Miracle-dz/UniFAR-FTUs huggingface dataset:
Blocking the effects of interleukin-6 in rheumatoid arthritis and other inflammatory rheumatic diseases: systematic literature review and meta-analysis informing a consensus statement

Background Suppression of the immunoinflammatory cascade by targeting interleukin 6 (IL-6) mediated effects constitutes a therapeutic option for chronic inflammatory diseases. Tocilizumab is the only IL-6 inhibitor (IL-6i) licensed for rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA), but also other agents targeting either IL-6 or its receptor are investigated in various indications. Objective To review published evidence on safety and efficacy of IL-6i in inflammatory diseases. Methods We performed systematic literature searches in Medline and Cochrane, screened EULAR and American College of Rheumatology meeting-abstracts, and accessed http://www.clinicaltrials. gov. Results Comprehensive evidence supports the efficacy of tocilizumab in RA in DMARD-naïve patients, and after DMARD- and TNFi-failure. Randomised comparisons demonstrate superiority of tocilizumab in JIA, but not ankylosing spondylitis (AS). Other indications are currently investigated. Additional IL-6i show similar efficacy; safety generally appears acceptable. Conclusions IL-6i is effective and safe in RA and JIA, but not in AS. Preliminary results in other indications need substantiation.
Astroblastoma: a distinct tumor entity characterized by alterations of the X chromosome and MN1 rearrangement

Astroblastoma is a rare, enigmatic tumor of the central nervous system (CNS) which shares some clinicopathologic aspects with other CNS tumors, especially ependymoma. To further clarify the nature of astroblastoma, we performed clinicopathologic and molecular genetic studies on eight cases of astroblastoma. The median age of the patients was 14.5 years, ranging from 5 to 60 years, and seven of the patients were female. All tumors arose in the cerebral hemisphere and radiologically appeared to be well‐bordered, nodular tumors often associated with cystic areas and contrast‐enhancement. Six of the seven patients with prognosis data survived without recurrences during the follow‐up periods ranging from six to 76 months. One patient had multiple recurrences and died six years later. All tumors exhibited salient microscopic features, such as being well demarcated from the surrounding brain tissue, perivascular arrangement of epithelioid tumor cells (represented by “astroblastic” pseudorosettes, trabecular alignment, and pseudopapillary patterns), and hyalinized blood vessels. Immunoreactivity for GFAP, S‐100 protein, Olig2, and EMA was variably demonstrated in all tumors, and IDH1 R132H and L1CAM were negative. Array comparative genomic hybridization revealed numerous heterozygous deletions on chromosome X in the four tumors studied, and break‐apart fluorescence in situ hybridization demonstrated rearrangement of MN1 in five tumors with successful testing. The characteristic clinicopathologic and genetic findings support the idea that astroblastoma is distinct from other CNS tumors, in particular, ependymoma. In addition, MN1 rearrangement and aberrations of chromosome X may partly be involved in the pathogenesis of astroblastoma.
Smoking, physical inactivity, and obesity: associations with social status.

BACKGROUND The author analyzed social-status-specific differences in tobacco smoking, physical inactivity, and obesity among men and women aged 18 years and above in Germany. METHODS The 2003 Telephone Health Survey carried out by the Robert Koch Institute from September 2002 to May 2003 (n = 8318) provided the data for this study. The subjects' current smoking status, physical inactivity, and obesity were assessed. Their social status was judged on the basis of the information they gave about their education and professional training, occupational position, and net household income. RESULTS Men of low social status were found to be more likely to smoke (OR = 1.89, 95% CI = 1.53-2.34), to be physically inactive (OR = 2.30, 95% CI = 1.87-2.84), and to be obese (OR = 1.34, 95% CI = 1.02-1.77) than men of high social status. For women, social status had just as large an effect on smoking and physical inactivity as it did in men (OR = 1.63, 95% CI = 1.30-2.09; and OR = 1.91, 95% CI = 1.58-2.33, respectively), while its effect on obesity was even greater than in men (OR = 3.20, 95% CI = 2.46-4.18). CONCLUSION These results imply that persons of low social status should be an important target group for preventive and health-promoting measures, both in health policy and in medical practice.
Understanding interprofessional communication: a content analysis of email communications between doctors and nurses

Summary Background: Clinical communication is recognized as a major source of errors in hospitals. The lack of documentation of communication, especially among verbal interactions, often creates hindrances and impedes improvement efforts. By providing smartphones to residents and encouraging nurses to communicate with residents by email shifted much of the communication to emails which permitted analysis of content. Objective: Description on the interprofessional email communication between doctors and nurses occurring on the general internal medicine wards at two academic hospitals. Design: A prospective analysis of email communications between doctors and nurses. Setting: 34 out of the 67 residents who were on the general medicine clinical teaching units consented to allow analysis of their emails over a 6 month period. Main measures: Statistical tabulations were performed on the volume and frequency of communications as well the response time of messages. Two physicians coded the content of randomly selected emails for urgency, emotion, language, type of interaction, and subject content. Key results: A total of 13,717 emails were available for analysis. Among the emails from nurses, 39.1% were requests for a call back, 18.9% were requests for a response by email and the remaining 42.0% indicated no response was required from physicians. For the messages requesting a response by email, only 50% received an email response. Email responses had a median response time of 2.3 minutes. Content analysis revealed that messages were predominantly non-urgent. The two most frequent purposes for communications were to convey information (91%) and to request action by the physician (36%). Conclusions: A smartphone-based email system facilitated the description and content analysis of a large amount of email communication between physicians and nurses. Our findings provide a picture of the communication between physicians, nurses and other healthcare professionals. This work may help inform the further development of information and communications technology that can improve clinical communication.
A case study of measuring process risk for early insights into software safety

In this case study, we examine software safety risk in three flight hardware systems in NASA's Constellation spaceflight program. We applied our Technical and Process Risk Measurement (TPRM) methodology to the Constellation hazard analysis process to quantify the technical and process risks involving software safety in the early design phase of these projects. We analyzed 154 hazard reports and collected metrics to measure the prevalence of software in hazards and the specificity of descriptions of software causes of hazardous conditions. We found that 49-70% of 154 hazardous conditions could be caused by software or software was involved in the prevention of the hazardous condition. We also found that 12-17% of the 2013 hazard causes involved software, and that 23-29% of all causes had a software control. The application of the TRPM methodology identified process risks in the application of the hazard analysis process itself that may lead to software safety risk.
Modeling of Wave Breaking and Wave-Structure Interactions by Coupling of Fully Nonlinear Potential Flow and Lattice-Boltzmann Models

In this work, we report on the development and initial validation of a new hybrid numerical model for strongly nonlinear free surface flows, including wave breaking and wave-structure interactions. Specifically, a two-dimensional numerical wave tank (NWT) based on Fully Nonlinear Potential Flow (FNPF) theory, and a higher-order Boundary Element Method (BEM), is used to simulate fully nonlinear wave generation and far-field propagation over a possibly complex, but generally sloping, bottom bathymetry. A particle-based Lattice Boltzmann (LB) model is coupled with (or nested within) the FNPF-NWT, in the region where breaking would normally occur (e.g., upper part of a slope) and interrupt FNPF simulations. The coupled model is able to capture breaking and post-breaking (or wave-interaction) phenomena that involve more complex physics than represented by FNPF theory. Turbulence, in particular, is represented in the LB model by a Large Eddy Simulation (LES) scheme, based on a Smagorinsky model. In applications, we first validate the model for a one-way weakly coupled scheme, in which the LB model is initialized in the near-field, and then possibly driven on its boundary, by the wave-induced far-field velocity and pressure and their derivatives, computed within the NWT. In the paper, we formulate a fully (or strongly) coupled approach, in which the flow is first decomposed into irrotational and viscous perturbation parts. The latter lead to new terms that, by analogy with Navier-Stokes (NS) equations, are expressed as volume forces, that drive LB simulations of the perturbation fields. Applications of this strong coupling approach will be presented at the conference.
A Novel Grid Resource Scheduling Model Based on Extended Second Price Sealed Auction

In resource-limited environment, grid users compete for limited resources, and how to guarantee tasks¡¯ victorious probabilities is one of the most primary issues that a resource scheduling model cares. In order to solve grid resources scheduling problems, a novel model, namely ESPSA (Extended Second Price Sealed Auction), is proposed. The ESPSA model introduces an analyst entity, and designs analyst¡¯s prediction algorithm based on Hidden Markov Model (HMM). In ESPSA model, grid resources are sold through second price sealed auction. Moreover, to achieve high victorious probabilities, the user brokers who are qualified to participate in the auctions will predict other players¡¯ bids and then carry out the most beneficial bids. The ESPSA model is simulated based on GridSim toolkit. Simulation results show that the ESPSA model assures a higher victorious probability and superior to other traditional algorithms. Moreover, we analyze the existence of Nash equilibrium based on simulation results.
Development of Digital Books Based on the RANDAI Learning Model Integrated with West Sumatra Local Wisdom on Environmental Change Material

Environmental damage can occur due to a person's lack of understanding about the environment, so the role of local wisdom needs to be revived to increase understanding regarding the environment. In understanding Environmental Change material, students need problem solving abilities. This problem-solving ability can be supported through problem-based learning models such as the RANDAI (Reciting, Analyzing, Narrating, Doing, Assesing & Implementing) learning model which is realized in the form of digital books. This type of research is development research using the Plomp model with preliminary research stages, prototyping phase, and assessment phase which are limited to practicality testing. The research subjects were three biology lecturers at Padang State University, two biology teachers and 26 students in class XI MIPA 3 at SMA Negeri 5 Pariaman. The instruments used were initial investigation questionnaires, self-evaluation questionnaires, expert review questionnaires, one to one evaluation questionnaires, small group evaluation questionnaires, field test questionnaires, and practicality questionnaires. Based on research conducted, the average validity value is 90.23% in the very valid category. The average practicality test by teachers and students is 88.21% in the practical category, so it can be concluded that the Digital Book Based on the Integrated RANDAI Learning Model of West Sumatra Local Wisdom on Environmental Change Material developed is very valid and practical
Association of parental pretransplant psychosocial assessment with post‐transplant morbidity in pediatric heart transplant recipients *

Abstract: Because parents assume the primary responsibility for providing ambulatory post‐transplant care to pediatric patients, pretransplant psychosocial evaluation in these recipients is usually focused on parents rather than on patients themselves. We sought to determine whether pretransplant parental psychosocial evaluation predicts post‐transplant medical outcome at current levels of psychosocial support. We compared relative risk (RR) of rejection and hospitalizations (days of all‐cause hospitalization) following initial discharge in patients in ‘risk’ and ‘control’ groups defined by their pretransplant parental psychosocial evaluation. We also compared the two groups of patients for the proportion of all outpatient trough cyclosporine A (CSA) or tacrolimus (FK) levels that were <50% of the target level (defined as the mid‐therapeutic range level). There were seven patients in the ‘risk’ group with a median age 0.25 yr (range 0.19–14.7 yr) and total follow up 20.5 patient‐yr. There were 21 patients in the ‘control’ groups with a median age of 2.1 yr (range 0.05–16.2 yr) and total follow up of 71.3 patient‐yr. There was no significant difference between the groups in rejection‐risk or days of all‐cause hospitalization early after transplant (first six months). During the late period (after the first six months), there were 11 rejection episodes in the ‘risk’ group over 17.4 patient‐yr and four rejection episodes in control group over 61.8 patient‐yr of follow up. After adjustment for age and race, patients in the ‘risk’ category had a RR of 3.4 for developing a rejection episode (p = 0.06) and 3.1 for being inpatient (p < 0.001) during the late period. Patients in the risk group were 2.9 times more likely to have subtherapeutic trough levels (<50% target level) of calcineurin inhibitor (CSA or FK) during both early and late periods (p < 0.01 for both periods) after adjustment for patient age and race. We conclude that pretransplant parental psychosocial risk assessment is associated with post‐transplant morbidity in children after cardiac transplantation. These patients may benefit from closer outpatient monitoring and a higher level of psychosocial support.
Mechanisms of the Free Fatty Acid-induced Increase in Hepatic Glucose Production Ffa and Gluconeogenesis Hepatic Insulin Signaling

nisms of the free fatty acid-induced increase in hepatic glucose production . —The associations between obesity, insulin resistance, and type 2 diabetes mellitus are well documented. Free fatty acids (FFA), which are often elevated in obesity, have been implicated as an important link in these associations. Contrary to muscle glucose metabolism, the effects of FFA on hepatic glucose metabolism and the associated mechanisms have not been extensively investigated. It is still controversial whether FFA have substantial effects on hepatic glucose production, and the mechanisms responsible for these putative effects remain unknown. We review recent progress in this area and try to clarify controversial issues regarding the mechanisms responsible for the FFA-induced increase in hepatic glucose production in the postab-sorptive state and during hyperinsulinemia. lipid; hepatic insulin resistance FREE FATTY ACIDS (FFA), which are often elevated in obese individuals (6, 15, 29, 70), have been implicated as an important causative link in the associations between obesity, insulin resistance, and type 2 diabetes mellitus (11, 48, 56, 73, 82). Elevated plasma FFA clearly impair the ability of insulin to stimulate muscle glucose uptake (45, 98). This effect is associated with a reduction in insulin receptor substrate (IRS)-1-associated phosphatidylinositol (PI) 3-kinase activity, an important step in the insulin-signaling cascade that has been shown to be inhibited by FFA-induced PKC activation in muscle (42, 53). In contrast, although a number of studies have indicated that elevated plasma FFA and high-fat diets can increase postabsorptive (referred to throughout this manuscript as " basal ") he-patic glucose production, the magnitude of these effects and the mechanisms involved remain controversial. Because elevated HGP and hepatic insulin resistance have been well documented in individuals with type 2 diabetes (12, 40, 85), studies that examine the effects of FFA on hepatic glucose metabolism are essential in understanding the pathogenesis of insulin resistance in type 2 diabetes. In this brief review, the physiological effects of FFA on hepatic glucose metabolism and the putative mechanisms of these effects will be discussed. Glucose is produced by glycogenolysis and gluconeo-genesis in the liver. FFA increase hepatic gluconeogen-esis both in vitro and in vivo (11, 20, 127). FFA stimulation of gluconeogenesis has been attributed to the production of 1) acetyl-CoA derived from FFA oxidation , which allosterically activates pyruvate carbox-ylase, 2) NADH, which is used for the formation of glyceraldehyde 3-phosphate from 1,3-bisphosphoglyc-erate, and 3) ATP, which is used as an energy source. Additionally, increased …
A behavioral animation system for autonomous actors personified by emotions

Presents a system dedicated to producing behavioral animation involving autonomous actors. To increase their believability, this system not only allows defining their behavior but also contains an emotional model which generates emotions felt by the actors. These emotions are defined by emergence conditions describing how and when they should emerge. The reactions selected by the actors in response are defined by their character. The use of an emotional model increases the believability of virtual actors by preventing the actors from reacting in same manner in identical contexts and gives the impression that each actor has its own distinct personality
Age‐related changes in the temporal and spatial distributions of fibrillin and elastin mRNAS and proteins in acute cutaneous wounds of healthy humans

Elasticity and resilience of the skin are determined largely by the elastin framework, whose microfibrillar scaffold is composed of fibrillin. To date, the spatial and temporal patterns of expression of human elastin and fibrillin during wound healing have not been described. Ninety healthy human subjects underwent 4 mm cutaneous punch biopsy wounds from the upper inner arm, which were re‐excised from day 3 to 3 months post‐wounding. There were marked changes in the patterns of distribution and the amounts of elastin and fibrillin in sun‐protected skin with ageing. However, there were no major age‐related differences in the mRNA levels for elastin, fibrillin‐1 and fibrillin‐2 using in situ hybridization. Elastin and fibrillin appeared in greatest amounts in the wounds of the elderly, particularly in females. A regenerative pattern of elastin and fibrillin arcades at the dermo‐epidermal junction was observed in the wounds of aged subjects. mRNA expression of elastin was greatest in the wounds of the aged (from day 3 to day 14 post‐wounding) with a similar spatial and temporal pattern to fibrillin‐1 expression; this suggests that fibrillin‐1 is the major contributor to dermal elastic fibre construction during wound repair. Fibrillin‐2 was expressed only in the wounds of the aged and expression was confined to areas proximal to dermal blood vessels. The clear‐cut differences in the localization of the two members of the fibrillin family suggest that these have well‐defined roles in normal skin and wound tissue. In summary, these data indicate that ageing is associated with increased expression of fibrillin and elastin during acute wound healing and concomitant restoration of the papillary dermal architecture with an improved quality of scarring. © 1997 by John Wiley & Sons, Ltd.
Phase Recognition Using Deep Convolutional Neural Network with Inertial Measurement

: Gait phase recognition is of great importance in the development of assistance-as-needed robotic devices, such as exoskeletons. In order for a powered exoskeleton with phase-based control to determine and provide proper assistance to the wearer during gait, the user’s current gait phase must ﬁrst be identiﬁed accurately. Gait phase recognition can potentially be achieved through input from wearable sensors. Deep convolutional neural networks (DCNN) is a machine learning approach that is widely used in image recognition. User kinematics, measured from inertial measurement unit (IMU) output, can be considered as an ‘image’ since it exhibits some local ‘spatial’ pattern when the sensor data is arranged in sequence. We propose a specialized DCNN to distinguish ﬁve phases in a gait cycle, based on IMU data and classiﬁed with foot switch information. The DCNN showed approximately 97% accuracy during an ofﬂine evaluation of gait phase recognition. Accuracy was highest in the swing phase and lowest in terminal stance.
Dystrophin-compromised sarcoglycan-δ-knockout diaphragm requires full wild-type embryonic stem cell reconstitution for correction

Limb-girdle muscular dystrophy-2F (LGMD-2F) is an incurable degenerative muscle disorder caused by a mutation in the sarcoglycan-δ (SGδ)-encoding gene (SGCD in humans). The lack of SGδ results in the complete disruption of the sarcoglycan complex (SGC) in the skeletal and cardiac muscle within the larger dystrophin–glycoprotein complex (DGC). The long-term consequences of SG ablation on other members of the DGC are currently unknown. We produced mosaic mice through the injection of wild-type (WT) embryonic stem cells (ESCs) into SGδ-knockout (KO) blastocysts. ESC-derived SGδ was supplied to the sarcolemma of 18-month-old chimeric muscle, which resulted in the restoration of the SGC. Despite SGC rescue, and contrary to previous observations obtained with WT/mdx chimeras (a mouse rescue paradigm for Duchenne muscular dystrophy), low levels of ESC incorporation were insufficient to produce histological corrections in SGδ-KO skeletal muscle or heart. The inefficient process of ESC rescue was more evident in the SGδ-KO diaphragm, which had reduced levels of dystrophin and no compensatory utrophin, and needed almost full WT ESC reconstitution for histological improvement. The results suggest that the SGδ-KO mouse model of LGMD is not amenable to ESC treatment.
Human nonsense-mediated mRNA decay factor UPF2 interacts directly with eRF3 and the SURF complex

Nonsense-mediated mRNA decay (NMD) is an mRNA degradation pathway that regulates gene expression and mRNA quality. A complex network of macromolecular interactions regulates NMD initiation, which is only partially understood. According to prevailing models, NMD begins by the assembly of the SURF (SMG1–UPF1–eRF1–eRF3) complex at the ribosome, followed by UPF1 activation by additional factors such as UPF2 and UPF3. Elucidating the interactions between NMD factors is essential to comprehend NMD, and here we demonstrate biochemically and structurally the interaction between human UPF2 and eukaryotic release factor 3 (eRF3). In addition, we find that UPF2 associates with SURF and ribosomes in cells, in an UPF3-independent manner. Binding assays using a collection of UPF2 truncated variants reveal that eRF3 binds to the C-terminal part of UPF2. This region of UPF2 is partially coincident with the UPF3-binding site as revealed by electron microscopy of the UPF2–eRF3 complex. Accordingly, we find that the interaction of UPF2 with UPF3b interferes with the assembly of the UPF2–eRF3 complex, and that UPF2 binds UPF3b more strongly than eRF3. Together, our results highlight the role of UPF2 as a platform for the transient interactions of several NMD factors, including several components of SURF.