bluuebunny/crossref_metadata_2025_split huggingface dataset:
The CGRP receptor antagonist BIBN4096 inhibits prolonged meningeal afferent activation evoked by brief local K+ stimulation but not cortical spreading depression-induced afferent sensitization
Authors: Zhao Jun , Levy Dan 
Published: December 2017

Abstract

Introduction:
Cortical spreading depression (CSD) is believed to promote migraine headache by enhancing the activity and mechanosensitivity of trigeminal intracranial meningeal afferents. One putative mechanism underlying this afferent response involves an acute excitation of meningeal afferents by cortical efflux of K+ and the ensuing antidromic release of proinflammatory sensory neuropeptides, such as calcitonin gene-related peptide (CGRP).

Objectives:
We sought to investigate whether (1) a brief meningeal K+ stimulus leads to CGRP-dependent enhancement of meningeal afferent responses and (2) CSD-induced meningeal afferent activation and sensitization involve CGRP receptor signaling.

Methods:
Extracellular single-unit recording were used to record the activity of meningeal afferents in anesthetized male rats. Stimulations included a brief meningeal application of K+ or induction of CSD in the frontal cortex using pinprick. Cortical spreading depression was documented by recording changes in cerebral blood flow using laser Doppler flowmetery. Calcitonin gene-related peptide receptor activity was inhibited with BIBN4096 (333 μM, i.v.).

Results:
Meningeal K+ stimulation acutely activated 86% of the afferents tested and also promoted in ∼65% of the afferents a 3-fold increase in ongoing activity, which was delayed by 23.3 ± 4.1 minutes and lasted for 22.2 ± 5.6 minutes. K+ stimulation did not promote mechanical sensitization. Pretreatment with BIBN4096 suppressed the K+-induced delayed afferent activation, reduced CSD-evoked cortical hyperemia, but had no effect on the enhanced activation or mechanical sensitization of meningeal afferents following CSD.

Conclusion:
While CGRP-mediated activation of meningeal afferents evoked by cortical efflux of K+ could promote headache, acute activation of CGRP receptors may not play a key role in mediating CSD-evoked headache.
18F-FDG PET/CT Findings of Mesenchymal Chondrosarcoma of the Orbit
Authors: Tsuchiya Mitsuteru , Masui Takayuki , Otsuki Yoshiro , Sakahara Harumi 
Published: December 2017

Abstract
Mesenchymal chondrosarcoma of the orbit is an extremely rare and aggressive tumor. We report image findings of 18F-fluorodeoxyglucose (FDG) positron emission/computed tomography (PET/CT) in 2 cases, one primary case and one recurrent case. The 18F-FDG PET/CT images revealed high uptake with an SUVmax of 6.7 and 11.7, respectively. In both cases, the HEY1-CoA2 gene fusion was positive. The high uptake of 18F-FDG in mesenchymal chondrosarcoma of the orbit well suggests the malignancy of this tumor.
Isolated Multinodular Soft-Tissue Rosai-Dorfman Disease on FDG PET/CT
Authors: Pucar Darko , Laskin William B. , Saperstein Lawrence 
Published: December 2017

Abstract
Rosai-Dorfman disease (sinus histiocytosis with massive lymphadenopathy) is a rare systemic histiocytic disorder of unknown etiology characterized by the accumulation of enlarged non-Langerhans histiocytes within lymph nodes and extranodal sites. The histiocytes display characteristic emperipolesis (nondestructive engulfment of inflammatory cells) and are CD68 and S100 positive and CD1a negative. Although extranodal disease frequently occurs with nodal involvement, isolated extranodal disease is uncommon. We report a case of isolated localized subcutaneous multinodular disease on FDG PET/CT. We also include a companion classic Rosai-Dorfman case with extensive nodal involvement and a characteristic benign clinical course with spontaneous improvement.
Epstein-Barr Virus–Associated Hemophagocytic Lymphohistiocytosis Mimicking Lymphoma on FDG PET/CT
Authors: Pan Qingqing , Luo Yaping , Wu Huanwen , Ma Yanru , Li Fang 
Published: December 2017

Abstract
A 15-year-old boy with fever, pancytopenia, and hepatosplenomegaly was diagnosed as hemophagocytic lymphohistiocytosis (HLH). 18F-FDG PET/CT showed hypermetabolic foci in the liver, spleen, and bone marrow, as well as multiple FDG-avid lymph nodes, which were highly suggestive of lymphoma. Specimens from splenectomy depicted a large number of macrophages/histiocytes with hemophagocytosis of erythrocytes, without evidence of malignancy. Considering increased Epstein-Barr virus (EBV) DNA in peripheral blood and positive staining for EBV-encoded RNA in the spleen, EBV-associated HLH was confirmed. This case indicates that FDG-avid foci in the liver, spleen, and bone marrow may also be seen in EBV-associated HLH.
The Americleft Project: Comparison of Ratings Using Two-Dimensional Versus Three-Dimensional Images for Evaluation of Nasolabial Appearance in Patients With Unilateral Cleft Lip and Palate
Authors: Jones Christine M. , Roth Benjamin , Mercado Ana M. , Russell Kathy A. , Daskalogiannakis John , Samson Thomas D. , Hathaway Ronald R. , Smith Andrea , Mackay Donald R. , Long Ross E. 
Published: December 2017

Abstract
This study was conducted to determine if nasolabial appearance is rated with comparable results and reliability on 3-dimensional stereophotogrammetric facial images versus standard clinical photographs (2-dimensional). Twenty-seven consecutively treated patients with repaired complete unilateral cleft lip and palate were selected. Six trained and calibrated raters assessed cropped 2- and 3-dimensional facial images. Nasolabial profile, nasolabial frontal, and vermillion border esthetics were rated with the 5-point scale described by Asher-McDade using the modified Q-sort method. Cropped 3-dimensional images were available for viewing by each rater, allowing for complete rotational control for viewing the images from all aspects. Two- and three-dimensional ratings were done separately and repeated the next day.
Interrater reliability scores were good for 2-dimensional (κ = 0.607–0.710) and fair to good for 3-dimensional imaging (κ = 0.374–0.769). Intrarater reliability was good to very good for 2-dimensional (κ = 0.749–0.836) and moderate to good for 3-dimensional imaging (κ = 0.554–0.855). Bland–Altman analysis showed satisfactory agreement of 2- and 3-dimensional scores for nasolabial profile and nasolabial frontal, but more systematic error occurred in the assessment of vermillion border.
Although 3-dimensional images may be perceived as more representative of a direct clinical facial evaluation, their use for subjective rating of nasolabial aesthetics was not more reliable than 2-dimensional images in this study. Conventional 2-dimensional images provide acceptable reliability while being readily accessible for most cleft palate centers.
Predicting Intestinal Adaptation in Pediatric Intestinal Failure
Authors: Belza Christina , Fitzgerald Kevin , de Silva Nicole , Avitzur Yaron , Steinberg Karen , Courtney-Martin Glenda , Wales Paul W. 
Published: December 2017

Objective:
The primary goal in intestinal failure (IF) is adaptation and enteral autonomy (EA). Our goals were to determine the proportion of patients treated for IF by an established intestinal rehabilitation program who achieved EA and to assess the predictors of EA.

Background:
There have been considerable advancements in the management of IF over the last 15 years, children with short bowel syndrome with a reduction in mortality. Several studies have discussed variables that may influence the ability to attain EA; however, majority were written when mortality rates were considerably higher compared with the current contemporary experience.

Methods:
A retrospective analysis of infants <12 months with short bowel syndrome referred between 2006 and 2013 (n = 120). Data was collected on IF-related factors and nutritional intake. The cohort was stratified based on achievement of EA. Statistical testing completed using t test, Chi Square, and Cox Proportional Hazards regression (P < 0.05).

Results:
EA was achieved in 84 (70.0%) patients. Patients who remained parenteral nutrition dependent were more likely to have volvulus (1.2 vs 22.2%, P < 0.001), shorter percent residual small bowel (29.4 vs 68.6%; P < 0.0001) and colon length (64.6 vs 86.0%; P = 0.001), and no ileocecal valve (61.1 vs 29.8%; P = 0.05). Mortality was also decreased in those who achieved EA (4 vs 22%; P = 0.004). Percent residual small bowel (HR = 1.03; 95% CI 1.02–1.03) and colon (HR = 1.01; 95% CI 1.00–1.02) length were positively associated with EA, while number of septic episodes was negatively associated (HR = 0.95; 95% CI 0.91–0.99).

Conclusion:
Seventy percent of infants with IF achieved EA. Residual small and large bowel length were the most important predictors of EA and septic events had a negative impact.
Benchmarking Complications Associated with Esophagectomy
Authors: Low Donald E. , Kuppusamy Madhan Kumar , Alderson Derek , Cecconello Ivan , Chang Andrew C. , Darling Gail , Davies Andrew , D’Journo Xavier Benoit , Gisbertz Suzanne S. , Griffin S. Michael , Hardwick Richard , Hoelscher Arnulf , Hofstetter Wayne , Jobe Blair , Kitagawa Yuko , Law Simon , Mariette Christophe , Maynard Nick , Morse Christopher R. , Nafteux Philippe , Pera Manuel , Pramesh C. S. , Puig Sonia , Reynolds John V. , Schroeder Wolfgang , Smithers Mark , Wijnhoven B. P. L. 
Published: December 2017

Objective:
Utilizing a standardized dataset with specific definitions to prospectively collect international data to provide a benchmark for complications and outcomes associated with esophagectomy.

Summary of Background Data:
Outcome reporting in oncologic surgery has suffered from the lack of a standardized system for reporting operative results particularly complications. This is particularly the case for esophagectomy affecting the accuracy and relevance of international outcome assessments, clinical trial results, and quality improvement projects.

Methods:
The Esophageal Complications Consensus Group (ECCG) involving 24 high-volume esophageal surgical centers in 14 countries developed a standardized platform for recording complications and quality measures associated with esophagectomy. Using a secure online database (ESODATA.org), ECCG centers prospectively recorded data on all resections according to the ECCG platform from these centers over a 2-year period.

Results:
Between January 2015 and December 2016, 2704 resections were entered into the database. All demographic and follow-up data fields were 100% complete. The majority of operations were for cancer (95.6%) and typically located in the distal esophagus (56.2%). Some 1192 patients received neoadjuvant chemoradiation (46.1%) and 763 neoadjuvant chemotherapy (29.5%). Surgical approach involved open procedures in 52.1% and minimally invasive operations in 47.9%. Chest anastomoses were done most commonly (60.7%) and R0 resections were accomplished in 93.4% of patients. The overall incidence of complications was 59% with the most common individual complications being pneumonia (14.6%) and atrial dysrhythmia (14.5%). Anastomotic leak, conduit necrosis, chyle leaks, recurrent nerve injury occurred in 11.4%, 1.3%, 4.7%, and 4.2% of cases, respectively. Clavien-Dindo complications ≥ IIIb occurred in 17.2% of patients. Readmissions occurred in 11.2% of cases and 30- and 90-day mortality was 2.4% and 4.5%, respectively.

Conclusion:
Standardized methods provide contemporary international benchmarks for reporting outcomes after esophagectomy.
PD-L1 Expression, Tumor-infiltrating Lymphocytes, and Clinical Outcome in Patients With Surgically Resected Esophageal Cancer
Authors: Yagi Taisuke , Baba Yoshifumi , Ishimoto Takatsugu , Iwatsuki Masaaki , Miyamoto Yuji , Yoshida Naoya , Watanabe Masayuki , Baba Hideo 
Published: December 2017

Objectives:
To examine the prognostic impact of the programmed death ligand 1 (PD-L1) expression, tumor-infiltrating lymphocyte (TIL) status, and their combination in esophageal cancer.

Summary Background Data:
PD-L1 has garnered much attention for its roles in tumor immunology and as an immune-based therapeutic target. To ensure a response to PD-L1 checkpoint inhibitor, a new framework based on PD-L1 expression and the presence or absence of TILs is required.

Methods:
Using a nonbiased database of 305 curatively resected esophageal cancers, we evaluated PD-L1 expression and TIL status (cluster of differentiation 8 (CD8) expression) by immunohistochemical analysis. The Cox proportional hazard model was used to compute the hazard ratio (HR) for mortality.

Results:
Compared with PD-L1 negative cases (n=252), PD-L1 positive cases (n = 53) showed significantly worse overall survival [log-rank P = 0.016; HR: 1.71; 95% confidence interval: 1.08–2.61; P = 0.024; multivariate HR: 1.69; 95% confidence interval: 1.05–2.67; P = 0.033]. TIL positivity was significantly correlated with longer overall survival (log-rank P < 0.0001) and high CD8 expression (P < 0.0001). A stratification based on PD-L1 expression and TIL status was also significantly associated with overall survival (log rank P < 0.0001).

Conclusions:
PD-L1 expression was associated with an unfavorable clinical outcome in esophageal cancer, supporting its role as a prognostic biomarker. In addition, the combination with TIL status enabled further classification patients according to clinical outcome. PD-L1 expression and TIL status may serve as predictive tissue biomarkers and can be used for patient selection in clinical trials of drugs targeting the PD-1/PD-L1 pathways.
Thirst in heart failure: what do we know so far?
Authors: Allida Sabine M. , Hayward Christopher S. , Newton Phillip J. 
Published: December 2017

Purpose of review
Thirst is a common and burdensome symptom of heart failure, which impacts adversely on quality of life. To date, there is limited research on the prevalence of thirst, the factors associated with thirst and interventions to help manage thirst in heart failure. This review summarizes key empirical research developments of thirst.

Recent findings
Recent research shows that the heart failure syndrome, medications, self-care practice such as fluid restriction and anxiety contributes greatly to increased thirst in patients with heart failure. In addition, predictors such as being younger, male patient, with high symptom burden and serum urea is also associated with thirst. There are no intervention studies to manage thirst, only reports of various strategies recommended to heart failure patients in clinical practice.

Summary
Despite the burden of thirst in heart failure patients, strategies to relieve thirst remains insufficiently addressed in literature. Further research to improve the understanding of the severity of thirst and its relationship to possible factors associated with thirst is required in order to develop future interventions to either prevent or alleviate troublesome thirst in patients with heart failure.
Palliative care needs assessment in chronic heart failure
Authors: Janssen Daisy J.A. , Johnson Miriam J. , Spruit Martijn A. 
Published: December 2017

Purpose of review
The unmet palliative care needs of patients with chronic heart failure (CHF) are well known. Palliative care needs assessment is paramount for timely provision of palliative care. The present review provides an overview of palliative care needs assessment in patients with CHF: the role of prognostic tools, the role of the surprise question, and the role of palliative care needs assessment tools.

Recent findings
Multiple prognostic tools are available, but offer little guidance for individual patients. The surprise question is a simple tool to create awareness about a limited prognosis, but the reliability in CHF seems less than in oncology and further identification and assessment of palliative care needs is required. Several tools are available to identify palliative care needs. Data about the ability of these tools to facilitate timely initiation of palliative care in CHF are lacking.

Summary
Several tools are available aiming to facilitate timely introduction of palliative care. Focus on identification of needs rather than prognosis appears to be more fitting for people with CHF. Future studies are needed to explore whether and to what extent these tools can help in addressing palliative care needs in CHF in a timely manner.
Caregiver anticipatory grief: phenomenology, assessment and clinical interventions
Authors: Coelho Alexandra , de Brito Maja , Barbosa António 
Published: December 2017

Purpose of review
This review aims to synthesize recent findings on anticipatory grief in caregivers, referring to its phenomenology, assessment and clinical interventions.

Recent findings
Recent literature illustrates the wide scope of the current use of the term anticipatory grief, reflecting caregivers’ experiences in different end-of-life trajectories. The anticipation of death is the distinctive aspect of anticipatory grief in the predeath grief continuum, encompassing several progressive losses, past and future. Recently developed assessment instruments capture key aspects of this experience, such as separation anxiety, anticipation of death and future absence of the person, denial and relational losses. Recent findings on prevalence of clinically significant predeath symptoms in caregivers range from 12.5 to 38.5%. Beyond personal and relational factors, difficult circumstances of end-of-life care significantly interfere in adjustment to anticipatory grief. Useful therapeutic interventions were identified, such as validation of grief feelings, increased coping and self-care, anticipation of future losses and reframing roles. However, rigorous interventional studies are needed to create guidelines and the manualization of specific therapeutic approaches to caregiver anticipatory grief.

Summary
Findings suggest that anticipatory grief dynamics in different end-of-life trajectories should be recognized and adequately assessed. Clinical interventions considered useful to support anticipatory grief caregivers are presented, but further research is needed to verify effectiveness.
Heat shock proteins and cancer: intracellular chaperones or extracellular signalling ligands?
Authors: Calderwood Stuart K. 
Published: December 2017

Heat shock proteins (HSPs) are found at elevated concentrations in tumour cells, and this increase reflects the proteotoxic stress experienced by the cells due to expanding levels of the mutated oncoproteins that drive tumorigenesis. The protection of oncogenic proteins by HSPs offers a window of vulnerability in tumour metabolism that has been exploited using Hsp90-targeting drugs. Such compounds have been shown to cause inhibition and degradation of a wide range of proteins essential for oncogenesis. Recently, Hsp90 has also been shown to be secreted by tumour cells and to interact in autocrine or paracrine manners with the surfaces of adjacent cells, leading to increased growth and metastasis. Future studies will address a number of key questions associated with these findings, including the relative importance of intracellular versus extracellular HSPs in tumorigenesis, as well as overcoming potential problems with normal tissue toxicity associated with Hsp90 drugs. Targeting individual members of HSP families and inactivating extracellular HSPs may be desirable future approaches that offer increased selectivity in targeting HSPs in cancer.This article is part of the theme issue ‘Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective’.
Membrane heat shock protein 70: a theranostic target for cancer therapy
Authors: Shevtsov Maxim , Huile Gao , Multhoff Gabriele 
Published: December 2017

Members of the 70 kDa stress protein family are found in nearly all subcellular compartments of nucleated cells where they fulfil a number of chaperoning functions. Heat shock protein 70 (HSP70), also termed HSPA1A, the major stress-inducible member of this family is overexpressed in a large variety of different tumour types. Apart from its intracellular localization, a tumour-selective HSP70 membrane expression has been determined. A membrane HSP70–positive tumour phenotype is associated with aggressiveness and therapy resistance, but also serves as a recognition structure for targeted therapies. Furthermore, membrane-bound and extracellularly residing HSP70 derived from tumour cells play pivotal roles in eliciting anti-tumour immune responses. Herein, we want to shed light on the multiplicity of different activities of HSP70, depending on its intracellular, membrane and extracellular localization with the goal to use membrane HSP70 as a target for novel therapies including nanoparticle-based approaches for the treatment of cancer.
This article is part of the theme issue ‘Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective’.
Immune tolerance therapies for autoimmune diseases based on heat shock protein T-cell epitopes
Authors: van Eden Willem 
Published: December 2017

Experimental models of autoimmune diseases have revealed the disease protective role of heat shock proteins (HSPs). Both the administration of exogenous extracellular, mostly recombinant, HSP and the experimental co-induction of endogenous intracellular HSP in models have been shown to lead to production of disease protective regulatory T cells (Tregs). Similar to HSP taken up from extracellular bodily fluids, due to stress-related autophagy upregulated HSP also from intracellular sources is a major provider for the major histocompatibility class II (MHCII) ligandome; therefore, both extracellular and intracellular HSP can be prominent targets of Treg. The development of therapeutic peptide vaccines for the restoration of immune tolerance in inflammatory diseases is an area of intensive research. In this area, HSPs are a target for tolerance-inducing T-cell therapy, because of their wide expression in inflamed tissues. In humans, in whom the actual disease trigger is frequently unknown, HSP peptides offer chances for tolerance-promoting interventions through induction of HSP-specific Treg. Recently, we have shown the ability of a bacterial HSP70-derived peptide, HSP70-B29, to induce HSP-specific Tregs that suppressed arthritis by cross-recognition of their mammalian HSP70 homologues, abundantly present in the MHCII ligandome of stressed mouse and human antigen-presenting cells in inflamed tissues.
This article is part of the theme issue ‘Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective’.
Real-time halo correction in phase contrast imaging
Authors: Kandel Mikhail E. , Fanous Michael , Best-Popescu Catherine , Popescu Gabriel 
Published: December 2017

AbstractAs a label-free, nondestructive method, phase contrast is by far the most popular microscopy technique for routine inspection of cell cultures. Yet, features of interest such as extensions near cell bodies are often obscured by a glow, which came to be known as the halo. Advances in modeling image formation have shown that this artifact is due to the limited spatial coherence of the illumination. Yet, the same incoherent illumination is responsible for superior sensitivity to fine details in the phase contrast geometry. Thus, there exists a trade-off between high-detail (incoherent) and low-detail (coherent) imaging systems. In this work, we propose a method to break this dichotomy, by carefully mixing corrected low-frequency and high-frequency data in a way that eliminates the edge effect. Specifically, our technique is able to remove halo artifacts at video rates, requiring no manual interaction ora prioripoint spread function measurements. To validate our approach, we imaged standard spherical beads, sperm cells, tissue slices, and red blood cells. We demonstrate the real-time operation with a time evolution study of adherent neuron cultures whose neurites are revealed by our halo correction. We show that with our novel technique, we can quantify cell growth in large populations, without the need for thresholds and calibration.