bluuebunny/crossref_metadata_2025 huggingface dataset:
High-dose biotin in progressive multiple sclerosis: A prospective study of 178 patients in routine clinical practice
Authors: Couloume Laura , Barbin Laetitia , Leray Emmanuelle , Wiertlewski Sandrine , Le Page Emmanuelle , Kerbrat Anne , Ory Solenn , Le Port Damien , Edan Gilles , Laplaud David-Axel , Michel Laure
Published: December 2019

Background:

A recent controlled trial suggested that high-dose biotin supplementation reverses disability progression in patients with progressive multiple sclerosis.

Objective:

To analyze the impact of high-dose biotin in routine clinical practice on disability progression at 12 months.

Methods:

Progressive multiple sclerosis patients who started high-dose biotin at Nantes or Rennes Hospital between 3 June 2015 and 15 September 2017 were included in this prospective study. Disability outcome measures, patient-reported outcome measures, relapses, magnetic resonance imaging (MRI) data, and adverse events were collected at baseline, 6, and 12 months.

Results:

A total of 178 patients were included. At baseline, patients were 52.0 ± 9.4 years old, mean Expanded Disability Status Scale (EDSS) score was 6.1 ± 1.3, mean disease duration was 16.9 ± 9.5 years. At 12 months, 3.8% of the patients had an improved EDSS score. Regarding the other disability scales, scores either remained stable or increased significantly. In total, 47.4% of the patients described stability, 27.6% felt an improvement, and 25% described a worsening. Four patients (2.2%) had a relapse. Of the 74 patients (41.6%) who underwent an MRI, 20 (27.0%) had new T2 lesions, 8 (10.8%) had gadolinium-enhancing lesions. Twenty-five (14%) reported adverse event.

Conclusion:

In this study, high-dose biotin did not seem to be associated with a clear improvement in disability.
Joining the party: Incentives and motivations of members and registered sympathizers in contemporary multi-speed membership parties
Authors: Gomez Raul , Ramiro Luis , Morales Laura , Aja Jaime
Published: December 2019

Many parties have updated their recruitment strategies and offer softer routes for joining their ranks. In some parties, registered sympathizers are given virtually the same rights as traditional members with substantially lower costs. This begs the question, why would somebody take the further step of joining such parties as full members rather than sympathizers? This article analyzes this question by using membership surveys from three left-wing Spanish parties. As such, it explores the usefulness of the general incentives model (GIM) for explaining the decisions of these two groups of affiliates. We find that full members and sympathizers differ in the motives they have to join the party and in their evaluations of the diverse types of incentives included in the GIM. Candidate selection incentives seem particularly important for sympathizers, whereas selective outcome incentives, selective process benefits, collective outcome benefits and altruistic motivations play a more significant role for members.
Modeling tourism demand: Theoretical and empirical considerations for future research
Authors: Dogru Tarik , Bulut Umit , Sirakaya-Turk Ercan
Published: December 2019

Although tourism literature is replete with tourism demand studies, numerous empirical and theoretical issues remain unresolved. The majority of the extant studies center around replication of well-established theory of tourism demand with applications of contemporary empirical techniques for different sets of tourist-originating and receiving countries. However, the application of empirical techniques, especially panel data methods that are utilized to model tourism demand, seems to be arbitrarily chosen without due consideration of theoretical and empirical ramifications. The purpose of this study is to present a critical review of the tourism demand literature. We assessed the theoretical and methodological inaccuracies when modeling tourism demand in general and when applying panel data models in particular. We provided a guide to application of panel data techniques when modeling tourism demand. The article ends with discussions of an agenda for future research to fill the gaps in the extant literature and advance tourism demand research.
Using the Onitor® Track for weight loss: A mixed methods study among overweight and obese women
Authors: Buchan Kelly , Morgan Heather M
Published: December 2019

Non-communicable disease rates associated with being overweight or obese are rising. Technologies warrant consideration as weight loss interventions. Cloudtag’s® Onitor® Track, a dual-position wearable plus smartphone application, monitors energy expenditure and provides tailored exercise programmes. This research aimed to undertake an experimental study of 20 overweight and obese women using the technology; explore its feasibility and acceptability through interviews; and investigate its behaviour change techniques. The primary outcome was decreased body weight (kg) at 4 weeks. Secondary outcomes were body mass index (kg/m2) and waist circumference (cm) changes. 15 overweight and obese women took part. Results indicated weight loss (median 2.7 kg, p < 0.05) and waist circumference decrease (median 4 cm, p < 0.05), but attrition was high (60%). Users reported dietary changes but few activity adjustments. They valued feedback. 27 behaviour change techniques were identified. The Onitor® Track shows potential for weight loss in overweight and obese women, but further work is needed.
Expectations, vote choice and opinion stability since the 2016 Brexit referendum
Authors: Grynberg Charlotte , Walter Stefanie , Wasserfallen Fabio
Published: December 2019

A surprising development in the post-referendum Brexit process has been that vote intentions have remained largely stable, despite the cumbersome withdrawal negotiations. We examine this puzzle by analyzing the role of voters’ expectations about the European Union’s willingness to accommodate the UK after the pro-Brexit vote. Using data from the British Election Study, we explore how these expectations are updated over time, and how they are related to vote intentions. We find that voters who were more optimistic about the European Union’s response were more likely to vote Leave. Over the course of the negotiations, Leavers have become more disillusioned. These adjustments, however, have not translated into shifts in vote intentions. Overall, we find evidence that motivated reasoning is an important driver of public opinion on Brexit.
The effect of malocclusion on dating prospects
Authors: Khela Sonia , Newton J Timothy , Jeremiah Huw G
Published: December 2019

Objective:

To establish whether the appearance of malocclusion affected dating prospects. The secondary objective was to identify any significant predictors relating to likelihood of dating.

Design:

Cross-sectional study.

Setting:

King’s College London.

Participants:

A total of 232 undergraduate students.

Methods:

Participants were shown images of either one man or one woman. The images had been manipulated using computer software to represent one of three differing dental appearances: post-orthodontic aligned teeth; pre-orthodontic crowded teeth; or pre-orthodontic missing teeth (developmentally absent maxillary lateral incisors). Sealed envelopes were randomly assigned to participants, who rated the individual in the image in relation to: attractiveness; intelligence; happiness; nervousness; and how much they would want to go on a date with them. The response format was a 100-mm visual analogue scale.

Results:

The aligned dental appearance received statistically significant higher ratings of attractiveness ( P < 0.001), intelligence ( P = 0.031), likelihood of dating ( P = 0.017) as well as lower ratings of nervousness ( P = 0.020). There was no statistically significant difference in relation to happiness ( P = 0.43), neither were there any statistically significant differences between the crowded and missing dental appearances. Regression analysis revealed that rated attractiveness was the most significant predictor in relation to likelihood of dating ( P < 0.001).

Conclusion:

Malocclusion did influence dating prospects. Photographs of individuals with aligned teeth were more likely to be rated highly in relation to attractiveness, intelligence and likelihood of dating, when compared with images of malocclusions. The most significant predictor of likelihood of dating was rated attractiveness.
Reasonable Reliance and Apparent Authority: East Asia Company Ltd v PT Satria Tirtatama Energindo [2019] UKPC 30
Authors: Campbell Mark
Published: December 2019

The Privy Council in East Asia Company Ltd v PT Satria Tirtatama Energindo (a case on appeal from Bermuda) has provided clarification on the correct approach to the reliance aspect of apparent authority. Reliance can be of particular importance where the third party has been put on notice as to the agent’s lack of authority: for example, when the transaction is unusual or especially onerous for the principal. The Privy Council concluded, albeit obiter, that the correct test is one of reasonable reliance by the third party. In doing so, it has rejected the approach adopted by Lord Neuberger NPJ in the Hong Kong case of Akai Holdings and subsequently followed in a number of English decisions: that is, reliance by the third party is presumed in the absence of dishonesty or irrationality.
Open our visualization eyes, individualization: On Albrecht Dürer’s 1515 wood cut celestial charts
Authors: d’Auriol Brian J
Published: December 2019

The position that visualization is an intimate part of human existence and associated with the human species is advanced in this work: visualization abounds delimited by the space of individuality across human history. Visualization involves two complementary aspects of the uniqueness deemed of individuals: individualization reflects individuals’ capabilities and personalization reflects designs that seek compatibility with individuals’ capabilities. This has a number of implications upon the design and evaluation of visualizations. For one, a suitable visualization model that expresses individualization and personalization is needed: a brief survey of models is presented. For another, addressing intellectual uniqueness requires deep analysis and selective objective balance due to the potentially humongous number of unique ideas that support visualization design and viewer experiences. The Engineering Insightful Serviceable Visualizations model is selected as a guide for a comprehensive visualization evaluation of Albrecht Dürer’s 1515 celestial charts. Motivating this choice of visualization is its significance as the first notable and influential European star chart intended for scientific use and mass viewership, and as a blending of science and art. In addition, there is a lack of discussion concerning this particular visualization in the visualization literature. Concluding remarks suggest the significance of approaching visualization from this point-of-view.
How US students’ geo-cultural knowledge and intercultural receptiveness is impacted through contact with international teachers
Authors: Ganley DeLacy , Kula Stacy M , Kallemeyn David
Published: December 2019

To understand how K-12 students in the USA are impacted by their interactions with international teachers (ie teachers visiting the USA from other countries), this study asked ‘ Does contact with an international teacher correlate with increased geo-cultural knowledge and/or receptiveness to non-USA countries, peoples and/or cultures?’. To address this question, the study drew on pre- and post-contact data from 1,082 students who had interactions with international teachers who were in the USA for a six-week educational program. Analysis of the data indicated that the students’ geo-cultural knowledge increased after having contact with an international teacher. Students were more likely to be able to identify the visiting teacher’s country as being real (as opposed to fictional), its geographic location ( vis-a-vis continent identification), and its dominant language and religion. Findings also showed that contact with international teachers correlated with increased receptiveness towards and interest in non-USA countries/peoples/culture among elementary and middle school students, but not so much among high school students. This study suggests programs supported by international teachers in schools can be effective at helping US youth gain needed intercultural competencies and, in the process, can promote global well-being.
The influence of manufacturing technology on the properties of layered composites with polyester–glass recyclate additive
Authors: Kyzioł Lesław , Panasiuk Katarzyna , Barcikowski Michał , Hajdukiewicz Grzegorz
Published: December 2019

The article describes the technologies of recycling polyester–glass waste and the influence of manufacturing technology on the properties of layered composites with polyester–glass recyclate additive. Milled polyester–glass waste was used as the recyclate. Polyester–glass composites with a specific content of recyclate were manufactured by means of manual laminating and vacuum bagging. The influence of the recyclate content and manufacturing method on the mechanical properties of composites was determined with the aid of specimens exposed to static tensile testing. Test results indicated that the composite without recyclate additive manufactured by means of vacuum bagging exhibits higher strength properties than the same composite manufactured by means of manual laminating. Additionally, its plasticity is much higher than that of the composite manufactured by means of manual laminating. The tests indicated that the tensile properties of the composite are, essentially, influenced by the content of recyclate (apart from the manufacturing method). Adding recyclate to the manufactured composite in the amount of 10% and 20% causes a significant decrease in its tensile properties in relation to the composite without the recyclate.
Reduced Brain Electric Activity and Functional Connectivity in Bipolar Euthymia: An sLORETA Source Localization Study
Authors: Painold Annamaria , Faber Pascal L. , Reininghaus Eva Z. , Mörkl Sabrina , Holl Anna K. , Achermann Peter , Saletu Bernd , Saletu-Zyhlarz Gerda , Anderer Peter , Dalkner Nina , Birner Armin , Bengesser Susanne , Kapfhammer Hans-Peter , Milz Patricia
Published: December 2019

Bipolar disorder (BD) is a chronic illness with a relapsing and remitting time course. Relapses are manic or depressive in nature and intermitted by euthymic states. During euthymic states, patients lack the criteria for a manic or depressive diagnosis, but still suffer from impaired cognitive functioning as indicated by difficulties in executive and language-related processing. The present study investigated whether these deficits are reflected by altered intracortical activity in or functional connectivity between brain regions involved in these processes such as the prefrontal and the temporal cortices. Vigilance-controlled resting state EEG of 13 euthymic BD patients and 13 healthy age- and sex-matched controls was analyzed. Head-surface EEG was recomputed into intracortical current density values in 8 frequency bands using standardized low-resolution electromagnetic tomography. Intracortical current densities were averaged in 19 evenly distributed regions of interest (ROIs). Lagged coherences were computed between each pair of ROIs. Source activity and coherence measures between patients and controls were compared (paired t tests). Reductions in temporal cortex activity and in large-scale functional connectivity in patients compared to controls were observed. Activity reductions affected all 8 EEG frequency bands. Functional connectivity reductions affected the delta, theta, alpha-2, beta-2, and gamma band and involved but were not limited to prefrontal and temporal ROIs. The findings show reduced activation of the temporal cortex and reduced coordination between many brain regions in BD euthymia. These activation and connectivity changes may disturb the continuous frontotemporal information flow required for executive and language-related processing, which is impaired in euthymic BD patients.
Joint sparing Kirschner-wire fixation for displaced proximal phalangeal neck fractures: randomized prospective comparative study
Authors: Sadek Ahmed Fathy
Published: December 2019

The aim of this study was to compare two joint sparing Kirschner-wire fixation techniques for displaced proximal phalangeal neck fractures. Forty-six patients with proximal phalangeal neck fractures managed by either percutaneous antegrade flexible intramedullary nailing (Group I) or crossed Kirschner-wires (Group II) were recruited for a randomized prospective comparative study. Clinical and radiological assessment of all patients was done in addition to the Kang scoring system, Disability of Arm, Shoulder and Hand score and total active motion. The mean time for radiological union for both groups was 5.8 weeks. The mean postoperative total active motion, Kang and the Disability of Arm, Shoulder and Hand scores were better in Group I patients, but without any statistically significant differences. Closed reduction and percutaneous Kirschner-wire fixation by a joint sparing approach will yield good functional results with no or minimal complications in proximal phalangeal neck fractures.

Level of evidence: II
Subordinate–Supervisor Friendship in Cyberspace: A Typological and Comparative Analysis of Hotel Employees
Authors: Yang Fiona X.
Published: December 2019

Individuals’ social and professional arenas entangle so easily today with the rise of social networking sites (SNS). Drawing upon the boundary and social exchange theories, this study investigates whether supervisor–subordinate interactions in cyberspace will spill over to the workplace. A two-dimensional typology of hotel employees is delineated on the basis of their SNS interaction behaviors. The moderating effect of individual type is also investigated. The results indicate that supervisor–subordinate SNS interactions could transition to favorable leader–member exchanges in the workplace that, in turn, promote employees’ organizational citizenship behaviors. In addition, the impact of SNS interaction on leader–member exchange is stronger for employees with proactive personalities and self-disclosure tendencies. This study fills the void of inadequate empirical literature on hierarchical friendship in cyberspace and advances research on the moderating effect of employee personality. Managerial implications are also discussed.
Sweet’s Syndrome: A Classical Presentation of a Rare Disease
Authors: Mollaeian Arash , Roudsari Hadi , Talebi Ebrahim
Published: December 2019

Sweet’s syndrome, also known as acute febrile neutrophilic dermatosis, is a rare disorder that typically presents with rapid appearance of tender skin lesions accompanied by fever and leukocytosis with neutrophilia. Its pathogenesis is not fully understood. The syndrome is generally classified into classical, malignancy-associated, and drug-induced categories, each of which has its specific characteristics. In this article, we present a case of classical Sweet’s syndrome in a woman who presented with an acute viral illness.
Manufacturing processes for fabrication of flip-chip micro-bumps used in microelectronic packaging: An overview
Authors: Datta Madhav
Published: December 2019

Electronic packaging is the methodology for connecting and interfacing the chip technology with a system and the physical world. The objective of packaging is to ensure that the devices and interconnections are packaged efficiently and reliably. Chip–package interconnection technologies currently used in the semiconductor industry include wire bonding, tape automated bonding and flip-chip solder bump connection. Among these interconnection techniques, the flip-chip bumping technology is commonly used in advanced electronic packages since this interconnection is an area array configuration so that the entire surface of the chip can be covered with bumps for the highest possible input/output (I/O) counts. The present article reviews the manufacturing processes for the fabrication of flip-chip bumps for chip–package interconnection. Various solder bumping technologies used in high-volume production include evaporation, solder paste screening and electroplating. Evaporation process produces highly reliable bumps, but it is extremely expensive and is limited to lead or lead-rich solders. Solder paste screening is cost-effective, but issues related to excessive void formation limits the process to low-end products. On the other hand, electrochemical fabrication of flip-chip bumps is an extremely selective and efficient process, which is extendible to finer pitch, larger wafers and a variety of solder compositions, including lead-free alloys. Electrochemically fabricated copper pillar bumps offer fine pitch capabilities with excellent electromigration performance. Due to these virtues, the copper pillar bumping technology is emerging as a lead-free bumping technology option for high-performance electronic packaging.
Correction to: Methods for trustworthy nutritional recommendations NutriRECS (Nutritional Recommendations and accessible Evidence summaries Composed of Systematic reviews): a protocol
Authors: Johnston Bradley C. , Alonso-Coello Pablo , Bala Malgorzata M. , Zeraatkar Dena , Rabassa Montserrat , Valli Claudia , Marshall Catherine , El Dib Regina , Vernooij Robin W. M. , Vandvik Per O. , Guyatt Gordon H.
Published: December 2019

Following publication of the original article [1], the authors reported a change in the ‘Competing interests’ section as described below.
Representation learning for clinical time series prediction tasks in electronic health records
Authors: Ruan Tong , Lei Liqi , Zhou Yangming , Zhai Jie , Zhang Le , He Ping , Gao Ju
Published: December 2019

Background

Electronic health records (EHRs) provide possibilities to improve patient care and facilitate clinical research. However, there are many challenges faced by the applications of EHRs, such as temporality, high dimensionality, sparseness, noise, random error and systematic bias. In particular, temporal information is difficult to effectively use by traditional machine learning methods while the sequential information of EHRs is very useful.

Method

In this paper, we propose a general-purpose patient representation learning approach to summarize sequential EHRs. Specifically, a recurrent neural network based denoising autoencoder (RNN-DAE) is employed to encode inhospital records of each patient into a low dimensional dense vector.

Results

Based on EHR data collected from Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, we experimentally evaluate our proposed RNN-DAE method on both mortality prediction task and comorbidity prediction task. Extensive experimental results show that our proposed RNN-DAE method outperforms existing methods. In addition, we apply the “Deep Feature” represented by our proposed RNN-DAE method to track similar patients with t-SNE, which also achieves some interesting observations.

Conclusion

We propose an effective unsupervised RNN-DAE method to summarize patient sequential information in EHR data. Our proposed RNN-DAE method is useful on both mortality prediction task and comorbidity prediction task.
High-sensitivity troponin I and B-type natriuretic peptide biomarkers for prediction of cardiovascular events in patients with coronary artery disease with and without diabetes mellitus
Authors: Wong Yuen-Kwun , Cheung Chloe Y. Y. , Tang Clara S. , Hai JoJo S. H. , Lee Chi-Ho , Lau Kui-Kai , Au Ka-Wing , Cheung Bernard M. Y. , Sham Pak-Chung , Xu Aimin , Lam Karen S. L. , Tse Hung-Fat
Published: December 2019

Background

High-sensitivity troponin I (hs-Tnl) and B-type natriuretic peptide (BNP) are promising prognostic markers for coronary artery disease (CAD). This prospective cohort study investigated whether a combination of these cardiac biomarkers with conventional risk factors would add incremental value for the prediction of secondary major adverse cardiovascular events (MACEs) in patients with CAD, with and without type 2 diabetes mellitus (T2DM).

Methods

Baseline plasma level of hs-Tnl and BNP was measured in 2275 Chinese patients with stable CAD. Patients were monitored for new-onset of MACE over a median of 51 months. Cox proportional hazard model and area under the receiver operating characteristic curve (AUC) were used to assess the association of cardiac biomarkers with MACE and their predictive values in relationship with or without T2DM.

Results

During the follow up period 402 (18%) patients experienced a new-onset MACE with hs-Tnl and BNP level significantly higher than in those without MACE. In multivariable analyses, patients with elevated hs-Tnl (hazard ratio, 1.75 [95% CI 1.41–2.17]; P < 0.001) and BNP (hazard ratio, 1.42 [95% CI 1.15–1.75]; P = 0.001) were significantly associated with an increased risk of MACE after adjustment for variables of a risk factor model of age, sex, T2DM and hypertension. The risk factor model had an AUC of 0.64 for MACE prediction. The AUC significantly increased to 0.68 by the addition of hs-Tnl to the risk factor model. Subgroup analyses showed that hs-Tnl and BNP remained significant predictors of MACE in both patients with and without T2DM in multivariable models with higher risk of MACE evident in those without T2DM. Among patients without T2DM, addition of each biomarker yielded greater predictive accuracy than in T2DM patients, with AUC further increased to 0.75 when a combination of hs-Tnl and BNP was added to the risk factor model (age, sex and hypertension).

Conclusions

Elevated hs-Tnl and BNP level are independent predictors of new-onset MACE in CAD patients, irrespective of diabetes status. Among CAD patients without T2DM, a combination of cardiac biomarkers hs-Tnl and BNP yield the greatest predictive value beyond conventional risk factors.
Carbonic anhydrase 2 (CAII) supports tumor blood endothelial cell survival under lactic acidosis in the tumor microenvironment
Authors: Annan Dorcas A. , Maishi Nako , Soga Tomoyoshi , Dawood Randa , Li Cong , Kikuchi Hiroshi , Hojo Takayuki , Morimoto Masahiro , Kitamura Tetsuya , Alam Mohammad Towfik , Minowa Kazuyuki , Shinohara Nobuo , Nam Jin-Min , Hida Yasuhiro , Hida Kyoko
Published: December 2019

Background

Tumor endothelial cells (TECs) perform tumor angiogenesis, which is essential for tumor growth and metastasis. Tumor cells produce large amounts of lactic acid from glycolysis; however, the mechanism underlying the survival of TECs to enable tumor angiogenesis under high lactic acid conditions in tumors remains poorly understood.

Methodology

The metabolomes of TECs and normal endothelial cells (NECs) were analyzed by capillary electrophoresis time-of-flight mass spectrometry. The expressions of pH regulators in TECs and NECs were determined by quantitative reverse transcription-PCR. Cell proliferation was measured by the MTS assay. Western blotting and ELISA were used to validate monocarboxylate transporter 1 and carbonic anhydrase 2 (CAII) protein expression within the cells, respectively. Human tumor xenograft models were used to access the effect of CA inhibition on tumor angiogenesis. Immunohistochemical staining was used to observe CAII expression, quantify tumor microvasculature, microvessel pericyte coverage, and hypoxia.

Results

The present study shows that, unlike NECs, TECs proliferate in lactic acidic. TECs showed an upregulated CAII expression both in vitro and in vivo. CAII knockdown decreased TEC survival under lactic acidosis and nutrient-replete conditions. Vascular endothelial growth factor A and vascular endothelial growth factor receptor signaling induced CAII expression in NECs. CAII inhibition with acetazolamide minimally reduced tumor angiogenesis in vivo. However, matured blood vessel number increased after acetazolamide treatment, similar to bevacizumab treatment. Additionally, acetazolamide-treated mice showed decreased lung metastasis.

Conclusion

These findings suggest that due to their effect on blood vessel maturity, pH regulators like CAII are promising targets of antiangiogenic therapy.

Graphical abstract
Long non-coding RNA BZRAP1-AS1 silencing suppresses tumor angiogenesis in hepatocellular carcinoma by mediating THBS1 methylation
Authors: Wang Weiwei , Chen Guoyong , Wang Bing , Yuan Zhenhua , Liu Guangbo , Niu Biao , Chen Yongfeng , Zhou Shaotang , He Junchuang , Xue Huanzhou
Published: December 2019

Background

Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer associated with a high mortality. Long non-coding RNAs (lncRNAs) have recently emerged as regulators in the development and progression of several cancers, and therefore represent an opportunity to uncover new targets for therapy. In the present study, we aimed to investigate the potential effect of lncRNA BZRAP1-AS1 on the angiogenesis of HCC.

Methods

Microarray-based data analysis was initially employed to screen genes and lncRNAs that are differentially expressed in HCC and the candidate BZRAP1-AS1 was identified as a hit. The expression of BZRAP1-AS1 and thrombospondin-1 (THBS1) in HCC tissues and cells were then determined using RT-qPCR. The gene methylation level was measured by methylation-specific PCR (MSP) and bisulfite sequencing PCR (BSP) assays. Next, the interactions between BZRAP1-AS1, DNA methyltransferase 3B (DNMT3b), and THBS1 were assessed by RIP, RNA pull-down and ChIP assays. Finally, the roles of BZRAP1-AS1, DNMT3b and THBS1 in angiogenesis in vitro as well as tumorigenesis in vivo were evaluated by a battery of the gain- and loss-of function experiments.

Results

BZRAP1-AS1 was identified as a highly expressed lncRNA in HCC tissues and cells. Down-regulation of BZRAP1-AS1 in HCC cells inhibited HUVEC proliferation, migration and angiogenesis. By interacting with DNMT3b, BZRAP1-AS1 induced methylation of the THBS1 promoter and inhibited the transcription of THBS1, resulting in promoted angiogenesis of HUVECs. Moreover, silencing of BZRAP1-AS1 repressed the angiogenesis as well as the tumor growth of HCC in vivo via up-regulating THBS1.

Conclusion

This study provides evidence that angiogenesis in HCC is hindered by silencing of BZRAP1-AS1. Thus, BZRAP1-AS1 may be a promising marker for the treatment of HCC.
X-ray microtomography and linear discriminant analysis enable detection of embolism-related acoustic emissions
Authors: De Baerdemaeker Niels J. F. , Stock Michiel , Van den Bulcke Jan , De Baets Bernard , Van Hoorebeke Luc , Steppe Kathy
Published: December 2019

Background

Acoustic emission (AE) sensing is in use since the late 1960s in drought-induced embolism research as a non-invasive and continuous method. It is very well suited to assess a plant’s vulnerability to dehydration. Over the last couple of years, AE sensing has further improved due to progress in AE sensors, data acquisition methods and analysis systems. Despite these recent advances, it is still challenging to detect drought-induced embolism events in the AE sources registered by the sensors during dehydration, which sometimes questions the quantitative potential of AE sensing.

Results

In quest of a method to separate embolism-related AE signals from other dehydration-related signals, a 2-year-old potted Fraxinus excelsior L. tree was subjected to a drought experiment. Embolism formation was acoustically measured with two broadband point-contact AE sensors while simultaneously being visualized by X-ray computed microtomography (µCT). A machine learning method was used to link visually detected embolism formation by µCT with corresponding AE signals. Specifically, applying linear discriminant analysis (LDA) on the six AE waveform parameters amplitude, counts, duration, signal strength, absolute energy and partial power in the range 100–200 kHz resulted in an embolism-related acoustic vulnerability curve (VCAE-E) better resembling the standard µCT VC (VCCT), both in time and in absolute number of embolized vessels. Interestingly, the unfiltered acoustic vulnerability curve (VCAE) also closely resembled VCCT, indicating that VCs constructed from all registered AE signals did not compromise the quantitative interpretation of the species’ vulnerability to drought-induced embolism formation.

Conclusion

Although machine learning could detect similar numbers of embolism-related AE as µCT, there still is insufficient model-based evidence to conclusively attribute these signals to embolism events. Future research should therefore focus on similar experiments with more in-depth analysis of acoustic waveforms, as well as explore the possibility of Fast Fourier transformation (FFT) to remove non-embolism-related AE signals.
Effectiveness and cost-effectiveness of Improving clinicians’ diagnostic and communication Skills on Antibiotic prescribing Appropriateness in patients with acute Cough in primary care in CATalonia (the ISAAC-CAT study): study protocol for a cluster randomised controlled trial
Authors: Ruiz Rafa , Moragas Ana , Trapero-Bertran Marta , Sisó Antoni , Berenguera Anna , Oliva Glòria , Borràs-Santos Alícia , García-Sangenís Ana , Puig-Junoy Jaume , Cots Josep M. , Morros Rosa , Mora Toni , Lanau-Roig Anna , Monfà Ramon , Troncoso Amelia , Abellana Rosa M. , Gálvez Pau , Medina-Perucha Laura , Bjerrum Lars , Amo Isabel , Barragán Nieves , Llor Carl
Published: December 2019

Background

Despite their marginal benefit, about 60% of acute lower respiratory tract infections (ALRTIs) are currently treated with antibiotics in Catalonia. This study aims to evaluate the effectiveness and efficiency of a continuous disease-focused intervention (C-reactive protein [CRP]) and an illness-focused intervention (enhancement of communication skills to optimise doctor-patient consultations) on antibiotic prescribing in patients with ALRTIs in Catalan primary care centres.

Methods/design

A cluster randomised, factorial, controlled trial aimed at including 20 primary care centres (N = 2940 patients) with patients older than 18 years of age presenting for a first consultation with an ALRTI will be included in the study. Primary care centres will be identified on the basis of socioeconomic data and antibiotic consumption. Centres will be randomly assigned according to hierarchical clustering to any of four trial arms: usual care, CRP testing, enhanced communication skills backed up with patient leaflets, or combined interventions. A cost-effectiveness and cost-utility analysis will be performed from the societal and national healthcare system perspectives, and the time horizon of the analysis will be 1 year. Two qualitative studies (pre- and post-clinical trial) aimed to identify the expectations and concerns of patients with ALRTIs and the barriers and facilitators of each intervention arm will be run. Family doctors and nurses assigned to the interventions will participate in a 2-h training workshop before the inception of the trial and will receive a monthly intervention-tailored training module during the year of the trial period. Primary outcomes will be antibiotic use within the first 6 weeks, duration of moderate to severe cough, and the quality-adjusted life-years. Secondary outcomes will be duration of illness and severity of cough measured using a symptom diary, healthcare re-consultations, hospital admissions, and complications. Healthcare costs will be considered and expressed in 2021 euros (year foreseen to finalise the study) of the current year of the analysis. Univariate and multivariate sensitivity analyses will be carried out.

Discussion

The ISAAC-CAT project will contribute to evaluate the effectiveness and efficiency of different strategies for more appropriate antibiotic prescribing that are currently out of the scope of the actual clinical guidelines.

Trial registration

ClinicalTrials.gov, NCT03931577.
Community interventions to prevent violence against women and girls in informal settlements in Mumbai: the SNEHA-TARA pragmatic cluster randomised controlled trial
Authors: Daruwalla Nayreen , Machchhar Unnati , Pantvaidya Shanti , D’Souza Vanessa , Gram Lu , Copas Andrew , Osrin David
Published: December 2019

Background

In a cluster randomised controlled trial in Mumbai slums, we will test the effects on the prevalence of violence against women and girls of community mobilisation through groups and individual volunteers. One in three women in India has survived physical or sexual violence, making it a major public health burden. Reviews recommend community mobilisation to address violence, but trial evidence is limited.

Methods

Guided by a theory of change, we will compare 24 areas receiving support services, community group, and volunteer activities with 24 areas receiving support services only. These community mobilisation activities will be evaluated through a follow-up survey after 3 years. Primary outcomes will be prevalence in the preceding year of physical or sexual domestic violence, and prevalence of emotional or economic domestic violence, control, or neglect against women 15–49 years old. Secondary outcomes will describe disclosure of violence to support services, community tolerance of violence against women and girls, prevalence of non-partner sexual violence, and mental health and wellbeing. Intermediate theory-based outcomes will include bystander intervention, identification of and support for survivors of violence, changes described in programme participants, and changes in communities.

Discussion

Systematic reviews of interventions to prevent violence against women and girls suggest that community mobilisation is a promising population-based intervention. Already implemented in other areas, our intervention has been developed over 16 years of programmatic experience and 2 years of formative research. Backed by public engagement and advocacy, our vision is of a replicable community-led intervention to address the public health burden of violence against women and girls.

Trial registration

Controlled Trials Registry of India, CTRI/2018/02/012047. Registered on 21 February 2018. ISRCTN,ISRCTN84502355. Registered on 22 February 2018.
Barriers to recruiting and retaining psychosis carers: a case study on the lessons learned from the Caring for Caregivers (C4C) trial
Authors: Hazell Cassie M. , Jones Christina J. , Pandey Aparajita , Smith Helen E.
Published: December 2019

Objective

Carers play an important role within the UK mental health system. Those carers who support persons with psychosis can experience a reduction in their own physical and mental health. As part of the Caring for Caregivers (C4C) trial, we piloted a writing intervention (Positive Written Disclosure) that has been shown to improve wellbeing in other populations. Although we reached our recruitment target, we encountered several barriers that made recruitment slower than anticipated. This paper synthesises the process data collected during the C4C trial that relates to the barriers to recruiting and retaining psychosis carers.

Results

We encountered four main carer-specific barriers to the recruitment and retention of participants in our study. These were: (1) poor relationship with mental health clinicians, (2) conflicting with the care recipient’s (CR) needs, (3) lack of spare time, and (4) lack of services for mental health carers. The interventions to assist carers need to be informed by robust evidence and this requires trials that reach their recruitment targets. By sharing our practical experiences other researchers and clinicians can modify their practices to minimise recruitment difficulties and delay.

Trial registration ISRCTN79116352. Retrospectively registered (before the final participant was recruited) on 23rd January 2017
Testing a MultiTEP-based combination vaccine to reduce Aβ and tau pathology in Tau22/5xFAD bigenic mice
Authors: Davtyan Hayk , Hovakimyan Armine , Kiani Shabestari Sepideh , Antonyan Tatevik , Coburn Morgan A. , Zagorski Karen , Chailyan Gor , Petrushina Irina , Svystun Olga , Danhash Emma , Petrovsky Nikolai , Cribbs David H. , Agadjanyan Michael G. , Blurton-Jones Mathew , Ghochikyan Anahit
Published: December 2019

Background

Alzheimer disease (AD) is characterized by the accumulation of beta-amyloid (Aβ) plaques and neurofibrillary tangles composed of hyperphosphorylated tau, which together lead to neurodegeneration and cognitive decline. Current therapeutic approaches have primarily aimed to reduce pathological aggregates of either Aβ or tau, yet phase 3 clinical trials of these approaches have thus far failed to delay disease progression in humans. Strong preclinical evidence indicates that these two abnormally aggregated proteins interact synergistically to drive downstream neurodegeneration. Therefore, combinatorial therapies that concurrently target both Aβ and tau might be needed for effective disease modification.

Methods

A combinatorial vaccination approach was designed to concurrently target both Aβ and tau pathologies. Tau22/5xFAD (T5x) bigenic mice that develop both pathological Aβ and tau aggregates were injected intramuscularly with a mixture of two MultiTEP epitope vaccines: AV-1959R and AV-1980R, targeting Aβ and tau, respectively, and formulated in AdvaxCpG, a potent polysaccharide adjuvant. Antibody responses of vaccinated animals were measured by ELISA, and neuropathological changes were determined in brain homogenates of vaccinated and control mice using ELISA and Meso Scale Discovery (MSD) multiplex assays.

Results

T5x mice immunized with a mixture of Aβ- and tau-targeting vaccines generated high Aβ- and tau-specific antibody titers that recognized senile plaques and neurofibrillary tangles/neuropil threads in human AD brain sections. Production of these antibodies in turn led to significant reductions in the levels of soluble and insoluble total tau, and hyperphosphorylated tau as well as insoluble Aβ42, within the brains of bigenic T5x mice.

Conclusions

AV-1959R and AV-1980R formulated with AdvaxCpG adjuvant are immunogenic and therapeutically potent vaccines that in combination can effectively reduce both of the hallmark pathologies of AD in bigenic mice. Taken together, these findings warrant further development of this vaccine technology for ultimate testing in human AD.
A patient with metformin-associated lactic acidosis successfully treated with continuous renal replacement therapy: a case report
Authors: Kinoshita Hiroki , Yanai Machi , Ariyoshi Koichi , Ando Motozumi , Tamura Ryo
Published: December 2019

Background

Metformin has been widely used as a first-line agent to treat type 2 diabetes mellitus. Lactic acidosis is a rare but serious adverse effect in patients treated with metformin. Recent studies noted a correlation between metformin accumulation and lactic acidosis. Continuous renal replacement therapy for the treatment of metformin-associated lactic acidosis has been documented in some case reports; however, there is currently no specific treatment for metformin-associated lactic acidosis.

Case presentation

A 70-year-old Japanese woman with type 2 diabetes mellitus presented to an emergency room with metformin-associated lactic acidosis. She was found to be hypotensive and laboratory examinations revealed severe lactic acidosis: pH 6.618, partial pressure of carbon dioxide in arterial blood 17.3 mmHg, bicarbonate 1.7 mmol/L, and lactate 18 mmol/L. Severe acidemia persisted despite supportive care including intravenously administered fluids, sodium bicarbonate, antibiotics, and vasopressors. Continuous renal replacement therapy was initiated in our intensive care unit. After dialysis for 3 days, her lactate level and pH value completely normalized. The concentration of metformin detected was 77.5 mg/L, which is one of the highest in metformin-associated lactic acidosis successfully treated without overdose.

Conclusions

The present case had one of the highest metformin concentrations in metformin-associated lactic acidosis successfully treated with continuous renal replacement therapy, and serum metformin concentrations may be useful for the diagnosis of metformin-associated lactic acidosis. Metformin-associated lactic acidosis is a rare but important etiology of lactic acidosis. Continuous renal replacement therapy is advantageous for the treatment of hemodynamically unstable patients with metformin-associated lactic acidosis.
Correction to: High in vitro survival rate of sheep in vitro produced blastocysts vitrified with a new method and device
Authors: Ledda Sergio , Kelly Jen M. , Nieddu Stefano , Bebbere Daniela , Ariu Federica , Bogliolo Luisa , Natan Dity , Arav Amir
Published: December 2019

In the original publication of this article [1], the author point out an error in Fig. 3. The correct Fig. 3 is below.
Thymoquinone ameliorates Pachycondyla sennaarensis venom-induced acute toxic shock in male rats
Authors: Alhazza Ibrahim M. , Ebaid Hossam , Abdel-Salam Bahaa , Al-Tamimi Jameel H. , Hassan Iftekhar , Rady Ahmed M. , Mashaly Ashraf M. A.
Published: December 2019

Background

For many decades, the sting of Samsun ant (Pachycondyla sennaarensis) has been a serious clinical challenge for the people living in some of the major Middle East and Asian countries. In the present study, the therapeutic potential ofNigella sativaderived plant extract component, thymoquinone (TQ) has been tested against the Samsun ant venom (SAV) at the toxic dose in the rats.

Methods

The adult male rats were divided into four groups (n = 10): control, SAV treated, SAV + TQ treated and TQ alone treated. It was found that the sub-lethal dose of SAV alters not only many of the kidney and liver function markers but also induces oxidative stress in the animals. Moreover, the SAV also disturbs various immunological parameters including expression of PMNs, CD-80, CD-86, interleukins and other cytokines compromising the affected organism towards mild to severe allergic reactions including life-risking anaphylaxis.

Results

The plant extract, TQ, effectively restores many of the biochemical and oxidative stress parameters comparable to the normal concomitant with improving the immunological aspects that might attributive in relieving from SAV-induced toxicity and allergic reactions in the affected organism to a greater extent.

Conclusion

Hence, TQ has an excellent antidote property against SAV-induced toxicities in vivo. Although the study is a vivid indication of the potential therapeutic potential of TQ against the SAV induced in vivo toxicity, yet the actual mechanism of interaction translating the toxicity amelioration warrants further investigations.
Anaesthetic management of Castleman’s disease associated with paraneoplastic pemphigus: report of a rare case
Authors: O. Rajasree , Gladston Divya V. , Jayadevan Arya , Koshy Rachel Cherian
Published: December 2019

Background

Castleman’s disease is a rare lymphoproliferative disease which can mimic other malignant tumours and can be associated with paraneoplastic pemphigus especially in the paediatric age group. This presentation can be challenging even to the seasoned anaesthesiologist when it comes to managing such a case presenting for laparotomy.

Case presentation

Here such a case in a 12-year-old who was initially diagnosed as retroperitoneal sarcoma complicated with paraneoplastic pemphigus and inferior venacaval thrombus is presented and its anaesthetic management and challenges are discussed. Special care needs to be taken while anaesthetizing such a patient keeping in mind the difficult airway, adrenocortical suppression, and exacerbation of skin lesions due to various anaesthetic procedures. For this case, the histopathology turned out to be Castleman’s disease.

Conclusion

The anaesthetic challenges associated with paraneoplastic pemphigus in paediatric age group receiving perioperative thromboprophylaxis need special mention. Here we are discussing the challenges and anaesthetic management of such a case as literature on this aspect is few.