Miracle-dz/UniFAR-FTUs huggingface dataset:
Myasthenia gravis and thymectomy: many doubts and few certainties.

Myasthenia gravis (MG) is a rare autoimmune disease affecting neuromuscular transmission. The thymus plays a central role in the complex pathogenesis and perpetuation of this disease, being implicated in mechanisms of self-tolerance and autoimmunity. Since the study of Blalock [1] in 1944, who published the results of transternal thymectomy in a series of 20 patients affected by MG, thymectomy has become an essential part of the integrated treatment of this disease, yielding positive results in terms of improvement and remission of symptoms. The report by Keijzers et al . [ 2] in this issue of EJCTS provides the neurological and surgical results of robotic thymectomy in a large cohort of patients affected by MG. This study summarizes the main concerns regarding the role of thymectomy in MG patients. Despite a general agreement on the beneficial role of thymectomy for MG patients, to date no prospective randomized trials have addressed the question whether thymectomy is superior to medical treatment. This question is the subject of an ongoing international multicentre randomized clinical trial comparing thymectomy and prednisone therapy with prednisone alone [3]. The best available data come from a meta-analysis of 28 controlled but nonrandomized studies that showed MG patients undergoing thymectomy were twice more likely to attain medication-free remission than unoperated patients, 1.6 times more likely to become asymptomatic and 1.7 times more likely to improve [4]. In addition to this low level of evidence supporting thymectomy, several controversies still exist regarding the selection of candidates for surgery, the extent of thymic resection and the best surgical approach to be used [5]. Thus, a consensus on the best clinical practice has never been reached. For these reasons, when considering thymectomy for MG patients, clinicians have to think imperatively over the ratio between expected benefits and risks guaranteeing the best balance between the extent of resection, morbidity, patient acceptance and results. In our view, three key points are of paramount importance: (i) Surgical risk-benefit balance: A variety of surgical approaches have been described for thymectomy ranging from open (basic transsternal or the more aggressive extended transcervical and transsternal maximal thymectomy), to minimally invasive approaches (transcervical or video-assisted thoracoscopic thymectomy). When compared, each approach has its benefits and drawbacks. At this time, only non-randomized retrospective case series are available for comparison of various operative approaches. The heterogeneity of patient selection, the different timing and type of surgery, the several clinical classifications used, the different methods applied for the evaluation of results and many other confounding factors have made the analysis complicated, if not impossible (Class III evidence) [6]. Ideally, the less invasive surgical technique is desirable, assum
Conserved features of type III secretion

Type III secretion systems (TTSSs) are essential mediators of the interaction of many Gram‐negative bacteria with human, animal or plant hosts. Extensive sequence and functional similarities exist between components of TTSS from bacteria as diverse as animal and plant pathogens. Recent crystal structure determinations of TTSS proteins reveal extensive structural homologies and novel structural motifs and provide a basis on which protein interaction networks start to be drawn within the TTSSs, that are consistent with and help rationalize genetic and biochemical data. Such studies, along with electron microscopy, also established common architectural design and function among the TTSSs of plant and mammalian pathogens, as well as between the TTSS injectisome and the flagellum. Recent comparative genomic analysis, bioinformatic genome mining and genome‐wide functional screening have revealed an unsuspected number of newly discovered effectors, especially in plant pathogens and uncovered a wider distribution of TTSS in pathogenic, symbiotic and commensal bacteria. Functional proteomics and analysis further reveals common themes in TTSS effector functions across phylogenetic host and pathogen boundaries. Based on advances in TTSS biology, new diagnostics, crop protection and drug development applications, as well as new cell biology research tools are beginning to emerge.
Improved cine displacement‐encoded MRI using balanced steady‐state free precession and time‐adaptive sensitivity encoding parallel imaging at 3 T

Cine displacement‐encoded MRI is a promising modality for quantifying regional myocardial function. However, it has two major limitations: low signal‐to‐noise ratio (SNR) and data acquisition efficiency. The purpose of this study was to incrementally improve the SNR and the data acquisition efficiency of cine displacement‐encoded MRI through the combined use of balanced steady‐state free precession (b‐SSFP) imaging, 3T imaging, echo‐combination image reconstruction, and time‐adaptive sensitivity encoding (TSENSE) parallel imaging. Phantom experiments were performed to empirically determine the optimal excitation angle (α) and to estimate the measurement errors in the presence of 130 Hz peak‐to‐peak static magnetic field (B0) variation. The optimal α was determined to be 20°. The intrinsic phase correction in the echo‐combination effectively reduced the phase error, which produced small displacement errors (0.11 versus 0.11 mm) and negligible strain errors (−0.001 versus −0.002). Six healthy volunteers were imaged in three short‐axis levels of the heart to evaluate the SNR and the relative accuracy of strain calculations. Compared with the 24‐heartbeat cine echo‐planar imaging acquisition, the 24‐heartbeat non‐accelerated b‐SSFP acquisition yielded approximately 65% higher SNR, and the 12‐heartbeat twofold accelerated b‐SSFP acquisition yielded approximately 28% higher SNR. The 12‐heartbeat twofold accelerated b‐SSFP acquisition yielded functional maps with spatial resolution of 3.6 × 3.6 mm, temporal resolution of 35 ms, and relatively high SNR (31.2 ± 5.4 at end diastole; 19.9 ± 3.6 at end systole; 10.3 ± 1.1 at late diastole; mean ± SD). The left ventricular strain values between the non‐accelerated and twofold accelerated b‐SSFP acquisitions correlated strongly (slope = 0.99; bias = 0.00; R2 = 0.91) and were in excellent agreement. The combined implementation of b‐SSFP imaging, 3T imaging, echo‐combination image reconstruction, and TSENSE parallel imaging can be used to incrementally improve the cine displacement‐encoded MRI pulse sequence. Copyright © 2007 John Wiley & Sons, Ltd.
The CRR1 Nutritional Copper Sensor in Chlamydomonas Contains Two Distinct Metal-Responsive Domains[C][W][OA]

The binding of the SBP domain of CRR1 to copper response elements of target promoters in vitro is blocked by Cu(II) or Hg(II), which also deactivate transcription in vivo. Mutagenesis of the SBP domain implicates a conserved His residue in interaction with copper ions, suggesting a mechanism for copper sensing. A metallothionein-like domain at the CRR1 C terminus is implicated in zinc homeostasis. Copper response regulator 1 (CRR1), an SBP-domain transcription factor, is a global regulator of nutritional copper signaling in Chlamydomonas reinhardtii and activates genes necessary during periods of copper deficiency. We localized Chlamydomonas CRR1 to the nucleus in mustard (Sinapis alba) seedlings, a location consistent with its function as a transcription factor. The Zn binding SBP domain of CRR1 binds copper ions in vitro. Cu(I) can replace Zn(II), but the Cu(II) form is unstable. The DNA binding activity is inhibited in vitro by Cu(II) or Hg(II) ions, which also prevent activation of transcription in vivo, but not by Co(II) or Ni(II), which have no effect in vivo. Copper inhibition of DNA binding is reduced by mutation of a conserved His residue. These results implicate the SBP domain in copper sensing. Deletion of a C-terminal metallothionein-like Cys-rich domain impacted neither nutritional copper signaling nor the effect of mercuric supplementation, but rendered CRR1 insensitive to hypoxia and to nickel supplementation, which normally activate the copper deficiency regulon in wild-type cells. Strains carrying the crr1-ΔCys allele upregulate ZRT genes and hyperaccumulate Zn(II), suggesting that the effect of nickel ions may be revealing a role for the C-terminal domain of CRR1 in zinc homeostasis in Chlamydomonas.
Metal-free transfer hydrogenation of olefins via dehydrocoupling catalysis

Significance For more than a century, hydrogenation has been limited to the use of transition metal-based catalysts. With the emerging focus on the chemistry of earth-abundant elements, the 21st century has seen a renaissance in main-group chemistry. In this work, an electrophilic phosphonium cation is shown to act as main-group catalyst effecting the dehydrocoupling of silane and amines, phenols, thiols, and carboxylic acids with the concurrent release of H2. In addition, performing the reactions in the presence of olefins, dehydrocoupling occurs with simultaneous hydrogenation of the olefin. This chemistry provides an unprecedented avenue to metal-free transfer hydrogenation catalysis of olefins. A major advance in main-group chemistry in recent years has been the emergence of the reactivity of main-group species that mimics that of transition metal complexes. In this report, the Lewis acidic phosphonium salt [(C6F5)3PF][B(C6F5)4] 1 is shown to catalyze the dehydrocoupling of silanes with amines, thiols, phenols, and carboxylic acids to form the Si-E bond (E = N, S, O) with the liberation of H2 (21 examples). This catalysis, when performed in the presence of a series of olefins, yields the concurrent formation of the products of dehydrocoupling and transfer hydrogenation of the olefin (30 examples). This reactivity provides a strategy for metal-free catalysis of olefin hydrogenations. The mechanisms for both catalytic reactions are proposed and supported by experiment and density functional theory calculations.
Cloud Computing Security

In this paper, the authors focus on Cloud Computing, which is a distributed architecture that centralizes server resources on quite a scalable platform so as to provide on demand' computing resources and services The authors outline what cloud computing is, the various cloud deployment models and the main security risks and issues that are currently present within the cloud computing industry.
Recent Improvements in the SMT Solver iSAT

Over the past decades embedded systems have become more and more complex. Furthermore, besides digital components they now often contain additional analog parts – making them to embedded hybrid systems. If such systems are used in safety critical environments, a formal correctness proof is highly desirable. The SMT solver iSAT aims at solving boolean combinations of linear and non-linear constraint formulas (including transcendental functions), and thus is suitable to verify safety properties of systems consisting of both, linear and nonlinear behaviour. To keep up with the ever increasing complexity of these systems we present recent improvements in various parts of iSAT. Experiments demonstrate that iSAT with all the presented improvements integrated typically gains a speedup between one and two orders of magnitude.
Genetic Diversity of Parasitic Dinoflagellates in the Genus Amoebophrya and Its Relationship to Parasite Biology and Biogeography

ABSTRACT. We determined 18S rRNA gene sequences of Amoebophrya strains infecting the thecate dinoflagellates Alexandrium affine and Gonyaulax polygramma from Korean coastal waters and compared those data with previously reported sequences of Amoebophrya from cultures, infected cells concentrated from field samples, and environmental 18S rRNA gene sequences obtained from a variety of marine environments. Further, we used these data to examine genetic diversity in Amoebophrya strains relative to geographic origin, host phylogeny, site of infection, and host specificity. In our analyses of known dinoflagellate taxa, the 13 available Amoebophrya sequences clustered together within the dinoflagellates as three groups forming a monophyletic group with high bootstrap support (maximum likelihood, ML: 100%) or a posterior probability (PP) of 1. When the Amoebophrya sequences were analyzed along with environmental sequences associated with Marine Alveolate Group II, nine subgroups formed a monophyletic group with high bootstrap support (ML: 100%) and PP of 1. Sequences known to be from Amoebophrya spp. infecting dinoflagellate hosts were distributed in seven of those subgroups. Despite differences in host species and geographic origin (Korea, United States, and Europe), Amoebophrya strains (Group II) from Gymnodinium instriatum, A. affine, Ceratium tripos (AY208892), Prorocentrum micans, and Ceratium lineatum grouped together by all of our tree construction methods, even after adding the environmental sequences. By contrast, strains within Groups I and III divided into several lineages following inclusion of environmental sequences. While Amoebophrya strains within Group II mostly developed within the host cytoplasm, strains in Groups I and III formed infections inside the host nucleus, a trait that appeared across several of the subgroups. Host specificity varied from moderately to extremely species‐specific within groups, including Group II. Taken together, our results imply that genetic diversity in Amoebophrya strains does not always reflect parasite biology or biogeography.
Bestimmungen von CRP und Neopterin sowie antiendotoxischer Antikörper bei Pferden mit Fieber

Zusammenfassung Gegenstand: Feldstudie zum Fieber unbekannter Genese beim Pferd. Ziel: Die routinemäßigen Laborparameter wurden hinsichtlich ihrer Wertigkeit für eine ätiologische Diagnose analysiert. Das diagnostische Profil wurde durch die Parameter CRP und Neopterin sowie durch antiendotoxische Antikörper erweitert. Grundlage der Studie war die Hypothese, dass Endotoxine mit ihrem fieberauslösenden Potenzial eine ätiologische Bedeutung haben könnten. Material und Methoden: Über einen Zeitraum von drei Jahren wurden 383 Fieberfälle untersucht und entsprechend der klinischen Symptomatik in vier verschiedene Fiebertypen eingeteilt. Die Voraussetzung für die Einordnung in die Gruppe 1 (Fieber unbekannter Genese) war der Ausschluss einer anderen Fieberursache bei der Erst- und den Nachuntersuchungen. Die Blutprobe wurde am ersten Untersuchungstag entnommen. Die Bestimmungen von CRP und Neopterin sowie der antiendotoxischen Antikörper erfolgten jeweils mit einem ELISA. In die Auswertung dieser Messergebnisse wurde deren Korrelation zu weiteren klinisch-chemischen Parametern einbezogen. Ergebnisse: Bei 195 (50,9%) Patienten wurde Fieber unbekannter Genese registriert. Während der mittlere CRP-Wert (8,08 g/l) im Normbereich lag, war die Neopterinkonzentration (7,29 mmol/l) erhöht. Die Mittelwerte für die antiendotoxischen Antikörpertiter der Immunglobulinklasse M waren pathologisch erhöht (Anti-Lipid-A-IgM 1,18 OD, Anti-Endotoxin-IgM 1,5 OD). Klinische Relevanz: Das pyrogene Potenzial der Endotoxine ist bei Fällen von Fieber unbekannter Genese in die ätiologischen Betrachtungen mit einzubeziehen. Nach Ausschluss anderer Fieberursachen ist eine diesbezügliche Erweiterung des labordiagnostischen Profils sinnvoll. Neopterin und CRP stellen unspezifische Effektparameter dar, die im Zusammenhang mit weiteren Befunden auch beim Pferd für die Beurteilung des Gesundheitszustandes wertvoll sein können.
Does preoperative anxiety felt by patients requested to participate in clinical trials related to general anesthesia before elective surgery depend on temperament?

Background Preoperative anxiety may differ according to patient temperament. It will be increased when patients are requested to participate in a study involving anesthesia. The purpose of this study was to show that the anxiety felt when patients are requested to participate may differ according to temperament in both patients who agree and disagree to participate. Methods Three hundred and twenty-one patients over age 18 with American Society of Anesthesiologists 1 and 2 completed a survey questionnaire. The degree of anxiety was measured according to patient temperament. It was compared on the basis of the State-Trait Anxiety Inventory (STAI) and visual analogue scale (VAS). Results In the agreed group, the degree of anxiety measured by “usual, present STAI” and VAS in the monitors (those who want to know as much as possible about anesthesia and surgery) was significantly higher than that in the blunters (those who want to know as little as possible) (P = 0.041 for the “usual STAI”, 0.017 for “present STAI”, and 0.001 for VAS, respectively). Among patients with a lower educational level, the numbers of blunters and monitors were 57 (79%) and 32 (59%), respectively, indicating that the ratio of blunters was significantly higher (P = 0.026). Conclusions Both traits of patients in each group were influenced by psychological burdens. The anxiety of the monitors who agreed to participate was significantly higher than that of blunters. In addition to temperament, education level affects participation. Obtaining consent for participation by understanding temperament and considering factors that may reduce the participation rate will be required.
Anti-phospholipid antibodies.

This editorial refers to Low-dose aspirin versus low-dose aspirin plus low-intensity warfarin in thromboprophylaxis: a prospective, multicentre, randomized, open, controlled trial, in patients positive for antiphospholipid antibodies (ALIWAPAS), by Maria J. Cuadrado et al., doi:10.1093/rheumatology/ket313, on pages 275-84.
Serum, plasma and saliva biomarkers for head and neck cancer

ABSTRACT Introduction: Head and neck squamous cell carcinoma (HNSCC) encompasses tumors arising from several locations (oral and nasal cavities, paranasal sinuses, salivary glands, pharynx, and larynx) and currently stands as the sixth most common cancer worldwide. The most important risk factors identified so far are tobacco and alcohol consumption, and, for a subgroup of HNSCCs, infection with high-risk types of human papillomavirus (HPV). Despite several improvements in the treatment of these tumors in the last decades, overall survival rates have only improved marginally, mainly due to the advanced clinical stage at diagnosis and the high rates of treatment failure associated with this late diagnosis. Areas covered: This review will focus on the feasibility of evaluating molecular-based biomarkers (mRNA, microRNA, lncRNA, DNA methylation and protein expression) in body fluids (serum, plasma, and saliva) as markers for diagnosis, prognosis, and surveillance. Expert commentary: The potential use of those markers in the clinical setting would allow for early diagnosis, prediction of treatment response, improvement in treatment selection and provide disease monitoring for early detection of tumor recurrence. It can ultimately be translated into better survival rates and improved quality of life for HNSCC patients.
Mutation Q95K enhances N155H-mediated integrase inhibitor resistance and improves viral replication capacity.

OBJECTIVES The genetic barrier to development of raltegravir resistance is considered to be low, requiring at least one primary integrase mutation: Y143C, Q148H/K/R or N155H to confer raltegravir therapy failure. However, during continued raltegravir treatment failure, additional mutations may be selected. In a patient failing raltegravir therapy, we investigated the impact of multiple integrase mutations on resistance and viral replication. Furthermore, in vivo fitness was investigated during failure of raltegravir-containing highly active antiretroviral therapy and after raltegravir was discontinued from the regimen. METHODS Patient-derived viral integrase genes were cloned into a reference strain. These recombinant viruses were used to determine the contribution of individual integrase mutations to raltegravir resistance and replication capacity in vitro. To determine in vivo fitness, the relative proportion of specific integrase mutations was monitored over time by in-depth clonal analysis of the viral integrase at baseline, during and after raltegravir treatment. RESULTS Raltegravir therapy failure was associated with the initial selection of primary resistance mutation N155H. This mutation conferred a 3.8-fold reduction in raltegravir susceptibility and a severe reduction in viral replication. Acquisition of integrase mutation Q95K increased resistance (6.2-fold) and partly restored viral replication. Selection of a third mutation, V151I, further increased raltegravir resistance (20-fold), but decreased viral replication. After prolonged raltegravir interruption, raltegravir resistance mutations were lost, demonstrating the reduced replication capacity of the resistant virus. CONCLUSIONS We describe selection of Q95K as a secondary resistance mutation during raltegravir therapy failure. In the background of N155H, Q95K enhances raltegravir and elvitegravir resistance and improves the impaired replication of the virus.
Irradiation as a Phytosanitary Treatment for Aspidiotus destructor (Homoptera: Diaspididae)

Abstract Coconut scale, Aspidiotus destructor Signoret (Homoptera: Diaspididae), is a quarantine pest of banana (Musa spp.) and many tropical crops. Irradiation was examined as a potential phytosanitary treatment to control coconut scale. Dose–response tests were conducted with second-stage nymphs, adult females without eggs, and adult females with eggs at a series of irradiation doses between 60 and 200 Gy to determine the most tolerant stage. The adult female with eggs was the most tolerant stage. In large-scale validation tests and dose–response tests, a total of 32,716 adult female scales with eggs irradiated with doses between 100 and 150 Gy produced no F1 adults with eggs. Irradiation treatment with a minimum absorbed dose of 150 Gy should provide quarantine security for coconut scale on exported commodities.
Muscle NaK-pump and fatigue responses to progressive exercise in normoxia and hypoxia

Sandiford, S. D. , H. J. Green, T. A. Duhamel, J. D. Schertzer, J. D. Perco, and J. Ouyang. Muscle Na-K-pump and fatigue responses to progressive exercise in normoxia and hypoxia. Am J Physiol Regul Integr Comp Physiol 289: R441–R449, 2005. First published April 28, 2005; doi:10.1152/ajpregu.00652. 2004. —To investigate the effects of hypoxia and incremental exercise on muscle contractility, membrane excitability, and maximal Na -K -ATPase activity, 10 untrained volunteers (age 20 0.37 yr and weight 80.0 3.54 kg; SE) performed progressive cycle exercise to fatigue on two occasions: while breathing normal room air (Norm; FIO2 0.21) and while breathing a normobaric hypoxic gas mixture (Hypox; FIO2 0.14). Muscle samples extracted from the vastus lateralis before exercise and at fatigue were analyzed for maximal Na -K -ATPase (K -stimulated 3-O-methylfluorescein phosphatase) activity in homogenates. A 32% reduction (P 0.05) in Na -K -ATPase activity was observed (90.9 7.6 vs. 62.1 6.4 nmol mg protein 1 h ) in Norm. At fatigue, the reductions in Hypox were not different (81 5.6 vs. 57.2 7.5 nmol mg protein 1 h ) from Norm. Measurement of quadriceps neuromuscular function, assessed before and after exercise, indicated a generalized reduction (P 0.05) in maximal voluntary contractile force (MVC) and in force elicited at all frequencies of stimulation (10, 20, 30, 50, and 100 Hz). In general, no differences were observed between Norm and Hypox. The properties of the compound action potential, amplitude, duration, and area, which represent the electomyographic response to a single, supramaximal stimulus, were not altered by exercise or oxygen condition when assessed both during and after the progressive cycle task. Progressive exercise, conducted in Hypox, results in an inhibition of Na -K -ATPase activity and reductions in MVC and force at different frequencies of stimulation; these results are not different from those observed with Norm. These changes occur in the absence of reductions in neuromuscular excitability.