bluuebunny/crossref_metadata_2025 huggingface dataset:
Biased Technical Change in Hospital Care and the Demand for Physicians
Authors: Blank Jos L.T. , Niaounakis Thomas K. , Valdmanis Vivian G.
Published: June 2020

Background The development of labour productivity is relevant for accurately planning future staffing requirements, especially in sectors where technological developments may drive labour substitution. The present study investigates how labour productivity has developed across Dutch medical specialists (2007-2017) and discusses its implications for workforce planning, also in relation to the existing literature.Methods A regression model is developed in which the number of full-time equivalents is related to production (admissions), hospital characteristics and a trend parameter. The trend parameter captures the average annual change in the number of full-time equivalents per production output and is a measure for labour productivity. The model is applied to a micro-data set of Dutch hospitals in the period 2007-2017 across 24 different specialties using regression methods. Results The results indicate an increase in the number of full-time equivalents per admission has increased for most specialisms and that labour productivity has thus decreased. However, there is considerable heterogeneity and uncertainty across different specialisms.Conclusions The results amplify the issue of medical personnel shortages driven by the growing demand for health care. The research outcomes are linked to the existing literature regarding physicians’ productivity. Changes in accountability such as using relative value units, incentive payments, use of staff and mid-level providers, and technology have been discussed and some consensus has been reached.
Cost-effectiveness analysis of repeated self-sampling for HPV testing in primary cervical screening: a randomized study
Authors: Aarnio Riina , Östensson Ellinor , Olovsson Matts , Gustavsson Inger , Gyllensten Ulf
Published: June 2020

Background Human papillomavirus (HPV) testing is recommended in primary cervical screening to improve cancer prevention. An advantage of HPV testing is that it can be performed on self-samples, which could increase population coverage and result in a more efficient strategy to identify women at risk of developing cervical cancer. Our objective was to assess whether repeated self-sampling for HPV testing is cost-effective in comparison with Pap smear cytology for detection of cervical intraepithelial neoplasia grade 2 or more (CIN2+) in increasing participation rate in primary cervical screening.Methods A cost-effectiveness analysis (CEA) was performed on data from a previously published randomized clinical study including 36 390 women aged 30–49 years. Participants were randomized either to perform repeated self-sampling of vaginal fluid for HPV testing (n = 17 997, HPV self-sampling arm) or to midwife-collected Pap smears for cytological analysis (n = 18 393, Pap smear arm). Results Self-sampling for HPV testing led to 1633 more screened women and 107 more histologically diagnosed CIN2+ at a lower cost vs. midwife-collected Pap smears (€ 229 446 vs. € 782 772). Conclusions This study resulted in that repeated self-sampling for HPV testing increased participation and detection of CIN2+ at a lower cost than midwife-collected Pap smears in primary cervical screening. Offering women a home-based self-sampling may therefore be a more cost-effective alternative than clinic-based screening.Trial registration Not registered since this trial is a secondary analysis of an earlier published study (1).
Evaluation of the Relationship between Malaria Infection and Significant Spread of Electrolyte Variation in Patients: Within and Outside Limit Analytic Model.
Authors: Ndako James A. , Okolie Charles E. , Dojumo Victor T. , Fajobi Victor O. , Akinwumi Jeremiah A.
Published: June 2020

Background: Malaria is one of the most common diseased conditions across most developing countries caused by one of four species of Plasmodium. Electrolyte imbalance and mineral disturbances are majorly identified clinical symptoms in various infectious diseases including malaria. Malaria infection has also been shown to be associated with abnormalities in fluids, electrolytes and acid base balances which are capable of enhancing disease severity. The aim of this study was to investigate the effects of malaria infection on electrolytes parameters. Methods: Finger prick blood samples were collected from Two-Hundred (200) malaria-suspected subjects representing all age groups and gender. The Giemsa-stained blood smears were carefully examined according to standard procedure. Demographic information was obtained using structured questionnaires. Results: Pearson's Correlation Coefficient technique was used to investigate the relationship, and the strength of association between the variables. The mean bound of patients’ sodium level was observed to fall within the specified normal limits of 125mmol/L – 145mmol/L; except for positive malaria patients belonging to the MP-(++) which will fall below the 125mmol/L (i.e. 126.25mmol/L – 1.77mmol/L = 124.48mmol/L). Conclusion: In our study we found that Plasmodium falciparum showed more alteration in electrolytes parameters than Plasmodium vivax. This study discovered a significant linear relationship based on the Pearson product-moment correlation between creatinine and urea, potassium and chloride, potassium and creatinine, potassium and urea. The mean sodium and chloride level of positive malaria [MP-(++)] patients were observed to fall outside the normal limit.
Rapamycin alleviates experimental autoimmune hepatitis by immunoregulation of Th1 and Th17 cells
Authors: Tian Yan , Liu Qingqing , Tian Haixia , Zhang Shuting , Zhou Jianjun , Fan Weiping
Published: June 2020

Background

Increasing evidence in recent years has suggested that Th1, Th17 cells act as a crucial regulatorin autoimmune hepatitis (AIH). Rapamycin, as a inhibitor of mammalian target of rapamycin (mTOR), which modulates T cell activation, differentiation and migration, is known to be able to selectively inhibit the activation of T helper cells including Th1 and Th17 subsets. However, little is known about the underlying regulatory mechanisms.
Results

In this study, we demonstrated that rapamycin ameliorated AIH in mice model by inhibiting Th1 and Th17 cells. Further analysis revealed that the suppressive function of rapamycin was associated with the downregulation of p70s6k-STAT3 signaling, which is downstream of mTOR, in AIH mice.
Conclusions

These findings suggest a previously unrecognized role for rapamycin immunoregulatory function and its protective effect on AIH, providing additional insight for the selection of alternative clinical protocols for autoimmune diseases.
Prognostic and clinicopathological significance of YAP in Colorectal carcinoma: A systematic review and meta-analysis
Authors: Dai Lu , Jin Xiao , Wang Jiayan , Ma Yilan , Yan Haihao , Jin Ye , Zhu Xiaojuan , Liu Zheng
Published: June 2020

Background: YAP is a protein encoded by the YAP gene in humans. Numerous studied showed that YAP expressed in colorecal carcinoma (CRC) and has a association with poor clinical outcomes. However, the association between YAP expression level with prognostic and clinicopathological features in CRC patients remains unclear. Therefore, we performed a meta-analysis to investigate the prognostics effect of YAP expression on CRC patients.Methods: A systematic search of the PubMed, Web of Science, Cochrane Library and Embase databases was conducted based on predefined selection criteria in April 26, 2020. The correlation between YAP expression level and survival outcomes or clinicopathological characteristic was analyzed by hazard ratios (HR) or odds ratios (OR) at 95% confdence intervals (CI).Results: 12 studies were included, with a total of 2286 CRC patients,in our meta-analysis.the results show the relationship between YAP expression level with overall survival (OS) in CRC patients HR (2.02, 95%CI 1.67-2.44 I2 =19.7% P= 0.25) . In addition to clinicpathological features, CRC patients with overexpression of YAP were tend to advanced TNM stage(OR:2.99, 95%CI 2.11-4.25, I2=0.0%, P=0.699), lymph node metastasis(OR:3.73, 95% CI 2.63-5.30, I2=4.8%, P=0.386), distant metastasis(OR:3.03, 95% CI 1.21-7.56, I2=65.3%, P=0.021), tumor invasion depth HR (2.82 95%CI 1.65-4.83 I2=0.0%, p=0.413), but have no associated with sex, tumor size, tumor location and tumor differentiation.Conclusion: The results of this meta-analysis show that high expression of YAP tended to have a worse progosis and have great influence on clinicpathological features. which means YAP may serve as a promising indicator in the prediction of prognosis and clinicopathological features in CRC patients.
Nucleation Heat Treatment on the Crystalline Fraction and Crystal Morphology of Lamav Cad Lithium Disilicate
Authors: Vallerini Bruna de Freitas , Villas-Bôas Mariana de Oliveira Carlos , Pinelli Lígia Antunes Pereira
Published: June 2020

The authors have withdrawn this preprint due to author disagreement.
Designing a nursing care plan based on Johnson's behavioral model in patients with wrist joint hematoma: A case study
Authors: Karkhah Samad , Ghazanfari Mohammad Javad , Norouzi Masoumeh , Khaleghdoust Tahereh , Dahka Samane Mirzaie , Taheri Zahra , ghanbari atefeh
Published: June 2020

BACKGROUND

Nurses can diagnose patients' problems using Johnson's pattern of behavior. This model is applicable and nurses can design and implement patient-based care in a clinical setting based on this model. This study was designed to use Johnson's behavioral model in the care of a middle-aged woman suffering from pain, edema and severe left wrist hematoma.
Methods

This study was conducted with the aim of determine the nursing care plan based on Johnson's behavioral model in patient with wrist joint hematoma in Iran since December 27, 2019 to January 4, 2020, on a case referred to Poursina Hospital in Rasht, Guilan Province, Iran. After assessing the patient, we propound seven main nursing diagnoses and planned them in 9 days according to the model.
Results

After evaluating the patient, the care program was implemented based on Johnson's behavioral model. We achieved caring goals after the intervention. Her appetite and sleep were better, and she became aware of the side effects of her lack of diet and care. She made more efforts to self-care. By using Johnson's care system after 9 days of inpatient care, she has improved her sense of independence, range of motion, self-esteem, sleep quality, increased desire for food, improved excretion and constipation, and we adjusted to reduce libido and use complementary therapies to improve it.
Conclusion

This model can be used as a general framework in the hospital to diagnose problems, evaluate and design a care program.
Follow Up The Children With Ocular Lesion Induced by Two Common Intrauterine Infections(Cytomegalovirus,Toxoplasmosis): A Cohort Study in Tehran,Iran
Authors: Vafaee-Shahi mohammad , noorbakhsh samileh , Tahernia leila , ashouri sarvenaz
Published: June 2020

Background: Intrauterine infections lead to involvement of various organs in fetus, including the eye. The aim of this study was to determine the frequency and clinical response of ocular lesions to specific drugs in infants with congenital Toxoplasma and cytomegalovirus infections.Methods: This historical cohort study was performed in the pediatric and ophthalmology department of Hazrat Rasool Akram Hospital in Tehran from October 2011 to November 2017. Patients included 78 infants with intrauterine infection (proven) and ocular involvement (cataracts, glaucoma, and retinitis). Infants who did not undergo additional and diagnostic tests, eye examinations, follow-up and did not receive effective treatment were excluded from the study. Three patients expired during the study. Finally, 37 patients (including 25 patients with cytomegalovirus and 12 patients with toxoplasma) were included to assess and the clinical response to ocular lesions was evaluated for one year.Results: Of 12 cases with toxoplasmosis, 5 patients received complete treatment and 4 patients had appropriate clinical responses. Of 25 patients with CMV, 18 patients received complete treatment and 9 patients had appropriate clinical responses.Conclusion: Successful treatment will be obtained in near 80% of ocular toxoplasmosis,so anti toxoplasma treatment is recommended in all confirmed cases .About 50% of CMV infected cases (with hearing loss, ocular involvement ) might respond well to antiviral therapy, We recommend anti CMV treatment in any age ( <2 years old) but it is not indicated in CMV infected cases with severe brain involvement.
Femtosecond Laser-Assisted Cataract Surgery in Glaucoma Patients, Case Series.
Authors: Alvarez-Ascencio Daniela , Prado-Larrea Carolina Fernanda , Jimenez-Roman Jesus , Castañeda-Diez Rafael
Published: June 2020

BackgroundWe aim to describe the short-term effect of femtosecond laser-assisted cataract surgery (FLACS) in intraocular pressure (IOP), visual acuity (VA), number of hypotensive medications, and visual fields (VF) in glaucomatous eyes.MethodsSingle-center consecutive case series study included patients with a previous glaucoma diagnosis that needed cataract surgery alone or combined with incisional glaucoma procedure. IOP was measured during surgery immediately before and after pretreatment docking with an indentation tonometer. Changes in visual acuity (VA), IOP, number of medications, and VF were evaluated with a 90 day follow up.ResultsTwenty-seven eyes of 27 patients were included. Mean patient age was 70 years, 70% (n = 19) were female. Glaucoma diagnoses were: twelve patients with primary open-angle glaucoma, 13 with angle-closure glaucoma, and 2 with pseudoexfoliation glaucoma. Twenty-one patients underwent cataract surgery alone and 6 combined with an incisional glaucoma procedure (trabeculectomy or glaucoma drainage device implantation). We found no significant differences between pre-docking IOP (17.59 mmHg ± 6.25 SD) and post-docking IOP (17.23 mmHg ± 7.74 SD) p = 0.7. No surgical complications were recorded. The 90-day postoperative follow up revealed no changes from baseline regarding VF mean deviation, mean IOP, and the number of glaucoma medications decreased in both groups.ConclusionFLACS appears to perform well in the short-term in eyes with glaucoma undergoing cataract surgery alone or with an incisional glaucoma procedure. Comparable outcomes to manual phacoemulsification were obtained regarding IOP, VA, and postoperative period evolution.Clinical SignificanceSafety and efficacy of FLACS have not been properly studied in the glaucoma population, we present a case series with different glaucoma diagnoses who underwent FLACS alone or with an incisional glaucoma procedure.
Hot spot identification by means of classification methods employing wavelet transform-based features
Authors: Tamulewicz Anna , Tkacz Ewaryst , Provazník Ivo
Published: June 2020

Background: Proteins can interact with one another by an interface composed of two proteins. Some of the interface residues - called hot spots - have the greatest impact on binding energy in a protein complex. This paper introduces the application of continuous wavelet transform based on the fast Fourier transform (CWTFT) to the analysis of hot spots in proteins.Results: The algorithm was evaluated by using data sets containing 30 proteins. From the number of tested classifiers the best 10 models were preferred. The classifiers achieved sensitivity of 52% - 71%, specificity of 70% - 83% and accuracy of 70% - 74%.Conclusion: The analyses show that the method combining CWTFT and classification algorithms is able to identify hot spot residues with valuable results.Methods: The basis of the algorithm is extraction of features from spectra obtained by using CWTFT with different wavelet functions including Morlet, m^th order derivative of Gaussian, Paul and Bump wavelets. Then, the classifiers that are able to separate hot spot from non-hot spot residues according to these features are applied.
High intensity versus low intensity family-based childhood obesity treatment programs: Effectiveness, engagement and implementation outcomes from a randomized controlled trial in medically underserved region
Authors: Zoellner Jamie , You Wen , Hill Jennie , Brock Donna-Jean , Yuhas Maryam , Price Bryan , Wilson Jonathon , Montague Danielle Renee , Estabrooks Paul
Published: June 2020

Background

Access to evidence- and family-based childhood obesity (FBCO) treatment interventions in the US is a challenge, especially in medically underserved regions where disparities in childhood obesity persist.
Methods

A comparative effectiveness RCT of two 6-month FBCO treatment interventions varied in structure and contact hours—iChoose (high intensity) and Family Connections (low intensity)—in a medically underserved region. Guided by a systems-based and community-based participatory research approach and the RE-AIM planning and evaluation framework, this paper reports on effectiveness (BMI z-scores) and implementation outcomes. Changes in parent outcomes, secondary outcomes (e.g. QOL, nutrition, physical activity), engagement, and implementation costs are also reported. Analyses included descriptive statistics and intention-to-treat Heckman treatment effect models with cluster robust inference adjustment.
Results
Enrolled children (n = 139, mean age 10.1 ± 1.7 years, 30% overweight, 70% obese, 45% black, 63% on Medicaid) were randomly assigned to iChoose (n = 70) or Family Connections (n = 69). Retention rates were 63% for iChoose and 84% for Family Connection. Among children, 6-month BMI z-score changes were not statistically significant within iChoose [BMI z-score 0.03 (95% CI = -0.13, 0.19)] or Family Connections [BMI z-score 0.00 (95% CI = -0.16, 0.16)]. Likewise, relative between condition effects were not statistically significant and similar null effects were found in parents’ BMI changes. Yet relative to iChoose, Family Connections parents had significant improvement in quality of life (p = 0.03). Both programs were delivered with high fidelity (77–100%). iChoose engagement was 30% family classes, 36% IVR calls, and 25% physical activity classes; Family Connections engagement was 52% parent classes and 61% IVR calls. Implementations costs per children with improved BMI z-score was $2,841 for iChoose and $955 for Family Connections.
Conclusions

Both FBCO treatment interventions were delivered with high fidelity; yet neither yielded significant improvements in child or parent BMI. Relative to iChoose, descriptive data indicated higher retention, better engagement, and lower costs for Family Connections—suggesting that a lower intensity program may better fit the intended audience’s context. Future research efforts need to address lack of program effects and further explore strategies to leverage higher engagement in lower intensity programs for populations in medically underserved areas.
Trial registration:

Clincialtrials.gov: NCT03245775. Registered 10 August 2017. https://clinicaltrials.gov/ct2/show/NCT03245775?term=NCT03245775&draw=2&rank=1
Alarming Symptoms Leading To Severe COVID-19 Pneumonia: A Meta-Analysis
Authors: Ji Weiping , Zhang Jing , Bishnu Gautam , Du Xudong , Chen Xinxin , Xu Hui , Guo Xiaoling , Cai Zhenzhai , Zhang Jun , Shen Xian
Published: June 2020

Background: To identify alarming symptoms that could potentially lead to severe form of COVID-19 pneumonia (i.e. novel coronavirus pneumonia: NCP), a disease that is now having pandemic spread.Methods: Articles from PubMed, Embase, Cochrane database and Google up to 24 February 2020 were systematically reviewed. 18 publications that had documented cases of COVID-19 pneumonia were identified. The relevant data were extracted, systematically reviewed and further evaluated using meta-analysis. We define severe COVID-19 pneumonia as the disease status that requires admission to the intensive care unit (ICU) and respiratory/circulatory support, which is in align with the guideline from the World Health Organization (WHO).Results: 14 studies including 1,424 patients were considered eligible and analyzed. Symptoms such as fever (89.2%), cough (67.2%), fatigue (43.6%) were quite common; but dizziness, hemoptysis, abdominal pain and conjunctival congestion/conjunctivitis were relatively rare. The incidence of dyspnea was significantly higher in patients with severe than non-severe COVID-19 pneumonia (42.7% vs.16.3%, p<0.0001). Similarly, fever and diarrhea were also drastically more common in patients with severe form (p=0.0374 and 0.0267). Further meta-analysis using three high-quality China-based studies confirmed such findings and showed that dyspnea, fever and diarrhea were 3.53 (OR: 3.53, 95%CI: 1.95-6.38), 1.70 (OR: 1.70, 95%CI: 1.01-2.87), and 1.80 (OR: 1.80, 95%CI: 1.06-3.03) folds higher respectively in patients with severe COVID-19 pneumonia.Conclusion: Dyspnea, fever and diarrhea are significantly more prevalent in patients with severe COVID-19 pneumonia, suggesting they are alarming symptoms that warrant close attention and timely management.
Variation in Seedling Germinationand Growth in Five Populations Ofvitellariaparadoxa C.F. Gaertn.subsp. Nilotica: A Threatenedusefulfruit Tree Species in Uganda
Authors: Odoi Juventine Boaz , Odong Thomas L. , Okia Clement Akias , Okullo JohnBosco Lomoris , Okao Moses , Kabasindi Harriet , Muchugi Alice , Gwali Samson
Published: June 2020

Background: We studied seedlings germination and growth performance in an economically and socially important fruit tree species of Vitellaria paradoxaC.F. Gaertn.subsp. nilotica (Kotschy) in Uganda. The study aimed at determining variability in germination of the five shea tree seed lots and seedlings growth performance based on their growth traits. Five populations were considered from four agroecological zones of Uganda and 180 candidates plus trees (16 ethnovarieties) selected as seed trees based on their traits for faster growth and high oil yield. A total of 1204 biological seeds were collected and sown in a general tree nursery at Ngetta Zonal Agricultural Research and Development Institute (NgeZARDI)during the month of June 2018 in a randomized incomplete block design with three replications. Results: Significant variation (χ = 526; p < 0.01) was observed in seedling phenotypic traits within and between populations. Regression equation for height growth and leaf size index were given asy = 0.3787 + 12.671x and y = 0.6483 + 15.413x respectively. Root collar diameter was more correlated to leaf size index (0.425) than to height growth (0.30). Clustering of shea tree seedlings based on phenotypic growth traits revealed one aggregated cluster indicating that most of the seedlings from the five populations were similar (Jaccard index 0.92, p < 0.01). However, clustering based on SNP markers revealed three different populations. We recorded higher growth (χ = 708; p< 0.001) in Arua shea population (19.69 cm)compared to the population average (19.04 cm). Red seeded; thin pulped and hairy fruited shea tree ethnovarieties assumed faster growth than the rest. Conclusions: The phenotypic analysis of shea tree seedlings revealed some fast-growing genotypes from the five studied populations. Thesegenotypes can be selected for faster growth for shea tree breeding in Uganda.
Identify Key Active Ingredients and Molecular Mechanisms of Jiangzhi Decoction on Non-alcoholic Fatty Liver Disease by Network Pharmacology Analysis
Authors: Wang Lei , Zhi Yin , Ye Ying , Zhang Miao , Ma Xing , Tie Hongyun , Xia Wei , Song Yanan
Published: June 2020

Background: Jiangzhi Decoction (JZD), a traditional herb mixture, has shown significant clinical efficacy against non-alcoholic fatty liver disease (NAFLD). However, its multicomponent and multitarget characteristics bring difficulty in deciphering its pharmacological mechanisms. Our study aimed to identify the key active ingredients and core molecular mechanisms of JZD against NAFLD. Methods: The active ingredients were searched from Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and Traditional Chinese Medicine Integrated Database (TCMID). The targets of those ingredients were identified using ChemMapper database based on 3D-structure similarity. NAFLD-related genes were searched from DisGeNET database and Gene Expression Omnibus (GEO) database. Then we obtained candidate targets of JZD against NAFLD by overlapping the active ingredient targets and NAFLD-related genes. We performed protein-protein interaction (PPI) analysis, functional enrichment analysis and constructed pathway networks of “herbs-active ingredients-candidate targets”, and identified the key active ingredients and core molecular mechanisms in the network. Results: We found 147 active ingredients in JZD, 1285 targets of active ingredients, 401 NAFLD-related genes, and 59 overlapped candidate targets of JZD against NAFLD. 22 core targets were obtained by PPI analysis. Finally, nuclear receptor transcription and lipid metabolism regulation were found as the core molecular mechanisms of JZD against NAFLD by functional enrichment analysis, and emodin, emodin anthrone, hyperin, questin, rhein, etc. were speculated as the key active ingredients of JZD. Conclusion: Our study will provide the scientific evidences of the clinical efficacy of JZD against NAFLD.
Association of coffee and caffeine intake with irritable bowel syndrome in adults
Authors: Koochakpoor Glareh , Salari-Moghaddam Asma , Keshteli Ammar Hassanzadeh , Esmaillzadeh Ahmad , Adibi Peyman
Published: June 2020

Background: The aim of this study was to investigate the association between coffee and caffeine intake and odds of IBS and its severity in adult population. Methods: In this cross-sectional study, dietary intakes of 3363 Iranian adults were examined using a validated dish-based 106-item Semi-quantitative Food Frequency Questionnaire (DS-FFQ). Coffee and caffeine intake was assessed using the DS-FFQ. IBS was assessed using a modified Persian version of Rome III questionnaire. Binary logistic regression, in which the effect of several potential confounders were controlled for, was used to examine the association between coffee and caffeine intake and prevalence of IBS and its subtypes. To identify the association with severity of IBS symptoms, we applied ordinal logistic regression. Results: After adjustment for potential confounders, we found that individuals who were taking coffee weekly or more had greater odds of IBS (OR:1.50; 95% CI: 1.07-2.11) than those who never drinking coffee. In addition, participants in the top tertile of caffeine intake had 49% greater odds of IBS compared to those in the bottom tertile (OR: 1.49; 95% CI: 1.16-1.90). By gender, this association was observed among women, but not in men (for coffee: OR: 1.50; 95% CI: 1.00-2.57 and for caffeine: OR: 1.50; 95% CI: 1.12-2.02). In addition, a significant positive association was seen between caffeine intake and odds of IBS among subjects with BMI≥25 kg/m2 (OR: 1.76; 95% CI: 1.22-2.53). There was no significant association between coffee and caffeine intake and IBS severity.Conclusion: Coffee and caffeine consumption was associated with increased odds of IBS, in particular among women and those with BMI ≥ 25 kg/m2.
MAG-DHA Induces Apoptosis and Autophagy in Breast Cancer Cells via Lipid Peroxidation-Mediated Endoplasmic Reticulum Stress
Authors: Zhang Jin-jie , Yang Yong , Wang Feng , Yang Wen-ge , zou Zuquan
Published: June 2020

Background: Epidemiologic and pre-clinical studies have shown that marine n-3 polyunsaturated fatty acids (n-3 PUFAs) elicit promising chemoprevention against breast cancer. Previous studies found that docosahexaenoic acid monoglyceride (MAG-DHA) does not required pancreatic lipase to be absorbed, unlike DHA-triglyceride which needs to be hydrolyzed by sn-1,3’ specific gastric and (colipase-dependent) pancreatic lipases as free fatty acids and monoglycerol prior to intestinal absorption. Therefore, this property confers increased absorption, and thus a better bioavailability when compared with other formulations such as DHA-free fatty acid, DHA-triglycerol (TAG-DHA), or DHA-ethyl ester (EE-DHA). However, the anti-cancer actions of n-3 PUFA monoglyceride on breast cancer remain to be assessed.Methods: SKBR3 and E0771 cells were exposed in vitro to MAG-DHA. Cell viability (by MTT), malondialdehyde (MDA) levels, cell apoptosis and autophagy (by western blot), Beclin1 knockout (by siRNA) was examined. Transmission electron microscopy (TEM) was used for analyzing cell apoptosis and autophagy in vivo breast cancer exnografts. Results: In this study, we showed that docosahexaenoic acid monoglyceride (MAG-DHA) caused oxidative stress as evidenced by MDA accumulation, which triggered endoplasmic reticulum (ER) stress and subsequently induced apoptosis in E0771 and SKBR3 breast cancer cells. In particular, MAG-DHA-induced apoptosis is associated with the activation of the PERK-eIF2α pathway and caspase-12. MAG-DHA treatment also strongly suppressed the growth of E0771 murine breast cancer xenografts, by ER-stress-induced cell apoptosis. In addition, we found that MAG-DHA-induced ER stress concomitantly triggered autophagy in these cancer cells, and the induction of autophagy suppressed its ability to induce apoptotic cell death. Conclusions: Together, our data suggested that MAG-DHA combined with autophagy inhibitors may be a useful therapeutic strategy in treating breast cancer.
Low NOX1 expression in the cytoplasm of GISTs correlates with poor prognosis
Authors: Wang Wei , You Wenjun , Huang Fang , He Xin , Yuan Ao , Zhu Huijun
Published: June 2020

Aim To investigate the protein expression and biological significance of NADPH oxidase l (NOX1) on the growth of human gastrointestinal stromal tumor (GIST), and to test the correlation between NOX1 expression level and patient prognosis.Methods We collected surgical specimens from a series of 146 GIST patients and used immunohistochemistry (IHC) coupled with a GIST tissue microarray to assess the expression pattern of NOXl in GIST. NOX1 mRNA expression in GIST was subsequently confirmed using the online database Oncomine.Results There was a significance association with mitotic index (χ2 = 9.476, p = 0.009) and tumor grade (χ2 = 11.392, p =0.010) in GIST cells with low cytoplasmic NOX1 cytoplasm staining, which comprised 78 of 146 (53.42%) of GIST samples. Univariate analysis showed that overall survival (OS) rate of GIST patients correlated positively with their NOX1 expression level (c2=2.429, p=0.014), tumor diameter (c2=2.048, p=0.004), mitotic index (c2=2.665, p<0.001), and grade (c2=3.162, p=0.001). Moreover, multivariate analyses demonstrated that low cytoplasm expression of NOX1 (c2=2.144, p=0.046) and mitotic index (c2=2.513, p=0.001) had striking effects on OS. Kaplan-Meier survival plots confirmed that patients with low cytoplasmic NOX1 expression and higher mitotic index had an unfavorable prognosis.Conclusion The present study unveils that cytoplasmic NOX1 cytoplasm expression and mitotic index is associated with the development of GIST, in support of NOX1-based gene therapy in treating GIST.
Percutaneous transforaminal endoscopic discectomy ameliorates postoperative reactive pain in patients with lumbar disc herniation
Authors: LI JUN , LI YANG , Wang Deguo
Published: June 2020

Background: Approximately one-third patients with lumbar disc herniation (LDH) who accepted traditional discectomy presented with reactive pain few days after operation, and this reactive pain affected short-term clinical outcomes and postoperative early functional exercise. Recent studies demonstrated that this reactive pain may be ascribed to the increased release of inflammatory mediators caused by surgical trauma. Percutaneous transforaminal endoscopic discectomy (PTED), one of the minimal invasive spinal surgical techniques, was demonstrated to be obviously associated with less soft tissue trauma. The aim of this study is to investigate the postoperative reactive pain in LDH patients undergoing PTED compared with open discectomy. Material and methods: This study included 72 patients (PTED vs. open discectomy: 41 vs. 31), and the incidence of reactive pain, as well as both the extent and duration of reactive pain, were evaluated in both patient groups. Furthermore, inflammation related markers in both blood and drainage fluid samples, including white blood cell (WBC) count, C-reactive protein (CRP), creatine kinase (CK), interleukin-6 (IL-6) and IL-1β, were tested before and/or after operation. Results: Compared with open discectomy, patients undergoing PTED showed lower CK and IL-6 in blood samples, as well as lower IL-6 and IL-1β in drainage fluid samples. Significantly greater number of patients undergoing open discectomy showed reactive pain compared to those undergoing PTED (13/31, 41.9% vs. 7/41, 17.0%; P < 0.05), and the duration of reactive pain is mildly longer in the former (P < 0.05). In both patient groups, the patients with reactive pain showed increased IL-6 and IL-1β in drainage fluid samples, as well as increased IL-6 in blood samples (P < 0.05), and there is significant correlation between the inflammation markers in drainage fluid and both duration and extent of reactive pain in both patient groups (P < 0.05). Conclusions: Local inflammatory substance accumulation may be potential cause for postoperative reactive pain, and PTED may effectively reduce the local inflammatory substances accumulation at the surgical site and reduce the risk of reactive pain.
Obesity Measures and Definitions of Sarcopenic Obesity in Singaporean Adults – the Yishun Study
Authors: Pang Benedict Wei Jun , Wee Shiou Liang , Lau Lay Khoon , Jabbar Khalid Abdul , Seah Wei Ting , Ng Daniella Hui Min , Tan Queenie Lin Ling , Chen Kenneth Kexun , Jagadish Mallya Ullal , Ng Tze Pin
Published: June 2020

Background: The prevalence of sarcopenic obesity (SO) and its effect on functional disability is of particular concern. Due to the lack of a uniform obesity definition, there is marked variability in reported SO prevalence and inconsistent data on observed adverse health outcomes.Objectives: We compare SO prevalence and the associations of SO with physical function using sarcopenia according to current AWGS guidelines with different obesity measures. We recommend that the most optimal SO diagnostic formulation would be one that is most significantly associated with reduced physical function.Design: 542 healthy, community-dwelling Singaporeans were recruited (21-90 years old, 57.9% women). We assessed anthropometry, body composition, and questionnaire-based physical and cognitive factors, and estimated SO prevalence with obesity defined according to waist circumference (WC), percentage body fat (PBF), fat mass index (FMI) and fat mass/fat-free mass ratio (FM/FFM). Muscle function was compared among phenotypes and obesity definitions using ANOVA. Differences across obesity measures were further ascertained using multiple linear regressions to determine their associations with the Short Physical Performance Battery (SPPB).Results: Overall prevalence of SO was 7.6% (WC-based), 5.1% (PBF-based), 2.7% (FMI-based), and 1.5% (FM/FFM-based). The SO phenotype consistently performed poorer than the obese group (p<.05) except for FM/FFM-based measure, and performed poorer than the sarcopenic group in SPPB (p<.05) only in the PBF and FMI-based measures. SO was significantly associated with SPPB only in the FMI and FM/FFM models (p<.05).Conclusions: Our findings suggest FMI as the most preferred measure for obesity and support its use as a diagnostic criteria for sarcopenic obesity.
Evaluation of Health Status of Children with Autoinflammatory Diseases During COVID-19 Pandemic
Authors: Haslak Fatih , Yildiz Mehmet , Adrovic Amra , Sahin Sezgin , Koker Oya , Aliyeva Ayten , Barut Kenan , Kasapcopur Ozgur
Published: June 2020

Since concerns have been raised that comorbidity is a significant risk factor for Coronavirus Disease-2019 (COVID-19), there is an urgent need to perform studies which evaluate patients with chronic diseases such as autoinflammatory diseases (AIDs). We prepared a web-based survey investigating the clinical findings and contagion histories. Patients with AIDs, were included in the study. Confirmed COVID-19 cases, patients with contact history and patients with symptoms which were highly suggestive of COVID-19 were called via phone or recruited to a video or face to face appointment. Data of AIDs were obtained from their medical records, retrospectively. Laboratory and screening findings were confirmed by using our national health registry website and they were re-examined, if required. There were 404 patients (217 female) eligible for the enrollment. During pandemic, 375 (93%) were on colchicine treatment, and 48 (11.8%) were receiving biologic treatment. 24 out of 404 patients had admission to hospital due to COVID-19 suspicion. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were identified through rhino-pharyngeal swabs in 7 patients, 6 of whom were only on colchicine treatment. Only one patient with no finding of any severe respiratory complications has been hospitalized. All of them recovered completely. Among patients on biologic drugs, neither a symptom nor a positive polymerase chain reaction test was detected that would have been suggestive of COVID-19. In conclusion, pediatric patients with AIDs, those receive either biologic treatment or colchicine may not be at increased risk for either being infected or having worse disease course.
Cerebrospinal Fluid Proteomic Changes in Older Non-Cardiac Surgical Patients with Postoperative Cognitive Dysfunction
Authors: VanDusen Keith W. , Qi Wenjing , Li Yi-ju , Cai Victor , Hall Ashley , Hiles Sarah , Thompson J. Will , Mosely M. Arthur , Hu Jessica , Cooter Mary , Acker Leah , Levy Jerrold H. , Ghadimi Kamrouz , Quiñones Quintin J. , Devinney Michael J. , Terrando Niccolò , Moretti Eugene W. , Browndyke Jeffrey N. , Mathew Joseph P. , Berger Miles
Published: June 2020

Background: Postoperative cognitive dysfunction (POCD) is a syndrome of cognitive deficits that occurs in 10-40% of patients age > 60 within 1-12 months after surgery, hypothesized to be caused in part by neuroinflammation. However, the specific neuroinflammatory pathways involved remain unclear. Unbiased mass spectrometry-based proteomic analyses have been used to identify neuro-inflammatory pathways in multiple neurologic diseases and syndromes but have not yet been used in the POCD field. Thus, we used unbiased mass spectrometry-based proteomics to compare cerebrospinal fluid (CSF) samples from patients with and without POCD to identify potential neuroinflammatory pathways for further investigation in future studies. Methods: We performed unbiased LC-MS/MS proteomics on immunodepleted CSF samples obtained before, 24 hours, and 6 weeks after major non-cardiac surgery in older adults who developed (n=8) or did not develop POCD (n=6). General linear mixed models were used to identify peptides and proteins with intensity differences between groups or over time by groups. Kyoto Encyclopedia of Genes and Genomes analysis was used to identify pathways containing proteins/peptides with q values < 0.25 in the mixed model. Results: Mass spectrometry quantified 8258 peptides from 1222 proteins in >50% of patient samples at all three time points. Twelve peptides from 11 proteins showed differences in expression over time between groups (POCD vs non-POCD) at q < 0.05, including several from proteins previously implicated in neurodegenerative disease pathophysiology. Additionally, 283 peptides from 182 proteins were identified with trend-level differences (q < 0.25) in expression over time between these patient groups. Of these 283 peptides with trend-level significance, pathway analysis revealed that 50 of them were from 17 proteins that mapped to the complement and coagulation pathways (q=2.44*10-13).Conclusions: These data demonstrate the feasibility of performing unbiased mass spectrometry on perioperative CSF samples to identify peptides, proteins, and pathways associated with POCD. Additionally, they provide hypothesis-generating evidence for CSF complement and coagulation pathway changes in patients with POCD.
HIF-1α and HIF-2α Mediated PARVB Expression Promotes Tumor Growth and Metastasis in Malignantmelanoma
Authors: Wang Ting , Wu Zhiqiang , Bi Yifeng , Sun Haitao , Wu Zhipeng , Wang Yao , Yan Wangjun , Wei Haifeng , Wang Chunmeng
Published: June 2020

BackgroundMalignant melanoma is the leading cause of skin cancer-related death. The role of PARVB in malignant melanoma remains unclear. Hypoxia is a hallmark of solid tumors including melanoma. But the regulation role of hypoxia in PARVB expression has not been reported.MethodsHuman malignant melanoma tissues, cell lines and their controls were collected. IHC staining, qRT-PCR and Western blot were performed to reveal the differential PARVB expression. The role of PARVB in tumor growth and metastasis of malignant melanoma was evaluated in vitro and in vivo. The regulation role and mechanism of hypoxia and HIFs in PARVB expression was validated by qRT-PCR, Western blot, ChIP-PCR and Luciferase reporter assays.ResultsPARVB was upregulated in malignant melanoma and correlated with patient survival. OverexpressionofPARVB promoted tumor growth and metastasis of malignant melanoma. Furthermore, hypoxia induced HIF-1α and HIF-2α expression activated PARVB transcription and expression through binding to the specific hypoxia-responsive element (HRE) in the promoter region of PARVB.ConclusionsIn malignant melanoma, Hypoxia induced HIF-1α and HIF-2α expression could directly activate PARVB expression, which further promoted tumor growth and metastasis, inducing poor prognosis. These results indicated that PARVB might be a potential therapeutic target for malignant melanoma.
Experimental and Numerical Study of Internal Gear Manufacturing by Flowforming Processand Investigation of Effective Parameters on Teeth Height
Authors: Khodadadi Majid , Khalili Khalil , Ashrafi Amir
Published: June 2020

Manufacturing of internal gears using flowforming process is a difficult to achieve but very interesting process in which the gear may be produced without the need for high forming forces and the need for high cost tooling. In this study, manufacturing of internal gears using flowforming process is studied. The process was numerically analyzed and simulated. Several controlled test were performed to evaluate the validity of simulation.A comparison ofsimulation and experimental results indicates pretty good agreement between these results. Once thesimulationis verified,theeffects of roller diameter, thickness reduction percentage, feed rateand attack angle on teeth height wereobtained using design of experiments (DOE) procedure.
BİLİŞSEL ESNEKLİĞİN BİLİŞSEL DUYGU DÜZENLEME ÜZERİNDEKİ ETKİSİ
Authors: DEMİRCİ Onur Okan , GÜNERİ Elif
Published: June 2020

Bilişsel esnekliğin bilişsel duygu düzenleme üzerindeki etkisinin incelendiği çalışmanın verileri öğrenim görmekte olan 300 üniversite katılımcısından elde edilmiştir. Bilişsel Esneklik Envanteri, Bilişsel Duygu Düzenleme Ölçeği ve Sosyodemografik Veri Formu kullanılmıştır. Çalışma sonucunda; bilişsel esneklikte “alternatif” düzeyinin, bilişsel duygu düzenlemede “diğerlerini suçlama”, “felaketleştirme”, “olumlu yeniden odaklanma”, “plan yapmaya yeniden odaklanma”, “olumlu yeniden değerlendirme” ile pozitif; “kendini suçlama” ve “ruminasyon” düzeylerini negatif yordadığı görülmektedir. Bilişsel esneklikte “kontrol” düzeyinin, bilişsel duygu düzenlemede “kendini suçlama”, “diğerlerini suçlama” düzeylerinin pozitif; “ruminasyon”, “olumlu yeniden odaklanma” ve “plan yapmaya yeniden odaklanma” boyutlarını ise negatif yordadığı görülmektedir. Ek olarak bilişsel duygu düzenlemede kadınların erkeklere göre daha yüksek düzeyde “diğerlerini suçlama” eğilimi gösterirken, erkeklerde kadınlara göre daha yüksek “felaketleştirme” eğilimi görülürken, bilişsel esneklik kadınlar ve erkeklerde bir farklılık göstermemektedir. Bilişsel esneklik ve bilişsel duygu düzenlemede yaş faktörü anlamlı bir farklılık oluşturmamıştır.
On Current Tendencies in Office Space Design
Authors: Novikova Marina Mikhailovna , Butnaru Natalia Georgievna
Published: June 2020

Abstract: the article is devoted to one of the directions of environmental design – office space design, analysis of the current state of office design, specifics of office interior design, stylistic models of modern office design.
Synthesis and Evaluation of Dapagliflozin Ester Prodrugs with Improved Hygroscopicity and Thermal Stability
Authors: Sung Si Young , Chae Yu Na , Lee Dae Young , Kim Kyeong Min , Kim Eun Jung , Han Ji Hye , Kim Wook , Yoon Sung-Hwa
Published: June 2020

Background:

Dapagliflozin, developed as an SGLT-2 inhibitor, has a low melting point
and high hygroscopicity, which needs extreme care during pharmaceutical production to keep the
active pharmacological property. Various attempts have been made to overcome these problematic
properties.

Objectives:

To develop dapagliflozin prodrugs that have similar pharmacological effects with improved
hygroscopicity and thermal stability.

Methods:

The novel dapagliflozin ester prodrugs containing pharmaceutically acceptable moieties
were synthesized and their pharmacokinetics (PK) and physical properties were compared with
dapagliflozin propanediol hydrate (DPD, Farxiga®). The PK in dog and rat, in vitro stability, hygroscopicity,
and physical property studies in accelerated conditions (40°C, 75% RH) were performed
with prodrugs.

Results and Discussion:

Among the eight synthesized prodrugs, Cmax and AUC0-48h values of prodrug
8b (1.35 μg/ml and 14.78 μg·h/ml, respectively) were similar to those of DPD (1.67 μg/ml and
14.27 μg·h/ml, respectively). However, the rest of the prodrugs 8a, 8c, 8d, 8e, 8f, 8g and 8h showed
significantly lower Cmax and AUC0-48h values than DPD. Prodrug 8b completely converted into parent
drug in the body.

Conclusion:

The novel prodrug 8b exhibited comparative PK profile to that of DPD, but with low
hygroscopic property and better thermal stability than DPD.
Rethinking the Use of Mobile Apps for Dietary Assessment in Medical Research (Preprint)
Authors: Khazen Wael , Jeanne Jean-François , Demaretz Laëtitia , Schäfer Florent , Fagherazzi Guy
Published: June 2020

UNSTRUCTURED

Food intake and usual dietary intake are among the key determinants of health to be assessed in medical research and important confounding factors to be accounted for in clinical studies. Although various methods are available for gathering dietary data, those based on innovative technologies are particularly promising. With combined cost-effectiveness and ease of use, it is safe to assume that mobile technologies can now optimize tracking of eating occasions and dietary behaviors. Yet, choosing a dietary assessment tool that meets research objectives and data quality standards remains challenging. In this paper, we describe the purposes of collecting dietary data in medical research and outline the main considerations for using mobile dietary assessment tools based on participant and researcher expectations.