Miracle-dz/UniFAR-FTUs huggingface dataset:
Interplay Between Phosphorylation and O-GlcNAcylation of Sarcomeric Proteins in Ischemic Heart Failure

Post-translational modifications (PTMs) of sarcomeric proteins could participate to left ventricular (LV) remodeling and contractile dysfunction leading in advanced heart failure (HF) with altered ejection fraction. Using an experimental rat model of HF (ligation of left coronary artery) and phosphoproteomic analysis, we identified an increase of desmin phosphorylation and a decrease of desmin O-N-acetylglucosaminylation (O-GlcNAcylation). We aim to characterize interplay between phosphorylation and O-GlcNAcylation for desmin in primary cultures of cardiomyocyte by specific O-GlcNAcase (OGA) inhibition with thiamet G and silencing O-GlcNAc transferase (OGT) and, in perfused heart perfused with thiamet G in sham- and HF-rats. In each model, we found an efficiency of O-GlcNAcylation modulation characterized by the levels of O-GlcNAcylated proteins and OGT expression (for silencing experiments in cells). In perfused heart, we found an improvement of cardiac function under OGA inhibition. But none of the treatments either in in vitro or ex vivo cardiac models, induced a modulation of desmin, phosphorylated and O-GlcNAcylated desmin expression, despite the presence of O-GlcNAc moities in cardiac desmin. Our data suggests no interplay between phosphorylation and O-GlcNAcylation of desmin in HF post-myocardial infarction. The future requires finding the targets in heart involved in cardiac improvement under thiamet G treatment.
Cultura de inovação em micro e pequenas empresas dos setores aeronáutico e de tecnologia da informação

This descriptive and quantitative study is motivated by the current relevance of innovation to the competitive advantage of organizations, having as a driving force an innovative organizational culture. Thus, the objective was to analyze the perceptions on the culture of innovation of employee at micro and small enterprises (MSEs) in the fields of aeronautics and information technology. In order to explore these concepts, a questionnaire measuring the culture of innovation, developed by Dobni (2008), was applied, and the data were analyzed in two phases: reliability analysis and path analysis using SmartPLS. The results reveal that there is initiative and commitment on the part of employee in the process of innovation, aided by the organizational support for sharing information. However, more subjective aspects of the culture of innovation, such as creativity, autonomy, and the use of skills by the organization, are still, in the view of employees, insufficient, signaling results that may be useful for future research on the subject as well as for the development of new solutions for the growth of MSEs.
A Novel Mouse Model for Cilia‐Associated Cardiovascular Anomalies with a High Penetrance of Total Anomalous Pulmonary Venous Return

Primary cilia are small organelles projecting from the cell surface of many cell types. They play a crucial role in the regulation of various signaling pathway. In this study, we investigated the importance of cilia for heart development by conditionally deleting intraflagellar transport protein Ift88 using the col3.6‐cre mouse. Analysis of col3.6;Ift88 offspring showed a wide spectrum of cardiovascular defects including double outlet right ventricle and atrioventricular septal defects. In addition, we found that in the majority of specimens the pulmonary veins did not properly connect to the developing left atrium. The abnormal connections found resemble those seen in patients with total anomalous pulmonary venous return. Analysis of mutant hearts at early stages of development revealed abnormal development of the dorsal mesocardium, a second heart field‐derived structure at the venous pole intrinsically related to the development of the pulmonary veins. Data presented support a crucial role for primary cilia in outflow tract development and atrioventricular septation and their significance for the formation of the second heart field‐derived tissues at the venous pole including the dorsal mesocardium. Furthermore, the results of this study indicate that proper formation of the dorsal mesocardium is critically important for the development of the pulmonary veins. Anat Rec, 302:136–145, 2019. © 2018 Wiley Periodicals, Inc.
Compound Binary Search Tree and Algorithms

The Binary Search Tree (BST) is average in computer science which supports a compact data structure in memory and oneself even conducts a row of quick algorithms, by which people often apply it in dynamical circumstance. Besides these edges, it is also with weakness on its own structure specially with poor performance at worst case. In this paper, we will develop this data structure into a synthesis to show a series of novel features residing in. Of that, there are new methods invented for raising the performance and efficiency nevertheless some existing ones in logarithm or linear time.
HMGA2 as a functional antagonist of PARP1 inhibitors in tumor cells

Poly(ADP‐ribose) polymerase 1 inhibitors alone or in combination with DNA damaging agents are promising clinical drugs in the treatment of cancer. However, there is a need to understand the molecular mechanisms of resistance to PARP1 inhibitors. Expression of HMGA2 in cancer is associated with poor prognosis for patients. Here, we investigated the novel relationship between HMGA2 and PARP1 in DNA damage‐induced PARP1 activity. We used human triple‐negative breast cancer and fibrosarcoma cell lines to demonstrate that HMGA2 colocalizes and interacts with PARP1. High cellular HMGA2 levels correlated with increased DNA damage‐induced PARP1 activity, which was dependent on functional DNA‐binding AT‐hook domains of HMGA2. HMGA2 inhibited PARP1 trapping to DNA and counteracted the cytotoxic effect of PARP inhibitors. Consequently, HMGA2 decreased caspase 3/7 induction and increased cell survival upon treatment with the alkylating methyl methanesulfonate alone or in combination with the PARP inhibitor AZD2281 (olaparib). HMGA2 increased mitochondrial oxygen consumption rate and spare respiratory capacity and increased NAMPT levels, suggesting metabolic support for enhanced PARP1 activity upon DNA damage. Our data showed that expression of HMGA2 in cancer cells reduces sensitivity to PARP inhibitors and suggests that targeting HMGA2 in combination with PARP inhibition may be a promising new therapeutic approach.
Subjective memory complaint as a useful tool for the early detection of Alzheimer’s disease

Purpose Despite their high prevalence in Alzheimer’s disease (AD), and the increasing level of concern they have generated, subjective memory complaints (SMCs) are poorly understood. This study investigated the accuracy with which SMC can separate mild cognitive impairment (MCI) and early AD from cognitive normal (CN), and explored whether the discrimination ability is similar to or better than that of the Mini-Mental State Exam (MMSE). Patients and methods This study recruited 175 CN subjects, 52 with MCI, and 66 with probable AD aged 60 years or older. To test the independent contributions of SMC and MMSE scores to the classification of cognitive status (CN vs MCI or early AD), logistic regression analyses were performed, adjusting for the following potential confounding variables: age, gender, Frontal Assessment Battery score, modified Hachinski Ischemic Scale score, and apolipoprotein E ε4 status. Receiver operating characteristic (ROC) curve analyses were used to determine the discrimination accuracy of SMC and MMSE scores, and area under the ROC curve (AUROC) was also calculated. Results In the highly educated (≥7 years), nondepressed (Geriatric Depression Scale ≤15) subgroup, SMC showed good accuracy in discriminating cognitively impaired subjects from CN after adjusting for potential confounding variables (the AUROC of the adjusted SMC was 0.841 for MCI discrimination, and it was 0.858 for MCI plus early AD discrimination). Both SMC and MMSE scores significantly contributed to differentiating between CN and MCI (OR=2.372, 95% CI=1.086–5.177; OR=0.730, 95% CI=0.566–0.941, respectively) after adjusting for the same covariates. However, in the highly educated and nondepressed subgroups, SMC showed significant predictive power for MCI from CN (OR=3.119, 95% CI=1.190–8.176; OR=3.328, 95% CI=1.320–8.396, respectively), whereas MMSE scores did not. Conclusion Our findings support the usefulness of SMC, which was comparable or even superior to MMSE scores, for detecting MCI or early AD.
Reversible self-assembly of superstructured networks

Chemically reversible hydrogels The dynamic reorganization of some cellular biopolymers in response to signals has inspired efforts to create artificial materials with similar properties. Freeman et al. created hydrogels based on peptide amphiphiles that can bear DNA strands that assemble into superstructures and that disassemble in response to chemical triggers. The addition of DNA conjugates induced transitions from micelles to fibers and bundles of fibers. The resulting hydrogels were used as an extracellular matrix mimic for cultured cells. Switching the hydrogel between states also switched astrocytes between their reactive and naïve phenotypes. Science, this issue p. 808 Large-scale redistribution of molecules in a supramolecular material generates chemically reversible superstructures. Soft structures in nature, such as protein assemblies, can organize reversibly into functional and often hierarchical architectures through noncovalent interactions. Molecularly encoding this dynamic capability in synthetic materials has remained an elusive goal. We report on hydrogels of peptide-DNA conjugates and peptides that organize into superstructures of intertwined filaments that disassemble upon the addition of molecules or changes in charge density. Experiments and simulations demonstrate that this response requires large-scale spatial redistribution of molecules directed by strong noncovalent interactions among them. Simulations also suggest that the chemically reversible structures can only occur within a limited range of supramolecular cohesive energies. Storage moduli of the hydrogels change reversibly as superstructures form and disappear, as does the phenotype of neural cells in contact with these materials.
Cheesomics: the future pathway to understanding cheese flavour and quality

Abstract Cheese is a fermented dairy product, harboring diverse microbial communities (microbiota) that change over time and vary depending on the type of cheese and their respective starter and adjunct cultures. These microorganisms play a crucial role in determining the flavor, quality and safety of the final product. Exploring the composition of cheese microbiota and the underlying molecular mechanisms involved in cheese ripening has been the subject of many studies. Recent advances in next generation sequencing (NGS) methods and the development of sophisticated bioinformatics tools have provided deeper insights into the composition and potential functionality of cheese microbiota far beyond the information provided by culture-dependent methods. These advances, which include rRNA gene amplicon sequencing and metagenomics, have been complemented and expanded in recent years by the application of metatranscriptomics, metaproteomics and metabolomics. This paper reviews studies in which application of these meta-omics technologies has led to a better understanding of the microbial composition and functionality of cheese and highlights opportunities by which the integration of outputs from diverse multi-omics analytical platforms (cheesomics) could be used in the future to advance our knowledge of the cheese ripening process and identify biomarkers for predicting cheese flavor, quality, texture and safety, and bioactive metabolites with potential to influence human health.
Impact of Mixed Equine Influenza Vaccination on Correlate of Protection in Horses

To evaluate the humoral immune response to mixed Equine Influenza vaccination, a common practice in the field, an experimental study was carried out on 42 unvaccinated thoroughbred weanling foals divided into six groups of seven. Three groups were vaccinated using a non-mixed protocol (Equilis® Prequenza-Te, Proteqflu-Te® or Calvenza-03®) and three other groups were vaccinated using a mix of the three vaccines mentioned previously. Each weanling underwent a primary EI vaccination schedule composed of two primary immunisations (V1 and V2) four weeks apart followed by a third boost immunisation (V3) six months later. Antibody responses were monitored until one-year post-V3 by single radial haemolysis (SRH). The results showed similar antibody responses for all groups using mixed EI vaccination and the group exclusively vaccinated with Equilis® Prequenza-TE, which were significantly higher than the other two groups vaccinated with Proteqflu-TE® and Calvenza-03®. All weanlings (100%) failed to seroconvert after V1 and 21% (9/42) still had low or no SRH antibody titres two weeks post-V2. All weanlings had seroconverted and exceeded the clinical protection threshold one month after V3. The poor response to vaccination was primarily observed in groups exclusively vaccinated with Proteqflu-Te® and Calvenza-03®. A large window of susceptibility (3–4.5-month duration) usually called immunity gap was observed after V2 and prior to V3 for all groups. The SRH antibody level was maintained above the clinical protection threshold for three months post-V3 for the groups exclusively vaccinated with Proteqflu-Te® and Calvenza-03®, and six months to one year for groups using mixed EI vaccination or exclusively vaccinated with Equilis® Prequenza-Te. This study demonstrates for the first time that the mix of EI vaccines during the primary vaccination schedule has no detrimental impact on the correlate of protection against EIV infection.
Treatment of patients with primary retroperitoneal sarcoma: predictors of outcome from an Australian specialist sarcoma centre

Several unanswered questions surround the management of retroperitoneal sarcoma (RPS). Guidelines recommend treatment by a multidisciplinary team at a specialized referral centre. The objective of this study was to describe the management of RPS at an Australian specialist sarcoma centre, comparing outcomes to international standards and analysing for predictors of local failure.
Estimated cost efficacy of U.S. Food and Drug Administration–approved treatments for acne

BACKGROUND Standard of practice in patients with acne is generally to attempt topical and oral therapies, often in a stepwise manner, before isotretinoin. OBJECTIVE To estimate the cost efficacy of US Food and Drug Administration approved treatments to facilitate comparison of therapeutic options, specifically against isotretinoin. METHODS Drug costs were obtained from the National Average Drug Acquisition Cost database maintained by the US Centers for Medicare & Medicaid Services (CMS). Laboratory fees were obtained from the CMS as well. Office fees are standard at our university. Cost calculations were standardized to seven months of treatment because this is when isotretinoin patients will have achieved the upper end of their weight-based cumulative dose. RESULTS Median prices for six classes of medications were calculated. Spironolactone was $350. Oral antibiotics were $501. Topical antibiotics were $920. Topical retinoids were $1,805. Topical combination antibiotics were $2,282. Topical combination antibiotics and retinoids were $3,770. The median cost for isotretinoin in males and females were $3,227 and $3,806 respectively. CONCLUSION Our study provides meaningful cost efficacy data that may influence treatment selection. Isotretinoin can be more cost effective in moderate to severe acne, particularly over extended treatment periods. This article is protected by copyright. All rights reserved.
Preventive effect of oral magnesium in postmastectomy pain: protocol for a randomised, double-blind, controlled clinical trial

Introduction Breast cancer affects 1 in 10 women worldwide, and mastectomy is a cause of chronic pain with neuropathic characteristics. N-methyl-D-aspartate receptor (NMDAR) antagonists such as ketamine, memantine, dextromethorphan or magnesium are used to treat refractory pain by blocking NMDAR. Oral memantine has been shown to prevent postmastectomy pain and cognitive impact and to maintain quality of life. Likewise, the present study is intended to assess the preventive effect of oral magnesium, administered ahead of mastectomy, on the development of neuropathic pain. As a physiological blocker of NMDAR, magnesium could be an interesting candidate to prevent postoperative pain and associated comorbidities, including cognitive and emotional disorders, multiple analgesic consumption and impaired quality of life. Methods and analysis A randomised double-blind controlled clinical trial (NCT03063931) will include 100 women with breast cancer undergoing mastectomy at the Oncology Hospital, Clermont-Ferrand, France. Magnesium (100 mg/day; n=50) or placebo (n=50) will be administered for 6 weeks, starting 2 weeks before surgery. Intensity of pain, cognitive and emotional function and quality of life will be assessed by questionnaires. The primary endpoint is pain intensity on a 0–10 numerical rating scale at 1 month postmastectomy. Data analysis will use mixed models; all tests will be two-tailed, with type-I error set at α=0.05. Ethics and dissemination The study protocol and informed consent form were approved in December 2016 by the French Research Ethics Committee (South East VI Committee). Results will be communicated in various congresses and published in international publications. Trial registration number NCT03063931.
The influence of language and culture on cognitive assessment tools in the diagnosis of early cognitive impairment and dementia

ABSTRACT Introduction: Cognitive assessment tools measure cognitive impairment and complement biomarkers to link cognitive symptoms with pathophysiological processes underlying dementia. However, language and cultural differences in multilingual populations can influence the interpretation of cognitive assessment tools when applied in cross-cultural and multinational studies. Areas covered: This article examines the influence of culture and language on the interpretation of the Mini-Mental State Examination, Montreal Cognitive Assessment, and Alzheimer’s Disease Assessment Scale-cognitive subscale, which are more commonly used worldwide. It discusses how this impacted multinational studies. Lastly, it presents language-neutral tools such as the Visual Cognitive Assessment Test, which do not require translation when applied in multilingual populations. Expert commentary: Linguistic and cultural variation within tools due to translation and differences in administration introduce method bias and differential item functioning, which influence the interpretation of cognitive scores in multinational studies. The ultimate goal is to have a tool that accurately measures cognitive impairment, yet with minimal influence from linguistic, cultural, educational, and demographic differences, through concerted international efforts to harmonize the development and validation of tools. While recently developed visual-based language-neutral tools show promise in the early detection of cognitive impairment, further validation will be required for these tools to be applied internationally.
Eyes on the future - evidence for trade-offs between growth, storage and defense in Norway spruce.

Carbon (C) allocation plays a central role in tree responses to environmental changes. Yet, fundamental questions remain about how trees allocate C to different sinks, for example, growth vs storage and defense. In order to elucidate allocation priorities, we manipulated the whole-tree C balance by modifying atmospheric CO2 concentrations [CO2 ] to create two distinct gradients of declining C availability, and compared how C was allocated among fluxes (respiration and volatile monoterpenes) and biomass C pools (total biomass, nonstructural carbohydrates (NSC) and secondary metabolites (SM)) in well-watered Norway spruce (Picea abies) saplings. Continuous isotope labelling was used to trace the fate of newly-assimilated C. Reducing [CO2 ] to 120 ppm caused an aboveground C compensation point (i.e. net C balance was zero) and resulted in decreases in growth and respiration. By contrast, soluble sugars and SM remained relatively constant in aboveground young organs and were partially maintained with a constant allocation of newly-assimilated C, even at expense of root death from C exhaustion. We conclude that spruce trees have a conservative allocation strategy under source limitation: growth and respiration can be downregulated to maintain 'operational' concentrations of NSC while investing newly-assimilated C into future survival by producing SM.
Integration of a 2D Touch Sensor with an Electroluminescent Display by Using a Screen-Printing Technology on Textile Substrate

Many types of solutions have been studied and developed in order to give the user feedback when using touchpads, buttons, or keyboards in textile industry. Their application on textiles could allow a wide range of applications in the field of medicine, sports or the automotive industry. In this work, we introduce a novel solution that combines a 2D touchpad with an electroluminescent display (ELD). This approach physically has two circuits over a flexible textile substrate using the screen-printing technique for wearable electronics applications. Screen-printing technology is widely used in the textile industry and does not require heavy investments. For the proposed solution, different layer structures are presented, considering several fabric materials and inks, to obtain the best results.
An exploratory study on the role of vitamin D supplementation in improving pain and disease activity in rheumatoid arthritis

Rheumatology Unit, University of Verona, Verona, Italy; Rheumatology Unit, Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy; Rheumatology Unit, University of Foggia, Foggia, Italy; Rheumatology Unit, Gaetano Pini Institute, Milan, Italy; Rheumatology Unit, Sant’Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy; Rheumatology Unit, University Federico II of Naples, Naples, Italy; Rheumatology Unit, Galateo San Cesario Hospital, San Cesari di Lecce, Italy