bluuebunny/crossref_metadata_2025_split huggingface dataset:
SMN1 and SMN2 copy numbers in cell lines derived from patients with spinal muscular atrophy as measured by array digital PCR
Authors: Stabley Deborah L. , Harris Ashlee W. , Holbrook Jennifer , Chubbs Nicholas J. , Lozo Kevin W. , Crawford Thomas O. , Swoboda Kathryn J. , Funanage Vicky L. , Wang Wenlan , Mackenzie William , Scavina Mena , Sol‐Church Katia , Butchbach Matthew E. R. 
Published: March 2015

AbstractProximal spinal muscular atrophy (SMA) is an early‐onset motor neuron disease characterized by loss of α‐motor neurons and associated muscle atrophy. SMA is caused by deletion or other disabling mutation of survival motor neuron 1 (SMN1). In the human genome, a large duplication of the SMN‐containing region gives rise to a second copy of this gene (SMN2) that is distinguishable by a single nucleotide change in exon 7. Within the SMA population, there is substantial variation in SMN2 copy number; in general, those individuals with SMA who have a high SMN2 copy number have a milder disease. Because SMN2 functions as a disease modifier, its accurate copy number determination may have clinical relevance. In this study, we describe the development of an assay to assess SMN1 and SMN2 copy numbers in DNA samples using an array‐based digital PCR (dPCR) system. This dPCR assay can accurately and reliably measure the number of SMN1 and SMN2 copies in DNA samples. In a cohort of SMA patient‐derived cell lines, the assay confirmed a strong inverse correlation between SMN2 copy number and disease severity. Array dPCR is a practical technique to determine, accurately and reliably, SMN1 and SMN2 copy numbers from SMA samples.
Reducing sensitivity losses due to respiration and motion in accelerated echo planar imaging by reordering the autocalibration data acquisition
Authors: Polimeni Jonathan R. , Bhat Himanshu , Witzel Thomas , Benner Thomas , Feiweier Thorsten , Inati Souheil J. , Renvall Ville , Heberlein Keith , Wald Lawrence L. 
Published: March 2015

PurposeTo reduce the sensitivity of echo‐planar imaging (EPI) auto‐calibration signal (ACS) data to patient respiration and motion to improve the image quality and temporal signal‐to‐noise ratio (tSNR) of accelerated EPI time‐series data.MethodsACS data for accelerated EPI are generally acquired using segmented, multishot EPI to distortion‐match the ACS and time‐series data. The ACS data are, therefore, typically collected over multiple TR periods, leading to increased vulnerability to motion and dynamic B0 changes. The fast low‐angle excitation echo‐planar technique (FLEET) is adopted to reorder the ACS segments so that segments within any given slice are acquired consecutively in time, thereby acquiring ACS data for each slice as rapidly as possible.ResultsSubject breathhold and motion phantom experiments demonstrate that artifacts in the ACS data reduce tSNR and produce tSNR discontinuities across slices in the accelerated EPI time‐series data. Accelerated EPI data reconstructed using FLEET‐ACS exhibit improved tSNR and increased tSNR continuity across slices. Additionally, image quality is improved dramatically when bulk motion occurs during the ACS acquisition.ConclusionFLEET‐ACS provides reduced respiration and motion sensitivity in accelerated EPI, which yields higher tSNR and image quality. Benefits are demonstrated in both conventional‐resolution 3T and high‐resolution 7T EPI time‐series data. Magn Reson Med 75:665–679, 2016. © 2015 Wiley Periodicals, Inc.
Autoimmune spontaneous chronic urticaria and generalized myasthenia gravis in a patient with polyglandular autoimmune syndrome type 3
Authors: De Marchi Sergio Umberto , Cecchin Emanuela , De Marchi Sergio 
Published: March 2015

ABSTRACTIntroduction: Autoimmune polyglandular syndromes (APS) are a group of disorders characterized by the presence of autoimmune processes in several endocrine and non‐endocrine organs that are classified into 4 types. Methods: We describe the case of a woman affected with APS type 3 who presented initially with Hashimoto thyroiditis and pernicious anemia and subsequently developed autoimmune chronic urticaria, myasthenia gravis, and type 1 diabetes mellitus. Results: This patient had a combination of components of APS types 3b, 3a, and 3c. She was referred for evaluation of chronic spontaneous urticaria and subsequently developed severe generalized myasthenia gravis, which was apparently unmasked by antihistamines used to control urticaria. Conclusions: Patients with APS should have a more thorough evaluation to better clarify their autoimmune background. Early detection of autoantibodies and latent organ‐specific dysfunction may help physicians take appropriate action to prevent full‐blown disease. Muscle Nerve 52:440–444, 2015
Three dimensional numerical simulation of residential building on shrink–swell soils in response to climatic conditions
Authors: Zhang Xiong , Briaud Jean‐Louis 
Published: March 2015

SummaryShrink–swell soils can cause distresses in buildings, and every year, the economic loss associated with this problem is huge. This paper presents a comprehensive system for simulating the soil–foundation–building system and its response to daily weather conditions. Weather data include rainfall, solar radiation, air temperature, relative humidity, and wind speed, all of which are readily available from a local weather station or the Internet. These data are used to determine simulation flux boundary conditions. Different methods are proposed to simulate different boundary conditions: bare soil, trees, and vegetation. A coupled hydro‐mechanical stress analysis is used to simulate the volume change of shrink–swell soils due to both mechanical stress and water content variations. Coupled hydro‐mechanical stress‐jointed elements are used to simulate the interaction between the soil and the slab, and general shell elements are used to simulate structural behavior. All the models are combined into one finite element program to predict the entire system's behavior. This paper first described the theory for the simulations. A site in Arlington, Texas, is then selected to demonstrate the application of the proposed system. Simulation results are shown, and a comparison between measured and predicted movements for four footings in Arlington, Texas, over a 2‐year period is presented. Finally, a three‐dimensional simulation is made for a virtual residential building on shrink–swell soils to identify the influence of various factors. Copyright © 2015 John Wiley & Sons, Ltd.
Fighting to the Death: Weapon Injuries in a Mass Grave (16th–17th Century) from Bucharest, Romania
Authors: Constantinescu M. , Gavrilă E. , Greer S. , Soficaru A. , Ungureanu D. 
Published: March 2015

AbstractArchaeological excavations carried out in 1972 and 2010–2011 in the University Square, Bucharest, Romania, brought to light 688 graves belonging to the Saint Sava Church Cemetery, dating between the middle of the 16th century and middle of the 19th century. At 35 metres from the western boundary of the cemetery, a mass grave containing three adult male skeletons was unearthed. The unusual position of the skeletons and the high incidence of traumatic injuries on the bones posed several questions concerning the historical and archaeological context of this grave. Osteological analysis of the skeletons revealed that all three individuals exhibited a series of occupational stress markers, indicating similar activities and associated with moderate physical activity during life. A total number of 24 perimortem lesions (caused mainly by sabres but also by blunt objects and projectiles) were recorded on the skeletal remains. The high percentage of cranial injuries may indicate that the head was the main target, demonstrating the intention to incapacitate the victims quickly and being different from those connected to executions in the period. Eight of these lesions were produced by sharp objects similar to sabres used by professional soldiers during the 16th–17th century in southeastern Europe.The osteological profile of the individuals and the injuries they sustained suggest that the victims had a military background and were probably killed at the end of the 16th century during a violent dispute. Copyright © 2015 John Wiley & Sons, Ltd.
The Retromolar Space: A Morphological Curiosity Observed Amongst the Protohistoric Arikara and Mandan
Authors: De la Cova C. 
Published: March 2015

AbstractThe retromolar space (RMS), defined in palaeoanthropology as a space posterior to the third molar, between the distal edge of the tooth and the anterior margin of the ascending ramus when the mandible is held in lateral view, has been described as an autapomorphic trait unique to Neanderthals despite its presence in anatomically modern humans. This study examined RMS prevalence in a sample of protohistoric Arikara and Mandan Amerindians to determine what craniofacial morphology is correlated with the RMS. It was hypothesised that the feature would be present in the Amerindians studied and associated with a long cranial length, a large nasal height, midfacial prognathism, a broad mandible, and dental wear. The results indicated that RMSs were present in the Arikara and Mandan and significantly correlated with cranial length, cranial breadth, nasal height, bizygomatic breadth, basion‐nasion length, basion‐nasiospinale, mandible length, gonial angle, bigonial breadth, and dental wear. Thus, RMSs are associated with a dolichocephalic skull, wide cranial and facial breadth, a prognathic face, large nose and a corresponding wide and long mandible with a reduced gonial angle. This suggests that the RMS is the result of these features merging together in the craniofacial complex and should not be considered a Neanderthal autapomorphy. Copyright © 2015 John Wiley & Sons, Ltd.
A Note on the Demographic and Health Pattern of a Historical Sleeping Sickness Cemetery at Letsholathebe Memorial Hospital, Maun, Botswana
Authors: Mosothwane M. N. 
Published: March 2015

AbstractA part of a historical cemetery used to bury victims of sleeping sickness in Maun, Botswana, was recently uncovered by a water supply improvement construction project. The cemetery had become obliterated from the surface and from the memories of the people resulting in the use of the land for residential purposes. Twelve skeletons were excavated along the water supply trench and have since been buried at one of the new village cemeteries. There were eight males, two females and two individuals of unknown sex. They were young adults ranging in age from 18 to 35 years at the time of death. Dental modifications were used to estimate the cultural identities of two individuals. Some of the remains had been buried with body clothing such as belts and necklaces. Poor dental health was most probably associated with poor nutrition and poor oral hygiene among the population. Copyright © 2015 John Wiley & Sons, Ltd.
Tetra‐ versus Pentavalent Inhibitors of Cholera Toxin
Authors: Fu Ou , Pukin Aliaksei V. , van Ufford H. C. Quarles , Branson Thomas R. , Thies‐Weesie Dominique M. E. , Turnbull W. Bruce , Visser Gerben M. , Pieters Roland J. 
Published: March 2015

AbstractThe five B‐subunits (CTB5) of the Vibrio cholerae (cholera) toxin can bind to the intestinal cell surface so the entire AB5 toxin can enter the cell. Simultaneous binding can occur on more than one of the monosialotetrahexosylganglioside (GM1) units present on the cell surface. Such simultaneous binding arising from the toxins multivalency is believed to enhance its affinity. Thus, blocking the initial attachment of the toxin to the cell surface using inhibitors with GM1 subunits has the potential to stop the disease. Previously we showed that tetravalent GM1 molecules were sub‐nanomolar inhibitors of CTB5. In this study, we synthesized a pentavalent version and compared the binding and potency of penta‐ and tetravalent cholera toxin inhibitors, based on the same scaffold, for the first time. The pentavalent geometry did not yield major benefits over the tetravalent species, but it was still a strong inhibitor, and no major steric clashes occurred when binding the toxin. Thus, systems which can adopt more geometries, such as those described here, can be equally potent, and this may possibly be due to their ability to form higher‐order structures or simply due to more statistical options for binding.
Efficient molecular subtype classification of high‐grade serous ovarian cancer
Authors: Leong Huei San , Galletta Laura , Etemadmoghadam Dariush , George Joshy ,   The Australian Ovarian Cancer Study, Köbel Martin , Ramus Susan J , Bowtell David 
Published: March 2015

AbstractHigh‐grade serous carcinomas (HGSCs) account for approximately 70% of all epithelial ovarian cancers diagnosed. Using microarray gene expression profiling, we previously identified four molecular subtypes of HGSC: C1 (mesenchymal), C2 (immunoreactive), C4 (differentiated), and C5 (proliferative), which correlate with patient survival and have distinct biological features. Here, we describe molecular classification of HGSC based on a limited number of genes to allow cost‐effective and high‐throughput subtype analysis. We determined a minimal signature for accurate classification, including 39 differentially expressed and nine control genes from microarray experiments. Taqman‐based (low‐density arrays and Fluidigm), fluorescent oligonucleotides (Nanostring), and targeted RNA sequencing (Illumina) assays were then compared for their ability to correctly classify fresh and formalin‐fixed, paraffin‐embedded samples. All platforms achieved > 90% classification accuracy with RNA from fresh frozen samples. The Illumina and Nanostring assays were superior with fixed material. We found that the C1, C2, and C4 molecular subtypes were largely consistent across multiple surgical deposits from individual chemo‐naive patients. In contrast, we observed substantial subtype heterogeneity in patients whose primary ovarian sample was classified as C5. The development of an efficient molecular classifier of HGSC should enable further biological characterization of molecular subtypes and the development of targeted clinical trials. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Gremlin regulates renal inflammation via the vascular endothelial growth factor receptor 2 pathway
Authors: Lavoz Carolina , Alique Matilde , Rodrigues‐Diez Raquel , Pato Janos , Keri Gyorgy , Mezzano Sergio , Egido Jesús , Ruiz‐Ortega Marta 
Published: March 2015

AbstractInflammation is a main feature of progressive kidney disease. Gremlin binds to bone morphogenetic proteins (BMPs), acting as an antagonist and regulating nephrogenesis and fibrosis among other processes. Gremlin also binds to vascular endothelial growth factor receptor‐2 (VEGFR2) in endothelial cells to induce angiogenesis. In renal cells, gremlin regulates proliferation and fibrosis, but there are no data about inflammatory‐related events. We have investigated the direct effects of gremlin in the kidney, evaluating whether VEGFR2 is a functional gremlin receptor. Administration of recombinant gremlin to murine kidneys induced rapid and sustained activation of VEGFR2 signalling, located in proximal tubular epithelial cells. Gremlin bound to VEGFR2 in these cells in vitro, activating this signalling pathway independently of its action as an antagonist of BMPs. In vivo, gremlin caused early renal damage, characterized by activation of the nuclear factor (NF)‐κB pathway linked to up‐regulation of pro‐inflammatory factors and infiltration of immune inflammatory cells. VEGFR2 blockade diminished gremlin‐induced renal inflammatory responses. The link between gremlin/VEGFR2 and NF‐κB/inflammation was confirmed in vitro. Gremlin overexpression was associated with VEGFR2 activation in human renal disease and in the unilateral ureteral obstruction experimental model, where VEGFR2 kinase inhibition diminished renal inflammation. Our data show that a gremlin/VEGFR2 axis participates in renal inflammation and could be a novel target for kidney disease. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Cerebrospinal fluid proteomics in children during induction for acute lymphoblastic leukemia: A pilot study
Authors: Priola Ginna M. , Foster Matthew W. , Deal Allison M. , Richardson Brenna M. , Thompson J. Will , Blatt Julie 
Published: March 2015

AbstractBackgroundThrombosis in patients with acute lymphocytic leukemia (ALL) can develop after treatment with L‐asparaginase (asp) and is often localized to the central nervous system (CNS). We hypothesize that changes in the cerebrospinal fluid (CSF) proteome will occur after asp therapy and will anticipate CNS clots.MethodsFive newly diagnosed patients, ages 1–11 years, with ALL (n = 4) or lymphoblastic lymphoma (LL) (n = 1) underwent serial lumbar punctures during induction. CSF was depleted of abundant plasma proteins and analyzed by gel‐free, label‐free quantitative proteomics.ResultsMore than 600 proteins were quantified across all CSF samples. In four subjects, the expression of proteins involved in coagulation such as protein C Inhibitor (SERPINA5) and heparin cofactor II (SERPIND1) changed over the course of asp therapy. Antithrombin III (ATIII) and plasminogen (PLMN) levels were shown to have decreased expression over time in one child who developed a CNS thrombosis, compared to other subjects.ConclusionsCSF proteomics is feasible and reproducible in ALL and LL. CSF ATIII and PLMN should be further investigated as predictive markers of CNS thrombosis. Pediatr Blood Cancer 2015;62:1190–1194. © 2015 Wiley Periodicals, Inc.
13‐valent pneumococcal conjugate vaccine (PCV13) is immunogenic and safe in children 6‐17 years of age with sickle cell disease previously vaccinated with 23‐valent pneumococcal polysaccharide vaccine (PPSV23): Results of a phase 3 study
Authors: De Montalembert Mariane , Abboud Miguel R. , Fiquet Anne , Inati Adlette , Lebensburger Jeffrey D. , Kaddah Normeen , Mokhtar Galila , Piga Antonio , Halasa Natasha , Inusa Baba , Rees David C. , Heath Paul T. , Telfer Paul , Driscoll Catherine , Al Hajjar Sami , Tozzi Alberto , Jiang Qin , Emini Emilio A. , Gruber William C. , Gurtman Alejandra , Scott Daniel A. 
Published: March 2015

BackgroundA large population of older children with sickle cell disease (SCD) is currently vaccinated with only 23‐valent pneumococcal polysaccharide vaccine (PPSV23). In immunocompetent adults, PPSV23 vaccination reduces immune responses to subsequent vaccination with a pneumococcal vaccine. The 13‐valent pneumococcal conjugate vaccine (PCV13), which addresses this limitation, may offer an advantage to this population at high risk of pneumococcal disease. [This article was corrected after initial online publication with an erratum. The National Clinical Trial (NCT) number was omitted from the article abstract. That number is NCT00918580.]ProcedureChildren with SCD 6–17 years of age previously vaccinated with PPSV23 at least 6 months before study enrollment received two doses of PCV13 6 months apart. Anti‐pneumococcal polysaccharide immunoglobulin G (IgG) geometric mean concentrations (GMCs) and opsonophagocytic activity (OPA) geometric mean titers (GMTs) were measured before, 1 month after each administration, and 1 year after the second administration.ResultsFollowing each PCV13 administration, IgG GMCs and OPA GMTs significantly increased, and antibody levels after doses 1 and 2 were generally comparable. Antibody levels declined over the year following dose 2. At 1 year after the second administration, OPA GMTs for all and IgG GMCs for most serotypes remained above pre‐vaccination levels. Most adverse events were due to vaso‐occlusive crises, a characteristic of the underlying condition of SCD.ConclusionsChildren with SCD who were previously vaccinated with PPSV23 responded well to 1 PCV13 dose, and a second dose did not increase antibody response. PCV13 antibodies persisted above pre‐vaccination levels for all serotypes 1 year after dose 2. Children with SCD may benefit from at least one dose of PCV13. Pediatr Blood Cancer 2015;62:1427–1436. © 2015 Wiley Periodicals, Inc.
A strategy to improve treatment‐related mortality and abandonment of therapy for childhood ALL in a developing country reveals the impact of treatment delays
Authors: Suarez Amaranto , Piña Martha , Nichols‐Vinueza Diana X. , Lopera John , Rengifo Lyda , Mesa Mauricio , Cardenas Marcela , Morrissey Lisa , Veintemilla Galo , Vizcaino Martha , Del Toro Ligia , Vicuna Victor , Fernandez Jorge , Neuberg Donna , Stevenson Kristen , Gutierrez Alejandro 
Published: March 2015

BackgroundTreatment‐related mortality and abandonment of therapy are major barriers to successful treatment of childhood acute lymphoblastic leukemia (ALL) in the developing world.ProcedureA collaboration was undertaken between Instituto Nacional de Cancerologia (Bogota, Colombia), which serves a poor patient population in an upper‐middle income country, and Dana‐Farber/Boston Children's Cancer and Blood Disorders Center (Boston, USA). Several interventions aimed at reducing toxic deaths and abandonment were implemented, including a reduced‐intensity treatment regimen and a psychosocial effort targeting abandonment. We performed a cohort study to assess impact.ResultsThe Study Population comprised 99 children with ALL diagnosed between 2007 and 2010, and the Historic Cohort comprised 181 children treated prior to the study interventions (1995–2004). Significant improvements were achieved in the rate of deaths in complete remission (13% to 3%; P = 0.005), abandonment (32% to 9%; P < 0.001), and event‐free survival with abandonment considered an event (47% to 65% at 2 years; P = 0.016). However, relapse rate did not improve. Medically unnecessary treatment delays were common, and landmark analysis revealed that initiating the PIII phase of therapy ≥4 weeks delayed predicted markedly inferior disease‐free survival (P = 0.016). Conversely, patients who received therapy without excessive delays had outcomes approaching those achieved in high‐income countries.ConclusionsImplementation of a twinning program was followed by reductions in abandonment and toxic deaths, but relapse rate did not improve. Inappropriate treatment delays were common and strongly predicted treatment failure. These findings highlight the importance of adherence to treatment schedule for effective therapy of ALL. Pediatr Blood Cancer 2015;62:1395–1402. © 2015 Wiley Periodicals, Inc.