bluuebunny/crossref_metadata_2025 huggingface dataset:
Antiviral Activity of Digoxin and Ouabain against SARS-CoV-2 Infection and Its Implication for COVID-19
Authors: Cho Junhyung , Lee Young Jae , Kim Je-Hyoung , Kim Sang il , Kim Sung Soon , Choi Byeong-Sun , Choi Jang-Hoon
Published: June 2020

The current coronavirus (COVID-19) pandemic is exacerbated by the absence of effective therapeutic agents. Notably, among patients with COVID-19, 10–40% of those with cardiac injury have more comorbidities such as acute heart failure and lymphocytopenia. An efficient strategy to response this issue is drug repurposing with expecting antiviral activity and therapeutic effect. Digoxin (DIG) and ouabain (OUA) are FDA drugs for heart diseases and have antiviral activity against several coronaviruses. Thus, we aimed this study to assess antiviral activity of DIG and OUA against SARS-CoV-2 infection. The half-maximal inhibitory concentration (IC50) of DIG, and OUA were determined at a nanomolar concentration. Progeny virus titers of single dose treatment of DIG and OUA were approximately 103 and 104-fold lower (> 99% inhibition) than that of non-treated control or chloroquine at 48 hour post-infection (hpi). Furthermore, therapeutic treatment of DIG and OUA inhibited over 99 % of SARS-CoV-2 replication, leading to viral inhibition at post entry stage of the virus life cycle. Collectively, these results suggested that DIG and OUA could be an alternative treatment for COVID-19 with potential therapeutic effect for patients with cardiovascular disease.
­­The Combined Outcomes of the COVID-19 Pandemic and a Collapsing Economy on Quality of Life: A Cross-Sectional Study
Authors: Sacre Hala , Hajj Aline , Badro Danielle A , Selwan Carla Abou , Aoun Randa , Salameh Pascale
Published: June 2020

BackgroundThis study aimed at examining the combined outcomes of the COVID-19 pandemic and a collapsing economy on the quality of life (QOL) of the general Lebanese population.MethodsA cross-sectional study was conducted from 10-18 May 2020, via an online-based questionnaire using the snowball sampling technique. It enrolled 502 adult participants.ResultsThe QOL had a mean of 14.80[14.37;15.24]. A lower QOL was associated with female gender (beta=-1.533[-2.324;-0.743]), university education (beta=-2.119[-3.353;-0.885]), fear of COVID-19 (beta=-0.131[-0.199;-0.063]), fear of poverty (beta=-0.232[-0.402;-0.063]), verbal violence at home (beta=-3.464[-5.137;-1.790]), and chronic disease (beta=-1.307[-2.283;-0.330]). Better family satisfaction (beta=0.380[0.235;0.525]) and better financial situation (beta=0.029[0.003;0.055]) were significantly correlated with better QOL. In the subsample of workers/looking for a job, additional factors affected QOL: physical exercise (beta=1.318[0.370;2.265]) was associated with better QOL, while previous waterpipe smoking, being self-employed before the crisis (beta=-1.22[-2.208;-0.231]), working from home since the economic crisis (-1.853[-3.692;-0.013]), closure of the institution (beta=-1.201[-2.607;0.204]), and worrying about long-term effects of the crisis on one's employment status (beta=-0.433[-0.650;-0.216]) were associated lower QOL; the fear of COVID-19 was not significantly associated with QOL (p>0.05).ConclusionThis study showed that during the pandemic, economic and other factors, directly or indirectly related to COVID-19, significantly affected quality of life. The fear of COVID-19 and fear of poverty mainly impacted the QOL of the general population; however, the fear of COVID-19 lost its significance among workers, who reported that factors negatively affecting their QOL are directly related to their employment and the already collapsing economy in Lebanon.
Effective programs and strategies on suicide prevention: combination of review of systematic reviews with expert opinions
Authors: Azizi Hosein , Farahbakhsh Mostafa , Fakhari Ali , Esmaeili Elham Davtalab , Mirzapour Mohammad , Aslrahimi Vahab , Barzegar Habibeh
Published: June 2020

Background
Suicide is a complex and ongoing public health crisis which is a misinterpreted course of death that strongly affects communities’ and individuals’ mental health and quality of life. Health managers often do not have adequate information for decision making on what strategy makes an effective impact on suicide prevention. Despite the availability of global Suicide Prevention Programs (SPP) around the world, no previous investigation has developed combinations of a review of systematic reviews with expert opinions. The present study was aimed to identify effective community-based strategies for suicide prevention.
Methods
We used two methods for selecting the best and effective SPP. 1) review of systematic reviews: we systematically searched to find relevant review studies through Medline, Cochrane Library, PsycINFO, and grey literatures, from January 1, 2011, and December 30, 2014. 2) Expert panel opinions: effective strategies identified from the previous step were combined with field and academic expert views via the Hanlon method. Then the strategies have been rated based on the following five criteria: feasibility, importance, cost-effectiveness, timeliness, acceptability.
Results
Of the total of 489 identified records, 9 reviews included in the review of systematic reviews. A total of 12 effective SPP were found. Expert panel then prioritized strategies based on Hanlon method as following: 1) case management of attempters to prevent future attempts, 2) identification and treatment of depression, 3) improving registry for suicide, 4) identification and investigation of suicidal behaviors’ risk factors, 5) public education campaigns in hotspots, 6) gatekeepers’ training, 7) conducting research, 8) school-based training 9) improving knowledge and attitudes, 10) restricting access to means of suicide, 11) screening of suicide ideation and at-risk people, and 12) mass media role, respectively.
Conclusion
Management of suicide attempters, developing a registry for suicide, and treatment of depression were three priority and basic interventions suggested after evidence combined with the expert panel. Suicide is a multifaceted phenomenon that is strongly affected by local beliefs. Effective management of suicide requires up-to-date information through a combination of evidence with expert views at the local level where SPP are implemented.
Gracilis Muscle Flap after Superficial Inguinal Lymphadenectomy in an Irradiated Inguinal Field: A Case Report
Authors: Valenzuela Cristian D. , Finlay David , Sabry Zakir , Mariadason James G. , Wallack Marc K.
Published: June 2020

Background: The sartorius muscle transposition flap is the traditional method of femoral vessel tissue coverage after superficial inguinal lymphadenectomy for regionally-metastatic cancers to the inguinal lymph nodes. Well-vascularized muscle is the best material to cover vessels. However, if the groin has undergone radiation therapy, the sartorius muscle is contained within the irradiated field, and may be problematic for wound healing, in addition to being thin and tendinous at its insertion and intimately related to several nerves. The gracilis muscle, which is a thick well-vascularized muscle, has been used for soft tissue defects and vascular graft infections, but its utility as an alternative to the sartorius muscle flap in the setting of radiation has never been reported. Here, we report the successful use of the retroflexed gracilis muscle flap for femoral vessel coverage after superficial inguinal lymphadenectomy, in a patient who previously underwent chemoradiation for locally-metastatic anal squamous cell carcinoma to the groin. Case Presentation: An 86-year old female presented with Stage IIIB anal squamous cell carcinoma metastatic to one left inguinal lymph node (T2N2M0). She underwent modified Nigro protocol chemoradiation treatment, which included radiation to bilateral inguinal node basins and subsequent boost radiation to the left side. A left superficial inguinal lymphadenectomy was performed with a retroflexed gracilis muscle flap to cover the femoral vessels. This was chosen over a sartorius flap because the gracilis muscle was not located within the field of radiation and was more robust to fill the defect. The patient developed a groin wound infection, and the gracilis muscle flap remained viable and successfully protected the major vessels. Conclusions: We report the gracilis muscle flap as a viable alternative to the sartorius transposition muscle flap for femoral vessel coverage after oncologic superficial inguinal lymphadenectomy in the irradiated groin.
ASPN is a Potential Promising Biomarker for Common Heart Failure
Authors: Zhang Kai , Wu Min , Qin Xianyu , Zhou Xianwu , Zhou Jianrong , Chen Shaoxian , Wen Pengju , Wu Yueheng , Zhuang Jian
Published: June 2020

Background: Heart failure (HF), the leading cause of adult mortality and morbidity worldwide, is the end-stage of various diseases, especially ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM). This study aimed to investigate the common molecular mechanism of ICM and DCM.Methods: Four gene expression datasets, GSE1869, GSE5406, GSE57338, and GSE79962, were obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) of ICM or DCM samples compared with those of nonfailing samples were identified. Gene ontology (GO) annotation, Kyoto encyclopedia of gene and genome (KEGG) pathway analysis, and the protein-protein network (PPI) of the coregulated DEGs in at least three datasets were performed using the online tools of DAVID, the KOBAS database, and the STRING database, respectively. Hub genes of HF were analyzed for their correlation with left ventricular ejection fraction (LVEF) in dataset GSE19303. The expression levels of notable DEGs were further validated in our tissue microarray (TMA).Results: Fifty-nine coregulated ICM and sixty-eight coregulated DCM relevant DEGs were identified (in at least three datasets). Moreover, 38 common DEGs between ICM and DCM relevant DEGs were obtained that were mainly involved in inflammatory/stress processes, proliferation, and some lipid metabolism pathways. Among the ten hub genes with top degrees, four genes showed a correlation with LVEF, and ASPN had the most significant correlation. Finally, the expression of ASPN protein was validated in our TMA and was significantly increased in ICM and DCM left ventricular samples.Conclusion: The present study revealed some common molecular mechanisms of HF with different causes. Furthermore, ASPN may be a potential promising biomarker for HF.
Compared with Two-Stage Revision, Destination Joint Spacers Have a Similar Infection-Relief Rate and a Higher Complication Rate
Authors: Cai Yuanqing , Fang Xinyu , Lin Yi , Huang Zida , Zhang Chaofan , Li Wenbo , Zhang Wenming , Guan Zhenpeng
Published: June 2020

Background: Two-stage revision is regarded as the “gold standard” for periprosthetic joint infection (PJI) treatment, in which antibiotic-impregnated spacers play an important role. However, some patients are unable to undergo reimplantation of the prosthesis after spacer implantation. The clinical outcomes of these patients remain unknown. The purpose of this research was to study the infection-relief rate and clinical outcome of these patients.Methods: From January 2006 to December 2017, data from PJI patients who underwent implantation with antibiotic-impregnated cement spacers in our center due to chronic PJI were collected retrospectively. Age, sex, body mass index (BMI) and laboratory test results were recorded, and the infection-relief rate and clinical outcomes were observed.Results: A total of 62 patients who were diagnosed with PJI were enrolled, with an age of 65.13 ±9.94 (39-88) years. There were 21 cases in the destination joint spacer group and 41 cases in the temporary spacer group (reimplantation of prosthesis after infection relief). The Charlson comorbidity index (CCI) in the destination joint spacer group was higher than that in the temporary spacer group. Our study showed that the infection-relief rate of destination joint spacers was similar to that of two-stage revision, but the incidence of complications was higher than that of two-stage revision, especially for the type I spacer used in this study.Conclusions: The infection-relief rate of destination joint spacers was similar to that of two-stage revision, but the complication rate was higher than that of two-stage revision (especially for the type I spacer).
Clinical Characteristics of Epstein–Barrvirus Infection in the Pediatric Nervous System
Authors: Cheng Huan , Chen DouDou , Peng XiaoLing , wu Peng , Jang Li , Hu Yue
Published: June 2020

Background: To investigate the clinical characteristics of Epstein–Barr virus (EBV) infection in the pediatric nervous system (NS).Methods: We retrospectively analyzed the clinical data and follow-up results of 89 children with neurological damage caused by EBV who were hospitalized in the children's hospital of Chongqing Medical University from January 2008 to April 2019.Results: EBV infection of the NS can occur at any time of the year. The highest incidence was seen in the age group of 0–4 years. Fever is the main clinical feature (74/89, 83.1%). The main clinical types were encephalitis/meningoencephalitis (64/89, 71.9%), acute myelitis (2/89, 2.2%), acute disseminated encephalomyelitis (ADEM) (3/89, 3.4%), Guillain–Barré Syndrome (GBS) (15/89, 16.9%), neurological damage caused by EBV-hemophagocytic lymphohistiocytosis (EBV-HLH) (4/89, 4.5%), and NS-post-transplant lymphoproliferative disorder (NS-PTLD) (1/89, 1.1%). Anti-N-methyl-D-aspartate receptor encephalitis was found during the convalescence of EBV encephalitis. EBV encephalitis/meningitis showed no symptoms of tonsillitis, lymph node enlargement, skin rash, hepatosplenomegaly. Acute motor axonal neuropathy is the chief complication in GBS caused by EBV.Conclusion: There were significant differences in neurological complications caused by EBV. The prognosis of EBV infection in the NS is generally good. These illnesses are often self-limiting. A few cases may show residual sequelae.
Serum Neutrophil Gelatinase-Associated Lipocalin at 3 Hours After Return of Spontaneous Circulation in Patients with Cardiac Arrest and Therapeutic Hypothermia: Early Predictor of Acute Kidney Injury
Authors: Choi Yoon Hee , Lee Dong Hoon , Lee Jae Hee
Published: June 2020

Background: Neutrophil gelatinase-associated lipocalin (NGAL) could be used as a predictive marker of acute kidney injury (AKI) in patients with return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest (OHCA) who are managed with targeted temperature management (TTM). However, the NGAL measurement timepoints vary. The primary objective of this study was to determine an association between AKI and NGAL, both immediately (ROSC-NGAL) and 3 hours after ROSC (3h-NGAL), in OHCA patients with TTM. The secondary objective was to ascertain the association between NGAL levels in the early post-ROSC phase and the neurologic outcomes at discharge.Methods: This prospective observational study was conducted between January 2016 and December 2018 and enrolled adult OHCA patients (≥18 years) with TTM after ROSC. Serum NGAL was measured immediately and 3 hours after ROSC. Univariate and multivariate analysis was performed to identify the associations between AKI, poor neurologic outcome, and NGAL.Results: Among 861 OHCA patients, 89 patients were enrolled. AKI occurred in 48 (55.1%) patients. On multivariate logistic regression analysis, 3h-NGAL was significantly associated with AKI (odds ratio [OR] 1.022; 95% confidence interval [CI] 1.009–1.035; p = 0.001). The AUROC of 3h-NGAL for AKI was 0.910 (95% CI 0.830–0.960), and a cut-off value of 178 ng/mL was identified. Both ROSC-NGAL and 3h-NGAL were not significantly associated with poor neurologic outcome on multivariate logistic regression analysis (ROSC-NGAL; OR 1.017; 95% CI 0.998–1.036; p = 0.084, 3h-NGAL; OR 0.997; 95% CI 0.992–1.001; p = 0.113) Conclusions: The serum NGAL concentration measured 3 hours after ROSC is an excellent early predictive marker for AKI in OHCA patients treated with TTM. Future research is needed to identify the optimal measurement timepoint to establish NGAL as a predictor of neurologic outcome and to validate the findings of this research.
Caspase 4 Overexpression in Clear Cell Renal Cell Carcinoma and Its Prognostic Role
Authors: Meng Lingfeng , Tian Zijian , Long Xingbo , Diao Tongxiang , Hu Maolin , Wang Miao , Zhang Wei , Zhang Yaoguang , Wang Jianye , He Yuhui
Published: June 2020

Background: Caspase 4 (CASP4) dysregulation is related to the occurrence, development, and outcome of many malignant tumors, but its role in clear cell renal cell carcinoma (ccRCC) is unclear. This study was conducted to investigate the expression level of CASP4 in tumor tissues and its relationship with clinical prognosis of patients with ccRCC. Methods: First, the Oncomine and The Cancer Genome Atlas databases were used to determine CASP4 mRNA expression in ccRCC and its association with ccRCC prognosis. We then performed immunohistochemical staining and evaluation of 30 paired ccRCC and adjacent normal tissues to confirm these results. The correlation between CASP4 expression and ccRCC prognosis was evaluated using Kaplan-Meier analysis, and related genes and pathways were obtained from The Cancer Genome Atlas database by gene set enrichment analysis and gene set variation analysis. Finally, we explored the co-expression of genes with CASP4 in ccRCC. Results: CASP4 mRNA expression in ccRCC was significantly higher than that in normal tissues (p < 0.001). Kaplan-Meier analysis showed that the overall survival of patients with ccRCC showing high CASP4 expression was significantly reduced (p < 0.001). We then used external datasets (Gene Expression Omnibus database and patients from our center) to verify the level of CASP4 expression and survival differences (all p < 0.05). We also found that differential expression levels of CASP4 were correlated with pathological grade and clinical TNM stage (all p < 0.05). Conclusions: Overall, our study shows that CASP4 is highly expressed in ccRCC and is an important factor affecting prognosis. Thus, CASP4 may be a potential prognostic biomarker of ccRCC.
LncRNA LINC00342 contributes to the growth and metastasis of colorectal cancer via targeting miR-19a-3p/NPEPL1
Authors: Shen Peng , Qu Lili , Wang Jingjing , Ding Quchen , Zhou Chuanwen , Xie Rui , Wang Honggang , Ji Guozhong
Published: June 2020

Background Long intergenic non-protein coding RNA 342 (LINC00342) has been identified as a novel oncogene, however, the functional role of LINC00342 in colorectal cancer (CRC) remained unclear. Methods The expression of LINC00342 was detected by real-time PCR. Cell proliferation, migration and invasion and xenograft model were examined to analyze the biological functions of LINC00342 in vitro and in vivo. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to identify the target interactions between LINC00342, miR-19a-3p and aminopeptidase like 1 (NPEPL1). Results LINC00342 was highly expressed in CRC. Downregulation of LINC00342 inhibited cell proliferation and metastasis of CRC cells. Moreover, knocking down LINC00342 could weaken the tumor growth in vivo. Mechanistic investigation revealed that LINC00342 may sponge miR-19a-3p to regulate NPEPL1 expression. Further investigation indicated that the oncogenesis facilitated by LINC00342 was inhibited by NPEPL1 depletion.Conclusion LINC00342 promoted CRC progression by competitively binding miR-19a-3p with NPEPL1.
Knockdown of lncRNA LINC01234 Suppresses The Tumorigenesis of Liver Cancer via Sponging miR-513a-5p
Authors: Xu Wen , Li Kesang , Song Changfeng , Wang Xiaotong , Li Yueqi , Bai Xue , Liang Xin , Deng Wanli , Wang Junqing , Liu Jianwen
Published: June 2020

Background: Liver cancer is a frequent malignancy with poor prognosis. It has been reported that many lncRNAs could regulate the progression of liver cancer. To identify potential therapeutic targets for liver cancer, we conducted bioinformatics analysis of lncRNAs in tumor tissues and adjacent normal tissues. Methods: The differential expression of lncRNAs between liver cancer tissues and adjacent normal tissues were examined by bioinformatics analysis. Cell proliferation was tested by CCK-8. Cell apoptosis in liver cancer was detected by flow cytometry. Gene and protein expression in liver cancer cells were measured by q-PCR and Western-blot, respectively. Xenograft tumor model was established to verify the function of LINC01234 on liver cancer in vivo.Results: LINC01234 was found to be notably upregulated in liver cancer tissues. In addition, knockdown of LINC01234 significantly inhibited the proliferation, invasion and induced the apoptosis of liver cancer cells. Meanwhile, miR-513a-5p was a downstream target of LINC01234 and USP4 was a direct target of miR-513a-5p. Moreover, downregulation of LINC01234 inhibited the tumorigenesis of liver cancer via inactivating TGF-β signaling.Conclusion: Downregulation of LINC01234 could inhibit the progression of liver cancer. Thus, LINC01234 may serve as a potential novel target for treatment of liver cancer.
Rapid screening for individualized chemotherapy optimization of colorectal cancer: a novel conditional reprogramming technology-based functional diagnostic assay.
Authors: Li YingJie , Guo Dagang , Zhang Yihong , Wang Lin , Sun Tingting , Li Zhongwu , Zhang Xiaoyan , Wang Shuai , Chen Yiyou , Wu Aiwen
Published: June 2020

In vitro patient tumor models such as patient-derived organoids (PDO) and conditionally reprogrammed (CR) cell culture are important for translational research and pre-clinical drug testing.In this study we present a personalized drug sensitivity test for late stage, potentially operable colorectal cancer (CRC) using patient-derived primary cell culture based on a new generation CR technology. We explored the clinical feasibility of using CR-based primary cell culture system to guide CRC chemotherapy, and established the correlation between in vitro drug sensitivity and patient clinical response.Our novel CR platform (termed i-CR) can be used to propagate primary colorectal tumor cells that represent individual patient tumors effectively by keeping the clonal heterogeneity and comparable drug responses.Therefore, our platform can be used to test and optimize therapeutic regimens pre-clinically, study cancer cell biology, and model tumor re-emergence to identify new targeted therapeutics from an effective personalized medicine standpoint.
Disruption of Plasmodium Falciparum Histidine-Rich Protein II can affect Heme Metabolism in the Blood Stage
Authors: Yang Yingchao , Tang Tongke , Feng Bo , Li Shanshan , Hou Nan , Ma Xiao , Jiang Lubin , Xin Xiaofang , Chen Qijun
Published: June 2020

Background. Heme is a key metabolic factor in the life of malaria parasite. In the blood stage it acquires host hemoglobin to generate amino acids for its own protein synthesis and by-product heme for metabolic use. The malaria parasite also can de novo synthesize heme by itself. Plasmodium falciparum-specific histidine-rich protein 2 (PfHRP2) is a histidine-rich protein and has a heme-binding site to mediate hemozoin formation, a bio-crystallized form of heme-aggregates. It is interesting to investigate the vibration of hemoglobin-derived heme metabolism and de novo heme-biosynthetic pathway in the Pfhrp2 disrupted parasites during the intraerythrocytic stages. Methods. A CRISPR-Cas9 system was used to disrupt the gene locus of Pfhrp2. DNA was extracted from the transgenic parasites and polymerase chain reaction (PCR), western blotting and southern blotting were used to manifest the successful establishment of transgenic parasites. RNA-seq and comparative transcriptome analysis were performed to identify the difference in gene expression between 3D7 and Pfhrp2- 3D7 parasites. Results. Pfhrp2- transgenic parasites were successfully established by the CRISPR/Cas9 system. The disruption of the exon 2 of Pfhrp2 can down-regulate the gene expression of Pfhrp3 which involved in hemoglobin-derived heme metabolism. It also up-regulates the gene expression level of enzymes of heme biosynthesis.Conclusion: These data support that although Pfhrp2 is a dispensable gene for intraerythrocytic stages parasite but heme metabolism’s stabilizing is very important. The disruption of Pfhrp2 can both affect the pathway of heme metabolism and biosynthesis. A co-operation mechanism may exist between the heme biosynthesis and metabolism pathways for parasite growth in blood stage.
Clients and professionals elicit long-term care preferences by using ‘What matters to me’: A process evaluation
Authors: Leersum Catharina Margaretha van , Moser Albine , Steenkiste Ben van , Wolf Judith R.L.M. , Weijden Trudy van der
Published: June 2020

Background
‘What matters to me’ is a five-category preference elicitation tool to assist clients and professionals in choosing long-term care. This study aimed to evaluate the use of and experiences with this tool.
Methods
A mixed-method process evaluation was applied. Participants were clients, relatives, and professionals. They were all involved in decision-making on long-term care. Data collection comprised online user activity logs (N = 71), questionnaires (N = 38), and interviews (N = 20). Descriptive statistics was used for quantitative data, and a thematic analysis for qualitative data.
Results
Sixty-nine percent of participants completed one or more categories in an average time of 6.9 (± 0.03) minutes. The tool was rated 6.63 (± 0.88) out of seven in the Post-Study System Usability Questionnaire (PSSUQ). Ninety-five percent experienced the tool as useful in practice. Suggestions for improvement included a separate version for relatives and a non-digital version. Although professionals thought the potentially extended consultation time could be problematic, all participants would recommend the tool to others.
Conclusion
‘What matters to me’ seems useful to assist clients and professionals with preference elicitation in long-term care. Evaluation of the impact on consultations between clients and professionals by using ‘What matters to me’ is needed.
Identification of a Repressor for the Two iol Operons Required for Inositol Catabolism in Geobacillus Kaustophilus
Authors: Yoshida Ken-ichi , Shirae Yusuke , Nishimura Ryo , Fukui Kaho , Ishikawa Shu
Published: June 2020

BackgroundGeobacillus kaustophilus HTA426, a thermophilic Gram-positive bacterium, grows on inositol as its sole carbon source, and an iol gene cluster required for inositol catabolism has been postulated with reference to the iol genes in Bacillus subtilis. The iol gene cluster consists of two tandem operons induced in the presence of inositol; however, the mechanism underlying the induction remains unclear. B. subtilis iolQ is known to be involved in the regulation of iolX encoding a scyllo-inositol dehydrogenase, and its homolog in HTA426 was found two genes upstream of the first gene (gk1899) of the iol gene cluster and termed as iolQ in G. kaustophilus.ResultsWhen iolQ was inactivated, not only the myo-inositol dehydrogenase activity in the cell due to the expression of gk1899 but also the transcription of the two iol operons became constitutive. IolQ was produced and purified as a C-terminal His-tag fusion in Escherichia coli and subjected to the in vitro gel mobility shift assay to examine its DNA binding property. It was observed that IolQ bound to the DNA fragments containing each of the two iol promoter regions, and its DNA binding was antagonized by myo-inositol. Moreover, DNase I footprint analyses were conducted to determine the two binding sites of IolQ within each of the iol promoter regions. By comparing the sequences of the binding sites, a consensus sequence for IolQ binding was deduced to be a palindrome of 5′-RGWAAGCGCTTSCY-3′ (where R = A or G, W = A or T, S = G or C, and Y = C or T).ConclusionIolQ functions as a transcriptional repressor regulating the induction of the two iol operons responding to myo-inositol.
Evaluation of maize lodging resistance based on the critical wind speed of stalk breaking during the late growth stage
Authors: Xue Jun , Ming Bo , Xie Ruizhi , Wang Keru , Hou Peng , Li Shaokun
Published: June 2020

Background
The accurate evaluation of the stalk-lodging resistance during the late stage of maize growth can provide a basis for the selection of cultivars, the evaluation of cultivation techniques, and timely mechanical grain harvesting. In this study, the critical wind speed of stalk breaking, plant morphology, stalk mechanical strength, and lodging rate were investigated in 10 maize cultivars to identify the parameters as evaluate lodging resistance during the later growth stage of maize, and clarify the relationship with the stalk mechanical strength, critical wind speed of stalk breaking, and natural lodging rate in the field.
Results
The results showed that, in the late growth stage, with increasing number of days after physiological maturity, (1) the stalk lodging rate gradually increased, (2) the stalk breaking force and rind penetration strength (RPS) of the third internode above the soil gradually decreased, and (3) the critical wind speed of stalk breaking increased first and then decreased, and was highest at about 16–24 days after physiological maturity. Furthermore, the stalk lodging rate was significantly negatively correlated with the critical wind speed of stalk breaking, however was not correlated with plant height, ear height, stalk breaking force, or the RPS. Additionally, the critical wind speed of stalk breaking was significantly positively correlated with the stalk breaking force and the RPS.
Conclusion
This indicates that the critical wind speed of stalk breaking is a superior way to determine the stalk lodging resistance compared to traditional indicators. These results suggest that, in the late growth stage, the decrease in the stalk mechanical strength is an important reason for the decrease in the critical wind speed of stalk breaking and the increase in the lodging rate.
Micro-haplotyping in polyploids using massively parallel amplicon sequencing
Authors: Geest Geert van , Willemsen Johan , Gujjula Krishna Reddy , Siddavatam Prasad , Willis Christopher Roy , Ramadhar Ravindra , Voorrips Roeland E , Arens Paul
Published: June 2020

Background

Haplotyping in polyploids is a very relevant but challenging task. Most methods based on short-read technologies require haplotype assembly, which is error-prone and computationally intensive. However, most (auto)polyploids have high SNP densities. Therefore, haplotyping could already be done in regions of a size that can be entirely covered by reads generated by current short-read sequencing techniques. Here, we used a method that enables massively parallel amplicon sequencing in order to generate such micro-haplotypes in autotetraploid potato and autohexaploid chrysanthemum.
Results

For potato, we generated 79 million reads to sequence 412 regions in 96 samples. The average region size was 154 base-pairs. On average, we found 2.4 haplotypes per locus per individual. For chrysanthemum, we generated a similar amount of reads to sequence 940 regions in 92 samples. The average region size here was 171 base-pairs. On average, 2.7 haplotypes per locus per individual were found. Concordance with dosage data based on SNP-arrays was up to 96.8% in potato and 94.2% in chrysanthemum.
Conclusions

Interpretation of genotyping data generated with next-generation sequencing can be challenging in polyploids, because estimation of allele dosages is often a requisite. Taking advantage of high SNP densities in many autopolyploids we show that massively parallel amplicon sequencing can generate high-quality data with high information content. This has a broad range of applications, including linkage mapping, diversity studies, and genomic selection.
Pharmacological intervention to restore connectivity deficits of neuronal networks derived from ASD patient iPSC with a TSC2 mutation
Authors: Alsaqati Mouhamed , Heine Vivi M , Harwood Adrian J.
Published: June 2020

BackgroundTuberous sclerosis complex (TSC) is a rare genetic multisystemic disorder resulting from autosomal dominant mutations in the TSC1 or TSC2 genes. It is characterised by hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1) pathway and has severe neurodevelopmental and neurological components including autism, intellectual disability and epilepsy. In human and rodent models, loss of the TSC proteins causes neuronal hyperexcitability and synaptic dysfunction, although the consequences of these changes for the developing central nervous system is currently unclear.MethodsHere we apply Multi-electrode array (MEA)-based assays to study the effects of TSC2 loss on neuronal network activity using Autism Spectrum Disorder (ASD) patient-derived iPSCs. We examine both temporal synchronisation of neuronal bursting, and spatial connectivity between electrodes across the network.ResultsWe find that TSC2 patient-derived neurons with a functional loss of TSC2, in addition to possessing neuronal hyperactivity, develop a dysfunctional neuronal network with reduced synchronisation of neuronal bursting and lower spatial connectivity. These deficits of network function are associated with elevated expression of genes for inhibitory GABA signalling and decreased expression of those for glutamate signalling, indicating an imbalance of synaptic inhibitory-excitatory signalling. mTORC1 activity functions within a homeostatic triad of protein kinases, AMP-dependent protein Kinase 1 (AMPK), mTORC1 and Unc-51 like Autophagy Activating Kinase 1 (ULK1) that orchestrate the interplay of anabolic cell growth and catabolic autophagy while balancing energy and nutrient homeostasis. The mTORC1 inhibitor rapamycin suppresses neuronal hyperactivity, but does not increase network activity, whereas activation of AMPK restores network activity without affecting the network burst length or regularity. In contrast, the ULK1 activator, LYN-1604 increases the network behaviour, shortens the network burst lengths, and reduces the number of uncorrelated spikes.LimitationsAlthough a robust and consistent phenotype is observed across multiple independent iPSC clones, the results are based on iPSC from one patient. There may be more subtle differences between patients with different TSC2 mutations or differences of polygenic background within their genomes. This may affect the severity of the network deficit or the pharmacological response between TSC2 patients.ConclusionsOur observations suggest that there is a reduction in the network connectivity of the in vitro neuronal network associated with ASD patients with TSC2 mutation, which may arise via an excitatory/inhibitory imbalance due to increased GABA signalling at inhibitory synapses. This deficit can be effectively suppressed via activation of ULK1.
Treating COVID-19 Positive Cancer Patients with Radiation Therapy: Case Report From Epicenter of The Pandemic.
Authors: Parashar Bhupesh , Ames John W , Lee Lucille , Madu Chika , Narayana Ashwatha , Potters Louis
Published: June 2020

Coronavirus -19 (Sars-cov-2 or Covid-19) pandemic has resulted in unprecedented clinical challenges across the globe. Outcomes of patients with this infection are likely dependent on underlying comorbidities that predicts worse outcome in older patients. However, it is unknown whether Covid-19 infected cancer patients receiving radiation therapy (RT) have any different outcome than non-infected patients. We present the first series of Covid-19 infected patients that received RT for malignancy, their outcome, and toxicities.
Characterization of the leaf microbiome from whole-genome sequencing data of the 3000 rice genomes project
Authors: Roman-Reyna Veronica , Pinili Dale , Borja Frances Nikki , Quibod Ian Lorenzo , Groen Simon C. , Alexandrov Nikolai , Mauleon Ramil , Oliva Ricardo
Published: June 2020

Background: The crop microbial communities are shaped by interactions between the host, microbes and the environment, however, their relative contribution is beginning to be understood. Here, we explore these interactions in the leaf bacterial community across 3,024 rice accessions.Findings: By using unmapped DNA sequencing reads as microbial reads, we characterized the structure of the rice bacterial microbiome. We identified central bacteria taxa that emerge as microbial “hubs” and may have an influence on the network of host-microbe interactions. We found regions in the rice genome that might control the assembly of these microbial hubs. To our knowledge this is one of the first studies that uses raw data from plant genome sequencing projects to characterize the leaf bacterial communities. Conclusion: We showed, that the structure of the rice leaf microbiome is modulated by multiple interactions among host, microbes, and environment. Our data provide insight into the factors influencing microbial assemblage in the rice leaf and also opens the door for future initiatives to modulate rice consortia for crop improvement efforts.
Clinical and pathological findings of SARS-CoV-2 infection and concurrent IgA nephropathy: A case report
Authors: Liu Liu
Published: June 2020

Background: Since the Coronavirus Disease 2019 (COVID-19) outbreak, there is limited data on the clinical characteristics, treatment strategies and prognosis of COVID-19 in patients with concurrent renal disease. The kidney is believed to have a predisposition for COVID-19 due to its abundant angiotensin-converting enzyme 2 (ACE2) expression, which acts as a cell entry receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Recent postmortem investigations reveal renal involvement in COVID-19, and case reports describe collapsing glomerulopathy in African American patients with COVID-19. However, there is limited data regarding IgA nephropathy in the setting of COVID-19.Case presentation: In the present case, we report a 65-year old Chinese woman who presented with macroscopic hematuria, worsening proteinuria and decreased renal function after COVID-19 infection. She received a renal biopsy during COVID-19 infection. The renal biopsy revealed IgA nephropathy without any evidence for SARS-Cov-2. The findings suggest that the renal abnormalities were a consequence of exacerbation of this patient’s underlying glomerular disease after COVID-19 infection. After a regimen of 3-day course of glucocorticoid and angiotensin II receptor blocker therapy, the patient recovered and remained stable upon follow-up. Conclusions: It is important to consider the underlying glomerular disease exacerbation rather than virus induced injury when dealing with renal abnormalities in patients with COVID-19.
Health and Support Service Needs of Individuals With Disability From Culturally and Linguistically Diverse Backgrounds: A Scoping Review Protocol
Authors: Pho Jacqueline Nhu Quynh , Tan Aidan Christopher , Chaudhary Katrina , Hines Sonia , Ellison Caroline , Isaac Vivian , Lim David
Published: June 2020

Background: All individuals should have the right to engage meaningfully in occupations that meet their aspirations and life goals as well as promote their health and wellbeing. For individuals with disability, meaningful engagement in occupations is supported by timely, effective and adaptive health and support services. However, research has revealed multiple barriers preventing utilisation of these services by individuals with disability from culturally and linguistically diverse (CALD) backgrounds. This review aims to identify gaps and solutions in health and support services of individuals with disability from CALD backgrounds to meaningfully engage in occupations.Methods: A scoping review will be conducted in accordance with the Joanna Briggs Institute (JBI) methodology for scoping reviews and follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Scoping Review guidelines. A detailed search strategy will be used to search CINAHL, PubMed, Embase, Scopus, PsychInfo, JBI and Cochrane Library, as well as grey literature in Trove, Mednar and OpenGrey. Studies will be screened for eligibility against specific inclusion and exclusion criteria for relevant studies. Data will be extracted using the JBI data extraction instrument and presented in a diagrammatic or tabular form accompanied with a narrative summary.Discussion: The scoping review will present the health and support service needs of individuals with disability from CALD backgrounds and will extend the current reviews as it focuses the engagement in meaningful occupation. Findings from this review have the potential to inform local policy discussions and practice-based disability care.
Examining aptitude and barriers to Evidence Based Medicine among trainees at an ACGME-I accredited program
Authors: Mahmoud Mai , Laws Saad , Kamal Antoun , Mohanadi Dabia Al , Mohammed Ahmed Al , Mahfoud Ziyad
Published: June 2020

Background Evidence-based medicine (EBM) promotes critical thinking and produces better patients’ outcome. Accreditation Council for Graduate Medical Education (ACGME) competencies require trainees to locate, appraise and apply clinical evidence to patients care. Despite the emphasis that ACGME place on EBM, few organizations provide adequate training in EBM. This is even more critical in regions where medical trainees matriculate from diverse backgrounds of undergraduate medical education, where EBM may not be emphasized nor taught at all. EBM practice has a history of research in the West, however, EBM has not been widely studied in the Middle East. Methods Clinicians and trainees at Hamad Medical Corporation (HMC) matriculate from many countries in the Middle East and North Africa (MENA) and Asia. Trainees’ various backgrounds in medical education hypothesize different levels and experiences of EBM. To assess trainees EBM attitudes and knowledge in the internal medicine department at HMC in Doha, Qatar, we surveyed residents and fellows using a two-part survey. The first part was adapted from the evidence-based practice inventory by Kaper to assess trainees’ attitudes and perceptions of EBM. Trainees were also asked to complete the ACE tool to assess their knowledge proficiency regarding different elements of EBM. The results from the two were analyzed. Results The average score on the ACE tool among the participants was around 9 out of 15. Most participants rated themselves as beginners or intermediate in their EBM capabilities. Higher ACE scores were observed from participants with educational background from South Asia, and among those with more favorable attitudes towards EBM. Participants also reported reasonable capabilities of doing EBM and favorable atmosphere at work for EBM implementation. Lack of knowledge, resources and time were the most reported barriers for doing EBM. Conclusions Earlier adoption of EBM education and practices leads to increased competence and it should be taught and evaluated in the undergraduate and GME programs. This's especially true since it's known that EBM practices lead to better patient outcomes. In a setting where matriculating clinicians arrive from heterogeneous educational backgrounds and EBM experiences, it is important to assess and continuously implement EBM training.
Education of Pharmacists in Ghana: Evolving Curriculum, Context and Practice in the Journey from Dispensing Certificate to Doctor of Pharmacy Certificate.
Authors: Koduah Augustina , Kretchy Irene , Sekyi-Brown Reginald , Asiedu-Danso Michelle , Ohene-Agyei Thelma , Duwiejua Mahama
Published: June 2020

Background: Understanding the origin and evolution of education of pharmacists is important for practice and health system reforms. In Ghana, education of pharmacists started in the 1880s with the training of dispensers in a government hospital. Over the years, the curriculum and institutional arrangements changed and currently pharmacists are trained in universities. In this study we explored how and why education of pharmacists evolved in Ghana. Methods: We used a case study design to systematically describe education of pharmacists reforms. Data was collected from October 2018 and December 2019 through document review and in-depth interviews. The data was analysed based on institutional arrangements and contextual factors influencing reforms from the 1880s through 2012, when the Doctor of pharmacy programme was initiated in Ghana. Results: Reforms occurred around four main periods when institutional arrangements including the certificate awarded and expected roles were modified by educators and government. These are: (1) the Certificate of dispensing with dispenser-in-training and nurse-dispenser schemes (1880s to 1942), when dispensers were trained to assist doctors in dispensing or directly diagnosing and treating specific disease conditions. (2) the Diploma and Certificate of competency with the dispenser-in-training and pupil pharmacist schemes (1943 to 1960), where in addition to existing roles, pharmacists operated village dispensers. (3) the Bachelor of pharmacy degree (1961 to 2017), when pharmacists were trained mainly as medicines experts with a strong science base on all aspects of medicines from production, distribution and use; and over time with a gradual move to patient-oriented practice. (4) the Doctor of pharmacy degree (2012 to date), where in addition to existing roles, trainees are exposed to advance professional practice experiences. Important factors influencing the reforms included, health systems demands for village dispensaries and clinically oriented pharmacists, and harmonization with regional and international training and practice. Conclusion: Reasons influencing education of pharmacists reforms are context specific and are driven by historical experiences, national and international expectations as well as educators and regulators abilities to influence change. These reforms call for direct corresponding change in professional practice laws and regulation to enable pharmacists contribute fully to health care delivery in Ghana.