Miracle-dz/UniFAR-FTUs huggingface dataset:
Vascular Calcification in Chronic Kidney Disease: The Role of Inflammation

Cardiovascular complications are extremely frequent in patients with chronic kidney disease (CKD) and death from cardiac causes is the most common cause of death in this particular population. Cardiovascular disease is approximately 3 times more frequent in patients with CKD than in other known cardiovascular risk groups and cardiovascular mortality is approximately 10-fold more frequent in patients on dialysis compared to the age- and sex-matched segments of the nonrenal population. Among other structural and functional factors advanced calcification of atherosclerotic plaques as well as of the arterial and venous media has been described as potentially relevant for this high cardiovascular morbidity and mortality. One potential explanation for this exceedingly high vascular calcification in animal models as well as in patients with CKD increased systemic and most importantly local (micro)inflammation that has been shown to favor the development of calcifying particles by multiple ways. Of note, local vascular upregulation of proinflammatory and proosteogenic molecules is already present at early stages of CKD and may thus be operative for vascular calcification. In addition, increased expression of costimulatory molecules and mast cells has also been documented in patients with CKD pointing to a more inflammatory and potentially less stable phenotype of coronary atherosclerotic plaques in CKD.
User-centric Privacy Engineering for the Internet of Things

User privacy concerns are widely regarded as a key obstacle to the success of modern smart cyber-physical systems. In this paper, we analyse, through an example, some of the requirements that future data collection architectures of these systems should implement to provide effective privacy protection for users. Then, we give an example of how these requirements can be implemented in a smart home scenario. Our example architecture allows the user to balance the privacy risks with the potential benefits and take a practical decision determining the extent of the sharing. Based on this example architecture, we identify a number of challenges that must be addressed by future data processing systems in order to achieve effective privacy management for smart cyber-physical systems.
Gamma‐Tocotrienol Attenuates the Hepatic Inflammation and Fibrosis by Suppressing Endoplasmic Reticulum Stress in Mice

SCOPE Gamma-tocotrienol (γT3), an unsaturated isoform of vitamin E, is implicated in the hepatoprotective effects. The aim is to determine the effectiveness of γT3 on nonalcoholic fatty liver disease (NAFLD). METHODS AND RESULTS C57BL/6 male mice are fed a diet containing high fat (45%) and cholesterol (0.2%) along with sucrose drink (HFCS) or HFCS diet supplemented with 0.1% γT3 (HFCS + γT3). The inclusion of γT3 robustly decreases the HFCS diet-induced de novo lipogenesis (DNL), ER stress, and inflammation leading to reduced hepatic steatosis and fibrosis. Next, mice are fed a methionine- and choline-deficient (MCD) diet or MCD diet with γT3 (MCD + γT3). The γT3 supplementation significantly reduces the MCD diet-induced hepatic ER stress and fibrosis despite the minimal impact on steatosis. To further investigate the role of ER stress, the mice with genetic ablation of CHOP are fed an MCD or MCD + γT3 diet. CHOP deletion abolishes the γT3-mediated suppression of hepatic fibrosis, suggesting that modulation of ER stress is a prerequisite to inhibit hepatic inflammation and fibrosis. CONCLUSION γT3 supplementation is effective in attenuating NAFLD and fibrosis through a synergistic mechanism of decreased DNL and hepatic ER stress. This work strongly supports the translational potential of γT3 supplementation against NAFLD.
Aberrant Splicing Is the Pathogenicity Mechanism of the p.Glu314Lys Variant in CYP11A1 Gene

Context: The cholesterol side chain cleavage enzyme (CYP11A1) catalyzes the conversion of cholesterol to pregnenolone, the first rate-limiting step of steroidogenesis. CYP11A1 mutations are associated with primary adrenal insufficiency (PAI) as well as disorders of sex development (DSD) in 46,XY patients. Objective: To define the pathogenicity mechanism for the p.Glu314Lys variant, previously reported, and found in four additional patients with CYP11A1 deficiency. Subjects and Methods: DNA of four patients presenting with delayed PAI and/or 46,XY DSD were studied by Sanger or Massively Parallel sequencing. Three CYP11A1 mutations were characterized in vitro and in silico, and one by mRNA analysis on testicular tissue. Results: All patients were compound heterozygous for the previously described p.Glu314Lys variant. In silico studies predicted this mutation as benign with no effect on splicing but mRNA analysis found that it led to incomplete exon 5 skipping. This mechanism was confirmed by minigene experiment. The protein carrying this mutation without exon skipping should conserve almost normal activity, according to in vitro studies. Two other mutations found in trans, the p.Arg120Gln and p.Arg465Trp, had similar activity compared to negative control, consistent with the in silico studies. Conclusions: We provide biological proof that the p. Glu314Lys variant is pathogenic due to its impact on splicing and seems responsible for the moderate phenotype of the four patients reported herein. The present study highlights the importance of considering the potential effect of a missense variant on splicing when it is not predicted to be disease causing.
Asthma-Related Educational Needs of Families With Children With Asthma in an Urban Pediatric Emergency Department

Objective The aim of this study was to identify the educational needs of inner-city children with persistent asthma and their caregivers who utilize the emergency department (ED) for asthma care as well as determine their guideline adherence, factors associated with ED use, and comfort with computers. Methods Cross-sectional survey of children aged 2 to 18 years with previous diagnosis of asthma presenting with asthma-related complaints or acute asthma exacerbations to an urban pediatric ED. Data on demographics, families' response to acute asthma, approach to asthma prevention, access to care, educational topics of interest, and sources of health information were collected. Results Of approximately 1500 asthma-related visits, 218 caregivers were approached, and 200 completed the survey. In the past 12 months, 31% had experienced at least 1 asthma-related hospitalization, and 55.5% had had at least 3 ED visits. Although 184 (92.9%) of 198 caregivers were able to identify a primary physician, 37% reported they were more likely to take their child to the ED in response to acute asthma during the day as opposed to their physician (17%). Approximately half of patients were not on any preventive medication, with 57% not having had received an Asthma Action Plan. Caregivers expressed the most interest in learning about long-term controller medications (44.2%), use of metered dose inhalers or nebulizers (44.2%), and trigger avoidance (35.2%). Most caregivers (approximately 68%) reported ease of use with computers and the Internet. Conclusion There was discordance between caregivers' reports of primary care provider teaching on asthma management and the use of the controller medications and possession of the Asthma Action Plans for persistent asthma. Education could focus on caregiver concerns of the safety and benefits of the controller medications.
Advances in acute toxicity testing: strengths, weaknesses and regulatory acceptance

Abstract Safety assessment of chemicals, pharmaceuticals, food and food ingredients, cosmetics, industrial products is very crucial prior to their approval for human uses. Since the commencement of toxicity testing (about 500 years ago, since 1520), significant advances have been made with respect to the 3Rs (reduction, refinement and replacement) alternative approaches. This review is focused on the update in acute systemic toxicity testing of chemicals. Merits and demerits of these advances were also highlighted. Traditional LD50 test methods are being suspended while new methods are developed and endorsed by the regulatory body. Based on the refinement and reduction approaches, the regulatory body has approved fixed dose procedure (FDP), acute toxic class (ATC) method and up and down procedure (UDP) which involves few numbers of animals. In terms of replacement approach, the regulatory body approved 3T3 neutral red uptake (NRU), the normal human keratinocyte (NHK), and the 3T3 neutral red uptake (NRU) phototoxicity test for acute phototoxicity. However, other promising replacement alternatives such as organ on chip seeded with human cells for acute systemic toxicity and 3T3 neutral red uptake (NRU) cytotoxicity test for identifying substances not requiring classification, as well as the in silico approaches are yet to receive regulatory approval. With this backdrop, a collaborative effort is required from the academia, industries, regulatory agencies, government and scientific organizations to ensure speedily regulatory approval of the prospective alternatives highlighted.
Imatinib rechallenge in patients with advanced gastrointestinal stromal tumors following progression with imatinib, sunitinib and regorafenib

Background: Rechallenge with imatinib is an option in advanced gastrointestinal stromal tumor (GIST) patients following progression with standard tyrosine-kinase inhibitors (TKIs), imatinib, sunitinib and regorafenib. We retrospectively collected data from metastatic Italian GIST patients treated with imatinib resumption after progression to conventional TKIs. Methods: A total of 104 eligible advanced GIST patients, previously treated with imatinib, sunitinib and regorafenib, were collected from six referral Italian institutions. Mutational analysis was recorded and correlated with survival and response according to RECIST 1.1 or CHOI criteria. Results: Overall, 71 patients treated with imatinib 400 mg as rechallenge were included. Mutational status was available in all patients. The median follow up was 13 months. In patients who received a rechallenge therapy, the median time to progression (TTP) was 5.4 months [95% confidence interval (CI) 1.9–13.5] and overall survival (OS) was 10.6 months (95% CI 2.8–26.9). A correlation between mutational status, response rate, TTP and OS was not found but comparing deleted versus nondeleted KIT exon 11 patients, a significant difference was identified in terms of TTP and OS (p = 0.04 and p = 0.02, respectively). Conclusions: Our retrospective data confirm that imatinib rechallenge is a reasonable option in advanced GIST. The prognostic value of the specific KIT mutations was confirmed in our series.
Energy-Efficient Mobile-Edge Computation Offloading for Applications with Shared Data

Mobile-edge computation offloading (MECO) has been recognized as a promising solution to alleviate the burden of resource-limited Internet of Thing (IoT) devices by offloading computation tasks to the edge of cellular networks (also known as {\em cloudlet}). Specifically, latency-critical applications such as virtual reality (VR) and augmented reality (AR) have inherent collaborative properties since part of the input&#x002F;output data are shared by different users in proximity. In this paper, we consider a multi-user fog computing system, in which multiple single-antenna mobile users running applications featuring shared data can choose between (partially) offloading their individual tasks to a nearby single-antenna cloudlet for remote execution and performing pure local computation. The mobile users' energy minimization is formulated as a convex problem, subject to the total computing latency constraint, the total energy constraints for individual data downloading, and the computing frequency constraints for local computing, for which classical Lagrangian duality can be applied to find the optimal solution. Based upon the semi-closed form solution, the shared data proves to be transmitted by only one of the mobile users instead of multiple ones. Besides, compared to those baseline algorithms without considering the shared data property or the mobile users' local computing capabilities, the proposed joint computation offloading and communications resource allocation provides significant energy saving.
BIM-GIS Integration as Dedicated and Independent Course for Geoinformatics Students: Merits, Challenges, and Ways Forward

Information mined from building information models as well as associated geographical data and Geographic Information System (GIS) analyses can increase the success of construction processes and asset management, including buildings, roads, and public facilities. The integration of information from both domains requires high expertise in both spheres. The existing B.Sc and M.Sc. programs linked to the built environment at the Technical University of Munich offer courses for the Building Information Model (BIM) and GIS that are distributed among study programs in Civil Engineering, Architecture, and Geomatics. Students graduating as professionals in one of these domains rarely know how to solve pre-defined technical problems associated with the integration of information from BIM and GIS. Students in such programs seldom practice skills needed for the integration of information from BIM and GIS at a level that is needed in working life. Conversely, the technologies in both domains create artificial boundaries that do not exist in reality—for example, water and electricity would not be of use if the utilities terminated in front of buildings. To bring a change and bridge the gap between BIM and GIS, a change in the teaching methods of BIM/GIS needs to be considered. The Technical University of Munich (TUM) has developed a master’s course (M.Sc. course) for students in Geoinformatics which focuses on competencies required to achieve BIM/GIS integration. This paper describes the course development process and provides a unique perspective on the curriculum and subjects. It also presents the course objective, course development, the selection and development of learning materials, and the assessment of the intended learning outcome of the course. The developed course is validated through a questionnaire, and feedback is provided by participants of the BIM/GIS integration workshop representing a panel of experts in the domain.
A Methodology for Planar Representation of Frescoed Oval Domes: Formulation and Testing on Pisa Cathedral

This paper presents an original methodology for planar development of a frescoed dome with an oval plan. Input data include a rigorous geometric survey, performed with a laser scanner, and a photogrammetry campaign, which associates a high-quality photographic texture to the 3D model. Therefore, the main topics include the development of geometry and, contextually, of the associated textures. In order to overcome the inability to directly develop the surface, an orthographic azimuthal projection is used. Starting from a prerequisite study of building methodology, the dome is divided into sectors and bands, each linked with the maximum acceptable deformations and the actual geometric discontinuities detectable by the analysis of Gaussian curvature. Upon definition of the development model, a custom automation script has been devised for geometry projection. This effectively generates a (u,v) map, associated to the model, which is used for model texturing and provides the planar development of the fresco.
The Cyber-Attacks in Vietnam During 2010-2016

This article focuses on the study of the cyber-attacks in Vietnam during 2010-2016, by using Asia Pacific Computer Emergency Response Team (APCERT)’s data, in order to (1) to find out the types and patterns of all cyber-attacks in Vietnam during 2010-2016, and (2) compare the cyber-attacks between Vietnam and Thailand during 2012-2016. Frequency, percentage, Z-score were employed for data analysis. The results are as follows: (1) There were 191,714 cyber-attacks in Vietnam during 2010-2016, (2) During 2010-2016, Deface was the highest cyber-attacks in Vietnam, followed by Malware, and Other, (3) Since 2015, there was an upward trend of cyber-attacks of Deface (Intrusion), Malware / Malicious Code, and Phishing (Fraud) whereas Other had a downward trend, (4) The comparison of Z-score in cyber-attacks between Vietnam and Thailand found that Thailand had higher cyber-attacks than Vietnam in Fraud and Malicious Code whereas Vietnam was at the top of Intrusion and Other.
Protocells and RNA Self-Replication.

SUMMARYThe general notion of an "RNA world" is that, in the early development of life on the Earth, genetic continuity was assured by the replication of RNA, and RNA molecules were the chief agents of catalytic function. Assuming that all of the components of RNA were available in some prebiotic locale, these components could have assembled into activated nucleotides that condensed to form RNA polymers, setting the stage for the chemical replication of polynucleotides through RNA-templated RNA polymerization. If a sufficient diversity of RNAs could be copied with reasonable rate and fidelity, then Darwinian evolution would begin with RNAs that facilitated their own reproduction enjoying a selective advantage. The concept of a "protocell" refers to a compartment where replication of the primitive genetic material took place and where primitive catalysts gave rise to products that accumulated locally for the benefit of the replicating cellular entity. Replication of both the protocell and its encapsulated genetic material would have enabled natural selection to operate based on the differential fitness of competing cellular entities, ultimately giving rise to modern cellular life.
The Argus-II Retinal Prosthesis Implantation; From the Global to Local Successful Experience

Over the past few years, visual prostheses (namely, Argus II retinal implant) and gene therapy have obtained FDA approval in treating blindness resulting from retinitis pigmentosa. Compared to gene therapy; Argus II is less costly with a demonstrated favorable outcome, though the vision is yet artificial. To obtain better results, expectation counseling and preoperative retinal assessment are critical. The global experience with Argus II has enrolled no more than 300 cases so far. The first Argus II retinal prosthesis in Iran was successfully implanted in Shiraz (October 2017). To date, Argus II artificial retina is implanted in four patients in Iran. Beside successful surgery and post-operative care, rehabilitation efforts with validated outcome measures including visual rehabilitation together with neurovisual, visuo-constructive and cognitive rehabilitation/empowerment approaches are expected to boost the functional outcome. A multidisciplinary approach within a cross-functional team would optimize strategies toward better patient outcomes. As such, establishing a collaborative network will foster organized research efforts to better define outcome assessment and rehabilitation strategies. This technology report paper has been an attempt to provide an overview of Argus-II retinal implant global experience as well as the clinical outcome of the so far cases in Iran. Insights from this report were communicated during the first “Brain Engineering and Computational Neuroscience Conference,” 31 January-2 February 2018 in Tehran.
Mortality and Recovery of Renal Function in Acute Kidney Injury Patients Treated with Prolonged Intermittent Hemodialysis Sessions Lasting 10 versus 6 Hours: Results of a Randomized Clinical Trial

Purpose This trial aimed to compare mortality and recovery of renal function in acute kidney injury (AKI) patients treated with different durations of prolonged hemodialysis (PHD) sessions (6 h versus 10 h). Methodology We included patients with sepsis-associated AKI, >18 years, who are in use of a norepinephrine (lower than 0.7 ucg/kg/min). Results One hundred and ninety-four patients were treated with 531 sessions of PHD (G1=104 and G2=90 patients). The two groups were similar in age and SOFA. There was no significant difference in hypotension, hypokalemia, and anticoagulation during PHD sessions. The two groups showed differences in filter clotting, hypophosphatemia, and treatment discontinuation (12.3 versus 23.1%, p=0.002; 15.5 versus 25.8%, p=0.005; and 7.9 versus 15.6%, p=0.008, respectively). There was no difference in fluid balance (FB) before and after PHD sessions. Death and complete recovery of renal function were similar (81.3 versus 82.2%, p=0.87 and 21 versus 31.2%, p=0.7, respectively). At logistic regression, the positive FB before and after dialysis was identified as risk factor for death, while volume overload after three PHD sessions and predialysis creatinine were negatively associated with recovery of renal function in 28 days. Conclusion There was no difference in the mortality and recovery of renal function of AKI patients submitted to different durations of PHD and sessions lasting 10 h presented higher filter clotting, hypophosphatemia, and treatment discontinuation. ISRCTN Registry number is ISRCTN33774458.
The Small-Compound Inhibitor K22 Displays Broad Antiviral Activity against Different Members of the Family Flaviviridae and Offers Potential as a Panviral Inhibitor

The virus family Flaviviridae encompasses several viruses, including (re)emerging viruses which cause widespread morbidity and mortality throughout the world. Members of this virus family are positive-strand RNA viruses and replicate their genome in close association with reorganized intracellular host cell membrane compartments. ABSTRACT The virus family Flaviviridae encompasses several viruses, including (re)emerging viruses which cause widespread morbidity and mortality throughout the world. Members of this virus family are positive-strand RNA viruses and replicate their genome in close association with reorganized intracellular host cell membrane compartments. This evolutionarily conserved strategy facilitates efficient viral genome replication and contributes to evasion from host cell cytosolic defense mechanisms. We have previously described the identification of a small-compound inhibitor, K22, which exerts a potent antiviral activity against a broad range of coronaviruses by targeting membrane-bound viral RNA replication. To analyze the antiviral spectrum of this inhibitor, we assessed the inhibitory potential of K22 against several members of the Flaviviridae family, including the reemerging Zika virus (ZIKV). We show that ZIKV is strongly affected by K22. Time-of-addition experiments revealed that K22 acts during a postentry phase of the ZIKV life cycle, and combination regimens of K22 together with ribavirin (RBV) or interferon alpha (IFN-α) further increased the extent of viral inhibition. Ultrastructural electron microscopy studies revealed severe alterations of ZIKV-induced intracellular replication compartments upon infection of K22-treated cells. Importantly, the antiviral activity of K22 was demonstrated against several other members of the Flaviviridae family. It is tempting to speculate that K22 exerts its broad antiviral activity against several positive-strand RNA viruses via a similar mechanism and thereby represents an attractive candidate for development as a panviral inhibitor.