bluuebunny/crossref_metadata_2025 huggingface dataset:
Utility of Genomic Analysis In Circulating Tumor DNA from Patients with Carcinoma of Unknown Primary
Authors: Kato Shumei , Krishnamurthy Nithya , Banks Kimberly C. , De Pradip , Williams Kirstin , Williams Casey , Leyland-Jones Brian , Lippman Scott M. , Lanman Richard B. , Kurzrock Razelle
Published: June 2017

Carcinoma of unknown primary (CUP) is a rare and difficult-to-treat malignancy, the management of which might be improved by the identification of actionable driver mutations. We interrogated 54 to 70 genes in 442 patients with CUP using targeted clinical-grade, next-generation sequencing of circulating tumor DNA (ctDNA). Overall, 80% of patients exhibited ctDNA alterations; 66% (290/442) ≥1 characterized alteration(s), excluding variants of unknown significance. TP53-associated genes were most commonly altered [37.8% (167/442)], followed by genes involved in the MAPK pathway [31.2% (138/442)], PI3K signaling [18.1% (80/442)], and the cell-cycle machinery [10.4% (46/442)]. Among 290 patients harboring characterized alterations, distinct genomic profiles were observed in 87.9% (255/290) of CUP cases, with 99.7% (289/290) exhibiting potentially targetable alterations. An illustrative patient with dynamic changes in ctDNA content during therapy and a responder given a checkpoint inhibitor–based regimen because of a mismatch repair gene anomaly are presented. Our results demonstrate that ctDNA evaluation is feasible in CUP and that most patients harbor a unique somatic profile with pharmacologically actionable alterations, justifying the inclusion of noninvasive liquid biopsies in next-generation clinical trials. Cancer Res; 77(16); 4238–46. ©2017 AACR.
Modulation of Endoplasmic Reticulum Stress Controls CD4+ T-cell Activation and Antitumor Function
Authors: Thaxton Jessica E. , Wallace Caroline , Riesenberg Brian , Zhang Yongliang , Paulos Chrystal M. , Beeson Craig C. , Liu Bei , Li Zihai
Published: June 2017

The endoplasmic reticulum (ER) is an energy-sensing organelle with intimate ties to programming cell activation and metabolic fate. T-cell receptor (TCR) activation represents a form of acute cell stress and induces mobilization of ER Ca2+ stores. The role of the ER in programming T-cell activation and metabolic fate remains largely undefined. Gp96 is an ER protein with functions as a molecular chaperone and Ca2+ buffering protein. We hypothesized that the ER stress response may be important for CD4+ T-cell activation and that gp96 may be integral to this process. To test our hypothesis, we utilized genetic deletion of the gp96 gene Hsp90b1 in a CD4+ T cell–specific manner. We show that gp96-deficient CD4+ T cells cannot undergo activation-induced glycolysis due to defective Ca2+ mobilization upon TCR engagement. We found that activating naïve CD4+ T cells while inhibiting ER Ca2+ exchange, through pharmacological blockade of the ER Ca2+ channel inositol trisphosphate receptor (IP3R), led to a reduction in cytosolic Ca2+ content and generated a pool of CD62Lhigh/CD44low CD4+ T cells compared with wild-type (WT) matched controls. In vivo IP3R-inhibited CD4+ T cells exhibited elevated tumor control above WT T cells. Together, these data show that ER-modulated cytosolic Ca2+ plays a role in defining CD4+ T-cell phenotype and function. Factors associated with the ER stress response are suitable targets for T cell–based immunotherapies. Cancer Immunol Res; 5(8); 666–75. ©2017 AACR.
Integrative Assessment of Pretreatment Inflammation-, Nutrition-, and Muscle-Based Prognostic Markers in Patients with Muscle-Invasive Bladder Cancer Undergoing Radical Cystectomy
Authors: Miyake Makito , Morizawa Yosuke , Hori Shunta , Marugami Nagaaki , Iida Kota , Ohnishi Kenta , Gotoh Daisuke , Tatsumi Yoshihiro , Nakai Yasushi , Inoue Takeshi , Anai Satoshi , Torimoto Kazumasa , Aoki Katsuya , Tanaka Nobumichi , Shimada Keiji , Konishi Noboru , Fujimoto Kiyohide
Published: June 2017

Objective: The present study evaluated the clinical relevance of an integrative preoperative assessment of inflammation-, nutrition-, and muscle-based markers for patients with muscle-invasive bladder cancer (MIBC) undergoing curative radical cystectomy (RC). Methods: The analysis enrolled 117 patients and the variables included age, body mass index (BMI), neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, platelet-to-lymphocyte ratio, modified Glasgow Prognostic Score (mGPS), prognostic nutritional index (PNI), Controlling Nutritional Status score, psoas muscle index (PMI), and peak expiratory flow (PEF). The correlations among the variables were evaluated and their prognostic values after RC were tested. Results: Three inflammation markers (ratios of blood cell counts) were positively correlated (p < 0.0001). The PNI and the BMI were positively correlated (p = 0.04), although they were inversely correlated with the three inflammation markers (p < 0.0001). Age was not significantly correlated with the inflammation markers and PMI, although older age was associated with lower PNI and lower PEF. The disease-specific survival was independently predicted by T4 tumor, positive N status, and decreased PNI. Overall survival was independently predicted by T4 tumor, mGPS, and pretreatment sarcopenia status. Conclusions: The inflammation-, nutrition-, and muscle-based markers would be useful risk assessment tools for MIBC.
Tubuloreticular Inclusions in the Absence of Systemic Lupus Erythematosus and HIV Infection: A Report of Three Pediatric Cases
Authors: Elmaghrabi Ayah , Brown Elizabeth , Khin Ei , Hassler Jared , Hendricks Allen R.
Published: June 2017

Tubuloreticular inclusions (TRIs) are subcellular structures located within the cisternae of endoplasmic reticulum. Formation of TRIs has been linked to the exposure of excess interferon (IFN), either from endogenous or exogenous sources. In renal disease, TRIs have been most commonly associated with systemic lupus erythematosus (SLE), and human immunodeficiency virus-associated nephropathy (HIVAN). Case reports of patients with renal biopsies showing TRIs without underlying SLE or HIV are infrequent in adults, and to our knowledge none have been reported in children. We report 3 pediatric cases in which the renal biopsy showed TRIs on electron microscopy without underlying SLE or HIV infection. The first patient presented at 2 years of age with nephrotic syndrome and renal failure. His renal biopsy revealed focal segmental glomerulosclerosis and TRIs. The second patient presented at 6 months of age with infantile nephrotic syndrome, and his renal biopsy revealed membranous glomerulopathy and TRIs. The last patient presented at 4 years of age with acute kidney injury of unclear etiology leading to chronic kidney disease. Her biopsy revealed acute and chronic tubulointerstitial nephritis with TRIs. Despite extensive evaluation in all 3 patients, including testing for HIV infection and SLE, we could not identify an underlying etiology to explain the presence of TRIs. In conclusion, renal biopsy with TRIs in the absence of underling SLE and HIV remains obscure. We propose a possible role for excess IFN triggered by an abnormal immune response to common viral infections in the formation of TRIs and renal injury.
A Toddler Presenting with Pulmonary Renal Syndrome
Authors: Aeschlimann Florence A. , Yeung Rae S.M. , Laxer Ronald M. , Hebert Diane , Cooper Ashley , Chami Rose , Noone Damien
Published: June 2017

Pulmonary renal syndrome refers to an association of pulmonary and glomerular disease and includes disorders, such as the ANCA-associated vasculitides, anti-glomerular basement membrane antibody disease, systemic lupus erythematosus, and IgA vasculitis (Henoch-Schönlein purpura). We present the medical history of a 26-month-old boy with an extensive purpuric rash, involving the limbs, trunk, and face, who developed clinically significant pulmonary hemorrhage and renal involvement. Rapid recognition of this rare but potentially life-threatening condition is crucial. In this report, we discuss the differential diagnosis, diagnostic studies, and treatment options to consider when facing a young child presenting with a pulmonary renal syndrome.
First-Line Treatment with Carboplatin plus nab-Paclitaxel and Maintenance Monotherapy with nab-Paclitaxel for a Thymic Carcinoma: A Case Report
Authors: Funaishi Kunihiko , Yamasaki Masahiro , Saito Naomi , Daido Wakako , Ishiyama Sayaka , Deguchi Naoko , Taniwaki Masaya , Ohashi Nobuyuki
Published: June 2017

Thymic carcinomas are rare malignant tumors, located in the anterior mediastinum. For the treatment of these carcinomas, several chemotherapy regimens have been suggested, including carboplatin plus paclitaxel. However, because of the rarity of these tumors, the standard chemotherapy regimen has not yet been established. Here, we report a case of thymic carcinoma that responded to first-line carboplatin plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel) therapy with continuation maintenance nab-paclitaxel monotherapy. A 78-year-old male presented to a hospital with the chief complaint of dyspnea. Cardiomegaly was detected on chest X-ray scans, and marked pericardial effusion was observed by echocardiography. Chest computed tomography scans revealed the presence of a mediastinal mass, pericardial thickening, and pericardial effusion. The serum levels of the tumor marker CYFRA 21-1 (cytokeratin-19 fragment) were elevated. Eventually, he was diagnosed with squamous cell carcinoma of the thymus, which was staged as cT4N3M0 or stage IV (according to the tumor-node-metastasis classification). Chemotherapy with carboplatin on day 1 and nab-paclitaxel on days 1, 8, and 15, every 4 weeks was initiated. After the administration of 4 cycles of this regimen, the tumor diameter appeared reduced, and the serum CYFRA 21-1 levels were normalized. After a 1-month interval, the serum CYFRA 21-1 levels increased again; therefore, maintenance nab-paclitaxel monotherapy was initiated. At the end of the treatment, the patient experienced a progression-free survival of 10.3 months. Carboplatin plus nab-paclitaxel may be an appropriate alternative first-line treatment for thymic carcinomas. Additionally, maintenance nab-paclitaxel monotherapy may prolong the progression-free survivals of patients with thymic carcinomas.
MiR-4673 Modulates Paclitaxel-Induced Oxidative Stress and Loss of Mitochondrial Membrane Potential by Targeting 8-Oxoguanine-DNA Glycosylase-1
Authors: Huang Hai-Li , Shi Ya-Peng , He Hui-Juan , Wang Ya-Hong , Chen Ting , Yang La-Wei , Yang Teng , Chen Jie , Cao Jun , Yao Wei-Min , Liu Gang
Published: June 2017

Background: Our previous study identified a novel microRNA, miR-4673, which is upregulated in A549 cells exposed to paclitaxel (PTX). In this study, we investigated the role of miR-4673 in PTX-induced cytotoxicity. Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, apoptosis assay, 5,5’,6,6’-Tetrachloro-1,1’,3,3’-tetraethyl-imidacarbocyanine iodide (JC-1) staining and 2’,7’-Dichlorofluorescein (DCFH) staining were used to evaluate cell viability, apoptosis, mitochondrial membrane potential (MMP) loss and reactive oxygen species (ROS) generation in A549 and H1299 cells. Bioinformatics analysis and Luciferase reporter assay were used to explore whether 8-oxoguanine-DNA glycosylase-1 (OGG1) is a target gene of miR-4673. Results: Enforced expression of miR-4673 decreased cell viability and increased PTX-induced apoptosis, MMP loss and reactive oxygen species (ROS) generation in A549 and H1299 cells. Bioinformatics analysis, which was used to identify potential target of miR-4673, revealed a binding site of miR-4673 in 3’UTR of OGG1. Luciferase reporters assays showed that miR-4673 specifically binds to ‘CUGUUGA’ in 3’UTR of OGG1. Enforced expression of miR-4673 decreased accumulation of OGG1. In addition, silencing OGG1 enhanced inhibitory effects of PTX on apoptosis, MMP loss and ROS generation, which is similar to effects of miR-4673. Moreover, enforced expression of OGG1 compromised promoting effects of miR-4673 on PTX-induced apoptosis, MMP loss and ROS generation. Conclusion: miR-4673 modulates PTX-induced apoptosis, MMP loss and ROS generation by targeting OGG1.
Mediator 1 Is Atherosclerosis Protective by Regulating Macrophage Polarization
Authors: Bai Liang , Li Zhao , Li Qianwei , Guan Hua , Zhao Sihai , Liu Ruihan , Wang Rong , Zhang Jin , Jia Yuzhi , Fan Jianglin , Wang Nanping , Reddy Janardan K. , Shyy John Y.-J. , Liu Enqi
Published: June 2017

Objective—

MED1 (mediator 1) interacts with transcription factors to regulate transcriptional machinery. The role of MED1 in macrophage biology and the relevant disease state remains to be investigated.

Approach and Results—

To study the molecular mechanism by which MED1 regulates the M1/M2 phenotype switch of macrophage and the effect on atherosclerosis, we generated MED1/apolipoprotein E (ApoE) double-deficient (MED1
ΔMac
/ApoE
−
/−
) mice and found that atherosclerosis was greater in MED1
ΔMac
/ApoE
−/−
mice than in MED1
fl/fl
/ApoE
−/−
littermates. The gene expression of M1 markers was increased and that of M2 markers decreased in both aortic wall and peritoneal macrophages from MED1
ΔMac
/ApoE
−/−
mice, whereas MED1 overexpression rectified the changes in M1/M2 expression. Moreover, LDLR (low-density lipoprotein receptor)–deficient mice received bone marrow from MED1
ΔMac
mice showed greater atherosclerosis. Mechanistically, MED1 ablation decreased the binding of PPARγ (peroxisome proliferator–activated receptor γ) and enrichment of H3K4me1 and H3K27ac to upstream region of M2 marker genes. Furthermore, interleukin 4 induction of PPARγ and MED1 increased the binding of PPARγ or MED1 to the PPAR response elements of M2 marker genes.

Conclusions—

Our data suggest that MED1 is required for the PPARγ-mediated M2 phenotype switch, with M2 marker genes induced but M1 marker genes suppressed. MED1 in macrophages has an antiatherosclerotic role via PPARγ-regulated transactivation.
Experimental and Computational Insight Into Human Mesenchymal Stem Cell Paracrine Signaling and Heterocellular Coupling Effects on Cardiac Contractility and Arrhythmogenicity
Authors: Mayourian Joshua , Cashman Timothy J. , Ceholski Delaine K. , Johnson Bryce V. , Sachs David , Kaji Deepak A. , Sahoo Susmita , Hare Joshua M. , Hajjar Roger J. , Sobie Eric A. , Costa Kevin D.
Published: June 2017

Rationale:

Myocardial delivery of human mesenchymal stem cells (hMSCs) is an emerging therapy for treating the failing heart. However, the relative effects of hMSC-mediated heterocellular coupling (HC) and paracrine signaling (PS) on human cardiac contractility and arrhythmogenicity remain unresolved.

Objective:

The objective is to better understand hMSC PS and HC effects on human cardiac contractility and arrhythmogenicity by integrating experimental and computational approaches.

Methods and Results:

Extending our previous hMSC–cardiomyocyte HC computational model, we incorporated experimentally calibrated hMSC PS effects on cardiomyocyte L-type calcium channel/sarcoendoplasmic reticulum calcium-ATPase activity and cardiac tissue fibrosis. Excitation–contraction simulations of hMSC PS-only and combined HC+PS effects on human cardiomyocytes were representative of human engineered cardiac tissue (hECT) contractile function measurements under matched experimental treatments. Model simulations and hECTs both demonstrated that hMSC-mediated effects were most pronounced under PS-only conditions, where developed force increased ≈4-fold compared with non–hMSC-supplemented controls during physiological 1-Hz pacing. Simulations predicted contractility of isolated healthy and ischemic adult human cardiomyocytes would be minimally sensitive to hMSC HC, driven primarily by PS. Dominance of hMSC PS was also revealed in simulations of fibrotic cardiac tissue, where hMSC PS protected from potential proarrhythmic effects of HC at various levels of engraftment. Finally, to study the nature of the hMSC paracrine effects on contractility, proteomic analysis of hECT/hMSC conditioned media predicted activation of PI3K/Akt signaling, a recognized target of both soluble and exosomal fractions of the hMSC secretome. Treating hECTs with exosome-enriched, but not exosome-depleted, fractions of the hMSC secretome recapitulated the effects observed with hMSC conditioned media on hECT-developed force and expression of calcium-handling genes (eg, SERCA2a, L-type calcium channel).

Conclusions:

Collectively, this integrated experimental and computational study helps unravel relative hMSC PS and HC effects on human cardiac contractility and arrhythmogenicity, and provides novel insight into the role of exosomes in hMSC paracrine-mediated effects on contractility.
Ḥusn at-takhalluṣ bei Ibn an-Nabīh und Ibn Sanāʾ al-Mulk
Authors: Wagner Ewald
Published: June 2017

Ḥusn al-takhalluṣ was the term that medieval Arabic literary critics used for the rhetorical device by which Arabic poets connected the different themes of the polythematic qaṣīdah. In early times poets often dispensed with a transition. In the ʿAbbāsid period however, the poets bestowed more effort on the shaping of ḥusn al-takhalluṣ. They also had to adjust it to changes in the nasīb, the opening part of the qaṣīdah. The article shows how two important poets of the Ayyūbid era, Ibn al-Nabīh and Ibn Sanāʾ al-Mulk, met the challenge, either by developing further the devices of earlier poets, or by creating totally new transitions.
The bryozoan genus Arbocuspis (Cheilostomata, Electridae) from the Indian Ocean, with description of a new species from off southwestern Thailand, Andaman Sea
Authors: ROSSO ANTONIETTA , SCIUTO FRANCESCO , SANFILIPPO ROSSANA , JONES MARY SPENCER
Published: June 2017

Arbocuspis is a bryozoan genus, so far lacking a fossil record. It includes a few, essentially intertropical, living species, all until recently considered as mere varieties of the genotype species Membranipora bellula Hincks, 1881. Scanning electron microscope images of type material are presented for the first time for Arbocuspis bicornis Hincks, 1881 from Ceylon and Arbocuspis multicornis Hincks, 1881 from Australian waters, together with a modern description for this latter species. A new species, Arbocuspis emanuelae n. sp., is erected for specimens from the Andaman Sea. Arbocuspis emanuelae is easily distinguishable from congeners because of its two symmetrically branching spines overarching the opesium, and the group of pointed unbranched spines between them. Species of Arbocuspis are especially adapted to colonise shallow-water habitats and ephemeral substrata, and their apparently wide distributions possibly result from natural and/or anthropogenic-mediated transport, and/or also point to complexes of cryptogenic species. The diagnosis of the genus is amended owing to the occurrence in A. emanuelae n. sp. of several kinds of kenozooids, which were unreported from previously known species.
Description of a new branchiate scale-worm (Polychaeta: Polynoidae) from the hydrothermal vent on Southwest Indian Ocean Ridge
Authors: ZHOU YADONG , ZHANG DONGSHENG , LU BO , WANG CHUNSHENG
Published: June 2017

During the Dive90 and Dive94 of Chinese manned submersible “Jiaolong”, some polychaete specimens were collected from the “Longqi” vent field on the Southwest Indian Ocean Ridge. A new species belonging to the genus Branchipolynoe, Branchipolynoe longqiensis n. sp., is described in this study. It can be easily distinguished from congeners by its biramous parapodia with relatively reduced notopodia, stout notosetae and branchiae with short terminal filaments.
Can the General Theory of Crime and General Strain Theory Explain Cyberbullying Perpetration?
Authors: Lianos Helen , McGrath Andrew
Published: June 2017

Cyberbullying is an increasingly common characteristic of contemporary online communication. The current study surveyed 320 Internet-active young adults and found up to 80% reported engaging in this behavior at least once. In addition, the ability of the general theory of crime and general strain theory to explain cyberbullying perpetration was tested. Evidence for both theories was observed, with both low self-control and higher levels of strain related to cyberbullying perpetration. Furthermore, opportunity (operationalized as moderate and high number of hours online) interacted with low self-control to increase perpetration, and anger partially mediated the relationship between strain and cyberbullying. Implications of the findings are discussed.
The Roadmap for Enhancing University–Industry Research Collaboration in India
Authors: Kumar Prateek , Gupta Roopali
Published: June 2017

In this age of technology-led development and stiff international competition over Intellectual Property Rights (IPRs), developing countries, with their limited financial capabilities, face the challenge of creating appropriate environment that could facilitate the creation and commercialisation of technologies. The recognition of poor scientific outputs as a hindrance to the growth of domestic industry has brought research on the development agenda.

This article focuses on university–industry research collaborations as one of the ways to kick-start innovation-led economic growth in India. It explores the evolution of relevant policy paradigm in India and presents the relevant highlights of National IPR Policy 2016. It identifies the impediments in the way of creative university–industry collaborations and offers solutions to attain optimum synergy between the academia and industry.
Right to Information Act, 2005 in India: A Decadal Experience
Authors: Ghuman B. S. , Sohail Mohammad
Published: June 2017

Right to Information (RTI) Act emerged as a powerful instrument for taming corruption in the functioning of public authorities by promoting transparency and accountability. The Act has completed ten years but the challenges hindering the successful implementation of the Act are still looming large. The Act is slowly moving away from its goal owing to many factors, such as lack of awareness, improper maintenance of records, poor compliance to public disclosure of information mentioned under Section 4 of the Act, inconvenient fee depositing mechanism, lack of sustained training mechanism for employees, misuse of the Act, pendency of appeals before Information Commissions and lack of legislative measures for protection of whistleblowers. For making the Act a success, it is essential to conduct massive awareness campaigns for citizens, to maintain proper official records for facilitating provision of information under the Act, ensuring suo motu disclosure of information mentioned under Section 4 of the Act, use of information and communication technology in the implementation of the Act, making available convenient fee depositing options, conducting training programmes for officials involved in the implementation of the Act, and, finally, enacting a strong whistleblowers’ protection Act.
Circulatory CNP Rescues Craniofacial Hypoplasia in Achondroplasia
Authors: Yamanaka S. , Nakao Kazumasa , Koyama N. , Isobe Y. , Ueda Y. , Kanai Y. , Kondo E. , Fujii T. , Miura M. , Yasoda A. , Nakao Kazuwa , Bessho K.
Published: June 2017

Achondroplasia is the most common genetic form of human dwarfism, characterized by midfacial hypoplasia resulting in occlusal abnormality and foramen magnum stenosis, leading to serious neurologic complications and hydrocephalus. Currently, surgery is the only way to manage jaw deformity, neurologic complications, and hydrocephalus in patients with achondroplasia. We previously showed that C-type natriuretic peptide (CNP) is a potent stimulator of endochondral bone growth of long bones and vertebrae and is also a potent stimulator in the craniofacial region, which is crucial for midfacial skeletogenesis. In this study, we analyzed craniofacial morphology in a mouse model of achondroplasia, in which fibroblast growth factor receptor 3 (FGFR3) is specifically activated in cartilage ( Fgfr3ach mice), and investigated the mechanisms of jaw deformities caused by this mutation. Furthermore, we analyzed the effect of CNP on the maxillofacial area in these animals. Fgfr3ach mice exhibited midfacial hypoplasia, especially in the sagittal direction, caused by impaired endochondral ossification in craniofacial cartilage and by premature closure of the spheno-occipital synchondrosis, an important growth center in craniomaxillofacial skeletogenesis. We crossed Fgfr3ach mice with transgenic mice in which CNP is expressed in the liver under the control of the human serum amyloid-P component promoter, resulting in elevated levels of circulatory CNP ( Fgfr3ach/SAP-Nppc-Tg mice). In the progeny, midfacial hypoplasia in the sagittal direction observed in Fgfr3ach mice was improved significantly by restoring the thickness of synchondrosis and promoting proliferation of chondrocytes in the craniofacial cartilage. In addition, the foramen magnum stenosis observed in Fgfr3ach mice was significantly ameliorated in Fgfr3ach/SAP-Nppc-Tg mice due to enhanced endochondral bone growth of the anterior intraoccipital synchondrosis. These results clearly demonstrate the therapeutic potential of CNP for treatment of midfacial hypoplasia and foramen magnum stenosis in achondroplasia.
Evaluating the Dimensionality of Self-Determination Theory’s Relative Autonomy Continuum
Authors: Sheldon Kennon M. , Osin Evgeny N. , Gordeeva Tamara O. , Suchkov Dmitry D. , Sychev Oleg A.
Published: June 2017

We conducted a theoretical and psychometric evaluation of self-determination theory’s “relative autonomy continuum” (RAC), an important aspect of the theory whose validity has recently been questioned. We first derived a Comprehensive Relative Autonomy Index (C-RAI) containing six subscales and 24 items, by conducting a paired paraphrase content analysis of existing RAI measures. We administered the C-RAI to multiple U.S. and Russian samples, assessing motivation to attend class, study a major, and take responsibility. Item-level and scale-level multidimensional scaling analyses, confirmatory factor analyses, and simplex/circumplex modeling analyses reaffirmed the validity of the RAC, across multiple samples, stems, and studies. Validation analyses predicting subjective well-being and trait autonomy from the six separate subscales, in combination with various higher order composites (weighted and unweighted), showed that an aggregate unweighted RAI score provides the most unbiased and efficient indicator of the overall quality of motivation within the behavioral domain being assessed.
Regulatory Forum Opinion Piece*: Imaging Applications in Toxicologic Pathology—Recommendations for Use in Regulated Nonclinical Toxicity Studies
Authors: Maronpot Robert R. , Nyska Abraham , Troth Sean P. , Gabrielson Kathleen , Sysa-Shah Polina , Kalchenko Vyacheslav , Kuznetsov Yuri , Harmelin Alon , Schiffenbauer Yael S. , Bonnel David , Stauber Jonathan , Ramot Yuval
Published: June 2017

Available imaging systems for use in preclinical toxicology studies increasingly show utility as important tools in the toxicologic pathologist’s armamentarium, permit longitudinal evaluation of functional and morphological changes in tissues, and provide important information such as organ and lesion volume not obtained by conventional toxicology study parameters. Representative examples of practical imaging applications in toxicology research and preclinical studies are presented for ultrasound, positron emission tomography/single-photon emission computed tomography, optical, magnetic resonance imaging, and matrix-assisted laser desorption ionization—imaging mass spectrometry imaging. Some of the challenges for making imaging systems good laboratory practice–compliant for regulatory submission are presented. Use of imaging data on a case-by-case basis as part of safety evaluation in regulatory submissions is encouraged.
Nicotine and cigarette smoke modulate Nrf2-BDNF-dopaminergic signal and neurobehavioral disorders in adult rat cerebral cortex#
Authors: Naha Nibedita , Gandhi DN , Gautam AK , Prakash J Ravi
Published: June 2017

Background:

Nicotine and cigarette smoking (CS) are associated with addiction behavior, drug-seeking, and abuse. However, the mechanisms that mediate this association especially, the role of brain-derived neurotrophic factor (BDNF), dopamine (DA), and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling in the cerebral cortex, are not fully known. Therefore, we hypothesized that overexpression of BDNF and DA, and suppression of Nrf2 contribute to several pathological and behavioral alterations in adult cerebral cortex.

Methodology/Principal Observations:

We treated Wistar rats with different doses of oral nicotine and passive CS for 4-week (short-term) and 12-week (long-term) duration, where doses closely mimic the human smoking scenario. Our result showed dose-dependent association of anxiogenic and depressive behavior, and cognitive interference with neurodegeneration and DNA damage in the cerebral cortex upon exposure to nicotine/CS as compared to the control. Further, the results are linked to upregulation of oxidative stress, overexpression of BDNF, DA, and DA marker, tyrosine hydroxylase (TH), with concomitant downregulation of ascorbate and Nrf2 expression in the exposed cerebral cortex when compared with the control.

Conclusion/Significance:

Overall, our data strongly suggest that the intervention of DA and BDNF, and depletion of antioxidants are important factors during nicotine/CS-induced cerebral cortex pathological changes leading to neurobehavioral impairments, which could underpin the novel therapeutic approaches targeted at tobacco smoking/nicotine’s neuropsychological disorders including cognition and drug addiction.
Pooled sample testing for Bonamia ostreae: A tale of two SYBR Green real-time PCR assays
Authors: Lane Henry S. , Jones J. Brian , McDonald Wendy L.
Published: June 2017

Pooled testing of samples is a common laboratory practice to increase efficiency and reduce expenses. We investigated the efficacy of 2 published SYBR Green real-time PCR assays when used to detect the haplosporidian parasite Bonamia ostreae in pooled samples of infected oyster tissue. Each PCR targets a different gene within the B. ostreae genome: the actin 1 gene or the 18S rRNA gene. Tissue homogenates (150 mg) of the New Zealand flat oyster Ostrea chilensis were spiked with ~1.5 × 103 purified B. ostreae cells to create experimental pools of 3, 5, and 10. Ten positive replicates of each pool size were assayed twice with each PCR and at 2 different amounts of DNA template. The PCR targeting the actin 1 gene was unable to reproducibly detect B. ostreae in any pool size. Conversely, the 18S rRNA gene PCR could reproducibly detect B. ostreae in pools of up to 5. Using a general linear model, there was a significant difference in the number of pools that correctly detected B. ostreae between each PCR ( p < 0.01) and each pool size ( p < 0.01). It is likely that the single copy actin 1 gene is more likely to be diluted and not detected by pooling than the multi-copy 18S rRNA gene. Our study highlights that validation data are necessary for pooled sample testing because detection efficacy may not be comparable to individual sample testing.
An Assessment of Database-Validated microRNA Target Genes in Normal Colonic Mucosa: Implications for Pathway Analysis
Authors: Slattery Martha L , Herrick Jennifer S , Stevens John R , Wolff Roger K , Mullany Lila E
Published: June 2017

Background:

Determination of functional pathways regulated by microRNAs (miRNAs), while an essential step in developing therapeutics, is challenging. Some miRNAs have been studied extensively; others have limited information. In this study, we focus on 254 miRNAs previously identified as being associated with colorectal cancer and their database-identified validated target genes.

Methods:

We use RNA-Seq data to evaluate messenger RNA (mRNA) expression for 157 subjects who also had miRNA expression data. In the replication phase of the study, we replicated associations between 254 miRNAs associated with colorectal cancer and mRNA expression of database-identified target genes in normal colonic mucosa. In the discovery phase of the study, we evaluated expression of 18 miRNAs (those with 20 or fewer database-identified target genes along with miR-21-5p, miR-215-5p, and miR-124-3p which have more than 500 database-identified target genes) with expression of 17 434 mRNAs to identify new targets in colon tissue. Seed region matches between miRNA and newly identified targeted mRNA were used to help determine direct miRNA-mRNA associations.

Results:

From the replication of the 121 miRNAs that had at least 1 database-identified target gene using mRNA expression methods, 97.9% were expressed in normal colonic mucosa. Of the 8622 target miRNA-mRNA associations identified in the database, 2658 (30.2%) were associated with gene expression in normal colonic mucosa after adjusting for multiple comparisons. Of the 133 miRNAs with database-identified target genes by non-mRNA expression methods, 97.2% were expressed in normal colonic mucosa. After adjustment for multiple comparisons, 2416 miRNA-mRNA associations remained significant (19.8%). Results from the discovery phase based on detailed examination of 18 miRNAs identified more than 80 000 miRNA-mRNA associations that had not previously linked to the miRNA. Of these miRNA-mRNA associations, 15.6% and 14.8% had seed matches for CRCh38 and CRCh37, respectively.

Conclusions:

Our data suggest that miRNA target gene databases are incomplete; pathways derived from these databases have similar deficiencies. Although we know a lot about several miRNAs, little is known about other miRNAs in terms of their targeted genes. We encourage others to use their data to continue to further identify and validate miRNA-targeted genes.
Turning a new page: cultural safety, critical creative literary interventions, truth and reconciliation, and the crisis of child welfare
Authors: de Leeuw Sarah , Greenwood Margo
Published: June 2017

Despite the recent Truth and Reconciliation Report in Canada, rates of Indigenous children being apprehended by the state remain disproportionality high when compared to non-Indigenous children. Starting with a critical decolonizing methodology, this article charts connections between historic and contemporary settler-colonial state interventions into lives and places of Indigenous families. We interrogate resiliencies of false settler-state logics based on “for their own good” logics about Indigenous peoples. We then turn to the recent ascendance of cultural safety, considering the concept’s positive possibility, and potential limitations, with reference to child-welfare and apprehension of Indigenous children. Finally, based on established evidence that child welfare is a crucial determinant of broader Indigenous health and well-being, the article concludes with thoughts about how those working with settler-colonial state apparatuses might achieve culturally safe engagements with Indigenous cultures in the contemporary colonial present. Our solutions are located in literary arts, where the article begins.
New insights into the burden and costs of multiple sclerosis in Europe: Results for Hungary
Authors: Péntek Márta , Kobelt Gisela , Berg Jenny , Capsa Daniela , Dalén Johan , Bíró Zita , Mátyás Klotild , Komoly Sámuel ,   The European Multiple Sclerosis Platform
Published: June 2017

Introduction:

To estimate the value of interventions in multiple sclerosis (MS) – where lifetime costs and outcomes cannot be observed – outcome data have to be combined with costs. This requires that cost data be regularly updated.

Objectives and methods:

This study is part of a cross-sectional retrospective study in 16 countries collecting data on resource consumption, work capacity, health-related quality of life (HRQoL) and prevalent symptoms for patients with MS. Descriptive analyses are presented by level of disability, from the societal perspective, in HUF 2015.

Results:

A total of 521 patients (mean age 47 years) participated; 85% were below retirement age, and of these, 47% were employed. Employment was related to disability and MS affected productivity at work for 82% of those working. Overall, 94% and 66% of patients experienced fatigue and cognitive difficulties as a problem, respectively. The mean utility and annual costs were 0.691 and 3,432,000HUF at Expanded Disability Status Scale (EDSS) 0–3, 0.491 and 5,262,000HUF at EDSS 4–6.5 and 0.076 and 6,235,000HUF at EDSS 7–9, respectively. The average cost of a relapse was estimated at 240,500HUF.

Conclusion:

This study illustrates the burden of MS on Hungarian patients and provides current data that are important for the development of health policies.
From subject to collaborator
Authors: Hancox Donna
Published: June 2017

New media technologies and the narrative turn in qualitative research have expanded the methods through which we gather and share the stories of groups who have traditionally been written about by others rather than telling their own stories to reveal the complexities of their experiences. There is a long tradition in community arts, community development and social activism that posits personal narratives as the building blocks for public understanding of complex social issues. In the fields of community storytelling, documentary and social activism, it is possible to see an emerging intersection between the affordances of digital technologies and the recognition of the stories of marginalized people. This article is particularly interested in the ways storytellers have repurposed the accepted conventions of transmedia storytelling to create projects that are able to offer a multiplicity of voices and to create stories that can represent complex issues without privileging a particular point of view or story form.
Combined effects of physical inactivity and acute hyperglycemia on arterial distensibility
Authors: Montero David , Dandanell Sune , Oberholzer Laura , Keiser Stefanie , Breenfeldt-Andersen Andreas , Haider Thomas , Merlini Mario , Meinild-Lundby Anne-Kristine , Lundby Carsten
Published: June 2017

Arterial distensibility, an independent predictor of cardiovascular events, is transiently increased with acute hyperglycemia (AHG) in healthy individuals. Whether this response interacts with physical inactivity remains unknown. We examined the effects of short-term bed rest (BR) on the response of carotid artery distensibility (CD) to AHG, and the influence of underlying changes in insulin resistance and blood volume. CD was assessed with ultrasonography before as well as 30 and 120 minutes following ingestion of 75 g of glucose prior to and after 3 days of BR in 15 healthy male volunteers. Plasma insulin/glucose concentrations and blood volumes were concomitantly determined. On day 4 of BR, blood volume was re-established to pre-BR levels by albumin infusion and CD and insulin/glucose concentrations were determined as in the previous experimental days. Basal CD was not affected by BR. AHG increased CD before and after BR but reached a higher peak increment after BR (12% vs 60% at 30 min OGTT, p=0.028). BR also increased the plasma insulin concentration during AHG ( p=0.007). In regression analyses, plasma insulin and glucose concentrations were positively correlated to CD, particularly after BR ( r=0.31, p<0.05). Restoration of the BR-induced loss (5%) in blood volume did not affect the response of CD to AHG. In conclusion, short-term physical inactivity strongly accentuates the initial increase in CD in response to AHG in healthy individuals. This effect is associated with concomitant increases in circulating insulin concentration attributable to early insulin resistance.
Eye Injuries in High School and Collegiate Athletes
Authors: Boden Barry P. , Pierpoint Lauren A. , Boden Rebecca G. , Comstock R. Dawn , Kerr Zachary Y.
Published: June 2017

Background:

Although eye injuries constitute a small percentage of high school and college sports injuries, they have the potential to be permanently debilitating.

Hypothesis:

Eye injury rates will vary by sport, sex, and between the high school and college age groups.

Study Design:

Descriptive epidemiology study.

Level of Evidence:

Level 3.

Methods:

Data from eye injury reports in high school and college athletes were obtained from the National High School Sports-Related Injury Surveillance System, High School Reporting Information Online (HS RIO) database over a 10-year span (2005-2006 through 2014-2015 school years) and the National Collegiate Athletic Association (NCAA) Injury Surveillance Program (ISP) over an 11-year span (2004-2005 through 2014-2015 school years). Injury rates per 100,000 athlete-exposures (AEs), injury rate ratios (RRs), and 95% CIs were calculated. Distributions of eye injuries by diagnosis, mechanism, time loss, and surgery needs were also examined.

Results:

A total of 237 and 273 eye injuries were reported in the HS RIO and the NCAA ISP databases, respectively. The sports with the highest eye injury rates (per 100,000 AEs) for combined high school and college athletes were women’s basketball (2.36), women’s field hockey (2.35), men’s basketball (2.31), and men’s wrestling (2.07). Overall eye injury rates at the high school and college levels were 0.68 and 1.84 per 100,000 AEs, respectively. Eye injury rates were higher in competition than practice in high school (RR, 3.47; 95% CI, 2.69-4.48) and college (RR, 3.13; 95% CI, 2.45-3.99). Most injuries were contusions (high school, 35.9%; college, 33.3%) and due to contact (high school, 89.9%; college, 86.4%). Only a small percentage of injuries resulted in time loss over 21 days (high school, 4.2%; college, 3.0%).

Conclusion:

Eye injury rates and patterns vary by sport, sex, and between the high school and college age groups. Although severe injuries do occur, most eye injuries sustained by high school and college athletes are minor, with limited time loss and full recovery.

Clinical Relevance:

Additional focus needs to be placed on preventing eye injuries at the collegiate level in women’s and men’s basketball, women’s field hockey, and men’s wrestling.
Johann Joseph Oppel (1855) on Geometrical–Optical Illusions: A Translation and Commentary
Authors: Wade Nicholas J. , Todorović Dejan , Phillips David , Lingelbach Bernd
Published: June 2017

The term geometrical–optical illusions was coined by Johann Joseph Oppel (1815–1894) in 1855 in order to distinguish spatial distortions of size and orientation from the broader illusions of the senses. We present a translation of Oppel’s article and a commentary on the material described in it. Oppel did much more than give a name to a class of visual spatial distortions. He examined a variety of figures and phenomena that were precursors of later, named illusions, and attempted to quantify and interpret them.
Combination targeted pulmonary hypertension therapy in the resolution of Dasatinib‐associated pulmonary arterial hypertension
Authors: Jose Arun , Rafei Hind , Ahari Jalil
Published: June 2017

Dasatinib is a small‐molecule tyrosine kinase inhibitor used in the treatment of hematological malignancies. Pulmonary arterial hypertension (PAH) is a rare but known complication. The mainstay of treatment is cessation of Dasatinib, and while clinical improvement is rapid, complete hemodynamic resolution of pulmonary hypertension (PH) still remains exceedingly uncommon. We present a case of Dasatinib‐induced PAH in a woman with chronic myeloid leukemia, who demonstrated rapid and complete clinical and hemodynamic resolution following treatment with combination pulmonary vasodilator therapy using an endothelin receptor antagonist and a phosphodiesterase‐5 inhibitor. This case suggests there may be an association between the use of targeted PH medication in combination and the complete resolution of dasatinib‐associated PAH, but further investigation is required.
Prevalence and risk factors for colorectal adenomas in patients with ulcerative colitis
Authors: Gordillo Jordi , Zabana Yamile , Garcia‐Planella Esther , Mañosa Míriam , Llaó Jordina , Gich Ignasi , Marín Laura , Szafranska Justyna , Sáinz Sergio , Bessa Xavier , Cabré Eduard , Domènech Eugeni
Published: June 2017

Background

Patients with ulcerative colitis (UC) have an increased risk of colorectal cancer. Scarce data regarding the development of adenomas in these patients are available both for normal and colitic mucosa.

Objective

The objective of this article is to evaluate the prevalence of adenomatous polyps and associated risk factors in patients with UC.

Methods

Patients with UC were identified from the databases of two tertiary referral centers. Medical, endoscopic and histologic reports were reviewed.

Results

A total of 403 patients were included (53% male; 33% extensive colitis) and 1065 colonoscopies (median per patient, 2) were recorded and analyzed. Seventy‐four adenomas in 47 patients (11.7%) and three cases of colorectal cancer were found during a median follow‐up of 6.3 years. The cumulative risk of colorectal adenoma was 4.7%, 16.7%, 23.6% and 34.4% at 10, 20, 30 and 40 years from UC diagnosis, respectively. The cumulative risk of developing metachronous colorectal adenoma was 66.7%, 87.9%, and 90.9% at 5, 10, and 15 years from first adenoma detection. Older age at UC diagnosis and longer disease duration were independent risk factors for colorectal adenoma development.

Conclusions

The prevalence of colorectal adenomas among UC patients seems to be higher than previously reported, although lower than in the background population.
Provider Advice About Weight Loss in a Primary Care Sample of Obese and Overweight Patients
Authors: Halbert Chanita Hughes , Jefferson Melanie , Melvin Cathy L. , Rice LaShanta , Chukwuka Kemi M.
Published: June 2017

Objective: Primary care providers play an important role in obesity prevention and reduction by advising patients about weight loss strategies. This study examined receipt of provider advice to lose weight among primary care patients who were overweight and obese. Methods: Observational study conducted among primary care patients (n = 282) who completed a survey that measured receipt of provider advice about weight loss/management, chronic health conditions, perceived weight status, and perceptions about shared decision making about weight loss/management. Results: Fifty-nine percent of participants had been advised by their physician to lose weight. Participants who were obese were more likely than those who were overweight to report provider advice (odds ratio [OR] = 1.31, 95% CI = 1.25-4.34, P = .001). Similarly, participants who believed they were obese/overweight had a greater likelihood of reporting provider advice compared with those who did not believe they were obese/overweight (OR = 1.40, 95% CI = 2.43-6.37, P = .0001). Shared decision making about weight loss/management was associated with an increased likelihood of reporting provider advice (OR = 3.30, 95% CI = 2.62-4.12, P = .0001). Conclusions: Patient beliefs about their weight status and perceptions about shared decision-making are important to receiving provider advice about weight loss/management among primary care patients. Practice Implications: Continued efforts are needed to enhance provider advice about weight loss/management among obese/overweight patients.