bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II Clinical Trial of Amatuximab, a Chimeric Antimesothelin Antibody with Pemetrexed and Cisplatin in Advanced Unresectable Pleural Mesothelioma
Authors: Hassan Raffit , Kindler Hedy L. , Jahan Thierry , Bazhenova Lyudmila , Reck Martin , Thomas Anish , Pastan Ira , Parno Jeff , O'Shannessy Daniel J. , Fatato Penny , Maltzman Julia D. , Wallin Bruce A. 
Published: September 2014

Abstract
Purpose: Amatuximab is a chimeric monoclonal antibody to mesothelin, a cell surface glycoprotein highly expressed in malignant pleural mesothelioma (MPM). On the basis of its synergy with chemotherapy in preclinical studies, we evaluated the antitumor activity of amatuximab plus pemetrexed and cisplatin in patients with unresectable MPM.
Experimental Design: In a single-arm phase II study, amatuximab (5 mg/kg) was administered on days 1 and 8 with pemetrexed (500 mg/m2) and cisplatin (75 mg/m2) on day 1 of 21-day cycles for up to six cycles. Patients with response or stable disease received amatuximab maintenance until disease progression. Primary endpoint was progression-free survival (PFS) at 6 months. Secondary endpoints were overall survival (OS), response rate, and safety.
Results: Eighty-nine patients were enrolled at 26 centers. Median of five cycles (range, 1–6) of combination treatment was administered, and 56 (63%) patients received amatuximab maintenance. Combination therapy resulted in no overlapping toxicities. Eleven patients (12.4%) had amatuximab-related hypersensitivity reactions. Responses included partial responses in 33 (40%) and stable disease in 42 (51%). Six-month PFS rate was 51% [95% confidence interval (CI), 39.1–62.3)], median PFS was 6.1 months (95% CI, 5.8–6.4), and median OS was 14.8 months (95% CI, 12.4–18.5) with 29 patients alive at data cut-off.
Conclusions: Amatuximab with pemetrexed and cisplatin was well tolerated with objective tumor response or stable disease rate of 90% by independent radiologic review. Although PFS was not significantly different from historical controls, the median OS was 14.8 months with a third of patients alive and 5 continuing to receive amatuximab at the time of analysis. Clin Cancer Res; 20(23); 5927–36. ©2014 AACR.
Hypoxia Promotes Dissemination and Colonization in New Bone Marrow Niches in Waldenström Macroglobulinemia
Authors: Muz Barbara , de la Puente Pilar , Azab Feda , Ghobrial Irene M. , Azab Abdel Kareem 
Published: September 2014

Abstract
Waldenström macroglobulinemia, a rare and indolent type of non–Hodgkin lymphoma, is characterized by widespread lymphoplasmacytic B cells in the bone marrow. Previous studies have shown that hypoxic conditions play a key role in the dissemination of other hematologic malignancies. In this study, the effect of hypoxia was tested on the progression and spread of Waldenström macroglobulinemia. Interestingly, tumor progression correlated with hypoxia levels in Waldenström macroglobulinemia cells and other cells in the bone marrow and correlated with the number of circulating tumor cells in vivo. Mechanistic studies demonstrated that hypoxia decreased cell progression and cell cycle, did not induce apoptosis, and reduced the adhesion between Waldenström macroglobulinemia cells and bone marrow stroma, through downregulation of E-cadherin expression, thus explaining increased egress of Waldenström macroglobulinemia cells to the circulation. Moreover, hypoxia increased the extravasation and homing of Waldenström macroglobulinemia cells to new bone marrow niches in vivo, by increased CXCR4/SDF-1–mediated chemotaxis and maintaining the VLA4-mediated adhesion. Re-oxygenation of hypoxic Waldenström macroglobulinemia cells enhanced the rate of proliferation and cell cycle progression and restored intercellular adhesion between Waldenström macroglobulinemia cells and bone marrow stroma. This study suggests that targeting hypoxic response is a novel strategy to prevent dissemination of Waldenström macroglobulinemia.
Implications: This study provides a better understanding of the biology of dissemination of Waldenström macroglobulinemia and opens new windows for investigation of new therapeutic targets in Waldenström macroglobulinemia based on tumor hypoxia mechanisms. Mol Cancer Res; 13(2); 263–72. ©2014 AACR.
The ultrasonography features of hyalinizing trabecular tumor of the thyroid gland and the role of fine needle aspiration cytology and core needle biopsy in its diagnosis
Authors: Choi Woo Jung , Baek Jung Hwan , Ha Eun Ju , Choi Young Jun , Hong Min Ji , Song Dong Eun , Sung Jin Yong , Yoo Hyunju , Jung So Lyung , Lee Ha Young , Lee Jeong Hyun 
Published: September 2014

Background Hyalinizing trabecular tumor (HTT) of the thyroid gland is a rare, benign neoplasm of follicular cell origin. Misdiagnosis of HTT as either papillary or medullary thyroid carcinoma after fine-needle aspiration (FNA) may lead to unnecessary surgery. Purpose To evaluate the ultrasonography (US) findings of HTT of the thyroid gland and the role of FNA cytology and core needle biopsy (CNB) in its diagnosis. Material and Methods Data from 24 patients with a histopathological diagnosis of HTT between January 2000 and May 2013 were retrospectively analyzed. US findings were categorized according to shape, margin, orientation, echogenicity, composition, calcification, and vascularity. Cytologic and histologic results of FNA, CNB, and surgery were reviewed. Results US revealed the following tumor features: oval-to-round (24/24), solid (22/24), smooth margin (21/24), hypoechoic or marked hypoechogenicity (18/24), and peri- and/or intranodular vascularity (17/17). Malignant US features such as marked hypoechogenicity ( n = 7) and a spiculated margin ( n = 3) were also observed. Final confirmation was by surgery in 22 patients and by CNB in two patients. All 19 patients who underwent FNA were initially misdiagnosed, including 12 with malignancies and five with atypia of undetermined significance. All four patients who underwent CNB were correctly diagnosed with HTT. The histology of CNB specimens suggested HTT, which was confirmed by immunostaining of MIB-1. Conclusion HTT should be suspected when the cytological diagnosis of papillary thyroid carcinoma is made after FNA without malignant US findings. CNB could prevent unnecessary surgery for HTT.
Musculoskeletal and Activity-Related Factors Associated With Plantar Heel Pain
Authors: Sullivan Justin , Burns Joshua , Adams Roger , Pappas Evangelos , Crosbie Jack 
Published: September 2014

Background: Despite the prevalence and impact of plantar heel pain, its etiology remains poorly understood, and there is no consensus regarding optimum management. The identification of musculoskeletal factors related to the presence of plantar heel pain could lead to the development of better targeted intervention strategies and potentially improve clinical outcomes. The aim of this study was to investigate relationships between a number of musculoskeletal and activity-related measures and plantar heel pain. Methods: In total, 202 people with plantar heel pain and 70 asymptomatic control participants were compared on a variety of musculoskeletal and activity-related measures, including body mass index (BMI), foot and ankle muscle strength, calf endurance, ankle and first metatarsophalangeal (MTP) joint range of motion, foot alignment, occupational standing time, exercise level, and generalized hypermobility. Following a comparison of groups for parity of age, analyses of covariance were performed to detect differences between the 2 groups for any of the variables measured. Results: The plantar heel pain group displayed a higher BMI, reduced ankle dorsiflexion range of motion, reduced ankle evertor and toe flexor strength, and an altered inversion/eversion strength ratio. There were no differences between groups for foot alignment, dorsiflexor or invertor strength, ankle inversion or eversion range of motion, first MTP joint extension range of motion, generalized hypermobility, occupational standing time, or exercise level. Conclusion: Plantar heel pain is associated with higher BMI and reductions in some foot and ankle strength and flexibility measures. Although these factors could be either causal or consequential, they are all potentially modifiable and could be targeted in the management of plantar heel pain. Level of Evidence: Level III, comparative study.
Fractures of the Hallux in Children
Authors: Petnehazy Thomas , Schalamon Johannes , Hartwig Charlotte , Eberl Robert , Kraus Tanja , Till Holger , Singer Georg 
Published: September 2014

Background: Foot fractures account for 5% to 13% of pediatric fractures. Fractures of the hallux require special attention due to its role in weight bearing, balance, and pedal motion. In this study, a large series of children with hallux fractures is presented. Methods: All children treated with fractures of the hallux between June 2004 and December 2011 were included. The medical records were analyzed and X-rays were reviewed. The fractures were classified according to their anatomic location and the type of fracture. Three hundred seventeen patients (mean age = 11.7 years; range, 1-18 years; 65% male) sustained a fracture of the hallux. Results: Most accidents (28%) occurred at sports facilities, and soccer was the most common cause of a fracture of the hallux (28%). Closed injuries were diagnosed in 92% of the patients; 8% of the children presented with open fractures. In 144 children, the growth plate was affected. Fifty-nine patients presented with diaphyseal fractures, 42 patients with osseous avulsions, and 40 patients with fractures of the distal part of the phalanx. Nineteen children had incomplete and 13 patients comminuted fractures. The vast majority of the children (86%) were treated conservatively. Operative interventions were required in 14% of the patients. Good outcome was achieved in both conservatively and operatively treated patients. Conclusion: In children, fractures of the hallux were most often caused by ball sports and had a good prognosis. The vast majority of these fractures could be treated conservatively yielding good outcome. Level of Evidence: Level IV, case series.
Fine-mapping of HLA associations with chronic lymphocytic leukemia in US populations
Authors: Gragert Loren , Fingerson Stephanie , Albrecht Mark , Maiers Martin , Kalaycio Matt , Hill Brian T. 
Published: September 2014

Key PointsPolymorphisms in HLA genes may impact the ability of the immune system to detect malignant cells and direct T cells to eliminate them. Several HLA alleles and haplotypes are associated with development of chronic lymphocytic leukemia across different US populations.
Bone marrow failure and the telomeropathies
Authors: Townsley Danielle M. , Dumitriu Bogdan , Young Neal S. 
Published: September 2014

AbstractOur understanding of the pathophysiology of aplastic anemia is undergoing significant revision, with implications for diagnosis and treatment. Constitutional and acquired disease is poorly delineated, as lesions in some genetic pathways cause stereotypical childhood syndromes and also act as risk factors for clinical manifestations in adult life. Telomere diseases are a prominent example of this relationship. Accelerated telomere attrition is the result of mutations in telomere repair genes and genes encoding components of the shelterin complex and related proteins. Genotype-phenotype correlations show genes responsible for X-linked (DKC1) and severe recessive childhood dyskeratosis congenita, typically with associated mucocutaneous features, and others (TERC and TERT) for more subtle presentation as telomeropathy in adults, in which multiorgan failure may be prominent. Telomerase mutations also are etiologic in familial pulmonary fibrosis and cryptic liver disease. Detection of a telomere disease requires awareness in the clinic, appropriate laboratory testing of telomere content, and genetic sequencing. In treatment decisions, genetic screening of related donors for hematopoietic stem cell transplantation is critical, and androgen therapy may be helpful. Telomeres shorten normally with aging, as well as under environmental circumstances, with regenerative stress and oxidative damage. Telomere biology is complexly related to oncogenesis: telomere attrition is protective by enforcing senescence or apoptosis in cells with a long mitotic history, but telomere loss also can destabilize the genome by chromosome rearrangement and aneuploidy.
FOXO1 repression contributes to block of plasma cell differentiation in classical Hodgkin lymphoma
Authors: Vogel Marion J. , Xie Linka , Guan Hanfeng , Tooze Reuben M. , Maier Thomas , Kostezka Ulrike , Maier Harald J. , Holzmann Karlheinz , Chan Fong Chun , Steidl Christian , Reichel Jonathan B. , Weitzer Clarissa D. , Gehringer Franziska , Kick Anita B. , Cesarman Ethel , Roshal Mikhail , Gascoyne Randy D. , Möller Peter , Wirth Thomas , Ushmorov Alexey 
Published: September 2014

Key Points
FOXO1 directly activates PRDM1α, the master regulator of PC differentiation, and it enriches a PC signature in cHL cell lines. PRDM1α is a tumor suppressor in cHL.
De novo assembly of the common marmoset transcriptome from NextGen mRNA sequences
Authors: Maudhoo Mnirnal D , Ren Dongren , Gradnigo Julien S , Gibbs Robert M , Lubker Austin C , Moriyama Etsuko N , French Jeffrey A , Norgren Robert B 
Published: September 2014

Abstract

Background
Nonhuman primates are important for both biomedical studies and understanding human evolution. Although research in these areas has mostly focused on Old World primates, such as the rhesus macaque, the common marmoset (Callithrix jacchus), a New World primate, offers important advantages in comparison to other primates, such as an accelerated lifespan. To conduct Next Generation expression studies or to study primate evolution, a high quality annotation of the marmoset genome is required. The availability of marmoset transcriptome data from five tissues, including both raw sequences and assembled transcripts, will aid in the annotation of the newly released marmoset assembly.

Findings
RNA was extracted from five tissues: skeletal muscle, bladder and hippocampus from a male common marmoset, and cerebral cortex and cerebellum from a female common marmoset. All five RNA samples were sequenced on the Illumina HiSeq 2000 platform. Sequences were deposited in the NCBI Sequence Read Archive. Transcripts were assembled, annotated and deposited in the NCBI Transcriptome Shotgun Assembly database.

Conclusions
We have provided a high quality annotation of 51,163 transcripts with full-length coding sequence. This set represented a total of 10,833 unique genes. In addition to providing empirical support for the existence of these 10,833 genes, we also provide sequence information for 2,422 genes that were not previously identified in the Ensembl annotation of the marmoset genome.
Chile’s dilemma: how to reinsert scientists trained abroad
Authors: Nunez-Parra Alexia , Ramos Maria-Paz 
Published: September 2014

Chile is recognized worldwide as an emergent economy, with a great power in natural resource exploitation. Nonetheless, despite being one of the most developed countries in Latin America, Chile imports most of the knowledge and technology necessary to drive innovation in the country. The tight budget that the Chilean government assigned to research and development and the absence of a long-term scientific agenda contributed to a limited supply of scientists over the years. In an effort to reverse this scenario, Chile has created several fellowships, such as the Becas Chile Program (BCP) to encourage new generations to pursue graduate studies to ultimately advance research and development in situ. More than 6000 fellows are now being trained abroad, accumulating an incredible potential to transform the Chilean scientific environment as we know it. Chile now faces a greater challenge: it has to offer infrastructure and job openings to the highly skilled professionals in whom it invested. Unfortunately no clear public policies to address this situation have been developed, partially due to the lack of a dedicated institution, such as a Ministry for Science and Technology which could focalize the necessary efforts to promote such policies. Therefore, in the meantime, Chilean scientist have been motivated to create different organizations, such as, Mas Ciencia para Chile and Nexos Chile-USA, to promote constructive discussion of the policies that could be implemented to improve the Chilean scientific situation. We hope that these and other organizations have a real impact on the generation of scientific guidelines that will finally contribute to the development of the country.
Sustainability Considerations for Health Research and Analytic Data
Infrastructures
Authors: Wilcox Adam , Randhawa Gurvaneet , Embi Peter , Cao Hui , Kuperman Gil 
Published: September 2014

Introduction: The United States has made recent large investments in creating data
infrastructures to support the important goals of patient-centered outcomes research
(PCOR) and comparative effectiveness research (CER), with still more investment planned.
These initial investments, while critical to the creation of the infrastructures, are
not expected to sustain them much beyond the initial development. To provide the maximum
benefit, the infrastructures need to be sustained through innovative financing models
while providing value to PCOR and CER researchers.Sustainability Factors: Based on our
experience with creating flexible sustainability strategies (i.e., strategies that are
adaptive to the different characteristics and opportunities of a resource or
infrastructure), we define specific factors that are important considerations in
developing a sustainability strategy. These factors include assets, expansion,
complexity, and stakeholders. Each factor is described, with examples of how it is
applied. These factors are dimensions of variation in different resources, to which a
sustainability strategy should adapt.Summary Observations: We also identify specific
important considerations for maintaining an infrastructure, so that the long-term
intended benefits can be realized. These observations are presented as lessons learned,
to be applied to other sustainability efforts. We define the lessons learned, relating
them to the defined sustainability factors as interactions between factors.Conclusion
and Next Steps: Using perspectives and experiences from a diverse group of experts, we
define broad characteristics of sustainability strategies and important observations,
which can vary for different projects. Other descriptions of adaptive, flexible, and
successful models of collaboration between stakeholders and data infrastructures can
expand this framework by identifying other factors for sustainability, and give more
concrete directions on how sustainability can be best achieved.
Sulfide stress cracking of nickel-containing low-alloy steels
Authors: Kappes Mariano , Iannuzzi Mariano , Rebak Raúl B. , Carranza Ricardo M. 
Published: September 2014

AbstractLow-alloy steels (LAS) are extensively used in oil and gas (O&G) production due to their good mechanical properties and low cost. Even though nickel improves mechanical properties and hardenability with low penalty on weldability, which is critical for large subsea components, nickel content cannot exceed 1-wt% when used in sour service applications. The ISO 15156-2 standard limits the nickel content in LAS on the assumption that nickel concentrations above 1-wt% negatively impact sulfide stress cracking (SSC) resistance. This restriction excludes a significant number of high-strength and high-toughness alloys, such as Ni-Cr-Mo (e.g., UNS G43200 and G43400), Ni-Mo (e.g., UNS G46200), and Ni-Cr-Mo-V grades, from sour service applications and can be used only if successfully qualified. However, the standard is based on controversial research conducted more than 40 years ago. Since then, researchers have suggested that it is the microstructure that determines SSC resistance, regardless of Ni content. This review summarizes the advantages and disadvantages of nickel-containing LAS in terms of strength, weldability, hardenability, potential weight savings, and cost reduction. Likewise, the state of knowledge on the effect of nickel on hydrogen absorption as well as SSC initiation and propagation kinetics is critically reviewed.
On the Koszul map of Lie algebras
Authors: Cornulier Yves 
Published: September 2014

Abstract
We motivate and study the reduced Koszul map, relating the invariant bilinear maps on a Lie algebra and the third homology. We show that it is concentrated in degree 0 for any grading in a torsion-free abelian group, and in particular it vanishes whenever the Lie algebra admits a positive grading. We also provide an example of a 12-dimensional nilpotent Lie algebra whose reduced Koszul map does not vanish. In an appendix, we reinterpret the results of Neeb and Wagemann about the second homology of current Lie algebras, which are closely related to the reduced Koszul map.
Adult Plant Development in Triticale (× Triticosecale Wittmack) Is Controlled by Dynamic Genetic Patterns of Regulation
Authors: Würschum Tobias , Liu Wenxin , Alheit Katharina V , Tucker Matthew R , Gowda Manje , Weissmann Elmar A , Hahn Volker , Maurer Hans Peter 
Published: September 2014

Abstract
Many biologically and agronomically important traits are dynamic and show temporal variation. In this study, we used triticale (× Triticosecale Wittmack) as a model crop to assess the genetic dynamics underlying phenotypic plasticity of adult plant development. To this end, a large mapping population with 647 doubled haploid lines derived from four partially connected families from crosses among six parents was scored for developmental stage at three different time points. Using genome-wide association mapping, we identified main effect and epistatic quantitative trait loci (QTL) at all three time points. Interestingly, some of these QTL were identified at all time points, whereas others appear to only contribute to the genetic architecture at certain developmental stages. Our results illustrate the temporal contribution of QTL to the genetic control of adult plant development and more generally, the temporal genetic patterns of regulation that underlie dynamic traits.
Using Drosophila melanogaster To Identify Chemotherapy Toxicity Genes
Authors: King Elizabeth G , Kislukhin Galina , Walters Kelli N , Long Anthony D 
Published: September 2014

Abstract
The severity of the toxic side effects of chemotherapy shows a great deal of interindividual variability, and much of this variation is likely genetically based. Simple DNA tests predictive of toxic side effects could revolutionize the way chemotherapy is carried out. Due to the challenges in identifying polymorphisms that affect toxicity in humans, we use Drosophila fecundity following oral exposure to carboplatin, gemcitabine and mitomycin C as a model system to identify naturally occurring DNA variants predictive of toxicity. We use the Drosophila Synthetic Population Resource (DSPR), a panel of recombinant inbred lines derived from a multiparent advanced intercross, to map quantitative trait loci affecting chemotoxicity. We identify two QTL each for carboplatin and gemcitabine toxicity and none for mitomycin. One QTL is associated with fly orthologs of a priori human carboplatin candidate genes ABCC2 and MSH2, and a second QTL is associated with fly orthologs of human gemcitabine candidate genes RRM2 and RRM2B. The third, a carboplatin QTL, is associated with a posteriori human orthologs from solute carrier family 7A, INPP4A&B, and NALCN. The fourth, a gemcitabine QTL that also affects methotrexate toxicity, is associated with human ortholog GPx4. Mapped QTL each explain a significant fraction of variation in toxicity, yet individual SNPs and transposable elements in the candidate gene regions fail to singly explain QTL peaks. Furthermore, estimates of founder haplotype effects are consistent with genes harboring several segregating functional alleles. We find little evidence for nonsynonymous SNPs explaining mapped QTL; thus it seems likely that standing variation in toxicity is due to regulatory alleles.