Miracle-dz/UniFAR-FTUs huggingface dataset:
Agreement of serum allergen test results with unblocked and blocked IgE against cross‐reactive carbohydrate determinants (CCD) and intradermal test results in atopic dogs

BACKGROUND Tests for allergen-specific immunoglobulin E (IgE) are used to select allergens for immunotherapy in atopic dogs. Antibodies against cross-reactive carbohydrate determinants (anti-CCD IgE) have been identified in serum samples of atopic dogs. Their presence in humans is a known cause of clinically irrelevant polysensitization to plant allergens. OBJECTIVES To compare the results of an intradermal test (IDT) and a serum test for allergen-specific IgE, with and without blocking anti-CCD IgE, before testing in dogs. ANIMALS Thirty-one privately owned dogs with atopic dermatitis. METHODS AND MATERIALS Dogs were prospectively skin tested and their serum samples were analysed for anti-CCD IgE. An Fc-ε receptor-based serum test for allergen-specific IgE was performed with and without blocking anti-CCD IgE. RESULTS In dogs with negative anti-CCD IgE samples, the agreement between the results of the serum test and the IDT was substantial (κ = 0.71). Dogs with positive anti-CCD IgE samples (38.7%) showed no agreement between serum and skin testing (κ = -0.35), blocking anti-CCD IgE in those samples resulted in a fair agreement (κ = 0.43). Anti-CCD IgE positive sera had multiple positive results for grass and weed allergens, and blocking decreased them markedly. CONCLUSION AND CLINICAL IMPORTANCE Intradermal testing agreed best with serum testing in dogs with no detectable anti-CCD IgE. Sera containing anti-CCD IgE had no agreement with IDT. Test agreement was improved by blocking the anti-CCD IgE. Apparent serum test polysensitization to plant allergens was associated with anti-CCD IgE.
Noninvasive Diagnosis of Irritable Bowel Syndrome via Bowel Sound Features: Proof of Concept

INTRODUCTION: Irritable bowel syndrome (IBS) is a common and debilitating disorder estimated to affect approximately 11% of the world's population. Typically, IBS is a diagnosis of exclusion after patients undergo a costly and invasive colonoscopy to exclude organic disease. Clinician's and researchers have identified a need for a new cost-effective, accurate, and noninvasive diagnostic test for IBS. METHODS: Using a diagnostic case-control study, we explored the use of bowel sounds to characterize IBS with a view to diagnostic use. We recruited participants with an existing clinical diagnosis of IBS or healthy (asymptomatic) digestive systems. We recorded bowel sounds for 2 hours after fasting and then for 40 minutes after a standard meal. RESULTS: We here report our results including our accuracy in characterizing IBS-related bowel sounds and differentiation between participants with IBS and healthy participants. Leave-one-out cross-validation of our model developed using the first 31 IBS and 37 healthy participants gave 90% sensitivity and 92% specificity for IBS diagnosis. Independent testing using the next 15 IBS and 15 healthy participants demonstrated 87% sensitivity and 87% specificity for IBS diagnosis. CONCLUSIONS: These preliminary results provide proof of concept for the use of bowel sound analysis to identify IBS. A prospective study is needed to confirm these findings. TRANSLATIONAL IMPACT: Our belt and model offer hope of a new approach for IBS diagnosis in primary practice. Combined with screening tests for organic disease, it would offer greater confidence to patients and could reduce the burden of unnecessary colonoscopies for health care systems and patients.
Allergic Signs in Glioma Pathology: Current Knowledge and Future Perspectives

Historically restrained to immune defense against parasite infections, allergic inflammation has been recently rediscovered to protect from a wide array of environmental triggers, such as xenobiotics and carcinogens, which can induce DNA damage and ultimately lead to cancer development. Moreover, cells and mediators typical of allergic responses can importantly modulate the tissue inflammatory milieu, which represents a crucial gatekeeper towards the acquisition of malignancy by cancer cells through immune escape. Numerous studies have described an inverse association between allergies and glioma development. Mast cells, key players of allergic reactions, have been recently found at increased numbers in glioblastoma multiforme (GBM), the most common and lethal primary brain tumor, and they have been implicated in GBM pathogenesis. In this review, we summarize epidemiological studies and discuss the main evidence highlighting a potential interplay between allergic responses, and glioma formation and progression. Last, we draw future lines of research for better clarification whether and through which mechanisms allergic inflammation might impact on gliomagenesis. The comprehension of the immune mechanisms favoring or counteracting tumor growth might open the path to novel immunotherapy approaches.
Regorafenib induces lethal autophagy arrest by stabilizing PSAT1 in glioblastoma

ABSTRACT GBM (glioblastoma multiforme) is the most common and aggressive brain tumor with no curative options available. Therefore, it is imperative to develop novel potent therapeutic drugs for GBM treatment. Here, we show that regorafenib, an oral multi-kinase inhibitor, exhibits superior therapeutic efficacy over temozolomide, the first-line chemotherapeutic agent for GBM treatment both in vitro and in vivo. Mechanistically, regorafenib directly stabilizes PSAT1 (phosphoserine aminotransferase 1), a critical enzyme for serine synthesis, to trigger PRKAA-dependent autophagy initiation and inhibit RAB11A-mediated autophagosome-lysosome fusion, resulting in lethal autophagy arrest in GBM cells. Maintenance of PSAT1 at a high level is essential for regorafenib-induced GBM suppression. Together, our data provide novel mechanistic insights of regorafenib-induced autophagy arrest and suggest a new paradigm for effective treatment of GBM. Abbreviations: 3-MA: 3-methyladenine; ACACA: acetyl coenzyme A carboxylase alpha; ACTB/β-actin: actin, beta; AMPK: adenosine monophosphate-activated protein kinase; ATG5: autophagy related 5; CTSD: cathepsin D; DN-: dominant-negative; GBM: glioblastoma multiforme; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; PIK3C3/VPS34: phosphatidylinositol 3-kinase catalytic subunit type 3; PRKAA/AMPKα: protein kinase AMP-activated catalytic subunit alpha; PSAT1: phosphoserine aminotransferase 1; SQSTM1/p62: sequestosome 1; TKIs: tyrosine kinase inhibitors.
CyTOF®: A New Tool to Decipher the Immunomodulatory Activity of Daratumumab

CD38-targeted therapy is emerging as one of the most effective immunotherapies ever developed for the treatment of multiple myeloma (MM) (1). CD38 is a transmembrane glycoprotein that serves as a receptor with a multifunctional ecto-enzymatic activity, which is highly expressed on plasmacells, but also on several other cells belonging to the hemopoietic as well as to the non-hemopoietic tissues (2). Daratumumab, a fully human IgG1-kappa monoclonal antibody, is the first-in-class antibody targeting CD38. It has rapidly become a cornerstone of the anti-MM treatment, showing activity both as single agent in heavily pretreated MM patients and in combination with other agents. To date, daratumumab has been approved for newly diagnosed MM patients not eligible for autologous transplant in combination with bortezomib-melphalan-prednisone (D-VMP), and for relapsed/refractory (RR)MM patients as monotherapy or in combination with lenalidomide-dexamethasone (D-Rd), bortezomib-dexamethasone (D-Vd) (in the European Union), and pomalidomide-dexamethasone (D-Pd) (in the United States). Despite the great efficacy displayed by daratumumab, all responding patients ultimately acquire resistance to the drug and progress while on therapy; a better knowledge of its mechanisms of action and of the various mechanisms of resistance is essential for optimal development and use of these treatment options. CD38-targeted therapy represents a unique opportunity to concurrently impact on tumor cells and tumor microenvironment (2) because CD38 is expressed on myeloma cells, immune effector cells (natural killer [NK] cells, cytotoxic T cells, B cells, Vγ9Vδ2 T cells), and inhibitory cells, such as regulatory T cells (Tregs), regulatory B cells (Bregs), and myeloid-derived suppressor cells (MDSCs). Daratumumab exploits classic Fc-dependent immune effector mechanisms, including antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), complement-dependent cytotoxicity (CDC), and apoptosis upon secondary cross-linking, which are dependent on CD38 expression on the tumor cells (3). Because CD38 is expressed on various immune cell populations, the potential immunomodulatory effects of daratumumab monotherapy in RRMM patients have recently been investigated, showing a multifaceted immunomodulatory role for daratumumab through the eradication of CD38-positive immune suppressor cells (e.g., Tregs, Bregs, and MDSCs) (4). The disappearance of an immunosuppressive contexture results in CD4+ and CD8+ T cell expansion, alloreactive functional T-cell responses, increased T-cell clonality, and in a potentially better host’s anti-tumor immune response. Moreover, it has been shown that daratumumab may also reduce adenosine production in the bone marrow microenvironment through the modulation of CD38 enzymatic activity both on tumor cells and on cytotoxic T cells, thus promoting their antitumor activity (5). The immunomodulatory functions of daratumumab contributed to elucidate the significant clinical benefits and
Shape Optimization of an Electric Dipole Array for 7 Tesla Neuroimaging

Radio-frequency (RF) arrays constructed using electric dipoles have potential benefits for transmit and receive applications using the ultra-high field (UHF) MRI. This paper examines some of the implementation barriers regarding dipole RF arrays for human head imaging at 7 T. The dipole array was constructed with conformal, meandered dipoles with dimensions selected utilizing an evolutionary-based optimization routine to shape-optimize the dipole structure. Coupling matrix synthesis (CMS) was utilized to decouple the dipole array. Mean and worst-case transmission between nearest-neighbour dipoles was −17.2 and −15.5 dB, respectively (±2.4 dB). Transmit efficiencies of 24.6 nT/V for the entire brain and 26.0 nT/V across the axial slice were observed. The total and peak 10-g SAR, normalized to 1 Watt accepted input power per channel, was 0.163 and 0.601 W/kg, respectively. Maximum and mean noise correlations were −17 dB and −32 dB, respectively. The use of both CMS and a novel shape optimization routine to design a dipole array translated into sufficient transmit uniformity with a simultaneous reduction in 10-g SAR in comparison to a non-optimized dipole array of the same geometry. As a receiver, the dipole array maintained high orthogonality between elements, resulting in strong parallel imaging performance.
Understanding the Model Size Effect on SEM Fit Indices

This study investigated the effect the number of observed variables (p) has on three structural equation modeling indices: the comparative fit index (CFI), the Tucker–Lewis index (TLI), and the root mean square error of approximation (RMSEA). The behaviors of the population fit indices and their sample estimates were compared under various conditions created by manipulating the number of observed variables, the types of model misspecification, the sample size, and the magnitude of factor loadings. The results showed that the effect of p on the population CFI and TLI depended on the type of specification error, whereas a higher p was associated with lower values of the population RMSEA regardless of the type of model misspecification. In finite samples, all three fit indices tended to yield estimates that suggested a worse fit than their population counterparts, which was more pronounced with a smaller sample size, higher p, and lower factor loading.
Non-equivalence of direct and indirect measures of unrealistic optimism

Individuals typically believe that they are less likely than the average person to experience negative events. Such ‘unrealistic optimism’ (UO) has been assessed in two ways: directly (via a single question, requiring comparison of own risk to that of the average person) and indirectly (via separate questions about own risk and that of the average person). The study examined the equivalence of the direct and indirect measures of female students' UO for unwanted pregnancy. Participants (n = 120) answered questions about their own risk, that of the average female student, and their own risk relative to that of the average female student; responses and response times were recorded. There was only a moderate association between direct- and indirect-UO. Direct-UO was strongly associated with estimate of own risk, but only moderately associated with estimate of the average student's risk. Response times for the comparative risk and own risk questions did not differ, but participants took significantly longer to answer the question about average student's risk. The results suggest that the two measures of UO are not equivalent, but, rather, that individuals answering a comparative risk question focus mainly on their own risk, at the expense of that of the average person.
Hippocampus Segmentation Based on Iterative Local Linear Mapping With Representative and Local Structure-Preserved Feature Embedding

Hippocampus segmentation plays a significant role in mental disease diagnoses, such as Alzheimer’s disease, epilepsy, and so on. Patch-based multi-atlas segmentation (PBMAS) approach is a popular method for hippocampus segmentation and has achieved a promising result. However, the PBMAS approach needs high computation cost due to registration and the segmentation accuracy is subject to the registration accuracy. In this paper, we propose a novel method based on iterative local linear mapping (ILLM) with the representative and local structure-preserved feature embedding to achieve accurate and robust hippocampus segmentation with no need for registration. In the proposed approach, semi-supervised deep autoencoder (SSDA) exploits unsupervised deep autoencoder and local structure-preserved manifold regularization to nonlinearly transform the extracted magnetic resonance (MR) patch to embedded feature manifold, whose adjacent relationship is similar to the signed distance map (SDM) patch manifold. Local linear mapping is used to preliminarily predict SDM patch corresponding to the MR patch. Subsequently, threshold segmentation generates a preliminary segmentation. The ILLM refines the segmentation result iteratively by ensuring the local constraints of embedded feature manifold and SDM patch manifold using a space-constrained dictionary update. Thus, a refined segmentation is obtained with no need for registration. The experiments on 135 subjects from ADNI dataset show that the proposed approach is superior to the state-of-the-art PBMAS and classification-based approaches with mean Dice similarity coefficients of 0.8852±0.0203 and 0.8783 ± 0.0251 for bilateral hippocampus segmentation of 1.5T and 3.0T datasets, respectively.
Extensive mechanical tension promotes annulus fibrosus cell senescence through suppressing cellular autophagy

Background: Mechanical load contributes a lot to the initiation and progression of disc degeneration. Annulus fibrosus (AF) cell biology under mechanical tension remains largely unclear. Objective: The present study was aimed to investigate AF cell senescence under mechanical tension and the potential role of autophagy. Methods: Rat AF cells were cultured and experienced different magnitudes (5% elongation and 20% elongation) of mechanical tension for 12 days. Control AF cells were kept static. Cell proliferation, telomerase activity, cell cycle fraction, and expression of senescence-related molecules (p16 and p53) and matrix macromolecules (aggrecan and collagen I) were analyzed to evaluate cell senescence. In addition, expression of Beclin-1 and LC3, and the ratio of LC3-II to LC3-I were analyzed to investigate cell autophagy. Results: Compared with the control group and 5% tension group, 20% tension group significantly decreased cell proliferation potency and telomerase activity, increased G1/G0 phase fraction, and up-regulated gene/protein expression of p16 and p53, whereas down-regulated gene/protein expression of aggrecan and collagen I. In addition, autophagy-related parameters such as gene/protein expression of Beclin-1 and LC3, and the ratio of LC3-II to LC3-I, were obviously suppressed in the 20% tension group. Conclusion: High mechanical tension promotes AF cell senescence though suppressing cellular autophagy. The present study will help us to better understand AF cell biology under mechanical tension and mechanical load-related disc degeneration.
Effects of topical negative pressure therapy on perfusion and microcirculation of human skin.

BACKGROUND Topical negative pressure wound therapy (TNPWT) is one of the most frequently used techniques in wound treatment. But the underlying mechanism remains unclear. One possible explanation is an improved microcirculation by TNPWT. OBJECTIVE This study investigated the influence of TNPWT on microcirculation on intact skin in real-time. METHODS In healthy individuals, we performed a combined tissue - laser/photo - spectrometry technique to monitor changes of 4 different microcirculation parameters in real-time: The local blood flow, the capillary-venous oxygen saturation, the blood flow velocity and the relative amount of hemoglobin. We compared these parameters using two different protocols: a continuously (VAC ON 60/OFF 60) and discontinuously (VAC ON 30/OFF 60/ON 5) application. RESULTS Our results demonstrate a significant increase of all four measured parameters during the active TNPWT and the pressure free period. The comparison of two different protocols shows an advantage of the examined parameters using a discontinuous TNPWT application. CONCLUSIONS Our study demonstrated the changes of the microvascular tissue perfusion in intact human skin under the conditions of negative pressure and may thereby offer a broader understanding about the mechanism of the TNPWT.
Dissipation of Three Fungicides and Their Effects on Anthocyanins and Color of Monastrell Red Wines

The effect of fungicides on fermentation is of paramount importance to control the quality and safety of wines. In this work, the quality (enological parameters, color, phenolic content, antioxidant activity, and fungicide residues) of wines from Monastrell grapes fortified with iprovalicarb, mepanipyrim, and tetraconazole fungicides was evaluated. Along the winemaking process, initial residues of mepanipyrim and tetraconazole were removed in more than 90% while the dissipation of iprovalicarb was around 73%. Significant statistical differences were found in the presence of iprovalicarb and mepanipyrim residues, especially at the highest concentration assayed. For both fungicides, increases in the volatile acidity (between 4 and 8.6 times), the lactic acid content (between 8.6 and 20.5 times), the percentage of polymeric anthocyanins (between 1.3 and 1.7 times), and also a slight increase of the total phenolic index and the total anthocyanin content determined by spectrophotometry were observed. On the contrary, the total monomeric anthocyanins content decreased about 16.3% and 28.6% in the presence of iprovalicarb and mepanipyrim, respectively. These results could be related to a higher development of acetic acid or lactic bacteria in the presence of these fungicides. The color of the final wines was also different in comparison with the control, with a higher yellow component, color intensity, tonality, and hue angle because of pH changes in the medium. Tetraconazole fermentations had a more similar trend to the control wine, probably due to the lower concentration of this fungicide in the grape must at the initial time. No effects on the antioxidant activity was observed for any of the target fungicides. A multivariate statistical analysis was done to view the interrelationships between different variables (color and anthocyanins profile). The obtained model allowed the wines to be separated according to the fungicide treatment applied.
Self-assessment of clinical competence with LGBT patients at a pediatric hospital

ABSTRACT Hospital social workers were asked to complete the LGBT-DOCSS, a validated self-assessment of clinical competence, attitudes, and knowledge about working with lesbian, gay, bisexual (LGB), and transgender patients. As a group, they held positive attitudes about LGBT patients (Mean 6.9/7, SD .22) but were less confident about their knowledge (Mean 5.9/7, SD 0.96) and clinical preparedness (Mean 5.0/7, SD 1.24). In addition, providers felt significantly less competent about working with transgender than LGB patients. Factors that affected domains of self-assessed competence including experience working with LGB or transgender patients and the year training was completed.
Sexual Selection, Agonistic Signaling, and the Effect of Beards on Recognition of Men’s Anger Displays

The beard is arguably one of the most obvious signals of masculinity in humans. Almost 150 years ago, Darwin suggested that beards evolved to communicate formidability to other males, but no studies have investigated whether beards enhance recognition of threatening expressions, such as anger. We found that the presence of a beard increased the speed and accuracy with which participants recognized displays of anger but not happiness (Experiment 1, N = 219). This effect was not due to negative evaluations shared by beardedness and anger or to negative stereotypes associated with beardedness, as beards did not facilitate recognition of another negative expression, sadness (Experiment 2, N = 90), and beards increased the rated prosociality of happy faces in addition to the rated masculinity and aggressiveness of angry faces (Experiment 3, N = 445). A computer-based emotion classifier reproduced the influence of beards on emotion recognition (Experiment 4). The results suggest that beards may alter perceived facial structure, facilitating rapid judgments of anger in ways that conform to evolutionary theory.
Training Analysts to Work With Unconscious Embodied Expressions: Theoretical Underpinnings and Practical Guidelines

In this paper it is suggested that by incorporating embodied practices from bodywork and the performing arts analytic training could be enriched and promote the development of countertransference awareness for body sensations and movement. The historical background and theoretical underpinnings of an analytical training program focusing on embodied subjectivity, intersubjectivity, and objectivity, aimed at integrating experiences of self, other, and interaction, is outlined. The paper describes and discusses the training program developed at the Norwegian Character Analytic Institute over a 10-year period, featuring nonverbal, embodied ways of presenting and working with cases at seminars and in connection with supervision.