bluuebunny/crossref_metadata_2025_split huggingface dataset:
Otoplasty techniques in children: a comparative study of outcomes
Authors: Punj Puvesh , Chong Hsu Phie , Cundy Thomas P. , Lodge Michelle , Woods Roger 
Published: May 2018

BackgroundNumerous otoplasty techniques have been described in the literature to correct prominent ears; however, few have focused on the complication rates. We reviewed our experience aiming to assess peri‐operative care requirements and complication rates.MethodWe conducted a retrospective review of 207 otoplasty procedures performed in 119 patients over a 5‐year period (2009–2014) at the Women's and Children's Hospital, Adelaide. Information pertaining to demographic details, length of stay, otoplasty technique and complications (early and late) were obtained.ResultsIn the study period, 97% of the 119 patients had an overnight stay. There was an early complication of 2.2% (return to theatre for bleeding) in the modified Chongchet technique and 0.9% (wound infection) in the Mustarde technique. Late complications included suture extrusion (1.9%) with the Mustarde technique and hypertrophic scarring (2.2%) in the modified Chongchet technique. The recurrence rate requiring revision following modified Chongchet technique was 10% and Mustarde technique was 2.9%. The Mustarde otoplasty technique was associated with a slightly lower antiemetic requirement than the Chongchet technique (3.2 versus 14.3%, P = 0.032). Both techniques had comparable opioid analgesic requirement of 30–35% post‐operatively (P = 0.248).ConclusionOur results are comparable to the huge variation in available literature. We note the higher revision rate following modified Chongchet technique. Both techniques had a low and acceptable rate of post‐operative analgesia and antiemetic requirement. We are considering either otoplasty technique as a day surgery procedure within our unit with the provision of adequate patient support as a safe and economical advance.
Incidence, timing and impact of comorbidity on second hip fracture: a population‐based study
Authors: Harvey Lara , Toson Barbara , Mitchell Rebecca , Brodaty Henry , Draper Brian , Close Jacqueline 
Published: May 2018

BackgroundTo quantify the incidence and timing of second hip fracture, and to evaluate the relative impact of comorbidities on risk of second hip fracture.MethodsHospitalization records for individuals aged ≥65, admitted to a New South Wales hospital for fall‐related hip fracture between 1 January 2005 and 31 December 2009 were linked. Comorbidities were identified from the records using a 1‐year look‐back period. To calculate second hip fracture rates, individuals were followed until death, fracture or end of study period (31 December 2012). Time‐dependent competing‐risk hazards regression was used to assess the relative contribution of each comorbidity to fracture risk, adjusting for age and sex.ResultsOf the 24 500 individuals who sustained at least one hip fracture, 2.9% experienced a second within a year, 6.1% within 3 years and 9.4% within 8 years. Malnutrition/cachexia (hazard ratio (HR): 2.47; 99.9% confidence interval (CI): 1.87–3.26), dementia (HR: 2.15; 99.9% CI: 1.80–2.57), congestive heart failure (HR: 1.62; 99.9% CI: 1.30–2.04), Parkinson's disease (HR: 1.51; 99.9% CI: 1.08–2.10), cerebrovascular disease (HR: 1.41; 99.9% CI: 1.06–1.89) and osteoporosis (HR: 1.36; 99.9% CI: 1.11–1.67) were associated with increased risk of second hip fracture within 3 years. Mortality was high; with 26% of individuals dying within a year, 44.9% within 3 years and 70.2% within 8 years.ConclusionsOne in 11 older individuals with an initial hip fracture sustained a second hip fracture. While the priority is to prevent the first hip fracture, those that have sustained a hip fracture should be seen as a high risk population and be targeted for future falls and fracture prevention strategies.
Influence diagnostics for censored regression models with autoregressive errors
Authors: Schumacher Fernanda L. , Lachos Victor H. , Vilca‐Labra Filidor E. , Castro Luis M. 
Published: May 2018

SummaryObservations collected over time are often autocorrelated rather than independent, and sometimes include observations below or above detection limits (i.e. censored values reported as less or more than a level of detection) and/or missing data. Practitioners commonly disregard censored data cases or replace these observations with some function of the limit of detection, which often results in biased estimates. Moreover, parameter estimation can be greatly affected by the presence of influential observations in the data. In this paper we derive local influence diagnostic measures for censored regression models with autoregressive errors of orderp(hereafter, AR(p)‐CR models) on the basis of theQ‐function under three useful perturbation schemes. In order to account for censoring in a likelihood‐based estimation procedure for AR(p)‐CR models, we used a stochastic approximation version of the expectation‐maximisation algorithm. The accuracy of the local influence diagnostic measure in detecting influential observations is explored through the analysis of empirical studies. The proposed methods are illustrated using data, from a study of total phosphorus concentration, that contain left‐censored observations. These methods are implemented in theRpackageARCensReg.
Altered exocytosis in chromaffin cells from mouse models of neurodegenerative diseases
Authors: de Diego A. M. García , García A. García 
Published: May 2018

AbstractChromaffin cells from the adrenal gland (CCs) have extensively been used to explore the molecular structure and function of the exocytotic machinery, neurotransmitter release and synaptic transmission. The CC is integrated in the sympathoadrenal axis that helps the body maintain homoeostasis during both routine life and in acute stress conditions. This function is exquisitely controlled by the cerebral cortex and the hypothalamus. We propose the hypothesis that damage undergone by the brain during neurodegenerative diseases is also affecting the neurosecretory function of adrenal medullary CCs. In this context, we review here the following themes: (i) How the discharge of catecholamines is centrally and peripherally regulated at the sympathoadrenal axis; (ii) which are the intricacies of the amperometric techniques used to study the quantal release of single‐vesicle exocytotic events; (iii) which are the alterations of the exocytotic fusion pore so far reported, in CCs of mouse models of neurodegenerative diseases; (iv) how some proteins linked to neurodegenerative pathologies affect the kinetics of exocytotic events; (v) finally, we try to integrate available data into a hypothesis to explain how the centrally originated neurodegenerative diseases may alter the kinetics of single‐vesicle exocytotic events in peripheral adrenal medullary CCs.
Gene expression profiles of CD4/CD8 double‐positive T cells in porcine peripheral blood
Authors: Okutani Mie , Tsukahara Takamitsu , Kato Yoshihiro , Fukuta Kikuto , Inoue Ryo 
Published: May 2018

AbstractA characteristic subset of T cells, known as double positive T cells (DPTC) and expressing both cluster of differentiation 4 (CD4) and CD8, is observed in porcine peripheral blood. Previous studies suggested that DPTC might be memory cells. However, detailed phenotypes and functions of DPTC are yet to be fully elucidated and thus, the relatedness of DPTC with memory phenotypes remains unclear. In this study, DPTC gene expression profiles in peripheral blood were analyzed by DNA microarray in Experiment 1 and compared with those of CD4 single positive T cells (4SPTC) and CD8 single positive T cells (8SPTC). Expressions of IFNG, CCL5, NCK2, CCR2 and ITGB1 were higher than that of 4SPTC and 8SPTC. In contrast, expressions of CCR7 and SELL were lower than that of 4SPTC and 8SPTC. These results suggested that DPTC were either effector T cells or effector memory T cells (TEM). Next, to determine whether DPTC were effector T cells or TEM, differences in the response of DPTC and 8SPTC against immunized/primed antigens were compared (Experiment 2). While DPTC showed quick elevation of IL2 and CD25 gene expressions against in vitro stimulation of primed/immunized antigens, 8SPTC did not. These results suggest that at least some DPTC likely belong to TEM.
A tale of two antibodies: obinutuzumab versus rituximab
Authors: Freeman Ciara L. , Sehn Laurie H. 
Published: May 2018

SummaryWhile rituximab has dramatically improved outcomes for patients with CD20+ malignancies for two decades, responses are not universal and resistance can develop. Obinutuzumab was developed to potentiate activity and overcome resistance. Pre‐clinical data suggests obinutuzumab is superior to rituximab at effecting B cell depletion; however recent phase III clinical trial results have been mixed. The decision of which antibody to employ will probably be further complicated by the approval of a subcutaneous preparation of rituximab and several anti‐CD20 biosimilars. Clinicians are now challenged with deciding whether to switch to obinutuzumab in approved settings, accepting the potential for increased toxicity and probable increased cost. The benefit conferred by obinutuzumab over rituximab may be context‐specific and vary based on histological subtype and immune integrity. This comprehensive review will explore the preclinical differences, investigate the proposed pathogenesis of rituximab resistance, compare the employed dosing strategies and interrogate available clinical results to help inform practice.
Management of post‐transplant lymphoproliferative disorders
Authors: DeStefano Christin B. , Desai Sanjal H. , Shenoy Aarthi G. , Catlett Joseph P. 
Published: May 2018

SummaryThe post‐transplant lymphoproliferative disorders (PTLDs) are a heterogeneous group of neoplasms that are one of the most serious complications of bone marrow and solid organ transplants. Because these disorders are rare, there are no randomized trials from which to derive optimal treatment. Management can be challenging and must balance the goal of PTLD eradication with the risks of graft rejection, graft‐versus‐host disease, further delays in immune reconstitution and life‐threatening infections, among others. This paper will provide a comprehensive review of PTLD following solid organ transplant and haematopoietic stem cell transplant with a focus on management. Included is a discussion of novel agents that are being studied in clinical trials and, when combined or sequenced with conventional therapy, have the potential to improve outcomes.
Skewed megakaryopoiesis in human induced pluripotent stem cell‐derived haematopoietic progenitor cells harbouring calreticulin mutations
Authors: Takei Hiraku , Edahiro Yoko , Mano Shuichi , Masubuchi Nami , Mizukami Yoshihisa , Imai Misa , Morishita Soji , Misawa Kyohei , Ochiai Tomonori , Tsuneda Satoshi , Endo Hiroshi , Nakamura Sou , Eto Koji , Ohsaka Akimichi , Araki Marito , Komatsu Norio 
Published: May 2018

SummarySomatic mutations in the calreticulin (CALR) gene have been found in most patients with JAK2‐ and MPL‐unmutated Philadelphia chromosome‐negative myeloproliferative neoplasms (MPNs). It has recently been shown that mutant CALR constitutively activates the thrombopoietin receptor MPL and, thus, plays a causal role in the development of MPNs. However, the roles of mutant CALR in human haematopoietic cell differentiation remain predominantly elusive. To examine the impact of the 5‐base insertion mutant CALR gene (Ins5) on haematopoietic cell differentiation, we generated induced pluripotent stem cells from an essential thrombocythaemia (ET) patient harbouring a CALR‐Ins5 mutation and from a healthy individual (WT). Megakaryopoiesis was more prominent in Ins5‐haematopoietic progenitor cells (Ins5‐HPCs) than in WT‐HPCs, implying that the system recapitulates megakaryocytosis observed in the bone marrow of CALR‐mutant ET patients. Ins5‐HPCs exhibited elevated expression levels of GATA1 and GATA2, suggesting a premature commitment to megakaryocytic differentiation in progenitor cells. We also demonstrated that 3‐hydroxy anagrelide markedly perturbed megakaryopoiesis, but not erythropoiesis. Collectively, we established an in vitro model system that recapitulates megakaryopoiesis caused by mutant CALR. This system can be used to validate therapeutic compounds for MPN patients harbouring CALR mutations and in detailed studies on mutant CALR in human haematological cell differentiation.
Yanshanian deformation along the northern margin of the North China Craton: Constraints from growth strata in the Shiguai Basin, Inner Mongolia, China
Authors: Wang Yongchao , Dong Shuwen , Chen Xuanhua , Shi Wei , Wei Lijuan 
Published: May 2018

AbstractThe evolution of Yanshanian structures, especially the timing of onset, is a key problem in reconstructing the Late Mesozoic structural framework of the North China Craton. Growth strata and progressive unconformities, coupled with related structures, have been recognized for the first time in the Jurassic Shiguai Basin, thus allowing us to constrain the timing of Yanshanian structures with greater precision. Growth geometries and detailed structural analysis indicate that the late Middle Jurassic Changhangou Formation can be considered as the earliest sedimentary response to the onset of Yanshanian deformation during 170–160 Ma. At this time interval, shortening deformation was dominantly controlled by N–S compression driven by the closure of the Mongol‐Okhotsk Ocean, and growth structures constituted a roughly forward thrusting sequence with a slow uplift rate in the early stages and a suddenly accelerated uplift rate in the final stage. Subsequently, due to the superposition of NW–SE compression during the Late Jurassic (160–145 Ma), the initial E–W‐trending structures were converted into a stepped geometry marked by several structural reentrants developing along strike. In addition, out of sequence thrusts represented by the Beilinshan thrust and its splays began to be active in the middle portion of the previous forward thrusting sequence. Northwestward subduction of the Izanagi plate along the eastern margin of Asia is generally considered to be responsible for this phase of deformation.
Return on investment for financial assistance for living kidney donors in the United States
Authors: Mathur Amit K. , Xing Jiawei , Dickinson David M. , Warren Patricia H. , Gifford Kimberly A. , Hong Barry A. , Ojo Akinlolu , Merion Robert M. 
Published: May 2018

AbstractBackgroundThe National Living Donor Assistance Center (NLDAC) enables living donor kidney transplants through financial assistance of living donors, but its return on investment (ROI) through savings on dialysis costs remains unknown.MethodsWe retrospectively reviewed 2012‐2015 data from NLDAC, the United States Renal Data System, and the Scientific Registry of Transplant Recipients to construct 1‐, 3‐, and 5‐year ROI models based on NLDAC applications and national dialysis and transplant cost data. ROI was defined as state‐specific federal dialysis cost minus (NLDAC program costs plus state‐specific transplant cost), adjusted for median waiting time (WT).ResultsA total of 2425 NLDAC applications were approved, and NLDAC costs were USD $6.76 million. Median donor age was 41 years, 66.1% were female, and median income was $33 759; 43.6% were evaluated at centers with WT >72 months. Median dialysis cost/patient‐year was $81 485 (IQR $74 489‐$89 802). Median kidney transplant cost/patient‐year was $30 101 (IQR $26 832‐$33 916). Overall, ROI varied from 5.1‐fold (1‐year) to 28.2‐fold (5‐year), resulting in $256 million in savings. Higher ROI was significantly associated with high WT, larger dialysis and transplant costs differences, and more NLDAC applicants completing the donation process.ConclusionsFinancial support for donor out‐of‐pocket expenses produces dramatic federal savings through incremental living donor kidney transplants.
Association of hypoglycaemia and risk of cardiac arrhythmia in patients with diabetes mellitus: A systematic review and meta‐analysis
Authors: Fitzpatrick Claire , Chatterjee Sudesna , Seidu Samuel , Bodicoat Danielle H. , Ng G Andre , Davies Melanie J. , Khunti Kamlesh 
Published: May 2018

AimsHypoglycaemia is associated with increased cardiovascular risk among individuals with diabetes mellitus. It has been hypothesized that hypoglycaemia may trigger autonomic changes leading to increased cardiac arrhythmia risk. We conducted a systematic review and meta‐analysis to explore this association.Materials and methodsOvid Medline, Embase, Scopus, Web of Science and Cochrane were searched from inception to October 10, 2017. We included studies of adults with diabetes (Type 1 or Type 2) that compared acute electrocardiogram (ECG) changes during episodes of hypoglycaemia and euglycaemia.ResultsOur search resulted in 4625 citations, among which 20 studies met the predefined inclusion criteria. Finally, 12 studies were included in the descriptive analysis and 15 in the meta‐analysis. Overall hypoglycaemia was associated with a reduction in heart rate variability and an increase in arrhythmia occurrence. QTc interval length was more significantly prolonged during hypoglycaemia compared to euglycaemia (pooled mean difference [95% confidence intervals] [0.64 (0.27‐1.01], P = ·001). Subgroup analysis based on diabetes type showed that QTc prolongation occurred in individuals with Type 1 and Type 2 diabetes; however, the change between euglycaemia reached statistical significance only among individuals with Type 1 diabetes.ConclusionOur findings suggest that hypoglycaemia results in ECG alterations that are associated with increased risk of cardiac arrhythmia, which is associated with increased cardiovascular events and mortality. More clinical studies are needed to determine the cardiac risks of hypoglycaemia in individuals with diabetes, especially in Type 2 diabetes.
Peripheral cannabinoid 1 receptor blockade mitigates adipose tissue inflammation via NLRP3 inflammasome in mouse models of obesity
Authors: Han Ji H. , Shin Hanho , Rho Jun G. , Kim Jung‐Eun , Son Dong H. , Yoon Juhwan , Lee Yong J. , Park Jung‐Hyuck , Song Byung J. , Choi Chang‐Sik , Yoon Seul G. , Kim Il Y. , Lee Eun K. , Seong Je K. , Kim Ki W. , Kim Wook 
Published: May 2018

AimTo analyze the metabolic parameters and adipose tissue inflammation via NLRP3 inflammasome following chronic treatment of mouse models of obesity with AJ5018 as the peripherally restricted cannabinoid 1 receptor (CB1R) antagonist.Materials and methodsThe selectivity for CB1R over CB2R, brain/plasma concentration ratio, and centrally mediated neurobehavioural effects of AJ5018, were assessed. The long‐term effects of AJ5018 and rimonabant on the metabolic parameters and adipose tissue inflammation were analyzed in diet‐induced obese (DIO) mice and diabetic db/db mice.ResultsAJ5018 had a higher degree of selectivity for CB1R over CB2R and markedly reduced brain penetrance, as reflected by the lower brain/plasma concentration ratio and the attenuated centrally mediated neurobehavioural effects, compared with its brain‐penetrant parent compound rimonabant. In DIO and db/db mice, AJ5018 exhibited comparable effects to rimonabant in improving metabolic abnormalities and suppressing macrophage infiltration into white adipose tissue, activation of the NLRP3 inflammasome, and production of proinflammatory cytokines.ConclusionsThese results suggest that peripheral CB1R blockade improves obesity‐induced insulin resistance by suppressing adipose tissue inflammation via the NLRP3 inflammasome.
Dispersion of Myzus persicae and transmission of Potato virus Y under elevated CO2 atmosphere
Authors: Bosquee Emilie , Boullis Antoine , Bertaux Morgane , Francis Frédéric , Verheggen François J. 
Published: May 2018

AbstractMost phytoviruses use insect vectors to spread and infect the surrounding crop plants. Because atmospheric gas concentrations alter the physiology and metabolism of plants, we hypothesize that the concentration of carbon dioxide (CO2) affects the spread of viruses, due to modifications in the feeding behavior of the vector. Tobacco plants, Nicotiana tabacum L. (Solanaceae), and green peach aphids, Myzus persicae (Sulzer) (Hemiptera: Aphididae), were cultivated under ambient (450 p.p.m., termed aCO2) and elevated (800 p.p.m., eCO2) concentrations of CO2. For each atmospheric condition, we first evaluated the ability of the Potato virus Y to spread in a small experimental design, from a central infected tobacco plant to two surrounding circles of healthy plants in presence of aphid vectors for 7 days. The number of aphids recovered on each plant and the infection status of the plants (i.e., healthy vs. infected) were assessed at the end of the experiment. We also evaluated the ability of aphids to transmit the virus under the two experimental atmospheres, by immediately transferring a single insect from an infected plant to a healthy one. The presence of virus in healthy plants was then determined. We found that aphid dispersal, as well as the associated spread of viruses, did not differ between the two atmospheres. On the other hand, we found that aphids grown under eCO2 were more efficient in transmitting viruses to healthy plants compared to aphids reared under aCO2 conditions. The results of this experiment indicate that: (1) the ability of an aphid vector to spread a phytovirus is not affected by the level of CO2 at short time and spatial scales, but (2) the concentration of CO2 may affect plant defenses or the feeding behavior of herbivorous insects, resulting in more efficient viral transmission from the vector to the host plant.
The genetic and molecular pathogenesis of myelodysplastic syndromes
Authors: Shallis Rory M. , Ahmad Rami , Zeidan Amer M. 
Published: May 2018

AbstractMyelodysplastic syndromes (MDS) comprise a diverse group of clonal and malignant myeloid disorders characterized by ineffective hematopoiesis, resultant peripheral cytopenias, and a meaningful increased risk of progression to acute myeloid leukemia. A wide array of recurring genetic mutations involved in RNA splicing, histone manipulation, DNA methylation, transcription factors, kinase signaling, DNA repair, cohesin proteins, and other signal transduction elements has been identified as important substrates for the development of MDS. Cytogenetic abnormalities, namely those characterized by loss of genetic material (including 5q‐ and 7q‐), have also been strongly implicated and may influence the clonal architecture which predicts such mutations and may provoke an inflammatory bone marrow microenvironment as the substrate for clonal expansion. Other aspects of the molecular pathogenesis of MDS continue to be further elucidated, predicated upon advances in gene expression profiling and the development of new, and improved high‐throughput techniques. More accurate understanding of the genetic and molecular basis for the development of MDS directly provides additional opportunity for treatment, which to date remains limited. In this comprehensive review, we examine the current understanding of the molecular pathogenesis and pathophysiology of MDS, as well as review future prospects which may enhance this understanding, treatment strategies, and hopefully outcomes.