Miracle-dz/UniFAR-FTUs huggingface dataset:
Toll or Interleukin-1 Receptor (TIR) Domain-containing Adaptor Inducing Interferon-β (TRIF)-mediated Caspase-11 Protease Production Integrates Toll-like Receptor 4 (TLR4) Protein- and Nlrp3 Inflammasome-mediated Host Defense against Enteropathogens*

Background: C. rodentium and E. coli induce noncanonical Nlrp3 inflammasome activation through caspase-11. Results: TLR4-TRIF are important for caspase-11 expression, caspase-1 activation, and downstream IL-1β and IL-18 production. Conclusion: TLR4-TRIF axis plays an important role in the up-regulation of caspase-11 and activation of noncanonical inflammasome. Significance: Our study identifies novel molecules upstream of caspase-11 that are involved in activation of noncanonical inflammasome. Enteric pathogens represent a major cause of morbidity and mortality worldwide. Toll-like receptor (TLR) and inflammasome signaling are critical for host responses against these pathogens, but how these pathways are integrated remains unclear. Here, we show that TLR4 and the TLR adaptor TRIF are required for inflammasome activation in macrophages infected with the enteric pathogens Escherichia coli and Citrobacter rodentium. In contrast, TLR4 and TRIF were dispensable for Salmonella typhimurium-induced caspase-1 activation. TRIF regulated expression of caspase-11, a caspase-1-related protease that is critical for E. coli- and C. rodentium-induced inflammasome activation, but dispensable for inflammasome activation by S. typhimurium. Thus, TLR4- and TRIF-induced caspase-11 synthesis is critical for noncanonical Nlrp3 inflammasome activation in macrophages infected with enteric pathogens.
Effects of supplemental phytase and phosphorus on histological, mechanical and chemical traits of tibia and performance of turkeys fed on soyabean-meal-based semi-purified diets high in phytate phosphorus

Tibial traits were investigated for turkey poults fed on soyabean-meal-based semi-purified diets high in phytate P (2·2 g/kg) with added phytase and inorganic P. Dietary treatments were: (1) 2·7 g non-phytate P (nP)/kg; (2) diet 1 + 1000 U phytase/kg diet; (3) 36 g nP/kg; (4) diet 3+800 U phytase; (5) 4·5 g nP/kg; (6) diet 5+600 U phytase; (7) 6·0 g nP/kg. Added phytase and nP increased (P < 0·006) tibial dry matter, ash weight and content, body-weight gain, feed intake and gain:feed. The Mg and Zn concentrations in the tibial ash were also increased (P < 0·001 and P < 0·09 respectively) by added phytase or nP; tibial P and Ca concentrations tended to be increased. Hypertrophy zone width of the tibial proximal end decreased (P < 0·001), while proliferating zone width, tibial length, and widths at the long and short axes increased (P < 0·003) as phytase and nP were added. The addition of phytase also tended to enlarge the cartilaginous zone width, which was linearly increased (P < 0·05) by added nP. Disorganization scores of the hypertrophy zone and trabecular bone were low, approaching normal (P < 0·05), for turkey poults fed on diets with phytase supplementation, and tibial abnormality scores were linearly decreased (P < 0·001) as nP levels increased (zero score is considered normal). Adding phytase and nP improved the orderliness of development, mineralization and arrangement of cartilage and bone cells, and alleviated the effects of P deficiency on the histological and gross structure of the tibias. Tibial shear stress increased (P < 0·04) as phytase and nP were added. In summary, similar improvements in bone characteristics were achieved for turkey poults fed on a P-deficient diet supplemented with either phytase or nP.
Differential expression and regulation of olig genes in zebrafish

The members of the Olig gene family encode for basic helix‐loop‐helix (bHLH) transcription factors involved in neural cell type specification. Three Olig genes (Olig1, Olig2 and Olig3) have been identified in all known vertebrate models and a fourth one in anamniotes (olig4). Here we have performed a global analysis of olig genes during zebrafish embryonic development and determined which signaling pathways control their induction and regionalization in the CNS. Interestingly, zebrafish olig3 and olig4 together establish most of the expression domains corresponding to mouse Olig3. According to our data, olig1 is specifically confined to the oligodendrocyte lineage, whereas the other members display stratified expression in diencephalon, hindbrain, and spinal cord. We observed differential expression of olig genes within specific motoneuron and interneuron domains of the spinal cord. olig2, olig3, and olig4 expression appears to be regulated by nodal and FGF signaling during gastrulation and early somitogenesis, by RA signaling in the hindbrain, and by BMP and Hh signals along the dorsoventral axis of the embryonic CNS. Our findings suggest a role for olig genes in CNS patterning as well as in multiple cell fate decisions during neural differentiation. J. Comp. Neurol. 515:378–396, 2009. © 2009 Wiley‐Liss, Inc.
Direct Cost of Depression: Analysis of Treatment Costs of Paroxetine versus Imipramine in Canada

Objective To assess the potential economic impact of new and more expensive antidepressants on the overall cost of treatment using cost-effectiveness analysis. Method For this analysis, a computerized decision tree of clinical practice was developed to model the 12-month treatment of moderate to severe depression in Canada. To complete the model, data were obtained from physician panels, the Ontario Ministry of Health, and clinical comparative trials of paroxetine, a selective serotonin reuptake inhibitor, and Imipramine, a tricyclic antidepressant. Results The overall cost of treatment when paroxetine 30 mg per day was used first-line was found to be lower than when generic imipramine was used as the initial therapy ($1697 versus $1793). The higher drug cost of paroxetine ($1.69 per day) versus imipramine ($0.05 per day) was offset by a higher rate of treatment failures with the tricyclic necessitating an alternate therapy, additional physician visits and/or hospitalization. Sensitivity analysis of key variables determined that drug price and relapse rates after discontinuation were relatively insensitive predictors of the overall cost of care. More important was the continuation rate while on different therapies. Conclusion Paroxetine demonstrated a cost-benefit relative to Imipramine when the continuation rate was ≥ 47%. Clinical trials of paroxetine have reported continuation rates of 41% to 65%, suggesting that paroxetine is a cost-effective alternative to Imipramine in the 1-year management of patients with moderate to severe depression.
Antioxidants in Detoxification of Arsenic-Induced Oxidative Injury in Rabbits: Preliminary Results

Abstract To assess the oxidative injuries caused by arsenic toxicity in rabbits and evaluate the detoxifying effects of exogenous antioxidants, we administered arsenic trioxide (3–5 mg/kg/day) in rabbits through a feeding tube for seven days. These rabbits were then treated with a recipe of vitamins, zinc, selenium (VZS) or a plant polyphenol or a placebo for the next seven days. Blood samples were collected from ear vein for spectrophotometric assay of reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARS), and nitrite/nitrate (NO x ; index of nitric oxide formation) before arsenic administration, seven days after arsenic administration, and seven days after antioxidant treatment. The total arsenic concentrations in hair and spot urine samples of rabbits before arsenic administration were 0.6 ± 0.21 µg/g and 34.0 ± 5.9 µg/L, respectively. Administration of arsenic trioxide significantly increased arsenic concentrations in hair and in urine to 2.8 ± 0.40 µg/g (p<0.001) and 7372 ± 1392.0 µg/L (p<0.001), respectively. Arsenic administration to rabbits significantly reduced GSH concentration (post-arsenic,17.5 ± 0.81 mg/dL vs. pre-arsenic, 32.0 ± 0.76 mg/dL, p<0.001), increased TBARS concentration (post-arsenic, 8 ± 1.1 µM vs. pre-arsenic, 5 ± 0.7 µM, p<0.05), and NO x concentration (post-arsenic, 465 ± 38.5 µM vs. pre-arsenic, 320 ± 24.7 µM, p<0.001) as compared to the pre-arsenic levels. There was a negative correlation between TBARS and GSH concentrations (r = −0.464, p<0.01) and between NO x and GSH concentrations (r = − 0.381, p<0.05) of intoxicated rabbits. The recovery of the depleted GSH was significantly greater in the polyphenols (77.0 ± 12.0%) or VZS (67.0 ± 17.0%) treatment groups compared with the placebo group (36.0 ± 7.0%). The decrease in NO x level of arsenic-treated rabbits was significantly greater in polyphenols treatment group than the placebo group (60.0 ± 9.0% vs. 17.0 ± 6.0%, p<0.001). These results indicate that arsenic induces toxicity in rabbits associated with an increase in lipid peroxidation. Arsenic toxicity increases nitric oxide production in the body. Exogenous antioxidants such as polyphenols and recipe of vitamins, zinc, and selenium are useful for arsenic detoxification.
Diagnosis and classi fi cation of polyarteritis nodosa q

Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis preferentially targeting medium-sized arteries and not associated with glomerulonephritis or small vessel involvement. Anti-neutrophil cytoplasmic antibodies are typically negative. PAN may be triggered by viral infections, particularly hepatitis B virus, but remains idiopathic in most cases. Clinical manifestations of PAN are multisystemic. Peripheral nerve and skin are the most frequently affected tissues. Involvement of the gastrointestinal tract, kidneys, heart, and central nervous system is associated with higher mortality. Laboratory abnormalities reveal a prominent acute phase response but are non-specific. Histologic confirmation of vasculitis in medium sized arteries is desirable and biopsies must be obtained from symptomatic organs if feasible. Skin or muscle and nerve are preferred because of higher diagnostic yield and safety. If biopsies are negative or cannot be obtained, visceral angiography, may reveal multiple micro-aneurysms supporting the diagnosis of PAN. Current treatment policy includes high-dose corticosteroids, which are combined with immunosuppressive agents when critical organ involvement or life-threatening complications occur. IV pulse cyclophosphamide in the remission induction phase, later switched to a safer immunosuppressant for remission maintenance is a frequently used therapeutic approach. A recent consensus algorithm for the classification of PAN has attempted to overcome some of the caveats of the 1990 American College of Rheumatology (ACR) classification criteria which have proven to be unsatisfactory, and has also confirmed the low prevalence of PAN compared to other systemic necrotizing vasculitides. European league against rheumatic diseases (EULAR)/ACR endorsed international cooperation to establish new diagnostic/classification criteria is currently under way. 2014 Elsevier Ltd. All rights reserved. Polyarteritis nodosa (PAN) is a primary systemic necrotizing vasculitis predominantly targeting medium-sized arteries defined as the main visceral arteries and their branches [1,2]. Small arteries may also be involved but small vessels, including arterioles, capillaries and venules, are characteristically spared (1). Consequently, glomerulonephritis is not part of the spectrum of PAN. Antineutrophil cytoplasmic antibodies (ANCA) are typically negative. These characteristics are useful to differentiate PAN from other systemic necrotizing vasculitis. PAN may encompass a spectrum of disorders. It may be idiopathic or triggered by specific agents. Themost typical is hepatitis B virus (HBV), although other viruses may be occasionally detected. ividad (SAF 11/30073). Marco cia y Tecnología (CONACyT), sitaris i de Recerca (AGAUR) ne Diseases, Hospital Clínic, 75774; fax: þ34 93 2271707. All rights reserved. PAN may be a systemic disease or be confined to single organs or systems [3].
Randomized controlled trial comparing outcomes of video capsule endoscopy with push enteroscopy in obscure gastrointestinal bleeding.

BACKGROUND Optimal management of obscure gastrointestinal bleeding (OGIB) remains unclear. OBJECTIVE To evaluate diagnostic yields and downstream clinical outcomes comparing video capsule endoscopy (VCE) with push enteroscopy (PE). METHODS Patients with OGIB and negative esophagogastroduodenoscopies and colonoscopies were randomly assigned to VCE or PE and followed for 12 months. End points included diagnostic yield, acute or chronic bleeding, health resource utilization and crossovers. RESULTS Data from 79 patients were analyzed (VCE n=40; PE n=39; 82.3% overt OGIB). VCE had greater diagnostic yield (72.5% versus 48.7%; P<0.05), especially in the distal small bowel (58% versus 13%; P<0.01). More VCE-identified lesions were rated possible or certain causes of bleeding (79.3% versus 35.0%; P<0.05). During follow-up, there were no differences in the rates of ongoing bleeding (acute [40.0% versus 38.5%; P not significant], chronic [32.5% versus 45.6%; P not significant]), nor in health resource utilization. Fewer VCE-first patients crossed over due to ongoing bleeding (22.5% versus 48.7%; P<0.05). CONCLUSIONS A VCE-first approach had a significant diagnostic advantage over PE-first in patients with OGIB, especially with regard to detecting small bowel lesions, affecting clinical certainty and subsequent further small bowel investigations, with no subsequent differences in bleeding or resource utilization outcomes in follow-up. These findings question the clinical relevance of many of the discovered endoscopic lesions or the ability to treat most of these effectively over time. Improved prognostication of both patient characteristics and endoscopic lesion appearance with regard to bleeding behaviour, coupled with the impact of therapeutic deep enteroscopy, is now required using adapted, high-quality study methodologies.
Amorphous GexSi1-xOy:H Microbolometers with High Responsivity

In current work, we report the design, fabrication and characterization of a-Ge<sub>0.85</sub>Si<sub>0.15</sub>O<sub>0.0236</sub>:H microbolometers. A sandwich structure of silicon nitride-silicon germanium oxide-silicon nitride was used to form the sensing layer. Due to moderately high resistivity of a-Ge<sub>0.85</sub>Si<sub>0.15</sub>O<sub>0.0236</sub> layer, the current flow through the sensing layer was made vertically and through the absorber layer laterally. Forming gas passivation was done at 250degC to reduce the 1/f-noise. A high responsivity of 1.05 times 10<sup>4</sup> V/W along with a high temperature coefficient of resistance of -4.8%/K was obtained at room temperature and in vacuum from a 40 mum times 40 mum pixel. The lowest value of thermal conductance achieved was 4 times 10<sup>-8</sup> W/K.
Stereo Matching Using Local Plane Fitting in Confidence-Based Support Window

SUMMARY This paper addresses stereo matching under scenarios of smooth region and obviously slant plane. We explore the ﬂexible handling of color disparity, spatial relation and the reliability of matching pixels in support windows. Building upon these key ingredients, a robust stereo matching algorithm using local plane ﬁtting by Conﬁdence-based Support Window (CSW) is presented. For each CSW, only these pixels with high conﬁdence are employed to estimate optimal disparity plane. Considering that RANSAC has shown to be robust in suppressing the disturbance resulting from outliers, we employ it to solve local plane ﬁtting problem. Compared with the state of the art local methods in the computer vision community, our approach achieves the better performance and time e ﬃ - ciency on the Middlebury benchmark.
Cardiac-specific troponin I levels and risk of coronary artery disease and graft failure following heart transplantation.

CONTEXT Previous studies have yielded conflicting data regarding whether a relationship exists between elevated cardiac troponin levels and acute allograft rejection in patients who have received heart transplants. OBJECTIVE To determine whether cardiac troponin I levels after heart transplantation were associated with a procoagulant microvasculature and long-term allograft outcome. DESIGN Prospective cohort study with a mean (SE) follow-up of 45.1 (2.5) months. Serum troponin I levels were measured 9.9 (0.2) times per patient during the first 12 months after heart transplantation. SETTING Heart transplant center in the United States. PATIENTS A total of 110 consecutive patients who received a heart transplant between 1989 and 1997 and survived at least 1 year after transplantation. MAIN OUTCOME MEASURES Histological and immunohistochemical biopsy findings, development of coronary artery disease (CAD), and graft failure in patients with vs without elevated serum cardiac troponin I levels. RESULTS All recipients had elevated troponin I levels during the first month after transplantation. Troponin I levels remained persistently elevated during the first 12 months in 56 patients (51%) and became undetectable in 54 patients (49%). Persistently elevated troponin I levels were associated with increasing fibrin deposits in microvasculature and cardiomyocytes (P<.001). Patients with persistently elevated levels of troponin I had significantly increased risk for subsequent development of CAD (odds ratio [OR], 4. 3; 95% confidence interval [CI], 1.8-10.1; P<.001) and graft failure (OR, 3.4; 95% CI, 1.2-9.7; P =.02), and also developed more severe CAD (OR, 4.2; 95% CI, 1.9-9.3; P<.001) and showed more disease progression (OR, 3.7; 95% CI, 1.3-10.4; P =.009). CONCLUSION In this study, elevated cardiac troponin I levels, which are considered to be a noninvasive surrogate marker of a procoagulant microvasculature, identified a subgroup of patients with high risk for developing CAD and graft failure after cardiac transplantation. JAMA. 2000;284:457-464
CYP2B6 SNPs are associated with methadone dose required for effective treatment of opioid addiction

Adequate methadone dosing in methadone maintenance treatment (MMT) for opioid addiction is critical for therapeutic success. One of the challenges in dose determination is the inter‐individual variability in dose‐response. Methadone metabolism is attributed primarily to cytochrome P450 enzymes CYP3A4, CYP2B6 and CYP2D6. The CYP2B6*6 allele [single nucleotide polymorphisms (SNPs) 785A>G (rs2279343) and 516G>T (rs3745274)] was associated with slow methadone metabolism. To explore the effects of CYP2B6*6 allele on methadone dose requirement, it was genotyped in a well‐characterized sample of 74 Israeli former heroin addicts in MMT. The sample is primarily of Middle Eastern/European ancestry, based on ancestry informative markers (AIMs). Only patients with no major co‐medication that may affect methadone metabolism were included. The stabilizing daily methadone dose in this sample ranges between 13 and 260 mg (mean 140 ± 52 mg). The mean methadone doses required by subjects homozygous for the variant alleles of the CYP2B6 SNPs 785A>G and 516G>T (88, 96 mg, respectively) were significantly lower than those of the heterozygotes (133, 129 mg, respectively) and the non‐carriers (150, 151 mg, respectively) (nominal P = 0.012, 0.048, respectively). The results remain significant after controlling for age, sex and the ABCB1 SNP 1236C>T (rs1128503), which was previously shown to be associated with high methadone dose requirement in this population (P = 0.006, 0.030, respectively). An additional 77 CYP2B6, CYP3A4 and CYP2D6 SNPs were genotyped. Of these, 24 SNPs were polymorphic and none showed significant association with methadone dose. Further studies are necessary to replicate these preliminary findings in additional subjects and other populations.
Treatment of metastatic osteosarcoma at diagnosis: a Pediatric Oncology Group Study.

PURPOSE To estimate the duration of survival (S) of patients with metastatic osteosarcoma (MOS) at diagnosis treated with a multiagent, ifosfamide-containing chemotherapeutic and surgical regimen and to evaluate the toxicity of this regimen. PATIENTS AND METHODS Thirty patients aged younger than 30 years received two courses of ifosfamide followed by surgery on the primary tumor and metastatic sites. Patients then received a postsurgical multiagent chemotherapeutic regimen that consisted of high-dose methotrexate (HDMTX), ifosfamide, doxorubicin, and cisplatin. RESULTS The 5-year event-free survival (EFS) rate was 46.7% (95% confidence interval [CI]; 28.5 to 64.9) and 5-year S rate was 53.3% (95% CI; 35.1 to 71.5). Three patients with bone metastases and one patient with lymph node metastases died. Twenty-six patients presented with pulmonary metastatic nodules only. Eight of these patients had at least eight nodules at diagnosis and had an estimated 5-year EFS rate of 25.0% compared with 66.7% for the 18 patients with less than eight nodules (P=.06). Fourteen patients presented with bilateral lung metastases and had a 5-year EFS rate of 35.7% compared with the 12 patients who presented with unilateral involvement and had a 5-year EFS rate of 75.0% (P=.03). The hematopoietic toxicity experienced by the patients during the entire regimen was relatively mild. Seven patients had renal toxicity characterized by hypophosphatemia and/or hypokalemia. CONCLUSION This ifosfamide-containing regimen is tolerable and effective in the treatment of patients with osteosarcoma (OS) who present with lung metastases. However, better regimens are required for this group of patients.
Influence of the gender on cerebral vascular diameters observed during the magnetic resonance angiographic examination of willis circle

The present study evaluated the calibers and anatomic configurations based on the Magnetic Resonance analysis (MRA), assaying the cerebral vascular territories and sex-linked variations. A randomized sample of 30 angiographic examinations in adult patients of both sexes was obtained and components of the circle of Willis were identified. Branch diameters were measured on a transversal cut 5mm from the vessel origin in a typical angiographic frontal incidence. For the comparative statistical analysis, tests were divided in the groups considering the patients' sex and age. The classical Circle of Willis configuration was oberved in only 15 samples (50%). Greater calibers were observed in the arteries of the posterior circulation and multiple linear regression analysis established that the caliber of the posterior circulation was influenced by an independent variable related to the gender. Additional variations included unilateral and bilateral fetal and hypoplasic Posterior communicating arteries. In the anterior cerebral artery (ACA), the presence of an accessory developed ACA, an ACA giving branches to the distal portion of the two hemispheres and a third median ACA the variants were observed. Gender influenced the variations on internal diameters of posterior circulation vessels, with larger measurements in men.