinic’s well-being index survey on 3 occasions over 3 years. Their scores were compared to those of providers nationally at baseline and at 1 and 2 years after implementing organizational and individualized techniques to enhance provider well-being. Lower well-being index scores reflected better well-being. Results: The average overall well-being index scores of our Institution’s providers decreased from 1.76 at baseline to 1.32 2 years later compared to an increase in well-being index scores of physicians nationally (1.73 to 1.85). Both male and female providers’ average well-being index scores at our Institution decreased over the 3 years of this study, from 1.72 to 1.58 for males and 1.78 to 1.21 for females, while physicians’ scores nationally increased for both genders. The average well-being index scores were highest for providers at our Institution who graduated from medical school less than 5 years earlier (2.0) and who graduated 15-24 years earlier (2.3), whereas the average lowest scores were observed in providers who graduated ³25 years earlier (1.37). Obstetricians/gynecologists and internal medicine physicians had the highest average well-being index scores (2.48 and 2.4, respectively) compared to other medical specialties. The turnover rate of our Institution’s providers was 5.6% in 2017 and 3.9% in 2019, reflecting a 30% decrease. Conclusion: This study serves as a model to reduce provider burnout and enhance well-being through both organizational and individual interventions.
Gene modules and non-coding RNAs involved in pancreatic tumorigenesis through acinar ductal metaplasia 
Authors: Zhang Huairong , Shi Bingyin , GAO ZU-HUA , GAO BO
Published: November 2020

Background: Acinar ductal metaplasia (ADM) is a recently identified precursor lesion that can progress through pancreatic ductal intraepithelial neoplasia (PanIN) to pancreatic ductal adenocarcinoma (PDAC). However, the genetic alterations and the transcriptional regulators at work during the process of ADM-driven PDAC tumorigenesis are largely unknown. We applied a multidimensional integration strategy to unveil the gene modules and non-coding RNAs that drive the ADM-PanIN-PDAC process. Methods: GSE40895 and the microarray datasets were integrated to unmask the regulators linked to ADM, PanIN and PDAC. Based on the differentially expressed genes and protein–protein interaction (PPI) networks for each stage, overlapping and crosstalk gene modules in ADM-PanIN-PDAC were identified using the search tool for the retrieval of interacting genes (STRING) and Cytoscape. The functions of these modules were elucidated by gene ontology (GO) analysis. The expression levels of hub genes and survival analysis were investigated in human PDAC via gene expression profiling interactive analysis (GEPIA). The MiRDB database was used to predict potential non-coding RNAs (ncRNAs) capable of regulating overlap and crosstalk genes.Results: We found several bridging ADM gene modules (e.g. SMARCA1 and H2AFZ), PanIN gene modules (e.g. HDAC11 and SMARCA2) and PDAC gene modules (e.g. OLFR239 and CLIP3). They were enriched in nucleosome assembly, chromatin organization and G-protein coupled receptor signalling pathways by GO analysis. MicroRNAs (e.g. mmu-miR-335-5p and mmu-miR-669n) and lncRNAs (e.g. H19 and Gm14207) took part in this ample crosstalk by regulating the gene expression. Conclusions: SMARCA1, SMARCA2 and CLIP3 were identified as novel crosstalk genes and potential prognostic biomarkers for ADM-driven PDAC carcinogenesis. After validation in clinical and functional studies, transcriptional regulatory non-coding RNAs targeting crosstalk and overlapping genes could represent effective targets for early PDAC intervention.