bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of severe immune-related adverse events requiring hospital admission in patients on immune checkpoint inhibitors: study of a population level insurance claims database from the USA
Authors: Kalinich Mark , Murphy William , Wongvibulsin Shannon , Pahalyants Vartan , Yu Kun-Hsing , Lu Chenyue , Wang Feicheng , Zubiri Leyre , Naranbhai Vivek , Gusev Alexander , Kwatra Shawn G , Reynolds Kerry L , Semenov Yevgeniy R
Published: March 2021

Background

Immune-related adverse events (irAEs) are a serious side effect of immune checkpoint inhibitor (ICI) therapy for patients with advanced cancer. Currently, predisposing risk factors are undefined but understanding which patients are at increased risk for irAEs severe enough to require hospitalization would be beneficial to tailor treatment selection and monitoring.

Methods

We performed a retrospective review of patients with cancer treated with ICIs using unidentifiable claims data from an Aetna nationwide US health insurance database from January 3, 2011 to December 31, 2019, including patients with an identified primary cancer and at least one administration of an ICI. Regression analyses were performed. Main outcomes were incidence of and factors associated with irAE requiring hospitalization in ICI therapy.

Results

There were 68.8 million patients identified in the national database, and 14 378 patients with cancer identified with at least 1 administration of ICI in the study period. Patients were followed over 19 117 patient years and 504 (3.5%) developed an irAE requiring hospitalization. The incidence of irAEs requiring hospitalization per patient ICI treatment year was 2.6%, rising from 0% (0/71) in 2011 to 3.7% (93/2486) in 2016. Combination immunotherapy (OR: 2.44, p<0.001) was associated with increased odds of developing irAEs requiring hospitalization, whereas older patients (OR 0.98 per additional year, p<0.001) and those with non-lung cancer were associated with decreased odds of irAEs requiring hospitalization (melanoma OR: 0.70, p=0.01, renal cell carcinoma OR: 0.71, p=0.03, other cancers OR: 0.50, p<0.001). Sex, region, zip-code-imputed income, and zip-code unemployment were not associated with incidence of irAE requiring hospitalization. Prednisone (72%) and methylprednisolone (25%) were the most common immunosuppressive treatments identified in irAE hospitalizations.

Conclusions

We found that 3.5% of patients initiating ICI therapy experienced irAEs requiring hospitalization and immunosuppression. The odds of irAEs requiring hospitalization were higher with younger age, treatment with combination ICI therapy (cytotoxic T lymphocyte-associated 4 and programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1)), and lower for other cancers compared with patients on PD-1 or PD-L1 inhibitors with lung cancer. This evidence from the first nationwide study of irAEs requiring hospitalization in the USA identified the real-world epidemiology, risk factors, and treatment patterns of these irAEs which may guide treatment and management decisions.
Complement C3a and C5a receptor blockade modulates regulatory T cell conversion in head and neck cancer
Authors: Gadwa Jacob , Bickett Thomas E , Darragh Laurel B , Knitz Michael William , Bhatia Shilpa , Piper Miles , Van Court Benjamin , Bhuvane Shiv , Nguyen Diemmy , Nangia Varuna , Kleczko Emily K , Nemenoff Raphael A , Karam Sana D
Published: March 2021

Background

Resistance to therapy is a major problem in treating head and neck squamous cell carcinomas (HNSCC). Complement system inhibition has been shown to reduce tumor growth, metastasis, and therapeutic resistance in other tumor models, but has yet to be explored in the context of HNSCC. Here, we tested the effects of complement inhibition and its therapeutic potential in HNSCC.

Methods

We conducted our studies using two Human Papilloma Virus (HPV)-negative HNSCC orthotopic mouse models. Complement C3aR and C5aR1 receptor antagonists were paired with radiation therapy (RT). Tumor growth was measured and immune populations from tumor, lymph node, and peripheral blood were compared among various treatment groups. Genetically engineered mouse models DEREG and C3-/- were used in addition to standard wild type models. Flow cytometry, clinical gene sets, and in vitro assays were used to evaluate the role complement receptor blockade has on the immunological makeup of the tumor microenvironment.

Results

In contrast to established literature, inhibition of complement C3a and C5a signaling using receptor antagonists accelerated tumor growth in multiple HNSCC cell lines and corresponded with increased frequency of regulatory T cell (Treg) populations. Local C3a and C5a signaling has importance for CD4 T cell homeostasis and eventual development into effector phenotypes. Interruption of this signaling axis drives a phenotypic conversion of CD4+ T cells into Tregs, characterized by enhanced expression of Foxp3. Depletion of Tregs reversed tumor growth, and combination of Treg depletion and C3a and C5a receptor inhibition decreased tumor growth below that of the control groups. Complete knockout of C3 does not harbor the expected effect on tumor growth, indicating a still undetermined compensatory mechanism. Dexamethasone is frequently prescribed to patients undergoing RT and inhibits complement activation. We report no deleterious effects associated with dexamethasone due to complement inhibition.

Conclusions

Our data establish Tregs as a pro-tumorigenic driver during complement inhibition and provide evidence that targeted C3a and C5a receptor inhibition may add therapeutic advantage when coupled with anti-Treg therapy.
COVID-19-induced hyperinflammation, immunosuppression, recovery and survival: how causal inference may help draw robust conclusions
Authors: Landewé Robert B M , Ramiro Sofia , Mostard Rémy L M
Published: March 2021

Background

The CHIC study (COVID-19 High-intensity Immunosuppression in Cytokine storm syndrome) is a quasi-experimental treatment study exploring immunosuppressive treatment versus supportive treatment only in patients with COVID-19 with life-threatening hyperinflammation. Causal inference provides a means of investigating causality in non-randomised experiments. Here we report 14-day improvement as well as 30-day and 90-day mortality.

Patients and methods

The first 86 patients (period 1) received optimal supportive care only; the second 86 patients (period 2) received methylprednisolone and (if necessary) tocilizumab, in addition to optimal supportive care. The main outcomes were 14-day clinical improvement and 30-day and 90-day survival. An 80% decline in C reactive protein (CRP) was recorded on or before day 13 (CRP >100 mg/L was an inclusion criterion). Non-linear mediation analysis was performed to decompose CRP-mediated effects of immunosuppression (defined as natural indirect effects) and non-CRP-mediated effects attributable to natural prognostic differences between periods (defined as natural direct effects).

Results

The natural direct (non-CRP-mediated) effects for period 2 versus period 1 showed an OR of 1.38 (38% better) for 14-day improvement and an OR of 1.16 (16% better) for 30-day and 90-day survival. The natural indirect (CRP-mediated) effects for period 2 showed an OR of 2.27 (127% better) for 14-day improvement, an OR of 1.60 (60% better) for 30-day survival and an OR of 1.49 (49% better) for 90-day survival. The number needed to treat was 5 for 14-day improvement, 9 for survival on day 30, and 10 for survival on day 90.

Conclusion

Causal inference with non-linear mediation analysis further substantiates the claim that a brief but intensive treatment with immunosuppressants in patients with COVID-19 and systemic hyperinflammation adds to rapid recovery and saves lives. Causal inference is an alternative to conventional trial analysis, when randomised controlled trials are considered unethical, unfeasible or impracticable.
A study on non-synonymous mutational patterns in structural proteins of SARS-CoV-2
Authors: Das Jayanta Kumar , Roy Swarup
Published: March 2021

SARS-CoV-2 is mutating and creating divergent variants across the world. An in-depth investigation of the amino acid substitutions in the genomic signature of SARS-CoV-2 proteins is highly essential for understanding its host adaptation and infection biology. A total of 9587 SARS-CoV-2 structural protein sequences collected from 49 different countries are used to characterize protein-wise variants, substitution patterns (type and location), and major substitution changes. The majority of the substitutions are distinct, mostly in a particular location, and lead to a change in an amino acid’s biochemical properties. In terms of mutational changes, envelope (E) and membrane (M) proteins are relatively more stable than nucleocapsid (N) and spike (S) proteins. Several co-occurrence substitutions are observed, particularly in S and N proteins. Substitution specific to active sub-domains reveals that heptapeptide repeat, fusion peptides, transmembrane in S protein, and N-terminal and C-terminal domains in the N protein are remarkably mutated. We also observe a few deleterious mutations in the above domains. The overall study on non-synonymous mutation in structural proteins of SARS-CoV-2 at the start of the pandemic indicates a diversity amongst virus sequences.
Effective Automatic Method Selection for Nonlinear Regression Modeling
Authors: Kalina Jan , Neoral Aleš , Vidnerová Petra
Published: March 2021

Metalearning, an important part of artificial intelligence, represents a promising approach for the task of automatic selection of appropriate methods or algorithms. This paper is interested in recommending a suitable estimator for nonlinear regression modeling, particularly in recommending either the standard nonlinear least squares estimator or one of such available alternative estimators, which is highly robust with respect to the presence of outliers in the data. The authors hold the opinion that theoretical considerations will never be able to formulate such recommendations for the nonlinear regression context. Instead, metalearning is explored here as an original approach suitable for this task. In this paper, four different approaches for automatic method selection for nonlinear regression are proposed and computations over a training database of 643 real publicly available datasets are performed. Particularly, while the metalearning results may be harmed by the imbalanced number of groups, an effective approach yields much improved results, performing a novel combination of supervised feature selection by random forest and oversampling by synthetic minority oversampling technique (SMOTE). As a by-product, the computations bring arguments in favor of the very recent nonlinear least weighted squares estimator, which turns out to outperform other (and much more renowned) estimators in a quite large percentage of datasets.
SYNTHESIS AND CHARACTERIZATION OF (ZNO)–(CO3O4) NANOCOMPOSITE VIA SPRAY PYROLYSIS PROCESS: THE USE OF THE BRUGGEMAN MODEL ON OPTICAL PROPERTIES PREVISION
Authors: BOUREGUIG K. M. E. , TABET-DERRAZ H. , SEDDIK T. , BENALI M. A.
Published: March 2021

In the present paper, (ZnO)–(Co3O4) nanocomposite thin films have been prepared by using spray pyrolysis deposition on a glass substrate at 350∘C. After that, the as-obtained films have been characterized and analyzed by X-ray diffraction (XRD), scanning electron microscopy (SEM), and the double beam UV-visible (UV-vis) spectrophotometer. Furthermore, the Bruggeman model is used to predict the evolution of the optical dielectric constant (real and imaginary parts: [Formula: see text] and [Formula: see text] to compare them with those obtained from the experimental results. The XRD pattern reveals that the nanocomposite film has diffraction peaks 2[Formula: see text], 36.95∘ corresponding respectively to the (220), (311) planes of cubic Co3O4 and another about of 2[Formula: see text] corresponding to the (101) plane of Wurtzite ZnO. Using the Debye Scherrer formula, the crystallite size of (ZnO)[Formula: see text]–(Co3O[Formula: see text] nanocomposite is found about 32[Formula: see text]nm, while the obtained thickness of this nanocomposite is about 780[Formula: see text]nm using the DekTak Stylus profilometer. Besides, the morphology analysis shows that the nanocomposite sample is well covered without holes and/or cracks and it has uniform dense grains. The evaluation of the transmittance, reflectance, refraction index, extinction coefficient, real and imaginary parts of dielectric constant as function of wavelength illustrates that the optical response of nanocomposite thin film (ZnO)[Formula: see text]–(Co3O[Formula: see text] depends on the influence of two mediums of pure materials ZnO and Co3O4 and their interaction. In addition, the direct band gap vs incident photon energy obtained from the Tauc plot equation shows that this nanocomposite has three values of band gap energy which are [Formula: see text][Formula: see text]eV, [Formula: see text][Formula: see text]eV (correspond to pure Co3O4 film) and [Formula: see text][Formula: see text]eV (correspond to pure ZnO film). Besides, the application of the Bruggeman equation indicates that the influence of the values of volume concentration and optical dielectric constant of the ingredient nanomaterials (ZnO and Co3O[Formula: see text] is significant on the value of the effective dielectric constant of nanocomposite thin film. The specific result of this study is the similarity between the spectra obtained from the Bruggeman model and the measured one, which proves that the application of this model is useful for the prediction of the optical properties of the composite.
Tailorable epsilon-negative and epsilon-near-zero behavior of TiC/CCTO metacomposites: Low-frequency plasma oscillation
Authors: Ding Baogang , Qu Yunpeng , Sun Kai , Fan Runhua
Published: March 2021

Epsilon-negative ([Formula: see text] < 0) and epsilon-near-zero (ENZ) property was demonstrated in titanium carbide/copper calcium titanate (TiC/CCTO) metacomposites. Benefiting from the moderate concentration of free electrons in TiC filler and its adjustable three-dimensional (3D) networks, weakly negative permittivity ([Formula: see text]200 at 20 MHz) was achieved. Not only that, tailoring the negative permittivity of metacomposites from [Formula: see text]200 to [Formula: see text]2060, [Formula: see text]4200, [Formula: see text]14000 and [Formula: see text]70000 at 20 MHz was realized by simply increasing TiC content. Besides, Drude model was used to explain the radio-frequency (RF) negative permittivity and quantified the collective plasma oscillation in TiC networks.
Growth of lithium iron silicates nanoplates with high energy facets via polymorphs transition for enhanced lithium-ion extraction/insertion reaction
Authors: Duan Anran , Qiao Huali , He Miao , Wang Ting , Wang Dan , Wang Tongshuai , Wang Hailong
Published: March 2021

The anisotropic functionalities of nanostructured silicates are highly attractive for various applications, whereas the silicates’ nanostructure heavily relies on the reactions in low temperature liquid conditions. Due to the stubborn [SiO4][Formula: see text] lattice foundation and most surfactants’ thermal instability, it is extremely difficult to manipulate the nanostructure and preserve high energy lattice facets in the high temperature solid state growth of silicates. In this report, the polymorphs transition of Li2FeSiO4 is found to open a precious window for adsorbate–crystal interactions. By adsorbing on the intermediates of phase transition, Ethlyene glycol effectively promotes the solid-state growth of Li2FeSiO4 nanoplates at high temperature, of which the high energy (020) facet becomes the dominant and exhibits high activity for fast charge transportation. The obtained Li2FeSiO4 nanoplates show greatly enhanced reactivity for Li[Formula: see text] ions’ extraction/insertion, and exhibit excellent capacities at high current density (1–10 C) as the cathode material for lithium-ion batteries.
Aged Co-Mo alloy thin film catalyst for hydrogen evolution reaction in acidic solution
Authors: Kuru Cihan
Published: March 2021

In this study, aged Co–Mo (3:10) alloy film has been demonstrated as an efficient and durable catalyst for hydrogen evolution reaction (HER) in acidic solution. The Co–Mo alloy films with varying Co/Mo atomic ratios have been deposited by magnetron sputtering. The catalytic activity of Mo film is outperformed by the Co–Mo alloys, among which the Co–Mo (3:10) alloy exhibits the highest HER activity with an overpotential of 310 mV at 10 mA cm[Formula: see text] current density, exchange current density of 1.74 × 10[Formula: see text] A cm[Formula: see text] and a Tafel slope of 61 mV dec[Formula: see text]. Combined with the good stability provided by the surface oxide layer, the aged Co–Mo (3:10) alloy is a promising catalyst for HER in acidic solutions.
Different shapes of nanoparticles on peristaltic transport of a Casson fluid in the presence of MHD, thermal radiation and Porous medium
Authors: Asha S. K. , Sunitha G. , Hadapad Chandrashekhar M.
Published: March 2021

The influence of different shapes of nanoparticles on peristaltic flow of Casson fluid in an asymmetric channel is studied in this paper. The suspension of Copper oxide nanoparticles of needle, platelet and lamina shapes is taken into account. The problem is modeled in partial differential equations with suitable slip boundary conditions. The standard nonlinear equations are solved by the Homotopy Analysis Method in Mathematica Software. The influences of different shapes of nanoparticles on concentration, velocity profile and temperature profile are analyzed through the graphs. It is observed that the different shape of nanoparticles has different thermal conductivity, but the lamina shaped nanoparticles have high thermal conductivity as compared to needle and platelet shaped nanoparticles.
Unsupervised Neural Machine Translation for Similar and Distant Language Pairs
Authors: Sun Haipeng , Wang Rui , Utiyama Masao , Marie Benjamin , Chen Kehai , Sumita Eiichiro , Zhao Tiejun
Published: March 2021

Unsupervised neural machine translation (UNMT) has achieved remarkable results for several language pairs, such as French–English and German–English. Most previous studies have focused on modeling UNMT systems; few studies have investigated the effect of UNMT on specific languages. In this article, we first empirically investigate UNMT for four diverse language pairs (French/German/Chinese/Japanese–English). We confirm that the performance of UNMT in translation tasks for similar language pairs (French/German–English) is dramatically better than for distant language pairs (Chinese/Japanese–English). We empirically show that the lack of shared words and different word orderings are the main reasons that lead UNMT to underperform in Chinese/Japanese–English. Based on these findings, we propose several methods, including artificial shared words and pre-ordering, to improve the performance of UNMT for distant language pairs. Moreover, we propose a simple general method to improve translation performance for all these four language pairs. The existing UNMT model can generate a translation of a reasonable quality after a few training epochs owing to a denoising mechanism and shared latent representations. However, learning shared latent representations restricts the performance of translation in both directions, particularly for distant language pairs, while denoising dramatically delays convergence by continuously modifying the training data. To avoid these problems, we propose a simple, yet effective and efficient, approach that (like UNMT) relies solely on monolingual corpora: pseudo-data-based unsupervised neural machine translation. Experimental results for these four language pairs show that our proposed methods significantly outperform UNMT baselines.
Passages
Authors: Groce Alex
Published: March 2021

Brian Harvey's Computer Science Logo Style (Volume 1: Symbolic Computing, Volume 2: Advanced Techniques, Volume 3: Beyond Programming) begins with the words: "This book isn't for everyone." There follows a brief account of the fact that not everyone needs to program computers, based on an economic (Marxist-flavored) tirade (that I mostly agree with). The closing of the introductory paragraphs is the part that matters, though: "This book is for people who are interested in computer programming because it's fun."
Risks to the Public
Authors: Neumann Peter G.
Published: March 2021

Mini-editorial (PGN) 2020 was a crazy year, with all kinds of risks on display. As usual, many of the lessons noted in past issues of SEN and RISKS have been largely ignored, and failures continue to mirror events from the past that have long been discussed here. Issues such as safety, security, and reliability always seem to need more foresight than they receive. Y2K con- tinues to hit somewhere each New Year's Day, when short- term remediations that demanded periodic upgrading have been forgotten. (I suppose old COBOL code will still ex- ist in year 2100, when there may be ambiguities relating to dates that could be 21xx or 20xx (although 19xx is unlikely), and the narrow windowing xes will fail even more dramati- cally.) Election integrity continues to be a real concern, where we are caught in the crosshairs between computer systems and networks that are not meaningfully trustworthy or au- ditable, and the nontechnological risks are still pervasive from unbalanced redistricting, creative dysinformation, poli- tics, Citzens United, and foreign interference. We need non- partisan scrutiny and defense against would-be subverters to overcome potential attacks and inadvertent mistakes. In pres- ence of potential risks in every part of the process, a strong sense of risk-awareness is required by voters, election officials, and the media (both proactively and remedially, as needed).
Software Engineering in Australasia
Authors: Licorish Sherlock A. , Treude Christoph , Grundy John , Blincoe Kelly , MacDonell Stephen , Tantithamthavorn Chakkrit , Li Li , Schneider Jean-Guy
Published: March 2021

Six months ago an important call was made for researchers globally to provide insights into the way Software Engineering is done in their region. Heeding this call, we hereby outline the position Software Engineering in Australasia (New Zealand and Australia). This article first considers the software development methods, practices and tools that are popular in the Australasian software engineering community. We then briefly review the particular strengths of software engineering researchers in Australasia. Finally, we make an open call for collaborators by reflecting on our current position and identifying future opportunities.
Report from the 2nd Int. Workshop on Education through Advanced Software Engineering and Artificial Intelligence (EASEAI '20)
Authors: Vanderose Benoît , Henry Julie , Frénay Benoît , Devroey Xavier
Published: March 2021

In the past years, with the development and widespread of digi- tal technologies, everyday life has been profoundly transformed. The general public, as well as specialized audiences, have to face an ever-increasing amount of knowledge and learn new abilities. The EASEAI workshop series addresses that challenge by look- ing at software engineering, education, and arti cial intelligence research elds to explore how they can be combined. Speci cally, this workshop brings together researchers, teachers, and practi- tioners who use advanced software engineering tools and arti cial intelligence techniques in the education eld and through a trans- generational and transdisciplinary range of students to discuss the current state of the art and practices, and establish new future directions. More information at https://easeai.github.io.
Influence of Various Doping Agents on Organic Semiconductors’ Physicochemical Properties
Authors: Filapek Michał , Hellwig Hubert , Gancarz Paweł , Szłapa-Kula Agata
Published: March 2021

Due to the electron-reach π-conjugated organic semiconductors system, chemical so-called p-type doping is easily achievable. Oxidation by some molecules, atoms, or ions called “dopants” or “doping agents” force the molecule to accept the positive electrical charge. In general, there are several “theoretical” ways to increase the conductivity of the semiconductors by the introduction, as mentioned above, of the charge carriers into the structure of the molecule. For this reason, it was designed and synthesized a model molecule possessing: (a) acidic hydrogen—a fragment able to undergo chemical oxidation; (b) a unit having a pi-excess ring—vulnerable to electrochemical oxidation; (c) a free electron pair—susceptible to protonation and methylation; and finally (d) a fragment that is Lewis base in nature—that is, it can form adducts with Lewis acid. In this paper, we are reporting a comprehensive study (with the aid of DFT calculation) concerning the different doping agents’ influence on physicochemical properties of the model (namely 2,5-bis(2-(2-thienyl)-thien-5-yl)thiazolo[5,4-d]thiazole) organic semiconductor.
From the Editor: Brain Gain in an Outsourcing/Off-shoring Global Economy
Authors: Rajeshwar Krishnan
Published: March 2021

Much has been written and discussed about globalization, outsourcing, and off-shoring in recent months. Clearly, domestic job losses in many sectors, paradoxically in a time of economic recovery, are getting intense scrutiny and political traction in an election year. However, there is a quieter and perhaps more ominous trend in the science, technology, engineering, and mathematics (STEM) disciplines that has important ramifications for the future.
From the Editor: Acronyms, Abbreviations, and Alphabet Soups
Authors: Rajeshwar Krishnan
Published: March 2021

The other day I was flipping through an automotive magazine when one trend caught my attention, namely, the sheer preponderance of acronyms and abbreviations in this industry. On any given page, the text would be sprinkled with SOHC or DOHC (single or double overhead cam), VCM (variable cylinder management), ABS (antilock brake system), AWD (all wheel drive), etc.
Pennington Corner: The Hydrogen Society
Authors: Calvo Roque J.
Published: March 2021

On June 25, 2003 the United States and the European Union agreed to collaborate on the acceleration of the development of the “hydrogen economy.” The U.S. government alone committed to spend $1.4 billion in new funding over the next five years to develop technologies to produce, store, and distribute hydrogen for use in fuel cell vehicles and in electricity generation.
State of the Union: Publishing ECS Content
Authors: Yess Mary E.
Published: March 2021

In this issue of Interface, Guest Editor Richard McCreery notes that if “one takes an optimistic view of molecular electronics, there is support for the idea of a paradigm shift of a scale as large as that from vacuum tubes to transistors that occurred in the 1950s and 1960s.” It is appropriate then, in this same issue, to report on a similar shift that is occurring in the field of scholarly publishing and on the challenges ECS faces in publishing its content.
Developing the Senses
Authors: Bruckner-Lea Cindy
Published: March 2021

The feature articles of this issue of Interface are devoted to areas of sensor research and development that are emerging and expected to grow in the coming years. Sensor research and development is the focus of the Sensor Division of The Electrochemical Society, and crosscuts most of the other ECS Divisions.
Four Examples of Unimolecular Electrical Rectifiers
Authors: Metzger Robert M.
Published: March 2021

Molecular electronics or unimolecular electronics (UE), defined narrowly, is the study of electrical phenomena on a molecular scale, while molecule based electronics, defined more widely, studies the electronic properties of molecules in crystals and polymers.
Suppression of Cathodic Reactions on Aluminum Alloy 2024-T3 Using Polyaniline Coating Systems
Authors: Seegmiller Jesse C.
Published: March 2021

A Summary Report to The Electrochemical Society for the 2004 Edward G. Weston Summer Research Fellowship.
Ozanimod, an S1PR1 ligand, attenuates hypoxia plus glucose deprivation-induced autophagic flux and phenotypic switching in human brain VSM cells
Authors: Wendt Trevor S. , Li Yu Jing , Gonzales Rayna J.
Published: March 2021

Vascular smooth muscle (VSM) cell phenotypic expression and autophagic state are dynamic responses to stress. Vascular pathologies, such as hypoxemia and ischemic injury, induce a synthetic VSM phenotype and autophagic flux resulting in a loss of vascular integrity and VSM cell death respectfully. Both clinical pilot and experimental stroke studies demonstrate that sphingosine-1-phosphate receptor (S1PR) modulation improves stroke outcome; however, specific mechanisms associated with a beneficial outcome at the level of the cerebrovasculature have not been clearly elucidated. We hypothesized that ozanimod, a selective S1PR type 1 ligand, will attenuate VSM synthetic phenotypic expression and autophagic flux in primary human brain VSM cells following acute hypoxia plus glucose deprivation (HGD; in vitro ischemic-like injury) exposure. Cells were treated with ozanimod and exposed to normoxia or HGD. Crystal violet staining, standard immunoblotting, and immunocytochemical labeling techniques assessed cellular morphology, vacuolization, phenotype, and autophagic state. We observed that HGD temporally decreased VSM cell viability and concomitantly increased vacuolization, both of which ozanimod reversed. HGD induced a simultaneous elevation and reduction in levels of pro- and antiautophagic proteins respectfully, and ozanimod attenuated this response. Protein levels of VSM phenotypic biomarkers, smoothelin and SM22, were decreased following HGD. Furthermore, we observed an HGD-induced epithelioid and synthetic morphological appearance accompanied by disorganized cytoskeletal filaments, which was rescued by ozanimod. Thus, we conclude that ozanimod, a selective S1PR1 ligand, protects against acute HGD-induced phenotypic switching and promotes cell survival, in part, by attenuating HGD-induced autophagic flux thus improving vascular patency in response to acute ischemia-like injury.
MicroRNA-195 regulates Tuft cell function in the intestinal epithelium by altering translation of DCLK1
Authors: Kwon Min S. , Chung Hee K. , Xiao Lan , Yu Ting-Xi , Wang Shelley R. , Piao Jun-Jie , Rao Jaladanki N. , Gorospe Myriam , Wang Jian-Ying
Published: March 2021

Intestinal Tuft cells sense luminal contents to influence the mucosal immune response against eukaryotic infection. Paneth cells secrete antimicrobial proteins as part of the mucosal protective barrier. Defects in Tuft and Paneth cells occur commonly in various gut mucosal disorders. MicroRNA-195 (miR-195) regulates the stability and translation of target mRNAs and is involved in many aspects of cell processes and pathologies. Here, we reported the posttranscriptional mechanisms by which miR-195 regulates Tuft and Paneth cell function in the small intestinal epithelium. Mucosal tissues from intestinal epithelial tissue-specific miR-195 transgenic (miR195-Tg) mice had reduced numbers of double cortin-like kinase 1 (DCLK1)-positive (Tuft) and lysozyme-positive (Paneth) cells, compared with tissues from control mice, but there were no effects on Goblet cells and enterocytes. Intestinal organoids expressing higher miR-195 levels from miR195-Tg mice also exhibited fewer Tuft and Paneth cells. Transgenic expression of miR-195 in mice failed to alter growth of the small intestinal mucosa but increased vulnerability of the gut barrier in response to lipopolysaccharide (LPS). Studies aimed at investigating the mechanism underlying regulation of Tuft cells revealed that miR-195 directly interacted with the Dclk1 mRNA via its 3′-untranslated region and inhibited DCLK1 translation. Interestingly, the RNA-binding protein HuR competed with miR-195 for binding Dclk1 mRNA and increased DCLK1 expression. These results indicate that miR-195 suppresses the function of Tuft and Paneth cells in the small intestinal epithelium and further demonstrate that increased miR-195 disrupts Tuft cell function by inhibiting DCLK1 translation via interaction with HuR.
VEGF/Src signaling mediated pleural barrier damage and increased permeability contributes to subpleural pulmonary fibrosis
Authors: Lu Yu-Zhi , Liang Li-Mei , Cheng Pei-Pei , Xiong Li , Wang Meng , Song Lin-Jie , Yu Fan , He Xin-Liang , Xiong Liang , Wang Xiao-Rong , Xin Jian-Bao , Ye Hong , Ma Wan-Li
Published: March 2021

The distribution of fibrosis in idiopathic pulmonary fibrosis (IPF) is subpleural with basal predominance. Alveolar epithelial cell was considered as the key cell in the initial phase of IPF. However, the idea of activation and damage of alveolar epithelial cells is very difficult to explain why fibrosis distributes in the subpleural area. In this study, human pleural mesothelial cell (PMC) line and primary rat PMC was used as in vitro model. Intraperitoneal injection of bleomycin was used for making a pulmonary fibrosis model. The integrity of cultured monolayer PMCs was determined by transepithelial electric resistance (TEER). Pleural permeability was estimated by measuring paracellular transport of fluorescein isothiocyanate (FITC)-conjugated dextran. Changes in lung tissue of patients with IPF were analyzed by Masson’s and immunofluorescence staining. We found bleomycin induced PMCs damage and increased PMCs permeability; increased PMCs permeability aggravated bleomycin-induced subpleural inflammation and pulmonary fibrosis. Moreover, bleomycin was found to activate VEGF/Src signaling which increased PMCs permeability. In vivo, inhibition of VEGF/Src signaling prevented bleomycin-induced subpleural pulmonary fibrosis. At last, activation of VEGF/Src signaling was confirmed in subpleural area in patients with IPF. Taken together, our findings indicate that VEGF/Src signaling mediated pleural barrier damage and increased permeability which contributes to subpleural pulmonary fibrosis.
Effects of induced local ischemia during a 4-km cycling time trial on neuromuscular fatigue development
Authors: Azevedo Rafael de Almeida , Cruz Ramon , Hasegawa Julio Satoshi , Gáspari Arthur Fernandes , Chacon-Mikahil Mara Patrícia Traina , Silva-Cavalcante Marcos David , Coelho Daniel Boari , Lima-Silva Adriano E. , Bertuzzi Romulo
Published: March 2021

The present study analyzed the effects of local ischemia during endurance exercise on neuromuscular fatigue (NMF). Nine cyclists performed, in a counterbalanced order, two separate 4-km cycling time trials (TT) with (ISCH) or without (CONTR) induced local ischemia. NMF was characterized by using isometric maximal voluntary contractions (IMVC), whereas central [voluntary activation (VA)] and peripheral fatigue [peak torque of potentiated twitch (TwPt)] of knee extensors were evaluated using electrically evoked contractions performed before (PRE) and 1 min after (POST) the TT. Electromyographic activity (EMG), power output (PO), oxygen uptake (V̇o2), and rating of perceived exertion (RPE) were also recorded. The decrease in IMVC (−15 ± 9% vs. −10 ± 8%, P = 0.66), VA (−4 ± 3% vs. −3 ± 3%, P = 0.46), and TwPt (−16 ± 7% vs. −19 ± 14%, P = 0.67) was similar in ISCH and CONTR. Endurance performance was drastically reduced in ISCH condition (512 ± 29 s) compared with CONTR (386 ± 17 s) ( P < 0.001), which was accompanied by lower EMG, PO, and V̇o2 responses (all P < 0.05). RPE was greater in ISCH compared with CONTR ( P < 0.05), but the rate of change was similar throughout the TT (8.19 ± 2.59 vs. 7.81 ± 2.01 RPE.% of total time−1, P > 0.05). These results indicate that similar end-exercise NMF levels were accompanied by impaired endurance performance in ISCH compared with CONTR. These novel findings suggest that the local reduced oxygen availability affected the afferent feedback signals to the central nervous system, ultimately increasing perceived effort and reducing muscle activity and exercise intensity to avoid surpassing a sensory tolerance limit before the finish line.
Assessing cerebellar-cortical connectivity using concurrent TMS-EEG: a feasibility study
Authors: Fernandez Lara , Biabani Mana , Do Michael , Opie George M. , Hill Aron T. , Barham Michael P. , Teo Wei-Peng , Byrne Linda K. , Rogasch Nigel C. , Enticott Peter G.
Published: March 2021

This is the first study to systematically assess the feasibility of obtaining TMS-evoked potentials from cerebellar stimulation with concurrent EEG. An innovative control condition using electrical stimulation was modified to mimic the sensory aspects of cerebellar stimulation with a double-cone coil, and a state-of-the art cleaning pipeline was trialled. The extent of artifact contamination in signals from stimulation of a cerebellar and an occipital/parietal control site using two TMS coil types was highlighted.
Assessing the Effectiveness of Mass Testing and Quarantine in the Spread of COVID‐19 in Beijing and Xinjiang, 2020
Authors: Li Feng , Jin Zhen , Zhang Juan
Published: March 2021

Coronavirus disease (COVID‐19) cases and COVID‐19‐related deaths have been increasing worldwide since the outbreak in 2019. Before the mass vaccination campaign for COVID‐19, the main methods for COVID‐19 control in China were mass testing and quarantine. Based on the transmission mechanism of COVID‐19, we constructed a dynamic model for COVID‐19 transmission in two typical regions: Beijing and Xinjiang. We calculated the basic reproduction number R0, proved the global stability of COVID‐19 transmission via the Lyapunov function technique, and introduced the final size. We assessed the effectiveness of mass testing and quarantine. Sensitivity analysis indicated that the more the people were tested per day, the larger is the quarantine proportionality coefficient, the earlier the source location was determined, and the better is the controlling effect. In addition, it was more effective to increase the coefficient of quarantine if the population density in the region was low. To eliminate the pandemic, the government has to expand testing and quarantine, requiring a large amount of continuous manpower, material, and financial resources. Therefore, new control measures should be developed.
[Retracted] False Financial Statement Identification Based on Fuzzy C‐Means Algorithm
Authors: Li Jixiao
Published: March 2021

Financial accountants falsify financial statements by means of financial techniques such as financial practices and financial standards, and when compared with conventional financial data, it is found that the falsified financial data often lack correlation or even contradict each other in terms of financial data indicators. At the same time, there are also inherent differences in reporting patterns from conventional financial data, but these differences are difficult to test manually. In this paper, the fuzzy C‐means (FCM) clustering method is used to amplify these differences and thus identify false financial statements. In the proposed algorithm, firstly, the normalization constraint of the FCM clustering algorithm on the sum of affiliation of individual samples is relaxed to the constraint on the sum of affiliation of all samples, thus reducing the sensitivity of the algorithm to noise and isolated points; secondly, a new affiliation correction method is proposed to address the problem that the difference in affiliation is too large after the relaxation of the constraint. In the discussion of this paper, most of the information comes from the annual reports of companies, administrative penalty decisions of the Securities Regulatory Commission, and some information comes from research reports made by securities institutions, which are limited sources of information. The proposed method can correct the affiliation to a reasonable range, effectively avoiding the problem that some samples have too much affiliation and become a class of their own and also avoiding the problem that it is difficult to choose the termination threshold of the algorithm iteration due to too little affiliation, and can ensure that the constraint on the sum of affiliation of all samples is always satisfied during the iteration of the algorithm. The method has the characteristics of high recognition accuracy and has the significance of theoretical method innovation.
Environment Perception Technologies for Power Transmission Line Inspection Robots
Authors: Chen Minghao , Tian Yunong , Xing Shiyu , Li Zhishuo , Li En , Liang Zize , Guo Rui
Published: March 2021

With the fast development of the power system, traditional manual inspection methods of a power transmission line (PTL) cannot supply the demand for high quality and dependability for power grid maintenance. Consequently, the automatic PTL inspection technology becomes one of the key research focuses. For the purpose of summarizing related studies on environment perception and control technologies of PTL inspection, technologies of three‐dimensional (3D) reconstruction, object detection, and visual servo of PTL inspection are reviewed, respectively. Firstly, 3D reconstruction of PTL inspection is reviewed and analyzed, especially for the technology of LiDAR‐based reconstruction of power lines. Secondly, the technology of typical object detection, including pylons, insulators, and power line accessories, is classified as traditional and deep learning‐based methods. After that, their merits and demerits are considered. Thirdly, the progress and issues of visual servo control of inspection robots are also concisely addressed. For improving the automation degree of PTL robots, current problems of key techniques, such as multisensor fusion and the establishment of datasets, are discussed and the prospect of inspection robots is presented.
Analysis of Factors Affecting Freight Demand Based on Input-Output Model
Authors: Lu Changxiang , Fu Shaochuan , Fang Jiaqi , Huang Jikai , Ye Yong
Published: March 2021

Freight demand is a highly variable process over economic and industrial structure, and accurate freight demand forecasting is the basis of transportation planning. In order to clarify the influencing factors of freight volume so as to analyze and predict the change trend of freight volume accurately, this paper analyzes the impact of changes in economic, industrial structure, and complete consumption coefficients on freight demand, through constructing an input-output model for transportation value analysis and forecasting freight volume by fitting data of transportation value and freight traffic. Studies have shown that the growth in economic aggregate is the main reason for the increase in the value of transportation, and the change in the complete consumption coefficient is the main reason for the increase in freight traffic.
Cooperative Antenna Selection Method for Directional Antenna Ad Hoc Networks Based on ALOHA
Authors: Zheng Bowen , Sun Songlin , Shao Guoyuan
Published: March 2021

In recent years, directional antennas or phased array antennas are being widely used in communication systems due to the higher antenna gains. However, without external time synchronization and angle synchronization, the unsynchronized node usually takes a long time to synchronize with the existing nodes due to the narrow beams. Although the multibeam transmission or the digital phased array antenna can reduce this problem, it is clear that the cost of the digital phased array antenna is currently too high. Without external time synchronization and angle synchronization, a cooperative antenna selection method based on directional antennas is proposed in this paper. Our method only uses the narrow beams to transmit and to receive and reduces the time for self‐synchronization. In this paper, we give the expression of the expected average time for the self‐synchronization of multiple nodes, transform the problem into the problem of finding the minimum value of the infinite norm of the sequence, and then propose a cooperative antenna selection method which calculates the optimal transmission probability distribution of the node in different directions through parameter sharing and relative geometric position relationship between nodes. Finally, we verify the proposed method through simulation, and the number of beams is set between 6 and 10. In a typical scenario of five nodes, our method reduces the maximum average self‐synchronization time by 50% averagely, compared with the traditional method which sends the different antenna beams at equal probability.
Perioperative Electroacupuncture Can Accelerate the Recovery of Gastrointestinal Function in Cancer Patients Undergoing Pancreatectomy or Gastrectomy: A Randomized Controlled Trial
Authors: Qiu Guotong , Huang Tao , Lu Yang , Zhang Lipeng , Zhao Yajie , Yuan Yong , Ren Hu , An Jun , Zhou Jincao , Li Rongjun , Du Yongxing , Wang Tuoran , Wang Peng , He Fang , Ding Yunqing , Zhang Jianwei , Han Bin , Lan Zhongmin , Qi Shulan , Li Zongze , Gao Jianyong , Gu Zongting , Sun Yuemin , Bai Xiaofeng , Aimaiti Saderbieke , Chu Yunmian , Wang Chengfeng
Published: March 2021

The effect of perioperative acupuncture on accelerating gastrointestinal function recovery has been reported in colorectal surgery and distal gastrectomy (Billroth-II). However, the evidence in pancreatectomy and other gastrectomy is still limited. A prospective, randomized controlled trial was conducted between May 2018 and August 2019. Consecutive patients undergoing pancreatectomy or gastrectomy in our hospital were randomly assigned to the electroacupuncture (EA) group and the control group. The patients in the EA group received transcutaneous EA on Bai-hui (GV20), Nei-guan (PC6), Tian-shu (ST25), and Zu-san-li (ST36) once a day in the afternoon, and the control group received sham EA. Primary outcomes were the time to first flatus and time to first defecation. In total, 461 patients were randomly assigned to the groups, and 385 were analyzed finally (EA group, n = 201; control group, n = 184). Time to first flatus (3.0 ± 0.7 vs 4.2 ± 1.0,

P
<
0.001

) and first defecation (4.2 ± 0.9 vs 5.4 ± 1.2,

P
<
0.001

) in the EA group were significantly shorter than those in the control group. Of patients undergoing pancreatectomy, those undergoing pancreaticoduodenectomy and intraoperative radiation therapy (IORT) surgery benefitted from EA in time to first flatus (

P
<
0.001

) and first defecation (

P
<
0.001

), while those undergoing distal pancreatectomy did not (

P

flatus

=
0.157

,

P

defecation

=
0.007

) completely. Of patients undergoing gastrectomy, those undergoing total gastrectomy and distal gastrectomy (Billroth-II) benefitted from EA (

P
<
0.001

), as did those undergoing proximal gastrectomy (

P
=
0.015

). Patients undergoing distal gastrectomy (Billroth-I) benefitted from EA in time to first defecation (

P
=
0.012

) but not flatus (

P
=
0.051

). The time of parenteral nutrition, hospital stay, and time to first independent walk in the EA group were shorter than those in the control group. No severe EA complications were reported. EA was safe and effective in accelerating postoperative gastrointestinal function recovery. Patients undergoing pancreaticoduodenectomy, IORT surgery, total gastrectomy, proximal gastrectomy, or distal gastrectomy (Billroth-II) could benefit from EA. This trial is registered with NCT03291574.