bluuebunny/crossref_metadata_2025 huggingface dataset:
Determination of Possible Adulteration and Quality Assessment in Commercial Honey
Authors: Aykas Didem P.
Published: January 2023

This study aims to predict several quality traits in commercial honey samples simultaneously and to reveal possible honey adulteration using a field-deployable portable infrared spectrometer without any sample preparation. A total of one hundred and forty-seven commercial honey samples were purchased from local and online markets in Turkey and the United States of America (USA), and their soluble solids (°Brix), pH, free acidity, moisture, water activity (aw), glucose, fructose, sucrose, and hydroxymethyl furfural (HMF) contents were determined using reference methods. The HMF (n = 11 samples) and sucrose (n = 21) concentrations were higher than the regulatory limits in some tested samples. The exceeding HMF content may imply temperature abuse during storage and prolonged storing. On the other hand, high sucrose content may indicate possible adulteration with commercial sweeteners. Therefore, soft independent modeling of class analogies (SIMCA) analysis was conducted to reveal this potential sweetener adulteration in the samples, and the SIMCA model was able to identify all the flagged samples. The suggested FT-IR technique may be helpful in regulatory bodies in determining honey authenticity issues as well as assessing the quality characteristics of honey samples in a shorter period and at a lower cost.
A Non-Racial Approach to Assessing Group Membership of Victims in a Mass Grave Using Cranial Data
Authors: Albanese John , Di Iorio Alyssa
Published: January 2023

In some jurisdictions, race, ancestry, or population affinity have been used for historical and po-litical, rather than biological, reasons in forensic anthropology when identifying individuals. The approach persists even though the genetic and skeletal data clearly demonstrate that human variation does not cluster into these groups. For over 60 years, these methods have consistently performed poorly when independently tested using large samples. By racializing the deceased, these methods have further marginalized the living. However, there is a need in the investigation of genocide and human rights violations to demonstrate that a specific group was targeted. Without relying on the outdated typological concepts of human variation, in this paper we present preliminary results for a method that can be used in a mass grave context to demonstrate that a specific group was targeted. Using samples from two identified reference collections, we created subsamples from one relatively homogeneous collection to model various mass grave scenarios and used the relatively heterogenous sample from the other collection as a reference for com-parison. In scenarios that varied by sample size and sex, it was possible to determine that a specific group was targeted if the sample size in a hypothetical mass grave was greater than 25 for a multi-sex sample, when sex is not known, and a minimum of 14 if sex could be estimated.
Finite-Time Stabilization Criteria of Delayed Inertial Neural Networks with Settling-Time Estimation Protocol and Reliable Control Mechanism
Authors: Wang Wenhao , Hua Lanfeng , Zhu Hong , Wang Jun , Shi Kaibo , Zhong Shouming
Published: January 2023

This work investigates the finite-time stability (FTS) issue for a class of inertial neural networks (INNs) with mixed-state time-varying delays, proposing a novel analytical approach. Firstly, we establish a novel FTS lemma, which is entirely different from the existing FTS theorems, and extend the current research results. Secondly, an improved discontinuous reliable control mechanism is developed, which is more valid and widens the application scope compared to previous results. Then, by using a novel non-reduced order approach (NROA) and the Lyapunov functional theory, novel sufficient criteria are established using FTS theorems to estimate the settling time with respect to a finite-time stabilization of INNs. Finally, the simulation results are given to validate the usefulness of the theoretical results.
Investigation of Egyptian Blue on a Fragmentary Egyptian Head Using ER-FTIR Spectroscopy and VIL Imaging
Authors: Wiseman Germain , Barnes Stephanie , Helwig Kate
Published: January 2023

Non-invasive techniques are being increasingly used for the study of heritage objects. This article describes the results of pigment analysis on a fragmentary Egyptian sculpture using two non-invasive infrared methods: external reflectance Fourier-transform infrared (ER-FTIR) spectroscopy and visible-induced infrared luminescence (VIL) photography. ER-FTIR spectroscopy was used to identify certain of the pigments used on the sculpture, including Egyptian blue, in variously coloured areas. An optimized VIL photographic technique, using a high-resolution camera combined with focus-stacking, permitted detailed mapping of the location of Egyptian blue on the sculpture, including sub-millimeter grains of the pigment scattered across the object’s surface, which were not visible to the naked eye.
Reactance, Decisional Procrastination, and Hesitation: A Latent Class Analysis of Clutter Behavior
Authors: Patel Devki A. , Graupmann Verena , Ferrari Joseph R.
Published: January 2023

During the 2019–2020 global pandemic, mandated time at home suggested engagement in personal projects, such as home decluttering. Clutter (an overabundance of possessions) may impede one’s quality of life by interfering with space livability and social connections and prompting negative affect and financial problems. The present study explored action–state orientation, psychological reactance, and decisional procrastination with 227 American adults (M age = 49.9 years old). A latent class analysis tested for differences in cognition across groups. Results supported that persons who struggle with clutter reflect clusters or “classes” given their self-reported cognitive processes, with hesitant and indecisive participants experiencing greater negative impacts of clutter than action-oriented and decisive participants. Our findings suggested improving the decision-making and goal-directed capacities of those struggling with clutter may be effective as preventive and/or interventive strategies. Future research might consider when hesitation to initiate challenging tasks and indecision emerge in the decluttering timeline and how those who are prone to these cognitions may be supported in managing their personal possessions.
ICT Training Perception of Professionals in Functional Diversity in Granada
Authors: Gallardo-Montes Carmen del Pilar , Caurcel-Cara María Jesús , Crisol-Moya Emilio , Peregrina-Nievas Paula
Published: January 2023

Training in Information and Communication Technologies (ICTs) has become very valuable in the current educational panorama, given the proliferation of digital resources available in the formal and non-formal education context. Fortunately, the field of attention to diversity has also benefited from it. For this reason, it is essential that the professionals who attend to people with functional diversity have a good attitude towards them, as well as training in accordance with their requirements. The aim of this study was to analyse how professionals in Granada (Spain) perceived their ICT training. A total of 404 specialists who worked in the field of attention to diversity were interviewed. In general, participants showed a favourable opinion towards ICT but they expressed a medium-low perception of their digital training. Nevertheless, these results are encouraging, as younger teachers showed a more favourable opinion and training towards ICT. In the long term, this will be a generation that is more educated and aware of the benefits, applicability and usefulness of these resources for working with people with functional diversity.
Willingness to Pay for a Dating App: Psychological Correlates
Authors: Rochat Lucien , Orita Elena , Jeannot Emilien , Achab Sophia , Khazaal Yasser
Published: January 2023

The smartphone dating app, Tinder, has become hugely popular in recent years. Although most people use a free version of the app, some pay for an augmented version to improve their experience. However, there is little evidence of the association between the willingness to pay for a dating app such as Tinder and users’ psychological characteristics. This study thus aims to compare Tinder paying versus non-paying users in terms of their pattern of use, excessive use of Tinder, motives for using Tinder, impulsivity traits, depressive mood, and sociodemographic variables, as well as to examine which variables best predict group membership. A total of 1159 Tinder users participated in an online survey. Group comparisons indicated that payers were more frequently male, reported greater motives for using Tinder than non-payers, and differed in their pattern of use compared with non-payers. Impulsivity traits did not significantly differ between the two groups. Being male and reporting greater motives for Tinder use significantly predicted being a payer. These findings provide insights into the processes that stimulate users’ greater consumption of online dating apps, such as reinforcement mechanisms and reward sensitivity.
Using Google Trends and Wikipedia to Investigate the Global Public’s Interest in the Pancreatic Cancer Diagnosis of a Celebrity
Authors: Gianfredi Vincenza , Nucci Daniele , Nardi Mariateresa , Santangelo Omar Enzo , Provenzano Sandro
Published: January 2023

A cross-sectional study was designed to assess the impact of a celebrity’s announcement of having been diagnosed with pancreatic cancer on the volume of cancer-related research on the Internet. Global searches were carried out on Google Trends (GT) for the period from 1 January 2004 to 20 November 2022 (since data prior to 2004 were not available) using the search words Tumore del Pancreas (pancreatic cancer), Tumore neuroendocrino (neuroendocrine tumor), and Fedez (the name of a popular Italian rapper). The frequency of specific page views for Fedez, Tumore del pancreas, and Tumore neuroendocrino was collected via Wikipedia Trends data. Statistical analyses were carried out using the Pearson correlation coefficient (r). The GT data revealed a strong correlation (r = 0.83) while the Wikipedia Trends data indicated a moderate correlation (r = 0.37) for Tumore neuroendocrino and Tumore del pancreas. The search peaks for the GT and Wikipedia pages occur during the same time period. An association was found between the celebrity’s announcement of his pancreatic cancer diagnosis and the volume of pancreatic-cancer-related online searches. Our findings demonstrate that media events and media coverage of health-related news can raise people’s curiosity and desire for health information.
HTA and Gastric Cancer: Evaluating Alternatives in Third- and Fourth-Line Patients
Authors: Ferrario Lucrezia , Asperti Federica , Aprile Giuseppe , Giuliani Jacopo
Published: January 2023

Metastatic gastric cancer (mGC) represents an economic and societal burden worldwide. The present study has two aims. Firstly, it evaluates the benefits and the added value of the introduction of trifluridine/tipiracil (FTD/TPI) in the Italian clinical practice, defining the comparative efficacy and safety profiles with respect to the other available treatment options (represented by the best supportive care (BSC) and FOLFIRI (5-FU, irinotecan, and leucovorin) regimens). Secondly, it assesses the potential economic and organizational advantages for hospitals and patients, focusing on third- and fourth-line treatments. For the achievement of the above objective, a health technology assessment study was conducted in 2021, assuming the NHS perspective within a 3-month time horizon. The literature reported a better efficacy of FTD/TPI with respect to both BSC and FOLFIRI regimens. From an economic perspective, despite the additional economic resources that would be required, the investment could positively impact the overall survival rate for the patients treated with the FTD/TPI strategy. However, the innovative molecule would lead to a decrease in hospital accesses devoted to chemotherapy infusion, ranging from a minimum of 34% to a maximum of 44%, strictly dependent on FTD/TPI penetration rate, with a consequent opportunity to take on a greater number of oncological patients requiring drug administration for the treatment of any other cancer diseases. According to experts’ opinions, lower perceptions of FTD/TPI emerged concerning equity aspects, whereas it would improve both individuals’ and caregivers’ quality of life. In conclusion, the results have demonstrated the strategic relevance related to the introduction of FTD/TPI regarding the coverage of an important unmet medical need of patients with metastatic gastric cancer who were refractory to at least two prior therapies, with important advantages for patients and hospitals, thus optimizing the clinical pathway of such frail patients.
Improving the Quality of Reclaimed Water via Applying Spirulina platensis to Eliminate Residual Nitrate
Authors: Jiang Xiaohua , Shan Xin , Li Fengmin
Published: January 2023

The application of reclaimed water has been recognized as the key approach for alleviating water scarcity, while its low quality, such as high nitrogen content, still makes people worry about the corresponding ecological risk. Herein, we investigated the feasibility of removing residual nitrate from reclaimed water by applying Spirulina platensis. It is found that 15 mg/L total nitrogen could be decreased to 1.8 mg/L in 5 days, equaling 88.1 % removal efficiency under the optimized conditions. The deficient phosphorus at 0.5–1.0 mg/L was rapidly eliminated but was already sufficient to support nitrate removal by S. platensis. The produced ammonia is generally below 0.2 mg/L, which is much lower than the standard limit of 5 mg/L. In such a nutrient deficiency condition, S. platensis could maintain biomass growth well via photosynthesis. The variation of pigments, including chlorophyll a and carotenoids, suggested a certain degree of influences of illumination intensity and phosphorus starvation on microalgae. The background cations Cu2+ and Zn2+ exhibited significant inhibition on biomass growth and nitrate removal; thus, more attention needs to be paid to the further application of microalgae in reclaimed water. Our results demonstrated that cultivation of S. platensis should be a very promising solution to improve the quality of reclaimed water by efficiently removing nitrate and producing biomass.
Informed Consent: Legal Obligation or Cornerstone of the Care Relationship?
Authors: Pallocci Margherita , Treglia Michele , Passalacqua Pierluigi , Tittarelli Roberta , Zanovello Claudia , De Luca Lucilla , Caparrelli Valentina , De Luna Vincenzo , Cisterna Alberto Michele , Quintavalle Giuseppe , Marsella Luigi Tonino
Published: January 2023

The topic of informed consent has become increasingly important in recent decades, both in the ethical-deontological field and as a duty of law. The review covered all sentences issued by the 13th section of the Civil Court of Rome during the period January 2016–December 2020. During this period, 156 judgments were found in which a breach of consent was required; in 24 of these, specific liability was proven, and the corresponding compensation liquidated. Moreover, 80% of the cases concerned the lack of information provided. The most involved branches were those related to surgical areas: general surgery, plastic surgery and aesthetic medicine and orthopaedics. The total amount of compensation paid was EUR 287,144.59. The research carried out has highlighted how, in a broad jurisprudential context, the damage caused by the violation of the right related to informed consent is considered, and how it impacts on the economic compensation of damages. Additionally, it showed that the areas most affected by the information deficit are those related to the performance of surgical activities, which are characterized by greater invasiveness and a higher risk of adverse events. The data reported underline the exigency to consider informed consent not as a mere documentary allegation but as an essential moment in the construction of a valid therapeutic alliance, which is also useful for avoiding unnecessary litigation that is becoming increasingly burdensome for healthcare systems all over the world.
The Efficiency of Energy Infrastructure Investment and Its Regional Economic Impact
Authors: Kuang Lixin , Han Xiangrong , Liu Guanyu
Published: January 2023

This study constructed an input–output and environmental indicator combination framework to evaluate the efficiency of energy infrastructure investment. Furthermore, the study used a three-stage DEA model to evaluate the efficiency of energy infrastructure investment projects in Jiangsu Province. Subsequently, the study constructed a system of indicators to measure regional economic development and assigns weights to them using the entropy value method, to obtain a comprehensive regional economic development score. Finally, this study analyzed the impact of energy investment efficiency on regional economic growth, economic stability, and industrial structure optimization. The study results show that the efficiency of energy infrastructure investment varies widely across Jiangsu and is highly correlated with the regional economic development model, the level of economic development, and the importance of the industry. The study also reveals that the improvement of energy infrastructure investment efficiency in Jiangsu fails to reflect the level of regional economic development; however, it has a crucial role in increasing social wealth and transforming the regional industrial structure and economy. Based on these results, this study further proposes countermeasures, such as planning a reasonable scale of investment, implementing differentiated regional investment, and upgrading management and technology.
Analysis on the Influence of Industrial Structure on Energy Efficiency in China: Based on the Spatial Econometric Model
Authors: Zheng Xin , Ye Zi , Fang Zhong
Published: January 2023

Compared with other developed countries, China’s energy efficiency level is not optimal, but it has indeed made remarkable achievements in its long-term development, mainly due to efforts targeting the adjustment of industrial structure. This research, therefore, uses a spatial econometric model to study the energy efficiency of 30 provinces in China with data from the panel from 2004 to 2019, and studies the impact of industrial structure on energy efficiency from the overall sample, for different time periods and across the three regional scales of eastern, central and western regions. The following conclusions are drawn from the empirical analysis. (1) China’s energy efficiency indicators have significant geographic spatial correlation and regional spatial structure differences. (2) In the full sample condition, the industrial structure has a positive impact on the energy efficiency of China’s provinces, but it also shows a significant negative spatial spillover effect. (3) Industrial structure was positively correlated with energy efficiency from 2004 to 2011. (4) The industrial structure in the east promotes energy efficiency, while the industrial structure in the central and western regions inhibits energy efficiency improvement. (5) Government intervention and scientific and technological innovation have had a spatial impact on energy efficiency in China’s provinces, while marketization and the average income of residents have had no significant impact.
Determinants of Food Waste in Cluj-Napoca (Romania): A Community-Based System Dynamics Approach
Authors: Archip Bianca Cezara , Banatean-Dunea Ioan , Petrescu Dacinia Crina , Petrescu-Mag Ruxandra Malina
Published: January 2023

This study identifies the most relevant causes of food waste according to the perceptions of key stakeholders in Cluj-Napoca, Romania. Community-Based System Dynamics (CBSD), a qualitative approach, was used to reveal the determinants of food waste. CBSD was intended to encourage the system thinking of participants in the field of food waste. Consequently, CBSD helped us map and visualize the role of each identified cause in the system and the nature of their interactions. For the present study, four categories of stakeholders were involved: consumers, public administration, food waste business, and the NGO sector involved in food waste reduction. The result of each modeling session was a loop diagram of the main food waste determinants. A common perception reflected within each stakeholder group was that food waste could be minimized through upstream actions. The participants highlighted pro-environmental knowledge, awareness, and values as the prerequisites for fighting food waste. It was found that the lack of education and awareness of food waste directly impacted food waste generation. In addition, the role of education was underlined by participants as a contributor to changing individual and household practices, such as overbuying. The lack of connection between consumers and the food production process, coupled with consumerist practices and the rejection of ‘ugly food’, contributed to the decrease in the overall value people attributed to food. Governmental intervention, through legislation, was indicated by the CBSD participants as being key to increasing societal awareness and shaping the behavior of food chain actors. We concluded that food waste is a ‘wicked problem’ and the interlocking of the economic, social, political, and environmental spheres and the multitude of stakeholders’ interests, values, and perceptions should be considered in designing sustainable solutions to combat food waste. Finally, this research testifies to the importance of engaging with diverse panels of stakeholders who, through the multitude of opinions and perspectives on the causes of food waste, can further create knowledge about the most appropriate ways to combat the food waste phenomenon.
Chemokine Dysregulation and Neuroinflammation in Schizophrenia: A Systematic Review
Authors: Ermakov Evgeny A. , Mednova Irina A. , Boiko Anastasiia S. , Buneva Valentina N. , Ivanova Svetlana A.
Published: January 2023

Chemokines are known to be immunoregulatory proteins involved not only in lymphocyte chemotaxis to the site of inflammation, but also in neuromodulation, neurogenesis, and neurotransmission. Multiple lines of evidence suggest a peripheral proinflammatory state and neuroinflammation in at least a third of patients with schizophrenia. Therefore, chemokines can be active players in these processes. In this systematic review, we analyzed the available data on chemokine dysregulation in schizophrenia and the association of chemokines with neuroinflammation. It has been shown that there is a genetic association of chemokine and chemokine receptor gene polymorphisms in schizophrenia. Besides, the most reliable data confirmed by the results of meta-analyses showed an increase in CXCL8/IL-8, CCL2/MCP-1, CCL4/MIP-1β, CCL11/eotaxin-1 in the blood of patients with schizophrenia. An increase in CXCL8 has been found in cerebrospinal fluid, but other chemokines have been less well studied. Increased/decreased expression of genes of chemokine and their receptors have been found in different areas of the brain and peripheral immune cells. The peripheral proinflammatory state may influence the expression of chemokines since their expression is regulated by pro- and anti-inflammatory cytokines. Mouse models have shown an association of schizophrenia with dysregulation of the CX3CL1-CX3CR1 and CXCL12-CXCR4 axes. Altogether, dysregulation in chemokine expression may contribute to neuroinflammation in schizophrenia. In conclusion, this evidence indicates the involvement of chemokines in the neurobiological processes associated with schizophrenia.
The Mycotoxin Patulin Inhibits the Mitochondrial Carnitine/Acylcarnitine Carrier (SLC25A20) by Interaction with Cys136 Implications for Human Health
Authors: Giangregorio Nicola , Tonazzi Annamaria , Calvano Cosima Damiana , Pierri Ciro Leonardo , Incampo Giovanna , Cataldi Tommaso R. I. , Indiveri Cesare
Published: January 2023

The effect of mycotoxin patulin (4-hydroxy-4H-furo [3,2c] pyran-2 [6H] -one) on the mitochondrial carnitine/acylcarnitine carrier (CAC, SLC25A20) was investigated. Transport function was measured as [3H]-carnitineex/carnitinein antiport in proteoliposomes reconstituted with the native protein extracted from rat liver mitochondria or with the recombinant CAC over-expressed in E. coli. Patulin (PAT) inhibited both the mitochondrial native and recombinant transporters. The inhibition was not reversed by physiological and sulfhydryl-reducing reagents, such as glutathione (GSH) or dithioerythritol (DTE). The IC50 derived from the dose–response analysis indicated that PAT inhibition was in the range of 50 µM both on the native and on rat and human recombinant protein. The kinetics process revealed a competitive type of inhibition. A substrate protection experiment confirmed that the interaction of PAT with the protein occurred within a protein region, including the substrate-binding area. The mechanism of inhibition was identified using the site-directed mutagenesis of CAC. No inhibition was observed on Cys mutants in which only the C136 residue was mutated. Mass spectrometry studies and in silico molecular modeling analysis corroborated the outcomes derived from the biochemical assays.
Association of GILZ with MUC2, TLR2, and TLR4 in Inflammatory Bowel Disease
Authors: Cari Luigi , Rosati Lucrezia , Leoncini Giuseppe , Lusenti Eleonora , Gentili Marco , Nocentini Giuseppe , Riccardi Carlo , Migliorati Graziella , Ronchetti Simona
Published: January 2023

Ulcerative colitis (UC) and Crohn’s Disease (CD) are chronic relapsing inflammatory diseases that are caused by genetic, environmental, and immune factors. Treatment strategies are currently based on symptomatic control by immunosuppression. The glucocorticoid-induced leucine zipper (GILZ), a mediator of several effects of glucocorticoids, was recently found to be secreted by goblet cells and play a role in inflammatory bowel disease (IBD). This study investigates which genes GILZ is associated with in its role in intestinal barrier functions. We examined datasets from the Gene Expression Omnibus (GEO) and ArrayExpress profiles of the gut of healthy subjects (HSs), as well as UC and CD patients. The human colonic epithelial HT29 cell line was used for in vitro validation experiments. GILZ was significantly correlated with MUC2, TLR2, and TLR4. In particular, an inverse correlation was found between the GILZ and MUC2 in HS and patients with IBD, mostly in those with an active disease. Further, direct pairwise correlations for GILZ/TLR2 and GILZ/TLR4 were found in HSs and UC patients, but not in CD patients. Overall, our results reveal the crosstalk at the transcription level between the GILZ, MUC2, and TLRs in the mucosal barrier through common pathways, and they open up new perspectives in terms of mucosal healing in IBD patients.
Addressing the Reciprocal Crosstalk between the AR and the PI3K/AKT/mTOR Signaling Pathways for Prostate Cancer Treatment
Authors: Raith Fabio , O’Donovan Daniel H. , Lemos Clara , Politz Oliver , Haendler Bernard
Published: January 2023

The reduction in androgen synthesis and the blockade of the androgen receptor (AR) function by chemical castration and AR signaling inhibitors represent the main treatment lines for the initial stages of prostate cancer. Unfortunately, resistance mechanisms ultimately develop due to alterations in the AR pathway, such as gene amplification or mutations, and also the emergence of alternative pathways that render the tumor less or, more rarely, completely independent of androgen activation. An essential oncogenic axis activated in prostate cancer is the phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway, as evidenced by the frequent alterations of the negative regulator phosphatase and tensin homolog (PTEN) and by the activating mutations in PI3K subunits. Additionally, crosstalk and reciprocal feedback loops between androgen signaling and the PI3K/AKT/mTOR signaling cascade that activate pro-survival signals and play an essential role in disease recurrence and progression have been evidenced. Inhibitors addressing different players of the PI3K/AKT/mTOR pathway have been evaluated in the clinic. Only a limited benefit has been reported in prostate cancer up to now due to the associated side effects, so novel combination approaches and biomarkers predictive of patient response are urgently needed. Here, we reviewed recent data on the crosstalk between AR signaling and the PI3K/AKT/mTOR pathway, the selective inhibitors identified, and the most advanced clinical studies, with a focus on combination treatments. A deeper understanding of the complex molecular mechanisms involved in disease progression and treatment resistance is essential to further guide therapeutic approaches with improved outcomes.
Role of Histone Tails and Single Strand DNA Breaks in Nucleosomal Arrest of RNA Polymerase
Authors: Gerasimova Nadezhda S. , Pestov Nikolay A. , Studitsky Vasily M.
Published: January 2023

Transcription through nucleosomes by RNA polymerases (RNAP) is accompanied by formation of small intranucleosomal DNA loops (i-loops). The i-loops form more efficiently in the presence of single-strand breaks or gaps in a non-template DNA strand (NT-SSBs) and induce arrest of transcribing RNAP, thus allowing detection of NT-SSBs by the enzyme. Here we examined the role of histone tails and extranucleosomal NT-SSBs in i-loop formation and arrest of RNAP during transcription of promoter-proximal region of nucleosomal DNA. NT-SSBs present in linker DNA induce arrest of RNAP +1 to +15 bp in the nucleosome, suggesting formation of the i-loops; the arrest is more efficient in the presence of the histone tails. Consistently, DNA footprinting reveals formation of an i-loop after stalling RNAP at the position +2 and backtracking to position +1. The data suggest that histone tails and NT-SSBs present in linker DNA strongly facilitate formation of the i-loops during transcription through the promoter-proximal region of nucleosomal DNA.
Flame-Retardant Cycloaliphatic Epoxy Systems with High Dielectric Performance for Electronic Packaging Materials
Authors: Jia Xiao-Wei , Mu Wen-Long , Shao Zhu-Bao , Xu Ying-Jun
Published: January 2023

Flame-retardant cycloaliphatic epoxy systems have long been studied; however, the research suffers from slow and unsatisfactory advances. In this work, we synthesized a kind of phosphorus-containing difunctional cycloaliphatic epoxide (called BCEP). Then, triglycidyl isocyanurate (TGIC) was mixed with BCEP to achieve epoxy systems that are rich in phosphorus and nitrogen elements, which were cured with 4-methylhexahydrobenzene anhydride (MeHHPA) to obtain a series of flame-retardant epoxy resins. Curing behaviors, flame retardancy, thermal behaviors, dielectric performance, and the chemical degradation behaviors of the cured epoxy system were investigated. BCEP-TGIC systems showed a high curing activity, and they can be efficiently cured, in which the incorporation of TGIC decreased the curing activity of the resin. As the ratio of BCEP and TGIC was 1:3, the cured resin (BCEP1-TGIC3) showed a relatively good flame retardancy with a limiting oxygen index value of 25.2%. In the cone calorimeter test, they presented a longer time to ignition and a lower heat release than the commercially available cycloaliphatic epoxy resins (ERL-4221). BCEP-TGIC systems presented good thermal stability, as the addition of TGIC delayed the thermal weight loss of the resin. BCEP1-TGIC3 had high dielectric performance and outperformed ERL-4221 over a frequency range of 1 HZ to 1 MHz. BCEP1-TGIC3 could achieve degradation under mild conditions in an alkali methanol/water solution. Benefiting from the advances, BCEP-TGIC systems have potential applications as electronic packaging materials in electrical and electronic fields.
Effective or Harmful—Evaluation of Locally Applied Antibiotics on Adipose Tissue during Lipofilling to the Breast—An In Vitro Study
Authors: Diehm Yannick F. , Gazyakan Emre , Wang Yiping , Siegwart Laura C. , Haug Valentin , Kotsougiani-Fischer Dimitra , Kneser Ulrich , Fischer Sebastian
Published: January 2023

Lipofilling is a frequently used and safe procedure for breast reconstruction. One of the most feared complications is soft tissue infection following lipofilling. Because of this, some surgeons propose the practice of rinsing fat grafts with antibiotics. This study investigates the effect of antibiotic rinses on fat grafts in an in vitro model. Adipocytes and stem cells were isolated from fat tissue harvested during 24 lipofilling procedures and incubated with different doses of clindamycin or cefazolin. Cell viability, metabolism, proliferation, and differentiation capacities were analyzed by gross morphology, fluorescence staining, -(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromid (MTT-), and Glyceraldehyde 3 Phosphate Dehydrogenase (G3PD)-assay as well as reactive oxygen species (ROS)-assay. Cefazolin and clindamycin led to significant reduction of cell viability of adipocytes. High doses of both antibiotics led to a rupture of adipocytes with visible free lipid droplets. Cell metabolism was significantly decreased after incubation with both antibiotics. There was a significant increase in ROS production. Exposure to clindamycin and cefazolin led to morphological changes in stem cells in a dose- and time-dependent manner. Furthermore, differentiation potential was significantly reduced. Antibiotic susceptibility testing, however, showed that low concentrations of antibiotics effectively inhibited bacterial growth in contaminated fat grafts. This study confirms that rinsing fat grafts with clindamycin or cefazolin not only overly prevents infection but also has cytotoxic and metabolic effects on adipocytes. Therefore, based on these results, the routine clinical application in high doses cannot be recommended.
Release of HMGB1 and Toll-like Receptors 2, 4, and 9 Signaling Are Modulated by Bifidobacterium animalis subsp. lactis BB-12 and Salmonella Typhimurium in a Gnotobiotic Piglet Model of Preterm Infants
Authors: Splichal Igor , Donovan Sharon M. , Kindlova Zdislava , Stranak Zbynek , Neuzil Bunesova Vera , Sinkora Marek , Polakova Katerina , Valaskova Barbora , Splichalova Alla
Published: January 2023

Gnotobiotic (GN) animals with defined microbiota allow us to study host–microbiota and microbiota–microbiota interferences. Preterm germ-free (GF) piglets were mono-associated with probiotic Bifidobacterium animalis subsp. lactis BB-12 (BB12) to ameliorate/prevent the consequences of infection with the Salmonella Typhimurium strain LT2 (LT2). Goblet cell density; expression of Toll-like receptors (TLRs) 2, 4, and 9; high mobility group box 1 (HMGB1); interleukin (IL)-6; and IL-12/23p40 were analyzed to evaluate the possible modulatory effect of BB12. BB12 prevented an LT2-induced decrease of goblet cell density in the colon. TLRs signaling modified by LT2 was not influenced by the previous association with BB12. The expression of HMGB1, IL-6, and IL12/23p40 in the jejunum, ileum, and colon and their levels in plasma were all decreased by BB12, but these changes were not statistically significant. In the colon, differences in HMGB1 distribution between the GF and LT2 piglet groups were observed. In conclusion, the mono-association of GF piglets with BB12 prior to LT2 infection partially ameliorated the inflammatory response to LT2 infection.
The Non-Invasive Assessment of Circulating D-Loop and mt-ccf Levels Opens an Intriguing Spyhole into Novel Approaches for the Tricky Diagnosis of NASH
Authors: Paolini Erika , Longo Miriam , Corsini Alberto , Dongiovanni Paola
Published: January 2023

Nonalcoholic fatty liver disease (NAFLD) is the commonest liver disease worldwide affecting both adults and children. Nowadays, no therapeutic strategies have been approved for NAFLD management, and hepatic biopsy remains the gold standard procedure for its diagnosis. NAFLD is a multifactorial disease whose pathogenesis is affected by environmental and genetic factors, and it covers a spectrum of conditions ranging from simple steatosis up to nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Several studies underlined the urgent need to develop an NAFLD risk prediction model based on genetics, biochemical indicators, and metabolic disorders. The loss of mitochondrial dynamics represents a typical feature of progressive NAFLD. The imbalance of mitochondrial lifecycle together with the impairment of mitochondrial biomass and function trigger oxidative stress, which in turn damages mitochondrial DNA (mtDNA). We recently demonstrated that the main genetic predictors of NAFLD led to mitochondrial dysfunction. Moreover, emerging evidence shows that variations in the displacement loop (D-loop) region impair mtDNA replication, and they have been associated with advanced NAFLD. Finally, lower levels of mitophagy foster the overload of damaged mitochondria, resulting in the release of cell-free circulating mitochondrial DNA (mt-ccf) that exacerbates liver injury. Thus, in this review we summarized what is known about D-loop region alterations and mt-ccf content during NAFLD to propose them as novel non-invasive biomarkers.
Biological Use of Nanostructured Silica-Based Materials Functionalized with Metallodrugs: The Spanish Perspective
Authors: Díaz-García Diana , Prashar Sanjiv , Gómez-Ruiz Santiago
Published: January 2023

Since the pioneering work of Vallet-Regí’s group on the design and synthesis of mesoporous silica-based materials with therapeutic applications, during the last 15 years, the potential use of mesoporous silica nanostructured materials as drug delivery vehicles has been extensively explored. The versatility of these materials allows the design of a wide variety of platforms that can incorporate numerous agents of interest (fluorophores, proteins, drugs, etc.) in a single scaffold. However, the use of these systems loaded with metallodrugs as cytotoxic agents against different diseases and with distinct therapeutic targets has been studied to a much lesser extent. This review will focus on the work carried out in this field, highlighting both the pioneering and recent contributions of Spanish groups that have synthesized a wide variety of systems based on titanium, tin, ruthenium, copper and silver complexes supported onto nanostructured silica. In addition, this article will also discuss the importance of the structural features of the systems for evaluating and modulating their therapeutic properties. Finally, the most interesting results obtained in the study of the potential therapeutic application of these metallodrug-functionalized silica-based materials against cancer and bacteria will be described, paying special attention to preclinical trials in vivo.
Dual Role of B Cells in Multiple Sclerosis
Authors: Kumar Gaurav , Axtell Robert C.
Published: January 2023

B cells have emerged as an important immune cell type that can be targeted for therapy in multiple sclerosis (MS). Depleting B cells with anti-CD20 antibodies is effective in treating MS. Yet, atacicept treatment, which blocks B-cell Activating Factor (BAFF) and A Proliferation-Inducing Ligand (APRIL), two cytokines important for B cell development and function, paradoxically increases disease activity in MS patients. The reason behind the failure of atacicept is not well understood. The stark differences in clinical outcomes with these therapies demonstrate that B cells have both inflammatory and anti-inflammatory functions in MS. In this review, we summarize the importance of B cells in MS and discuss the different B cell subsets that perform inflammatory and anti-inflammatory functions and how therapies modulate B cell functions in MS patients. Additionally, we discuss the potential anti-inflammatory functions of BAFF and APRIL on MS disease.
The Role of Complexes of Biogenic Metals in Living Organisms
Authors: Kostova Irena
Published: January 2023

Biogenic metals and their various inorganic, organometallic, and coordination compounds are comprehensively studied and extensively used in medical practice. Since the biogenic metals have various chemical properties corresponding to their position in the periodic table, their biological functions are different. Almost all of the discussed biogenic elements have an ability to form coordination complexes. Furthermore, the different accessible oxidation states occupied by most of these elements enables the body to catalyze oxy-reduction interactions, depending on the biological conditions. As they are biogenic in nature, their deficiency or their excess in the body leads to numerous pathological obstructions. The application of metal-based compounds as medications is connected with the oxy-reduction properties and the capability to form coordination complexes, which are involved in many bioreactions. The usefulness of these metals as therapeutic and diagnostic agents is also pointed out.
Skin Manifestation of Human Monkeypox
Authors: Wang Xue , Lun Wenhui
Published: January 2023

Monkeypox is a zoonotic infectious disease caused by the monkeypox virus (MPXV) infection, which is mainly manifested as characteristic rashes. It spreads mainly through direct skin-to-skin contact. In some cases, respiratory transmission occurs through contact with respiratory droplets when in close contact with an infected person for a long time. The monkeypox outbreak in 2022 frequently occurred in the MSM (men who have sex with men) population, raising concerns about whether monkeypox could be transmitted through sexual behavior. This article mainly reviews the research progress of skin manifestations of monkeypox, including typical and atypical rashes of monkeypox, and different skin manifestations in some special groups, such as children, pregnant women and individuals co-infected with HIV (human immunodeficiency virus) and MPXV. At present, dermatologists are not very familiar with the diagnosis and treatment of monkeypox, it is therefore necessary to review the skin manifestations of monkeypox, which can help clinicians diagnose the sporadic cases and monitor the occurrence of monkeypox early, particularly in people at higher risk of infection. Early clinical diagnosis and treatment can largely avoid serious complications and death from monkeypox.
Processing of 3-(Trimethoxysilyl)propyl Methacrylate (TMSPM) Functionalized Barium Titanate/Photopolymer Composites: Functionalization and Process Parameter Investigation
Authors: Zarinwall Ajmal , Mitkus Rytis , Marth Axel , Maurer Viktor , Sinapius Michael , Garnweitner Georg
Published: January 2023

To improve the performance of lead-free piezoelectric composites, the functionalization of the filler particles has been suggested as a successful strategy in several recent reports. The details of the functionalization process, however, are not clear, nor is its influence on the dielectric properties of the composites. This study reports a systematic investigation of the functionalization process parameters of barium titanate nanoparticles (BTONP) with 3-(trimethoxysilyl)propyl methacrylate (TMSPM) used as a linker to an acrylate-based matrix polymer. Functionalization process temperature, time, functionalization agent ratio, solvent, and catalyst influence on the functionalization degree were measured by thermogravimetric analysis (TGA), elemental analysis, and Fourier-transform infrared (FTIR) spectroscopy. Elevated temperature and average functionalization time led to the highest functionalization degree in the form of a TMSPM monolayer on the particle surface. Three solvents, with and without catalysts, were investigated and two types of functionalized BTONP were selected for composite manufacturing. To this end, the functionalized particles were used to manufacture 10 vol.% BTONP/photopolymer UV light-curable composite suspensions. After solidification of the suspensions by exposure to UV light, the microstructure and dielectric properties of the resulting composites were investigated. It was seen that functionalization improves the dispersion of particles, increases suspension viscosity, and decreases the curing depth and dielectric properties.
Human Hepatocellular Carcinoma Classification from H&E Stained Histopathology Images with 3D Convolutional Neural Networks and Focal Loss Function
Authors: Cinar Umut , Cetin Atalay Rengul , Cetin Yasemin Yardimci
Published: January 2023

This paper proposes a new Hepatocellular Carcinoma (HCC) classification method utilizing a hyperspectral imaging system (HSI) integrated with a light microscope. Using our custom imaging system, we have captured 270 bands of hyperspectral images of healthy and cancer tissue samples with HCC diagnosis from a liver microarray slide. Convolutional Neural Networks with 3D convolutions (3D-CNN) have been used to build an accurate classification model. With the help of 3D convolutions, spectral and spatial features within the hyperspectral cube are incorporated to train a strong classifier. Unlike 2D convolutions, 3D convolutions take the spectral dimension into account while automatically collecting distinctive features during the CNN training stage. As a result, we have avoided manual feature engineering on hyperspectral data and proposed a compact method for HSI medical applications. Moreover, the focal loss function, utilized as a CNN cost function, enables our model to tackle the class imbalance problem residing in the dataset effectively. The focal loss function emphasizes the hard examples to learn and prevents overfitting due to the lack of inter-class balancing. Our empirical results demonstrate the superiority of hyperspectral data over RGB data for liver cancer tissue classification. We have observed that increased spectral dimension results in higher classification accuracy. Both spectral and spatial features are essential in training an accurate learner for cancer tissue classification.