Miracle-dz/UniFAR-FTUs huggingface dataset:
Scattered podosomes and podosomes associated with the sealing zone architecture in cultured osteoclasts revealed by cell shearing, quick freezing, and platinum‐replica electron microscopy

Osteoclasts (OCs) can adhere to a variety of substrate surfaces by highly dynamic actin‐based cytoskeletal structures termed podosomes. This tight attachment is established by a sealing zone (SZ), which is made of interconnected individual podosomes. Compared with scattered podosomes in various cell types, the architecture of the SZ is still unclear. Especially, ultrastructural studies on the details of the cytoskeletal structure of an OC have been challenging, because the high density of filaments in their podosomes obscure visualization of individual filaments. Therefore, to study this organization in more exact detail, we employed shearing open combined with replica electron microscopy. The present study provides several new details of the podosome and SZ structure, which were previously unrecognized: (a) the SZ consists of recognizable podosomes with a dense actin network of interpodosomal regions characterized by multiple layers of crossing, branching and anastomosing actin filament networks; (b) the Arp2/3 complex is distributed throughout the actin network of podosomes and SZ, indicating that actin polymerization is concentrated at these regions; (c) a close spatial relationship between the podosome and the dorsal membrane; and (d) a network of membranous organelles in close proximity to the podosomes in the SZ. Taken together, the present study reveals that a more complicated interpodosomal actin network among neighboring individual podosomes, which is more complicated than previously thought, appears to form the SZ. Indeed, individual podosomes are not an isolated structural unit from other organelles; and, in turn, their dynamism might affect the surrounding interpodosomal cytoskeletons, membranous organelles, and plasma membrane.
Computer Vision Technology in the Differential Diagnosis of Cushing's Syndrome.

OBJECTIVE Cushing's syndrome is a rare disease characterized by clinical features that show morphological similarity with the metabolic syndrome. Distinguishing these diseases in clinical practice is challenging. We have previously shown that computer vision technology can be a potentially useful diagnostic tool in Cushing's syndrome. In this follow-up study, we addressed the described problem by increasing the sample size and including controls matched by body mass index. METHODS We enrolled 82 patients (22 male, 60 female) and 98 control subjects (32 male, 66 female) matched by age, gender and body-mass-index. The control group consisted of patients with initially suspected, but biochemically excluded Cushing's syndrome. Standardized frontal and profile facial digital photographs were acquired. The images were analyzed using specialized computer vision and classification software. A grid of nodes was semi-automatically placed on disease-relevant facial structures for analysis of texture and geometry. Classification accuracy was calculated using a leave-one-out cross-validation procedure with a maximum likelihood classifier. RESULTS The overall correct classification rates were 10/22 (45.5%) for male patients and 26/32 (81.3%) for male controls, and 34/60 (56.7%) for female patients and 43/66 (65.2%) for female controls. In subgroup analyses, correct classification rates were higher for iatrogenic than for endogenous Cushing's syndrome. CONCLUSION Regarding the advanced problem of detecting Cushing's syndrome within a study sample matched by body mass index, we found moderate classification accuracy by facial image analysis. Classification accuracy is most likely higher in a larger sample with healthy control subjects. Further studies might pursue a more advanced analysis and classification algorithm.
Neuromyelitis Optica Spectrum Disorder and Other Non-Multiple Sclerosis Central Nervous System Inflammatory Diseases.

PURPOSE OF REVIEW This article reviews the clinical features, diagnostic approach, treatment, and prognosis of central nervous system inflammatory diseases that mimic multiple sclerosis (MS), including those defined by recently discovered autoantibody biomarkers. RECENT FINDINGS The discovery of autoantibody biomarkers of inflammatory demyelinating diseases of the central nervous system (aquaporin-4 IgG and myelin oligodendrocyte glycoprotein IgG) and the recognition that, despite some overlap, their clinical phenotypes are distinct from MS have revolutionized this field of neurology. These autoantibody biomarkers assist in diagnosis and have improved our understanding of the underlying disease pathogenesis. This has allowed targeted treatments to be translated into clinical trials, three of which are now under way in aquaporin-4 IgG-seropositive neuromyelitis optica (NMO) spectrum disorder. SUMMARY Knowledge of the clinical attributes, MRI findings, CSF parameters, and accompanying autoantibody biomarkers can help neurologists distinguish MS from its inflammatory mimics. These antibody biomarkers provide critical diagnostic and prognostic information and guide treatment decisions. Better recognition of the clinical, radiologic, and laboratory features of other inflammatory MS mimics that lack autoantibody biomarkers has allowed us to diagnose these disorders faster and initiate disease-specific treatments more expeditiously.
A natural point mutation in the bitter taste receptor TAS2R16 causes inverse agonism of arbutin in lemur gustation

Bitter taste enables the detection of potentially harmful substances and is mediated by bitter taste receptors, TAS2Rs, in vertebrates. Few antagonists and inverse agonists of TAS2Rs have been identified, especially natural compounds. TAS2R16s in humans, apes and Old World monkeys (Catarrhini, Anthropoidea) recognize β-glucoside analogues as specific agonists. Here, we investigated responses of TAS2R16 to β-glucosides in non-anthropoid primates, namely lemurs (Lemuriformes, Strepsirrhini). Salicin acted as an agonist on lemur TAS2R16. Arbutin acted as an agonist in the ring-tailed lemur (Lemur catta) but as an inverse agonist in black lemur (Eulemur macaco) and black-and-white ruffed lemur (Varecia variegata). We identified a strepsirrhine-specific amino acid substitution responsible for the inverse agonism of arbutin. In a food preference test, salicin bitterness was inhibited by arbutin in the black lemur. Structural modelling revealed this locus was important for a rearrangement of the intracellular end of transmembrane helix 7 (TM7). Accordingly, arbutin is the first known natural inverse agonist of TAS2Rs, contributing to our understanding of receptor–ligand interactions and the molecular basis of the unique feeding habit diversification in lemurs. Furthermore, the identification of a causal point mutation suggests that TAS2R can acquire functional changes according to feeding habits and environmental conditions.
Hospice Philosophy in Practice—Toward an Authentic Death

This article examines how hospice philosophy works in contemporary Danish hospice practice. The still sparse literature on Danish hospices indicates that hospice philosophy is influencing professional practice. In international palliative care literature, hospice philosophy is challenged for being overly normative in its ideal of the good death or on the other hand as threatened by the medical model. Drawing on the idea of hospice philosophy as providing meaning for everyday practice, this article explores how it is incorporated within the institutional order of contemporary Danish hospices. An ethnographic study was informed by participant observation and 49 interviews with professionals, patients, and families at three hospices in Denmark. The findings contribute to further understanding of the complexity of maintaining hospice philosophy in contemporary practice. Hospice practice works in an interpretive way with hospice philosophy to offer a “lived” philosophy and a means to an authentic death.
Comparison of Air-QⓇ insertion techniques in pediatric patients with fiber-optic bronchoscopic assessment: a prospective randomized control trial

Background Air-QⓇ laryngeal mask airway (LMA) is a second-generation supraglottic airway device (SAD) providing adequate airway control despite the unfavorable airway anatomy in children. Several studies have assessed it as a conduit for tracheal intubation and compared its efficacy with that of other SADs, but there are no studies comparing the laryngeal view with midline and rotational insertion techniques of Air-Q. Therefore, this study compared the fiber-optic bronchoscopic (FOB) assessment of the Air-Q position using these two insertion techniques. Methods This randomized controlled trial included 80 patients of the American Society of Anesthesiologists physical status I/II of either sex (age group 5–12 years, weight 10–30 kg), who were scheduled for elective surgery in the supine position under general anesthesia. The patients were randomly subjected to rotational and midline technique groups (n = 40, each), and appropriate sized Air-Q, based on the weight of the patient, was inserted using the technique allocated to each patient. Time taken and number of attempts for successful insertion of the devices and any complications after removal of device were studied. Results FOB grade 1 (ideal position) was seen in 29/40 (72.5%) and 19/40 (47.5%) children subjected to the rotational and classic midline techniques, respectively (P = 0.045). The time taken to successfully insert the Air-Q was significantly lesser in the rotational technique group (7.2 ± 1.5 s) than in the classic midline technique group (10.2 ± 2.1 s) (P < 0.001), whereas complications were similar in both groups. Conclusions The rotational technique was associated with better FOB view, and was faster than the classic midline technique of Air-Q insertion in pediatric patients.
Improving the Classification Effectiveness of Intrusion Detection by Using Improved Conditional Variational AutoEncoder and Deep Neural Network

Intrusion detection systems play an important role in preventing security threats and protecting networks from attacks. However, with the emergence of unknown attacks and imbalanced samples, traditional machine learning methods suffer from lower detection rates and higher false positive rates. We propose a novel intrusion detection model that combines an improved conditional variational AutoEncoder (ICVAE) with a deep neural network (DNN), namely ICVAE-DNN. ICVAE is used to learn and explore potential sparse representations between network data features and classes. The trained ICVAE decoder generates new attack samples according to the specified intrusion categories to balance the training data and increase the diversity of training samples, thereby improving the detection rate of the imbalanced attacks. The trained ICVAE encoder is not only used to automatically reduce data dimension, but also to initialize the weight of DNN hidden layers, so that DNN can easily achieve global optimization through back propagation and fine tuning. The NSL-KDD and UNSW-NB15 datasets are used to evaluate the performance of the ICVAE-DNN. The ICVAE-DNN is superior to the three well-known oversampling methods in data augmentation. Moreover, the ICVAE-DNN outperforms six well-known models in detection performance, and is more effective in detecting minority attacks and unknown attacks. In addition, the ICVAE-DNN also shows better overall accuracy, detection rate and false positive rate than the nine state-of-the-art intrusion detection methods.
Sustained antigen availability during germinal center initiation enhances antibody responses to vaccination

Significance We explored the effect of nontraditional vaccine dosing profiles on antibody titers of vaccines and discovered that certain dosing profiles demonstrate >10-fold higher antibody production than the traditional single-dose prime–boost method. We also present a computational model that captures the experimental results and provides a mechanistic understanding of the biology behind the effectiveness of our strategy. This work has clinical significance in vaccine design because it is a simple method to increase the efficacy of subunit vaccines, which may lead to the development of efficacious vaccines for diseases such as HIV. Natural infections expose the immune system to escalating antigen and inflammation over days to weeks, whereas nonlive vaccines are single bolus events. We explored whether the immune system responds optimally to antigen kinetics most similar to replicating infections, rather than a bolus dose. Using HIV antigens, we found that administering a given total dose of antigen and adjuvant over 1–2 wk through repeated injections or osmotic pumps enhanced humoral responses, with exponentially increasing (exp-inc) dosing profiles eliciting >10-fold increases in antibody production relative to bolus vaccination post prime. Computational modeling of the germinal center response suggested that antigen availability as higher-affinity antibodies evolve enhances antigen capture in lymph nodes. Consistent with these predictions, we found that exp-inc dosing led to prolonged antigen retention in lymph nodes and increased Tfh cell and germinal center B-cell numbers. Thus, regulating the antigen and adjuvant kinetics may enable increased vaccine potency.
Whole body ultrasound in the operating room and intensive care unit

Whole body ultrasound can be used to improve the speed and accuracy of evaluation of an increasing number of organ systems in the critically ill. Cardiac and abdominal ultrasound can be used to identify the mechanisms and etiology of hemodynamic instability. In hypoxemia or hypercarbia, lung ultrasound can rapidly identify the etiology of the condition with an accuracy that is equivalent to that of computed tomography. For encephalopathy, ocular ultrasound and transcranial Doppler can identify elevated intracranial pressure and midline shift. Renal and bladder ultrasound can identify the mechanisms and etiology of renal failure. Ultrasound can also improve the accuracy and safety of percutaneous procedures and should be currently used routinely for central vein catheterization and percutaneous tracheostomy.
Gender differences in clinical, laboratory and polysomnographic features of restless legs syndrome

Restless legs syndrome is a common neurological disorder with a clear female predominance. This study aims to evaluate gender differences in clinical, laboratory and polysomnographic features in patients with restless legs syndrome. For this retrospective analysis, 42 women and 42 men from the Innsbruck RLS database matched by age and therapy were included. Demographic data as well as different severity scales (IRLS, RLS‐6 and CGI) were evaluated. Laboratory parameters included several indicators of serum iron status. In all patients, polysomnography was performed according to the AASM guidelines, and periodic leg movements during sleep were scored according to the AASM criteria. IRLS, RLS‐6 and CGI revealed more severe symptoms in women (IRLS median [range]: 17.5 [0–35] versus 13.5 [0–32], p = 0.028; RLS‐6 median [range]: 18 [0–39] versus 12 [1–42], p = 0.014). Women had lower serum ferritin levels than men (median [range] in μg L−1: 74 [9–346] versus 167 [15–389], p < 0.001). Twenty‐two women and eight men (53.7% versus 22.2%, p = 0.003) had ferritin values below 75 μg L−1. Periodic leg movements during sleep indices were significantly lower in women than in men (median [range] in number per hr: 11.4 [0–62.5] versus 40 [0–154], p = 0.004, and 12.6 [0–58.5] versus 40 [0.5–208], p = 0.002, for night I and night II, respectively). Restless legs syndrome severity as measured by validated scales was worse in women, while periodic leg movements during sleep indices were higher in men. These results suggest a possible gender difference in phenotypical presentation of restless legs syndrome, manifesting with predominantly sensory symptoms in women and predominantly motor symptoms in men.
Morphological and Molecular Species Identification of Termites Attacking Ironwood Trees, Casuarina equisetifolia (Fagales: Casuarinaceae), in Guam

Abstract Ironwood trees (Casuarina equisetifolia subsp. equisetifolia L.) are ecologically and economically important trees in tropical and subtropical regions of the Indo-Pacific. Ironwood is one of the dominant tree species in Guam, but since 2002, this tree has been declining dramatically. A previous study showed that numerous sick or dead trees were under termite attack. However, the species of termites were not identified. As a first step to investigate causal relationships between termites and ironwood tree death, we assigned termites collected from ironwood trees to species using a combination of morphological characters and DNA barcoding of the 12S, 16S, COI, COII, and ITS2 regions. Based on morphology and comparisons to reference sequences in NCBI GenBank, the most likely species assignments were Nasutitermes takasagoensis (Nawa) (Blattodea: Termitidae) found to infest 45 trees, followed by Coptotermes gestroi (Wasmann) (Blattodea: Rhinotermitidae) (2 trees), Microcerotermes crassus Snyder (Blattodea: Termitidae) (2 trees), and an additional unidentified Microcerotermes species (1 tree) with no close sequence match to identified species in NCBI GenBank. However, taxonomic revisions and broader representation of DNA markers of well-curated specimen in public databases are clearly needed, especially for the N. takasagoensis species complex.
Antioxidant and Photoprotection Networking in the Coastal Diatom Skeletonema marinoi

Little is known on the antioxidant activity modulation in microalgae, even less in diatoms. Antioxidant molecule concentrations and their modulation in microalgae has received little attention and the interconnection between light, photosynthesis, photoprotection, and antioxidant network in microalgae is still unclear. To fill this gap, we selected light as external forcing to drive physiological regulation and acclimation in the costal diatom Skeletonema marinoi. We investigated the role of light regime on the concentration of ascorbic acid, phenolic compounds and among them flavonoids and their connection with photoprotective mechanisms. We compared three high light conditions, differing in either light intensity or wave distribution, with two low light conditions, differing in photoperiod, and a prolonged darkness. The change in light distribution, from sinusoidal to square wave distribution was also investigated. Results revealed a strong link between photoprotection, mainly relied on xanthophyll cycle operation, and the antioxidant molecules and activity modulation. This study paves the way for further investigation on the antioxidant capacity of diatoms, which resulted to be strongly forced by light conditions, also in the view of their potential utilization in nutraceuticals or new functional cosmetic products.
Kinematical simulation based on a novel six degree of freedoms computer input device

Virtual reality technology utilizes computer to construct three dimensional dummy environment and users can act with it by the aid of special computer input/output devices. This paper introduces a novel computer input device based on the parallel mechanism technology. This computer input device provides six degree of freedoms (DoF) operation ability, as is more flexible than the conventional two dimensional mouse. All objects among the dummy environment can translate along any directions and rotate around any axis in three dimensional space when operator manipulates the computer input device. Three aspects, including operation principle, control system and application are analyzed. And method about how to establish the whole simulation system based on this six-DoFs computer input device is also given as an application example, which is very useful for the mechanism type synthesis, workspace analysis and kinematic characteristic investigation.
Normative Data for the Montreal Cognitive Assessment in Greek Older Adults With Subjective Cognitive Decline, Mild Cognitive Impairment and Dementia

Montreal Cognitive Assessment (MoCA) is among the most commonly used screening tools worldwide. Objective: The aim of the study was to provide normative data for the MoCA in a Greek cohort of people older than 60 years who meet criteria for subjective cognitive decline (SCD), mild cognitive impairment (MCI), or dementia in order to optimize cutoff scores for each diagnostic group. Method: Seven hundred forty-six community-dwelling older adults, visitors of the Day Center of Alzheimer Hellas were randomly chosen. Three hundred seventy-nine of them met the criteria for dementia, 245 for MCI and 122 for SCD. Results: Initial statistical analyses showed that the total MoCA score is not affected by gender (P = .164), or age (P = .144) but is affected by educational level (P < .001). A cutoff score of 23 for low educational level (≤6 years) can distinguish people with SCD from MCI (sensitivity 71.4%, specificity 84.2%), while 26 is the cutoff score for middle educational level (7-12 years; sensitivity 73.2%, specificity 67.0%) and high educational level (≥13 years; sensitivity 77.6%, specificity 74.7%). Montreal Cognitive Assessment can discriminate older adults with SCD from dementia, with a cutoff score of 20 for low educational level (sensitivity 100%, specificity 92.3%) and a cutoff score 23 for middle educational level (sensitivity 97.6%, specificity 92.7%) and high educational level (sensitivity 98.5%, specificity 100%). Conclusion: Montreal Cognitive Assessment is not affected by age or gender but is affected by the educational level. The discriminant potential of MoCA between SCD and MCI is good, while the discrimination of SCD from dementia is excellent.
Multiple GmWRI1s are redundantly involved in seed filling and nodulation by regulating plastidic glycolysis, lipid biosynthesis and hormone signalling in soybean (Glycine max)

Abstract It has been reported that lipid biosynthesis in plant host root cells plays critical roles in legume‐fungal or ‐rhizobial symbioses, but little is known about its regulatory mechanism in legume–rhizobia interaction. Soybean WRINKLED1 (WRI1) a and b, with their alternative splicing (AS) products a’ and b’, are highly expressed in developing seeds and nodules, but their functions in soybean nodulation are not known. GmWRI1a and b differently promoted triacylglycerol (TAG) accumulation in both Arabidopsis wild‐type and wri1 mutant seeds and when they ectopically expressed in the soybean hairy roots. Transcriptome analysis revealed that 15 genes containing AW boxes in their promoters were targeted by GmWRI1s, including genes involved in glycolysis, fatty acid (FA) and TAG biosynthesis. GmWRI1a, GmWRI1b and b’ differentially transactivated most targeted genes. Overexpression of GmWRI1s affected phospholipid and galactolipid synthesis, soluble sugar and starch contents and led to increased nodule numbers, whereas GmWRI1 knockdown hairy roots interfered root glycolysis and lipid biosynthesis and resulted in fewer nodules. These phenomena in GmWRI1 mutants coincided with the altered expression of nodulation genes. Thus, GmWRI1‐regulated starch degradation, glycolysis and lipid biosynthesis were critical for nodulation. GmWRI1 mutants also altered auxin and other hormone‐related biosynthesis and hormone‐related genes, by which GmWRI1s may affect nodule development. The study expands the views for pleiotropic effects of WRI1s in regulating soybean seed filling and root nodulation.