bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leptin down-regulates KCC2 activity and controls chloride homeostasis in the neonatal rat hippocampus.
Authors: Dumon Camille , Belaidouni Yasmine , Diabira Diabe , Appleyard Suzanne , Wayman Gary , Gaiarsa Jean-Luc 
Published: October 2020

Abstract
The canonical physiological role of leptin is to regulate hunger and satiety acting on specific hypothalamic nuclei. Beyond this key metabolic function; leptin also regulates many aspects of development and functioning of neuronal hippocampal networks throughout life. Here we show that leptin controls chloride homeostasis in the developing rat hippocampus in vitro. The effect of leptin relies on the down-regulation of the potassium/chloride extruder KCC2 activity and is present during a restricted period of postnatal development. This study confirms and extends the role of leptin in the ontogenesis of functional GABAergic inhibition and helps understanding how abnormal levels of leptin may contribute to neurological disorders.
Atypical presentations of pulmonary sarcoidosis: Three cases report and literature review
Authors: Zhang Qian , Huang Hui , Wang Na , Feng Ruie , Xu Zuojun 
Published: October 2020

Abstract
Background: Sarcoidosis is a systematic disease with unknown etiology and lung involved predominantly and also known as a “great mimicker” in lung disease for its characteristics of various appearances in radiology images.Case presentation: In this article, we present three sarcoidosis patients with atypical manifestation in their imaging performance, including cavitation sign, reversed-halo sign and distributed small nodules with ground glass opacities in both lungs resembled the manifestation of chronic hypersensitive pneumonia. They were diagnosed with sarcoidosis after the confirmation by pathological evidence and received relevant corticosteroid treatment. We also made a literature review from “pubmed” databases to analysis the atypical sarcoidosis performances in past five years. Conclusions: The atypical manifestation on HRCT of sarcoidosis patients presented in different types which could be ignored by clinicians. Pathology biopsy and clinical characteristics are valuable clues for precise diagnose of sarcoidosis. Thus, clinicians should be on high alert of differential diagnosis and reasonable treatment.
Parthenolide inhibits the growth of non-small cell lung cancer by targeting epidermal growth factor receptor
Authors: Li Xiaoling , Huang Riming , Li Mingyue , Zhu Zheng , Chen Zhiyan , Cui Liao , Luo Hui , Luo Lianxiang 
Published: October 2020

Abstract
Background: EGFR tyrosine kinase inhibitors (TKIs) have been developed for the treatment of EGFR mutated NSCLC. Parthenolide, a natural product of parthenolide, which belongs to the sesquiterpene lactone family and has a variety of biological and therapeutic activities, including anti-cancer effects. However, its effect on non-small cell lung cancer is little known. Methods: The CCK‑8 assay and colony formation assays were used to assess cell viability. Flow cytometry was used to measure the cell apoptosis. In silico molecular docking was used to evaluate the binding of parthenolide to EGFR. Network pharmacology analysis was was used to evaluate the key gene of parthenolide target NSCLC. Western blotting was used to evaluate the key proteins involved apoptosis and EGFR signalling. The effect of parthenolide treatment in vivo was determined by using a xenograft mouse model.Results: In this study, parthenolide could induce apoptosis and growth inhibition in the EGFR mutated lung cancer cells. Parthenolide also reduces the phosphorylation of EGFR as well as its downstream signaling pathways MAPK/ERK and PI3K/Akt. Molecular docking analysis of EGFR binding site with parthenolide show that the anti-cancer effect of parthenolide against NSCLC is mediated by a strong binding to EGFR. Network pharmacology analysis show parthenolide suppresses NSCLC via inhibition of EGFR expression. In addition, parthenolide inhibits the growth of H1975 xenografts in nude mice, which is associated with the inhibition of the EGFR signaling pathway. Conclusions: Taken together, these results demonstrate effective inhibition of parthenolide in NSCLC cell growth by targeting EGFR through downregulation of ERK and AKT expression, which could be promisingly used for patients carrying the EGFR mutation.
Epidermal Growth Factor Receptor-Mutant Non-Small Cell Lung Cancer and Choroidal Metastases: Long-Term Outcome and Response to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors
Authors: Bouchez Clémentine , Pluvy Johan , Soussi Ghassen , Nguenang Marina , Brosseau Solenn , Tourne Morgan , Collin Mégane , Théou-Anton Nathalie , Guyard Alice , Ammar Jamila , Khalil Antoine , Zalcman Gérard , Gounant Valérie 
Published: October 2020

Abstract
Background: Choroidal metastases are the most common eye metastatic site. The prevalence of choroidal metastases in NSCLC patients has been reported to vary from 0.2% to 7% in historical series. Although previously reported, little is known about choroidal metastasis in Epidermal Growth Factor Receptor (EGFR)-mutant Non-small cell lung cancer (NSCLC). This study sought to describe the prevalence of choroidal metastases among patients with EGFR-mutated NSCLC and their characteristics, and to estimate their impact on prognosis.Methods: We conducted a single-center retrospective study including all consecutive metastatic EGFR-mutant NSCLC patients, from Sept. 2015 to Oct. 2018. The EGFR-mutant NSCLC patients were identified via the Department of Genetics’ files. Patients who exhibited choroidal metastases were compared to patients without choroidal metastases. Kaplan-Meier analysis and log-rank test were conducted to assess median overall survival (OS) from diagnosis for the two groups. The study was approved by the IRB as CEPRO number #2020-010.Results: Prevalence of choroidal metastases in EGFR-mutated NSCLCs was 8.4% (7/83). Five were women, and four current or former smokers. Molecular analysis showed three tumors with exon 19 deletion, three with L858R mutation, and one with complex exon 21 mutation. The choroidal metastases were symptomatic in six/seven patients. Visual disturbances decreased in all but one symptomatic cases upon EGFR TKI, and the choroidal response was maintained over time.Median follow-up was 42.2 mo (95%CI [37.2 - 47.1]). Median OS in the choroidal metastasis group was 23.4 mo (95%CI [0.1 - 51.4]) versus 27.9 mo (95%CI [16.9 - 38.9]) in the non-choroidal metastasis group (p=0.32). In the choroidal metastasis group, 2-year and 5-year OS were 47.6% and 0%, respectively, versus 55.8% and 26.3% in the non-choroidal metastasis subset.Conclusions: Choroidal metastases in NSCLC EGFR-mutant patients are rare but should be systematically suspected in case of visual disturbance. TKIs are efficient for treating visual symptoms. Whether choroidal metastases confer a worse prognosis remains unclear owing to the third-generation EGFR TKI osimertinib first-line registration.
Pancreatic Cancer Stem Cells May Define Tumor Stroma Characteristics 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: October 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, 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.
Empowering Traditional Birth Attendants as Agents of Maternal and Neonatal Immunization Uptake in Nigeria: a repeated measures design.
Authors: IWU Chinedu Anthony , Uwakwe Kenechi , Oluoha Uchechukwu Raphael , Duru chukwuma , NWAIGBO ERNEST 
Published: October 2020

Abstract
Background: Adequate immunization coverage in rural communities remain a challenge in Nigeria. Traditional birth attendants (TBAs) form an integral part of the social, cultural and religious fabric in most rural communities in Nigeria. Despite their limitations in handling the complications of childbirth, TBAs are widely accepted and patronized, especially in rural areas. The objectives of the project were to empower TBAs and assess the use of a culturally adapted audio-visual workshop intervention to change their knowledge, attitude and willingness to promote immunization uptake.Methods: A repeated-measures design that used a convenience sampling technique to select 90 TBAs from the three geopolitical zones of Imo State, Nigeria. The TBAs were engaged through a culturally adapted audio-visual workshop. Data were collected before and immediately after intervention using a pretested questionnaire. Chi square test was done to determine any significant association with the zone of practice and paired sample t-test analysis to determine any significant pre and post intervention change. Level of significance was set at p ≤ ·05. Results: More than half of the TBAs had at most, a secondary level of education (54·4 %). The average length of time they practiced as TBAs was 16 years with an average of ten birth deliveries per month. After the intervention, all the respondents (100%) reported a willingness to always promote immunization uptake and also, there was a statistically significant increase in Knowledge (p<·000). Similarly, the level of knowledge in the post intervention period appeared to be significantly associated with the zone of practice (p= ·027). Conclusion: The workshop intervention empowered the TBAs irrespective of their zones of residence by successfully improving their knowledge, though at varying levels; and consequently, their willingness to always promote immunization uptake.
Altered striatal dopamine levels in Parkinson’s disease VPS35 D620N mutant transgenic aged mice
Authors: Vanan Sarivin , Zeng Xiaoxia , Chia Sook Yoong , Varnäs Katarina , Jiang Mei , Zhang Ke , Saw Wuan Ting , Padmanabhan Parasuraman , Yu Wei-Ping , Zhou Zhi-Dong , Halldin Christer , Gulyás Balázs , Tan Eng-King , Zeng Li 
Published: October 2020

Abstract
Vacuolar protein sorting 35 (VPS35) is a major component of the retromer complex that mediates the retrograde transport of cargo proteins from endosomes to the trans-Golgi network. Mutations such as D620N in the VPS35 gene have been identified in patients with autosomal dominant Parkinson’s disease (PD). However, it remains poorly understood whether and how VPS35 deficiency or mutation contributes to PD pathogenesis; specifically, the studies that have examined VPS35 thus far have differed in results and methodologies. We generated a VPS35 D620N mouse model using a Rosa26-based transgene expression platform to allow expression in a spatial manner, so as to better address these discrepancies. Here, aged (20-months-old) mice were first subjected to behavioral tests. Subsequently, DAB staining analysis of substantia nigra (SN) dopaminergic neurons with the marker for tyrosine hydroxylase (TH) was performed. Next, HPLC was used to determine dopamine levels, along with levels of its two metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in the striatum. Western blotting was also performed to study the levels of key proteins associated with PD. Lastly, autoradiography (ARG) evaluation of [3H]FE-PE2I binding to the striatal dopamine transporter DAT was carried out. We found that VPS35 D620N Tg mice displayed a significantly higher dopamine level than NTg counterparts. All results were then compared with that of current VPS35 studies to shed light on the disease pathogenesis. Our model allows future studies to explicitly control spatial expression of the transgene which would generate a more reliable PD phenotype.
Hepatocellular carcinoma: Intratumoral EpCAM-positive cancer stem cell heterogeneity identifies high-risk tumor subtype
Authors: Krause Jenny , von Felden Johann , Casar Christian , Fründt Thorben W. , Galaski Johanna , Schmidt Constantin , Jung Caroline , Ittrich Harald , Weidemann Sören Alexander , Krech Till , Heumann Asmus , Li Jun , Fischer Lutz , Sauter Guido , Lohse Ansgar W. , Wege Henning , Schulze Kornelius 
Published: October 2020

Abstract
Background: The translational interest in the intratumoral heterogeneity of hepatocellular carcinoma (HCC) has been increasing. The dismal prognosis of this pathology is linked to the features of the HCC harbouring cancer stem cells (CSC), represented by EpCAM-expression. However, the extent of the impact of intratumoral distribution of CSC-features, both on the recurrence after curative resection and on clinical outcome, remains unknown. To address this, we investigated the spatial heterogeneity of CSC-features with the aim of identifying the unique HCC patient subgroups amenable to adjuvant treatment.Methods: We designed a tissue microarray (TMA) from patients who had received liver resection between 2011 and 2017. Tumor specimens were sampled at multiple locations (n=3-8). EpCAM-positivity was assessed for intensity and proportion by applying a score dividing three groups: (i) negative (E-/-); (ii) heterogeneous (E-/+); and (iii) homogeneous (E+/+). The groups were further analysed with regard to time-to-recurrence (TTR) and recurrence-free-survival (RFS).Results: We included 314 tumor spots from 69 patients (76.8% male, median age 66 years, liver cirrhosis/fibrosis 75.8). The risk factors were alcohol abuse (26.2%), NASH (13.1%), HBV (15.5%), HCV (17.9%) and others (27.4%), representative of a typical Western cohort. E+/+ patients experienced significantly shorter TTR and RFS compared to E+/- (and E-/-) patients (TTR 5 vs. 19 months, p=0.022; RFS 5 vs. 14 vs. 21 months, p=0.016). Only homogeneous EpCAM-positivity correlated with higher AFP levels (>400 ng/ml, p=0.031).Conclusions: Spatial heterogeneity of EpCAM-expression was markedly present in the cohort. Of note, only homogeneous EpCAM-expression correlated significantly with early recurrence, whereas heterogeneous EpCAM-expression was associated with clinical endpoints comparable to EpCAM-negativity. We identified a unique HCC subtype associated with a high risk of tumor recurrence.
Common Causes and Characteristics of Adverse Drug Reactions in Older Adults: A Retrospective Study
Authors: Woo Seong-Dae , Yoon Jiwon , Doo Go-Eun , Park Youjin , Lee Youngsoo , Lee So-Hee , Lee Young-Hee , Ye Young-Min 
Published: October 2020

Abstract
Background: Aging populations are often accompanied by comorbidity and polypharmacy, leading to increases in adverse drug reactions (ADRs). We sought to evaluate the causes and characteristics of ADRs in older Korean adults (≥65 years) in comparison to younger individuals (<65 years).Methods: Of 37,523 cases reported at a Korean pharmacovigilance center from 2011 to 2018, we reviewed 18,842 ADRs of certain or probable causality on the basis of WHO-UMC criteria. We estimated the number of ADRs per 1,000 patients exposed to the major culprit drugs, and incidence rate ratios were obtained to assess high- and low-risk medications in older adults.Results: In total, 4,152 (22.0%) ADRs were reported for 3,437 older adults (mean age, 74.6 years and 57.3% female). Tramadol (rate ratio, 1.32; 95% confidence interval [CI], 1.21-1.44; P<0.001) and fentanyl (1.49, 1.16-1.92, P=0.002) posed higher risks of ADRs in the older adults, whereas nonsteroidal anti-inflammatory drugs (NSAIDs) (0.35, 0.30-0.40, P<0.001) and iodinated contrast media (ICM) (0.82, 0.76-0.89, P<0.001) posed lower risks. Ratios of serious ADRs to NSAIDs (odds ratio, 2.16; 95% CI, 1.48-3.15; P<0.001) and ICM (2.09, 1.36-3.21, P=0.001) were higher in the older adults than in the younger patients. Analgesics primarily elicited cutaneous ADRs in the younger patients and gastrointestinal reactions in the older adults. ICM more commonly led to anaphylaxis in the older adults than the younger patients (3.0% vs. 1.6%, P=0.019). Conclusion: For early detection of ADRs in older adults, better understanding of differences in the causes and characteristics thereof in comparison to the general population is needed.
Quantitative Proteomic Analyses Reveal That Energy Metabolism and Protein Biosynthesis Reinitiation are Responsible for the Initiation of Bolting Induced by High Temperature in Lettuce (Lactuca sativa L.)
Authors: Hao Jing-hong , Su He-Nan , Zhang Li-li , Liu Chao-jie , Han Ying-yan , Qin Xiao-xiao , Fan Shuang-xi 
Published: October 2020

Abstract
Background

Lettuce (Lactuca sativa L.), one of the most economically important leaf vegetables, exhibits early bolting under high-temperature conditions. Early bolting leads to loss of commodity value and edibility, leading to considerable loss and waste of resources. However, the initiation and molecular mechanism underlying early bolting induced by high temperature remains largely elusive.
Results

To better understand this phenomenon, the bolting initiation period of lettuce was defined, and a comparative proteomic analysis was conducted in the initiation period of bolting induced by a high temperature (33 °C) and a control temperature (20 °C) using iTRAQ-based proteomics, phenotypic measurement, and biological verification by RT-qPCR. Morphological and microscopic observation showed that the initiation of bolting occurred 8 days after high-temperature treatment. Fructose rapidly accumulated after high-temperature treatment. During bolting initiation, of the 3305 identified proteins, a total of 93 proteins exhibited differential abundances, 38 of which were up-regulated, and 55 were down-regulated. Approximately 38% of the proteins were involved in metabolic pathways and were mainly clustered in energy metabolism and protein synthesis. Furthermore, some proteins involved in sugar synthesis were differentially expressed, which were also associated with energy production.
Conclusions

This is the first report on the metabolic changes involved in bolting initiation in lettuce. Our study suggested that energy metabolism and ribosomal proteins are pivotal components during bolting initiation. This study could provide a potential regulatory mechanism for the initiation of early bolting by high temperature, which could have applications in the manipulation of lettuce for breeding.
Digital Insecticide-treated nets (ITNs) mass distribution campaign in the particular context of covid-19 pandemic in Benin: lessons learned and challenges.
Authors: AIKPON ROCK , Affoukou Cyriaque , Hounkpatin Benjamin , Eclou Dieu-Donné , Cyaka Yves , Egwu Elijah , Agbessi Narcisse , Tokponon Filémon , Salifou Sahidou , Salami Lamidhi , Hounto Aurore Ogouyemi 
Published: October 2020

Abstract
Background: In 2020, Benin has implemented a digital Insecticide-treated nets (ITNs) mass distribution campaign in the particular context of covid-19 pandemic and then, offered important lessons to share. This paper aims to describe the implementation process as well as the lessons learned and challenges from this campaign. Methods: A descriptive design was used for reporting the planning and implementation process of ITNs campaign. Moreover, the changes and adaptations related to covid-19 pandemic are well described. Results: A total of 3,175,773 households were registered corresponding to a total of 14,423,998 persons (13.55% more from projection). Moreover, 94.16 % (13,581,637 people) of enumerated population were protected. A total of 7,652,166 ITNs were distributed countrywide.Conclusions: High political commitment, engagement and support add to the financial and technical supports from partners were the essential factors that make 2020 ITNs mass campaign success in Benin despite the particular context of COVID-19 pandemic. It is essential to maintain the prevention activities for malaria and this could substantially reduce the overall impact of the COVID-19 pandemic in the populations at malaria risk.
Childhood stunting and associated factors among irrigation and non-irrigation user Northwest, Ethiopia: a comparative cross-sectional study
Authors: Sema Balew , Azage Muluken , Tirfie Mulat 
Published: October 2020

Abstract
Background: Stunting is a critical public health problem of developing countries like Ethiopia. Different interventions like irrigation activity have been carried out by the government of Ethiopia to improve the nutritional status of the community. However, there is scanty of data on childhood stunting and its associated factors between irrigation user and non-irrigation user. Objective: To assess the magnitude of childhood stunting and its associated factors between irrigation and non-irrigation user in North Mecha District, Northwest Ethiopia. Methods: A community-based comparative cross-sectional study design was employed from October to November 2019. A systematic sampling was used to draw mothers with children age 6-59 months (582 irrigated and 582 non- irrigated household users). Data were collected using questionnaire and anthropometric measurement tools. Multivariable logistic regression was used to identify the predictors of stunting. Adjusted odds ratios with 95% CI were used to determine the degree of association between independent and outcome variable. A-p-value <0.05 was used as cutoff point to declare statistically significant variables with the outcome variable. Results: The prevalence of childhood stunting (6-59 months) among irrigation users [32.8% at 95%CI (29-37)] was slightly higher than non-usurers [40.2% at 95%CI (36-44)]. However, the difference did not show significant variation. The odds of childhood stunting were higher among a child from a mother had no antenatal visit, a child whose age was between 12 and 47 months, a child from a mother who did not use water and soap always for washing hands, and a child who had fever. Conclusion: The prevalence of childhood stunting was high and did not show significant variation between irrigation and non-irrigation users. A child from mother had no antenatal visit, whose age was between 12 and 47 months, a mother who did not use water and soap always for washing hands, and who had fever were factors associated with higher child stunting. Thus, the identified modifiable factors should be strengthened to reduce stunting.