bluuebunny/crossref_metadata_2025 huggingface dataset:
Delirium in older patients undergoing aortic valve replacement: Incidence, predictors, and cognitive prognosis.
Authors: Humbert Marc , Büla Christophe J , Müller Olivier , Krief Hélène , Monney Pierre
Published: November 2020

Objectives: To determine delirium incidence, predictors, and relationship with cognitive performance at 3-month follow-up in older patients undergoing aortic valve replacement (AVR).Methods: Patients (N=93) aged 70 years and older, undergoing transcatheter (TAVR, N=66) or surgical (SAVR, N=27) aortic valve replacement in an academic medical center were enrolled in this prospective cohort study. Delirium was assessed using the Confusion Assessment Method (CAM) on postoperative days 1, 2, 3, and 7. Data on patients’ socio-demographics, functional status (including instrumental activities of daily living (IADL), and surgical risk scores (including Society of Thoracic Surgeons (STS) risk score), were collected at baseline. Cognitive status was assessed with the Mini-Mental Status Exam (MMSE) and the Clock Drawing Test (CDT) at baseline and 3 months after AVR.Results: Delirium occurred in 21 (22.6%) patients, within the first three postoperative days in 95% (20/21) of the cases. Delirium incidence was lower in TAVR (13/66=20%) than SAVR (8/27=30%) patients, but this difference was not statistically significant (p=.298). Patients with delirium had lower baseline cognitive performance (median MMSE score 27.0±3.0 vs 28.0±3.0, p=.029), lower performance in IADL (7.0 vs 8.0, p=.038), and higher STS risk scores (4.7±2.7 vs 2.9±2.3, p=.020). In multivariate analyses, patients with intermediate (score>3 to ≤8) and high (score>8) STS risk scores had 4.3 (95%CI 1.2-15.1, p=.025) and 16.5 (95%CI 2.0-138.2, p=.010), respectively, higher odds of incident delirium compared to patients with low (score≤3) STS risk scores. At 3-month follow-up (N=77), patients with delirium still had lower MMSE score (27.0±8.0 vs 28.0±2.0, p=.007) but this difference did not remain significant once adjusting for baseline MMSE (β-coefficient 1.11, 95%CI [-3.03-0.80], p=.248).Conclusions: Delirium occurred in about one in five older patients undergoing AVR, almost essentially within the first three postoperative days. Beside cognitive performance, STS risk score could enhance the identification of high-risk older patients to better target preventative interventions.
Disseminating evidence-based research on mental health and coping to adolescents facing adversity in Lebanon: A pilot of a psychoeducational comic book ‘Somoud’
Authors: Bosqui Tania Josiane , Mayya Anas , Younes Liliane , Baker Myriam Claire , Annan Ismat
Published: November 2020

Background Despite advances in the evidence base and scaling up of mental health and psychosocial interventions for children and adolescents affected by conflict and adversity, a theory-practice gap remains, with limited translation of research findings to affected communities. Methods In order to disseminate findings from a review on mental health and coping for children and adolescents, a psychoeducational comic book ‘Somoud’ was developed and piloted with adolescents and their caregivers in Lebanon, using a qualitative Grounded Theory approach.Results In total, 10 participants (5 adolescents, 5 parents), took part in the study. Using Thematic Content Analysis, 6 themes were identified; 1) psychoeducation versus misinterpretation, 2) balancing depth with accessibility, 3) aesthetic appeal, 4) contextual relevance and realism, 5) daily stressors, and 6) parental and social relationships. Conclusions The findings demonstrate the importance of cultural and contextual piloting of psychoeducational content, and the potential usefulness and accessibility of a comic book format to disseminate information to adolescents. Data from the pilot was used to inform the development of a new version of ‘Somoud’ for sharing with adolescents in Lebanon. Further research is required to establish the effectiveness of the psychoeducational book as a ‘self-help’ tool, and to further improve knowledge exchange between researchers and communities.
Nanomicelles potentiate histone deacetylase inhibitor efficacy in vitro.
Authors: Pisano Simone , Wang Xiong , Parra Jezabel Garcia , Gazze Andrea , Edwards Kadie , Feltracco Veronica , Hu Yanzhen , He Le , Gonzalez Deyarina , Francis Lewis , Conlan Robert Steven , Li Chao
Published: November 2020

Background. Amphiphilic block copolymers used as nanomicelle drug carriers can effectively overcome poor drug solubility and specificity issues. Hence, these platforms have a broad applicability in cancer treatment. In this study, Pluronic F127 was used to fabricate nanomicelles containing the histone deacetylase inhibitor SAHA, which has an epigenetic-driven anti-cancer effect in several tumor types. SAHA loaded nanomicelles were prepared using a thin-film drying method and characterized for size, surface charge, drug content and drug release properties. Loaded particles were tested for in vitro activity and their effect on cell-cycle and markers of cancer progression. Results. Following detailed particle characterization, cell proliferation experiments demonstrated that SAHA loaded nanomicelles more effectively inhibited the growth of HeLa and MCF-7 cell lines compared with free drug formulations. The 30nm SAHA containing nanoparticles were able to release up to 100% of the encapsulated drug over a 72h time window. Moreover, gene and protein expression analyses suggested that their cytoreductive effect was achieved through the regulation of p21 and p53 expression. SAHA was also shown to upregulate E-cadherin expression, potentially influencing tumor migration. Conclusions. This study highlights the opportunity to exploit pluronic-based nanomicelles for the delivery of compounds that regulate epigenetic processes, thus inhibiting cancer development and progression.
The amino acid transporter OsAAP4 contributes to rice tillering and grain yield by regulating neutral amino acid allocation through two splicing variants
Authors: Fang Zhongming , Wu Bowen , Ji Yuanyuan
Published: November 2020

Background: Amino acids, which are transported by amino acid transporters, are the major forms of organic nitrogen utilized by higher plants. Among the 19 Amino Acid Permease transporters (AAPs) in rice, only a small number of these genes have been reported to influence rice growth and development. However, whether other OsAAPs are responsible for rice growth and development is unclear.Results: In this study, we demonstrate that OsAAP4 promoter sequences are divergent between Indica and Japonica, with higher expression in the former, which produces more tillers and higher grain yield than does Japonica. Overexpression of two different splicing variants of OsAAP4 in Japonica ZH11 significantly increased rice tillering and grain yield as result of enhancing the neutral amino acid concentrations of Val, Pro, Thr and Leu. OsAAP4 RNA interference (RNAi) and mutant lines displayed opposite trends compared with overexpresing (OE) lines. In addition, exogenous Val or Pro at 0.5 mM significantly promoted the bud outgrowth of lines overexpressing an OsAAP4a splicing variant compared with ZH11, and exogenous Val or Pro at 2.0 mM significantly enhanced the bud outgrowth of lines overexpressing splicing variant OsAAP4b compared with ZH11. Of note, the results of a protoplast amino acid-uptake assay showed that Val or Pro at different concentrations was specifically transported and accumulated in these overexpressing lines. Transcriptome analysis further demonstrated that OsAAP4 may affect nitrogen transport and metabolism, and auxin, cytokinin signaling in regulating rice tillering.Conclusion: Our results suggested that OsAAP4 contributes to rice tiller and grain yield by regulating neutral amino acid allocation through two different splicing variants and that OsAAP4 might have potential applications in rice breeding.
Loss of MiR-192-5p Initiates a Hyperglycolysis and Stemness Positive Feedback in Hepatocellular Carcinoma.
Authors: Gu Yuanzhuo , Ji Fubo , Liu Niya , Zhao Yongzhi , Wei Xiyang , Hu Shiyuan , Jia Wei , Wang Xin Wei , Budhu Anuradha , Ji Juling , Zhao Bin , Roessler Stephanie , Zheng Xin , Ji Junfang
Published: November 2020

Background: Emerging studies revealed that cancer stem cells (CSCs) possessed peculiar metabolic properties, which however remained largely unknown in hepatocellular carcinoma (HCC). Genetic silencing of liver-abundant miR-192-5p was a key feature for multiple groups of CSC-positive HCCs. We thus aimed to investigate essential metabolic features of hepatic CSCs via using HCCs with miR-192-5p silencing as a model. Methods: Datasets from two independent HCC cohorts were used. Data integration analyses of miR-192-5p with metabolome and mRNA transcriptome in HCC cohort 1 were performed to investigate miR-192-5p related metabolic features, which was further validated in cohort 2. Cellular and molecular assays were performed to examine whether and how miR-192-5p regulated the identified metabolic feature. Co-culture systems consisting of HCC cells and LX2 (human hepatic stellate cell line) or THP1 (human monocyte cell line) were established to explore effects of the identified metabolic property on stemness features of HCC cells via interacting with co-cultured non-tumor cells. Results: High levels of glycolysis-related metabolites and genes presented in HCCs with low miR-192-5p and CSC-positive HCCs in two independent HCC cohorts. miR-192-5p knockout cells displayed CSC features and miR-192-5p loss led to an enhanced glycolytic phenotype via upregulating three bona fide targets, GLUT1 and PFKFB3 (two glycolytic enzymes) and c-Myc (regulating glycolytic genes’ expression). Meanwhile, c-Myc suppressed miR-192-5p transcription, ensuring a low-miR-192-5p/high-c-Myc loop to maintain hyperglycolysis. Moreover, over-produced lactic acid from hyperglycolytic HCC cells stimulated the ERK phosphorylation of co-cultured LX2 and THP1 non-tumor cells partially via NDRG3 and MCT1, which in turn promoted cell malignancy and stemness of HCC cells. Consistently, HCC patients with low level of miR-192-5p in their tumor tissues and high level of NDRG3 or MCT1 in their non-tumor tissues had the shortest overall survival. Conclusions: In CSC-positive HCCs, miR-192-5p loss enhanced glycolysis and over produced lactate might further increase HCC malignant features via interacting with environmental non-tumor cells.
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

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

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

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

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

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

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

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

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

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

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

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

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.
Improvements in the degree of understanding the treatment guidelines for schizophrenia and major depressive disorder in a nationwide dissemination and implementation study
Authors: Numata Shusuke , Nakataki Masahito , Hasegawa Naomi , Takaesu Yoshikazu , Takeshima Masahiro , Onitsuka Toshiaki , Nakamura Toshinori , Edagawa Reon , Edo Hiroaki , Miura Kenichiro , Matsumoto Junya , Yasui-Furukori Norio , Kishimoto Taishiro , Hori Hikaru , Tsuboi Takashi , Yasuda Yuka , Furihata Ryuji , Muraoka Hiroyuki , Ochi Shinichiro , Nagasawa Tatsuya , Kyou Yoshitaka , Murata Atsunobu , Katsumoto Eiichi , Ohi Kazutaka , Hishimoto Akitoyo , Inada Ken , Watanabe Koichiro , Hashimoto Ryota
Published: November 2020

Background: To implement clinical practice guidelines (CPGs), it is necessary for psychiatrists to deepen their understanding of existing CPGs. The Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE) project is a nationwide dissemination and implementation study of two sets of CPGs, including one for schizophrenia and one for major depressive disorder (MDD).Methods: A total of 413 psychiatrists (n=212 in 2016; n=201 in 2017) learned the two CPGs in the education program of the EGUIDE project over two days, and clinical knowledge of the two CPGs was evaluated by two 37-item questionnaires at baseline and after the EGUIDE programs. To improve the correct answer rate for clinical knowledge after the EGUIDE programs, we revised the lecture materials associated with items that had a low correct answer rate in 2016 and used the revised lecture materials with the CPGs in 2017. The rates of correct answers for each item after the EGUIDE programs were compared between the 2016 and 2017 groups.Results: The total clinical knowledge scores significantly increased after the EGUIDE program in both the 2016 groups and the 2017 groups. We revised lecture materials related to two items in the schizophrenia CPG and five items in the MDD CPG that had low correct answer rates after the EGUIDE programs. The correct answer rate of one item on the schizophrenia CPG and one item on the MDD CPG were increased (S-D5, p=0.038; D-C6, p=0.033) and that of one item on the MDD CPG was significantly improved (D-D3, p=0.00080) in the 2017 group compared to the rates of the 2016 group. The correct response rates of the other four items were not significantly improved.Conclusions: We reported improvements in clinical knowledge of CPGs after the EGUIDE program in the 2017 group following revisions of the lecture materials based on the results from the 2016 group. These attempts to improve the degree of understanding of CPGs may facilitate the successful dissemination and implementation of psychiatric guidelines in everyday practice.Trial registration: Effectiveness of Guideline for Dissemination and Education in Psychiatric Treatment, UMIN000022645, Registered 15 June 2016, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&recptno=R000026044&type=summary&language=J
Oncogenic 3D genome conformations identify novel therapeutic targets in ependymoma
Authors: Okonechnikov Konstantin , Camgoz Aylin , Park Donglim Esther , Chapman Owen , Hübner Jens-Martin , Chakraborty Abhijit , Pagadala Meghana , Bump Rosalind , Chandran Sahaana , Kraft Katerina , Acuna-Hidalgo Rocio , Reid Derek , Juarez Edwin F. , Robinson James T. , Pajtler Kristian W. , Mauermann Monika , Milde Till , Coufal Nicole G. , Levy Michael , Malicki Denise , Nahas Shareef , Snuderl Matija , Crawford John , Wechsler-Reya Robert J. , Mundlos Stefan , Schmitt Anthony , Carter Hannah , Michaelraj Kulandaimanuvel Antony , Kumar Sachin A. , Taylor Michael D. , Rich Jeremy , Buchholz Frank , Mesirov Jill P. , Pfister Stefan M. , Ay Ferhat , Dixon Jesse R. , Kool Marcel , Chavez Lukas
Published: November 2020

Ependymoma is a tumor of the brain or spinal cord. The two most common and aggressive molecular groups of ependymoma are the supratentorial RELA-fusion associated group and the posterior fossa ependymoma group A. In both groups, tumors occur mainly in young children and frequently recur after treatment1. Although the molecular mechanisms underlying these diseases have recently been uncovered, they remain difficult to target and innovative therapeutic approaches are urgently needed. Here, we use genome-wide chromosome conformation capture (Hi-C), complemented with CTCF (insulators) and H3K27ac (active enhancers) ChIP-seq as well as gene expression and whole-genome DNA methylation profiling in primary and relapsed ependymoma tumors and cell lines to identify chromosomal rearrangements and regulatory mechanisms underlying aberrant expression of genes that are essential for ependymoma tumorigenesis. In particular, we observe the formation of new topologically associating domains (‘neo-TADs’) by intra- and inter-chromosomal structural variants, tumor-specific 3D chromatin complexes of regulatory elements, and the replacement of CTCF insulators by DNA hyper-methylation as novel oncogenic mechanisms in ependymoma. Through inhibition experiments we validated that the newly identified genes, including RCOR2, ITGA6, LAMC1, and ARL4C, are highly essential for the survival of patient-derived ependymoma models in a disease subtype-specific manner. Thus, this study identifies potential novel therapeutic vulnerabilities in ependymoma and extends our ability to reveal tumor-dependency genes and pathways by oncogenic 3D genome conformations even in tumors that lack known genetic alterations.
Incidental Findings on Whole-body Computed Tomography in Major Trauma Patients: Who and What?
Authors: Liu Ping-Yuan , Kuo Ling-Wei , Liao Chien-Hung , Hsieh Chi-Hsun , Bajani Francesco , Fu Chih-Yuan
Published: November 2020

Background The use of whole-body computed tomography (WBCT) scans has greatly increased in the management of patients with major trauma. Sometimes, nontraumatic findings on WBCT are observed. In the current study, we aimed to investigate the proportion of nontraumatic findings on WBCT in major trauma patients and the characteristics of patients with nontraumatic findings on WBCT.Methods From June 2013 to May 2016, adult trauma patients who received WBCT were enrolled. The proportions of nontraumatic findings in different anatomical regions were studied. Nontraumatic findings were classified and evaluated as clinically important findings and findings that did not need further follow-up or treatment. The characteristics of patients with nontraumatic findings were analyzed and compared with those of patients without nontraumatic findings.Results A total of 217 patients were enrolled in this study during the 3-year study period, and 89 (41.0%) patients had nontraumatic findings. Nontraumatic findings were found more frequently in the abdomen (69.2%) than in the head/neck (17.3%) and chest regions (13.5%). In total, 31.3% of the findings needed further follow-up or treatment. Patients with nontraumatic findings that needed further management were significantly older than patients without nontraumatic findings (57.3 vs. 38.9, p<0.001), especially those with abdominal nontraumatic findings (57.9 vs. 41.3, p<0.001). A significantly higher proportion of females was observed in the group with head/neck nontraumatic findings that needed further management than in the group without nontraumatic findings (56.3% vs. 24.9%, p=0.015).Conclusions WBCT could provide alternative benefits for nontraumatic findings. The WBCT images should be read carefully for nontraumatic findings, especially for elderly patients. For female patients, the head/neck region should be carefully evaluated with WBCT for possible thyroid lesions. A comprehensive program for the follow-up of nontraumatic findings is needed.
Hyperbolic Metamaterials via Hierarchical Block Copolymer Nanostructures
Authors: Murataj Irdi , Channab Marwan , Cara Eleonora , Pirri Candido Fabrizio , Boarino Luca , Angelini Angelo , Lupi Federico Ferrarese
Published: November 2020

Hyperbolic metamaterials (HMMs) offer unconventional properties in the field of optics, enabling the opportunity for confinement and propagation of light at the nanoscale. In-plane orientation of the optical axis, in the direction coinciding with the anisotropy of the HMMs, is desirable for a variety of novel applications in nanophotonics and imaging. Here, we introduce a method for creating localized HMMs with in-plane optical axis based on block copolymers (BCPs) blend instability. The dewetting of BCP thin film over topographically defined substrates generates droplets composed of highly ordered lamellar nanostructures in hierarchical configuration. The hierarchical nanostructures represent a valuable platform for the subsequent pattern transfer into a Au/air HMM, exhibiting hyperbolic behavior in a broad wavelength range in the visible spectrum. A computed Purcell factor as high as 32 at 580 nm supports the strong reduction in the fluorescence lifetime of defects in nanodiamonds placed on top of the HMM.
Assessing the Quality of Reporting to China's National TB Surveillance Systems
Authors: Li Tao , YANG Lijia , SMITH-JEFFCOAT Sarah E. , WANG Alice , GUO Hui , CHEN Wei , DU Xin , ZHANG Hui
Published: November 2020

Background: The reliability of disease surveillance may be restricted by sensitivity or the ability of the system to capture all disease. Our objective was to quantify under-reporting and concordance of recording persons with tuberculosis (TB) in the national TB surveillance systems: Infectious Disease Reporting System (IDRS) and TB Information Management System (TBIMS). Methods: This retrospective review includes patients identified in 2016 from six counties in Guangdong, Jiangsu, Henan, Heilongjiang, Sichuan, and Yunnan provinces. County staff linked TB patients identified from facility-specific health and laboratory information systems with TB patients recorded in IDRS and TBIMS. Under-reporting was calculated as the percentage of TB patients not recorded in IDRS or TBIMS. Timeliness, patients recorded within 24 hours after diagnosis, and concordance, accuracy and completeness of key variables when compared to medical records, were analyzed through comparing sampled patient-records with corresponding patient-records in health facilities. Multivariable logistic regression was used to examine factors associated with under-reporting. Results: We found 505 (10.7%) patients diagnosed with TB were missing within IDRS and 1451 (30.9%) patients were missing within TBIMS. Of 171 patient-records reviewed in IDRS and 170 patient-records in TBIMS, 12.3% and 6.5% were found to be untimely, 10.7% and 7.1% were found having inconsistent home address. The risk of under-reporting to both IDRS and TBIMS was greatest in TB diagnosis at a tertiary health facilities and non-residents; the risk of under-reporting to TBIMS was greatest with patients aged 65 or older and extrapulmonary TB (EPTB).Conclusions: We found that more than one in four TB patients were not recorded in TBIMS. It is important to improve the reporting and recording of TB patients. Local TB programs that focus on training, and mentoring high-burden hospitals, facilities that cater to EPTB, and migrant patients may improve reporting and recording. Additional human resources for data collection and management, and monitoring and evaluation systems are needed to improve national surveillance systems and TB prevention, diagnosis and treatment services.
Forecasting the Carsharing Service Demand Using Uni and Multivariable Models
Authors: Alencar Victor Aquiles , Pessamilio Lucas Ribeiro , Silva Felipe Rooke da , Bernardino Heder Soares , Vieira Alex Borges
Published: November 2020

Car-sharing is an alternative to urban mobility that has been widely adopted. However, this approach is prone to several problems, such as fleet imbalance, due to the variance of the daily demand in large urban centers. In this work, we apply two time series techniques, namely, Long Short-Term Memory (LSTM) and Prophet, to infer the demand for three real car-sharing services. We also apply several state-of-the-art models on free-floating data in order to get a better understanding of what works best for this type of data. In addition to historical data, we also use climatic attributes in LSTM applications. As a result, the addition of meteorological data improved the model’s performance, especially on Evo: an average Mean Absolute Error (MAE) of approximately 61.13 travels was obtained with the demand data on Evo, while MAE equals 32.72 travels was observed when adding the climatic data, the other datasets also improved but none other improved this much. For the free-floating data test, we got the Boosting Algorithms (XGBoost, Catboost, and LightGBM) got the best performance short term, the worst one has an improvement of around 22% of MAE over the next best-ranked (Prophet). Meanwhile in the long term Prophet got the best MAE result, around 22.5% better than the second-best (LSTM).