bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of biomarkers correlated with hypertrophic cardiomyopathy with co‐expression analysis
Authors: Chen Ran , Ge Tiantian , Jiang Wanying , Huo Junyu , Chang Qing , Geng Jie , Shan Qijun
Published: May 2019

Hypertrophic cardiomyopathy (HCM) is reported to be the most common genetic heart disease. To identify key module and candidate biomarkers correlated with clinical prognosis of patients with HCM, we carried out this study with co‐expression analysis. To construct a co‐expression network of hub genes correlated with HCM, the Weighted Gene Co‐expression Network Analysis (WGCNA) was performed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed by Database for Annotation, Visualization and Integrated Discovery (DAVID). The protein‐protein interaction network analysis of central genes was performed to recognize the interactions of central genes. Gene set enrichment analyses were carried out to discover the possible mechanisms involved in the pathways promoted by hub genes. To validate the hub genes, quantitative real‐time polymerase chain reaction (RT‐PCR) was performed. Based on the results of topological overlap measure based clustering, 2,351 differentially expressed genes (DEGs) were identified. Those genes were included in six different modules. Of these modules, the yellow and the blue modules showed a pivotal correlation with HCM. DEGs were enriched in immune system procedure associated GO terms and KEGG pathways. We identified nine hub genes (TYROBP, STAT3, CSF1R, ITGAM, SYK, ITGB2, LILRB2, LYN, and HCK) affected the immune system significantly. Among the genes we validated with RT‐PCR, TYROBP, CSF1R, and SYK showed significant increasing expression levels in model HCM rats. In conclusion, we identified two modules and nine hub genes, which were prominently associated with HCM. We found that immune system may play a crucial role in the HCM. Accordingly, those genes and pathways might become therapeutic targets with clinical usefulness in the future.
MiR‐21 upregulation increases IL‐8 expression and tumorigenesis program in airway epithelial cells exposed to cigarette smoke
Authors: Pace Elisabetta , Di Vincenzo Serena , Di Salvo Eleonora , Genovese Sara , Dino Paola , Sangiorgi Claudia , Ferraro Maria , Gangemi Sebastiano
Published: May 2019

Background

Cigarette smoke exposure, increasing Toll‐like receptor 4 (TLR4) and reactive oxygen species (ROS), promotes inflammatory responses in airway epithelial cells. Chronic inflammation, microRNA (miRNA), and oxidative stress are associated with cancer development.

Aims

The present study was aimed to explore whether cigarette smoke exposure, altering miR‐21 expression, promoted inflammatory responses and tumorigenesis processes in airway epithelial cells.

Methods

Airway normal and cancer epithelial cells (16HBE and A549) were exposed to cigarette smoke extracts (CSE) or with/without agomiR‐21, and then it was assessed: a) miR‐21 expression; b) signal transducer and activator of transcription 3 (STAT3) nuclear protein expression and ERK1/2 activation; c) IL‐8 gene expression and protein release. An antagonist of TLR4 (CLI‐095) and the antioxidant flavonoid, apigenin, were also included to evaluate miR‐21 expression in CSE exposed cells.

Results

It was demonstrated that: a) A549 cells constitutively expressed higher levels of miR‐21 and IL‐8; b) CSE increased STAT3 nuclear expression in 16HBE; c) in both cell lines, CSE and agomiR‐21 increased: miR‐21 expression; ERK1/2 activation and IL‐8 gene expression and protein release; d) TLR4 inhibition counteracted the effects of CSE on miR‐21 in A549; e) apigenin reduced miR‐21 and IL‐8 gene expression in both cell lines.

Conclusions

Data herein provided identified for the first time new mechanisms supporting the crucial role of cigarette smoke‐induced miR‐21 expression in the amplification of inflammatory responses and in tumorigenesis processes within the airways.
Insights into simultaneous microbial chromium and nitrate reduction: inhibitory effects and molecular mechanisms
Authors: Hu Yutian , Chen Nan , Li Miao , Feng Chuanping , Liu Tong
Published: May 2019

BACKGROUND

The potential effect of chromium on the denitrification process has drawn much attention recently. The efficient remediation of groundwater contaminated by both hexavalent chromate [Cr(VI)] and nitrate (NO3−) was hampered due to the deficiency of denitrification in the presence of Cr(VI). The goal of this work was to understand the mechanisms of how Cr(VI) affected denitrification.

RESULTS

To better understand the underlying nature, Cr(VI) effects on denitrification were investigated in batch. Negative effects of Cr(VI) exposure on denitrification were confirmed and ascribed to restriction of bacterial activities, by regulating functional genes expression and altering community composition. Stronger inhibition of the expression of denitrifying genes was observed with increased Cr(VI) loading (0–50 mg L−1). The critical inhibitory concentration and IC50 of Cr(VI) on electron transport system activities were calculated to be 3.21 and 4.87 mg L−1, respectively. Further amplicon analysis revealed that Betaproteobacteria were enriched, implying their potential key role in simultaneously removing nitrate and Cr(VI). The presence of Cr(VI) also upregulated the metabolic activities related to apoptosis.

CONCLUSION

These findings shed light on the biogeochemical fates of Cr(VI) and NO3− in aquifers, and may contribute in enhancing their practical application for bioremediation using microbial processes. © 2019 Society of Chemical Industry
An exploration of novice genetic counselors’ transitional challenges: Commencement is just the beginning
Authors: Ramachandra Divya Baktha , McCarthy Veach Patricia , LeRoy Bonnie S. , Tryon Rebecca
Published: May 2019

Although transitional challenges exist in many professions, no research has explicitly investigated challenges novice genetic counselors encounter as they enter the workforce. This qualitative study explored challenges genetic counselors face when transitioning from student to practicing counselor and their strategies for managing them. Fifteen novice genetic counselors (~1–2 years post‐degree experience), recruited via the National Society of Genetic Counselors, participated in semi‐structured phone interviews. Interview questions explored professional and personal challenges faced in their first 6 months, how challenges changed over time, strategies they used to manage these challenges, and resources they thought would have been helpful to have from the beginning. Inductive analysis of interview data yielded themes including: interpersonal challenges with colleagues (e.g. handling differences of opinion); intrapersonal challenges (e.g. lacking confidence, not feeling ready to ‘go solo’); patient care challenges (e.g. being viewed as young/inexperienced); and logistical challenges (e.g. billing). Personal challenges included moving to a new location, preparing for boards, establishing a work‐life balance, and factors associated with one's significant others. Strategies to address challenges included seeking support and guidance from experienced genetic counselors and peers, using peer supervision groups, and involvement in community activities. Participants recommended connecting with recent graduates through national and local programs to facilitate the transition from student to genetic counselor. Results suggest the ‘transition years’ pose a variety of professional and personal challenges. Support and guidance are key to evolving from student to practicing counselor. Creating venues to help novice counselors make connections with colleagues and other recent graduates may be beneficial.
Recontact practices of cancer genetic counselors and an exploration of professional, legal, and ethical duty
Authors: Mueller Amy , Dalton Emily , Enserro Danielle , Wang Catharine , Flynn Maureen
Published: May 2019

The duty to recontact continues to be revisited in the field of clinical genetics and is currently relevant for cancer genetic counseling given the transition from single‐gene to multi‐gene panel testing. We recruited cancer genetic counselors through the National Society of Genetic Counselors list‐serv to complete an online survey assessing current practices and perspectives regarding recontacting patients about diagnostic genetic tests. Forty‐one percent of respondents reported that they have recontacted patients to offer updated (new) diagnostic genetic testing (40/97). A majority (61%, 17/28), of genetic counselors who reported recontact specifically for panel testing indicated that the availability of management recommendations for genes not previously tested routinely was an important factor in the decision to recontact. All respondents who recontacted patients reported “improved patient care” as a perceived benefit. Respondents indicated that recontact is mostly a patient responsibility (49%), followed by a shared responsibility between the provider and patient (43%). Few respondents (2%) reported a uniform ethical duty to recontact patients regarding new and updated testing, while the majority (89%) felt that there was some degree of ethical duty. A greater percentage of those who reported past recontact practices reported intention to recontact in the future (p = 0.001). There is little consensus among the genetic counselor respondents about how to approach the recontacting of patients to offer updated genetic testing.
Genetic counseling job market in the United States and Canada: An analysis of job advertisements 2014–2016
Authors: Burns Kaitlyn , Swanson Amy , Hoskovec Jennifer , Leonhard Jennifer , Hahn Susan , Stein Quinn P.
Published: May 2019

Genetic counseling careers continue to evolve, yet there remains a lack of information about hiring trends in the genetic counseling profession. In this study, job advertisements in the United States and Canada were analyzed, using the National Society of Genetic Counselors (NSGC) Job Connections and the American Board of Genetic Counseling (ABGC) eBlasts from 2014 to 2016 to appraise job roles, qualifications, settings, specialties, and type. NSGC had 1875 advertised openings from 2014 to 2016, while ABGC had 373 advertised openings. Jobs containing a “counseling” role increased as a percentage from 2014 to 2016 when advertised by NSGC (χ2 = 25.52, p < 0.000001) but decreased each year from 2014 to 2016 as a percentage when advertised through ABGC (χ2 = 14.29, p = 0.0008). In the ABGC job postings, it was noted that 36% of job postings were advertised for other specialties (not solely cancer, pediatric, or prenatal) in 2014, and increased to 67% in 2016 (χ2 = 10.09, p = 0.02). Examining the job specialties posted by ABGC and NSGC, several new or unique roles were found in the job advertisements such as ophthalmology counselor, variant curator, rare diseases information specialist, and clinical policy analyst. Roles for temporary, contract or fellowship positions are possibly becoming more common, along with small upturns in positions that are off‐site or remote. In analyzing the changing workforce, there was a statistically significant decrease identified in jobs advertised by NSGC in the laboratory setting from 28% in 2014 to 17% in 2016 (χ2 = 24.12, p = 0.000024). This information on the evolving career of genetic counseling is valuable for the current workforce and training programs as they adapt with the changing landscape of the profession.
Developing culturally informed genetic services for the Somali immigrants in Minnesota
Authors: Cheung Fook Yee , Pratt Rebekah , Shire Abdirashid , Bigalke Lauren , Ahmed Zahra , Zierhut Heather
Published: May 2019

Misinformation and distrust often prevent individuals from minority communities to seek adequate healthcare, including genetic services. Immigrants appear to be further burdened by factors that negatively impact their health outcomes and little is known about their experience with genetic services. We sought to identify attitudes and perception of genetic services in one immigrant group, the Somali community of Minnesota and to establish a culturally informed framework for caring for members. A qualitative study comprised of 11 semi‐structured key informant interviews was conducted and analyzed using a thematic approach. Main themes emerged from the analysis fell within one of four major topics: (a) Somali views and perspective on genetics and healthcare, (b) barriers to uptake of genetic services, (c) facilitators to uptake of genetic services, and (d) perspective on genetic service delivery subtypes. Somali views and perspective on genetics are often framed by religious and cultural values. These values, at times, conflicted with those common in the American healthcare system. Supports for different genetic service delivery subtypes also varied, ranging from little to no support in prenatal screening to generally positive support for pharmacogenetic testing. Future studies should prioritize topics with support and ways to better provide genetic counseling services within the Somali community.
Calling a Stranger to Lead
Authors: Harter Nathan
Published: May 2019

The classic analysis by Georg Simmel (1858–1918) described the stranger as someone with unusual freedoms, proximate yet distant culturally. As such, the stranger “brings qualities … that are not and cannot be indigenous”; represents a point of contact with a wider world; and holds up a mirror to the community. He or she allows us to know ourselves differently while at the same time bringing novel ideas from the outside and expanding possibilities. In this way, the stranger contributes to group leadership, ordinarily as an outsider. Nevertheless, groups do turn to the stranger for leadership.
Comparative study of plant growth‐promoting bacteria on the physiology, growth and fruit quality of strawberry
Authors: Morais Maria C , Mucha Ângela , Ferreira Helena , Gonçalves Berta , Bacelar Eunice , Marques Guilhermina
Published: May 2019

BACKGROUND

The strawberry (Fragaria × ananassa Duch.) is, among small fruits, the most cultivated and commercialized in Portugal. Recent studies have evidenced the positive effect of plant growth‐promoting bacteria (PGPB) inoculation on strawberry production and, at the same time, provided an alternative strategy to reduce the use of fertilizers. In this study the effects of root inoculation with three PGPB strains (Pedobacter sp. CC1, Bacillus safensis B106 and Bacillus subtilis B167A) on the physiology, growth, fruit production and quality of strawberry cv. Camarosa are presented.

RESULTS

PGPB inoculation significantly accelerated crop maturation, with inoculated plants fruiting about 2 weeks earlier than non‐inoculated plants. Inoculated plants with Pedobacter sp. CC1 and Bacillus safensis B106 influenced the gas exchange parameters of strawberry plants. The contents of total phenolics and flavonoids in strawberry leaves were found to be greater with Pedobacter sp. CC1, when compared with non‐inoculated plants. Furthermore, plants inoculated with the same bacterial strain showed enhancement in the dimensions of fruits, especially fruit length, and shape as well as in the total soluble solids content (°Brix).

CONCLUSIONS

The results showed that the PGPB Pedobacter sp. CC1 improved performance of strawberry plants, suggesting that it could be a potential biofertilizer for strawberry plant nutrition. © 2019 Society of Chemical Industry
Pepper fragrant essential oil (PFEO) and functionalized MCM‐41 nanoparticles: formation, characterization, and bactericidal activity
Authors: Jin Li , Teng Jing , Hu Linghao , Lan Xiuting , Xu Yue , Sheng Jie , Song Yishan , Wang Mingfu
Published: May 2019

BACKGROUND

It is well known that plant essential oils have good antimicrobial activity. However, their strong volatility and intense odor limit their application. Mesoporous silica (MCM‐41), a non‐toxic mesoporous material with excellent loading capability, is a promising delivery system for different types of food ingredients in the food industry.

RESULTS

In this study, we first performed component analysis of pepper fragrant essential oil (PFEO) by gas chromatography – mass spectrometry (GC–MS), then the MCM‐41 host was prepared, and the essential oil functionalized nanoparticles (EONs) were formed by embedding PFEO into mesoporous silica particles. Further analysis indicated that the particle size and zeta potential of EONs were 717 ± 13.38 nm and − 43.90 ± 0.67 mV, respectively. Transmission electron microscopy (TEM) images showed that EONs had an inerratic morphology and stable structure. The bactericidal activities of PFEO and EONs against Escherichia coli (E. coli), Salmonella enterica (S. enterica), Staphylococcus aureus (S. aureus) and Listeria monocytogenes (L. monocytogenes) were subsequently tested using the twofold dilution method. Results indicated that, after 48 h incubation, minimum bactericidal concentrations (MBC) of EONs used against gram‐negative bacteria were decreased to a greater degree than those of PFEO, suggesting that nanoencapsulation by MCM‐41 can improve antimicrobial activity. Atomic force microscopy (AFM) observation also confirmed that EONs showed a notable inhibitory effect against E. coli by disrupting cell membrane structure.

CONCLUSION

Pepper fragrant essential oil nanoencapsulation could be a very promising organic delivery system in food industry for antimicrobial activity enhancement. © 2019 Society of Chemical Industry
Industry Payments for Otolaryngology Research: A Four‐Year Analysis of the Open Payments Database
Authors: Brauer Philip R. , Morse Elliot , Mehra Saral
Published: May 2019

Objective

To characterize industry research payments to otolaryngologists.

Study Design

Cross‐sectional retrospective analysis.

Methods

We examined research payments made to otolaryngologists 2014 through 2017 included in the Open Payments Database. Trends in payment values over time were characterized and compared to other surgical specialties. Geographical and temporal trends in payments to specific principal investigators, along with the ties to specific companies, were analyzed.

Results

Among surgical specialties, otolaryngology was the second lowest paid in terms of total compensation from industry for research per active U.S. physician. The median (mean) payment to otolaryngologists was $819 ($5,514), $548 ($3,083), $771 ($3,484), and $1,000 ($5,768) in 2014, 2015, 2016, and 2017, respectively. There was typically a higher mean and median payment per otolaryngologists in the Northeast, although significant differences between each region varied by year. The 40 most highly funded recipients had total compensation that was on average spread over 3.35 years of the database, 2.975 different companies, and 7.35 distinct scientific studies—all significantly higher compared to otolaryngologists with less funding.

Conclusion

Research payments to otolaryngologists are concentrated in a small number of otolaryngologists; however, many of the most highly funded principal investigators worked on numerous studies with a variety of different companies over many years. Our characterization of the Open Payments Database over 4 years illustrates the depth of relationship between otolaryngology research and industry as well as raises awareness regarding the ease of connecting otolaryngologists to research payments.

Level of Evidence

NA Laryngoscope, 130:314–320, 2020
Hyperprogression after one dose of nivolumab in sinonasal cancer: A case report
Authors: Xiang Jenny J. , Uy Natalie F. , Minja Frank J. , Verter Erol E. , Burtness Barbara A.
Published: May 2019

In head and neck squamous cell carcinoma, immune checkpoint inhibitors (ICI) lead to improved outcomes. There has been reports of accelerated disease progression, or hyperprogression, after ICI initiation. We present a case of hyperprogression after one dose of nivolumab in maxillary sinus squamous cell carcinoma. The patient had complete vision loss due to disease progression into the orbit, as well as intracranial invasion, lytic metastases, and new widespread distal metastases. Hyperprogression can occur after the first dose of immunotherapy. Absent biomarkers regarding individual risk of hyperprogression, caution should be exercised in using ICI in sinonasal cancers with orbital abutting disease. Laryngoscope, 130:907–910, 2020
Variation in dissolved organic matter (DOM) stoichiometry in U.K. freshwaters: Assessing the influence of land cover and soil C:N ratio on DOM composition
Authors: Yates Christopher A. , Johnes Penny J. , Owen Alun T. , Brailsford Francesca L. , Glanville Helen C. , Evans Christopher D. , Marshall Miles R. , Jones David L. , Lloyd Charlotte E. M. , Jickells Tim , Evershed Richard P.
Published: May 2019

Dissolved organic matter (DOM) plays an important role in freshwater biogeochemistry. To investigate the influence of catchment character on the quality and quantity of DOM in freshwaters, 45 sampling sites draining subcatchments of contrasting soil type, hydrology, and land cover within one large upland‐dominated and one large lowland‐dominated catchment were sampled over a 1‐yr period. Dominant land cover in each subcatchment included: arable and horticultural, blanket peatland, coniferous woodland, and improved, unimproved, acid, and calcareous grasslands. The composition of the C, N, and P pool was determined as a function of the inorganic nutrient species (NO3−, NO2−, NH4+, and PO43−) and dissolved organic nutrient (dissolved organic carbon [DOC], dissolved organic nitrogen [DON], and dissolved organic phosphorus [DOP]) concentrations. DOM quality was assessed by calculation of the molar DOC : DON and DOC : DOP ratios and specific ultraviolet absorbance (SUVA254). In catchments with little anthropogenic nutrient inputs, DON and DOP typically composed > 80% of the total dissolved nitrogen (TDN) and total dissolved phosphorus (TDP) concentrations. By contrast, in heavily impacted agricultural catchments DON and DOP typically comprised 5–15% of TDN and 10–25% of TDP concentrations. Significant differences in DOC : DON and DOC : DOP ratios were observed between land cover class with significant correlations observed between both the DOC : DON and DOC : DOP molar ratios and SUVA254 (rs = 0.88 and 0.84, respectively). Analysis also demonstrated a significant correlation between soil C : N ratio and instream DOC : DON/DOP (rs = 0.79 and 0.71, respectively). We infer from this that soil properties, specifically the C : N ratio of the soil organic matter pool, has a significant influence on the composition of DOM in streams draining through these landscapes.
A glimpse of the prokaryotic diversity of the Large Aral Sea reveals novel extremophilic bacterial and archaeal groups
Authors: Shurigin Vyacheslav , Hakobyan Anna , Panosyan Hovik , Egamberdieva Dilfuza , Davranov Kakhramon , Birkeland Nils‐Kåre
Published: May 2019

During the last five decades, the Aral Sea has gradually changed from a saline water body to a hypersaline lake. Microbial community inhabiting the Aral Sea has been through a succession and continuous adaptation during the last 50 years of increasing salinization, but so far, the microbial diversity has not been explored. Prokaryotic diversity of the Large Aral Sea using cultivation‐independent methods based on determination of environmental 16S rRNA gene sequences revealed a microbial community related to typical marine or (hyper) saline‐adapted Bacteria and Archaea. The archaeal sequences were phylogenetically affiliated with the order Halobacteriales, with a large number of operational taxonomic units constituting a novel cluster in the Haloferacaceae family. Bacterial community analysis indicated a higher diversity with representatives belonging to Proteobacteria, Actinobacteria and Bacteroidetes. Many members of Alphaproteobacteria and Gammaproteobacteria were affiliated with genera like Roseovarius, Idiomarina and Spiribacter which have previously been found in marine or hypersaline waters. The majority of the phylotypes was most closely related to uncultivated organisms and shared less than 97% identity with their closest match in GenBank, indicating a unique community structure in the Large Aral Sea with mostly novel species or genera.
Cost‐Effectiveness of Deep Brain Stimulation With Movement Disorders: A Systematic Review
Authors: Dang Tho Thi Hai , Rowell David , Connelly Luke B.
Published: May 2019

Background

Movement disorders (MDs) are increasingly being managed with deep brain stimulation (DBS). High‐quality economic evaluations (EEs) are necessary to evaluate the cost‐effectiveness of DBS. We conducted a systematic review of published EEs of the treatment of MDs with DBS. The review compares and contrasts the reported incremental cost‐effectiveness ratios (ICERs) and methodology employed by trial‐based evaluations (TBEs) and model‐based evaluations (MBEs).

Methods

MeSH and search terms relevant to “MDs,” “DBS,” and “EEs” were used to search biomedical and economics databases. Studies that used a comparative design to evaluate DBS, including before‐after studies, were included. Quality and reporting assessments were conducted independently by 2 authors. Seventeen studies that targeted Parkinson's disease (PD), dystonia, and essential tremor (ET), met our selection criteria.

Results

Mean scores for methodological and reporting quality were 73% and 76%, respectively. The ICERs for DBS compared with best medical therapy to treat PD patients obtained from MBEs had a lower mean and range compared with those obtained from TBEs ($55,461–$735,192 per quality‐adjusted life‐year [QALY] vs. $9,301–$65,111 per QALY). Pre‐post ICER for DBS to treat dystonia was $64,742 per QALY. DBS was not cost‐effective in treating ET compared with focused‐ultrasound surgery. Cost‐effectiveness outcomes were sensitive to assumptions in health utilities, surgical costs, battery life‐span, model time horizons, and the discount rate.

Conclusions

The infrequent use of randomized, controlled trials to evaluate DBS efficacy, the paucity of data reporting the long‐term effectiveness and/or utility of DBS, and the uncertainty surrounding cost data limit our ability to report cost‐effectiveness summaries that are robust.
Genome‐wide survey of copy number variants finds MAPT duplications in progressive supranuclear palsy
Authors: Chen Zhongbo , Chen Jason A. , Shatunov Aleksey , Jones Ashley R. , Kravitz Stephanie N. , Huang Alden Y. , Lawrence Lauren , Lowe Jennifer K. , Lewis Cathryn M. , Payan Christine A. M. , Lieb Wolfgang , Franke Andre , Deloukas Panagiotis , Amouyel Philippe , Tzourio Christophe , Dartigues Jean‐François ,   NNIPPS and BBBIPPS Study Groups, Ludolph Albert , Bensimon Gilbert , Leigh P. Nigel , Bronstein Jeff M. , Coppola Giovanni , Geschwind Daniel H. , Al‐Chalabi Ammar
Published: May 2019

Background

Progressive supranuclear palsy is a neurodegenerative tauopathy manifesting clinically as a progressive akinetic‐rigid syndrome. In this study, we sought to identify genetic variants influencing PSP susceptibility through a genome‐wide association analysis of a cohort of well‐characterized patients who had participated in the Neuroprotection and Natural History in Parkinson Plus Syndromes and Blood Brain Barrier in Parkinson Plus Syndromes studies.

Methods

We genotyped single‐nucleotide polymorphisms in 283 PSP cases from the United Kingdom, Germany, and France and compared these with genotypes from 4472 controls. Copy number variants were identified from genotyping data.

Results

We observed associations on chromosome 17 within or close to the MAPT gene and explored the genetic architecture at this locus. We confirmed the previously reported association of rs1768208 in the MOBP gene (P = 3.29 × 10‐13) and rs1411478 in STX6 (P = 3.45 × 10‐10). The population‐attributable risk from the MAPT, MOBP, and STX6 single‐nucleotide polymorphisms was found to be 0.37, 0.26, and 0.08, respectively. In addition, we found 2 instances of copy number variants spanning the MAPT gene in patients with PSP. These copy number variants include tau but few other genes within the chromosome 17 haplotype region, providing additional support for the direct pathogenicity of MAPT in PSP.

Conclusions

Clinicians should also be aware of MAPT duplication as a possible genetic cause of PSP, especially in patients presenting with young age at onset. © 2019 International Parkinson and Movement Disorder Society
Diverse phenotypes in children with PAX2‐related disorder
Authors: Deng Haiyue , Zhang Yanqin , Xiao Huijie , Yao Yong , Liu Xiaoyu , Su Baige , Zhang Hongwen , Xu Ke , Wang Suxia , Wang Fang , Ding Jie
Published: May 2019

Background

The aim of this study was to analyze the diverse phenotypes of children with PAX2‐related disorder so as to improve our understanding of this disease.

Methods

The clinical data of ten children with PAX2 mutations, detected by targeted region capture sequencing or whole‐exome sequencing, were retrospectively analyzed. Family members of index cases were verified by Sanger sequencing and family segregation analysis was performed.

Results

The age of first symptom of 10 unrelated children (six girls and four boys) was 6.4 (ranged from postnatal day to 14.8) years old. Proteinuria, abnormal renal function, and structure were found in all patients. Renal hypoplasia and renal cysts were found in 10 of 10 and five of 10 cases, respectively. Three patients progressed to chronic kidney disease stage 5 and the onset age of end‐stage renal disease was 9.8–16.4 years old. PAX2‐related ocular abnormalities were found in five of seven cases and three patients were observed to have more than one ocular findings involved. In addition to diverse renal and ocular findings, new phenotypes including congenital ventricular septal defect, skeletal deformity (fourth metatarsal microsomia), ovarian teratoma, and relatively rare extrarenal manifestations such as growth retardation, gout, and microcephaly were also found. Three novel mutations were reported for the first time. De novo mutations occurred in all patients who were carried out segregation analysis. Patients with the same mutation had different manifestations. PAX2‐related disorder showed remarkable clinical variability and phenotypic heterogeneity.

Conclusion

We firstly reported skeletal deformity (fourth metatarsal microsomia), ovarian teratoma, and congenital ventricular septal defect as new phenotypes of PAX2‐related disorder which enlarged the phenotypic spectrum. Gout was firstly reported as the onset symptom of PAX2‐related disorder. The diagnosis of PAX2‐related disorder should be considered without family history due to a much higher percentage of De novo mutations.
States hardest hit by suicide share best‐practice experiences
Authors: Enos Gary
Published: May 2019

States can stem rising suicide rates through collaborative approaches that start with a governor's leadership and acknowledge that health care settings alone cannot be the sole focus for action, a new report from the National Governors Association (NGA) concludes.
A wideband loop‐type ground radiation antenna using ground mode tuning and optimum impedance level
Authors: Hassan Muhammad M. , Zahid Zeeshan , Khan Adnan A. , Maqsood Moazam
Published: May 2019

In this article, a wideband loop‐type ground radiation antenna is proposed for USB dongle applications. Wide bandwidth has been achieved using the orientation of the antenna embedded in the ground plane along with the impedance level of the feed structure. The ground clearance of the antenna is utilized so that the ground mode is tuned to the mid‐band frequency. The impedance level is controlled by using a series combination of a lumped inductor and a capacitor in the feed loop of the antenna. A good agreement between measured and simulated results has been observed. The measured bandwidth and peak total efficiency of the antenna are 1180 MHz and 88.27%, respectively.
Accumulation of the delivered treatment dose in volumetric modulated arc therapy with breath‐hold for pancreatic cancer patients based on daily cone beam computed tomography images with limited field‐of‐view
Authors: Ziegler Marc , Nakamura Mitsuhiro , Hirashima Hideaki , Ashida Ryo , Yoshimura Michio , Bert Christoph , Mizowaki Takashi
Published: May 2019

Background and purpose

Inter‐fractional changes of the daily anatomy of the patient are a source of error in radiotherapy. This effect is especially present in the abdomen, where there are daily differences in the filling of the stomach or the intestines. This study investigated the impact of inter‐fractional changes of pancreatic cancer patients who underwent breath‐hold volumetric modulated arc therapy on the applied dose by using deformable image registration.

Material and methods

Deformable image registration was used to determine a displacement field which maps the computed tomography (CT) used for treatment planning onto daily breath‐hold cone‐beam CT images with limited field‐of‐view (FOV) which were acquired at the beginning of every treatment fraction. Different B‐spline registration methods utilizing different metrics and regularizations were used and compared. The resulting deformed planning CT images were used to calculate the dose distributions on the anatomy of the day which can therefore be seen as a good estimation of the actually delivered dose during the treatment fractions. Additionally, the accumulated dose distribution was determined by accumulating all daily dose distributions using inverted deformation fields. The calculated dose distributions were then compared to the planned dose by comparison of dose volume histograms and dosimetric volumetric indices.

Results

Best registration results were obtained using a gradient magnitude metric and a regularization of λ = 0.05. The accumulated dose distributions showed that the mean dose delivered to the clinical target volume was on median reduced by 0.61 Gy after 15 fractions from the planned dose. For the organs at risk, the accumulated dose distributions were still fulfilling all clinical goals for the patient cohort used in this study. It was found that rotating and shearing motions of the tumor led to a greater reduction in the mean target dose which correlated with the proximity of the target to the spine (r = 0.54, P = 0.038).

Conclusion

With the proposed method, it is possible to generate a deformed planning CT image which matches the anatomy of the day based on cone beam computed tomography images with a limited FOV and calculating the dose distribution of the day. The dosimetric impact of the inter‐fractional variations was small for most patients but showed larger deviations if the tumor is located in close proximity to the spine.
Scatter correction for a clinical cone‐beam CT system using an optimized stationary beam blocker in a single scan
Authors: Liang Xiaokun , Jiang Yangkang , Zhao Wei , Zhang Zhicheng , Luo Chen , Xiong Jing , Yu Shaode , Yang Xiaoming , Sun Jihong , Zhou Qinxuan , Niu Tianye , Xie Yaoqin
Published: May 2019

Purpose

Scatter contamination in the cone‐beam CT (CBCT) leads to CT number inaccuracy, spatial nonuniformity, and loss of image contrast. In our previous work, we proposed a single scan scatter correction approach using a stationary partial beam blocker. Although the previous method works effectively on a tabletop CBCT system, it fails to achieve high image quality on a clinical CBCT system mainly due to the wobble of the LINAC gantry during scan acquisition. Due to the mechanical deformation of CBCT gantry, the wobbling effect is observed in the clinical CBCT scan, and more missing data present using the previous blocker with the uniformly distributed lead strips.

Methods

An optimal blocker distribution is proposed to minimize the missing data. In the objective function of the missing data, the motion of the beam blocker in each projection is estimated using the segmentation due to its high contrast in the blocked area. The scatter signals from the blocker are also estimated using an air scan with the inserted blocker. The final image is generated using the forward projection to compensate for the missing data.

Results

On the Catphan©504 phantom, our approach reduces the average CT number error from 86 Hounsfield unit (HU) to 9 HU and improves the image contrast by a factor of 1.45 in the high‐contrast rods. On a head patient, the CT number error is reduced from 97 HU to 6 HU in the soft‐tissue region and the image spatial nonuniformity is decreased from 27% to 5%.

Conclusions

The results suggest that the proposed method is promising for clinical applications.
NMR metabolomics to study the metabolic response of human osteoblasts to non‐poled and poled poly (L‐lactic) acid
Authors: Araújo Rita , Carneiro Tatiana J. , Marinho Paula , da Costa Marisa Maltez , Roque Ana , da Cruz e Silva Odete A. B. , Fernandes Maria Helena , Vilarinho Paula M. , Gil Ana M.
Published: May 2019

Untargeted nuclear magnetic resonance (NMR) metabolomics was employed, for the first time to our knowledge, to characterize the metabolome of human osteoblast (HOb) cells and extracts in the presence of non‐poled or negatively poled poly‐L‐lactic acid (PLLA). The metabolic response of these cells to this polymer, extensively used in bone regeneration strategies, may potentially translate into useful markers indicative of in vivo biomaterial performance.

We present preliminary results of multivariate and univariate analysis of NMR spectra, which have shown the complementarity of lysed cells and extracts in terms of information on cell metabolome, and unveil that, irrespective of poling state, PLLA‐grown cells seem to experience enhanced oxidative stress and activated energy metabolism, at the cost of storage lipids and glucose. Possible changes in protein and nucleic acid metabolisms were also suggested, as well as enhanced membrane biosynthesis. Therefore, the presence of PLLA seems to trigger cell catabolism and anti‐oxidative protective mechanisms in HOb cells, while directing them towards cellular growth. This was not sufficient, however, to lead to a visible cell proliferation enhancement in the presence of PLLA, although a qualitative tendency for negatively poled PLLA to be more effective in sustaining cell growth than non‐poled PLLA was suggested. These preliminary results indicate the potential of NMR metabolomics in enlightening cell metabolism in response to biomaterials and their properties, justifying further studies of the fine effects of poled PLLA on these and other cells of significance in tissue regeneration strategies.
Proximal location of explanted midurethral slings is associated with urinary storage symptoms
Authors: Dropkin Benjamin M. , Kowalik Casey G. , Jaunarena Jorge H. , Delpe Sophia D. , Reynolds William S. , Dmochowski Roger R. , Kaufman Melissa R.
Published: May 2019

Aim

To examine the location of midurethral slings (MUS) at the time of excision to determine associations between presenting symptoms and sling location at explant.

Methods

We performed an IRB approved, retrospective review of MUS explants between January 2011 and March 2016. Symptoms and physical examination findings were compared between women with slings explanted from the mid‐urethra (MU) and women with slings explanted from the proximal urethra/bladder neck (PU/BN).

Results

We included 95 consecutive women who underwent MUS explant in the analysis. Presenting symptoms included pain in 69 women (72.6%), urinary urgency in 66 (66.5%), voiding dysfunction in 55 (57.9%), urge urinary incontinence (UUI) in 41 (43.2%), stress urinary incontinence in 34 (35.8%), and recurrent urinary tract infections in 22 (23.2%). At sling explant, 2 (2.1%) slings were found at the distal urethra, 33 (34.7%) at the MU and 60 (63.2%) at the PU/BN. Women with slings explanted from the PU/BN were more likely to present with urgency (78.3% vs 54.5%; P = 0.017) and UUI (53.3% vs 27.3%; P = 0.015) and less likely to present with pain on examination (48.3% vs 75.8%; P = 0.01).

Conclusions

The majority of MUS requiring explant in this cohort were found at the PU/BN. The most common presenting symptom before MUS explant was pain, followed by urgency and voiding dysfunction. PU/BN location of MUS is likely a factor in the development of urgency and UUI in women who ultimately undergo explant.
Stochastic multiscale modeling of crack propagation in random heterogeneous media
Authors: Hun Darith‐Anthony , Guilleminot Johann , Yvonnet Julien , Bornert Michel
Published: May 2019

A stochastic approach to model crack propagation in random heterogeneous media, using mesoscopic representations of elastic and fracture properties, is presented. In order to obtain reference results, Monte‐Carlo simulations are first conducted on microstructural samples in which a pre‐existing crack is propagated by means of a phase‐field approach. These computations are used to estimate the subscale‐induced randomness on the macroscopic response of the domain. Mesoscopic descriptors are then introduced to investigate scale transition. Elasticity tensor random fields are specifically defined, at that stage, through a moving‐window upscaling approach. The mesoscopic fracture toughness, which is assumed homogeneous and deterministic, is identified by solving an inverse problem involving the macroscopic peak force. A stochastic model is subsequently constructed in which the mesoscopic elasticity is described as a non‐Gaussian random field. This model allows the multiscale‐informed elastic counterpart in the phase‐field formulation to be sampled without resorting to computational homogenization. The results obtained with the sample‐based and model‐based mesoscopic descriptions are finally compared with those corresponding to the full‐scale microscopic model. It is shown, in particular, that the mesoscopic elasticity‐phase‐field formulation associated with statically uniform boundary conditions enables the accurate predictions of the mean elastic response and mean peak force.
Attract Tomorrow's Water/Wastewater Workforce Today
Authors: Jones Don
Published: May 2019

The silver lining to the “silver tsunami” involves using a nontraditional recruitment strategy to build tomorrow's technically proficient workforce.
Use a Hold Study to Assess Distribution System Influent Water Quality
Authors: Alexander Matthew T. , Dugan Alison G. , Wahman David G.
Published: May 2019

Whether water is coming directly from a drinking water treatment plant or through a metered connection to a consecutive system, water utilities can improve water quality by assessing the stability of the distribution system's influent disinfectant residual and the corresponding potential for disinfection byproduct formation.
Innovating the Future of Water at ACE19
Authors: Moore Randy
Published: May 2019

ACE19, which will be held June 9–12 in Denver, will be the place to learn, connect, and be inspired to solve today's global water challenges. “Innovating the Future of Water” returns as this year's conference theme, with new technologies and water sector innovations highlighted throughout the conference. The Innovation Lounge in the exhibit hall will again be the focal point for exciting new technologies, ideas, and lively discussion about innovation in the water industry.
Linoleic acid in diets of mice increases total endocannabinoid levels in bowel and liver: modification by dietary glucose
Authors: Ghosh S. , O'Connell J. F. , Carlson O. D. , González‐Mariscal I. , Kim Y. , Moaddel R. , Ghosh P. , Egan J. M.
Published: May 2019

Aim

Linoleic acid (LA) is an essential fatty acid involved in the biosynthesis of arachidonic acid and prostaglandins. LA is known to induce obesity and insulin resistance. In this study, two concentrations of LA with or without added glucose (G) were fed to mice to investigate their effects on endocannabinoid (EC) biology.

Materials and Methods

Four groups of C57BL/6 mice were provided with diets containing 1% or 8% LA with or without added G (LAG) for 8 weeks. Body weights, food intake, circulating glucose and insulin levels were measured throughout the study. Following euthanasia, plasma, bowel and hepatic ECs, monoacylglycerol lipase and fatty acid amide hydroxylase protein levels (enzymes responsible for EC degradation) and transcriptional activity of PPARα in liver were quantified. Liver was probed for evidence of insulin receptor activity perturbation.

Results

Increasing dietary LA from 1% to 8% significantly increased circulating, small bowel and hepatic ECs. 1%LAG fed mice had lowest feed efficiency, and only liver levels of both ECs were reduced by addition of G. Addition of G to 1% LA diets resulted in elevated monoacylglycerol lipase and fatty acid amide hydroxylase protein levels (p < 0.001 and p < 0.001, respectively) in liver due to increased transcriptional activity of PPARα (p < 0.05). The reduced EC levels with addition of G also correlated with a measure of enhanced insulin action.

Conclusion

In conclusion, body weight of mice is influenced by the source of calorie intake. Furthermore, tissue EC/g are dependent on tissue‐specific synthesis and degradation that are modulated by dietary LA and G which also influence food efficiency, and down‐stream insulin signalling pathways. The findings could potentially be useful information for weight management efforts in humans.
Germline mutation and aberrant transcripts of WWOX in a syndrome with multiple primary tumors
Authors: Xu Ao , Wang Wei , Nie Jinfu , Lui Vivian WY , Hong Bo , Lin Wenchu
Published: May 2019

Multiple primary tumors are defined by the presence of two or more independent primary tumors in the same or different organs of an individual patient. However, the underlying genetic cause for the development of multiple primary tumors is largely unknown. In the study, we report a rare case with four synchronous distinct histological cancer types in a 26 years old Chinese female. In the patient, whole‐exome sequencing identified a homozygous germline insertion mutation in WWOX which encodes the DNA repair‐related enzyme, WW domain containing oxidoreductase. The mutation was found in a heterozygous state in her parents and brother without any cancer phenotype thus far. Surprisingly, we found multiple novel aberrant WWOX transcripts in the patient's normal colon tissue. The patient's colon metastasis from clear cell adenocarcinoma of the ovary showed a nonhypermutated profile enriched for C‐T transition, and harbored somatic pathogenic mutations of HRAS, BRCA2, SMAD4, CHEK2, and AKT1 genes. To our knowledge, this is the first study reporting WWOX gene aberrations in a young patient with the early occurrence of multiple primary tumors. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Psychosocial issues for adolescent and young adult cancer patients in a global context: A forward‐looking approach
Authors: Levin Nina Jackson , Zebrack Bradley , Cole Steve W.
Published: May 2019

The first decade of adolescent and young adult (AYA) oncology psychosocial care and research (2005–2015) was driven by a normative, developmental framework that assumed a generalizable life experience for AYAs that is distinct from both younger children and older adults. As we proceed through a second decade, new considerations emerge regarding diversity of life experiences as occurring within and influenced by a complex global context. The purpose of this paper is to review and provide commentary on the impact of global and contextual conditions on AYAs. We expound upon the effects of precarious labor conditions, changing timetables and priorities for developmental tasks, sexual and gender plurality, and expanding cultural diversity. We discuss the implications of social genomics and technology and social media for enhancing precision psychosocial medicine. To build a forward‐looking approach, this paper calls for tailored, multilevel treatments that consider variability of AYAs within the social and global contexts in which they live.