Miracle-dz/UniFAR-FTUs huggingface dataset:
The natural history of liver cirrhosis in HIV–hepatitis C virus-coinfected patients

Objective:To provide detailed information about the natural history of HIV–hepatitis C virus (HCV)-coinfected patients with cirrhosis. Methods:Prospective cohort including 340 HIV–HCV-coinfected patients with compensated (n = 248) or decompensated (n = 92) cirrhosis. We evaluated predictors of survival and of first hepatic decompensation. Results:The mortality rate for patients with decompensated and compensated cirrhosis was 27.14 deaths per 100 person-years [95% confidence interval (CI) 18.93–35.35] and 3.98 deaths per 100 person-years (95% CI 2.42–5.54), respectively. Rate of first hepatic decompensation in patients with compensated cirrhosis was 4.62 per 100 persons-years (95% CI 2.91–6.33). In the complete cohort, permanent HAART interruption during follow-up, CD4 cell count nadir and baseline Child-Pugh score (CPS) B or C were significantly associated with shorter survival. In patients with compensated cirrhosis factors significantly associated with decreased survival were having the first hepatic decompensation during follow-up, permanent HAART discontinuation, and CPS B and C at baseline. For patients with compensated cirrhosis, time since diagnosis of HCV infection, CPS B and C and permanent HAART discontinuation were significantly associated with the risk of first hepatic decompensation. Sustained viral response to anti-HCV therapy was not independently associated with better survival in patients with compensated cirrhosis. Conclusion:HIV–HCV-coinfected patients with cirrhosis have a relatively good 3-year survival (87%). In contrast, 2-year survival of patients with decompensated liver cirrhosis is only 50%. Three-year survival was mostly impacted by liver-related factors and HAART maintenance.
Preferential Development of CD4 and CD8 T Regulatory Cells in RasGRP1-Deficient Mice1

RasGRP1 and Sos are two Ras-guanyl-nucleotide exchange factors that link TCR signal transduction to Ras and MAPK activation. Recent studies demonstrate positive selection of developing thymocytes is crucially dependent on RasGRP1, whereas negative selection of autoreactive thymocytes appears to be RasGRP1 independent. However, the role of RasGRP1 in T regulatory (Treg) cell development and function is unknown. In this study, we characterized the development and function of CD4+CD25+Foxp3+ and CD8+CD44highCD122+ Treg lineages in RasGRP1−/− mice. Despite impaired CD4 Treg cell development in the thymus, the periphery of RasGRP1−/− mice contained significantly increased frequencies of CD4+Foxp3+ Treg cells that possessed a more activated cell surface phenotype. Furthermore, on a per cell basis, CD4+Foxp3+ Treg cells from mutant mice are more suppressive than their wild-type counterparts. Our data also suggest that the lymphopenic environment in the mutant mice plays a dominant role of favored peripheral development of CD4 Treg cells. These studies suggest that whereas RasGRP1 is crucial for the intrathymic development of CD4 Treg cells, it is not required for their peripheral expansion and function. By contrast to CD4+CD25+Foxp3+ T cells, intrathymic development of CD8+CD44highCD122+ Treg cells is unaffected by the RasGRP1−/− mutation. Moreover, RasGRP1−/− mice contained greater numbers of CD8+CD44highCD122+ T cells in the spleen, relative to wild-type mice. Activated CD8 Treg cells from RasGRP1−/− mice retained their ability to synthesize IL-10 and suppress the proliferation of wild-type CD8+CD122− T cells, albeit at a much lower efficiency than wild-type CD8 Treg cells.
Diagnostic accuracy of stress first-pass contrast-enhanced myocardial perfusion MRI compared with stress myocardial perfusion scintigraphy.

OBJECTIVE The purpose of this study was to determine the diagnostic accuracy of stress perfusion MRI acquired with saturation-recovery prepared turbo fast low-angle shot (turbo FLASH) compared with stress myocardial perfusion scintigraphy. Recent studies show that first-pass contrast-enhanced myocardial perfusion MRI can provide noninvasive detection of low-limiting stenosis in the coronary artery. MATERIALS AND METHODS First-pass contrast-enhanced MR images were acquired at rest and during stress in 40 patients with suspected coronary artery disease. All patients underwent thallium-201 SPECT without attenuation correction and coronary angiography. Two reviewers independently assigned one of five confidence grades without knowing the results of coronary angiography for receiver operating characteristic (ROC) analysis. Luminal stenosis >70% on coronary angiography was used as a reference standard. RESULTS On coronary angiography, 70% or greater diameter stenosis of the coronary artery was observed in 21 (52.5%) of 40 patients. The areas under the ROC curve for detection of significant stenosis in the individual coronary artery were 0.86 (observer 1) and 0.84 (observer 2) for MRI. These values were 0.79 (observer 1, p = not significant) and 0.72 (observer 2, p = not significant) for 201Tl SPECT. CONCLUSION The diagnostic accuracy of stress perfusion MRI acquired with saturation-recovery-prepared turbo FLASH was comparable with that of stress 201Tl SPECT. Stress first-pass contrast-enhanced MRI is a noninvasive technique that can be used as an alternative to stress myocardial perfusion scintigraphy.
Environmental and demographic risk factors for respiratory syncytial virus lower respiratory tract disease.

OBJECTIVE To critically review the literature examining risk factors for development of severe respiratory syncytial virus lower respiratory tract infection (RSV LRI). STUDY DESIGN A literature review was performed with the use of a MedLine search strategy. Clinical evidence of putative risk factors was rated by means of the US Preventive Services Task Force recommendations, and the quality of the data was critically assessed. Nonmedical risk factors examined included race/ethnicity, age of acquisition of RSV, sex, birth during the first half of the RSV season, breast-feeding, malnutrition, maternal education, socioeconomic status, crowding/siblings, day care, and tobacco smoke exposure. RESULTS There was sufficient evidence available to conclude that (1) male sex, (2) age <6 months, (3) birth during the first half of the RSV season, (4) crowding/siblings, and (5) day care exposure are significant risk factors for severe RSV LRI. There was insufficient evidence to evaluate the effect of race/ethnicity on severe RSV LRI. The evidence for tobacco smoke exposure is mixed. Low maternal education (as a proxy for lower socioeconomic status), lack of breast-feeding, and malnutrition did not appear to increase the risk of severe RSV LRI or RSV hospitalization. CONCLUSIONS Male sex, young age, birth in the first half of the RSV season, day care attendance, and crowding/siblings are independent risk factors for the development of severe RSV LRI.
Identification and functional characterization of an Src homology domain 3 domain‐binding site on Cbl

Cbl is an adaptor protein and ubiquitin ligase that binds and is phosphorylated by the nonreceptor tyrosine kinase Src. We previously showed that the primary interaction between Src and Cbl is mediated by the Src homology domain 3 (SH3) of Src binding to proline‐rich sequences of Cbl. The peptide Cbl RDLPPPPPPDRP(540–551), which corresponds to residues 540–551 of Cbl, inhibited the binding of a GST–Src SH3 fusion protein to Cbl, whereas RDLAPPAPPPDR(540–551) did not, suggesting that Src binds to this site on Cbl in a class I orientation. Mutating prolines 543–548 reduced Src binding to the Cbl 479–636 fragment significantly more than mutating the prolines in the PPVPPR(494–499) motif, which was previously reported to bind Src SH3. Mutating Cbl prolines 543–548 to alanines substantially reduced Src binding to Cbl, Src‐induced phosphorylation of Cbl, and the inhibition of Src kinase activity by Cbl. Expressing the mutated Cbl in osteoclasts induced a moderate reduction in bone‐resorbing activity and increased amounts of Src protein. In contrast, disabling the tyrosine kinase‐binding domain of full‐length Cbl by mutating glycine 306 to glutamic acid, and thereby preventing the previously described binding of the tyrosine kinase‐binding domain to the Src phosphotyrosine 416, had no effect on Cbl phosphorylation, the inhibition of Src activity by full‐length Cbl, or bone resorption. These data indicate that the Cbl RDLPPPP(540–546) sequence is a functionally important binding site for Src.
Behavioral Assessment of the Dysexecutive Syndrome Battery (BADS) in Schizophrenia: A Pilot Study in the Spanish Population

ObjectiveThe purposes of this study were to explore the diagnostic features of the behavioral assessment of the dysexecutive syndrome battery (BADS) in the Spanish population of chronic schizophrenia patients, its concurrent validity with other classic neuropsychologic tests of executive dysfunction, and its correlates with clinical variables. MethodsA cross-sectional study was conducted in a sample of 61 patients with chronic schizophrenia and in a control group of 35 healthy participants. The diagnostic characteristics of the test were studied. An evaluation was performed of the association of BADS with a gold standard battery of executive dysfunction, with the symptoms, and with functional performance. Several regression models were tested to assess the clinical effect of executive impairment in schizophrenia. ResultsBADS seems to offer good reliability, a 1-dimensional structure, and good convergent validity. The proportion of schizophrenia patients with impaired executive functioning in our sample was 47%. It was a risk factor for the inpatient status and for more illness severity. ConclusionsExecutive functioning in schizophrenia can be reliably and validly assessed with BADS. The diagnosis of impaired executive functioning may be of clinical usefulness as a marker of more illness severity and poorer functional status.
Occupational and environmental lead exposure to adolescent workers in battery recycling workshops

Lead (Pb), as other environmental neurotoxicant substances, has the capability to interfere with many biochemical events present in cells throughout the body. In the present study, the environmental and occupational exposure to Pb has been assessed by analyzing the scalp hair samples of male adolescents aged 12–15 years, who have worked for the last 12–36 months in Pb battery recycling workshops (BRWs). For comparative purposes, gender and age-matched subjects living in the vicinity of recycling workshops as well as in areas without industrial activity were used as controls. The scalp hair samples were oxidized by acid in a microwave oven prior to determination of Pb by electrothermal atomic absorption spectrometry. The results indicated that both workers and nonworking exposed subjects had higher levels of Pb than nonexposed controls. The contents of Pb in scalp hair of adolescent workers in the present study were compared with those reported in other studies.
Effect of vaginal and cervical deposition of semen on the fertility of sheep inseminated with frozen-thawed semen

The effect of vaginal and cervical deposition of frozen-thawed semen on the fertility of sheep was tested in a field trial in which 543 Norwegian crossbred ewes aged between six months and five-and-a-half years from 10 farms were inseminated after natural oestrus. Cervical insemination with 200 x 106 spermatozoa resulted in 25-day non-return and lambing rates of 75·4 and 72·7 per cent, respectively, and vaginal insemination gave rates of 71·3 and 67·4 per cent; the cervical inseminations produced significantly higher lambing rates (P=0·04). There were significant differences between the lambing rates for different rams (P=0·006) and different farmers (P=0·003), and there was a significant interaction between farmer and deposition site (P=0·03). After vaginal insemination fertility was encouragingly high, but the results varied with the farmer, and different flock and management conditions.
Role of endothelium-derived nitric oxide in coronary vasodilatation induced by pacing tachycardia in humans.

Endothelium-derived NO contributes to the control of coronary perfusion. We investigated the roles of NO in the metabolic coronary vasodilatation induced by rapid pacing in humans. We evaluated the dilatation of large epicardial and resistance coronary arteries during rapid atrial pacing before and after intracoronary infusion of NG-monomethyl-L-arginine (L-NMMA), an inhibitor of NO synthesis, in 19 patients without significant coronary artery disease. The diameter of the large epicardial coronary artery and coronary blood flow (CBF) were assessed by quantitative coronary arteriography and by a Doppler flow velocity measurement. An increase in the heart rate increased CBF (P < .01) and the coronary artery diameter (P < .05). L-NMMA at a total dose of 200 mumol reduced basal CBF but did not significantly affect basal coronary artery diameter, arterial pressure, or heart rate. L-NMMA inhibited the pacing-induced dilatation of the large coronary arteries (P < .05) but did not affect pacing-induced increases in CBF. L-NMMA inhibited the acetylcholine-induced increase in CBF (P < .01) and acetylcholine-induced dilatation of the large epicardial coronary artery (P < .05). These results show that the contribution of NO to the metabolic vasodilatation during rapid pacing may differ between large epicardial and resistance coronary arteries in patients without significant coronary artery disease.
Music performance anxiety in young musicians: comparison of playing classical or popular music.

OBJECTIVES Music performance anxiety (MPA) is an issue frequently experienced by musicians. It occurs not only in experienced musicians but also in children and adolescents. Furthermore, most research on MPA has been done with musicians who specialized in classical music. This study investigated the development of MPA across the ages in young musicians focusing on the classical and popular genres. METHODS In a cross-sectional survey, 239 students at German music schools, aged between 7 and 20 yrs, were asked about their perceived MPA and musical background. The data were analyzed according to musical genre and age. Multiple regression analyses were performed to investigate the influences of musical experiences on MPA. RESULTS The analyses yielded high levels of MPA for classical musicians between 7 and 16 yrs, which was reduced in older students; for popular musicians, low MPA was seen in the younger (7-11 yrs) and high MPA in the older (16+ yrs) musicians. MPA was influenced by gender and the number of performances in the classical music group and only by gender and age in the popular music group. CONCLUSION The results showed clear different trends for the development of MPA between musical genres that should be taken into account for educational aspects in musical training.
Consensus and disturbance attenuation in multi‐agent chains with nonlinear control and time delays

In this paper, we investigate consensus and disturbance attenuation in a chain of mobile agents, which include non‐autonomous agents, semi‐autonomous agents and autonomous agents. In particular, the nonlinear dynamics of non‐autonomous agents is given and cannot be designed, while the dynamics of semi‐autonomous and autonomous agents can be partially and fully designed, respectively. To improve the robustness of multi‐agent chains against disturbances, we propose a nonlinear control framework for semi‐autonomous and autonomous agents such that they mimic the behavior of non‐autonomous agents for compatibility while also exploiting long‐range connections with distant agents. This framework ensures the existence of a unique consensus equilibrium, which is independent of the network size, connectivity topologies, control gains and information delays. Robustness of multi‐agent chains against disturbances is investigated by evaluating the frequency response at the nonlinear level. For infinitely long multi‐agent chains with recurrent patterns, we also derive a condition that ensures the disturbance attenuation but only requires the analysis of the linearized model. A case study is conducted for a connected vehicle system where numerical simulations are used to validate the analytical results. Copyright © 2016 John Wiley & Sons, Ltd.
Effect of melatonin on cerebral vasospasm following experimental subarachnoid hemorrhage

Abstract Object: The current study was undertaken to determine whether melatonin therapy reverses vasospasm and prevents apoptosis by inhibiting lipid peroxidation in an experimental subarachnoid hemorrhage (SAH) model. Materials and methods: The rabbits were divided into four groups as follows: Group 1, SAH + melatonin (5 mg/kg/i.p. BID) simultaneously with SAH (n = 6); Group 2, SAH + melatonin (5 mg/kg/i.p. BID) treated 2 hours after SAH (n = 6); Group 3, control group (n = 4); Group 4, SAH only (n = 6). Light microscopic examinations of the basilar arteries were performed to demonstrate the pathophysiological changes of the arterial wall with hematoxylin– eosin. Apoptosis: Immunohistology using the ApopTag Peroxidase In Situ Apoptosis Detection Kit was used to demonstrate apoptosis in a cross section of basilary arteries. Apoptotic index was calculated as the number of the immunoreactive nuclei per total number of endothelial cells, and expressed as a percentage. Results: The results of measurements of diameters of the vessels between groups were significantly different (p = 0.028). While basilar arteries of the SAH only group showed 57% constriction, Groups 1 and 2 were calculated as 33 and 26% constriction, respectively, compared with the control group (p < 0.05). And also Groups 1 and 2 showed significant protection of apoptosis compared with Group 4. The difference between the four groups was tested by Kruskal–Wallis test and the significance between the two groups was tested by Mann– Whitney U-test. Conclusion: Melatonin with its strong antioxidant effect can prevent SAH-induced vasospasm and apoptosis of endothelial cells of vessels.
Lipid lowering in patients with diabetes mellitus: what coronary heart disease risk threshold should be used?

Objective: To examine the impact for the UK population of providing statin treatment for diabetic patients for the primary prevention of coronary heart disease at a coronary event risk lower than currently recommended by the National Service Framework (NSF) for coronary heart disease. Design: Cross sectional survey. Setting: England 1998. Participants: Nationally representative sample of 6879 subjects aged 35–74 years living in private households. Main outcome measures: The proportion of the UK population recommended for statin treatment according to the NSF for coronary heart disease, and the proportion of the population with diabetes at a coronary disease event risk of ≥ 15% over 10 years. Results: Of the 6879 subjects with total cholesterol measurements, 218 (3.2%) had diabetes mellitus. In this nationally representative sample, 6.3% of the subjects (95% confidence interval (CI), 5.7% to 6.9%) were candidates for statin treatment for the secondary prevention of coronary heart disease, including 0.7% (95% CI 0.5% to 0.9%) with diabetes. A further 2.4% (95% CI 2.0% to 2.8%), including 0.4% (0.2% to 0.6%) with diabetes, were identified as candidates for primary prevention of coronary heart disease according to the NSF for coronary heart disease. Lowering the primary prevention threshold for statin treatment to a coronary event risk of ≥ 15% over 10 years in diabetic patients identified an additional 0.5% of the population. Conclusions: Extending statin treatment to diabetic patients at a coronary heart disease risk of ≥ 15% over 10 years would have a relatively small numerical impact in the UK population. Thus patients with diabetes mellitus should, as a minimum, be targeted for statin treatment at this level of risk.
The Association Between Callus Formation, High Pressures and Neuropathy in Diabetic Foot Ulceration

The presence of an ulcer beneath callus on the diabetic foot has been a well‐documented and common clinical finding. We have conducted a prospective study to examine whether callus can be used to predict plantar intrinsic neuropathic diabetic foot ulcer formation. Sixty‐three diabetic patients (43 male, 25 Type 1), median age 62 years (IQ range 52, 67), median diabetes duration 17 years (IQ range 8,25) participated in the study. All had neuropathy and peak plantar foot pressures (measured using a dynamic optical pedobarograph) ⩾10 kg cm−2. Calluses and previous ulcers were documented and classified. All ulcers occurring prior to and during the study were recorded, re‐examination was 15.4 (range 10–22) months from baseline. Seven ulcers (6 patients) occurred during the study. Pressures were higher in the ulcer than non‐ulcer sub‐group (p = 0.04) with a relative risk of developing an ulcer of 4.7 for an area of elevated plantar pressure. This compares with a relative risk of 11.0 for an ulcer developing under an area of callus, and a relative risk of 56.8 for an ulcer developing on a site of previous ulceration. This study confirms that a history of previous ulceration is the highest risk factor for ulceration and demonstrates, for the first time, that the presence of plantar callus is highly predictive of subsequent ulceration. Careful history taking and examination of the foot to detect the presence of callus require no special training or equipment and callus should be recognized as a ‘high risk’ factor for foot ulceration.
Regulatory changes in the fucose system associated with the evolution of a catabolic pathway for propanediol in Escherichia coli

Wild-type strains of Escherichia coli are unable to use L-1,2-propanediol as a carbon and energy source. Strain 3, a mutant selected for the ability to grow on this compound at progressively more rapid rates, synthesizes constitutively a nicotinamide adenine dinucleotide-linked propanediol oxidoreductase. This enzyme is normally synthesized during anaerobic growth on L-fucose when it functions as a lactaldehyde reductase. Propanediol, the end product of this fermentation process, escapes irretrievably into the medium. The propanediol-utilizing mutant can no longer grow on fucose in either the presence or absence of molecular oxygen. In the present study nine independent lines of propanediol-positive mutants were characterized. One mutant, strain 418, attained a propanediol growth rate close to that of strain 3 without loss of the ability to grow on fucose. In all cases examined, however, prolonged selection on propanediol did result in the emergence of fucose-negative mutants. All of these mutants had enzyme patterns similar to that of strain 3; namely, fucose permease, fucose isomerase, and fuculose kinase were noninducible, whereas fuculose 1-phosphate aldolase was constitutive. In strain 418 and in the fucose-positive predecessors of the other mutants, the first four enzymes in the pathway remained inducible, as in the wild-type strain. Improvements in the growth rate on propanediol appeared to reflect principally the increased activity level of the oxidoreductase during the early stages of evolution. According to transductional analysis, the mutations affecting the ability to grow on propanediol and those that affect the expression of the first enzymes in the fucose pathway were very closely linked. The loss of the ability to grow on fucose is thought to be a mechanistic consequence incidental to the remodeling of the regulatory system in favor of the utilization of the novel carbon source.