bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sustained exposure to acute migraine medications combined with repeated noxious stimulation dysregulates descending pain modulatory circuits: Relevance to medication overuse headache
Authors: Nation Kelsey M , Dodick David W , Navratilova Edita , Porreca Frank 
Published: October 2018

Background Loss of conditioned pain modulation/diffuse noxious inhibitory controls has been demonstrated in patients with migraine and medication overuse headache. We hypothesized that exposure to acute migraine medications may lead to dysregulation of central pain modulatory circuits that could be revealed by evaluating diffuse noxious inhibitory controls and that prior noxious stimulus is required for a loss of the diffuse noxious inhibitory control response in rats exposed to these medications. Methods Rats were “primed” by continuous infusion of morphine or one of two doses of sumatriptan. Diffuse noxious inhibitory control was evaluated at the end of drug-priming (day 7) and again after sensory thresholds returned to baseline (day 21). The Randall-Selitto hindpaw pressure test was used as the test stimulus and forepaw capsaicin injection served as the conditioning stimulus. Results Morphine-primed rats showed opioid-induced hyperalgesia accompanied by a loss of diffuse noxious inhibitory controls on day 7. Sumatriptan-primed rats did not develop hyperalgesia or loss of diffuse noxious inhibitory controls on day 7. Morphine-primed and high-dose sumatriptan-primed rats only had a loss of diffuse noxious inhibitory control on day 21 if they received a capsaicin injection on day 7. Conclusions Prolonged exposure to migraine treatments followed by an acute nociceptive stimulation caused long-lasting alterations in descending pain modulation, shown by a loss of diffuse noxious inhibitory controls. Morphine was more detrimental than sumatriptan, consistent with clinical observations of higher medication overuse headache risk with opioids. These data suggest a mechanism of medication overuse headache by which migraine medications combined with repeated episodes of pain may amplify the consequences of nociceptor activation and increase the probability of future migraine attacks as well as risk of medication overuse headache.
Salvage surgery for recurrent or persistent tumour after radical (chemo)radiotherapy for locally advanced non-small cell lung cancer: a systematic review
Authors: Dickhoff Chris , Otten Rene H. J. , Heymans Martijn W. , Dahele Max 
Published: October 2018

Background: Once recurrent or persistent locoregional tumour after radical chemoradiotherapy (CRT) for non-small cell lung cancer (NSCLC) is identified, few curative-intent treatment options are available. Selected patients might benefit from surgical salvage. We performed a systematic review of the available literature for this emerging treatment option. Methods: A systematic literature search was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Publications about persistent or (locoregional) recurrent disease after radical/definitive CRT for locally advanced non-small cell lung cancer were identified. Results: Eight full papers were found, representing 158 patients. All were retrospective series and data were heterogeneous: definition and indication for salvage surgery varied and the median time from radiotherapy to surgery was 4.1–33 months. Complete resection (R0) was achieved in 85–100%, with vital tumour in 61–100%. A large number of pneumonectomies were performed, and additional structures were often resected. Where reported, 90-day mortality was 0–11.4%. Reported survival metrics varied but included median overall survival 9–46 months and 5-year survival 20–75%. Conclusion: There are limited, low-level, heterogeneous data in support of salvage surgery after radical CRT. Based on this, perioperative mortality appears acceptable and long-term survival is possible in (highly) selected patients. In suitable patients (fit, no distant metastases, tumour appears completely resectable and preferably with confirmed viable tumour), this treatment option should be discussed in an experienced multidisciplinary lung cancer team.
Effectiveness of different outreach strategies to identify individuals at high risk of diabetes in a heterogeneous population: a study in the Swedish municipality of Södertälje
Authors: Shahim Bahira , Hasselberg Sofia , Boldt-Christmas Oscar , Gyberg Viveca , Mellbin Linda , Rydén Lars 
Published: October 2018

Background Identifying type 2 diabetes mellitus (T2DM) is a prerequisite for the institution of preventive measures to reduce future micro and macrovascular complications. Approximately 50% of people with T2DM are undiagnosed, challenging the assumption that a traditional primary healthcare setting is the most efficient way to reach people at risk of T2DM. A setting of this kind may be even more suboptimal when it comes to reaching immigrants, who often appear to have inferior access to healthcare and/or are less likely to attend routine health checks at primary healthcare centres. Objectives The objective of this study was to identify the best strategy to reach individuals at high risk of T2DM and thereby cardiovascular disease in a heterogeneous population. Methods All 18–65-year-old inhabitants in the Swedish municipality of Södertälje ( n∼51,000) without known T2DM and cardiovascular disease were encouraged to complete the Finnish Diabetes Risk Score (FINDRISC: score > 15 indicating a high and > 20 a very high risk of future T2DM and cardiovascular disease) through the following communication channels: primary care centres, workplaces, Syrian orthodox churches, pharmacies, crowded public places, mass media, social media and mail. Data collection lasted for six weeks. Results The highest response rate was obtained through workplaces (27%) and the largest proportion of respondents at high/very high risk through the Syrian orthodox churches (18%). The proportion reached through primary care centres was 4%, of whom 5% were at elevated risk. The cost of identifying a person at elevated risk through the Syrian orthodox church was €104 compared with €8 through workplaces and €112 through primary care centres. Conclusions The choice of communication channels was important to reach high/very high-risk individuals for T2DM and for screening costs. In this immigrant-dense community, primary care centres were inferior to strategies using workplaces and churches in terms of both the proportion of identified at-risk individuals and costs.
Randomized Trials of Nasal Patency and Dermal Tolerability With External Nasal Dilators in Healthy Volunteers
Authors: Ward John , Ciesla Renee , Becker William , Shanga Gilbert Marava 
Published: October 2018

Background External nasal dilator strips are used as nonpharmacological therapy to reduce snoring and daytime sleepiness. In a product improvement initiative, a marketed strip (BRNS) and 2 prototype nasal strips were evaluated. Objective To compare the nasal patency and multiple-use dermal tolerability of the BRNS and prototype nasal strips using both objective and subject-reported outcome measures. Methods Two studies were conducted separately in healthy volunteers ≥18 years of age. A single-day nasal patency randomized crossover study assessed minimal cross-sectional area (MCA; second restriction) and nasal volume (using acoustic rhinometry); nasal inspiratory flow and resistance (using posterior rhinomanometry); and subject-reported evaluations of the BRNS compared with the butterfly strip and teardrop strip prototypes. A single-center, randomized, controlled, parallel-group, evaluator-blinded study assessed dermal tolerability of the BRNS and the butterfly strip over 7 consecutive nights of use, using the Dermal Response Scale (DRS) and subject-reported comfort and ease of removal. Results In the Patency study (N = 50), all 3 strips demonstrated significant improvement from baseline in MCA, nasal volume, and nasal flow parameters (resistance and peak flow). The prototype strips demonstrated significantly more improvement in nasal volume than the BRNS, and the butterfly strip showed significantly more improvement in MCA than the BRNS; all strips were similar with respect to nasal flow and subject-reported nasal breathing outcomes. In the Dermal Tolerability study (N = 82), all subjects scored 0 (no evidence of irritation) on the DRS at all 7 morning assessments; the BRNS was numerically, but not significantly, superior to the butterfly strip on subject-reported outcomes. Conclusion The Patency study demonstrated significant improvement from baseline in nasal dimensions and flow for all 3 evaluated strips; between-strip differences were confined to nasal dimensions. Both the BRNS and butterfly strip were generally well tolerated, with no evidence of dermal response over 7 consecutive nights of use. ClinicalTrials.gov identifiers: NCT01105949 and NCT01495494
Accounting for Growth Effects of Age Structure Transition through Public Education Expenditure: New Macroeconomic Evidence from India
Authors: Narayana M. R. 
Published: October 2018

This article quantifies the growth effects of age structure transition through current public education expenditure. Using the National Transfer Accounts’ (NTA) First Demographic Dividend (FDD) model, growth effects are accounted by the impact of current public education expenditure on economic support ratio (ESR) and labour productivity through human capital investments. The results offer new macroeconomic evidence. Age structure transition reduces the education dependency ratio (EDR) by all levels of education but the highest in the elementary education. This impacts on a long-term decline in enrolment in elementary education where the current gross enrolment ratio (GER) is close to 100 per cent and a decline in current public education expenditure. Other things being equal, the resultant potential savings, or the availability of extra budgetary resources, is a new way of financing the investment requirements for secondary and higher education with the aim of increasing national economic growth through human capital investments. In particular, growth effects are shown to be positive, higher and longer up to 2050, if the current public education spending is reallocated more for the secondary and higher education. Surprisingly, growth effects are explained less by the ESR than labour productivity. This justifies a higher human capital investment to enhance labour productivity for attainment of higher economic growth. The afore- mentioned macroeconomic framework, results and implications are of general relevance for other developing countries in South Asia and elsewhere in the world. JEL Classification: E65, H52, J11
Patient Preferences for the Treatment of Shoulder and Proximal Biceps Disorders Are Associated With Patient Age, Race, Sex, and Activity Level
Authors: Smith Matthew V. , Gosselin Michelle , Steger-May Karen , Matava Matthew J. , Wright Rick W. , Brophy Robert H. 
Published: October 2018

Background: Patient preference information has become increasingly more important in clinical decision making. Purpose: To assess patient preferences when making treatment decisions in the shoulder to determine which features are more important according to patient age, race, activity level, and sex. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Study participants aged ≥18 years were surveyed as to their preferences regarding surgical treatment for shoulder and proximal biceps abnormalities. Survey features included time to return to unrestricted activities, time to return to work, size and appearance of scars, the potential for persistent pain in the upper arm or shoulder, fatigue in the biceps with repetitive lifting, potential for muscle cramping, and deformity in the proximal biceps. Participants also completed a validated shoulder activity scale, and demographic data regarding age, race, and sex were collected. Results: A total of 349 participants (166 female, 183 male) with a mean age of 45 years (range, 18-81 years) completed the survey. Overall, time to return to unrestricted activities and residual pain were considered very important to the majority of the respondents, while the size and appearance of surgical scars were of little importance. Prior shoulder pain (ρ = –0.17; P = .01) and prior shoulder surgery (ρ = –0.16; P = .03) correlated to concern about time to return to unrestricted activities. Younger age (ρ = –0.11; P = .04) and a higher level of education (ρ = 0.14; P = .03) correlated with greater concern for time to return to work. Women and African Americans were more concerned about the size and appearance of surgical scars (ρ = –0.28; P < .0001 and ρ = –0.20; P = .0002, respectively) and biceps deformity. Respondents with a higher activity level (ρ = 0.20; P = .0002) and men (ρ = 0.11; P = .04) were more concerned about fatigue. Conclusion: Concerns about residual pain, time to return to unrestricted activities, and time away from work are important to patients when considering the treatment for shoulder lesions. Patient preferences are associated with age, sex, race, and shoulder activity level. These features should be considered when discussing treatment options for shoulder and proximal biceps tendon disorders.
Proteomic profiling identifies outcome-predictive markers in patients with peripheral T-cell lymphoma, not otherwise specified
Authors: Ludvigsen Maja , Bjerregård Pedersen Martin , Lystlund Lauridsen Kristina , Svenstrup Poulsen Tim , Hamilton-Dutoit Stephen Jacques , Besenbacher Søren , Bendix Knud , Møller Michael Boe , Nørgaard Peter , d’Amore Francesco , Honoré Bent 
Published: October 2018

Abstract
Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) constitutes a heterogeneous category of lymphomas, which do not fit into any of the specifically defined T-cell lymphoma entities. Both the pathogenesis and tumor biology in PTCL-NOS are poorly understood. Protein expression in pretherapeutic PTCL-NOS tumors was analyzed by proteomics. Differentially expressed proteins were compared in 3 distinct scenarios: (A) PTCL-NOS tumor tissue (n = 18) vs benign lymphoid tissue (n = 8), (B) clusters defined by principal component analysis (PCA), and (C) tumors from patients with chemosensitive vs refractory PTCL-NOS. Selected differentially expressed proteins identified by proteomics were correlated with clinico-pathological features and outcome in a larger cohort of patients with PTCL-NOS (n = 87) by immunohistochemistry (IHC). Most proteins with altered expression were identified comparing PTCL-NOS vs benign lymphoid tissue. PCA of the protein profile defined 3 distinct clusters. All benign samples clustered together, whereas PTCL-NOS tumors separated into 2 clusters with different patient overall survival rates (P = .001). Differentially expressed proteins reflected large biological diversity among PTCL-NOS, particularly associated with alterations of “immunological” pathways. The 2 PTCL-NOS subclusters defined by PCA showed disturbance of “stress-related” and “protein metabolic” pathways. α-Enolase 1 (ENO1) was found differentially expressed in all 3 analyses, and high intratumoral ENO1 expression evaluated by IHC correlated with poor outcome (hazard ratio, 2.09; 95% confidence interval, 1.17-3.73; P = .013). High expression of triosephosphate isomerase (TPI1) also showed a tendency to correlate with poor survival (P = .057). In conclusion, proteomic profiling of PTCL-NOS provided evidence of markedly altered protein expression and identified ENO1 as a novel potential prognostic marker.
Eculizumab in cold agglutinin disease (DECADE): an open-label, prospective, bicentric, nonrandomized phase 2 trial
Authors: Röth Alexander , Bommer Martin , Hüttmann Andreas , Herich-Terhürne Dörte , Kuklik Nils , Rekowski Jan , Lenz Veronika , Schrezenmeier Hubert , Dührsen Ulrich 
Published: October 2018

Abstract
Cold agglutinin disease (CAD) is a complement-dependent disorder, with extravascular and intravascular hemolysis resulting from initial or terminal complement activation, respectively. We tested the efficacy and safety of eculizumab, an inhibitor of the terminal complement pathway. Treatment-requiring patients received 600 mg eculizumab weekly for 4 weeks, followed 1 week later by 900 mg every other week through week 26. The primary end point was the difference in the lactate dehydrogenase level between the first and the last day of therapy. Twelve patients with chronic CAD and 1 patient with an acute cold agglutinin syndrome were included. The median lactate dehydrogenase level decreased from 572 U/L (interquartile range [IQR], 534-685) to 334 U/L (IQR, 243-567; P = .0215), paralleled by an increase in hemoglobin from 9.35 g/dL (IQR, 8.80-10.80) to 10.15 g/dL (IQR, 9.00-11.35; P = .0391; Wilcoxon signed-rank test). Three patients maintained and 8 patients acquired transfusion independence, and 1 patient each showed a reduced or increased transfusion requirement, respectively (P = .0215; exact McNemar’s test). Patients with cold agglutinins with a thermal amplitude of 37°C tended to have less pronounced lactate dehydrogenase responses than patients with cold agglutinins with narrower thermal amplitudes. In the latter, responses were observed at lower serum levels of eculizumab than they were in the former. In contrast to hemolysis, cold-induced circulatory symptoms remained unaffected. In conclusion, eculizumab significantly reduced hemolysis and transfusion requirement in patients with CAD. Suppression of hemolysis caused by cold agglutinins with a wide thermal amplitude may require higher eculizumab doses than used here. The trial is registered with EudraCT (#2009-016966-97) and www.clinicaltrials.gov (#NCT01303952).
Labor market mobility and the early-career outcomes of immigrant men
Authors: Javdani Mohsen , McGee Andrew 
Published: October 2018

AbstractWe examine the role of between- and within-firm mobility in the early-career outcomes of immigrant men. Among Canadian workers with less than 10 years of potential experience, we find that visible minority immigrants were significantly less likely to have been promoted with their initial employers than similar white natives but were just as likely to have moved to new employers over the course of a year between interviews. White immigrants, on the other hand, were just as likely to be promoted as white natives but much more likely to move to new employers—suggesting that they enjoyed more overall mobility than white natives and other immigrants. We present tentative evidence linking these mobility patterns to differences in wage growth and occupational change between immigrants and natives. Overall, our findings suggest that the between- and within-firm mobility of white immigrants may play an important role in their relative economic success in Canada, while adding to growing evidence that visible minority immigrants experience frictions in the labor market that hinder their mobility and thus their economic prospects.JEL Classification:J61, J71
Nanoengineered, cell-derived extracellular matrix influences ECM-related gene expression of mesenchymal stem cells
Authors: Ozguldez Hatice O. , Cha Junghwa , Hong Yoonmi , Koh Ilkyoo , Kim Pilnam 
Published: October 2018

Abstract

Background
Human mesenchymal stem cells (hMSCs) are, due to their pluripotency, useful sources of cells for stem cell therapy and tissue regeneration. The phenotypes of hMSCs are strongly influenced by their microenvironment, in particular the extracellular matrix (ECM), the composition and structure of which are important in regulating stem cell fate. In reciprocal manner, the properties of ECM are remodeled by the hMSCs, but the mechanism involved in ECM remodeling by hMSCs under topographical stimulus is unclear. In this study, we therefore examined the effect of nanotopography on the expression of ECM proteins by hMSCs by analyzing the quantity and structure of the ECM on a nanogrooved surface.

Methods
To develop the nanoengineered, hMSC-derived ECM, we fabricated the nanogrooves on a coverglass using a UV-curable polyurethane acrylate (PUA). Then, hMSCs were cultivated on the nanogrooves, and the cells at the full confluency were decellularized. To analyze the effect of nanotopography on the hMSCs, the hMSCs were re-seeded on the nanoengineered, hMSC-derived ECM.

Results
hMSCs cultured within the nano-engineered hMSC-derived ECM sheet showed a different pattern of expression of ECM proteins from those cultured on ECM-free, nanogrooved surface. Moreover, hMSCs on the nano-engineered ECM sheet had a shorter vinculin length and were less well-aligned than those on the other surface. In addition, the expression pattern of ECM-related genes by hMSCs on the nanoengineered ECM sheet was altered. Interestingly, the expression of genes for osteogenesis-related ECM proteins was downregulated, while that of genes for chondrogenesis-related ECM proteins was upregulated, on the nanoengineered ECM sheet.

Conclusions
The nanoengineered ECM influenced the phenotypic features of hMSCs, and that hMSCs can remodel their ECM microenvironment in the presence of a nanostructured ECM to guide differentiation into a specific lineage.
Adjuvant Gemcitabine Plus Docetaxel Followed by Doxorubicin Versus Observation for High-Grade Uterine Leiomyosarcoma: A Phase III NRG Oncology/Gynecologic Oncology Group Study
Authors: Hensley Martee L. , Enserro Danielle , Hatcher Helen , Ottevanger Petronella B. , Krarup-Hansen Anders , Blay Jean-Yves , Fisher Cyril , Moxley Katherine M. , Lele Shashikant B. , Lea Jayanthi S. , Tewari Krishnansu S. , Thaker Premal H. , Zivanovic Oliver , O’Malley David M. , Robison Katina , Miller David S. 
Published: October 2018

PurposeWe conducted a randomized phase III trial to determine whether adjuvant chemotherapy improves survival in women with uterine leiomyosarcoma.MethodsWomen with uterus-confined, high-grade leiomyosarcoma who were confirmed disease free by imaging were randomly assigned to four cycles of gemcitabine plus docetaxel, followed by four cycles of doxorubicin, or to observation. All were followed for evidence of recurrence. The primary end point was overall survival (OS).ResultsWith international collaboration, 38 of the targeted accrual of 216 patients were enrolled, after which the study was closed by the National Cancer Institute for accrual futility. Twenty patients were assigned to chemotherapy, 18 to observation. Among the 17 patients treated with at least one cycle of chemotherapy, grade 3 or 4 toxicities were observed in 47%; among the 18 patients assigned to observation, one had grade 3 hypertension. There were six deaths (chemotherapy, n = 5; observation, n = 1), all due to disease. The restricted mean survival time for OS was estimated as 34.3 months (95% CI, 25.3 to 43.3 months) in the chemotherapy arm and as 46.4 months (95% CI, 43.6 to 49.1 months) in the observation arm. There were eight recurrences in each arm. The restricted mean survival time for recurrence-free survival was estimated as 18.1 (95% CI, 14.2 to 22.0) months in the chemotherapy arm and as 14.6 months (95% CI, 10.3 to 19.0 months) in the observation arm. Neither survival outcome comparison was considered statistically robust, due to the small sample size.ConclusionDespite international collaboration to test the role of adjuvant chemotherapy in uterine-confined leiomyosarcoma, this study was closed for accrual futility. Although the sample size precludes robust statistical comparison, observed OS and recurrence-free survival data do not show superior outcomes with adjuvant chemotherapy.