bluuebunny/crossref_metadata_2025_split huggingface dataset:
FDA's Approach to Regulating Biosimilars
Authors: Lemery Steven J. , Ricci M. Stacey , Keegan Patricia , McKee Amy E. , Pazdur Richard 
Published: December 2016

Abstract
The Biologics Price Competition and Innovation (BPCI) Act, enacted as part of the Affordable Care Act, created a new licensure pathway for biological products demonstrated to be biosimilar with or interchangeable with an FDA-licensed biological product (the “reference product”). The FDA's approach to the regulation of biosimilars is based on the requirements set forth in the BPCI Act. A biosimilar product is highly similar to the reference product, notwithstanding minor differences in clinically inactive components, and there are no clinically meaningful differences between products in terms of safety, purity, and potency. The foundation of a biosimilar development program is an analytic similarity assessment that directly compares the structural/physiochemical and functional properties of the proposed biosimilar with the reference product. Data from clinical studies, which include an assessment of immunogenicity and pharmacokinetics/pharmacodynamics, are used to assess for clinically meaningful differences and not to independently establish the safety and effectiveness of the biosimilar. Like all products that the FDA regulates, the FDA requires that biosimilar products meet the agency's rigorous standards of safety and efficacy for approval. That means patients and health care professionals are able to rely upon the safety and effectiveness of biosimilar products in the same manner as for the reference product. Clin Cancer Res; 23(8); 1882–5. ©2016 AACR.
Absence of Cytomegalovirus in Glioblastoma and Other High-grade Gliomas by Real-time PCR, Immunohistochemistry, and In Situ Hybridization
Authors: Holdhoff Matthias , Guner Gunes , Rodriguez Fausto J. , Hicks Jessica L. , Zheng Qizhi , Forman Michael S. , Ye Xiaobu , Grossman Stuart A. , Meeker Alan K. , Heaphy Christopher M. , Eberhart Charles G. , De Marzo Angelo M. , Arav-Boger Ravit 
Published: December 2016

Abstract
Purpose: Reports of cytomegalovirus (CMV) detection in high-grade gliomas (HGG)/glioblastoma have been conflicting. We undertook a comprehensive approach to determine the presence or absence of CMV in tissue, plasma, and serum of HGG patients.
Experimental Design: In a retrospective arm, 25 fresh frozen tissues from glioblastoma patients were tested for CMV by real-time PCR. Tissue microarrays from 70 HGG patients were tested by IHC and 20 formalin-fixed paraffin-embedded (FFPE) glioblastoma tissues by IHC and chromogenic in situ hybridization (CISH), targeting CMV-encoded IE1/2 and pp65. In a prospective arm, 18 patients with newly diagnosed HGG provided tissue and blood samples.
Results: All retrospectively collected tissues were negative for CMV by all methods. In the prospective cohort, 18 patients with newly diagnosed HGG provided blood samples at the time of diagnosis and during follow-up. Of 38 plasma specimens, CMV DNA was detected in 3 of 18 samples at baseline and 1 of 20 follow-up samples. Serum CMV IgG was positive in 8 of 15 (53%) of patients. Among the FFPE samples tested in the prospective arm, all were negative for CMV by IHC, CISH, and PCR.
Conclusions: Utilizing 6 highly sensitive assays with three orthogonal technologies on multiple specimens and specimen types, no evidence for CMV in glioblastoma tissues was found. Our findings call for multicenter blinded analyses of samples collected from different geographical areas with agreed upon study designs and determination of causality or lack thereof of CMV in HGG/glioblastoma for future guidance on the necessary antiviral and/or CMV-based therapies. Clin Cancer Res; 23(12); 3150–7. ©2016 AACR.
Cross-Sectional Positive Association of Serum Lipids and Blood Pressure With Serum Sodium Within the Normal Reference Range of 135–145 mmol/L
Authors: Gao Shouguo , Cui Xiangqin , Wang Xujing , Burg Maurice B. , Dmitrieva Natalia I. 
Published: December 2016

Objective—
Serum sodium concentration is maintained by osmoregulation within normal range of 135 to 145 mmol/L. Previous analysis of data from the ARIC study (Atherosclerosis Risk in Communities) showed association of serum sodium with the 10-year risk scores of coronary heart disease and stroke. Current study evaluated the association of within-normal-range serum sodium with cardiovascular risk factors.

Approach and Results—
Only participants who did not take cholesterol or blood pressure medications and had sodium within normal 135 to 145 mmol/L range were included (n=8615), and the cohort was stratified based on race, sex, and smoking status. Multiple linear regression analysis of data from ARIC study was performed, with adjustment for age, blood glucose, insulin, glomerular filtration rate, body mass index, waist to hip ratio, and calorie intake. The analysis showed positive associations with sodium of total cholesterol, low-density lipoprotein cholesterol, and total cholesterol to high-density lipoprotein cholesterol ratio; apolipoprotein B; and systolic and diastolic blood pressure. Increases in lipids and blood pressure associated with 10 mmol/L increase in sodium are similar to the increases associated with 7 to 10 years of aging. Analysis of sodium measurements made 3 years apart demonstrated that it is stable within 2 to 3 mmol/L, explaining its association with long-term health outcomes. Furthermore, elevated sodium promoted lipid accumulation in cultured adipocytes, suggesting direct causative effects on lipid metabolism.

Conclusions—
Serum sodium concentration is a cardiovascular risk factor even within the normal reference range. Thus, decreasing sodium to the lower end of the normal range by modification of water and salt intake is a personalizable strategy for decreasing cardiovascular risks.
Thirty-Day Readmissions After Transcatheter Aortic Valve Replacement in the United States
Authors: Kolte Dhaval , Khera Sahil , Sardar M. Rizwan , Gheewala Neil , Gupta Tanush , Chatterjee Saurav , Goldsweig Andrew , Aronow Wilbert S. , Fonarow Gregg C. , Bhatt Deepak L. , Greenbaum Adam B. , Gordon Paul C. , Sharaf Barry , Abbott J. Dawn 
Published: December 2016

Background—
Readmissions after cardiac procedures are common and contribute to increased healthcare utilization and costs. Data on 30-day readmissions after transcatheter aortic valve replacement (TAVR) are limited.

Methods and Results—

Patients undergoing TAVR (
International Classification of Diseases
-Ninth Revision-CM codes 35.05 and 35.06) between January and November 2013 who survived the index hospitalization were identified in the Nationwide Readmissions Database. Incidence, predictors, causes, and costs of 30-day readmissions were analyzed. Of 12 221 TAVR patients, 2188 (17.9%) were readmitted within 30 days. Length of stay >5 days during index hospitalization (hazard ratio [HR], 1.47; 95% confidence interval [CI], 1.24–1.73), acute kidney injury (HR, 1.23; 95% CI, 1.05–1.44), >4 Elixhauser comorbidities (HR, 1.22; 95% CI, 1.03–1.46), transapical TAVR (HR, 1.21; 95% CI, 1.05–1.39), chronic kidney disease (HR, 1.20; 95% CI, 1.04–1.39), chronic lung disease (HR, 1.16; 95% CI, 1.01–1.34), and discharge to skilled nursing facility (HR, 1.16; 95% CI, 1.01–1.34) were independent predictors of 30-day readmission. Readmissions were because of noncardiac causes in 61.8% of cases and because of cardiac causes in 38.2% of cases. Respiratory (14.7%), infections (12.8%), bleeding (7.6%), and peripheral vascular disease (4.3%) were the most common noncardiac causes, whereas heart failure (22.5%) and arrhythmias (6.6%) were the most common cardiac causes of readmission. Median length of stay and cost of readmissions were 4 days (interquartile range, 2–7 days) and $8302 (interquartile range, $5229–16 021), respectively.

Conclusions—
Thirty-day readmissions after TAVR are frequent and are related to baseline comorbidities, TAVR access site, and post-procedure complications. Awareness of these predictors can help identify and target high-risk patients for interventions to reduce readmissions and costs.
On the Standards-Variantist Solution to Skepticism
Authors: Lee Kok Yong 
Published: December 2016

The skeptical puzzle consists of three independently plausible yet jointly inconsistent claims: (A) S knows a certain ordinary proposition op; (B) S does not know the denial of a certain skeptical hypothesis sh; and (C) S knows that op only if S knows that not-sh. The variantist solution (to the skeptical puzzle) claims that (A) and not-(B) are true in the ordinary context, but false in the skeptical one. Epistemic contextualism has offered a standards-variantist solution, which is the most prominent variantist solution on the market. In this paper, I argue that the standards-variantist solution in general (and the contextualist solution in particular) is epistemically uninteresting. Proponents of the variantist solution should opt for the position-variantist solution instead. I will discuss some important implications of my findings.
Early-life antibiotic treatment enhances the pathogenicity of CD4+ T cells during intestinal inflammation
Authors: Scheer Sebastian , Medina Tiago S , Murison Alex , Taves Matthew D , Antignano Frann , Chenery Alistair , Soma Kiran K , Perona-Wright Georgia , Lupien Mathieu , Arrowsmith Cheryl H , De Carvalho Daniel D , Zaph Colby 
Published: December 2016

Abstract
The incidence of inflammatory bowel diseases (IBDs) has steadily increased in recent decades—a phenomenon that cannot be explained by genetic mutations alone. Other factors, including the composition of the intestinal microbiome, are potentially important contributors to the increased occurrence of this group of diseases. Previous reports have shown a correlation between early-life antibiotic (Abx) treatment and an increased incidence of IBD. In this report, we investigated the effects of early-life Abx treatments on the pathogenicity of CD4+ T cells using an experimental T cell transfer model of IBD. Our results show that CD4+ T cells isolated from adult mice that had been treated with Abx during gestation and in early life induced a faster onset of IBD in Rag1-deficient mice compared with CD4+ T cells of untreated mice. Ex vivo functional analyses of IBD-inducing CD4+ T cells did not show significant differences in their immunologic potential ex vivo, despite their in vivo phenotype. However, genome-wide gene-expression analysis revealed that these cells displayed dysregulated expression of genes associated with cell-cycle regulation, metabolism, and cellular stress. Analysis of Abx-treated CD4+ T cell donors showed systemically elevated levels of the stress hormone corticosterone throughout life compared with untreated donors. The cohousing of Abx-treated mice with untreated mice decreased serum corticosterone, and a consequent transfer of the cells from cohoused mice into Rag1-deficient mice restored the onset and severity of disease to that of untreated animals. Thus, our results suggest that early-life Abx treatment results in a stress response with high levels of corticosterone that influences CD4+ T cell function.
Influence of short-term synoptic events and snow depth on DMS, DMSP, and DMSO dynamics in Antarctic spring sea ice
Authors: Carnat Gauthier , Brabant Frédéric , Dumont Isabelle , Vancoppenolle Martin , Ackley Stephen F. , Fritsen Chris , Delille Bruno , Tison Jean-Louis 
Published: December 2016

AbstractTemporal changes in the concentration profiles of dimethylsulfide (DMS), dimethylsulfoniopropionate (DMSP), and dimethylsulfoxide (DMSO) were measured in pack ice from the Bellingshausen Sea (Antarctica) during the winter-spring transition of 2007. Two sites with contrasting snow and ice thicknesses were sampled, with high concentrations of DMS, DMSP, and DMSO observed at both sites, especially in surface ice. These high concentrations were shown to correspond to the development of a surface ice microalgal community dominated by strong DMSP producers (flagellates and dinoflagellates) following flooding of the ice cover. Several short-term synoptic events were observed and shown to influence strongly the dynamics of sea ice DMS, DMSP, and DMSO. In particular, a cold spell event was associated with drastic changes in the environmental conditions for the sea ice microbial communities and to a remarkable increase in the production of dimethylated sulfur compounds at both sites. A good correlation between all dimethylated sulfur compounds, sea ice temperature, and brine salinity suggested that the observed increase was triggered mainly by increased thermal and osmotic stresses on microalgal cells. Atmospheric forcing, by controlling sea ice temperature and hence the connectivity and instability of the brine network, was also shown to constrain the transfer of dimethylated sulfur compounds in the ice towards the ocean via brine drainage. Analysis of the two contrasting sampling sites shed light on the key role played by the snow cover in the sea ice DMS cycle. Thicker snow cover, by insulating the underlying sea ice, reduced the amplitude of environmental changes associated with the cold spell, leading to a weaker physiological response and DMS, DMSP, and DMSO production. Thicker snow also hampered the development of steep gradients in sea ice temperature and brine salinity, thereby decreasing the potential for the release of dimethylated sulfur compounds to the ocean via brine drainage.
Assessment of the sea-ice carbon pump: Insights from a three-dimensional ocean-sea-ice-biogeochemical model (MPIOM/HAMOCC)
Authors: Grimm R. , Notz D. , Glud R.N. , Rysgaard S. , Six K.D. 
Published: December 2016

Abstract
It has been suggested that geochemical processes related to sea-ice growth and melt might be important for the polar carbon cycle via the so called sea-ice carbon pump (SICP). The SICP affects the air-sea CO2 exchange by influencing the composition of dissolved inorganic carbon (DIC) and total alkalinity (TA) in the surface ocean. Here we quantify the strength of the SICP-induced air-sea CO2 flux using the global three-dimensional ocean-sea-ice-biogeochemical model MPIOM/HAMOCC. Simulations prescribing the range of observed DIC and TA concentrations in the sea ice were performed under two idealized climate scenarios for the present-day and the future oceanic and sea-ice state, both forced with a fixed atmospheric CO2 concentration. Model results indicate that the SICP-induced air-sea CO2 uptake increases with higher ratios of TA:DIC prescribed in the sea ice relative to the basic oceanic TA:DIC ratios. Independent of the modeled scenario, the simulated strength of the SICP is larger in the Antarctic than in the Arctic, because of more efficient export of brine-associated DIC from the Antarctic mixed layer. On an annual basis, we generally find an enhanced SICP-induced oceanic CO2 uptake in regions with net sea-ice melt, and enhanced SICP-induced oceanic CO2 out-gassing in regions with net sea-ice growth. These general regional patterns are modified further by the blockage of air-sea gas exchange through sea-ice coverage. Integrated over the sea-ice zones of both hemispheres, the SICP-induced oceanic CO2 uptake ranges from 2 to 14 Tg C yr−1, which is up to 7% of the simulated net CO2 uptake in polar regions, but far less than 1% of the current global oceanic CO2 uptake. Hence, while we find that the SICP plays a minor role in the modern global carbon cycle, it is of importance for the regional carbon cycle at high latitudes.
Use of Biomarkers in Predicting the Onset, Monitoring the Progression, and Risk Stratification for Patients with Type 2 Diabetes Mellitus
Authors: Scirica Benjamin M 
Published: December 2016

AbstractBACKGROUNDAs the worldwide prevalence of type 2 diabetes mellitus (T2DM) increases, it is even more important to develop cost-effective methods to predict and diagnose the onset of diabetes, monitor progression, and risk stratify patients in terms of subsequent cardiovascular and diabetes complications.CONTENTNonlaboratory clinical risk scores based on risk factors and anthropomorphic data can help identify patients at greatest risk of developing diabetes, but glycemic indices (hemoglobin A1c, fasting plasma glucose, and oral glucose tolerance tests) are the cornerstones for diagnosis, and the basis for monitoring therapy. Although family history is a strong predictor of T2DM, only small populations of patients carry clearly identifiable genetic mutations. Better modalities for detection of insulin resistance would improve earlier identification of dysglycemia and guide effective therapy based on therapeutic mechanisms of action, but improved standardization of insulin assays will be required. Although clinical risk models can stratify patients for subsequent cardiovascular risk, the addition of cardiac biomarkers, in particular, high-sensitivity troponin and natriuretic peptide provide, significantly improves model performance and risk stratification.CONCLUSIONSMuch more research, prospectively planned and with clear treatment implications, is needed to define novel biomarkers that better identify the underlying pathogenic etiologies of dysglycemia. When compared with traditional risk features, biomarkers provide greater discrimination of future risk, and the integration of cardiac biomarkers should be considered part of standard risk stratification in patients with T2DM.
LEAN & HEALTHCARE ORGANIZATIONS - A SYSTEMATIC LITERATURE REVIEW WITH BIBLIOMETRIC ANALYSIS ON APPLICATION OF LEAN HEALTHCARE IN BRAZIL
Authors: Ferreira William De Paula , Da Silva Adriano Maniçoba , Tanaka Wilson Yoshio , Zampini Eugênio De Felice 
Published: December 2016

Despite having its roots in the Japanese automotive industry, Lean philosophy has been successfully applied in many companies of different sectors. In recent years several studies have been done regarding the potential of this managerial technology that may transform the healthcare organizations. The objective of this theoretical research paper is to conduct a Systematic Literature Review (SLR) with bibliometric analysis on application of Lean healthcare in Brazil. The aim is to understand the advancement of this research field in Brazil, investigating how Lean thinking has been put into practice and how this innovation has helped those companies to deliver more value to its customers. Peer reviewed articles were searched in 9 data sources. At first, a total of 5,473 articles were identified, which were reduced to 2,983 after Endnote software duplicate reference analysis. 789 articles were screened, after reviewing the adherence to the topic. Resulting in a sample of only 9 articles, after all inclusion criteria were match. The results suggest that Lean thinking has been applied successfully in many healthcare organizations. However, the research field in Brazil is quite new, having a great potential to increase.
Model Podejmowania Decyzji w Oparciu o Wartości Służący Ocenie Wariantów Systemu Monitorowania Stanu Technicznego Struktury Statków Powietrznych z Punktu Widzenia Wymagań Użytkownika Wojskowego
Authors: Klimaszewski Sławomir 
Published: December 2016

Streszczenie
Niniejszy artykuł opisuje model podejmowania decyzji w oparciu o wartości (ang. Value-Focused Thinking - VFT) opracowany w celu oceny różnych wariantów wdrożenia systemu monitorowania stanu technicznego struktury (ang. Structural Health Monitoring - SHM) wojskowego statku powietrznego. Rozpatruje się cztery warianty wspomnianego systemu (SHM) oparte na: kontroli wzrokowej (aktualne podejście), czujnikach piezoelektrycznych (PZT), czujnikach światłowodowych z siatką Bragga (FBG) i czujnikach próżniowych (Comparative Vacuum Monitoring - CVM). Przedstawiono przykład numeryczny w celu zilustrowania możliwości modelu. Analizy wrażliwości są wykonane dla takich wartości jak koszt, wydajność, dostępność statku powietrznego oraz poziom gotowości technologicznej (Technology Readiness Level - TRL), aby zbadać wpływ tych parametrów na całkowitą wartość informacji z zakresu stanu technicznego struktury dostarczanych przez określony wariant systemu SHM.
Egzemplifikacja Tomograficznej Metody Do Oceny Jakości Połączeń Spawanych Ze Stopu EN 5754 H22
Authors: Błachnio Józef , Kułaszka Artur , Chalimoniuk Marek , Woźny Piotr 
Published: December 2016

Streszczenie
Jakość połączeń spawanych zależna jest od wielu czynników. Przedmiotowe normy określają warunki techniczne oceny jakościowej spawów, co stanowi podstawę do uznania połączenia za zgodne z wymaganiami lub wadliwe. W praktyce wykonanie połączenia spawanego całkowicie pozbawionego wad jest trudne. Do kontroli wewnętrznej struktury połączenia wykorzystać można nieniszczącą metodę z zastosowaniem przemysłowego tomografu komputerowego. Ta nowoczesna metoda diagnozowania łączy badanie rentgenowskie z zaawansowaną technologią komputerową. Podstawową zaletą tomografii komputerowej jest badanie obiektów w trzech wymiarach oraz możliwość wykonania rekonstrukcji przestrzennych. Celem artykułu jest omówienie wykorzystania tej metody do oceny jakości połączeń spawanych stopów aluminium. Możliwości tomografii komputerowej przedstawiono na przykładzie próbek spawalniczych wykonanych metodą TIG przy różnych parametrach procesu. Dokonano analizy jakości próbek wykazujących najmniejsze i największe zewnętrzne, jak również wewnętrzne wady spawalnicze.
Niezawodność Przykładowego Systemu Technicznego Dla Założonych Funkcji Gęstości Uszkodzeń
Authors: Stępień Sławomir , Grzesik Justyna 
Published: December 2016

Streszczenie
Analiza niezawodności strukturalnej systemu technicznego, a zwłaszcza wyznaczenie zmiany niezawodności systemu w czasie, wymaga znajomości funkcji gęstości lub dystrybuant (zawodności) elementów wchodzących w skład struktury. Bazując na zarejestrowanych w przeszłości danych dotyczących uszkodzeń elementów, można w miarę łatwo wyznaczyć średni czas zdatnej pracy elementu oraz odchylenie standardowe dla tego czasu. Natomiast określenie postaci rozkładu nastręcza pewne trudności. Otóż z reguły nie dysponujemy dostateczną liczbą danych do weryfikacji hipotezy o postaci rozkładu. Z tego powodu powszechnie, w zależności od rozpatrywanego przypadku, zakłada się postać funkcji gęstości uszkodzeń. Powstaje pytanie: czy błędne określenie rodzajów rozkładów elementów powoduje duży błąd wyników oszacowania niezawodności i trwałości systemu? Niniejszy artykuł nie odpowie w pełni na to pytanie, ale zostanie dokonane porównanie wyników obliczeń dla kilku przypadków. Obliczenia zostały przeprowadzone dla przykładowego systemu technicznego.