Miracle-dz/UniFAR-FTUs huggingface dataset:
Anti-C1q antibodies and IgG subclass distribution in sera from Chinese patients with lupus nephritis.

UNLABELLED Objective. Anti-C1q antibodies are common in sera from patients with lupus nephritis (LN) and are associated with disease activity. The current study aimed to further investigate the prevalence of serum IgG anti-C1q antibody, its subclass distribution and their clinical and pathological association in patients with LN. METHODS Sera were collected from 150 patients with renal biopsy-proven LN, diagnosed from 2000 to 2006 in our hospital, 30 patients with systemic lupus erythematosus (SLE) without clinical evidence of renal involvement (non-renal SLE, NR-SLE) and 63 healthy donors. ELISA was used to detect serum IgG anti-C1q antibody and its subclass. Their clinical and pathological associations were further analysed. RESULTS The prevalence of IgG anti-C1q antibody in LN (84/150, 56%) was significantly higher than that in NR-SLE (6/30, 20%) and healthy controls (3/63, 4.8%) (P < 0.005, P < 0.001, respectively). The prevalence of anti-C1q antibody in patients with diffuse proliferative renal lesions (class IV) (59/82, 71.95%) was significantly higher than that in those with non-diffuse proliferative renal lesions (class II + III) (12/26, 46.15%, P = 0.016) and class V (13/42, 30.95%, P < 0.001). The prevalence of IgG2 (60/135, 44.44%) was significantly higher than that of IgG1 (37/135, 27.41%) and IgG3 (25/135, 18.52%) (P < 0.005, P < 0.001, respectively). IgG2 was associated with the occurrence of arthritis (P < 0.05), higher serum creatinine (P < 0.05) and lower serum C3 (P < 0.05). Of the 38 LN patients with sera both in active phase and in remission, 17 were anti-C1q antibody-positive in active phase and the antibody levels decreased in all and turned to negative in 9 (52.94%) in remission. Meanwhile, the ratio of turning negative of IgG1, IgG2 and IgG3 anti-C1q was 33%(2/6), 53.85% (7/13) and 100% (7/7), respectively. CONCLUSIONS Anti-C1q antibodies are prevalent in LN and are closely associated with diffuse proliferative lesions. IgG2 anti-C1q might be pathogenic and IgG3 anti-C1q might be a more specific biomarker for monitoring disease activity.
A soluble fumarate reductase in Trypanosoma brucei procyclic trypomastigotes.

The enzyme NADH-fumarate reductase associated with the membrane fraction of Trypanosoma brucei procyclic trypomastigotes, can be solubilized by more than 50% when increasing the ionic strength to the equivalent of 150 mM KCl. The apparent KMs for NADH (125 microM) and fumarate (50 microM) remain close to those previously reported for the membrane-bound form of this enzyme. Other electron acceptors (i.e. oxygen or cytochrome c) appear to accept electrons in the absence of fumarate (KM for cytochrome c = 50 microM). The drug L-092,201 (Merck, Sharp and Dohme Research Laboratories, Rahway, NJ), an inhibitor of the membrane-bound fumarate reductase, also blocked the solubilized enzyme. Given the relatively high ionic strength of the intracellular environment we propose that, in vivo, the enzyme fumarate reductase is in the mitochondrial matrix or in the soluble fraction of another intracellular compartment.
Which Neural Net Architectures Give Rise To Exploding and Vanishing Gradients?

We give a rigorous analysis of the statistical behavior of gradients in randomly initialized feed-forward networks with ReLU activations. Our results show that a fully connected depth $d$ ReLU net with hidden layer widths $n_j$ will have exploding and vanishing gradients if and only if $\sum_{j=1}^{d-1} 1/n_j$ is large. The point of view of this article is that whether a given neural net will have exploding/vanishing gradients is a function mainly of the architecture of the net, and hence can be tested at initialization. Our results imply that a fully connected network that produces manageable gradients at initialization must have many hidden layers that are about as wide as the network is deep. This work is related to the mean field theory approach to random neural nets. From this point of view, we give a rigorous computation of the $1/n_j$ corrections to the propagation of gradients at the so-called edge of chaos.
Microdose-Induced Drug–DNA Adducts as Biomarkers of Chemotherapy Resistance in Humans and Mice

We report progress on predicting tumor response to platinum-based chemotherapy with a novel mass spectrometry approach. Fourteen bladder cancer patients were administered one diagnostic microdose each of [14C]carboplatin (1% of the therapeutic dose). Carboplatin–DNA adducts were quantified by accelerator mass spectrometry in blood and tumor samples collected within 24 hours, and compared with subsequent chemotherapy response. Patients with the highest adduct levels were responders, but not all responders had high adduct levels. Four patient-derived bladder cancer xenograft mouse models were used to test the possibility that another drug in the regimen could cause a response. The mice were dosed with [14C]carboplatin or [14C]gemcitabine and the resulting drug–DNA adduct levels were compared with tumor response to chemotherapy. At least one of the drugs had to induce high drug–DNA adduct levels or create a synergistic increase in overall adducts to prompt a corresponding therapeutic response, demonstrating proof-of-principle for drug–DNA adducts as predictive biomarkers. Mol Cancer Ther; 16(2); 376–87. ©2016 AACR.
Mild Cognitive Impairment: An Operational Definition and Its Conversion Rate to Alzheimer’s Disease

Objective: Because of discrepant findings regarding the accuracy of mild cognitive impairment (MCI) in predicting Alzheimer’s disease (AD), further study of this construct and conversion rates is essential before use in clinical settings. We aimed to develop an operational definition of MCI consistent with criteria proposed by the Mayo Alzheimer’s Disease Center, and to examine its conversion rate to AD. Methods: Patients were identified from an inception cohort of patients with at least a 3-month history of memory problems, and referred to a 2-year university teaching hospital investigation by primary care physicians. We classified 161 nondemented patients at baseline using MCI criteria. Diagnostic workups were completed annually, and patients were classified as meeting criteria for AD or showing no evidence of dementia after 1 and 2 years. Results: Of 161 patients, 35% met MCI criteria at baseline. Conversion rates to AD were 41% after 1 year, and 64% after 2 years. Logistic regression analyses to examine predictive accuracy of MCI after 1 and 2 years, with age and education as covariates, were significant (p < 0.0001). After 1 year, MCI showed an optimal sensitivity of 91% and specificity of 79%, and after 2 years, these values were 88 and 83%, respectively. Conclusions: MCI is an accurate predictor of AD over 1 and 2 years in patients referred by their primary care physicians. Discrepancies in conversion rates may be due to the manner in which patients are recruited to studies as well as the use of different measures to operationalize the construct.
Detection of Coxsackie B Virus RNA sequences in whole blood samples from adult patients at the onset of type I diabetes mellitus

Enteroviruses may be linked to insulin‐dependent diabetes mellitus (IDDM). The prevalence of enteroviral (EV) infection at onset of adult IDDM was investigated by detection of specific EV sequences in peripheral blood using a reverse transcription and a seminested polymerase chain reaction (seminested RT‐PCR). EDTA‐treated whole blood samples taken from 12 newly diagnosed IDDM patients with ketosis or ketoacidosis were examined. The comparison groups were 12 adult patients suffering from metabolic decompensation in the course of IDDM, 12 adult patients with decompensated non‐IDDM, and 15 healthy adults without any presumed EV infection or metabolic disease. EV genome was detected in five of 12 (42%) newly diagnosed IDDM patients and in one of 12 (8%) patients in the course of IDDM. By contrast, none of the 12 non‐IDDM patients and none of the 15 healthy adults had EV sequences in whole blood. Subsequent sequencing of the EV PCR products from the six positive patients showed a significant homology with Coxsackie B3 or B4 viruses, and some common patterns were observed among the sequences. The present study demonstrates that Coxsackie B virus RNA sequences can be detected in peripheral blood from patients at the onset or in the course of IDDM and provides evidence for a role for enteroviruses in adult type I diabetes. J. Med. Virol. 52:121–127, 1997. © 1997 Wiley‐Liss, Inc.
A finely tuned strategy adopted by an egg parasitoid to exploit chemical traces from host adults

SUMMARY Scelionid egg parasitoids can obtain reliable information on the presence of host eggs by discriminating host gender on the basis of chemical footprints of their co-evolved hosts, with a strong preference for the footprint left by host females. Based on the concept of dietary specialization and infochemical use in natural enemies, it could be predicted that host gender discrimination in specialist species belonging to the genus Trissolcus is further tuned to specific cues from distinctive chemical traces left by host females as a consequence of copulation and/or oviposition. To test this hypothesis we used the system Murgantia histrionica – Trissolcus brochymenae. Our results showed that the females of the egg parasitoid search intensely on chemical traces left on the substrate by host females that had mated but had not yet laid host eggs compared with the chemical traces left by virgin or parous host females. This preference for mated females that had not yet laid host eggs was strictly related to the transfer of sperm and associated substances from males to females during copulation. The compounds that mediated the arrestment response of T. brochymenae females are part of the host cuticle, and those that play a role as gender-specific cues seemed to be present in the legs of the host adult. This result represents an interesting new piece of information regarding the exploitation of indirect host-related cues by egg parasitoids. It reveals the existence of a finely tuned strategy that allows the parasitoid to find newly laid host eggs, as chemical traces left by mated host females that have not yet laid eggs are strongly correlated with the moment of oviposition.
Prediction and prevention of stroke after transient ischemic attack in the short and long term

Over the last 5 years, a number of studies have shown the early risk of stroke following transient ischemic attack (TIA) to be of the order of 5–10% at 1 week and 10–20% at 3 months, considerably higher than previously estimated. Because these studies have been carried out in a variety of different clinical settings, their findings are likely to be generalizable. Various independent prognostic factors for this early risk of stroke have been identified and models, based on clinical features at presentation, have been derived and validated to predict risk of stroke within 7 and 90 days after TIA. At the same time, diffusion-weighted magnetic resonance imaging and carotid imaging provide prognostic information and are likely to refine risk prediction further, although no unified model combining clinical and imaging data currently exists. Uncertainty continues surrounding the most effective secondary prevention in the hyperacute phase after TIA, especially in the choice of antiplatelet agents, although clinical trials to address this question are ongoing. However, the need for carotid endarterectomy in patients with symptomatic carotid stenosis is well established. The risk of vascular disease in the medium term (1–5 years) following TIA has been more widely studied, and predictive models for this are available. Recent data on the long-term (10 years and beyond) vascular risk after TIA demonstrate ongoing mortality from both cerebrovascular and cardiovascular causes, highlighting the need for continued secondary prevention.
Inhibition of Lamin A/C Attenuates Osteoblast Differentiation and Enhances RANKL‐Dependent Osteoclastogenesis

Age‐related osteoporosis is characterized by low bone mass, poor bone quality, and impaired osteoblastogenesis. Recently, the Hutchinson‐Gilford progeria syndrome (HGPS), a disease of accelerated aging and premature osteoporosis, has been linked to mutations in the gene encoding for the nuclear lamina protein lamin A/C. Here, we tested the hypothesis that inhibition of lamin A/C in osteoblastic lineage cells impairs osteoblastogenesis and accelerates osteoclastogenesis. Lamin A/C was knocked‐down with small interfering (si)RNA molecules in human bone marrow stromal cells (BMSCs) differentiating toward osteoblasts. Lamin A/C knockdown led to an inhibition of osteoblast proliferation by 26% and impaired osteoblast differentiation by 48% based on the formation of mineralized matrix. In mature osteoblasts, expression levels of runx2 and osteocalcin mRNA were decreased by lamin A/C knockdown by 44% and 78%, respectively. Furthermore, protein analysis showed that osteoblasts with diminished levels of lamin A/C also secreted less osteocalcin and expressed a lower alkaline phosphatase activity (−50%). Lamin A/C inhibition increased RANKL mRNA and protein levels, whereas osteoprotegerin (OPG) expression was decreased, resulting in an increased RANKL/OPG ratio and an enhanced ability to support osteoclastogenesis, as reflected by a 34% increase of TRACP+ multinucleated cells. Our data indicate that lamin A/C is essential for proper osteoblastogenesis. Moreover, lack of lamin A/C favors an osteoclastogenic milieu and contributes to enhanced osteoclastogenesis.
Adenovirus-mediated gene transfer of human inducible nitric oxide synthase in porcine vein grafts inhibits intimal hyperplasia.

OBJECTIVE The aim of this study is to determine whether adenoviral inducible nitric oxide synthase (iNOS) gene transfer could inhibit intimal hyperplasia (IH) in porcine internal jugular veins interposed into the carotid artery circulation. METHODS Porcine internal jugular veins were transduced passively with 1 x 10(11) particles of an adenoviral vector carrying either the human iNOS (AdiNOS) or beta-galactosidase (AdlacZ) cDNA for 30 minutes and then interposed into the carotid artery circulation. Segments of each vein graft were maintained in an ex vivo organ culture to measure nitrite accumulation, a marker of nitric oxide synthesis. The grafts were analyzed immunohistochemically for the presence of neutrophils, macrophages, and leukocytes by staining for myeloperoxidase, ED1, and CD45, respectively, at 3 (n = 4) and 7 (n = 4) days. Morphometric analyses and cellular proliferation (Ki67 staining) were assessed at 3 (n = 4), 7 (n = 4), and 21 days (n = 8). RESULTS AdlacZ-treated vein grafts demonstrated high levels of beta-galactosidase expression at 3 days with a gradual decline thereafter. Nitrite production from AdiNOS-treated vein grafts was approximately fivefold greater than AdlacZ-treated grafts (P =.00001). AdiNOS or AdlacZ treatment was associated with minimal graft inflammation. Cellular proliferation rates were significantly reduced in AdiNOS-treated grafts as compared with controls at both 3 (41%, P =.000004) and 7 days (32%, P =.0001) after bypass. This early antiproliferative effect was most pronounced at the distal anastomosis (65%, P =.0005). The iNOS gene transfer reduced the intimal/medial area ratio in vein grafts at 7 (36%, P =.009) and 21 days (30%, P =.007) versus controls. This inhibition of IH was again more prominent in the distal segments of the grafts (P =.01). CONCLUSION Adenovirus-mediated iNOS gene transfer to porcine internal jugular vein grafts effectively reduced cellular proliferation and IH. Although iNOS gene transfer reduced IH throughout the entire vein graft, the most pronounced effect was measured at the distal anastomosis. These results suggest potential for iNOS-based genetic modification of vein grafts to prolong graft patency.
A practical approach for coherent signal surveillance and blind parameter assessment in asynchoronous DS-CDMA systems in multipath channel

A novel, robust and practical method for active user enumeration in asynchronous CDMA in multipath channel condition is proposed in this paper. Most of the previous works do not consider the fact that in practical case, user's signals with the help of receiver arrive asynchronously. The proposed method can be used practically in blind multi-user detection such as eavesdropping; moreover, the method is based on information theory criteria which outperform other methods. Minimum description length (MDL) has better performance than all other information criteria used in such scenarios. Unlike most of the pervious works, we do not exploit array antenna to gather necessary data of the users. However our proposed method needs a simple omnidirectional antenna which simplifies receiver's structure and reduces its costs. Also, this exploitation provides us the ability to use our proposed algorithm in coherent signal case. Similar to some other information criterion based methods, our method exploits the users' code length as an input which is not appropriate for blind active user enumeration. A novel Pseudo Noise (PN) code detection approach is also presented in this paper to tackle this problem. Presented numerical results confirm our claims and focus on efficiency of algorithm in detection and exact enumeration of active users in low SNRs and multipath environment.
Association between coronary atherosclerosis progression and in-stent neoatherosclerosis in patients with ST-elevation myocardial infarction at five-year follow-up.

AIMS The aim of the study was to investigate the association between in-stent neoatherosclerosis (NA) and atherosclerosis progression (AP) in non-culprit segments in patients with ST-elevation myocardial infarction at five years. METHODS AND RESULTS Sixty-two out of 169 consecutive patients included in the EXAMINATION study underwent optical coherence tomography (OCT) at five years. NA plaques were observed in 13 (21.0%), signal-rich bands (SRB) in 22 (35.5%) and AP in 11 (17.7%). NA plaques were more frequently observed in patients treated with two stents (53.8% vs. 20.4%; p=0.02). SRB were more frequently observed with longer stent length (29.8±11.6 vs. 22.5±9.1 mm; p<0.01), larger stent size (3.4±0.4 vs. 3.1±0.4 mm; p<0.01) and with bare metal stents (BMS) (68.2% vs. 40.0%; p=0.03). Patients with AP had higher levels of LDL-cholesterol (108.3±27.1 vs. 86.3±27.6 mg/dl; p=0.02). QCA of 744 non-culprit segments showed no association between NA plaques or SRB and reduction of lumen diameters. By multivariate analysis, NA plaques were associated with stent length; SRB were associated with stent length and BMS. AP was associated with mean LDL-cholesterol levels. CONCLUSIONS NA and SRB had no association with AP or with LDL-cholesterol. NA and SRB were associated with stent-related factors such as stent length and BMS. AP was associated with LDL-cholesterol levels.
Second dose of PGE2 vaginal insert versus Foley transcervical balloon for induction of labor after failure of cervical ripening with PGE2 vaginal insert

Abstract Purpose: To determine the success rate of induction of labor (IOL) using Foley transcervical balloon (FTB) versus prostaglandin E2 (PGE2) vaginal insert, following failure of cervical ripening with PGE2 vaginal insert. Materials and methods: A retrospective cohort study of all pregnant women admitted for IOL with either FTB or PGE2 vaginal insert. Either second dose of PGE2 vaginal insert or FTB was used as a second line treatment after failure (not giving birth in 24 h from insertion) of first PGE2 vaginal insert. Results: During the study period, 1162 women were admitted for IOL. Failure was reported in 322/852 (37.8%) in the FTB versus 162/310 (52.2%) in the PGE2 group (p < 0.001). Among 162 patients treated with PGE2 as first line who did not deliver after 24 h, 14 had spontaneous rupture of membranes, 15 underwent stripping and 42 were in still in active labor. The remainder were allocated to either second trial of PGE2 treatment (n = 58) or FTB (n = 33) with failure rate higher in the PGE2 group, not statistically significant (p = 0.23). Conclusion: IOL with FTB was not superior to PGE2 vaginal insert for IOL following failure of cervical ripening with PGE2 vaginal insert.
Organic solvent extraction as a versatile procedure to identify hydrophobic chloroplast membrane proteins

As a complementary approach to genome projects, proteomic analyses have been set up to identify new gene products. One of the major challenges in proteomics concerns membrane proteins, especially the minor ones. A procedure based on the differential extraction of membrane proteins in chloroform/methanol mixtures, was tested on the two different chloroplast membrane systems: envolope and thylakoid membranes. Combining the use of classical sodium dodecyl sulfate‐polyacrylamide gel electrophoresis (SDS‐PAGE) and mass spectrometry analyses, this procedure enabled identification of hydrophobic proteins. The propensity of hydrophobic proteins to partition in chloroform/methanol mixtures was directly correlated with the number of amino acid residues/number of putative transmembrane regions (Res/TM ratio). Regardless of the particular case of some lipid‐interacting proteins, chloroform/methanol extractions allowed enrichment of hydrophobic proteins and exclusion of hydrophilic proteins from both membrane systems, thus demonstrating the versatility of the procedure.
Assessment of Cotinine Reveals a Dose-Dependent Effect of Smoking Exposure on Long-term Outcomes After Renal Transplantation

Background Smoking is a risk factor for poor late outcomes in renal transplant recipients (RTR). Smoking exposure can be assessed by self-report and cotinine measurements. We investigated1 whether use of cotinine as a biomarker for smoking exposure can serve as an alternative for self-report and2 to compare associations of smoking exposure by self-report and cotinine with outcomes in RTR and assess dose dependency. Methods Renal transplant recipients were classified as never, former, light (⩽10 cigarettes/day), and heavy smokers (>10 cigarettes/day) according to self-report and analogous categories for urine and plasma cotinine. First, we assessed agreement of self-reported smoking exposure with smoking exposure according urine and plasma cotinine. Second, we compared the associations with graft failure and mortality. Results Of 603 RTR (age 51.5 ± 12.1 years, 55% men), 36.0% RTR were never, 42.3% former, 10.6% light, and 11.1% heavy smokers according to self-report. The majority (98.6%) of never smokers had nondetectable cotinine. However, 14 and 13 RTR reporting no active smoking had respective urine or plasma cotinine consistent with active smoking. Cotinine-based measurements were dose-dependently associated with mortality and graft failure. Conclusions Plasma and urine cotinine can serve as an alternative to self-report and were dose-dependently associated with poor late outcomes in RTR.