bluuebunny/crossref_metadata_2025 huggingface dataset:
Japanese Kampo Medicine Juzentaihoto Enhances Antitumor Immunity in CD1d−/− Mice Lacking NKT Cells
Authors: Takaku Shun , Shimizu Masumi , Takahashi Hidemi
Published: January 2020

Although the Japanese traditional herbal medicine (Kampo), Juzentaihoto (JTT), has been reported to have antitumor effects in several tumor models, its role in tumor immunology remains controversial. In the present study, we tested whether oral administration of JTT enhances antitumor immunity in CD1d−/− mice, in which immunosuppression was partially relieved due to the lack of NKT cells. In a subcutaneous murine syngeneic CT26 colorectal tumor model, JTT had no impact on tumor growth in wild type (WT) BALB/c mice. However, the growth rate of tumors was significantly slower in CD1d−/− mice than in WT mice. Surprisingly, JTT significantly delayed tumor growth in such CD1d−/− mice. In vivo depletion of CD8+ T cells revealed that CD8+ T cells are required for JTT’s antitumor activity. Moreover, tumor-reactive cytotoxic T-lymphocytes were detected exclusively in JTT-treated mice with well-controlled tumors. JTT did not affect the number of tumor-infiltrating CD4+ regulatory T cells. On the contrary, JTT increased the degranulation marker CD107a+ CD8+ T cells and decreased Ly6G+ Ly6Clo polymorphonuclear myeloid-derived suppressor cells in tumor-infiltrating lymphocytes, most probably contributing to the suppression of tumor growth in JTT-treated mice. Nonetheless, JTT had no impact on the proportion of monocytic myeloid-derived suppressor cells. In conclusion, our results indicate that in the absence of NKT cells, JTT augments antitumor immunity by CD8+ T cells, suggesting that this Kampo medicine is a promising anticancer adjuvant when negative immune regulation is partially relieved.
Quantitative optical coherence tomography angiography: A review
Authors: Yao Xincheng , Alam Minhaj N , Le David , Toslak Devrim
Published: January 2020

As a new optical coherence tomography (OCT) modality, OCT angiography (OCTA) provides a noninvasive method to detect microvascular distortions correlated with eye conditions. By providing unparalleled capability to differentiate individual plexus layers in the retina, OCTA has demonstrated its excellence in clinical management of diabetic retinopathy, glaucoma, sickle cell retinopathy, diabetic macular edema, and other eye diseases. Quantitative OCTA analysis of retinal and choroidal vasculatures is essential to standardize objective interpretations of clinical outcome. Quantitative features, including blood vessel tortuosity, blood vessel caliber, blood vessel density, vessel perimeter index, fovea avascular zone area, fovea avascular zone contour irregularity, vessel branching coefficient, vessel branching angle, branching width ratio, and choroidal vascular analysis have been established for objective OCTA assessment. Moreover, differential artery–vein analysis has been recently demonstrated to improve OCTA performance for objective detection and classification of eye diseases. In this review, technical rationales and clinical applications of these quantitative OCTA features are summarized, and future prospects for using these quantitative OCTA features for artificial intelligence classification of eye conditions are discussed.

Impact statement

OCT angiography (OCTA) provides a noninvasive method to detect microvascular distortions correlated with eye conditions. Quantitative analysis of OCTA is essential to standardize objective interpretations of clinical outcome. This review summarizes technical rationales and clinical applications of quantitative OCTA features.
Study on magnetorheological nano-polishing using low-frequency alternating magnetic field
Authors: Wu Jinzhong , Yin Shaohui , Yang Shengjie , Guo Yuanfan
Published: January 2020

With the development of electronics and optical industry, the high-efficiency ultra-precision polishing technologies of flat and curved surfaces are in high demand. The traditional magnetorheological polishing technology, using flexible polishing head, has the disadvantages of low polishing efficiency and small processing area. In this study, a novel tray-type magnetorheological polishing process using low-frequency alternating magnetic field excitation was developed to improve the efficiency of magnetorheological polishing for large surfaces and to make polishing magnetorheological cluster generate a cyclical fluctuation up and down, and then improve the cross-cutting effects of abrasives. With the developed excitation system, a large bowl-shaped varying magnetic field was generated in the working area, and the effects of current frequency, working gap, trough rotation speed, and workpiece rotation speed on the improvement rate of surface roughness and material removal rate were systematically investigated. A series of experiments were conducted on K9 glass specimens to verify the polishing performance. Experimental results show that the surface roughness of K9 glass was improved from 567.08 to 9.63 nm in 120 min.
Public transit network planning in small cites considering safety and convenience
Authors: Ma Changxi , Yang Dong
Published: January 2020

Scientific and rational public transit network planning, not only can effectively alleviate city traffic congestion, but also can reduce the risk of accidents. First, based on the data of residents’ travel survey, this article employs the multiple regression method to forecast the traffic generation and adopts the double-constrained gravity model to forecast the residents’ travel distribution of small cites. Second, by aiming at public transit planning objectives, the unsafe roads for public transit are screened, and the public transit trip-mode sharing rate is set as the interval value. According to the interval value, the public transit trip-mode sharing rate is divided into three cases, and the three alternatives of public transit network are calculated based on the network optimization method and the public transit-oriented development model. Next, the alternatives are evaluated by the set pair analysis method, and the optimal scheme is selected. Finally, this article takes the public transit network planning of Huaiyuan County in Anhui Province as an example, and the results show the proposed method is feasible.
Building semantic grid maps for domestic robot navigation
Authors: Qi Xianyu , Wang Wei , Yuan Mei , Wang Yuliang , Li Mingbo , Xue Lin , Sun Yingpin
Published: January 2020

This article proposes a semantic grid mapping method for domestic robot navigation. Occupancy grid maps are sufficient for mobile robots to complete point-to-point navigation tasks in 2-D small-scale environments. However, when used in the real domestic scene, grid maps are lack of semantic information for end users to specify navigation tasks conveniently. Semantic grid maps, enhancing the occupancy grid map with the semantics of objects and rooms, endowing the robots with the capacity of robust navigation skills and human-friendly operation modes, are thus proposed to overcome this limitation. In our method, an object semantic grid map is built with low-cost sonar and binocular stereovision sensors by correctly fusing the occupancy grid map and object point clouds. Topological spaces of each object are defined to make robots autonomously select navigation destinations. Based on the domestic common sense of the relationship between rooms and objects, topological segmentation is used to get room semantics. Our method is evaluated in a real homelike environment, and the results show that the generated map is at a satisfactory precision and feasible for a domestic mobile robot to complete navigation tasks commanded in natural language with a high success rate.
Settling Into Semantic Space: An Ambiguity-Focused Account of Word-Meaning Access
Authors: Rodd Jennifer M.
Published: January 2020

Most words are ambiguous: Individual word forms (e.g., run) can map onto multiple different interpretations depending on their sentence context (e.g., the athlete/politician/river runs). Models of word-meaning access must therefore explain how listeners and readers can rapidly settle on a single, contextually appropriate meaning for each word that they encounter. I present a new account of word-meaning access that places semantic disambiguation at its core and integrates evidence from a wide variety of experimental approaches to explain this key aspect of language comprehension. The model has three key characteristics. (a) Lexical-semantic knowledge is viewed as a high-dimensional space; familiar word meanings correspond to stable states within this lexical-semantic space. (b) Multiple linguistic and paralinguistic cues can influence the settling process by which the system resolves on one of these familiar meanings. (c) Learning mechanisms play a vital role in facilitating rapid word-meaning access by shaping and maintaining high-quality lexical-semantic knowledge throughout the life span. In contrast to earlier models of word-meaning access, I highlight individual differences in lexical-semantic knowledge: Each person’s lexicon is uniquely structured by specific, idiosyncratic linguistic experiences.
Authorship order and effects of changing bibliometrics practices
Authors: Helgesson Gert
Published: January 2020

Although the authorship order on published research plays a significant role for scientific merit in many research contexts, and therefore should be handled with great care not least for the sake of fairness, the practices of accrediting authorship positions vary greatly between different research areas. This paper makes the point, by help of a current example, that changes in bibliometrics practices may make an already disparate landscape even more confusing.
Epidemiology of stroke in urban northeast China: A population-based study 2018–2019
Authors: Xing Liying , Jing Li , Tian Yuanmeng , Wang Weizhong , Sun Jixu , Jiang Cuiqin , Shi Lei , Dai Dong , Liu Shuang
Published: January 2020

Background

Stroke has been emerging as the major public health challenge in China. In the present study, we sought to comprehensively estimate of stroke burden in urban northeast China.

Methods

We conducted the cross-sectional study in 5424 adults aged ≥ 40 years (response rate was 85.3%) living in urban northeast China. A multi-stage cluster sampling method was employed to ensure the population was representative. The prevalent stroke patients were defined as survivors on 31 March 2018. Stroke was defined based on the WHO criteria and was classified into ischemic stroke (IS) and hemorrhage stroke (HS) according to the imaging results.

Results

A total of 292 stroke cases were confirmed (IS-260, 35-HS, and IS concomitant HS-3). Crude prevalence of overall stroke, IS and HS were 5.4%, 4.8% and 0.6%, respectively, and the age-standardized prevalence was 3.8%, 3.4% and 0.5%, respectively. The prevalence of stroke was significantly higher in men compared to women. Among stroke population, 4.5% had disabilities and lived with consequences of stroke. Hypertension, dyslipidemia and diabetes were highly prevalent, accounting for 80.5%, 59.7% and 39.3%, respectively, in stroke population. However, the control rates of those comorbidities were unacceptably low (13.2%, 8.1% and 40.4%, respectively).

Conclusion

The considerable stroke burden was observed in urban northeast China with high proportion of stroke and related risk factors. Poorly controlled comorbidities are likely to contribute to the substantial burden in the future. Long-term primary and secondary prevention should be highlighted in urban northeast China.
Is the Landing Error Scoring System Reliable and Valid? A Systematic Review
Authors: Hanzlíková Ivana , Hébert-Losier Kim
Published: January 2020

Context:

The Landing Error Scoring System (LESS) is a clinical tool often used in research and practice to identify athletes presenting high injury-risk biomechanical patterns during a jump-landing task.

Objective:

To systematically review the literature addressing the psychometric properties of the LESS.

Data Sources:

Three electronic databases (PubMed, Web of Science, and Scopus) were searched on March 28, 2018, using the term “Landing Error Scoring System.”

Study Selection:

All studies using the LESS as main outcome measure and addressing its reliability, validity against motion capture system, and predictive validity were included. Original English-language studies published in peer-reviewed journals were reviewed. Studies using modified versions of the LESS were excluded.

Study Design:

Systematic literature review.

Level of Evidence:

Level 4.

Data Extraction:

Study design, population, LESS testing procedures, LESS scores, statistical analysis, and main results were extracted from studies using a standardized template.

Results:

Ten studies met inclusion criteria and were appraised using Newcastle-Ottawa Quality Assessment Scale adapted for cross-sectional studies. The overall LESS score demonstrated good-to-excellent intrarater (intraclass correlation coefficient [ICC], 0.82-0.99), interrater (ICC, 0.83-0.92), and intersession reliability (ICC, 0.81). The validity of the overall LESS score against 3-dimensional jump-landing biomechanics was good when individuals were divided into 4 quartiles based on LESS scores. The validity of individual LESS items versus 3-dimensional motion capture data was moderate-to-excellent for most of the items addressing key risk factors for anterior cruciate ligament (ACL) injury. The predictive value of the LESS for ACL and other noncontact lower-extremity injuries remains uncertain based on the current scientific evidence.

Conclusion:

The LESS is a reliable screening tool. However, further work is needed to improve the LESS validity against motion capture system and confirm its predictive validity for ACL and other noncontact lower-extremity injuries.
Association between upper extremity dysfunction and sleep disturbance in an elderly general population
Authors: Tajika Tsuyoshi , Kuboi Takuro , Endo Fumitaka , Shinagawa Satoshi , Kobayashi Hiroki , Hashimoto Shogo , Sakane Hideo , Hamano Noritaka , Sasaki Tsuyoshi , Ichinose Tsuyoshi , Shitara Hitoshi , Chikuda Hirotaka
Published: January 2020

Objective:

Several upper extremity disorders are associated with sleep disturbance in patient populations. This study evaluated the relation between self-assessment of upper extremity function and sleep disturbance in an elderly general population.

Methods:

A total of 159 participants (56 men, 103 women, 38–88 years old, mean age of 66.4 years) completed a self-administered questionnaire including items for sex, weight, height, and dominant hand. Upper extremity dysfunction was investigated using Quick Disabilities of the Arm, Shoulder, and Hand of the Japanese Society for Surgery of the Hand. The sleep disturbance severity was evaluated using a Japanese version of the Athens Insomnia Scale. Quality of life was assessed using the EuroQol-5-dimension-3-level, Japanese version. We measured the bilateral hand grip as an indicator of hand muscle function. Statistical tests were applied to clarify the association between upper extremity dysfunction and screening results for sleep disturbance.

Results:

Of 159 participants, 45 (28.3%) had sleep disturbance as assessed using Japanese version of the Athens Insomnia Scale (11 men and 34 women; mean age of 68.1 years). Japanese version of the Athens Insomnia Scale scores correlated with the EuroQol index; EuroQol visual analog scale; and Quick Disabilities of the Arm, Shoulder, and Hand scores. The Quick Disabilities of the Arm, Shoulder, and Hand score and dominant grip strength of the participants with sleep disturbance were significantly higher than those of the no sleep disturbance group. The EuroQol index score and visual analog scale of those reporting a sleep disturbance were significantly lower than those of the no sleep disturbance group.

Conclusion:

Self-administered upper extremity health condition as assessed using Quick Disabilities of the Arm, Shoulder, and Hand correlated with sleep disturbance. Our results suggest a link between upper extremity conditions and sleep disturbance.
Algorithmic Experts: Selling Algorithmic Lore on YouTube
Authors: Bishop Sophie
Published: January 2020

This article considers the growing influence of self-styled algorithmic “experts.” Experts build valuable brands, accumulate notoriety, and piece together careers by selling theorizations of algorithmic visibility on YouTube to aspiring and established creators. They function as intermediaries between sanctioned YouTube industries and the agency of cultural producers. Expertise is developed through research, strategies, and theories to help content creators mitigate platform-specific risks, particularly the risk of algorithmic invisibility. Experts develop entrepreneurial self-brands and position themselves as YouTube’s adversaries, performing “experiments” ostensibly to reveal or translate hidden algorithmic signals or correct “misleading” information. However, ultimately, they teach creators to be complicit with YouTube’s organizational strategies and business models. Studying algorithmic experts reveals insights into how new media producers negotiate platform visibility, but also speaks to long-standing questions about how the management of risk in cultural industries shapes symbolic production. I draw on a 3-year ethnography of YouTube industries to illustrate how experts interpret and instruct in how to become algorithmically (and advertiser) compliant on YouTube. In addition, I highlight their broader role as de facto producers and gatekeepers for aspiring and existing content producers. Meritocratic logic flows through experts’ outputs—meaning expertise is limited to individualized and patchwork solutions that do not address the significant socio-economic inequalities that are still inherent on social media platforms.
A cognitive window into Year 3 students’ social thinking processes
Authors: Knowles Anne L , Smith Thomas R
Published: January 2020

This work focused on increasing Year 3 students’ use of critical thinking and taking the second-person perspective (2ndPP) when interpreting and resolving life issues. Previous research indicated the Personal Viewpoints Pedagogy (PVP) elicited social thinking that exhibited strong perspective-taking and precursors to critical thinking – incipient critical thinking (ICrT). A 10-lesson curriculum with PVP applied to narratives from the Book of Acts, and a ‘do unto others’ focus (ActsPVP Curriculum) was taught. Pre- and post-test comparisons using a ‘Stealing Scenario’ to judge heart-based thoughts and attitudes (Heb 4:12) indicated that 2ndPP and ICrT increased support of the PVP’s impact on social thinking processes.
How the Interplay of Consumer-Brand Identification and Crises Influences the Effectiveness of Corporate Response Strategies
Authors: Ma Liang
Published: January 2020

Consumer-brand identification (CBI) establishes when consumers use the defining attributes of a brand to define themselves. This study examines whether and how CBI influences the effectiveness of corporate response strategies suggested by the situational crisis communication theory in preventable crises and whether this influence is moderated by a threat to the self-defining attributes shared between consumers and a brand. A total of 868 consumers of two brands took part in an online experiment. CBI increases the effectiveness of corporate response strategies at mitigating negative consumer reactions. Response strategies are even more effective when a crisis does not threaten the shared defining attributes. Additionally, compensation is the strategy that really reduces consumers’ negative reactions, instead of apology strategy. More theoretical and practical implications were discussed.
State-of-the-art methods and devices for the generation, exposure, and collection of aerosols from heat-not-burn tobacco products
Authors: Boué Stéphanie , Goedertier Didier , Hoeng Julia , Kuczaj Arkadiusz , Majeed Shoaib , Mathis Carole , May Anne , Phillips Blaine , Peitsch Manuel C , Radtke Falk , Schlage Walter K , Tan Wei Teck , Vanscheeuwijck Patrick
Published: January 2020

Tobacco harm reduction is increasingly recognized as a promising approach to accelerate the decline in smoking prevalence and smoking-related population harm. Potential modified risk tobacco products (MRTPs) must undergo a rigorous premarket toxicological risk assessment. The ability to reproducibly generate, collect, and use aerosols is critical for the characterization, and preclinical assessment of aerosol-based candidate MRTPs (cMRTPs), such as noncombusted cigarettes, also referred to as heated tobacco products, tobacco heating products, or heat-not-burn (HNB) tobacco products. HNB tobacco products generate a nicotine-containing aerosol by heating tobacco instead of burning it. The aerosols generated by HNB products are qualitatively and quantitatively highly different from cigarette smoke (CS). This constitutes technical and experimental challenges comparing the toxicity of HNB aerosols with CS. The methods and experimental setups that have been developed for the study of CS cannot be directly transposed to the study of HNB aerosols. Significant research efforts are dedicated to the development, characterization, and validation of experimental setups and methods suitable for HNB aerosols. They are described in this review, with a particular focus on the Tobacco Heating System version 2.2. This is intended to support further studies, the objective evaluation and verification of existing evidence, and the development of scientifically substantiated HNB MRTPs.
Maletoyvayamite, Au3Se4Te6, a new mineral from Maletoyvayam deposit, Kamchatka peninsula, Russia
Authors: Tolstykh Nadhezda D. , Tuhý Marek , Vymazalová Anna , Plášil Jakub , Laufek František , Kasatkin Anatoly V. , Nestola Fabrizio , Bobrova Olga V.
Published: January 2020

Maletoyvayamite, Au3Se4Te6, is a new mineral discovered in a heavy-mineral concentrate from the Gaching occurrence of the Maletoyvayam deposit, Kamchatka, Russia (60°19′51.87″N, 164°46′25.65″E). It forms anhedral grains (10 to 50 μm in size) and is found in intergrowths with native gold (Au–Ag), Au tellurides (calaverite), unnamed phases (AuSe, Au2TeSe and Au oxide), native tellurium, sulfosalts (tennantite, tetrahedrite, goldfieldite and watanabeite) and supergene tripuhyite. Maletoyvayamite has a good cleavage on {010} and {001}. In plane-polarised light, maletoyvayamite is grey, has strong bireflectance (grey to bluish grey), and strong anisotropy; it exhibits no internal reflections. Reflectance values for maletoyvayamite in air (Rmin,Rmaxin %) are: 38.9, 39.1 at 470 nm; 39.3, 39.5 at 546 nm; 39.3, 39.6 at 589 nm; and 39.4, 39.7 at 650 nm. Sixteen electron-microprobe analyses of maletoyvayamite gave an average composition: Au 34.46, Se 16.76, Te 47.23 and S 0.84, total 99.29 wt.%, corresponding to the formula Au2.90(Se3.52S0.44)Σ3.96Te6.14based on 13 atoms; the average of eleven analyses on synthetic analogue is: Au 34.20, Se 19.68 and Te 45.42, total 99.30 wt.%, corresponding to Au2.90Se4.16Te5.94. The calculated density is 7.98 g/cm3. The mineral is triclinic, space groupP1, witha= 8.901(2),b= 9.0451(14),c= 9.265(4) Å, α = 97.66(3), β = 106.70(2), γ = 101.399(14)°,V= 685.9(4) Å3andZ= 2. The crystal structure of maletoyvayamite represents a unique structure type resembling a molecular structure. There are cube-like [Au6Se8Te12] clusters linkedviavan der Waals interactions. The structural identity of maletoyvayamite with the synthetic Au3Se4Te6was confirmed by powder X-ray diffraction and Raman spectroscopy.
Integrated Care Search: development and validation of a PubMed search filter for retrieving the integrated care research evidence
Authors: Damarell Raechel A. , Lewis Suzanne , Trenerry Camilla , Tieman Jennifer J.
Published: January 2020

Background

Integrated care is an increasingly important principle for organising healthcare. Integrated care models show promise in reducing resource wastage and service fragmentation whilst improving the accessibility, patient-centredness and quality of care for patients. Those needing reliable access to the growing research evidence base for integrated care can be frustrated by search challenges reflective of the topic’s complexity. The aim of this study is to report the empirical development and validation of two search filters for rapid and effective retrieval of integrated care evidence in PubMed. One filter is optimised for recall and the other for precision.

Methods

An Expert Advisory Group comprising international integrated care experts guided the study. A gold standard test set of citations was formed from screening Handbook Integrated Care chapter references for relevance. This set was divided into a Term Identification Set (20%) for determining candidate terms using frequency analysis; a Filter Development Set (40%) for testing performance of term combinations; and a Filter Validation Set (40%) reserved for confirming final filter performance. In developing the high recall filter, recall was steadily increased while maintaining precision at ≥50%. Similarly, the high precision filter sought to maximise precision while keeping recall ≥50%. For each term combination tested, an approximation of precision was obtained by reviewing the first 100 citations retrieved in Medline for relevance.

Results

The gold standard set comprised 534 citations. The search filter optimised for recall (‘Broad Integrated Care Search’) achieved 86.0–88.3% recall with corresponding low precision (47–53%). The search filter optimised for precise searching (‘Narrow Integrated Care Search’) demonstrated precision of 73–95% with recall reduced to between 55.9 and 59.8%. These filters are now available as one-click URL hyperlinks in the website of International Foundation for Integrated Care.

Conclusions

The Broad and Narrow Integrated Care Search filters provide potential users, such as policy makers and researchers, seamless, reliable and ongoing access to integrated care evidence for decision making. These filters were developed according to a rigorous and transparent methodology designed to circumvent the challenges of information retrieval posed by this complex, multifaceted topic.
Profiling of the muscle-specific dystroglycan interactome reveals the role of Hippo signaling in muscular dystrophy and age-dependent muscle atrophy
Authors: Yatsenko Andriy S. , Kucherenko Mariya M. , Xie Yuanbin , Aweida Dina , Urlaub Henning , Scheibe Renate J. , Cohen Shenhav , Shcherbata Halyna R.
Published: January 2020

Background

Dystroglycanopathies are a group of inherited disorders characterized by vast clinical and genetic heterogeneity and caused by abnormal functioning of the ECM receptor dystroglycan (Dg). Remarkably, among many cases of diagnosed dystroglycanopathies, only a small fraction can be linked directly to mutations in Dg or its regulatory enzymes, implying the involvement of other, not-yet-characterized, Dg-regulating factors. To advance disease diagnostics and develop new treatment strategies, new approaches to find dystroglycanopathy-related factors should be considered. The Dg complex is highly evolutionarily conserved; therefore, model genetic organisms provide excellent systems to address this challenge. In particular,Drosophilais amenable to experiments not feasible in any other system, allowing original insights about the functional interactors of the Dg complex.

Methods

To identify new players contributing to dystroglycanopathies, we usedDrosophilaas a genetic muscular dystrophy model. Using mass spectrometry, we searched for muscle-specific Dg interactors. Next, in silico analyses allowed us to determine their association with diseases and pathological conditions in humans. Using immunohistochemical, biochemical, and genetic interaction approaches followed by the detailed analysis of the muscle tissue architecture, we verified Dg interaction with some of the discovered factors. Analyses of mouse muscles and myocytes were used to test if interactions are conserved in vertebrates.

Results

The muscle-specific Dg complexome revealed novel components that influence the efficiency of Dg function in the muscles. We identified the closest human homologs for Dg-interacting partners, determined their significant enrichment in disease-associations, and verified some of the newly identified Dg interactions. We found that Dg associates with two components of the mechanosignaling Hippo pathway: the WW domain-containing proteins Kibra and Yorkie. Importantly, this conserved interaction manages adult muscle size and integrity.

Conclusions

The results presented in this study provide a new list of muscle-specific Dg interactors, further analysis of which could aid not only in the diagnosis of muscular dystrophies, but also in the development of new therapeutics. To regulate muscle fitness during aging and disease, Dg associates with Kibra and Yorkie and acts as a transmembrane Hippo signaling receptor that transmits extracellular information to intracellular signaling cascades, regulating muscle gene expression.
A secretion biosensor for monitoring Sec-dependent protein export in Corynebacterium glutamicum
Authors: Jurischka Sarah , Bida Astrid , Dohmen-Olma Doris , Kleine Britta , Potzkei Janko , Binder Stephan , Schaumann Georg , Bakkes Patrick J. , Freudl Roland
Published: January 2020

Background

In recent years, the industrial workhorse Corynebacterium glutamicum has gained increasing interest as a host organism for the secretory production of heterologous proteins. Generally, the yield of a target protein in the culture supernatant depends on a multitude of interdependent biological and bioprocess parameters which have to be optimized. So far, the monitoring of such optimization processes depends on the availability of a direct assay for the respective target protein that can be handled also in high throughput approaches. Since simple assays, such as standard enzymatic activity assays, are not always at hand, the availability of a general protein secretion biosensor is highly desirable.

Results

High level secretion of proteins via the Sec protein export pathway leads to secretion stress, a phenomenon that is thought to be caused by the accumulation of incompletely or misfolded proteins at the membrane-cell envelope interface. We have analyzed the transcriptional responses of C. glutamicum to the secretory production of two different heterologous proteins and found that, in both cases, the expression of the gene encoding a homologue of the extracytosolic HtrA protease was highly upregulated. Based on this finding, a C. glutamicum Sec secretion biosensor strain was constructed in which the htrA gene on the chromosome was replaced by the eyfp gene. The fluorescence of the resulting reporter strain responded to the secretion of different heterologous proteins (cutinase from Fusarium solani pisi and alkaline phosphatase PhoA from Escherichia coli) in a dose-dependent manner. In addition, three differently efficient signal peptides for the secretory production of the cutinase could be differentiated by the biosensor signal. Furthermore, we have shown that an efficient signal peptide can be separated from a poor signal peptide by using the biosensor signal of the respective cells in fluorescence activated cell sorting experiments.

Conclusions

We have succeeded in the construction of a C. glutamicum biosensor strain that allows for the monitoring of Sec-dependent secretion of heterologous proteins in a dose-dependent manner, independent of a direct assay for the desired target protein.
Serum FFAs profile analysis of Normal weight and obesity individuals of Han and Uygur nationalities in China
Authors: Ma Yinghua , Qiu Tongtong , Zhu Jiaojiao , Wang Jingzhou , Li Xue , Deng Yuchun , Zhang Xueting , Feng Jiale , Chen Keru , Wang Cuizhe , Xie Jianxin , Zhang Jun
Published: January 2020

Background

Han and Uygur are the two main nationalities living in Xinjiang, China. There are significant differences in the incidence of metabolic diseases for two nationalities, but the specific reasons are not clear. Obesity is an important risk factor for the development of metabolic syndrome, which may be closely related to the increase of serum free fatty acids (FFAs) content. This study aims to use metabolomics to compare the changes of serum FFAs profiles between normal weight (NW) and obese (OB) individuals of two nationalities, screening out the differential FFAs, predicting and evaluating their relationship with diseases.

Methods

Thirty-four kinds of FFAs in serum were detected by ultra-high-pressure liquid chromatography–mass spectrometry (UHPLC-MS) and distinctions in FFAs profiles were evaluated using a metabolomics method while Receiver operating characteristics (ROC) and logistic regression models were used to explore FFAs significant for diagnosing obesity and obesity-associated comorbidities.

Results

In the Han nationality, ten kinds of FFAs (C7:0, C8:0, C9:0, C10:0, C11:0, C14:0, C18:2, C20:3, C20:4 and C22:6) showed significant differences between NW and OB individuals. These differential FFAs may be related to hypertension and gestational diabetes mellitus. In the Uygur nationality, C20:3 and C20:5 showed significant differences between NW and OB individuals. C9:0 and C19:0, which were screened out among the female subjects, showed a good ability to predict obesity status in Uygur females (AUC = 0.950).

Conclusion

In both the Han and Uygur nationalities, the FFAs profiles of NW individuals differed from those of OB individuals. The significantly differential FFAs are closely related to obesity and may be important risk factors for obesity and related metabolic diseases.
Assessment of left ventricular diastolic function after Transcatheter aortic valve implantation in aortic stenosis patients by echocardiographic according to different guidelines
Authors: Guo Yao , Sun Minmin , Chen Haiyan , Kong Dehong , Shu Xianhong , Pan Cuizhen
Published: January 2020

Background

To evaluate the detailed dynamic change of left ventricular diastolic function (LVDF) by echocardiography in aortic stenosis (AS) patients receiving transcatheter aortic valve implantation (TAVI) and compare LVDF classification according to 2009 ASE/EAE and 2016 ASE/EACVI recommendations.

Methods

Thirty-five AS patients receiving TAVI underwent echocardiography the day before operation (PRE), on the third day (3D), in the first-month (1 M) and the six-month (6 M) after TAVI. LVDF was analyzed using 2D and doppler imaging to get parameters including E/A, E/e’, isovolumic relaxation time (IVRT), deceleration time, LA area, LA volume index (LAVI) and systolic tricuspid regurgitation velocity (TR). LVDF classification was evaluated four times for each patient according to 2009 and 2016 recommendations respectively and the results were compared.

Results

The decrease of IVRT and TR occurred immediately post surgery up to 1-month. Improvement of E/e’ occurred late from 3-day to 1-month. LA area and LAVI decreased continuously shortly after operation till 6-month. Forty-four percent (62/140) by 2009 recommendations were reclassified with different grades when using 2016 guidelines. Comparing PRE and 6 M, with 2009 guidelines, 19 patients improved 1 grade, 8 patients improved 2 grades; with 2016 guidelines, 9 patients improved 1 grade, 13 patients improved 2 grades, 1 patient improved 3 grades.

Conclusions

The conventional 2D echocardiography could effectively reflect variation process of LVDF in AS patients after TAVI. For LVDD classification, obvious differences resulted by the 2009 and updated recommendations were found, and more patients can be regarded as benefiting from TAVI by 2016.

recommendations.
Retraction Note: Factors associated with induced abortion in Nepal: data from a nationally representative population-based cross-sectional survey
Authors: Mehata Suresh , Menzel Jamie , Bhattarai Navaraj , Sharma Sharad Kumar , Shah Mukta , Pearson Erin , Andersen Kathryn
Published: January 2020

The authors have retracted this article [1] because it contains significant conceptual and textual overlap with unpublished work from another group. Suresh Mehata, Jamie Menzel, Erin Pearson and Kathryn Andersen agree with this retraction. Navaraj Bhattarai, Sharad Kumar Sharma and Mukta Shah did not respond to correspondence regarding this retraction.
Safety results of ixekizumab with 1822.2 patient-years of exposure: an integrated analysis of 3 clinical trials in adult patients with psoriatic arthritis
Authors: Combe Bernard , Rahman Proton , Kameda Hideto , Cañete Juan D. , Gallo Gaia , Agada Noah , Xu Wen , Genovese Mark C.
Published: January 2020

Background

The long-term safety was assessed in patients with psoriatic arthritis who were treated with ixekizumab in three clinical trials (SPIRIT-P1/-P2/-P3).

Methods

Integrated safety data from three trials (controlled and uncontrolled), including two pivotal phase 3, randomized, double-blind clinical trials: SPIRIT-P1 and SPIRIT-P2, were assessed. Safety data were integrated from the all ixekizumab exposure safety population (defined as all patients receiving ≥ 1 dose of ixekizumab). We report exposure-adjusted incidence rates (IRs) per 100 patient-years (PY) at 1-year intervals up to 3 years for adverse events.

Results

Total exposure to IXE reached 1822.2 PY (1118 patients). The IRs/100 PY for the following treatment discontinuations were as follows: adverse events (5.3); serious infections (1.3); injection-site reactions (12.7); infections (34.2); and deaths (0.3). The IRs for treatment-emergent adverse events decreased or remained stable over time, the most common being upper respiratory tract infection, nasopharyngitis, and injection-site reactions. The IRs for serious adverse events and serious infections remained stable over time, whereas for injection-site reactions and general infections, IRs decreased with longer ixekizumab exposure. Opportunistic infections were limited to oral and esophageal candida and localized herpes zoster. No suicide or self-injury-related behaviors were reported. The IRs/100 PY for safety topics of special interest included inflammatory bowel disease (adjudicated; 0.1), depression (1.6), malignancies (0.7), and major adverse cardiovascular events (0.6).

Conclusions

The findings of this integrated safety analysis in patients with psoriatic arthritis are consistent with the known safety profile of ixekizumab. No unexpected safety signals were observed with ixekizumab treatment in patients with psoriatic arthritis.

Trial registration

SPIRIT-P1 (NCT01695239; Registered August 08, 2012), SPIRIT-P2 (NCT02349295; September 23, 2014), and SPIRIT-P3 (NCT02584855; August 04, 2015).
Hybridizing extended ant lion optimizer with sine cosine algorithm approach for abrupt motion tracking
Authors: Zhang Huanlong , Gao Zeng , Zhang Jie , Liu Junfeng , Nie Zhicheng , Zhang Jianwei
Published: January 2020

In view of the problem that the conventional tracker does not adapt to abrupt motion, we propose a tracking algorithm based on the hybrid extended ant lion optimizer with sine cosine algorithm (EALO-SCA) in this paper. Firstly, the multiple elites is used to replace the single elite in the standard ant lion optimizer (ALO). The extended ALO (EALO) can enhance the global exploration ability, which can handle abrupt motion. Secondly, considering that sine cosine algorithm (SCA) has strong local exploitation operator, a hybrid EALO-SCA tracker is proposed using the advantages of both EALO and SCA. The proposed approach can improve tracking accuracy and efficiency. Finally, extensive experimental results in both quantitative and qualitative measures prove that the proposed algorithm is very competitive compared to 7 state-of-the-art trackers, especially for abrupt motion tracking.
Asymptotical stability of Runge–Kutta methods for nonlinear impulsive differential equations
Authors: Zhang Gui-Lai
Published: January 2020

In this paper, asymptotical stability of the exact solutions of nonlinear impulsive ordinary differential equations is studied under Lipschitz conditions. Under these conditions, asymptotical stability of Runge–Kutta methods is studied by the theory of Padé approximation. And two simple examples are given to illustrate the conclusions.
3D supervirtual refraction interferometry
Authors: Lu Kai , Chávez-Pérez Sergio
Published: January 2020

We have developed the theory and practice of 3D supervirtual interferometry (SVI) for enhancing the signal-to-noise ratio (S/N) of refraction arrivals in 3D data. Unlike 2D SVI, 3D SVI requires an extra integration along the inline direction to compute the stationary source-receiver pairs for enhanced stacking of the refraction events. The result is a significant increase in the S/N of first arrivals in the far-offset traces. We have evaluated 3D synthetic and field data examples to demonstrate the effectiveness of the proposed method. For the synthetic data tests, SVI has extended the source-receiver offset range of pickable traces from 11 to 15 km. In the field data example, SVI has extended the source-receiver offset of traces with pickable first-arrival traveltimes from 12 km to a maximum of 18 km, and the total number of reliable traveltime picks has increased by 12%, which contributes to a deeper velocity update in the traveltime tomogram.
Spatiotemporal regulation of GSK3β levels by miRNA-26a controls axon development in cortical neurons
Authors: Lucci Cristiano , Mesquita-Ribeiro Raquel , Rathbone Alex , Dajas-Bailador Federico
Published: January 2020

Both the establishment of neuronal polarity and axonal growth are crucial steps in the development of the nervous system. The local translation of mRNAs in the axon provides precise regulation of protein expression, and is now known to participate in axon development, pathfinding and synaptic formation and function. We have investigated the role of miR-26a in early stage mouse primary cortical neuron development. We show that micro-RNA-26a-5p (miR-26a) is highly expressed in neuronal cultures, and regulates both neuronal polarity and axon growth. Using compartmentalised microfluidic neuronal cultures, we identified a local role for miR-26a in the axon, where the repression of local synthesis of GSK3β controls axon development and growth. Removal of this repression in the axon triggers local translation of GSK3β protein and subsequent transport to the soma, where it can impact axonal growth. These results demonstrate how the axonal miR-26a can regulate local protein translation in the axon to facilitate retrograde communication to the soma and amplify neuronal responses, in a mechanism that influences axon development.
The ciliary phosphatidylinositol phosphatase Inpp5e plays positive and negative regulatory roles in Shh signaling
Authors: Constable Sandii , Long Alyssa B. , Floyd Katharine A. , Schurmans Stéphane , Caspary Tamara
Published: January 2020

Sonic hedgehog (Shh) signal transduction specifies ventral cell fates in the neural tube and is mediated by the Gli transcription factors that play both activator (GliA) and repressor (GliR) roles. Cilia are essential for Shh signal transduction and the ciliary phosphatidylinositol phosphatase Inpp5e is linked to Shh regulation. In the course of a forward genetic screen for recessive mouse mutants, we identified a functional null allele of inositol polyphosphate-5-phosphatase E (Inpp5e), ridge top (rdg), with expanded ventral neural cell fates at E10.5. By E12.5, Inpp5erdg/rdg embryos displayed normal neural patterning and this correction over time required Gli3, the predominant repressor in neural patterning. Inpp5erdg function largely depended on the presence of cilia and on smoothened, the obligate transducer of Shh signaling, indicating that Inpp5e functions within the cilium to regulate the pathway. These data indicate that Inpp5e plays a more complicated role in Shh signaling than previously appreciated. We propose that Inpp5e attenuates Shh signaling in the neural tube through regulation of the relative timing of GliA and GliR production, which is important in understanding how the duration of Shh signaling regulates neural tube patterning.
In vivo interactions between myosin XI, vesicles and filamentous actin are fast and transient in Physcomitrella patens
Authors: Bibeau Jeffrey P. , Furt Fabienne , Mousavi S. Iman , Kingsley James L. , Levine Max F. , Tüzel Erkan , Vidali Luis
Published: January 2020

The actin cytoskeleton and active membrane trafficking machinery are essential for polarized cell growth. To understand the interactions between myosin XI, vesicles and actin filaments in vivo, we performed fluorescence recovery after photobleaching and showed that the dynamics of myosin XIa at the tip of the spreading earthmoss Physcomitrella patens caulonemal cells are actin-dependent and that 50% of myosin XI is bound to vesicles. To obtain single-particle information, we used variable-angle epifluorescence microscopy in protoplasts to demonstrate that protein myosin XIa and VAMP72-labeled vesicles localize in time and space over periods lasting only a few seconds. By tracking data with Hidden Markov modeling, we showed that myosin XIa and VAMP72-labeled vesicles exhibit short runs of actin-dependent directed transport. We also found that the interaction of myosin XI with vesicles is short-lived. Together, this vesicle-bound fraction, fast off-rate and short average distance traveled seem be crucial for the dynamic oscillations observed at the tip, and might be vital for regulation and recycling of the exocytosis machinery, while simultaneously promoting vesicle focusing and vesicle secretion at the tip, necessary for cell wall expansion.
Myo1e modulates the recruitment of activated B cells to inguinal lymph nodes
Authors: Girón-Pérez Daniel A. , Vadillo Eduardo , Schnoor Michael , Santos-Argumedo Leopoldo
Published: January 2020

The inclusion of lymphocytes in high endothelial venules and their migration to the lymph nodes are critical steps in the immune response. Cell migration is regulated by the actin cytoskeleton and myosins. Myo1e is a long-tailed class I myosin and is highly expressed in B cells, which have not been studied in the context of cell migration. By using intravital microscopy in an in vivo model and performing in vitro experiments, we studied the relevance of Myo1e for the adhesion and inclusion of activated B cells in high endothelial venules. We observed reduced expression of integrins and F-actin in the membrane protrusions of B lymphocytes, which might be explained by deficiencies in vesicular trafficking. Interestingly, the lack of Myo1e reduced the phosphorylation of focal adhesion kinase (FAK; also known as PTK2), AKT (also known as AKT1) and RAC-1, disturbing the FAK–PI3K–RAC-1 signaling pathway. Taken together, our results indicate a critical role of Myo1e in the mechanism of B-cell adhesion and migration.