bluuebunny/crossref_metadata_2025 huggingface dataset:
An exploration of perceptions and preferences for healthy eating in Dutch consumers: A qualitative pilot study
Authors: Coumans Juul M.J. , Bolman Catherine A.W. , Lechner Lilian , Oenema Anke
Published: October 2020

Background: Unhealthy dietary patterns are highly prevalent in Western countries, and they have been associated with depression, hypertension, heart disease, cancer, type 2 diabetes, and obesity. Many dietary interventions have been developed to promote healthier dietary behavior, yet most do not achieve the intended dietary change. This study aims to provide a better understanding of what Dutch consumers perceive as a healthy diet, how this relates to the current Dutch nutrition guidelines, and their preferences for how to eat more healthily. This is an essential consideration for the development of tailored interventions aimed to help people adopt changes in their dietary behavior. Methods: Seventy-eight participants filled in an online questionnaire containing both open-ended and closed-ended questions. The qualitative data was analyzed using content analysis resulting in a classification scheme. Two students then identified to which category each part of a participant’s answer belonged. Results: For both the perception of a healthy diet and how to eat healthily four major categories and a residual category were identified: dietary patterns, food processing, food products, content/nutrients, and non-food. These major categories consisted of several categories. The results showed that how people perceived a healthy diet was mostly represented at the level of food product (vegetables and fruit) and the content/nutrient level (carbohydrates); whereas how they would like to eat healthily was mostly represented at the level of food processing (preparation), food product (vegetables) and dietary patterns (amount). Conclusions: Our findings are mostly in line with how the Dutch dietary guidelines are communicated (“product level”). However, consumers primarily mention single aspects instead of naming the guidelines as a whole. Health policymakers can use this insight in future communications regarding guidelines to the general public. A challenge for future (eHealth) diet interventions is how to implement and tailor dietary information that optimally connects with the perceptions of the target population.
Clinicians’ Experience of Providing Care: A Rapid Review
Authors: Iqbal Maha Pervaz , Manias Elizabeth , Mimmo Laurel , Mears Stephen , Jack Briony , Hay Liz , Harrison Reema
Published: October 2020

BackgroundHealth care services internationally are refocussing care delivery towards patient centred, integrated care that utilises effective, efficient and innovative models of care to optimise patient outcomes and system sustainability. Whilst significant efforts have been made to examine and enhance patient experience, to date little has progressed in relation to provider experience. This review aims to explore this knowledge gap by capturing evidence of clinician experience, and how this experience is defined and measured in the context of health system change and innovation.Methods:A rapid review of published and grey literature review was conducted utilising a rapid evidence assessment methodology. 79 studies retrieved from the literature were included in the review. 14 articles were identified from the grey literature search and one article obtained via hand searching. In total, 94 articles were included in the review. This study was commissioned by and co-designed with the New South Wales, Ministry of Health.Results:Clinician experience of delivering health care is inconsistently defined in the literature, with identified articles lacking clarity regarding distinctions between experience, engagement and work-related outcomes such as job satisfaction. Clinician experience was commonly explored using qualitative research that focused on experiences of discrete health care activities or events in which a change was occurring. Such research enabled exploration of complex experiences. In these contexts, clinician experience was captured in terms of self-reported information that clinicians provided about the health care activity or event, their perceptions of its value, the lived impacts they experienced, and the specific behaviours they displayed in relation to the activity or event. Moreover, clinician’s experience has been identified to have a paucity of measurement tools. Conclusion:Literature to date has not examined clinician experience in a holistic sense. In order to achieve the goals identified in relation to value-based care, further work is needed to conceptualise clinician experience and understand the nature of measurement tools required to assess this. In health system application, a broader ‘clinician pulse’ style assessment may be valuable to understand the experience of clinical work on a continuum rather than in the context of episodes of change/care.
Virtual Screening on Indonesian Herbal Compounds as COVID-19 Supportive Therapy: Machine Learning and Pharmacophore Modelling Approaches
Authors: Erlina Linda , Paramita Rafika Indah , Kusuma Wisnu Ananta , Fadilah Fadilah , Tedjo Aryo , Pratomo Irandi Putra , Ramadhanti Nabila Sekar , Nasution Ahmad Kamal , Surado Fadhlal Khaliq , Fitriawan Aries , Istiadi Khaerunissa Anbar , Yanuar Arry
Published: October 2020

Background: The latest development of COVID-19 spread in Indonesia has reached 311,176 cases, with 11,374 patients died, updated on October 6, 2020. Unfortunately, these numbers continue to overgrow, and no drug has yet been approved for effective treatment. This study aims to determine the potential candidate compounds in Indonesian herbal medicine as a COVID-19 supportive therapy using a machine learning and pharmacophore modelling approach.Methods: For the machine learning approach, we used three classification methods that have different ways in decision making, such as Support Vector Machine (SVM), Multilayer Perceptron (MLP), and Random Forest (RF). Moreover, for the pharmacophore modelling approach, we performed a structure-based method on the 3D structure of the main protease SARS-CoV-2 (3CLPro) and used the SARS, MERS, and SARS-CoV-2 repurposing drugs known from the literature as data sets on the ligand-based method. Finally, we used molecular docking to analyse the interactions between the 3CLpro protein (main protease) and 14 hit compounds from the Indonesian Herbal Database (HerbalDB) and Lopinavir as a positive control.Results: The machine learning approach with SVM, RF, and MLP methods and pharmacophore modelling approach were used for screening in herbal compounds obtained from HerbalDB. Based on the screening on HerbalDB using these two prediction approaches, we got 14 hit compounds. We then performed molecular docking to determine the interaction of these compounds with the main protease SARS-CoV-2 as an inhibiting agent. From the molecular docking analysis, it was found that six potential compounds as the main proteases of the SARS-CoV-2 inhibitor, i.e. Hesperidin, Kaempferol-3,4'-di-O-methyl ether (Ermanin); Myricetin-3-glucoside, Peonidine 3-(4’-arabinosylglucoside); Quercetin 3-(2G-rhamnosylrutinoside); and Rhamnetin 3-mannosyl-(1-2)-alloside.Conclusions: We used layered virtual screening with machine learning and pharmacophore modelling approaches that could provide more objective and optimal virtual screening and avoid subjective decision making on research results. Herbal compounds from various plants have potential as antiviral candidates for SARS-CoV-2. Based on our research and literature study, one of Indonesia's potential commodity crops is Psidium guajava (guava), and people can use it directly as a preventive effort.
Investigation of early and lifetime clinical features and comorbidities for the risk of developing treatment-resistant depression in a 13-year nationwide cohort study 
Authors: Huang Shiau-Shian , Chen Hsi-Han , Wang Jui , Chen Wei J. , Chen Hsi-Chung , Kuo Po-Hsiu
Published: October 2020

Background: To investigate the risk of treatment-resistant depression (TRD) in patients with depression by examining their clinical features, early prescription patterns, and early and lifetime comorbidities. Methods: In total, 31,422 depressive inpatients were followed-up from diagnostic onset for more than 10-years. Patients were diagnosed with TRD if their antidepressant treatment regimen was altered ≥two times or if they were admitted after at least two different antidepressant treatments. Multiple Cox regression model were used to determine whether physical and psychiatric comorbidities, psychosis, and prescription patterns increased the risk of TRD by controlling for relevant demographic covariates. Survival analyses were performed for important TRD-associated clinical variables. Results: Females with depression (21.24%) were more likely to suffer from TRD than males (14.02%). Early anxiety disorders were more commonly observed in the TRD group than in the non-TRD group (81.48 vs. 58.96%, p<0.0001). Lifetime anxiety disorders had the highest population attributable fraction (42.87%). Seventy percent of patients with multiple psychiatric comorbidities developed TRD during follow-up. Cox regression analysis further identified that functional gastrointestinal disorders significantly increased TRD risk (aHR=1.19). Higher doses of antidepressants and benzodiazepines and Z drugs in the early course of major depressive disorder increased TRD risk (p<0.0001). Conclusion: Our findings indicate the need to monitor early comorbidities and polypharmacy patterns in patients with depression associated with elevated TRD risk.
Per-Protocol Analysis of The ZINC Trial for HIV Disease Among Alcohol Users
Authors: Lodi Sara , Freiberg Matthew , Gnatienko Natalia , Blokhina Elena , Yaroslavtseva Tatiana , Krupitsky Evgeny , Murray Eleanor , Samet Jeffrey H. , Cheng Debbie M.
Published: October 2020

Background. The ZINC trial randomized HIV-positive heavy drinkers to either daily zinc supplementation or placebo. The primary outcome was change in VACS index, a predictor of mortality, between baseline and 18 months. Because adherence and follow-up were suboptimal, the intention-to-treat analysis, which was not statistically significant, may have underestimated the effect of the zinc supplementation. Objective. We estimated the per-protocol effect of zinc versus placebo in the ZINC trial (i.e., the effect that would have been observed if all participants had had high adherence and none were lost to follow-up).Methods. Adherence was measured as the self-reported percentage of pills taken in the previous 6 weeks and assessed at all post-baseline visits. We used inverse probability weighting to estimate and compare the change in VACS index at 18 months in the zinc and placebo groups had all the trial participants had high adherence (i.e., cumulative adherence ≥80% at 18 months). To examine trends by level of adherence, we rerun the analyses using thresholds for high-adherence of 70% and 90% of average self-reported pill coverage.Results. The estimated (95% confidence interval) change in VACS index was –2.16 (-8.07, 3.59) and 5.84 (0.73, 11.80) under high adherence and no loss to follow-up in the zinc and placebo groups, respectively. The per-protocol effect estimate of the mean difference in change between the zinc and placebo group was -8.01 (-16.42, 0.01), somewhat larger than the intention-to-treat effect difference in change (-4.68 (-9.62, 0.25)), but it was still not statistically significant. The mean difference in change between individuals in the zinc and placebo group was -4.07 (-11.5,2.75) and -12.34 (-20.14,-4.14) for high adherence defined as 70% and 90% of pill-coverage, respectively. Conclusions. Overall, high adherence to zinc was associated with lower VACS score, but confidence intervals were wide and crossed 0. Further studies with larger sample size are needed to quantify the benefits of zinc supplementation in this population.Trial Registration. ClinicalTrials.gov Identifier: NCT01934803, August 30, 2013
Metastasis to lateral lymph nodes with no mesenteric lymph node involvement in low rectal cancer: a retrospective case series
Authors: Li Peng , Zhang Zhichun , Zhou Yuanda , Zeng Qingsheng , Zhang Xipeng , Sun Yi
Published: October 2020

Purpose The aim of this study is to examine the pattern of lymph node metastasis (lateral vs. mesenteric lymph nodes) in low rectal cancer.Methods This retrospective analysis included all patients undergoing laparoscopic total mesorectal excision plus lateral lymph node dissection for advanced low rectal cancer (up to 8 cm from the anal verge) during a period from July 1, 2017 to August 31, 2019 at the Department of Colorectal Surgery, Tianjin Union Medical Center. The decision to conduct lateral lymph node dissection was based on positive findings in preoperative imaging assessments.Results A total of 42 patients were included in data analysis. Surgery was successfully completed as planned, without conversion to open surgery in any case. A minimum of 10 mesenteric lymph nodes and 1 lateral lymph node on each side were dissected in all patients. Pathologic examination of resected specimens showed no metastasis to either mesenteric or lateral lymph nodes in 7 (16.7%) case, metastasis to both mesenteric and lateral lymph nodes in 26 (61.9%) cases, metastasis to mesenteric but not lateral lymph nodes in 4 (9.5%) cases, and metastasis to lateral but not mesenteric lymph nodes in 5 (11.9%) cases (n=2 in the obturator region; n=3 in the iliac artery region).Conclusion A clinically significant proportion of low rectal cancer patients have metastasis to lateral lymph nodes without involvement of mesenteric lymph nodes. More carefully planned prospective studies are needed to verify this preliminary finding.
Cytokine Profile During Occult Hepatitis B Virus Infection in Chronic Hepatitis C Patients
Authors: Ribeiro Camilla Rodrigues de Almeida , de Almeida Nathalia Alves Araújo , Martinelli Katrini Guidolini , Pires Marcia Amendola , Mello Carlos Eduardo Brandao , Barros José J. , De Paula Vanessa Salete
Published: October 2020

Background: The hepatitis B virus (HBV) is one of the leading causes of acute, chronic and occult hepatitis (OBI) representing a serious public health threat. Cytokines are known to be important chemical mediators that regulate the differentiation, proliferation and function of immune cells. Accumulating evidence indicate that the inadequate immune responses are responsible for HBV persistency. The aim of this study were to investigate the cytokines IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10 and IL-17A in patients with OBI and verify if there is an association between the levels of these cytokines with the determination of clinical courses during HBV occult infection. Methods: 114 patients with chronic hepatitis C were investigated through serological and molecular tests, the OBI coinfected patients were subjected to the test for cytokines using the commercial human CBA kit. As controls, ten healthy donors with no history of liver disease and 10 chronic HBV monoinfected patients of similar age to OBI patients were selected. Results: Among 114 HCV patients investigated, 11 individuals had occult hepatitis B. The levels of cytokines were heterogeneous between the groups, most of the cytokines showed higher levels of production detection among OBI/HCV individuals when compared to control group and HBV monoinfected pacients. We found a high level of IL-17A in the HBV monoinfected group, high levels of TNF-α, IL-10, IL-6, IL-4 and IL-2 in OBI/HCV patients.Conclusion: These cytokines could be involved in the persistence of HBV DNA in hepatocytes triggers a constant immune response, inducing continuous liver inflammation, which can accelerate liver damage and favor the development of liver cirrhosis in other chronic liver diseases.
IRLnc: A novel functional noncoding RNA contributes to intramuscular fat deposition
Authors: Wang Ligang , Zhou Zhong-Yin , Zhang Tian , Zhang Longchao , Hou Xinhua , Yan Hua , Wang Lixian
Published: October 2020

Background Intramuscular fat (IMF) is associated with meat quality and insulin resistance in animals. Research on genetic mechanism of IMF decomposition has positive meaning to pork quality and diseases such as obesity and type 2 diabetes treatment. In this study, an IMF trait segregation population was used to perform RNA sequencing and to analyze the joint or independent effects of genes and long intergenic non-coding RNAs (lincRNAs) on IMF. ResultsA total of 26 genes including six lincRNA genes show significantly different expression between high- and low-IMF pigs. Interesting, one lincRNA gene, named IMF related lincRNA (IRLnc) not only has a 292-bp conserved region in 100 vertebrates but also has conserved up and down stream genes (<10 kb) in pig and humans. Real-time quantitative polymerase chain reaction (RT-qPCR) validation study indicated that nuclear receptor subfamily 4 group A member 3 (NR4A3) which located at the downstream of IRLnc has similar expression pattern with IRLnc. RNAi-mediated loss of function screens identified that IRLnc silencing could inhibit both of the RNA and protein expression of NR4A3. And the in-situ hybridization co-expression experiment indicates that IRLnc may directly binding to NR4A3. As the NR4A3 could regulate the catecholamine catabolism, which could affect insulin sensitivity, we inferred that IRLnc influence IMF decomposition by regulating the expression of NR4A3.ConclusionsIn conclusion, a novel functional noncoding variation named IRLnc has been found contribute to IMF by regulating the expression of NR4A3. These findings suggest novel mechanistic approach for treatment of insulin resistance in human beings and meat quality improvement in animal.
Novel immune-related genes in the tumor microenvironment with prognostic value in breast cancer
Authors: Tan Wen , Liu Maomao , Wang Liangshan , Guo Yang , Wei Changsheng , Zhang Shuqi , Luo Chengyu , Liu Nan
Published: October 2020

Background: Breast cancer is one of the most frequently diagnosed cancers among women worldwide. Alterations in the tumor microenvironment (TME) have been increasingly recognized as key in the development and progression of breast cancer in recent years. To deeply comprehend the gene expression profiling of the TME and identify immunological targets, as well as determine the relationship between gene expression and different prognoses is highly critical. Results: The stromal/immune scores of breast cancer patients from The Cancer Genome Atlas were employed to comprehensively evaluate the TME. Although the TME did not correlate with the stages of breast cancer, it was closely associated with the subtypes of breast cancer and gene mutations (CDH1, TP53 and PTEN), and had immunological characteristics. Based on Gene Ontology (GO) functional enrichment analysis, the upregulated genes from the high vs low immune score groups were mainly involved in T cell activation, the external side of the plasma membrane, and receptor ligand activity. We further analyzed and screened the overlapping genes of the top 3 GO terms and upregulated differentially expressed genes (DEGs). Overall survival, time-dependent receiver operating characteristic (ROC), and protein-protein interaction (PPI) network analyses revealed that the genes of the top GO terms of the upregulated DEGs from the high vs low immune score groups exhibited better prognosis in breast cancer; 15 of them were related to good prognosis in breast cancer, especially CD226 and KLRC4-KLRK1.Conclusions: High CD226 and KLRC4-KLRK1 expression levels were identified and validated to correlate with better overall survival in specific stages or subtypes of breast cancer. CD226, KLRC4-KLRK1 and other new targets seem to be promising avenues for promoting antitumor targeted immunotherapy in breast cancer.
Integrated transcriptome and proteome analysis reveals potential mechanisms for differential abdominal fat deposition between divergently selected chicken lines
Authors: Wang Lijian , Leng Li , Ding Ran , Gong Pengfei , Liu Chang , Wang Ning , Li Hui , Du Zhi-Qiang , Cheng Bohan
Published: October 2020

Background: Genetic selection for meat production performance of broilers concomitantly causes excessive abdominal fat deposition, accompanied by several adverse effects, such as the reduction of feed conversion efficiency and reproduction performance. Our previous studies have identified important genes regulating chicken fat deposition, using the Northeast Agricultural University broiler lines divergently selected for abdominal fat content (NEAUHLF) as an animal model. However, the molecular mechanism underlying fat deposition differences between fat and lean broilers remains largely unknown.Results: Here, we integrated the transcriptome (RNA-Seq) and quantitative proteome (isobaric tags for relative and absolute quantitation, iTRAQ) profiling analyses on abdominal fat tissues from NEAUHLF chicken lines. Differentially expressed genes (466 DEGs) and proteins (231 DEPs) were identified, and enriched in pathways related to fatty acid metabolism, fatty acid biosynthesis, glycerophospholipid metabolism, and PPAR signaling, and in pathways mainly involved in protein processing, endocytosis and lipid metabolism, respectively. Moreover, several key DEGs and DEPs involved in long-chain fatty acid uptake, in situ lipogenesis (fatty acid and cholesterol synthesis), and lipid droplets accumulation were discovered, and most of them were up-regulated in the fat line, after integrated transcriptome and proteome analysis.Conclusions: Together, our findings provided a novel insight into abdominal fat content discrepancy between the fat and lean chicken lines.
Allogeneic Administration of Human Umbilical Cord-derived Mesenchymal Stem/Stromal Cells for Bronchopulmonary Dysplasia: Preliminary Outcomes in Four Vietnamese Infants.
Authors: Thanh Liem Nguyen , Trieu Thai T.H. , Bui Hue T.H. , Hoang Van T. , Nguyen Anh T.T , Trinh Nhung T.H. , Nguyen Kien T. , Hoang Duc M.
Published: October 2020

Background: Bronchopulmonary dysplasia (BPD) is a severe condition in premature infants that compromises lung function and necessitates oxygen support. Despite major improvements in perinatal care minimizing the devastating effects, BPD remains the most frequent complication of extreme preterm birth. Our study reports the safety of the allogeneic administration of umbilical cord-derived mesenchymal stem/stromal cells (allo-UC-MSCs) and the progression of lung development in four infants with established BPD. Methods : UC tissue was collected from a healthy donor, followed by propagation at the Stem Cell Core Facility at Vinmec Research Institute of Stem Cell and Gene Technology. UC-MSC culture was conducted under xeno- and serum-free conditions. Four patients with established BPD were enrolled in this study between May 25, 2018, and December 31, 2018. All four patients received two intravenous doses of allo-UC-MSCs (1 million cells/kg patient body weight (PBW) per dose) with an intervening interval of 7 days. Safety and patient conditions were evaluated during hospitalization and at 7 days and 1, 6 and 12 months postdischarge. Results: No intervention-associated severe adverse events or prespecified adverse events were observed in the four patients throughout the study period. At the time of this report, all patients had recovered from BPD and were weaned off of oxygen support. Chest X-rays and CT scans confirmed the progressive reductions in fibrosis. Conclusions: Allo-UC-MSC administration is safe in preterm infants with established BPD. Trial registration : This preliminary study was approved by the Vinmec International Hospital Ethics Board (approval number: 88/2019/QĐ-VMEC; retrospectively registered March 12, 2019).
Characterization of the Serum Levels of Meteorin-like in Patients with Inflammatory Bowel Disease and its Association with Inflammatory Cytokines 
Authors: Gholamrezayi Afsane , Mohamadinarab Maryam , Rahbarinejad Pegah , Fallah Soudabeh , Barez Shekufe Rezghi , Setayesh Leila , Moradi Nariman , Fadaei Reza , Chamani Elham , Tavakoli Tahmine
Published: October 2020

Background: Meteorin-like (Metrnl) is an adipokine with insulin sensitizing and anti-inflammatory properties that has been discovered recently. The relation among Metrnl, Inflammatory Bowel Disease (IBD), and obesity has been unexplored yet. Methods: The present study was conducted on 54 healthy control, 42 Ulcerative Colitis (UC), and 43 Crohn's disease (CD) patients who were diagnosed by pathological examination. In all participants, serum levels of adiponectin, Metrnl, interleukin (IL)-6, and Tumor necrosis factor (TNF-α) were measured using ELISA kits.Results: Metrnl concentration was considerably lower in both UC (85.25±36.55 pg/mL) and CD (76.93±27.92 pg/mL) patients in comparison to control (107.52 ± 35.33 pg/mL). In addition, it was seen that both patient groups have a decreased level of adiponectin compared to the controls. Besides that, the level of IL-6 and TNF-α were significantly greater in the patient groups. Moreover, the result showed that the level of Metrnl is inversely correlated with body mass index (BMI) in the controls and the patients. Metrnl levels are also inversely associated with IL-6, and TNF-α in both of the patient groups.Conclusions: The current study is the first one reporting the decreased levels of Metrnl in serum among patients with IBD, which is inversely related with BMI, TNF-α, and IL-6. These results suggested a possible relation of Metrnl with the pathogenesis of IBD, particularly through inflammatory process, although further studies are warranted to dissect the possible mechanism.
A multilevel analysis of the importance of oral health instructions for preventing tooth loss: The 8020 Promotion Foundation Study of Japanese Dental Patients
Authors: Saito Mizuki , Shimazaki Yoshihiro , Fukai Kakuhiro , Furuta Michiko , Aida Jun , Ando Yuichi , Miyazaki Hideo , Kambara Masaki
Published: October 2020

Background: Many studies have reported risk factors for tooth loss. Oral health instruction is considered effective at improving oral health behavior and oral health. However, few studies have examined the relationship of dental clinic factors, such as the number of dental hygienists and implementation of oral health instructions, with tooth loss. Here, we conducted a multilevel analysis to clarify the dental clinic risk factors associated with tooth loss.Methods: Baseline surveys were conducted at 1,216 dental clinics in 46 prefectures in Japan, and 12,399 dental patients aged 20 years and over underwent oral examinations and completed a questionnaire. The dental clinics also completed a questionnaire at baseline. A 3-year follow-up survey included 2,488 patients in 585 dental clinics. Multilevel multivariate logistic regression analysis was used to examine the risk of tooth loss at the patient and clinic levels.Results: Of the patient variables, older age, higher mean probing pocket depth, current or past smoking, and bleeding during tooth brushing were associated with higher risks of tooth loss. Individuals with many teeth who visited dental clinics for maintenance were at significantly lower risk of tooth loss. Of the clinic variables, patients attending dental clinics with four or more dental hygienists had a significantly lower risk of tooth loss (OR 0.68, 95% CI 0.50–0.99). Patients attending dental clinics that provide oral health instructions for 20 min or more had a significantly lower risk of tooth loss (OR 0.69, 95% CI 0.50–0.96).Conclusions: In addition to individual risk factors for tooth loss, dental clinic factors such as length of oral health instruction and number of dental hygienists are associated with tooth loss. In dental clinics, ensuring sufficient time for dental hygienists to provide oral health instructions can help prevent tooth loss in dental patients.
Steroid metabolites for diagnosing and predicting clinicopathological features in cortisol-producing adrenocortical carcinoma.
Authors: Suzuki Sawako , Minamidate Tomoki , Shiga Akina , Ruike Yutarou , Ishiwata Kazuki , Naito Kumiko , Ishida Akiko , Deguchi Hanna , Fujimoto Masanori , Koide Hisashi , Tatsuno Ichiro , Ikeda Jun-ichiro , Yamazaki Yuto , Sasano Hironobu , Yokote Koutaro
Published: October 2020

Background: Approximately 60% of adrenocortical carcinomas (ACC) are functional, and Cushing’s syndrome is the most frequent diagnosis that has been revealed to have a particularly poor prognosis. Since 30% of ACC present steroid hormone-producing disorganization, measurement of steroid metabolites in suspected ACC is recommended. Previous reports demonstrated that steroid hormone precursors or their urine metabolites, which can be assessed using liquid chromatography tandem mass spectrometry (LC-MS/MS) or gas chromatography mass spectrometry (GC-MS) respectively, are useful for distinguishing ACC from cortisol-producing adenomas (CPA); however, despite high precision, LC-MS/MS and GC-MS require a highly trained team, are expensive and have limited capacity.Methods: Here, we examined 12 serum steroid metabolites using an immunoassay, which is a more rapid and less costly method than LC-MS/MS, in cortisol-producing ACC and CPA. Further, the correlation of each steroid metabolite to the classification stage and pathological status in ACC was analyzed.Results: Reflecting disorganized steroidogenesis, the immunoassay revealed that all basal levels of steroid precursors were significantly increased in cortisol-producing ACC compared to CPA; in particular, 17-hydroxypregnenolone (glucocorticoid and androgen precursor) and 11-deoxycorticosterone (mineralocorticoid precursor) showed a large area under the ROC curve with high sensitivity and specificity when setting the cut-off at 1.78 ng/ml and 0.4 mg/ml, respectively. Additionally, a combination of androstenedione and DHEAS also showed high specificity with high accuracy. In cortisol-producing ACC, 11-deoxycortisol (glucocorticoid precursor) showed significant positive correlations with predictive prognostic factors used in ENSAT classification, while testosterone showed significant positive correlations to the Ki67-index in both men and women.Conclusion: Less expensive and more widely available RIA and ECLIA may also biochemically distinguish ACC from CPA and may predict the clinicopathological features of ACC.
Value of Biopsy in a Cohort of Children with High-Titer Celiac Serologies: Observation of Dynamic Policy Differences between Europe and North America
Authors: Badizadegan Kamran , Vanlandingham David M. , Hampton Wesley , Thompson Kimberly M.
Published: October 2020

Background: Healthcare systems implement change at different rates because of differences in incentives, organizational processes, key influencers, and management styles. A comparable set of forces may play out at the national and international levels as demonstrated in significant differences in the diagnostic management of pediatric Celiac Disease (CD) between European and North American practitioners. Methods: We use retrospective clinical cohorts of 27,868 serum tissue transglutaminase (tTG) immunoglobulin A levels and 7,907 upper gastrointestinal endoscopy pathology reports to create a dataset of 793 pathology reports with matching tTG results between July 1 of 2014 and July 1 of 2018. We use this dataset to characterize histopathological findings in the duodenum, stomach and esophagus of patients as a function of serum tTG levels. In addition, we use the dataset to estimate the local and national cost of endoscopies performed in patients with serum tTG levels greater than 10 times the upper limit of normal. Results: Using evidence from a US tertiary care center, we show that in the cohort of pediatric patients with high pre-test probability of CD as determined by serum tTG levels, biopsy provides no additional diagnostic value for CD, and that it counter-intuitively introduces diagnostic uncertainty in a number of patients. We estimate that using the European diagnostic algorithms could avoid between 4,891 and 7,738 pediatric endoscopies per year in the US for evaluation of CD. Conclusions: This study considers the North American and European management guidelines for the diagnosis of pediatric CD and highlights the slow adoption in North America of evidence-based algorithms developed and applied in Europe for triage of endoscopy and biopsy. We suggest that system dynamics influences that help maintain the status quo in North America include a variety of social and economic factors in addition to medical evidence. This work contributes to the growing body of evidence that the dynamics that largely favor maintaining status quo management policies in a variety of systems extend to clinical medicine and potentially influence clinical decisions at the level of individual patients and the population.
Using pollen DNA metabarcoding to profile nectar sources of urban beekeeping in Kōtō-ku, Tokyo
Authors: Tanaka Keiske , Nozaki Akinobu , Nakadai Hazuki , Shiwa Yuh , Shimizu-Kadota Mariko
Published: October 2020

ObjectiveApis mellifera is a species of honeybee that has been introduced around the world as an industrial beekeeping species. Recently, urban beekeeping has attracted attention as a means of ecosystem protection and urban greening. This study aimed to investigate nectar sources of urban beekeeping in Kōtō-ku, Tokyo using pollen DNA metabarcoding.ResultsWe extracted DNA from pollen collected by the honeybees of a local urban beekeeping operation. DNA metabarcoding analysis was carried out by sequencing a part of the rbcL region of the chloroplast genome. A total of 31 samples collected between mid-March, 2018 and mid-October, 2018 yielded 54 operational taxonomic units (OTUs) comprising 14 families, 32 genera, and 8 species. Whereas 5 OTUs were profiled throughout all seasons, 38 OTUs were season-specific (spring, summer, or autumn). Therefore, we were able to infer seasonal nectar sources for the beekeeping operation at the family or genus level, as well as at the species level to a lesser extent. Our pollen-sampling strategy was effective for profiling season-specific nectar sources, with the exception of a few anomalies that can be accounted for by out-of-season flowering associated with artificial gardening and/or pollen accumulation over multiple seasons.
Vagus nerve stimulation ameliorates L-NAME-induced preeclampsia-like symptoms in rats through inhibition of the inflammatory response
Authors: Zheng Linmei , Tang Rong , Shi Lei , Zhong Mei , Zhou Zhongyi
Published: October 2020

BackgroundPreeclampsia is characterized by an excessive inflammatory response. Recent studies have shown that vagus nerve stimulation (VNS) has anti-inflammatory properties in vivo. This study aims to investigate whether VNS is safe for use during pregnancy and to explore the therapeutic potential and underlying mechanisms of VNS in PE.MethodsPregnant Sprague-Dawley rats were randomly chosen to receive N-nitro-L-arginine methyl ester (L-NAME)-containing water (preeclampsia-like mouse model) or saline (normal pregnancy control) daily at gestational days 14.5-20.5. VNS and the α7nAChR antagonist methyllycaconitine citrate (MLA, 1 mg/kg/d) were given daily at the same time.ResultsVNS decreased the high systolic blood pressure and urinary protein observed in the PE rats. In addition, VNS mitigated abnormal pregnancy outcomes. Moreover, VNS alleviated the inflammatory response by decreasing the levels of inflammatory cytokines. VNS significantly increased the expression of α7nAChR and attenuated the activation of NF-κB p65 in the placenta.DiscussionOur findings indicate that maternal VNS treatment is safe during pregnancy and has a protective effect in a pregnant rat model of preeclampsia induced by L-NAME.
Machine learning based prognostic model and mobile application software platform for predicting infection susceptibility of COVID-19 using health care data
Authors: Srivat R , Indi Prithviraj N , Agrahari Swapnil , Menon Siddharth , Ashok S. Denis
Published: October 2020

From public health perspectives of COVID-19 pandemic, accurate estimates of infection severity of individuals are extremely valuable for the informed decision making and targeted response to an emerging pandemic. This paper presents machine learning based prognostic model for providing early warning to the individuals for COVID-19 infection using the health care data set. In the present work, a prognostic model using Random Forest classifier and support vector regression is developed for predicting the Infection Susceptibility Probability (ISP) score of COVID-19 and it is applied on an open health care data set containing 27 field values. The typical fields of the health care data set include basic personal details such as age, gender, number of children in the household, marital status along with medical data like Coma score, Pulmonary score, Blood Glucose level, HDL cholesterol etc. An effective preprocessing method is carried out for handling the numerical, categorical values (non-numerical), missing data in the health care data set. The correlation between the variables in the health care data is analyzed using the correlation coefficient and heat map with a color code is used to identify the influencing factors on the Infection Susceptibility Probability (ISP) score of COVID-19. Based on the accuracy, Precision, Sensitivity and F-scores, it is noted that the random forest classifier provides an improved classification performance as compared to Support vector regression for the given health care data set. Android based mobile application software platform is developed using the proposed prognostic approach for enabling the healthy individuals to predict the susceptibility infection score of COVID-19 to take the precautionary measures. Based on the results of the proposed method, clinicians and government officials can focus on the highly susceptible people for limiting the pandemic spread.
Health consequences of Drought in the WHO Eastern Mediterranean Region: hotspot areas and needed actions.
Authors: Bellizzi Saverio , Lane Chris , Elhakim Mohamed , Nabeth Pierre
Published: October 2020

Background: Over the past four decades, drought episodes in the Eastern Mediterranean Region (EMR) of the of the World Health Organization (WHO) have gradually become more widespread, prolonged and frequent. We aimed to map hotspot countries and identified key strategic actions for health consequences.Methods: We reviewed scientific literature and WHO EMR documentation on trends and patterns of the drought health consequences from 1990 through 2019. Extensive communication was also carried out with EMR WHO country offices to retrieve information on ongoing initiatives to face health consequences due to drought. An index score was developed to categorize countries according vulnerability factors towards drought. Results: A series of complex health consequences are due to drought in EMR, including malnutrition, vector-borne diseases, and water-borne diseases. The index score indicated how Afghanistan, Yemen and Somalia are “hotspots” due to poor population health status and access to basic sanitation as well as other elements such as food insecurity, displacement and conflicts/political instability. WHO country offices effort is towards enhancing access to water and sanitation and essential healthcare services including immunization and psychological support, strengthening disease surveillance and response, and risk communication. Conclusions: Drought-related health effects in the WHO EMR represent a public health emergency. Strengthening mitigation activities and additional tailored efforts are urgently needed to overcome context-specific gaps and weaknesses, with specific focus on financing, accountability and enhanced data availability.
Usability evaluation of an integrated electronic medication management system implemented in an Oncology setting using the Unified Theory of the Acceptance and Use of Technology.
Authors: Dabliz Racha , Poon Simon K. , Ritchie Angus , Burke Rosemary , Penm Jonathan
Published: October 2020

Background: Medication management processes in an Oncology setting are complex and difficult to examine in isolation from interrelated processes and contextual factors. This qualitative study aims to evaluate the usability of an Electronic Medication Management System (EMMS) implemented in a specialised oncology unit using the Unified Theory of Acceptance and Use of Technology (UTAUT) framework. Methods: The study was conducted in a 12-bed outpatient Oncology unit of a major teaching hospital six months following implementation of a commercial EMMS. In-depth semi-structured interviews were conducted with doctors, nurses and pharmacists using the system to assess usability. The UTAUT framework was used to analyse the results, which facilitated evaluation of interrelated aspects and provided a structured summary of user experience and usability factors. Results: Direct cross-comparison between user groups illustrated that doctors and pharmacists were generally satisfied with the facilitating conditions (hardware and training), but had divergent perceptions of performance (automation, standardised protocols and communication and documented) and effort (mental and temporal demand). In counterpoint, nurses were generally satisfied across all constructs. Prior experience using an alternative EMMS influenced performance and effort expectancy and was related to early dissatisfaction with the implemented system. Furthermore, whilst not originally designed for the healthcare setting, the flexibility of the UTAUT allowed for translation to the hospital environment. Conclusion: Nurses demonstrated overall satisfaction with the EMMS, whilst doctors and pharmacists perceived some usability problems, particularly related to restricted automaticity and system complexity, which hindered user uptake and EMMS success. The study demonstrates the feasibility and utility of the UTAUT framework to evaluate usability of an EMMS for multiple user groups in the Oncology setting.
circVAR database: genome-wide archive of genetic variants for human circular RNAs
Authors: Zhao Min , Qu Hong
Published: October 2020

Background: Circular RNAs (circRNAs) play important roles in regulating gene expression through binding miRNAs and RNA binding proteins. Genetic variation of circRNAs may affect complex traits/diseases by changing their binding efficiency to target miRNAs and proteins. There is a growing demand for investigations of the functions of genetic changes using large-scale experimental evidence. However, there is no online genetic resource for circRNA genes. Results: We performed extensive genetic annotation of 295,526 circRNAs integrated from circBase, circNet and circRNAdb. All pre-computed genetic variants were presented at our online resource, circVAR, with data browsing and search functionality. We explored the chromosome-based distribution of circRNAs and their associated variants. We found that, based on mapping to the 1000 Genomes and ClinVAR databases, chromosome 17 has a relatively large number of circRNAs and associated common and health-related genetic variants. Following the annotation of genome wide association studies (GWAS)-based circRNA variants, we found many non-coding variants within circRNAs, suggesting novel mechanisms for common diseases reported from GWAS studies. For cancer-based somatic variants, we found that chromosome 7 has many highly complex mutations that have been overlooked in previous research. Conclusion: We used the circVAR database to collect SNPs and small insertions and deletions (INDELs) in putative circRNA regions and to identify their potential phenotypic information. To provide a reusable resource for the circRNA research community, we have published all the pre-computed genetic data concerning circRNAs and associated genes together with data query and browsing functions at http://soft.bioinfo-minzhao.org/circvar .
Clinical Characteristics and Risk Factors of Fatal Patients with COVID-19: a Retrospective Cohort Study in Wuhan, China
Authors: Jin Meng , Lu Zequn , Wang Yanan , Tian Kunming , Wang Jing , Zhong Qiang , Ran Xiao , Yang Chunguang , Zeng Xing , Wang Lu , Li Yao , Zhang Shanshan , Dong Tianyi , Yue Xinying , Li Heng , Liu Bo , Chen Xin , Cui Hongyuan , Qi Jirong , Fan Haining , Li Haixia , Yang Xiang-Ping , Hu Zhiquan , Wang Shaogang , Tian Jianbo , Xiao Jun , Wang Zhihua
Published: October 2020

Background
The coronavirus disease 2019 (COVID-19) has caused global pandemic, resulting in considerable mortality. The risk factors, clinical treatments and especially comprehensive risk models for COVID-19 death are urgently warranted.
Methods
In this retrospective study, 281 non-survivors and 712 survivors with propensity score matching by age, sex and comorbidities were enrolled from January 13, 2020 to March 31, 2020.
Results
Higher SOFA, qSOFA, APACHE II and SIRS scores, hypoxia, elevated inflammatory cytokines, multi-organ dysfunction, decreased immune cells subsets and complications were significantly associated with the higher COVID-19 death risk. In addition to traditional predictors for death risk, including APACHE II (AUC = 0.83), SIRS (AUC = 0.75), SOFA (AUC = 0.70) and qSOFA scores (AUC = 0.61), another four prediction models that included immune cells subsets (AUC = 0.90), multiple organ damage biomarkers (AUC = 0.89), complications (AUC = 0.88) and inflammatory-related indexes (AUC = 0.75) were established. Additionally, the predictive accuracy of combining these risk factors (AUC = 0.950) was also significantly higher than that of each risk group alone, outperforming previous risk models, which was significant for early clinical management for COVID-19.
Conclusions
The potential risk factors could help to predict the clinical prognosis of COVID-19 patients at an early stage. The combined model might be more suitable for the death risk evaluation of COVID-19.
Factorial design study of total petroleum contaminated soil treatment using land farming technique
Authors: Okonofua Ehizonomhen Solomon , LASISI KAYODE HASSAN , Atikpo Eguakhide
Published: October 2020

Land farming technique was used to treat hydrocarbon contaminated soil collected from a crude oil spill sites in Edo State, Nigeria. Calibrated standard auger was used to collect soil samples from the site at depth below 30 cm. The samples were characterized and classified. Cow dung and NPK fertilizer were added as additives to complement the nutriments of the soil samples before total petroleum hydrocarbon quantification and remediation procedures. Factorial design was applied to vary the input parameters such as pH, mass of substrate, moisture content and turning times of land farming so to ascertain the optimal conditions for the procedure. The result revealed that the in-situ total petroleum hydrocarbon (TPH) value was 5,000 mg kg-1 on the average and after 90 days of treatment, TPH reduced to 645.907 mg kg-1. The turning rate, pH, moisture content and mass of substrate had 82.79%, 4.36%, 0.48% and 0.046% contributions respectively to the degradation process using land farming treatment. Numerical optimization techniques applied in the optimum point for land farming input parameters to achieve predicted maximum removal of 98.60% were evaluated as pH, mass of substrate, moisture content and turning rate to be 6.01, 1 kg, 10% and 5 times in a week respectively. TPH removed at this optimum point was 97.83% reducing from 5,000 to 635.907 mg kg-1. The high coefficient of determination (r2 = 0.9865) as observed in the closeness of predicted and experimental values reflects the reliability of the model and hence, land farming practice with close attention on turning rate as revealed by this study, is recommended for TPH contaminated soil remediation.