bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II study of bortezomib in combination with rituximab, cyclophosphamide and prednisone with or without doxorubicin followed by rituximab maintenance in patients with relapsed or refractory follicular lymphoma
Authors: Craig Michael , Hanna Wahid T. , Cabanillas Fernando , Chen Chien‐Shing , Esseltine Dixie‐Lee , Neuwirth Rachel , O'Connor Owen A. 
Published: July 2014

SummaryThis non‐comparative phase II study (ClinicalTrials.gov: NCT00715208) evaluated bortezomib in place of vincristine in established rituximab‐chemotherapy regimens in relapsed/refractory follicular (FL) or marginal zone lymphoma (MZL). Patients were allocated (physician/patient preference) to receive six 21‐d cycles of: bortezomib 1·6 mg/m2 (days 1, 8), rituximab 375 mg/m2 (day 1), cyclophosphamide 1000 mg/m2 (day 1) and prednisone 100 mg (days 1–5; VR‐CP; 47 FL, 1 MZL patients); or bortezomib, rituximab, prednisone per VR‐CP, cyclophosphamide 750 mg/m2 and doxorubicin 50 mg/m2 (day 1; VR‐CAP; 4 FL, 2 MZL, 1 chronic lymphocytic leukaemia patients). With VR‐CP, the response rate was 77%, with a 27% complete response rate. After a median follow‐up of 10·9 months, 40% of patients had relapsed/progressed or died. Median duration of response and progression‐free survival was 21·9 and 14·9 months, respectively. Common drug‐related grade ≥3 adverse events were neutropenia (25%), thrombocytopenia (6%) and lymphopenia (6%). Thirteen (27%) patients reported peripheral neuropathy (one grade 3). With VR‐CAP, one FL patient achieved complete response and three FL and two MZL patients achieved partial responses. Three patients reported drug‐related grade 1/2 peripheral neuropathy. Weekly bortezomib and rituximab represents an active, feasible treatment platform in FL. VR‐CP was active and well tolerated in patients with relapsed/refractory FL.
Amyloid‐Aβ Peptide in Olfactory Mucosa and Mesenchymal Stromal Cells of Mild Cognitive Impairment and Alzheimer's Disease Patients
Authors: Ayala‐Grosso Carlos A. , Pieruzzini Rosalinda , Diaz‐Solano Dylana , Wittig Olga , Abrante Ligia , Vargas Leslie , Cardier Jose 
Published: July 2014

AbstractPatients with mild cognitive impairment (MCI) or Alzheimer's disease (AD) might develop olfactory dysfunction that correlates with progression of disease. Alteration of olfactory neuroepithelium associated with MCI may be useful as predictor of cognitive decline. Biomarkers with higher sensitivity and specificity would allow to understand the biological progression of the pathology in association with the clinical course of the disease. In this study, magnetic resonance images, apolipoprotein E (ApoE) load, Olfactory Connecticut test and Montreal Cognitive Assessment (MoCA) indices were obtained from noncognitive impaired (NCI), MCI and AD patients. We established a culture of patient‐derived olfactory stromal cells from biopsies of olfactory mucosa (OM) to test whether biological properties of mesenchymal stromal cells (MSC) are concurrent with MCI and AD psychophysical pathology. We determined the expression of amyloid Aβ peptides in the neuroepithelium of tissue sections from MCI and AD, as well as in cultured cells of OM. Reduced migration and proliferation of stromal (CD90+) cells in MCI and AD with respect to NCI patients was determined. A higher proportion of anosmic MCI and AD cases were concurrent with the ApoE ε4 allele. In summary, dysmetabolism of amyloid was concurrent with migration and proliferation impairment of patient‐derived stem cells.
Sisyphean evolution in Darwin's finches
Authors: McKay Bailey D. , Zink Robert M. 
Published: July 2014

ABSTRACTThe trajectory of speciation involves geographic isolation of ancestral populations followed by divergence by natural selection, genetic drift or sexual selection. Once started, the process may experience fits and starts, as sometimes diverging populations intermittently reconnect. In theory populations might cycle between stages of differentiation and never attain species status, a process we refer to as Sisyphean evolution. We argue that the six putative ground finch species (genus Geospiza) of the Galápagos Islands represent a dramatic example of Sisyphean evolution that has been confused with the standard model of speciation. The dynamic environment of the Galápagos, closely spaced islands, and frequent dispersal and introgression have prevented the completion of the speciation process. We suggest that morphological clusters represent locally adapted ecomorphs, which might mimic, and have been confused with, species, but these ecomorphs do not form separate gene pools and are ephemeral in space and time. Thus the pattern of morphological, behavioural and genetic variation supports recognition of a single species of Geospiza, which we suggest should be recognized as Darwin's ground finch (Geospiza magnirostris). We argue that instead of providing an icon of insular speciation and adaptive radiation, which is featured in nearly every textbook on evolutionary biology, Darwin's ground finch represents a potentially more interesting phenomenon, one of transient morphs trapped in an unpredictable cycle of Sisyphean evolution. Instead of revealing details of the origin of species, the mechanisms underlying the transient occurrence of ecomorphs provide one of the best illustrations of the antagonistic effects of natural selection and introgression.
Adverse skeletal effects of drugs – beyond Glucocorticoids
Authors: O'Sullivan Susannah , Grey Andrew 
Published: July 2014

SummaryOsteoporotic fractures are an important public health problem with significant individual and societal costs. In addition to the major risk factors for osteoporotic fracture, low bone mineral density (BMD), age, low body weight and history of fracture or falls, some drugs are now considered to be important secondary risk factor for bone loss and fracture, particularly amongst predisposed individuals. Currently available data are often generated from small observational clinical studies, making risk assessment and development of management guidelines difficult. In many cases, the exposed population has a low baseline risk for fracture and additional assessment and treatment may not be necessary. In this review, we focus on drugs other than glucocorticoids identified as potentially causing adverse skeletal effects, summarizing the existing evidence from preclinical and clinical studies, and suggest recommendations for patient management.
Progressive microcephaly is caused by compound‐heterozygous mutations in QARS
Authors: Waltl S. 
Published: July 2014

Mutations in QARS, encoding glutaminyl‐tRNA synthetase, cause progressive microcephaly, cerebral–cerebellar atrophy, and intractable seizuresZhang et al. (2014)The American Journal of Human Genetics;94(4):547–558.
Strontium hydroxyapatite in situ gel‐forming system – a new approach for minimally invasive bone augmentation
Authors: Hao J. , Chou J. , Kuroda S. , Otsuka M. , Kasugai S. , Lang N. P. 
Published: July 2014

AbstractObjectivesTo achieve ideal functional and aesthetic requirements, ridge augmentation is often required before dental implant placement. Bone augmentation (especially vertical), which normally consists of complex and invasive surgeries, still remains challenge. This study seeks to investigate the feasibility of an injectable in situ gel‐forming system containing strontium hydroxyapatite (SrHA) and alginate for minimally invasive bone augmentation in a rat calvarial model.Material and methodsSrHA–alginate solution was prepared by mixing SrHA powder with alginate solution (20 mg/mL) to the final concentration of 0.5% (w/v). Each animal received a 200‐μL single subperiosteal injection of either SrHA–alginate solution or alginate solution. The new bone formation was assessed at 0, 4, and 8 weeks histologically and radiologically.ResultsThe SrHA–alginate solution materials could form solid gel once injected. As such, no sutures were required to close the injection site. Significantly greater amount of new bone formation was observed in the SrHA–alginate group compared with the alginate group both by micro‐CT and by histological section. The newly formed bone in the SrHA–alginate group originated both from the underlying original bone and from the elevated periosteum. A 2.3‐fold increase of the vertical bone height was observed in the SrHA–alginate group compared with 1.3‐fold increase in the alginate group.ConclusionsRat calvarial bone augmentation was achieved by a single subperiosteal injection of SrHA–alginate solution without any administration of stem cells or growth factors. The in situ gel‐forming material may hold potential therapeutic benefits for local bone augmentation in a minimally invasive manner.
A Postmortem Study to Compare Agonist and Antagonist 5‐HT1A Receptor‐binding Sites in Alzheimer's Disease
Authors: Becker Guillaume , Streichenberger Nathalie , Billard Thierry , Newman‐Tancredi Adrian , Zimmer Luc 
Published: July 2014

SummaryAimsPositron emission tomography (PET) imaging using 5‐HT1A receptor radioligands shows a decreased expression of this serotonin receptor in the hippocampus of patients with Alzheimer's disease (AD) at advanced stages. However, previous 5‐HT1A receptor radioligands used in human imaging were antagonists, thought to bind to 5‐HT1A receptors in different functional states (i.e., both the one which displays high affinity for agonists and is thought to mediate receptor activation, as well as the functional state which has low affinity for agonists). Comparing the PET imaging obtained using an agonist radioligand, which binds selectively to the functional state of the receptors, with the PET imaging obtained using an antagonist radioligand would therefore provide original information on 5‐HT1A receptor impairment during AD.MethodsQuantitative autoradiography using 18F‐F15599 and 18F‐MPPF, a 5‐HT1A agonist and antagonist, respectively, was measured in hippocampi of 18 patients with AD.ResultsFunctional 5‐HT1A receptors, labeled by 18F‐F15599, represented ~35% of total receptors, as estimated by 18F‐MPPF labeling. 18F‐F15599 binding decreased in dentate gyrus of patients with AD, as indicated by Braak's stages. In contrast, binding of 18F‐MPPF was statistically unchanged.ConclusionThese in vitro results support testing the concept of functional PET imaging using agonist radioligands in clinical studies.
Leaf traits influencing oviposition preference and larval performance of Cameraria ohridella on native and novel host plants
Authors: D'Costa Lilla , Simmonds Monique S.J. , Straw Nigel , Castagneyrol Bastien , Koricheva Julia 
Published: July 2014

AbstractLeaf traits are known to influence the preference and performance of phytophagous insects. Traits that influence oviposition can differ from traits that favour larval development, but in native hosts the association between traits usually leads to positive preference‐performance relationships. However, when herbivores interact with novel hosts, traits that influence oviposition and successful larval development can become decoupled, leading to poor preference‐performance relationships. We investigated traits associated with preference and performance of the horse‐chestnut leaf miner, Cameraria ohridella Deschka & Dimic (Lepidoptera: Gracillariidae), on its native host, Aesculus hippocastanum L. (Sapindaceae), and on other species of Aesculus that are novel hosts for the leaf miner. Cameraria ohridella laid eggs on all species of Aesculus, but showed preferences for A. hippocastanum and the phylogenetically closely related Japanese horse‐chestnut, Aesculus turbinata Blume. Successful mine development, however, was observed only on A. hippocastanum and A. turbinata, which indicates a partial mismatch between female oviposition and larval performance. The two susceptible Aesculus species were very similar in their leaf traits, which might explain why larvae performed equally well on these species. In contrast, species resistant to C. ohridella [Aesculus chinensis Bunge, Aesculus indica (Camb) Hook, and Aesculus flava Aiton] showed considerable variation in leaf traits, which suggests that different species of Aesculus might have different mechanisms of resistance to C. ohridella, supporting the idea of different defensive syndromes in different species of plants.
Impact of plant architecture and extraguild prey density on intraguild predation in an agroecosystem
Authors: Gagnon Annie‐Ève , Brodeur Jacques 
Published: July 2014

AbstractSeveral models and experimental studies conducted in confined environments have shown that intraguild predation (IGP) can modulate population abundances and structure communities. A number of ecological and abiotic factors determine the nature and frequency of IGP. This study examined the effect of plant architecture and extraguild prey density, and their interactions, on the occurrence of IGP between two species of ladybird, Harmonia axyridis (Pallas) and Propylea quatuordecimpunctata L. (both Coleoptera: Coccinellidae). Theoretical concepts predict that IGP levels would increase with a decrease of both extraguild prey density and plant structural complexity. We conducted a factorial experiment in an open soybean field into which coccinellid larvae were introduced in experimental plots for a period of 5 days. We tested two levels of soybean aphid [Aphis glycines Matsumara (Hemiptera: Aphididae)] density, low and high (100 and 1 000 aphids per plot, respectively), and two levels of plant complexity, low (by removing half of the branches from the soybean plants) and high (by leaving plants intact). We used species‐specific molecular markers to detect the presence of P. quatuordecimpunctata in the digestive tract of H. axyridis. Molecular gut‐content analysis of H. axyridis revealed that rates of IGP were higher (20%) at low aphid density than at high aphid density (<6%). Decreased plant complexity did not impact the frequency of IGP. In accordance with existing literature, this study demonstrates that IGP is amplified at low extraguild prey density. We conclude that considering environmental factors, such as extraguild prey density, is crucial to improve our ability to predict the impact of intraguild predation on community structure and, from an applied perspective, biological control.
Delays in time to surgery for minorities with temporal lobe epilepsy
Authors: Thompson Atalie C. , Ivey Susan L. , Lahiff Maureen , Betjemann John P. 
Published: July 2014

SummaryObjectivesTo determine whether adult minority patients with medically refractory temporal lobe epilepsy (TLE) experience significantly longer times to anterior temporal lobectomy (ATL) following presurgical evaluation.MethodsA retrospective cohort study of 223 adult patients with epilepsy (PWE) and unilateral mesial temporal sclerosis who completed presurgical evaluation in the epilepsy monitoring unit at University of California, San Francisco, between January 1, 1993 and December 31, 2010, with follow‐up through December 31, 2012. Log‐rank test was performed for Kaplan‐Meier survival curves of time to ATL stratified by race/ethnicity and by limited English proficiency (LEP). Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards and Weibull modeling.ResultsAfrican Americans (AAs) and Asian/Pacific Islanders (Asian/PIs) experienced significantly longer times to surgery than whites in Kaplan‐Meier plots (log‐rank test p = 0.02 and p = 0.005, respectively). AAs and Asian/PIs also had longer times to surgery after adjusting for frailty, LEP, sex, age, mesial temporal sclerosis (MTS) laterality, and nonconcordant ictal electroencephalography (EEG) (adjusted HR = 0.22, p = 0.006; adjusted HR = 0.25, p = 0.003, respectively). Patients with LEP experienced significantly longer times to surgery than patients proficient in English (log‐rank test p = 0.0085; adjusted HR = 0.48, p = 0.041). In Cox modeling, nonconcordant ictal EEG studies (adjusted HR = 0.47, p = 0.01), left‐sided MTS (adjusted HR = 0.69, p = 0.023), and female sex (adjusted HR = 0.72, p = 0.048) were risk factors for longer times to surgery.SignificanceAA and Asian/PI patients as well as those with LEP have significantly longer times to ATL following presurgical evaluation. Future studies should be aimed at identifying the source of these disparities and developing targeted interventions to address them.A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Why U.S. epilepsy hospital stays rose in 2006
Authors: Cárdenas Víctor M. , Román Gustavo C. , Pérez Adriana , Hauser W. Allen 
Published: July 2014

SummaryObjectiveWe observed a substantial increase in age‐adjusted hospitalization rates in the United States National Hospital Discharge Survey data from 1996 to 2010. We aimed to assess reasons for this increase.MethodsThe National Hospital Discharge Survey collected data on a national sample of short‐term hospital stays in nonfederal hospitals. We determined epilepsy‐related discharge diagnoses by age, gender, and region using weighted analysis, and estimated age‐adjusted rates and annual percent changes using regression analysis. We also looked at epilepsy as the principal discharge diagnosis in the Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project.ResultsIn the United States, on average, nearly 110,000 more admissions were reported each year with epilepsy as the principal discharge diagnosis in 2006–2010 than in 1996–2005, a 2.7‐fold increase in hospitalization rates from epilepsy. During this period, there were more hospitalizations with principal discharge diagnosis of epilepsy not otherwise specified, and among older patients. The number of discharges with seizure not otherwise specified dropped dramatically after 2006, and was more evident among pediatric patients. The age‐adjusted rates of hospital stays combining discharges with any mention of epilepsy (345.XX) or seizures unspecified (780.39) in seven discharge diagnoses, were similar in 1996–2005 and 2006–2010.
SignificanceWe postulate that the excess in hospitalizations with epilepsy as first discharge diagnosis in 2006–2010 in the United States was related to the changes in coding in 2006. Any use of U.S. hospital discharge data with epilepsy‐related diagnosis after that date will require further validation.A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Traumatic brain injury manifested as optic neuropathy in the horse: A commentary and clinical case
Authors: Brooks D. E. , Plummer C. E. , Craft S. L. M. , Struthers J. D. 
Published: July 2014

SummaryBlindness from head trauma is a serious debilitating disease in the horse. It appears that blunt trauma to the skull results in intracranial injury to the optic nerve at the optic chiasm from mechanical and vascular mechanisms. Systemically administered iron and calcium chelation therapy may enable some horses to recover vision.
Chemoprevention of photocarcinogenesis by lycopene
Authors: Ascenso Andreia , Ribeiro Helena , Marques Helena C. , Oliveira Helena , Santos Conceição , Simões Sandra 
Published: July 2014

AbstractThis review focuses on the photoprotection conferred by lycopene, one of the most potent anti‐oxidants. Lycopene has been recently proposed to play a critical role on anticarcinogenic action at different levels. The photoprotective properties of lycopene remain contradictory. Some studies point out a positive and others a negative effect in both in vitro and in vivo models. Currently, researchers recognise that crucial gaps exist in understanding the role of carotenoids as effective modulators of apoptosis, cell cycle dynamics and/or of their in vivo behaviour as cellular anti‐oxidants. The development of novel therapeutic strategies for skin disorders depends on our understanding of the molecular mechanism of UV damage on skin cells. The use of several effective phytocompounds, including lycopene, working through preventive and/or corrective pathways in the cell, may be an approach for reducing UV‐B‐generated damage.
Functional analysis of the fractalkine gene promoter in human aortic smooth muscle cells exposed to proinflammatory conditions
Authors: Gan Ana‐Maria , Butoi Elena , Manea Adrian , Pirvulescu Monica Madalina , Stan Daniela , Simion Viorel , Calin Manuela , Simionescu Maya , Manduteanu Ileana 
Published: July 2014

Fractalkine (Fk) and its receptor CX3C receptor 1 contribute effectively to the atherosclerotic process, mediating the recruitment of leukocytes and promoting the interactions between monocytes/macrophages and smooth muscle cells (SMCs). As Fk expression is significantly increased in SMCs during atherogenesis, we aimed to uncover the detailed molecular mechanisms of transcriptional regulation of the Fk gene. For this purpose, we cloned and characterized the human Fk promoter, and studied the specific roles of different transcription factors in its regulation in human aortic SMCs activated by interferon‐γ. In silico analysis of the Fk promoter indicated the presence of binding sites for various inflammatory modulators, such as nuclear factor‐κB (NF‐κB), signal transducer and activator of transcription (STAT)1/STAT3, and activator protein‐1. Using a luciferase reporter plasmid, we identified a 2046‐bp region spanning the transcriptional start point of the Fk gene, which has strong constitutive promoter activity in SMCs. The effects of interferon‐γ on both Fk reporter activity and endogenous transcription were abolished by silencing NF‐κB, STAT1, and STAT3. Transient overexpression of p65/NF‐κB and STAT1/STAT3 increased Fk promoter activity, whereas c‐Jun/activator protein‐1 overexpression had no effect. The results obtained with chromatin immunoprecipitation assays revealed the existence of physical interactions of p65 and STAT1/STAT3 with the predicted elements of the Fk promoter. Moreover, Fk‐promoted monocyte chemotaxis was dependent on the janus kinase–STAT pathway. Investigation of the detailed molecular mechanisms by cloning and characterizing potential transcriptional response elements has identified the Fk regulatory mechanism in activated human SMCs.
Effects of high‐severity fire drove the population collapse of the subalpine Tasmanian endemic conifer Athrotaxis cupressoides
Authors: Holz Andrés , Wood Sam W. , Veblen Thomas T. , Bowman David M.J.S. 
Published: July 2014

AbstractAthrotaxis cupressoides is a slow‐growing and long‐lived conifer that occurs in the subalpine temperate forests of Tasmania, a continental island to the south of Australia. In 1960–1961, human‐ignited wildfires occurred during an extremely dry summer that killed many A. cupressoides stands on the high plateau in the center of Tasmania. That fire year, coupled with subsequent regeneration failure, caused a loss of ca. 10% of the geographic extent of this endemic Tasmanian forest type. To provide historical context for these large‐scale fire events, we (i) collected dendroecological, floristic, and structural data, (ii) documented the postfire survival and regeneration of A. cupressoides and co‐occurring understory species, and (iii) assessed postfire understory plant community composition and flammability. We found that fire frequency did not vary following the arrival of European settlers, and that A. cupressoides populations were able to persist under a regime of low‐to‐mid severity fires prior to the 1960 fires. Our data indicate that the 1960 fires were (i) of greater severity than previous fires, (ii) herbivory by native marsupials may limit seedling survival in both burned and unburned A. cupressoides stands, and (iii) the loss of A. cupressoides populations is largely irreversible given the relatively high fuel loads of postfire vegetation communities that are dominated by resprouting shrubs. We suggest that the feedback between regeneration failure and increased flammability will be further exacerbated by a warmer and drier climate causing A. cupressoides to contract to the most fire‐proof landscape settings.