bluuebunny/crossref_metadata_2025 huggingface dataset:
LncRNA MT1JP Plays a Protective Role in Cholangiocarcinoma by Regulating miR-18a-5p/FBP1 Axie
Authors: Zhao Wei , Zhao Jing , Guo Xiao , Feng Yujie , Zhang Bingyuan , Tian Lantian
Published: August 2020

Background: Cholangiocarcinoma is a common malignant tumor of digestive system. LncRNA MT1JP has been reported to play tumor-suppressing roles in multiple cancers. However, the effect of MT1JP on cholangiocarcinoma has not been evaluated. Methods: The expression of MT1JP in cholangiocarcinoma specimens and paired para-carcinoma tissues were detected by real-time PCR. The overexpression plasmid and siRNA of MT1JP were transfected into cholangiocarcinoma cells to change the expression levels of MT1JP. CCK-8, flow cytometry and transwell assays were performed to measure proliferation, cell cycle transition, apoptosis, migration and invasion in cholangiocarcinoma cells. Dual-luciferase reporter assay, real-time PCR and western blot were carried out to screen the miRNA bound by MT1JP. In addition, xneograft experiment was used to determine the tumorigenesis of cholangiocarcinoma cells in nude. Results: MT1JP was downregulated in cholangiocarcinoma specimens, compared with para-carcinoma tissues, and its expression was related with tumor size, TNM stage and lymph node metastasis. Overexpression of MT1JP inhibited proliferation, cell cycle transition, migration and invasion, and induced apoptosis in cholangiocarcinoma cells. The knockdown of MT1JP led to opposite results. MT1JP bound to miR-18a-5p to facilitate the expression of fructose-1,6-bisphosphatase 1 (FBP1). MiR-18a-5p was increased in cholangiocarcinoma samples, and its expression was negatively correlated with that of MT1JP. In addition, MT1JP also suppressed tumorigenesis in nude mice. Conclusions: MT1JP alleviated proliferation, migration and invasion, and induced apoptosis in cholangiocarcinoma cells by regulating miR-18a-5p/FBP1 axie. These findings may provide novel insights for diagnosis and treatment of cholangiocarcinoma in clinic.
A randomized, multicenter, open-label, adaptive, proof of concept clinical trial of new antivirals working against Sars-CoV2: Direct Antivirals Working against the Novel coronavirus – Azithromycin (DAWn-AZITHRO) trial
Authors: Gyselinck Iwein , Liesenborghs Laurens , Landeloos Ewout , Belmans Ann , Verbeke Geert , Verhamme Peter , Vos Robin , Janssens Wim
Published: August 2020

Background: The rapid emergence and the high disease burden of the novel coronavirus Sars-CoV-2 has created a medical need for readily available drugs that can decrease viral replication or blunt the hyperinflammatory state leading to severe COVID-19 disease. Azithromycin is a macrolide antibiotic, known for its immunomodulatory properties. It has shown antiviral effect specifically against Sars-CoV-2 in vitro, and acts on cytokine signaling pathways that have been implicated in COVID-19.Methods: DAWn-Azithro is a randomized, open-label, phase 2 proof-of-concept, multicenter clinical trial, evaluating the safety and efficacy of azithromycin for treating hospitalized patients with COVID-19. It is part of a series of trials testing promising interventions for COVID-19, running in parallel and grouped under the name DAWn-studies. Patients hospitalized on dedicated COVID-wards are eligible for study-inclusion when they are symptomatic (i.e. clinical or radiological signs) and have been diagnosed with COVID-19 within the last 72 hours through PCR (nasopharyngeal swab or bronchoalveolar lavage), or chest CT scan showing typical features of COVID-19 and without alternate diagnosis. Patients are block-randomized (9 patients) with a 2:1 allocation to receive azithromycin plus standard of care versus standard of care alone. Standard of care is mostly supportive, but may comprise hydroxychloroquine, up to the treating physician’s discretion and depending on local policy and national health regulations. The treatment group receives azithromycin qd 500 mg during the first 5 consecutive days after inclusion. The trial will include 284 patients and recruits from 15 centers across Belgium. Primary outcome is time from admission (day 0) to life discharge or to sustained clinical improvement, defined as an improvement of two points on the WHO 7-category ordinal scale sustained for at least 3 days.Discussion: The trial investigates the urgent and still unmet global need for drugs that may impact on the disease course of COVID-19. It will either provide support or else justify the discouragement of the current widespread, uncontrolled use of azithromycin in patients with COVID-19. The analogous design of other parallel trials of the DAWN-consortium, will amplify the chance of identifying successful treatment strategies and allow comparison of treatment effects within an identical clinical context.Trial registration: EU Clinical trials register, EudraCT Nb 2020-001614-38. Start date 2020-04-22.
Determinants of Family Planning and Child Immunization Services Integration in Urban Areas of Nigeria: A Longitudinal Analysis
Authors: Sheahan Kate , Speizer Ilene , Orgill-Meyer Jennifer , Curtis Sian , Weinberger Morris , Paul John , Bennett Antonia V.
Published: August 2020

Background: Unmet need for contraception is high in the postpartum period. Research has identified the role that integration of family planning into child immunization services can have in addressing this need. However, evidence about the effects of family planning and immunization integration has been inconsistent and more evidence is required to determine whether and how to invest in integration. This study applies continuous facility-level family planning and child immunization integration index scores to: (1) determine whether facility-level integration changes over time, (2) assess the impact of the Nigerian Urban Reproductive Health Initiative (NURHI) - a program that aimed to increase modern contraceptive use - on integration, and (3) identify determinants of integration across facilities in urban areas of Nigeria. Methods: Longitudinal data from health facilities in six urban areas of Nigeria are available from 400 facilities at baseline and 385 facilities at endline. Difference-in-differences models are used to assess the impact of NURHI on Provider Integration and Facility Integration Index scores, and to identify facility-level determinants of integration. The two outcome measures, Provider and Facility Integration Index scores, measure attributes that support integrated service delivery. The independent variables are (1) time period (2) whether the facility received the NURHI intervention, and (3) facility-level characteristics. Results: Our results show that the Provider Integration Index scores increased significantly only among non-intervention facilities while Facility Integration Index scores did not increase significantly in either group. We find that NURHI did not have a significant effect on integration index scores. Results also pinpoint facility characteristics that influence integration, including public ownership and the proportion of providers who have received family planning training. Conclusion: Programs aiming to increase integration of family planning and immunization services should monitor and provide targeted support for the implementation of a well-defined integration strategy that considers the influence of facility characteristics and concurrent initiatives.
Childhood Sanitation Practices and Incidence of Diarrhea in Slum Communities With Implications for Community-Based Education in Less Developed Countries
Authors: Oduaran Akpovire B , Chukwudeh Okechukwu Stephen
Published: August 2020

Background Diarrhoea is a major cause of mortality among under-five children, especially in less developed countries. Previous studies on childhood diarrhoea have largely focused on biomedical methods with little attention given to community-based approach to reduce the prevalence of the disease in the slums, classified in literature among areas of high diarrhoea incidence. The key question is does childhood sanitation practices influence the incidence of diarrhea? This study, was therefore, designed to examine the association between childhood sanitation practices and incidence of diarrhea using community-based approach.Methods The value beliefs and planned behavior theories were adopted as framework, while cross-sectional survey was use to elicit data from 900 mothers of under-five children who had lived in the study locations for at least 12 months preceding the research and 10 In-depth interviews was conducted.Results There was a positive significant association between defecating with unimproved toilet facilities (χ2=42.167, p<0.05), cleaning buttocks with inappropriate materials (χ2=4.274, p<0.05), disposing faeces around household environments (χ2=10.542, p<0.05), and childhood diarrhea. The odds was higher among children whose mothers had no education (OR=1.560), widow (OR=5.542), poor (OR=1.556), and children that defecates with unhygienic toilet facilities (OR=7.806).Conclusion Community perceptions interact with poverty to influence unhygienic toilet practices in the slums. This has negative health implications on the lives of low-income and vulnerable slum dwellers. Thus, community-based education on improved sanitary practices is necessary to reduce diarrhoea prevalence.
A randomized, multicentre, open-label phase II proof-of-concept trial investigating the clinical efficacy and safety of the addition of convalescent plasma to the standard of care in patients hospitalized with COVID-19: the Donated Antibodies Working against nCoV (DAWn-Plasma) trial.
Authors: Devos Timothy , Geukens Tatjana , Schauwvlieghe Alexander , Ariën Kevin K , Barbezange Cyril , Cleeren Myriam , Compernolle Veerle , Dauby Nicolas , Desmecht Daniël , Grimaldi David , Lambrecht Bart N , Luyten Anne , Maes Piet , Moutschen Michel , Romano Marta , Seyler Lucie , Nevessignsky Michel Toungouz , Vandenberghe Katleen , Griensven Johan van , Verbeke Geert , Vlieghe Erika , Yombi Jean Cyr , Liesenborghs Laurens , Verhamme Peter , Meyfroidt Geert
Published: August 2020

Background: The COVID-19 pandemic has imposed an enormous burden on health care systems around the world. In the past, the administration of convalescent plasma of patients having recovered from SARS and severe influenza to patients actively having the disease, showed promising effects on mortality and appeared safe. Whether or not this also holds true for the novel SARS-CoV-2 virus is currently unknown.Methods: DAWn-Plasma is a multicentre nation-wide, randomized, open-label, phase II proof-of-concept clinical trial, evaluating the clinical efficacy and safety of the addition of convalescent plasma to the standard of care in patients hospitalized with COVID-19 in Belgium. Patients hospitalized with a confirmed diagnosis of COVID-19 are eligible when they are symptomatic (i.e. clinical or radiological signs) and have been diagnosed with COVID-19 in the 72 hours before study inclusion through a PCR (nasal/nasopharyngeal swab or bronchoalveolar lavage) or a chest-CT scan showing features compatible with COVID-19 in the absence of an alternative diagnosis. Patients are randomized in a 2:1 ratio to either standard of care and convalescent plasma (active treatment group) or standard of care only. The active treatment group receives 2 units of 200 to 250 mL of convalescent plasma within 12 hours after randomization, with a second administration of 2 units 24 to 36 hours after ending the first administration. The trial aims to include 483 patients and will recruit from 25 centres across Belgium. The primary endpoint is the proportion of patients that require mechanical ventilation or have died at day 15. The main secondary endpoints are clinical status on day 15 and day 30 after randomization, as defined by the WHO Progression 10-point ordinal scale, and safety of the administration of convalescent plasma.Discussion: This trial will either provide support or discourage the use of convalescent plasma as early intervention for the treatment of hospitalized patients with COVID-19 infection. Trial registration: Clinicaltrials.gov, Identifier: NCT04429854. Registered 12 June 2020 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04429854.
Associations of dietary inflammatory index, serum levels of MCP-1 and body composition in Iranian overweight and obese women: a cross-sectional study
Authors: Ghodoosi Nasim , Mirzababaei Atieh , Rashidbeygi Elahe , Badrooj Negin , Sajjadi Seyedeh Forough , Setayesh Leila , Yekaninejad Mir Saeed , Keshavarz Seyed Ali , Shiraseb Farideh , Mirzaei Khadijeh
Published: August 2020

Objective: The relationship between dietary inflammatory index (DII) and obesity-related parameters and inflammation has been examined in several studies but with controversial results. This study aimed to investigate this relationship in Iranian women.Results: Fat-free mass varied between DII groups, but no significant associations were observed between the DII and fat mass. Multivariable linear regression showed that fat-free mass increased by 1.5 kg in the anti-inflammatory diet group, compared to the pro-inflammatory diet group, with adjusted covariates including age, physical activity, economic and job status (β = 1.50, 95% CI 0, 3.01, p = 0.05). Furthermore, multivariable linear regression revealed lower MCP-1 serum levels in the lower DII group, with adjusted covariates including age, weight, physical activity, smoking, economic, and job status (β = -18.81, 95% CI -35.84, -1.79, p = 0.03). Anthropometric variables were not significantly different between the two groups. In conclusion : these findings suggest an inversely significant association between DII and fat-free mass level and a significant direct association between DII and serum MCP-1 levels. The results can be used for developing interventions that aim to promote healthy eating to prevent inflammation and the development of non-communicable diseases among overweight and obese people.
Role of Hakai in m6A modification pathway in Drosophila
Authors: Wang Yanhua , Zhang Lifeng , Ren Hang , Guo Jian , Mao Decai , Yan Dong
Published: August 2020

N6-methyladenosine (m6A), the most abundant internal modification in eukaryotic mRNA, is deposited by a multi-component writer complex. Hakai is an E3 ubiquitin ligase that interacts with several m6A writer subunits in proteomic studies, however, its role in m6A methylation in animals has not been systematically characterized. Here we show that Hakai colocalizes and interacts with other m6A writer components in Drosophila, and Hakai mutants exhibit typic m6A pathway phenotypes, such as lowered m6A levels in mRNA, aberrant Sxl alternative splicing, wing and behavior defects, common reduced m6A peaks and mis-regulated genes with Mettl3 and Mettl14 mutants. These results demonstrate that Hakai is a core component of the m6A writer complex comprised of seven conserved subunits. Interestingly, our stringent meRIP-seq experiments indicate that the effective m6A modification, which depends on the writer complex, is mostly distributed in 5’ UTR and near start codon in Drosophila, in contrast to the mammalian system. We define a set of high-confident m6A methylation sites in 5’ UTR in adult flies and it is unlikely the main function of m6A modification in Drosophila is through RNA degradation. Furthermore, we find that Hakai is required for the protein levels of other m6A writer components Fl(2)d and Flacc, but not Nito. Finally, Hakai does not mediate the stability of E-cadherin in wing discs, suggesting its major role as a nuclear protein.
Efficacy Of Mobile Phone Use On Adherence To Nevirapine Prophylaxis And Retention In Care Among The HIV-Exposed Infants In Prevention Of Mother To Child Transmission Of HIV: A Randomized Controlled Trial
Authors: Kebaya Lilian Maureen Nyatichi , Wamalwa Dalton , Kariuki Nyambura , Admani Bashir , Ayieko Philip , Nduati Ruth
Published: August 2020

Background: HIV is a major contributor to infant mortality. A significant gap remains between the uptake of infant and maternal antiretroviral regimens and only a minority of HIV-exposed infants receives prophylaxis and safe infant feeding. Losses to follow-up of HIV-exposed infants are associated with shortcomings of facility-based PMTCT models with weak community support of linkages. Use of mobile phones offers an opportunity to improving care and promoting retention for the mother-baby pairs and achievement of an HIV-free generation.Objectives: To compare self-reported adherence to infant Nevirapine (NVP) prophylaxis and retention in care over 10 weeks in HIV exposed infants randomized to 2-weekly mobile phone calls (intervention) versus no phone calls (control).Design: Open label Randomized controlled trial Methods: One hundred and fifty HIV infected women drawn from 3 health facilities in Western Kenya and their infants were randomly assigned to receive either phone-based reminders on PMTCT messages or standard health care messages (no calls) within 24 hours of delivery. Women in the intervention arm continued to receive fortnightly phone calls. At 6- and 10-weeks following randomization we collected data on infant adherence to Nevirapine, mode of infant feeding, early HIV testing and retention in care in both study arms. All analyses were intention to treat.Results: At 6 weeks follow-up, 90.7% (n = 68) of participants receiving phone calls reported adherence to infant NVP prophylaxis, compared with 72% (n = 54) of participants in the control group (p = 0.005). Participants in the intervention arm were also significantly more likely to remain in care than participants in the control group [78.7% (n = 59) vs. 58.7% (n = 44), p = 0.009 at 6 weeks and 69.3% (n = 52) vs. 37.3% (n = 28), p < 0.001 at 10 weeks].Conclusions: These results suggest that phone calls are potentially an important tool to improve adherence to infant NVP prophylaxis and retention in care for HIV-exposed infants.Trial registration: PACTR202007654729602. Registered 6 June 2018 - Retrospectively registered, https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=3449
Healthcare Providers and Caregivers’ Perspectives on Factors Underlying the Persistent Malnutrition of Children Aged 0-59 Months in Buhweju District, Southwestern Uganda
Authors: Catherine Abaasa N , Abaasa Catherine N , Rukundo Godfrey Zari , Ayesiga Savino , Atukunda Susan Pearl , Campisi Susan , O’Hearn Shawna , MacDonald Noni
Published: August 2020

Background Nutritional well-being is fundamental to the attainment of the full social, economic, mental and physical potential of individuals, communities and populations. The nutritional well-being of infants and young children is positively and negatively affected by economic, environmental and maternal factors that range from food intake, health, sanitation and care. Several initiatives such as growth monitoring, vitamin A distribution, deworming programs have been undertaken to reduce the impact of nutritional deficiency and promotion of health of children under five years in Uganda. All regions of Uganda have registered unacceptably high levels of childhood malnutrition over the years, although with an uneven distribution across regions. Western Uganda has persistently registered the highest levels of malnutrition with Buhweju district having the highest levels above the national average. This study assessed health provider and caregiver perspectives on factors responsible for persistent malnutrition among children aged 0-59 months in Engaju and Nyakishana sub counties in Buhweju district.Methods Focus group discussions and key informant interviews with Village Health Team members and care takers of children aged 0-59 months in Engaju and Nyakishana sub-counties and healthcare providers in Buhweju district were conducted respectively to explore their perceptives on the factors responsible for persistent malnutrition in Buhweju District in May 2018.Results Inadequate childcare services, poverty and economic occupation, parental alcoholism and domestic violence as well as historic and geographic challenges were identified as factors responsible for persistent malnutrition among children aged 0-59 months in Engaju and Nyakishana sub counties in Buhweju district Conclusion Several factors are responsible for persistent malnutrition of children aged 0-59 months in Buhweju. Some can be readily addressed and should lead to improvement in the nutrition status of children in Buhweju district.
Electronic Reporting of Integrated Disease Surveillance and Response: Lessons Learned from Northeast, Nigeria, 2019.
Authors: Ibrahim Luka Mangveep , Okudo Ifeanyi , Stephen Mary , Ogundiran Opeayo , Pantuvo Jerry Shitta , Oyaole Daniel Rasheed , Tegegne Sisay Gashu , Khalid Abdelrahim , Ilori Elsie , Ojo Olubunmi , Ihekweazu Chikwe , Baraka Fiona , Mulombo Walter Kazadi , Lasuba Clement Lugala Peter , Nsubuga Peter , Alemu Wondimagegnehu
Published: August 2020

Background: Electronic reporting of integrated disease surveillance and response (eIDSR) was implemented in two states in North-East Nigeria as an innovative strategy to improve disease reporting. Its objectives were to improve the timeliness and completeness of IDSR reporting by health facilities, prompt identification of public health events, timely information sharing, and public health action. We evaluated the project to determine whether it met its set objectives.Method: We conducted a cross-sectional study to assess and document the lessons learned from the project. We reviewed the performance of the Local Government Areas (LGAs) on rumors identification and reporting of IDSR data on the eIDSR and the traditional system using a checklist. Respondents were interviewed online on the relevance; efficiency; sustainability; project progress and effectiveness; effectiveness of management; and potential impact and scalability of the strategy using structured questionnaires. Quantitative data were analyzed and presented as proportions using an MS Excel spreadsheet. Qualitative data was cleaned, converted into an MS Excel database, and analyzed using Epi Info version 7.2 to obtain frequencies. Responses were also presented as direct quotes or word clouds.Results: The number of health facilities reporting IDSR increased from 103 to 228 (117%) before and after implementation of the eIDSR respectively. The completeness of IDSR reports in the last six months before the evaluation was ≥ 85%. Of the 201 rumors identified and verified, 161 (80%) were from the eIDSR pilot sites. The majority of the stakeholders interviewed believed that eIDSR met its predetermined objectives for public health surveillance. The benefits of eIDSR included timely reporting and response to alerts and disease outbreaks, improved completeness, and timeliness of reporting, and supportive supervision to the operational levels. The strategy helped the stakeholders to appreciate their roles in public health surveillance.Conclusion: The eIDSR increased the number of health facilities reporting IDSR, enabled early identification, reporting, and verification of alerts, improved completeness of reports, and supportive supervision on staff at the operational levels. It was well accepted by the stakeholder as a system that made reporting easy with the potential to improve the public health surveillance system in Nigeria.
The NeST (Neoadjuvant Systemic Therapy in Breast Cancer Study): National Practice Questionnaire of United Kingdom Multidisciplinary Decision Making
Authors: Whitehead Ian , Irwin Gareth , Bannon Finian , Coles Charlotte , Copson Ellen , Cutress Ramsey , Dave Rajiv , Gardiner Matthew , Grayson Margaret , Holcombe Chris , Irshad Sheeba , O'Brien Ciara , O'Connell Rachel , Palmieri Carlo , Shaaban Abeer , Sharma Nisha , Singh Jagdeep , Potter Shelley , McIntosh Stuart
Published: August 2020

Background: Neoadjuvant systemic therapy (NST) is increasingly used in the treatment of breast cancer, yet it is clear that there is significant geographical variation in its use in the UK. This study aimed to examine stated practice across UK breast units, in terms of indications for use, radiological monitoring, pathological reporting of treatment response, and post-treatment surgical management. Methods: Multidisciplinary teams (MDTs) from all UK breast units were invited to participate in the NeST study. A detailed questionnaire assessing current stated practice was distributed to all participating units in December 2017 and data collated securely usingREDCap. Descriptive statistics were calculated for each questionnaire item.Results: Thirty-nine MDTs from a diverse range of hospitals responded. All MDTs routinely offered neoadjuvant chemotherapy (NACT) to a median of 10% (range 5-60%) of patients. Neoadjuvant endocrine therapy (NET) was offered to a median of 4% (range 0-25%) of patients by 66% of MDTs. The principal indication given for use of neoadjuvant therapy was for surgical downstaging. There was no consensus on methods of radiological monitoring of response, and a wide variety of pathological reporting systems were used to assess tumour response. Twenty-five percent of centres reported resecting the original tumour footprint, irrespective of clinical/radiological response. Radiologically negative axillae at diagnosis routinely had post-NACT or post-NET sentinel lymph node biopsy (SLNB) in 73.0% and 84% of centres respectively, whereas 16% performed SLNB pre-NACT. Positive axillae at diagnosis would receive axillary node clearance at 60% of centres, regardless of response to NACT. Discussion: There is wide variation in the stated use of neoadjuvant systemic therapy across the UK, with general low usage of NET. Surgical downstaging remains the most common indication of the use of NAC, although not all centres leverage the benefits of NAC for de-escalating surgery to the breast and/or axilla. There is a need for agreed multidisciplinary guidance for optimising selection and management of patients for NST. These findings will be corroborated in phase II of the NeST study which is a national collaborative prospective audit of NST utilisation and clinical outcomes.
NQO1 as a marker of chemosensitivity and prognosis for colorectal liver metastasis: A cohort study
Authors: Hirose Yuki , Sakata Jun , Kobayashi Takashi , Miura Kohei , Yuza Kizuki , Nakano Mae , Ichikawa Hiroshi , Nagahashi Masayuki , Shimada Yoshifumi , Kameyama Hitoshi , Wakai Toshifumi
Published: August 2020

Background: NAD(P)H: quinone oxidoreductase-1 (NQO1) is an antioxidant and detoxifying protein, which contributes to chemoresistance in some types of cancer. This study aimed to evaluate how NQO1 affects the response to preoperative chemotherapy and survival after hepatectomy for patients with colorectal liver metastasis (CRLM).Methods: A retrospective analysis was conducted of 88 consecutive patients who underwent curative-intent hepatectomy for CRLM, with a median follow-up period of 65.4 months. Of the 88 patients, preoperative chemotherapy was administered to 30 patients, among which the association between NQO1 status and response to preoperative chemotherapy was evaluated. Immunohistochemistry of the resected specimens was conducted using monoclonal anti-NQO1 antibody.Results: According to NQO1 expression in tumor cells of CRLM, the 88 patients were classified into those with NQO1 expression (the NQO1-positive group) (n = 61) and those with loss of NQO1 expression (the NQO1-negative group) (n = 27). According to NQO1 expression in non-neoplastic epithelial cells of the large intrahepatic bile ducts, which typically show NQO1-positive expression, the 88 patients were classified into the NQO1 non-polymorphism group (positive expression, n = 69) and the NQO1 polymorphism group (loss of expression, n = 19). The NQO1-positive group had significantly worse overall survival than the NQO1-negative group (cumulative 5-year overall survival rate: 66.5% vs. 90.9%, p = 0.026), whereas NQO1 polymorphism status was not associated with overall survival. NQO1-positive expression was an independent adverse prognostic factor in multivariate analysis (hazard ratio: 5.296, p = 0.007). The presence of NQO1 polymorphism (loss of NQO1 expression in non-neoplastic epithelial cells of the large intrahepatic bile ducts) was significantly associated with a better response to preoperative chemotherapy for CRLM (p = 0.004).Conclusions: NQO1-positive expression may be an adverse prognostic factor after hepatectomy for CRLM. NQO1 polymorphism status may be a clinically useful biomarker for predicting the radiological response to preoperative chemotherapy for CRLM.
LAG-3 and PD-1/PD-L1 inhibitors might become a promising treatment for small cell lung cancer
Authors: Xu Yi , Zhang Liping , Wu Shengyu , Zhang Wei , Liu Yu , Chen Bin , Zhao Sha , Li Wei , Sun Chenglong , Wang Hao , Chen Peixin , Wu Chunyan , He Yayi
Published: August 2020

Background Immune therapy has achieved notable success in cancer treatment. A novel immunocheckpoint, Lymphocyte activing gene-3 (LAG-3), has shown promising therapeutic efficacy in non-small cell lung cancer (NSCLC). However, literature about LAG-3 in small cell lung cancer (SCLC) is scarce. We performed statistical analysis to explore LAG-3 expression in SCLC patients, the correlation with programmed death 1 (PD-1) and programmed death ligand 1 (PD-1), the survival predictive significance, and the possibility of becoming an immunotherapeutic checkpoint of SCLC.Methods In this study, we included 102 patients diagnosed with SCLC. The expression of protein was evaluated by immunohistochemistry (IHC) staining. We performed all the correlation analysis and survival analysis with SPSS software (version 17.0; SPSS, Inc.; Chicago, IL)Results In SCLC, none tumor cell expressed LAG-3. LAG-3-positive TILs existed in 39.2% patients. The expression of LAG-3 was remarkably associated to PD-1 and PD-L1 expression on TILs (p = 0.006, p = 0.001). LAG-3 was the only prediction for TILs PD-L1 expression (ORs = 0.161, 95% CI: 0.063–0.412, p < 0.01). Although LAG-3-positive patients had relatively longer RFS, LAG-3 expression had no statistically significant differences in predicting prognosis (p = 0.088).Conclusions LAG-3 is an important immune checkpoint closely related to PD-1/PD-L1. There was significant correlation of LAG-3, PD-1, PD-L1 expression. LAG-3 and PD-1/PD-L1 inhibitors might be a promising immune therapy for SCLC.
Differences in the effect of sleep deprivation on the postural stability among men and women
Authors: Ołpińska-Lischka Marta , Kujawa Karolina , Maciaszek Janusz
Published: August 2020

The authors have withdrawn this preprint due to author disagreement.
Propensity score-matched analysis of systemic chemotherapy versus salvage hysterectomy for persistent cervical cancer after definitive radiotherapy/concurrent chemoradiotherapy.
Authors: Takekuma Munetaka , Takahashi Fumiaki , Mabuchi Seiji , Kudaka Wataru , Horie Koji , Ikeda Mariko , Shikama Ayumi , Mitsuhashi Akira , Nagao Shoji , Suzuki Shiro , Mizuno Mika , Nishio Shin , Tokunaga Hideki , Ota Yukinobu , Kasamatsu Takahiro , Kitagawa Ryo , Toita Takafumi , Kobayashi Hiroaki , Ishikawa Mitsuya , Yaegashi Nobuo
Published: August 2020

Background: The aim of the current study was to evaluate oncologic outcomes of patients who were treated with salvage hysterectomy (HT), compared to systemic chemotherapy (CT) for persistent cervical cancer after definitive radiotherapy (RT)/ concurrent chemoradiotherapy (CCRT).Methods: Patients with persistent cervical cancer treated with definitive RT/CCRT at 35 institutions from 2005–2014 were reviewed retrospectively (n = 317). Those who underwent a HT for persistent cervical cancer after definitive RT/CCRT were matched with propensity scores for patients who underwent systemic CT. Oncologic outcomes between the two groups using a propensity score matched–cohort analysis were compared.Results: A total of 142 patients with persistent cervical cancer after definitive RT/CCRT were included after matching (HT: 71, systemic CT: 71). All background factors between HT and CT groups were well balanced. Median overall survival was 3.8 and 1.5 years in the HT and CT groups, respectively (p= 0.00193, hazards ratio [HR] 0.41, 95% confidence interval [CI] 0.23–0.73), Increasing residual tumor size was significantly associated with a high incomplete resection rate (p = 0.016, Odds Ratio 1.11, 95%CI 1.02-1.22). Severe late adverse events occurred in 7 patients (9.9%) in the HT cohort.Conclusion: The current study demonstrated that, when compared to systemic CT, the adoption of salvage HT for patients with persistent cervical cancer after definitive RT/CCRT reduced mortality rate by about 60%. This indicates that salvage HT could be curative treatment for those patients. Further prospective clinical trials with regard to salvage HT after RT/CCRT are warranted.
Pancreatic Cancer Stem Cells May Define Tumor Stromacharacteristics and Recurrence Patterns in Pancreatic Ductal Adenocarcinoma
Authors: Askan Gokce , Sahin Ibrahim Halil , Chou Joanne F. , Yavas Aslihan , Capanu Marinela , Iacobuzio-Donahue Christine A. , Basturk Olca , O'Reilly Eileen M
Published: August 2020

Background
Herein, we investigate the relationship between pancreatic stem cell markers (PCSC markers), CD44, and epithelial-specific antigen (ESA), tumor stroma, and the impact on recurrence outcomes in pancreatic ductal adenocarcinoma (PDAC) patients.
Methods
PDAC patients who underwent surgical resection between 01/2012 -06/2014 were identified. CD44 and ESA expression was assessed by immunohistochemistry. Stroma was classified as loose, moderate density, and dense based on fibroblast content. Overall survival (OS) and relapse-free survival (RFS) were estimated using the Kaplan-Meier method and compared between subgroups by log-rank test. The association between PCSC markers and stroma type was assessed by Fisher`s exact test.
Results
N = 93 PDAC patients were identified. The number of PDAC patients with dense, moderate density, and loose stroma was 11 (12%), 51 (54%), and 31 (33%) respectively. PDAC with CD44+/ESA− had highest rate of loose stroma (63%) followed by PDAC CD44+/ESA+ (50%), PDAC CD44−/ESA+ (35%), CD44−/ESA− (9%) (p = 0.0033). No local recurrence was observed in patients with dense stroma and 9 had distant recurrence. The highest rate of cumulative local recurrence observed in patients with loose stroma. No statistically significant difference in RFS and OS were observed among subgroups (P = 0.089).
Conclusions
These data indicate PCSCs may have an important role in stroma differentiation in PDAC. Although not reaching statistical significance, we observed more local recurrences in patients with loose stroma, and no local recurrence was seen in patients with dense stroma suggesting tumor stroma may influence the recurrence pattern in PDAC patients.
Development of a Scalable Tele-Monitoring Platform based on the Clinical Decision Support Systems
Authors: yazdani azita , Safdari Reza , Sharifian Roxana , zahmatkeshan maryam
Published: August 2020

Background: One of the most important types of information systems that play important role today in providing quality health care services are clinical decision support systems (CDSSs). These systems are effective in overcoming human resource constraint and intelligent analysis of information generated by Tele-monitoring systems. In spite of the many advantages of this architectures, these are single-purpose, meaning that only the CDSS of a disease is located on them. If we want to use the same model of architecture in the decision-making process of another disease, all the components of this architecture should be redevelopment with a new CDSS, which is time-consuming and costly. Due to the increasing demand for health information technology at low cost and mobile access in the health care industry, in this article, a scalable software platform(Patient Tele monitoring: PATEL) based on SOA for implementing and use different CDSSs on a common platform, for use in Tele-monitoring Systems, was created.Implementation: To develop PATEL platform, the component-based software development approach and hybrid programming approach to implementing various components used. In the evaluation phase of the proposed platform, the case study, accuracy and performance evaluation (transmission delays, patient data fetch, parsing overhead and inference time) used.Results: The results of the case study evaluation confirmed the scalability and interoperability between CDSSs on the platform. Based on performance evaluation, the proposed platform has responded to 89% of the requests in less than one second. Also, based on accuracy evaluation, the platform presented in this article was successful in diagnosing 91.6% of the cases.Conclusion: The proposed platform can support CDSSs of various diseases simultaneously and provides the necessary scalability to add a new CDSS. Tele-monitoring systems will be capable of service by connecting to this platform. Using this infrastructure is expected to be a lot of duplication in the implementation of tele-monitoring systems based CDSSs will be reduced.
De novo characterization of the genetic polymorphism and transcript abundance of Toll-like receptors (TLRs) in tissues of swamp buffaloes (Bubalus bubalis) from Guangxi, China
Authors: Shi Wei , Mei Xuefang , Kang Yangqun , Elsheikha Hany M. , Hu Changhong , Wang Yurui , Lu Kejing , Zhang Yaoyao , Sheng Zhaoan , Wang Dongying , Zhu Xingquan , Huang Weiyi
Published: August 2020

Background: Toll-like receptors (TLRs) are innate signaling receptors, which sense invading pathogens and play roles in induction of immune responses to counter infection. In this study, we for the first time, cloned, sequenced and characterized the coding sequences of TLRs 1-10 in the Chinese “swamp-type” Guangxi (GX) buffalo breed. Results: Protein sequence analysis of the 10 TLRs showed that GX buffalo share significant sequence similarity with river buffalo (94.7 to 99.9%) and other ruminants (89.6% to 99%), but similarity with non-ruminants was low (48% to 91%). Prediction of functional domains revealed the presence of Toll/IL-1 receptor domains and variable numbers of leucine-rich repeats (LRRs) in all TLRs of GX buffalo. Transmembrane domain and signal peptide were absent in TLRs 7, 9 and TLRs 1, 3, 9, 10, respectively. When comparing GX buffalo and Nili-Ravi (NR) buffalo, the similarity of TIR domains ranged from 95.9% to 100%, while variations were found in the number of LRR motifs between these two breeds. Phylogenetic analysis based on the coding DNA and protein sequences demonstrated that, GX buffalo and NR buffalo were closely related with respect to TLRs 1, 2, 4, 5, 7, 8 and 10. However, regarding TLRs 3, 6, and 9, GX buffalo clustered with genera Bos and Bison, but not NR buffalo. RT-qPCR analysis provided an overview of TLRs transcription in tissues of GX buffalo. Conclusions: Our study obtained and characterized the full sequences of 10 TLR genes of GX buffaloes, and comparatively quantified the mRNA expression of these genes across various tissues of GX buffaloes. These findings lay the groundwork for discovering breed-specific differences in the occurrence and progression of infections in buffalo.
Improving Drug Response Prediction Using Dual Similarity Regularization
Authors: EBADI ALI REZA , Soleimani Ali , GHADERZADEH ABDULBAGHI
Published: August 2020

Background:Anti-cancer medicine for a particular patient has been a personal medical goal. Many computational models have been proposed by researchers to predict drug response. But predictive accuracy still remains a challenge. Base on this concept which “Similar cells have similar responses to drugs”, we developed the basic method of matrix factorization method by adding fines to similarity. So that the distance of latent factors to two cell lines or (drug) should be inversely related to similarity. This means that two similar drugs or similar cell lines should have a short distance, whereas two similar cell lines or non-similar drugs should have a large gap with their latent factors.Results:We proposed a Dual similarity-regularized matrix factorization (DSRMF) model, then generated new data for drug similarity from the two-dimensional three-dimensional chemical structure, which were obtained from the CCLE and GDSC databases. In this research, by using the proposed model, and generating new drug similarity data we achieved the average Pearson correlation coefficient (PCC) about 0.96, and average mean square error (RMSE) Root about 0.30, between the observed value and the predicted value for the cell line response to the drug, Conclusions:Our analysis in this research showed, using heterogeneous data, has better results, and can be obtained with the proposed model, using other panels’ cancer cell lines, to calculate similarity between cells. Also, by imposing more restrictions on the similarity between cells, we were able to achieve more accurate prediction for the response of the cell line to the anticancer drug.
Factors Affecting Place of Delivery in Nepal: Evidence From the Nepal Demographic and Health Survey, 2016
Authors: Khatiwada Ganesh
Published: August 2020

Background: Maternal health is still a public health problem in Nepal though it has been improving in the last decade. In Nepal, choosing an institution for delivery and behavior searching for antenatal care (ANC) services have improved since the 1990s. However, a large percentage of women still deliver at home. Studies conducted in developing countries including Nepal presents that various demographic, socio-economic, and economic factors are associated with place of delivery. Methodology: The study was a cross-sectional study. Nepal Demographic and Health Survey (NDHS), 2016 data set were utilized. The likelihood of utilization of institutional delivery among 3998 ever-married women who had at least one live birth in the five years preceding the survey was analyzed in terms of women's demographic, socio-economic, and empowerment status in Nepal. Bivariate logistic regression analysis technique was used to examine the effects of these variables in the use of institutional delivery. Results: The study shows that large variation and gaps exist among women in Nepal in the utilization of an institution for delivery. Factors like women's age, parity, age at first birth, level of women's education, husband's education, household wealth status and women's decision making power strongly influence women to choose the place of delivery in Nepal. Conclusion: This study concludes that different maternal health programs ought to design in order to encourage women for institutional delivery. Coverage along with the quality of interventions that are under operation should be improved. Health programs should be targeted to poor, less educated, young women especially in rural, marginalized, and disadvantaged communities as these particular groups of women are less likely to utilize maternal health services. Finally, there is a need for qualitative research to explore the utilization of maternal health services among women.
Unraveling Historical Trends of Increasing Large-body Dissatisfaction: Disentangling Age-period-cohort Using the Case of South Korea
Authors: Han SeungYong , SturtzSreetharan Cindi , Brewis Alexandra
Published: August 2020

BackgroundOver the last two decades, body dissatisfaction appears to have increased globally, particularly concerns about being “fat”. These increasingly negative large-body norms reflect the intersections of complex socio-cultural phenomena. A range of anthropological theories derived from ethnographic observations across the globe have posited that both changing socioeconomics and internet exposures have increasingly commodified the value of the body in social advancement – especially for women. MethodsUsing demographic data, here we provide a first attempt to explore the sheer effects of individual (i.e., age) and contextual factors (i.e., period and cohort) on body dissatisfaction by using the Hierarchical Age-Period-Cohort (HAPC-CCREM) approach, with a particular emphasis on period effects of internet expansion and macro-economic shifts. The data are drawn from the Korean National Health and Nutrition Examination Survey (KNHANES) collected repeatedly over the period of 2001 to 2017. ResultsThe results show a higher level of body dissatisfaction among Korean women compared to men. Overall period effects indicate a significant increase in the level of body dissatisfaction in the early 2000s, particularly related to increased social media exposure. Although no overall cohort effect was found, early cohorts tend to have a substantial gap in body dissatisfaction levels when examined by socioeconomic status: those with high SES (people with college education and high household income) exhibit a high level of body dissatisfaction and those with low SES exhibit a low level of body dissatisfaction, but over time these begin to converge. ConclusionsThe results suggest a particular role for internet exposure, rather than labor market shifts, in increasing negative classifications of the person’s own body as unacceptably big.
Cigarette Smoking and All-cause Mortality in Rural Chinese Male Adults:15-year Follow-up of the Anqing Cohort Study
Authors: Ye Lijing , Yang Jie , Li Jingyi , Cheng Nannan , Zhang Yue , Lu Xiaofan , Zhou Ziyi , Wang Zhuo , Liu Lishun , Huang Xiao , Song Yun , Xing Shibo , Wang Dongqing , Li Junnong , Wang Binyan , Tang Genfu , Qin Xianhui , Zalloua Pierre , Zhang Huisheng , Yan Fangrong , Xu Xiping
Published: August 2020

Background — According to the Global Burden of Disease Study 2017, smoking is one of the leading four risk factors contributing to deaths in China. We aimed to evaluate the associations of smoking with all-cause mortality in a Chinese rural population.Methods—Male participants over age 45 (n=5,367) from a large familial aggregation study in rural China, were included in the current analyses. A total of 528 former smokers and 3849 current smokers accounted for 10% and 71.7% of the cohort, respectively. Generalized Estimating Equations were used to evaluate the association between baseline smoking status and mortality, adjusting for pertinent covariates. Results—There were 579 recorded deaths during the 15-year follow-up. Current smokers (odds ratio [OR],1.60; 95% CI,1.23-2.08) had higher all-cause mortality risks than nonsmokers. Relative to nonsmokers, current smokers of more than 40 pack-years ([OR],1.85; 95% CI,1.33-2.56) had a higher all-cause mortality risk. Compared to nonsmokers, current smokers who started smoking before age 20 ([OR],1.91; 95% CI,1.43-2.54) had a higher all-cause mortality risk, and former smokers in the lower pack-year group who quit after age 41 (median) ([OR],3.19; 95% CI,1.83-5.56) also had a higher risk of death after adjustment. Furthermore, former smokers who were also former drinkers had the highest significant risk of mortality than people who never smoke and drink.(P for interaction = 0.034).Conclusions—This study provides evidence that current smokers or former smokers have higher mortality risk than nonsmokers and would benefit from cessation at a younger age.