bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.
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

Abstract
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

Abstract
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

Abstract
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.