bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment With Topical Deferoxamine Improves Cutaneous Vascularity and Tissue Pliability in an Irradiated Animal Model of Tissue Expander–Based Breast Reconstruction
Authors: Dassoulas Kasandra R. , Mericli Alexander F. , Wang Jessica S. , Lei Serena S. , Kim Taeho , Cottler Patrick S. , Lin Kant Y.
Published: December 2018

Purpose

Postmastectomy radiation therapy is an important component of the multimodality approach to later-stage breast cancers. Unfortunately, despite its proven survival benefits, postmastectomy radiation therapy is deleterious to the skin and soft tissue, causing increased complications and worse aesthetic outcomes after breast reconstruction.

There is currently no effective pharmaceutical agent to mitigate the soft tissue fibrosis and hypovascularity associated with soft tissue radiation. We hypothesized that a novel topical formulation of deferoxamine (DFX) will result in improved cutaneous vascularity and soft tissue pliability in an animal model of irradiated tissue expander–based breast reconstruction.

Methods

This study consisted of 16 hairless rats divided into 4 equal groups: a control group (expander only), a tissue expanded and irradiated group, a tissue expanded + DFX group, and a tissue expanded/irradiated/DFX group. A novel topical formulation of DFX consisted of reconstituted drug dissolved in agents designed to enhance dermal penetrance. Vessels per high-power field (vHPF) were quantified histologically; micro–computed tomography angiography was used to assess vessel volume fraction (VVF) and vessel length density.

Results

Irradiated skin had less vascularity compared with control (3.81 vHPF vs 8.25 vHPF, P = 0.03; 0.79% VVF vs 1.53% VVF, P = 0.06). Treatment of irradiated skin with topical DFX reversed these effects, resulting in vascular findings similar to the control group histologically (7.94 vHPF vs 8.25 HPF, P = 0.985) and via micro–computed tomography angiography (1.05% VVF vs 1.53% VVF, P = 0.272). Similarly, radiation resulted in less volume expansion compared with controls (0.72 vs 0.8 mL, P = 0.04), whereas treatment with topical DFX reversed this effect, allowing for an expansion volume similar to the control group (0.81 vs 0.80 mL, P = 0.999).

Conclusions

In an animal model of irradiated tissue expander–based breast reconstruction, treatment with topical DFX improved the cutaneous vascularity and tissue pliability, resulting in vascular density and final tissue expansion volumes similar to those found in the nonirradiated control group. Topical DFX may be an effective agent for the treatment of soft tissue radiation injury; future studies are indicated to further characterize this novel drug formulation.
Mechanobiological Conditioning of Mesenchymal Stem Cells Enhances Therapeutic Angiogenesis by Inducing a Hybrid Pericyte-Endothelial Phenotype
Authors: Lee Jason , Henderson Kayla , Armenta-Ochoa Miguel , Veith Austin , Maceda Pablo , Yoon Eun , Samarneh Lara , Wong Mitchell , Dunn Andrew , Baker Aaron
Published: December 2018

Stem cell therapies have great promise for revolutionizing treatments for cardiovascular disease and other disorders but have not yet achieved their potential due to poor efficacy and heterogeneity in patient response. Here, we used a novel high throughput screening system to optimize the conditioning of mesenchymal stem cells using a combinatorial set of biochemical factors, pharmacological inhibitors and biomechanical forces. Our studies revealed that a combination of specific kinase inhibitors and a complex mechanical strain waveform dramatically increased the population of mesenchymal stem cells that express markers for both pericytes and endothelial cells. These mechanically and pharmacologically conditioned mesenchymal stem cells had superior properties in enhancing endothelial tube formation, production of angiogenic growth factors and induction of angiogenesis following implantation. Overall, our work supports that combinatorial optimization of mechanical conditioning and pharmacological treatments can significantly enhance the regenerative properties of mesenchymal stem cells.
The abundance of Nudix hydrolase 16 transcripts is elevated in human sepsis: perspectives gained during a hands-on reductionist investigation workshop.
Authors: Garand Mathieu , Rinchai Darawan , Kabeer Basirudeen Syed Ahamed , Toufiq Mohammed , Alfaki Mohamed , Roelands Jessica , Hendrickx Wouter , Boughorbel Sabri , Marr Nico , Bedognetti Davide , Chaussabel Damien
Published: December 2018

A hands-on training workshop was devised with omics data used as source material to emulate reductionist investigation approaches. NUDT16, a member of the Nudix hydrolase family was selected as a candidate gene on the basis of: 1) it being upregulated in neutrophils exposed in vitro to serum of patients with sepsis, AND 2) the absence of overlap between the NUDT16 and sepsis, inflammation or neutrophil literature. We next sought to corroborate the initial finding in five public transcriptome sepsis datasets in which NUDT16 transcript levels were measured. In each of these dataset NUDT16 transcript abundance was found to be significantly increased in septic patients in vivo in comparison to uninfected controls. Next, biological concepts were extracted from the NUDT16 literature. The main concepts to emerge from profiling this literature were RNA decapping, inosine triphosphate, and inosine diphosphate. Through these concepts, indirect links could be established between NUDT16 and the sepsis/inflammation/neutrophil literature. A potential role for NUDT16 could, in turn, be inferred in the degradation of mRNAs in activated neutrophils. Follow on experiments that would be necessary in order to further explore such inference are discussed.
Activation and in vivo evolution of the MAIT cell transcriptome in mice and humans reveals diverse functionality
Authors: Hinks Timothy SC , Marchi Emanuele , Jabeen Maisha , Olshansky Moshe , Kurioka Ayako , Pediongco Troi J , Meehan Bronwyn S , Kostenko Lyudmila , Turner Stephen J , Corbett Alexandra J , Chen Zhenjun , Klenerman Paul , McCluskey James
Published: December 2018

Mucosal-associated invariant T (MAIT) cells are MR1-restricted innate-like T cells conserved across mammalian species, including mice and humans. By sequencing RNA from sorted MR1-5-OP-RU tetramer+ cells derived from either human blood or murine lungs, we define the basic transcriptome of an activated MAIT cell in both species and demonstrate how this profile changes during resolution and reinfection phases of infection. We observe strong similarities between MAIT cells in humans and mice. Compared with previously published T cell transcriptomes, MAIT cells displayed most similarity to iNKT cells when activated, but to γδ T cells, after resolution of infection. In both species activation leads to strong expression of pro-inflammatory cytokines and chemokines, and also a strong tissue repair signature, recently described in murine commensal-specific H2-M3-restricted T cells. These data define the requirements for, and consequences of, MAIT cell activation, revealing a tissue repair phenotype expressed upon MAIT cell activation in both species.
Rapid reversible changes in compartments and local chromatin organization revealed by hyperosmotic shock
Authors: Amat Ramon , Böttcher René , Le Dily François , Vidal Enrique , Quilez Javier , Cuartero Yasmina , Beato Miguel , de Nadal Eulàlia , Posas Francesc
Published: December 2018

Nuclear architecture is decisive for the assembly of transcriptional responses. However, how chromosome organization is dynamically modulated to permit rapid and transient transcriptional changes in response to environmental challenges remains unclear. Here we show that hyperosmotic stress disrupts different levels of chromosome organization, ranging from A/B compartment changes to reduction in the number and insulation of topologically associating domains (TADs). Concomitantly, transcription is greatly affected, TAD borders weaken, and RNA Polymerase II runs off from hundreds of transcription end sites. Stress alters the binding profiles of architectural proteins, which explains the disappearance of local chromatin organization. These processes are dynamic, and cells rapidly reconstitute their default chromatin conformation after stress removal, uncovering an intrinsic organization. Transcription is not required for local chromatin reorganization, while compartment recovery is partially transcription-dependent. Thus, nuclear organization in mammalian cells can be rapidly modulated by environmental changes in a reversible manner.
Unsteady natural convection in a partially porous cavity having a heat-generating source using local thermal non-equilibrium model
Authors: Astanina Marina S. , Sheremet Mikhail , Umavathi C. Jawali
Published: December 2018

Purpose

The purpose of this study is a numerical analysis of transient natural convection in a square partially porous cavity with a heat-generating and heat-conducting element using the local thermal non-equilibrium model under the effect of cooling from the vertical walls. It should be noted that this research deals with a development of passive cooling system for the electronic devices.

Design/methodology/approach

The domain of interest is a square cavity with a porous layer and a heat-generating element. The vertical walls of the cavity are kept at constant cooling temperature, while the horizontal walls are adiabatic. The heat-generating solid element is located on the bottom wall. A porous layer is placed under the clear fluid layer. The governing equations, formulated in dimensionless stream function, vorticity and temperature variables with corresponding initial and boundary conditions, are solved using implicit finite difference schemes of the second order accuracy. The governing parameters are the Darcy number, viscosity variation parameter, porous layer height and dimensionless time. The effects of varying these parameters on the average total Nusselt number along the heat source surface, the average temperature of the heater, the fluid flow rate inside the cavity and on the streamlines and isotherms are analyzed.

Findings

The results show that in the case of local thermal non-equilibrium the total average Nusselt number is an increasing function of the interphase heat transfer coefficient and the porous layer thickness, while the average heat source temperature decreases with the Darcy number and viscosity variation parameter.

Originality/value

An efficient numerical technique has been developed to solve this problem. The originality of this work is to analyze unsteady natural convection within a partially porous cavity using the local thermal non-equilibrium model in the presence of a local heat-generating solid element. The results would benefit scientists and engineers to become familiar with the analysis of convective heat transfer in enclosures with local heat-generating heaters and porous layers, and the way to predict the heat transfer rate in advanced technical systems, in industrial sectors including transportation, power generation, chemical sectors and electronics.
Relational asymmetry, trust, and innovation in supply chain management: a non-linear approach
Authors: Michalski Marek , Montes Jose Luis , Narasimhan Ram
Published: December 2018

Purpose

The purpose of this paper is to examine the non-linear aspects of the asymmetry-performance relationship under varying conditions of trust and innovation. Its novel approach is useful for addressing the strategic elements of supply chain management (SCM) relationships based on trust and innovation decisions.

Design/methodology/approach

Results are based on a study of 90 managers from small- and medium-sized firms in Spain. Instead of a classical linear relationship analysis, the authors performed a non-linear analysis, using polynomial modeling and Warp 3 partial least squares method, which provides a more nuanced view of the data and constitutes an original approach to empirical research in SCM.

Findings

This study adds a new viewpoint on SC relationships by suggesting that not all trust and innovation development leads directly to performance improvement. The principal finding is, in varying trust and innovation contexts, that the influences of asymmetry on performance have uneven characteristics and follow non-linear paths.

Research limitations/implications

This study focuses on only one particular institutional environment in one country. The data are also cross-sectional, which makes it difficult to empirically test causality.

Practical implications

The findings provide rational insights to managers on when it is appropriate to reduce (or not) asymmetric relationships with partners.

Originality/value

Trust and innovation are important and ones of the key requirements of supply chain relationships in any environment, this study argues that the interactions of key SCM elements that drive members to better performance are more complex and non-linear.
The transition from relation-based to rule-based governance in East Asia
Authors: Li Shaomin , Park Seung Ho , Bao Rosey Shuji
Published: December 2018

Purpose

The purpose of this paper is to use the framework of rule-based and relation-based governance to examine the evolution of governance environment in the East Asian region including China, South Korea and Taiwan.

Design/methodology/approach

Both qualitative and quantitative evidences are presented to demonstrate the paths these East Asian countries take in their transitions from relation-based governance to rule-based governance. Based on the framework, this analysis sheds light on the debate on whether East Asian economies will eventually move away from relation-based governance to rule-based societies.

Findings

The authors find that relation-based governance has helped East Asian countries achieve rapid economic growth in the early stages of their development. However, as the scale and scope of East Asian economies expand, continuing to rely on it may hinder their further development and therefore these countries should adopt a rule-based governance system in order to be efficient and competitive in the world market. While South Korea and Taiwan have made substantial progress in this transition, China has just embarked on the process.

Originality/value

This paper is among the first to systematically review the theories and evidence of the transition and the challenges East Asian countries face during the process.
Older adults neglected by their caregivers: vulnerabilities and risks identified in an adult protective services sample
Authors: Ernst Joy Swanson
Published: December 2018

Purpose

Using a risk and vulnerability framework, the purpose of this paper is to describe the characteristics of older adults that Adult Protective Services (APS) substantiated for neglect by caregivers, their caregivers and the interrelationships between them.

Design/methodology/approach

The paper uses a qualitative study of 21 APS case record narratives using a template analysis.

Findings

Neglect related to withholding or refusing medical care was the most common. The older adults had multiple health conditions and geriatric syndromes. Caregivers had difficulties in carrying out caregiving role due to health and mental health issues, work responsibilities and lack of insight into older adults’ needs. The refusal to access or accept services by both the older adults and the caregivers was a predominant theme.

Research limitations/implications

The sample size was small, limited to one geographical area, and non-representative of all neglect cases. The data were extracted from written case narratives and not directly from the older adults and their family members. Case records varied in the case detail provided.

Practical implications

To protect vulnerable older adults and improve quality of life, APS involvement in cases of caregiver neglect needs strategies to get people to accept help and access services to address multiple health and psychosocial problems for both older adult victims and their caregivers.

Originality/value

This study provides in-depth information on APS cases involving caregiver neglect that add to understanding of this complex problem and points to areas for further study.
Numerical calculation of crack width in prestressed concrete beams with bond-slip effect
Authors: Liu Jinliang , Jia Yanmin , Zhang Guanhua , Wang Jiawei
Published: December 2018

Purpose

The calculation of the crack width is necessary for the design of prestressed concrete (PC) members. The purpose of this paper is to develop a numerical model based on the bond-slip theory to calculate the crack width in PC beams.

Design/methodology/approach

Stress calculation method for common reinforcement after beam crack has occurred depends on the difference in the bonding performance between prestressed reinforcement and common reinforcement. A numerical calculation model for determining the crack width in PC beams is developed based on the bond-slip theory, and verified using experimental data. The calculation values obtained by the proposed numerical model and code formulas are compared, and the applicability of the numerical model is evaluated.

Findings

The theoretical analysis and experimental results verified that the crack width of PC members calculated based on the bond-slip theory in this study is reasonable. Furthermore, the stress calculation method for the common reinforcement is verified. Compared with the model calculation results obtained in this study, the results obtained from code formulas are more conservative.

Originality/value

The numerical calculation model for crack width proposed in this study can be used by engineers as a reference for calculating the crack width in PC beams to ensure the durability of the PC member.
Life in interstitial space: Biocrusts inhibit exotic but not native plant establishment in semi‐arid grasslands
Authors: Slate Mandy L. , Callaway Ragan M. , Pearson Dean E.
Published: December 2018

Exotic plant species commonly exploit disturbances more successfully than native plants. This outcome is widely attributed to the fact that disturbance reduces biotic resistance from native plant competitors. However, biocrusts, communities of mosses, lichens, and micro‐organisms, are a prominent component of semi‐arid grasslands occurring in the interstitial spaces between vascular plants. Biocrusts may provide an important source of biotic resistance to invaders, different from native plant competition, but poorly understood.

We established a large‐scale field experiment to examine how intact versus disturbed biocrusts influenced the emergence and establishment of four native and four exotic plant species in intermountain bunchgrass systems over 2 years—one wet and one dry. We also conducted a complementary greenhouse experiment to explore how differences in moisture might influence biocrust effects on germination.

In the greenhouse, biocrusts inhibited the germination of both native and exotic plants in the high moisture treatment only. In field experiments, biocrusts inhibited the overall emergence of exotic seedlings in the wetter of the 2 years and inhibited the establishment of exotic seedlings in both years, but they had no overall effect on the emergence or establishment of native seedlings. We found that intact biocrusts in intermountain grasslands can suppress the establishment of some exotic plants, but have much weaker effects on natives. They also suggest that water availability may influence biocrust effects on seed germination.

Synthesis. Our results indicate that intact biocrusts may provide an important source of biotic resistance to exotic plant invasions in intermountain grasslands. Furthermore, precipitation inputs may mediate biocrust effects on plant establishment.
Do drivers of forestry vehicles also drive herb layer changes (1970–2015) in a temperate forest with contrasting habitat and management conditions?
Authors: Closset‐Kopp Déborah , Hattab Tarek , Decocq Guillaume
Published: December 2018

Managing ecosystems effectively for the maintenance of biodiversity and ecosystem functions and services requires to understand how these ecosystems are changing and what are the drivers behind these changes. The resurvey of plant communities sampled some decades ago is increasingly used for this purpose.

We used a life‐history trait‐based approach to test a number of hypothesized drivers behind decadal changes (1970–2015) in the herb layer of an ancient broadleaved lowland forest exhibiting contrasted soil and management types, while minimizing potential relocation and observer errors.

Process‐based hypotheses were tested using paired comparisons (old vs. new records) of community‐weighted means and conditional inference classification trees for a number of traits across soil and management types. We then investigated how these processes impacted species composition and diversity within stands, among stands and at the entire forest scale, using metrics of taxonomic, functional and phylogenetic diversity.

Though they have been continuously managed as regular high forest, managed stands experienced more pronounced vegetation changes than those left unmanaged. This could be directly or indirectly related to modifications in forest harvesting practices since 1970, via light availability at the forest floor, soil disturbance and local N deposition.

While forest specialists increased their abundance over the entire forest, managed stands showed the strongest compositional changes, especially on the soil types that were more susceptible to compaction. Increasingly heavy forestry vehicles that drive more frequently across forest stands likely generate microhabitats suitable for ferns, graminoids and N‐demanding forbs and also act as dispersal agents.

Species richness of vascular plants increased at both stand (α‐diversity) and forest (γ‐diversity) scales, due to the non‐random, directional colonization by the same suite of species, causing compositional, functional and phylogenetic homogenization among habitats (i.e. decreased β‐diversity).

Synthesis. Forest management, via the repeated passing of heavy forestry vehicles, emerged as the key driver of local vegetation changes. By altering canopy structure, it also increased the vulnerability of understories to climate warming and atmospheric deposits. Changes were not only taxonomic, but also functional, suggesting long‐term effects on ecosystem functioning and thus deserve attention from forest managers and conservationists.
Quality‐based ratings in Medicare and trends in kidney transplantation
Authors: Ouayogodé Mariétou H.
Published: December 2018

Objective

To assess the relationship between the 2007 Medicare regulation enforcing quality standards for transplant centers and trends in kidney transplantation.

Data Sources

Transplant centers’ biannual reports and the national registry for kidney transplantation from 2003 to 2010.

Study Design

Non‐compliant (low‐performing) centers were compared with centers in compliance with quality standards according to: number of transplants, waiting‐list registrations, and rates of graft failures, transfers, and deaths. Multivariate regressions were estimated to evaluate the association between the regulation and transplantation outcomes.

Data Extraction Methods

Patient characteristics and outcomes were aggregated to six‐month periods and linked to centers’ reports.

Principal Findings

Relative to average‐performing centers, 12 percent of transplants shifted away from low‐performing centers and high‐performing centers captured 6 percent of this decline. Low‐performing centers experienced a 2‐percentage point per period decline in 1‐year graft failure rates and a 15‐percent decrease in registrations post‐regulation, whereas high‐performing centers incurred a 5‐percent decrease in registrations relative to average‐performing centers.

Conclusions

Government oversight in kidney transplantation was associated with a small downward shift in overall kidney transplants. Reductions in graft failure rates at low‐performing centers may imply an increase in quality or a decline in transplantation of either marginal organs or riskier patients; whereas reductions in registrations may indicate risk aversion toward high‐risk patients. Policy makers should consider making less punitive requirements for programs, which employ new transplantation techniques to expand access.
Total oesophagogastric dissociation for severe gastro‐oesophageal reflux in children with previous upper gastrointestinal surgery: A new route for an old tract
Authors: To Ashley Hoi‐Man , Chung Patrick Ho‐Yu , Tang Michelle Yeuk‐Lam , Wong Kenneth Kak‐Yuen
Published: December 2018

The article reports the application of total oesophagogastric dissociation as an alternative to fundoplication for the treatment of severe gastro‐oesophageal reflux in children.
Changes in the distal esophageal microbiota in Chinese patients with reflux esophagitis
Authors: Yu Ying , Gao Feng , Chen Xue , Zheng Shuai , Zhang Jie
Published: December 2018

Objective

Changes in microbiota composition in the distal esophagus may be associated with the pathogenesis of gastroesophageal reflux disease. We aimed to compare the composition of distal esophageal microbiota between Chinese patients with reflux esophagitis (RE) and healthy volunteers using metagenomic high‐throughput DNA sequencing and bioinformatic analyses.

Methods

Healthy volunteers (controls) and patients with reflux esophagitis (RE) were enrolled. Distal esophageal (2 cm above the gastroesophageal junction) biopsy specimens were obtained under endoscopy. Microbial DNA was extracted from the specimens, followed by 16S rDNA gene amplification and Illumina sequencing. Bioinformatic tools were applied to dissect the community structure.

Results

No dramatic differences in microbiota were found in RE patients compared with the controls. At the phylum level, only Bacteroidetes differed between the groups, being less abundant in the RE group. The overall number and diversity of species tended to be lower in RE patients, but there were no significant differences between the groups. Three genera, Prevotella, Helicobacter, and Moraxella, were obviously depleted in RE patients, as revealed by linear discriminant analysis.

Conclusions

The composition of distal esophageal microbiota in Chinese patients with RE showed moderate changes compared with healthy controls. To what extent these changes are associated with the pathogenesis of RE needs further investigation.
Overcoming T790M mutant small cell lung cancer with the third‐generation EGFR‐TKI osimertinib
Authors: Tang Kejing , Jiang Neng , Kuang Yukun , He Qiong , Li Shuhua , Luo Jiping , Jiang Wenting , Chen Yangshan , Sun Yu , Chen Lili , Chen Yanyang , Zhu Junfeng , Cui Yongmei , Wan Han , Ke Zunfu
Published: December 2018

A large number of EGFR mutant non‐small cell lung cancer patients primordially benefit from first‐line treatment with first‐generation EGFR‐tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib. However, multiple acquired resistance mechanisms have been described that limit the clinical efficacy of first‐generation EGFR‐TKIs. Herein, we report a rare case of lung adenocarcinoma harboring an EGFR exon 19‐deletion mutation before the administration of target therapy. This patient acquired resistance to first‐generation EGFR‐TKIs through small cell lung cancer (SCLC) transformation accompanied by the T790M mutation. Unexpectedly, this SCLC patient maintained a sensitive response to the third‐generation EGFR‐TKI osimertinib. This special case may indicate that osimertinib represents an effective target drug for SCLC patients who harbor an EGFR T790M mutation.
Rollover risk and managerial cost adjustment decisions
Authors: Li Wu‐Lung , Zheng Kenneth
Published: December 2018

Rollover risk is the risk that a firm may not be able to refinance its debt when it becomes due. We investigate whether managers’ resource adjustment decisions are influenced by rollover risk and find that cost stickiness is decreasing in rollover risk. Additionally, the negative relationship between rollover risk and cost stickiness is stronger for firms with higher financial constraints and fewer financing sources. These results suggest that, when faced with elevated rollover risk, managers are willing to forego the benefits from a sticky cost behaviour. Finally, the use of an alternative firm‐specific measure of cost stickiness corroborates our main finding.
Identification of strategic corridors for restoring landscape connectivity: application to the Iberian lynx
Authors: Blazquez‐Cabrera S. , Ciudad C. , Gastón A. , Simón M. Á. , Saura S.
Published: December 2018

The conservation or creation of ecological corridors is a key to support species persistence in fragmented landscapes. However, little guidance exists on where to concentrate the restoration measures to improve corridor quality and functionality. Focusing on the emblematic Iberian lynx Lynx pardinus as the target species, and using a resistance surface parameterized through detailed telemetry data for the species, we applied a modeling approach that identifies corridors whose restoration would be more beneficial for enhancing landscape connectivity. Connectivity benefits were quantified, first, as the increase in the Probability of Connectivity metric (dPC) that results for the entire population network after reducing the effective distance along a particular corridor to its minimum possible value through restoration, and second, as dPC normalized by a proxy of the total restoration effort that would be required in each corridor. Results showed that the corridor restoration benefits were related to their effective distance (accumulated cost of movement along the corridor) and network centrality (potential frequency of use by dispersing individuals) in the current landscapes. Two corridors in which restoration efforts may be more desirable for the Iberian lynx were highlighted: the one linking the Doñana‐Aljarafe population with other populations and reintroduction areas further north, and a west‐east axis connecting the different populations in Sierra Morena. In general, the applied approach is a valuable tool to estimate how landscape connectivity may be affected when changes in the landscape are planned or can be predicted. This approach can be applied to potential corridors linking future reintroduction areas of the Iberian lynx, to case studies focusing on other landscapes and animal species, or to evaluate the impacts of corridor degradation or loss due to land use changes and other pressures.
Effect of instrumentation systems on endotoxin reduction from root canal systems: A systematic review of clinical studies and meta‐analysis
Authors: Neelakantan Prasanna , Ahmed Hany Mohamed Aly , Chang Jeffrey Wen Wei , Nabhan Mohamed Shady , Wei Xi , Cheung Gary Shun Pan , Gomes Brenda P. F. A.
Published: December 2018

This systematic review assessed the effect of different root canal instrumentation systems on endotoxin reduction from the root canal system. The literature search was conducted in two electronic databases (PubMed and Scopus) using specific key words. The search strategy followed the PRISMA guidelines. Qualitative synthesis and quantitative synthesis of the data were performed and data interpretation was done based on the guidelines in the Cochrane Handbook. The risk of bias was assessed using Cochrane criteria. The initial search yielded 600 citations, of which three papers met the criteria for inclusion in this review. Studies showed a significant reduction in endotoxin following rotary and reciprocating instrumentation, with no significant differences between them. The meta‐analysis showed no statistical significant difference between reciprocation and rotary files (P > 0.05). In conclusion, the instrumentation techniques compared in this review decrease endotoxin content from root canals, with no significant difference between them.
Phase I/II study of dasatinib and exploratory genomic analysis in relapsed or refractory non‐Hodgkin lymphoma
Authors: Umakanthan Jayadev M. , Iqbal Javeed , Batlevi Connie L. , Bouska Alyssa , Smith Lynette M. , Shostrom Valerie , Nutsch Heather , William Basem M. , Gregory Bociek R. , Lunning Matthew , Bierman Philip , Younes Anas , Armitage James O. , Vose Julie M.
Published: December 2018

Relapsed or refractory non‐Hodgkin lymphomas (NHLs) often carry poor prognosis and pose management challenges. We evaluated the safety and efficacy of dasatinib, a broad‐spectrum multi‐kinase inhibitor in relapsed/refractory NHL with correlative genomic analysis in a Phase I/II trial. The study included 33 patients with various sub‐types of NHL who had received at least one prior therapy. The most common sub‐types were diffuse large B‐cell lymphoma (24%), follicular lymphoma, grade 1/2 (21%) and peripheral T‐cell lymphoma not otherwise specified (PTCL‐NOS; 21%). Most patients were heavily pre‐treated, including 42% with more than four prior therapies, 67% with rituximab exposure and 24% with prior autologous transplant. In this cohort, dasatinib showed modest activity in evaluable patients with an objective response rate of 29% (7/24) and clinical benefit rate of 71% (17/24). In 32 patients with outcome data, median progression‐free survival was 3 months and median overall survival was 22·4 months. There were two patients with sustained complete responses, both with PTCL‐NOS histology. The side effect profile was consistent with prior studies, with pleural effusion being the most common non‐haematological toxicity. Exploratory genomic analysis showed two cases of PTCL‐NOS with sustained response had a common mutation in LRRK2 and high prevalence of FOXO1 mutation in relapsed/refractory follicular lymphoma.
Revolutionary Movements in Latin America after the Cold War: The Case of the Ejército del Pueblo Paraguayo
Authors: NICKSON ANDREW
Published: December 2018

This article addresses the debate concerning the reasons for the emergence of revolutionary movements in Latin America in the post‐Cold War period. It uses the example of the Ejército del Pueblo Paraguayo (EPP, Paraguayan People's Army) to question the hypothesis by McClintock that, whereas political factors were the principal cause of such movements during the Cold War, economic factors have dominated since then. After reviewing the structural context in which the EPP emerged, as well as its history, strategy and ideology, the article offers a contemporary understanding of the insurgency, examines its relevance to the debate about the prospects for revolution in post‐Cold War Latin America and proposes a reformulation of McClintock's hypothesis.
Understanding the Situation of China's Left‐Behind Children: A Mixed‐Methods Analysis
Authors: Chang Fang , Shi Yaojiang , Shen Amber , Kohrman Asa , Li Katherine , Wan Qinqin , Kenny Kaleigh , Rozelle Scott
Published: December 2018

This research uses a mixed‐methods analysis to examine how being left behind impacts the cognition/education, nutrition, and mental health outcomes of children in rural China. We find that parental migration increases household income and decreases care, and these impacts vary according to location, socioeconomic status, and age. We also find that families generally recognize these impacts. Our findings offer a more general view of the effects of being left behind on childhood outcomes than previous research, which often used small sample sizes from limited geographic areas or age ranges. Although our research focuses on China, the findings are relevant to other developing nations where working‐age individuals often migrate domestically or internationally in search of work, such as Mexico and the Philippines.
Adherence, persistence, glycaemic control and costs among patients with type 2 diabetes initiating dulaglutide compared with liraglutide or exenatide once weekly at 12‐month follow‐up in a real‐world setting in the United States
Authors: Mody Reema , Huang Qing , Yu Maria , Zhao Ruizhi , Patel Hiren , Grabner Michael , Landó Laura Fernández
Published: December 2018

Aims

To evaluate adherence, persistence, glycaemic control and costs at 12‐month follow‐up for patients initiating dulaglutide versus liraglutide or exenatide once weekly.

Materials and methods

The present retrospective observational claims study included patients with type 2 diabetes (T2D) and ≥ 1 pharmacy claim for dulaglutide, liraglutide or exenatide once weekly from the HealthCore Integrated Research Database. Adherence was defined as proportion of days covered ≥80%, and persistence was measured by time to discontinuation of index therapy. Change from baseline in glycated haemoglobin (HbA1c) concentration was assessed in a subset with pre‐ and post‐index HbA1c results. Propensity scores were used to match the cohorts.

Results

The baseline characteristics were balanced for the matched cohorts, dulaglutide versus liraglutide (n = 2471) and dulaglutide versus exenatide once weekly (n = 1891). Among those initiating dulaglutide there was a significantly higher proportion of adherent patients compared with the groups initiating liraglutide (51.2% vs. 38.2%; P < 0.001) and exenatide once weekly (50.7% vs. 31.9%; P < 0.001). At 12 months, 55% of patients in the dulaglutide group versus 43.8% in the liraglutide group (P < 0.001), and 54.9% in the dulaglutide versus 34.4% in the exenatide once‐weekly group (P < 0.001) were persistent. The dulaglutide group had a significantly greater reduction in HbA1c than the liraglutide group (−34.24 vs. −31.94 mmol/mol; P = 0.032), and a greater, but nonsignificant, reduction in HbA1c than the exenatide once‐weekly group (−34.46 vs. −31.94 mmol/mol; P = 0.056). The diabetes‐related total costs were not significantly different between the dulaglutide and the liraglutide group ($16,174 vs. $16,694; P = 0.184), and were significantly higher for dulaglutide than for exenatide once weekly ($15,768 vs. $14,615; P = 0.005).

Conclusions

Adherence and persistence are important considerations in patient‐centric treatment selection for patients with T2D. Higher adherence and persistence for dulaglutide compared with liraglutide or exenatide once weekly are relevant criteria when choosing glucagon‐like peptide‐1 receptor agonist treatment for patients with T2D.
Comparative effect of saxagliptin and glimepiride with a composite endpoint of adequate glycaemic control without hypoglycaemia and without weight gain in patients uncontrolled with metformin therapy: Results from the SPECIFY study, a 48‐week, multi‐centre, randomized, controlled trial
Authors: Gu Tianwei , Ma Jianhua , Zhang Qiu , Zhu Liangying , Zhang Hong , Xu Lan , Cheng Jinluo , Shi Bimin , Li Dongmei , Shao Jiaqing , Sun Zilin , Zhong Shao , Bi Yan , Zhu Dalong
Published: December 2018

Aims

To compare the efficacy and safety of saxagliptin and glimepiride in type 2 diabetes (T2D) patients who are inadequately controlled with metformin monotherapy.

Materials and methods

In this 48‐week, multi‐centre, open‐label, randomized, parallel trial (NCT02280486, clinicaltrials.gov), a total of 388 T2D patients were randomized 1:1 to saxagliptin or glimepiride groups. The primary endpoint was achievement of HbA1c <7.0%, without hypoglycaemia, defined as blood glucose <3.9 mmol/L and weight gain <3.0% after 48 weeks of treatment.

Results

Over 48 weeks, a greater proportion of patients achieved the primary endpoint with saxagliptin compared with glimepiride (43.3% vs 31.3%; odds ratio, 1.38, 95% CI, 1.05‐1.82; P = 0.019), especially among patients with baseline HbA1c <8.0%, duration <5 years or baseline BMI ≥25 kg/m2. Mean reduction in HbA1c was similar in the two treatment groups at Week 48 (−0.94% with saxagliptin vs −0.98% with glimepiride; P = 0.439). Bodyweight decreased with saxagliptin, but increased with glimepiride over the treatment period, and the treatment difference was −1.6 kg (P < 0.001) at Week 48. The proportion of patients experiencing hypoglycaemia was much lower with saxagliptin vs glimepiride (3.1% vs 12.8%; P < 0.001).

Conclusions

This study provides evidence that, compared to glimepiride, saxagliptin more effectively achieves a composite endpoint of adequate glycaemic control without hypoglycaemia and without weight gain in T2D patients who are inadequately controlled with metformin monotherapy, especially in overweight patients with moderate hyperglycaemia and a relatively short duration of diabetes.
Value of tissue‐tracking tricuspid annular plane by speckle‐tracking echocardiography for the assessment of right ventricular systolic dysfunction
Authors: Maniwa Naoki , Hozumi Takeshi , Takemoto Kazushi , Wada Teruaki , Kashiwagi Manabu , Shimamura Kunihiro , Shiono Yasutsugu , Kuroi Akio , Matsuo Yoshiki , Ino Yasushi , Kitabata Hironori , Kubo Takashi , Tanaka Atsushi , Akasaka Takashi
Published: December 2018

Background

Assessment of right ventricular (RV) function remains challenging because of its complex geometry. Application of speckle‐tracking echocardiography (STE) to the tricuspid annulus provides rapid and automated assessment of the midpoint of the tricuspid annular plane displacement (TAD). The aim of this study was to investigate the value of tissue‐tracking TAD for the assessment of RV systolic dysfunction.

Methods

We retrospectively studied 61 patients in whom RV ejection fraction (EF) measured by 3‐dimensional echocardiography was performed. STE‐derived displacement of the midpoint between the septal and lateral tricuspid annulus and its percentage of RV length at end‐diastole (MTAD) were automatically assessed. We performed comparative analyses between the RVEF ≥45% group and the RVEF <45% group in each parameter for the assessment of RV systolic function.

Results

MTAD was successfully assessed in 56 (91.2%). According to receiver operating characteristics analysis, RVEF <45% was best detected by MTAD <14.7% with area under curve (AUC) 0.97, sensitivity 93%, specificity 95%, followed by RV free wall longitudinal strain (AUC 0.86), RV fractional area change (AUC 0.84), tricuspid annular plane systolic excursion (AUC 0.79), and systolic peak velocity of tricuspid annulus (AUC 0.70), although there was no significant difference between MTAD and RV free wall strain (P = 0.14).

Conclusion

The present study showed that MTAD was simple index and useful for the assessment of RV systolic dysfunction.
Interleukin‐32ε induces caspase‐independent apoptosis mediated by N‐Myc interactor in macrophages infected with Mycobacterium tuberculosis
Authors: Li Zhongxia , Wang Yizhi , Liu Xin , Xing Xupeng , Zhang Yong
Published: December 2018

Mycobacterium tuberculosis (Mtb) is the pathogen responsible for tuberculosis, a leading cause of illness and death worldwide. Growing evidence suggests that the proinflammatory cytokine IL‐32 plays a major role in host defences against pathogens such as Mtb. IL‐32 exists in six alternatively spliced isoforms, but antituberculosis effects have been reported only for some of them. In this study, we examined the effect of all six IL‐32 isoforms on Mtb replication in the murine macrophage cell line RAW 264.7. Compared with cells transfected with the other isoforms, IL‐32ε‐transfected cells exhibited the strongest antituberculosis effect and the highest rate of Mtb‐induced apoptosis. Of note, this apoptosis pathway was independent of caspase‐3 activation. Instead, N‐Myc interactor (NMI), an inhibitor of Wnt signalling, was a key player in IL‐32ε‐mediated apoptosis by inhibiting Wnt/β‐catenin signalling and thereby activating c‐Myc‐mediated apoptosis. Moreover, we identified two cis‐acting elements that are binding sites for the transcriptional regulators paired box 6 (PAX6) and transcription factor CP2 (TFCP2) in the promoter of NMI and these elements proved essential for IL‐32ε‐induced upregulation of Nmi expression. Furthermore, IL‐32ε‐mediated activation of the mitogen‐activated protein kinase p38 also contributed to NMI upregulation. In conclusion, our results demonstrate that Mtb infection‐induced IL‐32ε‐mediated apoptosis in macrophages plays a key role in host defences against Mtb.
Some Remarks About the Future of Geographical Analysis: The Journal and the Sub‐Discipline
Authors: Griffith Daniel A.
Published: December 2018

This paper expands upon a GA 50th Anniversary panel presentation made at the 2018 New Orleans American Association of Geographers meeting. It notes that retrospectives for this topic already exist, both in terms of the journal and the sub‐discipline. This paper presents discussion about the following selected prominent transitional themes bridging the past and the future of geographical analysis: space–time data; geographic uncertainty and error; and, dimensional reduction spatial statistical modeling. It also presents discussion about the following three themes that are expected to receive considerable future attention: negative spatial autocorrelation; synergies between spatial statistics and spatial optimization; and, big spatial data. The first two of these topics essentially have been ignored in the literature to date.
Evangelii Gaudium
Authors: Alva Reginald
Published: December 2018

Renewal and reformation are indispensable for the growth of person or an institution. Every Christian as an individual and as a member of the church community is in need of renewal to proclaim boldly the gospel of Christ and bear witness through their lives. Secularization and depravity of moral values poses serious challenges to the faith life of a Christian. Moreover, the rise in fundamentalism, jingoism, consumerism, social and political inequity, and environmental degradation are breeding a state of hopelessness, angst, and ennui in the society. Christians and the church need spiritual renewal and transformation to be the salt of the earth and the light to the nations. The Holy Spirit is the principal agent of all genuine spiritual renewal and evangelization. Pope Francis, in his Apostolic Exhortation Evangelii Gaudium, invites all Christians and the church itself to seek renewal in the Holy Spirit by having a personal encounter with Jesus Christ and grow in his discipleship. In this paper, I shall examine the concrete steps the church and Christians need to take for genuine renewal in the Holy Spirit to do the work of evangelization, in the light of the teachings of Evangelii Gaudium. The main source for this paper is Evangelii Gaudium and other church documents.
Dermoscopic evaluation of melanocytic nevi changes after photo‐epilation techniques: a prospective study
Authors: Guicciardi F. , Ferreli C. , Rongioletti F. , Atzori L.
Published: December 2018

Background

The clinical and dermoscopic changes of melanocytic nevi under the effects of photo‐epilation are poorly known.

Objective

Prospective study on clinical and dermatoscopic effects of photoe‐pilation on melanocytic nevi.

Methods

Eighteen patients exposed to photo‐epilation gave consent to a follow‐up programme from 2008 to 2017 at the Videodermatoscopic Office of the Dermatology Clinic of Cagliari (Italy), with clinical and dermoscopic assessment.

Results

A mean 2‐year follow‐up was recorded for 73 lesions. The most frequent clinical change was nevi colour, clearer than basal pictures, sometimes with increased pigmentation at the periphery, or residual islands of pigmentation, with vanishing borders. Acute burn with crusting was noted in few cases. Only one case showed progressive growth. Corresponding dermoscopic findings were bleaching of nevi, followed by pigment network disruption, appearance of white structureless areas and grey–blue globules. Complete regression occurred in 32.8% of the lesions. The growing nevus was characterized by peripheral globules. Excision for histopathological examination showed a compound nevus with mild atypia.

Conclusions

Although malignant modifications of nevi after photo‐epilation have not been described, the clinical and dermoscopic changes we observed suggest to extend the follow for more than 24 months, as the potential long‐term adverse effects of photo‐epilation on melanocytic nevi are unknown.