Miracle-dz/UniFAR-FTUs huggingface dataset:
Tumor Markers in Pancreatic Cystic Fluids for Diagnosis of Malignant Cysts

Background and aim Early diagnosis of premalignant or malignant pancreatic cysts is essential to improve prognosis. Sampling of pancreatic cyst fluid by fine-needle aspiration during endoscopic ultrasonography (EUS) enables cytopathological examination combined with biochemical analysis. This study aimed to provide an aid based on biological markers for the preoperative management of patients with pancreatic cysts. Methods Pancreatic fluids obtained by EUS-guided fine-needle aspiration from 115 patients with cystic lesions were assayed for amylase, lipase, carcinoembryonic antigen (CEA), CA 19-9 and CA 72-4. In addition, chromogranin A (CgA) and neuron-specific enolase (NSE) were measured in 28 fluid samples. Results ROC curve analysis of the different markers for diagnosis of mucinous cysts showed that CEA had the highest area under the curve (0.93, 95% CI 0.87-0.97), with a sensitivity and specificity of 89% and 93%, respectively, at the cutoff value of 317 μg/L. The CgA and NSE concentrations in 5 NET cysts (median values of 210 [63-492] and 68.5 [9-496] μg/L, respectively) were higher than in 23 other cysts (median values of 8 [7-828] and 2.7 [0.5-35.8] μg/L, respectively) (p = 0.0015 and p = 0.0045, respectively). Conclusions CEA is the best marker for identifying a cyst as mucinous. In case of low levels of CEA, our results suggest that CgA and NSE measurements may be helpful in the diagnosis of a neuroendocrine tumor and therefore deserve further investigation.
Italian cultural adaptation of the Memorial Anxiety for Prostate Cancer scale for the population of men on active surveillance

Purpose: The Memorial Anxiety Scale for Prostate Cancer (MAX-PC) is a self-report questionnaire that was developed in English to assess prostate cancer (PCa)-related anxiety. The aim of this study was to perform a cultural adaptation for the tool to be used in a population of Italian men on active surveillance (AS). Methods: A total of 222 patients with localized PCa who were recruited for the Prostate Cancer Research International: Active Surveillance (PRIAS) protocol completed the MAX-PC. Psychometric analysis was performed to assess reliability indexes. A Spearman rank correlation was used to test the association between MAX-PC scales and other questionnaires and was used for longitudinal analysis. Results: Cronbach coefficients and item to total correlation demonstrated good internal consistency. Some items related to the repetition of the PSA test showed a large floor effect and thus were poorly effective in measuring anxiety for PSA testing in patients on AS. Confirmatory factor analysis partly failed to reproduce the structure of the original version. A modified version of MAX-PC, excluding the items with a large floor effect, was thus considered for AS patients. Factor analysis on this version demonstrated considerable consistency with the presence of 3 subscales: anxiety related to PCa, anxiety related to PSA testing, and anxiety related to the fear of tumor progression. Longitudinal analysis showed an acceptable validity over time. The MAX-PC was correlated with the anxious preoccupation subscale of the Mini-Mental Adjustment to Cancer scale. Conclusions: A slightly modified version of the MAX-PC was developed for use in Italian men on AS. This instrument appears to be a valid and reliable tool that measures anxiety in men with PCa who are enrolled in AS programs.
Interaction between intrinsically disordered regions in transcription factors Sp1 and TAF4

The expression of eukaryotic genes is precisely controlled by specific interactions between general transcription initiation factors and gene‐specific transcriptional activators. The general transcription factor TFIID, which plays an essential role in mediating transcriptional activation, is a multisubunit complex comprising the TATA box‐binding protein (TBP) and multiple TBP‐associated factors (TAFs). On the other hand, biochemical and genetic approaches have shown that the promoter‐specific transcriptional activator Sp1 has the ability to interact with one of the components of TFIID, the TBP‐associated factor TAF4. We herein report the structural details of the glutamine‐rich domains (Q‐domains) of Sp1 and TAF4 using circular dichroism (CD) and heteronuclear magnetic resonance (NMR) spectroscopy. We found that the two Q‐domains of Sp1 and four Q‐domains of TAF4 were disordered under physiological conditions. We also quantitatively analyzed the interaction between the Q‐domains of Sp1 and TAF4 by NMR and surface plasmon resonance, and detected a weak but specific association between them. Nevertheless, a detailed analysis of CD spectra suggested that any significant conformational change did not occur concomitantly with this association, at least at the level of the overall secondary structure. These results may represent a prominent and exceptional binding mode for the IDPs, which are not categorized in a well‐accepted concept of “coupled folding and binding. ”
Feedforward Coordinate Control of a Robotic Cell Injection Catheter

Remote and robotically actuated catheters are the stepping-stones toward autonomous catheters, where complex intravascular procedures may be performed with minimal intervention from a physician. This article proposes a concept for the positional, feedforward control of a robotically actuated cell injection catheter used for the injection of myogenic or undifferentiated stem cells into the myocardial infarct boundary zones of the left ventricle. The prototype for the catheter system was built upon a needle-based catheter with a single degree of deflection, a 3-D printed handle combined with actuators, and the Arduino microcontroller platform. A bench setup was used to mimic a left ventricle catheter procedure starting from the femoral artery. Using Matlab and the open-source video modeling tool Tracker, the planar coordinates (y, z) of the catheter position were analyzed, and a feedforward control system was developed based on empirical models. Using the Student’s t test with a sample size of 26, it was determined that for both the y- and z-axes, the mean discrepancy between the calibrated and theoretical coordinate values had no significant difference compared to the hypothetical value of µ = 0. The root mean square error of the calibrated coordinates also showed an 88% improvement in the z-axis and 31% improvement in the y-axis compared to the unmodified trial run. This proof of concept investigation leads to the possibility of further developing a feedfoward control system in vivo using catheters with omnidirectional deflection. Feedforward positional control allows for more flexibility in the design of an automated catheter system where problems such as systemic time delay may be a hindrance in instances requiring an immediate reaction.
Probing large viscosities in glass-formers with nonequilibrium simulations

Significance As a liquid cools, molecules move more slowly and the viscosity rises. A fundamental question is whether this trend continues smoothly down to zero temperature, or if flow stops at a finite temperature where the material undergoes a transition to a glass phase. Direct measurements of growing viscosities become difficult as the time for motion exceeds years or centuries. We describe and test an approach for obtaining large viscosities using nonequilibrium molecular dynamics simulations. Results agree with existing experiments on the model glass-former squalane and allow viscosities over 10 orders of magnitude larger to be predicted. The temperature dependence at fixed pressure or density is consistent with a gradual slowing of dynamics, rather than a finite-temperature divergence in viscosity. For decades, scientists have debated whether supercooled liquids stop flowing below a glass transition temperature Tg0 or whether motion continues to slow gradually down to zero temperature. Answering this question is challenging because human time scales set a limit on the largest measurable viscosity, and available data are equally well fit to models with opposite conclusions. Here, we use short simulations to determine the nonequilibrium shear response of a typical glass-former, squalane. Fits of the data to an Eyring model allow us to extrapolate predictions for the equilibrium Newtonian viscosity ηN over a range of pressures and temperatures that change ηN by 25 orders of magnitude. The results agree with the unusually large set of equilibrium and nonequilibrium experiments on squalane and extend them to higher ηN. Studies at different pressures and temperatures are inconsistent with a diverging viscosity at finite temperature. At all pressures, the predicted viscosity becomes Arrhenius with a single temperature-independent activation barrier at low temperatures and high viscosities (ηN>103 Pa⋅s). Possible experimental tests of our results are outlined.
Involvement of Fas/Fas ligand system‐mediated apoptosis in the development of concanavalin A‐induced hepatitis

Concanavalin A (Con A)‐induced hepatitis is an experimental hepatitis model in which hepatic injury is caused by the action of cytokines produced by T cells. Using IFN‐γ‐deficient mice, we previously demonstrated that IFN‐γ plays a central role in Con A‐induced hepatitis. Here, we show that development of the disease is completely suppressed in gld/gld mice, in which Fas ligand is defective. In contrast, suppression of the disease in lpr/lpr mice was incomplete, since a small amount of the fas mRNA was produced in these mice. The data indicate that activation of the Fas/Fas ligand system is a necessary step in the development of Con A‐induced hepatitis. Furthermore, we found that not only fas but also caspase‐1 expression was reduced in IFN‐γ‐deficient mice. Since caspase‐1 is an integral component of Fas signal transduction, these observations suggest that IFN‐γ‐induced activation of both fas and caspase‐1 expression causes enhancement of hepatocyte apoptosis resulting in the development of hepatitis.
Hypoxic Culture Promotes Dopaminergic-Neuronal Differentiation of Nasal Olfactory Mucosa Mesenchymal Stem Cells via Upregulation of Hypoxia-Inducible Factor-1α

Olfactory mucosa mesenchymal stem cells (OM-MSCs) display significant clonogenic activity and may be easily propagated for Parkinson’s disease therapies. Methods of inducing OM-MSCs to differentiate into dopaminergic (DAergic) neurons using olfactory ensheathing cells (OECs) are thus an attractive topic of research. We designed a hypoxic induction protocol to generate DAergic neurons from OM-MSCs using a physiological oxygen (O2) level of 3% and OEC-conditioned medium (OCM; HI group). The normal induction (NI) group was cultured in O2 at ambient air level (21%). The role of hypoxia-inducible factor-1α (HIF-1α) in the differentiation of OM-MSCs under hypoxia was investigated by treating cells with an HIF-1α inhibitor before induction (HIR group). The proportions of β-tubulin- and tyrosine hydroxylase (TH)-positive cells were significantly increased in the HI group compared with the NI and HIR groups, as shown by immunocytochemistry and Western blotting. Furthermore, the level of dopamine was significantly increased in the HI group. A slow outward potassium current was recorded in differentiated cells after 21 d of induction using whole-cell voltage-clamp tests. A hypoxic environment thus promotes OM-MSCs to differentiate into DAergic neurons by increasing the expression of HIF-1α and by activating downstream target gene TH. This study indicated that OCM under hypoxic conditions could significantly upregulate key transcriptional factors involved in the development of DAergic neurons from OM-MSCs, mediated by HIF-1α. Hypoxia promotes DAergic neuronal differentiation of OM-MSCs, and HIF-1α may play an important role in hypoxia-inducible pathways during DAergic lineage specification and differentiation in vitro.
Fully and quasi-dimensional constructions of schizotypy

This chapter concerns the dimensionality inherent to describe and understand schizotypy and schizotypal personality disorder (SPD). It concerns attempts that are being made to discover experimental paradigms to characterize the cognitive functioning of schizotypal and schizotypally disordered individuals; or, develop markers of cognitive nature that might be helpful in high-risk and genetics research. Two traditional views of dimensionality can be discerned, and roughly align to the psychiatric and psychological models. The psychiatric view of continuity is characteristically quasi-dimensional. Focusing on variations within the illness domain, and taking the abnormal state as its reference point, it construes dimensionality as degrees of expression of a disease process. Typical questions include diagnostic and nosological issues such as the relationship between full-blown psychosis and forms of personality disorder as possible formes frustes of disease: SPD in the case of schizophrenia. The fully dimensional takes normality or health as the starting point.
Extrusions are phagocytosed and promote Chlamydia survival within macrophages

The precise strategies that intracellular pathogens use to exit host cells have a direct impact on their ability to disseminate within a host, transmit to new hosts, and engage or avoid immune responses. The obligate intracellular bacterium Chlamydia trachomatis exits the host cell by two distinct exit strategies, lysis and extrusion. The defining characteristics of extrusions, and advantages gained by Chlamydia within this unique double‐membrane structure, are not well understood. Here, we define extrusions as being largely devoid of host organelles, comprised mostly of Chlamydia elementary bodies, and containing phosphatidylserine on the outer surface of the extrusion membrane. Extrusions also served as transient, intracellular‐like niches for enhanced Chlamydia survival outside the host cell. In addition to enhanced extracellular survival, we report the key discovery that chlamydial extrusions are phagocytosed by primary bone marrow‐derived macrophages, after which they provide a protective microenvironment for Chlamydia. Extrusion‐derived Chlamydia staved off macrophage‐based killing and culminated in the release of infectious elementary bodies from the macrophage. Based on these findings, we propose a model in which C. trachomatis extrusions serve as “trojan horses” for bacteria, by exploiting macrophages as vehicles for dissemination, immune evasion, and potentially transmission.
Buried Probe in Complex Congenital Nasolacrimal Duct Obstructions: Clinical Profiles and Outcomes

Purpose:To report the clinical profiles and outcomes of buried probe variant of complex congenital nasolacrimal duct obstruction (CNLDO). Methods:Retrospective chart review of all patients endoscopically diagnosed as a buried probe variant of complex CNLDO, over a 3.5 year period from a single surgeon’s (MJA) database were included in the study. A detailed lacrimal system evaluation was performed and intraoperative findings including nasal endoscopy were documented. A minimum follow up of 3 months following the final intervention was considered for analysis. Anatomical and functional success of the interventions was assessed at the final follow up. Results:Twenty-two eyes of 21 patients with buried probes were studied. The mean age at presentations was 41.2 months. Epiphora and discharge were the commonest presenting symptoms noted in 77.2% (17/22). Associated lacrimal anomalies include punctal agenesis, incomplete punctal canalization and atonic lacrimal sac. All patients underwent irrigation and probing under nasal endoscopic guidance. Further, 3 patients underwent endoscopic dacryocystorhinostomy for persistent CNLDO. At a mean follow up of 4.9 months, the final anatomical and functional successes were noted in 90.9% and 81.8%, respectively. Conclusions:Buried probe is a variant of complex CNLDO, noted more commonly in older children. Endoscopic guidance is crucial for its diagnosis and satisfactory outcomes.
Coping With Racism: Moderators of the Discrimination-Adjustment Link Among Mexican-Origin Adolescents.

What strategies help ethnic minority adolescents to cope with racism? The present study addressed this question by testing the role of ethnic identity, social support, and anger expression and suppression as moderators of the discrimination-adjustment link among 269 Mexican-origin adolescents (Mage = 14.1 years), 12-17 years old from the Midwestern U.S. Results from multilevel moderation analyses indicated that ethnic identity, social support, and anger suppression, respectively, significantly attenuated the relations between discrimination and adjustment problems, whereas outward anger expression exacerbated these relations. Moderation effects differed according to the level of analysis. By identifying effective coping strategies in the discrimination-adjustment link at specific levels of analysis, the present findings can guide future intervention efforts for Latino youth.
Nutritional and developmental regulation of insulin-like growth factors in fish.

The insulin-like growth factors (IGF) are evolutionarily ancient growth factors present in all vertebrates. The central importance of IGF for normal development and growth has been illustrated by the severe growth-retarded phenotype exhibited by IGF-I, IGF-II or IGF-I receptor "knockout" mice. Although we know much about the gross effects of IGF on the overall size of the fetus and the clinical manifestations that result from fetal and neonatal deficiency of IGF (i.e., severe growth retardation leads to dwarfism), very little is known about the in vivo actions of IGF during embryogenesis at the cellular and molecular levels. Most research on the developmental role of IGF has relied on rodent models, and attempts to elucidate the molecular and cellular basis of IGF actions have been hampered by the inaccessibility of the mammalian fetus enclosed in the uterus. During the past decade, there has been growing support for the concept that the IGF have been highly conserved in all vertebrates. Both IGF-I and IGF-II are present in fish, and their structures are highly conserved. Human and fish IGF-I are equally potent in mammalian and fish bioassay systems. Insulin-like growth factor mRNA is found in all life stages of fish, ranging from unfertilized egg to adult. The temporal and spatial expression patterns of fish IGF-I seem to be similar to those in mammals. Nutritional status and growth hormone both have a profound effect on IGF-I expression in fish, as they do in mammals. These features suggest that the IGF system is highly conserved between teleost fish and mammals. Because fish embryos develop externally, they provide excellent animal models for understanding the regulatory roles of IGF, IGF receptor and IGF-binding proteins in vertebrate embryonic development. Current research on the developmental and nutritional roles of IGF in fish will undoubtedly contribute to knowledge of the basic physiology of vertebrates in general.
The structure of categories: typicolity gradients, perceived linguistic familiarity and cross-linguistic comparisons

La presente etude porte sur les facteurs sous-adjacents a l'inegale representativite des exemplaires d'une categorie. Des sujets unilingues francophones et anglophones vivant dans le meme environnement physique ont evalue la typicalite (representativite) ainsi que leur familiarite linguistique (frequence du terme comme exemplaire de la categorie) avec ces memes exemplaires
Microscopic and Ultrastructural Changes of Müller’s Muscle in Patients With Simple Congenital Ptosis

Purpose: To study microscopic and ultrastructural changes of Müller’s muscle in patients with isolated congenital ptosis. Methods: In this prospective, observational case–control study, Müller’s muscle specimens were collected during ptosis surgical correction for 18 consecutive patients. Each specimen was divided into 2 parts. One part was embedded in formalin for light microscopy, and the other one was fixed in 3% glutaraldehyde for electron microscopy. A neuropathologist, serving as a masked evaluator, blindly reviewed all the different features for every case and counted the number of myocytes showing distinct myofilaments in the whole grid for every case. Statistical analysis using compare means and correlation tests was conducted to investigate potential associations and/or differences within and across groups. Results: Twelve Müller’s muscle specimens from patients with simple congenital ptosis of various severities and 6 specimens from patients with aponeurotic ptosis (controls) were collected and studied. Under light microscopy, congenital ptosis slides showed a small number of dispersed myocytes in a fibrotic background, whereas acquired ptosis slides showed a greater number of well-defined myocytes. Under electron microscopy, all congenital ptosis specimens had only a very small number of myocytes with clear, distinct myofilaments. Most myocytes in the aponeurotic ptosis group showed clear, distinct myofilaments, indicating a well-preserved muscle. No relationship existed between the number of clear, distinct myofilaments observed in the congenital ptosis group by transmission electron microscopy and patient age or ptosis severity. Conclusion: Substantial Müller’s muscle atrophy was observed in patients with different severities of isolated congenital ptosis.
Tics and Tourette: a clinical, pathophysiological and etiological review

Purpose of review Describe developments in the etiological understanding of Tourette syndrome. Recent findings Tourette syndrome is a complex heterogenous clinical syndrome, which is not a unitary entity. Pathophysiological models describe gamma-aminobutyric acid-ergic-associated disinhibition of cortico-basal ganglia motor, sensory and limbic loops. MRI studies support basal ganglia volume loss, with additional white matter and cerebellar changes. Tourette syndrome cause likely involves multiple vulnerability genes and environmental factors. Only recently have some vulnerability gene findings been replicated, including histidine decarboxylase and neurexin 1, yet these rare variants only explain a small proportion of patients. Planned large genetic studies will improve genetic understanding. The role of inflammation as a contributor to disease expression is now supported by large epidemiological studies showing an association with maternal autoimmunity and childhood infection. Investigation of blood cytokines, blood mRNA and brain mRNA expression support the role of a persistent immune activation, and there are similarities with the immune literature of autistic spectrum disorder. Current treatment is symptomatic, although there is a better appreciation of factors that influence treatment response. Summary At present, therapeutics is focused on symptom-based treatments, yet with improved etiological understanding, we will move toward disease-modifying therapies in the future.
Budget-Aware Activity Detection with A Recurrent Policy Network

In this paper, we address the challenging problem of efficient temporal activity detection in untrimmed long videos. While most recent work has focused and advanced the detection accuracy, the inference time can take seconds to minutes in processing each single video, which is too slow to be useful in real-world settings. This motivates the proposed budget-aware framework, which learns to perform activity detection by intelligently selecting a small subset of frames according to a specified time budget. We formulate this problem as a Markov decision process, and adopt a recurrent network to model the frame selection policy. We derive a recurrent policy gradient based approach to approximate the gradient of the non-decomposable and non-differentiable objective defined in our problem. In the extensive experiments, we achieve competitive detection accuracy, and more importantly, our approach is able to substantially reduce computation time and detect multiple activities with only 0.35s for each untrimmed long video.