Generalized Backpropagation Algorithm for Training Second-order Neural Networks

Abstract

The artificial neural network is a popular framework in machine learning. To empower individual neurons, we recently suggested that the current type of neurons could be upgraded to 2^nd order counterparts, in which the linear operation between inputs to a neuron and the associated weights is replaced with a nonlinear quadratic operation. A single 2^nd–order neurons already has a strong nonlinear modeling ability, such as implementing basic fuzzy logic operations. In this paper, we develop a general backpropagation (BP) algorithm to train the network consisting of 2^nd-order neurons. The numerical studies are performed to verify the generalized BP algorithm.

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How Valid Are GFR Estimation Results From the CKD-EPI Databases?

Levey et al1 concluded that current evidence does not support reporting estimated glomerular filtration rate using any other creatinine equation than CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). However, their results do not provide evidence of external validity; the original authors of the equation,2 after analyzing multiple models in the CKD-EPI database (n=3,896), stated "We selected a single model as the best equation for general use."2(p 605) A true external validation should not influence the equation coefficients or which equation is finally selected.

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In Reply to ‘How Valid Are GFR Estimation Results From the CKD-EPI Databases?’

We do not agree with the assertions by Björk et al.1 First, the coefficients for the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation were not modified using results from the external validation. Second, results from the CKD-EPI database have been confirmed in numerous studies2-5 despite variation in serum creatinine assays following standardization.6 Third, the reanalysis of the CKD-EPI data set by Björk et al does not show that the Lund-Malmö-revised (LMR) equation is more accurate than the CKD-EPI equation.

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C5aR activation in the absence of C5a - a new disease mechanism of Autoimmune Hemolytic Anemia in mice

Abstract

IgG Fc receptors (FcγRs) and the C5a anaphylatoxin receptor (C5aR) were identified as key regulators of type II autoimmune injury in mice. However, and with respect to C5aR, the relative importance of C5a for IgG autoantibody-induced cellular destruction remained unclear. Using an experimental model of autoimmune hemolytic anemia (AIHA), we here report marked differences in the development of AIHA between mice lacking C5aR and C5-deficient (Hc⁰) strain, indicating a limited role of C5 in this type of C5aR-regulated disease. Ex-vivo-analyses of liver homogenates from anemic Hc⁰ mice demonstrate C5a-independent C5aR activation, upregulation of FcγR expression and amplification of erythrophagocytosis by macrophages. As assessed by pharmacological inhibition studies, targeting of C5aR, but not of C5, is effective in treating experimental AIHA. Collectively, these results define a previously unrecognized disease mechanism of C5aR activation in AIHA that does not necessarily involve C5 and C5a.

This article is protected by copyright. All rights reserved

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Down-regulation of CASK in glucotoxicity-induced insulin dysfunction in pancreatic β cells

Abstract

High-glucose level exerts deleterious effects on pancreatic β cells, but the mechanisms remain unclear. Calcium/calmodulin-dependent serine protein kinase (CASK) plays a vital role in neural development and release of neurotransmitters, and probably plays a role in the anchoring of insulin on pancreatic β cell membrane. Hypoxia-inducible factor 1α (HIF1α) is involved in β-cell dysfunction. The aim of this study was to provide some basic evidence that CASK could be involved in glucotoxicity-induced insulin secretion dysfunction mediated by HIF1α in INS-1E cells. CASK overexpression plasmid, HIF1α agonist (CoCl₂), and HIF1α selective inhibitor (KC7F2) were used. The results showed that chronic stimulation with high glucose could induce insulin secretion dysfunction in INS-1E β cells. Overexpression of CASK partially reversed the effects of high glucose on insulin secretion. CoCl₂ reduced the expression of CASK, but KC7F2 reversed the glucotoxicity-induced CASK level reduction. These results suggest that glucotoxicity-induced insulin secretion defects in INS-1E cells could be mediated by HIF1α via the down-regulation of CASK.

http://ift.tt/2BQpj3x

Induction of autophagy and autophagy-dependent apoptosis in diffuse large B-cell lymphoma by a new antimalarial artemisinin derivative, SM1044

Abstract

Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin's lymphoma. R-CHOP is currently the standard therapy for DLBCL, but the prognosis of refractory or recurrent patients remains poor. In this study, we synthesized a new water-soluble antimalarial drug artemisinin derivative, SM1044. The treatment of DLBCL cell lines with SM1044 induces autophagy-dependent apoptosis, which is directed by an accelerated degradation of the antiapoptosis protein Survivin, via its acetylation-dependent interaction with the autophagy-related protein LC3-II. Additionally, SM1044 also stimulates the de novo synthesis of ceramide, which in turn activates the CaMKK2–AMPK–ULK1 axis, leading to the initiation of autophagy. Our findings not only elucidate the mechanism of autophagy-dependent apoptosis in DLBCL cells, but also suggest that SM1044 is a promising therapeutic molecule for the treatment of DLBCL, along with R-CHOP regimen.

Our research reported an artemisinin derivative, SM1044, induces autophagy-dependent apoptosis which is triggered by an increased acetylation of Survivin, a modification which induces its interaction with LC3-II and its degradation. We also unraveled that the activation of CaMKK2–AMPK–ULK1 axis was molecular basis of SM1044-dependent stimulation of autophagy. These investigations not only point to SM1044 as a promising molecule in fighting diffuse large B-cell lymphoma (DLBCL), but also unravel important information of the molecular pathways involved in the oncogenesis of DLBCL.

http://ift.tt/2C9AFPc

Effects of Th17 cells and IL-17 in the progression of cervical carcinogenesis with high-risk human papillomavirus infection

Abstract

The existence of Th17 cells and IL-17 was recently shown in several types of infectious diseases, but their distribution and functions in cervical lesions with high-risk human papillomavirus (HPV) infection have not been fully elucidated. In this study, the frequency of Th17 cells in peripheral blood samples obtained from 28 cervical squamous cell carcinoma patients, 26 CIN1 patients, 30 CIN2 patients, 29 CIN3 patients, 25 high-risk HPV-infected women with normal cervical cytology, and 30 healthy controls was determined by flow cytometry. Besides, the levels of IL-17 in peripheral blood samples as well as in supernatant of cervical tissue homogenate were assessed by enzyme-linked immunosorbent assay (ELISA) simultaneously. We found that during the disease progression of cervical lesions, the proportion of Th17 cells in the total CD4⁺ cells showed a gradually increased tendency compared with the controls (P < 0.05). Moreover, levels of IL-17 in serum and supernatant of cervical tissue homogenate showed the same tendency as the proportion of Th17 cells (P < 0.05). When compared in pairs, the levels of IL-17 in supernatant differed significantly among the study groups and the control group (P < 0.05), but no significant difference was observed in serum (P > 0.05). In conclusions, the results indicate that Th17 cells and IL-17 may play a role of immune enhancement in the infection of high-risk HPV especially in the cervical microenvironment, which contribute to the disease progression of its associated cervical lesions.

In this work, we evaluated the frequency of Th17 cells in peripheral blood samples obtained from cervical squamous cell carcinoma patients, CIN1 patients, CIN2 patients, CIN3 patients, high-risk HPV-infected women with normal cervical cytology, and healthy controls,as well as the levels of IL-17 in peripheral blood samples and in supernatant of cervical tissue homogenate. So we had come to the conclusion that Th17 cells and IL-17 may play a role of immune enhancement in the infection of high-risk HPV, which contribute to the disease progression of its associated cervical lesions.

http://ift.tt/2BEjFxb

Personality and breast cancer screening in women of the GAZEL cohort study

Abstract

The potential benefit of breast cancer screening is mitigated by the risk of false positives and overdiagnosis, thus advocating for a more personalized approach, based on the individual benefit-harm balance. Since personality might influence the women's appraisal of this balance, this prospective observational cohort study examined whether it could influence mammography use. A total of 2691 postmenopausal women of the GAZEL Cohort Study completed the Bortner Type A Rating Scale and the Buss and Durkee Hostility Inventory in 1993. Associations between personality scores and subsequent mammography use, self-reported through up to five triennial follow-up questionnaires, were estimated with Odds Ratio (OR) and 95% confidence interval (CI) with logistic mixed model regressions, adjusting for age, occupational grade, marital status, family history of breast cancer, age at menarche, age at first delivery, gynecological follow-up, hormone therapy use, and depressive symptoms. Individual propensity scores were used to weight the analyses to control for potential selection biases. More than 90% of the participants completed at least two follow-up questionnaires. Type A personality, but not hostility, was associated with mammography use in both univariate (crude OR [95% CI]: 1.62 [1.24–2.11], P < 0.001) and multivariate analyses (OR [95% CI]: 1.46 [1.13–1.90], P < 0.01). Type A personality traits (i.e., sense of time urgency, high job involvement, competitiveness) independently predicted mammography use among postmenopausal women. While paying more attention to the adherence of women with low levels of these traits, clinicians may help those with higher levels to better consider the risks of false positives and overdiagnosis.

Type A personality traits (i.e., sense of time urgency, high job involvement, competitiveness) independently predicted mammography use among 2691 postmenopausal women of the GAZEL Cohort Study (adjusted Odds Ratio [95% confidence interval]: 1.46: [1.13–1.90], P < 0.01). While paying more attention to the adherence of women with low levels of these traits, clinicians may help those with higher levels to better consider the risks of false positives and overdiagnosis.

http://ift.tt/2C9AW4U

The Ikaros family in lymphocyte development

Beate Heizmann | Philippe Kastner | Susan Chan

http://ift.tt/2zvb4uN

Qingxuan Jiangya Decoction Mitigates Renal Interstitial Fibrosis in Spontaneously Hypertensive Rats by Regulating Transforming Growth Factor-β1/Smad Signaling Pathway

Qingxuan Jiangya Decoction (QXJYD) is a traditional Chinese medicine commonly used in the clinical treatment of hypertension. Earlier studies had shown that QXJYD could inhibit the elevation of blood pressure in spontaneously hypertensive rats (SHRs) and prevent remodeling of arterial vessels. This study examines the therapeutic efficacy of QXJYD against elevated blood pressure using the SHR model, as well as the mechanisms behind its antihypertensive activity and protection against renal fibrosis. The results showed that QXJYD significantly attenuated the increase in blood pressure in SHRs and mitigated the development of renal interstitial fibrosis. In addition, QXJYD also robustly decreased the excess accumulation of extracellular matrix and attenuated the elevated expression of MMPs. The antihypertensive effects and renal protection of QXJYD were determined to be strongly associated with inhibition of TGF-β1/Smad signaling pathway.

http://ift.tt/2BQ3AIG

A Text-Based Chat System Embodied with an Expressive Agent

Life-like characters are playing vital role in social computing by making human-computer interaction more easy and spontaneous. Nowadays, use of these characters to interact in online virtual environment has gained immense popularity. In this paper, we proposed a framework for a text-based chat system embodied with a life-like virtual agent that aims at natural communication between the users. To achieve this kind of system, we developed an agent that performs some nonverbal communications such as generating facial expression and motions by analyzing the text messages of the users. More specifically, this agent is capable of generating facial expressions for six basic emotions such as happy, sad, fear, angry, surprise, and disgust along with two additional emotions, irony and determined. Then to make the interaction between the users more realistic and lively, we added motions such as eye blink and head movements. We measured our proposed system from different aspects and found the results satisfactory, which make us believe that this kind of system can play a significant role in making an interaction episode more natural, effective, and interesting. Experimental evaluation reveals that the proposed agent can display emotive expressions correctly 93% of the time by analyzing the users' text input.

http://ift.tt/2zsQv1X

Low Prevalence of Hepatitis B Vaccination Among Patients Receiving Medical Care for HIV Infection in the United States, 2009 to 2012

Background:

Persons with HIV infection are at increased risk for hepatitis B virus infection. In 2016, the World Health Organization resolved to eliminate hepatitis B as a public health threat by 2030.

Objective:

To estimate the prevalence of hepatitis B vaccination among U.S. patients receiving medical care for HIV infection ("HIV patients").

Design:

Nationally representative cross-sectional survey.

Setting:

United States.

Participants:

18 089 adults receiving HIV medical care who participated in the Medical Monitoring Project during 2009 to 2012.

Measurements:

Primary outcomes were prevalence of 1) no documentation of hepatitis B vaccination or laboratory evidence of immunity or infection (candidates to initiate vaccination), and 2) initiation of vaccination among candidates, defined as documentation of at least 1 vaccine dose in a 1-year surveillance period during which patients received ongoing HIV medical care.

Results:

At the beginning of the surveillance period, 44.2% (95% CI, 42.2% to 46.2%) of U.S. HIV patients were candidates to initiate vaccination. By the end of the surveillance period, 9.6% (CI, 8.4% to 10.8%) of candidates were vaccinated, 7.5% (CI, 6.4% to 8.6%) had no documented vaccination but had documented infection or immunity, and 82.9% (CI, 81.1% to 84.7%) remained candidates. Among patients at facilities funded by the Ryan White HIV/AIDS Program (RWHAP), 12.5% (CI, 11.1% to 13.9%) were vaccinated during the surveillance period versus 3.7% (CI, 2.6% to 4.7%) at facilities not funded by RWHAP. At the end of surveillance, 36.7% (CI, 34.4% to 38.9%) of HIV patients were candidates to initiate vaccination.

Limitation:

The study was not designed to describe vaccine series completion or actual prevalence of immunity.

Conclusion:

More than one third of U.S. HIV patients had missed opportunities to initiate hepatitis B vaccination. Meeting goals for hepatitis B elimination will require increased vaccination of HIV patients in all practice settings, particularly at facilities not funded by RWHAP.

Primary Funding Source:

Centers for Disease Control and Prevention.

http://ift.tt/2BAQMSj

Evaluating Slow-Release Oral Morphine to Narrow the Treatment Gap for Opioid Use Disorders

The opioid epidemic has garnered widespread attention and concern. Although evidence-based treatments for opioid use disorders (OUDs) exist, health system and regulatory barriers may limit their use. In this essay, the authors discuss the need for further investigation into slow-release oral morphine as a potential treatment for patients with OUDs.

http://ift.tt/2C90IpW

Blood Pressure Control: Missed Opportunity or Potential Holy Grail?

Mills and colleagues' meta-analysis assessed the comparative effectiveness of 8 implementation strategies for blood pressure control. The editorialists discuss the findings and speculate on why blood pressure control remains elusive 40 years after evidence documented that control improves patient outcomes.

http://ift.tt/2BAQJ95

Underutilization of Glucagon in the Prehospital Setting

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Comparative Effectiveness of Implementation Strategies for Blood Pressure Control in Hypertensive Patients A Systematic Review and Meta-analysis

Background:

The prevalence of hypertension is high and is increasing worldwide, whereas the proportion of controlled hypertension is low.

Purpose:

To assess the comparative effectiveness of 8 implementation strategies for blood pressure (BP) control in adults with hypertension.

Data Sources:

Systematic searches of MEDLINE and Embase from inception to September 2017 with no language restrictions, supplemented with manual reference searches.

Study Selection:

Randomized controlled trials lasting at least 6 months comparing the effect of implementation strategies versus usual care on BP reduction in adults with hypertension.

Data Extraction:

Two investigators independently extracted data and assessed study quality.

Data Synthesis:

A total of 121 comparisons from 100 articles with 55 920 hypertensive patients were included. Multilevel, multicomponent strategies were most effective for systolic BP reduction, including team-based care with medication titration by a nonphysician (−7.1 mm Hg [95% CI, −8.9 to −5.2 mm Hg]), team-based care with medication titration by a physician (−6.2 mm Hg [CI, −8.1 to −4.2 mm Hg]), and multilevel strategies without team-based care (−5.0 mm Hg [CI, −8.0 to −2.0 mm Hg]). Patient-level strategies resulted in systolic BP changes of −3.9 mm Hg (CI, −5.4 to −2.3 mm Hg) for health coaching and −2.7 mm Hg (CI, −3.6 to −1.7 mm Hg) for home BP monitoring. Similar trends were seen for diastolic BP reduction.

Limitation:

Sparse data from low- and middle-income countries; few trials of some implementation strategies, such as provider training; and possible publication bias.

Conclusion:

Multilevel, multicomponent strategies, followed by patient-level strategies, are most effective for BP control in patients with hypertension and should be used to improve hypertension control.

Primary Funding Source:

National Institutes of Health.

http://ift.tt/2ByP0Bm

Embryo Microinjection and Transplantation Technique for Nasonia vitripennis Genome Manipulation

Microinjection of Nasonia vitripennis embryos is an essential method for generating heritable genome modifications. Described here is a detailed procedure for microinjection and transplantation of Nasonia vitripennis embryos, which will greatly facilitate future genome manipulation in this organism.

http://ift.tt/2pwcHbJ

SwarmSight: Real-time Tracking of Insect Antenna Movements and Proboscis Extension Reflex Using a Common Preparation and Conventional Hardware

This protocol describes steps for using the novel software, SwarmSight, for frame-by-frame tracking of insect antenna and proboscis positions from conventional web camera videos using conventional computers. The free, open-source software processes frames about 120 times faster than humans and performs at better than human accuracy.

http://ift.tt/2kVD5aB

Dispersion of Nanomaterials in Aqueous Media: Towards Protocol Optimization

Here, we present a step-wise protocol for the dispersion of nanomaterials in aqueous media with real-time characterization to identify the optimal sonication conditions, intensity, and duration for improved stability and uniformity of nanoparticle dispersions without impacting the sample integrity.

http://ift.tt/2C23UAX

Protocol for HER2 FISH Using a Non-cross-linking, Formalin-free Tissue Fixative to Combine Advantages of Cryo-preservation and Formalin Fixation

Fluorescence in-situ hybridization (FISH) is often required in combination with histopathology and molecular diagnostics for selection of therapy in personalized medicine. A novel non-cross-linking, formalin-free tissue fixative that allows high quality morphologic, molecular and FISH analyses from the same specimen by addition of a post-fixation step before FISH is presented.

http://ift.tt/2C4qjhf

EMCrit Podcast 215 – A Disagreement of Toxicologists with Dantastic Mr. Tox/&Howard

Dantastic Mr. Tox/&Howard discuss some Tox stuff and Santa Beards

EMCrit Project by Scott Weingart.

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Tumor Burden and Intraosseous Metabolic Activity as Predictors of Bone Marrow Failure during Radioisotope Therapy in Metastasized Prostate Cancer Patients

Rationale. Radium-223-Dichloride (Ra-223) is an alpha-emitter, used to treat bone metastases. Patients with high metastatic burden and/or with increased trabecular bone uptake could present a higher incidence of hematologic toxicity. We hypothesized that these two factors are predictors of bone marrow failure. Material and Methods. A computer algorithm discriminated between trabecular bone () and tumor metastases () within pretherapeutic whole-body skeletal SPECT/CT (). The program calculated the metastatic invasion percent (INV%) as the ) ratio and extracted the mean counts. counts were correlated to % drop of hemoglobin (Hb), leukocytes (WBC), and platelets (PLT) after 3/6 Ra-223 cycles. Patient-specific and computational-derived parameters were tested as predictors of hematologic toxicity with MANOVA. Results. counts correlated with drop of Hb ( = 0,65, ) and PLT ( = 0,45, ). Appendicular counts showed a better correlation (, , and for Hb, WBC, and PLT, resp.). INV% directly correlated with counts ( = 0.68, ). At MANOVA, grade III/IV toxicity was predicted by INV% (), by long-bone invasion (), and by counts (). Conclusions. In patients with significant bone tumor burden, degree of bone invasion and trabecular bone uptake are predictors of subsequent bone marrow failure.

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Comparison of diagnostic performance of rapid and standard polymerase chain reaction laboratory test for influenza and respiratory syncytial virus detection in nasopharyngeal swabs from symptomatic lung transplant recipients

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Heterogeneous Periostin Expression in Different Histological Variants of Papillary Thyroid Carcinoma

Background. Periostin (PN) epithelial and stromal overexpression in tumor pathology has been studied according to tumor growth, angiogenesis, invasiveness, and metastasis, but a limited number of studies address PN in thyroid tumors. Aim. Our study aimed to analyze PN expression in different histological variants of PTC and to correlate its expression with the clinicopathological prognostic factors. Material and Methods. PN expression has been immunohistochemically assessed in 50 cases of PTC (conventional, follicular, oncocytic, macrofollicular, and tall cell variants), in tumor epithelial cells and intratumoral stroma. The association between PN expression and clinicopathological characteristics has been evaluated. Results. Our results show that PTC presented different patterns of PN immunoreaction, stromal PN being significantly associated with advanced tumor stage and extrathyroidal extension. No correlations were found between PN overexpression in tumor epithelial cells and clinicopathological features, except for specific histological variants, the highest risk of poor outcome being registered for the conventional subtype in comparison to the oncocytic type. Conclusions. Our study demonstrates differences in PN expression in histological subtypes of PTC. Our results plead in favor of a dominant protumorigenic role of stromal PN, while the action of epithelial PN is less noticeable.

http://ift.tt/2DbJMf1