bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preparation Ferrule Design Effect on Endocrown Failure Resistance
Authors: Einhorn Michael , DuVall Nicholas , Wajdowicz Michael , Brewster John , Roberts Howard 
Published: October 2017

AbstractPurposeTo evaluate the effect of preparation ferrule inclusion with fracture resistance of mandibular molar endocrowns.Materials and MethodsRecently extracted mandibular third molars were randomly divided into 3 groups (n = 12) with the coronal tooth structure removed perpendicular to the root long axis approximately 2 mm above the cemento‐enamel junction with a slow‐speed diamond saw. The pulp chamber was exposed using a diamond bur in a high‐speed handpiece with pulpal remnants removed and canals instrumented using endodontic hand instruments. The chamber floor was restored using a resin core material with a two‐step, self‐etch adhesive and photopolymerized with a visible light‐curing unit to create a 2 mm endocrown preparation pulp chamber extension. One and two millimeter ferrule height groups were prepared using a diamond bur in a high‐speed handpiece following CAD/CAM guidelines. Completed preparation surface area was determined using a digital measuring microscope. Scanned preparations were restored with lithium disilicate restorations with a self‐adhesive resin luting agent. All manufacturer recommendations were followed. Specimens were stored at 37°C/98% humidity and tested to failure after 24 hours at a 45° angle to the tooth long axis using a universal testing machine. Failure load was converted to MPa using the available bonding surface area with mean data analyzed using Kruskal‐Wallis/Dunn (p = 0.05).ResultsCalculated failure stress found no difference in failure resistance among the three groups; however, failure load results identified that the endocrown preparations without ferrule had significantly lower fracture load resistance. Failure mode analysis identified that all preparations demonstrated a high number of catastrophic failures.ConclusionsUnder the conditions of this study, ferrule‐containing endocrown preparations demonstrated significantly greater failure loads than standard endocrown restorations; however, calculated failure stress based on available surface area for adhesive bonding found no difference between the groups. Lower instances of catastrophic failure were observed with the endocrown preparations containing 1 mm of preparation ferrule design; however, regardless of the presence of ferrule, this study found that all endocrown restorations suffered a high proportion of catastrophic failures but at loads greater than reported under normal masticatory function.
Resistance characterization of ledipasvir and velpatasvir in hepatitis C virus genotype 4
Authors: Camus G. , Han B. , Asselah T. , Hsieh D. , Dvory‐Sobol H. , Lu J. , Svarovskaia E. , Martin R. , Parhy B. , Miller M. D. , Brainard D. M. , Kersey K. , Abergel A. , Mo H. 
Published: October 2017

SummaryHCV genotype 4 (GT4) has often been overlooked in drug development, even though it infects ~20 million people worldwide. Ledipasvir/sofosbuvir and sofosbuvir/velpatasvir were highly efficacious in GT4 HCV‐infected patients from GS‐US‐337‐1119 and GS‐US‐342‐1138. Here, we characterize the resistance profile of ledipasvir (LDV) and velpatasvir (VEL) in patients with GT4 HCV infection. NS5A deep‐sequencing was performed for 454 patients infected with HCV GT4 at baseline, including 44 patients enrolled in GS‐US‐337‐1119 and 116 patients enrolled in GS‐US‐342‐1138, and at relapse for patients with virologic failure. LDV and VEL susceptibilities of 56 patient isolates were determined. In GS‐US‐337‐1119, SVR12 rates were 100% for all subtypes except 4b and 4r. Phenotypic assessment of 56 HCV NS5A patient isolates from various GT4 subtypes indicated that LDV had high potency for the common subtypes 4a/d, and subtypes 4c/f/k/l/m/n/o/p/r/t despite the presence of resistance‐associated substitutions (RASs). For the rare GT4b, LDV median EC50 was higher, but with a broad range of individual values. Importantly, all GT4b isolates tested had 2‐4 NS5A RASs, some including Y93H. Similarly, the 2 GT4r infected patients who had virologic relapse had rare triple RASs. Reversion of these substitutions to the consensus residue significantly increased LDV susceptibility. In GS‐US‐342‐1138, all patients achieved SVR12, regardless of their subtype or presence of RASs. In vitro data confirmed that VEL is potent against all GT4 isolates tested.LDV and VEL are potent antiviral drugs, estimated to be effective against >95% and >99%, respectively, of GT4 HCV isolates.
Sustained virological response to ombitasvir/paritaprevir/ritonavir and dasabuvir treatment for hepatitis C: Real‐world data from a large healthcare provider
Authors: Weil C. , Mehta D. , Koren G. , Pinsky B. , Samp J. C. , Chodick G. , Shalev V. 
Published: October 2017

SummaryTreatment with ombitasvir/paritaprevir/ritonavir and dasabuvir, with or without ribavirin (OPrD ± RBV), was the first interferon‐free direct‐acting antiviral for hepatitis C virus (HCV) introduced to Israel's national basket of health services in February 2015. Patients with HCV genotype 1 (GT1) and advanced fibrosis (F3‐F4) were eligible for treatment in 2015. This study aimed to characterize patients initiating OPrD ± RBV and assess sustained virological response (SVR). A retrospective cohort study was performed using the database of Maccabi Healthcare Services (MHS), a 2‐million‐member health plan in Israel. The study population included adults who initiated OPrD ± RBV through December 2015 per health basket criteria. A gap in medication fills (>14 days between a fill's run‐out and the next fill) was used to estimate adherence. SVR was defined by the viral tests at least 12‐week post‐treatment. The study population consisted of 403 patients (56.3% male), with a mean age of 60.7 years (SD 11.0). Overall, 71.0% were naïve to prior HCV treatment, and 95.6% were treated with a 12‐week regimen. A total of 348 patients (86.4%) completed the regimen in the usual time frame (highly adherent), whereas 8.2% completed with a gap, and 4.7% purchased less than the recommended dose. SVR rates overall and among highly adherent patients were 395/403 (98.0%; 95% CI 96.1‐99.1) and 346/348 (99.4%; 95% CI 97.9‐99.9), respectively. GT1b patients on 12‐week regimens attained SVR rates of 194/196 (fibrosis F3) and 170/176 (cirrhosis). After a first year of provision of OPrD ± RBV with good adherence, high SVR rates were achieved in various patient subgroups and comorbidities.
Two‐year follow‐up of a postpartum weight loss intervention: Results from a randomized controlled trial
Authors: Huseinovic Ena , Bertz Fredrik , Brekke Hilde Kristin , Winkvist Anna 
Published: October 2017

AbstractWe recently reported that a 12‐week diet intervention among postpartum women produced a weight loss of 12% after 1 year, compared to 5% in controls. Here, we present 2‐year results after 1 year of unsupervised follow‐up. In total, 110 women with a self‐reported body mass index of ≥27 kg/m2 at 6–15‐week postpartum were randomized to diet group (D‐group) or control group (C‐group). D‐group received a 12‐week diet intervention by a dietitian followed by monthly e‐mails up to the 1‐year follow‐up. C‐group received a brochure on healthy eating. No contact was provided from 1 to 2 years to either group. Eighty‐nine women (81%) completed the 2‐year follow‐up. Median (1st; 3rd quartile) weight change from 0 to 2 years was −6.9 (−11.0; −2.2) kg in D‐group and −4.3 (−8.7; −0.2) kg in C‐group. There was no group by time interaction at 2 years (p = .082); however, when women with a new pregnancy between 1 and 2 years were excluded, the interaction became significant (−8.2 vs. −4.6 kg, p = .038). From 1 to 2 years, women in D‐ and C‐group gained 2.5 ± 5.0 kg and 1.1 ± 4.4 kg, respectively (p = .186). Women who gained weight from 1 to 2 years reported a decrease in self‐weighing frequency compared to women who maintained or lost weight (p = .008). Both groups achieved clinically relevant 2‐year weight loss, but the significant between‐group‐difference observed at 1 year was not maintained at 2 years in the main analysis. However, when women with a new pregnancy between 1 and 2 years were excluded, a significant weight loss effect was observed also at 2 years.
Novel bi‐allelic splice mutations in CARD9 causing adult‐onset Candida endophthalmitis
Authors: Gavino Christina , Mellinghoff Sibylle , Cornely Oliver A. , Landekic Marija , Le Catherine , Langelier Melanie , Golizeh Makan , Proske Susanna , Vinh Donald C. 
Published: October 2017

SummaryCARD9 deficiency (CANDF2; OMIM# 212050) is an autosomal‐recessive monogenic inborn error of immunity conferring susceptibility to invasive fungal diseases, including the very distinct syndrome of spontaneous central nervous system candidiasis, in which opportunistic yeast of the genus Candida infect the central nervous system (either brain parenchyma and/or meninges) in the absence of trauma, chemotherapy or underlying systemic disease. We present a patient with spontaneous endophthalmitis of the right eye due to Candida albicans; further investigations revealed concomitant cerebral abscess. She had a history of left endophthalmitis due to the dematiaceous mould, Aureobasidium pullulans, 15 years earlier. Targeted sequencing of the CARD9 gene revealed 2 novel variants (c.184G>A and c.288C>T). Analysis in silico predicted each variant altered splicing, which was confirmed by sequencing of cDNA from proband and carrier offsprings: c.184G>A results in a 4‐base pair frameshift deletion with loss of allelic expression; c.288C>T results in an in‐frame 36‐bp pair deletion with detectable protein. CARD9 deficiency can present with a phenotype of spontaneous candidal endophthalmitis. We report 2 novel mutations in CARD9, both affecting splicing, expanding the range of morbid variants causing CARD9 deficiency, emphasising the importance of both genomic and cDNA sequencing for this condition.
Approaching Negotiation at the Organizational Level
Authors: Borbély Adrian , Caputo Andrea 
Published: October 2017

AbstractHow can an organization improve its negotiation skills? The following article aims to answer this question by investigating how, and why, an organization's negotiation capability should be developed. We propose a four‐level Organizational Model of Negotiation (OMoN), in which the individual level (I) concerns how people interact at the negotiation table; the linkages level (II) concerns how different negotiations impact one another; the infrastructure level (III) concerns how an organization may organize its negotiation functions; and finally, the capability level (IV) concerns how negotiation can be the source of competitive advantage. Our framework opens the path for developing the understanding of this issue by presenting teaching resources and identifying a possible theoretical underpinning. The article also presents a broad research agenda, which offers the basis for future studies to integrate concepts from different fields of research, such as from the management and strategy literature, into the field of negotiation.
Evolutionary ecology of telomeres: a review
Authors: Olsson Mats , Wapstra Erik , Friesen Christopher R. 
Published: October 2017

AbstractTelomere‐induced selection could take place if telomere‐associated disease risk shortens reproductive life span and differently reduces relative fitness among individuals. Some of these diseases first appear before reproductive senescence and could thus influence ongoing selection. We ask whether we can estimate the components of the breeder's equation for telomeres, in which the response to selection (R, by definition “evolution”) is the product of ongoing selection (S) and heritability (h2). However, telomere inheritance is a conundrum: in quantitative genetics, traits can usually be allocated to categories with relatively high or low heritability, depending on their association with relative fitness. Telomere traits, however, show wide variation in heritability from zero to one, across taxa, gender, ethnicity, age, and disease status. In spite of this, there is divergence in telomere length among populations, supporting past and ongoing telomere evolution. Rates of telomere attrition and elongation vary among taxa with some, but not complete, taxonomic coherence. For example, telomerase is commonly referred to as “restricted to the germ line in mammals,” but inbred mice and beavers have telomerase upregulation in somatic tissue, as do many ectotherms. These observations provoke a simplistic understanding of telomere evolutionary biology—clearly much is yet to be discovered.
Strategies to retain properties of bone marrow–derived mesenchymal stem cellsex vivo
Authors: Zhou Yaxian , Tsai Tsung‐Lin , Li Wan‐Ju 
Published: October 2017

AbstractMesenchymal stem cells (MSCs) have been extensively used for cell therapies and tissue engineering. The current MSC strategy requires a large quantity of cells for such applications, which can be achieved through cell expansion in culture. In the body, stem cell fate is largely determined by their microenvironment, known as the niche. The complex and dynamic stem cell niche provides physical, mechanical, and chemical cues to collaboratively regulate cell activities. It remains a great challenge to maintain the properties of MSCs in culture. Constructing a microenvironment as an engineered stem cell niche in culture to maintain MSC phenotypes, properties, and functions is a viable strategy to address the issue. Here, we review the current understanding of MSC behavior in the bone marrow niche, describe different strategies to engineer anin vitromicroenvironment for maintaining MSC properties and functions, and discuss previous findings on environmental factors critical to the modulation of MSC activities in engineered microenvironments.
Pitfalls in using fluorescence tagging of nanomaterials: tecto‐dendrimers in skin tissue as investigated by Cluster‐FLIM
Authors: Volz Pierre , Schilrreff Priscila , Brodwolf Robert , Wolff Christopher , Stellmacher Johannes , Balke Jens , Morilla Maria J. , Zoschke Christian , Schäfer‐Korting Monika , Alexiev Ulrike 
Published: October 2017

AbstractTargeted topical application promises high drug concentrations in the skin and low systemic adverse effects. To locate drugs and drug‐delivery systems like nanocarriers, fluorescent dyes are commonly used as drug surrogates or nanocarrier labels in micrographs of tissue sections. Here, we investigate how labeling degree, concentration of fluorophore, and nanocarrier may affect the interpretation of these micrographs. False‐negative penetration results due to inter‐ and intramolecular quenching effects are likely. Using tecto‐dendrimers as an example, we present a detailed analysis of pitfalls in the (semi‐)quantitative evaluation of skin nanocarrier penetration. Fluorescence lifetime imaging microscopy (FLIM) allows distinguishing the target fluorescence of dye‐tagged nanocarriers from skin autofluorescence, providing a highly sensitive tool for clear‐cut localization of the nanocarriers. Cluster‐FLIM images reveal that FITC‐labeled tecto‐dendrimers penetrate the stratum corneum of human skin ex vivo and reconstructed human skin but do not cross the tight junction barrier.
Host–microbiota interplay in mediating immune disorders
Authors: Felix Krysta M. , Tahsin Shekha , Wu Hsin‐Jung Joyce 
Published: October 2017

AbstractTo maintain health, the immune system must maintain a delicate balance between eliminating invading pathogens and avoiding immune disorders such as autoimmunity and allergies. The gut microbiota provide essential health benefits to the host, particularly by regulating immune homeostasis. Dysbiosis, an alteration and imbalance of the gut microbiota, is associated with the development of several autoimmune diseases in both mice and humans. In this review, we discuss recent advances in understanding how certain factors, such as age and gender, affect the gut microbiota, which in turn can influence the development of autoimmune diseases. The age factor in microbiota‐dependent immune disorders indicates a window of opportunity for future diagnostic and therapeutic approaches. We also discuss unique commensal bacteria with strong immunomodulatory activity. Finally, we provide an overview of the potential molecular mechanisms whereby gut microbiota induce autoimmunity, as well as the evidence that gut microbiota trigger extraintestinal diseases by inducing the migration of gut‐derived immune cells. Elucidating the interaction of gut microbiota and the host immune system will help us understand the pathogenesis of immune disorders, and provide us with new foundations to develop novel immuno‐ or microbe‐targeted therapies.
Immunoprotective effects of a hemin‐binding peptide derived from hemagglutinin‐2 against infection with Porphyromonas gingivalis
Authors: Zhu Y.C. , An T. , Liu Y. , Zhang Z.L. , Yang Q.B. 
Published: October 2017

SummaryThe principal etiologic agent in periodontal disease, Porphyromonas gingivalis, generates cysteine proteases that bind heme with domains such as hemagglutinin‐2 (HA2). High‐affinity HA2–hemin binding supplies the porphyrin and ferric iron needed for growth and virulence. The DHYAVMISK peptide, recently identified at the hemin‐binding site of HA2, inhibits hemin binding. We now evaluate the protective effect of vaccination with DGFPGDHYAVMISK (termed DK) against P. gingivalis using a rat infection model. Rats immunized with DK generated anti‐peptide serum IgGs and salivary sIgAs (as measured by ELISA). In a subcutaneous abscess model, the protective effect of immunization was then investigated by measuring abscess size following subcutaneous injection with P. gingivalis. In an oral infection model, a ligature inoculated with P. gingivalis was used to induce periodontitis. The degree of bone erosion, ordinarily provoked by infection, was then evaluated by micro‐computed tomography. We found that anti‐peptide antibody titers of serum IgGs and salivary sIgAs for rats immunized with DK and adjuvant were significantly higher than for sham‐immunized rats (injected with adjuvant/PBS alone; P < .05). In the subcutaneous abscess model, the DK + adjuvant‐vaccinated rats recovered faster than sham‐vaccinated animals, with their abscess sizes significantly smaller (P < .05). Further, in the experimental periodontitis model, bone loss at the molar palatal side for DK + adjuvant‐vaccinated rats was significantly lower than for sham‐vaccinated animals (P < .05). Collectively, these data demonstrate the potential of (DK) peptide immunization in terms of eliciting an immunoprotective effect against infection with P. gingivalis.
Cacao biotechnology: current status and future prospects
Authors: Wickramasuriya Anushka M. , Dunwell Jim M. 
Published: October 2017

SummaryTheobroma cacao—The Food of the Gods, provides the raw material for the multibillion dollar chocolate industry and is also the main source of income for about 6 million smallholders around the world. Additionally, cocoa beans have a number of other nonfood uses in the pharmaceutical and cosmetic industries. Specifically, the potential health benefits of cocoa have received increasing attention as it is rich in polyphenols, particularly flavonoids. At present, the demand for cocoa and cocoa‐based products in Asia is growing particularly rapidly and chocolate manufacturers are increasing investment in this region. However, in many Asian countries, cocoa production is hampered due to many reasons including technological, political and socio‐economic issues. This review provides an overview of the present status of global cocoa production and recent advances in biotechnological applications for cacao improvement, with special emphasis on genetics/genomics, in vitro embryogenesis and genetic transformation. In addition, in order to obtain an insight into the latest innovations in the commercial sector, a survey was conducted on granted patents relating to T. cacao biotechnology.
A practical approach to estimate diffusional leakages of leaf chamber of open gas exchange systems using intact leaves
Authors: Kitao Mitsutoshi , Harayama Hisanori , Uemura Akira 
Published: October 2017

AbstractWe propose a novel approach to determine the coefficient of CO2 diffusional leakage (k_CO2) in the chamber of a portable open gas exchange system (Li‐6400, Li‐Cor Inc., NE, USA) using intact leaves. Assuming that dark respiration rate (Rn) is constant at various CO2 concentrations, at least in a short term, k_CO2 should be the value that makes the leak‐corrected Rn constant. We used 2 representative tree species native to northern Japan, Japanese white birch (Betula platyphylla var. japonica) and Japanese oak (Quercus mongolica var. crispula), to determine k_CO2, by measuring Rn at various CO2 concentrations. Irrespective of the species, k_CO2 estimated by the present approach was well correlated with the diffusional leak coefficient (k_flow) estimated by the generally used approach that utilizes CO2 concentrations inside and outside the chamber based on thermally killed leaves at various flow rates. Furthermore, the present approach does not require the ambient CO2 concentration outside the chamber (Ca) if Ca in the laboratory is stable, which provides a feasible way to correct the photosynthetic rate, taking diffusional leakage into account.
Recruiting a representative sample in adherence research—The MALT multisite prospective cohort study experience
Authors: Shemesh Eyal , Mitchell Jeffrey , Neighbors Katie , Feist Susan , Hawkins Andre , Brown Amanda , Wanrong Yin , Anand Ravinder , Stuber Margaret L. , Annunziato Rachel A. 
Published: October 2017

AbstractMedication adherence is an important determinant of transplant outcomes. Attempts to investigate adherence are frequently undermined by selection bias: It is very hard to recruit and retain non‐adherent patients in research efforts. This manuscript presents recruitment strategies and results from the MALT (Medication Adherence in children who had a Liver Transplant) multisite prospective cohort study. MALT sites recruited 400 pediatric liver transplant patients who agreed to be followed for 2 years. The primary purpose was to determine whether a marker of adherence, the Medication Level Variability Index (MLVI), predicts rejection outcomes. The present manuscript describes methods used in MALT to ensure that a representative sample was recruited, and presents detailed recruitment results. MALT sites were able to recruit a nationally representative sample, as determined by a comparison between the MALT cohort and a national sample of transplant recipients. Strategies that helped ensure that the sample was representative included monitoring of the outcome measure in comparison with a national sample, drastically limiting patient burden, and specific recruitment methods. We discuss the importance of a representative sample in adherence research and recommend that future efforts to study adherence pay special attention to sample characteristics.
Relational approaches to Frege's puzzle
Authors: Gray Aidan 
Published: October 2017

AbstractFrege's puzzle is a fundamental challenge for accounts of mental and linguistic representation. This piece surveys a family of recent approaches to the puzzle that posit representational relations. I identify the central commitments of relational approaches and present several arguments for them. I also distinguish two kinds of relationism—semantic relationism and formal relationism—corresponding to two conceptions of representational relations. I briefly discuss the consequences of relational approaches for foundational questions about propositional attitudes, intentional explanation, and compositionality.