bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment Outcomes of Clopidogrel in Patients With ACS and Diabetes Undergoing PCI-analysis of Beijing Medicare Database
Authors: Wang Weihao , Wang Xiaoxia , Zhang Lina , Zhang Jie , Man Fuli , Pan Qi , Guo Lixin
Published: August 2020

Background

There are several clinical trials that proved the efficacy of clopidogrel treatment for patients with percutaneous coronary intervention. There are few large-scale research to explore the mortality associated with different duration use of clopidogrel in patients with diabetes and ACS undergoing PCI in the Chinese population.
Objectives

The objective of this analysis was to determine the efficacy of long-term clopidogrel therapy(≥ 12 months) versus short-term use(< 12 months) in Chinese patients with diabetes after PCI.
Methods

Using the Beijing Medicare database provided by Beijing Medical Security Bureau. The Beijing Medicare database contains medical data of about 16 million people, including about 990,000 patients with diabetes and a history of taking antidiabetic medicines. Patients were divided into two groups, one group of 9,116 patients receiving consecutive clopidogrel for one year or more, and another group of 3290 patients receiving consecutive clopidogrel less than one year. The primary of this analysis was the risk of all-cause death, myocardial infarction and revascularization.
Results

In patients with diabetes after PCI, long-term clopidogrel treatment was associated with a reduced risk of all-cause death(HR, 0.57[95%CI, 0.49–0.67], P < 0.0001), myocardial infarction(HR, 0.79[95%CI, 0.68–0.93], P = 0.0035) and an increased risk of angina(HR, 1.18[95%CI, 1.10–1.27], P < 0.0001]) and revascularization(HR, 1.07[95%CI, 1.01–1.13], P = 0.02]). There was no significant difference in the incidence of all-cause re-hospitalization(P = 0.7529), diabetes-related re-hospitalization and cerebrovascular re-hospitalization.
Conclusion

The present study concluded that long-term dual anti-platelet therapy including clopidogrel and aspirin could decrease the risks of all-cause death, myocardial infarction. But it could increase the risks of angina and revascularization. Further studies should interpret the cause of this question.
COVID-19 and Ischemic Stroke
Authors: Sidig Amira , Abbasher Khabab , Abbasher Hussien , Alhusseini Radi Tofaha , Elsayed Mohamed , Abbasher Mohammed , N Sufian Khalid M. , Hajnoor Khalid , Malekaldar Mohammed , Digna Mutaz F. , Hussien Abbasher , Hamid Omer Eladil A.
Published: August 2020

Background: SARS-CoV-2 causes COVID-19 disease. It was identified in December 2019 and rapidly evolved into a pandemic. During the outbreak of COVID-19, researches demonstrated its effect on many systems, including the nervous system. In our clinic, we have reported an impact of SARS-CoV-2, causing the ischaemic stroke.Case Report: A 62-year-old Sudanese male with some comorbidities brought to the A&E with fever, chest symptoms, and acute evolving left-sided hemiplegia power grade 0/5 MRCS with left upper motor neuron facial palsy. Investigations: CT brain: right middle cerebral artery MCA infarction. CT- chest: bilateral ground-glass appearance. COVID-19 Test was positive. elevated D-dimer and C-reactive protein.Discussion: A retrospective study of data from the COVID-19 outbreak in China showed that the incidence of stroke among hospitalized patients was approximately 5%. The fact that COVID-19 is an acute inflammatory condition associated with an increased incidence of fatty plaques formation, injury of the vascular wall, and hypercoagulability, causing brain infarct can be a reasonable hypothesis.ConclusionPatients with COVID-19 are at increased risk of thrombo-embolization, leading to arterial and venous cerebrovascular accident. This case report enhances the importance of further studies to clarify the relationship between stroke and COVID-19.
A previously unknown source of reactor radionuclides in the Baltic Sea, identified by 233, 236, 238U and 127, 129I multi-fingerprinting
Authors: Qiao Jixin , Zhang Haitao , Steier Peter , Hain Karin , Hou Xiaolin , Vartti Vesa-Pekka , Henderson Gideon , Eriksson Mats , Aldahan Ala , Possnert Goran
Published: August 2020

We present the first application of multi-isotopic fingerprints (i.e., 236U/238U, 233U/236U, 236U/129I and 129I/127I) for the discovery of unrevealed radioactive sources. Our data indicate that, besides the reactor signature from the two European reprocessing plants and global fallout signature, there must be a previously undiscovered additional reactor 236U source in the Baltic Sea. This reactor 236U may come from unreported discharges from nuclear research facilities in Sweden, or it may come from accidental leakage from disposal of spent nuclear fuel on the Baltic seafloor, either reported or unreported. Such leakage would indicate potential problems with the safety of seafloor disposal, and may be accompanied by leakage of other radionuclides. The results demonstrate the high sensitivity of the multi-isotopic tracer systems, especially the newly accessible 233U/236U signature, to distinguish environmental emissions of unrevealed historical or present radioactive releases for nuclear safeguard and emergency preparedness, as well as tracing environmental processes from the releasing sites.
The Relationship between Intraoperative Cerebral Oximetry and Postoperative Delirium in Patients Undergoing off-pump Coronary Artery Bypass Graft Surgery: A Retrospective Study
Authors: Lim Leerang , Nam Karam , Lee Seohee , Cho Youn Joung , Yeom Chan-Woo , Jung Sang Hyup , Moon Jung Yoon , Jeon Yunseok
Published: August 2020

Background Cerebral oximetry has been widely used to measure regional oxygen saturation in brain tissue, especially during cardiac surgery. Despite its popularity, there have been inconsistent results on the use of cerebral oximetry during cardiac surgery, and few studies have evaluated cerebral oximetry during off pump coronary artery bypass graft surgery (OPCAB). Methods To evaluate the relationship between intraoperative cerebral oximetry and postoperative delirium in patients who underwent OPCAB, we included 1,439 patients who underwent OPCAB between October 2004 and December 2016 and among them, 815 patients with sufficient data on regional cerebral oxygen saturation (rSO2) were enrolled in this study. We retrospectively analyzed perioperative variables and the reduction in rSO2 below cut-off values of 75%, 70%, 65%, 60%, 55%, 50%, 45%, 40%, and 35%. Furthermore, we evaluated the relationship between the reduction in rSO2 and postoperative delirium. Results Delirium occurred in 105 of 815 patients. In both univariable and multivariable analyses, the duration of rSO2 reduction was significantly longer in patients with delirium at cut-offs of <50% and 45% (for every 5 min, adjusted odds ratio(OR) 1.007 [95% Confidence interval (CI) 1.001 to 1.014] and adjusted OR 1.012 [1.003 to 1.021]; p=0.024 and 0.011, respectively). The proportion of patients with an rSO2 reduction <45% was significantly higher among those with delirium (adjusted OR 1.737[1.064 to 2.836], p=0.027). Conclusions In patients undergoing OPCAB, intraoperative rSO2 was associated with postoperative delirium. The cut-off values for intraoperative rSO2 were 50% for the total patient population and 55% for patients younger than 68 years.
Assessing Fidelity to Family-Based Treatment: Expert, Therapist, Parent, and Peer Ratings
Authors: Couturier Jennifer , Kimber Melissa , Barwick Melanie , McVey Gail , Findlay Sheri , Webb Cheryl , Niccols Alison , Lock James
Published: August 2020

Introduction: Fidelity is an essential component for evaluating the clinical and implementation outcomes related to delivery of evidence-based practices (EBPs). Effective measurement of fidelity requires clinical buy-in, and as such, requires a process that is not burdensome for clinicians and managers. As part of a larger implementation study, we examined fidelity to Family-Based Treatment (FBT) measured by several different raters including an expert, a peer, therapists themselves, and parents, with a goal of determining a pragmatic, reliable and efficient method to capture treatment fidelity to FBT.
Methods: Each therapist audio-recorded at least one FBT case and submitted recordings from session 1, 2, and 3 from phase 1, plus one additional session from phase 1, two sessions from phase 2, and one session from phase 3. These submitted files were rated by an expert and a peer rater using a validated FBT fidelity measure. As well, therapists and parents rated fidelity immediately following each session and submitted ratings to the research team. Inter-observer reliability was calculated for each item using the intraclass correlation coefficient (ICC), comparing the expert ratings to ratings from each of the other raters (parents, therapists, and peer). Mean scale scores were compared using repeated measures ANOVA.
Results: Intraclass correlation coefficients revealed that agreement was the best between expert and peer, with excellent, good, or fair agreement in 7 of 13 items from session 1, 2 and 3. There were only four such values when comparing expert to parent agreement, and two such values comparing expert to therapist ratings. The rest of the ICC values indicated poor agreement. Scale level analysis indicated that expert fidelity ratings for phase 1 treatment sessions scores were significantly higher than the peer ratings and, that parent fidelity ratings tended to be significantly higher than the other raters across all three treatment phases. There were no significant differences between expert and therapist mean scores.
Conclusions: There may be challenges inherent in parents rating fidelity accurately. Peer rating or therapist self-rating may be considered pragmatic, efficient, and reliable approaches to fidelity assessment for real-world clinical settings.
Intergenerational neurocognitive effects of intrauterine hyperglycemia on male offspring
Authors: Zou Kexin , Ren Jun , Zhang Junyu , Zhou Chengliang , Luo Sisi , Tan Chengxi , Lv Pingping , Sun Xiao , Sheng Jianzhong , Huang Hefeng , Liu Xinmei , Ding Guolian
Published: August 2020

Background

Studies on human and animals suggest associations between gestational diabetes mellitus (GDM) with increased susceptibility to develop neurological disorders in offspring. However, researches have focused on the neurodevelopment consequences of the first filial (F1) offspring. We hypothesize that the intrauterine hyperglycemia exposure will alter epigenetic reprogramming in F1 sperm, and carry risks of passing on molecular defects to the second filial (F2).
Results

We found that intrauterine hyperglycemia exposure resulted in memory impairment in both F1 and F2 males from the F1-GDM male offspring. Transcriptome profiling of F1 and F2 hippocampi revealed that differentially expressed genes were enriched in learning, memory, cognition, neurotransmission, synaptic plasticity, and postsynaptic specialization. Again, enrichment curves computed by Gene set enrichment analysis (GSEA) of F1 hippocampi were highly consistent with F2. Interestingly, combined analysis of F1 sperm methylome and gene expression of F2 hippocampi screened out several hypermethylation-low expression genes which are associated with abnormal central nervous system development (particularly synapse development and homeostasis), such as Camk2b, Dlgap1, Wnt5a, Tubb2b and so on.
Conclusions

These findings implicate that the male germ line is a major player in transgenerational phenotypic transmission. Taken together, our results for the first time suggest that intrauterine hyperglycemia leads to transgenerational cognitive impairment, and, sperm methylome is a potential epigenetic mechanism for the effects of GDM.
WITHDRAWN: Bio-sensored Diagnostic Kit for Detecting Tuberculosis Using Artificial Intelligence Through Neural Networks
Authors: Tamilselvi S , Kumar N.M Saravana , Lavanya S , Hariprasath K , Kavinya A , Kaviyavarshini N
Published: August 2020

The advancement and well-developed technologies in global medical field, tuberculosis remains a major health problem. To solve the problem of tuberculosis, artificial intelligence (AI) provides the way for solving problem in real world and enlightens the world in bringing a human's brain to a machine. This paper aims to detect the presence of mycobacterium tuberculosis infection within a short span of time compared to ancient technique. It is designed in such a way that the breath of the infected person can be used to diagnose the disease at premier stage. The main objective is to design and implement a portable diagnostic kit for Tuberculosis using Neural Networks and Artificial Intelligence. The tool kit called Electronic Nose which is significant artificial intelligent component constructed through neural network contains a biosensor having an electrode coated with the galectin. The signals of hybridization on binding will be captured and processed by machine learning sensor and the output is displayed using artificial intelligence. Earlier case of diagnosis approached on the basis of grouping microorganisms days together. But this study faster to find the report in an hour. Therefore the time taken for diagnosing the presence of the bacterium can be reduced and this also paves the way for starting the treatment immediately.
Identification of Cancer Stem Cell-related Biomarkers in Intestinal-Type and Diffuse-Type Gastric Cancer by Stemness Index and Weighted Correlation Network Analysis
Authors: Guo Rui , Chu Aining , Gong Yuehua
Published: August 2020

BackgroundCancer stem cells (CSCs) play an important role in drug resistance, recurrence, and metastasis of tumors. Considering the heterogeneity of tumors, this study aimed to explore the key genes regulating stem cells in intestinal-type and diffuse-type gastric cancer (GC).MethodsRNA-seq data and related clinical information were downloaded from The Cancer Genome Atlas (TCGA). Based on the mRNA expression-based stemness index (mRNAsi), important modules and key genes were identified by weighted co-expression network analysis (WGCNA). The expression of key genes were further verified by Oncomine database.ResultsMRNAsi scores of GC were significantly higher than that of normal tissue. Besides mRNAsi scores of intestinal-type GC (IGC) were significantly higher than that of diffuse-type GC (DGC). WGCNA showed that the brown modules for both types of GC were the most significantly associated with mRNAsi. We screened out 7 and 43 key genes for IGC and DGC, and found that these genes were closely related, respectively. Functional analysis showed the relationship between the key genes confirmed in Oncomine database and fate of cells. ConclusionsIn this study, 7 and 43 genes related to the characteristics of CSCs were identified in IGC and DGC, respectively. These genes were associated with cell cycle and homologous recombination, which could serve as therapeutic targets for the inhibition of stem cells from both types of GC.
Organisational Measures and Strategies for a Healthy and Sustainable Extended Working Life and Employability
Authors: Nilsson Kerstin
Published: August 2020

Background: Due to the global demographic change, a larger amount of people will need to work until an older age, and organisations and enterprises need to make measures in order to facilitate an extended working life. The aim of this study was to investigate and find out organisational measures and suggestions to promote and make improvements for a healthy and sustainable working life for all ages in an extended working life.Methods: The data of the text analysis in this qualitative study was collected through focus group interviews and individual interviews including 133 participants: employees 55- 72 years (87), first line managers (33), trade union representatives (6), HR-professionals (7).Results: This study has identified various suggestions for measures and actions that would increase the employees’ ability to cope in working life until an older age. The measures have been sorted into different themes: to promote a good physical and mental work environment; to promote personal financial and social security; to promote social inclusion and social support in the work situation; and to promote creativity and intrinsic work motivation, i.e. based on the spheres of determination in the theoretical swAge-model. Conclusions: Based on the study results a tool for dialogue and discussion on employee work situation and career development has been developed, and attached to the article. Regular conversations, communication and close dialogue are needed and are a prerequisite for good working conditions and a sustainable working environment, as well as to be able to manage employees and develop the organisation further. The identified measures need to be taken care of regularly throughout employees’ entire working life, in order to enable a healthy and sustainable working life for all ages.
A Novel Circular RNA hsa_circRNA_103809/miR-377-3p/GOT1 Pathway Regulates Cisplatin-Resistance in Non-Small Cell Lung Cancer (NSCLC)
Authors: Zhu Xiang , Han Jing , Lan Huiyin , Lin Qingren , Wang Yuezhen , Sun Xiaojiang
Published: August 2020

Cisplatin is the first-line chemotherapeutic drug for non-small cell lung cancer (NSCLC), and emerging evidences suggested that targeting circular RNAs (circRNAs) became an effective strategy to increase cisplatin-sensitivity in NSCLC, but the detailed mechanisms are still not fully delineated. Based on this, this study identified a novel hsa_circRNA_103809/miR-377-3p/GOT1 signaling cascade contributed to cisplatin-resistance in NSCLC in vitro and in vivo. Mechanistically, the parental cisplatin-sensitive NSCLC (CS-NSCLC) cells were subjected to continuous low-dose cisplatin stimulation to generate cisplatin-resistant NSCLC (CR-NSCLC) cells, and we found that hsa_circRNA_103809 and GOT1 were upregulated, while miR-377-3p was downregulated in CR-NSCLC cells, instead of CS-NSCLC cells. Further experiments validated that hsa_circRNA_103809 sponged miR-337-3p to upregulate GOT1 in CS-NSCLC cells. Interestingly, the gain- and loss-function experiments validated that knock-down of hsa_circRNA_103809 enhanced the inhibiting effects of cisplatin on cell proliferation and viability, and induced cell apoptosis in CR-NSCLC cells, which were reversed by downregulating miR-377-3p and overexpressing GOT1. Consistently, overexpression of hsa_circRNA_103809 increased cisplatin-resistance in CS-NSCLC cells by regulating miR-377-3p/GOT1 axis. Furthermore, the xenograft tumor-bearing mice models were established by using the CR-NSCLC cells, and we proved that silencing of hsa_circRNA_103809 aggravated the inhibiting effects of cisplatin treatment on NSCLC cell growth in vivo. In general, analysis of data suggested that targeting hsa_circRNA_103809/miR-377-3p/GOT1 pathway increased susceptibility of CR-NSCLC cells to cisplatin, and this study provided novel agents to improve the therapeutic efficacy of cisplatin for NSCLC treatment in clinic.
Suspected Heparin-Induced Thrombocytopenia in a COVID-19 Patient on Extracorporeal Membrane Oxygenation Support: A Case Report.
Authors: Phan Xuan T. , Nguyen Tuan Huu , Tran Tung T. , Huynh Thu-Hien T. , Hoang Thuy-Ha T. , Nguyen Vinh-Chau V. , Pham Thao N. T.
Published: August 2020

Background: Extracorporeal membrane oxygenation (ECMO) support can be life-saving in critically ill COVID-19 patients. However, there are many complications associated with this procedure, including Heparin-induced thrombocytopenia (HIT.) Despite its rarity in ECMO cases, HIT can lead to devastating consequences and is difficult to manage.Case presentation: In this report, we present a case of a COVID-19 patient on ECMO support who was diagnosed with HIT and required intensive treatment. Initially, the patient showed no remarkable sign of thrombosis and HIT was only suspected due to newly-developed thrombocytopenia and oxygenator dysfunction. Regarding his treatment, since there was no recommended replacement to heparin available to us at the time of diagnosis, we decided to use Rivaroxaban temporarily. No adverse events were recorded during that period. The patient was able to make a full recovery.Conclusion: HIT may jeopardize patient’s care during ECMO. As COVID-19 may bring about a surge in the number of patients requiring ECMO support, we need consented guidance to optimize treatment in this specific situation.
Sports Nutritionists Adopt the Nutrition Care Process (NCP) Road Map to Develop Individualized Meal Planning for Athletes.
Authors: Mustafa Norashikin , Safii Nik Shanita , Mohamad Mohd Izham , Sameeha Mohd Jamil , Rahman Abdul Hadi Abdul , Ahmad Azimah , Yatiman Noor Hafizah , Zakaria Ahmad Zawawi , Talib Ruzita Abd , Poh Bee Koon
Published: August 2020

Background: It is considered that the implementation of nutrition care process (NCP) leads to more efficient and effective care, as well as enhancing the roles of dietetics and nutrition professionals in the clinical setting. However, little is known about the NCP being implemented in the sports nutrition setting to deliver nutrition care, especially in meal planning. Therefore, this study aims to identify the process that sports nutritionists (SNs) practise in meal planning to plan meals for athletes and identify the application of NCP.Methods: In-depth interviews, using semi-structured interview questions, were conducted with SNs employed at the National Sports Institute of Malaysia. Five SNs who managed different types of sports were recruited. The interviews were audio-recorded and transcribed verbatim. Data were entered into ATLAS.ti 8 and analyzed using thematic analysis.Results: The following processes were identified: (i) collecting pertinent data; (ii) analyzing the collected data; (iii) determining nutrition prescriptions; (iv) formulating goals and determining actions; (v) implementing actions and recommendations; and (vi) monitoring.Conclusions: This study identified 6 general processes practiced by sports nutritionists in meal planning that comprised of the NCP’s interrelated steps, except nutrition diagnosis statement from the Nutrition Diagnosis step of the NCP. A comprehensive process and workflow can help sports dietitians or nutritionists to develop individualized meal plans that can improve athletes’ nutritional status, adherence, health and sports performance.
Identification of Two Novel Genes SNX10 and PTGDS with Cervical Squamous Cell Carcinoma Prognosis
Authors: Jiang Pinping , Cao Ying , Gao Feng , Sun Wei , Liu Jinhui , Xie Manxin , Fu Shilong
Published: August 2020

Background: Cervical cancer (CC) is the primary cause of death in women. This study sought to investigate the therapeutic targets of CC. Methods: We downloaded four gene expression profiles from GEO. The RRA method was used to integrate and screen DEGs between CC and normal samples. Functional analysis was performed by clusterprofiler. We built PPI network by STRING and selected hub modules via MCODE. CMap was used to find molecules with therapeutic potential for CC. We also validated hub genes in GEO datasets, GEPIA, immunohistochemistry. Cox regression analysis, TCGA methylation analysis and ONCOMINE were carried out. ROC curve analysis and GSEA were also done to dig out the significance of hub genes. Results: Functional analysis revealed that DEGs were significantly enriched in binding, cell proliferation, transcriptional activity and cell cycle regulation. PPI network screened 30 prominent proteins, with CDK1 having the strongest association with CC. Cmap showed that apigenin, thioguanine and trichostatin A might be used to treat CC. Eight genes were screened out through GEPIA. Of them, only PTGDS and SNX10 have not been reported in CC related articles. The validation in GEO showed that PTGDS showed low expression in tumor tissues while SNX10 showed high expression in tumor tissues. Their expression profiles were consistent with the results in immunohistochemistry. They can distinguish CC and normal tissue and have good diagnostic efficiency. GSEA showed that the two genes were associated with the chemokine signaling pathway. TCGA methylation analysis showed that patients with low-expressed and hyper-methylated PTGDS had a bad prognosis than the patients with high-expressed and hypo-methylated PTGDS. Cox regression analysis showed that SNX10 and PTGDS were independent prognostic indicators for OS among CC patients. Conclusions: In conclusion, PTGDS and SNX10 showed abnormal expression and methylation in CC. Both genes could be used to develop new target treatments for CC.
Age-Related Changes in the Gut Microbiota Promote Atrial Fibrillation
Authors: Zhang Yun , Zhang Song , Li Bolin , Luo Yingchun , Gong Yongtai , Jin Xuexin , Zhang Jiawei , Zhou Yun , Zhuo Xiaozhen , Wang Zixi , Zhao Xinbo , Han Xuejie , Gao Yunlong , Yu Hui , Liang Desen , Zhao Shiqi , Sun Danghui , Wang Dingyu , Xu Wei , Qu Guangjin , Bo Wanlan , Li Dan , Wu Yue , Li Yue
Published: August 2020

Background: Aging is the most significant contributor to the increasing prevalence of atrial fibrillation (AF). The gut microbiota dysbiosis is involved in age-associated diseases. However, whether age-associated gut microbial dysbiosis contributes to AF is still unknown. The aim of this study was to evaluate the effect of gut microbiota on the susceptibility of aging-induced AF and to elucidate the underlying mechanisms. Results: The gut microbiota profiling of fecal samples in aged (22-24 months old) and young (2-3 months old) rats was performed by 16S ribosomal RNA gene analysis. A rat model of fecal microbiota transplantation (FMT) was established for analyzing the possible role of age-associated gut microbial dysbiosis in AF. Here, we found that aging process led to marked shift of the microbiota spectrum. The microbiota in young rats following FMT resembled that of aged microbiota and transmitted the increased AF susceptibility by elevation of circulating lipopolysaccharide (LPS). The mechanism for LPS-driven atrial pro-arrhythmic action was dependent on the activation of atrial nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing (NLRP3)-inflammasome. Inhibition of inflammasome by MCC950 resulted in lower atrial fibrosis and AF susceptibility. In addition, atrial fibrosis, plasma LPS concentration, plasma glucose to oral glucose tolerance test (OGTT), intestinal permeability, and gut pathology were significantly increased in elderly human subjects. Finally, altering the microbiota in aged recipient to resemble that of young restored the intestinal barrier dysfunction and LPS and impaired glucose tolerance, and the worse outcomes of aged dysbiosis on atrial fibrosis and AF susceptibility were abrogated. Conclusions: These data suggest that age-associated microbial dysbiosis induces circulating LPS and impairs glucose tolerance, and thereby promotes AF susceptibility through enhanced activity of atrial NLRP3-inflammasome.
Design of an Optimally-Diagnostic Skin Test With Fewer Samples for Diagnosis of Sensitivity to Eight Allergens: a First-In-Human Study of Dose Escalation and Simultaneous Administration in Chinese Subjects
Authors: Ning Xiaoyi , Kuang Yun , Zhao Shuwei , Yang Guoping , Hou Wenjing , Guo Chengxian , Xie Jinlian , Gong Liying , Zhu Xuerui , Cui Chang , Yang Shuang , Yang Xiaoyan , Guo Chengjun , Liu Ruiling , Xiang Yuxiang , Huang Jie
Published: August 2020

Background: Skin prick test is usually the preferred test in the diagnostic workup for allergic diseases, while there are few types of standardized allergen extracts available. Besides, standardization and composition give no assurance that the allergen extracts are within the concentration range that give the best chance of a true diagnosis. We designed a first-in-human diagnostic skin test with fewer samples to identify the optimally diagnostic concentration for eight standardized extracts from frequent native allergens, and to assess the safety of the eight allergens extracts’ simultaneous administration for supporting clinical allergen screening.Methods: Patients aged 18-45 years who had a history of allergic diseases were enrolled in this two-part open-label, parallel study: Study 1, each patient was given three concentrations of one allergen extract in turn. Study 2, each patient was given two concentrations of eight allergens extracts. Negative and positive controls were given each time the allergen was given. Both safety and sensitivity were evaluated to determine the optimally diagnostic concentration. Related-Samples Friedman's Two-Way Analysis was used to evaluate the difference of wheal diameter between different concentrations of each allergen. SPSS Statistics 26 was used for statistical analysis, and the significance test level was 0.05.Results: The sensitivity of allergens increased with the increasing of concentration. The eight investigated allergens showed good safety and did not reach the dose limit toxicity whether used alone or in combination. The optimally diagnostic concentration for eight aeroallergens were respectively determined as 33333 DU/mL, 12000 DU/mL, 8667 DU/mL, 50000 DU/mL, 40000 DU/mL, 3333 DU/mL, 7000 DU/mL, and 5000 DU/mL.Conclusions: This study designed a solution to determine the optimally diagnostic concentration with fewer subjects for further clinical trials of the eight investigated allergens and the results of this phase I clinical trial support further clinical research of investigated allergens. Trial registration: The trial was registered on www.chictr.org.cn (ChiCTR1900023952, 06/19/2019, retrospectively registered).
The Protein Tyrosine Kinase Inhibitor Genistein Suppresses Hypoxia-Induced Atrial Natriuretic Peptide Secretion Mediated by the PI3K/Akt-HIF-1α Pathway in Isolated Beating Rat Atria
Authors: Zhang Qiu-li , Bian Chao-chao , Li Ping , Hong Lan , Liu Li-ping , Cui Bai-ri , Cui Xun
Published: August 2020

Background

Genistein, an isoflavonoid that can inhibit protein tyrosine kinase (PTK) phosphorylation, was proved to play pivotal roles in the signal transduction pathways of hypoxic disorders.
Aim of the stud

y: In this study, we established a rat model of isolated beating atrium and investigated the regulator role of genistein and its downstream signaling pathways in acute hypoxia-induced ANP secretion.
Methods

Radio-immunoassay was used to detect the ANP content in the atrial perfusates. Western blot analysis was used to determine the protein level of hypoxia-inducible factor-1α (HIF-1α), and GATA4 in the atrial tissue.
Results

The results showed that acute hypoxia substantially promoted ANP secretion, whereas this effect was partly attenuated by the PTKs inhibitor genistein (3 µM). By western blotting analysis, we found that hypoxia-induced the increase in phosphorylation of Akt and transcriptional factors, including HIF-1α, were also reversed by genistein. The perfused HIF-1α inhibitors rotenone (0.5 µM) or CAY10585 (10 µM) plus genistein significantly abolished the enhanced ANP section induced by hypoxia. Additionally, the perfused PI3K/Akt agonist IGF-1 (30 µM) also abolished ANP secretion induced by genistein as well as inhibited expression of HIF-1α.
Conclusions

In summary, our data suggested that acute hypoxia markedly increased ANP secretion by PTKs through the PI3K/HIF-1α depended pathway.
Which factors may influence the implementation of drug dispensing in community pharmacies? A qualitative study
Authors: Cerqueira-Santos Sabrina , Rocha Kérlin Stancine Santos , Araújo Dyego Carlos Souza Anacleto , Júnior Genival Araujo Santos , Menezes Pedro Wlisses dos Santos , Sanchez Júlia Mirão , Mesquita Alessandra Rezende , Lyra Divaldo
Published: August 2020

Background: Implementation of clinical pharmacy services, such as drug dispensing, is a complex process. It is necessary to understand the challenges associated with this practice from the perspective of the actors involved to help ensure optimal service provision. Thus, this study aimed to understand the factors that may influence the implementation of drug dispensing in community pharmacies, according to the perceptions of pharmacists. Methods: This qualitative study was based on semi-structured, face-to-face interviews. The participants were pharmacists who worked in a chain of community pharmacies in Brazil, selected based on their direct participation in the implementation process. The interview recordings were transcribed full verbatim and were independently analyzed using thematic analysis, followed by consensus meetings between researchers. The factors identified by the participants were classified according to the Apoteca framework. This study was approved by the Committee of Ethics in Research and all participants signed an informed consent form. Results: We conducted 18 interviews, with 47 factors that may influence the implementation of drug dispensing in community pharmacies being identified. These factors were allocated to seven categories: support from community pharmacy chain (4), pharmacy infrastructure (11), characteristics of the pharmacy, medicines and other health products (4), pharmacist (16), dispensing work process (2), pharmacy team (2), and patient (8). The classification of factors according to the Apoteca framework allocated most of them to administrative (14) and technical (14) domains, followed by attitudinal (13) and political (5) domains. Conclusions: This study identified several factors that can influence the implementation of drug dispensing and classified them according to the domains of the Apoteca framework, highlighting the multifactorial nature of the implementation process. The results of this study can guide the planning of strategies aimed at providing efficient drug dispensing in community pharmacies.
A continuous data driven translational model to evaluate effectiveness of population-level health interventions: case study, smoking ban in public places on hospital admissions for acute coronary events.
Authors: Bonakdari Hossein , Pelletier Jean-Pierre , Martel-Pelletier Johanne
Published: August 2020

Background. An important task in developing accurate public health intervention evaluation methods based on historical interrupted time series (ITS) records is to determine the exact lag time between pre- and post-intervention. We propose a novel continuous transitional data-driven hybrid methodology using a non-linear approach based on a combination of stochastic and artificial intelligence methods that facilitate the evaluation of ITS data without knowledge of lag time. Understanding the influence of implemented intervention on outcome(s) is imperative for decision makers in order to manage health systems accurately and in a timely manner. Methods. To validate a developed hybrid model, we used, as an example, a published dataset based on a real health problem on the effects of the Italian smoking ban in public spaces on hospital admissions for acute coronary events. We employed a continuous methodology based on data preprocessing to identify linear and nonlinear components in which autoregressive moving average and generalized structure group method of data handling were combined to model stochastic and nonlinear components of ITS. We analyzed the rate of admission for acute coronary events from January 2002 to November 2006 using this new data-driven hybrid methodology that allowed for long-term outcome prediction. Results. Our results showed the Pearson correlation coefficient of the proposed combined transitional data-driven model exhibited an average of 17.74% enhancement from the single stochastic model and 2.05% from the nonlinear model. In addition, data demonstrated that the developed model improved the mean absolute percentage error and correlation coefficient values for which 2.77% and 0.89 were found compared to 4.02% and 0.76, respectively. Importantly, this model does not use any predefined lag time between pre- and post-intervention.Conclusions. Most of the previous studies employed the linear regression and considered a lag time to interpret the impact of intervention on public health outcome. The proposed hybrid methodology improved ITS prediction from conventional methods and could be used as a reliable alternative in public health intervention evaluation.
Evaluation of the Spanish Population Coverage of a Prospective HLA Haplobank of Induced Pluripotent Stem Cells.
Authors: Alvarez-Palomo Belen , Garcia-Martinez Iris , Gayoso Jorge , Raya Angel , Veiga Anna , Abad María Luisa , Eiras Adolfo , Guzman-Fulgencio Maria , Luis-Hidalgo Mar , Eguizabal Cristina , Santos Silvia , Balas Antonio , Alenda Raquel , Sanchez-Gordo Francisco , Verdugo Laura Ponce , Villa Juliana , Carreras Enric , Vidal Francisco , Madrigal Alejandro , Herrero María José , Rudilla Francesc , Querol Sergi
Published: August 2020

Background iPSC (Induced Pluripotent Stem Cells) banks of iPSC lines with homozygous HLA (Human Leukocyte Antigen) haplotypes (haplobanks) are proposed as an affordable and off-the-shelf approach to allogeneic transplantation of iPSC derived cell therapies. Cord blood banks offer an extensive source of HLA-typed cells suitable for reprogramming to iPSC. Several initiatives worldwide have been undertaken to create national and international iPSC haplobanks that match a significant part of a population. Methods To create an iPSC haplobank that serves the Spanish population (IPS-PANIA), we have searched the Spanish Bone Marrow Donor Registry (REDMO) to identify the most frequently estimated haplotypes. From the top ten donors identified, we estimated the population coverage using the criteria of zero mismatches in HLA-A, -B and -DRB1 with different stringencies: high resolution, low resolution and beneficial mismatch. Results We have calculated that ten cord blood units from homozygous donors stored at the Spanish cord blood banks can provide a HLA-A, HLA-B and HLA-DRB1 matching for 28,23% of the population. Conclusion We confirm the feasibility of using banked cord blood units to create an iPSC haplobank that will cover a significant percentage of the Spanish and international population for future advanced therapy replacement strategies.
PRDX2 Performs the Oncogenic Functions in Ewing’s Sarcoma
Authors: Xue Ruifeng , Fan Zhengfu , An Yunhe
Published: August 2020

Background: Ewing's sarcoma (ES) is the second most common malignant primary bone tumor in children and adolescents, characterized by malignant proliferation of small round cells. The survival rate of this disease continues to be low. Peroxiredoxin2 (PRDX2) is a multifunctional peroxidase family member with anti-oxidation, involvement in intracellular signaling, chaperones, and tumor. But the function and underlying mechanism of PRDX2 in ES is still unknown. Herein we investigated the role and mechanism of PRDX2 in the development of ES, and tested its potential for the treatment of ES.Methods: We explored the function of PRDX2 on ES through knocking down the expression of NKAP in A673 and RDES cells by siRNA interference (siPRDX2). We examined the effects of siPRDX2 on cell motility and apoptosis using CCK8, colony formation, transwell, gelatin zymography, flow cytometry, PI/Hoechst33342 double dye and western blot assays. In addition, western blot was used to analyze the activation of the AKT/mTOR signaling pathway.Results: Here we showed that downregulation of PRDX2 strongly inhibited the motility of A673 and RDES cells. Interestingly, siPRDX2 induced cell apoptosis. Furthermore, the expression of anti-apoptotic protein Bcl2 in siPRDX2 group was significantly decreased, while the expression of pro-apoptotic protein Bax and cleaved Caspase-9 was strongly increased. Finally to identify the molecular mechanisms involved, we examined related proteins of the AKT/mTOR signaling pathway and found that siPRDX2 significantly inhibited the phosphorylation of AKT and the expression of Cyclin D1.Conclusion: These observations suggest that siPRDX2 inhibited the ES cells motility and induced apoptosis in which the AKT/mTOR signaling pathway involved. The enhanced understanding to this molecular mechanism has provided a strong basis for the development of novel therapeutic strategies for ES.
Usefulness of tissue inhibitor of metalloproteinase 1 as a predictor of sustained remission in patients with antineutrophil cytoplasmic antibody-associated vasculitis
Authors: Ishizaki Jun , Takemori Ayako , Horie Kenta , Hiraoka Daisuke , Suemori Koichiro , Matsumoto Takuya , Sada Ken-ei , Amano Koichi , Harigai Masayoshi , Arimura Yoshihiro , Makino Hirofumi , Takenaka Katsuto , Takemori Nobuaki , Hasegawa Hitoshi
Published: August 2020

Background: We previously identified tissue inhibitor of metalloproteinase 1 (TIMP-1) as a biomarker of disease activity that distinguished mildly or highly active antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) from remission 6 months after the initiation of remission-induction therapy. In the present study, we investigated whether TIMP-1 is clinically useful as a predictor of relapse and sustained remission in AAV patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) during maintenance therapy.Methods: The relationship between serum TIMP-1 levels and clinical outcomes in AAV patients receiving maintenance therapy was assessed using the follow-up data of a Japanese large-cohort study (the RemIT-JAV-RPGN study) and data collected from AAV patients on maintenance therapy in our hospital (the MAAV-EU study).Results: In the RemIT-JAV RPGN study, serum levels of TIMP-1 were significantly higher in mildly active AAV patients with MPA and GPA (median BVAS 5) 6 months after the initiation of remission-induction therapy than in patients in remission. In contrast, no significant differences were observed in C-reactive protein (CRP) or myeloperoxidase-ANCA levels between these groups. Regarding maintenance therapy, elevated levels of TIMP-1 in patients in remission were associated with relapse and/or difficulty reducing the glucocorticoid dosage after 6 to 12 months. In the MAAV-EU study, serum levels of TIMP-1 were elevated in relapsed patients 6 months before relapse, earlier than the increase in serum levels of CRP. Analyses of both studies revealed that approximately 30% of patients in remission with a serum TIMP-1 level ≥ 150 ng/mL relapsed after 6 to 12 months, while the majority of patients with a TIMP-1 level < 150 ng/mL sustained remission for at least 12 months. This result suggests that a serum TIMP-1 level < 150 ng/mL reflects complete remission and ≥ 150 ng/mL indicates subclinical inflammation, even with BVAS 0.Conclusion: We herein demonstrated that TIMP-1 is more useful as a predictive biomarker of sustained remission than as a predictor of relapse in maintenance therapy for AAV. TIMP-1 levels < 150 ng/mL are important for the long-term maintenance of remission and may be an indicator for the tapering or cessation of treatment.
ABS Provides Opportunities for Indigenous and Local Communities in the Limpopo National Park. An ethnobotanical survey of plants used by the Changana community, Limpopo National Park, Mozambique
Authors: Nicosia Enrico , Valenti Roberto , Guillet Alfredo , Malatesta Luca , Tallone Giuliano , Mondlane Telo Da Silva Maximiano , Attorre Fabio
Published: August 2020

Background: Genetic resources are important for the livelihood of the rural population in developing countries and have an economic potential that, through an efficient Access and Benefit Sharing regime, can support sustainable economic development. Considering the wealth of genetic resources in Mozambique, its eligibility for Access and Benefit Sharing projects has been explored. Methods: The socio-economic status of the Changana community of the Limpopo National Park area was studied through a 500 questionnaires socio-economic survey. Considering the livelihood role that plant genetic resources could play for the local rural population, an ethnobotanical survey was conducted, with the support of villagers knowledgeable of wild plant resources and their use. Results: Several criticalities in the living condition of local communities and a generalized lack of adequate economic incomes have emerged from the socio-economic analysis. A list of 101 plant species with important commercial possibilities, mainly related to medical, food and cosmetic sectors, was provided by the ethnobotanical survey. Around 95% of the plant studied which could have effective medical properties showed the greatest potential.Conclusion: A significant potential for Mozambique to be included in Access and Benefit Sharing initiatives was recognized. The present work can contribute to the identification of Access and Benefit Sharing pilot projects, toward the evaluation of the policy efficacy and implementation of the Nagoya Protocol in the Country. The Limpopo National Park area can support Access and Benefit Sharing projects toward the economic development of the indigenous and local communities and the conservation of the Country’s biodiversity.
New World screwworm (Cochliomyia hominivorax) myiasis in feral swine of Uruguay: One Health and transboundary disease implications
Authors: Altuna Martín , Hickner Paul V. , Castro Gustavo , Mirazo Santiago , de León Adalberto A. Pérez , Arp Alex P
Published: August 2020

BackgroundFeral swine (Sus scrofa) are highly invasive and threaten animal and public health in the Americas. New World screwworm (Cochliomyia hominivorax) is listed by the World Organization for Animal Health as a notifiable infestation because myasis cases affect livestock, wildlife, and humans in endemic areas, and outbreaks can be of high socioeconomic consequence in regions where screwworm was eradicated. However, a knowledge gap exists on screwworm infestation of feral swine in South America where C. hominivorax is endemic. Here, we report infestation with C. hominivorax in feral swine harvested in the Department of Artigas where the Republic of Uruguay shares borders with Brazil and Argentina. MethodsMyiasis caused by the larvae of C. hominivorax were identified in feral swine with the support and collaboration of a local feral swine hunting club over a three-year period in the Artigas Department of Uruguay. Harvested feral swine were examined for the presence of lesions where maggots causing the myiasis could be sampled and processed for taxonomic identification. The sites of myiasis on the body of infested feral swine and geospatial data for each case were recorded. Feral swine sex and relative size were registered along with ambient temperature and precipitation.ResultsMyiases caused by screwworms were recorded in 27 of 618 feral swine harvested. Cases detected in males over 40 kg were associated with wounds that, because of their location, were likely caused by aggressive dominance behavior between adult males. The overall prevalence of screwworm infestation in feral swine was associated with ambient temperature, but not precipitation. Case numbers peaked in the warmer spring and summer months. ConclusionThis is the first report for South America of myasis caused by C. hominivorax in feral swine. In contrast to myasis in cattle that can reach deep into host tissues, screwworms in feral swine tended to cause superficial infestation. Feral swine present challenges to control screwworms in endemic areas. Screwworm populations maintained by feral swine may contribute to human cases in rural areas of Uruguay, which highlights the One Health importance of this invasive species-ectoparasite interaction.