bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exome sequencing identifies titin mutations causing hereditary myopathy with early respiratory failure (HMERF) in families of diverse ethnic origins
Authors: Toro Camilo , Olivé Montse , Dalakas Marinos C , Sivakumar Kumaraswami , Bilbao Juan M , Tyndel Felix , Vidal Noemí , Farrero Eva , Sambuughin Nyamkhishig , Goldfarb Lev G 
Published: March 2013

Abstract

Background
Hereditary myopathy with early respiratory failure (HMERF) was described in several North European families and recently linked to a titin gene (TTN) mutation. We independently studied HMERF-like diseases with the purpose to identify the cause, refine diagnostic criteria, and estimate the frequency of this disease among myopathy patients of various ethnic origins.

Methods
Whole exome sequencing analysis was carried out in a large U.S. family that included seven members suffering from skeletal muscle weakness and respiratory failure. Subsequent mutation screening was performed in further 45 unrelated probands with similar phenotypes. Studies included muscle strength evaluation, nerve conduction studies and concentric needle EMG, respiratory function test, cardiologic examination, and muscle biopsy.

Results
A novel TTN p.Gly30150Asp mutation was identified in the highly conserved A-band of titin that co-segregated with the disease in the U.S. family. Screening of 45 probands initially diagnosed as myofibrillar myopathy (MFM) but excluded based on molecular screening for the known MFM genes led to the identification of a previously reported TTN p.Cys30071Arg mutation in one patient. This same mutation was also identified in a patient with suspected HMERF. The p.Gly30150Asp and p.Cys30071Arg mutations are localized to a side chain of fibronectin type III element A150 of the 10th C-zone super-repeat of titin.

Conclusions
Missense mutations in TTN are the cause of HMERF in families of diverse origins. A comparison of phenotypic features of HMERF caused by the three known TTN mutations in various populations allowed to emphasize distinct clinical/pathological features that can serve as the basis for diagnosis. The newly identified p.Gly30150Asp and the p.Cys30071Arg mutation are localized to a side chain of fibronectin type III element A150 of the 10th C-zone super-repeat of titin.
A word of caution: do not wake sleeping dogs; micrometastases of melanoma suddenly grew after progesterone treatment
Authors: Mordoh Jose , Tapia Ivana Jaqueline , Barrio Maria Marcela 
Published: March 2013

AbstractBackgroundHormonal treatment might affect the immune response to tumor antigens induced in cancer patients who are being vaccinated.Case presentationA 33 years-old woman was diagnosed with cutaneous melanoma in May 2009. Her melanoma was located in the intermammary sulcus, had a Breslow thickness of 4 mm, a Clark’s level IV, it was ulcerated and highly melanotic. The bilateral sentinel node biopsy was negative. She entered into a randomized Phase II/III clinical study comparing a vaccine composed of irradiated melanoma cells plus BCG plus GM-CSF versus IFN-alpha 2b and she was assigned to the vaccine arm. During the two years treatment she remained disease-free; the final CAT scan being performed in August 2011. Between November and December 2011, her gynecologist treated her with three cycles of 200 mg progesterone/day for ten days, every two weeks, for ovary dysfunction. In November 2011 the patient returned to the Hospital for clinical and imaging evaluation and no evidence of disease was found. At the next visit in March 2012 an ultrasound revealed multiple, large metastases in the liver. A CAT scan confirmed the presence of liver, adrenal glands and spleen metastases. A needle biopsy of a liver lesion revealed metastatic melanoma of similar characteristics to the original tumor. We suggest that progesterone treatment triggered proliferation of so far dormant micrometastases that were controlled during CSF470 vaccine treatment.ConclusionThe use of progesterone in patients with melanoma that are under immunological treatments should be carefully considered, since progesterone could modify the balance of pro-inflammatory and Th1 functions to a regulatory and anti-inflammatory profile of the immune system that could have an impact in tumor progression.
The relationship between visceral fat thickness and bone mineral density in sedentary obese children and adolescents
Authors: Júnior Ismael Forte Freitas , Cardoso Jefferson Rosa , Christofaro Diego G Destro , Codogno Jamile Sanches , de Moraes Augusto César Ferreira , Fernandes Rômulo Araújo 
Published: March 2013

Abstract

Background
Among adults, obesity has been positively related to bone mineral density. However, recent findings have pointed out that abdominal obesity could be negatively related to bone density. The above mentioned relationship is not clear among pediatric populations. Therefore, this cross-sectional study analyzed the relationship between thickness of abdominal adipose tissue and bone mineral variables in sedentary obese children and adolescents.

Methods
One hundred and seventy five obese children and adolescents (83 male and 92 female) with ages ranging from 6 to 16 years-old were analyzed. Bone mineral content and density were estimated by dual-energy X-ray absorptiometry and ultrasound equipment which estimated the thickness of the abdominal adipose tissue. Pubertal stage was self-reported by the participants.

Results
The mean age was 11.1 (SD = 2.6). Thickness of the abdominal adipose tissue was negatively related to bone mineral density (r = −0.17 [r
95%CI: -0.03;-0.32]), independent of gender, pubertal stage and other confounders (β = −0.134 ± 0.042 [β95%CI: -0.217; -0.050]).

Conclusions
In sedentary obese children and adolescents abdominal obesity is negatively related to bone mineral density, suggesting a potential link between abdominal obesity and osteoporosis.
Screening NK-, B- and T-cell phenotype and function in patients suffering from Chronic Fatigue Syndrome
Authors: Curriu Marta , Carrillo Jorge , Massanella Marta , Rigau Josepa , Alegre José , Puig Jordi , Garcia-Quintana Ana M , Castro-Marrero Jesus , Negredo Eugènia , Clotet Bonaventura , Cabrera Cecilia , Blanco Julià 
Published: March 2013

Abstract

Background
Chronic Fatigue Syndrome (CFS) is a debilitating neuro-immune disorder of unknown etiology diagnosed by an array of clinical manifestations. Although several immunological abnormalities have been described in CFS, their heterogeneity has limited diagnostic applicability.

Methods
Immunological features of CFS were screened in 22 CFS diagnosed individuals fulfilling Fukuda criteria and 30 control healthy individuals. Peripheral blood T, B and NK cell function and phenotype were analyzed by flow cytometry in both groups.

Results
CFS diagnosed individuals showed similar absolute numbers of T, B and NK cells, with minor differences in the percentage of CD4+ and CD8+ T cells. B cells showed similar subset frequencies and proliferative responses between groups. Conversely, significant differences were observed in T cell subsets. CFS individuals showed increased levels of T regulatory cells (CD25+/FOXP3+) CD4 T cells, and lower proliferative responses in vitro and in vivo. Moreover, CD8 T cells from the CFS group showed significantly lower activation and frequency of effector memory cells. No clear signs of T-cell immunosenescence were observed. NK cells from CFS individuals displayed higher expression of NKp46 and CD69 but lower expression of CD25 in all NK subsets defined. Overall, T cell and NK cell features clearly clustered CFS individuals.

Conclusions
Our findings suggest that alterations in T-cell phenotype and proliferative response along with the specific signature of NK cell phenotype may be useful to identify CFS individuals. The striking down modulation of T cell mediated immunity may help to understand intercurrent viral infections in CFS.
A hybrid multi-path routing algorithm for industrial wireless mesh networks
Authors: Zuo Yun , Ling Zhihao , Yuan Yifeng 
Published: March 2013

Abstract
Multi-path routing, a routing technique that enables data transmission over multiple paths, is an effective strategy in achieving reliability in wireless sensor networks. However, multi-path routing does not guarantee deterministic transmission. This is because more than one path is available for transferring data from the source node to the destination node. A hybrid multi-path routing algorithm is proposed for industrial wireless mesh networks for improving reliability and determinacy of data transmission, as well as to effectively deal with link failures. The proposed algorithm adopts the enhanced Dijkstra’s algorithm for searching the shortest route from the gateway to each end node for first route setup. A virtual pheromone distinct from the regular pheromone is introduced to realize pheromone diffusion and updating. In this way, multiple routes are searched based on the ant colony optimization algorithm. The routes used for data transmission are selected based on their regular pheromone values, facilitating the delivery of data through better routes. Link failures are then handled using route maintenance mechanism. Simulation results demonstrate that the proposed algorithm outperforms traditional algorithms in terms of average end-to-end delay, packet delivery ratio, and routing overhead; moreover, it has a strong capacity to cope with topological changes, thereby making it more suitable for industrial wireless mesh networks.
Quantifiable diagnosis of muscular dystrophies and neurogenic atrophies through network analysis
Authors: Sáez Aurora , Rivas Eloy , Montero-Sánchez Adoración , Paradas Carmen , Acha Begoña , Pascual Alberto , Serrano Carmen , Escudero Luis M 
Published: March 2013

Abstract

Background
The diagnosis of neuromuscular diseases is strongly based on the histological characterization of muscle biopsies. However, this morphological analysis is mostly a subjective process and difficult to quantify. We have tested if network science can provide a novel framework to extract useful information from muscle biopsies, developing a novel method that analyzes muscle samples in an objective, automated, fast and precise manner.

Methods
Our database consisted of 102 muscle biopsy images from 70 individuals (including controls, patients with neurogenic atrophies and patients with muscular dystrophies). We used this to develop a new method, Neuromuscular DIseases Computerized Image Analysis (NDICIA), that uses network science analysis to capture the defining signature of muscle biopsy images. NDICIA characterizes muscle tissues by representing each image as a network, with fibers serving as nodes and fiber contacts as links.

Results
After a ‘training’ phase with control and pathological biopsies, NDICIA was able to quantify the degree of pathology of each sample. We validated our method by comparing NDICIA quantification of the severity of muscular dystrophies with a pathologist’s evaluation of the degree of pathology, resulting in a strong correlation (R = 0.900, P <0.00001). Importantly, our approach can be used to quantify new images without the need for prior ‘training’. Therefore, we show that network science analysis captures the useful information contained in muscle biopsies, helping the diagnosis of muscular dystrophies and neurogenic atrophies.

Conclusions
Our novel network analysis approach will serve as a valuable tool for assessing the etiology of muscular dystrophies or neurogenic atrophies, and has the potential to quantify treatment outcomes in preclinical and clinical trials.
Lack of association of rare functional variants in TSC1/TSC2 genes with autism spectrum disorder
Authors: Bahl Samira , Chiang Colby , Beauchamp Roberta L , Neale Benjamin M , Daly Mark J , Gusella James F , Talkowski Michael E , Ramesh Vijaya 
Published: March 2013

Abstract

Background
Autism spectrum disorder (ASD) is reported in 30 to 60% of patients with tuberous sclerosis complex (TSC) but shared genetic mechanisms that exist between TSC-associated ASD and idiopathic ASD have yet to be determined. Through the small G-protein Rheb, the TSC proteins, hamartin and tuberin, negatively regulate mammalian target of rapamycin complex 1 (mTORC1) signaling. It is well established that mTORC1 plays a pivotal role in neuronal translation and connectivity, so dysregulation of mTORC1 signaling could be a common feature in many ASDs. Pam, an E3 ubiquitin ligase, binds to TSC proteins and regulates mTORC1 signaling in the CNS, and the FBXO45-Pam ubiquitin ligase complex plays an essential role in neurodevelopment by regulating synapse formation and growth. Since mounting evidence has established autism as a disorder of the synapses, we tested whether rare genetic variants in TSC1, TSC2, MYCBP2, RHEB and FBXO45, genes that regulate mTORC1 signaling and/or play a role in synapse development and function, contribute to the pathogenesis of idiopathic ASD.

Methods
Exons and splice junctions of TSC1, TSC2, MYCBP2, RHEB and FBXO45 were resequenced for 300 ASD trios from the Simons Simplex Collection (SSC) using a pooled PCR amplification and next-generation sequencing strategy, targeted to the discovery of deleterious coding variation. These detected, potentially functional, variants were confirmed by Sanger sequencing of the individual samples comprising the pools in which they were identified.

Results
We identified a total of 23 missense variants in MYCBP2, TSC1 and TSC2. These variants exhibited a near equal distribution between the proband and parental pools, with no statistical excess in ASD cases (P > 0.05). All proband variants were inherited. No putative deleterious variants were confirmed in RHEB and FBXO45. Three intronic variants, identified as potential splice defects in MYCBP2 did not show aberrant splicing upon RNA assay. Overall, we did not find an over-representation of ASD causal variants in the genes studied to support them as contributors to autism susceptibility.

Conclusions
We did not observe an enrichment of rare functional variants in TSC1 and TSC2 genes in our sample set of 300 trios.
Crack Spacing and Width of Thick High Strength Reinforced Concrete Panels
Authors: Dawood Nabil F.A. , Marzouk H. 
Published: March 2013

Experimental program involved testing of eighteen panels to study the cracking behavior of thick high strength concrete panels subjected to in-plane tensile forces, was conducted. The influence of different parameters such as concrete strength fc′, reinforcement ratio ρeff, concrete cover to bar diameter ratio ( Cc/ db), and applying axial or biaxial loading, was critically examined. Model equations developed for predicting crack spacing and width of thick concrete plates were discussed. Using high strength concrete reduced the average crack width measured at every steel stress level. The bar spacing and the concrete cover showed a significant influence on the crack spacing and consequently on the measured crack width. Panels tested under biaxial loading triggered higher crack spacing and crack width compared with the corresponding panels subjected to axial loading. Design equations for predicting the crack spacing and width of thick concrete members are presented parallel with the available code provisions.
Intraoperative Vancomycin Pharmacokinetics in Cardiac Surgery With or Without Cardiopulmonary Bypass
Authors: Cotogni Paolo , Passera Roberto , Barbero Cristina , Gariboldi Angela , Moscato Donatella , Izzo Gennaro , Rinaldi Mauro 
Published: March 2013

BACKGROUND Vancomycin is administered as antimicrobial prophylaxis to patients undergoing cardiac surgery, an intervention that usually requires cardiopulmonary bypass (CPB). Previous studies reported that CPB modifies vancomycin pharmacokinetic parameters. OBJECTIVE To investigate intraoperative vancomycin pharmacokinetic changes in a large population of patients undergoing cardiac surgery with CPB (on-pump) and without CPB (off-pump). METHODS In this prospective study, patients undergoing cardiac surgery received a single dose of vancomycin 1000 mg in a 60-minute intravenous infusion, with skin incision performed between 16 and 120 minutes after the end of the infusion. For the on-pump group, arterial samples were drawn before CPB (end of infusion, skin incision), during CPB (5, 30, and 60 minutes, and then every 60 minutes until CPB end), and after CPB (wound closure). For the off-pump group, arterial samples were drawn time-matched to the CPB period of the on-pump group. RESULTS Two hundred thirty-six consecutive patients were enrolled: 215 in the on-pump group and 21 in the off-pump group. A total of 1682 serum vancomycin concentrations (median 7/patient) were measured. Vancomycin maximum concentration ([Cmax] on-pump, 45.6 mg/L; off-pump, 47.3 mg/L); area under the concentration-time curve, zero to 8 hours ([AUC0–8] on-pump, 104.6 mg*h/L; off-pump, 96.1 mg*h/L); volume of distribution ([Vd] on-pump, 31 L; off-pump, 28.2 L); and total body clearance ([Cl] on-pump, 6.23 L/h; off-pump, 7.05 L/h) were similar. Moreover, Cmax and AUC0-∞ (AUC, zero to infinity) showed values comparable to those found in previous studies performed on noncardiac surgery patients. CONCLUSIONS In our study there were no significant differences in vancomycin Cmax, AUC0–8, Vd, and Cl between the on-pump and off-pump groups. CPB does not seem to significantly modify intraoperative vancomycin pharmaco ki netics in patients undergoing cardiac surgery. The results of this study may contribute to increased knowledge of vancomycin pharmacokinetics.
Severe Cardiotoxicity Associated with Ixabepilone use in Metastatic Breast Cancer
Authors: Santiago Michael J , Hayes Bryan D , Butler Kenneth H 
Published: March 2013

OBJECTIVE To report a case of cardiogenic shock and fulminant heart failure associated with a single dose of ixabepilone. CASE SUMMARY A 32-year-old woman presented to the emergency department (ED) with abdominal pain and difficulty breathing within 1 hour after receiving a partial dose of ixabepilone (26 mg/m 2 ) at an oncologist's office. She had breast cancer, with metastases to the bone and liver and evidence of early liver failure. While in the ED, she developed acute respiratory failure requiring intubation. Bedside ultrasound imaging showed free abdominal fluid. Computed tomography (CT) scans showed evidence of right-sided heart failure and abdominal fluid consistent with ascites but no evidence of pulmonary embolism. After the CT scan, the patient experienced pulseless electrical activity cardiac arrest. All attempts at resuscitation were unsuccessful. DISCUSSION Ixabepilone is a novel drug for treatment of advanced breast cancer. The most commonly reported adverse effects are peripheral neuropathies and hematologic issues such as neutropenia. To our knowledge, this is the first detailed report of a severe adverse cardiac event associated with ixabepilone use. Many other chemotherapeutic agents have cardiotoxic effects. An objective causality assessment, using the Naranjo probability scale, revealed that an adverse drug event was probable. CONCLUSIONS Clinicians should maintain broad differential diagnoses that include adverse reactions to drugs relatively new to the market. Ixabepilone may have cardiotoxic effects that necessitate further study, particularly when the drug is administered after cardiotoxic chemotherapy.
The Effect of Comprehensive Smoking Bans in European Workplaces
Authors: Origo Federica , Lucifora Claudio 
Published: March 2013

Abstract
Many European countries have recently implemented comprehensive smoking bans to reduce exposure to tobacco smoke in public places and all indoor workplaces. We use a difference-in-differences approach and comparable microdata for a number of European countries to evaluate the impact of national comprehensive smoking bans on workers’ perceived health. Results show that the introduction of comprehensive smoking bans has a significant effect on the probability of both exposure to smoke and work-related respiratory problems. We also highlight unintended effects in terms of mental distress. The impact across countries is shown to vary with the degree of strictness of the bans.
Should Global Health be Tailored Toward the Rich? Altruism and Efficient R&D for Neglected Diseases
Authors: Jena Anupam B. , Mechoulan Stéphane , Philipson Tomas J. 
Published: March 2013

Abstract
We analyze the problem of incentivizing research and development (R&D) into developing world disease from an economic efficiency perspective. We view the problem as how to best promote R&D into goods with positive external effects in the sense that medicines that directly affect the health of the poor also indirectly affect the utility of the altruistic “rich.” We demonstrate why existing policy proposals – such as price concessions by manufacturers – adversely impact the poor by placing the burden of R&D only on innovators rather than all altruists in the rich world. We offer policy solutions that are based on economic efficiency and therefore rely on a broad sense of how the world values the treatment of developing world disease. We estimate that global altruism toward those with malaria is, at a minimum, valued between $835 million and $2.4 billion annually and for HIV/AIDS, between $9.1 billion and $26.6 billion annually. We argue that future policies toward neglected diseases need to better incorporate how efficient R&D meets the need of this global altruism.
Fire resistance of wood treated with various ionic liquids (ILs)
Authors: Miyafuji Hisashi , Fujiwara Yoshiyuki 
Published: March 2013

Abstract
Ionic liquids (ILs) have been investigated for their potential as reagents for enhancing the fire resistance of wood. The following ILs were in focus: 1-ethyl-3-methylimidazolium bromide, 1-ethyl-3-methylimidazolium tetrafluoroborate, and 1-ethyl-3-methylimidazolium hexafluorophosphate ([C2mim][PF6]). Supposedly, these ILs do not dissolve or degrade wood components to a large extent. No morphologic changes were observed in any IL-treated wood samples, but they showed an enhanced fire resistance compared with that of untreated wood. Scanning electron microscopy and energy-dispersive X-ray analysis demonstrated that the ILs are penetrated into the cell walls. The wood treated with [C2mim][PF6] exhibited the highest fire resistance based on thermogravimetric and differential thermal analyzer studies: it was more resistant against flaming at approximately 350°C and the subsequent glowing at higher temperatures. This enhanced fire resistance was interpreted by dehydration in the presence of the ILs under observation. In general, ILs are promising reagents for improving the thermal properties of wood.
Effect of maternal body mass index on oxytocin treatment for arrest of dilatation1)
Authors: Soni Shelly , Chivan Niraj , Cohen Wayne R. 
Published: March 2013

Abstract
To determine whether the effectiveness of oxytocin treatment of arrest of dilatation differed in obese compared to lean women, we did a retrospective analysis of 118 subjects in spontaneous labor whose arrest of dilatation was treated with oxytocin. Cases were stratified by maternal body mass index (BMI): Group A, <25 kg/m2; Group B, 25.0–29.9 kg/m2; Group C, 30.0–34.9 kg/m2; and Group D, ≥35 kg/m2. Groups were comparable in maternal age, parity, gestational age, birth weight, and the frequency of infection. Full dilatation was reached in about 90% of Group A and B, 72% of Group C, and 39% of Group D, the most obese women (P<0.001). The cesarean rate was directly related to maternal BMI, 11.4%, 22.9%, 34.3%, and 69.6% in Groups A through D, respectively (P<0.001). Significantly more oxytocin was used in group D than in the other groups during the first 3h of infusion in attempting to overcome the arrest (P=0.003). We conclude that oxytocin treatment of arrest of dilatation was less effective in obese than in lean women. This effect was most prominent in women with a BMI >35 kg/m2, who were, despite having received more oxytocin than those in the leaner groups, less than half as likely to attain full dilatation and more than twice as likely to deliver by cesarean.