Miracle-dz/UniFAR-FTUs huggingface dataset:
Emerging drugs for non-alcoholic fatty liver disease

Background: Non-alcoholic fatty liver disease (NAFLD) is a condition of emerging relevance that includes different forms of chronic liver damage, from a simple fatty infiltration (steatosis) of hepatocytes to steatohepatitis (NASH) with fibrosis. This last form may evolve to cirrhosis and hepatocellular carcinoma. Objective: To discuss therapeutic management of NAFLD. Theoretically, only patients with non-alcoholic steatohepatitis (NASH) need to be treated, as only NASH may evolve to cirrhosis. Differentiation between steatosis and NASH currently requires a liver biopsy. Methods: We discuss different therapeutic approaches proposed in literature for patients with NAFLD. Results: The treatment of associated conditions leads to an improvement of NAFLD and NASH. No specific drug is actually present to treat liver steatosis or NASH. Conclusions: The treatment of NAFLD depends on the individual characteristics of each patient. Diet and physical exercise may be considered a basal universal approach. Future research will discover possible specific liver drugs.
Microcontact Printing of Fibronectin on a Biodegradable Polymeric Surface for Skeletal Muscle Cell Orientation

Background and Objectives Micropatterning and microfabrication techniques have been widely used to control cell adhesion and proliferation along a preferential direction according to contact guidance theory. One of these techniques is microcontact printing, a soft lithographic technique based on the transfer of a “molecular ink” from an elastomeric stamp to a surface. This method allows the useful attachment of biomolecules in a few seconds on a variety of surfaces with sub-micrometer resolution and control, without modifying the biomolecule properties. The aim of this study is to develop an easy and versatile technique for in vitro production of arrays of skeletal muscle myofibers using microcontact printing technique on biodegradable substrata. Methods Microcontact printing of fibronectin stripes (10, 25, 50 μm in width) was performed onto biodegradable L-lactide/trimethylene carbonate copolymer (PLLA-TMC) films. C2C12, a murine myoblast cell line, was used for the production of parallel myofibers. Results This approach proved to be simple, reliable and effective in obtaining a stable pattern of fibronectin on the PLLA-TMC surface as observed by fluorescence microscopy. C2C12 cells were well aligned along the pattern 24 hours after seeding, especially on fibronectin stripes 10 and 25 μm in width. Seven days after confluence cells fused and formed aligned multinucleated cells expressing α-actinin. Conclusions Fibronectin patterning seems to be a useful method to induce cell alignment and to improve myotube formation. Further studies will be focused on the possibility of applying external stimuli to these structures to obtain healthy myotubes and to induce myofiber development.
Contribution of patient and physician factors to cardiac rehabilitation enrollment: a prospective multilevel study

Background Cardiac rehabilitation (CR) is an established means of reducing mortality, yet is grossly underutilized. This is due to both health system and patient-level factors; issues that have yet to be investigated concurrently. This study utilized a hierarchical design to examine physician and patient-level factors affecting verified CR enrollment. Design A prospective multisite study, using a multilevel design of 1490 coronary artery disease outpatients nested within 97 Ontario cardiology practices (mean 15 per cardiologist). Methods Cardiologists completed a survey regarding CR attitudes. Outpatients were surveyed prospectively to assess factors affecting CR enrollment. Patients were mailed a follow-up survey 9 months later to self-report CR enrollment This was verified with 40 CR sites. Results Five hundred and fifty (43.4%) outpatients were referred, and 469 (37.0%) enrolled in CR. In mixed logistic regression analyses, factors affecting verified CR enrollment were greater strength of physician endorsement (P = 0.005), shorter distance to CR (P = 0.001), being married (P = 0.01), and fewer perceived CR barriers (P = 0.03). Conclusion Both physician and patient factors play a part in CR enrollment. Patient CR barriers should be addressed during referral discussions, and reasons why physicians fail to uniformly endorse CR exploration. Although distance to CR was related to patient enrollment patterns, greater access to home-based CR services should be provided.
The effects of aspirin and hypothermia on platelet function in vivo

Patients undergoing hypothermic cardiopulmonary bypass are often receiving aspirin therapy. Hypothermia, aspirin and cardiopulmonary bypass can each induce a platelet function defect, but it is not known if the effects of aspirin and hypothermia are additive in this regard. To address this question in humans in vivo, the forearm skin temperature of healthy volunteers was equilibrated and maintained at either normothermia (32°C) or hypothermia (28°C or 22°C) before and 16 h after the ingestion of 650 mg aspirin. A standardized template bleeding time was performed on the forearm and the shed blood emerging from the wound was assayed for platelet surface P‐selectin expression by whole blood flow cytometry (reflecting α granule secretion) and thromboxane B2 (the stable metabolite of thromboxane A2) by radioimmunoassay. Hypothermia resulted in marked prolongation of the bleeding time. Aspirin resulted in prolongation of the bleeding time under normothermic conditions, but only minimally augmented the hypothermia‐induced prolongation of the bleeding time. Platelet surface P‐selectin up‐regulation in shed blood was abolished by hypothermia. Aspirin had no effect on maximal platelet surface P‐selectin expression under normothermic or hypothermic conditions. Both hypothermia and aspirin resulted in markedly reduced shed blood thromboxane B2. Although aspirin slightly augmented the hypothermia‐induced reduction in shed blood thromboxane B2, the concentration of thromboxane generated in shed blood under hypothermic conditions in the absence of aspirin had no effect on platelet surface P‐selectin or platelet aggregation in whole blood. In conclusion, as determined by three independent parameters of the shed blood emerging from a standardized bleeding time wound (bleeding time, platelet surface P‐selectin, and thromboxane B2), aspirin did not significantly augment hypothermia‐induced platelet dysfunction in vivo.
Experimental investigation of 650V superjunction IGBTs

650V superjunction IGBTs have been fabricated. Depending on IGBT structures as well as process conditions, competitive trade-off performances have been observed. Vcesat of 1.4V and tf around 35 ns at the collector current density of 250A/cm2 were obtained with the prototype of superjunction FS IGBT. The superjunction NPT IGBT also shows tf of 35ns with Vcesat of 1.9V, which is superior to the conventional trench FS IGBT. Integrating the superjunction technology into IGBT, we demonstrated that the superjunction IGBT is a viable IGBT technology option as a next generation IGBT technology.
Live demonstration: Modular multi-radio wireless sensor platform with plug&play modules connection

Summary form only given. The demo will present to the audience the new flexible research and development platform for Wireless Sensor and Actuator Networks (WSANs) and Internet of Things (IoT). The devices are built out of the hardware modules which are connected together in Plug&Play manner. The software modules are selected and optimized accounting for each node's structure. The platform enables wide variety of system-level experiments for future WSANs and heterogeneous communication systems.
Spatial and Intergeneric Variation in Physiological Indicators of Corals in the South China Sea: Insights Into Their Current State and Their Adaptability to Environmental Stress

It is well known that coral thermal bleaching is mainly caused by abnormally high temperatures, but the spatial/intergeneric variation in coral‐algal symbiosis and its linkage to coral bleaching susceptibility is not well understood. In this study, 654 coral samples were collected from six coral reef regions (CRRs) in the South China Sea (SCS), between the Nansha Islands (~10°N) and Daya Bay (22°50′N). They were analyzed to explore how geographical/environmental variation affects coral bleaching susceptibility. The results showed significant spatial and intergeneric variation in zooxanthellae density, Chl a content, and tissue biomass. Massive corals generally showed higher values than branching corals for all three parameters across CRRs. Spatial analysis showed that these parameters were lowest in the Nansha Islands and highest in Daya Bay, indicating increases with latitude. Several factors may have accounted for this trend, with the most important being sea surface temperature and nutrients. Additionally, we observed a relationship between physiological parameters and bleaching susceptibility, which was that branching corals had greater bleaching susceptibility than massive corals. Coral community composition and live coral cover data showing increasing dominance of massive corals in the SCS support the above inference. Relatively high‐latitude areas have been proposed as potential refuges for corals under continued global warming and the physiological parameters in the present study seem to support this. However, in spite of the aforementioned results, the smallest live coral cover was found in the northern CRRs. This suggests that this refuge function is currently compromised, mainly due to increasing destructive anthropogenic actions.
Hammering techniques in Greek and Roman jewellery and toreutics

This work traces the development of hammering techniques in Greek, Roman and related jewellery and toreutics based on the analysis of ancient tools used for manufacture of hammered metalwork, primarily punches and matrices with figural designs, and actual finds of metalwork and jewellery. The book offers essays on metalworkers' tools from Mycenean Greece until the Late Roman Period. It includes chapters on different categories of hammered metalwork in the corresponding periods and Excursus about particular matrices or punches and hoards of toreutics. Bringing together the tools of metalworkers and actual objects manufactured with them opens new perspectives on chronological and cultural attribution of ancient jewellery and toreutics and illuminates the role of mass production and artistic creativity in ancient history.
Pore properties and ionic block of the rabbit epithelial calcium channel expressed in HEK 293 cells

1 We have used the whole‐cell patch‐clamp technique to analyse the permeation properties and ionic block of the epithelial Ca2+ channel ECaC heterologously expressed in human embryonic kidney (HEK) 293 cells. 2 Cells dialysed with 10 mM BAPTA and exposed to Ca2+‐containing, monovalent cation‐free solutions displayed large inwardly rectifying currents. Their reversal potential depended on the extracellular Ca2+ concentration, [Ca2+]o. The slope of the relationship between reversal potential and [Ca2+]o on a logarithmic scale was 21 ± 4 mV, compared with 29 mV as predicted by the Nernst equation (n= 3‐5 cells). 3 Currents in mixtures of Ca2+ and Na+ or Ca2+ and Ba2+ showed anomalous mole fraction behaviour. We have described the current‐concentration plot for Ca2+ and Na+ by a kinetic permeation model, i.e. the ‘step’ model. 4 Extracellular Mg2+ blocked both divalent and monovalent currents with an IC50 of 62 ± 9 μM (n= 4) in Ca2+‐free conditions and 328 ± 50 μM (n= 4‐9) in 100 μM Ca2+ solutions. 5 Mono‐ and divalent currents through ECaCs were blocked by gadolinium, lanthanum and cadmium, with a blocking order of Cd2+ >> Gd3+ > La3+. 6 We conclude that the permeation of monovalent and divalent cations through ECaCs shows similarities with L‐type voltage‐gated Ca2+ channels, the main differences being a higher Ca2+ affinity and a significantly higher current density in micromolar Ca2+ concentrations in the case of ECaCs.
Effects of Intradialytic Resistance Exercise on Protein Energy Wasting, Physical Performance and Physical Activity in Ambulatory Patients on Dialysis: A Single‐Center Preliminary Study in a Japanese Dialysis Facility

Patients under hemodialysis present protein‐energy wasting (PEW), which is related with higher mortality rates. The study aimed to determine whether intradialytic resistance exercise training could improve physical performance, physical activity, and PEW in hemodialysis patients. In single center study, 75 hemodialysis patients were enrolled in an intradialytic resistance exercise training consisting of 20 min of adapted leg press, with a gymnastic ball, 3 days/week, during 9 months on the same day of hemodialysis therapy. Physical performance by short physical performance battery (SPPB), physical activity by life space assessment (LSA), and PEW score based on the nomenclature proposed by the International Society of Renal Nutrition and Metabolism in 2008 were assessed at baseline and after 9 months. Intradialytic resistance exercise training significantly improved SPPB score, LSA score, and PEW score (all, P < 0.05). In addition, intradialytic resistance exercise training improved SPPB score in patients with moderate and severe PEW subgroups (P < 0.05), associated with reduced prevalence of the patients with moderate to severe PEW (53% vs. 36%, P < 0.05). Intradialytic resistance exercise training was safe and effective to improve physical performance, physical activity, and PEW in hemodialysis patients.
Glucocorticoids and cardiovascular events in rheumatoid arthritis: a population-based cohort study.

OBJECTIVE To determine the relationship between glucocorticoid exposure and cardiovascular (CV) events in patients with rheumatoid arthritis (RA). METHODS A total of 603 adult residents of Rochester, Minnesota with incident RA between 1955 and 1995 were followed up through their medical records for a median of 13 years (total of 9,066 person-years). Glucocorticoid exposure was defined 3 ways: tertiles of cumulative exposure; recent use (< or =3 months) versus past use (>3 months); and average daily dosage (< or =7.5 mg/day or >7.5 mg/day). CV events, including myocardial infarction, heart failure, and death from CV causes, were defined according to validated criteria. Cox regression models were adjusted for demographic features, CV risk factors, and RA characteristics. RESULTS Rheumatoid factor (RF)-negative patients with exposure to glucocorticoids were not at increased risk of CV events, irrespective of the glucocorticoid dosage or timing of use, as compared with the reference group of RF-negative patients who had never been exposed to glucocorticoids. In contrast, RF-positive patients were at increased risk of CV events, particularly with higher cumulative exposure, higher average daily dosage, and recent use of glucocorticoids. RF-positive patients with high cumulative exposure to glucocorticoids had a 3-fold increased risk of CV events (hazard ratio 3.06 [95% confidence interval 1.81-5.18]), whereas RF-negative patients with high cumulative exposure were not at increased risk (hazard ratio 0.85 [95% confidence interval 0.39-1.87]). CONCLUSION RF-positive but not RF-negative patients were at increased risk of CV events following exposure to glucocorticoids. These findings suggest that glucocorticoids interact with RF status to modulate the occurrence of CV events in patients with RA. The mechanisms underlying this interaction are unknown and should be the subject of further research.
A Test of Two Models of Value Creation in Virtual Communities

Does a firm get any extra value from investing resources in sponsoring its own virtual community above and beyond the value that could be created for the firm, indirectly, via customer-initiated communities? If so, what explains the extra value derived from a firm-sponsored virtual community and how might this understanding inform managers about appropriate strategies for leveraging virtual communities as part of a value-creating strategy for the firm? We test two models of virtual community to help shed light on the answers to these questions. We hypothesize that in customer-initiated virtual communities, three attributes of member-generated information (MGI) drive value, while in firm-sponsored virtual communities, a sponsoring firm's efforts, as well as MGI, drive value. Drawing on information search and processing theories, and developing new measures of three attributes of MGI (consensus, consistency, and distinctiveness), we surveyed 465 consumers across numerous communities. We find that value can emerge via both models, but that in a firm-sponsored model, a sponsor's efforts are more powerful than MGI and have a positive, direct effect on the trust-building process. Our results suggest a continuum of value creation whereby firms extract greater value as they migrate toward the firm-sponsored model.
Pivotal study of iodine I 131 tositumomab for chemotherapy-refractory low-grade or transformed low-grade B-cell non-Hodgkin's lymphomas.

PURPOSE To evaluate the efficacy and safety of tositumomab and iodine I 131 tositumomab (Bexxar; Corixa Corp, Seattle, WA, and GlaxoSmithKline, Philadelphia, PA) in patients with chemotherapy-refractory low-grade or transformed low-grade non-Hodgkin's lymphoma (NHL) and to compare its efficacy to the patients' last qualifying chemotherapy (LQC) regimens. PATIENTS AND METHODS Sixty patients who had been treated with at least two protocol-specified qualifying chemotherapy regimens and had not responded or progressed within 6 months after their LQC were treated with a single course of iodine I 131 tositumomab. RESULTS Patients had received a median of four prior chemotherapy regimens. A partial or complete response (CR) was observed in 39 patients (65%) after iodine I 131 tositumomab, compared with 17 patients (28%) after their LQC (P <.001). The median duration of response (MDR) was 6.5 months after iodine I 131 tositumomab, compared with 3.4 months after the LQC (P <.001). Two patients (3%) had a CR after their LQC, compared with 12 (20%) after iodine I 131 tositumomab (P <.001). The MDR for CR was 6.1 months after the LQC and had not been reached with follow-up of more than 47 months after iodine I 131 tositumomab. An independent review panel verified that 32 (74%) of the 43 patients with nonequivalent durations of response (> 30 days difference) had a longer duration of response after iodine I 131 tositumomab (P <.001). Only one patient was hospitalized for neutropenic fever. Five patients (8%) developed human antimurine antibodies, and one (2%) developed an elevated TSH level after treatment. Myelodysplasia was diagnosed in four patients in follow-up. CONCLUSION A single course of iodine I 131 tositumomab was significantly more efficacious than the LQC received by extensively pretreated patients with chemotherapy-refractory, low-grade, or transformed low-grade NHL and had an acceptable safety profile.
Marr on Computational-Level Theories*

According to Marr, a computational-level theory consists of two elements, the what and the why. This article highlights the distinct role of the Why element in the computational analysis of vision. Three theses are advanced: (a) that the Why element plays an explanatory role in computational-level theories, (b) that its goal is to explain why the computed function (specified by the What element) is appropriate for a given visual task, and (c) that the explanation consists in showing that the functional relations between the representing cells are similar to the “external” mathematical relations between the entities that these cells represent.
The vfr gene product, required for Pseudomonas aeruginosa exotoxin A and protease production, belongs to the cyclic AMP receptor protein family

The synthesis of exotoxin A (ETA) by Pseudomonas aeruginosa is a complex, regulated event. Several ETA putative regulatory mutants of P. aeruginosa PA103 have previously been characterized (S. E. H. West, S. A. Kaye, A. N. Hamood, and B. H. Iglewski, Infect. Immun. 62:897-903, 1994). In addition to ETA production, these mutants, PA103-15, PA103-16, and PA103-19, were also deficient in the production of protease and in regA P1 promoter activity. RegA is a positive regulator of ETA transcription. We cloned a gene, designated vfr for virulence factor regulator, that restored ETA and protease production to parental levels in these mutants. In addition, transcription from the regA P1 promoter was restored. In Escherichia coli, when vfr was overexpressed from a phage T7 promoter, a protein with an apparent molecular mass of 28.5 kDa was produced. Analysis of the deduced amino acid sequence of vfr revealed that the expected protein is 67% identical and 91% similar over a 202-amino-acid overlap to the E. coli cyclic AMP receptor protein (CAP or Crp). The cloned vfr gene complemented the beta-galactosidase- and tryptophanase-deficient phenotypes of E. coli RZ1331, a crp deletion mutant. However, the E. coli crp gene under the control of the tac promoter did not complement the ETA-deficient or protease-deficient phenotype of PA103-15 or PA103-16. The ability of vfr to restore both ETA and protease production to these mutants suggests that vfr is a global regulator of virulence factor expression in P. aeruginosa.
Cutting Edge: Inflammasome Activation in Primary Human Macrophages Is Dependent on Flagellin

Murine NLR family, apoptosis inhibitory protein (Naip)1, Naip2, and Naip5/6 are host sensors that detect the cytosolic presence of needle and rod proteins from bacterial type III secretion systems and flagellin, respectively. Previous studies using human-derived macrophage-like cell lines indicate that human macrophages sense the cytosolic needle protein, but not bacterial flagellin. In this study, we show that primary human macrophages readily sense cytosolic flagellin. Infection of primary human macrophages with Salmonella elicits robust cell death and IL-1β secretion that is dependent on flagellin. We show that flagellin detection requires a full-length isoform of human Naip. This full-length Naip isoform is robustly expressed in primary macrophages from healthy human donors, but it is drastically reduced in monocytic tumor cells, THP-1, and U937, rendering them insensitive to cytosolic flagellin. However, ectopic expression of full-length Naip rescues the ability of U937 cells to sense flagellin. In conclusion, human Naip functions to activate the inflammasome in response to flagellin, similar to murine Naip5/6.