bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vasodilator-Stimulated Phosphoprotein Biomarkers Are Associated with Invasion and Metastasis in Colorectal Cancer
Authors: Pitari Giovanni M , Cotzia Paolo , Ali Mehboob , Birbe Ruth , Rizzo Wendy , Bombonati Alessandro , Palazzo Juan , Solomides Charalambos , Shuber Anthony P , Sinicrope Frank A , Zuzga David S 
Published: June 2018

Background and Aims: The benefit of adjuvant chemotherapy for stage II colorectal cancer (CRC) patients remains unclear, emphasizing the need for improved prognostic biomarkers to identify patients at risk of metastatic recurrence. To address this unmet clinical need, we examined the expression and phosphorylation status of the vasodilator-stimulated phosphoprotein (VASP) in CRC tumor progression. VASP, a processive actin polymerase, promotes the formation of invasive membrane structures leading to extracellular matrix remodeling and tumor invasion. Phosphorylation of VASP serine (Ser) residues 157 and 239 regulate VASP function, directing subcellular localization and inhibiting actin polymerization, respectively. Methods: The expression levels of VASP protein, pSer157-VASP, and pSer239-VASP were determined by immunohistochemistry in tumors and matched normal adjacent tissue from 141 CRC patients, divided into 2 cohorts, and the association of VASP biomarker expression with clinicopathologic features and disease recurrence was examined. Results: We report that changes in VASP expression and phosphorylation were significantly associated with tumor invasion and disease recurrence. Furthermore, we disclose a novel 2-tiered methodology to maximize VASP positive and negative predictive value performance for prognostication. Conclusion: VASP biomarkers may serve as prognostic biomarkers in CRC and should be evaluated in a larger clinical study.
Effect of Xanthine Oxidase Inhibition on Arterial Stiffness in Patients With Chronic Heart Failure
Authors: Alem Manal M , Alshehri Abdullah M , Cahusac Peter MB , Walters Matthew R 
Published: June 2018

Background: The xanthine oxidase inhibitor allopurinol improves endothelial function in different populations, including patients with chronic heart failure (CHF). Its effect on arterial stiffness parameters is less clear. We investigated the effect of short-term low-dose allopurinol therapy on arterial stiffness in Saudi patients with stable mild-moderate CHF. Methods: A prospective, randomized, double-blind, placebo-controlled study was performed on 73 patients with mild-moderate CHF. In all, 36 patients were randomized to allopurinol 300 mg daily for 3 months, while 37 patients were randomized to placebo. Arterial stiffness parameters, aortic pulse wave velocity (Ao-PWV) and heart rate corrected augmentation index (c-AIx), were assessed before and after treatment along with serum uric acid. Results: A total of 66 patients completed the study. Both groups were matched for age, sex, severity of heart failure, and arterial stiffness. Compared with placebo, allopurinol recipients had a significant fall in uric acid concentration from 6.31 ± 1.4 (SD) mg/dL to 3.81 ± 1.2 ( P < .001). Despite that, there was no significant change in arterial stiffness parameters between allopurinol and placebo groups. Post-treatment Ao-PWV was 9.79 ± 2.6 m/s in the allopurinol group and 10.07 ± 3.4 m/s in the placebo group, P = .723. Post-treatment c-AIx was 24.0% ± 9.1% and 22.0% ± 9.9%, respectively, P = .403. Conclusions: We have shown that allopurinol significantly reduced uric acid concentration in Saudi patients with CHF but was not associated with a change in arterial stiffness. Our cohort of patients had worse arterial stiffness values at baseline, which might make them more resistant to change using our study regimen. The study has been registered with the International Standard Randomized Controlled Trial Number registry with an identifier number of ISRCTN58980230.
A Feasibility Study for in vivo Dosimetry Procedure in Routine Clinical Practice
Authors: Falco Maria D. , Giancaterino Stefano , De Nicola Andrea , Adorante Nico , De Lorenzo Ramon Gimenez , Di Tommaso Monica , Vinciguerra Annamaria , Trignani Marianna , Perrotti Francesca , Allajbej Albina , Fidanzio Andrea , Greco Francesca , Grusio Mattia , Genovesi Domenico , Piermattei Angelo 
Published: June 2018

Purpose: The aim of the in vivo dosimetry, during the fractionated radiation therapy, is the verification of the correct dose delivery to patient. Nowadays, in vivo dosimetry procedures for photon beams are based on the use of the electronic portal imaging device and dedicated software to elaborate electronic portal imaging device images. Methods: In total, 8474 in vivo dosimetry tests were carried out for 386 patients treated with 3-dimensional conformal radiotherapy, intensity-modulated radiotherapy, and volumetric modulated arc therapy techniques, using the SOFTDISO. SOFTDISO is a dedicated software that uses electronic portal imaging device images in order to (1) calculate the R index, that is, the ratio between daily reconstructed dose and the planned one at isocenter and (2) perform a γ-like analysis between the signals, S, of a reference electronic portal imaging device image and that obtained in a daily fraction. It supplies 2 indexes, the percentage γ% of points with γ < 1 and the mean γ value, γmean. In γ-like analysis, the pass criteria for the signals agreement ΔS% and distance to agreement Δd have been selected based on the clinical experience and technology used. The adopted tolerance levels for the 3 indexes were fixed in 0.95 ≤ R ≤ 1.05, γ% ≥ 90%, and γmean ≤ 0.5. Results: The results of R ratio, γ-like, and a visual inspection of these data reported on a monitor screen permitted to individuate 2 classes of errors (1) class 1 that included errors due to inadequate standard quality controls and (2) class 2, due to patient morphological changes. Depending on the technique and anatomical site, a maximum of 18% of tests had at least 1 index out of tolerance; once removed the causes of class-1 errors, almost all patients (except patients with 4 lung and 2 breast cancer treated with 3-dimensional conformal radiotherapy) presented mean indexes values ([Formula: see text], [Formula: see text]%, and [Formula: see text] ) within tolerance at the end of treatment course. Class-2 errors were found in some patients. Conclusions: The in vivo dosimetry procedure with SOFTDISO resulted easily implementable, able to individuate errors with a limited workload.
Melanocortin 1 Receptor Targeted Imaging of Melanoma With Gold Nanocages and Positron Emission Tomography
Authors: Zhao Yongfeng , Pang Bo , Detering Lisa , Luehmann Hannah , Yang Miaoxin , Black Kvar , Sultan Deborah , Xia Younan , Liu Yongjian 
Published: June 2018

Purpose: Melanoma is a lethal skin cancer with unmet clinical needs for targeted imaging and therapy. Nanoscale materials conjugated with targeting components have shown great potential to improve tumor delivery efficiency while minimizing undesirable side effects in vivo. Herein, we proposed to develop targeted nanoparticles for melanoma theranostics. Method: In this work, gold nanocages (AuNCs) were conjugated with α-melanocyte-stimulating hormone (α-MSH) peptide and radiolabeled with 64Cu for melanocortin 1 receptor-(MC1R) targeted positron emission tomography (PET) in a mouse B16/F10 melanoma model. Results: Their controlled synthesis and surface chemistry enabled well-defined structure and radiolabeling efficiency. In vivo pharmacokinetic evaluation demonstrated comparable organ distribution between the targeted and nontargeted AuNCs. However, micro-PET/computed tomography (CT) imaging demonstrated specific and improved tumor accumulation via MC1R-mediated delivery. By increasing the coverage density of α-MSH peptide on AuNCs, the tumor delivery efficiency was improved. Conclusion: The controlled synthesis, sensitive PET imaging, and optimal tumor targeting suggested the potential of targeted AuNCs for melanoma theranostics.
Rethinking non-inferiority: a practical trial design for optimising treatment duration
Authors: Quartagno Matteo , Walker A Sarah , Carpenter James R , Phillips Patrick PJ , Parmar Mahesh KB 
Published: June 2018

BackgroundTrials to identify the minimal effective treatment duration are needed in different therapeutic areas, including bacterial infections, tuberculosis and hepatitis C. However, standard non-inferiority designs have several limitations, including arbitrariness of non-inferiority margins, choice of research arms and very large sample sizes.MethodsWe recast the problem of finding an appropriate non-inferior treatment duration in terms of modelling the entire duration–response curve within a pre-specified range. We propose a multi-arm randomised trial design, allocating patients to different treatment durations. We use fractional polynomials and spline-based methods to flexibly model the duration–response curve. We call this a ‘Durations design’. We compare different methods in terms of a scaled version of the area between true and estimated prediction curves. We evaluate sensitivity to key design parameters, including sample size, number and position of arms.ResultsA total sample size of ~ 500 patients divided into a moderate number of equidistant arms (5–7) is sufficient to estimate the duration–response curve within a 5% error margin in 95% of the simulations. Fractional polynomials provide similar or better results than spline-based methods in most scenarios.ConclusionOur proposed practical randomised trial ‘Durations design’ shows promising performance in the estimation of the duration–response curve; subject to a pending careful investigation of its inferential properties, it provides a potential alternative to standard non-inferiority designs, avoiding many of their limitations, and yet being fairly robust to different possible duration–response curves. The trial outcome is the whole duration–response curve, which may be used by clinicians and policymakers to make informed decisions, facilitating a move away from a forced binary hypothesis testing paradigm.
Transfusion Management of Incident Dialysis Patients in Canada: A Prospective Observational Study
Authors: Bello Aminu K. , Ribic Christine M. , Cournoyer Serge H. , Kiaii Mercedeh , LeBlanc Martine , Poulin-Costello Melanie , Churchill David N. , Muirhead Norman 
Published: June 2018

Background: Several studies have demonstrated harm associated with using erythropoiesis-stimulating agents (ESA) to achieve higher hemoglobin (Hb) levels. Subsequently, more conservative use of ESAs has changed anemia therapy in patients with chronic renal failure. Objective: The objectives were to identify transfusion rates in hemodialysis (HD) patients during the first year of therapy, to identify factors associated with the probability of transfusion, describe reasons for the transfusions, and identify the Hb values associated with each transfusion. An exploratory objective was to describe the age of red blood cell transfusions. Design: This was a multicenter prospective observational cohort study. Setting: There were 12 study sites in 5 Canadian provinces. The study was performed from 2012 to 2014. Methods: The study patients were adult incident chronic HD patients in these centers. Patients with acute kidney injury, peritoneal dialysis, and planned transfer to satellite units were excluded. Patients had to receive at least 1 month of chronic HD to be eligible. Data for 3 months prior to HD were obtained by retrospective chart review. Prospectively, charts were reviewed monthly for 12 months for data abstraction. Results: There were 314 patients enrolled and 79.9% completed 12 month follow-up. Ninety-four (29.9%) patients received at least 1 unit of blood. During the first 90 days, the transfusion episode rate was 148.4 per 100 patient-years compared with 62.6 per 100 patient-years post 90 days. The most frequent indication was a low Hb value (92%) with gastrointestinal bleeding, surgical blood loss, and fatigue accounting for 9.9%, 8.6%, and 4.5%, respectively. Some patients had >1 indication. The mean Hb values prior to transfusion episodes ranged from 75.3 to 78.6 g/L. Cox regression analysis on time to first transfusion and time to first hospitalization/death both showed an association with inpatient initiation of HD. Some 37.5% initiated HD as an inpatient and differed from those starting as an outpatient. They had less predialysis care and laboratory data suggested more inflammation. The mean and median ages of the blood units transfused were 24.9 (SD = 10.0) and 23 days (interquartile range = 17-33). Conclusions: This work reported the blood transfusion rate in incident HD patients in Canada during a period associated with conservative ESA prescription. The major indication for transfusion was a low Hb rather than clinical symptoms. Initiation of HD as an inpatient was independently associated with the probability of receiving a blood transfusion. These findings require further investigation.
The impact of YouTube peer feedback on attitudes toward recovery from non-suicidal self-injury: An experimental pilot study
Authors: Lewis Stephen P. , Seko Yukari , Joshi Poojan 
Published: June 2018

Background Non-suicidal self-injury (NSSI) is a serious public health concern facing adolescents and young adults worldwide. Despite growing concern that accessing NSSI content on the internet may negatively influence perceptions toward NSSI recovery, no studies have examined actual impacts. Objectives This experimental pilot study assessed the impact of exposure to hopeless versus hopeful peer messages on perceptions toward NSSI recovery. It was hypothesized that exposure to hopeless messages would lead to more negative perceptions about NSSI recovery whereas the opposite would occur for hopeful messages. Methods We developed fictional peer comments embedded in a screenshot of an NSSI-themed YouTube video and randomly assigned participants to either hopeless or hopeful recovery-oriented comments. Participants’ attitudes toward NSSI recovery, recovery-oriented subjective norms, and recovery self-efficacy were measured pre- and post-exposure using an online questionnaire. Results Sixty-one participants with a self-reported NSSI history (mean age 20.89 years) completed the online survey. There was a statistically significant effect for attitudes toward recovery. Within the hopeful comment condition, there was an increase in positive attitudes toward recovery and in recovery-oriented subjective norms. Participants exposed to hopeless peer messages did not report an increase in hopeless attitudes toward NSSI recovery. Conclusions Our pilot study indicated that exposure to hopeful online messages improved positive attitudes toward recovery and recovery-oriented subjective norms, while exposure to hopeless messages did not increase hopeless attitudes. Future research on the impacts of online peer comments on one’s attitude toward NSSI recovery and support-seeking behavior could further inform practices and policies.
COPD stands for complex obstructive pulmonary disease
Authors: Houben-Wilke Sarah , Augustin Ingrid M. , Vercoulen Jan H. , van Ranst Dirk , bij de Vaate Eline , Wempe Johan B. , Spruit Martijn A. , Wouters Emiel F.M. , Franssen Frits M.E. 
Published: June 2018

Chronic obstructive pulmonary disease (COPD) has extensively been reported as a complex disease affecting patients' health beyond the lungs with a variety of intra- and extrapulmonary components and considerable variability between individuals. This review discusses the assessment of this complexity and underlines the importance of transdisciplinary management programmes addressing the physical, emotional and social health of the individual patient.COPD management is challenging and requires advanced, sophisticated strategies meeting the patient's individual needs. Due to the heterogeneity and complexity of the disease leading to non-linear and consequently poorly predictable treatment responses, multidimensional patient profiling is crucial to identify the right COPD patient for the right treatment. Current methods are often restricted to general, well-known and commonly used assessments neglecting potentially relevant (interactions between) individual, unique “traits” to finally ensure personalised treatment. Dynamic, personalised and holistic approaches are needed to tackle this multifaceted disease and to ensure personalised medicine and value-based healthcare.
Frequency cycling to alleviate unknown frequency offsets for adiabatic half-passage pulses in surface nuclear magnetic resonance
Authors: Grombacher Denys , Dlugosch Raphael , Grunewald Elliot , Müller-Petke Mike , Auken Esben 
Published: June 2018

Adiabatic half-passage (AHP) pulses show great promise for significantly enhancing the signal-to-noise ratio of the surface nuclear magnetic resonance (NMR) free-induction decay measurement. Performing an AHP requires that the frequency sweep terminates when the transmit frequency is equal to the Larmor frequency, a condition that demands accurate knowledge of the true Larmor frequency. If the frequency sweep is terminated at an incorrect frequency, i.e., with an unknown offset between the transmit and Larmor frequency at the end of the pulse, the net excitation is affected and it can differ from that predicted by modeling that assumes a 0 Hz offset at the end of the sweep. Surface NMR surveys using a traditional single-frequency pulse have previously been shown to display degraded performance in the presence of an uncertain Larmor frequency estimate; the AHP pulse is also likely susceptible to such degraded performance. To ensure that reliable results can be produced by AHP pulses in the presence of an uncertain Larmor frequency estimate, we have developed an approach that adapts the frequency-cycling scheme for use with AHP pulses. We hypothesize that data collected using two similar AHP pulses, each with the exact same frequency sweep but where one sweeps toward the Larmor frequency from higher frequencies and the other from lower frequencies, can be stacked in such a manner that the impact of an unknown frequency offset is significantly reduced. We present synthetic and field results to demonstrate that frequency-cycling AHP pulse surface NMR data can ensure reliable performance even in the presence of an uncertain Larmor frequency estimate.
A Unique Case of Metastatic, Functional, Hereditary Paraganglioma Associated With anSDHC Germline Mutation
Authors: Ong Raquel Kristin S , Flores Shahida K , Reddick Robert L , Dahia Patricia L M , Shawa Hassan 
Published: June 2018

Abstract

Context
Mutations in genes encoding for the succinate dehydrogenase (SDH) complex are linked to hereditary paraganglioma syndromes. Paraganglioma syndrome 3 is associated with mutations inSDHC and typically manifests as benign, nonfunctional head and neck paragangliomas.

Design
We describe a case of a 51-year-old woman who initially presented with diarrhea and hypertension and was found to have a retroperitoneal mass, which was resected with a pathology consistent with paraganglioma. Five years later, her symptoms recurred, and she was found to have new retroperitoneal lymphadenopathy and lytic lesions in the first lumbar vertebral body and the right iliac crest, which were visualized on CT scan and octreoscan but not on iodine-123-meta-iodobenzylguanidine (123I-MIBG) and bone scans. She had significantly elevated 24-hour urine norepinephrine and dopamine. The patient received external beam radiation and a series of different antineoplastic agents. Her disease progressed, and she eventually expired within 2 years. Genetic testing revealed a heterozygousSDHC c.43C&gt;T, p.Arg15X mutation, which was also detected in her daughter and her grandson, both of whom have no biochemical or imaging evidence of paraganglioma syndrome yet.

Conclusion
We report a unique case of functional, metastatic abdominal paraganglioma associated withSDHC germline mutation. Our case exemplifies thatSDHC germline mutation has variable penetrance, which may manifest with an aggressive biology that could be missed by a123I-MIBG scan.
Convergence of the Core in Assignment Markets
Authors: Kanoria Yash , Saban Daniela , Sethuraman Jay 
Published: June 2018

We consider a two-sided assignment market with agent types and a stochastic structure, similar to models used in empirical studies. We characterize the size of the core in such markets. Each agent has a randomly drawn productivity with respect to each type of agent on the other side. The value generated from a match between a pair of agents is the sum of the two productivity terms, each of which depends only on the type (but not the identity) of one of the agents, and a third deterministic term driven by the pair of types. We prove, under reasonable assumptions, that when the number of agent types is kept fixed, the relative size of the core vanishes rapidly as the number of agents grows. Numerical experiments confirm that the core is typically small. Our results provide justification for the typical assumption of a unique core outcome in such markets, which is close to a limit point. Further, our results suggest that, given the market composition, wages are almost uniquely determined in equilibrium. The e-companion is available at https://doi.org/10.1287/opre.2017.1691 .
Multiple Organization Goals with Feedback from Shared Technological Task Environments
Authors: Hu Songcui , Bettis Richard A. 
Published: June 2018

Goals and the performance feedback on those goals are fundamental to organizational learning and adaptation. However, most research has focused on single overall, high-level organizational goals while ignoring important operational goals farther down in the goal hierarchy. This paper explores the important issue of interdependent feedback on multiple operational goals with shared task environments. We conjecture about the impact of shared technological task environments on feedback across goals. We then empirically examine these conjectures using panel vector autoregression (PVAR) analysis of performance feedback from three strategically important operational goals with shared technological task environments in the automobile industry. We find that interdependent feedback can lead to severe and misleading confusion regarding learning from feedback on such goals with shared task environments. Then, we discuss the implications of our findings. These include the following: the absolute intractability of the problem of meeting multiple goals with interdependent task environments as the number of goals increases; limits on the modularity of organization structure; and severe challenges in ex post credit assignment and ex ante planning when goals share technological task environments. Finally, we discuss the application of PVAR to interdependent feedback problems in organizations.The online appendices are available at https://doi.org/10.1287/orsc.2018.1207 .