bluuebunny/crossref_metadata_2025 huggingface dataset:
Reducing or Maintaining the Dose of Subcutaneous Tocilizumab in Patients With Rheumatoid Arthritis in Clinical Remission: A Randomized, Open‐Label Trial
Authors: Sanmarti Raimon , Veale Douglas J. , Martin‐Mola Emilio , Escudero‐Contreras Alejandro , González Carlos , Ercole Liliana , Alonso Rocío , Fonseca João E. ,   the ToSpace Study Group
Published: April 2019

Objective

To evaluate the efficacy and safety of increasing the dose interval of subcutaneous tocilizumab (TCZ‐SC) in patients with rheumatoid arthritis (RA) who are in clinical remission.

Methods

RA patients with active disease and an inadequate response to conventional synthetic disease‐modifying antirheumatic drugs (csDMARDs) or to a biologic agent were entered into a single‐arm treatment phase with 162 mg of TCZ‐SC administered once weekly (TCZ‐SC 162 mg qw) as monotherapy or in combination with a csDMARD for 24 weeks. Patients who achieved clinical remission at weeks 20 and 24 were randomized to continue with the same regimen or to switch to 162 mg TCZ‐SC administered every 2 weeks (TCZ‐SC 162 mg q2w) for 24 weeks (open‐label). Patients with a Disease Activity Score in 28 joints (DAS28) of <2.6 were considered to be in clinical remission.

Results

In total, 179 (45%) of 401 patients in the single‐arm phase achieved clinical remission and were randomized to continue to receive TCZ‐SC 162 mg qw (n = 89) or to switch to TCZ‐SC 162 mg q2w (n = 90) for 24 weeks. At week 48, significantly more patients treated with TCZ‐SC 162 mg qw remained in clinical remission compared to patients who received TCZ‐SC 162 mg q2w (90% versus 73%; P = 0.004). The results of other efficacy measures revealed greater efficacy with TCZ‐SC 162 mg qw, but none of the efficacy outcomes in this group were significantly different from those in patients treated with TCZ‐SC 162 mg q2w, except for the mean change from baseline in the DAS28 score at week 48 (mean change −4.07 points [SD 1.29] versus −3.65 points [SD 1.35]; P = 0.034). Tolerability and safety parameters were similar between the treatment groups.

Conclusion

Increasing the dose interval of TCZ‐SC in patients with RA was associated with a lower likelihood of maintaining remission after 24 weeks and was not associated with better tolerability. However, most patients were able to sustain remission with a half‐dose of TCZ‐SC, and therefore this strategy deserves further investigation.
Opinion convergence versus polarization: examining opinion distributions in online word‐of‐mouth
Authors: Huang Jianxiong , Boh Wai Fong , Goh Kim Huat
Published: April 2019

We examine how opinion distributions (i.e., opinion polarization and convergence over time) differ across product salient platforms (product platforms) versus product non‐salient platforms (non‐product platforms). Drawing on the theory of impression management, we hypothesize and explain when and why consumers choose to post their comments on different platforms, and how their behavior will be affected when they choose to post on online platforms. To test the hypotheses, we collected and text‐mined online posts from product platforms such as review aggregator sites, discussion forums, and consumer rating websites, and non‐product platforms such as microblogs. The results showed that product platforms have more polarized opinions, and exhibit more convergence in opinion across time, compared with non‐product platforms. Our findings advise researchers and practitioners to pay attention to the characteristics of online platforms, and how users' perceptions of the purpose of the online platform may affect their online posting behavior.
A comparison of unimodal and multimodal models for implicit detection of relevance in interactive IR
Authors: González‐Ibáñez Roberto , Esparza‐Villamán Aileen , Vargas‐Godoy Juan Carlos , Shah Chirag
Published: April 2019

Implicit detection of relevance has been approached by many during the last decade. From the use of individual measures to the use of multiple features from different sources (multimodality), studies have shown the feasibility to automatically detect whether a document is relevant. Despite promising results, it is not clear yet to what extent multimodality constitutes an effective approach compared to unimodality. In this article, we hypothesize that it is possible to build unimodal models capable of outperforming multimodal models in the detection of perceived relevance. To test this hypothesis, we conducted three experiments to compare unimodal and multimodal classification models built using a combination of 24 features. Our classification experiments showed that a univariate unimodal model based on the left‐click feature supports our hypothesis. On the other hand, our prediction experiment suggests that multimodality slightly improves early classification compared to the best unimodal models. Based on our results, we argue that the feasibility for practical applications of state‐of‐the‐art multimodal approaches may be strongly constrained by technology, cultural, ethical, and legal aspects, in which case unimodality may offer a better alternative today for supporting relevance detection in interactive information retrieval systems.
The Design and Use of Assessment Frameworks in Digital Curation
Authors: Becker Christoph , Maemura Emily , Moles Nathan
Published: April 2019

To understand and improve their current abilities and maturity, organizations use diagnostic instruments such as maturity models and other assessment frameworks. Increasing numbers of these are being developed in digital curation. Their central role in strategic decision making raises the need to evaluate their fitness for this purpose and develop guidelines for their design and evaluation. A comprehensive review of assessment frameworks, however, found little evidence that existing assessment frameworks have been evaluated systematically, and no methods for their evaluation. This article proposes a new methodology for evaluating the design and use of assessment frameworks. It builds on prior research on maturity models and combines analytic and empirical evaluation methods to explain how the design of assessment frameworks influences their application in practice, and how the design process can effectively take this into account. We present the evaluation methodology and its application to two frameworks. The evaluation results lead to guidelines for the design process of assessment frameworks in digital curation. The methodology provides insights to the designers of the evaluated frameworks that they can consider in future revisions; methodical guidance for researchers in the field; and practical insights and words of caution to organizations keen on diagnosing their abilities.
A review: Nanofibrous scaffold in possible prevention and treatment of coronary artery disease
Authors: Cheraghi Mostafa , Pooria Ali
Published: April 2019

Nanofibrous scaffolds have potential to improve coronary stent applications by promoting endothelial recovery on the stent surface and aids regeneration of cardiac tissues. Presently, scaffolds fabricated via electro‐spinning are been widely used because of their ability to bio‐mimic the precise anatomical structure of the protein fibers. Properties like convenience to spin on several components and functionalization with several bioactive molecules have signify the use of nanofibrous scaffolds for tissue engineering. This review highlights some recent applications of electrospun nanofibrous scaffolds in the treatment and management of cardiac arterial diseases and engineering new cardiac tissues.
Neue Ergebnisse zu epoxidharzbasiertem Polymerfeinbeton mit und ohne GFK‐Bewehrung
Authors: Arendt Stephan , La Magna Riccardo , Schmeck Michel , Schmid Volker , Gengnagel Christoph
Published: April 2019

Polymerbeton stellt, analog zum klassischen zementgebundenen Beton, ein heterogenes Gemisch aus Zuschlag und Bindemittel dar. Eine Substitution des Zements durch Epoxidharz hat tiefgreifende Auswirkungen auf die mechanischen und chemischen Eigenschaften sowie auf Herstellungsprozesse. Aufgrund seiner hohen Druck‐ und Zugfestigkeit, guten chemischen Beständigkeit, seines guten Haftverbunds auf unterschiedlichsten Werkstoffen und seiner kurzen Erhärtungszeit wird Polymerbeton bisher vorwiegend für Reparaturen von Normalbetonen und bei aggressiven Umweltbedingungen eingesetzt. Notwendige bauaufsichtliche Zulassungen beschränken sich meist auf Druckbeanspruchungen im Polymerbeton oder exakte Bauteilspezifikationen. Die hier vorgestellte Forschung beschäftigt sich mit dem Einsatz von GFK‐bewehrtem Polymerbeton zur Herstellung kaltgegossener lösbarer Verbindungsdetails in stabförmigen Tragwerken aus schlanken Holz‐ oder faserverstärkten Kunststoff‐Querschnitten. In diesem Beitrag werden zunächst neue Forschungsergebnisse zu unterschiedlichen mechanischen Eigenschaften von bewehrtem und unbewehrtem epoxidharzbasiertem Polymerfeinbeton vorgestellt. Basierend auf Druckversuchen an Prismen werden die Eigenschaften unterschiedlicher epoxidharzbasierter Polymerbetone in Abhängigkeit von den Komponenten Zuschlag, Bindemittel und Luftporengehalt dargestellt. Im Anschluss werden die mechanischen Eigenschaften unter Zug und Biegung präsentiert. Darüber hinaus wird ein Materialmodell zur Bestimmung des Elastizitätsmoduls von Polymerbetonen basierend auf der Zusammensetzung des Polymerbetons vorgestellt.
A Functionally Graded Cathode Architecture for Extending the Cycle‐Life of Potassium‐Oxygen Batteries
Authors: Gilmore Paul , Sundaresan Vishnu B.
Published: April 2019

Potassium‐Oxygen (K−O2) batteries have a high theoretical energy density of 935 Wh kg−1 due to a single‐electron redox process in the reversible formation of potassium superoxide. Despite this advantage, standard K−O2 batteries have limited cycle‐life (5‐10) due to molecular oxygen crossover from cathode to anode, resulting in side reactions forming undesired superoxide on the anode. In this article, a K−O2 battery fabricated with a functionally‐graded cathode (FGC) architecture is presented to address oxygen crossover at the cathode. This K−O2 battery lasts >125 cycles with minimal loss in coulombic efficiency when charged/discharged to 300 μAh (238 μAh cm−2). The FGC is comprised of a carbon fiber layer, microporous carbon and polypyrrole doped with hexafluorophosphate. It provides a scalable architecture for regulating K+ ion and oxygen transport at the cathode trilayer (liquid‐solid‐air) interface. The PPy(PF6) formed on the cathode is observed to have an ORR rate two orders greater than that of carbon‐based electrodes, as it promotes the reversible formation of potassium superoxide at the cathode, minimizes the transport of molecular oxygen into the electrolyte, and subsequently improves anode stability and cycle‐life of the K−O2 battery. These improvements in performance with FGC come at a marginal increase in K−O2 battery material cost, which is estimated to be $44 kWh−1. The combination of performance and cost kWh−1 makes this architecture the most cost‐effective electrochemical energy storage device for stationary applications.
Biomass catalytic gasification performance over unsupported Ni‐Ce catalyst for high‐yield hydrogen production
Authors: Granados‐Fernández Rafael , Cortés‐Reyes Marina , Poggio‐Fraccari Eduardo , Herrera Concepción , Larrubia María Á. , Alemany Luis J.
Published: April 2019

Catalytic gasification of a residual biomass, obtained from yellow horn (YH) (Xanthoceras sorbifolia Bunge), an energy crop, was conducted to obtain a fuel gas rich in hydrogen. Unsupported nickel‐based catalyst modified with cerium was developed, characterized, and used in the advanced catalytic gasification of this residual biomass, using H2O + CO2 as the gasifying agent. Tests were performed in a thermobalance coupled to a mass spectrometer to identify the different steps involved in the gasification process and to correlate them with the estimated kinetic parameters. The sequential processes identified were: dehydration‐devolatilization, pyrolysis and gasification. The main pyrolysis step presented a calculated activation energy value of 102 kJ mol−1. A positive effect was observed for the catalyst in the syngas obtained. A synergistic effect of CO2 and H2O used as gasifying agents was found in the gas yield. Hydrogen production was promoted by several reforming and cracking reactions, aided by CeO2‐NiO catalyst able to co‐activate H2O + CO2. © 2019 Society of Chemical Industry and John Wiley & Sons, Ltd
Membrane‐assisted biorefinery of microalgae to obtain enriched fractions of bioderived molecules
Authors: Djamai Wissam , Mazzei Rosalinda , Bazzarelli Fabio , Dahmani Benamar , Giorno Lidietta
Published: April 2019

Microalgae represent an important source of valuable bioproducts (such as food, nutraceuticals, antioxidants, and pigments) and biofuel. They grow spontaneously in surface water and represent a contaminant that has to be separated. There is thus an urgent need to develop technologies to harvest and refine them. Depending on the microalgae species, different biocompounds can be found and appropriate separation and purification methods must be refined and selected. In this work, microalgae harvested in the Hammam Boughrara dam, situated in Tlemcen (north‐west of Algeria), were used as source to recover and fractionate bio‐derived molecules using membrane‐assisted processes. This study identified a suitable strategy to fractionate biomolecules using ultrafiltration (UF) membranes. To maintain a stable permeate flux it was necessary to decrease the complexity of the solution prior to UF. This was achieved by separating triacylglycerols (TAGs) and pigments, after breaking cells, by solid–liquid–liquid extraction with a green solvent. The UF of the remaining aqueous phase permitted a recovery factor of 70% of the proteins and more than 85% of the carbohydrates in the retentate. The TAGs that were not recovered in the green solvent, and remained in the aqueous phase, were separated in the permeate with a purity of about 70% and a recovery factor of about 60%. © 2019 Society of Chemical Industry and John Wiley & Sons, Ltd
Association of IFT88 gene variants with nonsyndromic cleft lip with or without cleft palate
Authors: Barba Amanda , Urbina Christian , Maili Lorena , Greives Matthew R. , Blackwell Steven J. , Mulliken John B. , Chiquet Brett , Blanton Susan H. , Hecht Jacqueline T. , Letra Ariadne
Published: April 2019

Background

Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common birth defect with multifactorial etiology. Genetic studies have identified numerous gene variants in association with NSCLP. IFT88 (intraflagellar transport 88) has been suggested to play a major role in craniofacial development, as Ift88 mutant mice exhibit cleft palate and mutations in IFT88 were identified in individuals with NSCLP.

Objective

To investigate the association of IFT88 single nucleotide gene variants (SNVs) with NSCLP in a large family data set consisting of non‐Hispanic white (NHW) and Hispanic families.

Methods

Nine SNVs in/nearby IFT88 were genotyped in 482 NHW families and 301 Hispanic NSCLP families. Genotyping was performed using TaqMan® chemistry. Single‐ and pairwise‐SNV association analyses were performed for all families stratified by ethnicity and family history of NSCLP using the family‐based association test (FBAT), and association in the presence of linkage (APL). Bonferroni correction was used to adjust for multiple testing and p values ≤.0055 were considered statistically significant.

Results

Significant association was found between IFT88 rs9509311 and rs2497490 and NSCLP in NHW all families (p = .004 and .005, respectively), while nominal associations were found for rs7998361 and rs9509307 (p < .05). Pairwise association analyses also showed nominal associations between NSCLP in both NHW and Hispanic data sets (p < .05). No association was found between individual variants in IFT88 and NSCLP in Hispanics.

Conclusions

Our results suggest that variation in IFT88 may contribute to NSCLP risk, particularly in multiplex families from a non‐Hispanic white population.
Training behavioral technicians to implement naturalistic behavioral interventions using behavioral skills training
Authors: Jimenez‐Gomez Corina , McGarry Kacie , Crochet Emily , Chong Ivy M.
Published: April 2019

Training behavioral technicians mainly focuses on teaching accurate implementation of structured behavioral intervention programs. Often behavioral technicians are unable to adequately promote their clients' learning in less structured environments, which can limit opportunities for generalization of the clients' skills to the natural environment. The aim of the present study was to evaluate the effectiveness of using behavioral skills training to coach behavioral technicians on the implementation of naturalistic behavioral interventions. Naturalistic behavioral interventions take advantage of naturally occurring situations to teach new skills and practice mastered skills in natural settings, thus promoting generalization across environments and in the presence of natural contingencies. Five behavioral technicians were trained to implement a novel protocol based on play therapy. Specifically, they were coached to engage in well‐defined positive behaviors during their interactions with clients (e.g., labeled praise). All participants reached mastery criteria, maintained skills at follow‐up, and demonstrated generalization of skills with novel clients.
Reversing ROS‐mediated neurotoxicity by chlorogenic acid involves its direct antioxidant activity and activation of Nrf2‐ARE signaling pathway
Authors: Yao Juan , Peng Shoujiao , Xu Jianqiang , Fang Jianguo
Published: April 2019

Chlorogenic acid (CA), the ester of caffeic acid and quinic acid, is one of the most abundant polyphenols in coffee, and has multiple pharmacological functions. The present study is designed to explore the protection provided by CA against hydrogen peroxide (H2O2)‐induced oxidative damages in the rat pheochromocytoma cells, and the underlying mechanisms engaged in this process. CA displays robust free radical‐scavenging activity in vitro. More importantly, CA strikingly rescues the cells from the H2O2‐mediated oxidative insults. Mechanistic studies revealed that CA upregulates a panel of phase II cytoprotective species, such as heme oxygenase‐1, NAD(P)H: quinone oxidoreductase 1, glutathione, thioredoxin reductase 1, and thioredoxin 1. This neuroprotection is dependent on the activation of the transcription factor Nuclear factor erythroid 2‐related factor 2 (Nrf2), as knockdown of Nrf2 abolishes such effect. Our results demonstrate that CA provides dual neuroprotection via directly neutralizing free radicals and indirectly inducing expression of Nrf2‐driven cytoprotective enzymes, and suggest a potential therapeutic usage of CA as a neuroprotective agent. Coffee is one of the most popular drinks in the world, and our discovery may also contribute to understanding the beneficial effects of regular coffee consumption. © 2019 BioFactors, 45 (4):616–626, 2019
Antibacterial mechanisms of GN‐2 derived peptides and peptoids against Escherichia coli
Authors: Saporito Paola , Mojsoska Biljana , Løbner Olesen Anders , Jenssen Håvard
Published: April 2019

Escherichia coli is the main etiological agent of urinary trait infections, able to form biofilms in indwelling devices, resulting in chronic infections which are refractory to antibiotics treatment. In this study, we investigated the antimicrobial and anti‐biofilm properties exerted against E. coli ATCC 25922, by a set of peptoids and peptides modeled upon the peptide GN‐2, previously reported as a valid antimicrobial agent. The putative antimicrobials were designed to evaluate the effect of cationicity, hydrophobicity and their partitioning on the overall properties against planktonic cells and biofilms as well as on LPS binding, permeabilization of Gram‐negative bacteria membranes and hemolysis. The data demonstrated that peptides are stronger antimicrobials than the analogue peptoids which in return have superior anti‐biofilm properties. In this study, we present evidence that peptides antimicrobial activity correlates with enhanced LPS binding and hydrophobicity but is not affected by partitioning. The data demonstrated that the enhanced anti‐biofilm properties of the peptoids are associated with decreased hydrophobicity and increased penetration of the inner membrane, compared to that of their peptide counterpart, suggesting that the characteristic flexibility of peptoids or their lack of H‐bonding donors in their backbone, would play a role in their ability to penetrate bacterial membranes.
Educational avenues for promoting dialog on fascia
Authors: Pratt Rebecca L.
Published: April 2019

If your healthcare professional students have not heard about the importance of fascia they definitely should, and if your residents have not heard about the manifestations of fascia health they definitely will from their patients. While fascia may not be the sexiest of organ systems, it is one of the most influential. Fascia is gaining interest from researchers, physicians, and many subdivisions of manual medicine including massage therapists. The fascial system is now being recognized with roles in pathology, fluid movement, and proprioception. It is also important in skeletal muscle movement, perception of pain, protein regulation and expression, cell signaling, neoplastic growth, and hormone distribution in our body. It can be the reason why we feel chronic pain or why we feel tightness after physical activity. The primary responsibility of fascia is to connect systems so that the body works as a whole, which is what permits this topic to be easily embedded anywhere in our health curricula. Whether you teach students in schools of medical, veterinary, dental, physical therapy, physician assistant studies, or occupational therapy, fascia matters. Whether you teach in an integrated curriculum or a curriculum that is designed for problem‐based learning or a classical discipline‐based curriculum, connective tissue has a place in academia. So, in our cramped curriculum how do we make sure that our current undergraduate and graduate students understand the complexity of fascia without adding additional time to coursework? To answer this question, this article demonstrates how fascia can fit anywhere in the curriculum because it is found everywhere. Clin. Anat. 32:871–876, 2019. © 2019 Wiley Periodicals, Inc.
Risk of immune‐related pneumonitis for PD1/PD‐L1 inhibitors: Systematic review and network meta‐analysis
Authors: Huang Yafang , Fan Haiyu , Li Ning , Du Juan
Published: April 2019

Background

Immune‐related pneumonitis is a clinically relevant and potentially life‐threatening adverse event. We performed a systematic review and network meta‐analysis to compare the risk of immune‐related pneumonitis among different PD1/PD‐L1 inhibitor‐related therapeutic regimens.

Methods

Randomized controlled trials with PD1/PD‐L1 inhibitors were identified through comprehensive searches of multiple databases. Both published and unpublished data were extracted. Bayesian NMA was performed using random‐effects models. All‐grade (Grade 1‐5) and high‐grade (Grade 3‐5) immune‐related pneumonitis were estimated using odds ratios (ORs).

Results

A total of 25 studies involving 16 005 patients were included. Compared with chemotherapy, the ORs of immune‐related all‐grade and high‐grade pneumonitis were significant for nivolumab (all‐grade: OR = 6.29, 95% CrI: 2.67‐16.75; high‐grade: OR = 5.95, 95% CrI: 2.35‐17.29), pembrolizumab (all‐grade: OR = 5.78, 95% CrI: 2.79‐13.24; high‐grade: OR = 5.33, 95% CrI: 2.49‐12.97), and nivolumab plus ipilimumab therapy (all‐grade: OR = 14.82, 95% CrI: 5.48‐47.97; high‐grade: OR = 15.26, 95% CrI: 5.05‐55.52). Compared with nivolumab, nivolumab plus ipilimumab therapy was associated with an increased risk of all‐grade pneumonitis (OR = 2.34, 95% CrI: 1.07‐5.77). Nivolumab plus ipilimumab therapy had the highest risk of both all‐grade and high‐grade pneumonitis among PD1/PD‐L1 inhibitor‐related therapeutic regimens.

Conclusions

This study demonstrates that compared with chemotherapy, PD‐1 inhibitor may result in a higher risk of immune‐related pneumonitis. Nivolumab plus ipilimumab therapy had the highest pneumonitis risk. These findings could be taken into account by the physicians in decision making.
Determinants of quality prostate cancer survivorship care across the primary and specialty care interface: Lessons from the Veterans Health Administration
Authors: Radhakrishnan Archana , Henry Jennifer , Zhu Kevin , Hawley Sarah T. , Hollenbeck Brent K. , Hofer Timothy , Wittmann Daniela A. , Sales Anne E. , Skolarus Ted A.
Published: April 2019

Background

With over 3 million US prostate cancer survivors, ensuring high‐quality, coordinated cancer survivorship care is important. However, implementation of recommended team‐based cancer care has lagged, and determinants of quality care across primary and specialty care remain unclear. Guided by the theoretical domains framework (TDF), we explored multidisciplinary determinants of quality survivorship care in an integrated delivery system.

Methods

We conducted semistructured interviews with primary (4) and specialty (7) care providers across 6 Veterans Health Administration clinic sites. Using template analysis, we coded interview transcripts into the TDF, mapping statements to specific constructs within each domain. We assessed whether each construct was perceived a barrier or facilitator, examining results for both primary care providers (PCPs) and prostate cancer specialists.

Results

Cancer specialists and PCPs identified 2 primary TDF domains impacting their prostate cancer survivorship care: Knowledge and Environmental context and resources. Both groups noted knowledge (about survivorship care) and procedural knowledge (about how to deliver survivorship care) as positive determinants or facilitators, whereas resources/material resources (to deliver survivorship care) was noted as a negative determinant or barrier to care. Additional domains more commonly referenced by cancer specialists included Social/professional role and identity and Goals, while PCPs reported the domain Beliefs about capabilities as relevant.

Conclusions

We used the TDF to identify several behavioral domains acting as determinants of high‐quality, team‐based prostate cancer survivorship care. These results can inform prostate cancer survivorship care plan content, and may guide tailored, multidisciplinary implementation strategies to improve survivorship care across the primary and specialty care interface.
Association of sociodemographic and oncological features with decision on implant‐based versus autologous immediate postmastectomy breast reconstruction in Chinese patients
Authors: Yin Zhuming , Wang Yan , Sun Jingyan , Huang Qingfeng , Liu Jing , He Shanshan , Han Chunyong , Wang Shu , Ding Bowen , Yin Jian
Published: April 2019

Background and objectives

Immediate postmastectomy breast reconstruction (IPBR) has gained wide popularity in China. We sought to clarify the prevalence and predictors of implant‐based vs autologous IPBR among Chinese patients.

Methods

A retrospective cohort study was performed using a prospectively maintained database. Women who underwent IPBR during 2001‐2017 were included. The modality‐specific trends were deciphered by curve fitting analysis. The association of sociodemographic and oncological features with the decision for implant‐based vs autologous IPBR was investigated using multivariate logistic regression and structural equation modeling.

Results

Among 905 patients included in the study, 479 underwent implant‐based IPBR and 426 underwent autologous procedures. The implant/autologous ratio has increased exponentially over time. Multivariate analysis demonstrated that unmarried patients with BMI ≤ 24 kg/m2, earlier clinical tumor stage, and preoperative pathological diagnosis of noninvasive lesion are more likely to choose implant‐based IPBR compared to autologous procedures. The indirect effects of age, mastectomy type, and neoadjuvant chemotherapy were further demonstrated by the structural equations.

Conclusions

The sociodemographic and oncological features are directly or indirectly associated with the decision on type of IPBR. The findings may facilitate both patients and physicians to make a high‐quality decision by holistic evaluation of the sociodemographic and oncological features.
Prognostic implications of a molecular classifier derived from whole‐exome sequencing in nasopharyngeal carcinoma
Authors: Wang Hai‐Yun , Li Fugen , Liu Na , Liu Xiao‐Yun , Yang Xin‐Hua , Guo Yun‐Miao , Bei Jin‐Xin , Zeng Yi‐Xin , Shao Jian‐Yong
Published: April 2019

The aim of this study was to use whole‐exome sequencing to derive a molecular classifier for nasopharyngeal carcinoma (NPC) and evaluate its clinical performance. We performed whole‐exome sequencing on 82 primary NPC tumors from Sun Yat‐sen University Cancer Center (Guangzhou cohort) to obtain somatic single‐nucleotide variants, indels, and copy number variants. A novel molecular classifier was then developed and validated in another NPC cohort (Hong Kong cohort, n = 99). Survival analysis was estimated by the Kaplan‐Meier method and compared using the log‐rank test. Cox proportional hazards model was adopted for univariate and multivariate analyses. We identified three prominent NPC genetic subtypes: RAS/PI3K/AKT (based on RAS, AKT1, and PIK3CA mutations), cell‐cycle (based on CDKN2A/CDKN2B deletions, and CDKN1B and CCND1 amplifications), and unclassified (based on dominant mutations in epigenetic regulators, such as KMT2C/2D, or the Notch signaling pathway, such as NOTCH1/2). These subtypes differed in survival analysis, with good, intermediate, and poor progression‐free survival in the unclassified, cell‐cycle, and RAS/PI3K/AKT subgroups, respectively, among the Guangzhou, Hong Kong, and combined cohorts (n = 82, P = 0.0342; n = 99, P = 0.0372; and n = 181, P = 0.0023; log‐rank test). We have uncovered genetic subtypes of NPC with distinct mutations and/or copy number changes, reflecting discrete paths of NPC tumorigenesis and providing a roadmap for developing new prognostic biomarkers and targeted therapies.
Therapeutic bacteria to combat cancer; current advances, challenges, and opportunities
Authors: Sedighi Mansour , Zahedi Bialvaei Abed , Hamblin Michael R. , Ohadi Elnaz , Asadi Arezoo , Halajzadeh Masoumeh , Lohrasbi Vahid , Mohammadzadeh Nima , Amiriani Taghi , Krutova Marcela , Amini Abolfazl , Kouhsari Ebrahim
Published: April 2019

Successful treatment of cancer remains a challenge, due to the unique pathophysiology of solid tumors, and the predictable emergence of resistance. Traditional methods for cancer therapy including radiotherapy, chemotherapy, and immunotherapy all have their own limitations. A novel approach is bacteriotherapy, either used alone, or in combination with conventional methods, has shown a positive effect on regression of tumors and inhibition of metastasis. Bacteria‐assisted tumor‐targeted therapy used as therapeutic/gene/drug delivery vehicles has great promise in the treatment of tumors. The use of bacteria only, or in combination with conventional methods was found to be effective in some experimental models of cancer (tumor regression and increased survival rate). In this article, we reviewed the major advantages, challenges, and prospective directions for combinations of bacteria with conventional methods for tumor therapy.
Prognostic role of cyclin D2/D3 in multiple human malignant neoplasms: A systematic review and meta‐analysis
Authors: Ding Zuo‐you , Li Ran , Zhang Qi‐jie , Wang Yi , Jiang Yi , Meng Qing‐yang , Xi Qiu‐lei , Wu Guo‐hao
Published: April 2019

Cyclin D2/D3 (CCND2/3) are core components of the machinery that drives cell cycle progression and therefore, are associated with tumorigenesis. Currently, there are contradictory evidences on the function of CCND2/3 in tumorigenesis. Thus, we conducted a comprehensive meta‐analysis to derive a precise predictive value of CCND2/3 in various tumors. We searched PubMed, EMBASE, Web of Science for eligible studies up to October 8, 2018. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) of OS or DFS/PFS/RFS were calculated using Forest plot analysis to demonstrate their associations. A total of 14 studies were ultimately included in this meta‐analysis. Our results indicated CCND2/3 played an oncogenic role in all of the cancer patients (CCND2: pooled HR = 2.21, 95% CI: 1.67‐2.93; CCND3: pooled HR = 2.29, 95% CI: 1.05‐5.03). In tumor subgroup, CCND2 was associated with shorter OS in patients with gastric cancer (HR = 2.20, 95% CI: 1.66‐2.92), whereas it might be a tumor suppressor in NSCLC (HR = 0.28, 95% CI: 0.12‐0.64). In addition, CCND3 was correlated to reduced OS in breast cancer patients (HR = 1.64, 95% CI: 1.07‐2.52) and shorter DFS/PFS/RFS in bladder cancer patients (HR = 4.60, 95% CI: 1.89‐12.57). Taken together, CCND2/3 could be the promising biomarkers for predicting the prognosis of patients with malignant neoplasms.
Rieger Syndrome: Rehabilitation With Dental Implants
Authors: Pirih Flavia Q. , Casarin Maísa , Perussolo Jeniffer , Ozaki Mark , Carnio João G. , Camargo Paulo M. , Galvan Maria
Published: April 2019

Introduction

Axenfeld‐Rieger syndrome (ARS), also known as Rieger syndrome, is a rare autosomal dominant condition defined by craniofacial, ocular, dental, periumbilical, and systemic anomalies.

Case Presentation

This case report describes in detail a multidisciplinary approach to successfully restore the oral function and esthetics of a 22‐year‐old patient diagnosed with ARS. The patient's clinical evaluation revealed that the area corresponding with teeth #13, #12, #11, #21, #22, and #23 was occupied by four malformed and/or deciduous teeth. The four anterior teeth were extracted, and socket preservation was performed using bovine‐derived porous bone mineral. Six months after extractions, two implants were placed in the location of the lateral incisors and additional bone graft was performed. Two months after the initial healing, a temporary fixed partial was delivered and 9 months after implant placement the implants were restored with a porcelain‐fused‐to‐metal fixed partial denture.

Conclusions

The use of implant‐supported fixed partial dentures to restore missing teeth in patients with ARS provides biological and mechanical advantages over conventional, fixed, or removable prosthodontics. Further evaluation is needed to determine the longevity and long‐term prognosis of dental implants in patients with ARS.
Activation of prolyl hydroxylase‐2 for stabilization of mitochondrial stress along with simultaneous downregulation of HIF‐1α/FASN in ER + breast cancer subtype
Authors: Devi Uma , Singh Manjari , Roy Subhadeep , Gupta Pushpraj S. , Ansari Mohd. Nazam , Saeedan Abdulaziz S. , Kaithwas Gaurav
Published: April 2019

The present study was undertaken to inquest the chemical activation of prolyl hydroxylase‐2 for the curtailment of hypoxia‐inducible factor‐1α and fatty acid synthase. It was well documented that hypoxia‐inducible factor‐1α and fatty acid synthase were overexpressed in mammary gland carcinomas. After screening a battery of compounds, BBAP‐2 was retrieved as a potential prolyl hydroxylase‐2 activator and validates its activity using ER + MCF‐7 cell line and n‐methyl‐n‐nitrosourea‐induced rat in vivo model, respectively. BBAP‐2 was palpable for the morphological characteristics of apoptosis along with changes in the mitochondrial intergrity as visualized by acridine orange/ethidium bromide and JC‐1 staining against ER + MCF‐7 cells. BBAP‐2 also arrest the cell cycle of ER + MCF‐7 cells at G2/M phase. Afterward, BBAP‐2 has scrutinized against n‐methyl‐n‐nitrosourea‐induced mammary gland carcinoma in albino Wistar rats. BBAP‐2 restored the morphological architecture when screened through carmine staining, haematoxylin and eosin staining, and scanning electron microscopy. BBAP‐2 also delineated the markers of oxidative stress favourably. The immunoblotting and mRNA expression analysis validated that BBAP‐2 has a potentialty activate the prolyl hydroxylase‐2 with sequential downregulating effect on hypoxia‐inducible factor‐1α and its downstream checkpoint. BBAP‐2 also fostered apoptosis through mitochondrial‐mediated death pathway. The present study elaborates the chemical activation of prolyl hydroxylase‐2 by which the increased expression of HIF‐1α and FASN can be reduced in mammary gland carcinoma.
Mannopyranoside Glycolipids Inhibit Mycobacterial and Biofilm Growth and Potentiate Isoniazid Inhibition Activities in M. smegmatis
Authors: Mahapa Avisek , Samanta Gopal Ch , Maiti Krishnagopal , Chatterji Dipankar , Jayaraman Narayanaswamy
Published: April 2019

Lipomannan and lipoarabinomannan are integral components of the mycobacterial cell wall. Earlier studies demonstrated that synthetic arabinan and arabinomannan glycolipids acted as inhibitors of mycobacterial growth, in addition to exhibiting inhibitory activities of mycobacterial biofilm. Herein, it is demonstrated that synthetic mannan glycolipids are better inhibitors of mycobacterial growth, whereas lipoarabinomannan has a higher inhibition efficiency to biofilm. Syntheses of mannan glycolipids with a graded number of mannan moieties and an arabinomannan glycolipid are conducted by chemical methods and subsequent mycobacterial growth and biofilm inhibition studies are conducted on Mycobacterium smegmatis. Growth inhibition of (73±3) % is observed with a mannose trisaccharide containing a glycolipid, whereas this glycolipid did not promote biofilm inhibition activity better than that of arabinomannan glycolipid. The antibiotic supplementation activities of glycolipids on growth and biofilm inhibitions are evaluated. Increases in growth and biofilm inhibitions are observed if the antibiotic is supplemented with glycolipids, which leads to a significant reduction of inhibition concentrations of the antibiotic.
Fluorescent Probes for Studying Thioamide Positional Effects on Proteolysis Reveal Insight into Resistance to Cysteine Proteases
Authors: Liu Chunxiao , Barrett Taylor M. , Chen Xing , Ferrie John J. , Petersson E. James
Published: April 2019

Thioamide substitutions of the peptide backbone have been shown to reduce proteolytic degradation, and this property can be used to generate competitive protease inhibitors and to stabilize peptides toward degradation in vivo. Here, we present a straightforward sensor design that allows a systematic study of the positional effects of thioamide substitution by using real‐time fluorescence. Thioamide scanning in peptide substrates of five papain family cysteine proteases demonstrates that a thioamide at or near the scissile bond can slow proteolysis in all cases, but that the magnitude of the effects varies with position and protease in spite of high sequence homology. Mechanistic investigation of papain proteolysis reveals that the thioamide effects derive from reductions in both affinity (KM) and turnover number (kcat). Computational modeling allows these effects to be understood based on disruption of key enzyme–substrate hydrogen bonds, providing a model for future rational use of thioamides to confer cysteine protease resistance.
Exploring the Minimal RNA Substrate of Flexizymes
Authors: Fujino Tomoshige , Kondo Taishi , Suga Hiroaki , Murakami Hiroshi
Published: April 2019

Flexizymes are tRNA acylation ribozymes that have been successfully used to facilitate genetic code reprogramming. They are capable of charging acid substrates onto various tRNAs and tRNA analogues. However, their minimal RNA substrate has not been investigated. Here we have designed fluorescently labeled short RNAs corresponding to the four, three, and two bases (4bRNA, 3bRNA, 2bRNA) at the tRNA 3′‐end and explored the minimal RNA substrate of flexizymes, dFx and eFx. 3bRNA was the observed minimal RNA substrate of the flexizymes, but the efficiency of acylation of this short RNA was two to three times lower than that of 4bRNA. The efficiency of acylation of 4bRNA was comparable with that of the microhelix, a 22‐base RNA conventionally used as a tRNA analogue for analyzing acylation efficiency. We also compared the efficiencies of acylation of the microhelix and 4bRNA with various acid substrates. Thanks to the short length of 4bRNA, its acyl‐4bRNA products exhibited larger mobility shifts in gel electrophoresis than those exhibited by acyl‐microhelix products with every substrate tested. This indicated that 4bRNA was an ideal RNA substrate for analyzing the efficiency of acylation by flexizymes.
Hey, American College of Cardiology interventionalists: What are you thinking?
Authors: Butman Samuel M.
Published: April 2019

Key Points

There is large variation in the utilization of the appropriate Use‐Criteria (AUC).

There has been a significant decrease in the number of Percutaneous coronary intervention (PCI) cases deemed rarely appropriate.

The value of the AUC remains a questionable tool for many clinicians.
A match not made in heaven—TAVR prosthesis‐patient mismatch with contemporary valves
Authors: Safi Lucy M. , Turi Zoltan G.
Published: April 2019

Key Points

Prosthesis‐patient mismatch (PPM) in TAVR is relatively common

Valve oversizing can potentially prevent both paravalvular leak and PPM

PPM may be avoidable if the expected Effective Orifice Area/Body Surface Area ratio is considered in decision making pre‐TAVR.
A hot lead on reducing infarct size
Authors: Blankenship James C.
Published: April 2019

Key Points

The intracoronary hyperoxemic oxygen therapy study, designed to demonstrate the safety of supersaturated oxygen (SSO2) infused into the left main coronary after percutaneous coronary intervention for anterior ST‐elevation myocardial infarction (STEMI), demonstrated a net adverse clinical event rate of 7.1%, lower than the Food and Drug Administration‐set goal of 10.7%.

SSO2, which has reduced infarct size in clinical STEMI trials, might become an important strategy for treating anterior STEMIs.

Larger postmarketing trials are needed to determine whether decreases in infarct size are observed in real‐world populations, whether they translate into improved clinical outcomes, and whether modifications in technique can streamline the administration of SSO2 therapy.
Left ventricular end‐diastolic pressure in acute myocardial infarction: A loaded target in need of unloading
Authors: Kapur Navin K. , O'Neill William W.
Published: April 2019

Key Points

Left ventricular (LV) end‐diastolic pressure predicts short‐ and long‐term mortality and correlates with infarct size after ST‐segment elevation acute myocardial infarction.

Ventricular load refers to any variable that increases myocardial oxygen consumption including LV pressure, volume, or heart rate.

Clinical studies of ventricular “unloading” as a therapeutic approach for acute myocardial infarction with and without cardiogenic shock are ongoing.
Advances in the treatment of coronary perforations
Authors: Xenogiannis Iosif , Brilakis Emmanouil S.
Published: April 2019

Key Points

Coronary artery perforation is an infrequent, but potentially life‐threatening complication of percutaneous coronary intervention. There are four types of coronary perforation: (a) large vessel; (b) distal vessel; (c) septal collateral; and (d) epicardial collateral perforation.

Implantation of a covered stent is the cornerstone of large vessel perforation treatment and can be used in some distal vessel perforations, when embolization is not feasible. Until now the only available covered stent in the US was the Graftmaster stent (two bare metal stents with a PTFE membrane in‐between them), that has high profile and is challenging to deliver and expand. Use of the Graftmaster has been associated with high rates of in‐stent restenosis and stent thrombosis.

Availability of more deliverable covered stents, such as the BeGraft (Bentley InnoMed GmbH, Hechingen, Germany) and PK Papyrus (BIotronik, Lake Oswego, Oregon, that recently received FDA approval) will greatly facilitate treatment of large vessel coronary perforations.
Clinical utility of surveillance and clinically prompted right heart catheterization in patients listed for heart transplantation
Authors: Ahluwalia Monica , Jessup Mariell , Forde Kimberly A. , Sehgal Sankalp , Katz Stuart T. , Quiaoit Ylenia Ann A. , Hornsby Nicole , Owens Anjali T. , McLean Rhondalyn C.
Published: April 2019

Background and Objectives

The 2016 ISHLT guidelines recommend that patients listed for orthotopic heart transplantation (OHT) undergo periodic surveillance right heart catheterization (RHC) to re‐assess hemodynamics (Class I, level of evidence C). However, the impact of RHC on management remains unclear. The aim of this study was to determine the utility of both surveillance and clinically prompted RHCs in patients listed for OHT.

Methods

A retrospective study was conducted in adult patients listed for OHT at our hospital from 2006 through 2014. Each patient included had at least one RHC after being listed for OHT. The primary outcome was management change: hospitalization, surgery (OHT or mechanical circulatory support [MCS]), change in United Network for Organ Sharing (UNOS) status, or initiation/modification of vasoactive drugs, diuretics or neurohormonal blockade.

Results

Of the 194 patients included, 85 (43%) patients had more than one RHC. The median time between listing and transplantation was 115 days. Of the 376 RHCs performed, 187 (50%) were prompted by a clinical change; 189 (50%) were performed for surveillance. In 90.4% of clinically prompted RHCs and 42.9% of surveillance RHCs, a clinically important management change was implemented. Initiation/modification of vasoactive drugs, placement of MCS and/or change in UNOS transplant status occurred in 61 (33%) of the clinically prompted RHCs and 26 (14%) of the surveillance RHCs. Patients who underwent management change were more likely to receive a heart transplant (HR 1.58; CI 1.15–2.18) without an increased rate of death over the study period compared to those who did not have a management change. Multivariable analysis revealed that a hemoglobin level <12.2 g/dL (OR 2.96; CI 1.36–6.42) and a total bilirubin level >0.9 mg/dL (OR 5.07; CI 2.09–12.3) were predictors of management change.

Conclusions

In patients awaiting OHT, RHCs prompted by clinical instability or routine surveillance resulted in frequent management changes, including earlier heart transplant and MCS implant. Our study supports the Class I recommendation to perform surveillance RHC in patients listed for OHT and suggests that centers should consider maintaining a low threshold for repeat RHC during the formal waiting time.
Dose‐dependent elevation in amylase and lipase in response to teduglutide administration
Authors: Lee Joshua , Kim Myoung , Kim Dong Wook
Published: April 2019

Key Clinical Message

Teduglutide has been used for patients with short bowel syndrome. Teduglutide can be a dose‐dependent triggering factor to increased amylase and lipase. Serum amylase and lipase levels should be monitored routinely for patients on teduglutide, and they should be screened before the initiation of treatment.
Effectiveness of lenalidomide in relapsed primary cutaneous diffuse large B‐cell lymphoma, leg type
Authors: Al Dhafiri Mahdi , Sicre de Fontbrune Flore , Marinho Eduardo , Deschamps Lydia , Di‐Lucca Julie , Crickx Beatrice , Descamps Vincent
Published: April 2019

Key Clinical Message

The primary cutaneous diffuse large B‐cell lymphoma, leg type (PCDLBCL‐LT) has a poor prognosis. R‐CHOP with or without radiotherapy is the available recommendations for first‐line treatment. Relapses/refractory cases are frequent with no standardized therapeutic guidelines. Lenalidomide seems to be an excellent therapeutic option as a second‐line treatment of relapsed PCDLBCL‐LT.