Miracle-dz/UniFAR-FTUs huggingface dataset:
Impairment of GABAergic system contributes to epileptogenesis in glutaric acidemia type I

Glutaric acidemia type I (GA‐I) is an inherited neurometabolic disorder caused by deficiency of glutaryl‐CoA dehydrogenase (GCDH) and characterized by increased levels of glutaric, 3‐OH‐glutaric, and glutaconic acids in the brain parenchyma. The increment of these organic acids inhibits glutamate decarboxylase (GAD) and consequently lowers the γ‐aminobutyric acid (GABA) synthesis. Untreated patients exhibit severe neurologic deficits during development, including epilepsy, especially following an acute encephalopathy outbreak. In this work, we evaluated the role of the GABAergic system on epileptogenesis in GA‐I using the Gcdh−/− mice exposed to a high lysine diet (Gcdh−/−‐Lys).
Epidemiology of juvenile rheumatoid arthritis in Manitoba, Canada, 1975-92: cycles in incidence.

OBJECTIVE To determine the yearly incidence of juvenile rheumatoid arthritis (JRA) and to seek correlations between this and cyclic infections occurring in the province of Manitoba, Canada, during the same period. METHODS An estimate of the incidence of JRA in Manitoba was determined from a disease registry of the Pediatric Rheumatology Clinic, Children's Hospital, Winnipeg. The numbers of confirmed Mycoplasma pneumoniae and viral respiratory infections were determined from annual reports of Cadham Provincial Laboratory. Both facilities provide centralized services for the province. RESULTS Between 1975 and 1992 the onset of JRA occurred in 261 patients (136 with pauciarticular, 91 polyarticular, and 34 systemic onset). The average annual incidence of JRA for this period was 5.34/100,000. However, a cyclic incidence was apparent with peaks in 1979, 1982, 1986, and 1990-91. Increases in confirmed M. pneumoniae infections were concurrent with peaks in the incidence of JRA. A significant correlation was found between the incidence of JRA and the number of M. pneumoniae infections detected in the province between 1985 and 1992 (R = 0.76, p = 0.044). In contrast, there was no consistent variation in the incidence of seronegative spondyloarthropathies in children (n = 103 patients). CONCLUSION These data suggest the need for further study of a possible infectious etiology for JRA.
Thyrotoxic Periodic Paralysis: A Review

Thyrotoxic periodic paralysis (TPP) is an unusual complication of hyperthyroidism that frequently presents in a dramatic fashion, necessitating treatment in an emergency department or admission to an intensive care unit. Thyrotoxic periodic paralysis is characterized by transient, recurrent episodes of flaccid muscle paralysis affecting proximal more severely than distal muscles. Thyrotoxic periodic paralysis is most commonly a complication of Graves’ disease in Asian males, although in recent decades, an increasing number of patients from all racial and ethnic backgrounds have been reported. Thyrotoxic periodic paralysis has a higher predilection for men than women despite the fact that thyroid disease is more frequently diagnosed in women. The presence of both hypokalemia and elevated levels of triiodothyronine (T3) and thyroxine (T4) are important diagnostic features during the acute episode. Treatment of TPP involves 2 steps, immediate action to reverse the paralysis followed by measures to prevent future attacks by restoration of a euthyroid state. Although the mainstay of treating an acute attack of TPP is correction of hypokalemia to avoid fatal cardiac arrhythmias and reverse muscle weakness, it must be appreciated by treating physicians that patients with TPP do not have a total body deficiency of potassium. Close attention must be given to potassium replacement as overly aggressive treatment can result in hyperkalemia. Correction of hypokalemia and the underlying thyrotoxic state usually results in amelioration of the acute attack. This review summarizes the epidemiology, clinical manifestations, pathogenesis, diagnosis, and treatment of TPP.
Influence of overload on recovery of rat plantaris from partial denervation.

A functional index of neural adaptability is the capacity of motoneurons to extend and establish supernumerary connections with neighboring denervated muscle fibers. The purpose of this study was to guage this response in rat plantaris muscles subjected to increased levels of activity resulting from the surgical removal of the synergistic gastrocnemius and soleus muscles. Thirty-seven days of overload increased plantaris absolute (69%) and relative (82%) weight, whole muscle (35%) and individual fiber (37%) mean cross-sectional area, half-relaxation time (1/2RT; 25%), and maximum tetanic tension (P0; 21%). In a separate group of animals that had undergone 30 days of overload, three-quarters of the plantaris muscle fibers were denervated by sectioning radicular nerve L4. At 7 days postlesion, contractile responses were obtained from sprouting motor units remaining in radicular nerve L5, and the results compared to a nonoverloaded group that had undergone this same procedure. Twitch time to peak tension and 1/2RT were prolonged in normal partially denervated (PD) and overloaded partially denervated (OPD) muscles, and this response was significantly greater in the overloaded muscles. Both PD and OPD muscles increased twitch tension (38%) and peak tension developed at 25 Hz (34%) to a similar extent, during recovery from partial denervation. These increases, attributable to sprouting of L5 motor axon collaterals, were matched in PD muscles with a corresponding increase in P0, a response which did not occur in OPD muscles. Additionally, a more extensive decrease in P0 occurred as a result of partial denervation in OPD muscles compared with whole muscle P0 of nondenervated muscle (L4 plus L5 stimulation). (ABSTRACT TRUNCATED AT 250 WORDS)
Cost-Aware Streaming Workflow Allocation on Geo-Distributed Data Centers

The virtual machine (VM) allocation problem in cloud computing has been widely studied in recent years, and many algorithms have been proposed in the literature. Most of them have been successfully applied to batch processing models such as MapReduce; however, none of them can be applied to streaming workflow well because of the following weaknesses: 1) failure to capture the characteristics of tasks in streaming workflow for the short life cycle of data streams; 2) most algorithms are based on the assumptions that the price of VMs and traffic among data centers (DCs) are static and fixed. In this paper, we propose a streaming workflow allocation algorithm that takes into consideration the characteristics of streaming work and the price diversity among geo-distributed DCs, to further achieve the goal of cost minimization for streaming big data processing. First, we construct an extended streaming workflow graph (ESWG) based on the task semantics of streaming workflow and the price diversity of geo-distributed DCs, and the streaming workflow allocation problem is formulated into mixed integer linear programming based on the ESWG. Second, we propose two heuristic algorithms to reduce the computational space based on task combination and DC combination in order to meet the strict latency requirement. Finally, our experimental results demonstrate significant performance gains with lower total cost and execution time.
Impact of financial leverage on profitability of listed manufacturing firms in China

The purpose of the study is to explore how financial leverage influences profitability of 1,503 listed manufacturing firms in China. ,The sample of the study is composed of the listed manufacturing firms in China. For the manufacturing firms, the annual financial information from 2008 to 2016 is obtained from the ORBIS database. In this study, initially a simultaneous equation approach is used to control for potential endogeneity. Then, additional regression analyses are conducted with panel data over the period of 2008-2016 using OLS, Fixed-effects, First-difference, Random-effects and Arellano and Bond’s (1991) two-step Generalized Method of Moments (GMM) methods. ,The results reveal that the impact of leverage on profitability is inverted U-shaped. In this inverted U-shaped relationship, the positive impact of financial leverage on profitability could be attributed to tax shield, whereas the negative impact might be because of bankruptcy cost, financial distress, severe agency problems and information asymmetry that the listed Chinese firms suffer from because of some institutional characteristics of China. ,First, this study focuses on only listed manufacturing firms in China. Second, ownership types are not taken into account in this study. ,First, the Chinese government should direct its efforts toward developing the bond markets and promoting alternative privately owned loan creditors to state-owned banks. Parallel to this, the transformation process toward market economy should be accelerated to facilitate the privatization of state-owned enterprises (SOEs). In addition to this, development of the bond market and privatization of SOEs will also mitigate the agency conflict between creditors and managers and between shareholders and managers. ,To the best of the author’s knowledge, this is the first study which investigates the impact of capital structure on profitability of the listed firms in China.
Duloxetine and Venlafaxine-XR in the Treatment of Major Depressive Disorder: A Meta-Analysis of Randomized Clinical Trials

BACKGROUND Duloxetine has joined venlafaxine on the antidepressant market as a second serotonin–norepinephrine reuptake inhibitor. No previous studies have directly compared these drugs. OBJECTIVE To compare indirectly the efficacy and safety of extended-release (XR) venlafaxine and duloxetine, the 2 currently available serotonin–norepinephrine reuptake inhibitors (SNRIs) in treating major depressive disorder. METHODS Outcomes from published, randomized, placebo-controlled trials reporting on moderately to severely depressed patients (Hamilton Rating Scale for Depression [HAM-D] ≥15 or Montgomery-Åsberg Depression Rating Scale [MADRS] ≥18). A systematic literature search of Cochrane, EMBASE, and MEDLINE (1996–January 2005) was performed. Two independent reviewers judged the trials for acceptance, and last observation carried forward data were extracted. Differences in remission (8-week HAM-D score ≤7 or MADRS ≤10), response (50% decrease on either scale), and dropout rates from lack of efficacy and adverse events were meta-analyzed using a random effects model. Each rate was contrasted with placebo. Sensitivity analyses were performed to examine the robustness of the results. RESULTS Data were obtained from 8 trials evaluating 1754 patients for efficacy and 1791 patients for discontinuation/safety. Venlafaxine-XR rates were 17.8% (95% CI 9.0 to 26.5) and 24.4% (95% CI 15.0 to 37.7) greater than those with placebo for remission and response compared with 14.2% (95% CI 8.9 to 26.5) and 18.6% (95% CI 13.0 to 24.2) for duloxetine. Although numerically higher for venlafaxine-XR, no statistically significant differences were found between the drugs; however, both demonstrated overall remission and response rates significantly higher than the rates achieved with placebo (p < 0.001). Reported adverse events were comparable between drugs. CONCLUSIONS Venlafaxine-XR tends to have a favorable trend in remission and response rates compared with duloxetine. However, dropout rates and adverse events did not differ. A direct comparison is warranted to confirm this tendency.
Analytical Modeling of a Double Gate MOSFET Considering Source/Drain Lateral Gaussian Doping Profile

As the MOSFET is scaled into a nanoscale regime, spreading of source/drain (S/D) dopant into the channel region will facilitate the lateral electric field spread into the channel and in turn deteriorate the gate electrostatic integrity. The short channel effects and performance are aggravated with the increase in lateral straggle (σ<sub>L</sub>) of S/D Gaussian profile. In this paper, we have developed an analytical potential model that includes the effect of σ<sub>L</sub>. Subsequently, an expression for threshold voltage and linear/saturation region drain current is proposed and the effect of σ<sub>L</sub> over the transconductance (g<sub>m</sub>), output conductance (g<sub>ds</sub>), and intrinsic gain (A<sub>V0</sub>) is studied.
Axonal fasciculation and the role of polysialic acid‐neural cell adhesion molecule in rat cortical neurons

Axonal fasciculation is a mechanism deployed by growing axons to reach their targets during development of the nervous system. Published data have suggested the involvement of neuronal cell adhesion molecules (NCAM) in axonal fasciculation. We have characterized the formation of axonal fascicles in serum‐free, primary cultures of cortical neurons from embryonic rat brains. Unlike the published data, axonal fascicles in our system have a unique morphology: they are waveform, are rarely thicker than 20 μm, and can reach up to several millimeters in length. We observed an age and time dependence in the formation of fascicles. They formed only in cultures from embryonic day 15–17 brain and only between 4 days in vitro (DIV) and 11 DIV. Electron microscopy showed that the fascicles consisted of mostly axonal processes. Immunocytochemical staining confirmed that the fascicles were positive for the 66‐kDa neurofilament protein, NF66, but they contained few, if any, microtubule‐associated protein‐2‐positive or glial fibrillary acidic protein‐positive processes. Polysialic acids appeared to be critical in the formation of fascicles. Neuraminidase treatment prevented the formation of fascicles when added before 5 DIV. Addition of a specific inhibitor blocked the effect of neuraminidase. The cortical neurons in our model shared several important features with axon fasciculation in vivo and may provide a unique system for studying the molecular mechanisms involved in the formation of axonal tracts in the brain. © 2013 Wiley Periodicals, Inc.
Onset and Duration of Rocuronium and Succinylcholine at the Adductor Pollicis and Laryngeal Adductor Muscles in Anesthetized Humans

BackgroundRocuronium, a new nondepolarizing muscle relaxant, has a rapid onset of activity and may be suitable as a component of a rapid-sequence Induction of anesthesia. We evaluated a range of doses on onset and duration of effect at the larynx and the adductor pollicis and compared these characteristics with those of succinylcholine. MethodsForty-eight patients aged 18–70 yr, of ASA physical status 1–3, were randomly allocated to receive succinylcholine (1 mg/kg) or one of three doses of rocuronium (0.4, 0.8, or 1.2 mg/kg) during surgery. Anesthesia was induced and maintained with propofol and fentanyl. The trachea was intubated without the use of muscle relaxants, and the cuff of the endotracheal tube placed between the vocal cords. Neuromuscular transmission was monitored by mechanomyography at the laryngeal adductor and adductor pollicis muscles. Muscular activity was evoked with supramaximal stimuli in a train-of-four sequence every 12 s to the anterior branch of the recurrent laryngeal nerve and the ulnar nerve. ResultsAt the laryngeal adductors, peak effect exceeded 99% in all patients given succinylcholine and in none (0%), five (42%), and ten (83%) of those given rocuronium 0.4, 0.8, and 1.2 mg/kg, respectively. At the adductor pollicis, peak effect exceeded 99% in all study patients except two who received rocuronium 0.4 mg/kg (peak effects 91% and 97%). Onset of effect with succinylcholine was significantly more rapid at the laryngeal adductors (34 ± 12 s, mean ± SD) than at the adductor pollicis (56 ± 15 s); this was true also for rocuronium 0.4 mg/kg (92 ± 29 s and 155 ± 40 s for the laryngeal adductors and adductor pollicis, respectively). Onset times were similar at the two muscle groups with rocuronium 0.8 and 1.2 mg·kg-1: 96 ± 29 and 74 ± 36 s with 0.8 mg/kg and 54 ± 30 and 65 ± 21 s with 1.2 mg/kg at the laryngeal adductors and the adductor pollicis, respectively. ConclusionsThe laryngeal adductors are more resistant to the action of rocuronium than is the adductor pollicis. Consequently, the onset of effect of rocuronium, in doses greater than 0.8 mg/kg, is similar to that of succinylcholine at the adductor pollicis but Is significantly delayed compared with that of succinylcholine at the laryngeal adductors.
Discontinuation of anti-tumor necrosis factor therapy in inflammatory bowel disease patients: a prospective observation

Abstract Background: Discontinuation of anti-TNF therapy in patients with inflammatory bowel diseases (IBD) in remission remains a controversial issue. The aims of our study were to assess the proportion of patients who relapse after cessation of biological treatment, and to identify potential risk factors of disease relapse. Methods: Consecutive IBD patients who discontinued anti-TNF therapy in steroid-free clinical and endoscopic remission were prospectively followed. Multiple logistic regression and Cox proportional-hazards models were used to assess the predictors of disease relapse. Results: Seventy-eight IBD patients (Crohn's disease, CD 61; ulcerative colitis, UC 17) were included and followed for a median of 30 months (range 7–47). A total of 32 (53%) CD patients and nine (53%) UC patients relapsed by the end of the follow-up with a median time to relapse of 8 months (range 1–25) in CD patients and 14 months (range 4–37) in UC patients, respectively. The cumulative probabilities of maintaining remission at 6, 12, and 24 months were 82%, 59%, and 51% in CD patients, and 77%, 77%, and 64% in UC patients, respectively. Survival of CD patients who were in deep remission (clinical and endoscopic healing; faecal calprotectin <150 mg/kg; CRP ≤5 mg/l) was not better compared with those who did not fulfill these criteria. In multivariate models, only colonic CD protected patients from disease relapse. Conclusions: Approximately half of the IBD patients relapsed within 2 years after anti-TNF discontinuation. In CD patients, no difference between those who were or were not in deep remission was found. Colonic localization protected patients from relapse.
Effects of a 4-Week Intrinsic Foot Muscle Exercise Program on Motor Function: A Preliminary Randomized Control Trial.

Context: Intrinsic foot muscle (IFM) exercises are utilized clinically in the treatment of foot and ankle conditions. However, the effectiveness of training on IFM motor function is unknown. Objective: To study the effects of a 4-week IFM exercise program on motor function, perceived difficulty, and IFM motor activation measured using ultrasound imaging (USI) during 3 IFM exercises. Design: Single-blinded randomized control trial. Setting: Laboratory. Participants: A total of 24 healthy, recreationally active young adults without history of ankle-foot injury who have never performed IFM exercises participated (12 males and 12 females; mean age = 21.5 [4.8] y; body mass index = 23.5 [2.9] kg/m2) Intervention: Following randomization, participants allocated to the intervention group received a 4-week progressive home IFM exercise program performed daily. Participants in the control group did not receive any intervention. Main Outcome Measures: Clinician-assessed motor performance (4-point scale: 0 = does not initiate movement and 3 = performs exercise in standard pattern), participant-perceived difficulty (5-point Likert scale: 1 = very easy and 5 = very difficult), and USI motor activation measures (contracted measurementresting measurement) of the abductor hallucis, flexor digitorum brevis, quadratus plantae, and flexor hallucis brevis were assessed during toe-spread-out, hallux-extension, and lesser-toe-extension exercises. Results: The intervention group demonstrated significant improvement in motor performance in the toe-spread-out exercise (pre = 1.9 [0.5], post = 2.6 [0.5], P = .008) and less perceived difficulty in the toe-spread-out (pre = 3.1 [1.3], post = 2.3 [1.2], P = .01), hallux-extension (pre = 3.2 [1.5], post = 2.0 [1.2], P = .005), and lesser-toe-extension (pre = 1.9 [0.7], post = 1.2 [0.4], P = .03) exercises. Both groups demonstrated increased USI motor activation in the abductor hallucis during the toe-spread-out exercise (intervention: pre = 1.07 [0.06], post = 1.11 [0.08] and control: pre = 1.08 [0.06], post = 1.11 [0.06]; P = .05). No other significant main effects or group by time interactions were observed. Conclusion: A 4-week IFM exercise intervention resulted in improved motor performance and decreased perceived difficulty when performing the exercises, but not changes in USI measures of IFM activation compared with a control group.
Fetal Cholelithiasis: Antenatal Diagnosis and Neonatal Follow-Up in a Case of Twin Pregnancy – A Case Report and Review of the Literature

Abstract Fetal cholelithiasis is a rare finding during a third-trimester ultrasound with an average incidence rate of 0.07–1.15%. We report a case of fetal cholelithiasis in twins, observed in a patient with monochorionic diamniotic twin pregnancy hospitalized at our unit for signs of premature labor. We present the outcome of the 2 neonates with a clinical and sonographic follow-up. In addition, we offer a comprehensive review of the literature available to date.
Moesin Is Not a Receptor for Measles Virus Entry into Mouse Embryonic Stem Cells

ABSTRACT The involvement of moesin in measles virus (MV) entry was investigated with moesin-positive and -negative mouse embryonic stem (ES) cells. MV infection of these cells was very ineffective and was independent of moesin expression. Furthermore, when these cells were transfected to express human CD46, a 100-fold increase in syncytium formation was observed with these cells and was independent of the expression of moesin. The only obvious difference between moesin-positive and -negative ES cells was the shape of the syncytia formed. Moesin-negative ES cells expressing or not expressing human CD46 formed separate pieces of fragmented syncytia which were torn apart during spreading, whereas ES cells expressing moesin exhibited typical syncytia. In addition, moesin was not detected on the surface of any murine cells or cell lines that we have tested by a flow cytometric assay with moesin-specific antibodies. These findings indicate that murine moesin is neither a receptor nor a CD46 coreceptor for MV entry into mouse ES cells. Moesin is involved in actin filament-plasma membrane interactions as a cross-linker, and it affects only the spreading and shape of MV-mediated syncytia.