bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

AbstractBackgroundIn 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.MethodsGuided 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.DiscussionSystematic 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 registrationControlled 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

Abstract
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

Abstract
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

Abstract
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.
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

AbstractBackgroundFor 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.MethodsThe 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.ResultsThe 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.ConclusionHence, 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

Abstract
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.
Misfolded α-synuclein causes hyperactive respiration without functional deficit in live neuroblastoma cells
Authors: Ugalde Cathryn L. , Annesley Sarah J. , Gordon Shane E. , Mroczek Katelyn , Perugini Matthew A. , Lawson Victoria A. , Fisher Paul R. , Finkelstein David I. , Hill Andrew F. 
Published: December 2019

ABSTRACT
The misfolding and aggregation of the largely disordered protein, α-synuclein, is a central pathogenic event that occurs in the synucleinopathies, a group of neurodegenerative disorders that includes Parkinson's disease. While there is a clear link between protein misfolding and neuronal vulnerability, the precise pathogenic mechanisms employed by disease-associated α-synuclein are unresolved. Here, we studied the pathogenicity of misfolded α-synuclein produced using the protein misfolding cyclic amplification (PMCA) assay. To do this, previous published methods were adapted to allow PMCA-induced protein fibrillization to occur under non-toxic conditions. Insight into potential intracellular targets of misfolded α-synuclein was obtained using an unbiased lipid screen of 15 biologically relevant lipids that identified cardiolipin (CA) as a potential binding partner for PMCA-generated misfolded α-synuclein. To investigate whether such an interaction can impact the properties of α-synuclein misfolding, protein fibrillization was carried out in the presence of the lipid. We show that CA both accelerates the rate of α-synuclein fibrillization and produces species that harbour enhanced resistance to proteolysis. Because CA is virtually exclusively expressed in the inner mitochondrial membrane, we then assessed the ability of these misfolded species to alter mitochondrial respiration in live non-transgenic SH-SY5Y neuroblastoma cells. Extensive analysis revealed that misfolded α-synuclein causes hyperactive mitochondrial respiration without causing any functional deficit. These data give strong support for the mitochondrion as a target for misfolded α-synuclein and reveal persistent, hyperactive respiration as a potential upstream pathogenic event associated with the synucleinopathies.
This article has an associated First Person interview with the first author of the paper.
Medical error reporting software program development and its impact on pediatric units’ reporting medical errors
Authors: Unal Aysun , Seren İntepeler Seyda 
Published: December 2019

Objective: The purpose of this quasi-experimental study was to developing web-based, anonymous reporting system to increase reporting of medication errors, blood transfusion errors and patient falls in pediatric units and to compare the computerized system with the written system already in use at the institution.
Methods: This study was conducted in all pediatric units of a research hospital. All physicians and nurses working in these units agreed to participate in the study. All units were visited to introduce the new reporting system. The number and quality of the reports sent on the new system in years 2014 and 2015 were compared to the reports sent the previous year using the written system.
Results: There was considerable increase in rates of reporting: 234% increase in medication error reporting rate, and 100% increase in the reports of blood transfusion errors. One of the most important results of this study that near-miss errors were not reported at all while the written system of the study institution was being used, whereas it was the most commonly reported type of errors in the electronic error reporting system.
Conclusion: The web-based reporting system, which makes reporting easy, promoted the development of safety culture among doctors and nurses in common language.
doi: https://doi.org/10.12669/pjms.36.2.732
How to cite this:Unal A, Intepeler SS. Medical error reporting software program development and its impact on pediatric units’ reporting medical errors. Pak J Med Sci. 2020;36(2):10-15. doi: https://doi.org/10.12669/pjms.36.2.732
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.