bluuebunny/crossref_metadata_2025 huggingface dataset:
Green Synthesis of 2‐Substituted Imidazolines using Hydrogen Peroxide Catalyzed by Tungstophosphoric Acid and Tetrabutylammonium Bromide in Water
Authors: Liu Shuai , Li Wang , Pang Yiying , Xiao Hesheng , Zhou Yi , Wang Xiaoji
Published: January 2019

Various 2‐substituted imidazolines were constructed from aromatic aldehydes with ethylenediamine using hydrogen peroxide as an oxidant in water. Tungstophosphoric acid (HPW) was found to be active for this transformation due to its ubiquitous catalytic and oxidative nature, and further combination of tetrabutylammonium bromide (TBAB) made this transformation more efficient and attractive. It was found that the yields of the corresponding 2‐substituted imidazolines were markedly influenced by the position and nature of the substituents on the phenyl ring. A plausible mechanism was also proposed to clarify this catalytic oxidative system.
The Chemistry of Acetylpyrazoles and Its Utility in Heterocyclic Synthesis
Authors: Abdelhamid Abdou O. , Gomha Sobhi M.
Published: January 2019

A literature survey revealed that a great deal of interest has been focused on the synthesis of functionalized pyrazole derivatives due to their synthetic and biological potentialities. The pharmacological activities that have been found for some pyrazole derivatives include selective enzyme inhibition, antiviral, estrogen receptor agonist, anti‐inflammatory, anticancer, antiobesity, and antitumor properties. Other activities such as potential inhibitors of HIV‐1, pesticides, fungicides, and antihypertensive agents were reported for other pyrazole derivatives. This review summarizes the synthetic methods and reactions of 3‐acetyl‐pyrazoles, 4‐acetyl‐pyrazoles, and 3,4‐di‐acetyl‐pyrazoles. Most reaction types have been successfully applied and used in the production of biologically active compounds. The aim of this review is to focus mainly on the utility of acetylpyrazole derivatives in the synthesis of heterocyclic compounds during the period 1990–2018.
Diabetes mellitus burden among people living with HIV from the Asia‐Pacific region
Authors: Han Win M , Jiamsakul Awachana , Kiertiburanakul Sasisopin , Ng Oon T , Sim Benedict LH , Sun Ly P , Van Nguyen Kinh , Choi Jun Y , Lee Man P , Wong Wing W , Kamarulzaman Adeeba , Kumarasamy Nagalingeswaran , Zhang Fujie , Tanuma Junko , Do Cuong D , Chaiwarith Romanee , Merati Tuti P , Yunihastuti Evy , Pujari Sanjay , Ditangco Rossana , Khusuwan Suwimon , Ross Jeremy , Avihingsanon Anchalee ,   IeDEA Asia‐Pacific
Published: January 2019

Introduction

Comorbidities including diabetes mellitus (DM) among people living with HIV (PLHIV) are of increasing clinical concerns in combination antiretroviral therapy (cART) era. We aimed to determine the incidence and risk factors of new‐onset DM among PLHIV in Asian settings.

Methods

PLHIV from a regional observational cohort without DM prior to antiretroviral therapy (ART) initiation were included in the analysis. DM was defined as having a fasting blood glucose ≥126 mg/dL, glycated haemoglobin ≥6.5%, a two‐hour plasma glucose ≥200 mg/dL, or a random plasma glucose ≥200 mg/dL. A Cox regression model, stratified by site, was used to identify risk factors associated with DM.

Results and discussion

Of the 1927 participants included, 127 were diagnosed with DM after ART initiation. Median follow‐up time from ART initiation to DM diagnosis was 5.9 years (interquartile range (IQR): 2.8 to 8.9 years). The crude incidence rate of DM was 1.08 per 100 person‐years (100 PYS), 95% confidence interval (CI) (0.9 to 1.3). In the multivariate analysis, later years of follow‐up (2011 to 2013: HR = 2.34, 95% CI 1.14 to 4.79, p = 0.02; and 2014 to 2017: HR = 7.20, 95% CI 3.27 to 15.87, p < 0.001) compared to <2010, older age (41 to 50 years: HR = 2.46, 95% CI 1.39 to 4.36, p  = 0.002; and >50 years: HR = 4.19, 95% CI 2.12 to 8.28, p < 0.001) compared to <30 years, body mass index (BMI) >30 kg/m2 (HR = 4.3, 95% CI 1.53 to 12.09, p = 0.006) compared to BMI <18.5 kg/m2, and high blood pressure (HR = 2.05, 95% CI 1.16 to 3.63, p = 0.013) compared to those without high blood pressure, were associated with developing DM. The hazard was reduced for females (HR = 0.47, 95% CI 0.28 to 0.80, p = 0.006).

Conclusions

Type 2 DM in HIV‐infected Asians was associated with later years of follow‐up, high blood pressure, obesity and older age. This highlights the importance of monitoring and routine screening for non‐communicable diseases including DM as PLHIV age.
Non‐F HBV/HDV‐3 coinfection is associated with severe liver disease in Western Brazilian Amazon
Authors: Melo Da Silva Edinete , Kay Alan , Lobato Cirley , Muwonge Richard , Zoulim Fabien , Brites Carlos , Parana Raymundo , Trepo Christian
Published: January 2019

The clinical outcome of hepatitis B virus (HBV) infection may be related to host and viral genetic factors, as well as to the type of infection (monoinfection and coinfection). To analyze the distribution/combination of HBV/hepatitis D virus (HDV) genotypes and the associated clinical characteristics, 409 serum samples from patients with chronic HBV (94 of them coinfected by HDV) followed at the Viral Hepatitis Referral Center of Rio Branco, Brazil were enrolled. HBV DNA and HDV RNA were amplified, respectively, by polymerase chain reaction (PCR) and nested PCR using specific primers in the PreC/C region and the S gene, and by reverse‐transcription PCR and seminested PCR using specific primers in the delta antigen region and sequenced. The proportion of women (56.1%) was significantly higher than males in this cohort (
P < 0.01). Women were significantly younger (39.8 years; 8‐77 years) than males (44.7 years; 12‐79 years;
P < 0.01). Sixty‐eight (18%) patients were infected with HBV‐F genotype and 264 (69.8%) with HBV/non‐F genotypes. Coinfection by HDV was detected in 23.9% (94 of 409) of this population and was more frequent in male (54.2%, 51 of 94) than in female patients (44.7%, 42 of 94;
P = 0.015). HDV‐3 was the most prevalent (88.9%) genotype. Almost 70% of HDV‐3 coinfected patients were infected with HBV/non‐F genotypes. Severe liver disease was diagnosed in 41 patients, 60.9% (25 of 41) of them coinfected with HDV. HBV/HDV coinfection was associated with male sex, age above 30 years, severe liver disease, and increased alanine aminotransferase levels. HBV/HDV‐3 coinfection is associated with severe liver disease, in Rio Branco, Brazil.
Clinical outcomes after the introduction of direct antiviral agents for patients infected with genotype 1b hepatitis C virus depending on the regimens: A multicenter study in Korea
Authors: Kwon Jung Hyun , Yoo Sun Hong , Nam Soon Woo , Kim Hee Yeon , Kim Chang Wook , You Chan Ran , Choi Sang Wook , Cho Se Hyun , Han Joon‐Yeol , Song Do Seon , Chang U Im , Yang Jin Mo , Lee Sung Won , Lee Hae Lim , Han Nam Ik , Kim Seok‐Hwan , Song Myeong Jun , Sung Pil Soo , Jang Jeong Won , Bae Si Hyun , Choi Jong Young , Yoon Seung Kew
Published: January 2019

Background

A real‐life study is essential outside clinical trials. The aim is to evaluate the clinical outcomes of direct acting agents (DAA) for patients with chronic hepatitis C (CHC) in real practice.

Methods

We analyzed 590 consecutively enrolled patients with CHC‐1b who received DAAs since 2015, when DAAs were introduced in Korea. The patients were checked for resistance‐associated variants (RAV) against nonstructural protein 5A inhibitors and then daclatasvir/asunaprevir or sofosbuvir based regimens were chosen.

Results

The frequency of patients with cirrhosis and prior hepatocellular carcinoma (HCC) was 29.2% and 4.7%, respectively. For the RAV test, 10% were positive and in 3.6% the result was “indeterminate.” Overall, 518 patients were treated with a 24‐week regimen of daclatasvir/asunaprevir, 72 patients (RAV positive 75%) were treated with 12 weeks regimen of ledipasvir/sofosbuvir or daclatasvir/sofosbuvir. The SVR12 was 94.0% in the daclatasvir/asunaprevir, 98.2% in the ledipasvir/sofosbuvir, and 100% in the daclatasvir/sofosbuvir group. A total of 93.3% of SVR12 in the RAV‐“indeterminate” patients was not difference 95.0% in the RAV‐negative patients. Up to 1 year, de novo HCC occurrence and recurrence developed in 2.6% and 17.8%, respectively. HCC was more frequent in cirrhotic patients than in noncirrhotic patients (P = 0.000). α Fetoprotein (AFP) level at the end of treatment was a predicting factor for de novo HCC.

Conclusions

Optimizing the choice of DAAs according to RAV test resulted in high SVR among CHC‐1b Korean patients. This real practice multicenter cohort study suggests the importance of AFP and HCC surveillance in cirrhotic patients even after successful HCV therapy.
Viral evolution in the cell‐associated HIV‐1 DNA during early ART can lead to drug resistance and virological failure in children
Authors: Gopalan Bindu Parachalil , D’Souza Reena R. , Rajnala Niharika , Arumugam Karthika , Dias Mary , Ranga Udaykumar , Shet Anita
Published: January 2019

Using cell‐associated DNA and cell‐free RNA of human immunodeficiency virus type‐1 (HIV‐1), we investigated the role of drug‐resistant viral variants that emerged during early antiretroviral therapy (ART) in determining virological outcome. This case‐control study compared virologic nonresponder children (two viral loads [VLs] ≥ 200 copies/mL within 2 years of ART) and responder children (two VLs < 200 copies/mL after six months of ART) infected with HIV‐1 initiated on nonnucleoside reverse‐transcriptase inhibitor (NNRTI)‐based ART. The partial reverse‐transcriptase gene of HIV‐1 in cell‐associated DNA was genotyped using next‐generation sequencing (NGS; Illumina; threshold 0.5%; at baseline and month six of ART) and in cell‐free RNA (concurrently and at virological failure; VL > 1000 copies/mL at ≥ 12 months of ART) using the Sanger method. Among 30 nonresponders and 37 responders, baseline differences were insignificant while adherence, VL, and drug resistance mutations (DRMs) observed at month six differed significantly (
P ≥ 0.05). At month six, NGS estimated a higher number of DRMs compared with Sanger (50% vs 33%;
P = 0.001). Among the nonresponders carrying a resistant virus (86.6%) at virological failure, 26% harbored clinically relevant low‐frequency DRMs in the cell‐associated DNA at month six (0.5%‐20%; K103N, G190A, Y181C, and M184I). Plasma VL of > 3 log
10copies/mL (AOR, 30.4; 95% CI, 3.3‐281;
P = 0.003) and treatment‐relevant DRMs detected in the cell‐associated DNA at month six (AOR, 24.2; 95% CI, 2.6‐221;
P = 0.005) were independently associated with increased risk for early virological failure. Our findings suggest that treatment‐relevant DRMs acquired in cell‐associated DNA during the first six months of ART can predict virological failure in children initiated on NNRTI‐based ART.
The role of lipid rafts in cell entry of human metapneumovirus
Authors: Chen Suhua , He Hao , Yang Hui , Tan Bin , Liu Enmei , Zhao Xiaodong , Zhao Yao
Published: January 2019

Human metapneumovirus (hMPV) is a crucial pathogen in children. A cell entry is the first step for infection. Our previous study indicated that there was an endocytosis pathway for hMPV cell entry. Lipid raft is a specific structure at the cell surface and it has been demonstrated to play an important role in endocytosis process of many viruses. In this study, we investigated whether and how lipid raft can take part in the hMPV entry. The confocal microscope was used to detect colocalization of hMPV and lipid raft marker. We demonstrated that colocalizations were increased along with the viral infection and hMPV particles transferred to the perinuclear region with lipid raft. When specific lipid raft inhibitors: methyl‐β cyclodextrin and nystatin were used, hMPV cell entry was inhibited and viral titer decreased dramatically. With the replenishment of exogenous cholesterol, hMPV recovered quickly. These data suggest that lipid raft plays an important role in hMPV endocytosis and maybe one of the pathways for hMPV cell entry.
The association between consuming bivalves, and acute gastroenteritis and norovirus in Tokyo, Japan
Authors: Kobayashi Daiki , Saito Mayuko , Heike Yuji , Yokota Kyoko , Arioka Hiroko , Oshitani Hitoshi
Published: January 2019

A prospective matched case‐control study was conducted to evaluate associations between dietary histories, including consumption of bivalves, diarrhea, and norovirus positive diarrhea in adult ambulatory patients at an outpatient clinic of a hospital in Tokyo, Japan. Ambulatory cases with diarrhea were matched with nondiarrheal control patients, who visited the same clinic. A standardized questionnaire was used to obtain patients’ information, including histories of food consumption and clinical information. Norovirus infection was confirmed using real‐time reverse transcription polymerase chain reaction. A total of 207 patients, including 69 diarrheal cases and 138 nondiarrheal cases were included in the analysis. Among them, 60 (29.0%) participants reported consuming bivalves. Norovirus was detected in 35% (24/69) of diarrheal cases. Of those, 10 (41.7%) reported consumption of bivalves and of those, 6 (60.0%) consumed raw bivalves. The proportion of those who consumed raw bivalves was significantly higher in norovirus‐positive diarrheal cases than in norovirus‐negative diarrheal cases (25.0% vs 6.7%; odds ratio [OR], 4.67; 95% confidence interval [CI], 1.1‐20.7) and matched nondiarrheal controls (25.0% vs 6.3%, OR: 5.00; 95% CI, 1.1‐22.2). The attributable fraction of consuming raw bivalves for norovirus‐associated diarrhea to matched nondiarrheal controls was 20.0%. Consuming raw bivalves was substantially attributed to norovirus‐associated diarrhea in adult ambulatory patients and preventive measures for reducing the risk associated with consumption of raw bivalves could decrease the incidence of norovirus‐associated diarrhea.
Dengue virus serotypes and genotypic characterization from northeast India
Authors: Chetry Sumi , Khan Siraj A. , Dutta Prafulla , Apum Basumoti , Medhi Pranita S. , Saikia Durlov C. , Temsu Temjen , Mawii Lalhming , Marak Bichitrani C.
Published: January 2019

Dengue is a rapidly spreading acute arboviral infection transmitted through a human and Aedes mosquito cycle. Though northeast region of India has been experiencing dengue outbreaks regularly for over a decade, reports on genetic characterization of the virus from this region are limited. The present study was undertaken to detect the genotype and genetic composition of circulating dengue virus (DENV) in this region. Blood samples were collected from 918 suspected dengue patients of five northeast Indian states. Serological investigations, viz, nonstructural 1 (NS1) enzyme‐linked immunosorbent assay (ELISA), immunoglobulin M (IgM) ELISA, and immunoglobulin G (IgG) ELISA were performed followed by molecular detection. Sequence analysis and phylogenetic tree construction based on capsid‐premembrane (C‐prM) gene junction was done by BioEdit and MEGA6 software, respectively. Serological detection showed 35.34% NS1 and 18.12% IgM positivity. Secondary infection was observed in 24.53%. All four serotypes were detected. Phylogenetic analysis demonstrated circulation of genotype III of DENV‐1, genotype IV of DENV‐2, and genotype III of DENV‐3. Sequences from this region form distinct clades in the phylogenetic tree. Characterization of the C‐prM gene junction reveals divergence among the DENV strains. As genetic variation within the DENV is known to be associated with diverse clinical outcomes, information regarding the genetic composition of circulating virus could be beneficial in designing an effective intervention strategy.
Division model‐based distortion correction method for head‐mounted displays
Authors: Xiao Xue , Zhang Lin , Lin Xiao , Zang Jinliang , Tan Xiaodi
Published: January 2019

In this paper, we present a simple and efficient method for correcting the asymmetric and nonlinear geometrical distortion of a head‐mounted display (HMD). The method divides the object space into a number of quadratic triangular elements and applies a quadratic predistortion for each image section so that it can handle the distortion with any complex shapes caused by the decentering and tilted optics and improve the calibration accuracy. The errors introduced in the process of fabricating and assembling can also be eliminated. We investigated the use of a quadratic division model and two types of linear division models on an off‐axis HMD to correct the optical distortion. Experimental results demonstrated that the quadratic division model converged at a faster rate and produced higher accuracy over the typical linear model. The average root of mean square error (RMSE) after distortion correction was one pixel, and the maximum standard deviations in all rows and columns were 0.67 pixel and 0.57 pixel. In addition, the deformation continuity is maintained by using the quadratic element with connected midside nodes.
Value of Perfusion Parameters for Differentiating Hepatocellular Carcinoma and Liver Metastasis With Hypervascularity and a Normal Hepatic Background on Contrast‐Enhanced Ultrasound Imaging
Authors: Lu Qing , Zhang Xiao‐long , Han Hong , Huang Bei‐jian , Ding Hong , Wang Wen‐ping
Published: January 2019

Objectives

To retrospectively evaluate the value of contrast‐enhanced ultrasound (CEUS) perfusion parameters in the differential diagnosis of hepatocellular carcinomas (HCCs) and metastatic liver tumors (MLTs) with hypervascularity.

Methods

Sixty‐seven HCCs and 55 MLTs with arterial homogeneous/heterogeneous hyperenhancement on CEUS imaging and a normal liver background were included in this retrospective study. Six CEUS perfusion parameters were compared between HCCs and MLTs with different sizes and HCC differentiations: rise time (RT), time to peak (TTP), mean transit time, wash‐out time (WT), maximum intensity (IMAX), and area under the curve (AUC). The area under the receiver operating characteristic curve (AUROC) was determined to compare the diagnostic efficacy of the parameters.

Results

The RT, TTP, and WT were significant longer and the IMAX and AUC were significantly higher in HCCs than in MLTs. In distinguishing between HCCs and MLTs, the AUROC was highest for the WT (0.922; sensitivity, 85.1%; specificity, 89.6%); the AUC and IMAX had the second and third highest AUROCs (AUC: 0.855; sensitivity, 76.1%; specificity, 80.6%; IMAX: 0.827; sensitivity, 76.1%; specificity, 77.6%). The AUROC was lowest for the TTP and RT (TTP: 0.719; sensitivity, 70.1%; specificity, 61.2%; RT: 0.707; sensitivity, 67.2%; specificity, 65.7%). In HCCs, both the tumor size and degree of differentiation affected the IMAX, AUC, and WT. In MLTs, perfusion parameters were not influenced by the tumor size.

Conclusions

In HCCs and MLTs with hypervascularity and a normal liver background on CEUS imaging, various CEUS perfusion parameters, including IMAX, AUC, WT, RT, and TTP, differed significantly between tumor types. The WT may be the most useful parameter for differentiating between these tumors.
Comparison of the Ablation and Hyperechoic Zones in Different Tissues Using Microwave and Radio Frequency Ablation
Authors: Shi Jing‐wen , Huang Ying
Published: January 2019

Objectives

The aim of this study was to compare the differences between the ablation region and hyperechoic zones in microwave and radio frequency ablation of different tissues.

Methods

Microwave and radio frequency ablation were performed on fresh porcine muscle and liver with different power levels for 90 seconds. These 2 ablation methods were then performed on rabbit liver in vivo using 20 W for 60 seconds. The volumes of the ablation and hyperechoic zones were compared following different ablation methods.

Results

The ablation zones were significantly greater than the hyperechoic zones (P < .05) with the same power and duration when using 2 ablation methods. The differences of the ablation and hyperechoic zones between muscle and liver tissues were significantly different (P < .05). The difference values of the ablation and hyperechoic zones were also significantly different (P < .05) using 2 ablation methods.

Conclusions

The hyperechoic zone may have underestimated the extent of ablation using a specified ablation time. In the same tissue, the hyperechoic zone could more accurately estimate the ablation zones using microwave ablation.
Clinical applications of three‐dimensional printing in otolaryngology–head and neck surgery: A systematic review
Authors: Hong Chris J. , Giannopoulos Andreas A. , Hong Brian Y. , Witterick Ian J. , Irish Jonathan C. , Lee John , Vescan Allan , Mitsouras Dimitrios , Dang Wilfred , Campisi Paolo , de Almeida John R. , Monteiro Eric
Published: January 2019

Objectives

Medical three‐dimensional (3D) printing, the fabrication of handheld models from medical images, has the potential to become an integral part of otolaryngology–head and neck surgery (Oto‐HNS) with broad impact across its subspecialties. We review the basic principles of this technology and provide a comprehensive summary of reported clinical applications in the field.

Methods

Standard bibliographic databases (MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, Web of Science, and The Cochrane Central Registry for Randomized Trials) were searched from their inception to May 2018 for the terms: “3D printing,” “three‐dimensional printing,” “rapid prototyping,” “additive manufacturing,” “computer‐aided design,” “bioprinting,” and “biofabrication” in various combinations with the terms: “ptolaryngology,” “head and neck surgery,” and “otology.” Additional articles were identified from the references of retrieved articles. Only studies describing clinical applications of 3D printing were included.

Results

Of 5,532 records identified through database searching, 87 articles were included for qualitative synthesis. Widespread implementation of 3D printing in Oto‐HNS is still at its infancy. Nonetheless, it is increasingly being utilized across all subspecialties from preoperative planning to design and fabrication of patient‐specific implants and surgical guides. An emerging application considered highly valuable is its use as a teaching tool for medical education and surgical training.

Conclusions

As technology and training standards evolve and as healthcare moves toward personalized medicine, 3D printing is emerging as a key technology in patient care in Oto‐HNS. Treating physicians and surgeons who wish to stay abreast of these developments will benefit from a fundamental understanding of the principles and applications of this technology.

Laryngoscope, 129:2045–2052, 2019
Impact of treating facilities’ type and volume in patients with major salivary gland cancer
Authors: Bollig Craig A. , Zitsch Robert P.
Published: January 2019

Objectives/Hypothesis

Investigate the relationship between facility volume and type on overall survival (OS) in patients with major salivary gland cancer undergoing surgical treatment.

Study Design

Retrospective review of the National Cancer Database (NCDB) 2004–2015.

Methods

The NCDB was queried for patients with surgically treated major salivary gland cancer. The mean number of cases treated at each institution was calculated. High‐volume facilities (HVFs) were defined as the top 10% of centers. Univariate and multivariate propensity score‐matched analyses were performed to evaluate the impact of facility volume and type on OS.

Results

A total of 8,658 patients were analyzed. Distribution among facilities was highly skewed, with a median value of 1.38 cases/year (range, 0.11–23.25). On univariate analysis, treatment at HVFs was not associated with improved OS. However, there were significantly more patients with adverse clinical features treated at HVFs. Treatment at HVFs was associated with increased rates of concomitant neck dissections and lower rates of positive margins. In propensity‐score matched cohorts, OS was not significantly improved in patients treated at HVFs (hazard ratio [HR]: 0.979; 95% confidence interval [CI]: 0.879‐1.091) or academic/research institutions (HR: 0.914; 95% CI: 0.821‐1.018).

Conclusions

Regionalization of care is occurring in patients with major salivary gland malignancies. Patients treated at HVFs had greater rates of adverse clinical features and more commonly underwent neck dissections, although adjuvant radiotherapy rates were similar between facility types. There was no apparent survival benefit to patients treated at HVFs or academic/research institutions, although there were lower rates of positive margins at HVF.

Level of Evidence

NA

Laryngoscope, 129:2321–2327, 2019
Temporal dynamics of soil bacterial communities and multifunctionality are more sensitive to introduced plants than to microbial additions in a multicontaminated soil
Authors: Jiao Shuo , Du Nini , Zai Xiaoyu , Gao Xuee , Chen Weimin , Wei Gehong
Published: January 2019

Soil microbial communities are crucial for regulating the stability and degradation of contaminated land. However, the temporal response strategies of particular microbial groups to biotic introductions and their contributions to ecosystem functions and services (i.e., ‘multifunctionality’) in contaminated soils have yet to be investigated. Here, we present results from a 90‐day microcosm experiment aiming to evaluate the temporal changes in bacterial communities and functions in response to microbial and plant additions in a contaminated agricultural soil. In addition, we quantified the contributions of specific bacterial taxa with different response strategies over time to alterations in ecosystem multifunctionality in pollutant degradation (polyphenol oxidase) and the cycling of carbon (dehydrogenase), nitrogen (urease and available nitrogen), phosphorus (available phosphorus), and potassium (available potassium). Results showed that native bacterial communities exhibited strong resilience to the introduced microbial consortium and were altered by plant growth. Plant‐enriched bacterial taxa were located in the core and central positions of the co‐occurrence networks and had considerable influence on the other nodes. Plant growth substantially influenced soil multifunctionality, in a process driven by specific bacterial taxa with different response strategies. The more tolerant taxa contributed most to multienzyme activities, whereas the more affected taxa largely determined multinutrient levels in the soil. These results provide a new perspective in disentangling the roles of plant‐associated bacteria in the assembly of community interactions and ecosystem multifunctionality of contaminated agricultural soils.
A Multidisciplinary Approach to Pretransplant and Posttransplant Management of Cystic Fibrosis–Associated Liver Disease
Authors: Freeman A. Jay , Sellers Zachary M. , Mazariegos George , Kelly Andrea , Saiman Lisa , Mallory George , Ling Simon C. , Narkewicz Michael R. , Leung Daniel H.
Published: January 2019

Approximately 5%‐10% of patients with cystic fibrosis (CF) will develop advanced liver disease with portal hypertension, representing the third leading cause of death among patients with CF. Cystic fibrosis with advanced liver disease and portal hypertension (CFLD) represents the most significant risk to patient mortality, second only to pulmonary or lung transplant complications in patients with CF. Currently, there is no medical therapy to treat or reverse CFLD. Liver transplantation (LT) in patients with CFLD with portal hypertension confers a significant survival advantage over those who do not receive LT, although the timing in which to optimize this benefit is unclear. Despite the value and efficacy of LT in selected patients with CFLD, established clinical criteria outlining indications and timing for LT as well as disease‐specific transplant considerations are notably absent. The goal of this comprehensive and multidisciplinary report is to present recommendations on the unique CF‐specific pre‐ and post‐LT management issues clinicians should consider and will face.
Crosslinkable‐Chitosan‐Enabled Moisture‐Resistant Multilayer Gas Barrier Thin Film
Authors: Lazar Simone , Garcia‐Valdez Omar , Kennedy Emily , Champagne Pascale , Cunningham Michael , Grunlan Jaime
Published: January 2019

Chitosan‐based films exhibit good oxygen barrier that degrades when exposed to high humidity. In an effort to overcome this drawback, a multilayer nanocoating consisting of crosslinkable chitosan (CHQ) and poly(acrylic acid) [PAA] is deposited on polyethylene terephthalate (PET) using layer‐by‐layer assembly. Chitosan is functionalized with glycidyl methacrylate to introduce acrylic functionalities within the film. The deposited films are crosslinked using a free radical initiator and this crosslinking is confirmed by FTIR and reduced film thickness. A 10‐bilayer (BL) crosslinked CHQ/PAA film, which is only 165 nm thick, results in a 36× reduction of the oxygen transmission rate of PET at 90% relative humidity. To achieve these same results without crosslinking, a 15‐BL unmodified chitosan (CH)/PAA film, which is almost 5× thicker, must be deposited on PET. This environmentally friendly, transparent nanocoating is promising for food packaging or protection of flexible electronics, especially in high‐humidity environments.
A multidisciplinary approach to the clinical management of Prader–Willi syndrome
Authors: Duis Jessica , van Wattum Pieter J. , Scheimann Ann , Salehi Parisa , Brokamp Elly , Fairbrother Laura , Childers Anna , Shelton Althea Robinson , Bingham Nathan C. , Shoemaker Ashley H. , Miller Jennifer L.
Published: January 2019

Background

Prader–Willi syndrome (PWS) is a complex neuroendocrine disorder affecting approximately 1/15,000–1/30,000 people. Unmet medical needs of individuals with PWS make it a rare disease that models the importance of multidisciplinary approaches to care with collaboration between academic centers, medical homes, industry, and parent organizations. Multidisciplinary clinics support comprehensive, patient‐centered care for individuals with complex genetic disorders and their families. Value comes from improved communication and focuses on quality family‐centered care.

Methods

Interviews with medical professionals, scientists, managed care experts, parents, and individuals with PWS were conducted from July 1 to December 1, 2016. Review of the literature was used to provide support.

Results

Data are presented based on consensus from these interviews by specialty focusing on unique aspects of care, research, and management. We have also defined the Center of Excellence beyond the multidisciplinary clinic.

Conclusion

Establishment of clinics motivates collaboration to provide evidence‐based new standards of care, increases the knowledge base including through randomized controlled trials, and offers an additional resource for the community. They have a role in global telemedicine, including to rural areas with few resources, and create opportunities for clinical work to inform basic and translational research. As a care team, we are currently charged with understanding the molecular basis of PWS beyond the known genetic cause; developing appropriate clinical outcome measures and biomarkers; bringing new therapies to change the natural history of disease; improving daily patient struggles, access to care, and caregiver burden; and decreasing healthcare load. Based on experience to date with a PWS multidisciplinary clinic, we propose a design for this approach and emphasize the development of “Centers of Excellence.” We highlight the dearth of evidence for management approaches creating huge gaps in care practices as a means to illustrate the importance of the collaborative environment and translational approaches.
A novel fusion gene involving PDGFRB and GCC2 in a chronic eosinophilic leukemia patient harboring t(2;5)(q37;q31)
Authors: Iriyama Noriyoshi , Takahashi Hiromichi , Naruse Hiromu , Miura Katsuhiro , Uchino Yoshihito , Nakagawa Masaru , Iizuka Kazuhide , Hamada Takashi , Hatta Yoshihiro , Nakayama Tomohiro , Takei Masami
Published: January 2019

Background

Platelet‐derived growth factor receptor beta (PDGFRB) rearrangement has been reported in a number of patients with chronic eosinophilic leukemia (CEL), B‐acute lymphoblastic leukemia, myeloproliferative neoplasms, and juvenile myelomonocytic leukemia. Here, we report a case of CEL carrying a novel fusion gene involving PDGFRB and GRIP and coiled‐coil domain containing 2 (GCC2).

Patient and methods

A 54‐year‐old man presenting with a cough and dyspnea was diagnosed with acute eosinophilic pneumonia. Cytogenetic analysis of the bone marrow revealed the presence of t(2;5)(q37;q31). Fluorescence in situ hybridization analysis in the peripheral blood leukocytes revealed the presence of a split signal at PDGFRB gene. Imatinib treatment was effective, and disappearance of t(2;5)(q37;q31) in the bone marrow was confirmed after three months of imatinib therapy. Whole‐genome sequencing was performed in peripheral blood leukocytes collected before imatinib therapy.

Results

A novel fusion gene between exon 22 of GCC2 and exon 12 of PDGFRB was detected and the presence of GCC2‐PDGFRB was confirmed by PCR.

Conclusion

This is the first case report demonstrating the GCC2 gene as a partner of PDGFRB in the pathogenesis of CEL.
An analytical method for solving elastic system in inhomogeneous orthotropic media
Authors: Altunkaynak Meltem
Published: January 2019

In this paper, the three‐dimensional initial value problem for elastic system in inhomogeneous orthotropic media is considered and an analytical method is studied to solve this problem. The system is written in terms of Fourier images of displacements with respect to lateral variables. The resulting problem is reduced to integral equations of the Volterra type, whose solution is obtained by the method of successive approximations. Finally, using the real Paley‐Wiener theorem, it is shown that the solution of the initial value problem can be found by the inverse Fourier transform.
Derived mammographic masking measures based on simulated lesions predict the risk of interval cancer after controlling for known risk factors: a case‐case analysis
Authors: Hinton Benjamin , Ma Lin , Mahmoudzadeh Amir Pasha , Malkov Serghei , Fan Bo , Greenwood Heather , Joe Bonnie , Lee Vivian , Strand Fredrik , Kerlikowske Karla , Shepherd John
Published: January 2019

Purpose

Women with radiographically dense or texturally complex breasts are at increased risk for interval cancer, defined as cancers diagnosed after a normal screening examination. The purpose of this study was to create masking measures and apply them to identify interval risk in a population of women who experienced either screen‐detected or interval cancers after controlling for breast density.

Methods

We examined full‐field digital screening mammograms acquired from 2006 to 2015. Examinations associated with 182 interval cancers were matched to 173 screen‐detected cancers on age, race, exam date and time since last imaging examination. Local Image Quality Factor (IQF) values were calculated and used to create IQF maps that represented mammographic masking. We used various statistics to define global masking measures of these maps. Association of these masking measures with interval cancer vs screen‐detected cancer was estimated using conditional logistic regression in a univariate and adjusted model for Breast Imaging‐Reporting and Data System (BI‐RADS) density. Receiver operator curves were calculated in each case to compare specificity vs sensitivity, and area under those curves were generated. Proportion of screen‐detected cancer was estimated for stratifications of IQF features.

Results

Several masking features showed significant association with interval compared to screen‐detected cancers after adjusting for BI‐RADS density (up to P = 2.52E‐6), and the 10th percentile of the IQF value (P = 1.72E‐3) showed the strongest improvement in the area under the receiver operator curve, increasing from 0.65 using only BI‐RADS density to 0.69. The highest masking group had a 32% proportion of screen‐detected cancers while the low masking group had a 69% proportion.

Conclusions

We conclude that computer vision methods using model observers may improve quantifying the probability of breast cancer detection beyond using breast density alone.
Artifact correction in low‐dose dental CT imaging using Wasserstein generative adversarial networks
Authors: Hu Zhanli , Jiang Changhui , Sun Fengyi , Zhang Qiyang , Ge Yongshuai , Yang Yongfeng , Liu Xin , Zheng Hairong , Liang Dong
Published: January 2019

Purpose

In recent years, health risks concerning high‐dose x‐ray radiation have become a major concern in dental computed tomography (CT) examinations. Therefore, adopting low‐dose computed tomography (LDCT) technology has become a major focus in the CT imaging field. One of these LDCT technologies is downsampling data acquisition during low‐dose x‐ray imaging processes. However, reducing the radiation dose can adversely affect CT image quality by introducing noise and artifacts in the resultant image that can compromise diagnostic information. In this paper, we propose an artifact correction method for downsampling CT reconstruction based on deep learning.

Method

We used clinical dental CT data with low‐dose artifacts reconstructed by conventional filtered back projection (FBP) as inputs to a deep neural network and corresponding high‐quality labeled normal‐dose CT data during training. We trained a generative adversarial network (GAN) with Wasserstein distance (WGAN) and mean squared error (MSE) loss, called m‐WGAN, to remove artifacts and obtain high‐quality CT dental images in a clinical dental CT examination environment.

Results

The experimental results confirmed that the proposed algorithm effectively removes low‐dose artifacts from dental CT scans. In addition, we showed that the proposed method is efficient for removing noise from low‐dose CT scan images compared to existing approaches. We compared the performances of the general GAN, convolutional neural networks, and m‐WGAN. Through quantitative and qualitative analysis of the results, we concluded that the proposed m‐WGAN method resulted in better artifact correction performance preserving the texture in dental CT scanning.

Conclusions

The image quality evaluation metrics indicated that the proposed method effectively improves image quality when used as a postprocessing technique for dental CT images. To the best of our knowledge, this work is the first deep learning architecture used with a commercial cone‐beam dental CT scanner. The artifact correction performance was rigorously evaluated and demonstrated to be effective. Therefore, we believe that the proposed algorithm represents a new direction in the research area of low‐dose dental CT artifact correction.
Chronic immune sensorimotor polyradiculopathy: Report of a case series
Authors: Thammongkolchai Thananan , Suhaib Omer , Termsarasab Pichet , Li Yuebing , Katirji Bashar
Published: January 2019

Introduction

Chronic immune sensorimotor polyradiculopathy (CISMP) is a chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) variant affecting both sensory and motor nerve roots without evidence of peripheral nerve demyelination.

Methods

We report a case series of 9 patients with CISMP, identified from 2 tertiary centers. Clinical, electrodiagnostic, and neuroradiologic features, and treatment responses, were retrospectively reviewed.

Results

Patients presented with sensorimotor deficits and hypo‐/areflexia, predominantly involving lower extremities. Three had cranial nerve involvement. Electrodiagnostic findings in all patients localized to roots proximal to dorsal root ganglia, without evidence of peripheral nerve demyelination. Cerebrospinal fluid examination revealed an albuminocytologic association. Eight patients exhibited gadolinium enhancement and thickening of multiple spinal nerve roots and/or cranial nerves. All patients demonstrated good responses to immunotherapies.

Discussion

CISMP is similar to CIDP in many aspects, but lacks typical electrodiagnostic findings of peripheral nerve demyelination. It is important to recognize this unusual and treatable entity. Muscle Nerve 59:658–664, 2019
Decoupled epineurial and axonal deformation in mouse median and ulnar nerves
Authors: Sung Jaemyoung , Sikora‐Klak Jakub , Adachi Stephanie Y. , Orozco Elisabeth , Shah Sameer B.
Published: January 2019

Introduction

Peripheral nerves accommodate mechanical loads during joint movement. Hypothesized protective features include increased nerve compliance near joints and axonal undulation. How axons perceive nerve deformation is poorly understood. We tested whether nerves increase local axonal undulation in regions of high epineurial strain to protect nerve fibers from strain‐induced damage.

Methods

Regional epineurial strain was measured near the elbow in median and ulnar nerves of mice expressing axonal fluorescence before and after decompression. Regional axonal tortuosity was quantified under confocal microscopy.

Results

Nerves showed higher epineurial strain just distal to the medial epicondyle; these differences were eliminated after decompression. Axonal tortuosity also varied regionally; however, unlike in the epineurium, it was greater in proximal regions.

Discussion

In this study we have proposed a neuromechanical model whereby axons can unravel along their entire length due to looser mechanical coupling to the peri/epineurium. Our findings have major implications for understanding nerve biomechanics and dysfunction. Muscle Nerve 59:619–619, 2019
ALK inhibition in two emblematic cases of pediatric inflammatory myofibroblastic tumor: Efficacy and side effects
Authors: Brivio Erica , Zwaan C. Michel
Published: January 2019

There is an increasing interest for anaplastic lymphoma kinase (ALK) inhibitors in pediatric oncology for specific entities such as ALK‐driven inflammatory myofibroblastic tumor (IMT). IMT treatment can be challenging due to localization of the tumor and in rare cases of metastasis. When standard surgical treatment is not feasible, ALK inhibitors may play an important role, as recently reported for the first‐generation ALK inhibitors (crizotinib). However, data on the second‐generation ALK inhibitors are limited. We report two emblematic cases of IMT in pediatric patients, treated with the second‐generation ALK inhibitor ceritinib in the context of a clinical trial (NCT01742286).
The ethical climate in paediatric oncology—A national cross‐sectional survey of health‐care personnel
Authors: Pergert Pernilla , Bartholdson Cecilia , af Sandeberg Margareta
Published: January 2019

Objective

To describe health‐care personnel's (HCP's) perceptions of the ethical climate at their workplace in paediatric oncology.

Methods

A cross‐sectional survey was conducted using the Swedish version of the shortened Hospital Ethical Climate Survey (HECS‐S). HCP at all six paediatric oncology centres (POCs) in Sweden were invited to participate. Analysis included descriptive statistics, the Mann‐Whitney U test (differences between groups) and Spearman's rank correlation. Informed consent was assumed when the respondents returned the survey.

Results

A high response rate was achieved as 278 HCP answered the questionnaire. Medical doctors perceived the ethical climate to be more positive than registered nurses and nursing assistants. At the POC with the significantly lowest values concerning immediate manager, no significant correlation with the other items was found. At the POC with the poorest ethical climate, HCP also had the lowest perception of the possibility of practicing ethically good care.

Conclusions

Differences between centres and professional groups have been demonstrated. A negative perception of the immediate manager does not necessarily mean that the ethical climate is poor, but the manager's ability to provide the conditions for an open dialogue within the health‐care team is key to achieving an ethical climate.
Investigating the impact of self‐management behaviours on quality of life and fear of recurrence in head and neck cancer survivors: A population‐based survey
Authors: Dunne Simon , Coffey Laura , Sharp Linda , Desmond Deirdre , Cullen Claire , O'Connor Jean , O'Sullivan Eleanor , Timon Conrad , Gallagher Pamela
Published: January 2019

Objectives

Emerging cancer‐survivorship research suggests that self‐management can lead to improved outcomes. However, research examining the impact of self‐management behaviours on quality of life (QoL) and fear of recurrence (FoR) in cancer survivors is lacking. This study investigated the relationship between self‐management behaviours and QoL and FoR following treatment for head and neck cancer (HNC).

Methods

Postal surveys were sent to 734 eligible HNC survivors (ICD10 C01‐C14; C32) in the Republic of Ireland who were 12‐ to 60‐months post diagnosis. QoL and FoR were measured using the Functional Assessment of Cancer Therapy (FACT‐G and Head and Neck Cancer Subscale) measure and Fear of Relapse/Recurrence Scale, respectively. Seven self‐management behaviours were measured using the Health Education Impact Questionnaire.

Results

Three hundred and ninety‐five HNC survivors completed surveys (50.3% response rate). After controlling for sociodemographic and clinical characteristics, self‐management behaviours accounted for 20% to 39.4% of the variance in QoL and FoR. Higher scores on positive and active engagement in life, constructive attitudes and approaches, and skill and technique acquisition were significantly associated with higher global QoL and lower FoR, whilst higher scores on positive and active engagement in life and constructive attitudes and approaches only were significantly associated with higher HNC‐specific QoL. Additionally, lower scores on self‐monitoring and insight were significantly associated with higher HNC‐specific and global QoL and lower FoR.

Conclusions

The findings highlight the potential utility of self‐management interventions promoting active problem solving, positive self‐talk, and skill acquisition amongst cancer survivors. However, increased self‐monitoring may relate to negative outcomes in HNC, a finding that warrants further investigation.
DTT–Au NCs Interact with DNA to Form Raspberry‐Like Particles
Authors: Zhang Lixia , Li Zhenhua , Jing Jiangbo , Ding Han , Chen Zhijun
Published: January 2019

Noble metal nanoclusters (NCs) have emerged as intriguing nanomaterials with widespread interest. Previously, it was shown that dithiothreitol (DTT)‐conjugated gold nanoclusters (Au NCs) respond to copper ions in aqueous solution. Here, it is shown that these DTT–Au NCs can interact with DNA by forming raspberry‐like particles. The raspberry‐like structures protect the capped DNA from enzymatic attack and show excellent biocompatibility. Moreover, these supramolecular complexes cross the plasma membrane of yeast cells and express green fluorescent protein encoded by the DNA, suggesting that DTT–Au NCs can serve as an efficient carrier for gene delivery.