Miracle-dz/UniFAR-FTUs huggingface dataset:
Risk of HIV dementia and opportunistic brain disease in AIDS and zidovudine therapy

OBJECTIVE To determine the incidence of HIV dementia and opportunistic brain disease in AIDS relative to the use of licensed antiretoviral medication (zidovudine, zalcitabine, didanosine, and stavudine). METHOD Medical records were evaluated retrospectively in a longitudinal cohort of 1109 patients with AIDS during the period 1991–4. Treatment groups were defined by start and duration of zidovudine treatment, the drugs used most often during this period were: (a) no zidovudine, (b) zidovudine before AIDS, (c) zidovudine before and after AIDS, and (d) zidovudine used in AIDS. Main outcome measures were cumulative incidence and survival from AIDS to onset of HIV dementia, progressive multifocal leukoencephalopathy (PML), cerebral toxoplasmosis, and primary CNS lymphoma. RESULTS Risk of brain disease including HIV dementia and opportunistic brain disease was reduced in patients who started zidovudine before AIDS and continued in AIDS (relative risk (RR) 0.55, 95% confidence interval (95% CI) 0.36–0.84) as well as zidovudine initiated in AIDS (RR 0.27, 95% CI 0.17–0.45) compared with untreated subjects. Treatment effects were not constant over time, decreasing by 14%–32% for each six months of follow up. This was supported by unadjusted incidences across groups stratified by duration of zidovudine use, indicating reduced risk with treatment for up to 18 months but not with longer duration of use of zidovudine. Other antiretroviral drugs had no significant effect, although these were used by only 14% of patients in this cohort. CONCLUSION The time limited but effective neuroprotection offered by zidovudine monotherapy for <18 months suggests that non-specific mechanisms of cerebral immunological defence may benefit from antiretroviral treatment. Due to the limitations of a retrospective study these findings require confirmation and further investigation in the context of current combination drug treatments.
Coffee consumption, serum gamma-glutamyltransferase and risk of type II diabetes.

OBJECTIVES To study the joint association of coffee consumption and serum gamma-glutamyltransferase (GGT) levels on the risk of developing type II diabetes. DESIGN, SETTING AND SUBJECTS A total of 21,826 Finnish men and women who were 35-74 years of age and without any history of diabetes at baseline (years 1982, 1987, 1992 and 1997) were included in the present analyses. They were prospectively followed up for onset of type II diabetes (n=862 cases), death or until the end of the year 2002. Coffee consumption, serum GGT and other study parameters were determined at baseline using standardized measurements. Analyses were stratified by the serum GGT level classified into two classes using the 75th sex-specific percentiles as the cut point. RESULTS Coffee consumption was significantly and inversely associated with incident diabetes among both men and women. Serum GGT modified the association between coffee consumption and incident diabetes. Subjects in the high category of coffee consumption with the GGT level > or = 75th percentile showed a significant inverse association for women, and for both sexes combined. The association was not significant in subjects with the GGT level < or = 75th percentile. There was a significant interaction effect of GGT and coffee consumption on risk of type II diabetes in data of women (P=0.05) and in both sexes combined (P=0.02). CONCLUSIONS Habitual coffee consumption is associated with lower incidence of type II diabetes particularly in those with higher baseline serum GGT levels.
Study of operated patients of lateral internal anal sphincterotomy for chronic anal fissure.

INTRODUCTION Anal fissure causes significant morbidity in the population. It is proposed that elevated sphincter pressures may cause ischaemia of the anal lining and this may be responsible for the pain of anal fissures and their failure to heal. When pharmacologic therapy fails or fissures recur frequently, lateral internal sphincterotomy is the surgical treatment of choice. MATERIAL AND METHODS Retrospective analysis was done of admitted and operated patients of anal fissure by lateral anal internal sphincterotomy either by open or closed technique between April 2010 and November 2011 in Gujarat Medical Education & Research Society Medical College, Sola, Ahmedabad, India. The follow-up data of all patients was evaluated for pain relief, recurrence, wound infection, incontinence to flatus or stool or both for a period of up to 6 months. RESULTS Wound infection rate was 10.3% in open method and 4.2% in closed method. Incontinence to flatus was 8.3% in closed method and 3.4% in open method. This was temporary and controlled within a 1 week. Incontinence to stool was 3.4% in open method which was temporary and controlled within 2 weeks while none in closed method. None of the patients in either group had come with recurrence within 6 months follow-up. CONCLUSION Lateral anal internal sphincterotomy is safe regarding long term incontinence and effective regarding recurrence.
Food , drug , insect sting allergy , and anaphylaxis Stimulation of human T cells with sulfonamides and sulfonamide metabolites

Background: Exposure to sulfonamides is associated with a high incidence of hypersensitivity reactions. Antigen-specific T cells are involved in the pathogenesis; however, the nature of the antigen interacting with specific T-cell receptors is not fully defined. Objective: We sought to explore the frequency of sulfamethoxazole (SMX)– and SMX metabolite–specific T cells in hypersensitive patients, delineate the specificity of clones, define mechanisms of presentation, and explore additional reactivity with structurally related sulfonamide metabolites. Methods: SMXand SMX metabolite–specific T-cell clones were generated from 3 patients. Antigen specificity, mechanisms of antigen presentation, and cross-reactivity of specific clones were then explored. Low-lying energy conformations of drugs (metabolites) were modeled, and the energies available for protein binding was estimated. Results: Lymphocytes proliferated with parent drugs (SMX, sulfadiazine, and sulfapyridine) and both hydroxylamine and nitroso metabolites. Three patterns of drug (metabolite) stimulation were seen: 44% were SMX metabolite specific, 43% were stimulated with SMX metabolites and SMX, and 14% were stimulated with SMX alone. Most metabolite-responsive T cells were stimulated with nitroso SMX–modified protein through a hapten mechanism involving processing. In contrast to SMXresponsive clones, which were highly specific, greater than 50% of nitroso SMX–specific clones were stimulated with nitroso metabolites of sulfapyridine and sulfadiazine but not nitrosobenzene. Pharmacophore modeling showed that the summation of available binding energies for protein interactions
The structure of augmenter of liver regeneration crystallized in the presence of 50 mM CdCl2 reveals a novel Cd2Cl4O6 cluster that aids in crystal packing.

The crystal structure of the protein augmenter of liver regeneration containing a 14-residue hexahistidine purification tag (hsALR) has been determined to 2.4 Å resolution by Cd-SAD using a highly redundant data set collected on a rotating-anode home X-ray source and processed in 1998. The hsALR crystal structure is a tetramer composed of two homodimers bridged by a novel Cd(2)Cl(4)O(6) cluster via binding to the side-chain carboxylate groups of two solvent-exposed aspartic acid residues. A comparison with the native sALR tetramer shows that the cluster dramatically changes the hsALR dimer-dimer interface, which can now better accommodate the extra 14 N-terminal residues associated with the purification tag. The refined 2.4 Å resolution structure is in good agreement with both the X-ray data (R(cryst) of 0.165, R(free) of 0.211) and the expected stereochemistry (r.m.s. deviations from ideality for bond lengths and bond angles of 0.007 Å and 1.15°, respectively).
Extinction of LINE-1 activity coincident with a major mammalian radiation in rodents

LINE-1 transposable elements (L1s) are ubiquitous in mammals and are thought to have remained active since before the mammalian radiation. Only one L1 extinction event, in South American rodents in the genus Oryzomys, has been convincingly demonstrated. Here we examine the phylogenetic limits and evolutionary tempo of that extinction event by characterizing L1s in related rodents. Fourteen genera from five tribes within the Sigmodontinae subfamily were examined. Only the Sigmodontini, the most basal tribe in this group, demonstrate recent L1 activity. The Oryzomyini, Akodontini, Phyllotini, and Thomasomyini contain only L1s that appear to have inserted long ago; their L1s lack open reading frames, have mutations at conserved amino acid residues, and show numerous private mutations. They also lack restriction site-defined L1 subfamilies specific to any species, genus or tribe examined, and fail to form monophyletic species, genus or tribal L1 clusters. We determine here that this L1 extinction event occurred roughly 8.8 million years ago, near the divergence of Sigmodon from the remaining Sigmodontinae species. These species appear to be ideal model organisms for studying the impact of L1 inactivity on mammalian genomes.
Adjunctive brivaracetam for refractory partial-onset seizures

Objective: To explore efficacy and safety/tolerability of adjunctive brivaracetam (BRV), a novel, high-affinity synaptic vesicle protein 2A ligand, which also inhibits neuronal voltage-dependent sodium channels, in patients with refractory partial-onset seizures (POS). Methods: This was an exploratory, phase IIb, double-blind, randomized, parallel-group, placebo-controlled, dose-ranging study in patients 16–65 years with epilepsy experiencing ≥4 POS during 4-week baseline despite 1–2 concomitant antiepileptic drugs. Patients were randomized (1:1:1:1) to placebo, BRV 5 mg/day (BRV5), BRV 20 mg/day (BRV20), or BRV 50 mg/day (BRV50), administered BID without uptitration during a 7-week treatment period. Primary efficacy endpoint was POS frequency/week during the treatment period relative to placebo. Results: A total of 208 patients constituted the intention-to-treat population; 197 completed the study. Estimated percentage reductions over placebo in POS frequency/week were 9.8% (BRV5; p = 0.240), 14.9% (BRV20; p = 0.062), and 22.1% (BRV50; p = 0.004). Median percent reductions from baseline in POS frequency/week were 21.7% (placebo), 29.9% (BRV5; p = 0.086), 42.6% (BRV20; p = 0.014), and 53.1% (BRV50; p < 0.001); ≥50% responder rates were 16.7% (placebo), 32.0% (BRV5; p = 0.047), 44.2% (BRV20; p = 0.002), and 55.8% (BRV50; p < 0.001); seizure freedom rates (POS) during the 7-week treatment period were 1.9% (placebo), 8.0% (BRV5; p = 0.193), 7.7% (BRV20; p = 0.193), and 7.7% (BRV50; p = 0.201). BRV was well-tolerated. Most adverse events were mild to moderate and occurred with similar incidence in placebo and BRV groups, and discontinuations due to treatment-emergent adverse events were infrequent (placebo 3.7%; BRV 2.6%). Conclusions: This interventional study provides preliminary Class I evidence that adjunctive BRV was efficacious and well-tolerated in patients aged 16–65 years with POS.
Naming skills of children born preterm in comparison with their term peers at the ages of 9 and 16 years

The linguistic abilities of children born preterm at 32 weeks' gestation or earlier at Kuopio University Hospital during 1984 to 1986 were evaluated during successive phases of a prospective study. The study protocol included the Rapid Automatic Naming test and Wechsler Intelligence Scale for Children ‐ Revised at 9 years of age and a modified Stroop Color‐Word test and the Wechsler Intelligence Scale ‐ Revised at the age of 16 years. Fifty‐one children born preterm (26 males, 25 females) and 51 age‐matched and sex‐matched term controls (26 males, 25 females) were studied at the age of 9 years. At the age of 16 years, 40 children born preterm (19 males, 21 females) and 31 term controls (14 males, 17 females) participated in the study. The children born preterm scored significantly lower in two naming tasks than the controls at the age of 9 years. However, there was no difference between the study groups in naming skills at the age of 16 years or in verbal IQ in either study phase. Maternal education level was not associated with naming skills. Thus, the consequences of preterm birth seem to be minor in relation to linguistic skills during school age and diminish by adolescence.
Transformer les quartiers défavorisés. Les enjeux des politiques publiques zonées

This paper examines urban public policies for deprived areas in the light of urban economics theories and their lessons for the socio-economic organization of cities. While improving living conditions is indeed a factor in enhancing the socio-economic standing of urban neighbourhoods, the process operates by attracting wealthier new inhabitants and driving out the existing poorer ones. We emphasize that urban economics struggles to demonstrate the emergence of stable mixed urban patterns. Either such patterns must be considered as transitional stages between two states of equilibrium in terms of segregation or attempts must be made to establish sustainable positive social interaction between privileged and deprived households within neighbourhoods. Lastly, public action to promote urban regeneration, although subject to criteria of equity, enhances neighbourhood property values and may seek out leverage effects from private actors. The final question seems to be that of city-wide transformation : it is pointless reasoning on the scale of deprived neighbourhoods as if they were isolated. Geographical ? lock-in? causes friction that detracts from the success of area-specific policies. And conversely, social opening-up is not geographically neutral because policies can only transform the geography of urban segregation. Classification JEL : H31, R2, R31, R38, R58.
Semi-parametric Bayesian tail risk forecasting incorporating realized measures of volatility

Realized measures employing intra-day sources of data have proven effective for dynamic volatility and tail-risk estimation and forecasting. Expected shortfall (ES) is a tail risk measure, now recommended by the Basel Committee, involving a conditional expectation that can be semi-parametrically estimated via an asymmetric sum of squares function. The conditional autoregressive expectile class of model, used to implicitly model ES, has been extended to allow the intra-day range, not just the daily return, as an input. This model class is here further extended to incorporate information on realized measures of volatility, including realized variance and realized range (RR), as well as scaled and smoothed versions of these. An asymmetric Gaussian density error formulation allows a likelihood that leads to direct estimation and one-step-ahead forecasts of quantiles and expectiles, and subsequently of ES. A Bayesian adaptive Markov chain Monte Carlo method is developed and employed for estimation and forecasting. In an empirical study forecasting daily tail risk measures in six financial market return series, over a seven-year period, models employing the RR generate the most accurate tail risk forecasts, compared to models employing other realized measures as well as to a range of well-known competitors.
The Impact of the Banking Competition in Funding and Lending Markets on Lending Technology

During the last decades, banks have expanded the use of credit scoring technology to grant loan, challenging traditional relationship lending. I investigate the relationship between banking competition and technological change in lending, and its implications for efficiency. I consider a double Bertrand competition model, where banks compete both in one funding market and in two heterogeneous loan markets, and analyze the competition between banks employing different lending technologies. I show that competition may lead to inefficiency. This happens when a bank overbids in the funding market to enjoy monopoly power in all loan markets, and one of the markets is served by less efficient technology.
Demonstration of short-channel self-aligned Pt/sub 2/Si-FUSI pMOSFETs with low threshold voltage (-0.29 V) on SiON and HfSiON

Short gate-length Pt full-silicidation (FUSI) (PtSi and Pt2 Si) pMOSFETs were fabricated for the first time using a self-aligned Pt-FUSI process, demonstrating scalability (with no linewidth effects) down to ~ 60-nm gate lengths. The electrical results are compared to the Ni-FUSI (NiSi and Ni31Si12) pMOSFET devices. A low threshold voltage les|-0.29 V| was obtained for the Pt2Si-FUSI pMOSFETs on SiON and HfSiON indicating that the Pt2Si FUSI does not suffer from the Fermi-level pinning or gate-dielectric-charge effects on the HfSiON
Immunoglobulin light chains in uremia.

BACKGROUND Immunoglobulin light chains (IgLCs) are produced by B cells, slightly in excess of immunoglobulin heavy chains, and therefore are present in the serum of healthy adults in free form at low concentrations. Both the kappa and lambda form of these polyclonal IgLCs are mainly metabolized by the kidney and appear under normal conditions only in small amounts in the urine. In patients with a reduced or abolished kidney function, IgLC levels are increased. When overproduced in B cell lymphoproliferative disorders and deposited in the kidney, IgLCs can be, by themselves, a causative factor of renal diseases and the development of uremia. METHODS We compared the effect of treatment with different low- and high-flux membranes on IgLC concentrations. The effect of free IgLCs on neutrophils, cells of the first-line unspecific immune defense, was assessed in in vitro experiments. RESULTS We found that IgLC levels in hemodialysis and hemodiafiltration patients were higher than in pre-dialysis patients and that IgLC levels could not be brought into the normal range by currently available hemodialysis or hemodiafiltration treatments. IgLCs interfere with chemotaxis and the activation of glucose uptake, two essential neutrophil functions, and attenuate neutrophil apoptosis, the coordinated cell death that is crucial for the normal resolution of inflammation without tissue destruction. CONCLUSION IgLCs occurring at increased levels in sera of patients with kidney failure modulate essential functions and the apoptotic cell death of neutrophils, and as a consequence contribute to the increased susceptibility to bacterial infections in uremic patients.
Demographic consequences of increased winter births in a large aseasonally breeding mammal (Bos taurus) in response to climate change.

1. Studies examining changes in the scheduling of breeding in response to climate change have focused on species with well-defined breeding seasons. Species exhibiting year-round breeding have received little attention and the magnitudes of any responses are unknown. 2. We investigated phenological data for an enclosed feral population of cattle (Bos taurus L.) in northern England exhibiting year-round breeding. This population is relatively free of human interference. 3. We assessed whether the timing of births had changed over the last 60 years, in response to increasing winter and spring temperatures, changes in herd density, and a regime of lime fertilisation. 4. Median birth date became earlier by 1·0 days per year. Analyses of the seasonal distribution of calving dates showed that significantly fewer calves were born in summer (decline from 44% of total births to 20%) and significantly more in winter (increase from 12% to 30%) over the study period. The most pronounced changes occurred in winter, with significant increases in both the proportion and number of births. Winter births arise from conceptions in the previous spring, and we considered models that investigated climate and weather variables associated with the winter preceding and the spring of conceptions. 5. The proportion of winter births was higher when the onset of the plant growing season was earlier during the spring of conceptions. This relationship was much weaker during years when the site had been fertilised with lime, suggesting that increased forage biomass was over-riding the impacts of changing plant phenology. When the onset of the growing season was late, winter births increased with female density. 6. Recruitment estimates from a stage-structured state-space population model were significantly negatively correlated with the proportion of births in the preceding winter, suggesting that calves born in winter are less likely to survive than those born in other seasons. 7. This is one of the first studies to document changes in the phenology of a year-round breeder, suggesting that the impact of climate on the scheduling of biological events may be more extensive than previously thought and that impacts may be negative, even for species with relatively flexible breeding strategies.
Estradiol Promotes M1-like Macrophage Activation through Cadherin-11 To Aggravate Temporomandibular Joint Inflammation in Rats

Macrophages play a major role in joint inflammation. Estrogen is involved in rheumatoid arthritis and temporomandibular disorders. However, the underlying mechanism is still unclear. This study was done to verify and test how estrogen affects M1/M2-like macrophage polarization and then contributes to joint inflammation. Female rats were ovariectomized and treated with increasing doses of 17β-estradiol for 10 d and then intra-articularly injected with CFA to induce temporomandibular joint (TMJ) inflammation. The polarization of macrophages and expression of cadherin-11 was evaluated at 24 h after the induction of TMJ inflammation and after blocking cadherin-11 or estrogen receptors. NR8383 macrophages were treated with estradiol and TNF-α, with or without blocking cadherin-11 or estrogen receptors, to evaluate the expression of the M1/M2-like macrophage-associated genes. We found that estradiol increased the infiltration of macrophages with a proinflammatory M1-like predominant profile in the synovium of inflamed TMJ. In addition, estradiol dose-dependently upregulated the expressions of the M1-associated proinflammatory factor inducible NO synthase (iNOS) but repressed the expressions of the M2-associated genes IL-10 and arginase in NR8383 macrophages. Furthermore, estradiol mainly promoted cadherin-11 expression in M1-like macrophages of inflamed TMJ. By contrast, blockage of cadherin-11 concurrently reversed estradiol-potentiated M1-like macrophage activation and TMJ inflammation, as well as reversed TNF-α–induced induction of inducible NO synthase and NO in NR8383 macrophages. The blocking of estrogen receptors reversed estradiol-potentiated M1-like macrophage activation and cadherin-11 expression. These results suggested that estradiol could promote M1-like macrophage activation through cadherin-11 to aggravate the acute inflammation of TMJs.