bluuebunny/crossref_metadata_2025 huggingface dataset:
Social Media Adoption in Business-to-Business: IT and Industrial Companies Compared
Authors: Veldeman Céline , Van Praet Ellen , Mechant Peter
Published: February 2015

This article investigates Belgian business-to-business (B2B) companies’ perceptions of and attitudes toward social media, matching the findings with existing U.S., U.K., and Dutch research. Using survey data from a nonrepresentative judgment sample of 92 Belgian B2B companies, we show that 85.9% of Belgian B2B companies that participated in our research use social media to ensure their influence on target groups. The survey also reveals that 40.8% of IT companies implement a social media strategy against only 26.7% of industrial B2B companies. Relying on the technology acceptance model, we argue that IT companies are more inclined to adopt social media because they evaluate social media’s usefulness higher than industrial enterprises. Qualitative follow-up research (in-depth interviews with 11 B2B enterprises) further explains the observed differences and similarities between both sectors, analyzing perceived benefits and risks, social media knowledge, and strategies. We conclude the article by listing various suggested actions that can help B2B companies effectively leverage social media.
Midline Ectopic Thyroid Mimicking as a Thyroglossal Duct Cyst
Authors: Popli Manju Bala , Chaudhary Arun , Imam Nayer
Published: February 2015

Ectopic thyroid tissue is a rare developmental abnormality. A case is reported here of ectopic thyroid tissue that presented as a midline mass, mimicking a thyroglossal duct cyst. The thyroid gland was not visualized in its normal position. This report highlights the importance of imaging in the preoperative evaluation of a midline neck mass.
At the Heart of the Matter
Authors: Mayer Pamela
Published: February 2015

Echocardiography is an excellent method for evaluating cardiac morphology and dynamic function. It has a long history of innovative thinking mixed with some degree of serendipity. Its early applications were as a tool to evaluate the mitral valve, left ventricular characteristics, and pericardial effusion. Today it has evolved into a robust modality that allows for a very wide range cardiac interrogation, able to evaluate the valves, chambers, myocardium, and pericardium. The practice of echocardiography also is often separate from that of general or vascular sonography. The objective of this article is to provide the non–cardiac sonographer with an overview and appreciation of the basic principles and practices of echocardiography. It is not meant as a guide to scanning but rather, as a vehicle to spark the interest and imagination of the reader.
Sterno Clavicular Joint Osteoarthritis in a Patient With Rheumatoid Arthritis
Authors: Mondal Sumantro , Sinha Debanjali , Nag Arijit , Chakraborty Atanu , Ete Tony , Ghosh Alakendu
Published: February 2015

Osteoarthritis of the sternoclavicular joint (SCJ) is a common entity. Plain radiographs and computed tomographic scans are the modalities commonly used for diagnosis of SCJ osteoarthritis. Classical imaging findings are joint space narrowing, marginal sclerosis, and osteophyte formation. Widespread application of ultrasonography (US) in the evaluation of multiple musculoskeletal pathologies has been made recently. However, the sonographic features of SCJ osteoarthritis have not been reported. We report a case of unilateral SCJ osteoarthritis in a patient with rheumatoid arthritis (RA) and describe its typical sonographic features.
An Overview of Small Animal Veterinary Sonography
Authors: Albury Kelly
Published: February 2015

This article is an overview of the field of small animal veterinary sonography, including its history, examples of utilization, and a brief review of the small animal abdominal sonographic examination that includes images of normal examples and typical pathology.
von Willebrand factor biosynthesis, secretion, and clearance: connecting the far ends
Authors: Lenting Peter J. , Christophe Olivier D. , Denis Cécile V.
Published: February 2015

To understand the placement of a certain protein in a physiological system and the pathogenesis of related disorders, it is not only of interest to determine its function but also important to describe the sequential steps in its life cycle, from synthesis to secretion and ultimately its clearance. von Willebrand factor (VWF) is a particularly intriguing case in this regard because of its important auxiliary roles (both intra- and extracellular) that implicate a wide range of other proteins: its presence is required for the formation and regulated release of endothelial storage organelles, the Weibel-Palade bodies (WPBs), whereas VWF is also a key determinant in the clearance of coagulation factor VIII. Thus, understanding the molecular and cellular basis of the VWF life cycle will help us gain insight into the pathogenesis of von Willebrand disease, design alternative treatment options to prolong the factor VIII half-life, and delineate the role of VWF and coresidents of the WPBs in the prothrombotic and proinflammatory response of endothelial cells. In this review, an update on our current knowledge on VWF biosynthesis, secretion, and clearance is provided and we will discuss how they can be affected by the presence of protein defects.
Rare bleeding disorders: diagnosis and treatment
Authors: Palla Roberta , Peyvandi Flora , Shapiro Amy D.
Published: February 2015

Despite the worldwide prevalence of rare bleeding disorders (RBDs), knowledge of these conditions and their management is suboptimal; health care professionals often have little diagnostic and treatment experience with variable access to diagnostic modalities required for accurate identification. Therefore, patients often experience morbidity and mortality due to delayed diagnosis. As RBDs represent a small potential commercial market, few, if any, specific therapies exist for these conditions. As a result, affected individuals commonly face delayed diagnosis, incomplete laboratory evaluation, and limited treatment options. Standardization and customization of coagulation assays, full genome sequencing, and global clotting assays will significantly improve diagnosis of patients with RBDs. In addition, new therapeutic modalities, both recombinant and plasma derived, are emerging, at least in developed countries. Registries and clinical trials have demonstrated decreased bleeding and improved outcomes when patients are appropriately diagnosed and properly treated. Expansion and harmonization of international registries has been initiated to correlate genotype, laboratory, and clinical phenotypes including bleeding severity to improve the diagnosis and therapeutic approach. This review focuses on the latest advances in our understanding, diagnosis, and treatment of RBDs.
FVIII inhibitors: pathogenesis and avoidance
Authors: Astermark Jan
Published: February 2015

The pathogenesis of inhibitory antibodies has been the focus of major scientific interest over the last decades, and several studies on underlying immune mechanisms and risk factors for formation of these antibodies have been performed with the aim of improving the ability to both predict and prevent their appearance. It seems clear that the decisive factors for the immune response to the deficient factor are multiple and involve components of both a constitutional and therapy-related nature. A scientific concern and obstacle for research in the area of hemophilia is the relatively small cohorts available for studies and the resulting risk of confounded and biased results. Careful interpretation of data is recommended to avoid treatment decisions based on a weak scientific platform. This review will summarize current concepts of the underlying immunological mechanisms and risk factors for development of inhibitory antibodies in patients with hemophilia A and discuss how these findings may be interpreted and influence our clinical management of patients.
Aberrant TCRδ rearrangement underlies the T-cell lymphocytopenia and t(12;14) translocation associated with ATM deficiency
Authors: Jiang Wenxia , Lee Brian J. , Li Chen , Dubois Richard L. , Gostissa Monica , Alt Frederick W. , Zha Shan
Published: February 2015

Key Points

ATM-deficient T-cell lymphocytopenia is in part caused by defects in TCRδ rearrangements. Aberrant TCRδ arrangement is required for the recurrent t(12;14) translocations, but not chromosome 14 amplification, in ATM-deficient thymic lymphomas.
The Sweden Cancerome Analysis Network - Breast (SCAN-B) Initiative: a large-scale multicenter infrastructure towards implementation of breast cancer genomic analyses in the clinical routine
Authors: Saal Lao H , Vallon-Christersson Johan , Häkkinen Jari , Hegardt Cecilia , Grabau Dorthe , Winter Christof , Brueffer Christian , Tang Man-Hung Eric , Reuterswärd Christel , Schulz Ralph , Karlsson Anna , Ehinger Anna , Malina Janne , Manjer Jonas , Malmberg Martin , Larsson Christer , Rydén Lisa , Loman Niklas , Borg Åke
Published: February 2015

Background

Breast cancer exhibits significant molecular, pathological, and clinical heterogeneity. Current clinicopathological evaluation is imperfect for predicting outcome, which results in overtreatment for many patients, and for others, leads to death from recurrent disease. Therefore, additional criteria are needed to better personalize care and maximize treatment effectiveness and survival.

Methods

To address these challenges, the Sweden Cancerome Analysis Network - Breast (SCAN-B) consortium was initiated in 2010 as a multicenter prospective study with longsighted aims to analyze breast cancers with next-generation genomic technologies for translational research in a population-based manner and integrated with healthcare; decipher fundamental tumor biology from these analyses; utilize genomic data to develop and validate new clinically-actionable biomarker assays; and establish real-time clinical implementation of molecular diagnostic, prognostic, and predictive tests. In the first phase, we focus on molecular profiling by next-generation RNA-sequencing on the Illumina platform.

Results

In the first 3 years from 30 August 2010 through 31 August 2013, we have consented and enrolled 3,979 patients with primary breast cancer at the seven hospital sites in South Sweden, representing approximately 85% of eligible patients in the catchment area. Preoperative blood samples have been collected for 3,942 (99%) patients and primary tumor specimens collected for 2,929 (74%) patients. Herein we describe the study infrastructure and protocols and present initial proof of concept results from prospective RNA sequencing including tumor molecular subtyping and detection of driver gene mutations. Prospective patient enrollment is ongoing.

Conclusions

We demonstrate that large-scale population-based collection and RNA-sequencing analysis of breast cancer is feasible. The SCAN-B Initiative should significantly reduce the time to discovery, validation, and clinical implementation of novel molecular diagnostic and predictive tests. We welcome the participation of additional comprehensive cancer treatment centers.

Trial registration

ClinicalTrials.gov identifier NCT02306096.
Clinical and imaging features of mixed Alzheimer and vascular pathologies
Authors: Chui Helena C , Ramirez-Gomez Liliana
Published: February 2015

The co-occurrence of both Alzheimer disease (AD) pathology and vascular brain injury (VBI) is very common, especially amongst the oldest of old. In neuropathologic studies, the prevalence of AD, VBI, and mixed AD/VBI lesions ranks ahead of Lewy bodies and hippocampal sclerosis. In the modern era of structural magnetic resonance imaging (MRI) and amyloid positron emission tomography (PET) imaging, this review examines 1) the prevalence of mixed AD and VBI pathology, 2) the significance of these pathologies for cognitive impairment (AD and vascular cognitive impairment (VCI)), and 3) the diagnosis and treatment of mixed AD/VCI. Although epidemiologic studies report that vascular risk factors for arteriosclerosis increase the risk of incident AD, both autopsy and amyloid PET studies indicate that AD and VBI contribute additively, but independently, to the risk of dementia. The literature confirms the malignancy of AD and highlights the adverse effects of microinfarcts on cognitive function. For the clinical diagnosis of mixed AD/VCI, the presence of AD can be recognized by neuropsychological profile, structural imaging, cerebrospinal fluid biomarkers, and glucose PET and amyloid PET imaging. The diagnosis of VBI, however, still hinges predominantly on the structural MRI findings. Severe amnesia and atrophy of the hippocampus are characteristic of early AD, whereas the cognitive profile for VCI is highly variable and dependent on size and location of VBI. The cognitive profile of mixed AD/VBI is dominated by AD. With the notable exception of microinfarcts (which elude in vivo detection), infarcts, hemorrhages, and white matter hyperintensities on structural MRI currently represent the best markers for the presence VBI. Better markers that reflect the health and reactivity of intracerebral blood vessels are needed. For prevention and treatment, the type of underlying cerebrovascular disease (for example, arteriosclerosis or cerebral amyloid angiopathy) should be considered. It is likely that reduction of vascular risk factors for arteriosclerosis can significantly reduce vascular contributions to mixed dementia.
Granulosa cell-derived induced pluripotent stem cells exhibit pro-trophoblastic differentiation potential
Authors: Chuang Ching-Yu , Huang Mei-Chi , Chen Hsin-Fu , Tseng Li-Hui , Yu Chun-Ying , Stone Lee , Huang Hsiang-Po , Ho Hong-Nerng , Kuo Hung-Chih
Published: February 2015

Introduction

Human induced pluripotent stem cells (hiPSCs) have been derived from various somatic cell types. Granulosa cells, a group of cells which surround oocytes and are obtained from the (normally discarded) retrieved egg follicles of women undergoing infertility treatment, are a possible cell source for induced pluripotent stem cell (iPSC) generation. Here, we explored the possibility of using human granulosa cells as a donor cell type for iPSC reprogramming, and compared granulosa cell-derived iPSCs (iGRAs) with those derived from other cell sources, to determine the potential ability of iGRA differentiation.

Methods

Granulosa cells were collected from egg follicles retrieved from women undergoing infertility treatment. After short-term culture, the granulosa cells derived from different patients were mixed in culture, and infected with retroviruses encoding reprogramming factors. The resulting iPSC clones were selected and subjected to microsatellite DNA analysis to determine their parental origin. IGRAs were subjected to RT-PCR, immunofluorescence staining, and in vitro and in vivo differentiation assays to further establish their pluripotent characteristics.

Results

Microsatellite DNA analysis was used to demonstrate that hiPSCs with different parental origins can be simultaneously reprogrammed by retroviral transfection of a mixed human granulosa cell population obtained from multiple individuals. The iGRAs resemble human embryonic stem cells (hESCs) in many respects, including morphological traits, growth requirements, gene and marker expression profiles, and in vitro and in vivo developmental propensities. We also demonstrate that the iGRAs express low levels of NLRP2, and differentiating iGRAs possess a biased differentiation potential toward the trophoblastic lineage. Although NLRP2 knockdown in hESCs promotes trophoblastic differentiation of differentiating hESCs, it does not result in exit from pluripotency. These results imply that NLRP2 may play a role in regulating the trophoblastic differentiation of human pluripotent stem cells.

Conclusions

These findings provide a means of generating iPSCs from multiple granulosa cell populations with different parental origins. The ability to generate iPSCs from granulosa cells not only enables modeling of infertility-associated disease, but also provides a means of identifying potential clinical interventions through iPSC-based drug screening.
Evaluation of the applicability of the Immuno‐solid‐phase allergen chip (ISAC) assay in atopic patients in Singapore
Authors: Santosa Amelia , Andiappan Anand Kumar , Rotzschke Olaf , Wong Hung Chew , Chang Amanda , Bigliardi‐Qi Mei , Wang De‐Yun , Bigliardi Paul Lorenz
Published: February 2015

Background/Objective

Molecular‐based allergy diagnostics are gaining popularity in clinical practice. Our aim was to evaluate their role in the tropics, given the inherent genetic and environmental differences.

Methods

We recruited subjects with history of atopy and collected data on demographics and atopic symptoms using validated questionnaires. Subjects underwent a series of skin prick tests (SPT). Serum total and specific IgE levels were measured using ImmunoCAP FEIA and ImmunoCAP ISAC®, respectively. We describe their pattern of sensitization and agreement between test methods.

Results

A total of 135 subjects were recruited; mean ± SD age of 31.18 ± 12.72 years, 52.7% female. Allergic rhinitis (AR) was the most prevalent clinical manifestation of atopy (70.7%), followed by atopic dermatitis (AD) (50.5%) and asthma (26.2%). Polysensitization was seen in 51.1% of subjects by both SPT and ISAC. House dust mites (HDM) were the dominant allergen, with sensitization in 67.8% and 62% of subjects on SPT and ISAC, respectively. A group of subjects with monosensitization to B. tropicalis was identified. HDM sensitization was strongly associated with AR, while AD and asthma were not associated with sensitization to any allergen. Agreement between SPT and ISAC was mostly suboptimal. Greatest agreement was documented for the measurement of HDM sensitization with both methods (κ = 0.64). Sensitization to the bulk of the remaining allergens in the ISAC panel was infrequent.

Conclusion

Multiplex methods should not be used as a screening tool, especially in a population with lower rates of polysensitization and a dominant sensitizing allergen. There may be a role in adjusting the antigen spectrum in the ISAC panel to regional differences.
An approach version of fuzzy metric spaces including an ad hoc fixed point theorem
Authors: Roldán-López-de-Hierro Antonio-Francisco , de la Sen Manuel , Martínez-Moreno Juan , Roldán-López-de-Hierro Concepción
Published: February 2015

In this paper, inspired by two very different, successful metric theories such us the real view-point of Lowen’sapproach spacesand the probabilistic field of Kramosil and Michálek’sfuzzy metric spaces, we present a family of spaces, calledfuzzy approach spaces, that are appropriate to handle, at the same time, both measure conceptions. To do that, we study the underlying metric interrelationships between the above mentioned theories, obtaining six postulates that allow us to consider such kind of spaces in a unique category. As a result, the natural way in which metric spaces can be embedded in both classes leads to a commutative categorical scheme. Each postulate is interpreted in the context of the study of the evolution of fuzzy systems. First properties of fuzzy approach spaces are introduced, including a topology. Finally, we describe a fixed point theorem in the setting of fuzzy approach spaces that can be particularized to the previous existing measure spaces.
Convergence theorems for split equality mixed equilibrium problems with applications
Authors: Ma Zhaoli , Wang Lin , Chang Shih-sen , Duan Wen
Published: February 2015

In this paper, we introduce a new algorithm for solving split equality mixed equilibrium problems in the framework of infinite-dimensional real Hilbert spaces. The strong and weak convergence theorems are obtained. As application, we shall utilize our results to study the split equality mixed variational inequality problem and the split equality convex minimization problem. Our results presented in this paper improve and extend some recent corresponding results.
Parasympathetic reactivation after maximal CPET depends on exercise modality and resting vagal activity in healthy men
Authors: Cunha Felipe A , Midgley Adrian W , Gonçalves Thiago , Soares Pedro P , Farinatti Paulo
Published: February 2015

Purpose

The main purpose of this study was to investigate parasympathetic reactivation of the heart [evaluated through heart rate recovery (HRR) and HR variability (HRV)] after maximal cardiopulmonary exercise testing (CPET) using three different exercise modalities.

Methods

Twenty healthy men, aged 17 to 28 yr, performed three maximal CPETs (cycling, walking, and running) separated by 72 h and in a randomized, counter-balanced order. HRR was determined from the absolute differences between HRpeak and HR at 1–3 min after exercise. The root mean square of successive R-R differences calculated for consecutive 30-s windows (rMSSD30s) was calculated to assess the parasympathetic reactivation after maximal CPET.

Results

Lower HRpeak, VO2peak and energy expenditure were observed after the cycling CPET than the walking and running CPETs (P < 0.001). Both HRR and rMSSD30s were significantly greater during recovery from the cycling CPET compared to the walking and running CPETs (P < 0.001). Furthermore, Δ rMSSD (i.e. resting minus postexercise rMSSD every 30 s into the recovery period) was positively related to the resting high-frequency component (HF), rMSSD, and standard deviation of all normal R-R intervals (SDNN) (rs = 0.89 to 0.98; P < 0.001), and negatively related to the resting low-frequency component (LF) and sympathovagal balance (LF:HF ratio) after all exercise conditions (rs = −0.73 to −0.79 and −0.86 to −0.90, respectively; P < 0.001).

Conclusions

These findings support that parasympathetic reactivation after maximal CPET (as assessed by HRR and rMSSD30s) depends on exercise modality and cardiac autonomic control at rest.
The role of chitin, chitinases, and chitinase-like proteins in pediatric lung diseases
Authors: Mack Ines , Hector Andreas , Ballbach Marlene , Kohlhäufl Julius , Fuchs Katharina J , Weber Alexander , Mall Marcus A , Hartl Dominik
Published: February 2015

Chitin, after cellulose, the second most abundant biopolymer on earth, is a key component of insects, fungi, and house-dust mites. Lower life forms are endowed with chitinases to defend themselves against chitin-bearing pathogens. Unexpectedly, humans were also found to express chitinases as well as chitinase-like proteins that modulate immune responses. Particularly, increased levels of the chitinase-like protein YKL-40 have been associated with severe asthma, cystic fibrosis, and other inflammatory disease conditions. Here, we summarize and discuss the potential role of chitin, chitinases, and chitinase-like proteins in pediatric lung diseases.
Cytokine-induced monocyte MMP-1 is negatively regulated by GSK-3 through a p38 MAPK-mediated decrease in ERK1/2 MAPK activation
Authors: Zhang Yahong , Wahl Larry M
Published: February 2015

Elucidation of the signal transduction events leading to the production of MMPs by monocytes/macrophages may provide insights into the mechanisms involved in the destruction of connective tissue associated with chronic inflammatory lesions. Here, we show that GSK-3 is a negative regulator of cytokine-induced MMP-1 production by monocytes. Inhibition of monocyte GSK-3 pharmacologically with SB216763 or GSK-3β siRNA caused a significant enhancement of MMP-1 by TNF-α− and GM-CSF-activated monocytes, indicating that induction of MMP-1 by TNF-α and GM-CSF involved phosphorylation/inactivation of GSK-3. TNF-α- and GM-CSF-induced phosphorylation of GSK-3 and subsequent MMP-1 production was blocked with the PKC inhibitor Gö6976 but not by the AKT1/2 inhibitor AKT VIII, showing that cytokine phosphorylation of GSK-3 occurs primarily through a PKC pathway. Inhibition of GSK-3 resulted in decreased phosphorylation of p38 MAPK with a corresponding increase in phosphorylation of ERK1/2 MAPK. Enhanced MMP-1 production by treatment with SB216763 was a result of increased ERK1/2 activation, as demonstrated by inhibition of MMP-1 by PD98059, a specific ERK1/2 inhibitor. Conversely, the p38 MAPK inhibitor SB203580 enhanced cytokine activation of ERK1/2 and the production of MMP-1 similar to that of SB216763. These findings demonstrate that the degree of cytokine-mediated phosphorylation/inhibition of GSK-3 determines the level of MMP-1 production through a mechanism involving decreased activation of p38 MAPK, a negative regulator of ERK1/2 required for cytokine-induced production of MMP-1 by monocytes.
Triple-Modality Screening Trial for Familial Breast Cancer Underlines the Importance of Magnetic Resonance Imaging and Questions the Role of Mammography and Ultrasound Regardless of Patient Mutation Status, Age, and Breast Density
Authors: Riedl Christopher C. , Luft Nikolaus , Bernhart Clemens , Weber Michael , Bernathova Maria , Tea Muy-Kheng M. , Rudas Margaretha , Singer Christian F. , Helbich Thomas H.
Published: February 2015

Purpose

To evaluate the breast cancer screening efficacy of mammography, ultrasound, and magnetic resonance imaging (MRI) in a high-risk population and in various population subgroups.

Patients and Methods

In a single-center, prospective, nonrandomized comparison study, BRCA mutation carriers and women with a high familial risk (> 20% lifetime risk) for breast cancer were offered screening with mammography, ultrasound, and MRI every 12 months. Diagnostic performance was compared between individual modalities and their combinations. Further comparisons were based on subpopulations dichotomized by screening rounds, mutation status, age, and breast density.

Results

There were 559 women with 1,365 complete imaging rounds included in this study. The sensitivity of MRI (90.0%) was significantly higher (P < .001) than that of mammography (37.5%) and ultrasound (37.5%). Of 40 cancers, 18 (45.0%) were detected by MRI alone. Two cancers were found by mammography alone (a ductal carcinoma in situ [DCIS] with microinvasion and a DCIS with < 10-mm invasive areas). This did not lead to a significant increase of sensitivity compared with using MRI alone (P = .15). No cancers were detected by ultrasound alone. Similarly, of 14 DCISs, all were detected by MRI, whereas mammography and ultrasound each detected five DCISs (35.7%). Age, mutation status, and breast density had no influence on the sensitivity of MRI and did not affect the superiority of MRI over mammography and ultrasound.

Conclusion

MRI allows early detection of familial breast cancer regardless of patient age, breast density, or risk status. The added value of mammography is limited, and there is no added value of ultrasound in women undergoing MRI for screening.
Psychosocial Distress Screening Implementation in Cancer Care: An Analysis of Adherence, Responsiveness, and Acceptability
Authors: Zebrack Brad , Kayser Karen , Sundstrom Laura , Savas Sue Ann , Henrickson Chris , Acquati Chiara , Tamas Rebecca L.
Published: February 2015

Purpose

The American College of Surgeons Commission on Cancer has mandated implementation of a systematic protocol for psychosocial distress screening and referral as a condition for cancer center accreditation beginning in 2015. Compliance with standards requires evidence that distress screening protocols are carried out as intended and result in appropriate referral and follow-up when indicated. The purpose of this study was to examine the fidelity of distress screening protocols at two tertiary cancer treatment centers.

Methods

A retrospective review and analysis of electronic medical records over a 12-week period examined clinic adherence to a prescribed distress screening protocol and responsiveness to patients whose scores on the National Comprehensive Cancer Network Distress Thermometer (DT) indicated clinically significant levels of distress requiring subsequent psychosocial contact. A weekly online survey assessed clinician perspectives on the acceptability of the protocol.

Results

Across clinics, rates of adherence to the distress screening protocol ranged from 47% to 73% of eligible patients. For patients indicating clinically significant distress (DT score ≥ 4), documentation of psychosocial contact or referral occurred, on average, 50% to 63% of the time, and was more likely to occur at one of two participating institutions when DT scores were high (DT score of 8 to 10). Clinician assessments of the protocol's utility in addressing patient concerns and responding to patient needs were generally positive.

Conclusion

Systematic tracking of distress screening protocols is needed to demonstrate compliance with new standards of care and to demonstrate how well institutions are responding to their clinical obligation to address cancer patients' emotional and psychosocial needs.
Availability of Outpatient Clinical Nutrition Services for Patients With Cancer Undergoing Treatment at Comprehensive Cancer Centers
Authors: Platek Mary E. , Johnson Jordan , Woolf Kathleen , Makarem Nour , Ompad Danielle C.
Published: February 2015

Comprehensive cancer centers rely on referral-based clinical nutrition services, which are not always a part of multidisciplinary care. An in-depth comparison of clinical nutrition services among other approaches to cancer care is needed.
Establishment of a Regional Virtual Tumor Board Program to Improve the Process of Care for Patients With Hepatocellular Carcinoma
Authors: Salami Aitua C. , Barden Gala M. , Castillo Diana L. , Hanna Mina , Petersen Nancy J. , Davila Jessica A. , Naik Aanand D. , Anaya Daniel A.
Published: February 2015

A VTB program positively affected the process of care for patients with HCC by improving the quality and timeliness of the multidisciplinary evaluation process.
Mobile Mammography, Race, and Insurance: Use Trends Over a Decade at a Comprehensive Urban Cancer Center
Authors: Mizuguchi Sarah , Barkley Laura , Rai Shesh , Pan Jianmin , Roland Lane , Crawford Stacey , Riley Elizabeth C.
Published: February 2015

Although preliminary, these data suggest outreach efforts of mobile mammography are appropriately reaching certain targeted populations.
Financial Burden of Pediatric Cancer for Patients and Their Families
Authors: Warner Echo L. , Kirchhoff Anne C. , Nam Gina E. , Fluchel Mark
Published: February 2015

Efforts to reduce unexpected hospitalizations and employment disruptions by providing more comprehensive supportive care for pediatric patients with cancer could help ease families' financial burden.
Assessing the Development of Multidisciplinary Care: Experience of the National Cancer Institute Community Cancer Centers Program
Authors: Friedman Eliot L. , Chawla Neetu , Morris Paul T. , Castro Kathleen M. , Carrigan Angela C. , Das Irene Prabhu , Clauser Steven B.
Published: February 2015

This work provides a blueprint for health systems wishing to incorporate prospective multidisciplinary care into their cancer programs.
Survey of Patients Referred to a University Cancer Center for Benign Hematology: Quality Measures and Patient Understanding
Authors: Khimani Farhad , Curley Brendan , Almubarak Mohammed
Published: February 2015

Referral to outpatient clinics in a cancer center for benign hematologic diseases seems to increase psychological stress and anxiety among patients, who may perceive that they are being referred for evaluation of a cancer diagnosis.
Expanding the Scope of the National Practice Oncology Benchmark Would Be a Critical Source for Understanding Outpatient Oncology Practice Costs and Profits in a Time of Change
Authors: Conti Rena M.
Published: February 2015

Expanding the scope of National Practice Oncology Benchmark reporting would be critical for assessing practice-level effects of imminent national policies to improve the quality of cancer care and control costs.
Palliative Radiation Therapy for the Hospice Patient: Nuances of Care and Reimbursement
Authors: Meyers Deborah S.
Published: February 2015

The author applauds the creation of a palliative radiation program for hospice patients in their community, and says physicians can do a better job of guiding patients to hospice earlier.
Chronic Activation of FXR in Transgenic Mice Caused Perinatal Toxicity and Sensitized Mice to Cholesterol Toxicity
Authors: Cheng Qiuqiong , Inaba Yuka , Lu Peipei , Xu Meishu , He Jinhan , Zhao Yueshui , Guo Grace L. , Kuruba Ramalinga , de la Vega Rona , Evans Rhobert W. , Li Song , Xie Wen
Published: February 2015

The nuclear receptor farnesoid X receptor (FXR) (nuclear receptor subfamily 1, group H, member 4, or NR1H4) is highly expressed in the liver and intestine. Previous reports have suggested beneficial functions of FXR in the homeostasis of bile acids, lipids, and glucose, as well as in promoting liver regeneration and inhibiting carcinogenesis. To investigate the effect of chronic FXR activation in vivo, we generated transgenic mice that conditionally and tissue specifically express the activated form of FXR in the liver and intestine. Unexpectedly, the transgenic mice showed several intriguing phenotypes, including partial neonatal lethality, growth retardation, and spontaneous liver toxicity. The transgenic mice also displayed heightened sensitivity to a high-cholesterol diet-induced hepatotoxicity but resistance to the gallstone formation. The phenotypes were transgene specific, because they were abolished upon treatment with doxycycline to silence the transgene expression. The perinatal toxicity, which can be rescued by a maternal vitamin supplement, may have resulted from vitamin deficiency due to low biliary bile acid output as a consequence of inhibition of bile acid formation. Our results also suggested that the fibroblast growth factor-inducible immediate-early response protein 14 (Fn14), a member of the proinflammatory TNF family, is a FXR-responsive gene. However, the contribution of Fn14 induction in the perinatal toxic phenotype of the transgenic mice remains to be defined. Because FXR is being explored as a therapeutic target, our results suggested that a chronic activation of this nuclear receptor may have an unintended side effect especially during the perinatal stage.
The putative tumor suppressor geneEphA3fails to demonstrate a crucial role in murine lung tumorigenesis or morphogenesis
Authors: Lahtela Jenni , Pradhan Barun , Närhi Katja , Hemmes Annabrita , Särkioja Merja , Kovanen Panu E. , Brown Arthur , Verschuren Emmy W.
Published: February 2015

Treatment of non-small cell lung cancer (NSCLC) is based on histological analysis and molecular profiling of targetable driver oncogenes. Therapeutic responses are further defined by the landscape of passenger mutations, or loss of tumor suppressor genes. We report here a thorough study to address the physiological role of the putative lung cancer tumor suppressor EPHA3, a gene that is frequently mutated in human lung adenocarcinomas. Our data shows that homozygous or heterozygous loss of EphA3 does not alter the progression of mutant Kras- or loss of Trp53-driven murine adenocarcinomas. Moreover, consistent with the previous reports of the roles of EPH receptors in embryonic development, we find that in contrary to the low postnatal expression of EphA3 in adult mouse, EphA3 is detected in the distal mesenchyme of developing mouse lung, opposing the epithelial expression of its ephrin-A1 ligand. However, the partial loss of EphA3 leads only to subtle changes in epithelial Nkx2-1, endothelial Cd31 and mesenchymal Fgf10 RNA expression levels, and no macroscopic phenotypic effect on lung epithelial branching, mesenchymal cell proliferation, or abundance and localization of CD31-positive endothelia is measured. The lack of a discernible lung phenotype in EphA3 null mice may indicate lack of an overt role for EPHA3 in the murine lung, or imply functional redundancy between lung-expressed EPHA receptors. Moreover, our study shows how biological complexity can challenge in vivo functional validation of mutations identified in sequencing efforts, and provides an incentive for the design of knock-in or conditional models to assign the role of EPHA3 mutation during lung tumorigenesis.
MicroRNA regulation of p21 and TASK1 cellular restriction-factors enhances HIV-1 infection
Authors: Farberov Luba , Herzig Eytan , Modai Shira , Isakov Ofer , Hizi Amnon , Shomron Noam
Published: February 2015

MicroRNAs are short non-coding RNAs that play a central role in regulation of gene-expression by binding to target-gene mRNAs. Several studies have revealed alterations in cellular-miRNA profiles following HIV-1 infection, mostly inhibiting viral-infection. These miRNA expression modifications may also serve to block the innate HIV-1 inhibition mechanism. As a result, it is expected that during HIV-1 infection miRNAs target genes that hinder or prevent the progression of different steps in the HIV-1 replication cycle.

One of the major sets of genes known to inhibit the progression of HIV infection are cellular restriction factors. In this study, we identified a direct miRNA-target gene, which modulates viral spread in T-lymphocytes and HeLa-CCR5 cell-lines. Following infection, let-7c/miR-34a/miR-124a were up-regulated, which targeted and thus down-regulated p21 and TASK1 cellular proteins. This eventually led to increased virion release, and higher copy number of viral genome-transcripts in infected cells. Conversely, by down-regulating these miRNAs, we were able to suppress viral-replication and spread. Our data suggest that HIV-1 exploits the host miRNAs' cellular systems in order to block the innate-inhibition mechanism, allowing a more efficient infection process.
An active role for basement membrane assembly and modification in tissue sculpting
Authors: Morrissey Meghan A. , Sherwood David R.
Published: February 2015

Basement membranes are a dense, sheet-like form of extracellular matrix (ECM) that underlie epithelia and endothelia, and surround muscle, fat and Schwann cells. Basement membranes separate tissues and protect them from mechanical stress. Although traditionally thought of as a static support structure, a growing body of evidence suggests that dynamic basement membrane deposition and modification instructs coordinated cellular behaviors and acts mechanically to sculpt tissues. In this Commentary, we highlight recent studies that support the idea that far from being a passive matrix, basement membranes play formative roles in shaping tissues.
Adhesive pad differentiation in Drosophila melanogaster depends on the Polycomb group gene Su(z)2
Authors: Hüsken M. , Hufnagel K. , Mende K. , Appel E. , Meyer H. , Peisker H. , Tögel M. , Wang S. , Wolff J. , Gorb S.N. , Paululat A.
Published: February 2015

The ability of many insects to walk on vertical smooth surfaces such as glass or even on the ceiling has fascinated biologists for ages and has led to the discovery of highly specialized adhesive organs located at the distal end of the animals' legs. So far, research has primarily focused on structural and ultrastructural investigations leading to a deeper understanding of adhesive organ functionality and to the development of new bioinspired materials. Genetic approaches, e.g. the analysis of mutants, to achieve a better understanding of adhesive organ differentiation, have not been used so far. Here, we describe the first Drosophila melanogaster mutant that develops malformed adhesive organs, resulting in a complete loss of climbing ability on vertical smooth surfaces. Interestingly, these mutants fail to make close contact between the setal tips and the smooth surface, a crucial condition for wet adhesion mediated by capillary forces. Instead, these flies walk solely on their claws. Moreover, we were able to show that the mutation is caused by a P-element insertion into the Su(z)2 gene locus. Remobilization of the P-element restores climbing ability. Furthermore, we provide evidence that the P-element insertion results in an artificial Su(z)2 transcript, which most likely causes a gain of function mutation. We presume that this transcript causes deregulation of yet unknown target genes involved in pulvilli differentiation. Our results nicely demonstrate that the genetically treatable model organism Drosophila is highly suitable for future investigations on adhesive organ differentiation.
Larval nervous systems: true larval and precocious adult
Authors: Nielsen Claus
Published: February 2015

The apical organ of ciliated larvae of cnidarians and bilaterians is a true larval organ that disappears before or at metamorphosis. It appears to be sensory, probably involved in metamorphosis, but knowledge is scant. The ciliated protostome larvae show ganglia/nerve cords that are retained as the adult central nervous system (CNS). Two structures can be recognized, viz. a pair of cerebral ganglia, which form the major part of the adult brain, and a blastoporal (circumblastoporal) nerve cord, which becomes differentiated into a perioral loop, paired or secondarily fused ventral nerve cords and a small perianal loop. The anterior loop becomes part of the brain. This has been well documented through cell-lineage studies in a number of spiralians, and homologies with similar structures in the ecdysozoans are strongly indicated. The deuterostomes are generally difficult to interpret, and the nervous systems of echinoderms and enteropneusts appear completely enigmatic. The ontogeny of the chordate CNS can perhaps be interpreted as a variation of the ontogeny of the blastoporal nerve cord of the protostomes, and this is strongly supported by patterns of gene expression. The presence of ‘deuterostomian’ blastopore fates both in an annelid and in a mollusk, which are both placed in families with the ‘normal’ spiralian gastrulation type, and in the chaetognaths demonstrates that the chordate type of gastrulation could easily have evolved from the spiralian type. This indicates that the latest common ancestor of the deuterostomes was very similar to the latest common pelago-benthic ancestor of the protostomes as described by the trochaea theory, and that the neural tube of the chordates is morphologically ventral.
The role of G protein-coupled receptors in the early evolution of neurotransmission and the nervous system
Authors: Krishnan Arunkumar , Schiöth Helgi B.
Published: February 2015

The origin and evolution of the nervous system is one of the most intriguing and enigmatic events in biology. The recent sequencing of complete genomes from early metazoan organisms provides a new platform to study the origins of neuronal gene families. This review explores the early metazoan expansion of the largest integral transmembrane protein family, the G protein-coupled receptors (GPCRs), which serve as molecular targets for a large subset of neurotransmitters and neuropeptides in higher animals. GPCR repertories from four pre-bilaterian metazoan genomes were compared. This includes the cnidarian Nematostella vectensis and the ctenophore Mnemiopsis leidyi, which have primitive nervous systems (nerve nets), the demosponge Amphimedon queenslandica and the placozoan Trichoplax adhaerens, which lack nerve and muscle cells. Comparative genomics demonstrate that the rhodopsin and glutamate receptor families, known to be involved in neurotransmission in higher animals are also widely found in pre-bilaterian metazoans and possess substantial expansions of rhodopsin-family-like GPCRs. Furthermore, the emerging knowledge on the functions of adhesion GPCRs in the vertebrate nervous system provides a platform to examine possible analogous roles of their closest homologues in pre-bilaterians. Intriguingly, the presence of molecular components required for GPCR-mediated neurotransmission in pre-bilaterians reveals that they exist in both primitive nervous systems and nerve-cell-free environments, providing essential comparative models to better understand the origins of the nervous system and neurotransmission.
The search for ancestral nervous systems: an integrative and comparative approach
Authors: Satterlie Richard A.
Published: February 2015

Even the most basal multicellular nervous systems are capable of producing complex behavioral acts that involve the integration and combination of simple responses, and decision-making when presented with conflicting stimuli. This requires an understanding beyond that available from genomic investigations, and calls for a integrative and comparative approach, where the power of genomic/transcriptomic techniques is coupled with morphological, physiological and developmental experimentation to identify common and species-specific nervous system properties for the development and elaboration of phylogenomic reconstructions. With careful selection of genes and gene products, we can continue to make significant progress in our search for ancestral nervous system organizations.
Convergent evolution of neural systems in ctenophores
Authors: Moroz Leonid L.
Published: February 2015

Neurons are defined as polarized secretory cells specializing in directional propagation of electrical signals leading to the release of extracellular messengers – features that enable them to transmit information, primarily chemical in nature, beyond their immediate neighbors without affecting all intervening cells en route. Multiple origins of neurons and synapses from different classes of ancestral secretory cells might have occurred more than once during ~600 million years of animal evolution with independent events of nervous system centralization from a common bilaterian/cnidarian ancestor without the bona fide central nervous system. Ctenophores, or comb jellies, represent an example of extensive parallel evolution in neural systems. First, recent genome analyses place ctenophores as a sister group to other animals. Second, ctenophores have a smaller complement of pan-animal genes controlling canonical neurogenic, synaptic, muscle and immune systems, and developmental pathways than most other metazoans. However, comb jellies are carnivorous marine animals with a complex neuromuscular organization and sophisticated patterns of behavior. To sustain these functions, they have evolved a number of unique molecular innovations supporting the hypothesis of massive homoplasies in the organization of integrative and locomotory systems. Third, many bilaterian/cnidarian neuron-specific genes and ‘classical’ neurotransmitter pathways are either absent or, if present, not expressed in ctenophore neurons (e.g. the bilaterian/cnidarian neurotransmitter, γ-amino butyric acid or GABA, is localized in muscles and presumed bilaterian neuron-specific RNA-binding protein Elav is found in non-neuronal cells). Finally, metabolomic and pharmacological data failed to detect either the presence or any physiological action of serotonin, dopamine, noradrenaline, adrenaline, octopamine, acetylcholine or histamine – consistent with the hypothesis that ctenophore neural systems evolved independently from those in other animals. Glutamate and a diverse range of secretory peptides are first candidates for ctenophore neurotransmitters. Nevertheless, it is expected that other classes of signal and neurogenic molecules would be discovered in ctenophores as the next step to decipher one of the most distinct types of neural organization in the animal kingdom.