bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tamoxifen suppresses brain metastasis of estrogen receptor-deficient breast cancer by skewing microglia polarization and enhancing their immune functions
Authors: Wu Shih-Ying , Sharma Sambad , Wu Kerui , Tyagi Abhishek , Zhao Dan , Deshpande Ravindra Pramod , Watabe Kounosuke 
Published: November 2020

Abstract
Background: Brain metastasis of breast cancer exhibits exceedingly poor prognosis, and both triple negative (TN) and Her2 + subtypes have the highest incidence of brain metastasis. Although estrogen blockers are considered to be ineffective for their treatment, recent evidence indicates that estrogen blockade using tamoxifen showed certain efficacy. However, how estrogen affects brain metastasis of triple negative breast cancer (TNBC) remains elusive. Methods: To examine the effect of estrogen on brain metastasis progression, nude mice were implanted with brain metastatic cells and treated with either estrogen supplement, tamoxifen or ovariectomy for estrogen depletion. For clinical validation study, brain metastasis specimens from pre- and post-menopause breast cancer patients were examined for microglia polarization by immunohistochemistry. To examine the estrogen-induced M2 microglia polarization, microglia cells were treated with estrogen and the M1/M2 microglia polarization was detected by qRT-PCR and FACS. The estrogen receptor-deficient brain metastatic cells, SkBrM and 231BrM, were treated with conditioned medium (CM) derived from microglia that were treated with estrogen in the presence or absence of tamoxifen. The effect of microglia-derived CM on tumor cells was examined by colony formation assay and sphere forming ability. Results: We found that M2 microglia were abundantly infiltrated in brain metastasis of pre-menopausal breast cancer patients. A similar observation was made in vivo, when we treated mice systemically with estrogen. Blocking of estrogen signaling either by tamoxifen treatment or surgical resection of mice ovaries suppressed M2 microglial polarization and decreased the secretion of C-C motif chemokine ligand 5, resulting in suppression of brain metastasis. The estrogen modulation also suppressed stemness in TNBC cells in vitro. Importantly, estrogen enhanced the expression of signal regulatory protein α on microglia and restricted their phagocytic ability. Conclusions: Our results indicate that estrogen promotes brain metastasis by skewing polarity of M2 microglia and inhibiting their phagocytic ability, while tamoxifen suppresses brain metastasis by blocking the M2 polarization of microglia and increasing their anti-tumor phagocytic ability. Our results also highlight a potential therapeutic utility of tamoxifen for treating brain metastasis of hormone receptor deficient breast cancer.
A Quantitative Discriminant Method of Elbow Point for the Optimal Number of Clusters in Clustering Algorithm
Authors: Shi Congming , Wei Bingtao , Wei Shoulin , Wang Wen , Liu Hai , Liu Jialei 
Published: November 2020

Abstract
Clustering, as a traditional machine learning method, is still playing a significant role in data analysis. The most of clustering algorithms depend on a predetermined exact number of clusters, whereas, in practice, clusters are usually unpredictable. Although elbow method is one of the most commonly used methods to discriminate the optimal cluster number, the discriminant of the number of clusters depends on manual identification of the elbow points on the visualization curve, which will lead to the experienced analysts not being able to clearly identify the elbow point from the plotted curve when the plotted curve being fairly smooth. To solve this problem, a new elbow point discriminant method is proposed to work out a statistical metric estimating an optimal cluster number when clustering on a dataset. Firstly, the average degree of distortion obtained by Elbow method is normalized to the range of 0 to10; Secondly, the normalized results are used to calculate Cosine of intersection angles between elbow points; Thirdly, the above calculated Cosine of intersection angles and Arccosine theorem are used to compute the intersection angles between elbow points; Finally, the index of the above computed minimal intersection angles between elbow points is used as the estimated potential optimal cluster number. The experimental results based on simulated datasets and a public well-known dataset (Iris Dataset) demonstrated that the estimated optimal cluster number output by our newly proposed method is better than widely used Silhouette method.
Quasi-Optical Design of a Millimeter Wave Imaging System
Authors: Jadidi Faeze , Eslamimajd Abdollah , Erfaniyan Alireza , Armaki Seyed Hossein Mohseni 
Published: November 2020

Abstract
In this paper, we report a complete design and simulation of a quasi-optical millimeter wave imaging system using ZEMAX and FEKO software, respectively. A Fresnel lens and a horn antenna are combined in this this design. Compared to spherical and aspherical lenses, a Fresnel lens can be fabricated much easier at millimeter wavelengths. For focusing millimeter wave radiation, a Fresnel lens can be used to reduce the thickness of the focusing element and to lighten its weight from 25 Kg to 4.5 Kg. A horn antenna with a Gaussian profile and corrugated walls is designed for feeding this system at a central frequency of 94 GHz. The symmetrical radiation pattern of the designed corrugated Gaussian horn in E and H orthogonal planes, its wide bandwidth and low side lobe levels make it a good candidate for feeding a W-band millimeter wave imaging system. The designed quasi-optical imaging system is light-weighted, has high resolution and can be used in detecting hidden objects within a distance of 5 meters with a 30 mm resolution in W-band at a central frequency of 94 GHz.
An assessment of the potential miscalibration of cardiovascular disease risk predictions caused by a secular trend in cardiovascular disease in England
Authors: Pate Alexander , Staa Tjeerd van , Emsley Richard 
Published: November 2020

Abstract
Background: A downwards secular trend in the incidence of cardiovascular disease (CVD) in England was identified through previous work and the literature. Risk prediction models for primary prevention of CVD do not model this secular trend, this could result in over prediction of risk for individuals in the present day. We evaluate the effects of modelling this secular trend, and also assess whether it is driven by an increase in statin use during follow up. Methods: We derived a cohort of patients (1998 – 2015) eligible for cardiovascular risk prediction from the Clinical Practice Research Datalink with linked hospitalisation and mortality records (N = 3,855,660). Patients were split into development and validation cohort based on their cohort entry date (before/after 2010). The calibration of a CVD risk prediction model developed in the development cohort was tested in the validation cohort. The calibration was also assessed after modelling the secular trend. Finally, the presence of the secular trend was evaluated under a marginal structural model framework, where the effect of statin treatment during follow up is adjusted for. Results: Substantial over prediction of risks in the validation cohort was found when not modelling the secular trend. This miscalibration could be minimised if one was to explicitly model the secular trend. The reduction in risk in the validation cohort when introducing the secular trend was 35.68% and 33.24% in the female and male cohorts respectively. Under the marginal structural model framework, the reductions were 33.31% and 32.67% respectively, indicating increasing statin use during follow up is not the only the cause of the secular trend. Conclusions: Inclusion of the secular trend into the model substantially changed the CVD risk predictions. Models that are being used in clinical practice in the UK do not model secular trend and may thus overestimate the risks, possibly leading to patients being treated unnecessarily. Wider discussion around the modelling of secular trends in a risk prediction framework is needed.
Probiotics Mixture Reinforces Barrier Function to Ameliorate Necrotizing Enterocolitis by Regulating PXR-JNK Pathway
Authors: Zhao Xiuhao , Zhou Jin , Liang Wenhua , Sheng Qingfeng , Lu Li , Chen Tong , Chen Jianglong , Tan Kezhe , lv Zhibao 
Published: November 2020

Abstract
Background: Intestinal dysbiosis is believed to be one of the factors inducing neonatal necrotizing enterocolitis (NEC). Probiotics have been employed to treat NEC in a number of animal experiments and clinical trials, and some significant benefits of utilizing probiotics for the prevention or alleviation of NEC have been confirmed. However, the mechanism underlying the efficacy of probiotics in treating NEC has not been elucidated. Results: Impairment of the intestinal barrier, which was characterized by the decreased expression of tight junction components, was observed in the pathogenesis of NEC. The probiotic mixture alleviated this intestinal damage by enhancing the function of the barrier. Meanwhile, the probiotics remodeled the composition of the intestinal microbiota in NEC mice. Furthermore, increased expression of the pregnane X receptor ( PXR ) was observed after treatment with the probiotic mixture, and PXR overexpression in Caco-2 cells protected the barrier from lipopolysaccharide (LPS) damage. Further research showed that PXR could inhibit the phosphorylation of c-Jun N-terminal kinase (JNK) and could increase the expression of tight junction components. Conclusions: Our study confirmed that probiotics could ameliorate intestinal lesions by enhancing the function of the mucosal barrier. Specifically, probiotics may target PXR, which may subsequently enhance the expression of tight junction components by inhibiting the phosphorylation of JNK and enhancing the function of the barrier.
Mice with a cleavage-resistant N-cadherin exhibit synapse anomaly in the hippocampus and outperformance in spatial learning tasks
Authors: Asada-Utsugi Megumi , Uemura Kengo , Kubota Masakazu , Noda Yasuha , Tashiro Yasutaka , Uemura Maiko T , Yamakado Hodaka , Urushitani Makoto , Takahashi Ryosuke , Hattori Satoko , Miyakawa Tsuyoshi , Ageta-Ishihara Natsumi , Kobayashi Katsunori , Kinoshita Makoto , Kinoshita Ayae 
Published: November 2020

Abstract
N-cadherin is a homophilic cell adhesion molecule that stabilizes excitatory synapses, by connecting pre- and post-synaptic termini. Upon NMDA receptor (NMDAR) activation by glutamate, membrane-proximal domains of N-cadherin are cleaved serially by a-disintegrin-and-metalloprotease 10 (ADAM10) and then presenilin 1(PS1, catalytic subunit of the γ-secretase complex). To assess the physiological significance of the initial N-cadherin cleavage, we engineer the mouse genome to create a knock-in allele with tandem missense mutations in the mouse N-cadherin/Cadherin-2 gene (Cdh2 R714G, I715D, or GD) that confers resistance on proteolysis by ADAM10 (GD mice). GD mice showed a better performance in the radial maze test, with significantly less revisiting errors after intervals of 30 and 300 sec than WT, and a tendency for enhanced freezing in fear conditioning. Interestingly, GD mice reveal higher complexity in the tufts of thorny excrescence in the CA3 region of the hippocampus. Fine morphometry with serial section transmission electron microscopy (ssTEM) and three-dimensional (3D) reconstruction reveals significantly higher synaptic density, significantly smaller PSD area, and normal dendritic spine volume in GD mice. This knock-in mouse has provided in vivo evidence that ADAM10-mediated cleavage is a critical step in N-cadherin shedding and degradation and involved in the structure and function of glutamatergic synapses, which affect the memory function.
Gender equity at last: a national study of medical students considering a career in rural medicine
Authors: Kim Caleb , Ngo Hanh , Playford Denese 
Published: November 2020

Abstract
Background: The rural medical workforce internationally suffers from a significant imbalance between male- and female- identifying practitioners. Not only do male doctors outnumber female doctors, but additionally female doctors work fewer hours than their male counterparts. This has health implications for rural communities. In response, In Australia, Rural Clinical Schools (RCSs) are a national training strategy to increase the number of graduates entering the rural medical workforce. It has been observed that RCSs attract a greater number of female students than male students. However, the future work intentions of male versus female RCS students is not known. This paper therefore asked whether male and female RCS students have equivalent intent for future rural practice.Methods: Participants were all students who attended RCSs from 2015-2017, who completed an exit survey that gathered data on demographic, experiential and intentional variables. Univariate analyses examined differences between the sexes. A multivariate model was constructed to determine the independent predictors for rural intention.Results: There were 2,017 respondents across the three years, of whom 937 identified as male, and 1,138 identified as female. In univariate analysis, female-identifying students had significantly higher rural intention than male-identifying students. There were no other sex-based differences in age, rural background, overall perception of support, and overall excellence of clinical education whilst in RCS. However, in multivariate analysis, sex was not a significant predictor for rural work intention, whereas older age, rural background, and first preference for RCS were all predictive of increased rural intent, as expected from the literature. There were no differences between male and female students in their perceptions of the overall support and the clinical education provided by RCS. Conclusion: We conclude from this national study that sex is not an independent predictor for future rural work intention among RCS students. Considering the disproportionate number of female students entering RCS, this is reassuring for ultimately achieving rural workforce gender equity.
Electricity generation and pollutants removal of landfill leachate by osmotic microbial fuel cells with different forward osmosis membranes
Authors: Jiang Nan , Huang Li , Cai Teng , Song Jialing , Zheng Shengyang , Guo Jili , Kong Zhuang , Huang Manhong 
Published: November 2020

Abstract
In this study, thin-film composite with embedded polyester screen (TFC-ES), cellulose triacetate with a cast nonwoven (CTA-NW) and cellulose triacetate with embedded polyester screen (CTA-ES) were examined as the intermediate membranes in osmotic microbial fuel cells (OsMFCs). The reactors were fed with actual landfill leachate and the performance was studied in two operation modes: active layer facing draw solution (AL-DS) and active layer facing feed solution (AL-FS). The OsMFC with CTA-ES exhibited the best energy generation (maximum power density: 0.44 W m-2) and pollutant removal efficiency (ammonia nitrogen: 70.12 ± 0.28%, total nitrogen: 74.04 ± 0.33%) in the AL-FS mode, which could be ascribed to the lowest internal resistance (236.75 ohm) and highest microbial richness. Pseudomonas was the highest proportion of microbial in OsMFCs. The results of this study has demonstrated the potential of OsMFCs for landfill leachate treatment.
Role of ASM/Cer/TXNIP signaling module in the NLRP3 inflammasome activation
Authors: Jiang Jianjun , Yang Jin , Shi Yining , Cao Jiyu , Lu Youjin , Sun Gengyun 
Published: November 2020

Abstract
Background: The NOD-Like Receptor Protein 3 (NLRP3) inflammasome is a crucial component of an array of inflammatory conditions. It functions by boosting the secretion of pro-inflammatory cytokines: interleukin-1β (IL-1β) and interleukin-18 (IL-18). Previous studies have established the vital role of the acid sphingomyelinase (ASM)/ceramide (Cer) pathway in the functional outcome of cells, with a particular emphasis on the inflammatory processes. This study aimed to explore the effects and associated underlying mechanism of Cer-induced NLRP3 inflammasome activation.Methods: Lipopolysaccharide (LPS)/adenosine triphosphate (ATP)-induced NLRP3 inflammasome activation in J774A.1 cells was used as an in vitro inflammatory model. Western blotting and Real-time PCR (RT-PCR) were used to detect the protein and mRNA levels, respectively. IL-1β and IL-18 levels were evaluated using ELISA kits. ASM assay kit and immunofluorescence were used to detect ASM activity and Cer content.Results: Imipramine, a well-known inhibitor of ASM, significantly inhibited ASM activity and inhibited Cer accumulation, which indicated ASM activation. Besides, it also suppressed the LPS/ATP-induced expression of proteins and mRNA: thioredoxin interacting protein (TXNIP), NLRP3, caspase-1, IL-1β and IL-18. Interestingly verapamil, a TXNIP inhibitor, suppressed LPS/ATP-induced TXNIP/NLRP3 inflammasome activation; however, it did not affect LPS/ATP-induced ASM activation and ceramide production. Further analysis showed that the exogenous C2-Cer treated J774A.1 cells induced the overexpression of TXNIP, NLRP3, caspase-1, IL-1β and IL-18. Besides, TXNIP siRNA or verapamil inhibited C2-Cer-induced TXNIP overexpression and NLRP3 inflammasome activation.Conclusion: This study demonstrated the involvement of the ASM/Cer/TXNIP signaling pathway in NLRP3 inflammasome activation.
Polyparasitism with Schistosoma haematobium, Plasmodium and soil-transmitted helminths in school-aged children living in the urogenital schistosomiasis endemic focus of Muyuka-Cameroon following implementation of control measures: a cross sectional study
Authors: Sumbele Irene Ule Ngole , Otia Ofon Vitalis , Bopda Orelien Sylvain Mtopi , Ebai Calvin Bisong , Kimbi Helen KuoKuo , Nkuo-Akenji Theresa 
Published: November 2020

Abstract
Background: Despite the ubiquity of polyparasitism, its health impacts have been inadequately studied. The aim of this study was to determine the prevalence and determinants of polyparasitism with Schistosoma haematobium, Plasmodium and soil-transmitted helminths (STH) following sustained control measures, as well as evaluate the outcomes and clinical correlates of infection in school-aged children (SAC) living in the schistosomiasis endemic focus of Muyuka-Cameroon.Methods: In a cross-sectional study, urine, blood and stool samples were each collected from SAC (4-14 years) between March to June 2015. Microhaematuria in urine was detected using reagent strip and S. haematobium ova by filtration/microscopy methods. Plasmodium was detected using Giemsa stained blood films and complete blood count was obtained using an auto-haematology analyser. STH in stool was detected by the Kato-Katz method. Categorical and continuous variables were compared as required, Kappa value estimated and the adjusted odds ratio (AOR) in the multivariate analysis was used to evaluate association of the risk factors with infection.Results: Out of the 638 SAC examined, single infection was prevalent in 33.4% while polyparasitism was 19.9%. Prevalence of S. haematobium + Plasmodium was 7.8%; S. haematobium + STH was 0.8%; Plasmodium + STH was 0.8% while, S. haematobium + Plasmodium + STH was 0.9%. Higher preponderance of S. haematobium + Plasmodium infection occurred in females, those from Likoko, did not use potable water, practiced bathing in stream and carried out open defecation than their equivalents. However, being female (AOR =2.38, P=0.009) was the only significant risk factor identified. Anaemia was a common morbidity (74.3%) with a slight agreement with microscopy in predicting S. haematobium and Plasmodium infections. The sensitivity and specificity of haematuria (13.0%) in predicting S. haematobium infection was 46.5% and 100% with a moderate agreement with microscopy. Co-infection with S. haematobium and malaria parasite was significantly associated with 3-fold odds of history of fever in the last three days.Conclusions: Polyparasitism is a public health problem in the Ikata-Likoko area in Muyuka with females most at risk. Anaemia prevalence is exacerbated in co- and triple-infections and together with a history of fever are of value in predicting polyparasitism.
Multiorgan failure with fatal outcome after stem cell tourism
Authors: Večerić-Haler Željka , Borštnar Špela , Luzar Boštjan , Jerše Maja , Kojc Nika 
Published: November 2020

Abstract
Background: unproven stem cell treatments may involve serious health, personal and financial considerations. Due to worldwide spread, illegal stem cell therapies have become a major public health problem. We have already witnessed numerous reports in the mass media of severe and occasionally even fatal outcomes after such therapies. However, there are only few scientifically documented cases in which the causality between stem cell therapy and side effects cannot be refuted. Case presentation: here we present a case report of a 48-years old patient with serious side effects including disseminated skin ulcers, hepatitis and cardiomyopathy with eventual fatal outcome following unproven stem cell treatment. Conclusions: the case of the patient presented here draws attention to the worst possible outcome of stem cell tourism. To effectively combat this issue, professionals and patients should be empowered with the right knowledge on possible side effects.
A Comparison of Glycemic Parameters and Their Relationship with C-Peptide and Proinsulin Levels During the Honeymoon and Non-honeymoon Periods in Children with Type 1 Diabetes Mellitus - a Cross-Sectional Study
Authors: Yesiltepe-Mutlu Gul , Çapacı Merve , Can Ecem , Gökçe Tuğba , Bayrakçı Gizem , Muradoğlu Serra , İncir Said , Çakır Esra Papatya , Hatun Şükrü 
Published: November 2020

Abstract
Background : Currently, there is a lack of data relating to glycemic parameters and their relationship with C-peptide (CP) and proinsulin (PI) during the honeymoon period in type 1 diabetes mellitus (T1D). The aim of this study was to evaluate glycemic parameters in children with T1D who are in the honeymoon period using intermittently scanned continuous glucose monitoring systems (isCGMS) and to investigate any relationships between CP and PI levels.Methods: The study included 21 children who were in the honeymoon period and 31 children who were not. A cross-sectional, non-randomized study was performed. Demographic, clinical data were collected and 2 week- isCGMS data were retrieved.Results: The Serum CP showed a positive correlation with time-in-range in the honeymoon period (p:0.03), however PI showed no correlations with glycemic parameters in both periods. The Serum CP and PI levels and the PI:CP ratio were significantly higher in the honeymoon group than in the non-honeymoon group. In the non-honeymoon group, the PI level was below 0.1 pmol/L (which is the detectable limit) in only 2 of the 17 cases as compared with none in the honeymoon group. Similarly, only 2 of the 17 children in the non-honeymoon group had CP levels of less than 0.2 nmol / L, although both had detectable PI levels. Overall time-in-range (3.9-10 mmol/L) was significantly high in the honeymoon group. In contrast, the mean sensor glucose levels, time spent in hyperglycemia, and coefficient of variation levels (32.2vs 40.5%) were significantly low in the honeymoon group. Conclusions: While the CP levels did have an effect on glycemic parameters during the honeymoon period, there was no correlation between PI levels and glycemic parameters. In terms of glycemic parameters during the honeymoon period, the CP level had a significant correlation with the TIR value. CP seems to be a useful biochemical tool, while PI was not a sensitive biochemical parameter. Further studies are needed to determine if PI might prove to be a useful parameter in clinical follow-up.