bluuebunny/crossref_metadata_2025 huggingface dataset:
Paradoxical Hidradenitis Suppurativa during Biologic Therapy, an Emerging Challenge: A Systematic Review
Authors: Ruggiero Angelo , Martora Fabrizio , Picone Vincenzo , Marano Laura , Fabbrocini Gabriella , Marasca Claudio
Published: February 2022

Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease usually occurring after puberty with painful, deep-seated, inflammatory lesions in the apocrine gland-bearing areas of the body. Although HS pathogenesis is still unproven, recent major research advantages have increased our knowledge of the mechanisms behind HS lesions. Particularly, follicular occlusion followed by follicular rupture has been shown to be crucial to HS development, leading to immune response activation, and resulting in typical clinical HS lesions. Moreover, an increased and imbalanced cytokine production, such as interleukin (IL) 17 and tumor necrosis factor (TNF) α, may play a role in HS. In recent years, paradoxical adverse events have been described during treatment. Since the recent increased use of biologic treatments in HS, an increased number of paradoxical HS occurrences have been reported. In this review, we analyzed all current data on paradoxical HS triggered by biological drugs.
Purinergic Receptor P2Y2 Stimulation Averts Aortic Valve Interstitial Cell Calcification and Myofibroblastic Activation
Authors: Moschetta Donato , Di Maria Enrico , Valerio Vincenza , Massaiu Ilaria , Bozzi Michele , Songia Paola , D’alessandra Yuri , Myasoedova Veronika A. , Poggio Paolo
Published: February 2022

Rationale—Calcific aortic valve stenosis (CAVS) is a pathological condition of the aortic valve with a prevalence of 3% in the general population. It is characterized by massive rearrangement of the extracellular matrix, mostly due to the accumulation of fibro-calcific deposits driven by valve interstitial cells (VIC), and no pharmacological treatment is currently available. The aim of this study was to evaluate the effects of P2Y2 receptor (P2RY2) activation on fibro-calcific remodeling of CAVS. Methods—We employed human primary VICs isolated from CAVS leaflets treated with 2-thiouridine-5′-triphosphate (2ThioUTP, 10 µM), an agonist of P2RY2. The calcification was induced by inorganic phosphate (2 mM) and ascorbic acid (50 µg/mL) for 7 or 14 days, while the 2ThioUTP was administered starting from the seventh day. 2ThioUTP was chronically administered for 5 days to evaluate myofibroblastic activation. Results—P2RY2 activation, under continuous or interrupted pro-calcific stimuli, led to a significant inhibition of VIC calcification potential (p < 0.01). Moreover, 2ThioUTP treatment was able to significantly reduce pro-fibrotic gene expression (p < 0.05), as well as that of protein α-smooth muscle actin (p = 0.004). Conclusions—Our data suggest that P2RY2 activation should be further investigated as a pharmacological target for the prevention of CAVS progression, acting on both calcification and myofibroblastic activation.
Implications of Heterogeneity of Epithelial-Mesenchymal States in Acromegaly Therapeutic Pharmacologic Response
Authors: Gil Joan , Marques-Pamies Montserrat , Valassi Elena , García-Martínez Araceli , Serra Guillermo , Hostalot Cristina , Fajardo-Montañana Carmen , Carrato Cristina , Bernabeu Ignacio , Marazuela Mónica , Rodríguez-Lloveras Helena , Cámara Rosa , Salinas Isabel , Lamas Cristina , Biagetti Betina , Simó-Servat Andreu , Webb Susan M. , Picó Antonio , Jordà Mireia , Puig-Domingo Manel
Published: February 2022

Acromegaly is caused by excess growth hormone (GH) produced by a pituitary tumor. First-generation somatostatin receptor ligands (SRLs) are the first-line treatment. Several studies have linked E-cadherin loss and epithelial-mesenchymal transition (EMT) with resistance to SRLs. Our aim was to study EMT and its relationship with SRLs resistance in GH-producing tumors. We analyzed the expression of EMT-related genes by RT-qPCR in 57 tumors. The postsurgical response to SRLs was categorized as complete response, partial response, or nonresponse if IGF-1 was normal, had decreased more than 30% without normalization, or neither of those, respectively. Most tumors showed a hybrid and variable EMT expression profile not specifically associated with SRL response instead of a defined epithelial or mesenchymal phenotype. However, high SNAI1 expression was related to invasive and SRL-nonresponsive tumors. RORC was overexpressed in tumors treated with SRLs before surgery, and this increased expression was more prominent in those cases that normalized postsurgical IGF-1 levels under SRL treatment. In conclusion, GH-producing tumors showed a heterogeneous expression pattern of EMT-related genes that would partly explain the heterogeneous response to SRLs. SNAI1 and RORC may be useful to predict response to SRLs and help medical treatment decision making.
Minimum Effective Dose of DPP-4 Inhibitors for Treating Early Stages of Diabetic Retinopathy in an Experimental Model
Authors: Bogdanov Patricia , Ramos Hugo , Valeri Marta , Deàs-Just Anna , Huerta Jordi , Simó Rafael , Hernández Cristina
Published: February 2022

The neurovascular unit (NVU) plays an essential role in the development of diabetic retinopathy (DR). We previously reported that the topical administration (eye drops) of sitagliptin and saxagliptin, two dipeptidyl peptidase-4 inhibitors (DPP-4i), prevents retinal neurodegeneration and vascular leakage in db/db mice. The aim of the present study is to evaluate the minimum effective dose of the topical administration of these DPP-4i. For this purpose, sitagliptin and saxagliptin were tested at different concentrations (sitagliptin: 1 mg/mL, 5 and 10 mg/mL, twice per day; saxagliptin: 1 and 10 mg/mL, once or twice per day) in db/db mice. As end points of efficacy, the hallmarks of NVU impairment were evaluated: reactive gliosis, neural apoptosis, and vascular leakage. These parameters were assessed by immunohistochemistry, cell counting, and the Evans blue method, respectively. Our results demonstrated that the minimum effective dose is 5 mg/mL twice per day for sitagliptin, and 10 mg/mL twice per day for saxagliptin. In conclusion, this study provides useful results for the design of future preclinical regulatory studies and for planning clinical trials.
PEGylation of Metal Oxide Nanoparticles Modulates Neutrophil Extracellular Trap Formation
Authors: Snoderly Hunter T. , Freshwater Kasey A. , Martinez de la Torre Celia , Panchal Dhruvi M. , Vito Jenna N. , Bennewitz Margaret F.
Published: February 2022

Novel metal oxide nanoparticle (NP) contrast agents may offer safety and functionality advantages over conventional gadolinium-based contrast agents (GBCAs) for cancer diagnosis by magnetic resonance imaging. However, little is known about the behavior of metal oxide NPs, or of their effect, upon coming into contact with the innate immune system. As neutrophils are the body’s first line of defense, we sought to understand how manganese oxide and iron oxide NPs impact leukocyte functionality. Specifically, we evaluated whether contrast agents caused neutrophils to release web-like fibers of DNA known as neutrophil extracellular traps (NETs), which are known to enhance metastasis and thrombosis in cancer patients. Murine neutrophils were treated with GBCA, bare manganese oxide or iron oxide NPs, or poly(lactic-co-glycolic acid) (PLGA)-coated metal oxide NPs with different incorporated levels of poly(ethylene glycol) (PEG). Manganese oxide NPs elicited the highest NETosis rates and had enhanced neutrophil uptake properties compared to iron oxide NPs. Interestingly, NPs with low levels of PEGylation produced more NETs than those with higher PEGylation. Despite generating a low rate of NETosis, GBCA altered neutrophil cytokine expression more than NP treatments. This study is the first to investigate whether manganese oxide NPs and GBCAs modulate NETosis and reveals that contrast agents may have unintended off-target effects which warrant further investigation.
A Novel Enzyme-Free Ratiometric Fluorescence Immunoassay Based on Silver Nanoparticles for the Detection of Dibutyl Phthalate from Environmental Waters
Authors: Meng Hui , Yao Nannan , Zeng Kun , Zhu Nuanfei , Wang Yue , Zhao Biying , Zhang Zhen
Published: February 2022

A novel ratiometric fluorescent immunoassay was developed based on silver nanoparticles (AgNPs) for the sensitive determination of dibutyl phthalate (DBP). In the detection system, AgNPs were labeled on the secondary antibody (AgNPs@Ab2) for signal amplification, which aimed to regulate the H2O2 concentrations. When AgNPs-Ab2 and antigen–primary antibody (Ab1) were linked by specific recognition, the blue fluorescence of Scopoletin (SC) could be effectively quenched by the H2O2 added while the red fluorescence of Amplex Red (AR) was generated. Under the optimized conditions, the calculated detection of limit (LOD, 90% inhibition) reached 0.86 ng/mL with a wide linear range of 2.31–66.84 ng/mL, which was approximately eleven times lower than that by HRP-based traditional ELISA with the same antibody. Meanwhile, it could improve the inherent built-in rectification to the environment by the combination of the dual-output ratiometric fluorescence assays with ELISA, which also enhanced the accuracy and precision (recoveries, 87.20–106.62%; CV, 2.57–6.54%), indicating it can be applied to investigate the concentration of DBP in water samples.
Detection and Quantification of Tp53 and p53-Anti-p53 Autoantibody Immune Complex: Promising Biomarkers in Early Stage Lung Cancer Diagnosis
Authors: Song Keum-Soo , Nimse Satish Balasaheb , Warkad Shrikant Dashrath , Kim Jung-Hoon , Kim Hey-Jin , Kim Taisun
Published: February 2022

Lung cancer is a leading cause of death worldwide, claiming nearly 1.80 million lives in 2020. Screening with low-dose computed tomography (LDCT) reduces lung cancer mortality by about 20% compared to standard chest X-rays among current or heavy smokers. However, several reports indicate that LDCT has a high false-positive rate. In this regard, methods based on biomarker detection offer excellent potential for developing noninvasive cancer diagnostic tests to complement LDCT for detecting stage 0∼IV lung cancers. Herein, we have developed a method for detecting and quantifying a p53-anti-p53 autoantibody complex and the total p53 antigen (wild and mutant). The LOD for detecting Tp53 and PIC were 7.41 pg/mL and 5.74 pg/mL, respectively. The detection ranges for both biomarkers were 0–7500 pg/mL. The known interfering agents in immunoassays such as biotin, bilirubin, intra-lipid, and hemoglobin did not detect Tp53 and PIC, even at levels that were several folds higher levels than their normal levels. Furthermore, the present study provides a unique report on this preliminary investigation using the PIC/Tp53 ratio to detect stage I–IV lung cancers. The presented method detects lung cancers with 81.6% sensitivity and 93.3% specificity. These results indicate that the presented method has high applicability for the identification of lung cancer patients from the healthy population.
Factors Affecting the Repurchase Intention of Organic Tea among Millennial Consumers: An Empirical Study
Authors: Tian Huawei , Siddik Abu Bakkar , Masukujjaman Mohammad
Published: February 2022

The study aims to identify the factors affecting consumers’ intention to repurchase organic tea in an emerging country such as Bangladesh. The study adopted the Stimulus-Organism-Response (SOR) theory, which uses seven constructs as the predictor of repurchase intention. This is a quantitative and empirical study that adopted cross-sectional survey methods. The convenience sampling method was used to collect data from 340 young respondents who visited supermarkets in Dhaka between October and November 2021. In order to analyze the obtained primary data, the structural equation modeling (SEM) approach was used. The findings revealed that product satisfaction, perceived values and brand trust are the predictors of repurchase intention. Surprisingly, we did not find that promotional efforts effected repurchase intention. The study also identified food quality and information quality as the antecedents of perceived value and product satisfaction, while the antecedents of brand trust were product satisfaction, food quality, brand image, information quality and promotional effort. The study suggested numerous theoretical and policy implications to improve repurchase intention of organic tea in the context of emerging economies such as Bangladesh.
A Novel Shear Strengthening of Existing RC Shear Walls Using Steel Wire Mesh and Polymer Mortar
Authors: Xie Xinyao , Guo Zixiong , Basha Syed Humayun , Huang Qunxian
Published: February 2022

A new type of strengthening technique for existing reinforced concrete (RC) shear walls was proposed using steel wire mesh (SWM) and polymer mortar. The experimental campaign consists of testing one conventional RC shear wall specimen and four specimens strengthened using different configurations of steel wire mesh ratios and wrapping methods under cyclic lateral loading. The experimental results showed that the application of steel wire meshes and polymer mortar not only delayed the shear cracks formation but also effectively controlled the crack propagation. The average increase in cracking load of strengthened specimens was about 79%. The lateral load-carrying capacity of the strengthened specimens increased (about 55%) with the increase in the considered steel wire mesh reinforcement ratio compared to the control specimen. Wrapping of steel wire meshes around the shear wall surface prevented debonding of polymer mortar layers, and enhanced the performance compared to wrapping only on exposed surfaces. A theoretical expression to estimate the capacity of the strengthened shear walls was proposed based on the softened strut-and-tie model. The proposed expression fairly predicted the capacity of the strengthened specimens for the present and previous study.
Immune Reconstitution Inflammatory Syndrome Associated Kaposi Sarcoma
Authors: Poizot-Martin Isabelle , Brégigeon Sylvie , Palich Romain , Marcelin Anne-Geneviève , Valantin Marc-Antoine , Solas Caroline , Veyri Marianne , Spano Jean-Philippe , Makinson Alain
Published: February 2022

People living with HIV (PLWH) with advanced immunosuppression who initiate antiretroviral therapy (ART) are susceptible to the occurrence of an immune reconstitution inflammatory syndrome (IRIS). Although ART is responsible for AIDS- associated Kaposi sarcoma (KS) improvement and resolution, new onset (unmasking KS-IRIS) or sudden progression of preexisting KS (paradoxical KS-IRIS) can occur after a time delay of between a few days and 6 months after the initiation or resumption of ART, even in patients with a low degree of immunocompromise. KS-IRIS incidence varies from 2.4% to 39%, depending on study design, populations, and geographic regions. Risk factors for developing KS-IRIS include advanced KS tumor stage (T1), pre-treatment HIV viral load >5 log10 copies/mL, detectable pre-treatment plasma-KSHV, and initiation of ART alone without concurrent chemotherapy. Both paradoxical and unmasking KS-IRIS have been associated with significant morbidity and mortality, and thrombocytopenia (<100,000 platelets/mm3 at 12 weeks) has been associated with death. KS-IRIS is not to be considered as ART failure, and an ART regimen must be pursued. Systemic chemotherapy for KS in conjunction with ART is recommended and, in contrast with management of IRIS for other opportunistic infections, glucocorticoids are contra-indicated. Despite our preliminary results, the place of targeted therapies in the prevention or treatment of KS-IRIS needs further assessment.
A Contemporary Review of Molecular Therapeutic Targets for Adenoid Cystic Carcinoma
Authors: Miller Lauren E. , Au Vivienne , Mokhtari Tara E. , Goss Deborah , Faden Daniel L. , Varvares Mark A.
Published: February 2022

ACC is a rare malignant tumor of the salivary glands. In this contemporary review, we explore advances in identification of targetable alterations and clinical trials testing these druggable targets. A search of relevant articles and abstracts from national meetings and three databases, including PubMed, Medline, and Web of Science, was performed. Following keyword search analysis and double peer review of abstracts to ensure appropriate fit, a total of 55 manuscripts were included in this review detailing advances in molecular targets for ACC. The most researched pathway associated with ACC is the MYB–NFIB translocation, found to lead to dysregulation of critical cellular pathways and thought to be a fundamental driver in a subset of ACC disease pathogenesis. Other notable molecular targets that have been studied include the cKIT receptor, the EGFR pathway, and NOTCH1, all with limited efficacy in clinical trials. The ongoing investigation of molecular abnormalities underpinning ACC that may be responsible for carcinogenesis is critical to identifying and developing novel targeted therapies.
Urokinase Receptor uPAR Downregulation in Neuroblastoma Leads to Dormancy, Chemoresistance and Metastasis
Authors: Shmakova Anna A. , Klimovich Polina S. , Rysenkova Karina D. , Popov Vladimir S. , Gorbunova Anna S. , Karpukhina Anna A. , Karagyaur Maxim N. , Rubina Kseniya A. , Tkachuk Vsevolod A. , Semina Ekaterina V.
Published: February 2022

uPAR is a membrane receptor that binds extracellular protease urokinase, contributes to matrix remodeling and plays a crucial role in cellular adhesion, proliferation, survival, and migration. uPAR overexpression in tumor cells promotes mitogenesis, opening a prospective avenue for targeted therapy. However, uPAR targeting in cancer has potential risks. We have recently shown that uPAR downregulation in neuroblastoma promotes epithelial-mesenchymal transition (EMT), potentially associated with metastasis and chemoresistance. We used data mining to evaluate the role of uPAR expression in primary and relapsed human neuroblastomas. To model the decreased uPAR expression, we targeted uPAR using CRISPR/Cas9 and shRNA in neuroblastoma Neuro2a cells and evaluated their chemosensitivity in vitro as well as tumor growth and metastasis in vivo. We demonstrate that the initially high PLAUR expression predicts poor survival in human neuroblastoma. However, relapsed neuroblastomas have a significantly decreased PLAUR expression. uPAR targeting in neuroblastoma Neuro2a cells leads to p38 activation and an increased p21 expression (suggesting a dormant phenotype). The dormancy in neuroblastoma cells can be triggered by the disruption of uPAR-integrin interaction. uPAR-deficient cells are less sensitive to cisplatin and doxorubicin treatment and exhibit lower p53 activation. Finally, low uPAR-expressing Neuro2a cells formed smaller primary tumors, but more frequent metastasis in mice. To the best of our knowledge, this is the first study revealing the pathological role of dormant uPAR-deficient cancer cells having a chemoresistant and motile phenotype.
Physical Activity Is Associated with Improved Overall Survival among Patients with Metastatic Colorectal Cancer
Authors: Smit Karel C. , Derksen Jeroen W. G. , Beets Geerard L. O. , Belt Eric J. Th. , Berbée Maaike , Coene Peter Paul L. O. , van Cruijsen Hester , Davidis Marjan A. , Dekker Jan Willem T. , van Dodewaard-de Jong Joyce M. , Haringhuizen Annebeth W. , Helgason Helgi H. , Hendriks Mathijs P. , Hoekstra Ronald , de Hingh Ignace H. J. T. , IJzermans Jan N. M. , Janssen Johan J. B. , Konsten Joop L. M. , Los Maartje , Mekenkamp Leonie J. M. , Nieboer Peter , Peeters Koen C. M. J. , Peters Natascha A. J. B. , Pruijt Hans J. F. M. , Quarles van Ufford-Mannesse Patricia , Rietbroek Ron C. , Schiphorst Anandi H. W. , Schouten van der Velden Arjan , Schrauwen Ruud W. M. , Sie Mark P. S. , Sommeijer Dirkje W. , Sonneveld Dirk J. A. , Stockmann Hein B. A. C. , Tent Marleen , Terheggen Frederiek , Tjin-A-Ton Manuel L. R. , Valkenburg-van Iersel Liselot , van der Velden Ankie M. T. , Vles Wouter J. , van Voorthuizen Theo , Wegdam Johannes A. , de Wilt Johannes H. W. , Koopman Miriam , May Anne M. ,   on behalf of the PLCRC Study Group
Published: February 2022

Regular physical activity (PA) is associated with improved overall survival (OS) in stage I–III colorectal cancer (CRC) patients. This association is less defined in patients with metastatic CRC (mCRC). We therefore conducted a study in mCRC patients participating in the Prospective Dutch Colorectal Cancer cohort. PA was assessed with the validated SQUASH questionnaire, filled-in within a maximum of 60 days after diagnosis of mCRC. PA was quantified by calculating Metabolic Equivalent Task (MET) hours per week. American College of Sports and Medicine (ACSM) PA guideline adherence, tertiles of moderate to vigorous PA (MVPA), and sport and leisure time MVPA (MVPA-SL) were assessed as well. Vital status was obtained from the municipal population registry. Cox proportional-hazards models were used to study the association between PA determinants and all-cause mortality adjusted for prognostic patient and treatment-related factors. In total, 293 mCRC patients (mean age 62.9 ± 10.6 years, 67% male) were included in the analysis. Compared to low levels, moderate and high levels of MET-hours were significantly associated with longer OS (fully adjusted hazard ratios: 0.491, (95% CI 0.299–0.807, p value = 0.005) and 0.485 (95% CI 0.303–0.778, p value = 0.003), respectively), as were high levels of MVPA (0.476 (95% CI 0.278–0.816, p value = 0.007)) and MVPA-SL (0.389 (95% CI 0.224–0.677, p value < 0.001)), and adherence to ACSM PA guidelines compared to non-adherence (0.629 (95% CI 0.412–0.961, p value = 0.032)). The present study provides evidence that higher PA levels at diagnosis of mCRC are associated with longer OS.
The Role of Sulfated Materials for Biodiesel Production from Cheap Raw Materials
Authors: Lowe Brandon , Gardy Jabbar , Hassanpour Ali
Published: February 2022

There is an urgent need to reduce global greenhouse gas emissions, yet to date the decarbonization of the transportation industry has been slow and of particular difficulty. While fossil fuel replacements such as biodiesel may aid the transition to a less polluting society, production at the industrial scales required is currently heavily dependent on chemical catalysis. Conventional two-step homogenous routes require the challenging separation of catalyst from the obtained product; however, heterogenous solid catalysts bring new considerations such as material stability, surface area, porosity, deactivation effects, and reduced reactivities under mild conditions. Nanomaterials present an attractive solution, offering the high reactivity of homogenous catalysts without complex recyclability issues. Slightly less reactive, acidic sulfated nanomaterials may also demonstrate greater stability to feedstock impurity, extending lifetime and improved versatility to a range of starting feeds. There remains, however, much work to be done in demonstrating the full-scale feasibility of such catalysts. This review explores recent developments over time in acidic sulfated nanocatalysis for biodiesel production, with particular focus on metal oxides, magnetic nanoparticles, silica-supported nanomaterials, and acidic carbon nanocatalysts. Included are various summaries of current progress in the literature, as well as recommendations for future research.
Studies of Clinoptilolite-Rich Zeolitic Tuffs from Different Regions and Their Activity in Photodegradation of Methylene Blue
Authors: Pavlović Jelena , Šuligoj Andraž , Opresnik Mojca , Tušar Nataša Novak , Logar Nataša Zabukovec , Rajić Nevenka
Published: February 2022

The present study focuses on clinoptilolite (CLI)-rich natural zeolitic tuffs and their photocatalytic activity in the degradation of cationic organic dyes. CLI from different regions was tested in the photocatalytic degradation of methylene blue (MB) as a model cationic dye. The photocatalytic tests were performed at room temperature and atmospheric pressure under visible light irradiation. For all the CLI samples, the highest activity was observed at pH = 6. Total MB degradation varied between 70 and 91% (C0 = 10 mg dm–3, 0.2 g dm–3 of photocatalyst, during 300 min). It is suggested that the presence of Fe species in the studied tuffs is responsible for the photocatalytic activity. The activity increases linearly with the Fe content in the tuffs. The MB photodegradation follows the Langmuir–Hinshelwood kinetic model. The recyclability tests showed good stability and efficiency of the photocatalyst. The degradation rate decreased from 91 to 69% during three reaction cycles, indicating a promising potential of natural zeolites in the treatment of textile industry wastewater.
Effect of Pd/Ce Loading and Catalyst Components on the Catalytic Abatement of Toluene
Authors: Liang Wenjun , Shi Xiujuan , Li Qinglei , Ren Sida , Yin Guobin
Published: February 2022

Monolithic catalysts are widely used in industrial catalysis. However, in the preparation of a monolithic catalyst, the traditional methods have some drawbacks such as low washcoat uploading ratio and poor uniformity. In the present work, the effects of Pd/Ce loading and catalyst components on the catalytic abatement of toluene were investigated. The acid treatment of the substrate, the particle size of the slurry and the dispersant on the uniformity of the washcoat and the catalytic performance were also explored. Characterisation was achieved via BET, SEM, zeta potential and laser grain-size analyses. The results showed that the catalytic activity of the catalyst increased with the increasing of the Ce content. It was found that the 0.2Pd-0.3Ce/γ-Al2O3 catalysts had the best toluene catalytic activity. The pretreatment of the cordierite with 20% HCl could improve the properties of the cordierite. It was also found that reducing the particle size of the washcoat and adding dispersant PAA could effectively improve the stability of the suspension and the uniformity of the washcoat. When 20% HCl pretreatment was used, the toluene catalytic activity of the monolith catalyst prepared by cordierite increased, in which T10 and T90 decreased by about 5 °C. Decreasing the particle size and dispersant also promoted the efficiency of catalytic degradation.
Recent Advances in Catalytic [3,3]-Sigmatropic Rearrangements
Authors: Lee Huijin , Kim Ki Tae , Kim Min , Kim Cheoljae
Published: February 2022

Carbon–carbon bond formation by [3,3]-sigmatropic rearrangement is a fundamental and powerful method that has been used to build organic molecules for a long time. Initially, Claisen and Cope rearrangements proceeded at high temperatures with limited scopes. By introducing catalytic systems, highly functionalized substrates have become accessible for forming complex structures under mild conditions, and asymmetric synthesis can be achieved by using chiral catalytic systems. This review describes recent breakthroughs in catalytic [3,3]-sigmatropic rearrangements since 2016. Detailed reaction mechanisms are discussed to enable an understanding of the reactivity and selectivity of the reactions. Finally, this review is inspires the development of new cascade reaction pathways employing catalytic [3,3]-sigmatropic rearrangement as related methodologies for the synthesis of complex functional molecules.
Outcome Measures in Facioscapulohumeral Muscular Dystrophy Clinical Trials
Authors: Ghasemi Mehdi , Emerson Charles P. , Hayward Lawrence J.
Published: February 2022

Facioscapulohumeral muscular dystrophy (FSHD) is a debilitating muscular dystrophy with a variable age of onset, severity, and progression. While there is still no cure for this disease, progress towards FSHD therapies has accelerated since the underlying mechanism of epigenetic derepression of the double homeobox 4 (DUX4) gene leading to skeletal muscle toxicity was identified. This has facilitated the rapid development of novel therapies to target DUX4 expression and downstream dysregulation that cause muscle degeneration. These discoveries and pre-clinical translational studies have opened new avenues for therapies that await evaluation in clinical trials. As the field anticipates more FSHD trials, the need has grown for more reliable and quantifiable outcome measures of muscle function, both for early phase and phase II and III trials. Advanced tools that facilitate longitudinal clinical assessment will greatly improve the potential of trials to identify therapeutics that successfully ameliorate disease progression or permit muscle functional recovery. Here, we discuss current and emerging FSHD outcome measures and the challenges that investigators may experience in applying such measures to FSHD clinical trial design and implementation.
Defective Patient NK Function Is Reversed by AJ2 Probiotic Bacteria or Addition of Allogeneic Healthy Monocytes
Authors: Ko Meng-Wei , Kaur Kawaljit , Safaei Tahmineh , Chen Wuyang , Sutanto Christine , Wong Paul , Jewett Anahid
Published: February 2022

In this paper, we present the role of autologous and allogeneic monocytes from healthy individuals and those of the cancer patients, with a number of distinct cancers, in activating the function of natural killer (NK) cells, in particular, in induction of IFN-γ secretion by the NK cells and the functional capability of secreted IFN-γ in driving differentiation of the tumor cells. In addition, we compared the roles of CD16 signaling as well as sonicated probiotic bacteria AJ2 (sAJ2)-mediated induction and function of IFN-γ-mediated differentiation in tumor cells. We found that monocytes from cancer patients had lower capability to induce functional IFN-γ secretion by the autologous CD16 mAb-treated NK cells in comparison to those from healthy individuals. In addition, when patient monocytes were cultured with NK cells from healthy individuals, they had lower capability to induce functional IFN-γ secretion by the NK cells when compared to those from autologous monocyte/NK cultures from healthy individuals. Activation by sAJ2 or addition of monocytes from healthy individuals to patient NK cells increased the secretion of functional IFN-γ by the NK cells and elevated its functional capability to differentiate tumors. Monocytes from cancer patients were found to express lower CD16 receptors, providing a potential mechanism for their lack of ability to trigger secretion of functional IFN-γ. In addition to in vitro studies, we also conducted in vivo studies in which cancer patients were given oral supplementation of AJ2 and the function of NK cells were studied. Oral ingestion of AJ2 improved the secretion of IFN-γ by patient derived NK cells and resulted in the better functioning of NK cells in cancer patients. Thus, our studies indicate that for successful NK cell immunotherapy, not only the defect in NK cells but also those in monocytes should be corrected. In this regard, AJ2 probiotic bacteria may serve to provide a potential adjunct treatment strategy.
Research Status of Graphene Polyurethane Composite Coating
Authors: Fang Zhou , Huang Lijin , Fu Junjie
Published: February 2022

Graphene material has a variety of excellent properties and applications in energy storage, biomaterials, photoelectric devices, and other fields. With the progress of nanotechnology, graphene nanomaterials have shown their advantages in the field of new nano-corrosion coatings with their high barrier structure. In addition, polyurethane is also widely used in the field of anti-corrosion coatings due to its excellent chemical resistance, mechanical properties, and weathering resistance. The preparation of composite coatings by combining graphene nanomaterials with traditional polyurethane (PU) coatings has opened up a new way for the research and development of new anticorrotic coatings. In this paper, graphene polyurethane composite coating was first used as the research object, and the mechanism of graphene material in the new composite coating was analyzed. Then, graphene oxide (GO), a commonly used precursor material, was used as an entry point for a detailed study of the properties of GO materials and the advantages and disadvantages of its application in composites, and two types of modifications, covalent and non-covalent, were analyzed. In addition, the preparation methods and processes of graphene polyurethane composite coatings were summarized. Finally, the future research directions and research focus of GO were prospected.
Healthcare Disparities and Outcomes of Cancer Patients in a Community Setting from a COVID-19 Epicenter
Authors: Jones Brianna M. , Lehrer Eric J. , Saraf Anurag , Shafaee Zahra , Resende Salgado Lucas , Osborn Virginia W.
Published: February 2022

There have been numerous studies demonstrating how cancer patients are at an increased risk of mortality. Within New York City, our community hospital emerged as an epicenter of the first wave of the pandemic in the spring of 2020 and serves a unique population that is predominately uninsured, of a lower income, and racially/ethnically diverse. In this single institution retrospective study, the authors seek to investigate COVID-19 diagnosis, severity and mortality in patients with an active cancer diagnosis. Demographic, clinical characteristics, treatment, SARS-CoV-2 laboratory results, and outcomes were evaluated. In our community hospital during the first wave of the COVID-19 pandemic in the United States, patients with active cancer diagnosis appear to be at increased risk for mortality (30%) and severe events (50%) due to the SARS-CoV-2 infection compared to the general population. A higher proportion of active cancer patients with Medicaid insurance, Hispanic ethnicity, other race, and male sex had complications and death from COVID-19 infection. The pandemic has highlighted the health inequities that exist in vulnerable patient populations and underserved communities such as ours.
Treatment Access, Health Economics, and the Wave of a Magic Wand
Authors: Stewart David J. , Bradford John-Peter , Batist Gerald
Published: February 2022

New drugs are expensive, in part due to excessive drug development costs. Governments are trying to reduce drug prices. This can delay access to effective agents. A country’s access to new drugs correlates with prices they agree to pay. After Health Canada approves a drug, the Canadian Agency for Drug and Technologies in Health (CADTH) assesses it. CADTH’s approval is usually contingent on it costing ≤CAD 50,000 per quality adjusted life year (QALY) gained. This value (unchanged from the 1970s) is inappropriately low. An inflation-adjusted CAD 50,000 1975 QALY should translate into a CAD 250,000 2021 QALY. CADTH’s target also does not consider that drug development costs have risen much faster than inflation or that new precision therapies may only be used in small populations. In a separate process, proposals from the Patented Medicines Price Review Board (PMPRB) would decrease initial Canadian drug prices by 20%, but prices would fall further as sales increased, with ultimate price reductions of up to 80%. PMPRB claims its proposal would not reduce drug access, but multiple analyses strongly suggest otherwise. Government price controls target the symptom (high prices), not the disease. They translate into shortages without solving the problem. CADTH and PMPRB approaches both threaten access to effective drugs.
Biomarkers during COVID-19: Mechanisms of Change and Implications for Patient Outcomes
Authors: Chen Cheng-Han , Lin Sheng-Wen , Shen Ching-Fen , Hsieh Kai-Sheng , Cheng Chao-Min
Published: February 2022

As the COVID-19 (Coronavirus disease 19) pandemic spreads worldwide, the massive numbers of COVID-19 patients have created a considerable healthcare burden for every country. The clinical spectrum of SARS-CoV-2 infection is broad, ranging from asymptomatic to mild, moderate, severe, and critical. Most COVID-19 patients present with no or mild symptoms, but nearly one-fifth of all patients develop severe or life-threatening complications. In addition to localized respiratory manifestations, severe COVID-19 cases also show extra-pulmonary complications or induce multiorgan failure. Identifying, triaging, and treating patients at risk early is essential and urgent. This article reviews the potential prognostic value of various biomarkers at different clinical spectrum stages of COVID-19 infection and includes information on fundamental prognostic mechanisms as well as potential clinical implications. Biomarkers are measurable biochemical substances used to recognize and indicate disease severity or response to therapeutic interventions. The information they provide is objective and suitable for delivering healthcare providers with a means of stratifying disease state in COVID-19 patients. This, in turn, can be used to help select and guide intervention efforts as well as gauge the efficacy of therapeutic approaches. Here, we review a number of potential biomarkers that may be used to guide treatment, monitor treatment efficacy, and form individualized therapeutic guidance based on patient response. Implementation of the COVID-19 biomarkers discussed here may lead to significantly improved quality of care and patient outcomes for those infected with SARS-CoV-2 worldwide.
Evaluation of a Whole-Liver Dixon-Based MRI Approach for Quantification of Liver Fat in Patients with Type 2 Diabetes Treated with Two Isocaloric Different Diets
Authors: Brancato Valentina , Della Pepa Giuseppe , Bozzetto Lutgarda , Vitale Marilena , Annuzzi Giovanni , Basso Luca , Cavaliere Carlo , Salvatore Marco , Rivellese Angela Albarosa , Monti Serena
Published: February 2022

Dixon-based methods for the detection of fatty liver have the advantage of being non-invasive, easy to perform and analyze, and to provide a whole-liver coverage during the acquisition. The aim of the study was to assess the feasibility of a whole-liver Dixon-based approach for liver fat quantification in type 2 diabetes (T2D) patients who underwent two different isocaloric dietary treatments: a diet rich in monosaturated fatty acids (MUFA) and a multifactorial diet. Thirty-nine T2D patients were randomly assigned to MUFA diet (n = 21) and multifactorial diet (n = 18). The mean values of the proton density fat fraction (PDFF) over the whole liver and over the ROI corresponding to that chosen for MRS were compared to MRS-PDFF using Spearman’s correlation (ρ). Before–after changes in percentage of liver volume corresponding to MRI-PDFF above thresholds associated with hepatic steatosis (LV%TH, with TH = 5.56%, 7.97% and 8.8%) were considered to assess the proposed approach and compared between diets using Wilcoxon rank-sum test. Statistical significance set at p < 0.05. A strong linear relationship was found between MRS-PDFF and MRI-PDFFs (ρ = 0.85, p < 0.0001). Changes in LV%TH% were significantly higher (p < 0.05) in the multifactorial diet than in MUFA diet (25% vs. 9%, 35% vs. 12%, and 38% vs. 13% decrease, respectively, for TH = 5.56%, 7.97%, and 8.8%) and this was reproducible compared to results obtained using the standard liver fat analysis. A volumetric approach based on Dixon method could be an effective, non-invasive technique that could be used for the quantitative analysis of hepatic steatosis in T2D patients.
Analysis of the Osseointegration Process of Dental Implants by Electron Paramagnetic Resonance: An In Vivo Study
Authors: Kalinnikova Elena , Sadovnikova Margarita , Rodionov Alexander , Murzakhanov Fadis , Grishin Peter
Published: February 2022

This research work presents an analysis of the process of an implant’s osseointegration to the jawbone tissue. The purpose of this work was to describe the processes of assimilation and the biochemical dynamics which occur during dental implantation using implants with different macro-microstructure surfaces at the level of stable free radicals using the electron paramagnetic resonance (EPR) method. The experimental investigation was conducted on seven Vietnamese minipigs over twelve months old and weighing up to 30 kg using implants with various macro-microstructure surfaces (SLA, RBM, and HSTTM) and implantation systems, namely the Adin, Sunran, Biomed, and Osstem systems. The integration of the implant into the bone triggered biochemical processes with the formation of stable free radicals. The EPR method was used to identify the formed paramagnetic species and to study the dynamics of the interaction between the surface of the implant and the bone after one and two months. The concentration of carbonate surface centers increased with the time that the implant was connected to the hard tissue. The “Sunran” and “HSTTM” were established as the most suitable implantation system and surface type, respectively, thanks to the highest rate of osseointegration (assimilation) with the bone (hard) tissue. Thus, the EPR method provides the opportunity to study implantation processes.
Quality Control of Cell Lines Using DNA as Target
Authors: Carrillo-Ávila José Antonio , Catalina Purificación , Aguilar-Quesada Rocío
Published: February 2022

Cell lines are a widely used pre-clinical models for biomedical research. The accessibility and the relative simplicity of facilities necessary for the use of cell lines, along with the large number of potential applications, encourage many researchers to choose this model. However, the access to cell lines from a non-confident source or through the interlaboratory exchange results in uncontrollable cell lines of uncertain quality. Furthermore, the possibility of using cell lines as an endless resource through multiple passages can contribute to this uncontrolled scenario, the main consequence of which is the lack of reproducibility between the research results. Different initiatives have emerged to promote the best practices regarding the use of cell lines and minimize the effect on the scientific results reported, including comprehensive quality control in the frame of Good Cell Culture Practice (GCCP). Cell Banks, research infrastructures for the professional distribution of biological material of high and known quality and origin, are committed with these initiatives. Many of the quality controls used to test different attributes of cell lines are based on DNA. This review describes quality control protocols of cell lines whose target molecule is DNA, and details the scope or purpose and their corresponding functionality.
Frequency, Informativity and Word Length: Insights from Typologically Diverse Corpora
Authors: Levshina Natalia
Published: February 2022

Zipf’s law of abbreviation, which posits a negative correlation between word frequency and length, is one of the most famous and robust cross-linguistic generalizations. At the same time, it has been shown that contextual informativity (average surprisal given previous context) is more strongly correlated with word length, although this tendency is not observed consistently, depending on several methodological choices. The present study examines a more diverse sample of languages than the previous studies (Arabic, Finnish, Hungarian, Indonesian, Russian, Spanish and Turkish). I use large web-based corpora from the Leipzig Corpora Collection to estimate word lengths in UTF-8 characters and in phonemes (for some of the languages), as well as word frequency, informativity given previous word and informativity given next word, applying different methods of bigrams processing. The results show different correlations between word length and the corpus-based measure for different languages. I argue that these differences can be explained by the properties of noun phrases in a language, most importantly, by the order of heads and modifiers and their relative morphological complexity, as well as by orthographic conventions.
The Impact of COVID-19 on Airfares—A Machine Learning Counterfactual Analysis
Authors: Wozny Florian
Published: February 2022

This paper studies the performance of machine learning predictions for the counterfactual analysis of air transport. It is motivated by the dynamic and universally regulated international air transport market, where ex post policy evaluations usually lack counterfactual control scenarios. As an empirical example, this paper studies the impact of the COVID-19 pandemic on airfares in 2020 as the difference between predicted and actual airfares. Airfares are important from a policy makers’ perspective, as air transport is crucial for mobility. From a methodological point of view, airfares are also of particular interest given their dynamic character, which makes them challenging for prediction. This paper adopts a novel multi-step prediction technique with walk-forward validation to increase the transparency of the model’s predictive quality. For the analysis, the universe of worldwide airline bookings is combined with detailed airline information. The results show that machine learning with walk-forward validation is powerful for the counterfactual analysis of airfares.
Parents as Nomads: Journeys, In-Betweenness and Identity
Authors: Twomey Miriam
Published: February 2022

When considering the parent voice as an individual subjective reality, it is observed as unique to the parent and not shared by others. This research sought to explore if parent voices could constitute intersubjective realities; inviting narratives from parents and professionals that may reveal a shared existence. The first theme explored the journeys of the parent as a nomad in their search for services to support their children. The second theme describes the position of the parent during the period of their child’s assessment, diagnosis and intervention, as that of ‘in-betweenness’. The third theme describes parents’ experiences as those of journeys, during which their identities change. Qualitative, in-depth, longitudinal case studies were undertaken with parents of young children with ASD and professionals over eighteen months. Semi-structured interviews (n-83) were conducted. Autoethnography was critical as a methodological tenet in defense of a position that states that research is an extension of our lives. The findings of this research show evidence of parental isolation and marginalization when procuring services for their children or when children failed to experience inclusion. This research suggests that nomads navigate (difficult) ways of forming new multiple selves and identities.
On the Treatment and Diagnosis of Attention Deficit Hyperactivity Disorder with EEG Assistance
Authors: Freismuth David , TaheriNejad Nima
Published: February 2022

Attention deficit hyperactivity disorder (ADHD) is a mental disorder most notable in children. The disease may affect the ability to focus and cause a physical and mental restlessness and risky behavior. Recommended treatment consists of stimulant administration and behavioral therapy. However, medicating children is problematic since there are indications that brain development is affected by ADHD medication agents. Therefore, behavioral therapy is the preferred approach in ADHD treatment for children. In order to monitor and optimize the success of such behavioral therapies, neuro-feedback methods can be used. The most notable technology used in such methods is Electroencephalography (EEG). In this article, an overview of the pathology of ADHD, EEG and its usage as a diagnostic and therapeutic tool in the context of ADHD is given. Based on that knowledge, novel EEG measurement modes, new development principles, and system on chip implementations are presented and discussed.
Design of Ultra-Low Voltage/Power Circuits and Systems
Authors: Lanuzza Marco , De Rose Raffaele , Strangio Sebastiano
Published: February 2022

Over the last years, the Internet of Things (IoT), wireless sensor networks and the emergence of other energy-constrained applications have pushed the demand for low-cost systems-on-chip solutions, entailing tight area and small power/voltage budgets [...]