bluuebunny/crossref_metadata_2025 huggingface dataset:
Invasive form of ciliated muconodular papillary tumor of the lung: A case report and review of the literature
Authors: Miyai Kosuke , Takeo Hiroaki , Nakayama Takefumi , Obara Kiyohaya , Aida Shinsuke , Sato Kimiya , Matsukuma Susumu
Published: July 2018

We report a case of a 67‐year‐old woman with an invasive ciliated muconodular papillary tumor (CMPT) that developed in her right middle lobe. The current tumor was incidentally detected during a follow‐up imaging examination for a large cell carcinoma that was resected 10 years previously. Partial removal of the middle lobe showed a 2 cm‐sized, solid and myxoid tumor located in the peripheral region. Histologically, this tumor primarily consisted of ciliated columnar cells, mucous cells, and basal cells, all of which had relatively swollen nuclei and were proliferating in a lepidic or papillary/micropapillary manner. These features were consistent with those of previously reported CMPT. In addition, atypical spindle tumor cells with more swollen nuclei, which were partly continuous to less atypical basal tumor cells, were focally found and invaded fibrous stroma in a reticular fashion. Immunohistochemically, both basal cells and atypical spindle tumor cells were positive for pancytokeratin, cytokeratin 5/6, and p40. Increased p53 positivity was found in these invading spindle cells compared with basal tumor cells. Neither BRAF V600E nor V600K mutation was detected. We concluded that this tumor was an extremely rare invasive case of CMPT, possibly representing malignant transformation of basal tumor cell components of CMPT.
Investment in Environmental Process Improvement
Authors: Xiao Wenli , Gaimon Cheryl , Subramanian Ravi , Biehl Markus
Published: July 2018

We analyze a firm's investment in environmental process improvement (EPI) to reduce the environmental impact (EI) of its manufacturing processes in relation to various internal firm characteristics and in response to different external regulatory drivers. We provide a deep understanding of how these internal and external forces cause the firm to pursue EPI earlier or later in the planning horizon and at an increasing or a decreasing rate over time. In particular, we show how a regulator can drive different patterns of EPI over time through subsidies for EPI or penalties for EI. We also explore the impacts of two key operational capabilities of the firm—the production‐cost efficiency of EPI and the effectiveness of EPI in reducing EI—on the rate of EPI over time. We demonstrate that improvements in these operational capabilities contrastingly alter the timing of investments in EPI. Lastly, we demonstrate that a firm capable of leveraging EPI to enhance product functionality or command a reputational premium in the marketplace pursues a remarkably different pattern of EPI over time compared to a cost‐focused firm that only responds to regulatory forces.
A Fixed Rate Production Problem with Poisson Demand and Lost Sales Penalties
Authors: Faaland Bruce , McKay Mark , Schmitt Thomas
Published: July 2018

We solve a variation of a classic make‐to‐stock inventory problem introduced by Gavish and Graves. A machine is dedicated to a single product whose demand follows a stationary Poisson distribution. When the machine is on, items are produced one at a time at a fixed rate and placed into finished‐goods inventory until they are sold. In addition, there is an expense for setting up the machine to begin a production run. Our departure from Gavish and Graves involves the handling of unsatisfied demand. Gavish and Graves assumed it is backordered, while we assume it is lost, with a unit penalty for each lost sale. We obtain an optimal solution, which involves a produce‐up‐to policy, and prove that the expected time‐average cost function, which we derive explicitly, is quasi‐convex separately in both the produce‐up‐to inventory level Q and the trigger level R that signals a setup for production. Our search over the ( Q,  R) array begins by finding Q 0, the minimizing value of Q for R = 0. Total computation to solve the overall problem, measured in arithmetic operations, is quadratic in Q 0. At most 3 Q 0 cost function evaluations are required. In addition, we derive closed‐form expressions for the objective function of two related problems: one involving make‐to‐order production and another for control of an N‐policy M/ D/1 finite queue. Finally, we explore the possibility of solving the lost sales problem by applying the Gavish and Graves algorithm for the backorder problem.
Temporal and spatial progress of the diseases caused by the crinivirus tomato chlorosis virus and the begomovirus tomato severe rugose virus in tomatoes in Brazil
Authors: Macedo M. A. , Inoue‐Nagata A. K. , Silva T. N. Z. , Freitas D. M. S. , Rezende J. A. M. , Barbosa J. C. , Michereff‐Filho M. , Nascimento A. R. , Lourenção A. L. , Bergamin Filho A.
Published: July 2018

Efficient management of whitefly‐borne diseases remains a challenge due to the lack of a comprehensive understanding of their epidemiology, particularly of the diseases tomato golden mosaic and tomato yellowing. Here, by monitoring 16 plots in four commercial fields, the temporal and spatial distribution of these two diseases were studied in tomato fields in Brazil. In the experimental plots these diseases were caused by tomato severe rugose virus (ToSRV) and tomato chlorosis virus (ToCV), respectively. The incidence of each virus was similar in the plots within a field but varied greatly among fields. Plants with symptoms for both diseases were randomly distributed in three of four spatial analyses. The curves representing the progress of both diseases were similar and contained small fluctuations, indicating that the spread of both viruses was similar under field conditions. In transmission experiments of ToSRV and ToCV by Bemisia tabaci MEAM1 (former biotype B), these viruses had a similar transmission rate in single or mixed infections. It was then shown that primary and secondary spread of ToCV were not efficiently controlled by insecticide applications. Finally, in a typical monomolecular model of disease progress, simulation of the primary dissemination of ToSRV and ToCV showed that infected plants were predominantly randomly distributed. It is concluded that, although the manner of vector transmission differs between ToSRV (persistent) and ToCV (semipersistent), the main dispersal mechanisms are most probably similar for these two diseases: primary spread is the predominant mechanism, and epidemics of these diseases have been caused by several influxes of viruliferous whiteflies.
Administration of progesterone BioRelease LA inhibits follicular growth in llamas (Lama glama) regardless of follicle diameter at the start of treatment
Authors: Veiga Maria Fernanda , Trasorras Virginia Luz , Bianchi Carolina Paula , Aba Marcelo , Moncalvo Evangelina , Chaves Maria Graciela , Miragaya Marcelo Horacio
Published: July 2018

Contents

The aims of the study were twofold: first, the comparison of the pharmacokinetics parameters of two doses of Progesterone BioRelease® LA, (BioRelease Technologies, Lexington, KY, USA) one of 300 mg and other of 150 mg and their effects on ovarian dynamics in llamas. Based on the results from the first study, the aim of the second study was to evaluate the effect of the doses of 150 mg of progesterone on follicular activity considering the stage of the largest follicle at the beginning of treatment. The results in Study 1 showed that both doses of the formulation induced plasma progesterone concentrations higher than 1 ng/ml during the first 6 days of treatment in all females, progesterone concentrations steadily decline until Day 5 following by a slowly decrease. The total amount of progesterone released during treatment was higher in Group 300 than in Group 150 (p = 0.045). Mean maximum concentrations were 14.9 ± 2.24 and 14.3 ± 2.16 ng/ml for Group A versus Group B (p = 0.58), and they were registered on Day 1.5 ± 0.22 and 1.7 ± 0.34 days, respectively (p = 0.10). None of the animals of Group A showed progesterone concentration below 1 ng/ml during all studied period. The treatment applied in Study 2 was efficient in inhibiting the ovarian follicular dynamics and to start a superestimulatory treatment. The use of progesterone Biorelease® LA of 150 mg in comparison with the dose of 300 mg could be more effective in the use of synchronization protocols in llamas for AI or prior to the application of an ovarian superstimulatory treatment.
TaWRKY51 promotes lateral root formation through negative regulation of ethylene biosynthesis in wheat (Triticum aestivum L.)
Authors: Hu Zhaorong , Wang Rui , Zheng Mei , Liu Xingbei , Meng Fei , Wu Hualing , Yao Yingyin , Xin Mingming , Peng Huiru , Ni Zhongfu , Sun Qixin
Published: July 2018

Common wheat (Triticum aestivum L.) is an important staple food crop worldwide. Lateral roots (LRs), as the major component of root architecture, affect water and nutrient uptake in wheat. The phytohormone ethylene is known to affect LR formation; however, the factor(s) modulating ethylene during this process have not yet been elucidated in wheat. Here we identified wheat TaWRKY51 as a key factor that functions in LR formation by modulating ethylene biosynthesis. Wheat TaWRKY51RNA interference lines (TaWRKY51‐RNAi) and the homozygous mutants tawrky51‐2a and tawrky51‐2b all produced fewer LRs than the wild type and negative transgenic plants, whereas the TaWRKY51 overexpression lines (TaWRKY51‐OE) had the opposite phenotype. Transcription analysis revealed that 1‐aminocyclopropane‐1‐carboxylic acid synthase (ACS) genes (TaACS2, TaACS7 and TaACS8) involved in ethylene biosynthesis were downregulated in TaWRKY51‐OE lines but upregulated in TaWRKY51‐RNAi lines. The rate of ethylene production also decreased in TaWRKY51‐OE lines but increased in TaWRKY51‐RNAi lines compared with their respective negative transgenic controls. Electrophoretic mobility shift and transient expression assays revealed that TaWRKY51 inhibits the expression of ACS genes by binding to the W‐box cis‐element present in their promoter region. Moreover, overexpression of ACS2 or exogenous application of 1‐aminocyclopropane‐1‐carboxylic acid reversed the phenotype of enhanced LR number in TaWRKY51‐OE Arabidopsis lines, and overexpression of TaWRKY51 in the ethylene‐overproducing mutant eto1‐1 rescued its LR defect phenotype. In addition, genetic evidence demonstrates that TaWRKY51‐regulated LR formation is also dependent on ethylene and auxin signaling pathways. Our findings reveal a molecular genetic mechanism by which a WRKY gene coordinates ethylene production and LR formation in wheat.
ACOUSTICAL STANDARDS NEWS
Authors: Struck Christopher J.
Published: July 2018

American National Standards (ANSI Standards) developed by Accredited Standards Committees S1, S2, S3, S3/SC 1, and S12 in the areas of acoustics, mechanical vibration and shock, bioacoustics, animal bioacoustics, and noise, respectively, are published by the Acoustical Society of America (ASA). In addition to these standards, ASA publishes a catalog of Acoustical American National Standards. To receive a copy of the latest Standards catalog, please contact asastds@acousticalsociety.org.

Comments are welcomed on all material in Acoustical Standards News.

This Acoustical Standards News section in JASA, as well as the national catalog of Acoustical Standards and other information on the Standards Program of the Acoustical Society of America, are available via the ASA home page: http://acousticalsociety.org.
Analytic relaxation modulus expression for a viscoelastic liquid with complex viscosity following a Havriliak–Negami model
Authors: Janzen Jay , Gautesen Arthur K.
Published: July 2018

From results published by Rudolf Hilfer for the similar problem involving dielectric permittivities, we derive an explicit analytic expression for the step-strain relaxation modulus implied by the Havriliak–Negami model for complex viscosities.
Deep reinforcement learning for de novo drug design
Authors: Popova Mariya , Isayev Olexandr , Tropsha Alexander
Published: July 2018

We introduce an artificial intelligence approach to de novo design of molecules with desired physical or biological properties.
Temperature-dependent adaptation allows fish to meet their food across their species’ range
Authors: Neuheimer Anna B. , MacKenzie Brian R. , Payne Mark R.
Published: July 2018

Adult fish ensure that their young do not starve by timing reproduction so that food is available when their young need it.
Late Quaternary horses in Eurasia in the face of climate and vegetation change
Authors: Leonardi Michela , Boschin Francesco , Giampoudakis Konstantinos , Beyer Robert M. , Krapp Mario , Bendrey Robin , Sommer Robert , Boscato Paolo , Manica Andrea , Nogues-Bravo David , Orlando Ludovic
Published: July 2018

Ecological modeling based on radiocarbon dates sheds light on key questions on the biogeography of horses.
Cross-species systems analysis identifies gene networks differentially altered by sleep loss and depression
Authors: Scarpa Joseph R. , Jiang Peng , Gao Vance D. , Fitzpatrick Karrie , Millstein Joshua , Olker Christopher , Gotter Anthony , Winrow Christopher J. , Renger John J. , Kasarskis Andrew , Turek Fred W. , Vitaterna Martha H.
Published: July 2018

We identified gene networks linking sleep and affect, highlighting those oppositely perturbed by sleep loss and depression.
Multiple Optimal Phenotypes Overcome Redox and Glycolytic Intermediate Metabolite Imbalances in Escherichia coli pgi Knockout Evolutions
Authors: McCloskey Douglas , Xu Sibei , Sandberg Troy E. , Brunk Elizabeth , Hefner Ying , Szubin Richard , Feist Adam M. , Palsson Bernhard O.
Published: July 2018

A mechanistic understanding of how microbes are able to overcome the loss of a gene through regulatory and metabolic changes is not well understood. Eight independent adaptive laboratory evolution (ALE) experiments with
pgi
knockout strains resulted in eight phenotypically distinct endpoints that were able to overcome the gene loss. Utilizing multi-omics analysis, the coordinated mechanisms from genome to metabolome that lead to multiple optimal phenotypes after the loss of a major gene product were revealed.
Complete Genome Sequences of Erwinia amylovora Phages vB_EamP-S2 and vB_EamM-Bue1
Authors: Knecht Leandra E. , Born Yannick , Pothier Joël F. , Loessner Martin J. , Fieseler Lars
Published: July 2018

Phages vB_EamP-S2 (S2) and vB_EamM-Bue1 (Bue1) infect the plant pathogen
Erwinia amylovora
. S2 has a genome size of 45,495 bp and belongs to the genus
SP6virus
.
Characteristics of healthcare organisations struggling to improve quality: results from a systematic review of qualitative studies
Authors: Vaughn Valerie M , Saint Sanjay , Krein Sarah L , Forman Jane H , Meddings Jennifer , Ameling Jessica , Winter Suzanne , Townsend Whitney , Chopra Vineet
Published: July 2018

Background

Identifying characteristics associated with struggling healthcare organisations may help inform improvement. Thus, we systematically reviewed the literature to: (1) Identify organisational factors associated with struggling healthcare organisations and (2) Summarise these factors into actionable domains.

Methods

Systematic review of qualitative studies that evaluated organisational characteristics of healthcare organisations that were struggling as defined by below-average patient outcomes (eg, mortality) or quality of care metrics (eg, Patient Safety Indicators). Searches were conducted in MEDLINE (via Ovid), EMBASE, Cochrane Library, CINAHL, and Web of Science from database inception through February 8 2018. Qualitative data were analysed using framework-based synthesis and summarised into key domains. Study quality was evaluated using the Critical Appraisal Skills Program tool.

Results

Thirty studies (33 articles) from multiple countries and settings (eg, acute care, outpatient) with a diverse range of interviewees (eg, nurses, leadership, staff) were included in the final analysis. Five domains characterised struggling healthcare organisations: poor organisational culture (limited ownership, not collaborative, hierarchical, with disconnected leadership), inadequate infrastructure (limited quality improvement, staffing, information technology or resources), lack of a cohesive mission (mission conflicts with other missions, is externally motivated, poorly defined or promotes mediocrity), system shocks (ie, events such as leadership turnover, new electronic health record system or organisational scandals that detract from daily operations), and dysfunctional external relations with other hospitals, stakeholders, or governing bodies.

Conclusions

Struggling healthcare organisations share characteristics that may affect their ability to provide optimal care. Understanding and identifying these characteristics may provide a first step to helping low performers address organisational challenges to improvement.

Systematic review registration

PROSPERO: CRD42017067367.
Transcatheter aortic valve implantation in decompensated aortic stenosis within the same hospital admission: early clinical experience
Authors: Abdelaziz Mahmoud , Khogali Saib , Cotton James M , Meralgia Antonella , Matuszewski Maciej , Luckraz Heyman
Published: July 2018

Objective

Severe decompensated aortic valve stenosis is associated with noticeable reduction in survival. Until recently the options for such patients were either high-risk surgery or percutaneous balloon valvuloplasty and medical therapy which does not add any survival benefits and associated with high rate of complications. We present our experience in the use of transcatheter aortic valve implantation (TAVI) in patients with decompensated severe aortic stenosis requiring urgent intervention in the same hospital admission.

Methods

In this observational study, all patients who were admitted with decompensated severe aortic stenosis were enrolled. Elective patients were excluded from the study. Perioperative records were analysed and clinical, echocardiographic and survival data were presented.

Results

76 patients with a mean age of 81±6 years were enrolled. All patients presented with New York Heart Association (NYHA) IV status. Femoral approach was performed in 86.8%. Median postoperative hospital stay was 6 days and intensive care unit admission rate was 15%. At follow-up, 61.8% of patients were in NYHA status I/II. Moderate or more paravalvular leak occurred in 5.2% of patients. Permanent pacemaker was required in 14.4% of patients. The incidence of in-hospital death was 2.6%. Kaplan-Meier analysis indicated a survival rate of 81% at 1 year.

Conclusions

Urgent in-hospital TAVI is feasible as the first-line treatment in decompensated severe aortic stenosis. In our cohort, it showed to be safe and achieved satisfactory survival rates and symptom control.
Acute neurology simulation training
Authors: Galtrey Clare M , Styles Jessica , Gosling Nicholas , Nirmalananthan Niran , Pereira Anthony C
Published: July 2018

Acute neurology is the neurological care that a patient receives in an emergency or urgent care situation. This can be adapted successfully to training in a simulation where learners are immersed in realistic scenarios in a safe, controlled and reproducible environment. In addition to teaching important technical skills that improve knowledge of the diagnosis and management of acute neurology, the simulation laboratory provides a valuable setting to improve human factors and non-technical skills, such as teamwork and leadership. Simulations are best conducted in a multiprofessional group with scenarios that allow different team members (nurses, physician associates, core medical and specialist trainees) to participate in their actual role. These training sessions require clear learning objectives, and involve designing the scenarios, running the session and ending with a structured debriefing to consolidate learning. The ultimate aim is to improve the team’s effectiveness to deliver safe acute neurological care in the emergency department and on the wards.
Prevalence and clinical correlates of rheumatoid factor and anticitrullinated protein antibodies in patients with idiopathic inflammatory myopathy
Authors: Ide Veerle , Bossuyt Xavier , Blockmans Daniël , De Langhe Ellen
Published: July 2018

Objective

As rheumatoid factor (RF) and anticitrullinated protein antibodies (ACPAs) are not routinely tested in idiopathic inflammatory myositis (IIM), little is known about their prevalence and clinical implications in this patient group. In antisynthetase syndrome (ASS), presence of ACPA is reportedly associated with more severe and erosive arthritis. We aim to retrospectively determine the prevalence of RF and ACPA in a cross-sectional cohort of 121 patients diagnosed with IIM and to assess clinical associations.

Methods

Serum samples from 121 patients diagnosed with polymyositis (n=30), dermatomyositis (n=41), ASS (n=37), inclusion body myositis (n=1), necrotising autoimmune myopathy (n=5) or overlap myositis (n=7) were analysed. RF was evaluated by nephelometry (Immage 800, Beckman–Coulter); anti-CCP antibodies were identified using fluoro enzyme immunoassays (Immuno-Cap 250, Thermo Fisher). Values above 40 IU/mL and 7 U/mL were considered positive for RF and ACPA, respectively.

Results

The prevalence of RF and ACPA was 9.09% and 4.96%, respectively. No significant differences were observed between RF/ACPA positive versus negative patients. There was a numerical trend for RF-positive IIM patients to be older and have lower forced expiratory volume in 1 s levels.

Conclusions

RF and ACPA are prevalent in IIM, although we detected a lower prevalence than reported in previous studies. Presence of these antibodies in patients with IIM patients is not clinically relevant in our cohort.
Floods and Water Service Disruptions: Eliciting Willingness-to-Pay for Public Utility Pricing and Infrastructure Decisions
Authors: Price James I. , Lloyd-Smith Patrick R. , Dupont Diane P. , Adamowicz Wiktor L.
Published: July 2018

Devastating floods and ongoing droughts throughout the world highlight the infrastructure and management challenges facing water and wastewater utilities. While increasing variability in climate has been identified as the immediate culprit, the severity of events has been exacerbated by years of underinvestment in infrastructure improvements due to inadequate pricing of services. The American Water Works Association (2015) identifies a crucial step for decision-makers: identify clearly communities’ priorities with respect to water and wastewater management, both of which provide public or community-level goods and services. Using data from two separate choice experiments, collected in the same survey of Canadian households, the current paper estimates household willingness-to-pay (WTP) to reduce the likelihood of flood events and water service disruptions. Results from both choice experiments show a strong preference for policy scenarios that reduce these risks, although there is a substantial amount of heterogeneity. People living in the Prairie region, rural residents, and people living in areas with higher home values have a higher WTP. Although the results lend support to public infrastructure programs for addressing flood and water disruption risks, the degree to which these are preferred to private action is not clear.
Social-Ecological Systems Insights for Navigating the Dynamics of the Anthropocene
Authors: Reyers Belinda , Folke Carl , Moore Michele-Lee , Biggs Reinette , Galaz Victor
Published: July 2018

Social-ecological systems (SES) research offers new theory and evidence to transform sustainable development to better contend with the challenges of the Anthropocene. Four insights from contemporary SES literature on ( a) intertwined SES, ( b) cross-scale dynamics, ( c) systemic tipping points, and ( d) transformational change are explored. Based on these insights, shifts in sustainable development practice are suggested to recognize and govern the complex and codeveloping social and ecological aspects of development challenges. The potential susceptibility of SES to nonlinear systemic reconfigurations is highlighted, as well as the opportunities, agency, and capacities required to foster reconfigurative transformations for sustainable development. SES research proposes the need for diverse values and beliefs that are more in tune with the deep, dynamic connections between social and ecological systems to transform development practice and to support capacities to deal with shocks and surprises. From these perspectives, SES research offers new outlooks, practices, and novel opportunity spaces from which to address the challenges of the Anthropocene.
Compound-Specific Isotope Geochemistry in the Ocean
Authors: Close Hilary G.
Published: July 2018

Compound-specific isotope analysis encompasses a variety of methods for examining the naturally occurring isotope ratios of individual organic molecules. In marine environments, these methods have revealed heterogeneous sources and alteration processes that underlie the more commonly measured isotope ratios of bulk materials, as well as revealing signatures of marine metabolisms that may otherwise be impossible to isolate. Recently, compound-specific isotopic techniques have improved the reconstruction of metazoan diets and revealed a new potential of metazoan biomass as an archive of paleoecological information. Despite six decades of practice and a diversity of applications, the use of compound-specific isotopic techniques remains uncommon in marine studies. This review examines broad theoretical motivations behind compound-specific isotopic approaches, some applications to studies of marine carbon cycling and trophic relationships, and methodological limitations. In coming years, improvements in analytical efficiency and molecular or intramolecular specificity may transform compound-specific isotope analysis into a tool that can be applied more broadly and help to build global oceanographic data sets.
Therapeutic Approaches to the Treatment of Tinnitus
Authors: Langguth Berthold , Elgoyhen Ana Belen , Cederroth Christopher R.
Published: July 2018

Tinnitus is a highly prevalent condition that is associated with hearing loss in most cases. In the absence of external stimuli, phantom perceptions of sounds emerge from alterations in neuronal activity within central auditory and nonauditory structures. Pioneering studies using lidocaine revealed that tinnitus is susceptible to pharmacological interventions. However, lidocaine is not effective in all patients, and no other drug has been identified with clear efficacy for the long-term treatment of tinnitus. In this review, we present recent advances in tinnitus research, including more detailed knowledge of its pathophysiology and involved neurotransmitter systems. Moreover, we summarize results from animal and clinical treatment studies as well as from studies that identified tinnitus as a side effect of pharmacological treatments. Finally, we focus on challenges in the development of pharmacological compounds for the treatment of tinnitus, namely the limitations of available animal models and of standardized clinical research methodologies.
The Immunologic Role of Gut Microbiota in Patients with Chronic HBV Infection
Authors: Yang Ruilin , Xu Yao , Dai Zhifeng , Lin Xuhong , Wang Huichao
Published: July 2018

Hepatitis B can cause acute or chronic liver damage due to hepatitis B virus (HBV) infection. Cirrhosis or hepatocellular carcinoma (HCC) caused by chronic HBV infection often leads to increased mortality. However, the gut and liver have the same embryonic origin; therefore, a close relationship must exist in terms of anatomy and function, and the gut microbiota plays an important role in host metabolic and immune modulation. It is believed that structural changes in the gut microbiota, bacterial translocation, and the resulting immune injury may affect the occurrence and development of liver inflammation caused by chronic HBV infection based on the in-depth cognition of the concept of the “gut-liver axis” and the progress in intestinal microecology. This review aims to summarize and discuss the immunologic role of the gut microbiota in chronic HBV infection.
One-Piece Implants with Smooth Concave Neck to Enhance Soft Tissue Development and Preserve Marginal Bone Levels: A Retrospective Study with 1- to 6-Year Follow-Up
Authors: Axiotis Jean-Pierre , Nuzzolo Paolo , Barausse Carlo , Gasparro Roberta , Bucci Paolo , Pistilli Roberto , Sammartino Gilberto , Felice Pietro
Published: July 2018

Novel one-piece implants with concave smooth neck have been introduced to promote the formation of a thick mucosal layer and preserve marginal bone. A retrospective study on 70 patients with 1- to 6-year follow-up was carried out. Cumulative survival rates were assessed. Variations of marginal bone level were measured on periapical radiographs as distance of the implant-abutment junction from the bone crest. Influence of different variables on treatment outcome was evaluated. Cumulative success rate after 6 years was 99.4 % at implant level and 98.6 % at patient level. Marginal bone level changed in a significant way over time. After 4 months, an increase of radiographic bone level of 0.173 ± 1.088 mm at implant level and 0.18 ± 1.019 mm at patient level was recorded. Mean marginal bone loss after 5 years was 0.573 ± 0.966 mm at implant level and 0.783 ± 1.213 mm at patient level. Age, sex, smoking habits, implant sites, implant lengths and diameters, prosthetic retentions, and timing of loading did not influence marginal bone remodeling in a statistically significant way. At 4-year follow-up partial restorations lost a mean of 0.96 mm of more marginal bone compared with single restorations. This difference was statistically significant.
Human Endometrial Regenerative Cells Attenuate Bleomycin-Induced Pulmonary Fibrosis in Mice
Authors: Zhao Yiming , Lan Xu , Wang Yong , Xu Xiaoxi , Lu Shanzheng , Li Xiang , Zhang Baoren , Shi Ganggang , Gu Xiangying , Du Caigan , Wang Hao
Published: July 2018

Endometrial regenerative cells (ERCs) have been recently evaluated as an attractive novel type of stem cell therapy. Previous studies have demonstrated that most ERCs accumulated in the lung after injection and are successfully used to treat diseases such as cardiac fibrosis. However, relevant studies of ERCs in idiopathic pulmonary fibrosis (IPF) have not been reported. The present study was designed to examine the effects of ERCs on bleomycin-induced pulmonary fibrosis. All IPF models in C57BL/6 mice were induced by administrating 5 mg/kg bleomycin in PBS intratracheally. ERCs were isolated from healthy female menstrual blood and were injected (1 million/mouse, i.v.) 24 hours after induction. Wet/dry weight ratio assay, hydroxyproline content, pathological and immunohistological changes, MDA content, T-SOD activity, cytokine profiles, and RT-qPCR analysis were assessed 2 weeks after disease induction. The results showed that ERC treatment significantly decreased the wet/dry ratio and reduced collagen deposition. Histological analyses, Masson staining, and hydroxyproline content analysis indicated that ERCs could reduce collagen fiber production. Immunohistochemical staining revealed lower expression of TGF-βafter ERC treatment. Furthermore, mice treated with ERCs had lower levels of IL-1βand TNF-α, but a higher level of IL-10 in both the lung and serum. Gene expression analysis demonstrated that ERCs potently suppressed the proapoptotic gene Bax, while increasing the antiapoptotic gene Bcl-2 and antifibrosis genes HGF and MMP-9. Our results indicate that human ERCs protected the lung from pulmonary fibrosis in mice through immunosuppressive and antifibrosis effects. Moreover, these findings formed a foundation for the further use of ERCs in clinical treatment.
Mutational Profile of Metastatic Breast Cancer Tissue in Patients Treated with Exemestane Plus Everolimus
Authors: Omarini Claudia , Filieri Maria Elisabetta , Bettelli Stefania , Manfredini Samantha , Kaleci Shaniko , Caprera Cecilia , Nasso Cecilia , Barbolini Monica , Guaitoli Giorgia , Moscetti Luca , Maiorana Antonino , Conte Pier Franco , Cascinu Stefano , Piacentini Federico
Published: July 2018

Background.Everolimus has been shown to overcome endocrine resistance in hormone receptor positive advanced breast cancer patients. Predictive biomarkers of everolimus efficacy have been investigated in primary breast cancer tissue without finding univocal results. The goal of this study was to investigate the mutational burden in the metastatic site of endocrine-resistant tumors treated with everolimus plus exemestane.Patients and Methods.Mass Array Sequenom platform was used to analyse genetic status of 18 cancer-related genes in 25 archival tumor specimens from metastatic lesions and available primary matched breast cancer tissue of patients treated with everolimus and exemestane for advanced disease. An exploratory analysis of everolimus efficacy in terms of progression free survival benefit and single gene mutation was carried out.Results. The overall detection rate of mutation was 30% and 38% from metastatic and primary breast cancer samples, respectively.AKT1E17Kwas the most frequent mutated gene. No primary breast cancer and matched relapse maintained the same mutation profile. Considering molecular pathways, the most of the genes belong to PI3K pathway (AKT1E17K,PI3KCAE545K, andKITG565R,S709F). In patients with detected mutations in breast and/or recurrence tissue the median PFS was 5,6 months while in the subgroup of patients with no mutations the median PFS was 7,5 months.Conclusions. The mutational status of breast cancer recurrence allows the identification of some genes potentially correlating tumor response/resistance to everolimus. The most frequently mutated genes were involved in the PI3K/AKT/mTOR pathway highlighting that the deregulation of this pathway in the relapse plays a crucial role in the mechanisms of everolimus resistance/sensitivity. Owing to the small sample size and the retrospective nature of the study, these correlations need to be validated in a large prospective study.
Intraspinal Grafting of Serotonergic Neurons Modifies Expression of Genes Important for Functional Recovery in Paraplegic Rats
Authors: Miazga Krzysztof , Fabczak Hanna , Joachimiak Ewa , Zawadzka Małgorzata , Krzemień-Ojak Łucja , Bekisz Marek , Bejrowska Anna , Jordan Larry M. , Sławińska Urszula
Published: July 2018

Serotonin (5-hydroxytryptamine; 5-HT) plays an important role in control of locomotion, partly through direct effects on motoneurons. Spinal cord complete transection (SCI) results in changes in 5-HT receptors on motoneurons that influence functional recovery. Activation of 5-HT2Aand 5-HT7receptors improves locomotor hindlimb movements in paraplegic rats. Here, we analyzed the mRNA of 5-HT2Aand 5-HT7receptors (encoded byHtr2aandHtr7genes, resp.) in motoneurons innervating tibialis anterior (TA) and gastrocnemius lateralis (GM) hindlimb muscles and the tail extensor caudae medialis (ECM) muscle in intact as well as spinal rats. Moreover, the effect of intraspinal grafting of serotonergic neurons onHtr2aandHtr7gene expression was examined to test the possibility that the graft origin 5-HT innervation in the spinal cord of paraplegic rats could reverse changes in gene expression induced by SCI. Our results indicate that SCI at the thoracic level leads to changes inHtr2aandHtr7gene expression, whereas transplantation of embryonic serotonergic neurons modifies these changes in motoneurons innervating hindlimb muscles but not those innervating tail muscles. This suggests that the upregulation of genes critical for locomotor recovery, resulting in limb motoneuron plasticity, might account for the improved locomotion in grafted animals.
A Simple Model for Vertical Dynamic Interactions among a Group of Strip Footings Rested on Homogeneous Half‐Space
Authors: Wang Jue , Zhou Ding
Published: July 2018

A simple model for vertical dynamic interactions among a group of strip footings rested on half‐space is presented in this paper. An analytical method is presented to obtain the contact pressures and the impedance matrix for a group of surface strip footings. In order to conveniently solve the unknown contact pressures between the soil and footings, the soil‐footing interfaces are discretized into a series of strip elements. The Green function for each element under uniform harmonic force is derived and calculated by the piecewise integration and Cauchy principal value integral. The influences of footing and soil parameters on contact pressures and vertical dynamic impedances of footing groups are discussed in detail. The SSSI effect between adjacent footings increases with the decrease of the distance ratio S/L. For three footings in a group, the middle footing experiences greater cross‐interactional effect than the side ones. The present method has high accuracy, which is not only simple but also suitable for the high‐frequency analysis.
Acquired JHDM1D–BRAF Fusion Confers Resistance to FGFR Inhibition in FGFR2-Amplified Gastric Cancer
Authors: Sase Hitoshi , Nakanishi Yoshito , Aida Satoshi , Horiguchi-Takei Kana , Akiyama Nukinori , Fujii Toshihiko , Sakata Kiyoaki , Mio Toshiyuki , Aoki Masahiro , Ishii Nobuya
Published: July 2018

FGFR2 gene is frequently amplified in gastric cancer. Recently, targeting FGFR2 has drawn attention as a form of gastric cancer therapy, and FGFR-selective inhibitors have shown promising efficacy in clinical studies. Because overcoming acquired resistance is a common problem with molecular targeting drugs, we investigated a resistant mechanism of FGFR inhibitors using the gastric cancer cell line SNU-16, which harbors FGFR2 amplification. We established single-cell clones of FGFR inhibitor–resistant SNU-16 (AZD-R) by continuous exposure to AZD4547, a selective FGFR inhibitor. To screen the genetic alterations acquired in AZD-R, we ran a comparative genomic hybridization assay and found an amplification of Chr7q34 region. The chromosomal breakpoints were located between the 12th and the 13th exon of jumonji C domain containing histone demethylase 1 homolog D (JHDM1D) and between the 3rd and the 4th exon of BRAF. We sequenced cDNA of the AZD-R clones and found fusion kinase JHDM1D-BRAF, which has previously been identified in primary ovarian cancer. Because JHDM1D–BRAF fusion lacks a RAS-binding domain, the dimerization of JHDM1D–BRAF was enhanced. A cell growth inhibition assay using MEK inhibitors and RAF-dimer inhibitors indicated the dependence of AZD-R clones for growth on the MAPK pathway. Our data provide a clinical rationale for using a MEK or RAF dimer inhibitor to treat FGFR2-amplified gastric cancer patients who have acquired resistance through the JHDN1D–BRAF fusion. Mol Cancer Ther; 17(10); 2217–25. ©2018 AACR.
Gastroesophageal Reflux Disease-Related Disorders of Systemic Sclerosis Based on the Analysis of 66 Patients
Authors: Matsuda Rie , Yamamichi Nobutake , Shimamoto Takeshi , Sumida Hayakazu , Takahashi Yu , Minatsuki Chihiro , Kodashima Shinya , Ono Satoshi , Niimi Keiko , Tsuji Yosuke , Sakaguchi Yoshiki , Saito Itaru , Kataoka Yosuke , Asada-Hirayama Itsuko , Kakimoto Hikaru , Yakabi Seiichi , Takeuchi Chihiro , Matsumoto Yuta , Tamaki Zenshiro , Fujishiro Mitsuhiro , Asano Yoshihide , Sato Shinichi , Koike Kazuhiko
Published: July 2018

Background/Aims: Gastroesophageal reflux disease (GERD)-related disorders of systemic sclerosis (SSc) patients have not been adequately investigated. Methods: Sixty-six SSc patients (5 males and 61 females; 56.6 ± 14.6 years old) who underwent esophagogastroduodenoscopy were analyzed on the basis of 16 background factors. They were additionally compared with 116 matched non-SSc subjects controlling age, sex, and use of proton pump inhibitors (PPIs). Results: The mean disease duration of 66 patients was 5.1 ± 8.1 years, and their breakdown was as follows: 53 (80.3%) with GERD, 38 (57.6%) with GERD-related symptoms, and 20 (30.3%) with reflux esophagitis (RE; LA-A: 10, LA-B: 5, LA-C: 4, LA-D: 1). Use of PPI (p = 0.0455), complication of interstitial lung disease (p = 0.0242), and history of cyclophosphamide therapy (p = 0.0184) denoted significant association with GERD-related symptoms. Older age (p = 0.0211) was significantly associated with RE. None of GERD-related disorders showed any difference between 37 diffuse cutaneous SSc and 29 limited cutaneous SSc patients. The matched analysis indicated that SSc patients had higher prevalence of GERD (p < 0.0001), GERD-related symptoms (p = 0.0034), and RE (p = 0.0002). Conclusion: SSc patients tend to have worse GERD symptoms and severer RE. However, most SSc-associated factors did not show significant association with GERD-related disorders, indicating the difficulty in predicting GERD-related disorders among SSc patients.
Left Ventricular Strain and Dyssynchrony in Young and Middle-Aged Peritoneal Dialysis Patients and Healthy Controls: A Case-Matched Study
Authors: Shi Fei , Feng Sheng , Zhu Jing , Wu Yanni , Chen Jianchang
Published: July 2018

Background: This study aimed to evaluate the role of two-dimensional speckle-tracking imaging (2D-STI) and myocardial layer-specific analysis in evaluating early left ventricular (LV) myocardial function and systolic dyssynchrony in young and middle-aged uremic patients undergoing peritoneal dialysis (PD). Methods: We enrolled 31 PD patients aged ≤65 years with preserved LV ejection fraction (LVEF, ≥54%) as the PD group and 49 age-matched healthy people as the control group. Echocardiography was used to assess the left atrial diameter index (LADI, LAD/BSA), LV mass index (LVMI), LVEF, peak early diastolic velocity/late diastolic velocity (E/A) (measured by pulsed Doppler), and peak early diastolic velocity (by pulsed Doppler)/peak velocity of the early diastolic wave (by pulsed-wave tissue Doppler) (E/e′). Next, we used 2D-STI and myocardial layer-specific analysis to obtain longitudinal strains (LS) of the endocardium (LSendo), the myocardium (LSmyo), the epicardium (LSepi), and the global myocardium (GLS). Then, we measured the postsystolic index (PSI) to evaluate LV myocardial function. Time to peak LS (TTP) and peak strain dispersion (PSD) from 17 consecutive segments were assessed to quantify LV dyssynchrony. Results: Compared with the controls, PD patients had significantly increased LADI (p = 0.041), LVMI (p = 0.000), and E/e′ (p = 0.009), but reduced LVEF (p = 0.000) and E/A (p = 0.000). The average values of GLS (GLS avg) (p = 0.01) and GLS of the apical 2-chamber view (p = 0.003), including the LSendo (p = 0.024), LSmyo (p = 0.024), and LSepi (p = 0.032), were significantly decreased in patients with PD compared with controls. In PSI, segments of LS were markedly delayed in the anterior septum (p = 0.047), anterior (p = 0.000) and septum wall (p = 0.024) from basal segments, anterior wall (p = 0.001) from middle segments, and anterior (p = 0.024) and inferior (p = 0.024) wall from apical segments. Moreover, PSD was significantly increased in PD patients (p = 0.015), while TTP was evidently delayed in the anterior septum (p = 0.004), anterior (p = 0.000) and posterior (p = 0.042) wall from basal segments, and inferior wall (p = 0.048) from apical segments. Conclusions: Despite preserved LVEF, young and middle-aged PD patients developed LV dysfunction and myocardial systolic dyssynchrony earlier compared with controls.
Postmenopausal Squamous Atypia: Cytologic Features, Hybrid Capture 2 Tests and Contribution to the ASCUS Pool
Authors: McHugh Kelsey E. , Reynolds Jordan P. , Suarez Adrian A.
Published: July 2018

Objective: Postmenopausal squamous atypia (PSA) mimics squamous intraepithelial lesion (SIL). We investigate the PSA contribution to the atypical squamous cells of undetermined significance (ASCUS) pool, its cytologic features and Hybrid Capture 2 (HC2) relative light unit/cutoff (RLU/CO) values. Study Design: 658 ASCUS Pap tests in women ≥55 years were reviewed to select those with koilocyte-like cells and/or atypical parakeratosis. Follow-up was positive when a biopsy showed SIL or carcinoma or a later HC2 test was positive. Results: Sixty-nine cases (10.5%) were selected. Forty-two (60.9%) were HC2 negative, and 27 (39.1%) were HC2 positive. Follow-up was available for 23 (54.7%) HC2-negative and 19 (70.3%) HC2-positive cases. No HC2-negative (0%) and 8 HC2-positive (42.1%) cases were positive on follow-up. Within cases negative on follow-up, 3 were PSA on biopsy. PSA was characterized by perinuclear halos, mild nuclear enlargement, smooth nuclear contours, and smooth chromatin. PSA-associated RLU/CO values were 0.25–2.95. Cases with SIL or carcinoma had RLU/CO values from 3.78 to 1,241.59. Conclusions: PSA contributes 0.5–2.3% to the ASCUS pool in women ≥55 years old. HC2 testing with RLU/CO of ≥1 may result in PSA occasionally testing positive. A different cutoff is not recommended but awareness of this caveat is important.
АЛЕЛЬНИЙ ПОЛІМОРФІЗМ С-260Т ГЕНА CD14 У ДІТЕЙ ІЗ ПОВТОРНИМИ ЕПІЗОДАМИ ГОСТРОГО ОБСТРУКТИВНОГО БРОНХІТУ
Authors: Kens O. V. , Gnateyko O. Z. , Makukh G. V. , Lukyanenko N. S. , Bergtravm V. I.
Published: July 2018

У структурі захворюваності дітей віком 0–14 років хвороби органів дихання займають перше місце та складають 62,0–65, 0 %. Пильну увагу дослідники та практичні лікарі до вказаної патології прикуто як її медичною та соціальною значимістю, так і відсутністю чітких критеріїв діагностики, необхідністю диференційованого підходу до лікування та реабілітації дітей. Особливий інтерес представляють повторні обструкції нижніх дихальних шляхів у дітей унаслідок неоднорідності причин, що їх спричиняють, подібності клінічної симптоматики та обмеженої інформативності загальноприйнятих методів дослідження.Мета дослідження – пошук молекулярно-генетичних маркерів підвищеної схильності дітей до повторних епізодів гострого обструктивного бронхіту.Матеріали і методи. Обстежено 25 дітей у віці від 2 до 8 років із повторними епізодами гострого обструктивного бронхіту (ГОБ). Для порівняння отриманих даних дітей із повторними епізодами ГОБ було відібрано групу із 25 дітей у віці від 2 до 8 років, які хворіли на гострий бронхіт (ГБ) не частіше 1–2 разів на рік, і склали групу порівняння. Результати молекулярно-генетичного дослідження порівнювали з даними 25 осіб, які взяли методом випадкової вибірки, які увійшли до загальнопопуляційної групи контролю.Результати досліджень та їх обговорення. Не зареєстровано достовірно вищої частоти генотипів СС, СТ та ТТ поліморфного локусу С-260Т гена CD14 у дітей із повторними епізодами гострого обструктивного бронхіту.Висновки. Проведене дослідження показало, що генотип СС поліморфного локусу С-260Т гена CD14 зустрічається частіше в дітей із гострим бронхітом, порівняно з пацієнтами із повторними епізодами ГОБ (44,0 проти 28,0 %), хоча достовірної різниці не зафіксовано, що, на думку авторів, вимагає подальших досліджень і збільшення кількості спостережень.