bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fracture Healing Assessment Based on Impact Testing: In Vitro Simulation and Monitoring of the Healing Process of a Tibial Fracture with External Fixator
Authors: Di Puccio Francesca , Mattei Lorenza , Longo Antonia , Marchetti Stefano 
Published: October 2017

In clinical practice, bone healing is monitored with X-rays and manipulation. Its assessment is thus subjective, depending on the skills of the operator. Alternative and quantitative approaches have been proposed, generally based on the estimation of bone stiffness, which is known to increase with the healing process. The present study investigates the application of experimental modal analysis to fracture healing assessment focusing on fractures treated with an external fixator. The aim is to ascertain the capability of this approach to detect changes in the bone-callus stiffness as variations in the resonant frequencies despite the presence of the fixator, which might hide the bone response. In vitro tests were performed on a tibia phantom where the healing process was simulated creating three different types of callus surrogates, using glue and resin. The resonant frequencies of the phantom with screwed pins and of the phantom with the complete fixator were estimated. Results confirm an increase in the frequencies as the simulated bone-callus stiffness increases, encouraging the application of experimental modal analysis to fracture healing monitoring. This approach can offer remarkable advantages with respect to the actual standards: being non-invasive and quantitative, it would allow a more frequent healing monitoring.
Discovery of a Highly Selective NAMPT Inhibitor That Demonstrates Robust Efficacy and Improved Retinal Toxicity with Nicotinic Acid Coadministration
Authors: Zhao Genshi , Green Colin F. , Hui Yu-Hua , Prieto Lourdes , Shepard Robert , Dong Sucai , Wang Tao , Tan Bo , Gong Xueqian , Kays Lisa , Johnson Robert L. , Wu Wenjuan , Bhattachar Shobha , Del Prado Miriam , Gillig James R. , Fernandez Maria-Carmen , Roth Ken D. , Buchanan Sean , Kuo Ming-Shang , Geeganage Sandaruwan , Burkholder Timothy P. 
Published: October 2017

Abstract
NAMPT, an enzyme essential for NAD+ biosynthesis, has been extensively studied as an anticancer target for developing potential novel therapeutics. Several NAMPT inhibitors have been discovered, some of which have been subjected to clinical investigations. Yet, the on-target hematological and retinal toxicities have hampered their clinical development. In this study, we report the discovery of a unique NAMPT inhibitor, LSN3154567. This molecule is highly selective and has a potent and broad spectrum of anticancer activity. Its inhibitory activity can be rescued with nicotinic acid (NA) against the cell lines proficient, but not those deficient in NAPRT1, essential for converting NA to NAD+. LSN3154567 also exhibits robust efficacy in multiple tumor models deficient in NAPRT1. Importantly, this molecule when coadministered with NA does not cause observable retinal and hematological toxicities in the rodents, yet still retains robust efficacy. Thus, LSN3154567 has the potential to be further developed clinically into a novel cancer therapeutic. Mol Cancer Ther; 16(12); 2677–88. ©2017 AACR.
AKT1low Quiescent Cancer Cells Promote Solid Tumor Growth
Authors: Alves Cleidson P. , Dey-Guha Ipsita , Kabraji Sheheryar , Yeh Albert C. , Talele Nilesh P. , Solé Xavier , Chowdhury Joeeta , Mino-Kenudson Mari , Loda Massimo , Sgroi Dennis , Borresen-Dale Anne-Lise , Russnes Hege G. , Ross Kenneth N. , Ramaswamy Sridhar 
Published: October 2017

Abstract
Human tumor growth depends on rapidly dividing cancer cells driving population expansion. Even advanced tumors, however, contain slowly proliferating cancer cells for reasons that remain unclear. Here, we selectively disrupt the ability of rapidly proliferating cancer cells to spawn AKT1low daughter cells that are rare, slowly proliferating, tumor-initiating, and chemotherapy-resistant, using β1-integrin activation and the AKT1-E17K–mutant oncoprotein as experimental tools in vivo. Surprisingly, we find that selective depletion of AKT1low slow proliferators actually reduces the growth of a molecularly diverse panel of human cancer cell xenograft models without globally altering cell proliferation or survival in vivo. Moreover, we find that unusual cancer patients with AKT1-E17K–mutant solid tumors also fail to produce AKT1low quiescent cancer cells and that this correlates with significantly prolonged survival after adjuvant treatment compared with other patients. These findings support a model whereby human solid tumor growth depends on not only rapidly proliferating cancer cells but also on the continuous production of AKT1low slow proliferators. Mol Cancer Ther; 17(1); 254–63. ©2017 AACR.
Contemporary Risk Stratification After Myocardial Infarction in the Community: Performance of Scores and Incremental Value of Soluble Suppression of Tumorigenicity‐2
Authors: Gerber Yariv , Weston Susan A. , Enriquez‐Sarano Maurice , Jaffe Allan S. , Manemann Sheila M. , Jiang Ruoxiang , Roger Véronique L. 
Published: October 2017

Background

Current American Heart Association/American College of Cardiology guidelines recommend the
GRACE
(Global Registry of Acute Coronary Events) and
TIMI
(Thrombolysis in Myocardial Infarction) scores to assess myocardial infarction (
MI
) prognosis. Changes in the epidemiological characteristics of
MI
and the availability of new biomarkers warrant an assessment of the performance of these scores in contemporary practice. We assessed the following: (1) the performance of
GRACE
and
TIMI
to predict 1‐year mortality in a cohort of patients stratified by
ST
‐segment elevation MI (STEMI) and non‐STEMI (
NSTEMI
) and (2) the incremental discriminatory power of soluble suppression of tumorigenicity‐2, a myocardial fibrosis biomarker.

Methods and Results

Olmsted County, Minnesota, residents with incident
MI
(N=1401) were recruited prospectively from November 1, 2002 to December 31, 2012 (mean age, 67 years; 61% men; 79% with
NSTEMI
). Baseline data were used to calculate risk scores; soluble suppression of tumorigenicity‐2 was measured in stored plasma samples obtained at index
MI
.
C
‐statistics adapted to survival data were used to assess the discriminatory power of the risk scores and the improvement gained by adding other markers. During the first year of follow‐up, 190 patients (14%) died. The discriminatory performance to predict death was reasonable for
GRACE
and poor for
TIMI
, and was generally worse in those with NSTEMI versus those with STEMI. In people with
NSTEMI
, sequential addition of comorbidities and soluble suppression of tumorigenicity‐2 substantially improved the
c
‐statistic over
GRACE
(from 0.78 to 0.80 to 0.84) and
TIMI
(from 0.61 to 0.73 to 0.81), respectively (all
P
≤0.05).

Conclusions

Guideline‐recommended scores for risk assessment after
MI
underperform in contemporary community patients, particularly those with NSTEMI, which now represents most infarcts. Incorporating comorbidities and soluble suppression of tumorigenicity‐2 substantially improves risk prediction, thereby delineating opportunities to improve clinical care.
Extratropical Response to the MJO: Nonlinearity and Sensitivity to the Initial State
Authors: Lin Hai , Brunet Gilbert 
Published: October 2017

Previous studies have shown that the Madden–Julian oscillation (MJO) has a global impact that may provide an important source of skill for subseasonal predictions. The extratropical response was found to be the strongest when the tropical diabatic heating has a dipole structure with convection anomaly centers of opposite sign in the eastern Indian Ocean and the western Pacific. A positive (negative) MJO dipole heating refers to that with heating (cooling) in the eastern Indian Ocean and cooling (heating) in the western Pacific. In this study, two aspects of the extratropical response to the MJO are examined: 1) nonlinearity, which answers the question of whether the response to a positive MJO dipole heating is the mirror image of that to a negative MJO, and 2) sensitivity to the initial state, which explores the dependence of the extratropical response on the initial condition of the westerly jet. Ensemble integrations using a primitive-equation global atmospheric circulation model are performed with anomalous tropical thermal forcings that resemble a positive MJO (+MJO) and a negative MJO (−MJO). The response in the first week is largely linear. After that, significant asymmetry is found between the response in the positive MJO and the negative MJO. The 500-hPa negative geopotential height response in the North Pacific of the −MJO run is located about 30° east of the positive height response of the +MJO run. There is also an eastward shift of the extratropical wave train in the Pacific–North American region. This simulated nonlinearity is in agreement with the observations. The two leading response patterns among the ensemble members are identified by an empirical orthogonal function (EOF) analysis. EOF1 represents an eastward shift of the wave train, which is positively correlated with strengthening of the East Asian subtropical upper-troposphere westerly jet in the initial condition. On the other hand, EOF2 represents an amplification of the response, which is associated with a southward shift of the westerly jet in the initial state.
Post-recurrence survival analysis of stage I non-small-cell lung cancer
Authors: Lee Kanghoon , Kim Hyeong Ryul , Kim Dong Kwan , Kim Yong-Hee , Park Seung-Ill , Choi Se Hoon , Han Junhee 
Published: October 2017

Background The aim of this retrospective study was to review recurrence patterns of stage I non-small-cell lung cancer and identify prognostic factors for post-recurrence survival. Methods Among 940 patients with pathological stage I non-small-cell lung cancer who underwent curative resection, 261 experienced a recurrence; of these, 188 had adenocarcinoma and 62 had squamous cell carcinoma. Oligo-recurrence was defined as 1–3 recurrent lesions restricted to a single organ. Potentially curative local treatment included surgery, stereotactic radiotherapy, and photodynamic therapy. Results The median follow-up duration was 65 months (range 4–186 months). The most common site of recurrence was the lung in 145 patients, followed by mediastinal lymph nodes in 49, pleura in 30, and brain in 27. Local treatment for recurrent tumors included surgery in 59 patients, stereotactic radiotherapy in 46, photodynamic therapy in 2, and other radiotherapy in 41. Seventy-eight patients received chemotherapy only, and 35 received conservative treatment. Among 125 patients who were evaluated for an epidermal growth factor receptor gene mutation, 31 were treated with epidermal growth factor receptor-tyrosine kinase inhibitor. The 3- and 5-year post-recurrence survival rates were 49.1% and 33.8%, respectively. Age at recurrence, adenocarcinoma cell type, disease-free interval, epidermal growth factor receptor-tyrosine kinase inhibitor treatment, and potentially curative local treatment were independent prognostic factors for survival in multivariate analysis. Conclusions Local treatment for recurrence should be considered in selected candidates, and use of epidermal growth factor receptor-tyrosine kinase inhibitor I is reasonable if an epidermal growth factor receptor mutation is detected.
Macro Stress Testing of Indian Bank Groups
Authors: Dua Pami , Kapur Hema 
Published: October 2017

This study examines how various bank groups operating in India have fared macro stress events and conduct macro stress testing (MST) to trace the impact of certain macroeconomic stress scenarios on the credit quality of five Indian bank groups, that is, the State Bank of India (SBI) and its associates (SBGs), nationalised banks (NBs), old private sector banks (OPBs), new private sector banks (NPBs) and foreign banks (FBs), using panel data from 1997 to 2014. Credit quality is modelled as a function of both macroeconomic variables (output growth, interest rate, inflation rate and exchange rate) and idiosyncratic variables (profitability and size indicator of bank business activity). The model is estimated by employing a panel cointegration approach, and the impact of adverse scenarios on the estimated credit quality is computed. Empirical findings show that credit quality is pro-cyclical in nature and rises in the event of a slowdown in the economy. In general, the credit quality of Indian bank groups is found to be inversely and significantly related to the economy’s growth rate, inflation rate, exchange rate and profits of banks and positively and significantly related to the interest rate. Shock analysis also reveals that a downturn in the economy through certain adverse scenarios has a significant adverse impact on the credit quality. The shocks are quickly propagated across banks with substantial heterogeneities present in different bank groups. Thus, macroeconomic policy measures promoting growth with price stability are expected to impact credit quality positively. Further, measures at the bank level can improve credit quality by enhancing their profitability. JEL Classifications: C32, C58, E170, G21
Introduction of a dose-banding system for parenteral chemotherapy on a haematology–oncology day ward
Authors: O’Leary Caoimhe E , Collins Aisling , Henman Martin C , King Fionnuala 
Published: October 2017

Introduction The increasing incidence of cancer and the finite capacity of hospital aseptic compounding units pose a serious challenge to the provision of cancer care. Chemotherapy dose-banding is a method of rationalising parenteral chemotherapy dosing and supply, whereby patient-individualised doses are rounded to predetermined banded doses. The banded doses may be outsourced as stock items which increases the supply capacity of the aseptic compounding unit. Methods Kotter’s 8-step change management model was used to structure the implementation of dose-banding of 5-fluorouracil 46-h infusers on the haematology–oncology day ward in St. James’s Hospital, Dublin. The impact of dose-banding on local practice was assessed through pre- and post-implementation surveys of stakeholders. Results In-house surveys of pharmacy, medical and nursing staff identified a generally favourable attitude towards implementing changes in the parenteral chemotherapy supply system, with some resistance to change evident. Dose-banding of 5-fluorouracil 46-h infusers was implemented successfully on the haematology–oncology day ward. Dose rationalisation and flexibility of re-allocation of standard banded doses between patients were the primary benefits of dose-banding found. Post-implementation surveys showed that clinical staff were in favour of adopting dose-banding into standard practice; however, they were cautious about the degree to which the results of this limited study would be translated into substantive benefits if dose-banding was adopted for all suitable preparations. Conclusion The success of the implementation process and the favourable opinions of stakeholders shown in the post-implementation survey enabled the dose-banding service to be extended to a further nine drugs. Kotter’s 8-step change management model was a useful tool for structuring this process change in St. James’s Hospital.
Monoclonal antibodies for chronic pain: A practical review of mechanisms and clinical applications
Authors: Yeh Ju-Fen , Akinci Aysen , Al Shaker Mohammed , Chang Ming Hong , Danilov Andrei , Guillen Rocio , Johnson Kirk W , Kim Yong-Chul , El-Shafei Ahmed A , Skljarevski Vladimir , Dueñas Héctor J , Tassanawipas Warat 
Published: October 2017

Context Monoclonal antibodies are being investigated for chronic pain to overcome the shortcomings of current treatment options. Objective To provide a practical overview of monoclonal antibodies in clinical development for use in chronic pain conditions, with a focus on mechanisms of action and relevance to specific classes. Methods Qualitative review using a systematic strategy to search for randomized controlled trials, systematic and nonsystematic (narrative) reviews, observational studies, nonclinical studies, and case reports for inclusion. Studies were identified via relevant search terms using an electronic search of MEDLINE via PubMed (1990 to June 2017) in addition to hand-searching reference lists of retrieved systematic and nonsystematic reviews. Results Monoclonal antibodies targeting nerve growth factor, calcitonin gene-related peptide pathways, various ion channels, tumor necrosis factor-α, and epidermal growth factor receptor are in different stages of development. Mechanisms of action are dependent on specific signaling pathways, which commonly involve those related to peripheral neurogenic inflammation. In clinical studies, there has been a mixed response to different monoclonal antibodies in several chronic pain conditions, including migraine, neuropathic pain conditions (e.g., diabetic peripheral neuropathy), osteoarthritis, chronic back pain, ankylosing spondylitis, and cancer. Adverse events observed to date have generally been mild, although further studies are needed to ensure safety of monoclonal antibodies in early stages of development, especially where there is an overlap with non-pain-related pathways. High acquisition cost remains another treatment limitation. Conclusion Monoclonal antibodies for chronic pain have the potential to overcome the limitations of current treatment options, but strategies to ensure their appropriate use need to be determined.
Increased arterial stiffness in children with congenital heart disease
Authors: Häcker Anna-Luisa , Reiner Barbara , Oberhoffer Renate , Hager Alfred , Ewert Peter , Müller Jan 
Published: October 2017

Objective Central systolic blood pressure (SBP) is a measure of arterial stiffness and strongly associated with atherosclerosis and end-organ damage. It is a stronger predictor of cardiovascular events and all-cause mortality than peripheral SBP. In particular, for children with congenital heart disease, a higher central SBP might impose a greater threat of cardiac damage. The aim of the study was to analyse and compare central SBP in children with congenital heart disease and in healthy counterparts. Patients and methods Central SBP was measured using an oscillometric method in 417 children (38.9% girls, 13.0 ± 3.2 years) with various congenital heart diseases between July 2014 and February 2017. The test results were compared with a recent healthy reference cohort of 1466 children (49.5% girls, 12.9 ± 2.5 years). Results After correction for several covariates in a general linear model, central SBP of children with congenital heart disease was significantly increased (congenital heart disease: 102.1 ± 10.2 vs. healthy reference cohort: 100.4 ± 8.6, p < .001). The analysis of congenital heart disease subgroups revealed higher central SBP in children with left heart obstructions (mean difference: 3.6 mmHg, p < .001), transpositions of the great arteries after arterial switch (mean difference: 2.2 mmHg, p = .017) and univentricular hearts after total cavopulmonary connection (mean difference: 2.1 mmHg, p = .015) compared with the reference. Conclusion Children with congenital heart disease have significantly higher central SBP compared with healthy peers, predisposing them to premature heart failure. Screening and long-term observations of central SBP in children with congenital heart disease seems warranted in order to evaluate the need for treatment.
Cyclosporine or steroids as an adjunct to plasma exchange in the treatment of immune-mediated thrombotic thrombocytopenic purpura
Authors: Cataland Spero R. , Kourlas Peter J. , Yang Shangbin , Geyer Susan , Witkoff Leslie , Wu Haiwa , Masias Camila , George James N. , Wu Haifeng M. 
Published: October 2017

Key Points
Prednisone, as an adjunct to PEX, effectively suppresses the autoantibody inhibitor of ADAMTS13 in the treatment of iTTP.
Cadherin 17 mutation associated with leaky severe combined immune deficiency is corrected by HSCT
Authors: Smith Angela R. , Rota Ioanna A. , Maio Stefano , Massaad Michel J. , Lund Troy C. , Notarangelo Luigi D. , Holländer Georg A. , Blazar Bruce R. 
Published: October 2017

Key Points
CDH17 is expressed in human thymic epithelial cells. CDH17 mutations may be a rare cause of leaky severe combined immune deficiency that can be corrected by HSCT.
Identification of Clinical and Biologic Correlates Associated With Outcome in Children With Adrenocortical Tumors Without Germline TP53 Mutations: A St Jude Adrenocortical Tumor Registry and Children’s Oncology Group Study
Authors: Pinto Emilia Modolo , Rodriguez-Galindo Carlos , Pounds Stanley B. , Wang Lei , Clay Michael R. , Neale Geoffrey , Garfinkle Elizabeth A.R. , Lam Catherine G. , Levy Carolyn Fein , Pappo Alberto S. , Zambetti Gerard P. , Ribeiro Raul C. 
Published: October 2017

Purpose The clinical features, pathogenesis, and outcomes in children with adrenocortical tumors (ACTs) without germline TP53 mutations have not been systematically studied. Herein, we describe these correlates and analyze their association with outcome. Patients and Methods Genomic DNA was analyzed for TP53, CTNNB1, CDKN1C, ATRX, and chromosome 11p15 abnormalities. β-catenin expression and Ki-67 labeling index (LI) were evaluated by immunostaining. Primary end points were progression-free (PFS) and overall survival. Results Median age of 42 girls and 18 boys was 3.3 years (range, 0.25 to 21.7 years). Complete resection (stages I and II) was achieved in 32 patients, and 28 patients had stage III or IV disease. Constitutional abnormalities of chromosome 11p15 occurred in nine of 40 patients, with six patients not showing phenotype of Beckwith-Wiedemann syndrome. Three-year PFS and overall survival for all patients were 71.4% and 80.5%, respectively. In single-predictor Cox regression analysis, age, disease stage, tumor weight, somatic TP53 mutations, and Ki-67 LI were associated with prognosis. Ki-67 LI and age remained significantly associated with PFS after adjusting for stage and tumor weight. Three-year PFS for 27 patients with Ki-67 LI ≥ 15% was 48.5% compared with 96.2% for 29 patients with Ki-67 LI < 15% (log-rank P = .002), and the rate of relapse increased by 24% with each 1-year increase in age at diagnosis (hazard ratio, 1.24; P = .0057). Conclusion Clinicopathologic features and outcomes of children with ACTs without germline TP53 mutations overlapped those reported for children with germline TP53 mutations. Our findings highlight the central role of genetic or epigenetic alterations on chromosome 11p15 in pediatric ACTs. Ki-67 LI is a strong prognostic indicator and should be investigated to improve the histologic classification of pediatric ACTs.