Miracle-dz/UniFAR-FTUs huggingface dataset:
Poor response to alprostadil ICI test is associated with arteriogenic erectile dysfunction and higher risk of major adverse cardiovascular events.

INTRODUCTION Intracavernous alprostadil injection (ICI) test has been considered useless in assessing the vascular status of subjects with erectile dysfunction (ED). AIM To analyze the clinical correlates of ICI test in patients with ED and to verify the value of this test in predicting major adverse cardiovascular events (MACE). METHODS A consecutive series of 2,396 men (mean age 55.9 ± 11.9 years) attending our outpatient clinic for sexual dysfunction was retrospectively studied. A subset of this sample (N = 1,687) was enrolled in a longitudinal study. MAIN OUTCOME MEASURES Several clinical, biochemical, and instrumental (penile color Doppler ultrasound; PCDU) factors were evaluated. All patients underwent an ICI test, and responses were recorded on a four-point scale ranging from 1 = no response to 4 = full erection. RESULTS Among the patients studied, 16.4%, 41.2%, 40.2% and 2.2% showed grade 4, 3, 2, and 1 ICI test response, respectively. After adjusting for confounders, subjects with grade 1 ICI test response showed reduced perceived sleep-related, masturbation-related, and sexual-related erections when compared with the rest of the sample. In addition, a worse response to ICI test was associated with a higher prevalence of hypogonadism-related symptoms and signs along with lower testosterone levels. The prevalence of both diabetes mellitus and metabolic syndrome was inversely related to ICI test response. Accordingly, dynamic and basal peak systolic velocity (PSV), as well as acceleration at PCDU, decreased as a function of ICI test response. In the longitudinal study, after adjusting for confounders, grade 1 response was independently associated with a higher incidence of MACE (hazard ratio = 2.745 [1.200-6.277]; P < 0.05). These data were confirmed even when only subjects with normal PSV (>25 cm/s) were considered. CONCLUSIONS Our results demonstrate that poor ICI test response is associated with several metabolic disturbances and higher incidence of MACE. We strongly recommend performing ICI test with alprostadil in all ED subjects.
Proinflammatory Cytokine Production in Liver Regeneration Is Myd88-Dependent, but Independent of Cd14, Tlr2, and Tlr41

TNF and IL-6 are considered to be important to the initiation or priming phase of liver regeneration. However, the signaling pathways that lead to the production of these cytokines after partial hepatectomy (PH) have not been identified. Enteric-derived LPS appears to be important to liver regeneration, possibly by stimulating proinflammatory cytokine production after surgery. To determine whether LPS signaling pathways are involved in the regulation of the proinflammatory cytokines TNF and IL-6 during the priming phase of liver regeneration, we performed PH on mice lacking the TLRs Tlr4 and Tlr2, the LPS coreceptor, Cd14, and Myd88, an adapter protein involved in most TLR and IL-1R pathways. In MyD88 knockout (KO) mice after PH, both liver Tnf mRNA and circulating IL-6 levels were severely depressed compared with heterozygous or wild-type mice. Activation of STAT-3 and three STAT-3 responsive genes, Socs3, Cd14, and serum amyloid A2 were also blocked. In contrast, Tlr4, Tlr2, and Cd14 KO mice showed no deficits in the production of IL-6. Surprisingly, none of these KO mice showed any delay in hepatocyte replication. These data indicate that the LPS receptor TLR4, as well as TLR2 and CD14, do not play roles in regulating cytokine production or DNA replication after PH. In contrast, MyD88-dependent pathways appear to be responsible for TNF, IL-6, and their downstream signaling pathways.
The losartan renal protection study — rationale, study design and baseline characteristics of RENAAL (Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan)

The RENAAL Study is a double-blind, placebo-controlled trial to evaluate the renal protective effects of losartan in Type 2 diabetic patients with nephropathy. The study has enrolled 1513 patients and is expected to continue for 3.5 years after the last patient has been entered. Eligible patients must have a urinary albumin:creatinine ratio of at least 300 mg/g and serum creatinine between 1.3 to 3.0 mg/dL. Eligible hypertensive or normotensive patients are randomised to receive either losartan or placebo, in addition to their existing antihypertensive therapy. Medications that block angiotensin production or action, are excluded. The primary endpoint is a composite of the time to first event of doubling of serum creatinine, end-stage renal disease, or death; secondary endpoints include cardiovascular events, progression of renal disease, and changes in proteinuria; tertiary endpoints include quality of life, healthcare resource utilisation, and amputations. Patients include Caucasians (48.6%), Blacks (15.2%), Asians (16.7%), and Hispanics (18.2%). Baseline urinary albumin:creatinine ratio and serum creatinine levels average 1867 mg/g and 1.9 mg/dL, respectively. Mean systolic and diastolic blood pressures are 153 and 82 mmHg, respectively. RENAAL will document whether blockade of the AII receptor with losartan produces clinical benefits in patients with Type 2 diabetes and nephropathy.
Site-directed mutagenesis of the alpha-toxin gene of Staphylococcus aureus: role of histidines in toxin activity in vitro and in a murine model

Staphylococcus aureus alpha-toxin is a membrane-damaging exoprotein that oligomerizes to form transmembrane pores. Chemical modification of histidines with diethylpyrocarbonate has been shown to reduce the hemolytic activity of alpha-toxin, suggesting that one or more of the histidine residues is important for toxin function. To individually assess the functional importance of each of the four histidine residues (residues 35, 48, 144, and 259), we used oligonucleotide-directed mutagenesis of the cloned alpha-toxin gene to replace each histidine with leucine. The mutant toxins were expressed in S. aureus and evaluated for hemolytic activity in vitro and for lethality in an intraperitoneal murine model. Substitution of histidine 35 with leucine produced a mutant toxin (H35L) without hemolytic or lethal activity. Mutant toxins H48L, H144L, and H259L exhibited 7, 16, and 46%, respectively, of the hemolytic activity of wild-type toxin. Immunoblotting of purified H35L toxin incubated with liposomal membranes demonstrated intact membrane binding and hexamer formation that was clearly detectable but reduced compared with that of the wild-type toxin. This suggests that hexamer formation alone is not sufficient for the expression of alpha-toxin activity. The nature of the defect underlying the lack of activity of the H35L mutant toxin remains to be elucidated but may involve failure of the hexamer to span the lipid bilayer to form a transmembrane pore or a change in the internal surface and permeability characteristics of the pore.
k-means-: A Unified Approach to Clustering and Outlier Detection

We present a unified approach for simultaneously clustering and discovering outliers in data. Our approach is formalized as a generalization of the k-means problem. We prove that the problem is NP-hard and then present a practical polynomial time algorithm, which is guaranteed to converge to a local optimum. Furthermore we extend our approach to all distance measures that can be expressed in the form of a Bregman divergence. Experiments on synthetic and real datasets demonstrate the effectiveness of our approach and the utility of carrying out both clustering and outlier detection in a concurrent manner. In particular on the famous KDD cup network-intrusion dataset, we were able to increase the precision of the outlier detection task by nearly 100% compared to the classical nearest-neighbor approach.
Guillain‐Barré syndrome: diagnostic criteria, epidemiology, clinical course and prognosis

ABSTRACT‐ Thirty‐four patients were identified with Guillain‐Barré syndrome (GBS) on review of 266 neuropathy cases admitted to a Copenhagen county hospital from June 1977 to January 1984. The age‐adjusted incidence rate of GBS is 2.0 × 10−5 years−1. The natural history of the disease, antecedent events, symptoms and signs, autonomic dysfunction, sequelae, CSF findings and mortality are described. Six cancer patients with GBS differed significantly from the non‐cancer patients in a more protracted disease course and failure to improve. The National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) criteria for the diagnosis of GBS are discussed, and it is concluded that the criteria, although useful in comparative studies, are too restrictive when used in clinical practice.
Quantifying burned area for North American forests: Implications for direct reduction of carbon stocks

[1] A synthesis was carried out to analyze information available to quantify fire activity and burned area across North America, including a comparison of different data sources and an assessment of how variations in burned area estimate impact carbon emissions from fires. Data sets maintained by fire management agencies provide the longest record of burned area information. Canada and Alaska have the most well developed data sets consisting of the perimeters of large fires (>200 ha) going back to 1959 and 1950, respectively. A similar data set back to 1980 exists for the Conterminous U.S., but contains data only from federal land management agencies. During the early half of the 20th century, average burned area across North America ranged between 10 and 20 × 106 ha yr−1, largely because of frequent surface fires in the southeastern U.S. Over the past two decades, an average of 5 × 106 ha yr−1 has burned. Moderate-resolution (500–1000 m) satellite burned area products information products appear to either underestimate burned area (GFED3 and MCD45A1) or significantly overestimate burned area (L3JRC and GLOBCARBON). Of all the satellite data products, the GFED3 data set provides the most consistent source of burned area when compared to fire management data. Because they do not suitably reflect actual fire activity, the L3JRC and GLOBCARBON burned area data sets are not suitable for use in carbon cycle studies in North America. The MCD45A1 data set appears to map a higher fraction of burned area in low biomass areas compared to the GFED3 data set.
On Pole-Zero Model Estimation Methods Minimizing a Logarithmic Criterion for Speech Analysis

A speech production model consists of a linear, slowly time-varying filter. Pole-zero models are required for a good representation of certain types of speech sounds, like nasals and laterals. From a perceptual point of view, designing them by minimizing a logarithmic criterion appears as a very suitable approach. The most accurate available results are obtained by using Newton-like search algorithms to optimize pole and zero positions, or the coefficients of a decomposition into quadratic factors. In this paper, we propose to optimize the numerator and denominator coefficients instead. Experimental results show that this is the computationally most efficient approach, especially when the optimization criterion considers a psychoacoustical frequency scale. To illustrate its applicability in speech processing, we used the proposed method for formant and anti-formant tracking as well as speech resynthesis.
UNIFORMLY-STABLE FINITE ELEMENT METHODS FOR DARCY-STOKES-BRINKMAN MODELS

在这篇论文，我们认为 2D 和 3D Darcy 司烧连接问题。 这些方程与 Brinkman 模型有关震颤两个 Darcy 是法律并且司烧在 PDE，但是与强烈不连续的粘性系数和 zeroth 顺序的一种单个形式的方程称为系数。 我们在场构造一致地稳定的有限元素近似的三个不同方法。 开始的二个方法基于 Darcy-Stokes-Brinkman 方程的原来的弱明确的表达。 在我们考虑存在的第一个方法司烧元素。 我们证明一个马厩司烧如果并且仅当分离地没有分叉的速度暗示几乎到处没有分叉的，元素关于系数和 Darcy-Stokes-Brinkman 方程的 jumps 也是一致地稳定的。 在第二个方法，我们由修改遵守元素的一些著名 H (div ) 构造一致地稳定的元素。 我们以一个统一方法给一些新 2D 和 3D 元素。 在最后方法，我们与一个稳定术语修改 Darcy-Stokes-Brinkman 方程的原来的弱明确的表达。 我们证明所有传统的马厩司烧元素在这新明确的表达下面关于系数和他们的 jumps 是一致地稳定的。
Mining large distributed log data in near real time

Analyzing huge amounts of log data is often a difficult task, especially if it has to be done in real time (e.g., fraud detection) or when large amounts of stored data are required for the analysis. Graphs are a data structure often used in log analysis. Examples are clique analysis and communities of interest (COI). However, little attention has been paid to large distributed graphs that allow a high throughput of updates with very low latency. In this paper, we present a distributed graph mining system that is able to process around 39 million log entries per second on a 50 node cluster while providing processing latencies below 10 ms. We validate our approach by presenting two example applications, namely telephony fraud detection and internet attack detection. A thorough evaluation proves the scalability and near real-time properties of our system.
Therapeutic value of lymph node dissection for right middle lobe non-small-cell lung cancer.

BACKGROUND Superior mediastinal and #11i lymph node (LN) metastases are adverse prognostic factors in patients with middle lobe lung cancer. We aimed to clarify the benefit of thorough lymphadenectomy by LN station or zone in middle lobe non-small-cell lung cancer (NSCLC). METHODS Among 295 patients who underwent pulmonary resection and thorough lymphadenectomy for primary right middle lobe (RML) NSCLC at two institutions, we enrolled 68 patients (33 men, 35 women) and retrospectively studied their data. We divided each N1 location (i.e., #10, #11s and #11i) into N1(-)N2(+) and N1(+)N2(+) and divided the #12m location into N1(+)N2(-), N1(-)N2(+) and N1(+)N2(+). RESULTS Interlobar node involvement was rare in pN1 NSCLC when compared with that in other N1 nodes. Lymph node dissection (LND) was beneficial when the hilar zone (HZ)/interlobar zone (IZ) LNs were located at the intermediate point of the upper zones (UZs) and subcarinal zones (SCZs), with the therapeutic benefit at the SCZ being 2.8-fold higher than that at the UZ and 9.7-fold higher than that at the lower zone (LZ). Furthermore, LND evidently had greater therapeutic value for the SCZ than the UZ, which was compatible with skip N2 metastases. CONCLUSIONS For middle lobe NSCLC, mediastinal LND should be considered a priority in the SCZ than in the UZ. Moreover, the HZ/IZ is central to unfavourable prognoses in patients with pN2 middle lobe NSCLC.
Immunohistochemical Analysis of Non-Small Cell Lung Cancer: Correlation with Clinical Parameters and Prognosis

Non-small cell lung cancers (NSCLC) vary in their biologic behavior. Recurrence and tumor-related mortality may be attributable to molecular abnormalities in primary tumors. This study evaluated such immunophenotypes with regard to cell cycle regulation and proliferation, apoptosis, and angiogenesis, to determine their significance for patient outcome. Core biopsies from 219 patients with NSCLC were assembled on tissue microarrays, and the expressions of p16, p21, p27, cyclin B1, cyclin E, Ki-67, caspase-3, survivin, bcl-2, VEGF, and endostatin were evaluated by immunohistochemistry. Despite previously described prognostic relevance of some of the investigated molecules, many of those markers were not directly associated with recurrence or survival. However, there was a trend for p16 immunoreactivity to be associated with a good prognosis (57% vs. 42% in 5-yr survival) (p=0.071). bcl-2 expression was strongly correlated with a better outcome (65% vs. 45% in 5-yr survival) (p=0.029), and the hazard of death for bcl-2 positive patients was 0.42 times of that for bcl-2 negative patients (p=0.047). A multivariate analysis with Cox proportional hazards model confirmed that the lymph node status (p=0.043) and stage (p=0.003) were other independent prognostic factors. Our results suggest that p16 and bcl-2 provide prognostic information independent of the TNM stage in NSCLC.
The dark side of opioids in pain management: basic science explains clinical observation

Introduction: In the past 2 decades, opioids have been used increasingly for the treatment of persistent pain, and doses have tended to creep up. As basic science elucidates mechanisms of pain and analgesia, the cross talk between central pain and opioid actions becomes clearer. Objectives: We aimed to examine the published literature on basic science explaining pronociceptive opioid actions, and apply this knowledge to clinical observation. Methods: We reviewed the existing literature on the pronociceptive actions of opioids, both preclinical and clinical studies. Results: Basic science provides a rationale for the clinical observation that opioids sometimes increase rather than decrease pain. Central sensitization (hyperalgesia) underlies pain chronification, but can also be produced by high dose and high potency opioids. Many of the same mechanisms account for both central pain and opioid hyperalgesia. Conclusion: Newly revealed basic mechanisms suggest possible avenues for drug development and new drug therapies that could alter pain sensitization through endogenous and exogenous opioid mechanisms. Recent changes in practice such as the introduction of titration-to-effect for opioids have resulted in higher doses used in the clinic setting than ever seen previously. New basic science knowledge hints that these newer dosing practices may need to be reexamined. When pain worsens in a patient taking opioids, can we be assured that this is not because of the opioids, and can we alter this negative effect of opioids through different dosing strategies or new drug intervention?
Intrauterine Exposure to Maternal Diabetes Is Associated With Higher Adiposity and Insulin Resistance and Clustering of Cardiovascular Risk Markers in Indian Children

OBJECTIVE To test the hypothesis that maternal gestational diabetes increases cardiovascular risk markers in Indian children. RESEARCH DESIGN AND METHODS Anthropometry, blood pressure, and glucose/insulin concentrations were measured in 514 children at 5 and 9.5 years of age (35 offspring of diabetic mothers [ODMs], 39 offspring of diabetic fathers [ODFs]). Children of nondiabetic parents were control subjects. RESULTS At age 9.5 years, female ODMs had larger skinfolds (P < 0.001), higher glucose (30 min) and insulin concentrations, and higher homeostasis model assessment (HOMA) of insulin resistance and systolic blood pressure (P < 0.05) than control subjects. Male ODMs had higher HOMA (P < 0.01). Associations were stronger than at age 5 years. Female ODFs had larger skinfolds and male ODFs had higher HOMA (P < 0.05) than control subjects; associations were weaker than for ODMs. Associations between outcomes in control subjects and parental BMI, glucose, and insulin concentrations were similar for mothers and fathers. CONCLUSIONS The intrauterine environment experienced by ODMs increases diabetes and cardiovascular risk over genetic factors; the effects strengthen during childhood.
NRC Publications Archive Archives des publications du CNRC

Current MIDI recording and transmitting technology allows teachers to teach piano playing remotely (or off-line): a teacher plays a MIDI-keyboard at one place and a student observes the played piano keys on another MIDI-keyboard at another place. What this technology does not allow is to see how the piano keys are played, namely: which hand and ﬁnger was used to play a key. In this paper we present a video recognition tool that makes it possible to provide this information. A video-camera is mounted on top of the piano keyboard and video recognition techniques are then used to calibrate piano image with MIDI sound, then to detect and track pianist hands and then to annotate the ﬁngers that play the piano. The result of the obtained video annotation of piano playing can then be shown on a computer screen for further perusal by a piano teacher or a student.
CHRONIC PROGRESSIVE ENCEPHALITIS IN CHILDREN WITH X-LINKED HYPOGAMMAGLOBULINEMIA

This report is on six cases of a chronic relentlessly progressive encephalitis occurring in boys with congenital hypogammaglobulinemia presumably of the x-linked type, which are thought to represent a separate neurological entity. Intellectual deterioration, dysarthria, spasticity, ataxia, optic atrophy and an increase of lymphocytes in the cerebrospinal fluid, were the main clinical signs. The pathological picture was that of a viral encephalitis, but all virological investigations on brain biopsies and CSF were negative. The significance of intra-cisternal tubuloreticular inclusions in brain endothelial cells, similarities with chronic rubella encephalitis, and the role of the immunological deficiency are discussed. Sofar, the cause of this new type of encephalitis remains obscure.
Effect of Modulated Glucose Uptake on High‐Level Recombinant Protein Production in a Dense Escherichia coli Culture

Methyl α‐glucoside (α‐MG) is a metabolically inert glucose analog sharing the same phosphotransferase system with glucose. The potential of using this compound, which acts as a nontoxic competitive inhibitor, to modulate glucose uptake and subsequently reduce the acetate accumulation rate was investigated. In a complex medium, no significant effect on the growth rate was observed when the α‐MG to glucose ratio was low. The effect of α‐MG supplementation on the production of a model recombinant protein, CadA‐β‐galactosidase, under the regulation of a pH‐inducible promoter in a batch culture was also examined. It was observed that the amount of acetate accumulation was drastically reduced in the presence of α‐MG. More importantly, recombinant protein productivity was significantly improved. A very high volumetric productivity of approximately 1.6 g/L recombinant protein in a dense culture with an OD600 of 35 was obtained in a simple batch fermentation. Even at this high cell density, the specific protein productivity was maintained at a high level and was estimated to account for about 40% of the total cellular protein.
Couple involvement and network structure: A test of the dyadic withdrawal hypothesis.

A number of theorists have argued that increased romantic involvement of a couple with each other necessarily leads to decreased involvement with other members of their social network. A critical analysis of those arguments suggests that the withdrawal process is socially defined rather than existentially necessary,, and selective rather than universal. Data are presented on network structure for a sample of 419 university students involved in relationships ranging from occasional dating through marriage. The results indicate that as couples become more romantically involved, their friendship networks shrink and they become less involved with those friends who remain in the network. Kin networks do not shrink, although the variance in number of kin listed incredses dramatically at engagement and again at marriage. Results are discussed in terms of the interpersonal construction of definitions of relationships and the networks in which they are embedded.