bluuebunny/crossref_metadata_2025 huggingface dataset:
Aucubin alleviates oxidative stress and inflammation via Nrf2-mediated signaling activity in experimental traumatic brain injury
Authors: Wang Han , Zhou Xiaoming , Wu Lingyun , Liu Guangjie , Xu Weidong , Zhang Xiangsheng , Gao Yongyue , Tao Tao , Zhou Yan , Lu Yue , Wang Juan , Deng Chulei , Zhuang Zong , Hang Chunhua , Li Wei
Published: April 2020

Background: Aucubin (Au) has anti-oxidative and anti-inflammatory bioactivities; however, its effects on a traumatic brain injury (TBI) model remain unknown. We explored the potential role of Au in a H 2 O 2 -induced oxidant damage in primary cortical neurons and weight-drop induced-TBI in a mouse model. Methods: Neuronal apoptosis, brain water content, histological damages and neurological deficits and cognitive functions were measured. We performed western blot, TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, Nissl staining, quantitative real time polymerase chain reaction (q-PCR), immunofluorescence/immunohistochemistry and enzyme linked immunosorbent assay (ELISA). RNA interference experiments were performed to determine the effects of Nuclear factor erythroid-2 related factor 2 (Nrf2) on TBI mice with intraperitoneal injection of Au. Results: We found that Au enhanced the translocation of Nrf2 into the nucleus, activated antioxidant enzymes, suppressed excessive generation of reactive oxygen species (ROS) and reduced cell apoptosis in vitro and vivo experiments. In the mice model of TBI, Au markedly attenuated brain edema, histological damages and improved neurological and cognitive deficits. Au significantly suppressed high mobility group box 1(HMGB1)-mediated aseptic inflammation. Nrf2 knockdown in TBI mice blunted the antioxidant and anti-inflammatory neuroprotective effects of the Au. Conclusions: Taken together, our data suggest that Au provides a neuroprotective effect in TBI mice model by inhibiting oxidative stress and inflammatory responses; the mechanisms involve triggering Nrf2-induced antioxidant system.
Molecular assessment of kelch13 non-synonymous mutations in Plasmodium falciparum isolates from Central African Republic (2017–2019)
Authors: Nzoumbou-Boko Romaric , Panté-Wockama Chris-Boris Gildas , Ngoagoni Carine , Petiot Nathalie , Legrand Eric , Vickos Ulrich , Gody Jean-Chrysostome , Manirakiza Alexandre , Ndoua Christophe , Lombart Jean-Pierre , Menard Didier
Published: April 2020

Background: Over the last decade, Artemisinin-based Combination Therapies (ACT) have contributed substantially to the decrease in malaria-related morbidity and mortality. The emergence of Plasmodium falciparum parasites resistant to artemisinin derivatives in Southeast Asia and the risk of their spread or of local emergence in sub-Saharan Africa are a major threat to public health. This study thus set out to estimate the proportion of P. falciparum isolates, with PfKelch13 gene mutations associated with artemisinin resistance previously detected in Southeast Asia. Methods: Blood samples were collected in two sites of Bangui, the capital of the Central African Republic form 2017 to 2019. DNA was extracted and nested PCR were carried out to detect Plasmodium species and mutations in the propeller domain of the PfKelch13 gene. Results: A total of 255 P. falciparum isolates were analyzed. Among them, P. ovale DNA was found in four samples (1.57%, 4/255). Of 187 samples with interpretable PfKelch13 sequences, four isolates presented a mutation in the PfKelch13 gene (2.1%, 4/187), including one non-synonymous mutation (Y653N) (0.5%, 1/187). This mutation has never been described as associated with artemisinin resistance in Southeast Asia and its in vitro phenotype is unknown. Conclusion: This preliminary study indicates the need for a larger study on samples collected across the whole country along with the evaluation of in vitro and in vivo phenotype profiles of PfKelch13 mutant parasites to estimate the risk of artemisinin resistance in the CAR.
Casein phosphopeptide combined with fluoride enhances the inhibitory effect on initial adhesion of Streptococcus mutans to the saliva-coated hydroxyapatite disc
Authors: Wang Xiaodie , Liu Limin , Zhou Xiaoyan , Huo Yongbiao , Gao Jinlong , Gu Haijing
Published: April 2020

Background: Recent preventive strategies for dental caries focus on targeting the mechanisms underlying biofilm formation, including inhibiting bacterial adhesion. A promising approach to prevent bacterial adhesion is to modify the composition of acquired salivary pellicle. This in vitro study investigated the effect and possible underlying mechanism of pellicle modification by casein phosphopeptide (CPP) on Streptococcus mutans (S. mutans) initial adhesion, and the impact of fluoride on the efficacy of CPP. Methods: The salivary pellicle-coated hydroxyapatite (s-HA) discs were treated with phosphate buffered saline (blank control), heat-inactivated 2.5% CPP (negative control), 2.5% CPP (CPP) or 2.5% CPP supplemented with 900 ppm fluoride (CPP + F). After cultivation of S. mutans, the adherent bacteria were visualized by scanning electron microscopy (SEM) and quantitatively evaluated using the plate count method. Confocal laser scanning microscopy (CLSM) was used to evaluate the proportions of total and dead S. mutans. The concentrations of total, free, and bound calcium and fluoride in CPP and fluoride-doped CPP solutions were determined. The water contact angle and zeta potential of s-HA with and without modification were measured. The data were statistically analyzed using one-way ANOVA followed by a Turkey post hoc multiple comparison test.Results: Initial adhesion of S. mutans to s-HA was inhibited in response to pellicle modification by CPP and fluoride-doped CPP, and the latter was more efficient. CLSM analysis showed that the proportion of dead S. mutans did not differ between the groups. Water contact angle and zeta potential decreased after pellicle modification, and both were lowest in the CPP + F group. Conclusions: Pellicle modification by CPP inhibited S. mutans initial adhesion to s-HA, possibly by reducing hydrophobicity and negative charge on the s-HA surface, and incorporating fluoride into CPP enhanced its anti-adhesion effect.
Symptoms of ocular surface disease in construction workers: comparative study with office workers.
Authors: Hernandez-Llamas Sergio , Paz-Ramos Ana Karen , Marcos-González Patricio , Amparo Francisco , Garza Manuel
Published: April 2020

Purpose: To investigate and contrast the prevalence of dry eye symptoms in construction workers and office workers using the OSDI questionnaire.Methods: A cross-sectional, observational study was conducted using the OSDI questionnaire to evaluate dry eye symptoms and associated risk factors. Sampled size calculation with a power of 80% and a 95% degree of confidence suggested the inclusion of 298 participants. Results: We studied 304 subjects (149 construction workers and 155 office workers). More than half (55%) of the participants presented dry eye symptoms (OSDI > 12). The average OSDI score was 21.30 ± 22.20 points, being lower in the group of construction workers (12.45±17.50) than in-office workers (28.51±22.99) (p <0.001). Considering participants who had moderate and severe symptoms (23 to 100 points in OSDI), office workers presented dry eye symptoms 4.15 times more frequently than construction workers (OR 4.15, 95% CI 2.52, 6.85). Women presented statistical evidence of higher OSDI scores than men (32.47 ± 23.72 vs. 14.87 ± 18.48, respectively). Conclusions: Construction workers have four times less risk of presenting dry eye symptoms than people working in the average office space highlighting the pernicious effects of some of the conditions in the office environment to the ocular surface.
Socio-demographic and Clinical Variables associated with the variation of CD4 Cell Count and Body Mass Index (BMI) for HIV Positive adults receiving HAART, a joint longitudinal data analysis
Authors: Tegegne Awoke Seyoum , Ndlovu Principal Ndlovu , Zewotir Temesgen Zewotir
Published: April 2020

Background: The rate of prevalence of HIV among adults has been increasing in Sub-Sahara African countries over the last decade. Currently, an estimated number of 722, 248 people are living with HIV, 23, 000 people are newly infected with HIV and 11,000 people are died because of AIDS related illness. The objective of this study was to identify the most significant variables associated with the variation of CD4 cell count and body mass index (BMI) of HIV positive adults who initiated HAART at Felege Hiwot Teaching and Specialized Hospital, North-West Ethiopia. This study also aimed to compared the precision of parameter estimates conducted by separate and joint models.Methods: To analyze the long-term CD4 cells count and body mass index of HIV infected adults, a cohort longitudinal study of 792 HIV-infected patients was performed. A joint model was employed to identify the variables associated with the variation of CD4 cell count and body mass index of adults receiving treatment at Felege Hiwot Teaching and specialized Hospital. A random of 792 samples was taken among patients using individual charts in the hospital.Results: Among the main effects, Socio-demographic variables (Level of education, level of disclosure of the disease to persons living together and Marital status ), individuals factors(age, weight and gender), economic factors (ownership of cell phone, level of income), clinical factors (baseline CD4 cell count) retention (food and medication adherence, follow-up time/visit) significantly affected the variables of interests. Similarly, the interaction effects of follow-up times/visits * cell phone ownership, follow-up times/visits * gender, age * gender of patients significantly affected both response variables in current investigation.Conclusion: Socio-demographic, individual and Clinical variables had significant effect on CD4 cell count and BMI in HAART medication program. Follow-up time/visit in the HAART program had also direct and significant effect on the variables of interest. Older HIV patients should be targeted by appropriate public health actions, such as opportunistic screening and easier access to healthcare service. The patients should be advised to disclose the disease to get support from communities around them.
Calcium-dependent serine-threonine phosphatase, calcineurin inactivation mediated by baicalein attenuates prion protein-mediated neuronal cell damage
Authors: Hong Jeong-Min , Moon Ji-Hong , Park Sang-Youel
Published: April 2020

Prion diseases are a group of fatal neurodegenerative disorders characterized by neuronal cell death. Calcineurin and autophagy mediate prion-induced neurodegeneration, suggesting that inhibition of calcineurin and autophagy could be a target for therapy. Baicalein has been reported to exert neuroprotective effects against calcium-dependent neuronal cell death. In this study, we investigated the effects of baicalein on the development of prion diseases. We found that baicalein treatment inhibits prion protein-induced apoptosis. Baicalein inhibited calcium up-regulation and protected the cells against prion peptide‑induced neuron cell death by calcineurin inactivation. Furthermore, baicalein increased p62 protein levels and decrease LC3-II protein levels indicating autophagic flux inhibition and baicalein inhibited prion protein-induced neurotoxicity through autophagy flux inhibition. Taken together, this study demonstrated that baicalein attenuated prion peptide-induced neurotoxicity via calcineurin inactivation and autophagic flux reduction, and also suggest that baicalein may be an effective therapeutic drug against neurodegenerative diseases, including prion diseases.
The relations between the level of Mu-opioid receptor (μORs) and postoperative analgesic use in patients undergoing septoplasty: A prospective randomized controlled trial.
Authors: GENCER MUZAFFER , Göçmen Ayşe Yeşim
Published: April 2020

Background: In this study, the μ-Opioid receptor activity was examined before the septoplasty. We assessed preoperative μ-Opioid receptor activity association with postoperative pain level and second analgesic requirement in patients undergoing septoplasty.Methods: In our prospective study, 120 adult patients underwent septoplasty from June 2015 to January 2019 were randomly divided into preop 2 groups. The first group (n=60) was patients given tramadol (1-2 mgr/kg) for postop analgesia, and the second group (control group) (n=60) was initially performed only fentanyl (1 µg/ kg-i.v.) in the induction. The μ-Opioid receptors activities were investigated in preoperative blood samples and compared post-op pain level and requiring time for second analgesic agent. The visual analogue score(VAS) was used to evaluate the postoperative pain degree (0 no pain,10 worst pain). Patients' post op VAS scores were evaluated upon arrival to recovery room, and at 1st, 3rd, 7th, 10th, and 24th hours in postoperative period.Results: Demographic data and perioperative variables was similar in both study group (p<0.05). There was no significant difference between the receptor levels in both two groups and the mean receptor level was 200.94 pg/ml. While the highest receptor level was 489.92 pg/ ml, the lowest receptor level was 94.56 pg/ml. In patients who used tradomal, as the levels of μ-Opioid receptors increased, VAS scores of patients and second analgesic use decreased in post-operative period. Vas scores were lower in the tramadol group compared to the control group. Patients in Tramadol group needed second pain killer later than patients in the Control group.Conclusions: In this study, we revealed that postoperative pain level and second analgesic requirement decreased as μ-Opioid receptor levels increased in tramadol group.Trial registration: This trial was registered retrospectively (The ACTRN: ACTRN12619001652167, registration date: 26/11/2019).
GATA2 mutations in patients with non-tuberculous mycobacterial or fungal infections with unknown immunodeficiency in Brazil
Authors: Almeida Daniela Palheiro Mendes de , Andrade Francianne G. , Santos-Bueno Filipe V. dos , Freitas Dayvison F. Saraiva , Zancopé-Oliveira Rosely M. , Pombo-de-Oliveira Maria S.
Published: April 2020

Background Non-tuberculous mycobacteria (NTM) and invasive fungal infections (IFI) may be considered opportunistic infections in immunocompromised patients with GATA2 haplodeficiency. Sporadic or familial GATA2 mutations are associated with infection susceptibility, autoimmunity, and myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). This work aimed to investigate GATA2 status in patients with NTM and/or IFI with unknown causes for immunodeficiency . Methods A series of incident patients with NTM and/or IFI from the Division of Hematology of the Institute of Infectious Diseases-FIOCRUZ at Rio de Janeiro, Brazil, from 2015 to 2018 were subject to GATA2 genotyping. Patients with HIV positivity or other immunodeficiencies were excluded. Results. Twenty-two patients and 9 of their relatives were enrolled. Seventeen patients had IFI, 4 NTM, and one patient present both infections. In 6 patients, the occurrence of malignant disease was found along with this infection, with MDS/AML (n =3) being the most frequent. The pathogenic T354M mutation was found in 4.5% (1/22) of patients and asymptomatic offspring (2/9). We also found the GATA2 polymorphisms rs2335052 and rs369850507 in 18.2% and 4.5%, respectively, and the rs11708606 intronic polymorphisms in 27.3% of cases. Conclusions GATA2 mutations are substantial findings in patients with NTM and/or IFI without known immunosuppression. As it can indicate a primary immunodeficiency and lead to cancers - particularly MDS and AML- the presentation with NTM or IFI should trigger GATA2 mutation testing. The carriers should receive genetic counseling, subsequent infection prevention measures , and surveillance for hematologic malignancies.
Mechanistic exploration of Cangfu Daotan Decoction for patients with polycystic ovary syndrome by transcriptome sequencing
Authors: Chen Chunyue , Jiang Xuejuan , Wang Chenye , Ding Caifei
Published: April 2020

Background Polycystic ovary syndrome (PCOS) is a common and complex female endocrine disorder. The pathogenesis of PCOS is not fully elucidated. Cangfu Daotan Decoction is a kind of traditional Chinese medicine prescription widely used for PCOS patients.Methods In this study, we treated two PCOS patients with Cangfu Daotan Decoction (CDD) and both patients presented favorable responses to the treatment. We performed RNA-seq to explore the underlying molecular mechanism.Results After data analysis, we found 4 differential expressed genes including S1PR1 , which has been found to be involved in islet β-cell proliferation and cell apoptosis in diabetic mouse models. We also identified 28 differential expressed transcripts including NFATC2 , CD14 and FCGR3A , which are involved in many immune processes.Conclusions After GO enrichment analysis, we found that pathways including viral gene expression and immune response are involved in the efficacy of CDD treatment. Our study provides new evidence to better understand the pathogenesis of PCOS.
A multi-centre, pragmatic, three-arm, individually randomised, non-inferiority, open trial to compare Immediate Oral, Immediate Topical or Delayed Oral Antibiotics for Acute Otitis Media with Discharge in children: The Runny Ear Study (REST): Study protocol.
Authors: Curtis Kathryn , Moore Michael , Cabral Christie , Curcin Vasa , Horwood Jeremy , Morris Richard , Prasad Vibhore , Schilder Anne , Turner Nicholas , Wilkes Scott , Hay Alastair , Taylor Jodi
Published: April 2020

Background

Acute otitis media (AOM) is a common painful infection in children, with around 2.8 million cases presenting to primary care in England and Wales annually. Nearly all children who present to their general practitioner (GP) with AOM or AOM with discharge (AOMd) are treated with oral antibiotics. These can cause side effects; contribute to the growing problem of antimicrobial resistance, and more rarely, allergic reactions. Alternative treatments, such as an antibiotic eardrops or “delayed” oral antibiotics, could be at least as effective and safe as immediate oral antibiotics for children with AOMd.

Methods

REST is a pragmatic, three-arm, individually randomised, non-inferiority trial being conducted in 50 GP practices across the UK. The study aims to recruit 399 children aged (≥12m and <16yrs) presenting to their GP with AOMd. Children will be randomised to one of three arms: immediate ciprofloxacin 0.3% eardrops; delayed oral amoxicillin (clarithromycin if penicillin allergic); or immediate oral amoxicillin (clarithromycin).

Recruitment, including eligibility screening, randomisation and data collection, are conducted using the innovative, TRANSFoRm electronic trial management platform. Integrated within the primary care electronic medical records it provides automatic eligibility checking, part-filling of e-CRFs, study workflow management and routine NHS follow up data collection. The primary outcome is time to resolution of all significant symptoms and will be collected by the parent using a Symptom Recovery Questionnaire (SRQ). Secondary outcomes, including cost-effectiveness, duration of moderately bad or worse symptoms and repeat AOMd episodes, will be collected at day 14 and at 3 months.

Discussion

It is unclear whether prescribing oral antibiotics to children with AoMd results in a reduction in symptoms or a shorter duration of illness. The REST trial will allow us to compare the non-inferiority of: immediate topical ciprofloxacin ear drops, or delayed oral amoxicillin (clarithromycin) against immediate oral amoxicillin (clarithromycin). We aim to recruit 399 patients from 175 practices in the UK. Using the Transform software to randomise participants to the trial will enable recruitment for a relatively uncommon condition.
Molecular etiology of hereditary deafness using next generation sequencing in northwest China
Authors: Wang Suyang , Li Shujuan , Ding Wenjuan , Liu Xiaowen , Zhu Yiming , Duan Lei , Xu Baicheng , Guo Yufen
Published: April 2020

Objective: To analyze the molecular etiology of 92 hereditary deafness families and explore the genetic mechanism of newly identified genes in deafness heritability. Methods: We analyzed the medical history, audiology, imaging, and physical examination data of 92 probands and their family members. Probands were selected from the hereditary deafness database; they did not have any of the common genetic mutation sites. Genomic DNA was extracted from blood samples and next generation sequencing was performed on an Illumina platform, followed by co-segregation analysis of family members. The control group included the clinical data and blood samples from 207 normal hearing people. Results: Among the 92 samples, 30 homozygous variants were identified in 29 autosomal recessive hereditary deafness families, including 6 reported mutations and 26 novel mutations. Among them, MYO15A was the most frequently detected (6/92), followed by mutations in CDH23, OTOF, FGF3 (3/92 each), MYO7A, SLC26A4, MYO6 (2/92 each), BSND, CLDN14, DFNB59, ILDR1, LHFPL5, LRTOMT, TMPRSS3, TPRN, USH1C, and LOXHD1 (1/92 each). Conclusion: In patients with autosomal recessive deafness, the MYO15A, CDH23, OTOF, and FGF3 genes could be used as candidate genes for conventional genetic studies in northwest China.
“Two-colour capsules”: Self-management of health and the commonly used non-prescribed antibiotics amongst pharmacy customers
Authors: Torres Neusa F. , Solomon Vernon P. , Middleton Lyn E.
Published: April 2020

Background: Treating a variety of moderate and severe infections affecting human health is now possible thanks to the utilization of antibiotics. This explains why antibiotics are amongst the most commercialized, prescribed and utilized drugs in the world. Nevertheless, the persistent inappropriate use of these precious drugs is growing, with non-prescription sales and practices of self-medication with antibiotics (SMA) undermining the global efforts to rationalize the use and contain the antimicrobial resistance (AMR). This study aimed at identifying the commonly used antibiotics and the main health conditions leading to the practice of self-medication with antibiotics. Methods: Between October 2018 and March 2019 we conducted a qualitative study with 32 pharmacy customers and 17 pharmacists working in nine private pharmacies in Maputo city. In-depth interviews and focus group discussions (FGD) were conducted with customers while in-depth interviews were held with pharmacists. The interviews were audio-recorded, transcribed, coded and analysed using latent content analysis. The COREQ (Tong, 2007) checklist for interviews and FGD was performed. Results: The frequent use of non-prescribed antibiotics (NPA) was admitted by 30 of the 32 customers while 15 of the 17 pharmacists admitted NPA dispensing. The commonly used NPA were amoxicillin, cotrimoxazole, azithromycin, metronidazole, amoxicillin with clavulanic acid, tetracycline, doxycycline and erythromycin. Those were used after participants self-diagnosed or self-perceived health conditions related to sore throat, fever, cough, vaginal discharge, eye problem, common flu, urinary infection, respiratory infection, wounds and toothaches. Conclusion: The self-management of illness, the need to save time and the therapeutic itineraries customers adopt, together with the suboptimal dispensing practices of pharmacists, enabled the growing practices of SMA among pharmacies customers. These paves the way to the utilization of antibiotics as a daily basis as an approach to self-manage health problems. Contextual interventions are needed to involve public health stakeholders, pharmacists and healthcare professionals to enlighten customers regarding the inappropriate use of antibiotics at all levels.
Economic evaluation of sacubitril/valsartan versus enalapril in the treatment of heart failure with reduced ejection fraction
Authors: SANG Haiqiang , JIANG Yaohui , WANG Zhe , ZHENG Rujie
Published: April 2020

Background: In 2020, sacubitril/valsartan(formerly LCZ696) will implement the new negotiated price of medical insurance in China, and the cost of treatment will be significantly reduced. The aim of study is to evaluate the economy of sacubitril/valsartan(SAC/VAL) compared with an angiotensin converting enzyme inhibitor (ACEI) (enalapril) in the treatment of heart failure with reduced ejection fraction (HFrEF) in China.Method: A Markov model was developed to project clinical and economic outcomes of SAC/VAL versus enalapril for 64-year-old patients with HFrEF over 10 years from the Chinese medical and health system perspective. A cost-utility analysis was performed mostly based on data from the PARADIGM trial. Other transition probability, costs, and utilities were obtained from published literature and public databases. The primary outcome were total and incremental costs and quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER) for SAC/VAL relative to enalapril. The model was verified the uncertainty using the sensitivity analysis furtherly.Results: Compared with enalapril, SAC/VAL cost more than enalapril (¥96532 vs. ¥34560) and was more cost-effective (4.6 QALYs vs. 4.3 QALYs), resulting in an incremental cost-effectiveness ratio of ¥185720 per QALY gained for patients with HFrEF at a WTP threshold of ¥212676 per QALY. Sensitivity analysis demonstrated the robustness of the model, identifying the death on the SAC/VAL group as a significant drivers of the cost-effectiveness. At the national negotiation price (¥9.95 per 100mg), probability of SAC/VAL being cost-effective was about 53% at a WTP threshold of ¥212676 per QALY.Conclusion: SAC/VAL was associated with clinical benefit and may be cost-effective compared with an ACEI (the current standard of care) in patients with HFrEF.
Osteocyte-derived exosomes induced by mechanical strain promote human periodontal ligament stem cell proliferation and osteogenic differentiation in an inflammatory environment via the miR-181b-5p/PTEN/AKT signaling pathway
Authors: Lv Peiying , Gao Pengfei , Yang Yanyan , Wang Zihui , Sun Lu , Mo Feifei , Tian Guangjie , Kuang Mingjie , Wang Yonglan
Published: April 2020

Background: The oral cavity is a complex environment in which periodontal tissue is constantly stimulated by external microorganisms and mechanical forces. Proper mechanical force helps maintain periodontal tissue homeostasis and improper inflammatory response can break the balance. Periodontal ligament (PDL) cells plays crucial roles in responding these challenges and maintaining the homeostasis of periodontal tissue. However, the mechanisms underlying PDL cell property changes induced by inflammatory and mechanical force microenvironments are still unclear. Recent studies have shown that exosomes function as a mean of cell-cell and cell-matrix communication in biological processes. Methods: Human periodontal ligament stem cells (HPDLSCs) were tested by the CCK8 assay, EdU, alizarin red and ALP staining to evaluate the functions of exosomes induced by mechanical strain. MicroRNA sequencing was used to find the discrepancy miRNA in exosomes. In addition, RT-PCR, FISH, luciferase reporter assay and western blotting assay were used to investigated the mechanism of miR-181b-5p regulating proliferation and osteogenic differentiation through the PTEN/AKT pathway. Results: In this study, the exosomes secreted by MLO-Y4 cells exposed to mechanical strain (Exosome-MS) contributed to human periodontal ligament stem cell (HPDLSC) proliferation and osteogenic differentiation. High-throughput miRNA sequencing showed that miR181b-5p was upregulated in Exosome-MS compared to the exosomes derived from MLO-Y4 cells lacking MS. The luciferase reporter assay demonstrated that miR-181b-5p may target Phosphatase tension homolog deletion (PTEN). In addition, PTEN was negatively regulated by overexpressing miR-181b-5p. PCR and western blot analyses verified that miR‐181b-5p enhanced the protein kinase B (AKT) activity and improved downstream factor transcription. Furthermore, miR-181b-5p effectively ameliorated the inhibition of HPDLSC proliferation and osteogenesis induced by inflammation. Conclusions: This study concluded that exosomes induced by mechanical strain promote HPDLSC proliferation and osteogenic differentiation via the miR-181b-5p/PTEN/AKT signaling pathway, suggesting a potential mechanism for maintaining periodontal homeostasis.
Health care utilization and HIV clinical outcomes following Affordable Care Act implementation in California: A longitudinal study
Authors: Satre Derek D. , Parthasarathy Sujaya , Silverberg Michael J. , Horberg Michael , Young-Wolff Kelly C. , Williams Emily C. , Volberding Paul , Campbell Cynthia I.
Published: April 2020

Background: The Affordable Care Act (ACA) increased insurance coverage for people with HIV (PWH) in the United States, yet post-ACA health care utilization and HIV outcomes have rarely been examined. Methods: Among PWH newly enrolled in an integrated health care system (Kaiser Permanente Northern California) in 2014 (N=880), we examined use of health care and modeled associations between enrollment mechanisms (enrolled in a Qualified Health Plan through the California Exchange vs. other sources), deductibles (none, $1-$999 and >= $1000), receipt of benefits from the California AIDS Drug Assistance Program (ADAP), demographic factors, and three-year patterns of health service utilization (primary care, psychiatry, substance treatment, emergency, inpatient) and HIV outcomes (CD4 counts, viral suppression). Results: Health care use was greatest immediately after enrollment and decreased over three years. Those with high deductibles were less likely to use primary care (OR=0.64, 95% CI=0.49 - 0.83, p < 0.001) or psychiatry OR=0.58, 95% CI=0.36, 0.93, p=0.02) than those with low or no deductibles. Enrollment via the Exchange was associated with fewer psychiatry visits (rate ratio [RR]=0.38, 95% CI=0.17 - 0.83; p=0.02), but ADAP was positively associated with number of psychiatry visits (RR=2.22, 95% CI=1.22 – 4.05 p=0.01). There was no association between enrollment mechanism or deductibles and HIV outcomes, but ADAP enrollment was associated with viral suppression (OR=2.23, 95% CI=1.35 - 3.68, p<0.001). Non-white PWH were less likely to be virally suppressed, (OR=0.47, 95% CI= 0.31 - 0.71, p< 0.001). Conclusions: In this sample of PWH drawn from an integrated health care system in California, findings suggest that enrollment via the Exchange and higher deductibles were negatively associated with some aspects of service utilization but did not impact HIV outcomes; support from ADAP appeared to help patients achieve viral suppression; ethnic disparities remain important to address in post-ACA health services for PWH even among those with access to insurance coverage.
Determinants of Fairtrade Channel Choice and its Effect on Income of Coffee Farm Households
Authors: Kudama Gezahagn
Published: April 2020

This article attempts to identify factors determining Fairtrade coffee marketing channel choice and its effect on income of coffee farmers in Jimma zone, based on primary data generated from 153 randomly sampled respondents. The Probit model result ascertain that membership of cooperatives, literacy, access to market information and small-scale coffee farm enhances but remoteness from cooperatives reduces the probability of farmer’s participation in Fairtrade coffee market. Furthermore, OLS model result confirms that coffee farming experience, larger coffee farm, and participation in training lead to increase but access to credit lead to decrease income earning of farmers from coffee. The finding also designates that Fairtrade marketing participation yields considerable income over traditional markets. Based on these, policy measures that advance farmers’ capacity via training, physical access to market places, market information services, participation cooperatives and expansion of Fairtrade markets will lead to increase earning of farmers’ from coffee sector.
Distinct efficacy of postoperative radiotherapy in patients with resected pathological Stage IIIA-N2 lung squamous cell carcinoma
Authors: Tian Cuimeng , Li Baolan , Liu Guimei , Xu Yongxiang , Xia Guangrong , Zhang Tongmei , Huang Jiaqiang , Jiang Hui , Wang Ji Ming
Published: April 2020

Background. The beneficial effect of postoperative radiotherapy (PORT) on resected pathological IIIA-N2 (pIIIA-N2) non-small cell lung cancer (NSCLC) has been a subject of interest with controversy. The aim of this study was to distinguish the clinical efficacy of PORT on lung adenocarcinoma (LADC) and squamous cell carcinoma (LSCC) among pIIIA-N2 NSCLC. Methods. Between October 2010 and September 2016, 288 consecutive patients with resected pIIIA-N2 NSCLC at Beijing Chest Hospital were retrospectively analyzed. There were 194 cases of adenocarcinoma (ADC), 85 cases of squamous cell carcinoma (SCC), 5 cases of large cell carcinoma, 3 cases of adenosquamous carcinoma, and 1 case of clear cell carcinoma. In pIIIA-N2 LADC and LSCC 42 and 19 cases received PORT, respectively. Life Table was used for univariable analyses of factors affecting the rate of overall survival (OS), locoregional recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS). Multivariable Cox proportional hazard models were used to evaluate risk factors affecting OS, LRFS and DMFS. Results. In 194 cases of pIIIA-N2 LADC, smoking index (SI) < 400 (p = .000), a lower number of positive nodes (p = .009), a single N2 station (p = .012) and treatment with postoperative adjuvant chemotherapy (POCT) (p = .006) were independent prognostic factors for OS in multivariable analyses. Other beneficial factors included the use of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) or anaplastic lymphoma kinase (ALK) inhibitors in univariable analyses. PORT failed to show benefit in prolonging the OS of pIIIA-N2 LADC patients. In contrast, in 85 cases of pIIIA-N2 LSCC, PORT alone was a significant positive prognostic factor for OS (p = .027), LRFS (p = .014) and DMFS (p = .030) in multivariable analyses. Stratified analysis revealed older age (≥ 65 years) (p = .031) and lower T stage (p = .042) as predictors of longer OS in PORT group patients of pIIIA-N2 LSCC. Conclusions. Our analysis singled out pIIIA-N2 LSCC as a NSCLC sub population who benefited from PORT, which did not show effect on the OS in pIIIA-N2 LADC. Therefore, pIIIA-N2 LSCC represents a unique cohort among pIIIA-N2 NSCLC and should be considered as an independent patient group with strong indication for PORT.
Trade Agreement as a Model of Development: The Case of the Japan-Philippine Economic Partnership Agreement (JPEPA)
Authors: Navarrete Al Faithrich , Tatlonghari Virgilio
Published: April 2020

The Japan-Philippines Economic Partnership Agreement (JPEPA) includes comprehensive provisions that aims to foster economic growth. The provision on Tariff Elimination is expected to increase trade between the two countries. A modified Gravity Model was used in order to estimate the impact of Tariff Elimination to Exports of the Philippines to Japan using the weighted average of tariffs imposed by Japan to Philippine Exports. While a Two-Stage Least Squares (TSLS) was utilized to estimate its impact to Economic Development. Using quarterly data from 2001 to 2013, results shows that although the agreement is able to statistically increase exports of the Philippines to Japan, it may not be enough to induce significant Economic Growth to the Philippines.
Integrated analysis of lncRNA-miRNA-mRNA ceRNA network and the potential prognosis indicators in sarcomas
Authors: Zhang Ling , Gao Lu , Zhao Yu , Ma Xuelei
Published: April 2020

The ceRNA network has been demonstrated to play crucial roles in multiple biological processes and the development of neoplasms, which have the potential to become diagnostic and prognosis markers and therapeutic targets. In this work, we comparing the expression profiles between sarcoma identified differentially expressed genes (DEGs), lncRNAs (DELs) and miRNAs (DEMs) in sarcomas and normal tissue samples in GEO datasets. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were applied to investigate the major functions of the overlapping DEGs. Then, lncRNA-miRNA interactions and miRNA-mRNA interactions were predicted, and a ceRNA regulatory network was constructed. In addition, the mRNAs included in ceRNA network were used to construct the protein-protein interactions network, and the survival analysis of sarcomas was performed according to the biomarkers included in the ceRNA network. According to the RNA sequence data from GEO dataset, 1296 DEGs were identified in sarcoma samples by combining the GO and Pathway enrichment analysis, 338 DELs were discovered after re-annotating the probes, and 36 DEGs were ascertained through intersecting two different expression miRNAs sets. Further, 448 miRNA-mRNA interactions and 454 miRNA-lncRNA interactions were obtained through target gene prediction, and then, we constructed a lncRNA-miRNA-mRNA ceRNA network containing 9 miRNAs, 69 lncRNAs and 113 mRNAs. PPI network showed that the hub up-regulated nodes include IGF1, PRKCB and GNAI3, and the hub down-regulated nodes include AR, CYCS and PPP1CB. Survival analysis revealed that the expression levels of 12 RNAs involved in the ceRNA network were associated with overall survival of sarcoma patients. Our study showed that the ceRNA network in sarcomas based on that lncRNA could serve as ceRNA and discovered the potential indicators for prognosis of sarcoma patients.
Renegotiation and Stabilization Clauses in Nigeria’s Upstream Petroleum Industry’s Contracts: The Issues and the Options
Authors: OLUJOBI OLUSOLA JOSHUA
Published: April 2020

The authors have removed this preprint from Research Square.
Prevalence, mortality and healthcare economic burden of Tuberous Sclerosis in Hong Kong: a population-based retrospective cohort study (1995-2018)
Authors: Chu William Ching-Yuen , Chiang Lorraine Lok-Wing , Chan Dorothy Chi-Ching , Wong Wilfred Hing-Sang , Chan Godfrey Chi-Fung
Published: April 2020

Background:We aim to elucidate the disease impact by accounting the prevalence, survival rate, genetics, drug use and direct costs of tuberous sclerosis complex (TSC) in our local setting. TSC patients with documented visits to our local public hospitals in 1995-2018 were identified. The public hospitals captured most if not all local TSC patients. Demographics such as age, sex, death, genetic profiles were retrieved from the central electronic database. Data including prevalence, age distribution and survival rate were analysed. Direct cost was calculated with reference to the drug use and number of visits to various public hospital facilities.Results:We identified 284 surviving TSC patients (55.3% male) in Hong Kong. The age range was from 4.5 months to 89.9 years, with a median age of 27.2 years. Paediatrics (<18 years) to adult (≥18 years) ratio was 1:2.84. The overall prevalence of TSC patients was 3.87 in 100,000 (i.e. 1 in 25,833). Genetically, TSC1:TSC2 ratio is 1:2.7.Thirty seven patients died within the study period. The age of death ranged from 7.6 years to 77.8 years, with a median age of death at 36.6 years (IQR: 24.7-51.1 years). Most patients survived till adulthood. Survival rate at 20 and 50 years follow-up was 98.6% and 79.5% respectively. Forty seven (16.5%) TSC patients were prescribed with mTOR inhibitors within the study period. Healthcare facility utilization was further analysed in the 2008-2018 cohort. In particular, the mean number of specialist out-patient clinic visits per patient-year was 9.23 per patient-year, which was 4.91 times more than that of local general population.Conclusions:Prevalence of local TSC patients is within the range of that reported in the literature. Local TSC patients have fair long term survival, but they require disproportionally high healthcare cost when compared with the general population, particularly in terms of outpatient (OP) visits. Although effective disease-modifying agent (i.e. mTOR inhibitor) is available, it was not widely used yet in Hong Kong. Further research on quality of life and setting up a comprehensive patient registry are necessary for more accurate assessment of cost and benefit.
Association between dietary patterns and handgrip strength: analysis of the Korean National Health and Nutrition Examination Survey data between 2014 and 2017
Authors: Kang Yunkoo , Kim Jieun , Kim Do-Yeon , Kim Seung , Park Sowon , Lim Hyunjung , Koh Hong
Published: April 2020

Background Non-invasive anthropometric measurement methods such as those for measuring height and weight are crucial in pediatric patients. However, research focusing on the association between the type of dietary pattern and handgrip strength and handgrip-to-weight ratio in adolescents has not been carried out yet. Methods The current work aims to investigate the association between handgrip strength and dietary patterns in Korean adolescents. This cross-sectional analyses of the 2014-2017 Korean National Health and Nutrition Examination Survey assessed 2,327 adolescent (aged 10-18 years) who had measured handgrip strength and analyzed association between dietary pattern. The mean of three handgrip strength measurements, per hand, was used in the analysis. Handgrip-to-weight ratio was calculated by the following equation: Handgrip strength/body weight (kg)×100). The overall food intake data were subcategorized into 25 food groups from the Korean Nutrient Database. The clusters were examined for nutritional values, and the ready-to-eat , balanced, and western-style fast-food clusters were ultimately generated. The association between handgrip strength, handgrip-to-weight ratio, and dietary intake was analyzed. Results Overall, 85.6% of the participants were assigned to a ready-to-eat dietary pattern, 9.3% to a western-style fast-food dietary pattern, and 5.1% to a balanced dietary pattern. Compared with the participants following a balanced dietary pattern, those following a ready-to-eat dietary pattern were shown to have significantly lower handgrip strength and handgrip-to-weight ratio. However, no significant association was found between handgrip strength or handgrip-to-weight ratio when the western-style fast-food dietary pattern was compared to the balanced dietary pattern. Conclusions Decreased handgrip strength and handgrip-to-weight ratio value in participants following ready-to-eat dietary patterns indicate a diffuse problem in adolescents’ health and possibly imply an association between reduced muscle quality and dietary pattern. Moreover, the overall environmental factors potentially inducing such unhealthy dietary preferences should be investigated, and appropriate lifestyle changes in Korean adolescents should be encouraged.
Analyzing environmental parameters for drying of neem and moringa leaves in solar greenhouse dryer regions of southern India
Authors: K Rajesh , N Shenbaga Vinayaga Moorthi , E Sivakumar
Published: April 2020

The green foliage of plants plays a vital role in the Traditional Medical System(TMS). Especially neem and moringa contains rich nutrients and hence used for medicinal purpose, preserving and drying of these leaves are found to be most important. Using a solar greenhouse dryer(GHD) for this purpose reduces the cost of energy and maintains herbal’s own multifarious spectrum of constituent substances.Drying of these herbals in solar greenhouse dryer depends on the duration of sunshine hours in a particular day, atmospheric pressure, air temperature, relative humidity, wind speed, rainfall, turbidity parameters and transmission coefficients. In the above parameters, finding the longest duration sun shine hours and the best intensity rate of the sunshine are considered to be important to get better performance from the dryer. This communication throws light on the (1) Best time to start the drying process in a particular day ,month and year in GPS co-ordinates (12.2253° N, 79.0747° E) of Tiruvannamalai, Tamilnadu (2) Fabrication of the experimental setup of solar greenhouse dryer (3) Conducting the test for reduction of moisture up to safe limit of moisture content (4) Experimental results are to be validated with the theoretical results.
Dynamic changes of D-Dimer and Neutrophil-Lymphocyte Count Ratio as prognostic biomarkers in COVID-19
Authors: Ye Wenjing , Chen Guoxi , Li Xiaopan , Lan Xing , Ji Chen , Hou Min , Zhang Di , Zeng Guangwang , Wang Yaling , Xu Cheng , Lu Weiwei , Cui Ruolin , Cai Yuyang , Huang Hai , Yang Ling
Published: April 2020

Background Since December 2019, the outbreak of COVID-19 caused a large number of hospital admissions in China. Many patients with COVID-19 have symptoms of acute respiratory distress syndrome, even are in danger of death. This is the first study to evaluate dynamic changes of D-Dimer and Neutrophil-Lymphocyte Count Ratio (NLR) as a prognostic utility in patients with COVID-19 for clinical use.Methods In a retrospective study, we collected data from 349 hospitalized patients who diagnosed as the infection of the COVID-19 in Wuhan Pulmonary Hospital. We used ROC curves and Cox regression analysis to explore critical value (optimal cut-off point associated with Youden index) and prognostic role of dynamic changes of D-Dimer and NLR.Results 349 participants were enrolled in this study and the mortality rate of the patients with laboratory diagnosed COVID-19 was 14.9%. The initial and peak value of D-Dimer and NLR in deceased patients were higher statistically compared with survivors (P<0.001). There was a more significant upward trend of D-Dimer and NLR during hospitalization in the deceased patients, initial D-Dimer and NLR were lower than the peak tests (MD) -25.23, 95% CI:-31.81- -18.64, P <0.001; (MD) -43.73, 95% CI:-59.28- -31.17, P <0.001. The test showed a stronger correlation between hospitalization days, PCT and peak D-Dimer than initial D-Dimer. The areas under the ROC curves of peak D-Dimer and peak NLR tests were higher than the initial tests (0.94(95%CI: 0.90-0.98) vs. 0.80 (95% CI: 0.73-0.87); 0.93 (95%CI:0.90-0.96) vs. 0.86 (95%CI:0.82-0.91). The critical value of initial D-Dimer, peak D-Dimer, initial NLR and peak NLR was 0.73 mg/L, 3.78 mg/L,7.13 and 14.31 respectively. The multivariable Cox regression analysis showed that age (HR 1.04, 95% CI 1.00-1.07, P=0.01), the peak D-Dimer (HR 1.03, 95% CI 1.01-1.04, P<0.001) were prognostic factors for COVID-19 patients’ death.Conclusions To dynamically observe the ratio of D-Dimer and NLR was more valuable during the prognosis of COVID-19. The rising trend in D-Dimer and NLR, or the test results higher than the critical values may indicate a risk of death for participants with COVID-19.