bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunization coverage in Ethiopia among 12-23 month children: systematic review and meta-analysis.
Authors: Nour Tahir Yousuf , Farah1 Alinoor Mohamed , Ali Omer Moeline , Abate Kalkidan Hassen 
Published: February 2020

Abstract
Background: Immunization is cost-effective public health interventions strategies of the decade which under go long and careful process to ensure vaccine safeness before it reaches to the target children, it averts nearly three million mortality annually and immunization coverage is very low comparing all plans at national and regional. The aim of this systematic review and meta-analysis is to assess pooled immunization coverage in Ethiopia.Method: systematic search was done from PubMed, Google Scholar, Embase, and Hinari, SCOPUS, WHO’s Institutional Repository for Information Sharing (IRIS), African Journals Online databases, grey literature and reviewing reference lists of already identified articles. Checklist from the Joanna Briggs Institute was used to assess risk of bias of the included study while heterogeneity was assessed using I2. Funnel plot were used to assess publication bias. Meta-analysis using random effect model was used to estimate the pooled prevalence of immunization among 12-23 month children using STATA 13 software.Result: twenty eight articles were included in the meta-analysis with, a total sample size of 20,048 12-23 months children. The pooled prevalence of immunization among 12-23 month children in Ethiopia was found 47 % (95%, CI: 46.0, 47.0). Subgroup analysis by region indicated the lowest proportion of immunized children in Afar region, 21% (95%, CI: 18.0, 24.0) and the highest in Amhara region, 89% (95%, CI: 85.0, 92.0).Conclusion: Nearly 50% of 12-23 month children were fully vaccinated for this systematic review and meta-analysis but coverage is still low with clear disparity among regions. Mobile and outreach immunization sites should be planned for hard to reach area of pastoral and semi-pastoral regions. Immunization service should be integrated to private for profit and not for profit health facilities which cover 11% of health service coverage in Ethiopia.
Core-binding factor beta is required for osteoblast differentiation during fibula fracture healing
Authors: Guo Tuanmao , Xing Yan-Li , Chen Zhongning , Wang Xianhong , Zhu Hai-Yun , Yang Lan , Yan Yong 
Published: February 2020

Abstract
Background: Growing evidence has implicated core-binding factor beta (Cbfb) as a contributor to the osteoblast differentiation, which plays a key role in fracture healing. Here, we conducted the present study with the main objective to assess whether Cbfb affects osteoblast differentiation after fibula fracture. Methods: Initially, Cbfb conditional knockout mouse model was established. Immunohistochemical staining was carried out to detect the expression of proliferating cell nuclear antigen (PCNA) and Collagen II in the fracture end. Then osteoblasts were isolated from specific Cbfb conditional knockout mice and cultured. BrdU method, Alkaline phosphatase (ALP) staining and Von Kossa staining were followed to detect osteoblast proliferation, differentiation and mineralization, respectively. Western blot analysis and RT-qPCR were used to detect the expression of osteoblast differentiation-related genes. Cbfb conditional knockout mouse model was successfully constructed. Results: The mice treated with Cbfb knockout were shown to exhibit significantly decreased expression of PCNA and Collagen II, ALP activity and mineralization, as well as inhibited expression of Runx2, ALP, BglaPl, SPPl, Osteocalcin, Atf4 and Osterix. Further, Cbfb knockout showed no effects on osteoblast differentiation. Conclusion: Overall, these results demonstrated that the Cbfb could potentially promote fibula fracture healing and osteoblast differentiation and thus could comprise a potential means of impeding the progression of fibula fracture.
Determinants of delayed diagnosis and treatment of tuberculosis in high-burden countries: a mixed-methods systematic review and meta-analysis
Authors: Teo Alvin Kuo Jing , Singh Shweta R , Prem Kiesha , Hsu Li Yang , Yi Siyan 
Published: February 2020

Abstract
Background: Globally, 30 countries with the highest tuberculosis (TB) burden bears 87% of the world’s TB cases. Delayed diagnosis and treatment are detrimental to TB prognosis and sustain TB transmission in the community, making TB elimination a great challenge, especially in these countries. Our objective was to elucidate the determinants and duration of delayed diagnosis and treatment of pulmonary TB in high TB burden countries. Methods: We conducted a systematic review and meta-analysis of quantitative and qualitative studies by searching four databases for literature published between 2008 and 2018 following PRISMA guidelines. For quantitative studies, we performed narrative synthesis of the covariates that were significantly associated with patient, health system, treatment, and total delays. The pooled median duration of delay and effect sizes of covariates were estimated using random-effects meta-analyses. We identified key qualitative themes using thematic analysis. Results: We included 124 articles from 14 low-and lower-middle-income countries (LIC and LMIC) and five upper-middle-income countries (UMIC) in this review. The pooled median duration of patient, health system, and treatment delay were 28 days (95%CI 20–30), 11.5 days (95%CI 3.9–24.7), and six days (95%CI 1–28.4), respectively. We found that the duration of delays was consistently shorter among UMIC compared to LIC and LMIC. There was consistent evidence that being female and rural residence was associated with longer patient delay. Furthermore, patient delay was also associated with other individual, interpersonal, and community risk factors such as poor TB knowledge, long chains of care-seeking through private/multiple providers, perceived stigma, financial insecurities, and poor access to healthcare. Health system and treatment delay were mediated by organizational and policy factors. These factors included the lack of resources and complex administrative procedures and systems at the health facilities. We identified data gaps in 11 high burden countries. Conclusions: This review detailed the determinants of delayed TB diagnosis and treatment in high burden countries. The gaps identified at different socio-ecological levels could be addressed through tailored approaches, education, and at a higher level, through health system strengthening and provision of universal health coverage to reduce delays and improve access to TB diagnosis and care.
Tumor size measured by multidetector CT in resectable colon cancer: Correlation with regional lymph node metastasis
Authors: Mou Anna , Li Hang , Chen Xiaoli , Fan Fanghua , Pu Hong 
Published: February 2020

Abstract
Background : The aim of our study was to determine whether tumor size measured by multidetector computed tomography (MDCT) could be used to evaluate lymph node metastasis (LNM) in patients with resectable colon cancer. Methods: This retrospective study consisted of 106 consecutive patients with colon cancer who underwent radical surgery within 1 week after contrast enhanced-CT scan. Tumor size including tumor length (Tlen), tumor maximum diameter (Tdia), t umor maximum cross-sectional area (Tare) and tumor volume (Tvol) were measured on contrast enhanced-CT images and correlated with pathologic LNM and N stages using univariate analysis, logistic regression analysis and receiver operating characteristic (ROC) curve analysis. Results: The inter - (intraclass correlation coefficient [ICC]=0.94, 0.81, 0.97, 0.99) and intraobserver (ICC=0.95, 0.93, 0.91 and 0.99) reproducibility of Tlen, Tdia, Tare and Tvol parameters measurement is excellent. Univariate analysis showed Tlen, Tdia, Tare, and Tvol could predict LNM (all P <0.05), whereas Tvol was an independent risk factor for LNM (odds ratio =1.09; 95% confidence interval, 1.02-1.17; P =0.017) by logistic regression analysis. Tlen, Tdia, Tare and Tvol could distinguish between N0 and N1, N0 and N2, N0 and N1-2, and N0-1 and N2 disease (all P < 0.05). The area under the ROC (AUC) was higher for Tvol than for Tlen, Tdia and Tare in identifying LNM (AUC =0.83, 0.82, 0.69, 0.79, respectively) and distinguishing N0 from N1 (AUC =0.79, 0.78, 0.63, 0.74, respectively), N0 from N2 (AUC =0.92, 0.89, 0.80, 0.89, respectively), and N0-1 from N2 (AUC =0.84, 0.79, 0.76, 0.83, respectively). Conclusion: Tlen , Tdia, Tare and Tvol measured with MDCT correlated with regional LNM in resectable colon cancer. In particular, Tvol showed the most potential for noninvasive preoperative evaluation of regional LNM.
Long-term follow-up of intrahepatic biliary cystadenoma and cystadenocarcinoma following hepatectomy
Authors: Chen Jiangming , Geng Wei , Zhao Yijun , Xie Kun , Wang Guobin , Liu Fubao , Geng Xiaoping 
Published: February 2020

Abstract
Backgroud: We present our experiences, particularly long term followup, of 20 patients who underwent operations for BCA or BCAC over the last 15 years in an effort to formulate more effective management strategies Methods: Clinical data on patients with pathologically confirmed BCA or BCAC between June 2002 and May 2017 were retrospectively analyzed. Results: Twenty patients were pathologically diagnosed with intrahepatic BCA (12) or BCAC (8); the mean ages for these 2 groups were 46.3 years and 62.0 years, respectively (P = 0.000). The main imaging feature for most BCA patients (83.3%) was cystic mass with septations. The main imaging features for BCAC were unilocular or unilocular cysts with papillary projections or solid portions. All BCAC patients received surgical treatment. No BCA patients developed recurrent cystadenoma after complete excision. Five (62.5 per cent) of the 8 BCAC patients died during a median follow-up time of 61.8 months. Three deaths were due to metastasis. The median follow-up of BCAC patients without a recurrence was 90.7months (range 31–152). Conclusions: Factors associated with a higher likelihood of BCA or BCAC include being a middle-aged or older woman, having elevated serum CA19-9 levels, showing high-risk features on imaging, and having recurrent liver cyst(s). Radical excision is recommended to obtain long-term tumor-free survival.
Frequency-dependent gating of feedforward inhibition in thalamofrontal synapses
Authors: Lee Jungmin , Choi Joonho , Rah Jong Cheol 
Published: February 2020

Abstract
Thalamic recruitment of feedforward inhibition is known to enhance the fidelity of the receptive field by limiting the temporal window during which cortical neurons integrate excitatory inputs. Feedforward inhibition driven by the mediodorsal nucleus of the thalamus (MD) has been observed, but its physiological function and regulation remain unknown. Accumulating evidence suggests that elevated neuronal activity in the prefrontal cortex is required for short-term storage of information. Furthermore, the elevated neuronal activity is supported by the reciprocal connectivity between the MD and the medial prefrontal cortex (mPFC). Therefore, detailed knowledge about the synaptic connections during high-frequency activity is critical for understanding the mechanism of short-term memory. In this study, we examined how feedforward inhibition of thalamofrontal connectivity is modulated by activity frequency. We observed greater short-term synaptic depression during disynaptic inhibition than in thalamic excitatory synapses during high-frequency activity. The strength of feedforward inhibition became weaker as the stimulation continued, which, in turn, enhanced the range of firing jitter in a frequency-dependent manner. We postulated that this phenomenon was primarily due to the increased failure rate of evoking action potentials in parvalbumin-expressing inhibitory neurons. These findings suggest that the MD-mPFC pathway is dynamically regulated by an excitatory-inhibitory balance in an activity-dependent manner. During low-frequency activity, excessive excitation is inhibited, and firing is restricted to a limited temporal range by the strong feedforward inhibition. However, during high-frequency activity, such as during short-term memory, the activity can be transferred in a broader temporal range due to the decreased feedforward inhibition.
Neurofilament degradation is involved in laparotomy-induced cognitive dysfunction in aged rats
Authors: Cao Yiyun , Liu Taotao , Li Zhengqian , Yang Jiao , Ma Lijun , Qi Aihua , Zou Feng , Guo Xiangyang , Wang Aizhong 
Published: February 2020

Abstract
Background An excessive neuroinflammatory response involved in the pathogenesis of postoperative cognitive dysfunction (POCD), which increases morbidity and mortality. However, the precise mechanism remains unclear. Trichostatin A (TSA), a histone deacetylase inhibitor, has been shown to be anti-inflammatory. Therefore, we aimed to explore whether TSA can inhibit the surgery-induced neuroinflammation and improve POCD and further reveal the complex neuropathogenesis underlying POCD. Methods To explore the molecular mechanisms by which surgery-induced POCD in aged rats, TSA (1 mg/kg) was intraperitoneally injected, and hippocampal microglial activation and neuroinflammation were observed. We investigated changes in the protein profile of the hippocampus using a proteomics approach [isobaric tags for relative and absolute quantitation (iTRAQ) combined with nano liquid chromatography-mass spectrometry] at the peak of surgery-induced neuroinflammation, and significant alterations of proteins were verified using western blotting and immunofluorescence. Then, proteins associated with signaling pathways in the surgery + TSA and surgery groups were analyzed using the Kyoto Encyclopedia of Genes and Genomes (KEGG). Results After laparotomy, aged rats had prolonged escape latencies on days 4 and 5 postsurgery, spent less time in the target quadrant than control rats (p < 0.05), and exhibited excessive hippocampal microglia activation and IL-1β and TNF-α release. iTRAQ and bioinformatics analyses at 6 h after surgery showed that neurofilaments (NFs), including the NEFH, NEFM and NEFL proteins, were significantly upregulated, and TSA pretreatment could mitigate these changes. Subsequently, KEGG analysis revealed that nine pathways were enriched in the surgery + TSA group vs. the surgery group (p < 0.05). Among them, two signaling pathways, “focal adhesion” and “ECM-receptor interaction”, were associated with significant upregulation of collagen and downregulation of NF proteins, indicating these as possibly important pathways involved in NF degradation in the hippocampus of aged brains after surgery-induced POCD. Conclusion Surgery-induced neuroinflammation upregulated NFs, resulting NF degradation and aggregation in the hippocampus of aged rats, which might lead to hippocampus-independent learning and memory impairment, contributing to POCD. Additionally, TSA diminished surgery-induced neuroinflammatory responses and modulated the NF-associated changes in cognitive dysfunction in aged brains, which might be related to activation of the “focal adhesion” and “ECM-receptor interaction” pathways.
Human bone marrow mesenchymal stem cells-derived exosomes stimulates cutaneous wound healing thourgh TGF-β/Smad signaling
Authors: Jiang Tiechao , Wang Zhongyu , Sun Ji 
Published: February 2020

Abstract
Background: Cutaneous wound healing represents a morphogenetic response to injury, and it designed to restore anatomic and physiological function. Human bone marrow mesenchymal stem cells-derived exosomes (hBM-MSCs-Ex) is a promising source for cell-free therapy and skin regeneration. Methods: In this study, we investigated the therapeutic effects and underlying mechanism of hBM-MSCs-Ex on cutaneous wound healing in rats. We assessment of the role of hBM-MSCs-Ex in the two type of skin cell: human keratinocytes (HaCaT) and human dermal fibroblasts (HDFs). proliferation in vitro . Furthermore, we used a full-thickness skin wounds to evaluate the effects of hBM-MSCs-Ex on cutaneous wound healing in vivo. Results: Our results demonstrated that hBM-MSCs-Ex promote both two type of skin cell growth effectively and accelerate the cutaneous wound healing ( p <0.01). Then, we found that hBM-MSCs-Ex significantly down-regulated TGF-β1, Smad2, Smad3, and Smad4 expression, while up-regulated TGF-β3 and Smad7 expression ( p <0.05). Conclusions: In conclusion, our findings indicated that hBM-MSCs-Ex effectively promote the cutaneous wound healing through inhibiting the TGF-β/Smad signal pathway, providing a new sight for the therapeutic strategy of hBM-MSCs-Ex for the treatment of cutaneous wounds.
Marital status and survival analysis of patients with pure mucinous breast carcinoma: A SEER Population-Based Retrospective study
Authors: Tang Fan , Wei Xiaoqing , Dian Liping , Xu Rui , Ren Liping , Zhou Quzhi , Chen Qianjun , Zhang Yuzhu 
Published: February 2020

Abstract
Background The present study was conducted to investigate the influence of marital status on survival of pure mucinous breast carcinoma based on surveillance, epidemiology, and end results (SEER) databases.Methods Data were extracted from the SEER database on eligible patients diagnosed with pure mucinous breast carcinoma between 1998 and 2015. Patients were divided into married groups and the not married groups. Survival curves were generated by the Kaplan-Meier method, and survival differences were estimated by using the Log-Rank test. Multivariate Cox Proportional Hazards Models was used to assess independent risk factors for survival.Results A total of 14972 eligible pure mucinous breast carcinoma patients were enrolled from the SEER database, including 7462 (49.84%) married and 7510 (50.16%) not married patients. The OS and CSS were significantly greater in married patients than not married patients (79.27 vs 62.49% for OS and 96.07 vs 93.34% for CSS, both P= 0.000). Among patients older than 75, there were significantly more unmarried patients than married patients (21.5% vs. 44.1%). Compared to the not married patients, cancer stage were even lower (stage I) (69.6% vs. 62.6%), (stage II) (28.6% vs. 33.9%), (stage III) (0.6% vs. 0.9%), (stage IV) (1.3% vs. 2.5%), and more patients received breast conserving surgery (67.4% vs. 62.9%), chemotherapy (15.3% vs. 11.0%) and radiation therapy (54.3% vs. 43.1%). Compared with the not married group, the proportion of non-recurrent lymph node metastasis was (82.8% vs. 74.6%) (All P= 0.000). The Multivariate Cox Proportional Hazards Models showed that marriage is an independent protective factor for OS (HR =1.356, 95% CI: 1.271-1.446, P= 0.000) and CSS (HR =1.942, 95% CI: 1.681–2.644, P= 0.000).Conclusion Marital status was an independent prognostic indicator in pure mucinous breast carcinoma patients. Research data showed that married pure mucinous breast carcinoma patients can obtain better OS and CSS than the not married patients.
SUMOylation protects FASN against proteasomal degradation in breast cancer cells treated with grape leaf extract
Authors: Floris Andrea , Mazarei Michael , Yang Xi , Robinson Aaron Elias , Zhou Jennifer , Barberis Antonio , D’hallewin Guy , Azara Emanuela , Spissu Ylenia , Iglesias-Ara Ainhoa , Orru Sandro , Tomasi Maria Lauda 
Published: February 2020

Abstract
Background: Existing therapeutic strategies for breast cancer are limited by tumor recurrence and drug-resistance. Several epidemiological studies indicate that antioxidant plant-derived compounds such as flavonoids reduce adverse outcomes and have been identified as a potential source of antineoplastic agent with less undesirable side effects. Activation of lipid metabolism is an early event in carcinogenesis and a central hallmark in breast cancer. In fact, inhibition of fatty-acid synthesis in breast cancer results in cytotoxicity that triggers apoptosis. Here, we describe the novel regulation of lipid metabolism in breast cancer cells whereby the protein stability and degradation of fatty-acid synthase (FASN), the key enzyme in de novo fatty-acid synthesis, is regulated by SUMOylation.Methods: The phenolic characterization were analyzed by Liquid Chromatography-Mass Spectrometry (LCMS). Profile protein contents was evaluated by Mass Spectrometry (LC-MS/MS). The experiments were performed using MCF7, SKBR-3 human carcinoma cell lines and MCF-12A breast epithelial cell line treated with Vermentino hydroalcoholic extract in dose and time course responses. Protein and mRNA levels were analyzed by western blotting/Co-immunoprecipitation (Co-IP) and RT-PCR, respectively. The number of viable cells and the cell-surviving has been detected by MTT and clonogenicity assays. Apoptotic induction was determined by Flow Cytometric assay using Annexin V-FITC and sorted by A FACSC analysis.Results: We first tested the potential antitumorigenic effects of Vitis vinifera L. cv. Vermentino leaf hydroalcoholic extract in MCF-7 and SKBR-3 breast cancer cell lines and found that this compound demonstrated cytotoxic effects. We went on to determine that FASN and UBC9, the sole E2 enzyme required for SUMOylation, were significantly reduced by treatment with the Vermentino extract. Moreover, we found that FASN was SUMOylated in human breast cancer tissues and cell lines. Finally, lack of SUMOylation caused by SUMO2 silencing reduced FASN protein stability.Conclusion: Altogether, these results suggest that SUMOylation protects FASN against proteasomal degradation and may exert oncogenic activity through alteration of lipid metabolism in breast cancer. Importantly, we found that these effects were significantly inhibited by treatment with Vermentino leaf extract, which supports the additional validation of the therapeutic value of this compound.
Impact of changes in the methodology of external price referencing on medicine prices: discrete-event simulation
Authors: Vogler Sabine , Schneider Peter , Lepuschütz Lena 
Published: February 2020

Abstract
Background: Several governments apply the policy of external price referencing (EPR), which considers the prices of a medicine in one or more other countries for the purpose of setting the price in the own country. Different methodological choices can be taken to design the EPR policy. The study aimed to analyse whether, or not, and how changes in the methodology of EPR can impact medicine prices.Methods: The real-life EPR methodology as of Q1/2015 was surveyed in all European Union Member States, Iceland, Norway and Switzerland through a questionnaire responded by national pricing authorities. Different scenarios were developed related to the parameters of the EPR methodology. Discrete-event simulations of fictitious prices in the 28 countries of the study that had EPR in place were run for a period of 10 years. The continuation of the real-life EPR methodology in the countries as surveyed in 2015, without any change, served as base case.Results: Consideration of discounts (an assumed 20% discount in five large economies and the mandatory discount in Germany, Greece and Ireland) and determining the reference price based on the lowest price in the country basket would result in higher price reductions (on average -47.2% and -34.2% compared to the base case). An adjustment of medicine price data of the reference countries by purchasing power parities would lead to higher prices in some more affluent countries (e.g. Switzerland, Norway) and lower prices in lower-income economies (Bulgaria, Romania, Hungary, Poland). Regular price revisions and changes in the basket of reference countries would also impact medicine prices, however to a lesser extent.Conclusions: EPR has some potential for cost-containment. Medicine prices could be decreased further if certain parameters of the EPR methodology were changed. If public payers aim to apply EPR to keep medicine prices at more affordable levels, they are encouraged to explore the cost-containment potential of this policy and to take appropriate methodological choices in the design of EPR.