bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metaphyseal osteopathy in threeAustralianKelpie siblings
Authors: Greenwell CM , Brain PH , Dunn AL 
Published: March 2014

Case reportMetaphyseal osteopathy (MO) was diagnosed in three Australian Kelpie puppies that were presented for veterinary assessment of lameness. The three puppies were siblings. Each was from a different litter by the same breeding pair. The puppy in case one was seen by the authors, and the puppies in cases two and three were patients at other veterinary hospitals. However, the medical records and radiographs were examined and reviewed for this report. Radiographic investigation of the lameness revealed pathognomonic appearance ofMOaffecting the metaphyseal region of the long bones in all three puppies. The diagnosis was confirmed on histopathology in one patient.ConclusionMOis considered a disease of large and giant‐breed dogs, being rarely reported in non‐large‐breed dogs, and has not been reported in the Australian Kelpie, which is considered a medium‐breed dog. This case series suggests a previously unreported breed predisposition toMOin the Australian Kelpie.
Studies of the Safety, Pharmacokinetics and Immunogenicity of Repeated Doses of Intravenous Staphylococcal Protein A in Cynomolgus Monkeys
Authors: Bernton Edward , Haughey David 
Published: March 2014

AbstractThree Good Laboratory Practice safety studies were performed with intravenous injections of highly purified staphylococcal protein A (SPA) in cynomolgus monkeys, in support of a clinical development programme utilizing this protein as an immunomodulator. These studies established a no‐observable‐adverse‐effect level (NOAEL) for up to 12 weekly doses of SPA, as well as toxicokinetic profiles for SPA, evaluation of antiproduct antibodies and biomarkers to better characterize the pharmacodynamic response to SPA. Biomarkers included neopterin, C‐reactive protein (CRP), troponin I and the change in the blood absolute lymphocyte count (ALC) 24 hr after SPA dosing. The transient decrease in ALC noted at 24 hr after dosing was similar to that seen in human Phase 1 trials. The majority of active‐treated monkeys developed antibodies against SPA. Cmax was not affected by development of antidrug antibodies (ADAs), and after the first dose was 87 (SD 19) ng/mL, 330 (SD 84) ng/mL and 1191 (SD 208) ng/mL for 5, 25 and 100 μg/kg doses, respectively. The development of ADAs increased plasma clearance of SPA. By the sixth weekly dose, the AUC was decreased by 76%, 54% and 66% for the 5, 25 and 100 μg/kg dose groups, respectively. These results indicate that SPA can be administered intravenously to non‐human primates without observable toxicity at weekly doses of up to 100 μg/kg.
A phase II study of dose‐dense and dose‐intense ABVD (ABVDDD‐DI) without consolidation radiotherapy in patients with advanced Hodgkin lymphoma
Authors: Russo Filippo , Corazzelli Gaetano , Frigeri Ferdinando , Capobianco Gaetana , Aloj Luigi , Volzone Francesco , De Chiara Annarosaria , Bonelli Annamaria , Gatani Tindaro , Marcacci Gianpaolo , Donnarumma Daniela , Becchimanzi Cristina , de Lutio Elisabetta , Ionna Franco , De Filippi Rosaria , Lastoria Secondo , Pinto Antonello 
Published: March 2014

SummaryWe explored activity and safety of a dose‐dense/dose‐intense adriamycin, bleomycin, vinblastine and dacarbazine regimen (ABVDDD‐DI) in 82 patients with advanced Hodgkin Lymphoma. Patients entered a two‐stage Bryant‐Day Phase II study to receive six cycles of ABVDDD‐DI without consolidation radiotherapy. Cycles were supported with granulocyte colony‐stimulating factor and delivered every 21 d; drugs were administered on days 1 and 11 at the same doses of standard ABVD except for doxorubicin (35 mg/m2; first four cycles only). Co‐primary endpoints were complete response (CR) rate and severe acute cardiopulmonary toxicity; secondary endpoints were event‐free (EFS) and disease‐free survival (DFS). All patients received the four doxorubicin‐intensified courses and 96% concluded all six cycles (82·3% within the intended 18 weeks). This translated into a 66·9% increase of received dose‐intensity for doxorubicin and 31·8% for the other agents over standard ABVD. The CR rate was 95·1% (78/82) and 87·8% (72/82) achieved a metabolic CR after two cycles. Cardiopulmonary toxicity never exceeded grade 2 and affected 14·6% of patients. Most frequent toxicities were grade 4 neutropenia (10%) and anaemia (9%), grade 3 infection (17%) and grade 2 mucocutaneous changes (30%). Five‐year EFS and DFS was 88·3% and 93·7%, respectively. ABVDDD‐DI regimen was well‐tolerated and ensured substantial CR and EFS rates without radiotherapy.
Prostate tumour volumes: evaluation of the agreement between magnetic resonance imaging and histology using novel co‐registration software
Authors: Le Nobin Julien , Orczyk Clément , Deng Fang‐Ming , Melamed Jonathan , Rusinek Henry , Taneja Samir S. , Rosenkrantz Andrew B. 
Published: March 2014

ObjectiveTo evaluate the agreement between prostate tumour volume determined using multiparametric magnetic resonance imaging (MRI) and that determined by histological assessment, using detailed software‐assisted co‐registration.Materials and MethodsA total of 37 patients who underwent 3T multiparametric MRI (T2‐weighted imaging [T2WI], diffusion‐weighted imaging [DWI]/apparent diffusion coefficient [ADC], dynamic contrast‐enhanced [DCE] imaging) were included. A radiologist traced the borders of suspicious lesions on T2WI and ADC and assigned a suspicion score of between 2 and 5, while a uropathologist traced the borders of tumours on histopathological photographs. Software was used to co‐register MRI and three‐dimensional digital reconstructions of radical prostatectomy specimens and to compute imaging and histopathological volumes. Agreement in volumes between MRI and histology was assessed using Bland–Altman plots and stratified by tumour characteristics.ResultsAmong 50 tumours, the mean differences (95% limits of agreement) in MRI relative to histology were −32% (−128 to +65%) on T2WI and −47% (−143 to +49%) on ADC. For all tumour subsets, volume underestimation was more marked on ADC maps (mean difference ranging from −57 to −16%) than on T2WI (mean difference ranging from −45 to +2%). The 95% limits of agreement were wide for all comparisons, with the lower 95% limit ranging between −77 and −143% across assessments. Volume underestimation was more marked for tumours with a Gleason score ≥7 or a MRI suspicion score 4 or 5.ConclusionVolume estimates of prostate cancer using MRI tended to substantially underestimate histopathological volumes, with a wide variability in extent of underestimation across cases. These findings have implications for efforts to use MRI to guide risk assessment.
Mothers' work–family conflict and enrichment: associations with parenting quality and couple relationship
Authors: Cooklin A. R. , Westrupp E. , Strazdins L. , Giallo R. , Martin A. , Nicholson J. M. 
Published: March 2014

AbstractBackgroundEmployment participation of mothers of young children has steadily increased in developed nations. Combining work and family roles can create conflicts with family life, but can also bring enrichment. Work–family conflict and enrichment experienced by mothers may also impact children's home environments via parenting behaviour and the couple relationship, particularly in the early years of parenting when the care demands for young children is high.MethodsIn order to examine these associations, while adjusting for a wide range of known covariates of parenting and relationship quality, regression models using survey data from 2151 working mothers of 4‐ to 5‐year‐old children are reported.Results/ConclusionResults provided partial support for the predicted independent relationships between work–family conflict, enrichment and indicators of the quality of parenting and the couple relationship.
Views of primary care providers regarding the return of genome sequencing incidental findings
Authors: Strong K.A. , Zusevics K.L. , Bick D. , Veith R. 
Published: March 2014

AbstractSequencing of the entire exome or genome is increasingly used in clinical practice. Debate continues, however, regarding which incidental findings (IFs) should be returned and who should be involved in those decisions. Previous empirical research regarding stakeholder attitudes to the return of IFs has primarily involved genetics professionals; non‐genetics health professionals have not been widely surveyed. Given this, a survey regarding return of IFs was administered at the Best Practices in Pediatrics Conference following an educational presentation on genetics terminology and genetic condition examples. A total of 258 participants completed the survey. Of particular note, respondents who were positively disposed to sequencing did not always report wanting to learn about IFs, even if actionable. This is noteworthy given recent American College of Medical Genetics and Genomics guidelines recommending particular actionable IF be returned ‘without reference to patient preference’. This study's findings are important because they provide insight regarding the attitudes to the return of genome sequencing results for an important professional group, primary care providers. Ultimately, as likely gatekeepers to referrals for this technology, their opinions about the test will be key to its successful deployment.
High Cytochrome c Oxidase Expression Links to Severe Skeletal Energy Failure by 31P‐MRS Spectroscopy in Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke‐Like Episodes
Authors: Liu Ai‐Hua , Niu Feng‐Nan , Chang Lei‐Lei , Zhang Bing , Liu Zhuo , Chen Jie‐Yu , Zhou Qiang , Wu Hong‐Yan , Xu Yun 
Published: March 2014

SummaryAimsThe purpose of this study was to evaluate the energy metabolism and mitochondrial function in skeletal muscle from patients with Mitochondrial encephalomyopathy, lactic acidosis, and stroke‐like episodes (MELAS) or chronic progressive external ophthalmoplegia (CPEO) using phosphorus magnetic resonance spectroscopy (31P‐MRS), to determine whether abnormally increasing cytochrome c oxidase (COX), as detected in muscle biopsy, could be a cause for MELAS.Methods31P‐MRS was performed on the quadriceps femoris muscle of 12 healthy volunteers and 11 patients diagnosed as MELAS or CPEO by muscle biopsy and genetic analysis. All subjects experienced a state of rest, 5‐min exercise, and 5‐min recovery protocol in a supine position.ResultsCompared to CPEO, MELAS patients typically exhibited COX‐positive ragged‐red fibers (RRFs) as well as strongly SDH‐positive blood vessels (SSVs). However, based on 31P‐MRS results, MELAS showed a higher inorganic phosphate (Pi)/phosphocreatine (PCr) ratio and lower ATP/PCr ratio during exercise and delayed Pi/PCr and ATP/PCr recovery to normal.ConclusionsThis study suggests that high COX expression contributes to severe skeletal energy failure by 31P‐MRS spectroscopy in MELAS.
Estimating Climate Resilience for Conservation across Geophysical Settings
Authors: ANDERSON MARK G. , CLARK MELISSA , SHELDON ARLENE OLIVERO 
Published: March 2014

AbstractConservationists need methods to conserve biological diversity while allowing species and communities to rearrange in response to a changing climate. We developed and tested such a method for northeastern North America that we based on physical features associated with ecological diversity and site resilience to climate change. We comprehensively mapped 30 distinct geophysical settings based on geology and elevation. Within each geophysical setting, we identified sites that were both connected by natural cover and that had relatively more microclimates indicated by diverse topography and elevation gradients. We did this by scoring every 405 ha hexagon in the region for these two characteristics and selecting those that scored >SD 0.5 above the mean combined score for each setting. We hypothesized that these high‐scoring sites had the greatest resilience to climate change, and we compared them with sites selected by The Nature Conservancy for their high‐quality rare species populations and natural community occurrences. High‐scoring sites captured significantly more of the biodiversity sites than expected by chance (p < 0.0001): 75% of the 414 target species, 49% of the 4592 target species locations, and 53% of the 2170 target community locations. Calcareous bedrock, coarse sand, and fine silt settings scored markedly lower for estimated resilience and had low levels of permanent land protection (average 7%). Because our method identifies—for every geophysical setting—sites that are the most likely to retain species and functions longer under a changing climate, it reveals natural strongholds for future conservation that would also capture substantial existing biodiversity and correct the bias in current secured lands.
Assessment of resident and fellow knowledge of the organ donor referral process
Authors: Gupta Natasha , Garonzik‐Wang Jacqueline M. , Passarella Ralph J. , Salter Megan L. , Kucirka Lauren M. , Orandi Babak J. , Law Andrew H. , Segev Dorry L. 
Published: March 2014

AbstractMaximizing deceased donation rates can decrease the organ shortage. Non‐transplant physicians play a critical role in facilitating conversion of potential deceased donors to actual donors, but studies suggest that physicians lack knowledge about the organ donation process. As residency and fellowship are often the last opportunities for formal medical training, we hypothesized that deficiencies in knowledge might originate in residency and fellowship. We conducted a cross‐sectional survey to assess knowledge about organ donation, experience in donor conversion, and opinions of the process among residents and fellows after their intensive care unit rotations at the Johns Hopkins Hospital. Of 40 participants, 50% had previously facilitated donor conversion, 25% were familiar with the guidelines of the organ procurement organization (OPO), and 10% had received formal instruction from the OPO. The median score on the knowledge assessment was five of 10; higher knowledge score was not associated with level of medical training, prior training in or experience with donor conversion, or with favorable opinions about the OPO. We identified a pervasive deficit in knowledge among residents and fellows at an academic medical center with an active transplant program that may help explain attending‐level deficits in knowledge about the organ donation process.
Relation of Myocardial Systolic Mechanics to Serum Ferritin Level as a Prognosticator in Thalassemia Patients Undergoing Repeated Transfusion
Authors: Chen Ming‐Ren , Ko Ho‐Shun , Chao Tze‐Fan , Liu Hsi‐Che , Kuo Jen‐Yuan , Bulwer Bernard E. , Yeh Hung‐I , Hung Chung‐Lieh 
Published: March 2014

IntroductionMyocardial iron overload leading to congestive heart failure (HF) or arrhythmias is a recognized complication in thalassemia patients undergoing chronic blood transfusion. The relationship between myocardial iron load, subclinical systolic dysfunction, and clinical events remains less well known.Materials and MethodsWe studied a total of 77 subjects, comprising 37 thalassemia patients (mean age: 24.2 ± 5.5 years) with a history of repeated blood transfusions, in addition to 40 age‐ and gender‐matched controls (mean age: 24 ± 4.5 years). Serum ferritin levels were checked in all subjects, as well as semiautomated quantification of left ventricular (LV) longitudinal, circumferential, and radial deformations assessed by two‐dimensional (2D) speckle tracking analysis.ResultsCompared with the control group, thalassemia patients showed significantly larger LV mass index and lower myocardial deformations (P < 0.05), but left ventricular ejection fraction (LVEF) did not differ significantly (P = 0.233). There was a significant linear correlation between serum ferritin level and longitudinal (r = 0.44, P = 0.0078) and radial strain (r = −0.46, P = 0.0051), with optimal cutoff provided to be −15.48%, −21.31%, and 26.67% for longitudinal, circumferential, and radial strain in predicting clinical events, respectively. During a median of 802.5 days follow‐up, 11 clinical composites (HF incidence, ventricular tachyarrhythmia, and death) occurred (N = 9 subjects); subjects with composites had significantly reduced longitudinal and radial strain compared to those without (both P < 0.05). After adjusting for age, sex, serum ferritin level, and LV mass index, a worsening of longitudinal strain remained as an independent predictor of clinical events and death (HR: 6.05, P = 0.033).ConclusionSubclinical systolic dysfunction appears more likely in thalassemia subjects with a history of repeated blood transfusions, which further correlated with serum ferritin levels. In addition, worsening LV myocardial deformation parameters may play an independent role in predicting clinical outcomes beyond traditional measures in this population.
Abnormalities of quantities and functions of linker for activations of T cells in severe aplastic anemia
Authors: Sheng Weiwei , Liu Chunyan , Fu Rong , Wang Huaquan , Qu Wen , Ruan Erbao , Wang Guojin , Liu Hong , Wu Yuhong , Song Jia , Xing Limin , Guan Jing , Li Lijuan , Liu Hui , Shao Zonghong 
Published: March 2014

AbstractObjectiveSevere aplastic anemia (SAA) is a rare immune‐regulated disease characterized by severe pancytopenia and bone marrow failure, caused by destruction of hematopoietic cells by the activated T lymphocytes. Linker for activation of T cells (LAT), a transmembrane adaptor protein, plays a key role in T‐cell and mast cell functions. However, it remains unclear how LAT may change in patients with SAA. This study aims at understanding the role of lymphocyte LAT in SAA.MethodsThe expression of LAT, related signaling molecules, and T‐cell effector molecules was determined by flow cytometry. LAT mRNA was evaluated by quantitative real‐time PCR. Cytokine production by cultured T cells was determined by ELISA.ResultsPatients with SAA had an increased levels of LAT and both total phosphorylated LAT and of the related molecule (ZAP‐70) in circulating T cells compared with normal controls. In patients with SAA, the expression of LAT was positively associated with the expression of perforin and granzyme B in CD8+ T cells. Inhibition of LAT expression in T cells from patients with SAA decreased the activation of the CD4+ and CD8+ T‐cell subsets. Overexpression of LAT in T cells from normal controls increased the activation of CD4+ and CD8+ T‐cell subsets with increased apoptosis of K562 cells in coculture.ConclusionsOur findings demonstrate that dysregulation of LAT expression and activation may contribute to over‐function of T cells, imbalance of Th1/Th2 subsets and thus lead to hematopoiesis failure in SAA. Immunosuppressive therapy dramatically reduced the expression of LAT making it an attractive therapeutic target in SAA.
Intracellular calcium elevation during plateau potentials mediated by extrasynaptic NMDA receptor activation in rat hippocampal CA1 pyramidal neurons is primarily due to calcium entry through voltage‐gated calcium channels
Authors: Oda Yoshiaki , Kodama Satoshi , Tsuchiya Sadahiro , Inoue Masashi , Miyakawa Hiroyoshi 
Published: March 2014

AbstractWe reported previously that plateau potentials mediated by extrasynaptic N‐methyl‐d‐aspartate receptors (NMDARs) can be induced either by synaptic stimulation in the presence of glutamate transporter antagonist or by iontophoresis of NMDA in rat hippocampal CA1 pyramidal neurons. To examine whether the plateau potentials are accompanied by an elevation of intracellular Ca2+ and to determine the source of Ca2+ elevation, we performed Ca2+ imaging during the plateau potential. Neurons were loaded with Ca2+ indicator fluo‐4, and the plateau potentials were generated either synaptically in the presence of glutamate transporter antagonist or by iontophoretically applying NMDA. We have found that a transient elevation in intracellular Ca2+ accompanies the plateau potential. The synaptically induced plateau potential and the Ca2+ elevation were blocked by 5,7‐dichlorokynurenic acid (5,7‐dCK), an antagonist for the glycine‐binding sites of NMDAR. A mixture of Cd2+ and tetrodotoxin did not block NMDA‐induced plateau potentials, but completely abolished the accompanying Ca2+ elevation in both the presence and absence of Mg2+ ions in the bathing solution. The NMDA‐induced plateau potential was blocked by further adding 5,7‐dCK. Our results show that the NMDAR‐mediated plateau potential is accompanied by elevation of intracellular Ca2+ that is primarily caused by the influx of Ca2+ through voltage‐gated Ca2+ channels.
Contrast‐dependent OFF‐dominance in cat primary visual cortex facilitates discrimination of stimuli with natural contrast statistics
Authors: Liu Kefei , Yao Haishan 
Published: March 2014

AbstractBoth theoretical and experimental studies suggest that response properties in the visual system are shaped by signals in the natural environment. Recent studies showed that, in the primary visual cortex (V1), neurons preferring light decrements (OFF stimuli) outnumber those preferring light increments (ON stimuli). However, it is not clear whether the OFF‐dominance in V1 neurons is related to the contrast statistics in natural images. By analysing the distribution of negative and positive contrasts in natural images at several spatial scales, we showed that optimal coding of the natural contrast signals would lead to a contrast‐dependent OFF‐dominant response, with a stronger degree of OFF‐dominance at a higher contrast. Using bright and dark stimuli at various contrast levels to measure the receptive fields of neurons in cat V1, we found an increasing degree of OFF‐dominance of the neuronal population as the contrast was increased. By modeling receptive fields exhibiting OFF‐ and ON‐dominance, we found that contrast‐dependent OFF‐dominance facilitated the discrimination of stimuli with natural contrast distribution. Thus, by matching contrast‐dependent OFF‐dominance to the statistics of contrast distribution in natural images, V1 neurons may better discriminate contrast information in natural scenes.
Does recognized genetic management in supportive breeding prevent genetic changes in life‐history traits?
Authors: Chargé Rémi , Sorci Gabriele , Saint Jalme Michel , Lesobre Loïc , Hingrat Yves , Lacroix Frédéric , Teplitsky Céline 
Published: March 2014

AbstractSupportive breeding is one of the last resort conservation strategies to avoid species extinction. Management of captive populations is challenging because several harmful genetic processes need to be avoided. Several recommendations have been proposed to limit these deleterious effects, but empirical assessments of these strategies remain scarce. We investigated the outcome of a genetic management in a supportive breeding for theHoubara Bustard. At the phenotypic level, we found an increase over generations in the mean values of gamete production, body mass and courtship display rate. Using an animal model, we found that phenotypic changes reflected genetic changes as evidenced by an increase in breeding values for all traits. These changes resulted from selection acting on gamete production and to a lesser extent on courtship display. Selection decreased over years for female gametes, emphasizing the effort of managers to increase the contribution of poor breeders to offspring recruited in the captive breeding. Our results shed light on very fast genetic changes in an exemplary captive programme that follows worldwide used recommendations and emphasizes the need of more empirical evidence of the effects of genetic guidelines on the prevention of genetic changes in supportive breeding.