bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and safety of dovitinib in pretreated patients with advanced squamous non‐small cell lung cancer with FGFR1 amplification: A single‐arm, phase 2 study
Authors: Lim Sung Hee , Sun Jong‐Mu , Choi Yoon‐La , Kim Hye Ryun , Ahn Soomin , Lee Ji Yun , Lee Se‐Hoon , Ahn Jin Seok , Park Keunchil , Kim Joo Hang , Cho Byoung Chul , Ahn Myung‐Ju
Published: June 2016

BACKGROUND

Fibroblast growth factor receptor 1 (FGFR1) amplification is a potential driving oncogene in squamous cell cancer (SCC) of the lung. The current phase 2 study evaluated the efficacy and tolerability of dovitinib, an FGFR inhibitor, in patients with advanced SCC of the lung.

METHODS

Patients with pretreated advanced SCC of the lung whose tumors demonstrated FGFR1 amplification of > 5 copies by fluorescence in situ hybridization were enrolled. Dovitinib at a dose of 500 mg was administered orally, once daily, on days 1 to 5 of every week, followed by 2 days off. The primary endpoint was overall response. Secondary endpoints were progression‐free survival, overall survival, and toxicity.

RESULTS

All 26 patients were men with a median age of 68 years (range, 52‐80 years). The majority of patients were ever‐smokers. The median duration of dovitinib administration (28 days per cycle) was 2.5 months (range, 0.7‐8.6 months). The overall response rate was 11.5% (95% confidence interval [95% CI], 0.8%‐23.8%) and the disease control rate was 50% (95% CI, 30.8%‐69.2%), with 3 patients achieving partial responses. Response durations for the patients with partial responses were ≥4.5 months, ≥ 5.1 months, and 6.1 months, respectively. After a median follow‐up of 15.7 months (range, 1.2‐25.6 months), the median overall survival was 5.0 months (95% CI, 3.6‐6.4 months) and the median progression‐free survival was 2.9 months (95% CI, 1.5‐4.3 months). The most common grade 3 or higher adverse events were fatigue (19.2%), anorexia (11.5%), and hyponatremia (11.5%) (event severity was graded based on National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]).

CONCLUSIONS

Treatment with dovitinib demonstrated modest efficacy in patients with advanced SCC with FGFR1 amplification. Further studies to evaluate other biomarkers correlated with the efficacy of dovitinib in patients with SCC are warranted. Cancer 2016;122:3024‐3031. © 2016 American Cancer Society.
Randomized phase 2 neoadjuvant trial evaluating anastrozole and fulvestrant efficacy for postmenopausal, estrogen receptor–positive, human epidermal growth factor receptor 2–negative breast cancer patients: Results of the UNICANCER CARMINA 02 French trial (UCBG 0609)
Authors: Lerebours Florence , Rivera Sofia , Mouret‐Reynier Marie‐Ange , Alran Severine , Venat‐Bouvet Laurence , Kerbrat Pierre , Salmon Remy , Becette Veronique , Bourgier Céline , Cherel Pascal , Boussion Véronique , Balleyguier Corinne , Thibault Fabienne , Lavau‐Denes Sandrine , Nabholz Jean‐Marc , Sigal Brigitte , Trassard Martine , Mathieu Marie‐Christine , Martin Anne‐Laure , Lemonnier Jerome , Mouret‐Fourme Emmanuelle
Published: June 2016

BACKGROUND

Treatment strategies for locally advanced breast cancer in elderly patients too frail to receive neoadjuvant chemotherapy and the introduction of new classes of drugs in the early 2000s have led to the consideration of endocrine therapy as a neoadjuvant treatment for younger hormone receptor (HR)–positive, postmenopausal patients not eligible for primary breast‐conserving surgery (BCS).

METHODS

This was a multicenter, phase 2, randomized trial designed to evaluate as its primary objective the clinical response rate after up to 6 months of neoadjuvant endocrine therapy (NET) alone in HR‐positive/human epidermal growth factor receptor 2 (HER2)–negative patients with 1 mg of anastrozole (arm A) or 500 mg of fulvestrant (arm B). Secondary objectives included the BCS rate, tumor response assessment (breast ultrasound and magnetic resonance imaging), pathological response (Sataloff classification), safety profile, relapse‐free survival (RFS), and predictive markers of responses and outcomes.

RESULTS

From October 2007 to April 2011, 116 women (mean age, 71.6 years) with operable infiltrating breast adenocarcinoma (T2‐T4, N0‐N3, M0) were randomized to receive anastrozole or fulvestrant. The clinical response rates at 6 months were 52.6% (95% confidence interval [CI], 41%‐64%) in arm A and 36.8% (95% CI, 25%‐49%) in arm B. BCS was performed for 57.6% of arm A patients and 50% of arm B patients. The RFS rates at 3 years were 94.9% in arm A and 91.2% in arm B. The Preoperative Endocrine Prognostic Index status was significantly predictive of RFS. Both treatments were well tolerated.

CONCLUSIONS

Both drugs are effective and well tolerated as NET in postmenopausal women with HR‐positive/HER2‐negative breast cancer. NET could be considered a treatment option in this subpopulation. Cancer 2016;122:3032‐3040. © 2016 American Cancer Society.
Vessel segmentation from abdominal magnetic resonance images: adaptive and reconstructive approach
Authors: Goceri Evgin , Shah Zarine K. , Gurcan Metin N.
Published: June 2016

The liver vessels, which have low signal and run next to brighter bile ducts, are difficult to segment from MR images. This study presents a fully automated and adaptive method to segment portal and hepatic veins on magnetic resonance images. In the proposed approach, segmentation of these vessels is achieved in four stages: (i) initial segmentation, (ii) refinement, (iii) reconstruction, and (iv) post‐processing. In the initial segmentation stage, k‐means clustering is used, the results of which are refined iteratively with linear contrast stretching algorithm in the next stage, generating a mask image. In the reconstruction stage, vessel regions are reconstructed with the marker image from the first stage and the mask image from the second stage. Experimental data sets include slices that show fat tissues, which have the same gray level values with vessels, outside the margin of the liver. These structures are removed in the last stage. Results show that the proposed approach is more efficient than other thresholding‐based methods. Copyright © 2016 John Wiley & Sons, Ltd.
CAP Bench: a benchmark suite for performance and energy evaluation of low‐power many‐core processors
Authors: Souza Matheus A. , Penna Pedro Henrique , Queiroz Matheus M. , Pereira Alyson D. , Góes Luís Fabricio Wanderley , Freitas Henrique C. , Castro Márcio , Navaux Philippe O.A. , Méhaut Jean‐François
Published: June 2016

The constant need for faster and more energy‐efficient processors has been stimulating the development of new architectures, such as low‐power many‐core architectures. Researchers aiming to study these architectures are challenged by peculiar characteristics of some components such as networks‐on‐chip and lack of specific tools to evaluate their performance. In this context, the goal of this paper is to present a benchmark suite to evaluate state‐of‐the‐art low‐power many‐core architectures such as the Kalray MPPA‐256 low‐power processor, which features 256 compute cores in a single chip. The benchmark was designed and used to highlight important aspects and details that need to be considered when developing parallel applications for emerging low‐power many‐core architectures. As a result, this paper demonstrates that the benchmark offers a diverse suite of programs with regard to parallel patterns, job types, communication intensity, and task load strategies suitable for a broad understanding of performance and energy consumption of MPPA‐256 and upcoming many‐core architectures. Copyright © 2016 John Wiley & Sons, Ltd.
In Situ Generation of Active Molybdenum Octahedral Clusters for Photocatalytic Hydrogen Production from Water
Authors: Feliz Marta , Puche Marta , Atienzar Pedro , Concepción Patricia , Cordier Stéphane , Molard Yann
Published: June 2016

The photocatalytic hydrogen evolution reaction (HER) from water under homogeneous and heterogeneous conditions is explored for the {Mo6Bri8}4+ cluster core based unit starting from (TBA)2[Mo6Bri8Fa6] (TBA=tetra‐n‐butylammonium; “i” and “a” refer to the face‐capping inner and terminal apical ligand, respectively). The catalytic activity of {Mo6Bri8}4+ is enhanced by the in situ generation of [Mo6Bri8Fa5(OH)a]2−, [Mo6Bri8Fa3(OH)a3]2−, and [Mo6Bri8(OH)a6]2−, which are identified by ESIMS, luminescence, and NMR techniques. Full substitution of F− by OH− leads to the formation of (H3O)2[Mo6Bri8(OH)a6]⋅10 H2O; its structure was determined by single‐crystal XRD. The immobilization of the active {Mo6Bri8}4+ onto graphene oxide (GO) surfaces enhances its stability under catalytic conditions. The catalytic activity of the resulting (TBA)2Mo6Bri8@GO material is improved with respect to GO, but is reduced compared to the activity under homogeneous conditions because of changes in the GO semiconducting properties as well as lower activity and/or accessibility of the anchored cluster.
Fluorescence lifetime imaging of DAPI‐stained nuclei as a novel diagnostic tool for the detection and classification of B‐cell chronic lymphocytic leukemia
Authors: Yahav Gilad , Hirshberg Abraham , Salomon Ophira , Amariglio Ninette , Trakhtenbrot Luba , Fixler Dror
Published: June 2016

B‐cell chronic lymphocytic leukaemia (B‐CLL) and B‐cell precursor acute lymphoblastic leukaemia (B‐ALL) are the most common type of leukaemia in adults and children, respectively. Today, fluorescence in situ hybridization (FISH) is the standard for detecting chromosomal aberrations that reflect adverse and favorable outcome. This study revealed a new, simple, and fast diagnostic tool to detect pathological cells by measuring and imaging the fluorescence lifetime (FLT) using FLT imaging microscopy (FLIM) of the peripheral blood (PB) cells of B‐CLL samples that were labeled with the DNA binder, DAPI. The FLT of DAPI in healthy individuals was found to be 2.66 ± 0.12 ns. In contrast, PB cells of B‐CLL and BM cells of B‐ALL patients were characterized by a specific group distribution of the FLT values. The FLT of DAPI was divided into four subgroups, relative to 2.66 ns: short+, normal, prolonged, and prolonged+. These alterations could be related to different chromatin arrangements of B‐CLL and B‐ALL interphase nuclei. Notably, extremely long FLT of nuclear DAPI correlate with the presence of extra chromosome 12, while moderate increases compared to normal characterize the deletion of p53. Such correlations potentially enable a FLT‐based rapid automatic diagnosis and classification of B‐CLL even when the frequency of genetic and chromosomal abnormalities is low. © 2016 International Society for Advancement of Cytometry
A knock‐in allele of En1 expressing dre recombinase
Authors: Plummer Nicholas W. , de Marchena Jacqueline , Jensen Patricia
Published: June 2016

Engrailed 1 (En1) is a homeobox‐containing transcription factor expressed during development in diverse tissues, including the embryonic midbrain and anterior hindbrain. To facilitate investigation of genetic and developmental heterogeneity among cells with a history of En1 expression, we have generated En1Dre, a knock‐in allele expressing Dre recombinase. En1Dre can be used with existing Cre and Flp recombinase lines for genetic intersectional labeling, fate mapping, and functional manipulation of subpopulations of cells characterized by transient expression of En1. To avoid disrupting En1 function, the Dre cDNA is inserted at the 3′ end of the En1 coding sequence, together with a viral 2A peptide to mediate translation of separate EN1 and Dre proteins. Consequently, viable and fertile En1Dre homozygotes can be used to increase the proportion of useful genotypes produced in complex crosses. The pattern of Dre expression from En1Dre is indistinguishable from wild‐type En1 expression in mid‐gestation mouse embryos, and En1Dre controls Dre‐responsive indicator alleles by efficiently recombining rox sites in vivo. Through the application of genetic tools that allow manipulation of cells based on combinatorial expression of multiple distinct recombinases, En1Dre will significantly extend the ability to target important subpopulations of neurons and other cells within the broader En1 expression domain. genesis 54:447–454, 2016. Published 2016. This article is a US Government work and is in the public domain in the USA.
Temporal variation in selection on male and female traits in wild tree crickets
Authors: Ercit Kyla
Published: June 2016

Understanding temporal variation in selection in natural populations is necessary to accurately estimate rates of divergence and macroevolutionary processes. Temporal variation in the strength and direction of selection on sex‐specific traits can also explain stasis in male and female phenotype and sexual dimorphism. I investigated changes in strength and form of viability selection (via predation by wasps) in a natural population of male and female tree crickets over 4 years. I found that although the source of viability stayed the same, viability selection affected males and females differently, and the strength, direction and form of selection varied considerably from year to year. In general, males experienced significant linear selection and significant selection differentials more frequently than females, and different male traits experienced significant linear selection each year. This yearly variation resulted in overall weak but significant convex selection on a composite male trait that mostly represented leg size and wing width. Significant selection on female phenotype was uncommon, but when it was detected, it was invariably nonlinear. Significant concave selection on traits representing female body size was observed in some years, as the largest and smallest females were preyed on less (the largest may have been too heavy for flying wasps to carry). Viability selection was significantly different between males and females in 2 of 4 years. Although viability selection via predation has the potential to drive phenotypic change and sexual dimorphism, temporal variation in selection may maintain stasis.
Landscape genetics of the nonnative red fox of California
Authors: Sacks Benjamin N. , Brazeal Jennifer L. , Lewis Jeffrey C.
Published: June 2016

Invasive mammalian carnivores contribute disproportionately to declines in global biodiversity. In California, nonnative red foxes (Vulpes vulpes) have significantly impacted endangered ground‐nesting birds and native canids. These foxes derive primarily from captive‐reared animals associated with the fur‐farming industry. Over the past five decades, the cumulative area occupied by nonnative red fox increased to cover much of central and southern California. We used a landscape‐genetic approach involving mitochondrial DNA (mtDNA) sequences and 13 microsatellites of 402 nonnative red foxes removed in predator control programs to investigate source populations, contemporary connectivity, and metapopulation dynamics. Both markers indicated high population structuring consistent with origins from multiple introductions and low subsequent gene flow. Landscape‐genetic modeling indicated that population connectivity was especially low among coastal sampling sites surrounded by mountainous wildlands but somewhat higher through topographically flat, urban and agricultural landscapes. The genetic composition of populations tended to be stable for multiple generations, indicating a degree of demographic resilience to predator removal programs. However, in two sites where intensive predator control reduced fox abundance, we observed increases in immigration, suggesting potential for recolonization to counter eradication attempts. These findings, along with continued genetic monitoring, can help guide localized management of foxes by identifying points of introductions and routes of spread and evaluating the relative importance of reproduction and immigration in maintaining populations. More generally, the study illustrates the utility of a landscape‐genetic approach for understanding invasion dynamics and metapopulation structure of one of the world's most destructive invasive mammals, the red fox.
Sailboat‐Shaped Self‐Complexes that Function as Controllable Rotary Switches
Authors: Jiang Fei , Chen Mujuan , Liang Jidong , Gao Zhihong , Tang Mingfei , Xu Zhikai , Peng Bin , Zhu Shizheng , Jiang Lasheng
Published: June 2016

Bis(p‐phenylene)‐34‐crown‐10‐based substituted macrocycles bearing a dibenzylammonium side arm form sailboat‐shaped self‐complexes, in which the arm of the substituted macrocycle sticks into the cavity of the crown ether instead of threading into it. On the basis of this simple system, we easily constructed controllable rotary switches. The decomplexation/recomplexation process was realized by acid–base stimuli, and the switching process was successfully used to control the dethreading/rethreading of paraquat as a guest through the cavity of the BPP34C10 moiety of the substituted macrocycles, which rendered them promising candidates for fabricating more novel interlocked structures and molecular devices.
Synthesis of Functionalized 2‐(4‐Hydroxyphenyl)‐3‐methylbenzofuran Allosteric Modulators of Hsp90 Activity
Authors: Sattin Sara , Panza Matteo , Vasile Francesca , Berni Francesca , Goti Giulio , Tao Jiahui , Moroni Elisabetta , Agard David , Colombo Giorgio , Bernardi Anna
Published: June 2016

Hsp90 is a molecular chaperone that plays a pivotal role in the cell life cycle. ATP‐regulated internal dynamics are critical to Hsp90 function and we recently demonstrated that these dynamics can be modulated in an allosteric fashion; the protein C‐terminal domain (CTD) can be effectively targeted with a family of 2‐phenyl‐benzofuran derivatives. Here we describe the expansion of the initial library, reporting 28 new derivatives that explore the chemical space at opposite ends of the benzofuran scaffold. Interactions of the compounds with a full‐length protein homolog were explored by Saturation Transfer Difference (STD) NMR spectroscopy. In this context we also report the interaction epitope of Novobiocin, a known CTD inhibitor.
Overexpression of GRP78 enhances survival of CHO cells in response to serum deprivation and oxidative stress
Authors: Jiang Qing , Sun Yuanli , Guo Zilong , Fu Mingpeng , Wang Qiang , Zhu Huifen , Lei Ping , Shen Guanxin
Published: June 2016

Chinese hamster ovary (CHO) cells are regarded as one of the most commonly used mammalian hosts, which decreases the productivity due to loss in culture viability. Overexpressing antiapoptosis genes in CHO cells was developed as a means of limiting cell death upon exposure to environmental insults. Glucose‐regulated protein 78 (GRP78) is traditionally regarded as a major ER chaperone that participates in protein folding and other cell processes. It is also a potent antiapoptotic protein and plays a critical role in cell survival, proliferation, and metastasis. In this study, the impact of GRP78 on CHO cells in response to environmental insults such as serum deprivation and oxidative stress was investigated. First, it was confirmed that CHO cells were very sensitive to environmental insults. Then, GRP78 overexpressing CHO cell line was established and exposed to serum deprivation and H2O2. Results showed that GRP78 engineering increased the viability and decreased the apoptosis of CHO cells. The survival advantage due to GRP78 engineering could be mediated by suppression of caspase‐3 involved in cell death pathways in stressed cells. Besides, GRP78 engineering also enhanced yields of antibody against transferrin receptor in CHO cells. GRP78 should be a potential application in the biopharmaceutical industries.
Performance Analysis of a New Integrated Gasification Technology Driven by Biomass for Hydrogen and Electricity Cogeneration with a Dual Chemical Looping Process
Authors: Zhu Lin , Chen Hu , Zhang Zheng
Published: June 2016

A process based on biomass gasification integrated with a dual chemical looping technology, namely, chemical looping air separation and iron‐based chemical looping combustion, is proposed to investigate the performance of hydrogen and electricity cogeneration from a thermodynamic perspective. The effects of four vital ratios, namely, steam to biomass, oxygen to biomass, Fe2O3 to carbon, and flue gas to Mn2O3, on the thermodynamic performances of this process are investigated. Meanwhile, a T–Q diagram is involved in the validation of the feasibility of heat‐exchange networks in this process. In parallel, the system efficiencies (such as total energy efficiency and exergy efficiency) are evaluated. The exergy destruction of this process is also analyzed. As a result, the total energy and exergy efficiencies are calculated to be 66.23 and 58.10 %, respectively. Most exergy destruction is caused by the gasifier, which accounts for 40.90 % of the total exergy destruction.
Mixture toxicity of copper, cadmium, and zinc to barley seedlings is not explained by antioxidant and oxidative stress biomarkers
Authors: Versieren Liske , Evers Steffie , AbdElgawad Hamada , Asard Han , Smolders Erik
Published: June 2016

The analysis of metal mixture toxicity to plants is complicated by mutual interactions. In the present study, mixture effects of zinc (Zn), cadmium (Cd), and copper (Cu) on barley (Hordeum vulgare L.) root elongation were analyzed using oxidative stress parameters. The hypothesis was that toxic mixture effects on plant growth are better explained by biochemical parameters than by exposure information, because the former excludes interactions among metals for root uptake. Barley seedlings were exposed for 5 d or 14 d to these metals in nutrient solutions, added in isolation and as mixtures. Root elongation in Cu+Cd mixtures was well predicted from free metal ion concentrations in solution, using concentration addition (CA) or independent action (IA) reference models. In contrast, Zn acted antagonistically when combined with Cu and/or Cd, relative to both CA and IA. This protective effect of Zn correlated with the biomarkers measured in the long-term experiment; oxidative stress (indicated by malondialdehyde level, for example) decreased after addition of Zn. In addition, it was found that some biomarkers were sensitive to both Cu and Cd dosed in isolation, but not to Cu+Cd mixtures. Overall, the exposure explained mixture effects better than most of the 16 measured biomarkers (i.e., the biochemical effects). It is concluded that these biomarkers are not robust indicators for metal mixture toxicity, potentially because different metals have different parallel modes of action on growth that are insufficiently indexed by the biomarkers. Environ Toxicol Chem 2017;36:220–230. © 2016 SETAC
Effects of the antimicrobial contaminant triclocarban, and co-exposure with the androgen 17β-trenbolone, on reproductive function and ovarian transcriptome of the fathead minnow (Pimephales promelas)
Authors: Villeneuve Daniel L. , Jensen Kathleen M. , Cavallin Jenna E. , Durhan Elizabeth J. , Garcia-Reyero Natàlia , Kahl Michael D. , Leino Richard L. , Makynen Elizabeth A. , Wehmas Leah C. , Perkins Edward J. , Ankley Gerald T.
Published: June 2016

Triclocarban (TCC) is an antimicrobial agent routinely detected in surface waters that has been hypothesized to interact with the vertebrate endocrine system. The present study examined the effects of TCC alone and in combination with the model endocrine disruptor 17β-trenbolone (TRB) on fish reproductive function. Adult Pimephales promelas were continuously exposed to either 1 µg TCC/L or 5 µg TCC/L, to 0.5 µg TRB/L, or to a mixture (MIX) of 5 µg TCC/L and 0.5 µg TRB/L for 22 d, and a variety of reproductive and endocrine-related endpoints were examined. Cumulative fecundity was significantly reduced in fathead minnows exposed to TRB, MIX, or 5 µg TCC/L. Exposure to 1 µg TCC/L had no effect on reproduction. In general, both TRB and MIX treatments caused similar physiological effects, evoking significant reductions in female plasma vitellogenin, estradiol, and testosterone, and significant increases in male plasma estradiol. Based on analysis of the ovarian transcriptome, there were potential pathway impacts that were common to both TRB- and TCC-containing treatment groups. In most cases, however, those pathways were more plausibly linked to differences in reproductive status than to androgen-specific functions. Overall, TCC was reproductively toxic to fish at concentrations at or near those that have been measured in surface water. There was little evidence that TCC elicits reproductive toxicity through a specific mode of endocrine or reproductive action, nor that it could augment the androgenic effects of TRB. Nonetheless, the relatively small margin of safety between some measured environmental concentrations and effect concentrations suggests that concern is warranted. Environ Toxicol Chem 2017;36:231–242. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.
What moves us? How mobility and movement are at the center of human evolution
Authors: Kuhn Steven L. , Raichlen David A. , Clark Amy E.
Published: June 2016

Movement is central to the survival of all free‐living organisms. Consequently, movement and what anthropologists often refer to as mobility, which is the sum of small‐scale movements tracked across larger geographic and temporal scales, are key targets of selection. Movement and mobility also underpin many of the key features that make us human and that allowed our lineage to adapt to changing environments across the globe. The most obvious example is the evolution of humans' singular mode of locomotion. Bipedalism is arguably the most important derived anatomical trait of the hominin lineage. The mechanisms and circumstances that gave rise to this novel mode of movement remain subjects of intense research.
Home‐range size in large‐bodied carnivores as a model for predicting neandertal territory size
Authors: Churchill Steven Emilio , Walker Christopher Scott , Schwartz Adam Michael
Published: June 2016

Adult human foragers expend roughly 30–60 kcal per km in unburdened walking at optimal speeds.1,2 In the context of foraging rounds and residential moves, they may routinely travel distances of 50–70 km per week, often while carrying loads.3 Movement on the landscape, then, is arguably the single most expensive item in the activity budgets of hunter‐gatherers. Mobility costs may have been greater still for Neandertals. They had stocky, short‐limbed physiques that were energetically costly to move4 and lived in relatively unproductive Pleistocene environments5 that may have required greater movement to deal with problems of biodepletion and resource patchiness.6 But just how mobile were the Neandertals?
Postoperative axonal changes in the contralateral hemisphere in children with medically refractory epilepsy: A longitudinal diffusion tensor imaging connectome analysis
Authors: Jeong Jeong‐Won , Asano Eishi , Juhász Csaba , Behen Michael E. , Chugani Harry T.
Published: June 2016

To determine brain plasticity changes due to resective epilepsy surgery in children, we performed a longitudinal connectome analysis on the pattern of axonal connectivity in the contralateral hemisphere. Pre‐ and postoperative diffusion tensor imaging (DTI) data were acquired from 35 children with intractable focal epilepsy. A total of 54 brain regions of interest (ROIs) were generated in the hemisphere contralateral to the resection. Within a 54 × 54 connectivity matrix, a pairwise connectivity score was calculated for each connection between two ROIs, based on the DTI fiber streamline number in each connection. A permuted Spearman's ρ‐rank analysis was used to identify specific inter‐regional connections showing a significant association between the postoperative change of connectivity score and clinical variables. Nineteen connections in the contralateral hemisphere showed postoperative increases in the strength of connectivity. Postoperative increase in connectivity between insular–inferior frontal operculum regions as well as that between superior frontal orbital and mid frontal orbital regions were both significantly associated with a larger surgical resection volume (ρ > +0.40) and a younger patient age (ρ > −0.34). These increases were more robust in patients with frontal resection and in those achieving seizure freedom. Neuropsychological evaluation on subsets of patients revealed that such increases in connectivity were associated with preserved or improved cognitive functions such as visual memory and planning. Resective epilepsy surgery may lead to increased contralateral axonal connectivity in children with focal epilepsy. Our data lead to a hypothesis that such increased connectivity may be an imaging marker of postoperative brain plasticity to compensate for cognitive function. Hum Brain Mapp 37:3946–3956, 2016. © 2016 Wiley Periodicals, Inc.
Decreasing expression of glucose‐regulated protein GRP78/BiP as a significant prognostic predictor in patients with advanced laryngeal squamous cell carcinoma
Authors: Kaira Kyoichi , Toyoda Minoru , Shimizu Akira , Imai Hisao , Sakakura Koichi , Nikkuni Osamu , Suzuki Masami , Iijima Misa , Asao Takayuki , Chikamatsu Kazuaki
Published: June 2016

Background

The immunoglobulin heavy chain binding protein (BiP)/glucose‐regulated protein 78 (GRP78) is important in the endoplasmic reticulum stress, and is highly expressed in various human cancers. The clinical and pathological features of GRP78/BiP are unclear in patients with advanced laryngeal squamous cell carcinoma (SCC). The purpose of this study was to investigate the clinicopathological significance of GRP78/BiP as a prognostic marker for laryngeal SCC.

Methods

A total of 59 patients with advanced laryngeal SCC (stage III/IV) were analyzed, and tumor specimens were stained by immunohistochemistry for GRP78/BiP and Ki‐67. Microvessel density was determined by immunohistochemical staining for CD34 and p53.

Results

Expression of GRP78/BiP was confirmed in 87% of cases. Decreased expression of GRP78/BiP was highly associated with positive expression of p53. Decreased GRP78/BiP expression was identified on multivariate analysis as an independent factor of decreased progression‐free survival (PFS).

Conclusion

GRP78/BiP was found to be commonly expressed in laryngeal SCC, whereas its downregulation was found to serve a significant prognostic role for predicting poor survival in patients with laryngeal SCC with advanced disease. GRP78/BiP may be a potentially attractive target for the treatment of various human neoplasms. © 2016 Wiley Periodicals, Inc. Head Neck 38: First–1544, 2016
Synthesis and Antimicrobial Activity of Racemic 1,5‐Diols: 2‐(1,3‐Diaryl‐3‐hydroxypropyl)cyclohexan‐1‐ol Derivatives
Authors: Gezegen Hayreddin , Tutar Uğur , Ceylan Mustafa
Published: June 2016

A series of novel racemic 2‐(1,3‐diaryl‐3‐hydroxypropyl)cyclohexan‐1‐ol derivatives were synthesized from 1,5‐diketones. All the synthesized compounds were characterized by spectroscopic methods. The antibacterial activities of obtained chiral 1,5‐diols were investigated against four Gram‐positive and three Gram‐negative bacteria by determining of minimum inhibitory concentrations (MICs) in vitro. Compounds 3b, 3c, and 3d were found to be active against Enterococcus faecalis and Escherichia coli. In addition, compound 3j were found to be moderately active against all tested bacterial strains.
Association between prolonged neutropenia and reduced relapse risk in pediatric AML: A report from the children's oncology group
Authors: Sung Lillian , Aplenc Richard , Alonzo Todd A. , Gerbing Robert B. , Wang Yi‐Cheng , Meshinchi Soheil , Gamis Alan S.
Published: June 2016

Objective was to describe the relationship between the number of sterile site infections and duration of neutropenia during the first four cycles of chemotherapy and the risk of recurrence and overall survival in children with newly diagnosed acute myeloid leukemia (AML). AAML0531 was a Children's Oncology Group randomized phase 3 clinical trial that included 1022 children with de novo AML. For this analysis, we focused on non‐Down syndrome favorable and standard risk patients who completed at least 4 cycles of chemotherapy without recurrence or withdrawal during protocol therapy. Those receiving hematopoietic stem cell transplantation in first remission were excluded. Five hundred and sixty‐nine patients were included; 274 (48.2%) were favorable risk. The median cumulative time with neutropenia between Induction II to completion of Intensification II was 96 (range 54–204) days. Number of sterile site infections did not influence the risk of relapse or overall survival. However, longer duration of neutropenia was associated with a lower risk of relapse (hazard ratio 0.81 per 20 days neutropenia, p = 0.007). Longer duration of neutropenia was associated with a reduced risk of relapse for children with favorable and standard risk AML. Toxicity may be influenced by pharmacogenomics suggesting that individualized chemotherapy dosing may be an effective strategy.
USING A COGNITIVE BEHAVIORAL FRAMEWORK TO TRAIN STAFF SERVING INDIVIDUALS WHO EXPERIENCE CHRONIC HOMELESSNESS
Authors: Pontoski Taylor Kristin , Cunningham Amy , Schultz Luke , Jager‐Hyman Shari , Sposato Rosanna , Evans Arthur , Beck Aaron T. , Creed Torrey A.
Published: June 2016

Training in evidence‐based practices may better prepare providers to address the effect of behavioral health concerns on chronic homelessness. Through the Beck Initiative, a community–academic partnership, case managers (n = 19) were selected to incorporate a cognitive‐behavioral therapy (CBT) framework into services for chronic homelessness at seven sites in Philadelphia, PA. Details of the training components and development are presented. This training program demonstrated feasibility within these low‐demand shelter settings (79% completed training, 10% left employment during training, 10% did not complete). Feedback measures indicated positive feedback regarding acceptability, usefulness, and quality of training. Planned discharges from the shelters were significantly more frequent in the 6 months posttraining compared with the 6 months before training. The CBT framework shows early promise for improving services for people experiencing chronic homelessness. This program also demonstrates the benefit of involving community stakeholders and academic partners to address one aspect of chronic homelessness.
A FIRST LOOK AT NATURAL MENTORING AMONG PREADOLESCENT FOSTER CHILDREN
Authors: Greeson Johanna K. P. , Weiler Lindsey M. , Thompson Allison E. , Taussig Heather N.
Published: June 2016

This study describes natural mentoring among preadolescent children placed in out‐of‐home care and examines the association between natural mentoring and demographic, maltreatment, placement, and psychosocial characteristics. Cross‐sectional data from a sample of 263 children and their out‐of‐home caregivers were analyzed. Caregivers rated children's social skills, and children reported on their perceived opportunities and attachment to peers and adults, including natural mentors. About half the sample endorsed having natural mentors, with school personnel being the most common type of mentor. Children with natural mentors were older, more likely to be living in congregate care, and had stronger attachment to friends. Marginally significant findings suggested that children with natural mentors had been in out‐of‐home care for fewer months, and children who were sexually abused were less likely to have natural mentors with whom they had current contact. Future research is needed that examines the longitudinal course of natural mentoring among this population.
SCHOOL INCLUSION: A MULTIDIMENSIONAL FRAMEWORK AND LINKS WITH OUTCOMES AMONG URBAN YOUTH WITH DISABILITIES
Authors: McMahon Susan D. , Keys Christopher B. , Berardi Luciano , Crouch Ronald , Coker Crystal
Published: June 2016

As schools move toward inclusion of students with disabilities, there is need for a common framework for school inclusion, as well as assessment of inclusion in relation to student educational experiences. We propose an ecological framework that suggests school inclusion is best examined as a multidimensional construct with subtypes of inclusive best practices (organizational, academic, assessment and planning, and social). This study examines the extent to which schools (N= 11) are practicing each type of inclusion and the links between teacher‐reported inclusion practices and student‐ and school‐reported academic and social outcomes among African American and Latina/o youth with disabilities (N= 76). Results show that organizational inclusion and assessment and planning were associated with greater school belonging and school satisfaction; academic inclusion was associated with higher academic achievement, school belonging, and school satisfaction; and social inclusion was associated with higher academic achievement and school belonging. Implications for research, theory, and school practices are discussed.
In situ cultured preantral follicles is a useful model to evaluate the effect of anticancer drugs on caprine folliculogenesis
Authors: Guerreiro Denise Damasceno , Lima Laritza Ferreira de , Rodrigues Giovanna Quintino , Carvalho Adeline. de Andrade , Castro Simone Vieira , Campello Cláudio Cabral , Pessoa Cláudia do Ó , Gadelha Carla Renata Figueiredo , Figueiredo José Ricardo de , Bordignon Vilceu , Rodrigues Ana Paula Ribeiro
Published: June 2016

Despite the increase in the incidence of cancer, the number of women who survive cancer treatment is growing. However, one of the principal results of chemotherapy is premature ovarian failure (POF). The aim of this study was to use the in situ culture preantral follicles as an in vitro model to evaluate the toxicity of two anticancer drugs, doxorubicin (DXR) and paclitaxel (PTX), on the integrity and development of ovarian follicles. Fragments of the ovarian cortex of goats were cultured in vitro for 1 or 7 days in α‐MEM+ supplemented with different concentrations of DXR (0.003, 0.03, or 0.3 µg/mL) and PTX (0.001, 0.01, or 0.1 µg/mL). Analyses were performed before and after culture to evaluate tissue integrity by classical histology, apoptosis by TUNEL assay, DNA laddering kit and the detection of activated caspase 3, and DNA damage by the immune detection of phosphorylated histone H2A.x (H2AXph139). Both DXR and PTX reduced the number of morphologically normal primordial and developing follicles. Positive staining for TUNEL and active caspase 3 was detected in all the samples (P < 0.05). Therefore, we propose the in situ culture of caprine preantral follicles as a useful experimental model for assessing the toxic effects of the chemotherapeutic agents on ovarian folliculogenesis. Microsc. Res. Tech. 79:773–781, 2016. © 2016 Wiley Periodicals, Inc.
Hermitian Adjacency Matrix of Digraphs and Mixed Graphs
Authors: Guo Krystal , Mohar Bojan
Published: June 2016

The article gives a thorough introduction to spectra of digraphs via its Hermitian adjacency matrix. This matrix is indexed by the vertices of the digraph, and the entry corresponding to an arc from x to y is equal to the complex unity i (and its symmetric entry is ) if the reverse arc is not present. We also allow arcs in both directions and unoriented edges, in which case we use 1 as the entry. This allows to use the definition also for mixed graphs. This matrix has many nice properties; it has real eigenvalues and the interlacing theorem holds for a digraph and its induced subdigraphs. Besides covering the basic properties, we discuss many differences from the properties of eigenvalues of undirected graphs and develop basic theory. The main novel results include the following. Several surprising facts are discovered about the spectral radius; some consequences of the interlacing property are obtained; operations that preserve the spectrum are discussed—they give rise to a large number of cospectral digraphs; for every , all digraphs whose spectrum is contained in the interval are determined.
Note on Perfect Forests in Digraphs
Authors: Gutin Gregory , Yeo Anders
Published: June 2016

A spanning subgraph F of a graph G is called perfect if F is a forest, the degree of each vertex x in F is odd, and each tree of F is an induced subgraph of G. Alex Scott (Graphs Combin 17 (2001), 539–553) proved that every connected graph G contains a perfect forest if and only if G has an even number of vertices. We consider four generalizations to directed graphs of the concept of a perfect forest. While the problem of existence of the most straightforward one is NP‐hard, for the three others this problem is polynomial‐time solvable. Moreover, every digraph with only one strong component contains a directed forest of each of these three generalization types. One of our results extends Scott's theorem to digraphs in a nontrivial way.
Synthesis and Characterization of Novel 1,2,4‐oxadiazoline Derivatives Containing Pyrazole Moiety by 1,3‐Dipolar Cycloaddition
Authors: Fei Ting‐Hong , Zhou Ying‐Lei , Huang Le , Liu Fang‐Ming
Published: June 2016

A series of novel pyrazolyl‐oxadiazoline derivatives bearing 1,2,4‐triazole moiety 4a, 4b, 4c, 4d, 4e, 4f, 4g, 4h, 4i, 4j, 4k, 4l, 4m, 4n, 4o, 4p were synthesized by schiff bases of 3‐methyl‐1‐phenyl−5‐(1,2,4‐triazole‐1‐yl)‐4‐formylpyrazole 3a, 3b, 3c, 3d and various benzohydroximinoyl chlorides in the presence of Et3N via 1,3‐dipolar cycloaddition reaction. The target products were confirmed by IR, 1H‐NMR, MS, elemental analysis. In addition, the structure of compound 4d was defined by X‐ray crystallography.
Synthesis of N‐(2‐diethylamino‐ethyl)‐4‐(4‐fluoro‐benzamido)‐2‐methoxybenzamide (desiodo‐MIP‐1145) by coupling technique and its radioiodination: a potential melanoma imaging agent
Authors: Aglan H. , Kandil S. A. , EL‐Kafrawy A. F. , Seddik U.
Published: June 2016

Radioiodinated MIP‐1145, which specifically targets melanin, is an ideal candidate for targeted therapy of melanoma. An analogue of MIP‐1145 lacking the iodo‐substituent (desiodo‐MIP‐1145) was synthesized as a labeling precursor in three simple steps. The radioiodination of desiodo‐MIP‐1145 by iodine‐125 was carried out via an electrophilic substitution reaction. An optimization study for the iodination reaction was carried out. The labeled compound was isolated and purified by means of electrophoresis and HPLC. The maximum radiochemical yield, 76%, was obtained with radiochemical purity greater than 99%. The log P value for [125I]MIP‐1145 was measured as 4.5.
Stable and high‐yielding intrinsic 59Fe‐radiolabeling of the intravenous iron preparations Monofer and Cosmofer
Authors: Jensen Andreas I. , Severin Gregory W. , Andreasen Hans B. , Rasmussen Palle H.
Published: June 2016

Commercial iron supplements Monofer® and Cosmofer® were intrinsically radiolabeled with 59Fe for the purpose of tracing iron absorption in vivo. Optimized procedures aimed at introducing 59Fe into the macromolecular construct in a form that was as chemically equivalent to the matrix iron as possible. This was determined by challenging the labeled constructs with diethylenetriaminepentaacetic acid (DTPA) followed by separation by size‐exclusion and measurements of radioactivity and iron in the eluted fractions. The final procedures were simple and involved heating aqueous dispersions of the supplements in the presence of [59Fe]FeCl3 for 24 h at 95 °C for Monofer, and 85 °C for Cosmofer, resulting in radiochemical yields greater than 94%. High performance size exclusion chromatography, UV‐VIS spectroscopy, and dynamic light scattering were used to show that the supplements remained unchanged after radiolabeling, underscoring the applicability of the methodology for radiolabeling commercial iron preparations.
Relationship between the chondrocyte maturation cycle and the endochondral ossification in the diaphyseal and epiphyseal ossification centers
Authors: Pazzaglia Ugo E. , Congiu Terenzio , Sibilia Valeria , Pagani Francesca , Benetti Anna , Zarattini Guido
Published: June 2016

The chondrocyte maturation cycle and endochondral ossification were studied in human, fetal cartilage Anlagen and in postnatal meta‐epiphyses. The relationship between the lacunar area, the inter‐territorial fibril network variations, and calcium phosphorus nucleation in primary and secondary ossification centers were assessed using light microscopy and scanning electron microscopy (SEM) morphometry. The Anlage topographic, zonal classification was derived from the anatomical nomenclature of the completely developed long bone (diaphysis, metaphyses and epiphyses). A significant increase in the chondrocyte lacunar area was documented in the Anlage of epiphyseal zones 4 and 3 to zone 2 (metaphysis) and zone 1 (diaphysis), with the highest variation from zone 2 to zone 1. An inverse reduction in the intercellular matrix area and matrix interfibrillar empty space was also documented. These findings are consistent with the osmotic passage of free cartilage water from the interfibrillar space into the swelling chondrocytes, which increased the ion concentrations to a critical threshold for mineral precipitation in the matrix. The mineralized cartilage served as a scaffold for osteoblast apposition both in primary and secondary ossification centers and in the metaphyseal growth plate cartilage, though at different periods of bone Anlage development and with distinct patterns for each zone. All developmental processes shared a common initial pathway but progressed at different rates, modes and organization in diaphysis, metaphysis and epiphysis. In the ossification phase the developing vascular supply appeared to play a key role in determining the cortical or trabecular structure of the long bones. J. Morphol. 277:1187–1198, 2016. © 2016 Wiley Periodicals, Inc.
Climatic variability over the last 30 000 years recorded in La Piscina de Yuriria, a Central Mexican crater lake
Authors: Holmes Jonathan A. , Metcalfe Sarah E. , Jones Heather L. , Marshall Jim D.
Published: June 2016

The Trans‐Mexican Volcanic Belt (TMVB) provides an excellent setting for reconstruction of late Quaternary climate from different natural archives. Moreover, human impact on the landscape since the mid‐Holocene provides a good opportunity to investigate the complex interplay of natural and anthropogenic forcing of landscape change. However, despite the wealth of records, understanding of the environmental history of the region and its wider significance for climate change across the northern neotropics remains incomplete. We present a radiocarbon‐dated, multiple‐proxy (sedimentology, sedimentary geochemistry, ostracods, diatoms, stable isotopes) record of climatic and environmental change based on the lacustrine sediments from La Piscina de Yuriria, a hydrologically closed volcanic crater in the northern TMVB. Much of the last glacial interval was characterized by low effective moisture associated with a weakened North American Monsoon (NAM) although the interval from 30 000 to 27 500 a BP experienced abrupt changes in rainfall. The period corresponding to the Lateglacial stadial was also dry and the lake may have dried out at this time. There was a change to wetter but variable conditions during the early Holocene as the NAM strengthened. Progressive drying during the later Holocene was accompanied by phases of catchment disturbance, which were partly the result of human impact.