bluuebunny/crossref_metadata_2025 huggingface dataset:
A positive feedback loop between Wnt/β‐catenin signaling and hTERT regulates the cancer stem cell‐like traits in radioresistant nasopharyngeal carcinoma cells
Authors: Chen Kaihua , Chen Li , Li Ling , Qu Song , Yu Binbin , Sun Yongchu , Wan Fangzhu , Chen Xishan , Liang Renba , Zhu Xiaodong
Published: February 2020

Radioresistance may be induced by cancer stem cells (CSCs), while the biological traits of CSCs need to be retained by telomerase. The telomerase activity mainly depends on the transcriptional regulation of human telomerase reverse transcriptase (hTERT). Moreover, Wnt/β‐catenin signaling is also considered essential for maintaining the CSC phenotypes. In the previous study, we discovered that the radioresistant nasopharyngeal carcinoma cells CNE‐2R displayed CSC‐like traits, as well as high expression of hTERT and β‐catenin, but whether hTERT and β‐catenin were involved in regulating the CSC‐like traits and radiosensitivity of CNE‐2R cells remained unclear. In this study, our results suggested that hTERT could positively regulate the expression of CSC‐related proteins, as well as the cytoplasm‐ and nucleus‐β‐catenin, but it could not markedly regulate the expression of total β‐catenin in CNE‐2R cells. Meanwhile, Wnt/β‐catenin signaling had a positive regulatory effect on the expression of hTERT and CSC‐related proteins. Moreover, there was a β‐catenin/hTERT protein complex in CNE‐2R cells, indicating that β‐catenin could directly interact with hTERT protein. Our results also revealed that silencing hTERT or suppressing Wnt/β‐catenin signaling could attenuate telomerase activity and radioresistance of CNE‐2R cells; while suppressing Wnt/β‐catenin signaling, the telomerase activity and radioresistance could be reversed through overexpressing hTERT. Taken together, we have outlined a positive feedback loop between Wnt/β‐catenin signaling and hTERT in CNE‐2R cells, which can regulate the telomerase activity and CSC‐like traits, thus regulating the radiosensitivity. Therefore, blocking Wnt/β‐catenin signaling transduction and interfering with hTERT expression may be a promising approach for targeting radioresistant nasopharyngeal carcinoma cells with CSC‐like traits.
Inhibition of MAGEA2 regulates pluripotency, proliferation, apoptosis, and differentiation in mouse embryonic stem cells
Authors: Park Song , Han Jee Eun , Kim Hyeon‐Gyeom , Kim Hee‐Yeon , Kim Min‐Gi , Park Jin‐Kyu , Cho Gil‐Jae , Huang Hai , Kim Myoung Ok , Ryoo Zae Young , Han Se‐Hyeon , Choi Seong‐Kyoon
Published: February 2020

Mouse embryonic stem cells (mESCs) exhibit self‐renewal and pluripotency, can differentiate into all three germ layers, and serve as an essential model in stem cell research and for potential clinical application in regenerative medicine. Melanoma‐associated antigen A2 (MAGEA2) is not expressed in normal somatic cells but rather in different types of cancer, especially in undifferentiated cells, such as in the testis, differentiating cells, and ESCs. However, the role of MAGEA2 in mESCs remains to be clarified. Accordingly, in this study, we examined the expression and functions of MAGEA2 in mESCs. MAGEA2 messenger RNA (mRNA) expression was decreased during mESCs differentiation. MAGEA2 function was then evaluated in knockdown mESC. MAGEA2 knockdown resulted in decreased pluripotency marker gene expression in mESCs consequent to increased Erk1/2 phosphorylation. Decreased MAGEA2 expression inhibited mESC proliferation via S phase cell cycle arrest with a subsequent decrease in cell cycle‐associated genes Cdk1, Cdk2, Cyclin A1, Cyclin D1, and Cdc25a. Apoptotic mESCs markedly increased along with cleaved forms of caspases 3, 6, and 7 and PARP expression, confirming caspase‐dependent apoptosis. MAGEA2 knockdown significantly decreased embryoid body size in vitro when cells were differentiated naturally and teratoma size in vivo, concomitant with decreased ectoderm marker gene expression. These findings suggested that MAGEA2 regulates ESC pluripotency, proliferation, cell cycle, apoptosis, and differentiation. The enhanced understanding of the regulatory mechanisms underlying diverse mESC characteristics will facilitate the clinical application of mESCs.
microRNA expression profiles and the potential competing endogenous RNA networks in NELL‐1‐induced human adipose‐derived stem cell osteogenic differentiation
Authors: Yu Liyuan , Cen Xiao , Xia Kai , Huang Xinqi , Sun Wentian , Zhao Zhihe , Liu Jun
Published: February 2020

Studies have indicated that Nel‐like molecule‐1 (NELL‐1) was an osteoblast‐specific cytokine and some specific microRNAs (miRNAs) could serve as competing endogenous RNA (ceRNA) to partake in osteogenic differentiation of human adipose‐derived stem cells (hASCs). The aim of this study was to explore the potential functional mechanisms of recombinant human NELL‐1 protein (rhNELL‐1) during hASCs osteogenic differentiation. rhNELL‐1 was added to osteogenic medium to activate osteogenic differentiation of hASCs. High‐throughput RNA sequencing (RNA‐Seq) was performed and validated by real‐time quantitative polymerase chain reaction. Gene ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway analysis were performed to detect the functions of differentially expressed miRNAs and genes. Coding‐noncoding gene co‐expression network and ceRNA networks were constructed to predict the potential regulatory role of miRNAs. A total of 1010 differentially expressed miRNAs and 1762 differentially expressed messenger RNAs (mRNAs) were detected. miRNA‐370‐3p, bone morphogenetic protein 2 (BMP2), and parathyroid hormone like hormone (PTHLH) were differentially expressed during NELL‐1‐induced osteogenesis. Bioinformatic analyses demonstrated that these differentially expressed miRNAs and mRNAs enriched in Rap1 signaling pathway, PI3K‐Akt signaling pathway, p53 signaling pathway, Glucagon signaling pathway, and hypoxia‐inducible factor‐1 signaling pathway, which were important pathways related to osteogenic differentiation. In addition, miRNA‐370‐3p and has‐miR‐485‐5p were predicted to interact with circ0001543, circ0002405, and ENST00000570267 in ceRNA networks. Based on the gain or loss of functional experiments by transfection, the results showed that miR‐370‐3p was a key regulator in osteogenic differentiation by targeting BMP2 and disturbing the expression of PTHLH, and participated in NELL‐1‐stimulated osteogenesis. The present study provided the primary data and evidence for further exploration on the roles of miRNAs and ceRNAs during NELL‐1‐induced ossification of hASCs.
LINC02595 promotes tumor progression in colorectal cancer by inhibiting miR‐203b‐3p activity and facilitating BCL2L1 expression
Authors: Yang Zhidong , An Yue , Wang Ningning , Dong Xihua , Kang Hui
Published: February 2020

Colorectal cancer (CRC) is one of the most prevalent tumors worldwide. Recently, long noncoding RNAs (lncRNAs) have been recognized as key regulators in postgenomic biology. Numerous lncRNAs have been identified as diagnostic biomarkers and therapeutic targets. However, the molecular mechanisms underlying the role of lncRNAs in CRC progression are not fully understood. Differentially expressed lncRNAs and messenger RNAs were investigated using a microarray approach in five paired primary CRC tumor tissues and the corresponding nontumor tissues and confirmed in an additional 116 paired tissues and 21 inflammatory bowel disease tissues and 15 adjacent normal tissues by a quantitative real‐time polymerase chain reaction. We also performed comprehensive transcriptome profiling analysis on Gene Expression Omnibus and The Cancer Genome Atlas datasets. We identified LINC02595 and evaluated its clinical significance as a plasma biomarker. The function of LINC02595 was evaluated using a panel of in vivo and vitro assays, including cell counting kit‐8, colony formation, cell cycle, apoptosis, RNA fluorescence in situ hybridization, luciferase reporter, immunohistochemistry, and CRC xenografts. We found that LINC02595 is upregulated in tumor tissues and blood samples of patients with CRC and CRC cell lines. Functional research found that LINC02595 promotes CRC cell growth, influences the cell cycle, and reduces apoptosis in vitro and vivo. Mechanistically, LINC02595 promoted BCL2‐like 1 (BCL2L1) expression through miR‐203b‐3p sponging. Our research demonstrated that LINC02595 is an oncogene in CRC and established the presence of a LINC02595‐miR‐203b‐BCL2L1 axis in CRC, which might provide a new diagnostic biomarker and therapeutic targets for the treatment of this disease.
Mannuronic Acid in Low‐Risk and Intermediate‐1‐Risk Myelodysplastic Syndromes
Authors: Ghaderi Afshin , Nodehi Sayyed Reza Safaee , Bakhtiari Tahereh , Aslani Mona , Aghazadeh Zahra , Matsuo Hidenori , Rehm Bernd H. A. , Cuzzocrea Salvatore , Mirshafiey Abbas
Published: February 2020

The discovery of hematologic improvement and bone marrow modification by the drug β‐D mannuronic acid (M2000) during treatment of rheumatoid arthritis in phase 1/2/3 clinical trials prompted us to design a new trial to target hematologic deficits in myelodysplastic syndromes (MDS). In this open‐label, randomized phase 2 clinical trial, the potential effect and tolerability of drug M2000 was assessed in patients with low‐ and intermediate‐1‐risk MDS. The primary efficacy end point was hematologic improvement after 12 weeks of β‐D‐mannuronic acid therapy. Among 34 enrolled patients, half received their conventional therapy plus β‐D‐mannuronic acid, and the other half received only conventional drugs. In the conventional + β‐D mannuronic acid treatment group, hematologic improvement and development of transfusion independence and/or reduction in transfusion requirements were seen in 12 patients (92.3%) and 1 patient (7.7%), respectively. Moreover, 5 patients (38.5%), 2 patients (15.4%), and 1 patient (7.7%) in the β‐D‐mannuronic acid‐treated group showed hematologic improvement of the major parameters of erythroid, neutrophil, and platelet responses, respectively, based on the International Working Group criteria), whereas in the conventional treatment group as control, no hematologic improvements including erythroid, neutrophil, and platelet response was seen. In this trial, the addition of β‐D mannuronic acid to conventional treatment showed promising results in MDS patients with low and intermediate‐1 risk with effects on hematologic improvements without significant adverse effect.
Random walk hitting times and effective resistance in sparsely connected Erdős‐Rényi random graphs
Authors: Sylvester John
Published: February 2020

We prove a bound on the effective resistance between two vertices of a connected graph which contains a suitably well‐connected subgraph. We apply this bound to the Erdős‐Rényi random graph with , proving that concentrates around , that is, the sum of reciprocal degrees. We also prove expectation and concentration results for the random walk hitting times, Kirchoff index, cover cost, and the random target time (Kemeny's constant) on in the sparsely connected regime .
Long‐range reservoir inflow forecasts using large‐scale climate predictors
Authors: Moradi Amir M. , Dariane Alireza B. , Yang Guang , Block Paul
Published: February 2020

Identifying significant large‐scale climate indicators has the potential to improve long‐range streamflow forecasts. In this research, we develop streamflow forecasts for Lake Urmia basin, Iran, specifically for inflow into the Boukan and Mahabad reservoirs. In doing so, two types of inflow forecast models are considered: a single site univariate model ignoring the cross correlation between streamflow at different stations, and a multi‐site multivariate forecast model which takes into consideration the cross correlations among stations. Predictor selection is performed through a principal component analysis and an adaptive‐network‐based fuzzy inference system is used to forecast streamflow. Forecast performance is investigated by employing different combinations of large‐scale climatic information and hydrologic data. We found that gridded ocean‐atmospheric circulation variables, including surface precipitation rate and omega (pressure vertical velocity), have the highest correlations (about 0.7) with annual streamflow. In general, multivariate models are able to better preserve the annual cross‐correlations between streamflow at different stations, as expected, without sacrificing forecast skill as compared to the univariate forecast model approach. Additionally, as compared with the baseline feed‐forward artificial neural network‐ and traditional multiple linear regression‐forecast models, the results were approximately the same. This similarity in the forecast performance between the linear and nonlinear models is likely due to the short of data (44‐sample record).
Environmental and Psychological Factors that Influence the Creative Excellence of Brazilian and Portuguese Women
Authors: Mundim Maria Célia Bruno , Wechsler Solange Muglia , Morais Maria de Fátima
Published: February 2020

There is increasing recognition of the importance of creativity for social development. The purpose of this study was to investigate whether there were differences among Brazilian and Portuguese women recognized for their creative excellence in relation to the psychological and environmental factors that might impact their achievements. The sample was composed of 33 women; 18 who were socially recognized for excellence in creativity in different areas (nine Brazilian, nine Portuguese) were compared to 15 who were not recognized (nine Brazilian, six Portuguese). The instruments used were the Biographical Questionnaire of Creative Women, a semi‐structured interview guide, and the Creative Production Analysis Guide. Non‐parametric tests indicated significant differences in environmental factors and personal cognitive characteristics between the creative and non‐creative women when compared within each country. However, no significant differences among Brazilian and Portuguese creative women were found, thus indicating that they present similar psychological profiles.
Successful knowledge management in high‐sociability organizations
Authors: Kimble Chris
Published: February 2020

Depending on the type of business, the core activity of knowledge management can take different forms. An analysis of high‐sociability organizations shows that in those enterprises, second‐generation knowledge management—which emphasizes the role of groups, such as communities of practice—appears to be well matched to the way in which those entities function. Using a two‐dimensional framework based on sociability and solidarity, this study focuses on the links between high‐sociability organizations and knowledge management. Its conclusions point to three broad actions that high‐sociability organizations can undertake to manage knowledge more effectively: fostering a culture of knowledge sharing, nurturing interpersonal relationships, and creating appropriate organizational structures.
Enhancing experiential learning through business simulation and emulation: TBC Corporation creates competitive advantage
Authors: Conine, Thomas E. , Peratoner B. Carlo , Cuozzo Peter J. , Hoskins Terri F.
Published: February 2020

One of North America's largest marketers of automotive replacement tires, TBC Corporation emerged from a joint venture in 2018 with an aggressive organizational development strategy, launching two major leadership programs as its cornerstone. The company's president and CEO, Erik R. Olsen, recognized the need to accelerate the “forming‐storming‐norming‐performing” curve that many new joint ventures experience. TBC's new talent development framework is based on two leadership programs created in partnership with TRI Corporation, specialists in experiential learning. Designed for TBC employees at various stages of their career, Business Value Added (BVA) and Business Essentials Program (BEP) both use a blended learning approach that is experience‐, relationship‐, and education‐based to create an interactive and highly experiential learning environment. Differing in the learning methodologies they employ—a competitive simulation and action learning projects for BVA and a collaborative emulation and financial projects for BEP—they helped TBC executives translate leadership theory into practice across all of TBC's business units.
Pure rotational coherent anti‐Stokes Raman scattering spectroscopy of nitric oxide: Determination of Raman tensor invariants
Authors: Satija Aman , Chai Ning , Arendt Michael T. , Lucht Robert P.
Published: February 2020

Coherent anti‐Stokes Raman scattering (CARS) measurements of the pure rotational Raman spectrum of nitric oxide were performed. Measurements were performed in a room‐temperature gas cell using a dual‐broadband pure rotational CARS configuration. In this configuration, a broadband dye laser was used to generate the pump and Stokes beams, and the 355‐nm third‐harmonic beam from a Nd:YAG laser was used as the probe beam. The Raman spectrum of NO is of significant theoretical interest because of the spin splitting in the ground electronic level of NO. A detailed model of the pure rotational Raman spectrum of NO was developed based on an irreducible tensor analysis using Hund's case (a) wave functions as basis states for the analysis. The pure rotational Raman polarizability tensor element
in the molecular frame was determined for NO based on fitting pure rotational CARS spectra of mixtures of NO and nitrogen (N2). In addition to the pure rotational CARS spectrum featuring 2Π1/2→2Π1/2 and 2Π3/2→2Π3/2 transitions, there is an electronic Raman transition at 121 cm−1 between the spin split 2Π1/2 and 2Π3/2 ground electronic levels that has been the subject of previous theoretical interest, but the value of the tensor invariant
that contributes to the intensity of the electronic Raman transitions has not been quantitatively determined. Analysis of our pure rotational CARS spectra indicates that the magnitude of this term is much smaller than indicated in previous work, but the analysis is complicated by the weakness of the electronic Raman transitions compared with pure rotational transitions in the same spectral region. Future experiments to more definitively determine the magnitude and sign of the
polarizability tensor element are proposed.
Comparing machine and human reviewers to evaluate the risk of bias in randomized controlled trials
Authors: Armijo‐Olivo Susan , Craig Rodger , Campbell Sandy
Published: February 2020

Background

Evidence from new health technologies is growing, along with demands for evidence to inform policy decisions, creating challenges in completing health technology assessments (HTAs)/systematic reviews (SRs) in a timely manner. Software can decrease the time and burden by automating the process, but evidence validating such software is limited. We tested the accuracy of RobotReviewer, a semi‐autonomous risk of bias (RoB) assessment tool, and its agreement with human reviewers.

Methods

Two reviewers independently conducted RoB assessments on a sample of randomized controlled trials (RCTs), and their consensus ratings were compared with those generated by RobotReviewer. Agreement with the human reviewers was assessed using percent agreement and weighted kappa (κ). The accuracy of RobotReviewer was also assessed by calculating the sensitivity, specificity, and area under the curve in comparison to the consensus agreement of the human reviewers.

Results

The study included 372 RCTs. Inter‐rater reliability ranged from κ = −0.06 (no agreement) for blinding of participants and personnel to κ = 0.62 (good agreement) for random sequence generation (excluding overall RoB). RobotReviewer was found to use a high percentage of “irrelevant supporting quotations” to complement RoB assessments for blinding of participants and personnel (72.6%), blinding of outcome assessment (70.4%), and allocation concealment (54.3%).

Conclusion

RobotReviewer can help with risk of bias assessment of RCTs but cannot replace human evaluations. Thus, reviewers should check and validate RoB assessments from RobotReviewer by consulting the original article when not relevant supporting quotations are provided by RobotReviewer. This consultation is in line with the recommendation provided by the developers.
Use of mineral multi‐elemental analysis to authenticate geographical origin of different cultivars of tea in Guizhou, China
Authors: Zhang Jian , Yang Ruidong , Li Yuncong C , Wen Xuefeng , Peng Yishu , Ni Xinran
Published: February 2020

BACKGROUND

The geographical origin of tea (Camellia sinensis) can be traced using mineral elements in its leaves as fingerprints. However, the role that could be played by soil mineral elements in the geographical authentication of tea leaves has been unclear. In this study, 22 mineral elements in 73 pairs of tea leaves and soils from three regions (Pu'an, Duyun, and Liping) in Guizhou, China, were determined using inductively coupled plasma mass spectrometry (ICP‐MS) and inductively coupled plasma atomic emission spectrometry (ICP‐AES). The mineral element concentrations were processed by multivariate statistical analysis, including one‐way analysis of variance (ANOVA), correlation analysis, principal component analysis (PCA), and stepwise linear discriminant analysis (S‐LDA).

RESULTS

Based on a one‐way ANOVA, tea leaves and soils with different origins possessed unique mineral element fingerprints. Sixteen mineral element concentrations in tea leaves were significantly correlated with those in soils (P < 0.05). The geographical origins of tea leaves were effectively differentiated using the 16 correlated mineral elements combined with PCA. The S‐LDA model offered a 100% differentiation rate, and six indicative elements (phosphorus, Sr, U, Pb, Cd, and Cr) were selected as important fingerprinting markers for the geographic traceability of tea leaves. The accurate discrimination rate of geographical origin was unaffected by the cultivars of tea in the S‐LDA model.

CONCLUSIONS

Mineral elements in soils played an important role in the geographical authentication of tea leaves. Mineral elemental concentrations with significant correlations between tea leaves and soils could be robust, and could be used to trace the geographical origins of tea leaves. © 2020 Society of Chemical Industry
The Relationship Between Cisplatin‐related and Age‐related Hearing Loss During an Extended Follow‐up
Authors: Skalleberg Jakob , Småstuen Milada Cvancarova , Oldenburg Jan , Osnes Terje , Fosså Sophie D. , Bunne Marie
Published: February 2020

Objectives

Cisplatin‐related hearing loss (HL) is claimed to progress after treatment. This controlled longitudinal study with extended follow‐up investigates HL in testicular cancer survivors (TCSs) after cisplatin‐based chemotherapy (CBCT).

Study Design

Controlled longitudinal study.

Methods

Eighty‐two TCSs treated with CBCT between 1980 and 1994 in Norway participated in two surveys (S1/S3), including pure‐tone audiograms (0.125–8 kHz) and self‐reported HL, 12 and 31 years after treatment, respectively. Hearing thresholds were age‐adjusted based on age‐matched hearing thresholds from the general population (controls). Hearing loss was defined as thresholds >20 dB at any frequency.

Results

Between the two surveys, the prevalence of high‐frequency HL (4, 6, and 8 kHz) increased from 73% to 94% but approached those of the aging general population after age adjustment. In TCSs aged >40 years at first survey, HL at the subsequent survey equaled that of controls. Self‐reported HL increased from seven (9%) at S1 to 20 (26%) at S3. At S1, age‐adjusted HL was identified in all (seven) TCSs reporting decreased hearing whereas at S3, hearing thresholds did not differ from controls in seven out of 20 patients reporting HL.

Conclusion

CBCT‐related ototoxicity causes high‐frequency HL, but in contrast to reports from follow‐up studies from the first post‐treatment decade, no major progression was found beyond the first post‐treatment decade for frequencies 0.125–8 kHz. Importantly, with extended follow‐up, hearing thresholds of patients approach those of the general population, possibly due to a less‐than‐additive effect with age‐related hearing loss (ARHL) in CBCT‐treated patients. Age‐and sex‐matching is strongly advised in long‐term follow‐up of CBCT‐related ototoxicity. Specificity for detecting ototoxicity with self‐reported questionnaires decreases with extended follow‐up.

Level of Evidence

3 Laryngoscope, 130:E515–E523, 2020
Trust as a Predictor of Patient Perceptions Regarding Overlapping Surgery and Trainee Independence
Authors: Langerman Alexander , Brelsford Kathleen M. , Diehl Carolyn J. , Harris Coleman R. , Stewart Thomas G.
Published: February 2020

Objectives

To examine opinions on trainee independence and attending presence among a cross‐section of the general population and explore how perceptions of trust, past experiences, and demographics interacted with comfort consenting to these surgical scenarios.

Study Design

Mixed‐methods

Methods

Based on prior qualitative analysis, we designed a survey of patient preferences and values that focused on trust in healthcare practitioners and processes, which also included comfort ratings of three surgical scenarios (including overlapping surgery). The survey was administered to a sample from the general public using Mechanical Turk. We identified discreet domains of trust and examined the association of responses to these domains with comfort ratings, prior healthcare experiences, and demographics.

Results

We analyzed 225 surveys and identified four patient subgroups based on responses to the surgical scenarios. Subjects that were more comfortable with overlapping surgery were more trusting of trainees and delegation by the attending. Past experiences in healthcare (positive and negative) were associated with multiple domains of trust (in trainees, surgeons, and the healthcare system). Demographics were not predictive of trust responses or comfort ratings.

Conclusion

Patients express varying degrees of comfort with overlapping surgery, and this is not associated with demographics. Past negative experiences have an impact on trust in the healthcare system overall, and trust in trainees specifically predicts comfort with attending absence from the operating room. Efforts to increase patient comfort with overlapping surgery and surgical training should include strategies to address past negative experiences and foster trust in trainees and the delegation process.

Level of Evidence

IV Laryngoscope, 130:2728–2735, 2020
Cochlear Implantation in Children with Single‐Sided Deafness
Authors: Deep Nicholas L. , Gordon Steven A. , Shapiro William H. , Waltzman Susan B. , Roland J. Thomas , Friedmann David R.
Published: February 2020

Objective

To describe our experience with children undergoing unilateral cochlear implantation (CI) for treatment of single‐sided deafness (SSD).

Study Design

Retrospective case series.

Methods

A retrospective case review from a tertiary referral center involving 14 pediatric patients (<18 years) with SSD who underwent unilateral CI. Speech perception testing in quiet and noise in the CI‐only and bimodal conditions with at least 1 year of device use and device usage from data logs represent the main outcome measures.

Results

The mean age at CI was 5.0 years (median 4.4, range 1.0–11.8 years). The mean duration of deafness was 3.0 years (median 2.4, range 0.6–7.0 years). Mean follow‐up was 3.4 years. Speech perception testing with a minimum of 1 year post‐CI was available in eight patients. The mean word recognition scores (WRS) in the CI‐only condition was 56%; a significant improvement from baseline. Testing in background noise with spatially separated speech and noise revealed that patients scored as well or better with the CI‐on versus CI‐off in all conditions and in no cases was interference from the CI noted. Data logs were reviewed for device usage which revealed an average use of 6.5 hr/d.

Conclusion

Cochlear implantation is a viable treatment option for pediatric SSD in this self‐selected cohort. Open‐set speech and improvement in background noise can be achieved. Careful patient selection and thorough counseling on expectations is paramount to achieving successful outcomes.

Level of Evidence

IV Laryngoscope, 131:E271–E277, 2021
High‐Risk Cutaneous Squamous Cell Cancer of the Head and Neck: Risk Factors for Recurrence and Impact of Adjuvant Treatment
Authors: Trosman Samuel J. , Zhu Angela , Nicolli Elizabeth A. , Leibowitz Jason M. , Sargi Zoukaa B.
Published: February 2020

Objectives

The behavior of advanced cutaneous squamous cell carcinoma of the head and neck (HNcSCC) remains poorly understood, with highly variable risk factors and a paucity of data for adjuvant treatment. The objective of our study was to review the oncologic outcomes of patients with high‐risk HNcSCC treated with surgery and to identify risk factors for treatment failure.

Study Design

Retrospective cohort study.

Methods

Retrospective review of patients treated for HNcSCC with definitive surgery involving at least parotidectomy and neck dissection at a tertiary care academic center from 2011 to 2017 was conducted. The primary outcome was disease‐free survival (DFS).

Results

One‐hundred four patients with a median age of 68 years (range = 42–91 years) were reviewed. Twenty‐one patients were treated with surgery alone, 45 patients underwent adjuvant radiotherapy (RT), and 38 patients underwent adjuvant chemoradiotherapy (CRT). The 2‐year DFS for patients treated with surgery, surgery + RT, and surgery + CRT were 71%, 65%, and 58%, respectively, with no significant difference between the groups (P = .70). On multivariate analyses, tumor size (P = .006) and perineural invasion (PNI, P = .04) independently predicted recurrence. The addition of chemotherapy did not appear to improve DFS, neither for those patients with extranodal extension and/or positive margins (P = .93) nor for the entire cohort (P = .43).

Conclusions

Advanced HNcSCC has a high recurrence rate despite adjuvant treatment. Tumor size >2 cm was a strong independent risk factor for recurrence. Out of the traditional mucosal HNcSCC risk factors, PNI was most strongly associated with worse DFS. There was no observed survival benefit to the addition of chemotherapy.

Level of Evidence

4. Laryngoscope, 131:E136–E143, 2021
Pediatric Subperiosteal Abscess Secondary to Acute Sinusitis: A Systematic Review and Meta‐analysis
Authors: Adil Eelam A. , Muir Molly E. , Kawai Kosuke , Dombrowski Natasha D. , Cunningham Michael J.
Published: February 2020

Objectives/Hypothesis

The surgical versus medical management of subperiosteal abscess can be controversial. The purpose of this study was to summarize current literature and provide pooled analyses to help direct management decisions.

Study Design

Systematic review and meta‐analysis.

Methods

Patients <18 years old with subperiosteal abscess secondary to acute sinusitis were reviewed, and a meta‐analysis was conducted. Studies including five or more patients written in English were the primary search focus.

Results

Thirty‐eight studies met inclusion criteria for the systematic review, and seven studies contained sufficient data for the meta‐analysis. A total of 1,167 patients between the ages of 10 days and 18 years were included. Eleven sign/symptom categories were identified, with restricted ocular motility (n = 289, 45.9%), proptosis (n = 277, 44%), and fever (n = 223, 35.4%) being most frequent. Staphylococcus aureus was the most common pathogen isolated from cultures. Patients with abscess volume greater than the threshold specified in each individual study were over three times more likely to require surgical intervention compared to those with smaller abscess volume (pooled risk ratio [RR] = 3.61, 95% confidence interval [CI]: 2.40‐5.44). Proptosis and gaze restriction also significantly predicted surgical intervention (pooled RR = 1.65: 95% CI: 1.29‐2.12 for proptosis/pooled RR = 1.90; 95% CI: 1.20‐3.00 for gaze restriction).

Conclusions

Approximately half of patients with a subperiosteal abscess undergo surgical drainage. Abscess volume appears to be the most significant predictive risk factor. Detailed data from future studies regarding radiologic and ophthalmologic parameters are needed to provide more definitive values predictive of which patients are likely to fail medical therapy.

Level of Evidence

2a Laryngoscope, 2020
Metachronous Bilateral Vestibular Schwannomas
Authors: Elsayed Mohamed , Hochet Baptiste , Torres Renato , Sterkers Olivier , Nguyen Yann , Lahlou Ghizlene , Kalamarides Michel
Published: February 2020

Bilateral vestibular schwannoma (BVS) is the hallmark of neurofibromatosis type 2 (NF2), both of them being present at diagnosis. We report four cases of metachronous BVS, a contralateral intracanalicular vestibular schwannomas (VS) being visible 2 to 13 years after resection of a unilateral VS. NF2 workup was negative except in one case where two NF2 gene mutations were found in tumor analysis. These cases raise the questions of whether the contralateral VS occurred by chance and how to manage it on the only hearing ear. Otologists should be aware of this rare eventuality for decision making of the first unilateral VS. Laryngoscope, 131:E250–E254, 2021
The changed – and changing – landscape of serials publishing: Review of the literature on emerging models
Authors: Herman Eti , Akeroyd John , Bequet Gaelle , Nicholas David , Watkinson Anthony
Published: February 2020

This article presents an up‐to‐date portrayal of the greatly changed landscape of scholarly journal publishing and identifies the emerging trends characterizing it. We consider the attributes, novelty, and disruptive potential of different models, which range from improvements to the extant model to attempts at reconfiguration and transformation. We propose that journal transition can be seen as falling into three categories. The first is enhanced models of the traditional scholarly journal, which typically afford enriched functionality that breaks the bonds of the printed page whilst otherwise remaining wholly traditional in their offerings. The second category is innovative models of the traditional scholarly journal, which aim at supporting the journal in performing its traditional roles through convention‐altering ways. The third category is the possible alternatives to the traditional journal, which represent a move towards alternative modes of knowledge dissemination. This review shows that each of the models identified makes contributions to enriching the reporting and showcasing of scholarly output. They also make it more effective and more efficient. However, we conclude that none of the possible alternatives being discussed can serve as a full‐fledged alternative to the journal.
Neurotoxin injection in benign submandibular gland hypertrophy: A first choice treatment
Authors: Karapantzou Chrisanthi , Jakob Mark , Canis Martin
Published: February 2020

Background

Various benign clinical entities with a symptomatology of hypertrophic submandibular glands like sialadenitis, sialadenosis, sialolithiasis, or an ageing neck have been described. Botulinum toxin type A is an elegant tool in the management of these conditions.

Methods

This article is an original article, describing the Munich Concept of treating persistent submandibular swelling with Botulinum Toxin Type A from aesthetic and functional aspect. To shrink the affected tissue, 15 Units of Botox or Xeomin are applied in a single injection technique and under ultrasound guidance into the glands. Therefore, the 100 Units vial is being diluted with 3.5 of NaCl.

Results

Intraglandular injections, using a specific dilution and dosage of the neurotoxin preparations, are very effective in the management of these swellings, offering safe and long‐lasting results, with a high satisfaction rate. Our working group treated in the last 18 months 23 patients with benign, bilateral submandibular gland hypertrophies, which did not have any major complications.

Conclusion

As there is not yet described an ideal therapeutic strategy for the management of this symptomatology, we suggest, based on our experience, a concept with very promising results from functional and cosmetic aspect.
A Phytosterolemic Mixture of Sterols Inhibits Cholesterol Synthesis, Esterification, and Low‐Density Lipoprotein Receptor mRNA Abundance in HepG2 Cells
Authors: Davis April , Cole Laura K. , Min Kevin Kyung‐Jun , Chow Sidney , Choy Patrick C. , Mymin David , Hatch Grant M.
Published: February 2020

HepG2 cells were incubated with a 16.5:1.7:1 ratio of cholesterol:sitosterol:campesterol (CSC), a ratio of the major sterols observed in the plasma of phytosterolemia patients, or with cholesterol alone in combination with [14C]acetate for 24 h and the radioactivity incorporated into lipids determined. Cells incubated with CSC exhibited a 40% reduction in cholesterol esterification (p < 0.05) compared to cells incubated with cholesterol alone. In addition, a 17.5‐fold reduction (p < 0.05) in total cholesterol (cholesterol plus cholesteryl ester) synthesis from [14C]acetate was observed in cells incubated with CSC compared to cholesterol alone. Low‐density lipoprotein receptor (LDLR) mRNA abundance was lower in cells incubated with CSC compared to cells incubated with cholesterol alone. Our results suggest that incubation of HepG2 cells with a ratio of sterols that mimic the plasma concentration seen in phytosterolemia patients reduces cholesterol esterification, total cholesterol synthesis, and inhibits LDLR mRNA abundance. We suggest that future cell and animal‐based work on phytostosterolemia might employ this methodology to serve as a novel paradigm of the disease.
Characteristics of Bubble Oscillations During Laser‐Activated Irrigation of Root Canals and Method of Improvement
Authors: Lukač Matjaž , Lukač Nejc , Jezeršek Matija
Published: February 2020

Background and Objectives

Laser‐activated irrigation of dental root canals is being increasingly used as its efficacy has been shown to be superior compared with conventional techniques. The method is based on laser‐initiated localized fluid evaporation and subsequent rapid bubble expansions and collapses, inducing microfluid flow throughout the entire volume of the cavity. The irrigation efficacy can be further improved if optimally delayed “SWEEPS” double laser pulses are delivered into the canal. This study aims to show that the irrigation efficacy, as measured by the induced pressure within the canal, is related to the double pulse delay, with the maximal pressure generated at an optimal delay. The second aim is to find a method of determining the optimal delay for different cavity dimensions and/or laser parameters.

Study Design/Materials and Methods

Experiments were made in transparent models of root canals where Er:YAG laser (λ = 2.94 μm, pulse duration tp = 25 or 50 microseconds, and pulse energies up to EL = 40 mJ) was used with a combination of cylindrical and conical fiber‐tip geometries (diameters 400 and 600 µm). High‐speed photography (60,000 fps) and average pressure measurements inside the canal were used for process characterization.

Results

The results show that a pressure amplification of more than 1.5 times occurs if the laser pulse delay approximately coincides with the bubble oscillation time. Correlations between normalized oscillation time and canal diameter for a wide range of laser pulse energies (R2 = 0.96) and between the average pressure within the canal and the bubble oscillation periods (R2 = 0.90) were found. A relationship between the bubble oscillation time and the diameter of the treated cavity was found depending on the bubble oscillation time in an infinite fluid reservoir.

Conclusions

The bubble oscillation time within a constrained volume can be determined based on the known oscillation time in infinite space, which offers a fast and simple solution for optimization of the laser parameters. These findings enable determination of optimal conditions for shock wave generation, and improvement of root canal irrigation at the same dose of laser energy input, leading to improved treatment efficacy and safety. Lasers Surg. Med. © 2020 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals, Inc.
Enhancement of β‐Phase Crystalline Structure and Piezoelectric Properties of Flexible PVDF/Ionic Liquid Surfactant Composite Nanofibers for Potential Application in Sensing and Self‐Powering
Authors: Mahdavi Varposhti Arezo , Yousefzadeh Maryam , Kowsari Elaheh , Latifi Masoud
Published: February 2020

Polyvinylidene fluoride (PVDF) is a piezo‐polymer which among its crystalline phases, the β‐phase has been researched for the improvement of piezoelectric properties. In this study, to improve the β‐phase contents and thereby the piezoelectric response of the polymer, the effect of adding self‐synthesized ionic liquid surfactant (ILS) in PVDF nanofibers is studied. This material is added in different weight percentages into the PVDF solution and the nanofibers are produced by electrospinning to prepare active piezoelectric thin layers. SEM, XRD, FTIR, and piezo‐tests are employed for assessing the effect of the ILS on the enhancement of β‐phase in electrospun nanofibers and their piezoelectric performance. The results indicate ≈98.6% β‐phase formation in the sample containing 4 wt% ILS and in comparison with the pure nanofibers, the output voltage and its power density are improved 186.9% and 275%, respectively. Considering the results, it is suggested that the ILS can improve the piezoelectric response of the polymer in the fabricated structure by simple mixing in solution compared to other additives.
Identification of potential hub genes via bioinformatics analysis combined with experimental verification in colorectal cancer
Authors: Zhou Hongrui , Yang Zhe , Yue Jiaxin , Chen Yang , Chen Tianqiao , Mu Teng , Liu Hongsheng , Bi Xiuli
Published: February 2020

Colorectal cancer (CRC) is a kind of malignant cancer with high morbidity and mortality. The purpose of this study was to explore potential regulated key genes involved in CRC through bioinformatics analysis and experimental verification. The gene expression profile data were downloaded from the Gene Expression Omnibus, and the differential expression genes were detected in cancerous and paracancerous samples of CRC patients, respectively. Then functional enrichment analysis, such as the Kyoto Encyclopedia of Genes and Genomes pathway analysis as well as the protein‐protein interaction network were constructed, and the highly related genes were clustered by Molecular COmplex DEtection algorithm to find out the core interaction in different genes' crosstalk. The genes affecting CRC prognosis were screened by the Human Protein Atlas database. In addition, the expression level of core genes was detected by GEPIA database, and the core genes' changes in large‐scale cancer genome data set were directly analyzed by cBioPortal database. The expression of the predicted hub genes DSN1, AHCY, and ERCC6L was verified by reverse‐transcription quantitative polymerase chain reaction in CRC cells. The gene function of DSN1 was analyzed by wound healing and colony formation assays. The results showed that silencing of DSN1 could significantly reduce the migration and proliferation of CRC cells. Further, BUB1B, the potential interacting protein of DSN1, was also predicted via bioinformatics analysis. Above all, this study shows that bioinformatics analysis combined with experimental method verification provide more potential vital genes for the prevention and therapy of CRC.
Extending the Phenotypic Spectrum Associated with STUB1 Mutations: A Case of Dystonia
Authors: Olszewska Diana A. , Kinsella Justin A.
Published: February 2020

Background

Mutations in the STIP1 homology and U‐box containing protein 1 gene were first described in 2013 and lead to disorders with symptoms including ataxia and dysarthria, such as spinocerebellar autosomal‐recessive ataxia type 16 (SCAR16), Gordon‐Holmes syndrome, and spinocerebellar ataxia type 48. There have been 15 families described to date with SCAR16.

Cases

We describe a 45‐year‐old right‐handed woman with dysarthria, ataxia, and cervical dystonia with SCAR16 with 2 compound heterozygous variants in the STIP1 homology and U‐box containing protein 1 gene, and a family history significant for her 47‐year‐old sister with dysarthria and cognitive problems.

Conclusion

We present a comprehensive overview of the phenotypic data of all 15 families with SCAR16 and expand the phenotype by describing a third patient with SCAR16 and dystonia reported to date in the literature.
Security and trust preserving inter‐ and intra‐cloud VM migrations
Authors: Aslam Mudassar , Bouget Simon , Raza Shahid
Published: February 2020

This paper focus on providing a secure and trustworthy solution for virtual machine (VM) migration within an existing cloud provider domain, and/or to the other federating cloud providers. The infrastructure‐as‐a‐service (IaaS) cloud service model is mainly addressed to extend and complement the previous Trusted Computing techniques for secure VM launch and VM migration case. The VM migration solution proposed in this paper uses a Trust_Token based to guarantee that the user VMs can only be migrated and hosted on a trustworthy and/or compliant cloud platforms. The possibility to also check the compliance of the cloud platforms with the pre‐defined baseline configurations makes our solution compatible with an existing widely accepted standards‐based, security‐focused cloud frameworks like FedRAMP. Our proposed solution can be used for both inter‐ and intra‐cloud VM migrations. Different from previous schemes, our solution is not dependent on an active (on‐line) trusted third party; that is, the trusted third party only performs the platform certification and is not involved in the actual VM migration process. We use the Tamarin solver to realize a formal security analysis of the proposed migration protocol and show that our protocol is safe under the Dolev‐Yao intruder model. Finally, we show how our proposed mechanisms fulfill major security and trust requirements for secure VM migration in cloud environments.
H(div) finite elements based on nonaffine meshes for 3D mixed formulations of flow problems with arbitrary high order accuracy of the divergence of the flux
Authors: Remy Bernard Devloo Philippe , Durán Omar , Monteiro Farias Agnaldo , Maria Gomes Sônia
Published: February 2020

Effects of nonaffine elements on the accuracy of 3D H(div)‐conforming finite elements are studied. Instead of convergence order k+1 for the flux and the divergence of the flux obtained with Raviart‐Thomas or Nédélec spaces with normal traces of degree k, based on affine hexahedra or triangular prisms, reduced orders k for the flux and k−1 for the divergence of the flux may occur for distorted elements. To improve this scenario, a hierarchy of enriched flux approximations is considered, by adding internal shape functions up to a higher degree k+n, n>0, while keeping the original normal traces of degree k. The resulting enriched approximations, using multilinear transformations, keep the original flux accuracy (of order k+1 with affine elements or reduced order k otherwise), but enhanced divergence (of order k+n+1, in the affine case, or k+n−1 otherwise) can be reached. The reduced flux accuracy due to quadrilateral face distortions cannot be corrected by including higher order internal functions. The enriched spaces are applied to the mixed finite element formulation of Darcy's model. The computational cost of matrix assembly increases with n, but the condensed system to be solved has the same dimension and structure as the original scheme.