Miracle-dz/UniFAR-FTUs huggingface dataset:
Spinal use‐dependent plasticity of synaptic transmission in humans after a single cycling session

The spinal cord is able to express use‐dependent plasticity, as demonstrated in spinalized cats following treadmill training. In humans, spinal use‐dependent plasticity is inferred from modifications in the size of H reflex, which are often more prominent after skilled motor training. Plasticity can develop at synaptic connections between afferent fibres and/or descending tracts and motoneurones or interneurones interposed in the spinal pathways. Here we explore whether skilled training induces a change in synaptic efficacy at the synapse between Ia afferents and soleus (Sol) motoneurones. Synaptic efficacy can be modulated presynaptically through changes of the probability of transmitter release (homosynaptic depression, HD). The frequency‐related depression of the Sol H reflex, thought to reflect HD, was tested at rest, before and after one single skilled (14 subjects) or non‐skilled (9 subjects) cycling training session. Performance improved in both groups but to a larger extent with skilled training, while HD increased immediately after and the day following skilled training in the absence of changes with non‐skilled training. These results support the view that spinal cord function is able to encode a local motor memory.
Inflammation-based scoring is a useful prognostic predictor of pulmonary resection for elderly patients with clinical stage I non-small-cell lung cancer.

OBJECTIVES The number of elderly lung cancer patients requiring surgery has been increasing due to the ageing society and less invasive perioperative procedures. Elderly people usually have various comorbidities, but there are few simple and objective tools that can be used to determine prognostic factors for elderly patients with clinical stage I non-small-cell lung cancer (NSCLC). The aim of this retrospective study was to evaluate the prognostic factors of surgically treated, over 80-year old patients with clinical stage I NSCLC. METHODS The preoperative data of 97 over 80-year old patients with clinical stage I NSCLC were collected at Nagasaki University Hospital from 1990 to 2012. As prognostic factors, inflammation-based scoring systems, including the Glasgow Prognostic Score (GPS) determined by serum levels of C-reactive protein and albumin, the neutrophil lymphocyte ratio (NLR) and the platelet lymphocyte ratio (PLR) were evaluated, as well as other clinicopathological factors, including performance status, body mass index, carcinoembryonic antigen, Charlson comorbidity index and type of surgical procedure. RESULTS The median age was 82 (range, 80-93) years. There were 62 (64.0%) clinical stage IA cases and 35 IB cases. Operations included 64 (66.0%) lobectomies, 15 segmentectomies and 18 wedge resections. The pathological stage was I in 76 (78.4%) patients, II in 12 (12.4%), III in 8 (8.2%) and IV in 1 (1.0%). Twelve (12.4%) patients underwent mediastinal lymph node dissection. Overall survival and disease-specific 5-year survival rates were 55.5 and 70.0%, respectively. The average GPS score was 0.4 (0-2). Disease-specific 5-year survival was significantly longer with GPS 0 than with GPS 1-2. (74.2%, 53.7%, respectively, P = 0.03). Overall 5-year survival was significantly longer with GPS 0 than with GPS 1-2. (59.7%, 43.1%, respectively, P = 0.005). Both the NLR (median value = 1.9) and the PLR (median value = 117) were not correlated with disease-specific and overall 5-year survival. On multivariate analysis, pathological stage I (P = 0.01) and GPS 0 (P = 0.04, hazard ratio: 2.13, 95% confidence interval 1.036-4.393) were significant prognostic factors. CONCLUSIONS The preoperative GPS appears to be a useful predictor of overall survival and could be a simple prognostic tool for elderly patients with clinical stage I NSCLC.
Obesity and free fatty acids: double trouble.

The socio-economic impact of obesity, one of the most prevalent medical disorders in Western society, is mainly due to its association with a higher risk of coronary heart disease. It is likely that atherosclerosis develops against a background of obesity as a result of the insulin resistance that is invariably present in overweight and obese subjects. Fasting plasma lipids may be normal in obese subjects, but they are usually affected by postprandial hyperlipidemia, which is probably due to competition between chylomicrons and VLDL for the same metabolic pathways. The basis for the impaired clearance of atherogenic chylomicron remnants is the fact that obesity causes hepatic apo B-VLDL overproduction, and thus leads to competition with chylomicrons and their remnants at the lipolytic pathway (lipoprotein lipase and hepatic lipase) and receptor level (LDL-receptor and remnant-receptor). The overproduction of VLDL is probably caused by an enhanced hepatic flux of free fatty acids in both the postprandial (from the lipolysis of triglyceride rich particles) and postabsorptive states (from adipocytes). Weight reduction by means of life-style changes, supported by medical interventions with inhibitors of intestinal fat absorption (e.g. Orlistat) or appetite suppressants (e.g. Sibutramine), is essential in order to decrease the risk of atherosclerosis. Furthermore, improvement of risk factors can be achieved by means of fibrate treatment to modulate fasting and postprandial triglyceride levels. Treatment with cholesterol synthesis inhibitors ("statins") may reduce hepatic VLDL production and increase the clearance of atherogenic remnants by upregulating LDL-receptors, thus leading to improved fasting lipid levels and enhanced clearance of chylomicron remnants. Finally, the use of thiazolidinedione derivatives to improve insulin sensitivity may be one of the options for reducing the risk of atherosclerosis in obese subjects.
The Performance of Crossbar-Based Binary Hypercubes

Wormhole routing is an attractive routing technique offering low latency communication without the need to buffer an entire packet in a single node. A new queueing-theoretic model for obtaining throughput and latency of binary hypercubes supporting wormhole routing is developed here. The model is very accurate in predicting the performance of an actual multicomputer over a range of network sizes, packet lengths, and input port priority mappings. Utilizing the model, the performance of networks with identical topologies but different node architectures is estimated. >
Zebrafish as an in Vivo Screen for Early Black Cranberry Proanthocyanidin Biomolecular Activity

Antioxidants have been widely studied in various naturally occurring substances as a bioavailable cancer prevention treatment. Proanthocyanidins (PACs), which are abundant polyphenols in Early Black (EB) Cranberry (Vaccinium macrocarpon), are readily available and we have shown their anticancer activity in several cancer cell lines. This work focused on the activity of these compounds when incorporated into the zebrafish (Danio rerio) system. We began investigating the in vivo effect of these phytochemicals, the protective role of several other cranberry compounds, and the metabolic activity of the vertebrate model organism. Proanthocyanidin fractions were separated from fresh EB Cranberry fruit by chromatography on Sephadex LH-20 in order to acquire a workable stock solution in DMSO. Various concentrations of proanthocyanidins in solution were tested against fish ranging in age from 1-cell stage to adult level of growth. Acridine orange apoptosis indicator dye was incorporated into the treatment protocol, and it was observed that irregular epithelial cell death was occurring in treated embryos but not in the control group. Further apoptosis assays were carried out utilizing Dihydroethidium (DHE) superoxide sensitive dye in the treatment protocol. Fluorescing red nuclei were visible along the outer surface of the epithelium cell layer; an indication of superoxide release within cells leading to the nicking of DNA within the nucleus. It was also possible to screen for superoxide release in PACs treated CCD-CO18 and HT-29 cells using confocal microscopy and cell apoptosis was investigated by trypan blue cytotoxicity assay; cell apoptosis results were statistically significant as confirmed by ANOVA analysis. Results indicate that the phytochemicals may induce apoptosis in rapidly dividing cells.
Reduction of stress‐induced analgesia but not of exogenous opioid effects in mice lacking CB1 receptors

CB1 cannabinoid receptors are widely distributed in the central nervous system where they mediate most of the cannabinoid‐induced responses. Here we have evaluated the interactions between the CB1 cannabinoid receptors and the endogenous opioid system by assaying a number of well‐characterized opioid responses, e.g. antinociception and stress‐mediated effects, on mutant mice in which the CB1 receptor gene was invalidated. The spontaneous responses to various nociceptive stimuli (thermal, mechanical and visceral pain) were not changed in mutant CB1 mice. Furthermore, the absence of the CB1 cannabinoid receptor did not modify the antinociceptive effects induced by different opioid agonists: morphine (preferential mu opioid agonist), d‐Pen2‐d‐Pen5‐enkephalin (DPDPE) and deltorphin II (selective delta opioid agonists), and U‐50,488H (selective kappa opioid agonist) in the hot‐plate and tail‐immersion tests. In contrast, the stress‐induced opioid mediated responses were modified in CB1 mutants. Indeed, these mutants did not exhibit antinociception following a forced swim in water at 34 °C and presented a decrease in the immobility induced by the previous exposure to electric footshock. However, the antinociception induced by a forced swim in water at 10 °C was preserved in CB1 mutants. These results indicate that CB1 receptors are not involved in the antinociceptive responses to exogenous opioids, but that a physiological interaction between the opioid and cannabinoid systems is necessary to allow the development of opioid‐mediated responses to stress.
Retrograde Mastoidectomy with Canal Wall Reconstruction: A Single-Stage Technique for Cholesteatoma Removal

The goal of this retrospective study was to report the preliminary results of the retrograde mastoidectomy technique with canal wall reconstruction used as a primary treatment method for cholesteatoma. This synthesis of canal wall up (CWU) and canal wall down (CWD) techniques was performed in 70 patients (75 ears; 35 pediatric, 40 adult) with an average 45-month follow-up. Surgical intervention involved removal of a portion of the canal wall for exposure and extirpation of the cholesteatoma, followed by reestablishment of the canal wall during reconstruction in a single stage. This leaves the mucosa relatively undisturbed and limits the extent of canal wall removal, facilitating mastoid aeration and preservation of anatomy. Recurrent disease occurred in 5% of cases. The hearing improvement was statistically significant (p < .05), with an average preoperative 4-frequency pure tone average air-bone gap of 27.2 dB improving to 11.5 dB. No patient had a worsening of hearing. The surgery takes less time than traditional techniques, is reproducible and easily taught, and can be universally applied to all cholesteatoma patients as primary treatment.
Relationship Between Intermittent Separation and Vortex Structure in a Three-Dimensional Shock/Boundary-Layer Interaction

The relationship between the three-dimensional vortex structures and flow-separation zones generated by a shock wave/boundary-layer interaction within a low-aspect-ratio duct was studied using stereoscopic particle imaging velocimetry measurements. In this configuration, the interaction of the incident shock with all walls was important in controlling the flowfield; the three interactions coupled to produce a strongly distorted flowfield. Conditional sampling was used to construct the local probability of reverse flow maps, and thus quantify the distribution of regions of intermittent separation on both bottom-walls and side-walls. The latter regions were found to be significantly larger and more likely to separate than the former. Thus, it was concluded that the sidewall and corner flow interactions dominate in this configuration. A triple decomposition of motion was used to construct a three-dimensional representation of the vortex features generated by the interaction. The results indicated that the fl.
Open-label study of dexmethylphenidate hydrochloride in children and adolescents with attention deficit hyperactivity disorder.

BACKGROUND This pilot study examined the efficacy and duration of the effect of dexmethylphenidate (d-MPH) given once-daily in subjects with attention deficit hyperactivity disorder (ADHD). METHOD Subjects aged 6-18 years (inclusive) with ADHD were enrolled in this 8-week, openlabel study. Outcome measures included the Conners'Teacher and Parent Rating Scales, the Attention Deficit Disorder Rating Scale (ADDRS), the Clinical Global Impression (CGI) Scale, and teacher and parent visual analog scales to estimate the duration of efficacy. d-MPH was initiated at a dose of 2.5 mg/day. The dose was flexible, based on response and tolerability, and could be increased in increments of 2.5 mg/day to a maximum daily dose of 30 mg/day. RESULTS Twenty-two subjects (mean age, 8.7 +/- 0.4 years) were treated. Significant improvements (p <0.0001) from baseline occurred in the Conners' Teacher and Parent Rating Scales after 8 weeks. Of the evaluated subjects, 85.7% (18 of 21) showed at least a 30% improvement from baseline on the Conners' Teacher Rating Scale, and 86.4% (19 of 22) of subjects showed at least a 30% improvement from baseline on the Conners' Parent Rating Scale. Most subjects demonstrated an improvement on the ADDRS and the CGI-Improvement (CGI-I) scale. Median duration of effect was estimated at 6.2 hours (teachers) and at 7.5 hours (parents). On average, patients gained 2.4 pounds over the course of the study. CONCLUSIONS A single daily dose of d-MPH was effective in controlling ADHD in children and was well tolerated. Future studies are needed to confirm these findings and to evaluate chronic dosing with d-MPH.
Pharmacy Practice, Research, Education, and Advocacy for Older Adults American College of Pharmacy

In the United States, older adults have become the fastest growing segment of the population and are expected to double in number to 70 million by 2030. As a whole, older adults have different health care needs than younger patients, and some of these needs should be met by pharmacists. Clinical pharmacy practice affecting older adults occurs in a variety of settings, including community, ambulatory care, primary care, hospital, assisted living, nursing home, home health care, hospice, and Alzheimer's disease units. Although specialty training in geriatrics or gerontology is not required for pharmacists to care for older adults, it is extremely helpful. Pharmacy education related to the care of older adults has improved slightly in the past several years but will need to increase even more to provide all pharmacists with the basic skills and knowledge to care for this unique group of patients. In addition, pharmacotherapy research targeting older adults needs to increase. Although it can be challenging, funding for this type of research is available. Patient and political advocacy is also important to support this growing population.
Identification of volatile compounds in cultivars barker, collinson, fortuna and geada of avocado (Persea americana, Mill.) fruit

The objective of this paper was to determine the volatile profile of four cultivars - Barker, Collinson, Fortuna and Geada of avocado (Persea americana, Mill.) fruit and to perform a detailed study on the effect of volatiles extraction conditions. The best conditions for extraction for Collinson and Fortuna cultivars were by using a mixture of pentane and ethyl ether (2:1) as solvent for 80 min, while for Barker and Geada cultivars, the solvents were hexane and pentane-ether (2:1), respectively but for a shorter extraction period of 60 min. A total number of 158 compounds were separated in all 4 avocado cultivars, among them eighty-four volatile compounds were identified. The principal volatile compounds viz. hexanal, ethyl acetate, methyl dodecanoate, 2,5-dimethyl furan, 1,3-butanediol, 2-ethylphenol, 2-butanol, α−bergamotene, β−caryophyllene, (E)-2-decenal were common in all the 4 cultivars. (E)-2-pentenal which possesses fruity aroma was found only in the cultivar Fortuna while ethyl acetate possessing fresh fruity flavor was present in higher content in Collinson cultivar. Benzaldehyde which possesses characteristic fruity and nutty odor note was present at a higher concentration (4.3%) in only Geada cultivar and in traces in Barker cultivar but it was not detected in Collinson and Fortuna cultivars.
Pathology of the glaucomas.

In the normal eye, the main resistance to aqueous outflow is in the outermost region of the trabecular meshwork, which is adjacent to and forms the inner wall of Schlemm's canal. In primary open-angle glaucoma, there is increased resistance to outflow, and we assume that the abnormal additional resistance is in the same location. Examinations of pathological anatomy show scarring and sclerosis in the trabecular meshwork, but the specimens are usually taken from advanced cases and it has not been decided to what degree trabecular changes may be due to damage secondary to long-standing elevated intraocular pressure rather than the primary defect. Electron microscopy, which Dr. Tripathi will cover in detail, shows fewer vacuoles in the endothelium of Schlemm's canal in patients with glaucoma. Again, it is not clear whether the fewer vacuoles account for diminished outflow facility or whether they merely reflect alterations in flow dynamics because of resistance elsewhere in the outflow pathway. For example, chemical changes in the juxtacanalicular connective tissue could result in impaired fluid flow with no apparent morphological alteration, but the altered flow pattern might be reflected in the endothelium. Some evidence seems to show occlusion of collector channels in cases of established glaucoma, but it is again a problem to decide if this is the primary event or if collapse of channels is induced mechanically by elevated intraocular pressure acting on resistance in the trabecular region. Pseudoexfoliative glaucoma and pigmentary glaucoma seem to be related to primary open-angle glaucoma. What is not at all clear is whether the pseudoexfoliative and pigmentary materials contribute to the outflow obstruction or whether the material is simply trapped in the meshwork which has poor outflow facility to begin with.
Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma.

BACKGROUND The standard treatment for patients with multiple myeloma who are not candidates for high-dose therapy is melphalan and prednisone. This phase 3 study compared the use of melphalan and prednisone with or without bortezomib in previously untreated patients with multiple myeloma who were ineligible for high-dose therapy. METHODS We randomly assigned 682 patients to receive nine 6-week cycles of melphalan (at a dose of 9 mg per square meter of body-surface area) and prednisone (at a dose of 60 mg per square meter) on days 1 to 4, either alone or with bortezomib (at a dose of 1.3 mg per square meter) on days 1, 4, 8, 11, 22, 25, 29, and 32 during cycles 1 to 4 and on days 1, 8, 22, and 29 during cycles 5 to 9. The primary end point was the time to disease progression. RESULTS The time to progression among patients receiving bortezomib plus melphalan-prednisone (bortezomib group) was 24.0 months, as compared with 16.6 months among those receiving melphalan-prednisone alone (control group) (hazard ratio for the bortezomib group, 0.48; P<0.001). The proportions of patients with a partial response or better were 71% in the bortezomib group and 35% in the control group; complete-response rates were 30% and 4%, respectively (P<0.001). The median duration of the response was 19.9 months in the bortezomib group and 13.1 months in the control group. The hazard ratio for overall survival was 0.61 for the bortezomib group (P=0.008). Adverse events were consistent with established profiles of toxic events associated with bortezomib and melphalan-prednisone. Grade 3 events occurred in a higher proportion of patients in the bortezomib group than in the control group (53% vs. 44%, P=0.02), but there were no significant differences in grade 4 events (28% and 27%, respectively) or treatment-related deaths (1% and 2%). CONCLUSIONS Bortezomib plus melphalan-prednisone was superior to melphalan-prednisone alone in patients with newly diagnosed myeloma who were ineligible for high-dose therapy. (ClinicalTrials.gov number, NCT00111319.)
Analysis and Experimental Study of a Silicon Photonic Single MRM-Assisted MZI PAM-4 Modulator

We report on the analysis and experimental study of a silicon photonic single microring modulator (MRM) assisted Mach–Zehnder interferometer for high-speed four-level pulse amplitude modulation (PAM-4). The static extinction ratio (ER) of the proposed device is 18 dB larger than that of a single MRM with the same design parameters. Under 0 V reverse bias voltage, the measured 3-dB electro-optic bandwidth of the device is 20 GHz. Based on the enhancement of the ER, the measured 40 Gb/s on–off keying eye diagram of the device shows larger modulation amplitude than that of the single MRM. We further present 76 Gb/s PAM-4 using the proposed device in a back-to-back configuration, with the measured bit error rate below the hard-decision forward error correction threshold of 3.8 × 10–3.
PULMONARY FUNCTION TESTS VERSUS COMPUTED TOMOGRAPHY IN SHEEP WITH EXPERIMENTAL EMPHYSEMA

The authors explored the relative utility of pulmonary function tests (PFTs) and computed tomography (CT) to characterize the progression of papain induced emphysema in sheep (n = 12). PFT included plethysmography (FRCpleth), helium dilution (FRCHe), and expired reserve volume (ERV). Following papain, FRCpleth and FRCHe were unchanged; ERV decreased hence residual volume increased significantly (RV + 270 mL, +86%, P = .02). In contrast, FRC by CT increased in 10 of 12 sheep (+264 mL +21%, P = .008). We conclude that plethysmography was insensitive to emphysema, but the effect on ERV (i.e., trapped gas volume) and FRC by CT were very similar, and in line with the morphologic changes in this animal model.
Emergent Time Windows in Nonlinear Neural Models

In order to study how n to 1 convergence sharpens timing information, we have used a simple time-window (TW) model in which the target neuron fires the first time it has received m action potentials in the previous ε milleseconds. Although the TW is convenient for proving theorems and Monte-Carlo simulations, it is a natural question whether it represents well the physiological reality. We first present simulations that show, in the case n = 3, m = 3, that the Hodgkin-Huxley model has a very sharp time window but the leaky integrate-and-fire model (LIF) does not. Simulations also show that other non-linear models including quadratic-integrate-and-fire (QIF), the theta model, and the Fitzhugh-Nagumo model also have sharp time window behavior. We then give a complete analytical treatment of the LIF and QIF models to explain why the first does not have a sharp time window but the second does. This suggests that TW neurons may give a better approximation to physiological reality than LIF neurons.