Miracle-dz/UniFAR-FTUs huggingface dataset:
Ultrastructural changes to the tegumental system and the gastrodermal cells in adult Fasciola hepatica following in vivo treatment with the experimental fasciolicide, compound alpha

SUMMARY Sheep infected with the triclabendazole-susceptible, Cullompton isolate of Fasciola hepatica were dosed with 15 mg/kg of compound alpha at 12 weeks post-infection. Adult flukes were recovered from the bile ducts at 24, 48 and 72 h post-treatment (p.t.). Ultrastructural changes to the flukes were assessed using transmission electron microscopy (TEM), with a view to gathering information on the mechanism(s) of action for compound alpha and on the possible route of its entry into F. hepatica. The tegumental syncytium was more severely affected than the gut at all time-points p.t. with compound alpha, suggesting a predominantly trans-tegumental route of uptake. Disruption to the tegumental system became increasingly severe over time. A stress response was observed at 24 h p.t. and took the form of blebbing and increases in the production and transport of secretory bodies. By 72 h p.t. , extensive tegumental loss and degeneration of the tegumental cell bodies had occurred. Degeneration of subtegumental tissues and internal flooding were also observed. Changes in the gastrodermal cells were slow to develop: reduced secretory activity was evident at 72 h p.t. There was progressive disruption to the somatic muscle layers, with disorganization of the muscle blocks and loss of muscle fibres.
Rac1 Activation in Podocytes Induces Rapid Foot Process Effacement and Proteinuria

ABSTRACT The kidney's vital filtration function depends on the structural integrity of the glomerulus, the proximal portion of the nephron. Within the glomerulus, the architecturally complex podocyte forms the final cellular barrier to filtration. Injury to the podocyte results in a morphological change called foot process effacement, which is a ubiquitous feature of proteinuric diseases. The exact mechanism underlying foot process effacement is not known, but recently it has been proposed that this change might reflect activation of the Rac1 GTPase. To test this hypothesis, we generated a podocyte-specific, inducible transgenic mouse line that expressed constitutively active Rac1. When the Rac1 transgene was induced, we observed a rapid onset of proteinuria with focal foot process effacement. Using superresolution imaging, we verified that the induced transgene was expressed in damaged podocytes with altered foot process morphology. This work sheds new light on the complex balance of Rho GTPase signaling that is required for proper regulation of the podocyte cytoskeleton.
Degradation of collagen in the bone‐resorbing compartment underlying the osteoclast involves both cysteine‐proteinases and matrix metalloproteinases

The site of action of cysteine‐proteinases (CPs) and matrix metalloproteinases (MMPs) in the degradation of bone collagen by osteoclasts was investigated by evaluating the effects of the CP‐inhibitor trans‐epoxy‐succinyl‐L‐leucylamido (4‐guanidino)‐butane (E‐64) and the MMP‐inhibitor N‐(3‐N‐benzyloxycarbonyl amino‐1‐R‐carboxypropyl)‐L‐leucyl‐O‐methyl‐L‐tyrosine N‐methylamide (Cl‐1) in an in vitro model system of PTH‐stimulated mouse calvaria. In the presence of each of the two inhibitors a large area of collagen free of mineral crystallites was seen adjacent to the ruffled border of the osteoclasts. Following a culture period of 24 h this area proved to be about 10 times larger in inhibitor‐treated explants than in controls. Moreover the percentage of osteoclasts in close contact with such demineralized bone areas appeared to be significantly higher in inhibitor‐treated explants than in control specimens (60% and 5%, respectively). These effects were not apparent when the osteoclastic activity was inhibited with calcitonin. No significant differences were found between the effects of the two inhibitors, E‐64 and Cl‐1. Our observations indicate that under the influence of inhibitors of MMPs and CPs demineralization of bone by osteoclasts proceeded up to a certain point whereas matrix degradation was strongly inhibited. It is concluded that within the osteoclastic resorption lacuna both CPs and MMPs participate in the degradation of the collagenous bone matrix.
Differences in age and body site distribution of the histological subtypes of basal cell carcinoma. A possible indicator of differing causes.

OBJECTIVE To assess if there are any significant differences in the sex, anatomical site, and age distribution of patients with different histological subtypes of basal cell carcinoma (BCC). DESIGN Histopathology reports were analyzed with respect to the subtype of BCC, site of a tumor, and age and sex of a patient. SETTING Histopathology reports were reviewed from 1 private laboratory that derived its cases from general practitioners, surgeons, and dermatologists. PATIENTS Patients with BCC (N = 3885) for whom case data were received by the pathology laboratory from January 2, 1991, to June 12, 1991, were included in the study. INTERVENTIONS None. MAIN OUTCOME MEASURES Superficial BCCs differed from other subtypes of BCC by occurring more commonly on the trunk and in younger patients. RESULTS The mean age (56.8 years) of the patients with superficial BCCs was significantly lower than that of the patients with other subtypes of BCC who were examined (P < .001); the mean ages of the patients with these other subtypes were as follows: nodulosuperficial BCC, 62.9 years; nodular BCC, 63.9 years; nodulomorpheic BCC, 66.1 years; and morpheic BCC, 66.0 years. The majority of superficial BCCs occurred on the trunk and limbs (73.3%), while the majority of all other subtypes occurred on the head and neck. CONCLUSIONS Superficial BCC differs from the other subtypes of BCC in terms of patient age and tumor site, and these findings may reflect differences in the etiology.
Sulindac independently modulates extracellular signal–regulated kinase 1/2 and cyclic GMP–dependent protein kinase signaling pathways

Colorectal cancer is the second leading cause of cancer mortality in the United States. Substantial human and animal data support the ability of nonsteroidal anti-inflammatory drugs to cause regression of existing colon tumors and prevent new tumor formation. The mechanism by which the nonsteroidal anti-inflammatory drug sulindac prevents tumor growth is poorly understood and seems complex as sulindac can modulate several growth-related signaling pathways. Sulindac metabolites simultaneously (a) increase cellular cyclic GMP and subsequently activate cyclic GMP–dependent protein kinase (PKG); (b) activate c-jun NH2-terminal kinase (JNK); (c) inhibit extracellular signal–regulated kinase 1/2 (ERK1/2); and (d) decrease β-catenin protein expression at times and doses consistent with apoptosis. The purpose of this study was to determine if PKG, ERK1/2, JNK, and β-catenin are independent targets for sulindac in vitro. Pharmacologic activation of PKG with YC-1 increases JNK phosphorylation and induces apoptosis in colon cancer cells without modulating ERK1/2 phosphorylation or β-catenin protein expression. Inhibition of ERK1/2 with U0126 induces apoptosis but fails to activate JNK phosphorylation or down-regulate β-catenin protein expression. Cotreatment with U0126 and YC-1 synergistically increases apoptosis in colorectal cancer cells and recapitulates the effects of sulindac treatment on ERK1/2, JNK, and β-catenin. These results indicate that sulindac metabolites modulate ERK1/2 and PKG pathways independently in colon cancer cells and suggest that the full apoptotic effect of sulindac is mediated by more than one pathway. Using similar combinatorial approaches in vivo may provide more effective, less toxic chemopreventive and chemotherapeutic strategies. Such therapies could dramatically reduce the incidence and death rate from colorectal cancer. [Mol Cancer Ther 2006;5(3):746–54]
Randomized trial comparing the efficacy of a novel manual breast pump with a standard electric breast pump in mothers who delivered preterm infants.

OBJECTIVE The benefits of human milk for preterm infants are widely recognized, yet technological advances in milk expression have been slow. We compared the efficacy of a standard electric pump (EP; Egnell) used in 94% of United Kingdom neonatal units with a novel manual pump (MP; Avent ISIS) designed to operate more physiologically by simulating the infant's compressive action on the areola during breastfeeding. METHODS We randomized 145 women who delivered infants of <35 weeks' gestation to use the MP or the EP and measured total milk volume expressed while using the randomized pump during the infant's hospital stay, pattern of milk output and creamatocrit of milk expressed during a test period in the second week, and pump characteristics by maternal questionnaire. RESULTS Mothers who used the EP, who frequently double pumped, showed shorter expression times but produced no more milk than mothers who used the MP. When both pumped sequentially, however, mothers who used the MP showed significantly greater milk flow and total volume over 20 minutes. Creamatocrit was unaffected by pump type. The MP was rated significantly higher than the EP on 5 major characteristics. CONCLUSIONS When compared on equal terms (sequential pumping), mothers who used the MP showed greater milk flow, perhaps reflecting more physiologic pump design. Even with double pumping, mothers who used the EP did not advantage their infants with greater milk production. We believe that this novel, effective MP, preferred by mothers and costing a fraction of the EP price, reflects a significant advance in milk expression for high-risk infants.breast pumps, randomized trial, preterm infants.
Anatomical parameters of cardiopulmonary system in three different lines of chickens: further evidence for involvement in ascites syndrome

The present study was designed to compare the anatomical parameters of the cardiopulmonary system in three different lines of chickens with different susceptibility to ascites syndrome. Eggs from three different genetic lines—commercial broiler and layer lines and one native to Iran—were incubated and hatched, and 1-day-old chicks used. The relative heart and lung weights, the volumes of the heart, lung and thorax cavity, the incidence of ascites, and the related physiological parameters in these chickens were followed. Lung weight as a percentage of body weight, the relative lung and heart volume, and the volumes of the thorax cavity, before and after removing heart and lung tissues, were lower in fast-growing broiler chickens compared with the layer and native chickens. Additionally, most of these parameters (e.g. relative lung weight, lung volume and thorax cavity) were significantly decreased with age in broiler chickens but were increased in layer and native chickens, which was concomitant with the incidence of ascites in broiler chickens. Our data indicate that all cardiopulmonary parameters investigated are extremely unfavourable to broiler chickens and suggest a reduction in gas exchange area in broilers, and therefore higher susceptibility to pulmonary hypertension and ascites.
Trajectorial organisation of cytokeratins within the subapical region of umbrella cells.

The subapical region of umbrella cells in the urinary bladder contains a dense cytokeratin (CK) network. Yet, this network should enable a very intensive traffic of specific fusiform vesicles involved in alterations of the surface area of the apical membrane. Therefore, the cytokeratins should be organised in a way to be both mechanically strong and also passable for fusiform vesicles. The supramolecular organisation of the CKs in the subapical region of umbrella cells in mice was studied by conventional fluorescence, confocal laser microscopy, and TEM. It has been found that the first 150 to 300 nm under the apical membrane is filled with fusiform vesicles and only below that the CK network begins. The CK 7 and CK 20 compose a subapical network, which is created as an array of parallel trajectories pointing to the apical plasma membrane. The network is framed by a strong wall of CK, which is parallely aligned in neighbouring cells. The double labelling of the urothelial-specific membrane proteins, uroplakins, and CKs proved the presence of fusiform vesicles within these trajectories. The measurements proved that the trajectory diameter in the upper half of the network is smaller than in the lower half. The diameters of the trajectories in animals with distended bladders exceeded those in contracted bladders for 70%, which most likely facilitates the transport of fusiform vesicles to the apical membrane. Discovery of the subapical CK network elucidates the until now undescribed supramolecular organisation of CKs in the apical region of urothelial cells.
Normalized Convolutional Neural Network

In this paper, we propose Normalized Convolutional Neural Network(NCNN). NCNN is more fitted to a convolutional operator than other nomralizaiton methods. The normalized process is similar to a normalization methods, but NCNN is more adapative to sliced-inputs and corresponding the convolutional kernel. Therefor NCNN can be targeted to micro-batch training. Normalizaing of NC is conducted during convolutional process. In short, NC process is not usual normalization and can not be realized in deep learning framework optimizing standard convolution process. Hence we named this method 'Normalized Convolution'. As a result, NC process has universal property which means NC can be applied to any AI tasks involving convolution neural layer . Since NC don't need other normalization layer, NCNN looks like convolutional version of Self Normalizing Network. (SNN). Among micro-batch trainings, NCNN outperforms other batch-independent normalization methods. NCNN archives these superiority by standardizing rows of im2col matrix of inputs, which theoretically smooths the gradient of loss. The code need to manipulate standard convolution neural networks step by step. The code is available : this https URL NormalizedCNN.
Decellularized Native and Engineered Arterial Scaffolds for Transplantation

More than 570,000 coronary artery bypass grafts are implanted each year, creating an important demand for small-diameter vascular grafts. For patients who lack adequate internal mammary artery or saphenous vein, tissue-engineered arteries may prove useful. However, the time needed to tissue engineer arteries (7 weeks or more) is too long for many patients. Decellularized cadaveric human arteries are another possible source of vascular conduit, but limited availability and the potential for disease transmission limit their widespread use. In contrast, decellularized tissue-engineered arteries could serve as grafts for immediate implantation, as scaffolds onto which patients' cells could be seeded, or as carriers for genetically engineered cells to aid cell transplantation. The goal of this study was to quantify the effects of decellularization on vascular matrix and mechanical properties. Specifically, we compared cellular elimination, extracellular matrix retention, and mechanical characteristics of porcine carotid arteries before and after treatment with three decellularization methods. In addition, for the first time, tissue-engineered arteries were decellularized. Decellularized native arteries were also used as a scaffold onto which vascular cells were seeded. These studies identified a decellularization method for native and engineered arteries that maximized cellular elimination, without greatly compromising mechanical integrity. We showed that engineered tissues could be decellularized, and demonstrated the feasibility of reseeding decellularized vessels with vascular cells.
Under what conditions is feedback microwave thermotherapy (ProstaLund Feedback Treatment) cost-effective in comparison with alpha-blockade in the treatment of benign prostatic hyperplasia and lower urinary tract symptoms?

Objective. Lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) are a common condition in men, and their incidence increases with age. The objective of this study was to evaluate the potential cost-utility of microwave thermotherapy, specifically the ProstaLund Feedback Treatment (PLFT), versus alpha-blockade in Swedish patients with LUTS due to BPH. Material and methods. A health-economic simulation model, based on long-term disease progression and costs, was developed to analyse the cost-utility of PLFT in comparison with alpha-blockade over a 3-year period based on data from published literature, treatment programmes and official price lists. Outcome measures used in the analysis were quality of life, survival and reduction in International Prostate Symptom Score. Sensitivity analyses were performed for a number of essential variables. The perspective of the study is the healthcare sector. All costs are expressed as 2003 prices. Results. Three years after an intervention with PLFT or initiation of drug treatment the cost-utility of PLFT was estimated at ≈€6600–9500 per quality-adjusted life-year gained. The cost-utility was further improved over a longer time period, and PLFT appears to be cost-saving after 5 years. One important finding from the model simulation was that PLFT also seems to be favourable in patients with less pronounced symptoms. This result may be further validated when additional results from controlled clinical trials become available. Conclusions. The present model simulation indicates that treatment with PLFT seems to be cost-effective compared with drug therapy with alpha-blockade. The result shows that the time-frame of the analysis has a great impact on the cost-effectiveness ratio.
Circulating microRNAs in patients with ST-elevation myocardial infarction

Objective: The aim of this study was to evaluate the expression levels of cardiac-related circulating microRNAs (miRNAs) in ST-elevation myocardial infarction (STEMI) patients. Methods: This study has a prospective experimental cohort design. A total of 12 consecutive patients with acute chest pain within 12 h admitted to emergency department (STEMI group) and 13 adult patients with normal coronary angiography during the same period were enrolled (control group) in this study. Changes in the expression of miR-122, miR-208, miR-375, miR-22, miR-133b, miR-92b, miR-21, miR-133a, miR-423-5p, miR-27b, miR-30a-3p, miR-17, miR-30d, miR-642, and miR-95 were analyzed using quantitative reverse transcription-polymerase chain reaction. Blood samples were collected before angiography and 24 h after angiography. Data were analyzed using the Statistical Package for the Social Sciences v19. Results: The STEMI group included 12 patients (7 males) with an average age of 56.5±8.3 (range, 44–69) years. The control group included 13 patients (9 males) with an average age of 59±11 (range, 42–80) years. When fold differences were calculated for the miRNA expression values, only miR-30d and miR-423-5p expression levels in STEMI patients showed significant differences in expression levels compared with control patients. The miRNA levels were 2.3-fold higher for miR-30d (p=0.034) and 6.9-fold higher for miR-423-5p (p=0.017). There was no significant correlation between troponin I and miR-30d or miR-423-5p levels (p>0.05). Conclusion: In this study, the expression levels of miRNAs related to cardiac disease were evaluated in peripheral blood. The circulating miR-423-5p and miR-30d levels in peripheral blood were found to be higher in STEMI cases than in the control group. Further studies should be conducted to evaluate their potential use as biomarkers in STEMI cases. (Anatol J Cardiol 2016; 16; 392-6)
Frequency and phenotype of peripheral blood Th17 cells in ankylosing spondylitis and rheumatoid arthritis.

OBJECTIVE To analyze the frequency, surface phenotype, and cytokine secretion of CD4+ T cells in peripheral blood mononuclear cells (PBMCs) from patients with ankylosing spondylitis (AS) compared with both healthy control subjects and patients with rheumatoid arthritis (RA). METHODS Eight-color flow cytometry was used to analyze the surface phenotype and cytokine production of PBMCs from 20 patients with AS, 12 patients with RA, and 16 healthy control subjects, following stimulation ex vivo with phorbol myristate acetate and ionomycin for 5 hours. Secretion of interleukin-17 (IL-17) by PBMCs was measured by enzyme-linked immunosorbent assay, following stimulation with anti-CD3/CD28 for 4 days. RESULTS The percentages of IL-17-positive CD4+ T cells and IL-22-positive CD4+ T cells were increased in the PBMCs of both patients with AS and patients with RA compared with healthy control subjects, whereas there were no differences in the percentages of interferon-gamma (IFNgamma)-positive or IL-10-positive CD4+ T cells. Likewise, concentrations of IL-17 in supernatants from patients with AS were significantly higher compared with those from healthy control subjects. In patients with RA, the concentrations of IL-17 were increased but not significantly. There was a correlation between the percentages of IL-17-positive CD4+ T cells detected in PBMCs and the amounts of IL-17 in culture supernatants (r=0.414, P=0.0034). All IL-17-producing cells were CD4+CD45RO+; most expressed both CCR6 and CCR4, but only 50% expressed the IL-23 receptor (IL-23R). Nevertheless, there was a positive relationship between the percentage of IL-23R-positive CD4+ T cells and the frequency of IL-17-positive CD4+ T cells or IL-22-positive CD4+ T cells (r=0.57, P<0.0001 and r=0.46, P=0.001, respectively). A significant proportion of cells that produced IL-17 also produced IL-22 and IFNgamma, but none produced IL-10. CONCLUSION The frequencies of IL-17-positive and IL-22-positive CD4+ T cells were increased in PBMCs from patients with AS and patients with RA, resulting in secretion of higher quantities of IL-17 by PBMCs following stimulation. These data support the hypothesis that Th17 cells, particularly when present in excess of IL-10-producing cells, are involved in the pathogenesis of inflammatory arthritis.
Nerve Growth Factor Induces Apoptosis in Human Medulloblastoma Cell Lines that Express TrkA Receptors

Neurotrophins act through their cognate receptors to promote the differentiation and/or survival of neuronal progenitor cells, immature neurons, and other cells. Here, we examined the effects of nerve growth factor (NGF) and its cognate receptor (Trk or TrkA) on the survival of a common childhood brain tumor, i.e., medulloblastoma, a tumor that resembles CNS neuroepithelial progenitor cells. To do this, we engineered two human medulloblastoma cell lines (i.e., D283MED and DAOY cells) to express human TrkA using a retroviral expression vector. Surprisingly, NGF-treated medulloblastoma cells expressing the TrkA receptor (D283trk and DAOYtrk cells) grown in the presence or absence of serum underwent massive apoptosis, but similar treatment did not induce apoptosis in wild-type uninfected cells, cells expressing an empty vector, or cells expressing the TrkC receptor. Furthermore, D283MED cells engineered to express the human p75 NGF receptor (D283p75) also did not undergo apoptosis. Significantly, NGF-induced apoptosis in D283trk and DAOYtrk cells can be inhibited by anti-NGF antibodies and by K-252a, an inhibitor of TrkA tyrosine phosphorylation and mimicked by high concentrations of NT3. Because NGF treatment primarily eliminated D283trk cells from the S phase of the cell cycle, this form of NGF-mediated apoptosis is cell cycle-dependent. These findings suggest that a NGF/TrkA signal transduction pathway could activate apoptotic cell death programs in CNS neuroepithelial progenitor cells and in childhood brain tumors.