bluuebunny/crossref_metadata_2025_split huggingface dataset:
The importance of genetic factors for the development of arthropathy: a longitudinal study of children and adolescents with haemophilia A
Authors: Gomperts Edward D. , Schwarz John , Donfield Sharyne M. , Lail Alice E. , Astermark Jan , Hoots W. Keith , Winkler Cheryl A. , Berntorp Erik 
Published: December 2016

SummaryHaemophilia A is a congenital bleeding disorder characterised by recurrent haemorrhages into the major joints. Haemophilic arthropathy is a well-established outcome of recurrent joint bleeding; however, it is clear that multiple factors determine the extent and severity of its occurrence. We sought to identify genetic factors related to abnormalities in range of motion (ROM) in the knees, ankles and elbows in a cohort of children and adolescents with haemophilia A not treated primarily with regular prophylaxis. Using data from the Haemophilia Growth and Development Study, we examined associations between 13,342 genetic markers and ROM scores measured at six-month intervals for up to seven years. As a first step, ordered logistic regression models were fit for each joint separately. A subset of SNP markers showing significant effects (p<0.01) on the right and left sides for at least two joints were included in a full model fit using a multivariate generalised linear mixed model assuming an ordinal response. The models contained all ROM scores obtained at all visits. Twenty-five markers analysed in the full model showed either increased or decreased risk of ROM abnormalities at the p<0.001 level. Several genes identified at either the first or second stage of the analysis have been associated with arthritis in a variety of large studies. Our results support the likelihood that risk for haemophilic arthropathy is associated with genetic factors, the identification of which holds promise for further advancing the individualisation of treatment.
Nucleoside Diphosphate Kinase-C Suppresses cAMP Formation in Human Heart Failure
Authors: Abu-Taha Issam H. , Heijman Jordi , Hippe Hans-Jörg , Wolf Nadine M. , El-Armouche Ali , Nikolaev Viacheslav O. , Schäfer Marina , Würtz Christina M. , Neef Stefan , Voigt Niels , Baczkó István , Varró András , Müller Marion , Meder Benjamin , Katus Hugo A. , Spiger Katharina , Vettel Christiane , Lehmann Lorenz H. , Backs Johannes , Skolnik Edward Y. , Lutz Susanne , Dobrev Dobromir , Wieland Thomas 
Published: December 2016

Background:
Chronic heart failure (HF) is associated with altered signal transduction via β-adrenoceptors and G proteins and with reduced cAMP formation. Nucleoside diphosphate kinases (NDPKs) are enriched at the plasma membrane of patients with end-stage HF, but the functional consequences of this are largely unknown, particularly for NDPK-C. Here, we investigated the potential role of NDPK-C in cardiac cAMP formation and contractility.

Methods:
Real-time polymerase chain reaction, (far) Western blot, immunoprecipitation, and immunocytochemistry were used to study the expression, interaction with G proteins, and localization of NDPKs. cAMP levels were determined with immunoassays or fluorescent resonance energy transfer, and contractility was determined in cardiomyocytes (cell shortening) and in vivo (fractional shortening).

Results:

NDPK-C was essential for the formation of an NDPK-B/G protein complex. Protein and mRNA levels of NDPK-C were upregulated in end-stage human HF, in rats after long-term isoprenaline stimulation through osmotic minipumps, and after incubation of rat neonatal cardiomyocytes with isoprenaline. Isoprenaline also promoted translocation of NDPK-C to the plasma membrane. Overexpression of NDPK-C in cardiomyocytes increased cAMP levels and sensitized cardiomyocytes to isoprenaline-induced augmentation of contractility, whereas NDPK-C knockdown decreased cAMP levels. In vivo, depletion of NDPK-C in zebrafish embryos caused cardiac edema and ventricular dysfunction. NDPK-B knockout mice had unaltered NDPK-C expression but showed contractile dysfunction and exacerbated cardiac remodeling during long-term isoprenaline stimulation. In human end-stage HF, the complex formation between NDPK-C and Gα
i2
was increased whereas the NDPK-C/Gα
s
interaction was decreased, producing a switch that may contribute to an NDPK-C–dependent cAMP reduction in HF.

Conclusions:

Our findings identify NDPK-C as an essential requirement for both the interaction between NDPK isoforms and between NDPK isoforms and G proteins. NDPK-C is a novel critical regulator of β-adrenoceptor/cAMP signaling and cardiac contractility. By switching from Gα
s
to Gα
i2
activation, NDPK-C may contribute to lower cAMP levels and the related contractile dysfunction in HF.
Management of Posterior Glottal Insufficiency With Use of a Buccal Graft
Authors: Helman Samuel N. , Karle William , Pitman Michael J. 
Published: December 2016

Objective: Posterior glottal insufficiency manifests as a rough, breathy voice with poor vocal projection, air hunger, and decreased phonatory efficiency. There are limited medical and surgical therapies. This study reports the use of insetting a buccal mucosa graft into the posterior interarytenoid space to close the posterior glottic gap for phonatory rehabilitation. Methods: Our study is a retrospective case series of 2 female patients undergoing buccal mucosa graft inset to repair acquired posterior glottic insufficiency as a result of prolonged intubation and laryngeal tuberculosis infection. Patients selected for this procedure had posterior glottal insufficiency due to erosion of posterior glottal tissue. They also had dysphonia refractory to voice therapy and injection augmentation. Conclusions: Interarytenoid buccal graft for posterior glottal insufficiency is effective with excellent vocal rehabilitation and minimal donor site morbidity.
Implementation of a triage system in Pakistan: the need of the hour
Authors: Majid Zain , Masood Irfan 
Published: December 2016

In today’s world, an effective emergency department (ED) cannot function properly without having a triage system. Though available in various forms, this essentially categorises patients according to the seriousness of their condition and the priority of their need. Pakistan is yet to introduce this system and where it exists, it is in its infancy. A disaster-prone country such as ours, which is frequently faced with both man-made and natural calamities, could benefit tremendously from its introduction. The activity of EDs would be streamlined and precious lives would be saved.
Serum 25-OH vitamin D level in treatment-naïve systemic lupus erythematosus patients: Relation to disease activity, IL-23 and IL-17
Authors: Shahin D , El-Farahaty R M , Houssen M E , Machaly S A , Sallam M , ElSaid T O , Neseem N O 
Published: December 2016

Objectives The aim of this study was to assess the vitamin D status in treatment-naïve SLE patients and its association with clinical and laboratory markers of disease activity, including serum levels of IL-17 and IL-23. Methods Fifty-seven treatment-naïve SLE patients along with 42 matched controls were included. SLEDAI score was used to estimate disease activity. Serum levels of 25(OH) D, IL-17 and IL-23 were measured. Results The median level of 25(OH) D in SLE patients (40.8; 4–70 ng/ml) was significantly lower than in the controls (47; 25–93 ng/ml) ( P = 0.001). A total of 38.6% of SLE cases had 25 (OH) D levels < 30 ng/ml (hypovitaminosis D) vs. 4.8% of the controls ( P < 0.0001). Apart from thrombocytopenia, vitamin D was not associated with clinical signs of SLE. There were negative correlations between serum 25(OH) D and serum levels of IL-17, IL-23 and ANA (rho = −0.5, −0.8, −0.5, P ≤ 0.05) in SLE patients. Conclusion Hypovitaminosis D is prevalent in treatment naïve SLE patients. It contributes to ANA antibody production and is associated with high serum levels of IL-23 and IL-17; thus they may trigger the inflammatory process in SLE.
The Japanese LupusPRO: A cross-cultural validation of an outcome measure for lupus
Authors: Inoue M , Shiozawa K , Yoshihara R , Yamane T , Shima Y , Hirano T , Jolly M , Makimoto K 
Published: December 2016

Objective This study aimed to validate the Japanese version of the LupusPRO questionnaire for use with systemic lupus erythematosus patients. Methods Participants were 205 lupus patients recruited from three rheumatology centers in Japan. Demographic data were collected and quality of life was assessed using the LupusPRO and the Short Form Health Survey-12. Disease activity was evaluated by physicians using the Systemic Lupus Erythematosus Activity Index. Some participants completed questionnaires 10–14 days after the first survey. Internal consistency reliability, test-retest reliability, content validity and convergent validity were examined, and confirmatory factor analysis was performed. Results Participants’ mean age was 47.8 ± 13.6 years. Older participants scored lower on physical quality of life and higher on coping than younger participants. The LupusPRO showed satisfactory test-retest reliability ( n = 111). Test-retest reliability was lower for the mental and social aspects of quality of life, indicating fluctuations in quality of life during the two-week interval. Internal consistency reliability was good and convergent validity with the corresponding domains of the Short Form Health Survey-12 was satisfactory. Confirmatory factor analysis showed a good model fit. Conclusion The Japanese LupusPRO is a reliable and valid measure to evaluate treatment interventions for systemic lupus erythematosus.
Serum osteoprotegrin (OPG) in subclinical atherosclerosis in systemic lupus erythematosus
Authors: Kiani A N , Aukrust P , Ueland T , Hollan I , Barr E , Magder L S , Petri M 
Published: December 2016

Introduction Osteoprotegerin (OPG) is a member of the tumor necrosis factor (TNF) receptor family. It has recently been demonstrated that OPG is produced by a variety of tissues, including the cardiovascular system (heart, arteries, veins), lung, kidney, immune tissues, and bone. The OPG-RANKL signaling pathway is strongly related to vascular calcification. We determined the association of this biomarker with subclinical atherosclerosis in systemic lupus erythematous (SLE). Methods We measured OPG and markers of subclinical atherosclerosis (coronary artery calcium (CAC), carotid intima-media thickness (cIMT) carotid plaque) in 166 SLE patients (91% female, 64% Caucasian, 31% African American, 5% others, mean age 45 years). Subgroups of patients with different levels of OPG level were compared with respect to average levels of CAC, cIMT, and with respect to presence of carotid plaque. Age was adjusted for using multiple regression. Results OPG was highly correlated with age ( p < 0.0001). Individuals with higher levels of OPG tended to have higher measures of CAC, cIMT, and more carotid plaque. However, after adjustment for age, these associations, while still positive, were no longer statistically significant. Conclusion In our study much of the association observed was due to confounding by age, and after adjusting for age, our findings do not rule out the possibility of a null association.
Brain abscess due to Listeria monocytogenes after HELLP syndrome in a patient with antiphospholipid syndrome
Authors: Fervienza A , Bodro M , Castro P , Hernández S , Teixidó I , Espinosa G , Cervera R 
Published: December 2016

Objective To illustrate an unusual case of Listeria cerebral abscess. Material and methods A 32-year-old pregnant woman with thrombotic antiphospholipid syndrome (APS) received corticotherapy for two weeks due to hemolysis, elevated liver enzymes, low platelet (HELLP) syndrome. After delivery she presented with neurological symptoms and fever. Results The MRI scan confirmed the presence of a brain abscess, and Listeria monocytogenes was isolated in blood cultures. After eight weeks of antibiotic treatment, the patient presented no sequelae. Conclusion L. monocytogenes should be included in the differential diagnosis of patients with fever and neurological dysfunction, especially in those with a recent history of corticotherapy.
3D printing guiding stent graft fenestration: A novel technique for fenestration in endovascular aneurysm repair
Authors: Huang Jianhua , Li Gan , Wang Wei , Wu Keming , Le Tianming 
Published: December 2016

Objective To describe a novel approach, 3D printing guiding stent graft fenestration, for fenestration during endovascular aneurysm repair for juxtarenal abdominal aortic aneurysm. Methods A 69-year-old male with juxtarenal abdominal aortic aneurysm underwent endovascular aneurysm repair with “off the label” fenestrated stent graft. To precisely locate the fenestration position, we reconstructed a 3D digital abdominal aortic aneurysm model and created a skin template covering this abdominal aortic aneurysm model. Then the skin template was physically printed and the position of the visceral vessel was hollowed out, thereby helping in locating the fenestration on stent graft. Results and conclusions With the help of this 3D printed skin template, we fenestrated the stent graft accurately and rebuilt the bilateral renal artery successfully. This is the first clinical case that used 3D printing guiding stent graft fenestration, which is a novel approach for precise fenestration on stent graft on the table during endovascular aneurysm repair.
Air bubbles are released by thoracic endograft deployment: An in vitro experimental study
Authors: Inci Kamuran , Koutouzi Giasemi , Chernoray Valery , Jeppsson Anders , Nilsson Håkan , Falkenberg Mårten 
Published: December 2016

Purpose: Embolic stroke is a dreaded complication of thoracic endovascular aortic repair. The prevailing theory about its cause is that particulate debris from atherosclerotic lesions in the aortic wall are dislodged by endovascular instruments and embolize to the brain. An alternative source of embolism might be air trapped in the endograft delivery system. The aim of this experimental study was to determine whether air is released during deployment of a thoracic endograft. Methods: In an experimental benchtop study, eight thoracic endografts (five Medtronic Valiant Thoracic and three Gore TAG) were deployed in a water-filled transparent container drained from air. Endografts were prepared and deployed according to their instructions for use. Deployment was filmed and the volume of air released was collected and measured in a calibrated syringe. Results: Air was released from all the endografts examined. Air volumes ranged from 0.1 to 0.3 mL for Medtronic Valiant Thoracic and from <0.025 to 0.04 mL for Gore TAG. The largest bubbles had a diameter of approximately 3 mm and came from the proximal end of the Medtronic Valiant device. Conclusion: Air bubbles are released from thoracic endografts during deployment. Air embolism may be an alternative cause of stroke during thoracic endovascular aortic repair.
A Validation Study of a Novel 3-Dimensional MRI Modeling Technique to Identify the Anatomic Insertions of the Anterior Cruciate Ligament
Authors: Hui Catherine , Pi Yeli , Swami Vimarsha , Mabee Myles , Jaremko Jacob L. 
Published: December 2016

Background: Anatomic single bundle anterior cruciate ligament (ACL) reconstruction is the current gold standard in ACL reconstructive surgery. However, placement of femoral and tibial tunnels at the anatomic center of the ACL insertion sites can be difficult intraoperatively. We developed a “virtual arthroscopy” program that allows users to identify ACL insertions on preoperative knee magnetic resonance images (MRIs) and generates a 3-dimensional (3D) bone model that matches the arthroscopic view to help guide intraoperative tunnel placement. Purpose: To test the validity of the ACL insertion sites identified using our 3D modeling program and to determine the accuracy of arthroscopic ACL reconstruction guided by our “virtual arthroscopic” model. Study Design: Descriptive laboratory study. Methods: Sixteen cadaveric knees were prescanned using routine MRI sequences. A trained, blinded observer then identified the center of the ACL insertions using our program. Eight knees were dissected, and the centers of the ACL footprints were marked with a screw. In the remaining 8 knees, arthroscopic ACL tunnels were drilled into the center of the ACL footprints based on landmarks identified using our virtual arthroscopic model. Postprocedural MRI was performed on all 16 knees. The 3D distance between pre- and postoperative 3D centers of the ACL were calculated by 2 trained, blinded observers and a musculoskeletal radiologist. Results: With 2 outliers removed, the postoperative femoral and tibial tunnel placements in the open specimens differed by 2.5 ± 0.9 mm and 2.9 ± 0.7 mm from preoperative centers identified on MRI. Postoperative femoral and tibial tunnel centers in the arthroscopic specimens differed by 3.2 ± 0.9 mm and 2.9 ± 0.7 mm, respectively. Conclusion: Our results show that MRI-based 3D localization of the ACL and our virtual arthroscopic modeling program is feasible and does not show a statistically significant difference to an open arthrotomy approach. However, additional refinements will be required to improve the accuracy and consistency of our model to make this an effective tool for surgeons performing anatomic single-bundle ACL reconstructions. Clinical Relevance: Arthroscopic anatomic single-bundle ACL reconstruction is the current gold standard for ACL reconstruction; however, the center of the ACL footprint can be difficult to identify arthroscopically. Our novel modeling can improve the identification of this important landmark intraoperatively and decrease the risk of graft malposition and subsequent graft failure.
Longitudinal Changes in Proportions of Dental Services Provided by Australian Dentists, 1983 to 2010
Authors: Ju X. , Teusner D.N. , Spencer A.J. , Brennan D.S. 
Published: December 2016

The objective of the study was to estimate the longitudinal change over a 26-y period in the proportion of dental services provided in 10 main service provision areas by Australian dentists. A random sample of Australian dentists was surveyed approximately every 5 y, commencing 1983 to 1984. The mean proportion of dental services provided was calculated from practitioner activity logs. Mixed effects regression models estimated the longitudinal change in the proportion of services provided, by dentists’ age and birth-year cohort. Response rates across data collection waves ranged from 67% to 76%. Between 1983 to 1984 and 2009 to 2010, the mean proportion of diagnostic, preventive, and crown/bridge services provided tended to increase, and the mean proportion of restorative, oral surgery, and prosthodontic services tended to decrease. Mean proportions of endodontic and orthodontic services fluctuated. Relative to the youngest cohort (born after 1984), across cohorts of older to younger dentists, the proportions of diagnostic and preventive services increased, and restorative and prosthodontic decreased. Older cohorts provided the lowest proportions of diagnostic and preventive services (oldest cohort born before 1918: β = −32.1 ± 4.8; cohort born 1934 to 1938: β = −11.6 ± 3.2, respectively). Older cohorts provided the highest proportions of restorative and prosthodontic services (born before 1918: β = 27.3 ± 5.6; born 1919 to 1923: β = 10.5 ± 2.4, respectively). Some service area trends varied across birth-year cohorts. Endodontic service provision was declining for younger cohorts but increasing for older cohorts. Preventive service provision was increasing for younger cohorts but declining for older cohorts. This study identified trends not evident in previous time-series analysis. First, provision of restorative and oral surgery services, as a proportion of all services provided, was declining. Second, there were competing intercohort trends. These may indicate that new norms in dental education are influencing clinical decision making and that new trends in dental service provision may emerge as older dentists retire. Knowledge Transfer Statement: This study identified several trends in dental service provision and indicated that not all trends were consistent across all birth-year cohorts. Findings inform dental health care policy and priorities for dental education. In addition, the identified trends have implications for the future composition of the oral health workforce.
SurvivalGWAS_Power: a user friendly tool for power calculations in pharmacogenetic studies with “time to event” outcomes
Authors: Syed Hamzah , Jorgensen Andrea L. , Morris Andrew P. 
Published: December 2016

Abstract
Background
Power calculators are currently available for the design of genetic association studies of binary phenotypes and quantitative traits, but not for “time to event” outcomes, which are of particular relevance in pharmacogenetics. With the rapid emergence of pharmacogenetic association studies of single nucleotide polymorphisms (SNPs), and the complexity of clinical outcomes they consider, there is a need for software to perform power calculations of time to event data over a range of design scenarios and analytical methodologies.

Results
We have developed the user friendly software tool SurvivalGWAS_Power to perform power calculations for time to event outcomes over a range of study designs and different analytical approaches. The software calculates the power to detect SNP association with a time to event outcome over a range of study design scenarios. The software enables analyses under a Cox proportional hazards model or Weibull regression model, and can account for treatment and SNP-treatment interaction effects. Simulated data sets can also be generated by SurvivalGWAS_Power to enable analyses with methods that are not currently supported by the power calculator, thereby increasing the flexibility of the software.

Conclusions
SurvivalGWAS_Power addresses the need for flexible and user-friendly software for power calculations for genetic association studies of time to event outcomes, with particular design features of relevance in pharmacogenetics.
Mitochondrial co-chaperone protein Tid1 is required for energy homeostasis during skeletal myogenesis
Authors: Cheng Li-Hao , Hung Kai-Feng , Lee Te-Chang , Huang Chih-Yang , Chiu Wen-Ting , Lo Jeng-Fan , Huang Tung-Fu 
Published: December 2016

Abstract
Background
Tid1 is a mitochondrial co-chaperone protein and its transcript is abundantly expressed in skeletal muscle tissues. However, the physiological function of Tid1 during skeletal myogenesis remains unclear.

Methods
In vitro induced differentiation assay of mouse myoblast C2C12 cells was applied to examine the physiological role of Tid1 during skeletal myogenesis. In addition, transgenic mice with muscle specific (HSA-Cre) Tid1 deletion were established and examined to determine the physiological function of Tid1 during skeletal muscle development in vivo.

Results
Expression of Tid1 protein was upregulated in the differentiated C2C12 cells, and the HSA-Tid1f/f mice displayed muscular dystrophic phenotype. The expression of myosin heavy chain (MyHC), the protein served as the muscular development marker, was reduced in HSA-Tid1f/f mice at postnatal day (P)5 and P8. The protein levels of ATP sensor (p-AMPK) and mitochondrial biogenesis protein (PGC-1α) were also significantly reduced in HSA-Tid1f/f mice. Moreover, Tid1 deficiency induced apoptotic marker Caspase-3 in muscle tissues of HSA-Tid1f/f mice. Consistent with the in vivo finding, we observed that downregulation of Tid1 not only reduced the ATP production but also abolished the differentiation ability of C2C12 cells by impairing the mitochondrial activity.

Conclusion
Together, our results suggest that Tid1 deficiency reduces ATP production and abolishes mitochondrial activity, resulting in energy imbalance and promoting apoptosis of muscle cells during myogenesis. It will be of importance to understand the function of Tid1 during human muscular dystrophy in the future.