bluuebunny/crossref_metadata_2025 huggingface dataset:
Tubulin mutations in brain development disorders: Why haploinsufficiency does not explain TUBA1A tubulinopathies
Authors: Aiken Jayne , Buscaglia Georgia , Aiken A. Sophie , Moore Jeffrey K. , Bates Emily A.
Published: October 2019

The neuronal cytoskeleton performs incredible feats during nervous system development. Extension of neuronal processes, migration, and synapse formation rely on the proper regulation of microtubules. Mutations that disrupt the primary α‐tubulin expressed during brain development, TUBA1A, are associated with a spectrum of human brain malformations. One model posits that TUBA1A mutations lead to a reduction in tubulin subunits available for microtubule polymerization, which represents a haploinsufficiency mechanism. We propose an alternative model for the majority of tubulinopathy mutations, in which the mutant tubulin polymerizes into the microtubule lattice to dominantly “poison” microtubule function. Nine distinct α‐tubulin and ten β‐tubulin genes have been identified in the human genome. These genes encode similar tubulin proteins, called isotypes. Multiple tubulin isotypes may partially compensate for heterozygous deletion of a tubulin gene, but may not overcome the disruption caused by missense mutations that dominantly alter microtubule function. Here, we describe disorders attributed to haploinsufficiency versus dominant negative mechanisms to demonstrate the hallmark features of each disorder. We summarize literature on mouse models that represent both knockout and point mutants in tubulin genes, with an emphasis on how these mutations might provide insight into the nature of tubulinopathy patient mutations. Finally, we present data from a panel of TUBA1A tubulinopathy mutations generated in yeast α‐tubulin that demonstrate that α‐tubulin mutants can incorporate into the microtubule network and support viability of yeast growth. This perspective on tubulinopathy mutations draws on previous studies and additional data to provide a fresh perspective on how TUBA1A mutations disrupt neurodevelopment.
Dose‐dependent effect of aerobic exercise on inflammatory biomarkers in a randomized controlled trial of women at high risk of breast cancer
Authors: Haley Jeremy S. , Hibler Elizabeth A. , Zhou Shouhao , Schmitz Kathryn H. , Sturgeon Kathleen M.
Published: October 2019

Background

Increased levels of inflammation are associated with many diseases, including cancer. Physical activity can lower breast cancer risk as well as levels of inflammation. The Women In Steady Exercise Research (WISER) Sister trial was a randomized controlled trial that investigated the effects of a dosed, moderate to vigorous, aerobic exercise intervention on levels of inflammation in premenopausal women who were at high risk of developing breast cancer.

Methods

Participants were randomized to control (<75 minutes per week; 41 patients), low‐dose exercise (150 minutes per week; 38 patients), or high‐dose exercise (300 minutes per week; 37 patients) groups. The 5‐menstrual cycles–long, home‐based treadmill exercise intervention gradually increased in minutes per week and intensity up to a maximum of 80% of the age‐predicted maximum heart rate. Blood was collected at baseline and at follow‐up and assayed for chemokine (C‐C motif) ligand 2 (CCL2), interleukin 10 (IL‐10), interleukin 12 (IL‐12), and tumor necrosis factor α (TNF‐α).

Results

A linear dose‐response relationship was observed for the proinflammatory biomarkers CCL2 (%Δ of −5.44% in the control group, −0.03% in the low‐dose exercise group, and 1.54% in the high‐dose exercise group), IL‐12 (%Δ of −21.5% in the control group, 38.2% in the low‐dose exercise group, and 25.8% in the high‐dose exercise group,) and TNF‐α (%Δ of −4.69% in the control group, 9.51% in the low‐dose exercise group, and 15.7% in the high‐dose exercise group) but not for the anti‐inflammatory biomarker IL‐10 (%Δ of 5.05% in the control group, 6.05% in the low‐dose exercise group, and 10.6% in the high‐dose exercise group). For IL‐12 and TNF‐α, the percentage change was significantly higher in the low‐dose (IL‐12: P < .001; and TNF‐α: P = .01) and high‐dose (IL‐12: P < .001; and TNF‐α: P < .001) exercise groups compared with the control group.

Conclusions

Moderate to vigorous aerobic exercise appeared to increase levels of proinflammatory biomarkers in a dose‐dependent manner in a population of healthy women at high risk of developing breast cancer. The results of the current study suggest that for healthy premenopausal women, the mechanism of reduced breast cancer risk observed in physically active individuals may not be a result of reduced levels of inflammation.
Evaluation of the use of a guided bur during preclinical teaching of tooth preparation: A pilot study
Authors: Yee Soho , Richert Raphaël , Viguie Gilbert , Couraud Sébastien , Dehurtevent Marion , Fages Michel , Corne Pascale , Ducret Maxime
Published: October 2019

Objectives

An innovative calibrated bur, aiming to improve precision during reduction of the incisal edge, was recently proposed to guide practitioners during tooth preparation. However, limited information is available concerning its usefulness in dental preclinical education. The aim of this study was to evaluate whether using this innovative guided bur improves learning experience quality and the performance of students during tooth preparation.

Material and methods

After having provided written consent, 60 second‐year students were divided into two groups. One group used a 1‐mm rounded bur to perform depth grooves, whereas the second group used the innovative guided bur, consisting in a 2‐mm‐depth marker with a stopping surface. Once the grooves were obtained, they were then connected using the same wheel bur in both groups. The aim was to obtain a final 2‐mm reduction of the incisal edge. Quality of the learning experience (stress level, motivation to restart, self‐evaluation of the preparation, and difficulty) was quantified using a visual analog scale. Duration of the procedure was also measured in both groups. 3D measurements for each tooth were performed using an STL comparison software.

Results

There were no significant differences between groups in terms of stress and self‐evaluation of the preparation. Students in the guided bur group reported significantly lower perception of exercise difficulty (p < .001) and significantly higher motivation to restart the procedure (p < .001). The guided bur group performed the procedure in 16.4% less time than the rounded bur group. The use of the guided bur led to a 23% over‐reduction, whereas the use of the rounded bur led to a 10% under‐reduction.

Conclusions

Overall, the present study shows that the guided bur provides significant improvement in the student's learning experience with increased motivation and decreased perception of difficulty. It shortens the duration of procedure performance, but it also induces a reduction in preparation accuracy.
A note on mutually beneficial exchange and discrimination
Authors: Duncan Thomas K. , Farhat Daniel
Published: October 2019

We use Hammond and Axelrod's (Hammond, R. A. & Axelrod, R. (2006). The evolution of ethnocentrism. Journal of Conflict Resolution, 50, 6: 926–936) agent‐based model of ethnocentrism to show how people's willingness to cooperate with outsiders is affected by mutually beneficial exchange. In environments where one person gains at the expense of others (“charity economies”), we find discrimination to be a dominant behavior. However, non‐discrimination becomes the dominant behavior when an environment contains productive investment and mutually beneficial exchange (“investment economies”). These results point to market‐improving policy prescriptions to reduce racial/ethnic tension and the conflict that arise from it.
Flow Cytometric Immunophenotypic Analysis in the Diagnosis and Prognostication of Plasma Cell Neoplasms
Authors: Wang Hao‐Wei , Lin Pei
Published: October 2019

This review focuses on the roles of flow cytometric immunophenotyping has in the differential diagnosis of plasma cell neoplasms and the post‐therapy monitoring of minimal (measurable) residual disease. The need to integrate flow cytometry data with clinical, laboratory, radiographic, morphological, and molecular genetic findings is emphasized. The challenges of and strategies for evaluating plasma cells in the setting of targeted therapy are also highlighted. © 2019 International Clinical Cytometry Society
Estimation of the commercial height of trees with laser meter: a viable alternative for forest management in the Brazilian Amazon
Authors: Sales Agust , Antonio Siviero Marco , Cezar Gomes Pereira Paulo , Benmuyal Vieira Sabrina , Alves Berberian Ghaby , Maia Miranda Bárbara
Published: October 2019

Commercial height of the tree is a key variable for estimating the wood stock in tropical forests managed for timber production purposes. Most available measurement devices suffer limitations in this type of forest, promoting low precision measurements with high variation errors. The laser meter device appears as a viable alternative, as in addition to using trigonometric principles, it is not necessary that the device is close to the eyes of the meter to carry out the measurement. The device can be used to measure commercial height of trees on flat or sloping terrain, at different distances from the tree. However, there are no studies evaluating the precision of this device. The objective of this study was to determine the precision of the laser meter method for estimating the commercial height of trees, as compared to the actual measurement in a tropical forest in the Brazilian Amazon. Measurements were made on 300 trees with commercial height between 7 and 14 m. Actual commercial heights were measured with graduated ruler. Applied tests were paired t test, graphical analysis of residuals and calculations of bias statistics, mean absolute deviation, standard deviation of differences, and coefficient of determination (R2). Paired t test indicated that the mean of the heights measured by the laser meter is statistically equal to that of the graduated ruler. Measurements with laser meter did not show bias and had mean error of 0.0745. The standard deviation of the differences indicated dispersion of errors of 0.97, equal to that shown in the graduated rule. Laser meter presents an alternative method for estimating the commercial height of trees in tropical forest in the Brazilian Amazon. There was no tendency to underestimate or overestimate the commercial heights of trees. Use of the laser meter is potentially of use for measuring the commercial height of trees in tropical forests.
Population structure, connectivity, and demographic history of an apex marine predator, the bull shark Carcharhinus leucas
Authors: Pirog Agathe , Ravigné Virginie , Fontaine Michaël C. , Rieux Adrien , Gilabert Aude , Cliff Geremy , Clua Eric , Daly Ryan , Heithaus Michael R. , Kiszka Jeremy J. , Matich Philip , Nevill John E. G. , Smoothey Amy F. , Temple Andrew J. , Berggren Per , Jaquemet Sébastien , Magalon Hélène
Published: October 2019

Knowledge of population structure, connectivity, and effective population size remains limited for many marine apex predators, including the bull shark Carcharhinus leucas. This large‐bodied coastal shark is distributed worldwide in warm temperate and tropical waters, and uses estuaries and rivers as nurseries. As an apex predator, the bull shark likely plays a vital ecological role within marine food webs, but is at risk due to inshore habitat degradation and various fishing pressures. We investigated the bull shark's global population structure and demographic history by analyzing the genetic diversity of 370 individuals from 11 different locations using 25 microsatellite loci and three mitochondrial genes (CR, nd4, and cytb). Both types of markers revealed clustering between sharks from the Western Atlantic and those from the Western Pacific and the Western Indian Ocean, with no contemporary gene flow. Microsatellite data suggested low differentiation between the Western Indian Ocean and the Western Pacific, but substantial differentiation was found using mitochondrial DNA. Integrating information from both types of markers and using Bayesian computation with a random forest procedure (ABC‐RF), this discordance was found to be due to a complete lack of contemporary gene flow. High genetic connectivity was found both within the Western Indian Ocean and within the Western Pacific. In conclusion, these results suggest important structuring of bull shark populations globally with important gene flow occurring along coastlines, highlighting the need for management and conservation plans on regional scales rather than oceanic basin scale.
Multiple freshwater invasions of the tapertail anchovy (Clupeiformes: Engraulidae) of the Yangtze River
Authors: Cheng Fangyuan , Wang Qian , Maisano Delser Pierpaolo , Li Chenhong
Published: October 2019

Freshwater fish evolved from anadromous ancestors can be found in almost all continents. The roles of paleogeographic events and nature selection in speciation process often are under focus of research. We studied genetic diversity of anadromous and resident tapertail anchovies (Coilia nasus species complex) in the Yangtze River Basin using 4,434 nuclear loci, and tested the history of freshwater invasion of C. nasus. We found that both C. brachygnathus and C. nasus were valid species, but the resident C. nasus taihuensis and the anadromous C. nasus were not different genetically based on Bayes factor species delimitation (BFD*). Maximum likelihood tree, Network, PCA and STRUCTURE analyses all corroborated the results of BFD*. Two independent freshwater invasion events of C. nasus were supported, with the first event occurring around 4.07 Ma and the second happened around 3.2 Ka. The time of the two freshwater invasions is consistent with different paleogeographic events. Estimation showed that gene flow was higher within ecotypes than between different ecotypes. F‐DIST analyses identified 120 disruptive outliers by comparing C. brachygnathus to anadromous C. nasus, and 21 disruptive outliers by comparing resident C. nasus to anadromous C. nasus. Nine outliers were found to be common between the two comparisons, indicating that independent freshwater invasion of C. nasus might involve similar molecular pathways. The results of this study suggest that adaptation to landlocked freshwater environment of migratory fish can evolve multiple times independently, and morphology of landlocked ecotypes may cause confusion in their taxonomy.
Dinuclear Copper Complexes Triply Bridged by a Tetraphosphane, rac‐Ph2PCH2P(Ph)CH2P(Ph)CH2PPh2
Authors: Tanase Tomoaki , Otaki Risa , Okue Ayumi , Nakamae Kanako , Nakajima Takayuki
Published: October 2019

Invited for the cover of this issue is the group of Tomoaki Tanase at Nara Women's University, Japan. The cover image shows a dinuclear copper(I) complex triply bridged by rac‐dpmppm with a series of diimino ligands as a “dicopper firefly” that switches its luminescence mechanisms to emit rapid fluorescence in dichloromethane solution and 3MLCT phosphorescence in the solid state.
Linseed and Complex Rosin Ester Oils Additivated with MWCNTs and Nanopearls for Gears/Wheel‐Rail Systems
Authors: Pérez‐de Brito Andrey Fabio , Ponce Suhey , Pérez‐Robles Juan Francisco , Higuera‐Ciapara Inocencio , Toro Alejandro , Esparza Rodrigo , Medina Dora Iliana , Villaseñor‐Ortega Francisco , Luna‐Barcenas Gabriel
Published: October 2019

An innovative biolubricant for gears/wheel‐rail systems is formulated; it is produced inexpensively using high‐viscosity vegetable oils modified with additives of unpurified carbon nanopearls (CNPs) and MWCNTs produced via carbon‐vapor deposition. Traditional lubricants made from non‐renewable sources can be replaced with such additive‐based oils. The addition of both unpurified carbon nanopearls and nanotubes containing nanoparticles of Fe, Ni, Co, or SiO2 is a simple way to improve the tribological properties of biolubricants. Therefore, carbon nanostructures used as additives are not required to be purified or functionalized, thus reducing production costs. Tribological testing is performed with ball‐on‐disc, four‐ball, and twin‐disc machines for two high‐viscosity biolubricants. A complex rosin ester and linseed oil additivated with commercial and raw CNPs/MWCNTs are tested. Scanning electron microscope characterization is used to assess the morphology and structure of both the carbon nanopearls and the multiwalled carbon nanotube particles in addition to the worn metal surfaces. Additionally, X‐ray diffraction, FTIR spectroscopy, and inductively coupled plasma atomic emission spectroscopy are used to characterize the MWCNTs additives.

Practical Applications: Biolubricant additivation with raw unpurified MWCNTs and CNPs for enhanced tribological performance. Presence of Fe, Ni, Co, and Si nanoparticles helps fine‐tune the friction coefficient and anti‐wear rates. The proposed method may prove useful in biolubricant formulation for applications in gears/wheel‐rail and metal machining systems.
Synthesis of Isotopically Labelled Disparlure Enantiomers and Application to the Study of Enantiomer Discrimination in Gypsy Moth Pheromone‐Binding Proteins
Authors: Pinnelli Govardhana R. , Terrado Mailyn , Hillier N. Kirk , Lance David R. , Plettner Erika
Published: October 2019

To study the binding mechanism of disparlure (7,8)‐epoxy‐2‐methyloctadecane enantiomers with pheromone‐binding proteins (PBPs) of the gypsy moth, oxygen‐17 or 18 and 5,5,6,6‐deuterium labelled disparlure enantiomers were prepared in an efficient, enantioselective route. Key steps involve the asymmetric α‐chlorination of dodecanal by SOMO catalysis and Mitsunobu inversion of a 1,2‐chlorohydrin. The pheromone, (+)‐disparlure (7R, 8S), was tested in two infested zones, demonstrating that it is very attractive towards male gypsy moths. Studies of the binding of (+)‐disparlure and its antipode to gypsy moth PBPs by 2H &17O NMR at 600 MHz are reported. Chemical shifts, spin‐lattice relaxation decay times (T1) and transverse relaxation decay times (T2) of deuterium atoms of disparlure enantiomers in 2H NMR show that the binding of disparlure enantiomers to PBP1 differs from binding to PBP2, as expected from their opposite binding preferences (PBP1 binds (–)‐disparlure, and PBP2 binds (+)‐disparlure more strongly). Models of the disparlure enantiomers bound to one internal binding site and two external binding sites of both PBPs were constructed. The observed chemical shift changes of deuterated ligand signals, from non‐bound to bound, T1 and T2 values are correlated with results from the simulations. Together these results suggest that the disparlure enantiomers adopt distinct conformations within the binding sites of the two PBPs and interact with residues that line the sites.
Preparation of Unsymmetrical Disulfides from Thioacetates and Thiosulfonates
Authors: Delarue Bizzini Lorenzo , Zwick Patrick , Mayor Marcel
Published: October 2019

A method for the transformation of organic thioacetates, a widely used functionality for the preparation of self‐assembled monolayers on gold surfaces, into unsymmetrical disulfides is reported. Disulfides are readily immobilized on gold in contrast to thioacetates, which usually require a deprotection step prior to bonding to the metal surface. The potential of the method for the controlled preparation of unsymmetrical disulfides has been demonstrated with model compounds comprising several thioacetates, which were readily converted into the corresponding unsymmetrical disulfides.
In Situ Growth of BiOI/MoS2 Heterostructure as Pt Supports for Visible Light‐Assisted Electrocatalytic Methanol Oxidation Reaction
Authors: Zhang Hongmin , Zhai Chunyang , Yang Peizhou , Yuan Chen , Fu Nianqing , Zhu Mingshan
Published: October 2019

A two‐dimensional BiOI/MoS2 heterojunction is fabricated by in situ growth of MoS2 on BiOI nanosheets through a hydrothermal method and then as a carrier for loading on Pt nanoparticles. Transmission electron microscopy shows that Pt nanoparticles are decorated uniformly on the surface of BiOI/MoS2 nanosheets. The obtained Pt‐BiOI/MoS2 is utilized as an electrocatalyst for the methanol oxidation reaction in alkaline conditions under visible light irradiation. Electrochemical evaluations indicate that as‐prepared Pt‐BiOI/MoS2 expresses the highest methanol oxidation reaction activity and stability, and the maximum current density reaches 1007.2 mA mg−1Pt under visible light irradiation, which is 12 and 3.5 times higher compared with Pt‐BiOI and commercial Pt/C electrodes, respectively, in the traditional electrocatalytic process. The results suggest that a synergy of photo‐ and electro‐processes improves the photoelectrocatalytic performance of Pt‐BiOI/MoS2 in the methanol oxidation reaction.
Highly Structured Nanofiber Zeolite Materials for Biogas Upgrading
Authors: Zhang Wenjing , Narang Kritika , Simonsen Søren Bredmose , Vinkel Nadja Maria , Gudik-Sørensen Mads , Han Li , Akhtar Farid , Kaiser Andreas
Published: October 2019

Hierarchical zeolite composite nanofibers are designed using an electrospinning technique with post‐carbonization processing to form mechanically strong pellets for biogas upgrading. A ZSM‐5 nanopowder (zeolite) and a polyvinylpyrrolidone (PVP) polymer are electrospun to form ZSM/PVP composite nanofibers, which are transformed into a ZSM and carbon composite nanofiber (ZSM/C) by a two‐step heat treatment. The ZSM/C nanofibers show a 30.4% increase in Brunauer–Emmett–Teller (BET) surface area compared with the non‐structured ZSM‐5 nanopowder. Using ideal adsorbed solution theory, CO2‐over‐CH4 selectivity of 20 and CO2 uptake of 2.15 mmolg−1 at 293 K at 1 bar for ZSM/C nanofibers are obtained. For the efficient use of adsorbents in pressure swing adsorption operation, the nanofibers are structured into ZSM/C pellets that offer a maximum tensile strength of 6.46 MPa to withstand pressure swings. In the breakthrough tests, the CO2 uptake of the pellets reach 3.18 mmolg−1 at 293 K at 4 bar after 5 breakthrough adsorption–desorption cycles, with a much higher mass transfer coefficient of 1.24 ms−1 and CO2 uptake rate of 2.4 mg of CO2 g−1s−1, as compared with other structured zeolite adsorbents.
Study on the disaster reduction mechanism of presplitting blasting and reasonable blasting parameters for shallowly buried remnant pillars
Authors: Yuan Yong , Yuan Chao‐feng , Zhu Cheng , Liu Han‐xiang , Wang Sheng‐zhi
Published: October 2019

Disasters such as support crushing easily occur at the mining face under a shallowly buried remnant pillar; therefore, a method for presplitting blasting remnant pillars to relieve stress concentrations and reduce disaster occurrence is proposed. Based on the geological conditions of Nanliang Mine, combining theoretical analysis and numerical simulation to study the bearing characteristics and stress distribution characteristics of remnant pillars, the influence mechanism of presplitting blasting on remnant pillars in terms of the uncoupling factor, axial charge factor, blast hole arrangement, and detonation method is analyzed, revealing the presplitting blasting and disaster reduction mechanism of shallowly buried remnant pillars; furthermore, reasonable blasting parameters are determined. The results show that the rock is affected by the concentrated load within 40 m below the coal pillar; the reasonable blasting parameters are the uncoupled charge coefficient of 1.5, the axial charge factor of 1.0, and the simultaneous detonation of staggered holes. Blasting coal pillars can reduce the transmission effect of the overlying load and ensure the safe use of low‐resistance hydraulic support.
The efficiency and market‐power interpretations of the multinational enterprise: Two out of three ain't bad
Authors: Clougherty Joseph A. , Skousen Bradley R.
Published: October 2019

Research Summary

We contend that contemporary scholarship must embrace the foundational approach in global business and strategy to consider the relevance of both efficiency and market‐power effects in factoring the implications of multinational activity. We empirically test the degree to which efficiency and market‐power effects manifest in a comprehensive sample of 4,370 cross‐border acquisitions materializing between 1986 and 2010. Specifically, we employ three different measurement approaches to distinguish efficiency enhancing from market‐power increasing cross‐border acquisitions. Empirical results indicate that efficiency enhancing transactions manifest in two‐thirds and market‐power increasing transactions manifest in one‐third of our sampled activities. Accordingly, our results affirm the literature's focus on efficiency effects, yet market‐power effects are sufficiently sizable to merit scholarly attention.

Managerial Summary

Contemporary wisdom generally considers multinational activities to be characterized by efficiency properties. While it is understood that market power may manifest in multinational activity, most observers implicitly assume that anti‐competitive effects are dominated by more‐healthy efficiency effects. Yet, the justification behind the prior that efficiency effects dominate market‐power effects is not evident, as multinational activities conceivably involve substantial market power. Accordingly, we test the received wisdom regarding the dominance of efficiency effects in an extensive sample of cross‐border investments. Our empirical results affirm prevailing assumptions as efficiency enhancing transactions constitute the majority of cross‐border investment activities. However, market‐power increasing transactions manifest as a sizable minority of cross‐border investments; thus, market‐power effects should not be neglected.
Influence of emotional complexity on the neural substrates of affective theory of mind
Authors: Caillaud Marie , Bejanin Alexandre , Laisney Mickael , Gagnepain Pierre , Gaubert Malo , Viard Armelle , Clochon Patrice , de La Sayette Vincent , Allain Philippe , Eustache Francis , Desgranges Béatrice
Published: October 2019

Affective theory of mind (ToM) depends on both the decoding of emotional expressions and the reasoning on emotional mental states from social situations. While previous studies characterized the neural substrates underlying these processes, it remains unclear whether the nature of the emotional state inferred from others can influence the brain activation associated with affective ToM. In the present study, we focused on two types of emotions: basic emotions (BEs) (e.g., anger and surprise), which are innate and universal and self‐conscious emotions (e.g., pride and embarrassment), which correspond to a special class of emotions involving the self and including a representation of one's relative reactions to internal and external standards. Specifically, we used an ecological functional MRI paradigm, on 21 healthy young subjects, to compare brain activations during the decoding of and the reasoning on others' self‐conscious, basic and neutral mental states. Our results showed that compared to neutral states, the inference of self‐conscious and basic emotional states from others elicited more activation in several core regions of affective ToM. Direct comparisons between emotional conditions revealed more activation for self‐conscious than BEs in the right temporoparietal junction during the reasoning process and in left middle occipital regions during the decoding process. Further analyses using a localizer task showed that the extrastriate body area was more recruited for decoding others' self‐conscious versus BEs, which emphasize the importance of body clues to properly infer these emotions. Using an original task allowing for an ecological assessment of the affective ToM, these results demonstrate that the complexity of the emotion inferred to others can influence the recruitment of ToM network. This study also validates the use of our task as an ecological tool to assess the affective ToM, constituting an avenue for the characterization of ToM impairments in neurological conditions.
Review of emerging biomarkers in head and neck squamous cell carcinoma in the era of immunotherapy and targeted therapy
Authors: Hsieh Jason Chia‐Hsun , Wang Hung‐Ming , Wu Min‐Hsien , Chang Kai‐Ping , Chang Pei‐Hung , Liao Chun‐Ta , Liau Chi‐Ting
Published: October 2019

Background

Biomarkers in head and neck squamous cell carcinoma (HNSCC) emerge rapidly in recent years, especially for new targeted therapies and immunotherapies.

Methods

Recent, relevant peer‐reviewed evidence were critically reviewed and summarized.

Results

This review article briefly introduces essential biomarker concepts, including purposes and classifications (predictive, prognostic, and diagnostic markers), and the phases of biomarker development. We summarize current biomarkers in order of clinical utility; p16 and human papillomavirus status remain the most important and validated biomarkers in HNSCC. The rationale for biomarker study design continues to evolve with technological advances, especially whole‐exome or whole‐genomic sequencing. Noninvasive body fluid and liquid biopsy biomarkers appear to hold strong potential for development as tools for early cancer detection, cancer diagnosis, monitoring of disease recurrence, and outcome prediction. In light of discrepancies among different technologies, standardized approaches are needed.

Conclusion

Biomarkers from cancer tissue or blood in HNSCC could direct new anticancer therapies.
Effects of oral and oropharyngeal cancer on speech intelligibility using acoustic analysis: Systematic review
Authors: Balaguer Mathieu , Pommée Timothy , Farinas Jérôme , Pinquier Julien , Woisard Virginie , Speyer Renée
Published: October 2019

Background

The development of automatic tools based on acoustic analysis allows to overcome the limitations of perceptual assessment for patients with head and neck cancer. The aim of this study is to provide a systematic review of literature describing the effects of oral and oropharyngeal cancer on speech intelligibility using acoustic analysis.

Methods

Two databases (PubMed and Embase) were surveyed. The selection process, according to the preferred reporting items for systematic reviews and meta‐analyses (PRISMA) statement, led to a final set of 22 articles.

Results

Nasalance is studied mainly in oropharyngeal patients. The vowels are mostly studied using formant analysis and vowel space area, the consonants by means of spectral moments with specific parameters according to their phonetic characteristic. Machine learning methods allow classifying “intelligible” or “unintelligible” speech for T3 or T4 tumors.

Conclusions

The development of comprehensive models combining different acoustic measures would allow a better consideration of the functional impact of the speech disorder.
Prognostic implications of human papillomavirus status and p16 expression in laryngeal squamous cell carcinoma
Authors: Zhu Yingying , Xia Xin , Gross Neil , Dahlstrom Kristina R. , Gao Liming , Liang Zhiyong , Gao Zhiqiang , Wei Peng , Liu Chuan , Li Guojun , Li Yuncheng , Chen Xingming
Published: October 2019

Background

The purpose of this study was to investigate significance of HPV16 DNA/p16 for survival of patients with laryngeal squamous cell carcinoma (LSCC).

Methods

HPV16 DNA and p16 status in 812 LSCC patients were determined. The survival was performed using Kaplan‐Meier estimates and Cox model.

Results

Compared with HPV negativity, adjusted HRs for HPV16 positivity were 0.57, 95% CI, 0.38 to 0.87; 0.60, 0.40 to 0.88; and 0.65, 0.46 to 0.94 for disease‐specific survival (DSS), recurrence‐free survival (RFS), and overall survival (OS), respectively. Additionally, for p16 expression, aHRs were 0.68, 95% CI, 0.48 to 0.96; 0.72, 0.52 to 0.98; and 0.73, 0.54 to 0.99 for DSS, RFS, and OS, respectively. Finally, for combined analysis, patients with both HPV16‐positivity/p16‐positivity had much better prognosis than those with either negativity. Such above survivals are more significantly better in never smokers.

Conclusion

Our findings suggest that HPV16/p16 may affect survival outcomes of LSCC patients, particularly in never smokers.
Comparison of interventions to treat prompt dependence for children with developmental disabilities
Authors: Gorgan Ella M. , Kodak Tiffany
Published: October 2019

Prior research has examined interventions to prevent prompt dependence from occurring during the training of novel skills. Nevertheless, the relative efficacy and efficiency of different intervention procedures may be idiosyncratic across learners, suggesting the potential benefit of an individualized assessment. The purpose of the current study was to extend the literature on prompt dependence by comparing interventions for 3 participants with developmental disabilities who consistently engaged in correct responses following prompts but did not perform tasks independently. We compared the efficacy and efficiency of 3 interventions including differential reinforcement, prompt fading, and extended response interval. Intervention results differed across participants, indicating that the most efficacious and efficient intervention for prompt dependence should be individualized via assessment.
Effectiveness and acceptability of parent training via telehealth among families around the world
Authors: Tsami Loukia , Lerman Dorothea , Toper‐Korkmaz Ozlem
Published: October 2019

Teaching parents to conduct functional analyses and to implement functional communication training is an efficacious approach for treating socially maintained problem behavior (Derby et al., 1997). Research has found that delivering this assessment and intervention package via telehealth technologies is efficient and acceptable to caregivers in the United States (Wacker et al., 2013b). We replicated this work with families residing in rural and urban areas of eight countries. Two behavior therapists located in the United States conducted appointments in the participants' native languages, using interpreters as needed. Parent‐implemented functional analyses and treatment with functional communication training were highly effective in reducing problem behavior in children diagnosed with autism. Furthermore, parents rated the procedures as acceptable and indicated that the treatment would be effective with their children. These findings indicate that telehealth technologies are a viable option for clinicians to provide behavior analysis services to families around the world.
Photobiomodulation therapy in knee osteoarthritis reduces oxidative stress and inflammatory cytokines in rats
Authors: Yamada Eloá F. , Bobinski Franciane , Martins Daniel F. , Palandi Juliete , Folmer Vanderlei , da Silva Morgana D.
Published: October 2019

Knee osteoarthritis (OA) is a chronic disease that causes pain and gradual degeneration of the articular cartilage. In this study, MIA‐induced OA knee model was used in rats to test the effects of the photobiomodulation therapy (PBM). We analyzed the inflammatory process (pain and cytokine levels), and its influence on the oxidative stress and antioxidant capacity. Knee OA was induced by monosodium iodoacetate (MIA) intra‐articular injection (1.5 mg/50 μL) and the rats were treated with eight sessions of PBM 3 days/week (904 nm, 6 or 18 J/cm2). For each animal, mechanical and cold hyperalgesia and spontaneous pain were evaluated; biological analyses were performed in blood serum, intra‐articular lavage, knee structures, spinal cord and brainstem. Cytokine assays were performed in knee, spinal cord and brainstem samples. The effects of the 18 J/cm2 dose of PBM were promising in reducing pain and neutrophil activity in knee samples, together with reducing oxidative stress damage in blood serum and spinal cord samples. PBM improved the antioxidant capacity in blood serum and brainstem, and decreased the knee pro‐inflammatory cytokine levels. Our study demonstrated that PBM decreased oxidative damage, inflammation and pain. Therefore, this therapy could be an important tool in the treatment of knee OA.
MicroRNA‐9 overexpression suppresses vulnerable atherosclerotic plaque and enhances vascular remodeling through negative regulation of the p38MAPK pathway via OLR1 in acute coronary syndrome
Authors: Yu Dao‐Rui , Wang Tao , Huang Jing , Fang Xing‐Yue , Fan Hao‐Fei , Yi Guo‐Hui , Liu Qiang , Zhang Yu , Zeng Xiang‐Zhou , Liu Qi‐Bing
Published: October 2019

Acute coronary syndrome (ACS) is characterized by atherosclerotic plaque rupture with a high incidence of recurrent ischemic events. Several microRNAs are found to be aberrantly expressed in atherosclerotic plaques. This study aims to investigate the effects of microRNA‐9 (miR‐9) on vulnerable atherosclerotic plaque and vascular remodeling in ACS and underlying mechanisms. Microarray‐based gene expression profiling was used to identify differentially expressed genes related to ACS and regulatory miRNAs. Oxidized low‐density lipoprotein (lectin‐like) receptor 1 (OLR1) was identified to be aberrantly activated in ACS and regulated by miR‐9. OLR1 was verified as a target gene of miR‐9 by bioinformatics prediction and dual luciferase reporter gene assay. The atherosclerotic models were induced in ApoE−/− mice, in which the agomir or antagomir of miR‐9, or small interfering RNA (siRNA) against OLR1 were separately introduced. Serum lipid levels and expression of vascular remodeling and inflammatory response‐related factors were determined, respectively. On the basis of the obtained results, in the atherosclerosis mice treated with the agomir of miR‐9 and siRNA against OLR1, the p38‐mitogen‐activated protein kinase (p38MAPK) pathway was inhibited; levels of triglyceride, total cholesterol, low‐density lipoprotein cholesterol, tumor necrosis factor‐α, interleukin‐6, and vascular endothelial growth factor were reduced, but the high‐density lipoprotein cholesterol level was increased, along with decreased vulnerable atherosclerotic plaque area and enhanced vascular remodeling. Taken together, these findings suggested an inhibitory role miR‐9 acts in the formation of vulnerable atherosclerotic plaques in ACS mice, along with a promoted vascular remodeling, via a negative feedback regulation of OLR1‐mediated p38MAPK pathway.
Large‐Sized Ammonia Clusters and Solvation Energies of the Proton in Ammonia
Authors: Malloum Alhadji , Fifen Jean J. , Conradie Jeanet
Published: October 2019

The absolute solvation energies (free energies and enthalpies) of the proton in ammonia are used to compute the pKa of species embedded in ammonia. They are also used to compute the solvation energies of other ions in ammonia. Despite their importance, it is not possible to determine experimentally the solvation energies of the proton in a given solvent. We propose in this work a direct approach to compute the solvation energies of the proton in ammonia from large‐sized neutral and protonated ammonia clusters. To undertake this investigation, we performed a geometry optimization of neutral and protonated ammonia 30‐mer, 40‐mer, and 50 mer to locate stable structures. These structures have been fully optimized at both APFD/6‐31++g(d,p) and M06‐2X/6‐31++g(d,p) levels of theory. An infrared spectroscopic study of these structures has been provided to assess the reliability of our investigation. Using these structures, we have computed the absolute solvation free energy and the absolute solvation enthalpy of the proton in ammonia. It comes out that the absolute solvation free energy of the proton in ammonia is calculated to be −1192 kJ mol–1, whereas the absolute solvation enthalpy is evaluated to be −1214 kJ mol–1. © 2019 Wiley Periodicals, Inc.
Intramolecular cross‐dehydrogenative coupling of benzaldehyde derivatives: A novel and efficient route to benzocyclic ketones
Authors: Chen Jun , Sheykhahmad Fatima Rashid
Published: October 2019

Benzocyclic ketones are not only found throughout many natural products and synthetic pharmaceutically active compounds but also used as versatile building blocks in organic synthesis. In view of their importance, many researchers have been working to explore novel and efficient synthetic routes for this class of carbonyl compounds. Recently, cross‐dehydrogenative coupling reactions have emerged as one of the most versatile and powerful synthetic strategies to construct various carbon‐carbon and carbon‐heteroatom bonds. In this regard, direct acylation of (hetero)arenes with aldehydes through C(sp2)‐H activation opened up a new page on the synthesis of the titled compounds. In this focus‐review, we discuss the most representative and important reports on the synthesis of cyclic diaryl ketones through intramolecular cross‐dehydrogenative coupling reactions of corresponding benzaldehydes with emphasis on the mechanistic aspects of the reactions.
Association between nucleotide excision repair gene polymorphism and colorectal cancer risk
Authors: Zhang Yujie , Wu Shenshen , Zhou Xiumei , Huang Fang , Chen Rui , Wang Yigang , Wu Jiong
Published: October 2019

Background

The nucleotide excision repair system removes a wide variety of DNA lesions from the human genome, and plays an important role in maintaining genomic stability. Single nucleotide polymorphisms (SNPs) in nucleotide excision repair are associated with the various forms of tumor susceptibility. However, the relationship between NER polymorphism and colorectal cancer is not clear.

Methods

In this study, three candidate SNPs including ERCC4 (rs6498486), ERCC1 (rs3212986), and ERCC5 (rs17655) were analyzed in 1101colorectal cancer patients and 1175 healthy control patients from Jiangsu province (China). Then, we performed Immunohistochemistry, qPCR, and luciferase assay to determine the potential mechanisms.

Results

The ERCC4 rs6498486 AC/CC genotypes show lower susceptibility to CRC than those carrying rs6498486 AA (Adjusted OR = 0.82, 95% CI = 0.69‐0.97). However, we did not observe any association between the colorectal cancer risk and the rs3212986(ERCC1) and rs17655(ERCC5) polymorphisms. Immunohistochemistry, qPCR, and luciferase assay revealed that rs6498486 A > C polymorphism in the ERCC4 promoter region could lessen the expression level of ERCC4 by impacting the binding ability of the transcription factor NF‐kB, thereby affecting the transcription activity of the ERCC4 gene and decreased ERCC4 gene expression.

Conclusion

In brief, our finding demonstrated that ERCC4 rs6498486 serves as a potential biomarker of CRC susceptibility for the development of colorectal cancer.
Overcoming trastuzumab resistance in HER2‐positive breast cancer using combination therapy
Authors: Derakhshani Afshin , Rezaei Zohreh , Safarpour Hossein , Sabri Morteza , Mir Atefeh , Sanati Mohammad Amin , Vahidian Fatemeh , Gholamiyan Moghadam Ali , Aghadoukht Ali , Hajiasgharzadeh Khalil , Baradaran Behzad
Published: October 2019

Human epidermal growth factor receptor 2 (HER2)‐positive breast cancer (BC) comprises around 20–30% of all BC subtypes and is correlated with poor prognosis. For many years, trastuzumab, a monoclonal antibody, has been used to inhibit the HER2 activity. Though, the main resistance to trastuzumab has challenged the use of this drug in the management of HER2‐positive BC. Therefore, the determination of resistance mechanisms and the incorporation of new agents may lead to the development of a better blockade of the HER family receptor signaling. During the last few years, some therapeutic drugs have been developed for treating patients with trastuzumab‐resistant HER2‐positive BC that have more effective influences in the management of this condition. In this regard, the present study aimed at reviewing the mechanisms of trastuzumab resistance and the innovative therapies that have been investigated in trastuzumab‐resistant HER2‐positive BC subjects.
Long noncoding RNA LINC00657 induced by SP1 contributes to the non‐small cell lung cancer progression through targeting miR‐26b‐5p/COMMD8 axis
Authors: Zhang Rui , Niu Zequn , Pei Honghong , Peng Zhuo
Published: October 2019

Non‐small‐cell lung cancer (NSCLC) is a kind of lung cancer with high incidence and poor outcomes all over the world. Studies have validated that the upregulation of long noncoding RNA LINC00657 is related to several cancers. Nevertheless, the underlying regulatory mechanism of LINC00657 in NSCLC has not been well elucidated. In the present study, quantitative reverse‐transcription polymerase chain reaction (RT‐qPCR) revealed that LINC00657 level was apparently elevated in NSCLC cells. Loss‐of function assays demonstrated that LINC00657 silence retarded cell proliferation and migration in NSCLC cells. Moreover, the chromatin immunoprecipitation result identified the transcription factor SP1 could bind with LINC00657 promoter, and RT‐qPCR proved SP1 positively regulated LINC00657 expression in NSCLC cells. In addition, the mechanistic investigations unveiled that LINC00657 was an endogenous sponge of miR‐26b‐5p and therefore boosted the expression of copper metabolism MURR1 domain‐containing 8 (COMMD8), one of the targets of miR‐26b‐5p. Besides, miR‐26b‐5p could negatively regulate LINC00657 or COMMD8 in NSCLC cells. With the application of rescue assays, we uncovered that overexpression of COMMD8 partly mitigated the impairment of LINC00657 repression on NSCLC cell proliferation and migration. Together, our study illustrated that SP1‐stimulated LINC00657 promoted NSCLC progression through targeting miR‐26b‐5p/COMMD8 axis, offering a novel potential therapeutic target for NSCLC.
The potential role of stromal cell‐derived factor‐1α/CXCR4/CXCR7 axis in adipose‐derived mesenchymal stem cells
Authors: Ji Fukang , Wang Yicheng , Yuan Jinxue , Wu Qiong , Wang Jinhuang , Liu Dalie
Published: October 2019

To investigate the potential role of stromal cell‐derived factor‐1α (SDF‐1α)/CXCR4/CXCR7 axis in adipose‐derived mesenchymal stem cells (ADSCs), quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) was employed to screen the effective small interfering RNA against CXCR4 and CXCR7 in ADSCs. The messenger RNA (mRNA) and proteins abundances of AKT (p‐AKT), ERK (p‐ERK), JNK (p‐JNK), and p38 (p‐p38) in different groups were identified by qRT‐PCR, western blot, and immunofluorescence staining method. Meanwhile, cell migration and cell proliferation with SDF‐1 treated were examined by a 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay and transwell permeable assay, respectively. Moreover, the interaction between CXCR4 and CXCR7 was examined by a GST pull‐down assay. CXCR4 small interfering RNA3 (siRNA3) and CXCR7 siRNA3 have been proved to the most effective tools for knockdown CXCR4 and CXCR7 expressions. mRNA abundance of JNK and p38 could be affected by SDF‐1α/CXCR4/CXCR7 axis. However, western blot analysis of p‐AKT, p‐ERK, p‐JNK, and p‐p38 in CXCR43‐treated ADSCs was significantly higher than that in the control group. Moreover, the immunofluorescence staining analysis revealed that the expressions of p‐ATK and p‐JNK proteins were significantly higher in NC‐ and SDF‐1‐treated subgroups than that in the CXCR4 and CXCR7 groups. p‐ATK and p‐JNK proteins in CXCR4 group were similar to that in CXCR7 group. Cell migration analysis of CXCR4‐treated ADSCs suggested that knockdown CXCR4 could effectively promote cell migration (p < .05). Moreover, CXCR4 could interact with CXCR7. The results in this study could provide a better understanding of SDF‐1α/CXCR4/CXCR7 axis during ADSCs development.