Miracle-dz/UniFAR-FTUs huggingface dataset:
Risk factors for bronchiolitis obliterans in allogeneic hematopoietic stem-cell transplantation for leukemia.

STUDY OBJECTIVES Reported risk factors for bronchiolitis obliterans (BO) in allogeneic hematopoietic stem-cell transplant recipients come from modest-sized studies and are limited to experiences of single institutions. We sought to identify risk factors for BO using data from the International Bone Marrow Transplant Registry. METHODS Registry data on 6,275 adult patients with leukemia who received human leukocyte antigen-identical sibling transplants from 1989 to 1997 and survived at least 100 days after transplantation were evaluated for the study. Risk factors for BO were analyzed using proportional hazards regression. RESULTS Seventy-six patients were found to have BO, with an incidence rate of 1.7% at 2 years after transplantation. The Kaplan-Meier estimate of median time to onset of BO was 431 days. Histologic evaluation was performed in 36 patients (47%). In 28 patients (37%), diagnosis was based on pulmonary function tests, CT scans of the chest, or a combination of both. On multivariate analysis, the factors that were associated with an increased risk for BO included the following: peripheral blood-derived stem cell, a busulfan-based conditioning regimen, interval from diagnosis to transplant > or = 14 months, female donor to male recipient sex match, prior interstitial pneumonitis, and an episode of moderate-to-severe acute graft-vs-host disease (GVHD). CONCLUSION In addition to corroborating previously reported risk factors, such as acute GVHD and a busulfan-based conditioning regimen, we found that peripheral blood stem-cell transplantation, long duration to transplant, female donor to male recipient, and a prior episode of interstitial pneumonitis are associated with an increased risk for BO.
Combining ability of biological yield and harvest index in diallel cross of wheat cultivars under drought and non-drought stress conditions.

Summary In order to determine the mode of inheritance, genes action, general and specifi c combining abilities and eff ect of various environmental conditions on genetic parameters of harvest index and biological yield in bread wheat, diallel crosses design with eight parents was used. Parents and F1 progenies were sown in a randomized complete block design with three replications under drought stress and non-stress conditions in experimental fi eld of Shahrekord Agricultural Research Center during 2011-2013 growing season. Th e data were analyzed according to method of Hallauer and Miranda as well as fi xed model of Griffi ng’s method II. Jinks-Hayman model was used to estimate broad and narrow-sense heritabilities and mean degree of dominance. Th ere were signifi cant diff erences between genotypes for mentioned traits in both conditions. Studying mean square of general combining ability (GCA) and specifi c combining ability (SCA), the ratio of GCA to SCA mean square and portion of additive and dominance variances showed importance of both additive and nonadditive genes eff ects for harvest index in both conditions, but in biological yield heredity, additive eff ect was more important. Estimating broad-sense and narrowsense heritabilities showed low effi ciency of harvest index and high effi ciency of biological yield for selection programs in both conditions.
Spontaneous remission of proteinuria is a frequent event in phospholipase A2 receptor antibody-negative patients with membranous nephropathy.

BACKGROUND Phospholipase A2 receptor antibodies (PLA2R-Ab) and thrombospondin type-1 domain-containing 7A antibodies (THSD7A-Ab) are present in 70-80% of patients with membranous nephropathy (MN). Little, however, is known about the pathogenesis of MN and the clinical outcome in PLA2R-Ab- and THSD7A-Ab-negative patients. METHODS In this prospective multicentre observational study, the clinical outcome of 37 patients with biopsy-proven MN who were negative for PLA2R-Ab and THSD7A-Ab in the serum was analysed. RESULTS A total of 198 patients were screened for inclusion in the study. Of these, 157 patients were positive for PLA2R-Ab and 4 patients for THSD7A-Ab. The remaining 37 patients were negative for both antibodies were and included in this study. Six patients died during the follow-up, five because of malignant diseases and one of an infection. One patient went into end-stage renal disease, and two patients were lost to follow-up. The remaining 28 patients were followed for at least 24 months (35.6 ± 8.9 months). Seventeen patients received immunosuppressive (IS) therapy, and 11 received supportive care only. At the end of the follow-up, 14 of the 17 patients treated with immunosuppressants and 10 of 11 patients on supportive therapy had a remission of proteinuria. The time to reach remission of proteinuria and serum creatinine levels at the end of the follow-up were not different between both groups. A univariate Cox regression analysis indicated that the use of immunosuppression did not alter the chance to reach a remission of proteinuria. CONCLUSIONS A high number of PLA2R-Ab- and THSD7A-Ab-negative patients with MN have a good prognosis and might not need IS therapy.
Short-course chemotherapy with TMC207 and rifapentine in a murine model of latent tuberculosis infection.

RATIONALE Multidrug-resistant and extensively drug-resistant tuberculosis (MDR/XDR-TB) is an emerging global health threat. Proper management of close contacts of infectious patients is increasingly important. However, no evidence-based recommendations for treating latent TB infection (LTBI) after MDR/XDR-TB exposure (DR-LTBI) exist. An ultrashort regimen for LTBI caused by drug-susceptible strains (DS-LTBI) is also desirable. TMC207 has bactericidal and sterilizing activity in animal models of TB and improves the activity of current MDR-TB therapy in patients. OBJECTIVES The objective of this study was to determine whether TMC207 might enable short-course treatment of DR-LTBI and ultrashort treatment of DS-LTBI. METHODS Using an established experimental model of LTBI chemotherapy in which mice are aerosol-immunized with a recombinant bacillus Calmette-Guérin vaccine before low-dose aerosol infection with Mycobacterium tuberculosis, the efficacy of TMC207 alone and in combination with rifapentine was compared with currently recommended control regimens as well as once-weekly rifapentine + isoniazid and daily rifapentine ± isoniazid. MEASUREMENTS Outcomes included monthly lung colony-forming unit counts and relapse rates. MAIN RESULTS Lung colony-forming unit counts were stable at about 3.75 log(10) for up to 7.5 months postinfection in untreated mice. Rifamycin-containing regimens were superior to isoniazid monotherapy. TMC207 exhibited sterilizing activity at least as strong as that of rifampin alone and similar to that of rifampin + isoniazid, but daily rifapentine +/- isoniazid was superior to TMC207. Addition of TMC207 to rifapentine did not improve the sterilizing activity of rifapentine in this model. CONCLUSIONS TMC207 has substantial sterilizing activity and may enable treatment of DR-LTBI in 3-4 months.
Wavelength dependence of oxidative DNA damage induced by UV and visible light.

DNA damage induced by UV radiation and visible light (290-500 nm) in AS52 Chinese hamster cells was analysed by an alkaline elution assay with specific repair endonucleases. Cells were exposed to extensively filtered monochrome or broad-band radiation. Between 290 and 315 nm, the ratio of base modifications sensitive to Fpg protein (i.e. 8-hydroxyguanine and formamidopyrimidines) and T4 endonuclease V (i.e. cyclobutane pyrimidine dimers) was constant (approximately 1:200), indicating that the direct excitation of DNA is responsible for both types of damage in this range of the spectrum. While the yield of pyrimidine dimers per unit dose continued to decrease exponentially beyond 315 nm, the yield of Fpg-sensitive modifications increased to a second maximum between 400 and 450 nm. The damage spectrum in this wavelength range consisted of only a few other modifications (strand breaks, abasic sites and pyrimidine modifications sensitive to endonuclease III) and is attributed to endogenous photosensitizers that give rise to oxidative DNA damage via singlet oxygen and/or type I reactions. The generation of Fpg-sensitive modifications by visible light was not linear with dose but followed a saturation curve. It is calculated that the exposure of the cells to low doses of solar radiation results in the formation of cyclobutane pyrimidine dimers and Fpg-sensitive modifications in a ratio of 10:1.
Protein interactome mining defines melatonin MT1 receptors as integral component of presynaptic protein complexes of neurons

In mammals, the hormone melatonin is mainly produced by the pineal gland with nocturnal peak levels. Its peripheral and central actions rely either on its intrinsic antioxidant properties or on binding to melatonin MT1 and MT2 receptors, belonging to the G protein‐coupled receptor (GPCR) super‐family. Melatonin has been reported to be involved in many functions of the central nervous system such as circadian rhythm regulation, neurotransmission, synaptic plasticity, memory, sleep, and also in Alzheimer's disease and depression. However, little is known about the subcellular localization of melatonin receptors and the molecular aspects involved in neuronal functions of melatonin. Identification of protein complexes associated with GPCRs has been shown to be a valid approach to improve our understanding of their function. By combining proteomic and genomic approaches we built an interactome of MT1 and MT2 receptors, which comprises 378 individual proteins. Among the proteins interacting with MT1, but not with MT2, we identified several presynaptic proteins, suggesting a potential role of MT1 in neurotransmission. Presynaptic localization of MT1 receptors in the hypothalamus, striatum, and cortex was confirmed by subcellular fractionation experiments and immunofluorescence microscopy. MT1 physically interacts with the voltage‐gated calcium channel Cav2.2 and inhibits Cav2.2‐promoted Ca2+ entry in an agonist‐independent manner. In conclusion, we show that MT1 is part of the presynaptic protein network and negatively regulates Cav2.2 activity, providing a first hint for potential synaptic functions of MT1.
A Summary Analysis of Police Deaths in Australia: Implications for Prevention

This paper summarises the dimensions and immediate causes of officer deaths on‐duty in Australia from the establishment of police forces in the nineteenth century to 2007. Official police records were used to identify the year and the immediate circumstances of deaths. The results strongly support an emerging international knowledge base about police deaths: that up to three‐quarters are ‘'accidental'’ and as few as one‐quarter are the result of an attack by an offender; that the very large majority of accidents involve motor vehicles; that as a result of improvements in procedures and technology, in the post World War Two period, officer fatalities have been declining as a proportion of police numbers; and, that further reductions are obtainable through stricter application of a wider range of prevention strategies. The paper concludes by mapping out some key strategies, including curtailing speeding in police vehicles; keeping police off the road at vehicle stops and roadblocks; and, better risk management procedures in raids, sieges, arrests, and the serving of warrants.
A Low-Latency and High-Power-Efficient On-Chip LVDS Transmission Line Interconnect for an RC Interconnect Alternative

This paper demonstrates a low voltage differential signaling (LVDS)-type on-chip transmission line (TL) interconnect to solve delay issues on a global interconnect. The proposed TL interconnect can achieve 10 Gbps signaling with 2.7 mW power consumption. The on-chip LVDS TL interconnect has the best power efficiency for on-chip interconnects at over 1 mm. Delay variation of the TL interconnect is 89 % smaller than that of the conventional RC interconnect.
Lamina‐specific distribution of synaptopodin, an actin‐associated molecule essential for the spine apparatus, in identified principal cell dendrites of the mouse hippocampus

Synaptopodin is an actin‐associated molecule found in a subset of telencephalic spines. It is an essential component of the spine apparatus, a Ca2+‐storing organelle and has been implicated in synaptic plasticity (Deller et al. [ 2003 ] Proc Natl Acad Sci U S A 100:10494–10499). In the rodent hippocampus, Synaptopodin is distributed in a characteristic region‐ and lamina‐specific manner. To learn more about the cellular basis underlying this distribution, the regional, laminar, and cellular localization of Synaptopodin and its mRNA were analyzed in mouse hippocampus. First, Synaptopodin puncta densities were quantified after immunofluorescent labeling using confocal microscopy. Second, the dendritic distribution of Synaptopodin‐positive puncta was studied using three‐dimensional confocal reconstructions of Synaptopodin‐immunostained and enhanced green fluorescence protein (EGFP)‐labeled principal neurons. Synaptopodin puncta located within dendrites of principal neurons were primarily found in spines (>95%). Analysis of dendritic segments located in different layers revealed lamina‐specific differences in the percentage of Synaptopodin‐positive spines. Densities ranged between 37% (outer molecular layer) and 14% (stratum oriens; CA1). Finally, synaptopodin mRNA expression was studied using in situ hybridization, laser microdissection, and quantitative reverse transcriptase‐polymerase chain reaction. Expression levels were comparable between all regions. These data demonstrate a lamina‐specific distribution of Synaptopodin within dendritic segments of identified neurons. Within dendrites, the majority of Synaptopodin‐positive puncta were located in spines where they represent spine apparatuses. We conclude, that this organelle is distributed in a region‐ and layer‐specific manner in the mouse hippocampus and suggest that differences in the activity of afferent fiber systems could determine its distribution. J. Comp. Neurol. 487:227–239, 2005. © 2005 Wiley‐Liss, Inc.
Insulin-mediated Targeting of Phosphatidylinositol 3-Kinase to GLUT4-containing Vesicles (*)

Phosphatidylinositol (PI) 3-kinase is hypothesized to be a signaling element in the acute redistribution of intracellular GLUT4 glucose transporters to the plasma membrane in response to insulin. However, some receptors activate PI 3-kinase without causing GLUT4 translocation, suggesting specific cellular localization may be critical to this PI 3-kinase function. Consistent with this idea, complexes containing PI 3-kinase bound to insulin receptor substrate 1 (IRS-1) in 3T3-L1 adipocytes are associated with intracellular membranes (Heller-Harrison, R., Morin, M. and Czech, M. (1995) J. Biol. Chem. 270, 24442-24450). We report here that in response to insulin, activated complexes of IRS-1•PI 3-kinase can be immunoprecipitated with anti-IRS-1 antibody from detergent extracts of immunoadsorbed GLUT4-containing vesicles prepared from 3T3-L1 adipocytes. The targeting of PI 3-kinase to rat adipocyte GLUT4-containing vesicles using vesicles prepared by sucrose velocity gradient ultracentrifugation was also demonstrated. Insulin treatment caused a 2.3-fold increase in immunoreactive p85 protein in these GLUT4-containing vesicles while anti-p85 immunoprecipitates of PI 3-kinase activity in GLUT4-containing vesicle extracts increased to a similar extent. HPLC analysis of the GLUT4 vesicle-associated PI 3-kinase activity showed insulin-mediated increases in PI 3-P, PI 3,4-P, and PI 3,4,5-P when PI, PI 4-P, and PI 4,5-P were used as substrates. Our data demonstrate that insulin directs the association of PI 3-kinase with GLUT4-containing vesicles in 3T3-L1 and rat adipocytes, consistent with the hypothesis that PI 3-kinase is involved in the insulin-regulated movement of GLUT4 to the plasma membrane.
Results of a Zika Virus (ZIKV) Immunoglobulin M-Specific Diagnostic Assay Are Highly Correlated With Detection of Neutralizing Anti-ZIKV Antibodies in Neonates With Congenital Disease.

BACKGROUND Usually, immunoglobulin M (IgM) serologic analysis is not sufficiently specific to confirm Zika virus (ZIKV) infection. However, since IgM does not cross the placenta, it may be a good marker of infection in neonates. METHODS We tested blood from 42 mothers and neonates with microcephaly and collected cerebrospinal fluid (CSF) specimens from 30 neonates. Molecular assays were performed for detection of ZIKV, dengue virus, and chikungunya virus; IgM enzyme-linked immunosorbent assays and plaque-reduction neutralization tests (PRNTs) were performed to detect ZIKV and dengue virus. No control neonates without microcephaly were evaluated. RESULTS Among neonates, all 42 tested positive for ZIKV IgM: 38 of 42 serum specimens (90.5%) were positive, whereas 30 of 30 CSF specimens (100%) were positive. ZIKV IgM-specific ELISA ratios, calculated as the mean optical density (OD) of the test sample when reacted on viral antigen divided by the mean OD of the negative control when reacted with viral antigen, were higher in CSF specimens (median, 14.9 [range, 9.3-16.4]) than in serum (median, 8.9 [range, 2.1-20.6]; P = .0003). All ZIKV IgM-positive results among the neonates were confirmed by the detection of neutralizing antibodies. Mother/neonate pairs with primary ZIKV infection had neutralizing antibodies to ZIKV only, and mother/neonate pairs with ZIKV virus infection secondary to infection with another flavivirus had high titers of neutralizing antibodies to ZIKV. Among secondary infections, median titers in serum were 2072 (range, 232-12 980) for mothers and 2730 (range, 398-12 980) for neonates (P < .0001), and the median titer in CSF was 93 (range, 40-578) among neonates (P < .0001). CONCLUSIONS Among neonates, detection of ZIKV IgM in serum is confirmatory of congenital ZIKV infection, and detection of ZIKV IgM in CSF is confirmatory of neurologic infection. Therefore, we recommend testing for ZIKV IgM in neonates suspected of having congenital ZIKV infection and performance of PRNTs in equivocal cases.
Distinct kinetic binding propeties of N‐[3H]‐methylscopolamine afford differential labeling and localization of M1, M2, and M3 muscarinic receptor subtypes in primate brain

Three classes of muscarinic receptors in mammalian brain have been postulated on the basis of equilibrium and kinetic binding data. However, equilibrium binding assays alone have not permitted a clear demonstration of the localization of putative M1, M2, and M3 receptor subtypes in the brain because of the overlaping affinities of virtually all muscarinic antagonists. In the present study, the conditions for selective occupancy of the M1, M2, and M3 receptor subtypes in the brain of the rhesus monkey were based on the distinct kinetic and equilibrium binding properties of N‐[3H]‐methylscopolamine (NMS) at cloned m1–m4 muscarinic receptor subtypes expressed in A9L transfected cells. Quantitative autoradiography of the M1, M2, and M3 muscarinic receptor subtypes in the primate brain was performed according to the following strategy. The M1 (m1) receptor subtype was labeled directly with a non‐saturating concentration of [3H]‐pirenzepine. The M2 (m2) subtype was labeled by incubations consisting of short, two minute pulses of [3H]‐NMS after a preincubation with 0.3 μM pirenzepine to occlude m1, m3, and m4 sites. Selective occupancy of the M3 (m3) receptor (subtype) was achieved by pre‐incubation with 0.5 nM unlabeled NMS to partially occlude the m1, m2, and m4 sites, equilibrium with 0.5 nM [3H]‐NMS, followed by a 60 minute tracer dissociation in the presence of 1 μM atropine.
Iron status and cardiovascular risk factors in patients with haemodialysis versus patients with ischaemic heart disease

Aim: The study aimed to investigate whether imbalanced iron status in patients with haemodialysis coexisted with abnormal lipid profile, higher inflammatory status and altered growth hormone–insulin‐like growth factor (GH–IGF)‐I axis and to compare these biochemical markers with patients with ischaemic heart disease.
Agreement of invasive versus non‐invasive blood pressure in preterm neonates is not dependent on birth weight or gestational age

Purpose: Blood pressure constitutes an important parameter in the assessment of the cardiovascular status in preterm infants. Invasive arterial blood pressure (IBP) is considered the ‘gold‐standard’, but non‐invasive blood pressure (NIBP) is used frequently in preterm infants. The aim of this prospective study was to compare mean IBP and mean NIBP arterial blood pressure measurements in three subsets of preterm infants (>1500 g; 1000–1500 g, and <1000 g, and >31 weeks, 28–31 weeks, and <28 weeks of gestation).
A U5 small nuclear ribonucleoprotein particle protein involved only in the second step of pre-mRNA splicing in Saccharomyces cerevisiae

The PRP18 gene, which had been identified in a screen for pre-mRNA splicing mutants in Saccharomyces cerevisiae, has been cloned and sequenced. Yeast strains bearing only a disrupted copy of PRP18 are temperature sensitive for growth; even at a low temperature, they grow extremely slowly and do not splice pre-mRNA efficiently. This unusual temperature sensitivity can be reproduced in vitro; extracts immunodepleted of PRP18 are temperature sensitive for the second step of splicing. The PRP18 protein has been overexpressed in active form in Escherichia coli and has been purified to near homogeneity. Antibodies directed against PRP18 precipitate the U4/U5/U6 small nuclear ribonucleoprotein particle (snRNP) from yeast extracts. From extracts depleted of the U6 small nuclear RNA (snRNA), the U4 and U5 snRNAs can be immunoprecipitated, while no snRNAs can be precipitated from extracts depleted of the U5 snRNA. PRP18 therefore appears to be primarily associated with the U5 snRNP. The antibodies against PRP18 inhibit the second step of pre-mRNA splicing in vitro. Together, these results imply that the U5 snRNP plays a role in the second step of splicing and suggest a model for the action of PRP18.
Frequentist inference for WiFi fingerprinting 3D indoor positioning

Weighted k-Nearest Neighbors (WkNN) algorithms based on WiFi fingerprinting are a popular choice for 3D indoor position estimation. Performance of these schemes strongly depends however on the number of k Reference Points (RPs) used for the estimation. In this work a novel WiFi fingerprinting WkNN algorithm is proposed, that aims at improving position accuracy and robustness to variations of the value of k. The proposed algorithm relies on frequentist theory of inference combined with a measure of similarity given by the Pearson's correlation R statistical index. The algorithm uses the p-value probabilities as defined in frequentist inference to determine the relevance of each RP. The algorithm is compared with preexisting WkNN algorithms as well as with a WkNN algorithm relying on the R index, also defined in this work. Experimental results show that the proposed algorithm leads to higher positioning accuracy and higher robustness to sub-optimal selection of the value k.