bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bone Pain Induced by Multiple Myeloma Is Reduced by Targeting V-ATPase and ASIC3
Authors: Hiasa Masahiro , Okui Tatsuo , Allette Yohance M. , Ripsch Matthew S. , Sun-Wada Ge-Hong , Wakabayashi Hiroki , Roodman G. David , White Fletcher A. , Yoneda Toshiyuki 
Published: March 2017

Abstract
Multiple myeloma patients experience severe bone pain (MMBP) that is undertreated and poorly understood. In this study, we studied MMBP in an intratibial mouse xenograft model that employs JJN3 human multiple myeloma cells. In this model, mice develop MMBP associated in bone with increased sprouting of calcitonin gene-related peptide-positive (CGRP+) sensory nerves and in dorsal root ganglia (DRG) with upregulation of phosphorylated ERK1/2 (pERK1/2) and pCREB, two molecular indicators of neuron excitation. We found that JJN3 cells expressed a vacuolar proton pump (V-ATPase) that induced an acidic bone microenvironment. Inhibition of JJN3-colonized bone acidification by a single injection of the selective V-ATPase inhibitor, bafilomycin A1, decreased MMBP, CGRP+ sensory neuron sprouting, and pERK1/2 and pCREB expression in DRG. CGRP+ sensory nerves also expressed increased levels of the acid-sensing nociceptor ASIC3. Notably, a single injection of the selective ASIC3 antagonist APETx2 dramatically reduced MMBP in the model. Mechanistic investigations in primary DRG neurons cocultured with JJN3 cells showed increased neurite outgrowth and excitation inhibited by bafilomycin A1 or APETx2. Furthermore, combining APETx2 with bafilomycin A1 reduced MMBP to a greater extent than either agent alone. Finally, combining bafilomycin A1 with the osteoclast inhibitor zoledronic acid was sufficient to ameliorate MMBP, which was refractory to zoledronic acid. Overall, our results show that osteoclasts and multiple myeloma cooperate to induce an acidic bone microenvironment that evokes MMBP as a result of the excitation of ASIC3-activated sensory neurons. Furthermore, they present a mechanistic rationale for targeting ASIC3 on neurons along with the multiple myeloma-induced acidic bone microenvironment as a strategy to relieve MMBP in patients. Cancer Res; 77(6); 1283–95. ©2017 AACR.
Recommended Guidelines for Validation, Quality Control, and Reporting of TP53 Variants in Clinical Practice
Authors: Leroy Bernard , Ballinger Mandy L. , Baran-Marszak Fanny , Bond Gareth L. , Braithwaite Antony , Concin Nicole , Donehower Lawrence A. , El-Deiry Wafik S. , Fenaux Pierre , Gaidano Gianluca , Langerød Anita , Hellstrom-Lindberg Eva , Iggo Richard , Lehmann-Che Jacqueline , Mai Phuong L. , Malkin David , Moll Ute M. , Myers Jeffrey N. , Nichols Kim E. , Pospisilova Sarka , Ashton-Prolla Patricia , Rossi Davide , Savage Sharon A. , Strong Louise C. , Tonin Patricia N. , Zeillinger Robert , Zenz Thorsten , Fraumeni Joseph F. , Taschner Peter E.M. , Hainaut Pierre , Soussi Thierry 
Published: March 2017

Abstract
Accurate assessment of TP53 gene status in sporadic tumors and in the germline of individuals at high risk of cancer due to Li–Fraumeni Syndrome (LFS) has important clinical implications for diagnosis, surveillance, and therapy. Genomic data from more than 20,000 cancer genomes provide a wealth of information on cancer gene alterations and have confirmed TP53 as the most commonly mutated gene in human cancer. Analysis of a database of 70,000 TP53 variants reveals that the two newly discovered exons of the gene, exons 9β and 9γ, generated by alternative splicing, are the targets of inactivating mutation events in breast, liver, and head and neck tumors. Furthermore, germline rearrange-ments in intron 1 of TP53 are associated with LFS and are frequently observed in sporadic osteosarcoma. In this context of constantly growing genomic data, we discuss how screening strategies must be improved when assessing TP53 status in clinical samples. Finally, we discuss how TP53 alterations should be described by using accurate nomenclature to avoid confusion in scientific and clinical reports. Cancer Res; 77(6); 1250–60. ©2017 AACR.
Advances in the Classification and Treatment of Mastocytosis: Current Status and Outlook toward the Future
Authors: Valent Peter , Akin Cem , Hartmann Karin , Nilsson Gunnar , Reiter Andreas , Hermine Olivier , Sotlar Karl , Sperr Wolfgang R. , Escribano Luis , George Tracy I. , Kluin-Nelemans Hanneke C. , Ustun Celalettin , Triggiani Massimo , Brockow Knut , Gotlib Jason , Orfao Alberto , Schwartz Lawrence B. , Broesby-Olsen Sigurd , Bindslev-Jensen Carsten , Kovanen Petri T. , Galli Stephen J. , Austen K. Frank , Arber Daniel A. , Horny Hans-Peter , Arock Michel , Metcalfe Dean D. 
Published: March 2017

Abstract
Mastocytosis is a term used to denote a heterogeneous group of conditions defined by the expansion and accumulation of clonal (neoplastic) tissue mast cells in various organs. The classification of the World Health Organization (WHO) divides the disease into cutaneous mastocytosis, systemic mastocytosis, and localized mast cell tumors. On the basis of histomorphologic criteria, clinical parameters, and organ involvement, systemic mastocytosis is further divided into indolent systemic mastocytosis and advanced systemic mastocytosis variants, including aggressive systemic mastocytosis and mast cell leukemia. The clinical impact and prognostic value of this classification has been confirmed in numerous studies, and its basic concept remains valid. However, refinements have recently been proposed by the consensus group, the WHO, and the European Competence Network on Mastocytosis. In addition, new treatment options are available for patients with advanced systemic mastocytosis, including allogeneic hematopoietic stem cell transplantation and multikinase inhibitors directed against KIT D816V and other key signaling molecules. Our current article provides an overview of recent advances in the field of mastocytosis, with emphasis on classification, prognostication, and emerging new treatment options in advanced systemic mastocytosis. Cancer Res; 77(6); 1261–70. ©2017 AACR.
MiR-15b-5p Regulates Collateral Artery Formation by Targeting AKT3 (Protein Kinase B-3)
Authors: Zhu Ling-Ping , Zhou Ji-Peng , Zhang Jia-Xiong , Wang Jun-Yao , Wang Zhen-Yu , Pan Miao , Li Ling-Fang , Chen Lin , Li Chuan-Chang , Wang Kang-Kai , Bai Yong-Ping , Zhang Guo-Gang 
Published: March 2017

Objective—
To identify circulating microRNAs that are differentially expressed in severe coronary heart disease with well or poorly developed collateral arteries and to investigate their mechanisms of action in vivo and in vitro.

Approach and Results—
In our study, we identified a circulating microRNA, miR-15b-5p, with low expression that, nevertheless, characterized patients with sufficient coronary collateral artery function. Moreover, in murine hindlimb ischemia model, in situ hybridization identified that miR-15b-5p was specifically expressed in vascular endothelial cells of adductors in sham group and was remarkably downregulated after femoral artery ligation. Overexpressed miR-15b-5p significantly inhibited arteriogenesis and angiogenesis in mice. In vitro, both under basal and vascular endothelial growth factor stimulation, loss-of-function or gain-of-function studies suggested that miR-15b-5p significantly promoted or depressed the migration and proliferation of endothelial cells. We identified AKT3 (protein kinase B-3) as a direct target of miR-15b-5p. Interestingly, AKT3 deficiency by injection with Chol-AKT3-siRNA obviously suppressed arteriogenesis and the recovery of blood perfusion after femoral ligation in mice.

Conclusions—
These results indicate that circulating miR-15b-5p is a suitable biomarker for discriminating between patients with well-developed or poorly developed collaterals. Moreover, miR-15b-5p is a key regulator of arteriogenesis and angiogenesis, which may represent a potential therapeutic target for ischemic disease.
Beneficial Effect of Renal Denervation on Ventricular Premature Complex Induced Cardiomyopathy
Authors: Yamada Shinya , Lo Li‐Wei , Chou Yu‐Hui , Lin Wei‐Lun , Chang Shih‐Lin , Lin Yenn‐Jiang , Liu Shin‐Huei , Cheng Wen‐Han , Tsai Tsung‐Ying , Chen Shih‐Ann 
Published: March 2017

Background

Frequent ventricular premature complexes (
VPC
s) can lead to the development of dilated cardiomyopathy and sudden cardiac death. Renal artery sympathetic denervation (
RDN
) may protect the heart from remodeling. This study aimed to investigate the effect of frequent
VPC
s on structural and electrical properties and whether
RDN
can protect the heart from remodeling.

Methods and Results

Eighteen rabbits were randomized to control (n=6),
VPC
(n=6), and
VPC
‐
RDN
(n=6) groups. Surgical and chemical
RDN
s were approached through bilateral retroperitoneal flank incisions in the
VPC
‐
RDN
group. Pacemakers were implanted to the left ventricular apex to produce 50%
VPC
burden for 5 weeks in the
VPC
and
VPC
‐
RDN
groups. In addition, ventricular myocardium was harvested for western blot and trichrome stain. Echocardiographic results showed left ventricular enlargement after 5‐week pacing in the
VPC
group, but not in the
VPC
‐
RDN
group, when compared to baseline. In biventricles, ion channel protein expressions of Nav1.5, Cav1.2, Kir2.1, and
SERCA
2 were similar among 3 groups. However, the degree of biventricular fibrosis was extensive in the
VPC
group, compared to the control and
VPC
‐
RDN
groups. Importantly, ventricular fibrillation inducibility was higher in the
VPC
group (41%) when comparing to the control (13%;
P
<0.05) and
VPC
‐
RDN
groups (13%;
P
<0.05), respectively.

Conclusions

Frequent
VPC
s are associated with the development of cardiac structural remodeling and high ventricular fibrillation inducibility.
RDN
prevents cardiac remodeling and the occurrence of ventricular arrhythmia through antifibrosis.
Enhancing Dynamical Seasonal Predictions through Objective Regionalization
Authors: Satti Saleh , Zaitchik Benjamin F. , Badr Hamada S. , Tadesse Tsegaye 
Published: March 2017

AbstractImproving seasonal forecasts in East Africa has great implications for food security and water resources planning in the region. Dynamically based seasonal forecast systems have much to contribute to this effort, as they have demonstrated ability to represent and, to some extent, predict large-scale atmospheric dynamics that drive interannual rainfall variability in East Africa. However, these global models often exhibit spatial biases in their placement of rainfall and rainfall anomalies within the region, which limits their direct applicability to forecast-based decision-making. This paper introduces a method that uses objective climate regionalization to improve the utility of dynamically based forecast-system predictions for East Africa. By breaking up the study area into regions that are homogenous in interannual precipitation variability, it is shown that models sometimes capture drivers of variability but misplace precipitation anomalies. These errors are evident in the pattern of homogenous regions in forecast systems relative to observation, indicating that forecasts can more meaningfully be applied at the scale of the analogous homogeneous climate region than as a direct forecast of the local grid cell. This regionalization approach was tested during the July–September (JAS) rain months, and results show an improvement in the predictions from version 4.5 of the Max Plank Institute for Meteorology’s atmosphere–ocean general circulation model (ECHAM4.5) for applicable areas of East Africa for the two test cases presented.
Retrieving Fall Streaks within Cloud Systems Using Doppler Radar
Authors: Pfitzenmaier Lukas , Dufournet Yann , Unal Christine M. H. , Russchenberg Herman W. J. 
Published: March 2017

AbstractThe interaction of ice crystals with supercooled liquid droplets in mixed-phase clouds leads to an enhanced growth of ice particles. However, such processes are still not clearly understood although they are important processes for precipitation formation in midlatitudes. To better understand how ice particles grow within such clouds, changes in the microphysical parameters of a particle population falling through the cloud have to be analyzed. The Transportable Atmospheric Radar (TARA) can retrieve the full 3D Doppler velocity vector based on a unique three-beam configuration. Using the derived wind information, a new fall streak retrieval technique is proposed so that microphysical changes along those streaks can be studied. The method is based on Doppler measurements only. The shown examples measured during the Analysis of the Composition of Clouds with Extended Polarization Techniques (ACCEPT) campaign demonstrate that the retrieval is able to capture the fall streaks within different cloud systems. These fall streaks can be used to study changes in a single particle population from its generation (at cloud top) until its disintegration. In this study fall streaks are analyzed using radar moments or Doppler spectra. Synergetic measurements with other instruments during ACCEPT allow the detection of liquid layers within the clouds. The estimated microphysical information is used here to get a better understanding of the influence of supercooled liquid layers on ice crystal growth. This technique offers a new perspective for cloud microphysical studies.
Local Intraluminal Irrigation With Argatroban During Free Flap Repair in a Patient With Heparin-Induced Thrombocytopenia
Authors: Macias David , Kwon Daniel I. , Walker Paul C. , Peterson Nathaniel R. 
Published: March 2017

Objective: This study describes a case of a successful free flap repair using argatroban for local intraluminal irrigation as a substitute to heparin in a patient with heparin-induced thrombocytopenia. Methods: Case report and review of literature. Results: The patient had an uneventful postoperative course, and the free flap survived without complications. Conclusions: The use of argatroban during microvascular surgery is likely to be safe and simple and may be effective in preventing micro-thrombotic complications during microvascular surgery, and it should be considered as an alternative to heparinized saline for local intraluminal irrigation.
A comparative study on assessment procedures and metric properties of two scoring systems of the Coma Recovery Scale-Revised items: standard and modified scores
Authors: Sattin Davide , Lovaglio Piergiorgio , Brenna Greta , Covelli Venusia , Rossi Sebastiano Davide , Duran Dunja , Minati Ludovico , Giovannetti Ambra Mara , Rosazza Cristina , Bersano Anna , Nigri Anna , Ferraro Stefania , Leonardi Matilde 
Published: March 2017

Objective: The study compared the metric characteristics (discriminant capacity and factorial structure) of two different methods for scoring the items of the Coma Recovery Scale-Revised and it analysed scale scores collected using the standard assessment procedure and a new proposed method. Design: Cross sectional design/methodological study. Setting: Inpatient, neurological unit. Participants: A total of 153 patients with disorders of consciousness were consecutively enrolled between 2011 and 2013. Intervention: All patients were assessed with the Coma Recovery Scale-Revised using standard (rater 1) and inverted (rater 2) procedures. Main outcome measures: Coma Recovery Scale-Revised score, number of cognitive and reflex behaviours and diagnosis. Results: Regarding patient assessment, rater 1 using standard and rater 2 using inverted procedures obtained the same best scores for each subscale of the Coma Recovery Scale-Revised for all patients, so no clinical (and statistical) difference was found between the two procedures. In 11 patients (7.7%), rater 2 noted that some Coma Recovery Scale-Revised codified behavioural responses were not found during assessment, although higher response categories were present. A total of 51 (36%) patients presented the same Coma Recovery Scale-Revised scores of 7 or 8 using a standard score, whereas no overlap was found using the modified score. Unidimensionality was confirmed for both score systems. Conclusion: The Coma Recovery Scale Modified Score showed a higher discriminant capacity than the standard score and a monofactorial structure was also supported. The inverted assessment procedure could be a useful evaluation method for the assessment of patients with disorder of consciousness diagnosis.
Conflicts and con-fusions confounding compassion in acute care: Creating dialogical moral space
Authors: Jones Jenny , Strube Petra , Mitchell Marion , Henderson Amanda 
Published: March 2017

Background: Compassion, understood as empathy for another who is experiencing physical, mental, emotional and/or spiritual suffering, is an essential element of our shared understandings of nursing and the constitution of the professional nurse. Theoretical foundation: Charles Taylor account of ethics which concerns ‘what or who is it good to be’ rather than the predominant analytical moral philosophy approach which concentrates on ‘what ought one to do’ is the core concern of this discussion. An ontological appreciation of our shared human condition is the premise upon which the discussion is based. Discussion: This article proposes that concept by opening a dialogical space, nurses can engage in reflection and sense making wherein they explore individually and collectively the conflicts and confusions encountered in their day-to-day work. Through their dialogues, nurses – individually and collectively – orient and reorient themselves and each other towards what they see as meaningful and purposeful in their lives and in doing so they are well positioned to reaffirm their commitment to compassion as a value which both anchors and orients their day-to-day work. Implications: The provision of opportunities in the workplace, in the form of dialogue, to articulate often unspoken assumptions and frameworks in which nursing work is carried out can not only initiate the building of pathways of support but also assist nurses reaffirm their compassion – arguably the essence of their nursing practice.
First Tarsometatarsal Joint Derotational Arthrodesis for Flexible Hallux Valgus: Results from Follow-Up of 3–8 Years
Authors: Klemola T. , Savola O. , Ohtonen P. , Ojala R. , Leppilahti J. 
Published: March 2017

Purpose: We report 3- to 8-year follow-up results for the first tarsometatarsal joint derotational arthrodesis. Methods: A total of 70 patients (88 feet) with symptomatic flexible hallux valgus were operated between 2003 and 2009. In all, 66 patients (94.3%) with 84 (95.5%) feet were enrolled in retrospective analysis; of those, 58 (87.9%) patients with 76 (90.5%) feet were followed for a mean of 5.1 (range: 3.0–8.3) years. Preoperative, 6 week postoperative, and late follow-up weightbearing radiographs were evaluated along with clinical examination and questionnaires. Results: The mean hallux valgus angle improved 13.4° (95% confidence interval: 11.6–15.1, p < .001) at the latest follow-up, while the mean intermetatarsal angle correction was 4.5° (95% confidence interval: 3.7–5.2, p < .001). There were three (4.0%) nonunions, and seven (9.2%) feet needed reoperation during follow-up. Conclusion: First tarsometatarsal joint derotational arthrodesis is an effective procedure for correcting flexible hallux valgus deformity and provides a satisfactory long-term outcome.
The Introduction of Adult Appendicitis Score Reduced Negative Appendectomy Rate
Authors: Sammalkorpi H. E. , Mentula P. , Savolainen H. , Leppäniemi A. 
Published: March 2017

Background and Aims: Implementation of a clinical risk score into diagnostics of acute appendicitis may provide accurate diagnosis with selective use of imaging studies. The aim of this study was to prospectively validate recently described diagnostic scoring system, Adult Appendicitis Score, and evaluate its effects on negative appendectomy rate. Material and Methods: Adult Appendicitis Score stratifies patients into three groups: high, intermediate, and low risk of appendicitis. The score was implemented in diagnostics of adult patients suspected of acute appendicitis in two university hospitals. We analyzed the effects of Adult Appendicitis Score on diagnostic accuracy, imaging studies, and treatment. The study population was compared with a reference population of 829 patients suspected of acute appendicitis originally enrolled for the study of construction of the Adult Appendicitis Score. Results: This study enrolled 908 patients of whom 432 (48%) had appendicitis. The score stratified 49% of all appendicitis patients into high-risk group with specificity of 93.3%. In the low-risk group, prevalence of appendicitis was 7%. The histologically confirmed negative appendectomy rate decreased from 18.2% to 8.7%, p<0.001, compared to the original dataset. Conclusion: Adult Appendicitis Score is a reliable tool for stratification of patients into selective imaging, which results in low negative appendectomy rate.
Shear wave elastography: Can it be a new radiologic approach for the diagnosis of erectile dysfunction?
Authors: Turkay Rustu , Inci Ercan , Yenice Mustafa Gurkan , Tugcu Volkan 
Published: March 2017

Introduction Erectile dysfunction (ED) is a common health problem among males, and radiology has limited use in its diagnosis and treatment. Shear wave elastography (SWE) is a new sonographic technique. In this study, we examined the significance of SWE in the diagnosis of ED. Methods The study included a total number of 70 participants. The mean age of the participants was 54.14 ± 8.03 years (range: 39 and 71 years old). We composed two groups. Group 1 had 35 patients who presented to the urology clinic in our hospital complaining of ED, and had a score of 17 or lower from the International Index of Erectile Function (IIEF) questionnaire. Group 2 consisted of 35 healthy volunteers who did not have ED. SWE measurements were performed from corpus cavernosum penis in both groups, and the results were noted. Differences between the groups were evaluated statistically. Results The difference between the mean SWE measurements of two groups (Group 1: 20.94 ± 6.23 kPa and group 2: 24.63 ± 7.58 kPa) was found to be statistically significant ( p = 0.027; p < 0.05). For a cut-off value of 17.1 kPa, the SWE method has specificity, sensitivity, positive predictive value, and negative predictive value regarding diagnosis of ED as 94.29%, 34.29%, 85.71%, and 58.93%, respectively. The mean age of the groups did not show a statistically significant difference ( p = 0.287; p > 0.05). Conclusions Due to its high specificity and positive predictive value, SWE can offer useful data in the radiologic evaluation of ED cases.