bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Spectrin in Endocytosis
Authors: Li Donghai
Published: August 2022

Cytoskeletal spectrin is found in (non)erythroid cells. Eukaryotic endocytosis takes place for internalizing cargos from extracellular milieu. The role of spectrin in endocytosis still remains poorly understood. Here, I summarize current knowledge of spectrin function, spectrin-based cytoskeleton and endocytosis of erythrocytes, and highlight how spectrin contributes to endocytosis and working models in different types of cells. From an evolutionary viewpoint, I discuss spectrin and endocytosis in a range of organisms, particularly in plants and yeast where spectrin is absent. Together, the role of spectrin in endocytosis is related to its post-translational modification, movement/rearrangement, elimination (by proteases) and meshwork fencing.
Pharmacological Activation of Potassium Channel Kv11.1 with NS1643 Attenuates Triple Negative Breast Cancer Cell Migration by Promoting the Dephosphorylation of Caveolin-1
Authors: Jiang Ying , Senyuk Vitalyi , Ma Ke , Chen Hui , Qin Xiang , Li Shun , Liu Yiyao , Gentile Saverio , Minshall Richard D.
Published: August 2022

The prevention of metastasis is a central goal of cancer therapy. Caveolin-1 (Cav-1) is a structural membrane and scaffolding protein shown to be a key regulator of late-stage breast cancer metastasis. However, therapeutic strategies targeting Cav-1 are still lacking. Here, we demonstrate that the pharmacological activation of potassium channel Kv11.1, which is uniquely expressed in MDA-MB-231 triple negative breast cancer cells (TNBCs) but not in normal MCF-10A cells, induces the dephosphorylation of Cav-1 Tyr-14 by promoting the Ca2+-dependent stimulation of protein tyrosine phosphatase 1B (PTP1B). Consequently, the dephosphorylation of Cav-1 resulted in its disassociation from β-catenin, which enabled the accumulation of β-catenin at cell borders, where it facilitated the formation of cell–cell adhesion complexes via interactions with R-cadherin and desmosomal proteins. Kv11.1 activation-dependent Cav-1 dephosphorylation induced with NS1643 also reduced cell migration and invasion, consistent with its ability to regulate focal adhesion dynamics. Thus, this study sheds light on a novel pharmacological mechanism of promoting Cav-1 dephosphorylation, which may prove to be effective at reducing metastasis and promoting contact inhibition.
LL-37, a Multi-Faceted Amphipathic Peptide Involved in NETosis
Authors: Radic Marko , Muller Sylviane
Published: August 2022

Innate immunity responds to infections and inflammatory stimuli through a carefully choreographed set of interactions between cells, stimuli and their specific receptors. Of particular importance are endogenous peptides, which assume roles as defensins or alarmins, growth factors or wound repair inducers. LL-37, a proteolytic fragment of cathelicidin, fulfills the roles of a defensin by inserting into the membranes of bacterial pathogens, functions as alarmin in stimulating chemotaxis of innate immune cells, and alters the structure and efficacy of various cytokines. Here, we draw attention to the direct effect of LL-37 on neutrophils and the release of extracellular traps (NETs), as NETs have been established as mediators of immune defense against pathogens but also as important contributors to chronic disease and tissue pathogenesis. We propose a specific structural basis for LL-37 function, in part by highlighting the structural flexibility of LL-37 and its ability to adapt to distinct microenvironments and interacting counterparts.
The Protective Action of Metformin against Pro-Inflammatory Cytokine-Induced Human Islet Cell Damage and the Mechanisms Involved
Authors: Giusti Laura , Tesi Marta , Ciregia Federica , Marselli Lorella , Zallocco Lorenzo , Suleiman Mara , De Luca Carmela , Del Guerra Silvia , Zuccarini Mariachiara , Trerotola Marco , Eizirik Decio L. , Cnop Miriam , Mazzoni Maria R. , Marchetti Piero , Lucacchini Antonio , Ronci Maurizio
Published: August 2022

Metformin, a drug widely used in type 2 diabetes (T2D), has been shown to protect human β-cells exposed to gluco- and/or lipotoxic conditions and those in islets from T2D donors. We assessed whether metformin could relieve the human β-cell stress induced by pro-inflammatory cytokines (which mediate β-cells damage in type 1 diabetes, T1D) and investigated the underlying mechanisms using shotgun proteomics. Human islets were exposed to 50 U/mL interleukin-1β plus 1000 U/mL interferon-γ for 48 h, with or without 2.4 µg/mL metformin. Glucose-stimulated insulin secretion (GSIS) and caspase 3/7 activity were studied, and a shotgun label free proteomics analysis was performed. Metformin prevented the reduction of GSIS and the activation of caspase 3/7 induced by cytokines. Proteomics analysis identified more than 3000 proteins in human islets. Cytokines alone altered the expression of 244 proteins (145 up- and 99 down-regulated), while, in the presence of metformin, cytokine-exposure modified the expression of 231 proteins (128 up- and 103 downregulated). Among the proteins inversely regulated in the two conditions, we found proteins involved in vesicle motility, defense against oxidative stress (including peroxiredoxins), metabolism, protein synthesis, glycolysis and its regulation, and cytoskeletal proteins. Metformin inhibited pathways linked to inflammation, immune reactions, mammalian target of rapamycin (mTOR) signaling, and cell senescence. Some of the changes were confirmed by Western blot. Therefore, metformin prevented part of the deleterious actions of pro-inflammatory cytokines in human β-cells, which was accompanied by islet proteome modifications. This suggests that metformin, besides use in T2D, might be considered for β-cell protection in other types of diabetes, possibly including early T1D.
Psychosocial Factors and Sociodemographic Characteristics Associated with Suicidality Risk in Chilean Adolescents
Authors: Zulic-Agramunt Christianne Milena , Guzmán-Guzmán Iris Paola , Delgado-Floody Pedro , Saavedra Monserrat Belén Cerda , De La Fuente Patricio Gutierrez , Solano Mario Meza , Berrios Claudia Sagredo , Testor Carles Pérez
Published: August 2022

Background: Suicidality in adolescents is a growing concern and is currently a public health issue in Chile and the world. Objective: To determine the association between the risk of suicidality with self-harm, sociodemographic parameters (that is, gender and type of school), psychosocial variables, and social and family support in Chilean adolescents. Methods: In a cross-sectional study, 829 (377, 45.5% girls) children/adolescents between 10 and 19 years of age participated. Suicidality, self-esteem, health-related quality of life (HRQoL), and social support perception were evaluated by standard, validated questionnaires. The presence of self-harm, dating violence, and family dysfunction was also evaluated through a self-report survey. Results: Suicidality risk was related to low self-esteem (OR = 9.73; 95%; CI = 6.62–14.28; p < 0.001), low HRQoL (OR = 5.0; 95%; CI = 3.51–7.13; p < 0.001), low social support (OR; 3.38, 95%; CI; 2.48–4.6; p < 0.001), and self-harm (OR = 8.03; 95%; CI = 5.69–11.33; p < 0.001). In family terms, suicidality risk was associated with exposure to physical (OR = 2.47, 95%CI; 1.69–3.6; p < 0.001) and psychological (OR = 1.78, 95; 1.33–2.39; p < 0.001) aggression between parents, and with considering their family dysfunctional (OR = 2.41 95%; CI = 1.69–3.41; p < 0.001). Finally, suicidality was associated with feeling mistreated by a boyfriend/girlfriend (OR = 2.18; 95% CI = 1.19–3.98; p = 0.011). Conclusion: Suicidality was associated with self-harm, low social, psychological and family well-being, and/or feeling mistreated by a boyfriend/girlfriend.
Prevalence and Manifestations of Dental Ankylosis in Primary Molars Using Panoramic X-rays: A Cross-Sectional Study
Authors: Eşian Daniela , Bica Cristina , Stoica Oana , Dako Timea , Vlasa Alexandru , Bud Eugen , Salcudean Denisa , Beresescu Liana
Published: August 2022

Dental ankylosis is a serious condition defined as the process that causes the fusion between the dentin or the cementum of the root and the alveolar bone, with the obliteration of the periodontal ligament becoming progressively replaced by bone tissue. The aim of the study was to determine the prevalence, location, severity, and association of dental ankylosis in primary molars with other dental anomalies such as the agenesis of permanent buds. For this study 150 panoramic x-rays were selected from patients with temporary or mixed dentition, aged six to twelve years old, from a private dentistry office and from the Pediatric Dentistry Department of UMFST in Targu-Mures, Romania. In order to identify the cases with dental ankylosis, the presence and severity of the infraocclusion, displacements of the neighboring teeth, the appearance of the root area, and the relationship with the bone tissue were examined. For evaluation of the categorical data we used Fischer’s exact test and the Chi-squared test and the chosen significance level was set at 0.05. The results showed that the highest percentage of cases with ankylosis was found in the first group (six to nine years old), respectively, with 72% of cases compared with the second group (ten to twelve years old) with 28% of cases. Findings showed that there was no positive association between dental ankylosis and gender, but a strong correlation was found regarding the location on the dental arches. Most cases were identified on the lower arch with a higher percentage in quadrant three. Of the two primary molars, the most affected by ankylosis was the first molar in quadrant three, followed by the second molar, and finally the first molar in quadrant four. Most cases diagnosed with ankylosis had a mild to moderate degree of infraocclusion; therefore, changes in the functional balance of the dental arch and on neighboring teeth were insignificant. There were some differences obtained between our results and studies from the literature, especially regarding the localization in the lower left dental arch, but these differences can be attributed to the number of the subjects selected and from the methodology of dental ankylosis diagnosis. Based on the data obtained, it was concluded that ankylosis is a dental condition which occurs in children in early mixed dentition, especially in the lower arch, with the first primary molar being the most affected tooth. The presence of infraocclusion and the absence of dental mobility, especially during the stage of primary molars’ root resorption, are the main signs which must be followed to make an early diagnosis and prevent further complications.
Design, Optimization and Cutting Performance Evaluation of an Internal Spray Cooling Turning Tool
Authors: Liu Leping , Shu Shengrong , Li Huimin , Chen Xuan
Published: August 2022

The traditional flood cooling method applied in the internal turning process has disadvantages, such as having a low cooling efficiency and being environmentally unfriendly. In the present work, an internal spray cooling turning tool was designed, and the performance was numerically and experimentally accessed. The heat transfer simulation model of the internal spray cooling turning tool was established by ANSYS Fluent, and the tool cooling structure parameters were optimized by the Taguchi method based on the CFD simulations, and obtains the diameters of the upper and lower nozzles of 3 mm and 1.5 mm, respectively; the distance between the upper nozzle and the tool tip of 18.5 mm. To evaluate the cutting and cooling performance of the optimized tool, internal turning experiments were conducted on QT500-7 workpieces. Results show that the optimized tool with internal spray cooling led to lower workpiece surface roughness and chip curling, compared to the conventional tools.
An Analysis of Mobility Influence in Optoelectronics Parameters in an InGaN/GaN Blue LED
Authors: Zarate-Galvez Sarai , Garcia-Barrientos Abel , Ambrosio-Lazaro Roberto , Garcia-Ramirez Mario , Stevens-Navarro Enrique , Plaza-Castillo Jairo , Hoyo-Montaño Jose , Perez-Cortes Obed
Published: August 2022

Simulations on mobility influence in optoelectronics parameters from an InGaN/GaN blue LED using the Nextnano++ software arepresented in this paper. These simulations were performed by changing the hole and electron mobility value for the material compounds according to experimental, theoretical, and doping-concentration data already reported in the literature. The power law mobility is used for the current calculation in the quantum drift-diffusion model. The results indicate the lower hole and electron leakage currents correspond to the lowest mobility values for the InGaN alloy, the greatest amount of recombination occurs in the extreme wells within the active layer of the LED and the stable emission is at 3.6 V with peak wavelength λ^LED=456.7 nm and full width at half maximum FWHM~11.1 nm for the three mobilities. Although experimental and theoretical mobility values reach higher carrier density and recombination, the photon emission is broader and unstable. Additionally, the doping-concentration mobility results in lower wavelength shifts and narrows FWHM, making it more stable. The highest quantum efficiency achieved by doping-concentration mobility is only in the breakdown voltage (ηdop−max=60.43%), which is the IQE value comparable to similar LEDs and is more useful for these kinds of semiconductor devices.
The Mechanism of PEDOT: PSS Films with Organic Additives
Authors: Lien Shui-Yang , Lin Po-Chen , Chen Wen-Ray , Liu Chuan-Hsi , Lee Kuan-Wei , Wang Na-Fu , Huang Chien-Jung
Published: August 2022

This article demonstrates changes in the structures of poly (3,4-ethylene dioxythiophene): polystyrene sulfonate (PEDOT: PSS) with the addition of organic additives. The mechanisms of PEDOT: PSS are analyzed using X-ray photoelectron spectroscopy (XPS), cross-sectional images obtained from scanning electron microscopy (SEM), and contact angles. In this paper, a bond-breaking reaction and phase separation are successfully found to occur between PEDOT: PSS molecules and the organic additives. Our research also finds that this bond-breaking reaction and phase separation exist in the PEDOT: PSS–sorbitol–maltitol film at the same time. The addition of organic additives will improve the optical properties and the moisture stability of PEDOT: PSS films.
Integrated Approaches to Identify miRNA Biomarkers Associated with Cognitive Dysfunction in Multiple Sclerosis Using Text Mining, Gene Expression, Pathways, and GWAS
Authors: Prabahar Archana , Raja Kalpana
Published: August 2022

Multiple sclerosis (MS), a chronic autoimmune disorder, affects the central nervous system of many young adults. More than half of MS patients develop cognition problems. Although several genomic and transcriptomic studies are currently reported in MS cognitive impairment, a comprehensive repository dealing with all the experimental data is still underdeveloped. In this study, we combined text mining, gene regulation, pathway analysis, and genome-wide association studies (GWAS) to identify miRNA biomarkers to explore the cognitive dysfunction in MS, and to understand the genomic etiology of the disease. We first identified the dysregulated miRNAs associated with MS and cognitive dysfunction using PubTator (text mining), HMDD (experimental associations), miR2Disease, and PhenomiR database (differentially expressed miRNAs). Our results suggest that miRNAs such as hsa-mir-148b-3p, hsa-mir-7b-5p, and hsa-mir-7a-5p are commonly associated with MS and cognitive dysfunction. Next, we retrieved GWAS signals from GWAS Catalog, and analyzed the enrichment analysis of association signals in genes/miRNAs and their association networks. Then, we identified susceptible genetic loci, rs17119 (chromosome 6; p = 1 × 10−10), rs1843938 (chromosome 7; p = 1 × 10−10), and rs11637611 (chromosome 15; p = 1.00 × 10−15), associated with significant genetic risk. Lastly, we conducted a pathway analysis for the susceptible genetic variants and identified novel risk pathways. The ECM receptor signaling pathway (p = 3.98 × 10−8) and PI3K/Akt signaling pathway (p = 5.98 × 10−5) were found to be associated with differentially expressed miRNA biomarkers.
Comparison of Multiple Radiomics Models for Identifying Histological Grade of Pancreatic Ductal Adenocarcinoma Preoperatively Based on Multiphasic Contrast-Enhanced Computed Tomography: A Two-Center Study in Southwest China
Authors: Liao Hongfan , Li Yongmei , Yang Yaying , Liu Huan , Zhang Jiao , Liang Hongwei , Yan Gaowu , Liu Yanbing
Published: August 2022

Background: We designed and validated the value of multiple radiomics models for diagnosing histological grade of pancreatic ductal adenocarcinoma (PDAC), holding a promise of assisting in precision medicine and providing clinical therapeutic strategies. Methods: 198 PDAC patients receiving surgical resection and pathological confirmation were enrolled and classified as 117 low-grade PDAC and 81 high-grade PDAC group. An external validation group was used to assess models’ performance. Available radiomics features were selected using GBDT algorithm on the basis of the arterial and venous phases, respectively. Five different machine learning models were built including k-nearest neighbour, logistic regression, naive bayes model, support vector machine, and random forest using ten times tenfold cross-validation. Multivariable logistic regression analysis was applied to establish clinical model and combined model. The models’ performance was assessed according to its predictive performance, calibration curves, and decision curves. A nomogram was established for visualization. Survival analysis was conducted for stratifying the overall survival prior to treatment. Results: In the training group, the RF model demonstrated the optimal predictive ability and robustness with an AUC of 0.943; the SVM model achieved the secondary performance, followed by Bayes model. In the external validation group, these three models (Bayes, RF, SVM) also achieved the top three predictive ability. A clinical model was built by selected clinical features with an AUC of 0.728, and combined model was established by an RF model and a clinical model with an AUC of 0.961. The log-rank test revealed that the low-grade group survived longer than the high-grade group. Conclusions: The multiphasic CECT radiomics models offered an accurate and noninvasive perspective to differentiate histological grade in PDAC and advantages of machine learning models including RF, SVM and Bayes were more remarkable.
‘Sweet Acid’ An Interpretative Phenomenological Analysis of Students’ Navigating Regenerative Higher Education
Authors: van den Berg Bas , Poldner Kim A. , Sjoer Ellen , Wals Arjen E. J.
Published: August 2022

Regenerative forms of higher education are emerging, and required, to connect with some of the grand transition challenges of our times. This paper explores the lived experience of 21 students learning to navigate a regenerative form of higher education in the Mission Impact course at The Hague University of Applied Sciences. This semester-length course ran for two iterations with the intention of connecting the students with local transitions towards a more circular society, one where products are lasting and have multiple lives when they are shared, refurbished, or become a source for a new product. At the end of each iteration, the students reflected on their experience using the Living Spiral Framework, which served as basis for an interpretative phenomenological analysis of their journey navigating this transformative course. The results of this study include four themes; (1) Opting in—Choosing RHE, (2) Learning in Regenerative Ways, (3) Navigating Resistance(s), and (4) Transformative Impacts of RHE. These themes can be used by practitioners to design and engage with regenerative forms of higher education, and by scholars to guide further inquiry.
Communicating and Collaborating with Others through Digital Competence: A Self-Perception Study Based on Teacher Trainees’ Gender
Authors: Rodríguez-García Antonio-Manuel , Cardoso-Pulido Manuel-Jesús , De la Cruz-Campos Juan-Carlos , Martínez-Heredia Nazaret
Published: August 2022

Digital competence in teaching can be understood as the set of skills, attitudes and abilities to use technologies critically and creatively, both in the personal and professional environment. Likewise, it is one of the eight key competencies for lifelong learning. In this paper, in line with the Common Digital Competence Framework (DigComp), we analyze the self-perception of teacher trainees’ digital competence to communicate and collaborate with other people. Additionally, we state the existence of statistically significant differences from a gender perspective (women/men). In this sense, we have carried out non-experimental quantitative research that has a descriptive nature. To this end, we used a questionnaire as an instrument for collecting information, with a total sample of 698 pre-service teachers in Andalusia (Spain). The results show that teacher trainees have an intermediate level in terms of their abilities to communicate and collaborate with other people through digital technologies. At the same time, significant differences are highlighted regarding participants’ gender, which implies that gender can still be considered a limitation in the use of ICTs, thereby decreasing participants’ digital competence. Finally, this study sheds light on the need to improve future teachers’ digital competence.
Hardware-in-the-Loop Simulations: A Historical Overview of Engineering Challenges
Authors: Mihalič Franc , Truntič Mitja , Hren Alenka
Published: August 2022

The design of modern industrial products is further improved through the hardware-in-the-loop (HIL) simulation. Realistic simulation is enabled by the closed loop between the hardware under test (HUT) and real-time simulation. Such a system involves a field programmable gate array (FPGA) and digital signal processor (DSP). An HIL model can bypass serious damage to the real object, reduce debugging cost, and, finally, reduce the comprehensive effort during the testing. This paper provides a historical overview of HIL simulations through different engineering challenges, i.e., within automotive, power electronics systems, and different industrial drives. Various platforms, such as National Instruments, dSPACE, Typhoon HIL, or MATLAB Simulink Real-Time toolboxes and Speedgoat hardware systems, offer a powerful tool for efficient and successful investigations in different fields. Therefore, HIL simulation practice must begin already during the university’s education process to prepare the students for professional engagements in the industry, which was also verified experimentally at the end of the paper.
Development and Space-Qualification of a Miniaturized CubeSat’s 2-W EDFA for Space Laser Communications
Authors: Carrasco-Casado Alberto , Shiratama Koichi , Kolev Dimitar , Trinh Phuc V. , Ishola Femi , Fuse Tetsuharu , Toyoshima Morio
Published: August 2022

The Japanese National Institute of Information and Communications Technology (NICT) is currently developing a high-performance laser-communication terminal for CubeSats aimed at providing a high-datarate communication solution for LEO satellites requiring transmission of large volumes of data from orbit. A key aspect of the communication system is a high-power optical amplifier capable of providing enough gain to the transmitted signals to be able to close the link on its counterpart’s receiver with the smallest impact in terms of energy and power on the CubeSat’s platform. This manuscript describes the development of a miniaturized 2-W space-grade 2-stage erbium-doped fiber amplifier (EDFA) compatible with the CubeSat form factor, showing the best power-to-size ratio for a space-qualified EDFA to the best of the authors’ knowledge. Performance results under realistic conditions as well as full space qualification and test are presented, proving that this module can support short-duration LEO-ground downlinks as well as long-duration intersatellite links.
A Combination of Novel Nucleic Acid Cross-Linking Dye and Recombinase-Aided Amplification for the Rapid Detection of Viable Salmonella in Milk
Authors: Feng Xiaoyan , Zhou Donggen , Gan Bei , Xie Guoyang , Xu Hengyi
Published: August 2022

Salmonella, as an important foodborne pathogen, can cause various diseases, such as severe enteritis. In recent years, various types of nucleicacid-intercalating dyes have been utilized to detect viable Salmonella. However, in principle, the performance of existing nucleic acid dyes is limited because they depend on the integrity of cell membrane. Herein, based on the metabolic activity of bacteria, a novel DNA dye called thiazole orange monoazide (TOMA) was introduced to block the DNA from dead bacteria. Recombinase-aided amplification (RAA) was then performed to detect viable Salmonella in samples. In this study, the permeability of TOMA to the cell membrane of Salmonella was evaluated via confocal laser scanning microscopy and fluorescence emission spectrometry. The limit of detection (LOD) of the TOMA–RAA method was 2.0 × 104 CFU/mL in pure culture. The feasibility of the TOMA–RAA method in detecting Salmonella was assessed in spiked milk. The LOD for Salmonella was 3.5 × 102 CFU/mL after 3 h of enrichment and 3.5 × 100 CFU/mL after 5 h of enrichment. The proposed TOMA–RAA assay has great potential to be applied to accurately detect and monitor foodborne pathogens in milk and its byproducts.
Encapsulation of Mesona chinensis Benth Extract in Alginate Beads Enhances the Stability and Antioxidant Activity of Polyphenols under Simulated Gastrointestinal Digestion
Authors: Wongverawattanakul Chonnipa , Suklaew Phim on , Chusak Charoonsri , Adisakwattana Sirichai , Thilavech Thavaree
Published: August 2022

The aim of this study was to investigate the stability and antioxidant activity of the polyphenols from Mesona chinensis Benth extract (MCE) and its alginate-based encapsulation by extrusion technique during simulated gastrointestinal digestion. The encapsulation efficacy ranged from 41.1 ± 4.7 to 56.7 ± 3.4% with different concentrations of MCE (50–75% v/v), sodium alginate (1.2–1.8% w/v), and CaCl2 solution (3–5% w/v). The optimal condition for MCE-loaded alginate beads (MCB) was composed of 75% MCE, 1.5% alginate, and 3% CaCl2 solution, which provided the highest encapsulation efficiency with a spherical structure and a mean particle diameter of 1516.67 ± 40.96 μm. Fourier transform infrared spectroscopy (FT-IR) reported no chemical interaction between alginate and MCE. The release of total phenolic content (TPC) was only 8.9% after placing MCB in water for 4 h. After simulated digestion, changes in TPC and ferric reducing antioxidant power (FRAP) of MCE significantly decreased by 25.0% and 29.7%, respectively. Interestingly, the incorporation of MCB significantly increased TPC and FRAP in the digesta compared to those of MCE during gastrointestinal tract conditions. The findings suggest that the encapsulation of MCE with alginate as a carrier helps to improve the bioaccessibility and biological activity of M. chinensis polyphenols.
Two Ascophyllum nodosum Fucoidans with Different Molecular Weights Inhibit Inflammation via Blocking of TLR/NF-κB Signaling Pathway Discriminately
Authors: Wang Lilong , Wang Linlin , Yan Chunhong , Ai Chunqing , Wen Chengrong , Guo Xiaoming , Song Shuang
Published: August 2022

The present study aimed to clarify the potential mechanism of fucoidans found in Ascophyllum nodosum on anti-inflammation and to further explore the relationship between their structures and anti-inflammation. Two novel fucoidans named ANP-6 and ANP-7 and found in A. nodosum, were separated and purified and their structures were elucidated by HPGPC, HPLC, GC-MS, FT-IR, NMR, and by the Congo red test. They both possessed a backbone constructed of →2)-α-L-Fucp4S-(1→, →3)-α-L-Fucp2S4S-(1→, →6)-β-D-Galp-(1→, and →3,6)-β-D-Galp4S-(1→ with branches of →2)-α-L-Fucp4S-(1→ and →3)-β-D-Galp-(1→. Moreover, ANP-6 and ANP-7 could prevent the inflammation of the LPS-stimulated macrophages by suppressing the NO production and by regulating the expressions of iNOS, COX-2, TNF-α, IL-1β, IL-6, and IL-10. Their inhibitory effects on the TLR-2 and TLR-4 levels suggest that they inhibit the inflammation process via the blocking of the TLR/NF-κB signal transduction. In addition, ANP-6, with a molecular weight (63.2 kDa), exhibited stronger anti-inflammatory capabilities than ANP-7 (124.5 kDa), thereby indicating that the molecular weight has an influence on the anti-inflammatory effects of fucoidans.
An 11-Year Analysis of Bacterial Foodborne Disease Outbreaks in Zhejiang Province, China
Authors: Chen Lili , Wang Jikai , Zhang Ronghua , Zhang Hexiang , Qi Xiaojuan , He Yue , Chen Jiang
Published: August 2022

Background: Foodborne diseases are a growing public health problem and contribute significantly to the global burden of disease and mortality. Bacteria are the most common foodborne pathogens. We aimed to explore characteristics of bacterial foodborne disease outbreaks (FBDOs) in Zhejiang Province and to provide data support for foodborne disease prevention and control. Methods: Descriptive statistical methods were used to analyze the data reported by centers for disease control (CDCs) at all levels in Zhejiang Province through Foodborne Disease Outbreaks Surveillance System (FDOSS) during 2010–2020. Results: CDCs in Zhejiang Province reported 517 bacterial FBDOs in 11 years, resulting in 7031 cases, 911 hospitalizations, and 3 deaths. Vibrio parahaemolyticus had the highest number of outbreaks, accounting for 58.41% of the total bacterial outbreaks, followed by Salmonella (18.38%). In all settings, restaurants (37.14%), staff canteens (11.99%), and households (11.80%) were responsible for the large number of outbreaks. Aquatic products (42.08%), meat and meat products (23.56%), cereals (10.81%), and flour products (9.27%) were the most common single foods reported. Further analysis showed that the settings and food vehicles of outbreaks caused by different pathogens were different. Conclusions: Bacterial outbreaks are the most common type of FBDOs in Zhejiang Province. By analyzing the epidemiological characteristics of common pathogenic bacteria, we can identify the etiology, food, and setting that the government needs to focus on, and issue relevant targeted policies to reduce the number of FBDOs.
Hepatosplenic T-Cell Lymphoma Mimicking Acute Onset of Cholestatic Hepatitis in a Young Immunocompetent Man: A Case Report
Authors: Metelli Flavio , Solimando Riccardo , Alemanni Luigina Vanessa , Gafà Roberta , Marasco Giovanni
Published: August 2022

We herein report a case of hepatosplenic T-cell lymphoma (HSTCL) incidentally found in a 30-year-old man who came to the emergency department after an ankle trauma. At admission, laboratory tests revealed abnormal liver enzymes and pancytopenia, and imaging showed mild hepatosplenomegaly. During hospitalization, the patient’s clinical condition worsened rapidly, with a concomitant increase in cholestatic enzymes, severe jaundice, and the worsening of pancytopenia. Causes of liver injury, including many infectious diseases, were explored until the diagnosis of HSTCL was made by liver and bone marrow biopsies. Subsequently, the patient underwent six cycles of chemotherapy with a CHOP (cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone or prednisolone) regimen and one with Hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone) but, despite this aggressive treatment, died due to disease progression 2 months after diagnosis. This rare disease should be considered in the diagnostic workup of acute cholestatic hepatitis presenting with concomitant hepatosplenomegaly and cytopenia.
Dextrin-Based Nanohydrogels for Rokitamycin Prolonged Topical Delivery
Authors: Tannous Maria , Lucia Appleton Silvia , Hoti Gjylije , Caldera Fabrizio , Argenziano Monica , Monfared Yousef Khazaei , Matencio Adrián , Trotta Francesco , Cavalli Roberta
Published: August 2022

Macrolides are widely used antibiotics with a broad spectrum of activity. The development of drug carriers to deliver this type of antibiotics has attracted much research. The present study aims at developing new swellable dextrin-based nanohydrogels for the topical delivery of rokitamycin, as model macrolide. Rokitamycin is a synthetic analogous of macrolides with advantageous characteristics as far as bacterial uptake and post-antibiotic effect are concerned. It is also indicated for the treatment of severe infections caused by Acanthamoeba and for topical infections. The nanohydrogels have been prepared from two types of cross-linked polymers obtained by using β-cyclodextrin or Linecaps® was provided by the Roquette Italia SPA (Cassano Spinola, Al, Italy) as building blocks. The cross-linked polymers have been then formulated into aqueous nanosuspensions refined and tuned to achieve the incorporation of the drug. Cross-linked β-cyclodextrin (β-CD) and Linecaps® (LC) polymers formed dextrin-based nanohydrogels with high swelling degree and mucoadhesion capability. Rokitamycin was loaded into the nanohydrogels displaying an average size around 200 nm with negative surface charge. In vitro kinetic profiles of free and loaded drug in nanohydrogels were compared at two pH levels. Interestingly, a sustained and controlled release was obtained at skin pH level due to the high degree of swelling and a pH responsiveness possibly. The results collected suggest that these nanohydrogels are promising for the delivery of rokitamycin and may pave the way for the topical delivery of other macrolide antibiotics.
Prediction of Alzheimer’s Disease by a Novel Image-Based Representation of Gene Expression
Authors: Kalkan Habil , Akkaya Umit Murat , Inal-Gültekin Güldal , Sanchez-Perez Ana Maria
Published: August 2022

Early intervention can delay the progress of Alzheimer’s Disease (AD), but currently, there are no effective prediction tools. The goal of this study is to generate a reliable artificial intelligence (AI) model capable of detecting the high risk of AD, based on gene expression arrays from blood samples. To that end, a novel image-formation method is proposed to transform single-dimension gene expressions into a discriminative 2-dimensional (2D) image to use convolutional neural networks (CNNs) for classification. Three publicly available datasets were pooled, and a total of 11,618 common genes’ expression values were obtained. The genes were then categorized for their discriminating power using the Fisher distance (AD vs. control (CTL)) and mapped to a 2D image by linear discriminant analysis (LDA). Then, a six-layer CNN model with 292,493 parameters were used for classification. An accuracy of 0.842 and an area under curve (AUC) of 0.875 were achieved for the AD vs. CTL classification. The proposed method obtained higher accuracy and AUC compared with other reported methods. The conversion to 2D in CNN offers a unique advantage for improving accuracy and can be easily transferred to the clinic to drastically improve AD (or any disease) early detection.
Prediction of the Effects of Missense Mutations on Human Myeloperoxidase Protein Stability Using In Silico Saturation Mutagenesis
Authors: Sobitan Adebiyi , Edwards William , Jalal Md Shah , Kolawole Ayanfeoluwa , Ullah Hemayet , Duttaroy Atanu , Li Jiang , Teng Shaolei
Published: August 2022

Myeloperoxidase (MPO) is a heme peroxidase with microbicidal properties. MPO plays a role in the host’s innate immunity by producing reactive oxygen species inside the cell against foreign organisms. However, there is little functional evidence linking missense mutations to human diseases. We utilized in silico saturation mutagenesis to generate and analyze the effects of 10,811 potential missense mutations on MPO stability. Our results showed that ~71% of the potential missense mutations destabilize MPO, and ~8% stabilize the MPO protein. We showed that G402W, G402Y, G361W, G402F, and G655Y would have the highest destabilizing effect on MPO. Meanwhile, D264L, G501M, D264H, D264M, and G501L have the highest stabilization effect on the MPO protein. Our computational tool prediction showed the destabilizing effects in 13 out of 14 MPO missense mutations that cause diseases in humans. We also analyzed putative post-translational modification (PTM) sites on the MPO protein and mapped the PTM sites to disease-associated missense mutations for further analysis. Our analysis showed that R327H associated with frontotemporal dementia and R548W causing generalized pustular psoriasis are near these PTM sites. Our results will aid further research into MPO as a biomarker for human complex diseases and a candidate for drug target discovery.
A Novel Intragenic Duplication in the HDAC8 Gene Underlying a Case of Cornelia de Lange Syndrome
Authors: Lucia-Campos Cristina , Valenzuela Irene , Latorre-Pellicer Ana , Ros-Pardo David , Gil-Salvador Marta , Arnedo María , Puisac Beatriz , Castells Neus , Plaja Alberto , Tenes Anna , Cuscó Ivon , Trujillano Laura , Ramos Feliciano J. , Tizzano Eduardo F. , Gómez-Puertas Paulino , Pié Juan
Published: August 2022

Cornelia de Lange syndrome (CdLS) is a multisystemic genetic disorder characterized by distinctive facial features, growth retardation, and intellectual disability, as well as various systemic conditions. It is caused by genetic variants in genes related to the cohesin complex. Single-nucleotide variations are the best-known genetic cause of CdLS; however, copy number variants (CNVs) clearly underlie a substantial proportion of cases of the syndrome. The NIPBL gene was thought to be the locus within which clinically relevant CNVs contributed to CdLS. However, in the last few years, pathogenic CNVs have been identified in other genes such as HDAC8, RAD21, and SMC1A. Here, we studied an affected girl presenting with a classic CdLS phenotype heterozygous for a de novo ~32 kbp intragenic duplication affecting exon 10 of HDAC8. Molecular analyses revealed an alteration in the physiological splicing that included a 96 bp insertion between exons 9 and 10 of the main transcript of HDAC8. The aberrant transcript was predicted to generate a truncated protein whose accessibility to the active center was restricted, showing reduced ease of substrate entry into the mutated enzyme. Lastly, we conclude that the duplication is responsible for the patient’s phenotype, highlighting the contribution of CNVs as a molecular cause underlying CdLS.
Chronic Kidney Disease in a Large National Human Immunodeficiency Virus Treatment Program
Authors: Paengsai Ninutcha , Noppakun Kajohnsak , Jourdain Gonzague , Cressey Tim Roy , Salvadori Nicolas , Chaiwarith Romanee , Tantraworasin Apichat , Mary Jean Yves , Bowonwatanuwong Chureeratana , Bhakeecheep Sorakij , Traisathit Patrinee , Kosachunhanun Natapong
Published: August 2022

Tenofovir disoproxil fumarate (TDF) is associated with a risk of chronic kidney disease (CKD), especially in Asian populations. Data from the Thai national health insurance system was used to assess CKD incidence in patients receiving antiretroviral therapy in real-world practice. We analyzed data from patients who initiated one of the following first-line regimens: zidovudine + lamivudine + nevirapine (AZT + 3TC + NVP); zidovudine + lamivudine + efavirenz (AZT + 3TC + EFV); tenofovir + lamivudine + nevirapine (TDF + 3TC + NVP); tenofovir + lamivudine/emtricitabine + efavirenz (TDF + 3TC/FTC + EFV); and tenofovir +lamivudine +lopinavir/ritonavir (TDF + 3TC + LPV/r). CKD was defined as glomerular filtration rate <60 mL/min/1.73 m2 for >3 months, or a confirmed 2010 WHO diagnosis (ICD-10 code N183, N184, or N185). Death competing risk survival regression models were used. Among 27,313 participants, with a median age of 36.8 years and median follow-up of 2.3 years, 245 patients (0.9%) were diagnosed with CKD (incidence 3.2 per 1000 patient-years; 95% CI 2.8–3.6). Compared with patients receiving AZT + 3TC + NVP, the risk of CKD measured by adjusted sub-distribution hazard ratio (aSHR) was 6.5 (95% CI 3.9–11.1) in patients on TDF + 3TC + LPV/r, 3.8 (95% CI 2.3–6.0) in TDF + 3TC + NVP, and 1.6 (95% CI 1.2–2.3) in TDF + 3TC/FTC + EFV. Among patients receiving TDF, compared with those receiving TDF + 3TC/FTC + EFV, the aSHR was 4.0 (95% CI 2.3–6.8) in TDF + 3TC + LPV/r and 2.3 (95% CI 1.4–3.6) in TDF + 3TC + NVP. TDF was associated with an increased risk of CKD, especially when combined with LPV/r or NVP.
Analyzing Factors Associated with the Behavior-Change Stage of Colorectal Cancer Screening
Authors: Lee Jisun
Published: August 2022

This study attempted to identify the stages of colorectal cancer screening (CRCS) behavior change by applying the precaution adoption process model (PAPM) and to examine the factors affecting each stage. A quantitative, descriptive, cross-sectional design was used. A total of 305 workers at one of the largest industrial complexes in South Korea were allocated using convenience sampling. Data were analyzed using independent t-test, one way ANOVA and multi-nominal logistic regression using SPSS 25.0 (SPSS Inc., Chicago, IL, USA). Most of the subjects were in the undecided-to-act stage. The factors affecting each stage were gender, marital status, family history, private insurance subscription, perceived barrier, and self-efficacy. It is critical to select a target group considering the behavioral change stage to establish a strategy for improving the CRCS rate. Developing and implementing a CRCS education program in consideration of the behavioral change stage will be a strategy to increase the examination of effectiveness of CRCS.
Nutrient Content with Different Fertilizer Management and Influence on Yield and Fruit Quality in Apple cv. Gala
Authors: Mota Mariana , Martins Maria João , Policarpo Gonçalo , Sprey Layanne , Pastaneira Mafalda , Almeida Patrícia , Maurício Anabela , Rosa Cristina , Faria João , Martins Miguel B. , de Sousa Miguel L. , Santos Ricardo , de Sousa Rui M. , da Silva Anabela B. , Ribeiro Henrique , Oliveira Cristina M.
Published: August 2022

Assessing a plant’s nutritional status and fertilizer rates and types that can optimize fruit quality and yield are critical in intensive apple orchards. The aim of this work was to identify correlations between nutrients in the different organs that allow the early diagnosis of the nutritional status and to assess the impact on the optimal nutrient content in apple leaves, as well as in the yield and quality of chemical and organic fertilization. Five orchards of ‘Gala’ were fertilized with different levels of NPK over a period of four years. Macro and micronutrients of buds, flowers, 45 and 90–110 days after full bloom (DAFB) leaves and 60 DAFB and 15 days before harvest (DBH) fruits were determined. Boron was the only element for which strong correlations, 0.7 < r < 0.9, were observed between all organ pairs. The fertilization treatments did not affect the nutrient concentrations in the leaves of 90–110 DAFB other than P, Ca and Mg and did not affect the macronutrients in the fruit. In one of the five orchards, the yield increased by 26% with double fertilization compared to standard fertilization and, for the other four orchards, the impact depended on the year. Fruit size was more related to crop load than to fertilization and TSS and firmness were not affected by the type or amount of fertilizers. Replacing part of the chemical fertilizer with organic materials did not affect productivity or fruit quality.
Organizational Justice and Health: A Survey in Hospital Workers
Authors: Magnavita Nicola , Chiorri Carlo , Acquadro Maran Daniela , Garbarino Sergio , Di Prinzio Reparata , Gasbarri Martina , Matera Carmela , Cerrina Anna , Gabriele Maddalena , Labella Marcella
Published: August 2022

In complex systems such as hospitals, work organization can influence the level of occupational stress and, consequently, the physical and mental health of workers. Hospital healthcare workers were asked to complete a questionnaire during their regular occupational health examination, in order to assess the perceived level of organizational justice, and to verify whether it was associated with occupational stress, mental health, and absenteeism. The questionnaire included the Colquitt Organizational Justice (OJ) Scale, the Karasek/Theorell demand-control-support (DCS) questionnaire for occupational stress, and the General Health Questionnaire (GHQ12) for mental health. Workers were also required to indicate whether they had been absent because of back pain in the past year. Organizational justice was a significant predictor of occupational stress. Stress was a mediator in the relationship between justice and mental health. Occupational stress was more closely related to perceptions of lack of distributive justice than to perceptions of procedural, informational, and interpersonal justice. Physicians perceived significantly less distributive justice than other workers. In adjusted univariate logistic regression models, the perceptions of organizational justice were associated with a significant reduction in the risk of sick leave for back pain (OR 0.96; CI95% 0.94–0.99; p < 0.001), whereas occupational stress was associated with an increased risk of sick leave (OR 6.73; CI95% 2.02–22.40; p < 0.002). Work organization is a strong predictor of occupational stress and of mental and physical health among hospital employees.
Anabasine and Anatabine Exposure Attributable to Cigarette Smoking: National Health and Nutrition Examination Survey (NHANES) 2013–2014
Authors: Bendik Patrick B. , Rutt Sharyn M. , Pine Brittany N. , Sosnoff Connie S. , Blount Benjamin C. , Zhu Wanzhe , Feng June , Wang Lanqing
Published: August 2022

Anabasine and anatabine are minor alkaloids in tobacco products and are precursors for tobacco-specific nitrosamines (TSNAs). The levels of these two compounds have been used to differentiate tobacco product sources, monitor compliance with smoking cessation programs, and for biomonitoring in TSNA-related studies. The concentrations of urinary anabasine and anatabine were measured in a representative sample of U.S. adults who smoked cigarettes (N = 770) during the 2013–2014 National Health and Nutrition Examination Survey (NHANES) study cycle, which was the first cycle where urinary anabasine and anatabine data became available. Weighted geometric means (GM) and geometric least squares means (LSM) with 95% confidence intervals were calculated for urinary anabasine and anatabine categorized by tobacco-use status [cigarettes per day (CPD) and smoking frequency] and demographic characteristics. Smoking ≥20 CPD was associated with 3.6× higher anabasine GM and 4.8× higher anatabine GM compared with smoking <10 CPD. Compared with non-daily smoking, daily smoking was associated with higher GMs for urinary anabasine (1.41 ng/mL vs. 6.28 ng/mL) and anatabine (1.62 ng/mL vs. 9.24 ng/mL). Urinary anabasine and anatabine concentrations exceeded the 2 ng/mL cut point in 86% and 91% of urine samples from people who smoke (PWS) daily, respectively; in comparison, 100% of them had serum cotinine concentrations greater than the established 10 ng/mL cut point. We compared these minor tobacco alkaloid levels to those of serum cotinine to assess their suitability as indicators of recent tobacco use at established cut points and found that their optimal cut point values would be lower than the established values. This is the first time that anabasine and anatabine are reported for urine collected from a U.S. population-representative sample of NHANES study participants, providing a snapshot of exposure levels for adults who smoked during 2013–2014. The results of this study serve as an initial reference point for future analysis of NHANES cycles, where changes in the national level of urinary anabasine and anatabine can be monitored among people who smoke to show the effect of changes in tobacco policy.