bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of CRISPR/Cas9 Tools for Genome Editing in the White-Rot Fungus Dichomitus squalens
Authors: Kowalczyk Joanna E. , Saha Shreya , Mäkelä Miia R.
Published: October 2021

Dichomitus squalens is an emerging reference species that can be used to investigate white-rot fungal plant biomass degradation, as it has flexible physiology to utilize different types of biomass as sources of carbon and energy. Recent comparative (post-) genomic studies on D. squalens resulted in an increasingly detailed knowledge of the genes and enzymes involved in the lignocellulose breakdown in this fungus and showed a complex transcriptional response in the presence of lignocellulose-derived compounds. To fully utilize this increasing amount of data, efficient and reliable genetic manipulation tools are needed, e.g., to characterize the function of certain proteins in vivo and facilitate the construction of strains with enhanced lignocellulolytic capabilities. However, precise genome alterations are often very difficult in wild-type basidiomycetes partially due to extremely low frequencies of homology directed recombination (HDR) and limited availability of selectable markers. To overcome these obstacles, we assessed various Cas9-single guide RNA (sgRNA) ribonucleoprotein (RNP) -based strategies for selectable homology and non-homologous end joining (NHEJ) -based gene editing in D. squalens. We also showed an induction of HDR-based genetic modifications by using single-stranded oligodeoxynucleotides (ssODNs) in a basidiomycete fungus for the first time. This paper provides directions for the application of targeted CRISPR/Cas9-based genome editing in D. squalens and other wild-type (basidiomycete) fungi.
Heat Shock Cognate 70 kDa Protein Is the Target of Tetradecyl 2,3-Dihydroxybenzoate for Neuritogenic Effect in PC12 Cells
Authors: Cheng Lihong , Wang Yanhui , Xiang Lan , Qi Jianhua
Published: October 2021

Tetradecyl 2,3-dihydroxybenzoate (ABG-001) is a lead compound derived from gentisides with a remarkable neuritogenic activity. However, the target of ABG-001 is yet to be defined to date. In this study, the potential target of ABG-001 was investigated via an activity-based protein profiling (ABPP) analysis, which is a chemical proteomic method for target identification by using chemical probes. Results indicated that the potential target proteins of ABG-001 were heat shock cognate 70 kDa protein (Hsc70), 78 kDa glucose-regulated protein (GRP78), and 14-3-3 theta protein. Then, the potential target of ABG-001 was confirmed by using inhibitors, the cellular thermal shift assay (CETSA) and small-interfering RNA (siRNA) analysis. The inhibitor of Hsc70 and siRNA significantly decreased the neurite outgrowth induced by ABG-001. Furthermore, ABG-001 induced neurite outgrowth was reduced by siRNA against Hsc70, and the results of CETSA suggested that Hsc70 showed a significant thermal stability-shifted effect upon ABG-001 treatment. These results indicated that Hsc70 is the target protein of ABG-001 in PC12 cells.
Pulsed Radiofrequency Upregulates Serotonin Transporters and Alleviates Neuropathic Pain-Induced Depression in a Spared Nerve Injury Rat Model
Authors: Ma Kuo-Hsing , Cheng Cheng-Yi , Chan Wei-Hung , Chen Shih-Yu , Kao Li-Ting , Sung Chun-Sung , Hueng Dueng-Yuan , Yeh Chun-Chang
Published: October 2021

Neuropathic pain (NP) is difficult to treat due to complex pathophysiological mechanisms. Pulsed radiofrequency (RRF) has been used widely with neuromodulation effect in refractory chronic pain treatment. A recent study found that PRF treatment may decrease chronic pain-related anxiety-depressant symptoms in patients, even though the mechanisms are unclear. Additionally, accumulated evidence has shown serotonin uptake is correlated with various neuropsychiatric diseases. Therefore, we investigated the effects and underlying mechanisms of PRF on depression-like behaviors, resulting from spared nerve injury (SNI)-induced NP. We examined the indexes of mechanical allodynia, cold allodynia, depression-like behavior, and blood cytokines by dynamic plantar aesthesiometry, acetone spray test, forced swimming test, and ProcartaPlex multiplex immunoassays in male Wistar rats, respectively. Serotonin transporters (SERTs) in rat brains were examined by using 4-[18F]-ADAM/PET imaging. We found that specific uptake ratios (SURs) of SERTs were significantly decreased in the brain regions of the thalamus and striatum in rats with SNI-induced NP and depression-like behaviors. Additionally, the decrease in SERT density was correlated with the development of a depression-like behavior indicated by the forced swimming test results and pronounced IL-6 cytokines. Moreover, we demonstrated that PRF application could modulate the descending serotoninergic pathway to relieve pain and depression behaviors.
Transcranial versus Direct Cortical Stimulation for Motor-Evoked Potentials during Resection of Supratentorial Tumors under General Anesthesia (The TRANSEKT-Trial): Study Protocol for a Randomized Controlled Trial
Authors: Abboud Tammam , Asendorf Thomas , Heinrich Jutta , Faust Katharina , Krieg Sandro M. , Seidel Kathleen , Mielke Dorothee , Matthies Cordola , Ringel Florian , Rohde Veit , Szelényi Andrea
Published: October 2021

Background: Monitoring of motor function during surgery for supratentorial tumors under general anesthesia applies either transcranial electrical stimulation (TES) or direct cortical stimulation (DCS) to elicit motor-evoked potentials. To date, there is no guideline that favor one method over the other. Therefore, we designed this randomized study to compare between both methods regarding the prediction of postoperative motor deficits and extent of tumor resection. Methods: This is a multicenter (six centers in Germany and one in Switzerland), double blind, parallel group, exploratory, randomized controlled clinical trial. Patients without or with mild paresis, who are scheduled for surgical resection of motor-eloquent brain tumors under general anesthesia will be randomized to surgical resection under TES or surgical resection under DCS. The primary endpoint is sensitivity and specificity in prognosis of motor function 7 days after surgery. The main secondary endpoint is the extent of tumor resection. The study is planned to include 120 patients within 2 years. Discussion: The present exploratory study should compare TES and DCS regarding sensitivity and specificity in predicting postoperative motor deficit and extent of tumor resection to calculate the required number of patients in a confirmatory trial to test the superiority of one method over the other.
The Association between Use of ICS and Psychiatric Symptoms in Patients with COPD—A Nationwide Cohort Study of 49,500 Patients
Authors: Jordan Alexander , Sivapalan Pradeesh , Eklöf Josefin , Vestergaard Jakob B. , Meteran Howraman , Saeed Mohamad Isam , Biering-Sørensen Tor , Løkke Anders , Seersholm Niels , Jensen Jens Ulrik Stæhr
Published: October 2021

Psychiatric side effects are well known from treatment with systemic corticosteroids. It is, however, unclear whether inhaled corticosteroids (ICS) have psychiatric side effects in patients with COPD. We conducted a nationwide cohort study in all Danish COPD outpatients who had respiratory medicine specialist-verified COPD, age ≥40 years, and no previous cancer. Prescription fillings of antidepressants and risk of admissions to psychiatric hospitals with either depression, anxiety or bipolar disorder were assessed by Cox proportional hazards models. We observed a dose-dependent increase in the risk of antidepressant-use with ICS cumulated dose (HR 1.05, 95% CI 1.03–1.07, p = 0.0472 with low ICS exposure, HR 1.10, 95% CI 1.08–1.12, p < 0.0001 with medium exposure, HR 1.15, 95% CI 1.11–1.15, p < 0.0001 with high exposure) as compared to no ICS exposure. We found a discrete increased risk of admission to psychiatric hospitals in the medium and high dose group (HR 1.00, 95% CI 0.98–1.03, p = 0.77 with low ICS exposure, HR 1.07, 95% CI 1.05–1.10, p < 0.0001 with medium exposure, HR 1.13, 95% CI 1.10–1.15, p < 0.0001 with high exposure). The association persisted when stratifying for prior antidepressant use. Thus, exposure to ICS was associated with a small to moderate increase in antidepressant-use and psychiatric admissions.
Managing Sleep in Adults with ADHD: From Science to Pragmatic Approaches
Authors: Surman Craig B. H. , Walsh Daniel M.
Published: October 2021

Background: Sleep disorders and sleep problems commonly occur in adults with ADHD and add to functional impairment. Evidence-based treatments for sleep could improve function in the adult ADHD population. Methods: A literature review was conducted to present the clinical science informing treatment of sleep in adults with ADHD. Results: Six systematic prospective studies of sleep intervention in adults with ADHD were identified. Three of these, all including well-characterized ADHD patients, offered evidence for a significant effect of morning light therapy. Across the studies, preliminary evidence for melatonin, behavioral therapy, and weighted blankets were also found. Implication: Low-risk interventions such as light therapy may improve sleep in adults with ADHD, but many sleep interventions currently in use remain unstudied in the ADHD population. Considerations for evidence-informed practice and future research directions are discussed.
Involvement of Kynurenine Pathway in Hepatocellular Carcinoma
Authors: Krishnamurthy Shivani , Gilot David , Ahn Seong Beom , Lam Vincent , Shin Joo-Shik , Guillemin Gilles Jackie , Heng Benjamin
Published: October 2021

As the second and third leading cancer-related death in men and the world, respectively, primary liver cancer remains a major concern to human health. Despite advances in diagnostic technology, patients with primary liver cancer are often diagnosed at an advanced stage. Treatment options for patients with advanced hepatocarcinoma (HCC) are limited to systemic treatment with multikinase inhibitors and immunotherapy. Furthermore, the 5-year survival rate for these late-stage HCC patients is approximately 12% worldwide. There is an unmet need to identify novel treatment options and/or sensitive blood-based biomarker(s) to detect this cancer at an early stage. Given that the liver harbours the largest proportion of immune cells in the human body, understanding the tumour–immune microenvironment has gained increasing attention as a potential target to treat cancer. The kynurenine pathway (KP) has been proposed to be one of the key mechanisms used by the tumour cells to escape immune surveillance for proliferation and metastasis. In an inflammatory environment such as cancer, the KP is elevated, suppressing local immune cell populations and enhancing tumour growth. In this review, we collectively describe the roles of the KP in cancer and provide information on the latest research into the KP in primary liver cancer.
Particle Beam Therapy Tolerance and Outcome on Patients with Autoimmune Diseases: A Single Institution Matched Case–Control Study
Authors: Riva Giulia , Vischioni Barbara , Gandini Sara , Cavalieri Stefano , Ronchi Sara , Barcellini Amelia , Bonora Maria , Chalaszczyk Agnieszka , Ingargiola Rossana , Vitolo Viviana , Fiore Maria Rosaria , Iannalfi Alberto , Orlandi Ester
Published: October 2021

It is unclear whether autoimmune diseases (ADs) may predispose patients to higher radiation-induced toxicity, and no data are available regarding particle therapy. Our objective was to determine if cancer patients with ADs have a higher incidence of complications after protons (PT) or carbon ion (CIRT) therapy. METHODS. In our retrospective monocentric study, 38 patients with ADs over 1829 patients were treated with particle therapy between 2011 and 2020. Thirteen patients had collagen vascular disease (CVD), five an inflammatory bowel disease (IBD) and twenty patients an organ-specific AD. Each patient was matched with two control patients without ADs on the basis of type/site of cancer, type of particle treatment, age, sex, hypertension and/or diabetes and previous surgery. RESULTS. No G4–5 complications were reported. In the AD group, the frequency of acute grade 3 (G3) toxicity was higher than in the control group (15.8% vs. 2.6%, p = 0.016). Compared to their matched controls, CVD–IBD patients had a higher frequency of G3 acute complications (27.7 vs. 2.6%, p = 0.002). There was no difference between AD patients (7.9%) and controls (2.6%) experiencing late G3 toxicity (p = 0.33). The 2 years disease-free survival was lower in AD patients than in controls (74% vs. 91%, p = 0.01), although the differences in terms of survival were not significant. CONCLUSIONS. G3 acute toxicity was more frequently reported in AD patients after PT or CIRT. Since no severe G4–G5 events were reported and in consideration of the benefit of particle therapy for selected cancers, we conclude that particle therapy should be not discouraged for patients with ADs. Further prospective studies are warranted to gain insight into toxicity in cancer patients with ADs enrolled for particle therapy.
Basal Cell Carcinoma Treated with High Dose Rate (HDR) Brachytherapy—Early Evaluation of Clinical and Dermoscopic Patterns during Irradiation
Authors: Krzysztofiak Tomasz , Kamińska-Winciorek Grażyna , Tukiendorf Andrzej , Suchorzepka Magdalena , Wojcieszek Piotr
Published: October 2021

Basal cell carcinoma (BCC) is the most frequent malignancy of the Caucasian population. Dermoscopy is an established diagnostic method providing the bridge between clinical and pathological examination. Surface skin high dose rate (HDR) brachytherapy is an organ sparing treatment method used for non-surgical candidates. This prospective study aimed to observe clinical and dermoscopic features and their evolution in 23 patients with pathologically confirmed BCC that have been treated with HDR brachytherapy. In all cases, custom-made surface moulds were used. HDR brachytherapy was performed with 192Ir, dose 45Gy was delivered to the tumour in nine fractions of 5Gy, three times a week. The evolution of clinical and dermoscopic features was followed up at the beginning of treatment, and on the day of every fraction (t1–t9). Dermoscopic evaluation of neoplastic and non-neoplastic structures was based on current diagnostic criteria according to current literature. Univariate logistic regression showed a decreasing number of clinical and pathological features of basal cell carcinoma with every treatment fraction. The effect was more strongly pronounced for cancer-related dermoscopic structures compared with non-neoplastic features. We used multivariate ordinal logistic regression with random effects to prove that the patients’ age corresponds with the tumour’s response to radiation—which may implicate a better response to treatment among older patients. High dose rate brachytherapy decreases the number of clinical and dermoscopic features typical for basal cell carcinoma. The effect is more pronounced among older patients.
Tumor Cells and the Extracellular Matrix Dictate the Pro-Tumoral Profile of Macrophages in CRC
Authors: Coletta Sara , Lonardi Silvia , Sensi Francesca , D’Angelo Edoardo , Fassan Matteo , Pucciarelli Salvatore , Valzelli Arianna , Biccari Andrea , Vermi William , Della Bella Chiara , Barizza Annica , D’Elios Mario Milco , de Bernard Marina , Agostini Marco , Codolo Gaia
Published: October 2021

Tumor-associated macrophages (TAMs) are major components of the tumor microenvironment. In colorectal cancer (CRC), a strong infiltration of TAMs is accompanied by a decrease in effector T cells and an increase in the metastatic potential of CRC. We investigated the functional profile of TAMs infiltrating CRC tissue by immunohistochemistry, flow cytometry, ELISA, and qRT-PCR and their involvement in impairing the activation of effector T cells. In CRC biopsies, we evidenced a high percentage of macrophages with low expression of the antigen-presenting complex MHC-II and high expression of CD206. Monocytes co-cultured with tumor cells or a decellularized tumor matrix differentiated toward a pro-tumoral macrophage phenotype characterized by decreased expression of MHC-II and CD86 and increased expression of CD206 and an abundant release of pro-tumoral cytokines and chemokines. We demonstrated that the hampered expression of MHC-II in macrophages is due to the downregulation of the MHC-II transactivator CIITA and that this effect relies on increased expression of miRNAs targeting CIITA. As a result, macrophages become unable to present antigens to CD4 T lymphocytes. Our data suggest that the tumor microenvironment contributes to defining a pro-tumoral profile of macrophages infiltrating CRC tissue with impaired capacity to activate T cell effector functions.
Current Management of Oligometastatic Lung Cancer and Future Perspectives: Results of Thermal Ablation as a Local Ablative Therapy
Authors: Ghosn Mario , Solomon Stephen B.
Published: October 2021

A growing body of evidence shows improved overall survival and progression-free survival after thermal ablation in non-small cell lung carcinoma (NSCLC) patients with a limited number of metastases, combined with chemotherapy or tyrosine kinase inhibitors or after local recurrence. Radiofrequency ablation and microwave ablation are the most evaluated modalities, and target tumor size <3 cm (and preferably <2 cm) is a key factor of technical success and efficacy. Although thermal ablation offers some advantages over surgery and radiotherapy in terms of repeatability, safety, and quality of life, optimal management of these patients requires a multidisciplinary approach, and further randomized controlled trials are required to help refine patient selection criteria. In this article, we present a comprehensive review of available thermal ablation modalities and recent results supporting their use in oligometastatic and oligoprogressive NSCLC disease along with their potential future implications in the emerging field of immunotherapy.
Re-Expression of Poly/Oligo-Sialylated Adhesion Molecules on the Surface of Tumor Cells Disrupts Their Interaction with Immune-Effector Cells and Contributes to Pathophysiological Immune Escape
Authors: Jarahian Mostafa , Marofi Faroogh , Maashi Marwah Suliman , Ghaebi Mahnaz , Khezri Abdolrahman , Berger Martin R.
Published: October 2021

Glycans linked to surface proteins are the most complex biological macromolecules that play an active role in various cellular mechanisms. This diversity is the basis of cell–cell interaction and communication, cell growth, cell migration, as well as co-stimulatory or inhibitory signaling. Our review describes the importance of neuraminic acid and its derivatives as recognition elements, which are located at the outermost positions of carbohydrate chains linked to specific glycoproteins or glycolipids. Tumor cells, especially from solid tumors, mask themselves by re-expression of hypersialylated neural cell adhesion molecule (NCAM), neuropilin-2 (NRP-2), or synaptic cell adhesion molecule 1 (SynCAM 1) in order to protect themselves against the cytotoxic attack of the also highly sialylated immune effector cells. More particularly, we focus on α-2,8-linked polysialic acid chains, which characterize carrier glycoproteins such as NCAM, NRP-2, or SynCam-1. This characteristic property correlates with an aggressive clinical phenotype and endows them with multiple roles in biological processes that underlie all steps of cancer progression, including regulation of cell–cell and/or cell–extracellular matrix interactions, as well as increased proliferation, migration, reduced apoptosis rate of tumor cells, angiogenesis, and metastasis. Specifically, re-expression of poly/oligo-sialylated adhesion molecules on the surface of tumor cells disrupts their interaction with immune-effector cells and contributes to pathophysiological immune escape. Further, sialylated glycoproteins induce immunoregulatory cytokines and growth factors through interactions with sialic acid-binding immunoglobulin-like lectins. We describe the processes, which modulate the interaction between sialylated carrier glycoproteins and their ligands, and illustrate that sialic acids could be targets of novel therapeutic strategies for treatment of cancer and immune diseases.
Combustion-Synthesized Porous CuO-CeO2-SiO2 Composites as Solid Catalysts for the Alkenylation of C(sp3)-H Bonds Adjacent to a Heteroatom via Cross-Dehydrogenative Coupling
Authors: Le Ha V. , Nguyen Vy B. , Pham Hai H. , Nguyen Khoa D. , Ho Phuoc H. , Trens Philippe , Di Renzo Francesco
Published: October 2021

A series of mixed oxides of CuO, CeO2, and SiO2 were prepared by gel combustion and employed for the first time as efficient solid catalysts in a solvent-less liquid-phase cross-dehydrogenative coupling. The facile one-pot catalyst synthesis resulted in highly porous materials presenting large specific surface areas and strong metal–support interactions. The interaction with highly dispersed CeO2 enhanced the redox properties of the CuO species. The CuO-CeO2-SiO2 composites exhibited excellent catalytic performance for the selective coupling between 1,1-diphenylethylene and tetrahydrofuran with a yield up to 85% of 2-(2,2-diphenylvinyl)-tetrahydrofuran in the presence of di-tert-butyl peroxide (DTPB) and KI. Albeit both CuO and CeO2 species are proved to be responsible for the catalytic conversion, a great synergistic improvement in the catalytic activity was obtained by extended contact between the oxide phases by high porosity in comparison with the reactions using individual Cu or Ce catalysts. The activity of the composite catalyst was shown to be highly stable after five successive reaction cycles. Furthermore, the study scope was extended to the synthesis of different derivatives via composite-catalyzed coupling of C(sp2)-H with C(sp3-H) adjacent to a heteroatom. The good yields recorded proved the general validity of this composite for the cross-dehydrogenative coupling reaction rarely performed on solid catalysts.
The Involvement of Macrophage Colony Stimulating Factor on Protein Hydrolysate Injection Mediated Hematopoietic Function Improvement
Authors: Wang Shimiao , Zhang Yuchong , Meng Weiqi , Dong Yihao , Zhang Sujie , Teng Lesheng , Liu Yang , Li Lanzhou , Wang Di
Published: October 2021

Protein hydrolysate injection (PH) is a sterile solution of hydrolyzed protein and sorbitol that contains 17 amino acids and has a molecular mass of 185.0–622.0 g/mol. This study investigated the effect of PH on hematopoietic function in K562 cells and mice with cyclophosphamide (CTX)-induced hematopoietic dysfunction. In these myelosuppressed mice, PH increased the number of hematopoietic cells in the bone marrow (BM) and regulated the concentration of several factors related to hematopoietic function. PH restored peripheral blood cell concentrations and increased the numbers of hematopoietic stem cells and progenitor cells (HSPCs), B lymphocytes, macrophages, and granulocytes in the BM of CTX-treated mice. Moreover, PH regulated the concentrations of macrophage colony stimulating factor (M-CSF), interleukin (IL)-2, and other hematopoiesis-related cytokines in the serum, spleen, femoral condyle, and sternum. In K562 cells, the PH-induced upregulation of hematopoiesis-related proteins was inhibited by transfection with M-CSF siRNA. Therefore, PH might benefit the BM hematopoietic system via the regulation of M-CSF expression, suggesting a potential role for PH in the treatment of hematopoietic dysfunction caused by cancer therapy.
A Class of Copula-Based Bivariate Poisson Time Series Models with Applications
Authors: Alqawba Mohammed , Fernando Dimuthu , Diawara Norou
Published: October 2021

A class of bivariate integer-valued time series models was constructed via copula theory. Each series follows a Markov chain with the serial dependence captured using copula-based transition probabilities from the Poisson and the zero-inflated Poisson (ZIP) margins. The copula theory was also used again to capture the dependence between the two series using either the bivariate Gaussian or “t-copula” functions. Such a method provides a flexible dependence structure that allows for positive and negative correlation, as well. In addition, the use of a copula permits applying different margins with a complicated structure such as the ZIP distribution. Likelihood-based inference was used to estimate the models’ parameters with the bivariate integrals of the Gaussian or t-copula functions being evaluated using standard randomized Monte Carlo methods. To evaluate the proposed class of models, a comprehensive simulated study was conducted. Then, two sets of real-life examples were analyzed assuming the Poisson and the ZIP marginals, respectively. The results showed the superiority of the proposed class of models.
Gamification as a Strategy to Increase Motivation and Engagement in Higher Education Chemistry Students
Authors: Chans Guillermo M. , Portuguez Castro May
Published: October 2021

In the last year, educational experiences have become increasingly challenging due to teaching classes remotely. For this reason, it has been necessary to develop educational strategies that accompany the use of new technologies to maintain student interest. One of these methodologies is gamification, implemented in school environments more frequently due to the pandemic and whose impact on student motivation and engagement needs to be explored. The literature shows that student participation in these contexts should be increased when applying this methodology, where teachers can also provide greater support. This research proposes improving these aspects by developing a gamification strategy that can be easily replicated in other environments. This study was carried out for a chemistry course at a university in central Mexico. This proposal details the short-, medium-, and long-term bonuses which stimulated and motivated students and achieved specific objectives. We also present the quantitative results of a questionnaire applied to 48 engineering students to identify their perceptions of how gamification could increase motivation and engagement in learning the subject of chemistry. In addition, pre- and post-knowledge tests were applied to determine whether there were changes in the learning outcomes. The results indicated that gamification increased student motivation and engagement, improved attitudes, promoted actions such as keeping the camera on during lectures and regular attendance, and improved student grades. This study fills the need for planning strategies to help improve student motivation in online classes and proposes an instrument to measure the results. It can be helpful to those interested in applying or adapting it in other disciplines.
Considerations for Developing a Reassessment Process: Report from the Canadian Real-World Evidence for Value of Cancer Drugs (CanREValue) Collaboration’s Reassessment and Uptake Working Group
Authors: Dai Wei Fang , Arciero Vanessa , Craig Erica , Fraser Brent , Arias Jessica , Boehm Darryl , Bosnic Nevzeta , Caetano Patricia , Chambers Carole , Jones Barry , Lungu Elena , Mitera Gunita , Potashnik Tanya , Reiman Anthony , Ritcher Trevor , Beca Jaclyn M. , Denburg Avram , Mercer Rebecca E. , Parmar Ambica , Tadrous Mina , Takhar Pam , Chan Kelvin K. W. ,   on behalf of the CanREValue Collaboration Reassessment and Uptake Working Group
Published: October 2021

The Canadian Real-world Evidence for Value in Cancer Drugs (CanREValue) Collaboration was established to develop a framework for generating and using real-world evidence (RWE) to inform the reassessment of cancer drugs following initial health technology assessment (HTA). The Reassessment and Uptake Working Group (RWG) is one of the five established CanREValue Working Groups. The RWG aims to develop considerations for incorporating RWE for HTA reassessment and strategies for using RWE to reassess drug funding decisions. Between February 2018 and December 2019, the RWG attended four teleconferences (with follow-up surveys) and two in-person meetings to discuss recommendations for the development of a reassessment process and potential barriers and facilitators. Modified Delphi methods were used to gather input. A draft report of recommendations (to December 2018) was shared for public consultation (December 2019 to January 2020). Initial considerations for developing a reassessment process were proposed. Specifically, reassessment can be initiated by diverse stakeholders, including decision makers from public drug plans or industry stakeholders. The reassessment process should be modelled after existing deliberation and recommendation frameworks used by HTA agencies. Proposed reassessment outcome categories include maintaining status quo, revisiting funding criteria, renegotiating price, or disinvesting. Overall, these initial considerations will serve as the basis for future advancements by the Collaboration.
Quality and Reliability of Halitosis Videos on YouTube as a Source of Information
Authors: Ramadhani Atik , Zettira Zenobia , Rachmawati Yuanita Lely , Hariyani Ninuk , Maharani Diah Ayu
Published: October 2021

Halitosis is a common condition that adversely affects quality of life. Through YouTube, people access oral health information. This study aimed to analyze the quality and comprehensiveness of the content, and reliability of halitosis videos hosted on YouTube. In total, 300 videos were collected based on three search keywords, and the number of likes, dislikes, views, duration, interaction index, viewing rate, and source category. Subsequently, the video score, which represents the content quality and comprehensiveness was used to categorize videos as poor, good, and excellent. DISCERN score was used to assess video reliability. Of the 105 videos analyzed, 68 (64.8%) were uploaded by personal users. In general, videos were categorized as poor and have low reliability. Videos sourced from healthcare professionals showed the highest quality, comprehensiveness of the content, and reliability (p < 0.05). There was no difference in the number of viewers for video duration less than or more than 4 min (p > 0.05). YouTube users prefer low-quality videos over high-quality ones, indicating that viewers cannot differentiate between reliable and potentially biased content. It is critical to enable viewers to critically assimilate information hosted on YouTube to make effective oral healthcare decisions.
Du Bois–Reymond Type Lemma and Its Application to Dirichlet Problem with the p(t)–Laplacian on a Bounded Time Scale
Authors: Mawhin Jean , Skrzypek Ewa , Szymańska-Dȩbowska Katarzyna
Published: October 2021

This paper is devoted to study the existence of solutions and their regularity in the p(t)–Laplacian Dirichlet problem on a bounded time scale. First, we prove a lemma of du Bois–Reymond type in time-scale settings. Then, using direct variational methods and the mountain pass methodology, we present several sufficient conditions for the existence of solutions to the Dirichlet problem.
Quantum Probes for the Characterization of Nonlinear Media
Authors: Candeloro Alessandro , Razavian Sholeh , Piccolini Matteo , Teklu Berihu , Olivares Stefano , Paris Matteo G. A.
Published: October 2021

Active optical media leading to interaction Hamiltonians of the form H=λ˜(a+a†)ζ represent a crucial resource for quantum optical technology. In this paper, we address the characterization of those nonlinear media using quantum probes, as opposed to semiclassical ones. In particular, we investigate how squeezed probes may improve individual and joint estimation of the nonlinear coupling λ˜ and of the nonlinearity order ζ. Upon using tools from quantum estimation, we show that: (i) the two parameters are compatible, i.e., the may be jointly estimated without additional quantum noise; (ii) the use of squeezed probes improves precision at fixed overall energy of the probe; (iii) for low energy probes, squeezed vacuum represent the most convenient choice, whereas for increasing energy an optimal squeezing fraction may be determined; (iv) using optimized quantum probes, the scaling of the corresponding precision with energy improves, both for individual and joint estimation of the two parameters, compared to semiclassical coherent probes. We conclude that quantum probes represent a resource to enhance precision in the characterization of nonlinear media, and foresee potential applications with current technology.
Entropy and Wealth
Authors: Koutsoyiannis Demetris , Sargentis G.-Fivos
Published: October 2021

While entropy was introduced in the second half of the 19th century in the international vocabulary as a scientific term, in the 20th century it became common in colloquial use. Popular imagination has loaded “entropy” with almost every negative quality in the universe, in life and in society, with a dominant meaning of disorder and disorganization. Exploring the history of the term and many different approaches to it, we show that entropy has a universal stochastic definition, which is not disorder. Hence, we contend that entropy should be used as a mathematical (stochastic) concept as rigorously as possible, free of metaphoric meanings. The accompanying principle of maximum entropy, which lies behind the Second Law, gives explanatory and inferential power to the concept, and promotes entropy as the mother of creativity and evolution. As the social sciences are often contaminated by subjectivity and ideological influences, we try to explore whether maximum entropy, applied to the distribution of a wealth-related variable, namely annual income, can give an objective description. Using publicly available income data, we show that income distribution is consistent with the principle of maximum entropy. The increase in entropy is associated to increases in society’s wealth, yet a standardized form of entropy can be used to quantify inequality. Historically, technology has played a major role in the development of and increase in the entropy of income. Such findings are contrary to the theory of ecological economics and other theories that use the term entropy in a Malthusian perspective.
The Resolved Mutual Information Function as a Structural Fingerprint of Biomolecular Sequences for Interpretable Machine Learning Classifiers
Authors: Bohnsack Katrin Sophie , Kaden Marika , Abel Julia , Saralajew Sascha , Villmann Thomas
Published: October 2021

In the present article we propose the application of variants of the mutual information function as characteristic fingerprints of biomolecular sequences for classification analysis. In particular, we consider the resolved mutual information functions based on Shannon-, Rényi-, and Tsallis-entropy. In combination with interpretable machine learning classifier models based on generalized learning vector quantization, a powerful methodology for sequence classification is achieved which allows substantial knowledge extraction in addition to the high classification ability due to the model-inherent robustness. Any potential (slightly) inferior performance of the used classifier is compensated by the additional knowledge provided by interpretable models. This knowledge may assist the user in the analysis and understanding of the used data and considered task. After theoretical justification of the concepts, we demonstrate the approach for various example data sets covering different areas in biomolecular sequence analysis.
Evaluating Soil Carbon as a Proxy for Erosion Risk in the Spatio-Temporal Complex Hydropower Catchment in Upper Pangani, Northern Tanzania
Authors: Amasi Aloyce I. M. , Wynants Maarten , Kawala Remigius A. , Sawe Shovi F. , Blake William H. , Mtei Kelvin M.
Published: October 2021

Land use conversion is generally accompanied by large changes in soil organic carbon (SOC). SOC influences soil erodibility through its broad control on aggregate stability, soil structure and infiltration capacity. However, soil erodibility is also influenced by soil properties, clay mineralogy and other human activities. This study aimed to evaluate soil organic carbon as proxy of soil erosion risk in the Nyumba ya Mungu (NYM) catchment in Northern Tanzania. Soil organic carbon (SOC) was measured by an AgroCares scanner from which the soil organic matter (SOM) was derived using the conversional van Bemmelen factor of 1.72. A regression analysis performed between the measured loss on ignition (LOI) values and SOM from the AgroScanner showed a strong positive correlation in all land use classes (LOIFL R2 = 0.85, r = 0.93, p < 0.0001; LOICL R2 = 0.86, r = 0.93, p = 0.0001; LOIGL R2 = 0.68, r = 0.83, p = 0.003; LOIBS R2 = 0.88, r = 0.94, p = 0.0001; LOIBL R2 = 0.83, r = 0.91, p = 0.0002). This indicates that SOC from the soil scanner provided a good representation of the actual SOM present in soils. The study also revealed significant differences in the soil aggregate stability (WSA) and SOM stock between the different land use types in the Upper Pangani Basin. The WSA decreases approximately in the following order: grassland > forest land > bare land > cultivated > bush land. Land use change can thus potentially increase the susceptibility of soil to erosion risk when SOC is reduced. Since WSA was directly related to SOM, the study indicates that, where formal measurements are limited, this simple and inexpensive aggregate stability test can be used by farmers to monitor changes in their soils after management changes and to tentatively assess SOC and soil health.
The Use of the Kahoot! Learning Platform as a Type of Formative Assessment in the Context of Pre-University Education during the COVID-19 Pandemic Period
Authors: Toma Florentina , Diaconu Daniel Constantin , Popescu Cristina Maria
Published: October 2021

The present study aims to display how using a personal assessment environment based on the interactive Kahoot! platform actively supports the teaching–learning process. The goal is to improve the instructive–educational process by applying a learning platform based on play and digital technology that favors a qualitative educational endeavor. The use of the Kahoot! platform as form of assessment had a significant and direct positive effect on the educational process during the COVID-19 pandemic.
Data Distribution Service Converter Based on the Open Platform Communications Unified Architecture Publish–Subscribe Protocol
Authors: Sim Woongbin , Song ByungKwen , Shin Junho , Kim Taehun
Published: October 2021

The open platform communications unified architecture (OPC UA) is a major industry-standard middleware based on the request–reply pattern, and the data distribution service (DDS) is an industry standard in the publish–subscribe form. The OPC UA cannot replace fieldbuses at the control and field levels. To facilitate real-time connectionless operation, the OPC Foundation added the publish–subscribe model—a new specification that supports broker functions, such as message queuing telemetry transport (MQTT), and advanced message queuing protocol (AMQP)—to the OPC UA Part 14 standard. This paper proposes a protocol converter for incorporation into the application layer of the DDS subscriber to facilitate interoperability among publisher–subscriber pairs. The proposed converter comprises a DDS gateway and bridge. The former exists inside the MQTT and AMQP brokers, which convert OPC UA publisher data into DDS messages prior to passing them on to the DDS subscriber. The DDS bridge passes the messages received from the DDS gateway to the OPC UA subscriber in the corresponding DDS application layer. The results reported in existing studies, and those obtained using the proposed converter, allow all devices supporting the OPC UA and OPC UA PubSub standards to realize DDS publish–subscribe interoperability.
Estimation of Tire Mileage and Wear Using Measurement Data
Authors: Chang Wei-Hsuan , Juang Rong-Terng , Huang Min-Hsiang , Sung Min-Feng
Published: October 2021

Tire mileage and wear provide important information for vehicle applications. There are more and more studies discussing intelligent tires, but few focus on the role of tire mileage and wear. The conventional tire pressure monitoring system (TPMS) is one of the intelligent tire applications, but there has been no significant advancement in recent years in this regard. In order to increase the additional functions of intelligent tire applications, we propose a method that estimates the mileage and wear information of tires. The proposed method uses a three-axis sensor and a Hall sensor to implement the function. The proposed method also has a low power design to reduce the power consumption of the Hall sensor. The experimental results show the trend of tire wear status, rendering this method effective. This method also requires more accurate mileage information to support tire wear estimation. This experiment found that the correct rate of the proposed mileage estimation method is 99.4% and provides sufficient and correct mileage information for tire wear methods. If this method is used in autonomous vehicle applications, the autonomous control strategy algorithm has more conditions to plan the control strategy. The strategy system processes more meticulous control that increases the safety of autonomous vehicles.
Malware Detection Based on Graph Attention Networks for Intelligent Transportation Systems
Authors: Catal Cagatay , Gunduz Hakan , Ozcan Alper
Published: October 2021

Intelligent Transportation Systems (ITS) aim to make transportation smarter, safer, reliable, and environmentally friendly without detrimentally affecting the service quality. ITS can face security issues due to their complex, dynamic, and non-linear properties. One of the most critical security problems is attacks that damage the infrastructure of the entire ITS. Attackers can inject malware code that triggers dangerous actions such as information theft and unwanted system moves. The main objective of this study is to improve the performance of malware detection models using Graph Attention Networks. To detect malware attacks addressing ITS, a Graph Attention Network (GAN)-based framework is proposed in this study. The inputs to this framework are the Application Programming Interface (API)-call graphs obtained from malware and benign Android apk files. During the graph creation, network metrics and the Node2Vec model are utilized to generate the node features. A GAN-based model is combined with different types of node features during the experiments and the performance is compared against Graph Convolutional Network (GCN). Experimental results demonstrated that the integration of the GAN and Node2Vec models provides the best performance in terms of F-measure and accuracy parameters and, also, the use of an attention mechanism in GAN improves the performance. Furthermore, node features generated with Node2Vec resulted in a 3% increase in classification accuracy compared to the features generated with network metrics.
Fabrication of Planar Heating Chuck Using Nichrome Thin Film as Heating Element for PECVD Equipment
Authors: Im Dong-Hyeok , Yoon Tae-Woong , Min Woo-Sig , Hong Sang-Jeen
Published: October 2021

Improving semiconductor equipment and components is an important goal of semiconductor manufacture. Especially during the deposition process, the temperature of the wafer must be precisely controlled to form a uniform thin film. In the conventional plasma-enhanced chemical vapor deposition (PECVD) chuck, heating rate, and temperature uniformity are limited by the spiral pattern and volume of the heating element. To overcome the structural limitation of the heating element of conventional chuck, we tried to develop the planar heating chuck (PHC), a 6-inch PECVD chuck with a planar heating element based on NiCr thin film that would be a good candidate for rapidly and uniformly heating. The time for the temperature elevation from room temperature to 330 °C was 398 s. In a performance evaluation, the fabricated PHC successfully completed a SiO2 PECVD process.
Using a Flexible IoT Architecture and Sequential AI Model to Recognize and Predict the Production Activities in the Labor-Intensive Manufacturing Site
Authors: Yuan Cadmus , Wang Chic-Chang , Chang Ming-Lun , Lin Wen-Ting , Lin Po-An , Lee Chang-Chi , Tsui Zhe-Luen
Published: October 2021

Under the pressures of global market uncertainty and rapid production changes, the labor-intensive industries demand instant manufacturing site information and accurate production forecasting. This research applies sensor modules with noise reduction, information abstracting, and wireless transmission functions to form a flexible internet of things (IoT) architecture for acquiring field information. Moreover, AI models are used to reveal human activities and predict the output of a group of workstations. The IoT architecture has been implemented in the actual shoe making site. Although there is a 5% missing data issue due to network transmission, neural network models can successfully convert the IoT data to machine utilization. By analyzing the field data, the actual collaboration among the worker team can be revealed. Furthermore, a sequential AI model is applied to learn to capture the characteristics of the team working. This AI model only requires training by 15 min of IoT data, then it can predict the current and next few days’ productions within 10% error. This research confirms that implementing the IoT architecture and applying the AI model enables instant manufacturing monitoring of labor-intensive manufacturing sites and accurate production forecasting.
Adaptive Fading Extended Kalman Filtering for Mobile Robot Localization Using a Doppler–Azimuth Radar
Authors: Li Bin , Lu Yanyang , Karimi Hamid Reza
Published: October 2021

In this paper, the localization problem of a mobile robot equipped with a Doppler–azimuth radar (D–AR) is investigated in the environment with multiple landmarks. For the type (2,0) robot kinematic model, the unknown modeling errors are generally aroused by the inaccurate odometer measurement. Meanwhile, the inaccurate odometer measurement can also give rise to a type of unknown bias for the D–AR measurement. For reducing the influence induced by modeling errors on the localization performance and enhancing the practicability of the developed robot localization algorithm, an adaptive fading extended Kalman filter (AFEKF)-based robot localization scheme is proposed. First, the robot kinematic model and the D–AR measurement model are modified by considering the impact caused by the inaccurate odometer measurement. Subsequently, in the frame of adaptive fading extended Kalman filtering, the way to the addressed robot localization problem with unknown biases is sought out and the stability of the developed AFEKF-based localization algorithm is also discussed. Finally, in order to testify the feasibility of the AFEKF-based localization scheme, three different kinds of modeling errors are considered and the comparative simulations are conducted with the conventional EKF. From the comparative simulation results, it can be seen that the average localization error under the developed AFEKF-based localization scheme is [0.0245 m0.0224 m0.0039 rad]T and the average localization errors using the conventional EKF are [1.0405 m2.2700 m0.1782 rad]T, [0.4963 m0.3482 m0.0254 rad]T and [0.2774 m0.3897 m0.0353 rad]T, respectively, under the three cases of the constant bias, the white Gaussian stochastic bias and the bounded uncertainty bias.