Miracle-dz/UniFAR-FTUs huggingface dataset:
Using cell nuclei features to detect colon cancer tissue in hematoxylin and eosin stained slides

Currently, diagnosis of colon cancer is based on manual examination of histopathological images by a pathologist. This can be time consuming and interpretation of the images is subject to inter‐ and intra‐observer variability. This may be improved by introducing a computer‐aided diagnosis (CAD) system for automatic detection of cancer tissue within whole slide hematoxylin and eosin (H&E) stains. Cancer disrupts the normal control mechanisms of cell proliferation and differentiation, affecting the structure and appearance of the cells. Therefore, extracting features from segmented cell nuclei structures may provide useful information to detect cancer tissue. A framework for automatic classification of regions of interest (ROI) containing either benign or cancerous colon tissue extracted from whole slide H&E stained images using cell nuclei features was proposed. A total of 1,596 ROI's were extracted from 87 whole slide H&E stains (44 benign and 43 cancer). A cell nuclei segmentation algorithm consisting of color deconvolution, k‐means clustering, local adaptive thresholding, and cell separation was performed within the ROI's to extract cell nuclei features. From the segmented cell nuclei structures a total of 750 texture and intensity‐based features were extracted for classification of the ROI's. The nine most discriminative cell nuclei features were used in a random forest classifier to determine if the ROI's contained benign or cancer tissue. The ROI classification obtained an area under the curve (AUC) of 0.96, sensitivity of 0.88, specificity of 0.92, and accuracy of 0.91 using an optimized threshold. The developed framework showed promising results in using cell nuclei features to classify ROIs into containing benign or cancer tissue in H&E stained tissue samples. © 2017 International Society for Advancement of Cytometry
Loss of function of mouse Pax‐Interacting Protein 1‐associated glutamate rich protein 1a (Pagr1a) leads to reduced Bmp2 expression and defects in chorion and amnion development

Background: Human PAX‐Interacting Protein 1 (PAXIP1)‐associated glutamate rich protein 1 (PAGR1, also known as PA1) originally was discovered as part of a complex containing PAXIP1 and histone H3K4 methyltransferases MLL3 and MLL4, suggesting a role in epigenetic gene regulation. Further in vitro studies suggested additional functions in DNA damage repair and transcription. However, in vivo analysis of PAGR1 function has been lacking. Results: Here we show that expression of the cognate mouse gene Pagr1a is found predominately in the extraembryonic and chorionic ectoderm from pregastrulation stages and is up‐regulated within the embryo proper after gastrulation. Embryos with a germ line deletion of Pagr1a establish the anterior–posterior axis, and show normal neuroectodermal, mesodermal, and endodermal patterning, but fail to develop beyond the four‐ to five‐somite stage or to undergo axial rotation. Pagr1a−/− embryos also show abnormal development of extraembryonic tissues with defects seen in the amnion, chorion and visceral yolk sac. At the molecular level, Pagr1a−/− embryos have reduced expression of BMP2, a known regulator of extraembryonic development. Conclusions: Loss of mouse Pagr1a function leads to defective extraembryonic development, likely due at least in part to altered BMP signaling, contributing to developmental arrest. Developmental Dynamics 243:937–947, 2014. © 2014 Wiley Periodicals, Inc.
Neural mechanisms of smooth pursuit eye movements in schizotypy

Patients with schizophrenia as well as individuals with high levels of schizotypy are known to have deficits in smooth pursuit eye movements (SPEM). Here, we investigated, for the first time, the neural mechanisms underlying SPEM performance in high schizotypy. Thirty‐one healthy participants [N = 19 low schizotypes, N = 12 high schizotypes (HS)] underwent functional magnetic resonance imaging at 3T with concurrent oculographic recording while performing a SPEM task with sinusoidal stimuli at two velocities (0.2 and 0.4 Hz). Behaviorally, a significant interaction between schizotypy group and velocity was found for frequency of saccades during SPEM, indicating impairments in HS in the slow but not the fast condition. On the neural level, HS demonstrated lower brain activation in different regions of the occipital lobe known to be associated with early sensory and attentional processing and motion perception (V3A, middle occipital gyrus, and fusiform gyrus). This group difference in neural activation was independent of target velocity. Together, these findings replicate the observation of altered pursuit performance in highly schizotypal individuals and, for the first time, identify brain activation patterns accompanying these performance changes. These posterior activation differences are compatible with evidence of motion processing deficits from the schizophrenia literature and, therefore, suggest overlap between schizotypy and schizophrenia both on cognitive‐perceptual and neurophysiological levels. However, deficits in frontal motor areas observed during pursuit in schizophrenia were not seen here, suggesting the operation of additional genetic and/or illness‐related influences in the clinical disorder. Hum Brain Mapp, 36:340–353, 2015. © 2014 Wiley Periodicals, Inc.
A novel soft-commutating isolated boost full-bridge ZVS-PWM DC-DC converter for bidirectional high power applications

A soft-commutating method and control scheme for an isolated boost full bridge converter is proposed in this paper to implement dual operation of the well-known soft switching full bridge DC/DC (buck) converter for bi-directional high power applications. It provides a unique commutation logic to minimize a mismatch between current in the current-fed inductor and current in the leakage inductance of the transformer when commutation takes place, significantly reducing the power rating for a voltage clamping snubber and enabling use of a simple passive clamped snubber. To minimize the mismatch, the method and control scheme utilizes the resonant tank and freewheeling path in the existing full bridge inverter at the voltage-fed side to preset the current in the leakage inductance of the transformer in a resonant manner. Zero-voltage-switching (ZVS) is also achieved for all the switches at the voltage-fed side inverter in boost mode operation. The proposed soft-commutating method is verified through boost mode operation of a 3 kW bidirectional isolated full bridge DC/DC converter developed for fuel cell electric vehicle (EV) applications.
Emerging Physical Unclonable Functions With Nanotechnology

Physical unclonable functions (PUFs) are increasingly used for authentication and identification applications as well as the cryptographic key generation. An important feature of a PUF is the reliance on minute random variations in the fabricated hardware to derive a trusted random key. Currently, most PUF designs focus on exploiting process variations intrinsic to the CMOS technology. In recent years, progress in emerging nanoelectronic devices has demonstrated an increase in variation as a consequence of scaling down to the nanoregion. To date, emerging PUFs with nanotechnology have not been fully established, but they are expected to emerge. Initial research in this area aims to provide security primitives for emerging integrated circuits with nanotechnology. In this paper, we review emerging nanotechnology-based PUFs.
Inhibition of CD26/dipeptidyl peptidase IV activity in vivo prolongs cardiac allograft survival in rat recipients.

The CD26 antigen, one of the major costimulatory molecules in T cell activation, was shown to possess dipeptidyl peptidase IV (DPP IV) activity. Previously, we demonstrated that immunosuppressed kidney transplant patients exhibit lower DPP IV serum activity as compared with healthy individuals. In the present study, we analyzed the role of CD26/DPP IV in the immune cascade triggered by organ transplantation and leading to acute rejection of cardiac allografts in rat recipients. Transplantation of hearts from (Lewis x Brown Norway)F1 donors into Lewis hosts resulted in an early (24 hr) increase in cellular CD26 expression, followed by a rise in DPP IV serum activity, which peaked at day 6, i.e., before the time of actual graft loss. Specific targeting of DPP IV activity with a novel, low-molecular-weight inhibitor of the diphenyl-phosphonate group (prodipine) abrogated acute rejection and prolonged cardiac allograft survival to 14.0+/-0.9 days (P<0.0001). Prodipine treatment prevented the early peak of cellular CD26 expression and thoroughly suppressed systemic DPP IV activity. The inhibition of DPP IV was associated with severely impaired host cytotoxic T lymphocyte responses in vitro. These results demonstrate the role of CD26/DPP IV in alloantigen-mediated immune regulation in vivo and provide the first direct evidence that CD26/DPP IV plays an important role in the mechanism of allograft rejection. The model of targeting CD26/DPP IV may reveal essential interactions on the level of costimulatory alternate T cell activation pathways, allowing a more subtle approach for more selective immunosuppression in transplant recipients.
Non-uniform PPM and context tree models

The problem of optimizing PPM with the help of different choices of estimators and their parameters for different subsets of nodes in the context tree is considered. Methods of such optimization for Markov chain and context tree models for individual files and over given sets of files are presented, and it is demonstrated that the extension from Markov chain models to context tree models is necessary to receive significant improvements of the compression ratio.
[Follow-up of patients with osteosarcoma and Ewing's sarcoma: a retrospective cost-benefit analysis].

PURPOSE Determination of the respective roles of clinical investigation, laboratory tests and various imaging techniques in the follow up of children and adolescents with osteosarcoma and Ewing's sarcoma. METHODS In a retrospective monocenter analysis, charts of 72 patients with osteosarcoma and 47 patients with Ewing's sarcoma were reviewed with respect to ability of different diagnostic methods to detect the relapse, and correlated outcome. RESULTS In about 25% of relapses, a second remission could be achieved. The most sensitive methods to detect a potentially curable relapse were clinical investigations and chest x-ray in the case of osteosarcoma and chest x-ray and whole body scintigraphy in the case of Ewing's sarcoma. CONCLUSIONS The different value of diagnostic methods in the follow-up of the two illnesses may be explained by the different tumor biologies and by distinct therapeutic strategies for the treatment of relapses in the two tumor entities. However, an ongoing evaluation of current follow-up strategies is necessary to take into account new therapeutic developments which may shift the importance of certain imaging techniques.
Lectin binding sites on human endocervix: A comparison with secretory and proliferative endometrium

Endocervix and corresponding endometrium of women of reproductive age were studied histochemically with 13 fluorescein isothiocyanate‐labeled lectins to delineate the differences between the epithelial cells in two anatomical sites. Lectin from Maclura pomifera (MPA), Ulex europaeus (UEA‐I), Glycine max (SBA), and Vicia villosa (VVA) bound only to endocervical epithelium and were the only four lectins that distinguished endocervical from endometrial epithelium. These differences were independent of menstrual cyclic changes and blood group antigen secretion. These data show that lectins can be used to histochemically distinguish endocervical from endometrial glands.
Dynamic Contrast-Enhanced Magnetic Resonance Imaging for Assessing Tumor Vascularity and Vascular Effects of Targeted Therapies in Renal Cell Carcinoma

Traditional cross-sectional tumor imaging focuses solely on tumor morphology. With the introduction of targeted biological therapies in human trials, morphologic change may lag behind other physiologic measures of response on clinical images. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a new imaging method for assessing the physiologic state of tumor vascularity in vivo. DCE-MRI, which uses available imaging techniques and contrast agents, assays the kinetics of tumor enhancement during bolus i.v. contrast administration. Modeling of the temporal enhancement pattern yields physiologic variables related to tumor blood flow and microvessel permeability. Changes in these variables after vascular-targeted therapy can then be quantified to evaluate the tumor vascular response. As these responses may precede morphologic tumor shrinkage, DCE-MRI might serve as a noninvasive means of monitoring early tumor response to vascular-targeted therapy. Renal cell carcinoma provides an excellent model for assessing the effect on DCE-MRI in clinical trials. The vascular richness of renal tumors provides a large dynamic scale of DCE-MRI measures. Patients with disseminated renal cell carcinoma frequently present with one or several large tumors, creating an easy imaging target for DCE-MRI evaluation. Finally, renal cell carcinoma is clearly susceptible to therapies that target tumor angiogenesis. DCE-MRI can be used to monitor the vascular changes induced by such therapies. Future efforts must be directed to standardizing image acquisition and analysis techniques to quantify tumor vascular responses.
Effects of self-action observation on standing balance learning: A change of brain activity detected using functional near-infrared spectroscopy.

BACKGROUND Studies suggest that the observation of others' actions leads to enhanced motor skill learning. OBJECTIVE We examined whether others' or self-action observation is effective for standing balance learning. In addition, we examined cortical activation during action observation using functional near-infrared spectroscopy. METHODS Thirty-nine healthy young subjects were assigned randomly to the Control, Other-Observation (O-O), and Self-Observation (S-O) groups. The subjects learned to stand on a tilting platform while maintaining a horizontal position. The Control group alternated each trial with a rest period. The O-O and S-O groups were provided with information related to their performance during the rest period: the O-O group observed another person, while the S-O group observed their previous performance. Cortical activation was assessed by changes of hemoglobin oxygenation (oxyHb). RESULTS A 2-way analysis of variance with repeated measures on balance performance revealed a significant difference in post-training (p < 0.05) and retention (p < 0.01) only in the S-O group. And an increase of oxyHb levels at post-training in the S-O group was observed in the supplementary motor area. CONCLUSION Self-action observation improved standing balance and brain activity during training and at 24 h after training.
Cell-Kinetic Evidence for Increased Recruitment of Cycling Epidermal Cells in Psoriasis: The Ratio of Histone and Ki-67 Antigen Expression Is Constant

Background: One of the hallmarks of the psoriatic plaque is increased epidermal proliferation. Whether this is the result of an increased recruitment of cycling epidermal cells or a decrease in cell cycle time has been a matter of debate for years. Objective: Calculating cell-kinetic information from the number of S phase cells in psoriasis by in situ hybridisation using a histone probe and the number of cycling epidermal cells by immunohistochemistry using the MIB-1 antibody. Methods: Immunohistochemistry and non-isotopic in situ hybridisation were performed on serial sections of 33 untreated psoriatic samples and 14 tacalcitol-treated samples. Results: The labelling index (number of cells in S phase/number cycling cells per millimetre length of section) in psoriatic untreated as well as in treated plaques is 16%. The amount of S phase cells in our experiment is equal compared with the number of cells in S phase as determined by BrdU incorporation. Conclusion: Using this direct approach to study cell-kinetic behaviour of psoriatic skin, we reconfirm that the psoriatic abnormality is due to a defect in the G₀–G1 recruitment mechanism (by increased recruitment of G₀ cells), a decrease in apoptosis or an increase in the number of cell divisions in the transit-amplifying compartment, rather than a reduction in the cell cycle time.
An Improvement in Virologic Response to Highly Active Antiretroviral Therapy in Clinical Practice From 1996 Through 2002

Early studies of highly active antiretroviral therapy (HAART) use in clinical practice suggested suboptimal rates of viral suppression. HAART regimens and expertise in the use of HAART have since evolved, and we sought to determine how virologic response to HAART has changed in clinical practice. We compared all patients who started a first HAART regimen from 1996 through 2002 in a longitudinal cohort of HIV-infected patients in care in Baltimore. There were significant improvements in suppressing HIV RNA to <400 copies/mL, ranging from 43.8% (1996) to 72.4% (2001-2002) by 6 months and from 60.1% (1996) to 79.9% (2001-2002) by 12 months (both P < 0.01 for trend). There were also significant improvements in CD4 cell response. Over time, there was a significant increase in the use of a nonnucleoside reverse transcriptase inhibitor (NNRTI) or boosted protease inhibitor (PI) regimen compared with a single PI as well as an increase in the number of patients who were antiretroviral (ARV) naive. There was also a significant temporal trend from 1996 through 2002 in achieving a suppressed HIV RNA level, adjusting for being ARV naive, specific HAART regimen, CD4 cell count, HIV-1 RNA level, and demographic factors. This suggests that improved virologic response may also be attributable to other factors such as a greater focus on medication adherence, improved ARV tolerability, and ease of dosing.
Bioaccumulation of waterborne Ni in Dreissena polymorpha: A stable isotope experiment to assess the effect of zinc, calcium, and dissolved organic matter

The effect of Ca, Zn, and dissolved natural organic matter (NOM) on waterborne Ni accumulation was investigated in a freshwater mussel. An enriched stable metal isotope tracer was required to measure the Ni uptake rate accurately. Zebra mussels were exposed to environmentally relevant concentrations of 62Ni (from 0.5 to 8 µg/L) for 48 h in media spiked with Ca, Zn, or dissolved NOM. The 62Ni uptake was inhibited by Ca (from 0.138 ± 0.021 to 0.061 ± 0.010 L/g/d for Ca concentrations ranging from 43 to 133 mg/L) and enhanced by Zn (from 0.051 ± 0.006 to 0.109 ± 0.007 L/g/d for Zn concentrations ranging from 6.6 to 38.3 µg/L). The mechanisms behind the synergistic effect of Zn remain unclear, yet it can be hypothesized that Ni uptake is facilitated by Zn‐dependent transport sites. To formalize the effects of Ca and Zn, a model was proposed to express the Ni uptake rate as a function of the mussels' filtration rate and of Ca and Zn concentrations. The 62Ni uptake increased at low NOM concentrations and decreased at higher concentrations. This could be explained by the influence of NOM on both the speciation of Ni and the filtration activity of mussels. At high NOM concentrations, a modification of the membrane's permeability might also have favored Ni uptake, although this was not clearly established in this study. Therefore, the effect of water composition on Ni bioavailability to zebra mussels cannot be predicted by competition and complexation models alone, because it also influences the animal's physiology. Environ. Toxicol. Chem. 2012;31:819–827. © 2012 SETAC
Factors contributing to mental health professionals' decision to use seclusion.

OBJECTIVE The authors constructed an explanatory model of factors contributing to the decision to use seclusion. METHODS Experts helped develop 64 vignettes that manipulated multiple patient and environmental variables. Eighty-two mental health professionals working on inpatient wards in four institutes in the Netherlands rated the vignettes. A univariate general linear model examined vignette variables and rater characteristics influencing the decision to use seclusion. RESULTS Almost half of the decision to seclude (46%) could be explained by a combination of rater characteristics and vignette variables. Rater characteristics explained 31.7%, and vignette variables explained 27.9% (with a 13.6% interaction effect). Rater characteristics, in order of explanatory influence, were type of care provided by the professional (such as on a crisis-intensive care or an observation-diagnostic unit), current frequency of participation in seclusion, the specific institute where the professional was employed (of the four participating institutes), experience using seclusion (number of years), and being in training to be a psychiatrist or a community mental health nurse. The primary vignette variables, in order of influence, were the approachability of the patient, seriousness of danger, availability of patient rooms and space, primary diagnosis, the professional's perceived trust in colleagues, staff-patient ratio during the shift, and voluntary or involuntary status. CONCLUSIONS The model explained nearly half of the decision by mental health professionals to seclude vignette patients. Rater characteristics were at least as important as patient variables, including problem behaviors and diagnosis, and ward features. Because perceived approachability of the patient was a key factor, seclusion reduction policies should focus on supporting professionals in their efforts to manage inpatients with problem behaviors in an appropriate way.
Vesiculo-erosive Oral Mucosal Disease—Management with Topical Corticosteroids: (1) Fundamental Principles and Specific Agents Available

Vesiculo-erosive diseases of the oral mucosa pose a major challenge in oral medicine, because they are chronic, painful, and interfere with the daily activities and quality of life of the patients, including disturbing eating, drinking, talking, and personal relationships. Many are autoimmune diseases, and corticosteroid therapy is currently central to their treatment. These diseases present with inflammation and alterations to epithelial integrity, through cell and/or humoral immunity-mediated attack on epithelial-connective tissue targets. Until recently, despite their serious adverse effects, it was necessary to prescribe systemic corticosteroids to control severe erosive oral diseases. Now, however, many of these diseases can be controlled by high-potency topical corticosteroids, which have proved to be highly efficacious and to cause fewer adverse effects compared with systemic corticosteroids. Nevertheless, although topical corticosteroids are still the most widely used drugs in the practice of oral medicine, the scientific body of evidence for their use in the oral cavity is virtually non-existent, and therefore many of the protocols followed are, of necessity, drawn from experience of their use in a dermatological setting. This review aims to set out the key aspects of the use of topical corticosteroids in oral medicine. The issues covered include the indications and basic rules for their use, the types of corticosteroids, the drug selection, and the specific formulations.