bluuebunny/crossref_metadata_2025 huggingface dataset:
Living With a Stigmatized Identity; Perceptions of Disclosure, Coping, and Medication Adherence Among Adolescent Boys and Young Men in Chiredzi-Zimbabwe
Authors: Kanyemba Roselyn , Govender Kaymarlin , Jimu Christopher
Published: December 2021

There is limited research on adolescent boys and young men (ABYM)'s initial and onward HIV seropositive status disclosure, coping strategies and treatment adherence journeys especially in Zimbabwe. This qualitative exploratory study employed in-depth individual interviews at Chiredzi General Hospital in Zimbabwe to explore the dynamics of disclosure, coping and treatment adherence among ABYM. Twenty-one HIV positive ABYM with ages ranging from 14 to 21 were recruited from their scheduled visit to collect medication at the hospital. Findings indicate that ABYM disclosure journeys began with shock, confusion or misunderstanding and ended in a positive life outlook. Treatment adherence among ABYM was very poor due to poverty, erratic food supply, feeling sick after taking medication, forgetfulness and the public nature of medication collection centers. The study concluded that ABYM maintained secrecy in order to be accepted by their peers but also to protect themselves from stigma and isolation.
ESBL Producing Escherichia coli in Faecal Sludge Treatment Plants: An Invisible Threat to Public Health in Rohingya Camps, Cox's Bazar, Bangladesh
Authors: Hossain Md. Sakib , Ali Sobur , Hossain Monir , Uddin Salman Zahir , Moniruzzaman M. , Islam Mohammad Rafiqul , Shohael Abdullah Mohammad , Islam Md. Shafiqul , Ananya Tazrina Habib , Rahman Md. Mominur , Rahman Mohammad Ashfaqur , Worth Martin , Mondal Dinesh , Mahmud Zahid Hayat
Published: December 2021

Introduction: Human faecal sludge contains diverse harmful microorganisms, making it hazardous to the environment and public health if it is discharged untreated. Faecal sludge is one of the major sources of E. coli that can produce extended-spectrum β-lactamases (ESBLs).

Objective: This study aimed to investigate the prevalence and molecular characterization of ESBL-producing E. coli in faecal sludge samples collected from faecal sludge treatment plants (FSTPs) in Rohingya camps, Bangladesh.

Methods: ESBL producing E. coli were screened by cultural as well as molecular methods and further characterized for their major ESBL genes, plasmid profiles, pathotypes, antibiotic resistance patterns, conjugation ability, and genetic similarity.

Results: Of 296 isolates, 180 were phenotypically positive for ESBL. All the isolates, except one, contained at least one ESBL gene that was tested (blaCTX−M−1, blaCTX−M−2, blaCTX−M−8, blaCTX−M−9, blaCTX−M−15, blaCTX−M−25, blaTEM, and blaSHV). From plasmid profiling, it was observed that plasmids of 1–211 MDa were found in 84% (151/180) of the isolates. Besides, 13% (24/180) of the isolates possessed diarrhoeagenic virulence genes. From the remaining isolates, around 51% (79/156) harbored at least one virulence gene that is associated with the extraintestinal pathogenicity of E. coli. Moreover, 4% (3/156) of the isolates were detected to be potential extraintestinal pathogenic E. coli (ExPEC) strains. Additionally, all the diarrhoeagenic and ExPEC strains showed resistance to three or more antibiotic groups which indicate their multidrug-resistant potential. ERIC-PCR differentiated these pathogenic isolates into seven clusters. In addition to this, 16 out of 35 tested isolates transferred plasmids of 32–112 MDa to E. coli J53 recipient strain.

Conclusion: The present study implies that the faecal sludge samples examined here could be a potential origin for spreading MDR pathogenic ESBL-producing E. coli. The exposure of Rohingya individuals, living in overcrowded camps, to these organisms poses a severe threat to their health.
A Systematic Review to Guide Future Efforts in the Determination of Genetic Causes of Pregnancy Loss
Authors: Carey Andrew Z. , Blue Nathan R. , Varner Michael W. , Page Jessica M. , Chaiyakunapruk Nathorn , Quinlan Aaron R. , Branch D. Ware , Silver Robert M. , Workalemahu Tsegaselassie
Published: December 2021

Background: Pregnancy loss is the most common obstetric complication occurring in almost 30% of conceptions overall and in 12–14% of clinically recognized pregnancies. Pregnancy loss has strong genetic underpinnings, and despite this consensus, our understanding of its genetic causes remains limited. We conducted a systematic review of genetic factors in pregnancy loss to identify strategies to guide future research.

Methods: To synthesize data from population-based association studies on genetics of pregnancy loss, we searched PubMed for relevant articles published between 01/01/2000-01/01/2020. We excluded review articles, case studies, studies with limited sample sizes to detect associations (N < 4), descriptive studies, commentaries, and studies with non-genetic etiologies. Studies were classified based on developmental periods in gestation to synthesize data across various developmental epochs.

Results: Our search yielded 580 potential titles with 107 (18%) eligible after title/abstract review. Of these, 54 (50%) were selected for systematic review after full-text review. These studies examined either early pregnancy loss (n = 9 [17%]), pregnancy loss >20 weeks' gestation (n = 10 [18%]), recurrent pregnancy loss (n = 32 [59%]), unclassified pregnancy loss (n = 3 [4%]) as their primary outcomes. Multiple genetic pathways that are essential for embryonic/fetal survival as well as human development were identified.

Conclusion: Several genetic pathways may play a role in pregnancy loss across developmental periods in gestation. Systematic evaluation of pregnancy loss across developmental epochs, utilizing whole genome sequencing in families may further elucidate causal genetic mechanisms and identify other pathways critical for embryonic/fetal survival.
Performance of Urochloa and Megathyrsus Forage Grasses in Smallholder Farms in Western Kenya
Authors: Mwendia Solomon Waweru , Odhiambo Ruth , Juma Alfred , Mwangi David , Notenbaert An
Published: December 2021

Livestock productivity has remained low in sub-Saharan African countries compared to other places on the globe. The feeding component is the major limitation, in both quantity and quality. Among other inputs, feeding takes 55–70% of the costs involved. Livestock play a major role especially in smallholder mixed farms through provision of household nutrition and income through milk and meat. Equally, fertilization of cropland benefits from livestock manure, and livestock often act as insurance and savings by providing liquidity for unforeseen and urgent financial needs. Increasing livestock productivity would enhance the fore-mentioned benefits contributing to well-being and livelihoods. Toward this endeavor and with smallholder dairy farmers' participation, we undertook an evaluation of 10 selected forages from Urochloa Syn. Brachiaria and Megathyrsus syn. Panicum genus and compared them with Napier grass, i.e., Cenchrus purpureus Syn. Pennisetum purpureum commonly grown by farmers. For detailed and robust evaluation, we established the species in eight trial sites spread in four administrative counties in Western Kenya (Bungoma, Busia, Kakamega, and Siaya). In each site, the forages were established in plots in a randomized complete block design, replicated three times. Each site was linked to a group of farmers interested in dairy. For 2 years, dry matter production, plant height, and leaf-to-stem ratio was determined across all sites. Further, we guided farmers to generate participatory forage evaluation criteria, which they later administered across their respective forage demonstration sites individually on plot-by-plot basis to generate preference rating compared to what they normally grow—Napier grass. The results showed significant differences across the forage types within and between the sites. Cumulative dry matter yields ranged 13.7–49.9 t/ha over 10 harvestings across forage types and the counties, while values for crude protein were 1.85–6.23 t/ha and 110,222–375,988 MJ/ha for metabolizable energy. Farmer preferences emerged that highlighted forages with likely better chances of adoption with weighed scores ranging 5.5–7.6 against a scale of 1–9, across the counties. The observations provide additional and well-performing forage options for the farmers and possibly in similar production systems and ecologies. Awareness creation targeting livestock and dairy producers would be key, reaching, and informing them on alternative forage options, with potential to increase livestock productivity.
Auranofin and ICG-001 Emerge Synergistic Anti-tumor Effect on Canine Breast Cancer by Inducing Apoptosis via Mitochondrial Pathway
Authors: Lin Zhaoyan , Lin Zixiang , Zhao Ying , Cheng Nan , Zhang Di , Lin Jiahao , Zhang Hong , Lin Degui
Published: December 2021

Canine breast cancer (CBC) is the most common spontaneous tumor in intact female dogs, especially in developing countries. The effective anti-tumor agents or therapies for the clinical treatment of CBC are still in need. Auranofin (AF) is a gold complex that has been attested by FDA for treating human rheumatism, which has been found as a great anti-tumor agent in recent years. ICG-001 is a small molecule inhibitor of Wnt/β-catenin pathway. In the present study, we demonstrated that a combination of AF and ICG-001 could synergistically suppress the proliferation of CBC in vitro and in vivo. Moreover, the synergistical effect was related with apoptosis caused by mitochondrial damage and ROS production. In conclusion, combination of AF and ICG-001 could synergistically suppress the growth of CBC in vitro and in vivo by leading apoptosis via mitochondrial signaling pathway and might provide a novel potential choice for the clinical treatment of CBC.
Comparing Hip Dysplasia in Dogs and Humans: A Review
Authors: Willemsen Koen , Möring Michelle M. , Harlianto Netanja I. , Tryfonidou Marianna A. , van der Wal Bart C. H. , Weinans Harrie , Meij Björn P. , Sakkers Ralph J. B.
Published: December 2021

Hip dysplasia (HD) is common in both humans and dogs. This interconnection is because humans and dogs descended from a common ancestor and therefore have a similar anatomy at micro- and macroscopic levels. Furthermore, dogs are the animals of choice for testing new treatments for human hip dysplasia and orthopedic surgery in general. However, little literature exists comparing HD between the two species. Therefore, the aim of this review is to describe the anatomy, etiology, pathogenesis, diagnostics, and treatment of HD in humans and dogs. HD as an orthopedic condition has many common characteristics in terms of etiology and pathogenesis and most of the differences can be explained by the evolutionary differences between dogs and humans. Likewise, the treatment of HD shows many commonalities between humans and dogs. Conservative treatment and surgical interventions such as femoral osteotomy, pelvic osteotomy and total hip arthroplasty are very similar between humans and dogs. Therefore, future integration of knowledge and experiences for HD between dogs and humans could be beneficial for both species.
Case Report: Primary Diffuse Leptomeningeal Oligodendrogliomatosis in a Young Adult Cat
Authors: Chludzinski Elisa , Puff Christina , Weber Jürgen , Hewicker-Trautwein Marion
Published: December 2021

A 2-year-old cat was presented with progressive ataxia. Despite treatment the animal died. Pathomorphological examination revealed a widespread leptomeningeal mass at all levels of the central nervous system accentuated on the cervical spinal cord and the medulla oblongata without presence of a primary intraaxial tumor. The neoplasm was mainly composed of round, uninucleate cells with hyperchromatic nuclei, which were immunopositive for OLIG2, doublecortin, MAP2, synaptophysin, and vimentin, indicating components of both oligodendroglial and neuronal differentiation. Ki-67 immunohistochemistry indicated a high proliferation activity of the neoplasm. Few GFAP positive and Iba-1 positive cells were interpreted as reactive astrocytes and macrophages or microglia, respectively. The tumor was immunonegative for CD3, CD20, PAX5, MUM1, pan-cytokeratin, S100, NSE, p75NTR, NeuN and periaxin. These findings led to the diagnosis of primary diffuse leptomeningeal oligodendrogliomatosis. This is the first reported case of this entity in a young cat, which should be considered as a differential diagnosis for diffuse subarachnoidal round cell infiltrates.
An Active Fault-Tolerant Control for Robotic Manipulators Using Adaptive Non-Singular Fast Terminal Sliding Mode Control and Disturbance Observer
Authors: Nguyen Van-Cuong , Le Phu-Nguyen , Kang Hee-Jun
Published: December 2021

In this study, a fault-tolerant control (FTC) tactic using a sliding mode controller–observer method for uncertain and faulty robotic manipulators is proposed. First, a finite-time disturbance observer (DO) is proposed based on the sliding mode observer to approximate the lumped uncertainties and faults (LUaF). The observer offers high precision, quick convergence, low chattering, and finite-time convergence estimating information. Then, the estimated signal is employed to construct an adaptive non-singular fast terminal sliding mode control law, in which an adaptive law is employed to approximate the switching gain. This estimation helps the controller automatically adapt to the LUaF. Consequently, the combination of the proposed controller–observer approach delivers better qualities such as increased position tracking accuracy, reducing chattering effect, providing finite-time convergence, and robustness against the effect of the LUaF. The Lyapunov theory is employed to illustrate the robotic system’s stability and finite-time convergence. Finally, simulations using a 2-DOF serial robotic manipulator verify the efficacy of the proposed method.
In Vitro Evaluation and Genome Mining of Bacillus subtilis Strain RS10 Reveals Its Biocontrol and Plant Growth-Promoting Potential
Authors: Iqbal Sajid , Ullah Nimat , Janjua Hussnain Ahmed
Published: December 2021

Recently, crop management has involved excessive use of chemical fertilizers and pesticides, compromising public health and environmental integrity. Rhizobacteria, which can enhance plant growth and protect plants from phytopathogen, are eco-friendly and have been attracting increasing attention. In the current study, Bacillus subtilis RS10 isolated from the rhizosphere region of Cynodon dactylon, inhibited the growth of indicator strains and exhibited in vitro plant growth-promoting traits. A whole-genome analysis identified numerous biosynthetic gene clusters encoding antibacterial and antifungal metabolites including bacillibactin, bogorol A, fengycin, bacteriocin, type III polyketides (PKs), and bacilysin. The plant growth-promoting conferring genes involved in nitrogen metabolism, phosphate solubilization, hydrogen sulfide, phytohormones, siderophore biosynthesis, chemotaxis and motility, plant root colonization, lytic enzymes, and biofilm formation were determined. Furthermore, genes associated with abiotic stresses such as high salinity and osmotic stress were identified. A comparative genome analysis indicated open pan-genome and the strain was identified as a novel sequence type (ST-176). In addition, several horizontal gene transfer events were found which putatively play a vital role in the evolution and new functionalities of a strain. In conclusion, the current study demonstrates the potential of RS10 antagonism against important pathogens and plant growth promotion, highlighting its application in sustainable agriculture.
Identification of Geographical Origin of Chinese Chestnuts Using Hyperspectral Imaging with 1D-CNN Algorithm
Authors: Li Xingpeng , Jiang Hongzhe , Jiang Xuesong , Shi Minghong
Published: December 2021

The adulteration in Chinese chestnuts affects the quality, taste, and brand value. The objective of this study was to explore the feasibility of the hyperspectral imaging (HSI) technique to determine the geographical origin of Chinese chestnuts. An HSI system in spectral range of 400–1000 nm was applied to identify a total of 417 Chinese chestnuts from three different geographical origins. Principal component analysis (PCA) was preliminarily used to investigate the differences of average spectra of the samples from different geographical origins. A deep-learning-based model (1D-CNN, one-dimensional convolutional neural network) was developed first, and then the model based on full spectra and optimal wavelengths were established for various machine learning methods, including partial least squares-discriminant analysis (PLS-DA) and particle swarm optimization-support vector machine (PSO-SVM). The optimal results based on full spectra for 1D-CNN, PLS-DA, and PSO-SVM models were 97.12%, 97.12%, and 95.68%, respectively. Competitive adaptive reweighted sampling (CARS) and a successive projections algorithm (SPA) were individually utilized for wavelengths selection, and the results of simplified models generally improved. The contrasting results demonstrated that the prediction accuracies of SPA-PLS-DA and 1D-CNN both reached 97.12%, but 1D-CNN presented a higher Kappa coefficient value than SPA-PLS-DA. Meanwhile, the sensitivities and specificities of SPA-PLS-DA and 1D-CNN models were both above 90% for the samples from each geographical origin. These results indicated that both SPA-PLS-DA and 1D-CNN models combined with HSI have great potential for the geographical origin identification of Chinese chestnuts.
Neuroprotective Effects of Black Pepper Cold-Pressed Oil on Scopolamine-Induced Oxidative Stress and Memory Impairment in Rats
Authors: Mostafa Nada M. , Mostafa Ahmed M. , Ashour Mohamed L. , Elhady Sameh S.
Published: December 2021

Oxidative stress is usually associated with many neurodegenerative diseases. In this study, the gas chromatography–mass spectrometry (GC–MS) analysis of cold-pressed oil (CPO) from black pepper (Piper nigrum) fruits was performed and its neuroprotective effects were evaluated for the first time. The analysis of CPO revealed the presence of the lignan sesamin (39.78%), the alkaloid piperine (33.79%), the monoterpene hydrocarbons 3-carene (9.53%) and limonene (6.23%), and the sesquiterpene β-caryophyllene (10.67%). Black pepper hydrodistilled oil (HDO) was also comparatively analyzed by GC–MS to show the impact of oil isolation by two different methodologies on their components and class of compounds identified. HDO analysis revealed 35 compounds (99.64% of the total peak areas) mainly composed of monoterpene hydrocarbons (77.28%), such as limonene (26.50%), sabinene (21.36%), and β-pinene (15.53%), and sesquiterpene hydrocarbons (20.59%) represented mainly by β-caryophyllene (19.12%). Due to the low yield obtained for HDO (0.01% v/w), only CPO was chosen for the evaluation of its neuroprotective potential. Alzheimer-type dementia was induced in rats by scopolamine intraperitoneal injection (1.5 mg/kg/day) for seven days. CPO was administered orally (100 mg/kg) for a week before scopolamine administration and then concomitantly for another week. Donepezil (1 mg/kg, orally) was used as a reference drug. CPO administration significantly improved the rat behaviors as evaluated by the Morris water maze test, evident from prolongation in time spent in the platform quadrant (262.9%, compared to scopolamine) and increasing in the crossing time by 18.18% compared to the control group. The rat behavior tested by passive avoidance, showed prolongation in the step-through latency compared to control. Moreover, CPO significantly (p < 0.05) ameliorated the activities of antioxidant enzymes such as catalase, superoxide dismutase (SOD) and reduced malondialdehyde (MDA) equivalents by 22.48%, 45.41%, and 86.61%, respectively, compared to scopolamine. Furthermore, CPO administration decreased scopolamine-induced elevated acetylcholinesterase levels in rats’ hippocampi by 51.30%. These results were supported by histopathological and in silico molecular docking studies. Black pepper oil may be a potential antioxidant and neuroprotective supplement.
AGEs and sRAGE Variations at Different Timepoints in Patients with Chronic Kidney Disease
Authors: Molinari Paolo , Caldiroli Lara , Dozio Elena , Rigolini Roberta , Giubbilini Paola , Romanelli Massimiliano M. Corsi , Messa Piergiorgio , Vettoretti Simone
Published: December 2021

Patients with chronic kidney disease (CKD) are affected by enhanced oxidative stress and chronic inflammation, and these factors may contribute to increase advanced glycation end-products (AGEs). In this study we quantified AGEs and soluble receptors for AGE (sRAGE) isoforms and evaluated the association between their variations and eGFR at baseline and after 12 months. We evaluated 64 patients. AGEs were quantified by fluorescence intensity using a fluorescence spectrophotometer, and sRAGE by ELISA. Median age was 81 years, male patients accounted for 70%, 63% were diabetic, and eGFR was 27 ± 10 mL/min/1.73 m2. At follow up, sRAGE isoforms underwent a significant decrement (1679 [1393;2038] vs. 1442 [1117;2102], p < 0.0001), while AGEs/sRAGE ratios were increased (1.77 ± 0.92 vs. 2.24 ± 1.34, p = 0.004). Although AGEs and AGEs/sRAGE ratios were inversely related with eGFR, their basal values as well their variations did not show a significant association with eGFR changes. In a cohort of patients with a stable clinical condition at 1 year follow-up, AGEs/sRAGE was associated with renal function. The lack of association with eGFR suggests that other factors can influence its increase. In conclusion, AGEs/sRAGE can be an additional risk factor for CKD progression over a longer time, but its role as a prognostic tool needs further investigation.
The Protective Effects of Carrageenan Oligosaccharides on Intestinal Oxidative Stress Damage of Female Drosophila melanogaster
Authors: Yang Kun , Li Qiaowei , Zhang Guocai , Ma Chao , Dai Xianjun
Published: December 2021

Carrageenan oligosaccharides (COS) have been reported to possess excellent antioxidant activities, but the underlying mechanism remains poorly understood. In this study, H2O2 was applied to trigger oxidative stress. The results showed that the addition of COS could effectively extend the lifespan of female Drosophila, which was associated with improvements by COS on the antioxidant defense system, including a decrease in MDA, the enhanced activities of SOD and CAT, the reduction of ROS in intestinal epithelial cells, and the up-regulation of antioxidant-relevant genes (GCL, GSTs, Nrf2, SOD). Meanwhile, the axenic female Drosophila fed with COS showed almost no improvement in the above measurements after H2O2 treatment, which highlighted the antioxidant mechanism of COS was closely related to intestinal microorganisms. Then, 16S rDNA high-throughput sequencing was applied and the result showed that the addition of COS in diets contributed to the diversity and abundance of intestinal flora in H2O2 induced female Drosophila. Moreover, COS significantly inhibited the expression of gene mTOR, elevated its downstream gene 4E-BP, and further inhibited autophagy-relevant genes (AMPKα, Atg1, Atg5, Atg8a) in H2O2 induced female Drosophila. The inhibition of the mTOR pathway and the activation of autophagy was probably mediated by the antioxidant effects of COS. These results provide potential evidence for further understanding of COS as an intestinal antioxidant.
SDBD Flexible Plasma Actuator with Ag-Ink Electrodes: Experimental Assessment
Authors: Papadimas Viktoras , Doudesis Christos , Svarnas Panagiotis , Papadopoulos Polycarpos K. , Vafakos George P. , Vafeas Panayiotis
Published: December 2021

In the present work, a single dielectric barrier discharge (SDBD)-based actuator is developed and experimentally tested by means of various diagnostic techniques. Flexible dielectric barriers and conductive paint electrodes are used, making the design concept applicable to surfaces of different aerodynamic profiles. A technical drawing of the actuator is given in detail. The plasma is sustained by audio frequency sinusoidal high voltage, while it is probed electrically and optically. The consumed electric power is measured, and the optical emission spectrum is recorded in the ultraviolet–near infrared (UV–NIR) range. High-resolution spectroscopy provides molecular rotational distributions, which are treated appropriately to evaluate the gas temperature. The plasma-induced flow field is spatiotemporally surveyed with pitot-like tube and schlieren imaging. Briefly, the actuator consumes a mean power less than 10 W and shows a fair stability over one day, the average temperature of the gas above its surface is close to 400 K, and the fluid speed rises to 4.5 m s−1. A long, thin layer (less than 1.5 mm) of laminar flow is unveiled on the actuator surface. This thin layer is interfaced with an outspread turbulent flow field, which occupies a centimeter-scale area. Molecular nitrogen-positive ions appear to be part of the charged heavy species in the generated filamentary discharge, which can transfer energy and momentum to the surrounding air molecules.
PERFORM: A Metric for Evaluating Autonomous System Performance in Marine Testbed Environments Using Interval Type-2 Fuzzy Logic
Authors: Dalpe Allisa J. , Thein May-Win L. , Renken Martin
Published: December 2021

Trust and confidence in autonomous behavior is required to send autonomous vehicles into operational missions. The authors introduce the Performance Evaluation and Review Framework Of Robotic Missions (PERFORM), a framework to enable a rigorous and replicable autonomy test environment, thereby filling the void between that of merely simulating autonomy and that of completing true field missions. A generic architecture for defining the missions under test is proposed and a unique Interval Type-2 Fuzzy Logic approach is used as the foundation for the mathematically rigorous autonomy evaluation framework. The test environment is designed to aid in (1) new technology development (i.e., providing direct comparisons and quantitative evaluations between autonomy algorithms), (2) the validation of the performance of specific autonomous platforms, and (3) the selection of the appropriate robotic platform(s) for a given mission type (e.g., for surveying, surveillance, search and rescue). Three case studies are presented to apply the metric to various test scenarios. Results demonstrate the flexibility of the technique with the ability to tailor tests to the user’s design requirements accounting for different priorities related to acceptable risks and goals of a given mission.
Peracetic Acid: A Practical Alternative to Formalin for Disinfection of Extracted Human Teeth
Authors: Ali Riaz , Bartholomew Justin , Coffey Randolph , Carrico Caroline , Kitten Todd , Madurantakam Parthasarathy
Published: December 2021

Extracted human teeth provide the closest approximation to teeth in situ and play important roles in dental education and materials research. Since extracted teeth are potentially infectious, the Centers for Disease Control recommend their sterilization by autoclaving or disinfection by formalin immersion to ensure safe handling. However, autoclaving is not recommended for teeth with amalgam fillings and formalin is hazardous. The goal of the present study was to investigate the potential of peracetic acid (PA) as an alternative method to achieve reliable disinfection of freshly extracted teeth. A total of 80 extracted teeth were collected for this study. Whole teeth were incubated in one of four solutions for defined periods of time: sterile water (2 weeks), formalin (2 weeks), PA 1000 ppm (2 weeks), and PA 2000 ppm (1 week). After sectioning, the crown and root fragments were transferred into separate tubes containing brain–heart infusion broth and incubated at 37 °C under anaerobic conditions for 72 h. Absence of broth turbidity was used to assess effectiveness of disinfection. No turbidity was observed in any of the formalin-treated or peracetic acid-treated samples, signifying complete disinfection. Our results indicate that PA can effectively disinfect extracted human teeth, providing a reliable alternative to formalin and autoclaving.
IFP35 Is a Relevant Factor in Innate Immunity, Multiple Sclerosis, and Other Chronic Inflammatory Diseases: A Review
Authors: De Masi Roberto , Orlando Stefania , Bagordo Francesco , Grassi Tiziana
Published: December 2021

Discovered in 1993 by Bange et al., the 35-kDa interferon-induced protein (IFP35) is a highly conserved cytosolic interferon-induced leucine zipper protein with a 17q12-21 coding gene and unknown function. Belonging to interferon stimulated genes (ISG), the IFP35 reflects the type I interferon (IFN) activity induced through the JAK-STAT phosphorylation, and it can homodimerize with N-myc-interactor (NMI) and basic leucine zipper transcription factor (BATF), resulting in nuclear translocation and a functional expression. Casein kinase 2-interacting protein-1 (CKIP-1), retinoic acid-inducible gene I (RIG-I), and laboratory of genetics and physiology 2 Epinephelus coioides (EcLGP2) are thought to regulate IFP35, via the innate immunity pathway. Several in vitro and in vivo studies on fish and mammals have confirmed the IFP35 as an ISG factor with antiviral and antiproliferative functions. However, in a mice model of sepsis, IFP35 was found working as a damage associated molecular pattern (DAMP) molecule, which enhances inflammation by acting in the innate immune-mediated way. In human pathology, the IFP35 expression level predicts disease outcome and response to therapy in Multiple Sclerosis (MS), reflecting IFN activity. Specifically, IFP35 was upregulated in Lupus Nephritis (LN), Rheumatoid Arthritis (RA), and untreated MS. However, it normalized in the MS patients undergoing therapy. The considered data indicate IFP35 as a pleiotropic factor, suggesting it as biologically relevant in the innate immunity, general pathology, and human demyelinating diseases of the central nervous system.
Therapeutic Effects of Fenofibrate Nano-Emulsion Eye Drops on Retinal Vascular Leakage and Neovascularization
Authors: Huang Li , Liang Wentao , Zhou Kelu , Wassel Ronald , Ridge Zachary , Ma Jian-Xing , Wang Bing
Published: December 2021

Macular edema caused by retinal vascular leakage and ocular neovascularization are the leading causes of severe vision loss in diabetic retinopathy (DR) and age-related macular degeneration (AMD) patients. Oral administration of fenofibrate, a PPARα agonist, has shown therapeutic effects on macular edema and retinal neovascularization in diabetic patients. To improve the drug delivery to the retina and its efficacy, we have developed a nano-emulsion-based fenofibrate eye drop formulation that delivered significantly higher amounts of the drug to the retina compared to the systemic administration, as measured by liquid chromatography–mass spectrometer (LC-MS). The fenofibrate eye drop decreased leukocytes adherent to retinal vasculature and attenuated overexpression of multiple inflammatory factors in the retina of very low-density lipoprotein receptor knockout (Vldlr−/−) mice, a model manifesting AMD phenotypes, and streptozotocin-induced diabetic rats. The fenofibrate eye drop also reduced retinal vascular leakage in these models. The laser-induced choroidal neovascularization was also alleviated by the fenofibrate eye drop. There were no detectable ocular toxicities associated with the fenofibrate eye drop treatment. These findings suggest that fenofibrate can be delivered efficiently to the retina through topical administration of the nano-emulsion eye drop, which has therapeutic potential for macular edema and neovascularization.
Antioxidative Properties of Baltic Sea Keystone Macroalgae (Fucus vesiculosus, Phaeophyceae) under Ocean Warming and Acidification in a Seasonally Varying Environment
Authors: Graiff Angelika , Karsten Ulf
Published: December 2021

The keystone macroalga Fucus vesiculosus (Phaeophyceae), dominating shallow hard bottom zones, encounters a strongly and rapidly changing environment due to anthropogenic change over the last decades in the Baltic Sea. Thus, in four successive benthic mesocosm experiments, the single and joint effects of increased temperature (Δ + 5 °C) and pCO2 (1100 ppm) under ambient irradiances were experimentally tested on the antioxidative properties of western Baltic F. vesiculosus in all seasons. The antioxidative properties (superoxide dismutase activity and lipid peroxidation) as well as the sensitivity of F. vesiculosus photosynthetic performance (i.e., effective quantum yield) to oxidative stress under these global change scenarios were seasonally examined. F. vesiculosus exhibited high and relatively constant photosynthetic performance under artificial hydrogen peroxide (H2O2) stress in all seasons. High activities of superoxide dismutase and a relatively low degree of the biomarker for lipid peroxidation (malondialdehyde concentration) were found in F. vesiculosus. Thus, Baltic F. vesiculosus is equipped with a high antioxidative potential to tolerate strong oxidative stress for at least short periods. Antioxidative properties of F. vesiculosus were more strongly affected by warming than by acidification, resulting in significantly increased malondialdehyde concentrations under elevated temperature levels in all seasons. Oxidative stress was enhanced in F. vesiculosus under warming but seem to be modulated by seasonally varying environmental conditions (e.g., high and low irradiances) and pCO2 levels. However, more frequent summer heatwaves reaching and surpassing lethal temperatures in shallow coastal waters may determine the F. vesiculosus population’s overall persistence in the Baltic Sea.
Zero-Fluoroscopy Cardiac Ablation: Technology Is Moving Forward in Complex Procedures—A Novel Workflow for Atrial Fibrillation
Authors: Bertini Matteo , Pompei Graziella , Tolomeo Paolo , Malagù Michele , Fiorio Alessio , Balla Cristina , Vitali Francesco , Rapezzi Claudio
Published: December 2021

Background and Rationale. A fluoroscopy-based approach to an electrophysiological procedure is widely validated and has been recognized as the gold standard for a long time. The use of fluoroscopy exposes both the healthcare staff and the patient to a non-negligible dose of radiation. To minimize the risks associated with the use of fluoroscopy, it would be reasonable to perform ablation procedures with zero fluoroscopy. This approach is widely used in simple ablation procedures, but not in complex procedures. In atrial fibrillation (AF) ablation procedures, fluoroscopy remains the main technology used, in particular to guide the transseptal puncture. Main results and Implications. We present a workflow to perform a complete zero-fluoroscopy ablation for AF ablation procedures using a 3D electro-anatomical mapping system, intracardiac echocardiography and a novel steerable guiding sheath that can be visualized on the mapping system. We present two cases, one with paroxysmal AF and the other one with persistent AF during which we applied this novel workflow achieving a successful pulmonary vein isolation without complications and complete zero-fluoroscopy exposure.
A System-Level Mechanism of Anmyungambi Decoction for Obesity: A Network Pharmacological Approach
Authors: Jang Dongyeop , Jeong Hayeong , Kim Chang-Eop , Leem Jungtae
Published: December 2021

Obesity is a low-grade systemic inflammatory disease involving adipocytokines. As though Anmyungambi decoction (AMGB) showed significant improvement on obesity in a clinical trial, the molecular mechanism of AMGB in obesity remains unknown. Therefore, we explored the potential mechanisms of action of AMGB on obesity through network pharmacological approaches. We revealed that targets of AMGB are significantly associated with obesity-related and adipocyte-elevated genes. Evodiamine, berberine, genipin, palmitic acid, genistein, and quercetin were shown to regulate adipocytokine signaling pathway proteins which mainly involved tumor necrosis factor receptor 1, leptin receptor. In terms of the regulatory pathway of lipolysis in adipocytes, norephedrine, pseudoephedrine, quercetin, and limonin were shown to affect adrenergic receptor-beta, protein kinase A, etc. We also found that AMGB has the potentials to enhance the insulin signaling pathway thereby preventing type II diabetes mellitus. Additionally, AMGB was discovered to be able to control not only insulin-related proteins but also inflammatory mediators and apoptotic regulators and caspases, hence reducing hepatocyte injury in nonalcoholic fatty liver disease. Our findings help develop a better understanding of how AMGB controls obesity.
Effects of Low-Dose Atorvastatin on the Peripheral Blood Mononuclear Cell Secretion of Angiogenic Factors in Type 2 Diabetes
Authors: Wesołowska Anna , Winiarska Hanna , Owoc Jakub , Borowska Magdalena , Domagała Joanna , Mikołajczak Przemysław Łukasz , Iskakova Saule , Dworacki Grzegorz , Dworacka Marzena
Published: December 2021

The aim of this study was to investigate the influence of statins on the secretion of angiogenesis mediators by the peripheral blood mononuclear cells (PBMCs) derived from patients suffering from type 2 diabetes. The study group comprised 30 participants and included: 10 statin-treated patients with diabetes, 10 statin-free diabetic subjects, and 10 statin-free non-diabetic individuals. PBMCs isolated from the blood were cultured in vitro in standard conditions and in an environment mimicking hyperglycemia. Culture supernatants were evaluated for VEGF, MCP-1, Il-10, and Il-12 by flow cytometry using commercial BDTM. Cytometric Bead Array tests. The secretion of VEGF, MCP-1 and Il-12 by PBMCs, cultured both in standard and hyperglycemic conditions, was significantly lower in the statin-treated patients with type 2 diabetes in comparison with the statin-free diabetic patients. Conversely, the secretion of Il-10 was higher in the statin-treated than in the statin-free diabetic patients. VEGF, MCP-1 and Il-12 levels in PBMCs supernatants from the glucose-containing medium were higher than those from the standard medium in each of the diabetic groups. The results of the study suggest that statins in low doses exhibit an antiangiogenic activity, reducing the secretion of potent proangiogenic factors, such as VEGF and MCP-1, and increasing the secretion of antiangiogenic Il-10 by PBMCs, also under hyperglycemic conditions characteristic for type 2 diabetes.
Peripheral Cytokine Levels as a Prognostic Indicator in Gastric Cancer: A Review of Existing Literature
Authors: Yang Elton , Chua Wei , Ng Weng , Roberts Tara Laurine
Published: December 2021

Although strong connections exist between the carcinogenesis of gastric cancer and chronic inflammation, gastric cancer is unique in that the chronic gastritis which frequently precedes carcinogenesis is strongly associated with H. pylori infection. The interplay between H. pylori virulence factors and host immune cells is complex but culminates in the activation of inflammatory pathways and transcription factors such as NF-κB, STAT3, and AP-1, all of which upregulate cytokine production. Due to the key role of cytokines in modulating the immune response against tumour cells as well as possibly stimulating tumour growth and proliferation, different patterns of cytokine secretion may be associated with varying patient outcomes. In relation to gastric cancer, interleukin-6, 8, 10, 17A, TNF, and IFN-γ may have pro-tumour properties, although interleukin-10, TNF, and IFN-γ may have anti-tumour effects. However, due to the lack of studies investigating patient outcomes, only a link between higher interleukin-6 levels and poorer prognosis has been demonstrated. Further investigations which link peripheral cytokine levels to patient prognosis may elucidate important pathological mechanisms in gastric cancer which adversely impact patient survival and allow treatments targeting these processes to be developed.
Patient-Derived Xenografts of High-Grade Serous Ovarian Cancer Subtype as a Powerful Tool in Pre-Clinical Research
Authors: Cybula Magdalena , Wang Lin , Wang Luyao , Drumond-Bock Ana Luiza , Moxley Katherine M. , Benbrook Doris M. , Gunderson-Jackson Camille , Ruiz-Echevarria Maria J. , Bhattacharya Resham , Mukherjee Priyabrata , Bieniasz Magdalena
Published: December 2021

(1) Background. PDX models have become the preferred tool in research laboratories seeking to improve development and pre-clinical testing of new drugs. PDXs have been shown to capture the cellular and molecular characteristics of human tumors better than simpler cell line-based models. More recently, however, hints that PDXs may change their characteristics over time have begun to emerge, emphasizing the need for comprehensive analysis of PDX evolution. (2) Methods. We established a panel of high-grade serous ovarian carcinoma (HGSOC) PDXs and developed and validated a 300-SNP signature that can be successfully utilized to assess genetic drift across PDX passages and detect PDX contamination with lymphoproliferative tissues. In addition, we performed a detailed histological characterization and functional assessment of multiple PDX passages. (3) Results. Our data show that the PDXs remain largely stable throughout propagation, with marginal genetic drift at the time of PDX initiation and adaptation to mouse host. Importantly, our PDX lines retained the major histological characteristics of the original patients’ tumors even after multiple passages in mice, demonstrating a strong concordance with the clinical responses of their corresponding patients. (4) Conclusions. Our data underline the value of defined HGSOC PDXs as a pre-clinical tumor model.
SALL Proteins; Common and Antagonistic Roles in Cancer
Authors: Álvarez Claudia , Quiroz Aracelly , Benítez-Riquelme Diego , Riffo Elizabeth , Castro Ariel F. , Pincheira Roxana
Published: December 2021

SALL proteins are a family of four conserved C2H2 zinc finger transcription factors that play critical roles in organogenesis during embryonic development. They regulate cell proliferation, survival, migration, and stemness; consequently, they are involved in various human genetic disorders and cancer. SALL4 is a well-recognized oncogene; however, SALL1–3 play dual roles depending on the cancer context and stage of the disease. Current reviews of SALLs have focused only on SALL2 or SALL4, lacking an integrated view of the SALL family members in cancer. Here, we update the recent advances of the SALL members in tumor development, cancer progression, and therapy, highlighting the synergistic and/or antagonistic functions they perform in similar cancer contexts. We identified common regulatory mechanisms, targets, and signaling pathways in breast, brain, liver, colon, blood, and HPV-related cancers. In addition, we discuss the potential of the SALL family members as cancer biomarkers and in the cancer cells’ response to therapies. Understanding SALL proteins’ function and relationship will open new cancer biology, clinical research, and therapy perspectives.
State of the Art and New Concepts in Giant Cell Tumor of Bone: Imaging Features and Tumor Characteristics
Authors: Parmeggiani Anna , Miceli Marco , Errani Costantino , Facchini Giancarlo
Published: December 2021

Giant cell tumor of bone (GCTB) is classified as an intermediate malignant tumor due to its locally aggressive behavior, burdened by high local recurrence rate. GCTB accounts for about 4–5% of all primary bone tumors and typically arises in the metaphysis and epiphyses of the long tubular bones. Mutation of gene H3F3A is at the basis of GCTB etiopathogenesis, and its immunohistochemical expression is a valuable method for practical diagnosis, even if new biomarkers have been identified for early diagnosis and for potential tumor recurrence prediction. In the era of computer-aided diagnosis, imaging plays a key role in the assessment of GCTB for surgical planning, patients’ prognosis prediction and post treatment evaluation. Cystic changes, penetrating irregular margins and adjacent soft tissue invasion on preoperative Magnetic Resonance Imaging (MRI) have been associated with a higher rate of local recurrence. Distance from the tumor edge to the articular surface and thickness of unaffected cortical bone around the tumor should be evaluated on Computed Tomography (CT) as related to local recurrence. Main features associated with local recurrence after curettage are bone resorption around the graft or cement, soft tissue mass formation and expansile destruction of bone. A denosumab positive response is represented by a peripherical well-defined osteosclerosis around the lesion and intralesional ossification. Radiomics has proved to offer a valuable contribution in aiding GCTB pre-operative diagnosis through clinical-radiomics models based on CT scans and multiparametric MR imaging, possibly guiding the choice of a patient-tailored treatment. Moreover, radiomics models based on texture analysis demonstrated to be a promising alternative solution for the assessment of GCTB response to denosumab both on conventional radiography and CT since the quantitative variation of some radiomics features after therapy has been correlated with tumor response, suggesting they might facilitate disease monitoring during post-denosumab surveillance.
Characterizing Malignant Melanoma Clinically Resembling Seborrheic Keratosis Using Deep Knowledge Transfer
Authors: Spyridonos Panagiota , Gaitanis George , Likas Aristidis , Bassukas Ioannis
Published: December 2021

Malignant melanomas resembling seborrheic keratosis (SK-like MMs) are atypical, challenging to diagnose melanoma cases that carry the risk of delayed diagnosis and inadequate treatment. On the other hand, SK may mimic melanoma, producing a ‘false positive’ with unnecessary lesion excisions. The present study proposes a computer-based approach using dermoscopy images for the characterization of SΚ-like MMs. Dermoscopic images were retrieved from the International Skin Imaging Collaboration archive. Exploiting image embeddings from pretrained convolutional network VGG16, we trained a support vector machine (SVM) classification model on a data set of 667 images. SVM optimal hyperparameter selection was carried out using the Bayesian optimization method. The classifier was tested on an independent data set of 311 images with atypical appearance: MMs had an absence of pigmented network and had an existence of milia-like cysts. SK lacked milia-like cysts and had a pigmented network. Atypical MMs were characterized with a sensitivity and specificity of 78.6% and 84.5%, respectively. The advent of deep learning in image recognition has attracted the interest of computer science towards improved skin lesion diagnosis. Open-source, public access archives of skin images empower further the implementation and validation of computer-based systems that might contribute significantly to complex clinical diagnostic problems such as the characterization of SK-like MMs.
Digital Identities of Young People from the South of Spain: An Online Sexual Differentiation
Authors: García-Navarro E. Begoña , Gil Bermejo Jose Luis , Araujo-Hernández Miriam
Published: December 2021

Through a mixed methodological approach, we want to know how adolescents aged between 14 and 16 years from the south of Spain express and identify themselves on social networks, with respect to their sex. As such differences can determine gender inequality, we will analyse differences between females and males regarding the expression of identity on social networks. Analysis of obtained results demonstrates that many relevant attributes still emerge such as the socio-cultural representation of gender as sex in social networks. Differences emerged between the identity expressions of females and males which can generate inequalities favouring females and males. This implies a series of repercussions and, ultimately, defines the so-called digital gender divide. Taking into account these results we could intervene in the population of children to carry out prevention activities focused on social networks.