Miracle-dz/UniFAR-FTUs huggingface dataset:
Identifying nonalcoholic fatty liver disease patients with active fibrosis by measuring extracellular matrix remodeling rates in tissue and blood

Excess collagen synthesis (fibrogenesis) in the liver plays a causal role in the progression of nonalcoholic fatty liver disease (NAFLD). Methods are needed to identify patients with more rapidly progressing disease and to demonstrate early response to treatment. We describe here a novel method to quantify hepatic fibrogenesis flux rates both directly in liver tissue and noninvasively in blood. Twenty‐one patients with suspected NAFLD ingested heavy water (2H2O, 50‐mL aliquots) two to three times daily for 3‐5 weeks prior to a clinically indicated liver biopsy. Liver collagen fractional synthesis rate (FSR) and plasma lumican FSR were measured based on 2H labeling using tandem mass spectrometry. Patients were classified by histology for fibrosis stage (F0‐F4) and as having nonalcoholic fatty liver or nonalcoholic steatohepatitis (NASH). Magnetic resonance elastography measurements of liver stiffness were also performed. Hepatic collagen FSR in NAFLD increased with advancing disease stage (e.g., higher in NASH than nonalcoholic fatty liver, positive correlation with fibrosis score and liver stiffness) and correlated with hemoglobin A1C. In addition, plasma lumican FSR demonstrated a significant correlation with hepatic collagen FSR. Conclusion: Using a well‐characterized cohort of patients with biopsy‐proven NAFLD, this study demonstrates that hepatic scar in NASH is actively remodeled even in advanced fibrosis, a disease that is generally regarded as static and slowly progressive. Moreover, hepatic collagen FSR correlates with established risks for fibrotic disease progression in NASH, and plasma lumican FSR correlates with hepatic collagen FSR, suggesting applications as direct or surrogate markers, respectively, of hepatic fibrogenesis in humans. (Hepatology 2017;65:78‐88).
Color, anthocyanin, and antioxidant characteristics of young wines produced from spine grapes (Vitis davidii Foex) in China

ABSTRACT Background: Spine grape has gained attention in the field of wine science due to its good growth characteristics. Spine grape wine has been made by local residents for a long time. However, the scientific evaluation of spine wine has not been systemically documented compared to Vitis vinifera grape wines Methods: We compared 11 spine wines from south China (W1–W11) with 7 high-quality international wines (W12–W18). The total phenolic content, the total anothcyanin content and the antioxidant activity of these wines were analyzed and compared. Meanwhile, anthocyanin profiles of these wines were also documented. Results: Compared with other wines most of the spine wines had a strong red intensity with a blue hue. Malvidin-3,5-O-diglucoside and malvidin-3-O-(6-O-coumaroyl)-glucoside-5-glucoside appeared to be the major anthocyanins in these wines. The scavenging capacity analyses of these wines using ABTS, DPPH, and CUPRAC assays indicated that spine wines possessed high antioxidant properties, especially spine wine W3, W4, W6 and W8. Their high antioxidant properties were mainly related to the high levels of the total phenolic content and anthocyanins. Conclusion: These results suggested that spine wine might be considered a good wine source for the Chinese wine industry and provided useful information on the knowledge of spine grape.
A NOVEL MODULAR SYMMETRICAL MULTILEVEL CONVERTER WITH REDUCED NUMBER OF CIRCUIT DEVICES

In this paper a novel symmetric multilevel converter structure based on cascaded converter family is proposed. This inverter is likely to be used in low/medium voltage applications. The proposed topology is analyzed and then compared with conventional multilevel cascade converters. Comparison depicts the proposed inverter superiority over the conventional inverters. In this topology, all the desired voltage levels can be obtained using a lower number of devices. The suggested multilevel converter reduces the requirements for circuit elements including switches and their gate drivers. As a result, the total cost is significantly reduced and the control scheme is simpler. Both the simulation and experimental results are provided to demonstrate the practicability and the good performance of the suggested converter. The simulation and experimental results are in good agreement which shows the effectiveness of the proposed inverter.
Outcomes-based funding for vocational services and employment of people with mental health conditions.

OBJECTIVE This study explored the likelihood of and identified the factors related to securing and sustaining jobs for people with psychiatric disabilities in New York State who received vocational services through an outcomes-based reimbursement program. METHODS Quantitative and qualitative data were collected over two years to characterize placement and retention through the performance-based contracting demonstration. Seven social service agencies located statewide were contracted by the New York State Office of Mental Health to provide vocational services to people with mental health conditions through the performance-based contracting milestone structure, which established incremental steps toward the goal of sustained integrated competitive employment at which providers were reimbursed. Intake was continuous throughout the demonstration period, from December 2000 to December 2002. Key outcomes included placement in employment, time to placement, and job retention. RESULTS Data were examined for the 171 participants who were still active in the demonstration at the end of the study period. A total of 108 participants (63 percent) were successful in securing jobs. Among those placed, 79 (73 percent) retained work at the end of the demonstration, a rate comparable to other best-practice models. Factors related to these outcomes included number of provider hours spent assisting consumers weekly, length of time to placement, consumer enrollment in the state's rehabilitation services program, and quality of the jobs developed. CONCLUSIONS Outcomes funding was associated with successful employment for people with psychiatric disabilities. The performance-based funding structure may encourage providers to work more intensively with consumers early in the placement process, find jobs that consumers want to keep, and coordinate more effectively with the state rehabilitation agency.
The CXCR4 chemokine receptor in acute and chronic leukaemia: a marrow homing receptor and potential therapeutic target

Chemokine (C‐X‐C motif) receptor 4 (CXCR4) is essential for homing and maintenance of haematopoietic stem cells in distinct stromal cell niches within the marrow. Chemotactic responsiveness of haematopoietic stem cells is restricted to the ligand for CXCR4, stromal cell‐derived factor‐1 (SDF‐1/CXCL12), which is constitutively secreted by marrow stromal cells. Myeloid and lymphoid leukaemia cells also express CXCR4 that induces leukaemia cell chemotaxis and migration beneath marrow stromal cells. CXCR4 expression levels have a major prognostic impact in acute myeloid leukaemia. There is growing in vitro and in vivo evidence that CXCR4 expression by leukaemia cells allows for homing and their retention within the marrow. As such, leukaemia cells appear to utilise CXCR4 to access niches that are normally restricted to progenitor cells, and thereby reside in a microenvironment that favours their growth and survival. CXCR4‐ and integrin‐mediated contact between leukaemia cells and stromal cells protects leukaemia cells from spontaneous and chemotherapy‐induced cell death and therefore may represent a mechanism to explain minimal residual disease and subsequent relapses commonly seen in the treatment of these diseases. This review summarises our current knowledge regarding the importance of CXCR4 in acute and chronic leukaemia, discusses the importance of CXCR4 detection by flow cytometry in the diagnostic workup of leukaemia patients, and introduces the potential role of CXCR4‐targeting compounds for the treatment of leukaemia patients.
A Review of Prevalence of Obesity in Saudi Arabia

Over the past 3 decades, the prevalence of overweight and obesity has increased dramatically worldwide. The rising trend of obesity indicates that this increase is not only confined to the developed world, but also extending towards the developing world. In the context, Saudi Arabia is now among the nations with the highest obesity and overweight prevalence rates due to a number of factors. This research explores and evaluates the prevalence of obesity in Saudi Arabia on the basis of the findings of previous literature. The research reveals that the rate of obesity is significantly high in the country among different age groups and occupations; at different locations in the country; and among both males and females. The main factors causing obesity include family history, diet pattern and eating habits, genetic factors, marital status, hypertension and lack of physical activities; while, the major consequences are cardiovascular diseases, diabetes, cancers, and Ischemic heart disease. The research stresses on the need to raise awareness regarding obesity and design efforts and strategies to combat it in the country.
Serum MMP‐8 levels increase in colorectal cancer and correlate with disease course and inflammatory properties of primary tumors

Matrix metalloproteinases (MMPs) form a family of zinc‐dependent endoproteases participating in cancer pathogenesis by promoting invasion and regulating growth signaling, apoptosis, angiogenesis and immune responses. MMP‐8 is an intriguing MMP with recently discovered antitumor activity and immunoregulatory properties, but its role in colorectal cancer (CRC) has not been studied extensively. Preoperative serum MMP‐8 levels (S‐MMP‐8) of 148 CRC patients and 83 healthy controls were measured using an immunofluorometric assay and related to clinical and pathological parameters. The patients had higher S‐MMP‐8 than the controls (median 63.0 vs. 17.2 ng/ml, p = 1.5E − 9), and a receiver operating characteristics analysis yielded an area under the curve of 0.751 in differentiating the groups. In univariate analyses, S‐MMP‐8 correlated positively with disease stage (p = 4.5E − 4), the degree of primary tumor necrosis (p = 0.0024) and blood neutrophil count (Pearson r = 0.523, p = 2.5E − 9). Particular interest was also addressed to the inflammatory properties of the tumors, and both variables studied, peritumoral tumor‐destructing inflammatory infiltrate and Crohn's‐like lymphoid reaction (CLR), showed a negative correlation with S‐MMP‐8 (p = 0.041 and p = 0.0057, respectively). In a multiple linear regression analysis, high S‐MMP‐8 associated with elevated blood neutrophil count, distant metastases, low‐grade CLR and low body mass index. Overall, our results indicate that MMP‐8 is involved in the course and progression of CRC influencing the immune response against the tumor and contributing to the resolution of necrosis. Serum or plasma MMP‐8 may prove to be a worthy biomarker for CRC.
Immune Reconstitution After Allogeneic Hematopoietic Stem Cell Transplantation and Association With Occurrence and Outcome of Invasive Aspergillosis.

BACKGROUND Invasive aspergillosis (IA) remains a leading cause of morbidity and mortality in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). To date, no reliable immunological biomarkers for management and outcome of IA exist. Here, we investigated reconstitution of antifungal immunity in patients during the first 12 months after HSCT and correlated it with IA. METHODS Fifty-one patients were included, 9 with probable/proven IA. We determined quantitative and qualitative reconstitution of polymorphonuclear (PMN), CD4, CD8, and natural killer (NK) cells against Aspergillus fumigatus over 5 time points and compared the values to healthy donors. RESULTS Absolute CD4 and CD8 cell counts, antigen-specific T-cell responses, and killing capacity of PMN against A. fumigatus were significantly decreased in all patients over 12 months. In patients with probable/proven IA, reactive oxygen species (ROS) production tended to be lower compared to patients without IA, and absolute NK-cell counts remained below 200 cells/µL. Patients with well-controlled IA showed significantly higher ROS production and NK-cell counts compared to patients with poor outcome. CONCLUSIONS This study highlights the importance of functional PMN, T-cell, and NK-cell immunity for the outcome of IA. Larger multicenter studies should address the potential use of NK-cell counts for the management of antifungal therapy.
The role of Ag in the pulsed laser growth of YBCO thin films

We have studied systematically the role of silver in improving microstructure and properties of Y1Ba2Cu3O7−δ (YBCO) thin films. We have more than doubled the grain size to nearly 1.8 μm and reduced processing temperatures by incorporating Ag in the YBCO films, which is accomplished by using a composite target containing 15% by weight of Ag. These films show approximately four times higher Jc than the best films obtained on MgO(001) substrates deposited from stoichiometric Y1Ba2Cu3O7−δ targets. Study of the silver content in the film as a function of the deposition temperature shows clearly a decreasing concentration with increasing temperature and a segregation of the Ag to the surface. The increased oxygen content in the films is also observed at lower processing temperatures, providing strong support for the efficient oxygenation of YBCO via the presence of silver. A qualitative model suggests that the formation of silver oxide, rapid surface diffusion of Ag on MgO surfaces, and the nonreactivity of Ag .
Accelerometer vs. Electromyogram in Activity Recognition

In this study, information from wearable sensors is used to recognize human activities. Commonly the approaches are based on accelerometer data while in this study the potential of electromyogram (EMG) signals in activity recognition is studied. The electromyogram data is used in two different scenarios: 1) recognition of completely new activities in real life and 2) to recognize the individual activities. In this study, it was shown that in gym settings electromyogram signals clearly outperforms the accelerometer data in recognition of completely new sets of gym movements from streaming data even though the sensors would not be positioned directly to the muscles trained. Nevertheless, in recognition of individual activities the EMG itself does not provide enough information to recognize activities accurately.
The Regulation of DWARF4 Expression Is Likely a Critical Mechanism in Maintaining the Homeostasis of Bioactive Brassinosteroids in Arabidopsis1

Mutants that are defective in brassinosteroid (BR) biosynthesis or signaling display severely retarded growth patterns due to absence of growth-promoting effects by BRs. Arabidopsis (Arabidopsis thaliana) DWARF4 (DWF4) catalyzes a flux-determining step in the BR biosynthetic pathways. Thus, it is hypothesized that the tissues of DWF4 expression may represent the sites of BR biosynthesis in Arabidopsis. Here we show that DWF4 transcripts accumulate in the actively growing tissues, such as root, shoot apices with floral clusters, joint tissues of root and shoot, and dark-grown seedlings. Conforming to the RNA gel-blot analysis, DWF4:β-glucuronidase (GUS) histochemical analyses more precisely define the tissues that express the DWF4 gene. Examination of the endogenous levels of BRs in six and seven different tissues of wild type and brassinosteroid insensitive1-5 mutant, respectively, revealed that BRs are significantly enriched in roots, shoot tips, and joint tissues of roots and shoots. In addition, DWF4:GUS expression was negatively regulated by BRs. DWF4:GUS activity was increased by treatment with brassinazole, a BR biosynthetic inhibitor, and decreased by exogenous application of bioactive BRs. When DWF4:GUS was expressed in a different genetic background, its level was down-regulated in brassinazole resistant1-D, confirming that BRASSINAZOLE RESISTANT1 acts as a negative regulator of DWF4. Interestingly, in the brassinosteroid insensitive2/dwf12-1D background, DWF4:GUS expression was intensified and delocalized to elongating zones of root, suggesting that BRASSINOSTEROID INSENSITIVE2 is an important factor that limits DWF4 expression. Thus, it is likely that the DWF4 promoter serves as a focal point in maintaining homeostasis of endogenous bioactive BR pools in specific tissues of Arabidopsis.
MECHANISMS OF DIRECT PERITONEAL RESUSCITATION-MEDIATED SPLANCHNIC HYPERPERFUSION FOLLOWING HEMORRHAGIC SHOCK

Conventional resuscitation (CR) from hemorrhagic shock causes a persistent and progressive splanchnic vasoconstriction and hypoperfusion despite hemodynamic restoration with intravenous fluid therapy. Adjunctive direct peritoneal resuscitation (DPR) with a clinical peritoneal dialysis solution instilled into the peritoneal cavity has been shown to restore splanchnic tissue perfusion, down-regulate the gut-derived exaggerated systemic inflammatory response, promote early fluid mobilization, and improve overall outcome. This study was conducted to define the molecular mechanisms of DPR-induced gut hyperperfusion after hemorrhagic shock. Male rats were bled to 50% baseline mean arterial pressure and resuscitated with the shed blood plus two volumes of saline (CR). In vivo videomicroscopy and Doppler velocimetry were used to assess terminal ileal microvascular diameters and blood flow. Direct peritoneal resuscitation animals received CR and topical application of a clinical glucose-based peritoneal dialysis solution (Delflex). Inhibitors, glibenclamide (K+ATP channels), N-monomethyl-L-arginine (L-NMMA) (nitric oxide synthase), 8-cyclopentyl-1,3-diprophylxanthine (DPCPX) (A1 adenosine receptor), tetrabutylammonium (K+Ca2+ channels), and mefenamic acid (cyclooxygenase) were topically applied (individually or in combination) with DPR according to protocol; BQ-123 (endothelin A receptor antagonist) and BQ-788 (endothelin B receptor antagonist) were used topically with CR to define the mechanism of post-CR vasoconstriction and hypoperfusion. Conventional resuscitation caused a persistent progressive intestinal vasoconstriction and hypoperfusion that can be abolished with endothelin antagonists. In contrast, adjunctive DPR caused an instantaneous sustained vasodilation and hyperperfusion. Glibenclamide or L-NMMA partially attenuated DPR-induced vasodilation, whereas the addition of DPCPX to the two inhibitors eliminated the dilation. Cyclooxygenase and K+Ca2+channels were not active in DPR-mediated microvascular effects. In conclusion, DPR improves splanchnic tissue perfusion by endothelium-dependent mechanisms mediated by activations of glibenclamide-sensitive K+ channels (KATP), adenosine A1 receptor subtype activation, and nitric oxide release. Direct peritoneal resuscitation preserves endothelial dilatory functions, thereby overriding any endothelium-derived constrictor response triggered by hemorrhagic shock and CR.
The Effect of Breast Cancer Resistance Protein (Bcrp) and P-glycoprotein (Mdr1a/1b) on the Brain Penetration of Flavopiridol, Gleevec, Prazosin and PF-407288 in Mice

: The role of breast cancer resistance protein (Bcrp) and the combined activities of Bcrp and P-glycoprotein (P-gp, Mdr1a/1b) in limiting the brain penetration of drugs at blood-brain barrier (BBB) were investigated using wild-type FVB, Mdr1a/1b (-/-, -/-) , Bcrp (- /-) , and Mdr1a/1b (-/-, -/-) Bcrp (-/-) mice. Four drugs, flavopiridol, gleevec, PF-407288 and prazosin, with different transport specificity for BCRP/Bcrp and MDR1/Mdr1a were selected, and the drug levels in plasma, cerebrospinal fluid (CSF) and brain of mice were determined. Flavopiridol and prazosin were identified as substrates for both mouse Bcrp and Mdr1a with greater transport associated with Bcrp. The brain/plasma (B/P) ratios at 0.5 and 2 hr in Mdr1a/1b (-/-, -/-) and Bcrp (-/-) mice were 1-2-fold for both compounds, while the ratios in Mdr1a/1b (-/-, -/-) Bcrp (-/-) mice were more than 5-fold of those observed in FVB mice. Whereas for gleevec, a better substrate of P-gp than Bcrp, the B/P ratios in Bcrp (-/-) were comparable to those in FVB mice, while the B/P ratios in Mdr1a/1b (-/-, -/-) and Mdr1a/1b (-/-, -/-) Bcrp (-/-) mice were more than 4-fold and 28-fold of those in FVB mice at both time points, respectively. Finally, the Bcrp specific substrate PF-407288 exhibited comparable B/P ratios in Mdr1a/1b (-/-, -/-) and Bcrp (-/-) mice, and slightly but significantly increased B/P ratios in Mdr1a/1b (-/-, -/-) Bcrp (-/-) mice compared with FVB mice. The B/P ratios of compounds in Mdr1a/1b (-/-, -/-) Bcrp (-/-) compared with those in Mdr1a/1b (-/-, -/-) clearly demonstrate that Bcrp impairs the brain penetration of its substrates. Moreover, P-gp and Bcrp at BBB function synergistically to limit the brain penetration of shared substrates.
A Model for NBTI in Nitrided Oxide MOSFETs Which Does Not Involve Hydrogen or Diffusion

The negative bias temperature instability (NBTI) is, arguably, the single most important reliability problem in present day metal-oxide-silicon field-effect transistor (MOSFET) technology. This paper presents a model for the NBTI which is radically different from the quite widely utilized reaction diffusion models which dominate the current day NBTI literature. The proposed model is relevant to technologically important nitrided oxide pMOSFETs. The model is clearly not, at least in its entirety, relevant to pure silicon dioxide gate pMOSFETs. The reaction diffusion models involve hydrogen/silicon bond breaking events at the silicon/silicon dioxide interface initiated by the presence of an interface hole, followed by the diffusion of a hydrogenic species from the interface as well as the potential rebonding of hydrogen and interface trap defect centers. This model does not invoke hydrogen in any form whatsoever but does simply account for the observed NBTI power law response with a reasonable, at least very plausible, assumption about defect distribution and provides a reasonably accurate value for this exponent. (Without making any assumption about defect distribution, the model still provides a time response semiquantitatively consistent with the observations, reasonable agreement considering the simplifying assumptions in the calculations.) The model also provides a reasonable explanation for the recovery which includes a simple explanation for the extremely rapid rate of recovery at short times. In addition, the model provides a very simple explanation why the introduction of nitrogen greatly enhances the NBTI. The model, as presented in this paper, should be viewed as a first-order approximation; it contains several simplifying assumptions. Finally, the model is consistent with recent electron paramagnetic resonance studies of NBTI defect chemistry in nitrided oxide pMOSFETs.
Association of angiotensinogen gene M235T polymorphism with the risk of IgA nephropathy: a meta-analysis

Abstract The association between angiotensinogen (AGT) M235T gene polymorphism and IgA nephropathy (IgAN) risk remains elusive. Our aim was to evaluate the association between AGT M235T gene polymorphism and IgAN susceptibility by performing a meta-analysis. Eligible studies were searched according to predefined criteria using electronic databases. Eight studies were identified for the analysis of the association between AGT M235T gene polymorphism and IgAN risk. M allele/MM genotype were not associated with IgAN risk in overall populations, Caucasians and Asians (overall populations: p = 0.448 and 0.861, Caucasians: p = 0.618 and 0.886, Asians: p = 0.566 and 0.652). TT/MT genotype were not associated with IgAN risk in overall populations, Caucasians and Asians (overall populations: p = 0.703 and 0.454, Caucasians: p = 0.975 and 0.946, Asians: p = 0.697 and 0.353). No evidence of publication bias was observed. In conclusion, AGT M235T gene polymorphism may not be correlated with IgAN susceptibility in overall populations, Caucasians and Asians. However, more studies should be performed in the future.