bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prescription Drug Coverage and Outcomes of Myeloma Therapy Among Medicare Beneficiaries
Authors: Olszewski Adam J. , Dusetzina Stacie B. , Trivedi Amal N. , Davidoff Amy J. 
Published: August 2018

Purpose Novel parenteral (bortezomib) and oral (lenalidomide) therapies have improved survival in myeloma, but the standard Medicare benefit covers only parenteral drugs. We examined the association between prescription drug coverage, receipt of therapy, and survival among Medicare beneficiaries with myeloma. Methods Using SEER-Medicare data, we identified enrollment in a Medicare Part D plan (PDP) or other creditable prescription drug coverage (OCC) among 9,755 beneficiaries who were diagnosed with myeloma in 2006 to 2011. We examined the receipt of active myeloma therapy and that of classic cytotoxic agents or bortezomib as first-line regimen and overall survival. We report relative risk (RR) for binary outcome comparisons and 3-year restricted mean survival time (RMST) ratios, with 95% CI, adjusting for baseline patient- and disease-related characteristics. Beneficiaries with diffuse large B-cell lymphoma, a cancer that is uniformly treated with parenteral chemotherapy, served as a comparison cohort. Results Compared with beneficiaries without prescription drug coverage, PDP or OCC enrollees were more likely to receive active myeloma care, and PDP enrollees were less frequently treated with parenteral agents (adjusted RR, 0.86; 95% CI, 0.80 to 0.93) or classic cytotoxic agents in particular (RR, 0.62; 95% CI, 0.51 to 0.76). Overall survival was significantly better for beneficiaries with PDP coverage (adjusted RMST ratio, 1.16; 95% CI, 1.11 to 1.20) or OCC (RMST ratio, 1.16; 95% CI, 1.12 to 1.21). In contrast, we observed no survival differences by prescription drug coverage status in the control cohort with lymphoma. Conclusion Prescription drug coverage is associated with decreased use of classic cytotoxic chemotherapy and better survival among Medicare beneficiaries with myeloma, which suggests improved access to all existing treatment options. As oral targeted agents increasingly replace parenteral chemotherapy in oncology, adjustments in coverage policy are needed to ensure access to optimal treatment.
Evaluation of the HER/PI3K/AKT Family Signaling Network as a Predictive Biomarker of Pathologic Complete Response for Patients With Breast Cancer Treated With Neratinib in the I-SPY 2 TRIAL
Authors: Wulfkuhle Julia D. , Yau Christina , Wolf Denise M. , Vis Daniel J. , Gallagher Rosa I. , Brown-Swigart Lamorna , Hirst Gillian , Voest Emile E. , DeMichele Angela , Hylton Nola , Symmans Fraser , Yee Douglas , Esserman Laura , Berry Donald , Liu Minetta , Park John W. , Wessels Lodewyk F.A. , van’t Veer Laura , Petricoin Emanuel F. 
Published: August 2018

Purpose In the I-SPY 2 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis 2), the pan–erythroblastic oncogene B inhibitor neratinib was available to all hormone receptor (HR)/human epidermal growth factor receptor 2 (HER2) subtypes and graduated in the HR-negative/HER2-positive signature. We hypothesized that neratinib response may be predicted by baseline HER2 epidermal growth factor receptor (EGFR) signaling activation/phosphorylation levels independent of total levels of HER2 or EGFR proteins. Materials and Methods Complete experimental and response data were available for between 130 and 193 patients. In qualifying analyses, which used logistic regression and treatment interaction analysis, 18 protein/phosphoprotein, 10 mRNA, and 12 DNA biomarkers that related to HER family signaling were evaluated. Exploratory analyses used Wilcoxon rank sum and t tests without multiple comparison correction. Results HER pathway DNA biomarkers were either low prevalence or nonpredictive. In expression biomarker analysis, only one gene ( STMN1) was specifically associated with response to neratinib in the HER2-negative subset. In qualifying protein/phosphoprotein analyses that used reverse phase protein microarrays, six HER family markers were associated with neratinib response. After analysis was adjusted for HR/HER2 status, EGFR Y1173 (pEGFR) showed a significant biomarker-by-treatment interaction ( P = .049). Exploratory analysis of HER family signaling in patients with triple-negative (TN) disease found that activation of EGFR Y1173 ( P = .005) and HER2 Y1248 (pHER2) ( P = .019) were positively associated with pathologic complete response. Exploratory analysis in this pEGFR/pHER2–activated TN subgroup identified elevated levels of estrogen receptor α ( P < .006) in these patients. Conclusion Activation of HER family phosphoproteins associates with response to neratinib, but only EGFR Y1173 and STMN1 appear to add value to the graduating signature. Activation of HER2 and EGFR in TN tumors may identify patients whose diseases respond to neratinib and implies that there is a subset of patients with TN disease who paradoxically exhibit HER family signaling activation and may achieve clinical benefit with neratinib; this concept must be validated in future studies.
Complete Kisspeptin Receptor Inactivation Does Not Impede Exogenous GnRH-Induced LH Surge in Humans
Authors: Hugon-Rodin Justine , Yoshii Keisuke , Lahlou Najiba , Flandrin Jennifer , Gompel Anne , de Roux Nicolas 
Published: August 2018

Abstract

Context
Mutations in the kisspeptin receptor (KISS1R) gene have been reported in a few patients with normosmic congenital hypogonadotropic hypogonadism (nCHH) (OMIM #146110).

Objectives
To describe a female patient with nCHH and a novel homozygous KISS1R mutation and to assess the role of kisspeptin pathway to induce an ovulation by GnRH pulse therapy.

Design, Setting, and Intervention
Observational study of a patient including genetic and kisspeptin receptor functions and treatment efficiency using a GnRH pump.

Main Outcome Measure
Response to pulsatile GnRH therapy

Results
A partial isolated gonadotropic deficiency was diagnosed in a 28-year-old woman with primary amenorrhea and no breast development. A novel homozygous c.953T&gt;C variant was identified in KISS1R. This mutation led to substitution of leucine 318 for proline (p.Leu318Pro) in the seventh transmembrane domain of KISS1R. Signaling via the mutated receptor was profoundly impaired in HEK293-transfected cells. The mutated receptor was not detected on the membrane of HEK293-transfected cells. After several pulsatile GnRH therapy cycles, an LH surge with ovulation and pregnancy was obtained.

Conclusion
GnRH pulsatile therapy can induce an LH surge in a woman with a mutated KISS1R, which was previously thought to be completely inactivated in vivo.
The GCs-SGK1-ATP Signaling Pathway in Spinal Astrocytes Underlied Presurgical Anxiety-Induced Postsurgical Hyperalgesia
Authors: Zhang ZuoXia , Wu Hao , Liu Yue , Gu XiaoPing , Zhang Wei , Ma ZhengLiang 
Published: August 2018

BACKGROUND:
Patients undergoing surgery often feel anxious. Accumulating evidence indicated that presurgical anxiety was related to the more severe postsurgical pain. An animal model was established that exposed Sprague-Dawley rats to a single-prolonged stress (SPS) procedure to induce presurgical anxiety-like behaviors. The experiment revealed that presurgical anxiety not only aggravated but also prolonged postsurgical pain. However, the underlying mechanisms were unknown.

METHODS:
The rats in group C + Cort, group I + Cort, group A + Cort, and group AI + Cort were injected with corticosterone. The rats in group C + RU486, group I + RU486, group A + RU486, and group AI + RU486 were injected with mifepristone (RU486). The rats in group C + GSK650394 and group AI + GSK650394 were injected with GSK650394. The rats in group C + FC1 and group AI + FC1 were injected with fluorocitrate (FC) 30 minutes before SPS, 30 minutes before incision, and on postoperative days 1, 2, 3, 4, and 5. The rats in group C + FC2 and group AI + FC2 were injected with FC on postoperative days 7, 8, 9, 10, 11, 12, and 13. The paw withdrawal mechanical threshold was assessed 24 hours before SPS and from postoperative days 1 to 28. The level of corticosterone was determined by enzyme-linked immunosorbent assay. The expression of serum/glucocorticoid regulated kinase 1 (SGK1), interleukin-1β, and tumor necrosis factor-α was visualized by Western blot. The concentrations of adenosine triphosphate (ATP) were measured by ATP assay kit.

RESULTS:
This study showed SPS elevated plasma glucocorticoids and ATP release from astrocytes, which meant the mechanical pain hypersensitivity in presurgical anxiety-induced postsurgical hyperalgesia was dependent on GCs-SGK1-ATP signaling pathway. SGK1 protein level in astrocytes was increased in response to the glucocorticoid stimuli and enhanced the extracellular release of ATP. Furthermore, spinal astrocytes played a key role in the maintenance. Targeting spinal astrocytes in maintenance phase prevented the pathological progression.

CONCLUSIONS:
These data suggested an important signaling pathway that affected the pain sensitivity after operation caused by presurgical anxiety.
Factors Associated With Recovery Room Intravenous Opiate Requirement After Pediatric Outpatient Operations
Authors: Nafiu Olubukola O. , Thompson Aleda , Chiravuri S. Devi , Cloyd Benjamin , Reynolds Paul I. 
Published: August 2018

BACKGROUND:
Many children recovering from anesthesia experience pain that is severe enough to warrant intravenous (IV) opioid treatment within moments of admission to the postanesthesia care unit (PACU). Postoperative pain has several negative consequences; therefore, preventing significant PACU pain in children is both a major clinical goal and a moral/ethical imperative. This requires identifying patient-level and perioperative factors that may be used to predict PACU IV opioid requirement. This should allow for the development of personalized care protocols to prevent clinically significant PACU pain in children. Our objective was to develop prediction models enabling practitioners to identify children at risk for PACU IV opioid requirement after various painful ambulatory surgical procedures.

METHODS:
After Institutional Review Board approval, clinical, demographic, and anthropometric data were prospectively collected on 1256 children 4–17 years of age scheduled for painful ambulatory surgery (defined as intraoperative administration of analgesia or local anesthetic infiltration). Three multivariable logistic regression models to determine possible predictors of PACU IV opioid requirement were constructed based on (1) preoperative history; (2) history + intraoperative variables; and (3) history + intraoperative variables + PACU variables. Candidate predictors were chosen from readily obtainable parameters routinely collected during the surgical visit. Predictive performance of each model was assessed by calculating the area under the respective receiver operating characteristic curves.

RESULTS:
Overall, 29.5% of patients required a PACU IV opioid, while total PACU analgesia requirement (oral or IV) was 41.1%. Independent predictors using history alone were female sex, decreasing age, surgical history, and non-Caucasian ethnicity (model area under the receiver operating characteristic curve [AUROC], 0.59 [95% confidence interval {CI}, 0.55–0.63]). Adding a few intraoperative variables improved the discriminant ability of the model (AUROC for the history + intraoperative variables model, 0.71 [95% CI, 0.67–0.74]). Addition of first-documented PACU pain score produced a substantially improved model (AUROC, 0.85 [95% CI, 0.82–0.87]).

CONCLUSIONS:
Postoperative pain requiring PACU IV opioid in children may be determined using a small set of easily obtainable perioperative variables. Our models require validation in other settings to determine their clinical usefulness.
Studying the differential efficacy of postsymptom antitoxin treatment in type A versus type B botulism using a rabbit spirometry model
Authors: Torgeman Amram , Schwartz Arieh , Diamant Eran , Baruchi Tzadok , Dor Eyal , Ben David Alon , Pass Avi , Barnea Ada , Tal Arnon , Rosner Amir , Rosen Osnat , Zichel Ran 
Published: August 2018

ABSTRACT
Botulinum neurotoxin (BoNT) serotypes A, B and E are responsible for most cases of human botulism. The only approved therapy for botulism is antitoxin treatment administered to patients after symptom onset. However, a recent meta-analysis of antitoxin efficacy in human botulism cases over the past century concluded that a statistically significant reduction in mortality is associated with the use of type E and type A antitoxin, but not with type B antitoxin. Animal models could be highly valuable in studying postsymptom antitoxin efficacy (PSAE). However, the few attempts to evaluate PSAE in animals relied on subjective observations and showed ∼50% protection. Recently, we developed a novel spirometry model for the quantitative evaluation of PSAE in rabbits and used it to demonstrate full protection against BoNT/E. In the current study, a comparative evaluation of PSAE in botulism types A and B was conducted using this quantitative respiratory model. A lethal dose of each toxin induced a comparable course of disease both in terms of time to symptoms (TTS, 41.9±1.3 and 40.6±1.1 h, respectively) and of time to death (TTD, 71.3±3.1 and 66.3±1.7 h, respectively). However, in accordance with the differential serotypic PSAE observed in humans, postsymptom antitoxin treatment was fully effective only in BoNT/A-intoxicated rabbits. This serotypic divergence was reflected by a positive and statistically significant correlation between TTS and TTD in BoNT/A-intoxicated rabbits (r=0.91, P=0.0006), but not in those intoxicated with BoNT/B (r=0.06, P=0.88). The rabbit spirometry system might be useful in the evaluation toolkit of botulism therapeutics, including those under development and intended to act when antitoxin is no longer effective.
Predictors of Dropout in Exercise Trials in Older Adults: The Generation 100 Study
Authors: VIKEN HALLGEIR , REITLO LINE SKARSEM , ZISKO NINA , NAUMAN JAVAID , ASPVIK NILS PETTER , INGEBRIGTSEN JAN ERIK , WISLØFF ULRIK , STENSVOLD DORTHE 
Published: August 2018

ABSTRACT

Purpose
Dropout from exercise programs, both in the real world and in research, is a challenge, and more information on dropout predictors is needed for establishing strategies to increase the likelihood of maintaining participants in a prescribed exercise program. The aim of the present study was to determine the dropout rate and its predictors during a 3-yr exercise program in older adults.

Methods
In total, 1514 men and women (mean ± SD age = 72.4 ± 1.9 yr) were included in the present study. Participants were randomized to either a supervised exercise intervention or to follow national guidelines for physical activity (PA). Self-reported demographics (e.g., education), general health, morbidity (e.g., heart disease, memory loss, and psychological distress), smoking, and PA were examined at baseline. Cardiorespiratory fitness (CRF) and grip strength were directly measured at baseline. Dropout rate was evaluated after 1 and 3 yr. Multivariate logistic regression analysis was used to identify dropout predictors.

Results
The total dropout rate was 11.0% (n = 166) after 1 yr and 14.9% (n = 225) after 3 yr. Significant predictors of dropout after 1 yr were low education, low grip strength, lower cardiorespiratory fitness, low PA level, and randomization to supervised exercise. The same predictors of dropout were significant after 3 yr, with reduced memory status as an additional predictor.

Conclusion
This is the largest study to identify dropout predictors in a long-term exercise program in older adults. Our findings provide new and important knowledge about potential risk factors of dropout in long-term exercise programs in older adults.
Preliminary study on the inhibitory effect of seaweed Gracilaria verrucosa extract on biofilm formation of Candida albicans cultured from the saliva of a smoker
Authors: Mubarak Zaki , Humaira Adintya , Gani Basri A. , Muchlisin Zainal A. 
Published: August 2018

Background: Candida albicans is an opportunistic fungus that might infect the oral cavity. Increased colony numbers of C. albicans in the mouth can be caused by multiple factors, such as smoking, weakened immune system, antibiotics use and immune-compromised condition. Smoking can increase expression of virulence factors of C. albicans and make it stronger. One virulence factor of C. albicans is biofilm formation. The ability of creating biofilm makes C. albicans more tolerant to commercial antifungal agents. The objective of this preliminary study was to examine the ability of the seaweed G. verrucosa extracts to inhibit the formation of biofilm by C. albicans isolated from the saliva of a smoker. Methods: The extract of G. verrucosa was prepared by maceration using 96% methanol and subjected for phytochemical analysis. C. albicans was isolated from the saliva of a smoker who voluntarily participated in the study after providing informed consent. In triplicate, the fungus was cultured in the growth medium containing increased concentrations of G. verrucosa (6.25, 12.5, 25, 50, 75 and 100% ).The same reaction using fluconazole 0.31 µg/ml C. albicans was prepared as positive control. Biofilm formation was accessed based on optical density of cell mixtures using an ELISA reader. The data obtained were subjected to Kruskal-Wallis test at a significance limit of 0.05. Results: Methanol extract of seaweed G. verrucosa contained three bio-active compounds namely steroids, terpenoid, and tannins. Inhibitory activity of seaweed extracts on C. albicans biofilm formation increased as their concentration increased. The highest inhibitory effect was recorded at fungus culture treated with seaweed concentration of 25% at 24 hours of time exposure. Conclusions: Seaweed G. verrucosa extract contained steroids, terpenoids and tannins that were able to effectively inhibit the formation of biofilm by C. albicans at the concentration of 25% after 24 hours of time exposure.
Usos e abusos da leitura de Proust: reflexões em torno de Como Proust pode mudar sua vida (Alain de Botton) e Proust e os signos (Gilles Deleuze)
Authors: Tucherman Ieda 
Published: August 2018

A proposta deste texto é antiga, tratando de uma indagação que retorna por meios contemporâneos: a arte deve ser medida ou produzida com um sentido de utilidade? Sem julgamento a priori, as duas propostas das leituras que apresentamos se relacionam de maneira contrastante com esta inquietação: a leitura de Alan de Botton é quase terapêutica; Proust, um dos mais herméticos escritores do século XX, aparece a partir de rubricas que podemos associar aos títulos da literatura de autoajuda. Em Deleuze, ela reside no fato de ser a literatura a experiência de gaguejar na própria língua, produzir mundos possíveis no campo da arte e dos sistemas de pensamento. Neste caso, ao contrário de acalmar ou indicar caminhos, sua função é nos lançar na zona do inesperado.
Guiando públicos: proposições de consumo de Fortaleza como cidade-sede da Copa do Mundo FIFA 2014.
Authors: Silva Emylianny Brasil , Belmino Sílvia Helena 
Published: August 2018

Resumo Na posição de cidade-sede da Copa do Mundo FIFA 2014 Fortaleza colocou-se em uma trajetória de exibição global de atributos. Um contexto de realocação de imagem apoiada em discursos de apresentação e orientação de consumo de Fortaleza. O questionamento em que se baseia este artigo é: Quem são os públicos e como eles são referidos nos guias de cidade-sede? A partir da metodologia de Análise Crítica do Discurso, foram analisadas seções de guias de cidade lançados para o megaevento.
Vaidapé na Rua: uma proposta dialógica da Rádio Comunitária
Authors: Albano da Silva Júlia Lúcia De Oliveira 
Published: August 2018

Este texto objetiva mostrar no contexto das mídias digitais em rede, a experiência de interação baseada no diálogo entre a Rádio Comunitária Cidadã FM e o programa Vaidapé na Rua que integra a programação semanal da emissora localizada na região Oeste do município de São Paulo. Partindo da compreensão das dinâmicas dialógicas e discursivas inerentes aos processos comunicacionais e estudadas pelo jornalista e teórico Vilém Flusser, o texto objetiva evidenciar as possibilidades que um ambiente comunicacional pode desencadear para uma prática efetivamente comunitária. Para a compreensão sobre a rádio comunitária na conhecida “sociedade em rede”, o texto situa brevemente o surgimento e desenvolvimento do movimento das rádios comunitárias no Brasil, iniciado nas últimas duas décadas do século XX, quando motivadas pelas experiências das rádios livres, atuaram na luta contra a opressão dos poderes estatal e econômico e pela democratização do acesso aos meios de comunicação de massa. Além da pesquisa bibliográfica, o estudo recorre à pesquisa documental e de campo na realização de entrevistas qualitativas. Conclui-se que além da necessária desmitificação tecnológica e sua apropriação popular, a dinâmica dialógica em equilíbrio com a discursiva atua para o surgimento de ambientes comunicacionais propícios para o compartilhamento de conhecimentos e prática da cidadania.
Correlation between skin and bone parameters in women with postmenopausal osteoporosis
Authors: Aurégan Jean-Charles , Bosser Catherine , Bensidhoum Morad , Bégué Thierry , Hoc Thierry 
Published: August 2018

Skin and bone share similarities in terms of biochemical composition. Some authors have hypothesized that their properties could evolve concomitantly with age, allowing the estimation of the parameters of one from those of the other. We performed a systematic review of studies reporting the correlation between skin and bone parameters in women with postmenopausal osteoporosis. Fourteen studies – including 1974 patients – were included in the review. Three of these studies included two groups of participants – osteoporotic and non-osteoporotic – in order to compare skin parameters between them: two studies found a significant difference between the two groups and one did not. Eleven of these studies included one population of interest and compared its skin and bone parameters in a continuous manner: eight studies compared dermal thickness to bone mineral density (seven found a significant correlation [R = 0.19–0.486] and one did not); two studies compared skin elasticity to bone mineral density (both found a significant correlation [R = 0.44–0.57); and one study compared skin collagen to bone mineral density and found a significant correlation (R = 0.587). It can be assumed that the estimation of skin alterations from ageing could help in estimating concomitant bone alterations. Cite this article: EFORT Open Rev 2018;3:449-460. DOI: 10.1302/2058-5241.3.160088