bluuebunny/crossref_metadata_2025_split huggingface dataset:
Time‐dependent risk and predictors of venous thromboembolism in breast cancer patients: A population‐based cohort study
Authors: Brand Judith S. , Hedayati Elham , Bhoo‐Pathy Nirmala , Bergh Jonas , Hall Per , Humphreys Keith , Ludvigsson Jonas F. , Czene Kamila 
Published: October 2016

BACKGROUNDVenous thromboembolism (VTE) is a serious complication of cancer and its treatment. The current study assessed the risk and clinical predictors of VTE in breast cancer patients by time since diagnosis.METHODSThis Swedish population–based study included 8338 breast cancer patients diagnosed from 2001 to 2008 in the Stockholm‐Gotland region with complete follow‐up until 2012. Their incidence of VTE was compared with the incidence among 39,013 age‐matched reference individuals from the general population. Cox and flexible parametric models were used to examine associations with patient, tumor, and treatment characteristics, accounting for time‐dependent effects.RESULTSOver a median follow‐up of 7.2 years, 426 breast cancer patients experienced a VTE event (cumulative incidence, 5.1%). The VTE incidence was 3‐fold increased (hazard ratio [HR], 3.28; 95% confidence interval [CI], 2.87‐3.74) in comparison with the incidence in the general population and was highest 6 months after diagnosis (HR, 8.62; 95% CI, 6.56‐11.33) with a sustained increase in risk thereafter (HR at 5 years, 2.19; 95% CI, 1.80‐2.67). Independent predictors of VTE included the following: older age, being overweight, preexisting VTE, comorbid disease, tumor size > 40 mm, progesterone receptor (PR)–negative status, more than 4 affected lymph nodes, and receipt of chemo‐ and endocrine therapy. The impact of chemotherapy was limited to early‐onset VTE, whereas comorbid disease and PR‐negative status were more strongly associated with late‐onset events.CONCLUSIONSThis study confirms the long‐term risk of VTE in breast cancer patients and identifies a comprehensive set of clinical risk predictors. Temporal associations with patient, tumor, and treatment characteristics provide insight into the time‐dependent etiology of VTE. Cancer 2017;123:468–475. © 2016 American Cancer Society.
Difficult relationships between parents and physicians of children with cancer: A qualitative study of parent and physician perspectives
Authors: Mack Jennifer W. , Ilowite Maya , Taddei Sarah 
Published: October 2016

BACKGROUNDPrevious work on difficult relationships between patients and physicians has largely focused on the adult primary care setting and has typically held patients responsible for challenges. Little is known about experiences in pediatrics and more serious illness; therefore, we examined difficult relationships between parents and physicians of children with cancer.METHODSThis was a cross‐sectional, semistructured interview study of parents and physicians of children with cancer at the Dana‐Farber Cancer Institute and Boston Children's Hospital (Boston, Mass) in longitudinal primary oncology relationships in which the parent, physician, or both considered the relationship difficult. Interviews were audiotaped, transcribed, and subjected to a content analysis.RESULTSDyadic parent and physician interviews were performed for 29 relationships. Twenty were experienced as difficult by both parents and physicians; 1 was experienced as difficult by the parent only; and 8 were experienced as difficult by the physician only. Parent experiences of difficult relationships were characterized by an impaired therapeutic alliance with physicians; physicians experienced difficult relationships as demanding. Core underlying issues included problems of connection and understanding (n = 8), confrontational parental advocacy (n = 16), mental health issues (n = 2), and structural challenges to care (n = 3). Although problems of connection and understanding often improved over time, problems of confrontational advocacy tended to solidify. Parents and physicians both experienced difficult relationships as highly distressing.CONCLUSIONSAlthough prior conceptions of difficult relationships have held patients responsible for challenges, this study has found that difficult relationships follow several patterns. Some challenges, such as problems of connection and understanding, offer an opportunity for healing. However, confrontational advocacy appears especially refractory to repair; special consideration of these relationships and avenues for repairing them are needed. Cancer 2017;123:675–681. © 2016 American Cancer Society.
Nicotinic acetylcholine receptors regulate vestibular afferent gain and activation timing
Authors: Morley Barbara J. , Lysakowski Anna , Vijayakumar Sarath , Menapace Deanna , Jones Timothy A. 
Published: October 2016

ABSTRACTLittle is known about the function of the cholinergic efferents innervating peripheral vestibular hair cells. We measured vestibular sensory evoked potentials (VsEPs) in α9 knockout (KO) mice, α10 KO mice, α7 KO mice, α9/10 and α7/9 double KO mice, and wild‐type (WT) controls. We also studied the morphology and ultrastructure of efferent terminals on vestibular hair cells in α9, α10, and α9/10 KOs. Both type I and type ll vestibular hair cells express the α9 and α10 subunits. The efferent boutons on vestibular cells in α9, α10, and α9/10 KOs appeared normal, but a quantitative analysis was not performed. Mean VsEP thresholds were significantly elevated in α9 and α9/10 KO animals. Some α9 and α9/10 KO animals, however, had normal or near‐normal thresholds, whereas others were greatly affected. Despite individual variability in threshold responses, latencies were consistently shortened. The double α7/9 KO resulted in decreased variance by normalizing waveforms and latencies. The phenotypes of the α7 and α10 single KOs were identical. Both α7 and α10 KO mice evidenced normal thresholds, decreased activation latencies, and larger amplitudes compared with WT mice. The data suggest a complex interaction of nicotinic acetylcholine receptors (nAChRs) in regulating vestibular afferent gain and activation timing. Although the α9/10 heteromeric nAChR is an important component of vestibular efferent activity, other peripheral or central nAChRs involving the α7 subunit or α10 subunit and α9 homomeric receptors are also important. J. Comp. Neurol. 525:1216–1233, 2017. © 2016 Wiley Periodicals, Inc.
Molecular heterogeneity of aggrecan‐based perineuronal nets around five subclasses of parvalbumin‐expressing neurons in the mouse hippocampus
Authors: Yamada Jun , Jinno Shozo 
Published: October 2016

ABSTRACTSubsets of GABAergic neurons are surrounded by perineuronal nets (PNNs), which play a critical role in the regulation of neural plasticity and neuroprotection. Although the plant lectin Wisteria floribunda agglutinin (WFA) has been commonly used to label PNNs, WFA only detects N‐acetyl‐d‐galactosamine on aggrecan, a member of the lectican family. In this study, we used WFA and the antibody against the core protein of aggrecan (ACAN) to investigate the molecular heterogeneity of aggrecan‐based PNNs around five subclasses of parvalbumin‐expressing (PV+) γ‐aminobutyric acid (GABA)ergic neurons in the CA1 and CA3 regions of the mouse hippocampus. The vast majority of ACAN+ PNNs were colocalized with WFA in the stratum pyramidale, whereas a substantial population of ACAN+ PNNs lacked WFA labeling in the stratum oriens. We then defined the subclasses of PV+ neurons based on their cellular locations, molecular expression, and septal projection. Like the WFA+ PNNs, ACAN+ PNNs surrounded PV+ basket cells and bistratified cells but not axo‐axonic cells. Unlike the WFA+ PNNs, ACAN+ PNNs frequently surrounded PV+ oriens‐lacunosum moleculare cells and hippocampo‐septal cells. Interestingly, the relative densities of GABAergic synapses were higher around PV+ neurons with ACAN+ PNNs than around those without ACAN+ PNNs. Degradation of WFA+ PNNs by chondroitinase ABC did not affect the GABAergic synaptic densities around PV+ neurons. Our findings suggest that the molecular composition of aggrecan‐based PNNs around PV+ neurons may differ in a subclass‐specific manner, and also might help determine the functional involvement of PNNs in the regulation of GABAergic synapses around PV+ neurons in the hippocampus. J. Comp. Neurol. 525:1234–1249, 2017. © 2016 Wiley Periodicals, Inc.
Whole Blood Analysis of Leukocyte‐Platelet Aggregates
Authors: Gerrits Anja J. , Frelinger Andrew L. , Michelson Alan D. 
Published: October 2016

AbstractIn inflammatory and thrombotic syndromes, platelets aggregate with circulating leukocytes, especially monocytes and neutrophils. This leukocyte‐platelet aggregate formation is initiated primarily through platelet surface expression of P‐selectin (CD62P), following activation‐dependent degranulation of α‐granules, binding to its constitutively expressed counter‐receptor, P‐selectin glycoprotein ligand 1 (PSGL‐1), on leukocytes. Monocyte‐platelet aggregates are a more sensitive marker of platelet activation than platelet surface P‐selectin. Detection of leukocyte‐platelet aggregates is relatively simple by whole‐blood flow cytometry. Light scatter and at least one leukocyte‐specific antibody are used to gate the desired population, and the presence of associated platelets is detected by immunostaining for abundant platelet‐specific markers. © 2016 by John Wiley & Sons, Inc.
Flow Analysis and Sorting of Plant Chromosomes
Authors: Vrána Jan , Cápal Petr , Šimková Hana , Karafiátová Miroslava , Čížková Jana , Doležel Jaroslav 
Published: October 2016

AbstractAnalysis and sorting of plant chromosomes (plant flow cytogenetics) is a special application of flow cytometry in plant genomics and its success depends critically on sample quality. This unit describes the methodology in a stepwise manner, starting with the induction of cell cycle synchrony and accumulation of dividing cells in mitotic metaphase, and continues with the preparation of suspensions of intact mitotic chromosomes, flow analysis and sorting of chromosomes, and finally processing of the sorted chromosomes. Each step of the protocol is described in detail as some procedures have not been used widely. Supporting histograms are presented as well as hints on dealing with plant material; the utility of sorted chromosomes for plant genomics is also discussed. © 2016 by John Wiley & Sons, Inc.
Coalition structure generation problems: optimization and parallelization of the IDP algorithm in multicore systems
Authors: Cruz Francisco , Espinosa Antonio , Moure Juan C. , Cerquides Jesus , Rodriguez‐Aguilar Juan A. , Svensson Kim , Ramchurn Sarvapali D. 
Published: October 2016

SummaryThe coalition structure generation problem is well known in the area of multi‐agent systems. Its goal is to establish coalitions between agents while maximizing the global welfare. Among the existing different algorithms designed to solve the coalition structure generation problem, DP and IDP are the ones with smaller temporal complexity. After analyzing the operation of the dynamic programming and improved dynamic programming algorithms, we have identified which are the most frequent operations and propose an optimized method. In addition, we study and implement a method for dividing the work into different threads. To describe incremental improvements of the algorithm design, we first compare performance of an improved single central processing unit core version where we obtain speedups ranging from 7 × to 11 × . Then, we describe the best resource use in a multi‐thread optimized version where we obtain an additional 7.5 × speedup running in a 12‐core machine.
Acylglycine Analysis by Ultra‐Performance Liquid Chromatography‐Tandem Mass Spectrometry (UPLC‐MS/MS)
Authors: Hobert Judith A. , Liu Aiping , Pasquali Marzia 
Published: October 2016

AbstractQuantitative analysis of urine acylglycines has shown to be a highly sensitive and specific method with proven clinical utility for the diagnosis of several inherited metabolic disorders including: medium chain acyl‐CoA dehydrogenase deficiency, multiple acyl‐CoA dehydrogenase deficiency, short chain acyl‐CoA dehydrogenase deficiency, 3‐methylcrotonyl‐CoA carboxylase deficiency, 2‐methylbutyryl‐CoA dehydrogenase deficiency, isovaleric acidemia, propionic academia, and isobutyryl‐CoA dehydrogenase deficiency. Here, a method that is currently performed using ultra‐performance liquid chromatography/tandem mass spectrometry (UPLC‐MS/MS) is described. © 2016 by John Wiley & Sons, Inc.
Direct Electron Transfer of Cellobiose Dehydrogenase on Positively Charged Polyethyleneimine Gold Nanoparticles
Authors: Tavahodi Mojtaba , Ortiz Roberto , Schulz Christopher , Ekhtiari Ali , Ludwig Roland , Haghighi Behzad , Gorton Lo 
Published: October 2016

AbstractEfficient conjugation between biomolecules and electrode materials is one of the main challenges in the field of biosensors. Cellobiose dehydrogenase (CDH) is a monomeric enzyme, which consists of two separate domains: one catalytic dehydrogenase domain (DHCDH) carrying strongly bound flavin adenine dinucleotide (FAD) in the active site and a cytochrome domain (CYTCDH) carrying a b‐type heme connected by a flexible linker region. Herein, we report on the development of a lactose biosensor, based on direct electron transfer (DET) from CDH from Phanerochaete sordida (PsCDH) electrostatically attached onto polyethyleneimine‐stabilized gold nanoparticles (PEI@AuNPs) used to cover a conventional polycrystalline solid gold disk electrode. PEI@AuNPs were synthesized in aqueous solution using PEI as reducing agent for AuIII and as stabilizer for the nanoparticles. The heterogeneous electron‐transfer (ET) rate (ks) for the redox reaction of immobilized PsCDH at the modified electrodes was calculated based on the Laviron theory and was found to be (39.6±2.5) s−1. The proposed lactose biosensor exhibits good long term stability as well as high and reproducible sensitivity to lactose with a response time less than 5 s and a linear range from 1 to 100 μm.
Synthesis of Cross‐linked Ionic Poly(styrenes) and their Application as Catalysts for the Synthesis of Carbonates from CO2 and Epoxides
Authors: Bobbink Felix D. , Van Muyden Antoine P. , Gopakumar Aswin , Fei Zhaofu , Dyson Paul J. 
Published: October 2016

AbstractA series of dicationic styrene‐functionalized imidazolium‐based salts, in which the two imidazolium rings are bridged by a functionalized spacer, are prepared. The salts are polymerized to afford cross‐linked imidazolium‐based ionic polystyrene materials, which, owing to the presence of the functionalized spaces, should be highly active organocatalysts for the cycloaddition of CO2 to epoxides to afford cyclic carbonates (CCE reaction). The catalytic activities of the polymers are evaluated in the CCE reaction. The most active catalyst incorporates a diol functionality and is active at 80 °C and a pressure of 4 bar at a loading of 5 mol %, which is comparable to the most active organocatalysts. Moreover, high yields can be obtained under atmospheric pressure upon increasing the temperature to 120 °C. Under harsher conditions, the catalyst is highly active at a loading one order of magnitude lower, highlighting the importance of benchmark conditions for the CCE reaction. Moreover, the polymer catalysts are advantageous because they can be used at low catalyst loadings, the carbonate product is easily isolated in pure form, and loss of activity of the recovered polymer catalyst is not observed during reuse.
Protein Interaction Profile Sequencing (PIP‐seq)
Authors: Foley Shawn W. , Gregory Brian D. 
Published: October 2016

AbstractEvery eukaryotic RNA transcript undergoes extensive post‐transcriptional processing from the moment of transcription up through degradation. This regulation is performed by a distinct cohort of RNA‐binding proteins which recognize their target transcript by both its primary sequence and secondary structure. Here, we describe protein interaction profile sequencing (PIP‐seq), a technique that uses ribonuclease‐based footprinting followed by high‐throughput sequencing to globally assess both protein‐bound RNA sequences and RNA secondary structure. PIP‐seq utilizes single‐ and double‐stranded RNA‐specific nucleases in the absence of proteins to infer RNA secondary structure. These libraries are also compared to samples that undergo nuclease digestion in the presence of proteins in order to find enriched protein‐bound sequences. Combined, these four libraries provide a comprehensive, transcriptome‐wide view of RNA secondary structure and RNA protein interaction sites from a single experimental technique. © 2016 by John Wiley & Sons, Inc.
Isolation of Primary Fibroblast Culture from Wildlife: the Panthera onca Case to Preserve a South American Endangered Species
Authors: Mestre‐Citrinovitz Ana Cecilia , Sestelo Adrián Jorge , Ceballos María Belén , Barañao José Lino , Saragüeta Patricia 
Published: October 2016

AbstractCell line establishment of somatic cells is a valuable resource to preserve genetic material of rare, difficult‐to‐find, endangered and giant species like Jaguar (Panthera onca), the largest South American felid. This unit focuses on the isolation and culture of fibroblasts from Jaguar skin and muscle biopsies, and ear cartilage dissection immediately after death to preserve one of the several endangered species in this biome. These culture techniques enabled us to contribute 570 samples from 45 autochthonous and endangered species, including Jaguar. The fibroblasts obtained are a part of the Genetic Bank of Buenos Aires Zoo with the 6700 samples, including tissues such as muscle, ovarian, testicular, blood, fibroblast cultures, sperm, hair, and fluids and cells from 450 individuals of 87 different species. © 2016 by John Wiley & Sons, Inc.
GILA, a Replacement for the Soft‐Agar Assay that Permits High‐Throughput Drug and Genetic Screens for Cellular Transformation
Authors: Izar Benjamin , Rotem Asaf 
Published: October 2016

AbstractFor the last five decades, measuring the ability of cells to grow in soft agar has served as the gold standard assay for in vitro cellular transformation. Nevertheless, the soft agar colony formation assay is time consuming and ill‐suited for high‐throughput screens. This unit describes an equally qualitative and quantitative assay known as growth in low attachment or GILA. The GILA assay is suitable for high‐throughput pharmacological or genetic screens and allows the simultaneous examination of multiple cell lines and experimental perturbations. GILA conditions are specific and relevant to the transformed state because they depend on a property of cancer cells that is not shared by non‐transformed cells. The GILA assay enables ex vivo drug sensitivity testing of patient‐derived tumor cells to define precise treatments for individual patients. © 2016 by John Wiley & Sons, Inc.
Elevated IL‐17A and IL‐22 regulate expression of inducible CD38 and Zap‐70 in chronic lymphocytic leukemia
Authors: Kouzegaran Samaneh , Siroosbakht Soheila , Farsad Bahram Fariborz , Rezakhaniha Bijan , Dormanesh Banafshe , Behnod Vahid , Tanha Amir Saber 
Published: October 2016

BackgroundIn this study, we investigated the role and expression of interleukin (IL)−17A and IL‐22 in chronic lymphocytic leukemia.MethodsWe evaluated the expression of markers above on CLL by ELISA, qRT‐PCR, flow cytometric analysis and nonparametric Kruskal–Wallis test.ResultsQuantitative RT‐PCR revealed that the mRNA levels of IL‐17A and IL‐22 in PBMCs of CLL patients were upregulated compared with those from healthy subjects (mean ± SD: 1.96 ± 0.232 vs.0.72 ± 0.15,P < 0.001 and mean ± SD: 2.45 ± 0.534 vs.0.81 ± 0.26,P < 0.001, respectivily). In addition, findings showed that the IL‐17A and IL‐22 plasma level was significantly elevated than that from healthy control group (P < 0.001). The median IL‐17A and IL‐22 in CLL patients and healthy control group were 48.28 ± 17.2 pg mL−1; 20.01 ± 11.16 pg mL−1and 58.68 ± 23.4 pg mL−1;16.47 ± 10.31P < 0.001, respectively. The levels of IL‐17A and IL‐22 was not significantly associated with the different stages of disease (Rai stages; Kruskal–Wallis testP > 0.05).No significant relationship was found between expression of CD38 and higher median serum levels of IL‐17A in patients, but patients with negative expression of ZAP‐70 showed a significant association with higher median serum levels of IL‐17A compared with healthy subjects. (57.84 pg mL−1vs. 31.67 pg mL−1;P = 0.016).ConclusionIL‐22 is elevated and associated with CD38 and Zap‐70 expression in patients with CLL. No significant correlation was found between expression of CD38 and increased levels of IL‐17A, negative expression of ZAP‐70 showed a significant association with increased levels of IL‐17A. © 2016 International Clinical Cytometry Society
Generation of a NK1R‐CreER knockin mouse strain to study cells involved in Neurokinin 1 Receptor signaling
Authors: Huang Huizhen , Kuzirian Marissa S. , Cai Xiaoyun , Snyder Lindsey M. , Cohen Jonathan , Kaplan Daniel H. , Ross Sarah E. 
Published: October 2016

AbstractThe Neurokinin 1 Receptor (NK1R), which binds Substance P, is expressed in discrete populations of neurons throughout the nervous system, where it has numerous roles including the modulation of pain and affective behaviors. Here, we report the generation of a NK1R‐CreER knockin allele, in which CreERT2 replaces the coding sequence of the TACR1 gene (encoding NK1R) in order to gain genetic access to these cells. We find that the NK1R‐CreER allele mediates recombination in many regions of the nervous system that are important in pain and anxiety including the amygdala, hypothalamus, frontal cortex, raphe nucleus, and dorsal horn of the spinal cord. Other cell types that are labeled by this allele include amacrine cells in the retina and fibroblasts in the skin. Thus, the NK1R‐CreER mouse line is a valuable new tool for conditional gene manipulation enabling the visualization and manipulation of cells that express NK1R.
Inducible gene modification in the gastric epithelium of Tff1‐CreERT2, Tff2‐rtTA, Tff3‐luc mice
Authors: Thiem Stefan , Eissmann Moritz F. , Stuart Emma , Elzer Joachim , Jonas Anna , Buchert Michael , Ernst Matthias 
Published: October 2016

AbstractTemporal and spatial regulation of genes mediated by tissue‐specific promoters and conditional gene expression systems provide a powerful tool to study gene function in health, disease, and during development. Although transgenic mice expressing the Cre recombinase in the gastric epithelium have been reported, there is a lack of models that allow inducible and reversible gene modification in the stomach. Here, we exploited the gastrointestinal epithelium‐specific expression pattern of the three trefoil factor (Tff) genes and bacterial artificial chromosome transgenesis to generate a novel mouse strain that expresses the CreERT2 recombinase and the reverse tetracycline transactivator (rtTA). The Tg(Tff1‐CreERT2;Tff2‐rtTA;Tff3‐Luc) strain confers tamoxifen‐inducible irreversible somatic recombination and allows simultaneous doxycycline‐dependent reversible gene activation in the gastric epithelium of developing and adult mice. This strain also confers luciferase activity to the intestinal epithelium to enable in vivo bioluminescence imaging. Using fluorescent reporters as conditional alleles, we show Tff1‐CreERT2 and Tff2‐rtTA transgene activity in a partially overlapping subset of long‐term regenerating gastric stem/progenitor cells. Therefore, the Tg(Tff1‐CreERT2;Tff2‐rtTA;Tff3‐Luc) strain can confer intermittent transgene expression to gastric epithelial cells that have undergone previous gene modification, and may be suitable to genetically model therapeutic intervention during development, tumorigenesis, and other genetically tractable diseases. Birth Defects Research (Part A) 106:626–635, 2016. © 2016 Wiley Periodicals, Inc.