bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating sources of uncertainty and variability in rock glacier inventories
Authors: Brardinoni Francesco , Scotti Riccardo , Sailer Rudolf , Mair Volkmar
Published: May 2019

This paper aims to evaluate sources of uncertainty and variability associated with rock glacier inventories compiled from remotely sensed imagery. To this end, we ran three mapping exercises in Kaiserbergtal, Austria. To evaluate interactions between mapping style and imagery resolution, we asked six operators to map and assess the degree of activity of all rock glaciers they could identify – first on Google Earth™ (GE) imagery and then on a set of higher‐resolution orthophotos and LiDAR‐derived images (LO) (Exercise 1). To compare the mapping attributes on a common set of rock glaciers, we asked 14 operators to delineate the outline of four designated rock glaciers (Exercise 2) and to classify the activity of 15 designated rock glaciers (Exercise 3) on LO. Results show strikingly high inter‐operator variability. Specifically, we show that the number of mapped rock glaciers on GE can vary up to a factor of 3, and that using LO lowers this figure to a factor of 2, while producing an increase in the number of mapped landforms, which become systematically smaller (Exercise 1). Examination of polygon outlines identifies highest inter‐operator variability at the transition with the rooting zone and, in polymorphic rock glaciers, on adjacent creeping lobes. Variability is higher for relict landforms (Exercise 2). Operators’ activity assessments, evaluated against an independent quantitative activity index (RGI), display reasonable agreement for active and relict landforms, whereas inactive counterparts meet least consensus and therefore are problematic (Exercise 3). We further show that this variability in mapping outcomes propagates across compound variables, and must be considered when assessing uncertainties and confidence levels of environmental evaluations that rely on rock glacier inventories, such as the lower altitudinal limit of discontinuous permafrost, or water storage potential. We call for an international effort to establish guidelines for rock glacier classification and mapping, towards more homogeneous inventories. © 2019 John Wiley & Sons, Ltd.
Arbeitsintegrierte Verdichtungskontrolle während der Rütteldruckverdichtung
Authors: Nagy Péter , Adam Dietmar
Published: May 2019

Die Rütteldruckverdichtung ist ein Bodenverbesserungsverfahren, das bei der tief reichenden Verdichtung von grobkörnigen Böden weltweit angewendet wird. Die wesentlichen Vorteile dieser Technologie bestehen in der Vorwegnahme von Setzungen durch Bodenverdichtung und der Homogenisierung des Untergrunds. Trotz langjähriger Tradition des Verfahrens basieren heutzutage die Festlegung von Prozessparametern sowie die Kontrolle und der Nachweis des Verdichtungserfolgs in erster Linie auf Erfahrungen der ausführenden Firmen.

Im vorliegenden Beitrag wird die Möglichkeit zur arbeitsintegrierten Verdichtungskontrolle auf Basis des Bewegungsverhaltens des Tiefenrüttlers aufgezeigt und diskutiert. Die dynamische Wechselwirkung zwischen einem Tiefenrüttler und dem zu verdichtenden Boden wurde in großmaßstäblichen experimentellen Untersuchungen auf einem Versuchsfeld bei weitestgehend bekannten Untergrundverhältnissen messtechnisch erfasst und dokumentiert. Die theoretische Untersuchung des Rüttler‐Boden‐Interaktionssystems ermöglichte eine Quantifizierung des Verdichtungserfolgs in Form eines unmittelbar aus der Rüttlerbewegung ableitbaren Indikators. Dieser lässt eine tiefenabhängige Verdichtungskontrolle entlang der Verdichtungsstrecke zu und erteilt Informationen über die Homogenität des erzeugten Bodenkörpers im Versuchsboden, wodurch eine raumfüllende Kontrolle der Verdichtungsarbeiten gewährleistet werden kann.
Risk stratification of fine‐needle aspiration cytology of parotid neoplasms based on the Milan system—Experience from a tertiary center in Asia
Authors: Choy Kevin C. C. , Bundele Manish M. , Li Hao , Fu Ernest W. , Rao Nandini C. L. , Lim Ming Yann
Published: May 2019

Background

The recently described Milan system provides a unified way of categorizing salivary gland fine‐needle aspiration (FNA) cytology. We aim to use this system to stratify risk of malignancy in parotid FNAs.

Methods

In this retrospective case series, 376 FNAs were preoperatively performed for 573 parotidectomies over 14 years.

Results

Risk of malignancy on FNA is as follows: nondiagnostic 14.5%, non‐neoplastic 26.7%, atypia of undetermined significance 29.3%, benign neoplasm 2.7%, neoplasm of uncertain malignant potential 19.1%, suspicious for malignancy 87.5%, and malignant 100%. The specific diagnoses of pleomorphic adenoma and Warthin tumor on FNA have high positive predictive value of 97.5% and 96.6%, respectively. Multivariate regression associates smaller size of lesion with a nondiagnostic or indeterminate result. Seniority of operator is associated with a lower likelihood of a nondiagnostic result.

Conclusions

This large Asian series validates the Milan system as a valuable tool in stratifying malignancy risk of parotid FNAs.
A new era for sterilization based on supercritical CO2 technology
Authors: Ribeiro Nilza , Soares Gonçalo C. , Santos‐Rosales Víctor , Concheiro Angel , Alvarez‐Lorenzo Carmen , García‐González Carlos A. , Oliveira Ana L.
Published: May 2019

The increasing complexity in morphology and composition of modern biomedical materials (e.g., soft and hard biological tissues, synthetic and natural‐based scaffolds, technical textiles) and the high sensitivity to the processing environment requires the development of innovative but benign technologies for processing and treatment. This scenario is particularly applicable where current conventional techniques (steam/dry heat, ethylene oxide, and gamma irradiation) may not be able to preserve the functionality and integrity of the treated material. Sterilization using supercritical carbon dioxide emerges as a green and sustainable technology able to reach the sterility levels required by regulation without altering the original properties of even highly sensitive materials. In this review article, an updated survey of experimental protocols based on supercritical sterilization and of the efficacy results sorted by microbial strains and treated materials was carried out. The application of the supercritical sterilization process in materials used for biomedical, pharmaceutical, and food applications is assessed. The opportunity of supercritical sterilization of not only replace the above mentioned conventional techniques, but also of reach unmet needs for sterilization in highly sensitive materials (e.g., single‐use medical devices, the next‐generation biomaterials, and medical devices and graft tissues) is herein unveiled.
Synthesis of hydrated furans: Analysis of the Prins reaction mechanism
Authors: Sharipova Gulnaz M. , Gerchikov Anatoly Ya. , Safarova Irina V. , Тukhvatshin Vadim S. , Spivak Semen I. , Ilyina Margarita G.
Published: May 2019

Mechanistic analysis of hydrogenated furan synthesis by the Prins reaction was carried out using mathematical modeling. The direct and inverse chemical kinetic problems are solved for the rate constants of all elementary steps. A probable mechanism is derived from the obtained quantitative kinetic parameters and the kinetic patterns of the reaction. These include kinetic curves from the concentration changes of all species in the reaction.
Temperature‐programmed reduction of silver(I) oxide using a titania‐supported silver catalyst under a H2 atmosphere
Authors: Kay Lup Andrew Ng , Abnisa Faisal , Wan Daud Wan Mohd Ashri , Aroua Mohamed Kheireddine
Published: May 2019

Reduction kinetics of silver(I) oxide using a titania‐supported silver catalyst was analyzed using temperature‐programmed reduction (TPR) with hydrogen as a reducing gas. Ag2O reduction to Ag was observed in all samples as a single reduction step occurring at two reduction peaks. Observation of these reduction peaks indicates the existence of different lattice oxygen species, that is, surface and bulk, which are, respectively, attributed to surficial and pore‐deposited Ag2O aggregates. The powdered samples exhibited high reducibility with average final oxidation states ranging from 0 to +0.18. The apparent activation energies for Ag2O reduction to Ag metal were 73.35 and 81.71 kJ/mol for surficial and pore‐deposited Ag2O aggregates, respectively. In this study, a unimolecular decay model was reported to accurately describe the reduction mechanism of Ag/TiO2 catalysts. Hence, this would also infer that the catalyst reduction is rate‐limited by the nucleation of Ag metal instead of the topochemical reaction and the diffusion of hydrogen and oxygen molecules.
Conducting psychotherapy in the Trump era: Therapists’ perspectives on political self‐disclosure, the therapeutic alliance, and politics in the therapy room
Authors: Solomonov Nili , Barber Jacques P.
Published: May 2019

Objective

To examine therapists’ perspectives on political self‐disclosure, perceived shared values with patients, and the therapeutic alliance.

Method

Therapists from all US states completed a structured survey (N = 268; 62% Democrats; 7% Republicans; 23% independents; 8% others).

Results

Most therapists (87%) reported they discussed politics in‐session; 63% reported political self‐disclosure (21% explicit; 42% implicit). Therapists who perceived political similarity with most patients were more likely to report political discussions and self‐disclosure. Therapists who reported shared political views with a higher percentage of patients, and those who explicitly disclosed, also reported stronger alliances. Clinton supporters reported significant observed preelection–postelection increases in political discussions, increases in patients’ expression of negative emotions, and decreases in positive emotions. Trump supporters reported the opposite phenomenon.

Conclusions

Politics play an important role in therapeutic processes as in‐session political discussions are common and perceived political similarity may affect decisions to self‐disclose and alliance quality.
Prospect of circular RNA in osteogenesis: A novel orchestrator of signaling pathways
Authors: Huang Xinqi , Cen Xiao , Zhang Bo , Liao Yuwei , Zhu Guanyin , Liu Jun , Zhao Zhihe
Published: May 2019

Circular RNAs (circRNAs) were initially regarded as by‐products of aberrant splicing. But now, there are substantial evidence on their various roles in the regulation of genes during the development of organs and diseases. Consistent with these breakthroughs, it is experiencing rapid growth that circRNAs function as the important checkpoints during the osteogenesis. Therefore, characterizing the roles of circRNAs is useful and critical to better understanding the process of osteogenic differentiation, which could provide new avenues for the diagnosis and treatment of bone diseases, such as bone defects and osteoporosis. In this review, we presented a map of the interaction between circRNAs and the molecules of signaling pathways associated with osteogenesis, summarized the current knowledge of the biological functions of circRNAs during the osteogenic differentiation, figured out the limits of existing research works, and provided a novel look on the diagnostic and therapeutic methods of bone diseases based on circRNAs.
Osteogenic potential of hexane and dichloromethane fraction of Cissus quadrangularis on murine preosteoblast cell line MC3T3‐E1 (subclone 4)
Authors: Toor Rabail H. , Malik Shabana , Qamar Haleema , Batool Faiza , Tariq Maira , Nasir Zainab , Tassaduq Raazia , Lian Jane B. , Stein Janet L. , Stein Gary S. , Shakoori Abdul R.
Published: May 2019

In continuation of the investigation of osteogenic potential of solvent fractions of ethanolic extract of Cissus quadrangularis (CQ), an ancient medicinal plant, most notably known for its bone‐healing properties, to isolate and identify antiosteoporotic compounds. In the current study, we report the effect of hexane fraction (CQ‐H) and dichloromethane fraction (CQ‐D) of CQ on the differentiation and mineralization of mouse preosteoblast cell line MC3T3‐E1 (subclone 4). Growth, viability, and proliferation assays revealed that low concentrations (0.1, 1, and 100 ng/ml) of both solvent fractions were nontoxic, whereas higher concentrations were toxic to the cells. Differentiation and mineralization of MC3T3‐E1 with nontoxic concentrations of CQ‐D and CQ‐H revealed that CQ‐D delayed the mineralization of MC3T3‐E1 cells. However, early and enhanced mineralization was observed in cultures treated with nontoxic concentrations of CQ‐H, as indicated by Von Kossa staining and expression profile of osteoblast marker genes such as osterix, Runx2, alkaline phosphatase (ALP), collagen (Col1a1), integrin‐related bone sialoprotein (IBSP), osteopontin (OPN), and osteocalcin (OCN). These findings suggest CQ‐H as the most efficacious solvent fraction for further investigation to isolate and identify the active compounds in CQ‐H.
Supervised risk predictor of central gland lesions in prostate cancer using 1H MR spectroscopic imaging with gradient offset‐independent adiabaticity pulses
Authors: Gholizadeh Neda , Greer Peter B. , Simpson John , Fu Caixia , Al‐iedani Oun , Lau Peter , Heerschap Arend , Ramadan Saadallah
Published: May 2019

Background

Due to the histological heterogeneity of the central gland, accurate detection of central gland prostate cancer remains a challenge.

Purpose

To evaluate the efficacy of in vivo 3D 1H MR spectroscopic imaging (3D 1H MRSI) with a semi‐localized adiabatic selective refocusing (sLASER) sequence and gradient‐modulated offset‐independent adiabatic (GOIA) pulses for detection of central gland prostate cancer. Additionally four risk models were developed to differentiate 1) normal vs. cancer, 2) low‐ vs. high‐risk cancer, 3) low‐ vs. intermediate‐risk cancer, and 4) intermediate‐ vs. high‐risk cancer voxels.

Study Type

Prospective.

Subjects

Thirty‐six patients with biopsy‐proven central gland prostate cancer.

Field Strength/Sequence

3T MRI / 3D 1H MRSI using GOIA‐sLASER.

Assessment

Cancer and normal regions of interest (ROIs) were selected by an experienced radiologist and 1H MRSI voxels were placed within the ROIs to calculate seven metabolite signal ratios. Voxels were split into two subsets, 80% for model training and 20% for testing.

Statistical Tests

Four support vector machine (SVM) models were built using the training dataset. The accuracy, sensitivity, and specificity for each model were calculated for the testing dataset.

Results

High‐quality MR spectra were obtained for the whole central gland of the prostate. The normal vs. cancer diagnostic model achieved the highest predictive performance with an accuracy, sensitivity, and specificity of 96.2%, 95.8%, and 93.1%, respectively. The accuracy, sensitivity, and specificity of the low‐ vs. high‐risk cancer and low‐ vs. intermediate‐risk cancer models were 82.5%, 89.2%, 70.2%, and 73.0%, 84.7%, 60.8%, respectively. The intermediate‐ vs. high‐risk cancer model yielded an accuracy, sensitivity, and specificity lower than 55%.

Data Conclusion

The GOIA‐sLASER sequence with an external phased‐array coil allows for fast assessment of central gland prostate cancer. The classification offers a promising diagnostic tool for discriminating normal vs. cancer, low‐ vs. high‐risk cancer, and low‐ vs. intermediate‐risk cancer.

Level of Evidence: 2

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2019;50:1926–1936.
Nucleus–cytoplasm cross‐talk in the aging brain
Authors: Benvegnù Stefano
Published: May 2019

Aging is a primary risk factor for fatal neurodegenerative disorders, yet the mechanisms underlying physiological healthy aging and pathological aging, and how these mechanisms can divert one scenario to the other, are not completely understood. In recent years, reports indicate that alterations in nucleocytoplasmic transport may be a hallmark of both healthy and pathological aging. In this review, I summarize recent evidence supporting this information, specifically focusing on the association between the nucleocytoplasmic transport and aging of the brain, indicating both common and case‐specific mechanisms and their interplay, and pointing out alterations of these mechanisms as regulatory “switches” for the fate of the aging brain. Importantly, some of these alterations are intervenable druggable targets, paving the way to a future pharmacotherapeutic intervention.
Spatio‐temporal analysis for extreme temperature indices over the Levant region
Authors: Salameh Ala A. M. , Gámiz‐Fortis Sonia R. , Castro‐Díez Yolanda , Abu Hammad Ahmad , Esteban‐Parra María Jesús
Published: May 2019

The temporal and spatial trends of 16 climate extreme indices based on daily maximum and minimum temperatures during the period 1987–2016 at 28 stations distributed across Israel and Palestine territories in the Levant region were annually and seasonally analysed. The nonparametric Man‐Kendall test and the Sen's slope estimator were employed for the trend analysis. Results showed that the region has significantly experienced a dominant warming trend for the last three decades, with more intense changes for minimum temperatures than for maximum. At annual scale, maximum values of minimum temperatures exhibited significant increasing trends up to 0.68°C/decade. For percentile‐based extreme temperature indices, changes detected were more pronounced than those for the absolute extreme temperature indices, with 93 and 89% of stations significantly showed increasing trends in TX90p and TN90p, respectively. The duration and fixed threshold extreme indices confirmed the trend toward a warming, with the 86% of the stations exhibited significant increasing trends in the annual occurrence of summer days (SU25) and tropical nights (TR20). Moreover, 57% of stations showed significant increasing trends in their very summer days (SU30) index. At seasonal scale, the analysis of trends for extreme temperature indices showed intense and broad significant increasing trends in all absolute extreme temperature indices. In summer, more than 75% of total stations exhibited significant increasing trends for warm days and warm nights (TX90p and TN90p). In winter and spring, 71% of the total stations also showed significant increasing trends in SU25 index, whereas the percentage of stations reached 82% in summer and 64% in autumn for significant increasing trends in TR20 index. Finally, the influence of large‐scale circulation patterns on temperature extremes was examined. The results highlighted the presence of significant correlations between most of the selected extreme temperature indices and the North Sea‐Caspian pattern at annual and seasonal scales.
Separation of high‐purity eicosapentaenoic acid and docosahexaenoic acid from fish oil by pH‐zone‐refining countercurrent chromatography
Authors: Li Haoze , Yang Zhen , Cao Xueli , Han Tian , Pei Hairun
Published: May 2019

The evidence for unique effects of eicosapentaenoic acid and docosahexaenoic acid is growing. Further understanding and exploration of their independent effects in the nutraceutical and pharmaceutical industry is calling for the more efficient separation techniques to overcome the equivalent chain length rule of fatty acids. In this study, free eicosapentaenoic and docosahexaenoic acid were successfully separated by pH‐zone‐refining countercurrent chromatography for the first time. The different solvent systems and the influence of retainer and eluter concentration on the separation efficiency were investigated. A two‐phase solvent system composed of n‐heptane/methanol/water (100:55:45, v/v) was selected with 50 mM of trifluoroacetic acid as retainer in the organic phase and 40 mM of ammonium hydroxide as an eluter in the aqueous phase for the separation of 500 mg of free fatty acids from a refined fish oil sample. 79.6 mg of eicosapentaenoic acid and 328.3 mg docosahexaenoic acid were obtained with the purities of 95.5 and 96.9% respectively determined by gas chromatography with mass spectrometry after methyl esterification. The scale‐up separation of 1 g of samples from both refined and crude fish oil after urea complexation were also achieved successfully with a markedly increased concentration 150 mM of retainer, producing satisfactory yields and purities of targets.
Perimatrix of middle ear cholesteatoma: A granulation tissue with a specific transcriptomic signature
Authors: Jovanovic Ivan , Zivkovic Maja , Djuric Tamara , Stojkovic Ljiljana , Jesic Snezana , Stankovic Aleksandra
Published: May 2019

Objectives/Hypothesis

To establish comprehensive transcriptomic profiles of cholesteatoma perimatrix tissue and granulation tissue from chronic otitis media (COM) that did not develop cholesteatoma, which can indicate molecular pathways involved in the cholesteatoma perimatrix pathology and invasiveness.

Study Design

Retrospective Case Series.

Methods

Transcriptome data were obtained from cholesteatoma perimatrix tissue and COM granulation tissue by an Illumina iScan microarray. Differentially expressed genes (DEGs) were subsequently analyzed using both bioinformatical functional annotation and network analysis. Expression of candidate genes (MMP9 and LCN2) was validated by quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) on a larger group of samples.

Results

Analysis of the transcriptome led to the identification of 169 differentially expressed genes between investigated tissues. Bioinformatic analysis suggested that most significant biological processes involving DEGs were previously described in cholesteatoma pathology. Network analysis identified ERBB2, TFAP2A, and TP63 as major hubs of the DEGs molecular network. Furthermore, it was observed that the cellular component most significantly enriched in DEGs was extracellular space containing 47 DEGs. Using qRT‐PCR, it was confirmed that mRNA levels of the major extracellular hub (MMP9) are increased, whereas its interacting molecule (LCN2) mRNA levels were decreased in cholesteatoma perimatrix tissue compared to COM granulation tissue.

Conclusions

The current study approach offers an overall look at molecular mechanisms that describe the cholesteatoma entity by focusing exclusively on the perimatrix processes in comparison to COM granulation tissue. The observed differences in gene expression between cholesteatoma perimatrix and COM granulation tissue could suggest novel markers potentially influenced by the perimatrix–matrix molecular interplay, which is not present in COM without cholesteatoma.

Level of Evidence

NA

Laryngoscope, 130:E220–E227, 2020
Imaging findings in pediatric single‐sided deafness and asymmetric hearing loss
Authors: Lipschitz Noga , Kohlberg Gavriel D. , Scott Michael , Greinwald John H.
Published: May 2019

Objective

To examine the imaging findings on computer tomography (CT) and magnetic resonance imaging (MRI) in pediatric single‐sided deafness (SSD) and asymmetric hearing loss (ASH).

Methods

The medical records of 189 pediatric patients with SSD and ASH were retrospectively reviewed, and imaging findings were compared. SSD was defined as unilateral profound hearing loss and contralateral normal hearing ear. In the ASH group, ASHw was defined as the worse hearing ear with profound hearing loss, while ASHb was defined as the better hearing ear with mild‐moderate hearing loss.

Results

There were 170 patients with SSD and 19 patients with ASH. In the SSD group, 83 patients (48.8%) had imaging findings associated with hearing loss. In the ASH group, such imaging findings were found in six (31.6%) of the ASHw and in five (26.3%) of the ASHb ears. The most common finding in the SSD group was cochlear nerve deficiency (50.6%), followed by cochlear dysplasia (39.8%) and enlarged vestibular aqueduct (26.5%). In the ASH groups, cochlear dysplasia was seen in three (50%) of ASHw ears and in two (40%) of the ASHb ears, and enlarged vestibular aqueduct was seen in three (50%) of ASHw ears and in two (40%) of the ASHb ears.

Conclusion

Imaging studies identified the etiology in half of the cases of SSD and in one‐third of ASH patients. Our findings strongly support the use of imaging studies in the evaluation of pediatric SSD and ASH.

Level of Evidence

4

Laryngoscope, 130:1007–1010, 2020
N‐Acylisoindigo Derivatives as Polymer Acceptors for “All‐Polymer” Bulk‐Heterojunction Solar Cells
Authors: Cruciani Federico , Babics Maxime , Liu Shengjian , Carja Daniela , Mantione Daniele , Beaujuge Pierre M.
Published: May 2019

Polymer acceptors are a class of “non‐fullerene” electron‐transporting materials that can replace [6,6]‐phenyl C61/71 butyric acid (PC61/71BM) in bulk‐heterojunction (BHJ) solar cells. In this contribution is reported the use of N‐acyl‐substituted isoindigo (IID) motifs (IID(CO)) as electron‐deficient units in the design of polymer acceptors for “all‐polymer” BHJ solar cells. While IID motifs are commonly used in the design of polymer donors for efficient BHJ solar cells with the fullerene PC61/71BM acceptors, here it is shown that IID(CO) building units used in conjunction with suitable co‐monomers represent a practical avenue for polymer acceptors with electron affinity values comparable to that of PC61/71BM (i.e., 4.2 eV).
Small molecule inhibitors of epithelial‐mesenchymal transition for the treatment of cancer and fibrosis
Authors: Feng Ya‐Long , Chen Dan‐Qian , Vaziri Nosratola D. , Guo Yan , Zhao Ying‐Yong
Published: May 2019

Tissue fibrosis and cancer both lead to high morbidity and mortality worldwide; thus, effective therapeutic strategies are urgently needed. Because drug resistance has been widely reported in fibrotic tissue and cancer, developing a strategy to discover novel targets for targeted drug intervention is necessary for the effective treatment of fibrosis and cancer. Although many factors lead to fibrosis and cancer, pathophysiological analysis has demonstrated that tissue fibrosis and cancer share a common process of epithelial‐mesenchymal transition (EMT). EMT is associated with many mediators, including transcription factors (Snail, zinc‐finger E‐box‐binding protein and signal transducer and activator of transcription 3), signaling pathways (transforming growth factor‐β1, RAC‐α serine/threonine‐protein kinase, Wnt, nuclear factor‐kappa B, peroxisome proliferator‐activated receptor, Notch, and RAS), RNA‐binding proteins (ESRP1 and ESRP2) and microRNAs. Therefore, drugs targeting EMT may be a promising therapy against both fibrosis and tumors. A large number of compounds that are synthesized or derived from natural products and their derivatives suppress the EMT by targeting these mediators in fibrosis and cancer. By targeting EMT, these compounds exhibited anticancer effects in multiple cancer types, and some of them also showed antifibrotic effects. Therefore, drugs targeting EMT not only have both antifibrotic and anticancer effects but also exert effective therapeutic effects on multiorgan fibrosis and cancer, which provides effective therapy against fibrosis and cancer. Taken together, the results highlighted in this review provide new concepts for discovering new antifibrotic and antitumor drugs.
Amplicon targeted resequencing for SLC2A9 and SLC22A12 identified novel mutations in hypouricemia subjects
Authors: Zhou Zhaowei , Wang Ke , Zhou Juan , Wang Can , Li Xinde , Cui Lingling , Han Lin , Liu Zhen , Ren Wei , Wang Xuefeng , Zhang Keke , Li Zhiqiang , Pan Dun , Li Changgui , Shi Yongyong
Published: May 2019

Background

To identify potential causative mutations in SLC2A9 and SLC22A12 that lead to hypouricemia or hyperuricemia (HUA).

Methods

Targeted resequencing of whole exon regions of SLC2A9 and SLC22A12 was performed in three cohorts of 31 hypouricemia, 288 HUA and 280 normal controls.

Results

A total of 84 high‐quality variants were identified in these three cohorts. Eighteen variants were nonsynonymous or in splicing region, and then included in the following association analysis. For common variants, no significant effects on hypouricemia or HUA were identified. For rare variants, six single nucleotide variations (SNVs) p.T21I and p.G13D in SLC2A9, p.W50fs, p.Q382L, p.V547L and p.E458K in SLC22A12, occurred in totally six hypouricemia subjects and were absent in HUA and normal controls. Allelic and genotypic frequency distributions of the six SNVs differed significantly between the hypouricemia and normal controls even after multiple testing correction, and p.G13D in SLC2A9 and p.V547L in SLC22A12 were newly reported. All these mutations had no significant effects on HUA susceptibility, while the gene‐based analyses substantiated the significant results on hypouricemia.

Conclusion

Our study first presents a comprehensive mutation spectrum of hypouricemia in a large Chinese cohort.
Characterization of BRCA1 and BRCA2 genetic variants in a cohort of Bahraini breast cancer patients using next‐generation sequencing
Authors: Al Hannan Fatima , Keogh Michael B. , Taha Safa , Al Buainain Latifa
Published: May 2019

Background

Breast cancer is the most common malignancy in women worldwide. About 5%–10% are due to hereditary predisposition. The contribution of BRCA1/2 mutations to familial breast cancer in Bahrain has not been explored. The objective of this study was to investigate the spectrum of BRCA1/2 genetic variants and estimate their frequencies in familial breast cancer. We also aim to test the efficiency of the next‐generation sequencing (NGS) as a powerful tool for detecting genetic variation within BRCA1/2 genes.

Methods

Twenty‐five unrelated female patients diagnosed with familial breast cancer were screened for BRCA1/2 variants. All targeted coding exons and exon–intron boundaries of BRCA1/2 genes were amplified with 167 pairs of primers by NGS.

Results

We have identified two deleterious BRCA1/2 variants in two patients, one in BRCA1 gene (c.4850C>A) and other in BRCA2 gene (c.67+2T>C). In addition to the deleterious variants, we identified 24 distinct missense variants of uncertain significance, 10 of them are seen to confer minor but cumulatively significant risk of breast cancer.

Conclusion

Our data suggest that BRCA1/2 variants may contribute to the pathogenesis of familial breast cancer in Bahrain. It also shows that NGS is useful tool for screening BRCA1/2 genetic variants of probands and unaffected relatives.
Role of genomics literacy in reducing the burden of common genetic diseases in Africa
Authors: Mboowa Gerald , Sserwadda Ivan
Published: May 2019

Background

In Africa, health practitioners and the current knowledge of the public on genetics and genomics is still very low and yet this has potential to reduce the burden of common genetic diseases. Many initiatives have promoted genomic research, infrastructure, and capacity building in Africa. What remains to be done is to improve genomics literacy among populations and communities while utilizing an array of strategies. Genomic literacy and awareness are key in the management of genetic diseases which includes diagnosis, prevention of complications and therapy. Africa is characterized by great cultural and language diversity thereby requiring a multidisciplinary approach to improving public and community genomics literacy and engagement. However, this is further complicated by having the fact that sub‐Saharan Africa is comprised of countries with the lowest literacy rates in the world.

Methods

We applied the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines to review genomic literacy in Africa using PubMed database.

Results

We found very limited evidence of genomics literacy for genetic diseases in Africa.

Conclusion

We propose a number of approaches that if adopted will significantly increase the genomic literacy and reduce the burden of genetic diseases in Africa.
Quinoxalinones Based Aldose Reductase Inhibitors: 2D and 3D‐QSAR Analysis
Authors: Masand Vijay H. , Elsayed Nahed N. , Thakur Sumersingh D. , Gawhale Nandkishor , Rathore Mithilesh M.
Published: May 2019

In the present work, 2D‐ and 3D‐quantitative structure‐activity relationship (QSAR) analysis has been employed for a diverse set of eighty‐nine quinoxalinones to identify the pharmacophoric features with significant correlation with the aldose reductase inhibitory activity. Using genetic algorithm (GA) as a variable selection method, multivariate linear regression (MLR) models were derived using a pool of molecular descriptors. All the six‐descriptor based GA‐MLR QSAR models are statistically robust with coefficient of determination (R2)>0.80 and cross‐validated R2>0.77. The derived GA‐MLR models were thoroughly validated using internal and external and Y‐scrambling techniques. The CoMFA like model, which is based on a combination of steric and electrostatic effects and graphically inferred using contour plots, is highly robust with R2>0.93 and cross‐validated R2>0.73. The established QSAR and CoMFA like models are proficient in identify key pharmacophoric features that govern the aldose reductase inhibitory activity of quinoxalinones.
Local and global Hopf bifurcation in a neutral population model with age structure
Authors: Duan Daifeng , Niu Ben , Wei Junjie
Published: May 2019

In this paper, an age‐structured population model with the form of neutral functional differential equation is studied. We discuss the stability of the positive equilibrium by analyzing the characteristic equation. Local Hopf bifurcation results are also obtained by choosing the mature delay as bifurcation parameter. On the center manifold, the normal form of the Hopf bifurcation is derived, and explicit formulae for determining the criticality of bifurcation are theoretically given. Moreover, the global continuation of Hopf bifurcating periodic solutions is investigated by using the global Hopf bifurcation theory of neutral equations. Finally, some numerical examples are carried out to support the main results.
An update of the regulatory factors of sperm migration from the uterus into the oviduct by genetically manipulated mice
Authors: Xiong Wenfeng , Wang Zhugang , Shen Chunling
Published: May 2019

Mammalian reproductive processes involve spermatogenesis, which occurs in the testis, and fertilization, which takes place in the female genital tract. Fertilization is a successive, multistep, and extremely complicated event that usually includes sperm survival in the uterus, sperm migration through the uterotubal junction (UTJ) and the oviduct, sperm penetration through the cumulus cell layer and the zona pellucida, and sperm–egg fusion. There may be a complex molecular mechanism to ensure that the above processes run smoothly. Previous studies have discovered essential factors for these fertilization steps through in vitro fertilization experiments. However, recent gene disruption approaches in mice have revealed that many of the factors previously described as important for fertilization are largely dispensable in gene‐knockout animals, and some previously unknown factors are emerging. As a result, the molecular mechanisms of fertilization, especially sperm migration from the uterus into the oviduct, have recently been revised by the emergence of genetically modified animals. In this review, we only focus on and update the essential genes for sperm migration through the UTJ and describe recent advances in our knowledge of the basis of mammalian sperm migration.
Population‐based Bayesian regularization for microstructural diffusion MRI with NODDIDA
Authors: Mozumder Meghdoot , Pozo Jose M. , Coelho Santiago , Frangi Alejandro F.
Published: May 2019

Purpose

Information on the brain microstructure can be probed by Diffusion Magnetic Resonance Imaging (dMRI). Neurite Orientation Dispersion and Density Imaging with Diffusivities Assessment (NODDIDA) is one of the simplest microstructural model proposed. However, the estimation of the NODDIDA parameters from clinically plausible dMRI acquisition is ill‐posed, and different parameter sets can describe the same measurements equally well. A few approaches to resolve this problem focused on developing better optimization strategies for this non‐convex optimization. However, this fundamentally does not resolve ill‐posedness. This article introduces a Bayesian estimation framework, which is regularized through knowledge from an extensive dMRI measurement set on a population of healthy adults (henceforth population‐based prior).

Methods

We reformulate the problem as a Bayesian maximum a posteriori estimation, which includes as a special case previous approach using non‐informative uniform priors. A population‐based prior is estimated from 35 subjects of the MGH Adult Diffusion data (Human Connectome Project), acquired with an extensive acquisition protocol including high b‐values. The accuracy and robustness of different approaches with and without the population‐based prior is tested on subsets of the MGH dataset, and an independent dataset from a clinically comparable scanner, with only clinically plausible dMRI measurements.

Results

The population‐based prior produced substantially more accurate and robust parameter estimates, compared to the conventional uniform priors, for clinically feasible protocols, without introducing any evident bias.

Conclusions

The use of the proposed Bayesian population‐based prior can lead to clinically feasible and robust estimation of NODDIDA parameters without changing the acquisition protocol.
A local multiple proper generalized decomposition based on the partition of unity
Authors: Ibáñez Rubén , Abisset‐Chavanne Emmanuelle , Chinesta Francisco , Huerta Antonio , Cueto Elías
Published: May 2019

It is well known that model order reduction techniques that project the solution of the problem at hand onto a low‐dimensional subspace present difficulties when this solution lies on a nonlinear manifold. To overcome these difficulties (notably, an undesirable increase in the number of required modes in the solution), several solutions have been suggested. Among them, we can cite the use of nonlinear dimensionality reduction techniques or, alternatively, the employ of linear local reduced order approaches. These last approaches usually present the difficulty of ensuring continuity between these local models. Here, a new method is presented, which ensures this continuity by resorting to the paradigm of the partition of unity while employing proper generalized decompositions at each local patch.
Microscopic design and optimization of hydrodynamically lubricated dissipative interfaces
Authors: Çakal Berkay Alp , Temizer İlker , Terada Kenjiro , Kato Junji
Published: May 2019

A homogenization‐based topology optimization framework is developed, which can endow hydrodynamically lubricated interfaces with a micro‐texture, to achieve optimal macroscopic responses by addressing both dissipative and nondissipative physics at the interface. With respect to the homogenization aspects of the problem, the thermodynamic consistency of the two‐scale formulation is explicitly analyzed and verified. With respect to the topology optimization aspects, a variational approach to sensitivity analysis is pursued. Subsequently, these are employed in micro‐texture design studies, which address microscopic and macroscopic objectives. The influence of dissipation on the optimization results is demonstrated through extensive numerical investigations, which also highlight the importance of working in a sufficiently flexible design space that can deliver nearly optimal micro‐texture geometries.
Dietary intake of glucoraphanin prevents the reduction of dopamine transporter in the mouse striatum after repeated administration of MPTP
Authors: Pu Yaoyu , Qu Youge , Chang Lijia , Wang Si‐ming , Zhang Kai , Ushida Yusuke , Suganuma Hiroyuki , Hashimoto Kenji
Published: May 2019

Aims

Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder. Although diet may influence the development of PD, the precise mechanisms underlying relationship between diet and PD pathology are unknown. Here, we examined whether dietary intake of glucoraphanin (GF), the precursor of a natural antioxidant sulforaphane in cruciferous vegetables, can affect the reduction of dopamine transporter (DAT) in the mouse striatum after repeated administration of MPTP (1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine).

Methods

Normal food pellet or 0.1% GF food pellet was given into male mice for 28 days from 8‐week‐old. Subsequently, saline (5 mL/kg × 3, 2‐hour interval) or MPTP (10 mg/kg × 3, 2‐hour interval) was injected into mice. Immunohistochemistry of DAT in the striatum was performed 7 days after MPTP injection.

Results

Repeated injections of MPTP significantly decreased the density of DAT‐immunoreactivity in the mouse striatum. In contrast, dietary intake of 0.1% GF food pellet significantly protected against MPTP‐induced reduction of DAT‐immunoreactivity in the striatum.

Conclusion

This study suggests that dietary intake of GF food pellet could prevent MPTP‐induced dopaminergic neurotoxicity in the striatum of adult mice. Therefore, dietary intake of GF‐rich cruciferous vegetables may have beneficial effects on prevention for development of PD.
Intra‐Abdominal Adipose Tissue Quantification by Alternative Versus Reference Methods: A Systematic Review and Meta‐Analysis
Authors: Murphy Jessica , Bacon Simon L. , Morais José A. , Tsoukas Michael A. , Santosa Sylvia
Published: May 2019

Objective

This meta‐analysis aimed to assess the agreement between intra‐abdominal adipose tissue (IAAT) quantified by alternative methods and the reference standards, computed tomography (CT) and magnetic resonance imaging (MRI).

Methods

MEDLINE and EMBASE electronic databases were systematically searched to identify studies that quantified IAAT thickness, area, or volume by a comparator method and CT or MRI. Using an inverse variance weighted approach (random‐effects model), the mean differences and 95% limits of agreement (LoA) were pooled between methods.

Results

The meta‐analysis included 24 studies using four comparator methods. The pooled mean differences were −0.3 cm (95% LoA: −3.4 to 3.2 cm; P = 0.400) for ultrasound and −11.6 cm2 (95% LoA: −43.1 to 19.9 cm2; P = 0.004) for bioelectrical impedance analysis. Dual‐energy x‐ray absorptiometry (DXA) quantified both IAAT area and volume with mean differences of 8.1 cm2 (95% LoA: −98.9 to 115.1 cm2; P = 0.061) and 10 cm3 (95% LoA: −280 to 300 cm3; P = 0.808), respectively.

Conclusions

Ultrasound and DXA measure IAAT with minimal bias from CT or MRI, while bioelectrical impedance analysis systematically underestimates IAAT. However, with the exception of DXA for IAAT volume, the wide LoA caution against clinical or research use of the comparator methods and emphasize the need to optimize alternatives to the reference standards.
Three Decades of New Zealand Adults Obesity Trends: An Estimation of Energy Imbalance Gaps Using System Dynamics Modeling
Authors: Fallah‐Fini Saeideh , Vandevijvere Stefanie , Rezaei Tannaz , Heke Ihirangi , Swinburn Boyd
Published: May 2019

Objective

The energy imbalance gap (EIG) captures the average daily excess energy intake and governs the speed of change in body mass. This study quantifies the dynamics of the EIG over time and across different ethnic, sex, and weight groups in New Zealand.

Methods

A novel method in system dynamics was used to estimate the trends/dynamics of the EIG among Pacific, Māori, Asian, and European/other men and women over the past 3 decades in New Zealand. The model was calibrated using data from the national New Zealand Health Survey (1988‐2014/15).

Results

All ethnic/sex subpopulations except European/other women and Pacific men showed a drop in their EIGs starting in early to mid‐2000. For European/other subpopulations, the EIG was positive in 2014/15 but lower than it was in previous years, meaning that the prevalence of obesity still increased but at a slower pace. For the Pacific subpopulation, increasing trends of the EIG across all BMI classes in 2014/15 implied that obesity prevalence for this subpopulation increased at a rate faster than before. Among Asian women, almost all BMI classes showed a negative EIG in 2012 to 2014/15, implying decreasing prevalence of obesity in this subpopulation. Māori populations with obesity showed a negative EIG in 2014/15.

Conclusions

The detailed heterogeneous trends of the EIG explain the obesity patterns for different ethnic, sex, and BMI subgroups in New Zealand and suggest the need for customizing targets/policy interventions for different subpopulations.
Zero‐order asymptotic solution of a class of singularly perturbed linear‐quadratic problems with weak controls in a critical case
Authors: Kurina Galina , Thi Hoai Nguyen
Published: May 2019

We consider a linear‐quadratic optimal control problem where the second power of a small parameter stands in front of the derivative and a control in a state equation and in front of a quadratic form with respect to control in a performance index; moreover, in the state equation, the nonhomogeneity has the first order of the power of a small parameter, and a matrix in front of the state variable is singular if the small parameter is equal to zero. Using immediate substituting a postulated asymptotic expansion of a solution, containing a regular series and four boundary layer functions series, into the problem condition, we obtain problems for finding asymptotic terms of the zero order for the optimal control and the first order for the optimal trajectory. An illustrative example is given.
Description of complementary actions of mineral and organic additives in thermoplastic polymer composites by Flame Retardancy Index
Authors: Vahabi Henri , Laoutid Fouad , Movahedifar Elnaz , Khalili Reza , Rahmati Negar , Vagner Christelle , Cochez Marianne , Brison Loic , Ducos Franck , Ganjali Mohammad Reza , Saeb Mohammad Reza
Published: May 2019

This work visualizes the complementary actions of organic and mineral additives in model thermoplastic polymer composites in terms of Flame Retardancy Index (FRI). Thermal and flame retardancy behaviors of ethylene‐vinyl acetate copolymer (EVA) composites containing calcium carbonate (CC) mineral and ammonium polyphosphate (APP) organic additives were studied varying composition of additives in the 80/20 EVA/(xCC + (20 − x)APP) composites with x denoting 0, 5, 10, 15, and 20 wt%. Thermogravimetric analysis (TGA) revealed that the onset temperature of composites and the remaining residue were increased by combination of APP and CC, while cone calorimetry results were indicative of a promising flame retardancy performance at a given composition of APP and CC. Based on FRI values, we made distinguished samples from flame retardancy performance viewpoint, where the best flame retardancy was obtained by combination of 15 wt% APP and 5 wt% CC, as reflected in FRI value of 3.08. By contrast, samples containing only APP or CC revealed low resistance against flame, as signaled by FRI values of 0.99 and 0.89, respectively. X‐ray diffraction (XRD) analysis was made on remaining residue collected at the end of cone calorimetry measurements. Moreover, Raman analysis confirmed barrier effect of flame retardancy for EVA/(5APP + 15CC) sample, featured by a higher graphitization level as well as a thicker yet more homogenous char layer. Mechanical behavior analysis of composites revealed an acceptable level of properties, particularly high elongation at break, which was almost independent of formulation. However, a minor loss in yield stress was observed, especially for EVA(10CC + 10APP) sample.