Miracle-dz/UniFAR-FTUs huggingface dataset:
Use of Fluorescence In situ Hybridization (FISH) to Distinguish Intranodal Nevus From Metastatic Melanoma

With the increase in sentinel lymph node biopsies in melanoma patients, pathologists are frequently confronted with small deposits of morphologically bland melanocytes in the node, which occasionally cannot be readily classified as benign nodal nevi or melanoma. As most melanomas harbor characteristic chromosomal aberrations which can be used to distinguish them from benign nevi, we used fluorescence in-situ hybridization (FISH) with markers for 3 regions on chromosome 6 and 1 on chromosome 11 to determine the presence of chromosomal aberrations in sentinel lymph node specimens with small foci of melanocytes that had been diagnosed as metastatic melanoma or nodal nevi by histopathology. Fifty-nine tissue samples from 41 patients (24 lymph node metastases, 17 with nodal nevi, and 18 of the available corresponding primary melanomas) were analyzed by FISH. Twenty of 24 (83%) cases diagnosed as metastatic melanoma showed aberrations by FISH. Of the 4 negative cases, 3 were unequivocal melanoma metastases, whereas 1 on re-review was histopathologically equivocal. Of the 17 nodal nevi, 1 (6%) also showed aberrations by FISH, whereas the remainder was negative. Multiple aberrations were present in the positive case, some of which were also found in the corresponding primary tumor, suggesting that this case represents a deceptively bland melanoma metastasis that had been misclassified by histomorphology. Our data indicate that FISH is a useful adjunct tool to traditional methods in the diagnostic workup of deposits of melanocytes in lymph nodes that are histopathologically ambiguous.
Single and Multiple Oral Dose Fluvoxamine Kinetics in Young and Elderly Subjects

The pharmacokinetics of fluvoxamine maleate was studied in two separate studies in healthy young and elderly subjects. In a single and multiple oral dose administration study, six healthy young subjects received an initial 50 mg oral dose followed by 50 mg tablets every 12 h for 28 days. In a second study, 13 elderly subjects received 50 mg tablets every 12 h for 28 days. Fluvoxamine peak plasma concentrations were reached in ∼5–6 h following : oral administration of single and multiple 50 mg doses to healthy young and elderly volunteers. The area under the curve (AUC) of fluvoxamine tended to be larger following multiple (873 ng · h/ml) as compared to single-dose administration (652 ng · h/ml). Also the terminal half-life after chronic dosing (22 ± 6 h) tended to be longer than after single dosing. Steady-state plasma levels were obtained within 10 days' administration. The pharmacokinetics of fluvoxamine in elderly healthy subjects were no different from those recorded in young subjects. These results suggest that it is not necessary to adjust the dosage of fluvoxamine in elderly depressed patients, on the basis of pharma-cokinetic arguments. Independent of the age group, ∼3% of a dose was recovered as unchanged drug in the urine.
Multi-Task Learning via Conic Programming

When we have several related tasks, solving them simultaneously is shown to be more effective than solving them individually. This approach is called multi-task learning (MTL) and has been studied extensively. Existing approaches to MTL often treat all the tasks as uniformly related to each other and the relatedness of the tasks is controlled globally. For this reason, the existing methods can lead to undesired solutions when some tasks are not highly related to each other, and some pairs of related tasks can have significantly different solutions. In this paper, we propose a novel MTL algorithm that can overcome these problems. Our method makes use of a task network, which describes the relation structure among tasks. This allows us to deal with intricate relation structures in a systematic way. Furthermore, we control the relatedness of the tasks locally, so all pairs of related tasks are guaranteed to have similar solutions. We apply the above idea to support vector machines (SVMs) and show that the optimization problem can be cast as a second order cone program, which is convex and can be solved efficiently. The usefulness of our approach is demonstrated through simulations with protein super-family classification and ordinal regression problems.
RGTE: A Reputation-Based Global Trust Establishment in VANETs

In recent years Trust Management has become a main method to ensure the security of vehicular ad-hoc networks (VANETs). However, most of the existing trust establishment approaches cannot handle the rapidly changing environment of VANET appropriately. In this paper, we propose a Reputation-based Global Trust Establishment scheme (RGTEs). The scheme introduces a solution to share the trust information in VANET safely by applying statistical laws, which makes it more efficient and accurate to establish trust in rapidly changing environment. Moreover, we detect a bad node by dynamic threshold according to real-time reputation status of the network. Analysis shows that RGTEs is more effective in confidence-building, security assurance and adaptability.
Clinical developments for treating ARDS

Acute respiratory distress syndrome (ARDS), is characterised by capillary permeability and pulmonary oedema formation and may complicate a variety of medical and surgical illnesses. As a self-perpetuating state of inflammatory derangement, acute lung injury (ALI)/ARDS is manifest clinically as rapid development of radiographic infiltrates, severe hypoxaemia and reduced lung compliance. Over the years, researchers have made significant progress in elucidating the pathophysiology of this complex syndrome. Therapies targeting specific pathophysiologic steps in the development or persistence of this syndrome are in various stages of laboratory and clinical testing. Results to date have shown nitric oxide (NO) to improve oxygenation in the majority of patients but fail to improve mortality. Surfactant replacement has had limited success in adults, but new formulations and delivery methods may prove beneficial. Several inflammatory mediator-targeted therapies have progressed successfully through early clinical evaluation. Among these, neutrophil elastase inhibitors have shown the most promise and are currently undergoing Phase III trials. Other mediator-targeted therapies, such as prostaglandin E1, IL-10 and platelet activating factor antagonists, have not been found efficacious in large clinical trials of ARDS. However, these therapies, along with coagulation modulators, may have a favourable impact on ARDS by improving outcomes in sepsis, the greatest risk factor for developing this condition. In the interim, supportive care through improvements in mechanical ventilation are beneficial, while specific fluid balance and nutrition strategies may prove advantageous.
MOUSE MACROPHAGES AS HOST CELLS FOR THE MOUSE HEPATITIS VIRUS AND THE GENETIC BASIS OF THEIR SUSCEPTIBILITY.

Much of the mystery of pathogenesis of animal virus disease lies in the realm of specificity of virus effect on cell type and in the differing effect of a given virus on different hosts. Tissue culture, despite its great contributions to other aspects of cytopathology, has not so far furnished significant clues to these basic problems. We have recently found that an acute virus disease of mice, mouse hepatitis," 2 has a selective destructive effect for cells derived from the reticulo-endothelial system (macrophages) and that the apparent genetic difference in susceptibility of different strains of mice is reflected in the behavior of macrophages from these strains in tissue culture. Tests of hybrids resulting from crosses between resistant and susceptible strains indicate that susceptibility is inherited and that genetic segregation of susceptibility and resistance occurs in the F2 and backeross generations. Materials and Methods. -The macrophages were obtained by explanting fragments of liver from newborn (1-3 days old) mice into roller tubes either directly onto the glass or onto a reconstituted collagen substrate.3' 4 The collagen was prepared according to the method of Ehrmann and Gey by extraction of 0.1 per cent acetic acid, dialysis against distilled water, and reconstitution to an agar-like slant with ammonium hydroxide vapors. The supernatant medium, except in otherwise specified cases; consisted of 60 per cent Gey's balanced salt solution, 10 per cent chick embryo extract (50 per cent), and 30 per cent horse serum (obtained from Microbiological Associates), with 0.004 per cent phenol red, 100 units of penicillin, and 10 micrograms of streptomycin. In some experiments, as designated in the text, chicken serum or a combination of chicken serum and horse serum was used. The chicken serum was obtained from White Leghorns kept for routine bleeding in our laboratory. The cultures were incubated in a roller drum and maintained in this manner at 370C throughout the experiments. The cultures were inoculated with the virus three to four days following explantation. The medium was renewed every two to three days until the end of the particular experiment. Supernatant fluids were frozen at -40'C and reserved for titration in mice. The cells were observed directly in the roller tube and their
Send Orders of Reprints at Reprints@benthamscience.org Mtor Inhibitors in Tuberous Sclerosis Complex

Tuberous sclerosis complex (TSC) is a genetic multiple organ system disorder that is characterized by the development of tumor-like lesions (hamartomas) and neurodevelopmental disorders. Mutations in the TSC1 and TSC2 tumor suppressor genes occur in the majority of patients with TSC, resulting in hyperactivation of the mammalian target of rapamycin (mTOR) signaling pathway and subsequent abnormalities in numerous cell processes. As a result, mTOR inhibitors such as sirolimus and everolimus have the potential to provide targeted therapy for patients with TSC. Everolimus is the first mTOR inhibitor approved as a treatment option in the USA and in Europe for patients with subependymal giant-cell astrocytomas (SEGAs) associated with TSC. The clinical evidence to date supports the use of mTOR inhibitors in a variety of TSC-associated disease manifestations, including SEGAs, renal angiomyolipoma, skin manifestations, and epilepsy. Furthermore, ongoing clinical trials evaluating mTOR inhibitors in TSC are underway, and the results of these studies are expected to provide further evidence that will firmly establish their role in this setting. This article will discuss the role of the mTOR pathway in TSC and review the pharmacokinetics, pharmacodynamics, clinical efficacy, and tolerability of mTOR inhibitors, along with their current place in clinical practice.
Cardiac magnetic resonance imaging in pulmonary arterial hypertension

Cardiac magnetic resonance imaging (CMRI) provides accurate information about right ventricular (RV) mass, RV volumes and other markers of RV function. CMRI is proving to be a particularly useful tool in pulmonary arterial hypertension (PAH), as measures of RV function have been shown to be prognostic of long-term outcomes in this disease. Changes in RV function can also provide important information about a patient's disease course and response to treatment. As CMRI is noninvasive it can be used to regularly monitor patients with PAH, which is an important advantage over invasive right heart catheterisation. This review will explore the use of CMRI in the context of existing monitoring tools for PAH and will explore the forthcoming developments that are likely to be important in the future monitoring of patients with PAH.
MEG reveals a fast pathway from somatosensory cortex to occipital areas via posterior parietal cortex in a blind subject

Cross-modal activity in visual cortex of blind subjects has been reported during performance of variety of non-visual tasks. A key unanswered question is through which pathways non-visual inputs are funneled to the visual cortex. Here we used tomographic analysis of single trial magnetoencephalography (MEG) data recorded from one congenitally blind and two sighted subjects after stimulation of the left and right median nerves at three intensities: below sensory threshold, above sensory threshold and above motor threshold; the last sufficient to produce thumb twitching. We identified reproducible brain responses in the primary somatosensory (S1) and motor (M1) cortices at around 20 ms post-stimulus, which were very similar in sighted and blind subjects. Time-frequency analysis revealed strong 45–70 Hz activity at latencies of 20–50 ms in S1 and M1, and posterior parietal cortex Brodmann areas (BA) 7 and 40, which compared to lower frequencies, were substantially more pronounced in the blind than the sighted subjects. Critically, at frequencies from α-band up to 100 Hz we found clear, strong, and widespread responses in the visual cortex of the blind subject, which increased with the intensity of the somatosensory stimuli. Time-delayed mutual information (MI) revealed that in blind subject the stimulus information is funneled from the early somatosensory to visual cortex through posterior parietal BA 7 and 40, projecting first to visual areas V5 and V3, and eventually V1. The flow of information through this pathway occurred in stages characterized by convergence of activations into specific cortical regions. In sighted subjects, no linked activity was found that led from the somatosensory to the visual cortex through any of the studied brain regions. These results provide the first evidence from MEG that in blind subjects, tactile information is routed from primary somatosensory to occipital cortex via the posterior parietal cortex.
Parent Report and Actigraphically Defined Sleep in Children with and without Developmental Coordination Disorder; Links with Fatigue and Sleepiness

Background Impaired sleep is associated with negative effects on quality of life and daytime functioning. Higher rates of sleep disturbance are reported in children with various developmental disorders. However, little is known about sleep in children with developmental coordination disorder (DCD), a condition characterized by everyday movement difficulties. Previously, in a preliminary study, we found higher rates of parent-reported sleep disturbance in children with DCD compared to controls. Aims To examine sleep in DCD using objective measures and to examine links with daytime fatigue and sleepiness. Methods Two groups (primary and secondary school-aged) of 15 children with DCD, plus matched controls, participated. Parent-reported child sleep was assessed using the Children’s Sleep Habits Questionnaire and actigraphy provided an objective measure of sleep–wake patterns over 1 week (including weekdays and weekend). Pediatric restless legs syndrome (RLS) semi-structured diagnostic interview was conducted with each child and parent to capture symptoms of RLS. Aspects of self-rated child functioning were assessed with questionnaires (Pre-sleep Arousal Scale, Pediatric Daytime Sleepiness Scale, PedsQL Multidimensional Fatigue Scale) and mothers’ reported thoughts about child sleep with the Maternal Cognitions about Infant Sleep Questionnaire. Results The DCD groups had greater parent-reported sleep disturbance. Actigraphy results suggested that for secondary aged children with DCD their sleep quality was impaired and there were differences in the timing of sleep compared to controls (including some differences in the variation between weekday and weekend sleep times). The actigraphy of the primary age group with DCD was unremarkable compared to controls. No child in the study met the criteria for RLS. Exploratory analyses suggested that daytime fatigue, aspects of pre-sleep arousal, and daytime sleepiness were reported as greater in the DCD groups and were particularly related to objective sleep parameters in the DCD groups. Maternal thoughts about sleep did not differ between the DCD and control groups. Conclusion The nature and underlying cause of sleep disturbance and how it might be linked with aspects of daytime functioning in adolescents with DCD requires further research. Meanwhile, clinical awareness of the risk of atypical sleep patterns/sleep problems in DCD is important to ensure early identification and implementation of appropriate support.
The prognostic value of global haemostatic tests in the intensive care unit setting

Background: Global haemostatic tests are often abnormal in critically ill patients, secondary to activation or consumption of coagulation factors or inhibitors. Methods for analysing plasma levels of these factors are, however, not widely available, and the predictive value of global tests is not known. We examined the clinical applicability to predict the outcome of the global haemostatic tests used at most hospitals.
Molecular Mechanisms of Epigenetic Variation in Plants

Natural variation is defined as the phenotypic variation caused by spontaneous mutations. In general, mutations are associated with changes of nucleotide sequence, and many mutations in genes that can cause changes in plant development have been identified. Epigenetic change, which does not involve alteration to the nucleotide sequence, can also cause changes in gene activity by changing the structure of chromatin through DNA methylation or histone modifications. Now there is evidence based on induced or spontaneous mutants that epigenetic changes can cause altering plant phenotypes. Epigenetic changes have occurred frequently in plants, and some are heritable or metastable causing variation in epigenetic status within or between species. Therefore, heritable epigenetic variation as well as genetic variation has the potential to drive natural variation.
Aroma evaluation of wines from early-harvested grapes in view of climate change

In view of climate change, the scheduling of an early harvest may be an agronomic option to limit wine alcohol 13 provided that, a satisfactory content of secondary metabolites is ensured in grapes. In order to better understand the link between grape ripening, seasonal trend and wine aroma, the aromatic expression of Barbera and Pinot Noir wines produced with early-harvested grapes was assessed. Major attention was focused on norisoprenoids 16 during both alcoholic fermentation and after three months of storage. At the end of fermentation, the highest 17  -damascenone content was detected in wines obtained from less ripe grapes, then its content increased 18 significantly after 3 months of storage. Inversely, the levels of  -ionone decreased significantly during the 19 same period. The reduction of wine alcohol assessed by harvesting earlier especially for Barbera, was 20 associated to optimal aromatic levels as well as to good technological parameters.
M-GEAR: Gateway-Based Energy-Aware Multi-hop Routing Protocol for WSNs

In this research work, we advise gateway based energy-efficient routing protocol (M-GEAR) for Wireless Sensor Networks (WSNs). We divide the sensor nodes into four logical regions on the basis of their location in the sensing field. We install Base Station (BS) out of the sensing area and a gateway node at the centre of the sensing area. If the distance of a sensor node from BS or gateway is less than predefined distance threshold, the node uses direct communication. We divide the rest of nodes into two equal regions whose distance is beyond the threshold distance. We select cluster heads (CHs)in each region which are independent of the other region. These CHs are selected on the basis of a probability. We compare performance of our protocol with LEACH (Low Energy Adaptive Clustering Hierarchy). Performance analysis and compared statistic results show that our proposed protocol perform well in terms of energy consumption and network lifetime.
Pedundulatory robotic locomotion: Centipede and polychaete modes in unstructured substrates

The present paper considers a novel class of robotic systems, termed pedundulatory locomotors, which can be thought of as undulatory robots augmented by multiple pairs of lateral paddle-like appendages (“parapodia”). Bio-inspired strategies for synchronizing the movement of the parapodia with the body undulations, emulating organisms like the centipedes and the polychaete worms, are presented, giving rise to distinct pedundulatory modes. These modes are investigated and comparatively assessed, both in simulation and via experiments with the Nereisbot prototype locomoting on sand and on several other unstructured substrates. Our studies demonstrate the rich gait repertoire and enhanced performance of pedundulatory systems, compared to purely undulatory ones.
Comparison of the Effects of 3 Methods of Intrathecal Bupivacaine, Bupivacaine-Fentanyl, and Bupivacaine-Fentanyl-Magnesium Sulfate on Sensory Motor Blocks and Postoperative Pain in Patients Undergoing Lumbar Disk Herniation Surgery

Background: The aim of this study was to investigate the effects of adding intrathecal (IT) fentanyl and magnesium sulfate (MgSO4) to bupivacaine on sensory motor blocks and postoperative pain in patients undergoing lumbar disk herniation surgery. Methods: In a double-blind randomized clinical trial, the patients undergoing lumbar disk herniation surgery were allocated to receive hyperbaric bupivacaine (A), or hyperbaric bupivacaine and fentanyl (B), hyperbaric bupivacaine, fentanyl and MgSO4 (C) IT. Data were collected regarding the onset of sensory block and time to regression to T10, time to complete motor block and full motor recovery, time to first analgesic requirement, postoperative pain score, and analgesic consumption and side effects. P<0.05 was considered to be statistically significant. Results: A total of 105 patients were randomized and assigned to 3 groups (n=35 in each groups). There were no significant differences between groups in regard to time to reach the T10 level of sensory block (P=0.82), time to regression to T10 (P=0.11), and the time to complete motor block (P=0.58). Meanwhile, the time to complete recovery of motor function was significantly longer in group C (116.4±18.4, 126.4±25.5, 130.2±15.7 min, respectively, P=0.016). Time to first analgesic requirement was also significantly longer in group C (3.26±1.12, 5.57±0.92, 6.91±1.27 h, respectively, P<0.001). Total morphine consumption was significantly less in group C (14.3±4.3, 8.3±3.5, 6±3.6 mg, respectively, P<0.001). The severity of pain was significantly less in C group (P<0.001). Conclusion: In patients undergoing lumbar disk herniation surgery, IT MgSO4 in combination with bupivacaine-fentanyl can decrease severity of postoperative pain and analgesic consumption without additional side effect.