bluuebunny/crossref_metadata_2025 huggingface dataset:
Traditional Chinese medicine for ischemic heart disease: clinical manifestations and objective indicators
Authors: Liao Jiangquan , Tian Jiaxing , Shao Mingjing , Wang Zhe , Wei Kangkang , Chang Jiangmeng , Zhang Xiaoqiong , Chen Ming , Li Xianlun , Du Jinhang
Published: April 2020

Background: The clinical practice of Traditional Chinese medicine (TCM) has a history of more than 2000 years. Modern clinical trials and experimental researches of TCM have been conducted for decades and provided support for the application of TCM in the prevention and treatment of ischemic heart disease (IHD). However the level of evidence and the proper application of TCM were still barely satisfactory.Methods: In this study, we divided IHD into 5 different stages, including stable angina, unstable angina, acute myocardial infarction, post myocardial infarction and chronic heart failure. Then we systematically reviewed and meta-analyzed the existing RCTs on both clinical manifestations and objective indicators, in these 5 aspects.Results: The results indicate that TCM can both improve the clinical manifestations and ameliorate the objective parameters in different courses of IHD. Some of the improvements lead to potential long-term benefits.Conclusions: TCM is effective on CVD in different stages of diseases, both in improving clinical manifestations and objective indicators. To acquire more solid and comprehensive evidence of TCM in treating CVD, more rigorously designed RCTs with longer follow-up duration are warranted.
Quantified CT Evaluation in coronavirus disease (COVID-19): A study of 30 Patients in Chongqing, China
Authors: Zhao Wei , Li Ji , Yang Jia , Ye Sikuan , Xiang Ying , Bao Yixi
Published: April 2020

Background Chest computed tomography (CT) provides insight into the progression and prognosis of COVID-19 pneumonia. Purpose To quantify the chest CT scans of patients with CODIV-19 pneumonia using the pulmonary inflammation index (PII)and associate it with the severity of pneumonia. Methods A total of thirty inpatients admitted between January 30 and February 29, 2020 with confirmed COVID-19 infection were enrolled in this retrospective review. Patients were classified as “severe”(those who met the severe pneumonia criteria) or “mild”. Chest CT scans and clinical statistics data were obtained at four milestones (the date of admission, 3 days after treatment, 1 week after treatment and the time the last CT scan was obtained before discharge orthe completionof our research). Results Thirty patients (18 males and 12 females, age 20–74 years) with confirmed COVID-19pneumonia were evaluated. Increased neutrophilswere noted in 11 (36.7%) patients and decreased in 3 (10%) patients. Elevation of C-reactive protein (CRP) in 22 (73.3%) patients and erythrocyte sedimentation rate in 27 (90%) patient were observed, but elevation of procalcitonin was not obvious. Seven (53.8%) patients had elevation of lactate dehydrogenase (LDH).The presentation of CT opacities was mainly in the form of distribution in both the severe andmild groups. The mean PII score in the severe group was 58% and 13.7% in the mild group. The score in the severe group was more than 50%and less than 20%in the mild group at every milestone. The score in the severe group was always higher than the mild group, therefore, the severity of the disease may be positively correlated with PII score. Conclusion The pulmonary inflammation index (PII) score of chest CT scans correlated with coronavirus disease (COVID-19) progression and could be used to indicate severity in patients.
Acceptability, Appropriateness, and Preliminary Effects of the PrEP Diffusion Training for Lay HIV Workers: Increased PrEP Knowledge, Decreased Stigma, and Diffusion of Innovation
Authors: Wu Yumeng , Yang Gang , Meyers Kathrine
Published: April 2020

Background Training lay health workers is a critical strategy for HIV pre-exposure prophylaxis (PrEP) implementation, but little is known about effective approaches to conducting and evaluating such trainings. We evaluated the effect of the PrEP Diffusion Training, a one-day participatory training informed by the Diffusion of Innovation theory, on knowledge, PrEP stigma, implementation behavior, and diffusion of PrEP innovation among lay HIV workers in China.Methods Nine PrEP Diffusion Trainings were delivered to 220 lay HIV workers. We conducted multi-time-point surveys to assess acceptability, appropriateness, and preliminary effects of the training on participants’ knowledge, PrEP stigma, determinants of implementation behavior, and diffusion of PrEP information. We used an observation-based checklist to evaluate implementation fidelity.Results All trainings were delivered with high fidelity to the standardized manual, with little variability across sites. Acceptability and appropriateness of training were high. PrEP knowledge score significantly increased by 65% from pre-training to post-training, and remained high one month after the training. We observed a significant decrease in PrEP stigma and a positive influence on determinants of implementation behaviors. All participants surveyed one-month after the training reported having shared PrEP information in their social networks, and 43% reported integrating PrEP education into their routine HIV prevention work on a regular basis.Conclusions The PrEP Diffusion Training is a practical and effective strategy to build lay HIV workers’ capacity to participate in PrEP implementation. Longer-term follow up post training would be ideal to further assess actual PrEP uptake and sustained effects of intervention on PrEP implementation.
A Study on the Benefits of Participation in an Electronic Tracking Physical Activity Program and Motivational Interviewing During a Three-Month Period
Authors: Johnson Urban , Ivarsson Andreas , Parker James , Svetoft Ingrid , Andersen Mark B.
Published: April 2020

Background The purpose of the study was to investigate if participation in a three-month electronic tracking outdoor physical activity and a motivational interviewing (MI) intervention led to positive behavioural, psychological, and physiological outcomes. Method Based on a two-group pre-post experimental design, 12 women and 6 men were randomly assign to an experimental (mean age = 51.9 years) and an control group (mean age = 48.9 years) based on the inclusion criteria: (a) having a primarily sedentary job, (b) limited exercise activity in the past year and (c) employed within the Halmstad Municipal Council. Physical activity data were collected continuously by wrist-worn activity sensors, and pre-post data were collected on the GHQ-12, the BREQ-2, body mass, body fat mass and total body muscle. Measures of cardiovascular fitness (time to exhaustion) were also taken pre to post. The experimental group was supported through individual MI coaching sessions and individual resistance-training programs specifically designed for use in an outdoor gym. Magnitude based inferences (MBI) were calculated based on the disposition of the confidence limits for the mean differences to the smallest worthwhile changes. Results MBI analysis of baseline measures showed differences in body fat between the groups. The experimental group had a small and beneficial increase in in physical activity behaviour (steps). Moreover, the control group had a medium decrease in identified regulation, but the experimental group maintained the same level at the post-measure. Conclusion Participation in the outdoor physical activity and MI intervention resulted in a small increase in in physical activity behaviour (steps) as well as a maintained level of identified regulation in the experimental group. The latter result may be related to a possible combined effect of MI and continuous feedback from the activity tracker. Although there are many questions that remain unanswered, the public health implications of using fitness technology to promote behaviour change seem worthwhile to study. Potential implications for future studies are provided.
Symbiotic microbiome Staphylococcus aureus from human nasal mucus modulates IL-33-mediated type 2 immune responses in allergic nasal mucosa
Authors: Jeon Yung Jin , Gil Chan Hee , Won Jina , Jo Ara , Kim Hyun Jik
Published: April 2020

Background: The host-microbial commensalism can shapes the innate immune responses in respiratory mucosa and nasal microbiome also modulates front-line immune mechanism in the nasal mucosa. Inhaled allergens encounter the host immune system first in the nasal mucosa, and microbial characteristics of nasal mucus directly impact the mechanisms of initial allergic responses in nasal epithelium. However, the roles of the nasal microbiome in allergic nasal mucosa remain uncertain. We sought to determine the distribution of nasal microbiomes in allergic nasal mucosa and elucidate the interplay between nasal microbiome Staphylococcus species and Th2 cytokines in allergic rhinitis (AR) models.Results: Staphylococcus aureus (AR-SA) and S. epidermidis (AR-SE) were isolated from the nasal mucosa of patients with AR. The influence of nasal microbiome Staphylococcus species on allergic nasal mucosa was also tested with in vitro and in vivo AR models. Pyrosequencing data showed that colonization by S. epidermidis and S. aureus was more dominant in nasal mucus of AR subjects. The mRNA and protein levels of IL-33 and TSLP were significantly higher in AR nasal epithelial (ARNE) cells which were cultured from nasal mucosa of AR subjects, and exposure of ARNE cells to AR-SA reduced IL-33 mRNA and secreted protein levels. Particularly, OVA-driven AR mice inoculated with AR-SA by intranasal delivery exhibited significantly reduced IL-33 in their nasal mucosa. In the context of these results, allergic symptoms and Th2 cytokine levels were significantly downregulated after intranasal inoculation of AR-SA in vivo AR mice. Conclusion: Colonization by Staphylococcus species was more dominant in allergic nasal mucosa, and nasal commensal S. aureus from subjects with AR mediates anti-allergic effects by modulating IL-33-dependent Th2 inflammation. The results demonstrate the role of host-bacterial commensalism in shaping human allergic inflammation.
Correlation of sagittal configuration of the sacrum and pelvic incidence evaluated by computed tomography measurements
Authors: Chen Hongfang , Tian Haijun , Zhou Yifan , Zhang Henghui , Zhao Changqing
Published: April 2020

Objective To measure the sagittal configurations of the sacrum using computed tomography (CT), and to investigate the correlation between the sagittal configuration of the sacrum and pelvic incidence. Methods The computed topographies of complete pelvic imaging between 2006 and 2018 was retrospectively studied. Measurements of pelvic and sacral morphological parameters were performed on the midsagittal plane of the 2D reconstruction images of computed tomography. Pelvic incidence (PI) (STA) were measured as previously described, and sacral table angle, sacral incidence (SI), sacral segmental vertebral angle (SSVA), sacral segmental kyphosis (SSK), central angle (SCA), arc length (SAL) as well as arc radius (SAR) were introduced to describe the segmental morphology of sacrum. Pearson Correlation Coefficient and Stepwise Regression Analysis were used to determine the relationship between PI and sacral morphological parameters. Results A total of 304 subjects were finally included in this study. The average age of the patients were 46.22 ± 15.92 years, and the average PI was 45.24±8.68°. Most of the sacral morphological parameters were not different as affected by gender or age. The morphological parameters of S1: S1I, SSVA1 and STA were finally confirmed to be closely correlated with PI, while no significant correlation between sacral curvature (SCA) and PI was identified, and morphological parameters of other sacral segments were not correlated to PI either. Conclusion The morphological parameters of S1 are more closely correlated with PI, and the sacral incidence of S1 might serve as a useful tool for the calculation of PI.
Body composition impact on sleep in young adults: The mediating role of sedentariness, physical activity, and diet
Authors: Carneiro-Barrera Almudena , Amaro-Gahete Francisco J. , Acosta Francisco M. , Ruiz Jonatan R.
Published: April 2020

The authors have requested that this preprint be withdrawn due to author disagreement.
Integration of human cell lines gene expression and chemical properties of drugs for Drug Induced Liver Injury prediction
Authors: Lesiński Wojciech , Mnich Krzysztof , Golińska Agnieszka Kitlas , Rudnicki Witold R.
Published: April 2020

Motivation: Drug-induced liver injury (DILI) is one of the primary problems in drug development. Early prediction of DILI can bring a significant reduction in the cost of clinical trials. In this work we examined whether occurrence of DILI can be predicted using gene expression profile in cancer cell lines and chemical properties of drugs. Methods: We used gene expression profiles from 13 human cell lines, as well as molecular properties of drugs to build Machine Learning models of DILI. To this end, we have used a robust cross-validated protocol based on feature selection and Random Forest algorithm. In this protocol we first identify the most informative variables and then use them to build predictive models. The models are first built using data from single cell lines, and chemical properties. Then they are integrated using Super Learner method with several underlying methods for integration. The entire modelling process is performed using nested cross-validation. Results: We have obtained weakly predictive ML models when using either molecular descriptors, or some individual cell lines (AUC: 0.55-0.61). Models obtained with the Super Learner approach have a significantly improved accuracy (AUC=0.73), which allows to divide substances in two categories: low-risk and high-risk.
Evidence of integrated primary-secondary health care in low-and middle-income countries: protocol for a scoping review
Authors: Hasan Md Zabir , Singh Shalini , Arora Dinesh , Jain Nishant , Gupta Shivam
Published: April 2020

Background: Integrated care is a people-centered health delivery approach that ensures the comprehensiveness, quality, and continuity of service across the settings and levels of health systems. The World Health Organization (WHO) recommends integration across levels and building-blocks of health systems as a prerequisite of Universal Health Coverage (UHC). While health systems of low and middle-income countries (LMICs) are often fragmented and led by siloed service delivery structure, several LMICs – including India – have attempted health system integration. Several systematic reviews of evidence on healthcare integration from developed countries exist, but to date, no synthesis from LMICs was reported. This review will provide an overview of existing Integrated Primary Secondary Care Systems (IPSCS) in the context of LMICs, aiming to support policy decisions for the effective integration of health delivery systems in India. Methods: The review will be conducted following the six steps recommend by Arksey and O’Malley. Scientific and grey literature will be systematically selected from PubMed, Embase, Scopus, Web of Science, Global Index Medicus, and electronic repositories of the WHO, World Bank, Health Policy Plus, and OpenGrey. Using a comprehensive search strategy, literature written in English and published between 2000-2019 will be selected, and two independent authors will screen their titles and abstracts. The result will be charted using a data extraction form and reported using tables, figures, and in narrative form. Discussion: No ethical approval is necessary for the review. The review will be conducted between December 2019 and April 2020. The final report will be developed with the consultation of other stakeholders and disseminated through workshops, conference papers, and peer review articles. The review will serve as a guiding tool to approach, implement, and test the IPSCS model in India and other LMICs.
Genetic deletion of microRNA-22 blunts the inflammatory transcriptional response to status epilepticus and exacerbates epilepsy in mice
Authors: Silva Luiz FA , Reschke Cristina R , Nguyen Ngoc T , Langa Elena , Rodriguez Amaya Sanz , Temp Fernanda R. , Freitas Mayara L. , Gerbatin Rogerio R , Conroy Ronan M , Brennan Gary P , Engel Tobias , Henshall David C
Published: April 2020

MicroRNAs perform important roles in the post-transcriptional regulation of gene expression. Sequencing as well as functional studies using antisense oligonucleotides, indicate important roles for microRNAs during the development of epilepsy through targeting transcripts involved in neuronal structure, gliosis and inflammation. MicroRNA-22 (miR-22) has been reported to protect against the development of epileptogenic brain networks through suppression of neuroinflammatory signalling. Here, we used mice with a genetic deletion of miR-22 to extend these insights. Mice lacking miR-22 displayed normal behaviour and brain structure and developed similar status epilepticus after intraamygdala kainic acid compared to wildtype animals. Continuous EEG monitoring after status epilepticus revealed an accelerated and exacerbated epilepsy phenotype whereby spontaneous seizures began sooner, occurred more frequently and were of longer duration in miR-22-deficient mice. RNA sequencing analysis of the hippocampus during the period of epileptogenesis revealed a specific suppression of inflammatory signalling in the hippocampus of miR-22-deficient mice. Taken together, these findings indicate a role for miR-22 in establishing early inflammatory responses to status epilepticus. Inflammatory signalling may serve anti-epileptogenic functions and cautions the timing of anti-inflammatory interventions for the treatment of status epilepticus.
Risk-benefit analysis of isoniazid monotherapy to prevent tuberculosis in patients with rheumatic diseases exposed to prolonged, high-dose glucocorticoids
Authors: Park Jun Won , Curtis Jeffrey R , Lee Hajeong , Lee Jung-Kyu , Song Yeong Wook , Lee Eun Bong
Published: April 2020

Objective To investigate the incidence of tuberculosis (TB) in patients with rheumatic diseases receiving high-dose glucocorticoids and to evaluate the preventive effect of isoniazid (INH). Methods This study included 1618 treatment episodes of prolonged (≥4 weeks), high-dose steroids (≥30mg/day of prednisone) in 1160 patients. Of these, INH was administered in 152 (9.4%) treatment episodes (INH group), while others received no prophylaxis (control group). The high-risk subgroup (n=92) was defined as patients with 1) incomplete adherence to treatment of previous TB, 2) positive interferon-γ release assay, and/or 3) linear/reticular fibrotic lesions on chest radiographs. Primary outcome was 1-year incidence of TB in each group. Results During 1579.8 person-years, 21 cases of TB occurred. The high-risk subgroup showed a significantly higher TB incidence than the non-high-risk subgroup (Incidence rate ratio=8.29). INH did not significantly affect the 1-year TB incidence in the whole population but numerically reduced it only in the high-risk subgroup [adjusted hazards ratio=0.48 (95% CI, 0.003–5.46)]. The incidence of adverse drug reactions (ADRs) related to INH was 111.6 (89.3–137.9)/100 person-years, including one fatal occurrence of fulminant hepatitis. The number needed to treat (NNT) to prevent one case of TB was lower than the number needed to harm (NNH) for one case of serious ADR only in the high-risk subgroup (3 vs. 11). Conclusion INH treatment to prevent TB might be effective in high-risk patients but has a risk of frequent ADRs, which limits its use in general practice in patients not at a high risk of developing TB.
NLRP3 inflammasome inhibitor MCC950 attenuates primary dysmenorrhea in mice via the NF-κB/COX-2/PG pathway
Authors: biao tang , Dan Liu , Lingyu Chen , yu liu
Published: April 2020

Background: Primary dysmenorrhea (PD) constitutes a common gynecological disease among young women. The NLRP3 inflammasome may be activated and expressed in PD, but the mechanistic link between NLRP3 inflammasome activation and PD is still unclear.Methods: To investigate the potential role of NLRP3 inflammasome activation in the pathogenesis of PD, thirty female Kunming mice without pregnancy were used for experiments. The PD mouse model was constructed by 11 days of successive co-treatment with estradiol and oxytocin. MCC950, a potent and specific small-molecule inhibitor of the NLRP3 inflammasome, was used to treat PD mice. The disease level was assessed by the writhing response and hot water tail-flick test. The levels of prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2α) in the uterine tissues of mice were detected by ELISA. The expression levels of protein and cytokines, including NLRP3, cysteine aspartic acid-specific protease 1 (caspase-1), interleukin (IL)-1β, IL-18, nuclear factor kappa B (NF-κB) p65, phospho-NF-κB p65, and cyclooxygenase-2 (COX-2) were revealed by western blot analysis.Results: MCC950 greatly ameliorated the writhing response induced by the combination of oxytocin and estradiol, with an increasing length of tail-flick latency. MCC950 also significantly decreased the levels of PGF2α and PGE2, and the expressions of NLRP3, caspase-1, IL-1β, IL-18, phospho-NF-κB p65, NF-κB p65, and COX-2 in the uterus.Conclusions: MCC950 markedly alleviated the pain and pathological damage in PD mice by inhibiting NLRP3 activation. The underlying mechanism may be related to hypoactive uterine inflammation via suppression of NLRP3 activation and the NF-κB/COX-2/PG pathway in uteruses of PD mice.
Situational judgment test validity: An exploratory model of the participant response process using cognitive and think-aloud interviews
Authors: Wolcott Michael D. , Lobczowski Nikki G. , Zeeman Jacqueline M. , McLaughlin Jacqueline E.
Published: April 2020

Background: Situational judgment tests (SJTs) are used in health sciences education to measure knowledge using case-based scenarios. Despite their popularity, there is a significant gap in the validity evidence and research on the response process that demonstrate how SJTs measure their intended constructs. Models of the SJT response process have been proposed in the literature; however, few studies explore and expand these models beyond surface-level attributes. The purpose of this study was to describe the factors and strategies involved in the cognitive process examinees use as they respond to SJT items.Methods: Thirty participants—15 students and 15 experienced practitioners—completed a 12-item SJT designed to measure empathy. Each participant engaged in a think-aloud interview while completing the SJT followed by a cognitive interview probing their decision-making processes. Interviews were transcribed and independently coded by three researchers to identify salient themes and factors that contributed to the response process. Results: Results suggested that the SJT response process included the complex integration of comprehension, retrieval, judgment, and response selections. Each of these response process stages were influenced by attributes such as perceived objective of the task, job-specific knowledge, assumptions about the scenario, and item setting. Conclusions: This study provides an evaluation of the SJT response process and contributes exploratory information to the validity evidence of SJTs; these findings can inform the design, interpretation, and utility of SJTs.
General practice trainee strategies for seeking in-consultation assistance from supervisors, and their perceptions of patient-related barriers to help-seeking: a survey study
Authors: Sturman Nancy , Tapley Amanda , Driel Mieke van , Holliday Elizabeth , Ball Jean , Davey Andrew , Fielding Alison , Fitzgerald Kristen , Spike Neil , Magin Parker
Published: April 2020

Background General practice (GP) trainees may seek supervisor assistance when hesitant to complete patient consultations independently. Trainees describe patient-related barriers to this in-consultation help-seeking, despite its key role in supervisory oversight. Little is known, however, about trainee strategies for seeking assistance, or the frequency and associations of trainee concerns about these barriers. Methods Australian GP trainees rated their frequency of use of five specific strategies for obtaining in-consultation assistance, perceived change in patient impressions of their competence after this assistance, and relative trainee comfort presenting patients outside, compared to within, patients’ hearing. Statistical analyses included descriptive statistics and multivariable logistic regression. Results Responses were received from 778 Australian GP trainees (response rate 89%). Help-seeking strategies did not differ between trainees at different training stages, except for greater use of electronic messaging in later stages. In-consultation assistance was most commonly provided by phone between trainee and supervisor consulting rooms, or outside the trainee’s patient’s hearing. Supervisor assistance in the trainee’s room face-to-face with the patient was reported as either never or rarely obtained by 12% of respondents. More trainees (25%) perceived that patient impressions of their competence increased after help-seeking than perceived that these impressions decreased (19%). Most trainees (55%) preferred to present patients outside their hearing. Trainee age was the only variable associated with both patient-related barriers. Conclusion Supervisors appear to have considerable influence over trainee help-seeking barriers and strategies, including whether or not face-to-face in-consultation supervision is sought. In-consultation supervision may actually increase trainee perceptions of patient impressions of their competence. Many supervisors and trainees may benefit from additional educational and workplace interventions to facilitate comfortable and effective trainee help-seeking in front of patients. More work is required to understand the clinical and educational implications of different help-seeking strategies when trainees require ‘just in time’ supervisor assistance.
Construction of a Semi-automatic ICD-10 Coding System
Authors: Zhou Lingling , Cheng Cheng , Ou Dong , Huang Hao
Published: April 2020

Background The International Classification of Diseases, 10th Revision (ICD-10) has been widely used to describe the diagnosis information of patients. Automatic ICD-10 coding is important because manually assigning codes is expensive, time consuming and error prone. Although numerous approaches have been developed to explore automatic coding, few of them have been applied in practice. Our aim is to construct a practical, automatic ICD-10 coding machine to improve coding efficiency and quality in daily work. Methods In this study, we propose the use of regular expressions (regexps) to establish a correspondence between diagnosis codes and diagnosis descriptions in outpatient settings and at admission and discharge. The description models of the regexps were embedded in our upgraded coding system, which queries a diagnosis description and assigns a unique diagnosis code. Like most studies, the precision (P), recall (R), F-measure (F) and overall accuracy (A) were used to evaluate the system performance. Our study had two stages. The datasets were obtained from the diagnosis information on the homepage of the discharge medical record. The testing sets were from October 1, 2017 to April 30, 2018 and from July 1, 2018 to January 31, 2019. Results The values of P were 89.27% and 88.38% in the first testing phase and the second testing phase, respectively, which demonstrate high precision. The automatic ICD-10 coding system completed more than 160,000 codes in 16 months, which reduced the workload of the coders. In addition, a comparison between the amount of time needed for manual coding and automatic coding indicated the effectiveness of the system-the time needed for automatic coding takes nearly 100 times less than manual coding. Conclusions Our automatic coding system is well suited for the coding task. Further studies are warranted to perfect the description models of the regexps and to develop synthetic approaches to improve system performance.
MiR-137 Boosts the Neuroprotective Effect of Endothelial Progenitor Cell Derived-Exosomes in Oxyhemoglobin Treated SH-SY5Y Cells Partially via COX2/PGE2 Pathway
Authors: Li Yuchen , Wang Jinju , Chen Shuzhen , Wu Pei , Xu Shancai , Wang Chunlei , Shi Huaizhang , Bihl Ji
Published: April 2020

Background: We have previously verified the beneficial effects of exosomes from endothelial progenitor cells (EPC-EXs) in ischemic stroke. However, the effects of EPC-EXs in hemorrhagic stroke have not been investigated. Additionally, miR-137 is reported to regulate ferroptosis and to be involved in the neuroprotection against ischemic stroke. Hence, the present work explored the effects of miR-137-overexpressing EPC-EXs on apoptosis, mitochondrial dysfunction, and ferroptosis in oxyhemoglobin (oxyHb)-injured neurons.Methods: The lentiviral miR-137 was transfected into EPCs and then the EPC-EXs were collected. RT-PCR was used to detect the miR-137 level in EPCs, EXs and neurons. The uptake mechanisms of EPC-EXs in neurons were explored by the co-incubation of Dynasore, Pitstop 2, Ly294002 and Genistein. After the transfection of different types of EPC-EXs, flow cytometry and expression of cytochrome c and cleaved caspase-3 were used to detect the apoptosis of oxyHb-injured neurons. Neuronal mitochondrial function was assessed by reactive oxygen species (ROS) level, mitochondrial membrane potential (MMP) depolarization, and cellular ATP content. Cell ferroptosis was measured by lipid peroxidation, iron overload, degradation of glutathione and glutathione peroxidase 4. Additionally, recombinational PGE2 was used to detect if activation of COX2/PGE2 pathway could reverse the protection of miR-137 overexpression.Results: The present work showed 1) EPC-EXs could be taken in by SH-SY5Y cells via caveolin-/clathrin-mediated pathways and macropinocytosis; 2) miR-137 was decreased in neurons after oxyHb treatment, and EXs miR-137 could restore the miR-137 levels; 3) EXs miR-137 worked better than EXs in reducing the number of apoptotic neurons and pro-apoptotic protein expression after oxyHb treatment; 4) EXs miR-137 are more effective in improving the cellular MMP, ROS and ATP level; 5) EXs miR-137 , but not EXs, protected oxyHb-treated neurons against lipid peroxidation, iron overload, degradation of glutathione and glutathione peroxidase 4; 6) EXs miR-137 suppressed the expression of the COX2/PGE2 pathway, and activation of the pathway could partially reverse the neuroprotective effects of EXs miR-137 .Conclusion: MiR-137 overexpression boosts the neuroprotective effects of EPC-EXs against apoptosis and mitochondrial dysfunction in oxyHb-treated neurons. Furthermore, EXs miR-137 rather than EXs can restore the decrease in miR-137 levels and inhibit ferroptosis, and the protection mechanism might involve the miR-137-COX2/PGE2 signaling pathway.
Correlated factors of acute oral mucosal and skin reaction induced by radiotherapy in hypopharyngeal carcinoma
Authors: Yan Wang , Lu Xiaoxu , Huang Rong , Li Tianyuan , Tang Tian , Liu Wenhang , Wu Hui
Published: April 2020

Background This present retrospective single center study was intended to investigate the factors associated with acute radiation oral mucositis or dermatitis during hypopharyngeal carcinoma radiotherapy.Methods From May 2012 to December 2018, previously untreated 93 patients with hypopharyngeal squamous cell carcinoma received radiotherapy in Affiliated Cancer Hospital of Zhengzhou University were enrolled. Radiation Therapy Oncology Group (RTOG) scoring criteria were used for assessing the severity of toxicities. Patients are therefore classified into “mild reaction group” (G0~G1) and “acute reaction group” (G2~G4). Single variate was applied to screen out factors with significant difference between mild and acute reaction groups, multivariate analysis was used to detect independent risk factors from those related. A total of 16 medical and laboratory indexes were included to examine, i.e., gender, age, smoking history, primary site, history of hypotension and diabetes, treatment modalities, dose, T (tumor) staging, N (reginal lymph node) staging, as well as hemoglobin value (1 week before radiotherapy). Relevant data used for the study were collected from clinical records.Results Total of 93 subjects completed radiotherapy. Acute mucositis occurred in 75 patients, and 27 cases developed acute radiation dermatitis. Smoking history, post-operative radiotherapy, concurrent chemotherapy, T staging, N staging, total dose (Gy) for GTV, single fraction dose (Gy) for GTV, and hemoglobin value (1 week before radiotherapy) showed significant differences between G0~G1 and G2~G4 groups of oral mucosa reaction; significant differences between mild and acute dermatitis reaction groups were found in diabetes history, hemoglobin value, age, total dose (Gy). Multivariate analysis showed that higher hemoglobin value ( OR = 1.120, P = 0.031), smoking history ( OR = 0.070, P = 0.031) were independent risk factor of acute OM; significant relationships for acute skin reaction were found with hemoglobin value ( OR = 1.059, P = 0.034) and older age ( OR = 1.068, P = 0.036).Conclusion Multivariate analysis showed higher hemoglobin value and smoking history to be the most relevant factors independently predicting grades 2 or higher OM; higher hemoglobin value and older age were found to be significantly associated with acute skin reaction.
Improved health-related quality of life in patients treated with topical sirolimus for facial angiofibroma associated with tuberous sclerosis complex
Authors: Hatano Takashi , ohno Yuki , Imai YU , Moritake Jun , Endo Katsuhisa , Tamari Mayumi , Egawa Shin
Published: April 2020

Background : Tuberous sclerosis complex (TSC) is a rare autosomal dominant disorder forming hamartomas throughout the body. Facial angiofibromas (FAs) occur in 75% of TSC patients, which are often enlarged, impairing the appearance of the face, and reducing the patient's quality of life (QOL). The aim of this study was to characterize the impact of topical sirolimus treatment on the health-related QOL in patients with FA associated with TSC. Methods : We investigated a total of 33 patients who received sirolimus gel treatment for FA associated with TSC and assessed the changes in the health-related QOL using the Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey. SF-36 surveys were performed before and after three months of treatment. The conditions of the patients after using the sirolimus gel were categorized into the following three categories: "improved," "unchanged," and "aggravated." Adverse events were investigated using the CTCAE v5.0-JCOG. Results : After 3 months of sirolimus gel treatment, three scale scores of the SF-36, vitality (VT), social function (SF), and mental health (MH), were significantly improved compared to before the treatment. The VT and SF in patients who had improved FA were significantly better than those in the other patients. There were no significant differences in any scale scores between patients with and without adverse events at three months after the initiation of sirolimus gel treatment. Conclusions : This is the first report regarding improved health-related quality of life in patients treated with sirolimus gel for FA associated with TSC by using the SF-36. The three scale scores associated with mental health were significantly improved compared to before the treatment. The health-related QOL in patients receiving sirolimus gel treatment is more strongly affected by the treatment efficacy than adverse events.
Oxycodone versus other opioids analgesia after laparoscopic surgery: a meta-analysis
Authors: Li Yan , Dou Zhi , Yang Liqiang , Wang Qi , Ni Jiaxiang , Ma Jun
Published: April 2020

Background Intravenous opioids are administered for management of visceral pain after laparoscopic surgery. Whether oxycodone has an advantage over other opioids in the treatment of visceral pain is not yet clear. Methods This article evaluates the analgesic efficiency and adverse events of oxycodone and other opioids including alfentany, sufentanyl, fentanyl and morphine for the treatment of post laparoscopic surgery visceral pain. This review was conducted according to the methodological standards described in the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. The PubMed, Embase and Cochrane libraries were searched in December 2019. Results Ten studies were included in this review. The sample size was 815 participants. The results showed that compared with morphine and fentanyl, oxycodone had a more potent analgesic efficacy at the first day after laparoscopic surgery, especially during the first 0.5h. There was no significant difference in sedation between the two groups. Compared to morphine and fentanyl, oxycodone was more likely to increase the risk of dizziness and drowsiness. The overall patients satisfaction had no significant difference between oxycodone versus other opioids. Conclusions Oxycodone is a superior analgesic within 24h after laparoscopic surgery with careful regards to its adverse effects.
Effect of fecal microbiota transplantation on neurological restoration in a spinal cord injury mouse model: involvement of brain-gut axis
Authors: Jing Yingli , Yu Yan , Bai Fan , Wang Limiao , Yang Degang , Zhang Chao , Qin Chuan , Yang Mingliang , Zhang Dong , Zhu Yanbing , Li Jianjun , Chen Zhiguo
Published: April 2020

Background: Spinal cord injury (SCI) patients display disruption of gut microbiome and gut dysbiosis exacerbate neurological impairment in SCI models. Cumulative data support an important role of gut microbiome in SCI. Here, we investigated the hypothesis that fecal microbiota transplantation (FMT) may exert a neuroprotective effect on SCI mice. Results: We found that FMT facilitated functional recovery, promoted neural axonal regeneration, improved animal weight gain and metabolic profiling, and enhanced intestinal barrier integrity and GI motility. High-throughput sequencing revealed that levels of phylum Firmicutes, genus Blautia, Anaerostipes and Lactobacillus were reduced in fecal samples of SCI mice, and FMT remarkably reshaped gut microbiome. Also, FMT-treated SCI mice showed increased amount of fecal short-chain fatty acids (SCFAs), which correlated with alteration of intestinal permeability and locomotor recovery. Furthermore, FMT down-regulated IL-1β/NF-κB signaling in spinal cord and NF-κB signaling in gut. Conclusion: Our study demonstrates that reprogramming of gut microbiota by FMT improves locomotor and GI functions in SCI mice, possibly through the anti-inflammatory functions of SCFAs.
Magnitude Of Rise In Proneurotensin Is Related To Amount Of Triglyceride Appearance In Blood After A Standardized Oral Intake Of Both Saturated And Unsaturated Fat
Authors: Fawad Ayesha , Fernandez Celine , Bergmann Andreas , Struck Joachim , Nilsson Peter M , Bennet Louise , Orho-Melander Marju , Melander Olle
Published: April 2020

Background: In rodents, neurotensin contributes to high fat diet induced obesity by facilitation of intestinal fat absorption. The effect of oral lipid load on plasma proneurotensin and relationship with plasma triglycerides in humans is unknown.Aim: To investigate the acute effects of an oral lipid load (including both cream and olive oil) on proneurotensin and plasma triglycerides and their interrelationships in healthy individuals.Setting/ Methods: Twenty-two healthy subjects were given 150 ml of full milk cream (54g fat) and 59 ml of pure olive oil (54 g fat) in the fasted state at two different occasions separated by at least 1 week in random order. Venous blood samples were drawn at fasting,and hourly up to 4 hours after fat ingestion. We compared post-ingestion values of proneurotensin and plasma triglycerides with fasting levels. Further, post ingestion Area Under the Curve (AUC) of proneurotensin was correlated with the AUC of plasma triglycerides.Results: Rise of plasma proneurotensin and plasma triglycerides were observed after ingestion of cream with maximum increase at 2 hours for proneurotensin [mean (95% confidence interval)] of 22 (12-31) pmol/L (P<0.001) and at 3 hours for triglycerides of 0.60 (0.43-0.78) mmol/L (P<0.001). Similarly, plasma proneurotensin and plasma triglycerides increased after ingestion of olive oil with maximum increase of proneurotensin at 3 hours of 62 (46-78) pmol/L (P<0.001) and plasma triglycerides at 3 hours of 0.32 (0.18-0.45) mmol/L (P<0.001). The post lipid load AUC for proneurotensin correlated significantly with the AUC for plasma triglycerides both after cream (r=0.49, P=0.021) and olive oil (r=0.55, P=0.008), respectively.Conclusion: Proneurotensin increases after an oral lipid load of both cream and olive oil and the degree of rise of post-ingestion proneurotensin is significantly related to the rise of post-ingestion plasma triglycerides. Our human data support recent results from animal studies suggesting that neurotensin contributes to intestinal absorption of lipids into the blood stream.
Enhancing Clinical Reasoning Skills through Structured Reflection Models
Authors: ALMOMANI EMAD ALI , Attallah Karim
Published: April 2020

Background:Clinical reasoning is an essential skill to all health care practitioners. McGlynn et al, 2015 mention that lower level of clinical reasoning skills are associated with higher rates of medical and diagnostic errors.. To enhance the clinical reasoning through reflection Hamad Medical Corporation (HMC) – Qatar established a new educational initiative under the title of reflective learning conversation and debriefing.Method:A prospective cross sectional exploratory of mixed methodology research conducted at Qatar- Hamad Medical Corporation (HMC) – In the critical care and trauma units. Anonymous self-reported questionnaires were collected from 236 critical care and trauma nurses who attended the reflective learning conversation and debriefing activities. Semi structured Interviews conducted for 10 nurses who facilitated the reflective learning conversation and debriefing activities. Content analysis and thematic analysis were applied.Results:Attending the reflective learning conversations and debriefing educational activities have a significant positive impact on the clinical reasoning skills of the critical care and trauma nurses. Moreover, attending the group level reflection, feeling threatened, are limitations and barriers for the reflective learning conversation and debriefing. Additionally, reflective practice can be encouraged and enhanced through; having reflective conversation and debriefing models and guidelines, and reflecting on both good and bad experiences.Conclusion:There is a positive correlation between the clinical reasoning and the structured reflections in the format of reflective learning conversation and debriefing. Reflective practice can be enhanced through attending the reflective learning conversation and debriefing activities. There are some limitations and challenges to the reflective learning conversation and debriefing method.
The association of erythropoietin-stimulating agents and increased risk for AV-fistula dysfunction in hemodialysis patients. A retrospective analysis.
Authors: Waerme Anna VB , Hadimeri Henrik , Nasic Salmir , Stegmayr Bernd
Published: April 2020

Background Patients in maintenance hemodialysis (HD) need a patent vascular access for optimal treatment. Recommended first choice is a native arteriovenous fistula (AVF). Complications of AVF are frequent and include thrombosis, stenosis and infections leading to worsening of dialysis efficacy. Purpose The aim was to investigate if there are significant variables associated with dysfunctional AVF: s that could be intervened to adjust. Methods This retrospective observational study included 153 chronic HD patients referred to a total of 473 radiological investigations due to clinically suspected complications of their native AVF. Another group of chronic HD patients (n=52) who had a native AVF, but were without history of previous complications for at least 2 years were used as controls. Statistical analyses used were ANOVA, logistic regression, parametric and non-parametric methods such as Student's T-test and Mann-Whitney test. Results Among Cases at least one significant stenosis (>50% of the lumen) was detected in 348 occasions. Subsequent PTA was performed in (71%, n=248). Median erythropoiesis- stimulating agent (ESA) weekly doses were higher in the Cases than in the Controls (8000 IU vs 5000, p<0.001). Cases received higher doses of intravenous iron/week than the Controls before the intervention (median 50 mg vs 25 mg, p=0.004) and low molecular weight heparin (LMWH, p=0.028). In comparison to the Controls, Cases had a lower level of parathyroid hormone (median 25 vs 20 ρmol/L, p=0.009). In patients with diabetes mellitus, HbA1c was higher among Cases than Controls (50 vs 38 mmol/mol, p<0.001). There was no difference between the groups regarding variables such as blood hemoglobin, serum CRP or plasma ferritin. Conclusion The study indicated that AVF problems were related to higher doses of ESA, iron administration and LMWH. Optimizing glycemic control in patients with diabetes mellitus may be beneficial.
Comprehensive analysis of miRNA sequencing profiles identifies novel deregulated and prognostic biomarkers in hepatocellular carcinoma
Authors: Zhang Hui , Ni Senmiao , Li Changxian , Zhou Haoming , Bai Jianling , Pan Xiongxiong , Wu Zhengshan
Published: April 2020

Background: Liver cancer is the fourth most common cause of cancer-related death and rank sixth in terms of incident cases. We aim to identify a set of miRNAs and a miRNA-based signature related to tumorigenesis and prognosis in patients with hepatocellular carcinoma (HCC). Methods: We analyzed the miRNA sequencing profiles of 373 HCC patients downloaded from The Cancer Genome Atlas LIHC program. The isoform quantification profiles were transformed into 5p and 3p mature miRNA names. Differentially expressed (DE) miRNAs between tumor and adjacent normal tissues were identified by Wald test based on the negative binomial distribution. Prognostic miRNAs associated with overall survival were confirmed by multivariate Cox proportional hazards models. The miRNA-based signatures were obtained from the linear predictors of cox regression, and the prognostic performance was compared by Harrel’s C-index and revealed by the restricted mean survival (RMS) curve. Results: The selected twelve DE miRNAs showed a good performance to classify tumor tissues from normal tissues. Meanwhile, a miRNA-based prognostic signature of eight mature miRNAs was constructed, which significantly stratified patients into high- vs low-risk groups in terms of overall survival (hazard ratio, 4.11; 95% CI, 2.71-6.24; P<0.001). When integrated with clinical information, the composite miRNA-clinical signature showed improved prognostic accuracy relative to the eight-miRNA signature alone. As we set the follow-up time at 5 years, the estimated RMST difference between low- and high-risk group stratified by miRNA index was 1.39 (95% CI: 0.95-1.83) months, which is lesser than the difference between miRNA-clinical risk groups (1.63, 95%CI: 1.20-2.06). Functional enrichment analysis indicated that the target mRNAs of selected miRNAs were mainly enriched in cancer-related pathways and vital cell biological processes. Conclusions: The proposed DE miRNAs and miRNA-clinical signature are promising biomarkers for discrimination and predicting overall survival respectively in HCC patients. These biomarkers may have significant relevance for development of new drug research and targeting therapies for HCC patients.