bluuebunny/crossref_metadata_2025 huggingface dataset:
Organic and Inorganic Biocidal Energetic Materials for Agent Defeat Weapons: An Overview and Research Perspectives
Authors: Reverberi Andrea , Meshalkin Valery , Butusov Oleg , Chistyakova Tamara , Ferretti Maurizio , Cardinale Anna , Fabiano Bruno
Published: January 2023

A critical survey concerning biocidal energetics is proposed according to a classification depending on their chemical structure. The need of optimizing the performances of such compounds is an important target for the inertization of biological weapons, requiring a synergy between the thermal effects of combustion/detonation with the biocidal effects of reaction products released into the environment. The main physicochemical aspects related to the synthesis technique, the thermodynamic variables and the antimicrobial activity have been discussed and compared. In particular, different kinds of biocides have been taken into account, with particular attention to the role of iodine as one of the most promising and eco-friendly chemical species to this purpose, in line with the paradigms of environmental protection and the rational utilization of chemicals. Furthermore, the protocols adopted to assess the effectiveness of biocidal agents have been thoroughly examined according to the recent studies proposed by some of the most reputable research groups in the field. Finally, some insights for future investigations are proposed.
Improved Higher Order Compositions for Nonlinear Equations
Authors: Deep Gagan , Argyros Ioannis K.
Published: January 2023

In the present study, two new compositions of convergence order six are presented for solving nonlinear equations. The first method is obtained from the third-order one given by Homeier using linear interpolation, and the second one is obtained from the third-order method given by Traub using divided differences. The first method requires three evaluations of the function and one evaluation of the first derivative, thereby enhancing the efficiency index. In the second method, the computation of a derivative is reduced by approximating it using divided differences. Various numerical experiments are performed which demonstrate the accuracy and efficacy of the proposed methods.
Do Noncoding and Coding Sites in Angiosperm Chloroplast DNA Have Different Mutation Processes?
Authors: Morton Brian R.
Published: January 2023

Fourfold degenerate sites within coding regions and intergenic sites have both been used as estimates of neutral evolution. In chloroplast DNA, the pattern of substitution at intergenic sites is strongly dependent on the composition of the surrounding hexanucleotide composed of the three base pairs on each side, which suggests that the mutation process is highly context-dependent in this genome. This study examines the context-dependency of substitutions at fourfold degenerate sites in protein-coding regions and compares the pattern to what has been observed at intergenic sites. Overall, there is strong similarity between the two types of sites, but there are some intriguing differences. One of these is that substitutions of G and C are significantly higher at fourfold degenerate sites across a range of contexts. In fact, A → T and T → A substitutions are the only substitution types that occur at a lower rate at fourfold degenerate sites. The data are not consistent with selective constraints being responsible for the difference in substitution patterns between intergenic and fourfold degenerate sites. Rather, it is suggested that the difference may be a result of different epigenetic modifications that result in slightly different mutation patterns in coding and intergenic DNA.
Skin Phototype and Disease: A Comprehensive Genetic Approach to Pigmentary Traits Pleiotropy Using PRS in the GCAT Cohort
Authors: Farré Xavier , Blay Natalia , Cortés Beatriz , Carreras Anna , Iraola-Guzmán Susana , de Cid Rafael
Published: January 2023

Human pigmentation has largely been associated with different disease prevalence among populations, but most of these studies are observational and inconclusive. Known to be genetically determined, pigmentary traits have largely been studied by Genome-Wide Association Study (GWAS), mostly in Caucasian ancestry cohorts from North Europe, identifying robustly, several loci involved in many of the pigmentary traits. Here, we conduct a detailed analysis by GWAS and Polygenic Risk Score (PRS) of 13 pigmentary-related traits in a South European cohort of Caucasian ancestry (n = 20,000). We observed fair phototype strongly associated with non-melanoma skin cancer and other dermatoses and confirmed by PRS-approach the shared genetic basis with skin and eye diseases, such as melanoma (OR = 0.95), non-melanoma skin cancer (OR = 0.93), basal cell carcinoma (OR = 0.97) and darker phototype with vitiligo (OR = 1.02), cataracts (OR = 1.04). Detailed genetic analyses revealed 37 risk loci associated with 10 out of 13 analyzed traits, and 16 genes significantly associated with at least two pigmentary traits. Some of them have been widely reported, such as MC1R, HERC2, OCA2, TYR, TYRP1, SLC45A2, and some novel candidate genes C1QTNF3, LINC02876, and C1QTNF3-AMACR have not been reported in the GWAS Catalog, with regulatory potential. These results highlight the importance of the assess phototype as a genetic proxy of skin functionality and disease when evaluating open mixed populations.
Long Non-Coding RNA SNHG4 Expression in Women with Endometriosis: A Pilot Study
Authors: Szaflik Tomasz , Romanowicz Hanna , Szyłło Krzysztof , Smolarz Beata
Published: January 2023

Background: Endometriosis is a chronic disease of the genital organs that mainly affects women of reproductive age. The analysis of long non-coding RNA (lncRNA) in endometriosis is a novel field of science. Recently, attention has been drawn to SNHG4, which is incorrectly expressed in various human diseases, including endometriosis. Aim: The aim of this pilot study was to analyze the expression of lncRNA small nucleolar RNA host gene 4 (SNHG4) and to investigate its significance in endometriosis. Material and methods: LncRNA SNHG4 expression was investigated in paraffin blocks in endometriosis patients (n = 100) and in endometriosis-free controls (n = 100) using a real-time PCR assay. Results: This study revealed a higher expression of SNHG4 in endometriosis patients than in controls. A statistically significant relationship between expression level and SNHG4 was found in relation to The Revised American Society for Reproductive Medicine classification of endometriosis, 1996, in the group of patients with endometriosis. Conclusion: This pilot study has revealed that gene expression in SNHG4 plays an important role in the pathogenesis of endometriosis.
Protocol for the Phase 2 EDELIFE Trial Investigating the Efficacy and Safety of Intra-Amniotic ER004 Administration to Male Subjects with X-Linked Hypohidrotic Ectodermal Dysplasia
Authors: Schneider Holm , Hadj-Rabia Smail , Faschingbauer Florian , Bodemer Christine , Grange Dorothy K. , Norton Mary E. , Cavalli Riccardo , Tadini Gianluca , Stepan Holger , Clarke Angus , Guillén-Navarro Encarna , Maier-Wohlfart Sigrun , Bouroubi Athmane , Porte Florence
Published: January 2023

X-linked hypohidrotic ectodermal dysplasia (XLHED) is a rare genetic disorder characte-rised by abnormal development of the skin and its appendages, such as hair and sweat glands, the teeth, and mucous glands of the airways, resulting in serious, sometimes life-threatening complications like hyperthermia or recurrent respiratory infections. It is caused by pathogenic variants of the ectodysplasin A gene (EDA). Most affected males are hemizygous for EDA null mutations that lead to the absence or inactivity of the signalling protein ectodysplasin A1 (EDA1) and, thus, to the full-blown phenotype with inability to perspire and few if any teeth. There are currently no long-term treatment options for XLHED. ER004 represents a first-in-class protein replacement molecule designed for specific, high-affinity binding to the endogenous EDA1 receptor (EDAR). Its proposed mechanism of action is the replacement of missing EDA1 in yet unborn patients with XLHED. Once bound to EDAR, ER004 activates the EDA/NFκB signalling pathway, which triggers the transcription of genes involved in the normal development of multiple tissues. Following preclinical studies, named-patient use cases demonstrated significant potential of ER004 in affected males treated in utero during the late second and third trimesters of pregnancy. In order to confirm these results, we started the EDELIFE trial, a prospective, open-label, genotype-match controlled, multicentre clinical study to investigate the efficacy and safety of intra-amniotic ER004 administration as a prenatal treatment for male subjects with XLHED. This article summarises the rationale, the study protocol, ethical issues of the trial, and potential pitfalls.
Genomic Analysis of Non-B Nucleic Acids Structures in SARS-CoV-2: Potential Key Roles for These Structures in Mutability, Translation, and Replication?
Authors: Bidula Stefan , Brázda Václav
Published: January 2023

Non-B nucleic acids structures have arisen as key contributors to genetic variation in SARS-CoV-2. Herein, we investigated the presence of defining spike protein mutations falling within inverted repeats (IRs) for 18 SARS-CoV-2 variants, discussed the potential roles of G-quadruplexes (G4s) in SARS-CoV-2 biology, and identified potential pseudoknots within the SARS-CoV-2 genome. Surprisingly, there was a large variation in the number of defining spike protein mutations arising within IRs between variants and these were more likely to occur in the stem region of the predicted hairpin stem-loop secondary structure. Notably, mutations implicated in ACE2 binding and propagation (e.g., ΔH69/V70, N501Y, and D614G) were likely to occur within IRs, whilst mutations involved in antibody neutralization and reduced vaccine efficacy (e.g., T19R, ΔE156, ΔF157, R158G, and G446S) were rarely found within IRs. We also predicted that RNA pseudoknots could predominantly be found within, or next to, 29 mutations found in the SARS-CoV-2 spike protein. Finally, the Omicron variants BA.2, BA.4, BA.5, BA.2.12.1, and BA.2.75 appear to have lost two of the predicted G4-forming sequences found in other variants. These were found in nsp2 and the sequence complementary to the conserved stem-loop II-like motif (S2M) in the 3′ untranslated region (UTR). Taken together, non-B nucleic acids structures likely play an integral role in SARS-CoV-2 evolution and genetic diversity.
The Frequency and Characteristics of Severe Liver-Related Adverse Events in Patients with Chronic Liver Diseases after Vaccination against Severe Acute Respiratory Syndrome Coronavirus 2: A Retrospective Study
Authors: Bat-Erdene Oyunjargal , Miura Kouichi , Maeda Hiroshi , Watanabe Shunji , Tsukui Mamiko , Takaoka Yoshinari , Nomoto Hiroaki , Goka Rie , Morimoto Naoki , Yamamoto Hironori
Published: January 2023

Background: Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is recommended for patients with chronic liver diseases as the vaccine can prevent and/or reduce the severity of SARS-CoV-2 infection. However, we have little information on the often-reported liver-related adverse events (LrAEs) caused by the mRNA vaccine. Methods: We retrospectively investigated the frequency and details of severe LrAEs and changes in liver function tests in patients with chronic liver diseases. Results: Among 431 patients with chronic liver diseases, 416 (96.5%) had received the SARS-CoV-2 vaccine ≥ 2 times. Among the 345 patients included in the analysis, 6 (1.7%) had severe LrAEs; 3 ascites, 2 increases in transaminases, and 1 an increase in total bilirubin. Multivariate analysis demonstrated that cirrhosis and autoimmune disease were risk factors for severe LrAEs. In contrast, the liver function reserve assessed by the Child–Pugh and ALBI scores did not markedly change after vaccination in patients with cirrhosis and/or autoimmune diseases despite a small increase in transaminase levels. Conclusion: SARS-CoV-2 mRNA vaccines, which were used in most of our patients, are safe in patients with chronic liver diseases, but the frequency of severe LrAEs is slightly increased in patients with cirrhosis and/or autoimmune diseases.
Enjoyment or Indulgence? Social Media Service Usage, Social Gratification, Self-Control Failure and Emotional Health
Authors: Liu Yan , Yi Hongfa , Jiang Crystal
Published: January 2023

Social networking site smartphone applications have been widely used among Chinese young adults. However, less is known about their effects on emotional health and the mechanisms through which they function. This study analyzes the relationship between college students’ smartphone social networking service use patterns, social gratification, social media self-control failure, and emotional health. Data was collected from 360 college students in China via application log tracking and a self-administered questionnaire. Structural equation modeling results showed that, after controlling for demographic variables, the use of video social networking site smartphone applications was associated with decreased social gratification, and ultimately, adverse emotional health. Using social networking site smartphone applications late at night exhibited worse emotional health via more social media self-control failure. The implications for designing and using social media applications are discussed.
Harmonious Passion at Work: Personal Resource for Coping with the Negative Relationship between Burnout and Intrinsic Job Satisfaction in Service Employees
Authors: Benitez Miriam , Orgambídez Alejandro , Cantero-Sánchez Francisco J. , León-Pérez Jose M.
Published: January 2023

Research about harmonious passion as a personal resource that can have a protective effect in situations of stress and burnout is scarce but growing. Considering the job demands-resources (JD-R) model, the present study aims to address the above gaps by exploring the moderating role of harmonious passion at work in the relationship between burnout (physical fatigue, cognitive weariness, and emotional exhaustion) and intrinsic job satisfaction. The study sample consisted of 748 workers from service organizations (front-line employees) in southern Spain (Mage = 35.51, SD = 10.06, 52% women). Using statistical program R (R Core Team, 2022), the results of the regression models showed the moderating role of harmonious passion on the negative relationships between physical fatigue and intrinsic job satisfaction. In particular, at high levels of physical fatigue, employees with high scores on harmonious passion at work presented higher levels of intrinsic satisfaction compared with employees with low passion at work. That is, although service employees have high levels of physical fatigue, when they are passionate, they still possess satisfaction with their work. Therefore, our findings extend the JD-R theory by considering harmonious passion as a motivational resource that reduce feelings of burnout in service employees. Hence, it shows the importance of promoting the autonomous internalization of work, (through, i.e., job enrichment), which allows the development of harmonious passion at work and, therefore, increasing intrinsic job satisfaction.
Assisting Homeless Women in a City in Brazil during the COVID-19 Pandemic in the Context of a Street Outreach Office: The Perceptions of Health Professionals
Authors: Barbosa Nayara Gonçalves , Pereira Hellen Aparecida de Azevedo , dos Santos Marcelo Vinicius Domingos Rodrigues , Mendes Lise Maria Carvalho , Gomes-Sponholz Flávia Azevedo , Monteiro Juliana Cristina dos Santos
Published: January 2023

This study aimed to understand the perception of Street Outreach Office professionals regarding the health care offered to homeless women during the COVID-19 pandemic. This is a qualitative and descriptive study developed with nine health professionals of a Street Outreach Office team from a large city in the countryside of São Paulo State (Brazil) from December 2020 to April 2021. Data were obtained through interviews using a semi-structured script with questions about care practices directed to homeless women. The data were analyzed according to content analysis in the thematic modality. Two thematic categories were identified: (i) the reorganization of the Street Outreach Office to meet the demands of the population and (ii) the challenges in caring for homeless women during the pandemic. The activities were intensified with the team’s expansion and distribution of supplies such as masks and alcohol-based hand sanitizers. Our findings showed that the primary problem faced was pregnancy during the pandemic. The lack of material and structural resources and social apparatus to care for homeless women was also evidenced. It was possible to conclude that even with all the adversities, the professionals employed creative strategies, contributing, within their limitations, to the care of homeless women.
Digital Leisure Engagement and Positive Outcomes in the Workplace: A Systematic Literature Review
Authors: Gellmers Joschka , Yan Nanxi
Published: January 2023

The rise of the Internet and information and communication technologies (ICTs) has led to employees spending increasingly more time on non-work-related digital activities at work. A vast literature base exists that is devoted to the potential adverse effect of such activities in the form of cyberloafing. However, not much is known about the positive outcomes of such activities conceptualized as digital leisure. The present review systematically examines current literature on digital leisure activities and how these contribute to positive outcomes in the workplace. Additionally, possible moderating and mediating variables are investigated. Using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) framework, eight peer-reviewed studies were identified that met inclusion criteria. The results indicate that resource recovery processes and employee well-being, as well as employee productivity are positively associated with digital leisure in the workplace. Age was found to moderate the relationship between digital leisure and self-reported employee productivity, while employee satisfaction was found to mediate the relationship between digital leisure and employee productivity. Future research directions are outlined and implications for the work context are discussed.
Renminbi Internationalization Process: A Quantitative Literature Review
Authors: Orăștean Ramona , Mărginean Silvia Cristina
Published: January 2023

As China’s position in the global economy has gradually improved, the importance of debates on the role of the renminbi in the international monetary system has significantly increased. This paper uses bibliometric methods—Bibliometrix R-package and its web-based graphical interface Biblioshiny—applied to data imported from Web of Science and Scopus to investigate and synthesize the renminbi literature published in English between 1995 and 2021. Science mapping offers a visual representation of different networks and clusters of authors’ keywords. The performance analysis, a quantitative evaluation of the most published sources, authors and papers on renminbi internationalization in the last 25 years, shows that the interest on the topic has grown, particularly after 2009 and 2016, respectively. There is also a high degree of concentration in the field, considering that out of the 802 analyzed papers, published in 393 sources, five authors and four journals had the highest impact. The content analysis identifies the main directions in the renminbi internationalization literature and future research questions to further explore this subject. The COVID-19 pandemic and post-Ukraine war era could generate a deeper reform of the international monetary system, in which the Chinese currency will strengthen its global position alongside the US dollar and the euro.
SNAI2 Attenuated the Stem-like Phenotype by Reducing the Expansion of EPCAMhigh Cells in Cervical Cancer Cells
Authors: Liu Xian , Zhang Ni , Chen Qian , Feng Qian , Zhang Yanru , Wang Zhiqiang , Yue Xiong , Li Hongbao , Cui Nan
Published: January 2023

SNAI2 (Snai2) is a zinc-finger transcriptional repressor that belongs to the Snail family. The accumulated evidence suggests that SNAI2 exhibits biphasic effects on regulating a stem-like phenotype in various types of cells, both normal and malignant. In this study, by exogenously expressing SNAI2 in SiHa cells, SNAI2 exhibited the capacity to inhibit a stem-like phenotype in cervical cancer cells. The SNAI2-overexpressing cells inhibited cell growth, tumorsphere formation, tumor growth, enhanced sensitivity to cisplatin, reduced stem cell-related factors’ expression, and lowered tumor initiating frequency. In addition, the EPCAMhigh cells sorted from SiHa cells exhibited an enhanced capacity to maintain a stem-like phenotype. Further study demonstrated that the trans-suppression of EPCAM expression by SNAI2 led to blockage of the nuclear translocation of β-catenin, as well as reduction in SOX2 and c-Myc expression in SiHa and HeLa cells, but induction in SNAI2 knockdown cells (CaSki), which would be responsible for the attenuation of the stem-like phenotype in cervical cancer cells mediated by SNAI2. All of these results demonstrated that SNAI2 could attenuate the stem-like phenotype in cervical cancer cells through the EPCAM/β-catenin axis.
Warburg Effect as a Novel Mechanism for Homocysteine-Induced Features of Age-Related Macular Degeneration
Authors: Samra Yara A. , Zaidi Yusra , Rajpurohit Pragya , Raghavan Raju , Cai Lun , Kaddour-Djebbar Ismail , Tawfik Amany
Published: January 2023

Age-related macular degeneration (AMD) is a major cause of blindness. Recent studies have reported impaired glycolysis in AMD patients with a high lactate/pyruvate ratio. Elevated homocysteine (Hcy) (Hyperhomocysteinemia, HHcy) was observed in several clinical studies, reporting an association between HHcy and AMD. We established the effect of HHcy on barrier function, retinal pigment epithelium (RPE) structure, and induced choroidal neovascularization (CNV) in mice. We hypothesize that HHcy contributes to AMD by inducing a metabolic switch in the mitochondria, in which cells predominantly produce energy by the high rate of glycolysis, or “Warburg”, effect. Increased glycolysis results in an increased production of lactate, cellular acidity, activation of angiogenesis, RPE barrier dysfunction, and CNV. Evaluation of cellular energy production under HHcy was assessed by seahorse analysis, immunofluorescence, and western blot experiments. The seahorse analysis evaluated the extracellular acidification rate (ECAR) as indicative of glycolysis. HHcy showed a significant increase in ECAR both in vivo using (Cystathionine β-synthase) cbs+/− and cbs−/− mice retinas and in vitro (Hcy-treated ARPE-19) compared to wild-type mice and RPE cells. Moreover, HHcy up-regulated glycolytic enzyme (Glucose transporter-1 (GlUT-1), lactate dehydrogenase (LDH), and hexokinase 1 (HK1)) in Hcy-treated ARPE-19 and primary RPE cells isolated from cbs+/+, cbs+/−, and cbs−/− mice retinas. Inhibition of GLUT-1 or blocking of N-methyl-D-aspartate receptors (NMDAR) reduced glycolysis in Hcy-treated RPE and improved albumin leakage and CNV induction in Hcy-injected mice eyes. The current study suggests that HHcy causes a metabolic switch in the RPE cells from mitochondrial respiration to glycolysis during AMD and confirms the involvement of NMDAR in this process. Therefore, targeting Glycolysis or NMDAR could be a novel therapeutic target for AMD.
CRISPR/Cas9-Mediated Enrichment Coupled to Nanopore Sequencing Provides a Valuable Tool for the Precise Reconstruction of Large Genomic Target Regions
Authors: Lopatriello Giulia , Maestri Simone , Alfano Massimiliano , Papa Roberto , Di Vittori Valerio , De Antoni Luca , Bellucci Elisa , Pieri Alice , Bitocchi Elena , Delledonne Massimo , Rossato Marzia
Published: January 2023

Complete and accurate identification of genetic variants associated with specific phenotypes can be challenging when there is a high level of genomic divergence between individuals in a study and the corresponding reference genome. We have applied the Cas9-mediated enrichment coupled to nanopore sequencing to perform a targeted de novo assembly and accurately reconstruct a genomic region of interest. This approach was used to reconstruct a 250-kbp target region on chromosome 5 of the common bean genome (Phaseolus vulgaris) associated with the shattering phenotype. Comparing a non-shattering cultivar (Midas) with the reference genome revealed many single-nucleotide variants and structural variants in this region. We cut five 50-kbp tiled sub-regions of Midas genomic DNA using Cas9, followed by sequencing on a MinION device and de novo assembly, generating a single contig spanning the whole 250-kbp region. This assembly increased the number of Illumina reads mapping to genes in the region, improving their genotypability for downstream analysis. The Cas9 tiling approach for target enrichment and sequencing is a valuable alternative to whole-genome sequencing for the assembly of ultra-long regions of interest, improving the accuracy of downstream genotype–phenotype association analysis.
The Polymorphism Asn680Ser on the FSH Receptor and Abnormal Ovarian Response in Patients with Normal Values of AMH and AFC
Authors: Baldini Giorgio Maria , Catino Assunta , Palini Simone , Sciorio Romualdo , Ferri Daniele , Vinciguerra Marina , Baldini Domenico
Published: January 2023

After the controlled ovarian stimulation (COS), the number of cumulus oocyte complexes collected is lower than predicted. The aim of this study is to understand if there is a possible reason for that deficient ovarian response. It was hypothesized that this is associated with the SNP (single-nucleotide polymorphism) of the FSH receptor (FSHr), specifically c.2039A > G, resulting in Asn680Ser. Two groups of patients were enrolled for this purpose: the normal (n = 36) and abnormal responses (n = 31). To predict the number of retrievable oocytes, according to the anti-Mũllerian hormone (AMH) and the antral follicle count (AFC), the following formula was applied in a log scale: the number of oocytes retrieved = 2.584 − 0.015 × (age) − 0.035 × (FSH) + 0.038 × (AMH) + 0.026 × (AFC). Then, when the number of oocytes collected was less than 50% of the calculated value, it was proposed that the patients result in an abnormal response. DNA sample blood was collected from the women, and then the genetic assessment for the Asn680Ser of the FSHr was evaluated in both groups. The differences between the two categories were statistically analyzed with an independent samples t test, a Mann–Whitney U test and a Chi-squared test. In a patient with an abnormal response, a significant prevalence of the amino acid serine at position 680 of the FSHr compared to the counterpart group (p < 0.05) was detected. In conclusion, according to the results, the genetic evaluation of the FSHr could represent an accurate and predictive feature for patients undergoing assisted reproductive technology treatment.
Jatrophane Diterpenoids from Euphorbia peplus Linn. as Activators of Autophagy and Inhibitors of Tau Pathology
Authors: Yan Ying , Zhou Qi , Ran Xiaoqian , Lu Qingyun , Zhang Cuishan , Peng Mingyou , Tang Lei , Luo Rongcan , Di Yingtong , Hao Xiaojiang
Published: January 2023

Ten jatrophane diterpenoids were isolated from the whole plant Euphorbia peplus Linn. including seven new ones, named euphjatrophanes A-G (labeled compounds 1, 2, 4–8). Their structures were elucidated with a combination of spectroscopic and single-crystal X-ray crystallography, enabling the identification of compounds 3, 9, and 10 as the previously published euphpepluones G, K, and L, respectively. All compounds were evaluated for their bioactivity with flow cytometry in assays of autophagic flux in HM Cherry-GFP-LC3 (human microglia cells stably expressing the tandem monomeric mCherry-GFP-tagged LC3) cells. Euphpepluone K (9) significantly activated autophagic flux, an effect that was verified with confocal analysis. Moreover, cellular assays showed that euphpepluone K (9) induced autophagy and inhibited Tau pathology.
Curcumin Has Beneficial Effects on Lysosomal Alpha-Galactosidase: Potential Implications for the Cure of Fabry Disease
Authors: Monticelli Maria , Hay Mele Bruno , Allocca Mariateresa , Liguori Ludovica , Lukas Jan , Monti Maria Chiara , Morretta Elva , Cubellis Maria Vittoria , Andreotti Giuseppina
Published: January 2023

Fabry disease is a lysosomal storage disease caused by mutations in the GLA gene that encodes alpha-galactosidase (AGAL). The disease causes abnormal globotriaosylceramide (Gb3) storage in the lysosomes. Variants responsible for the genotypic spectrum of Fabry disease include mutations that abolish enzymatic activity and those that cause protein instability. The latter can be successfully treated with small molecules that either bind and stabilize AGAL or indirectly improve its cellular activity. This paper describes the first attempt to reposition curcumin, a nutraceutical, to treat Fabry disease. We tested the efficacy of curcumin in a cell model and found an improvement in AGAL activity for 80% of the tested mutant genotypes (four out of five tested). The fold-increase was dependent on the mutant and ranged from 1.4 to 2.2. We produced evidence that supports a co-chaperone role for curcumin when administered with AGAL pharmacological chaperones (1-deoxygalactonojirimycin and galactose). The combined treatment with curcumin and either pharmacological chaperone was beneficial for four out of five tested mutants and showed fold-increases ranging from 1.1 to 2.3 for DGJ and from 1.1 to 2.8 for galactose. Finally, we tested a long-term treatment on one mutant (L300F) and detected an improvement in Gb3 clearance and lysosomal markers (LAMP-1 and GAA). Altogether, our findings confirmed the necessity of personalized therapies for Fabry patients and paved the way to further studies and trials of treatments for Fabry disease.
Hybrid-Type Transparent Organic Light Emitting Diode with High Contrast Using Switchable Windows
Authors: Choi Seongwook , Lee Chang-Hee , Choi Ju-Hyeok , Choi Sung-Hoon , Kang Bongsoon , Lee Gi-Dong
Published: January 2023

Transparent organic light emitting diode (OLED) display is one of the most promising devices among next-generation information displays because of beneficial characteristics, such as self-emissive and optically clear properties. Nevertheless, in conventional transparent OLED display devices, there are serious intrinsic problems in terms of the transmittance in the dark state because of empty windows in the cell, so the contrast ratio of the transparent OLED display would be deteriorated even though it can exhibit excellent bright state. In general, the transparent mode using the OLED device applies an empty area in each pixel because an emitting device could never reveal the background image, so the transparent OLED should contain the empty area in the pixel for transparent images. This may cause the optical degradation in the dark state. To solve this problem, we propose hybrid-type transparent OLED display modes that apply a liquid crystal (LC) to the transparent window part of the empty space. In this paper, we applied two dichroic LC modes— which use an electrically controlled birefringence (ECB) mode (Heilmeier type) for the polarized mode and a cholesteric LC mode (Guest-Host mode) for the non-polarized mode—to the empty area. In each hybrid mode, we have observed optical performance, including the transmittance in the dark/bright state, contrast ratio and response time as a function of cell parameters. As a result, we confirmed that the dark state and the contrast ratio could be improved by applying the proposed modes without serious decay of the transmittance in the bright state.
Revealing the Tick Microbiome: Insights into Midgut and Salivary Gland Microbiota of Female Ixodes ricinus Ticks
Authors: Wiesinger Anna , Wenderlein Jasmin , Ulrich Sebastian , Hiereth Stephanie , Chitimia-Dobler Lidia , Straubinger Reinhard K.
Published: January 2023

The ectoparasite Ixodes ricinus is an important vector for many tick-borne diseases (TBD) in the northern hemisphere, such as Lyme borreliosis, rickettsiosis, human granulocytic anaplasmosis, or tick-borne encephalitis virus. As climate change will lead to rising temperatures in the next years, we expect an increase in tick activity, tick population, and thus in the spread of TBD. Consequently, it has never been more critical to understand relationships within the microbial communities in ticks that might contribute to the tick’s fitness and the occurrence of TBD. Therefore, we analyzed the microbiota in different tick tissues such as midgut, salivary glands, and residual tick material, as well as the microbiota in complete Ixodes ricinus ticks using 16S rRNA gene amplicon sequencing. By using a newly developed DNA extraction protocol for tick tissue samples and a self-designed mock community, we were able to detect endosymbionts and pathogens that have been described in the literature previously. Further, this study displayed the usefulness of including a mock community during bioinformatic analysis to identify essential bacteria within the tick.
Deep Semantic Segmentation of Angiogenesis Images
Authors: Ibragimov Alisher , Senotrusova Sofya , Markova Kseniia , Karpulevich Evgeny , Ivanov Andrei , Tyshchuk Elizaveta , Grebenkina Polina , Stepanova Olga , Sirotskaya Anastasia , Kovaleva Anastasiia , Oshkolova Arina , Zementova Maria , Konstantinova Viktoriya , Kogan Igor , Selkov Sergey , Sokolov Dmitry
Published: January 2023

Angiogenesis is the development of new blood vessels from pre-existing ones. It is a complex multifaceted process that is essential for the adequate functioning of human organisms. The investigation of angiogenesis is conducted using various methods. One of the most popular and most serviceable of these methods in vitro is the short-term culture of endothelial cells on Matrigel. However, a significant disadvantage of this method is the manual analysis of a large number of microphotographs. In this regard, it is necessary to develop a technique for automating the annotation of images of capillary-like structures. Despite the increasing use of deep learning in biomedical image analysis, as far as we know, there still has not been a study on the application of this method to angiogenesis images. To the best of our knowledge, this article demonstrates the first tool based on a convolutional Unet++ encoder–decoder architecture for the semantic segmentation of in vitro angiogenesis simulation images followed by the resulting mask postprocessing for data analysis by experts. The first annotated dataset in this field, AngioCells, is also being made publicly available. To create this dataset, participants were recruited into a markup group, an annotation protocol was developed, and an interparticipant agreement study was carried out.
Prospective Evaluation of Children with Robin Sequence following Tübingen Palatal Plate Therapy
Authors: Effert Josephine , Uhlig Simone , Wiechers Cornelia , Quante Mirja , Poets Christian F. , Schulz Matthias C. , Reinert Siegmar , Krimmel Michael , Koos Bernd , Weise Christina
Published: January 2023

Background: To assess the long-term functional orthodontic outcome of the Tübingen palatal plate (TPP) in children with Robin sequence (RS) in comparison to age- and sex-matched healthy controls. Methods: Between 09/2019 and 10/2020, we performed orthodontic assessments in 41 children at our Department of Orthodontics. Included were patients with RS (17 non-syndromic; four syndromic) and healthy controls (n = 22, average age in both groups 9.9 y). Facial analyses of 2D images, digital study casts and cephalometric measurements were made. Results: The orthodontic examinations showed no statistically significant group differences regarding functional extraoral, intraoral and pharyngeal parameters, or in skeletal patterns. The relationship between the upper and lower incisors was significantly increased (overjet 4 (2–10) vs. 3 (0–9) mm; p = 0.01) with a significant deficit in the lower face proportions (Jaw Index 4.15 (1.9–9.6) vs. 2.98 (0–9); p = 0.02; Facial convexity angle 157 (149–173) vs. 159 (149–170); p = 0.01). Conclusion: Children with RS treated with the TPP showed normal long-term functional orthodontic outcomes, thanks to the functional adaption of the stomatognathic system. However, soft tissue growth did not completely match skeletal growth, resulting in a more convex facial profile.
Perineural Invasion Predicts Local Recurrence and Poor Survival in Laryngeal Cancer
Authors: Shin Hyun-Il , Bang Joo-In , Kim Geun-Jeon , Sun Dong-Il , Kim Sang-Yeon
Published: January 2023

(1) Background: Perineural invasion (PNI) in head and neck cancer is associated with a poor prognosis; however, the effect of PNI on the prognosis of laryngeal cancer remains under debate. This retrospective study aimed to investigate the effect of PNI in fresh or salvaged larynges on survival in patients who had undergone laryngectomy for squamous cell carcinoma. (2) Methods: This study enrolled 240 patients diagnosed with laryngeal cancer who had undergone open surgery at Seoul St. Mary’s Hospital, Korea. The effects of PNI, other histopathologic factors, and treatment history on survival and recurrence patterns were assessed. (3) Results: PNI was observed in 30 of 240 patients (12.5%). PNI (HR: 3.05; 95% CI: 1.90–4.88; p = 0.01) was a significant predictor of poor 5-year disease-free survival. In fresh cases, preepiglottic invasion (HR: 2.37; 95% CI: 1.45–3.88; p = 0.01) and PNI (HR: 2.96; 95% CI: 1.62–2.96; p = 0.01) were negative prognostic factors for 5-year disease-free survival. In the salvage group, however, only PNI (HR: 2.74; 95% CI: 1.26–5.92; p = 0.01) was a significant predictor of disease-free survival. Further, PNI significantly influenced high local recurrence (HR: 5.02, 95% CI: 1.28–9.66; p = 0.02). (4) Conclusions: Independent of treatment history, PNI is a prognostic factor for poor survival and local recurrence in laryngeal cancer.
Chronic Recurrent Multifocal Osteomyelitis (CRMO) and Juvenile Spondyloarthritis (JSpA): To What Extent Are They Related?
Authors: Koné-Paut Isabelle , Mannes Inès , Dusser Perrine
Published: January 2023

Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory disease occurring mainly in the pediatric age group (before 16 years) and generally presents as a separate entity. Synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome combines osteoarticular and cutaneous involvement, similar to CRMO, and falls into the spectrum of spondyloarthritis (SpA). The fact that a patient can progress from one disease to another raises the question of whether CRMO, like SAPHO, could fall within the spectrum of SpA, ranging from a predominantly osteoarticular form to an enthesitic form with more or less marked skin involvement. In this review, we set out to discuss this hypothesis by highlighting the differences and similarities between CRMO and juvenile SpA in clinical, radiological and pathophysiological aspects. A common hypothesis could potentially consider intestinal dysbiosis as the origin of these different inflammatory diseases. Interindividual factors such as gender, environment, genetics and/or epigenetic background could act as combined disease modifiers. This is why we suggest that pathophysiology, rather than clinical phenotype, be used to reclassify these diseases.
Proximal Femur Fractures in the Elderly—A Novel Modality to Predict Mortality: The Neutrophil-to-Lymphocyte Ratio
Authors: Marom Omer , Paz Inbar , Segal David , Topaz Guy , Abelson Nitzan , Tavdi Alex , Behrbalk Refael , Palmanovich Ezequiel , Ohana Nissim , Yaacobi Eyal
Published: January 2023

Background: The assessment and identification of elderly patients with proximal femur fractures (PFF) who are at high risk of postoperative mortality may influence the treatment decision-making process. The purpose of this study was to determine whether the neutrophil-to-lymphocyte ratio (NLR) could be used to predict postoperative mortality in the elderly population. Methods: A four-year retrospective cohort study of electronic medical records was conducted at a single tertiary care hospital between 2015 and 2018. Data from 1551 patients aged 65 years and older who underwent surgical treatment for PFF were collected and analyzed. The data included complete blood counts at admission, demographic information, underlying illnesses, type of surgery, and postoperative mortality and complications during the first year of follow-up. A survival analysis model was utilized. Results: The mean age was 90.76 ± 1.88 years, 1066 (68.7%) women. Forty-four (2.8%) patients experienced postoperative infection. A higher NLR0 was independently associated with higher all-cause mortality rates in patients who underwent surgical treatment for PFF (p = 0.041). Moreover, the mean NLR0 value was higher when the death occurred earlier after surgery (p < 0.001). Conclusions: When combined with other clinical and laboratory findings, NLR0 levels may serve as a potentially valuable, inexpensive, and reliable prognostic biomarker to improve risk stratification for elderly patients who are candidates for PFF surgery. Furthermore, with additional research, we could potentially develop a treatment algorithm to identify patients at high risk of postoperative mortality.
A Preliminary Investigation of Special Types of Honey Marketed in Morocco
Authors: Mehdi Rania , Zrira Saadia , Vadalà Rossella , Nava Vincenzo , Condurso Concetta , Cicero Nicola , Costa Rosaria
Published: January 2023

Background: This work aimed to perform a comprehensive investigation of organic Moroccan honeys obtained from plants of euphorbia, arbutus, and carob, based on the determination of physico-chemical profiles and volatile fingerprints. Methods: The selected analytical approach involved different techniques, including physico-chemical procedures for determination of humidity, acidity, diastase activity; solid-phase microextraction (SPME) coupled to GC-MS for aromatic fraction exploration; and ICP-MS for multi-element analysis. Results: The results obtained from the physico-chemical analyses were highly comparable to those of other commercial honeys. In 50% of samples investigated, the diastase number was just above the legal limit fixed by Honey Quality Standards. The analysis of the volatile fraction highlighted the presence of numerous compounds from the terpenoid group along with characteristic molecules such as furfural, isophorone, and derivatives. In most cases, VOCs were distinct markers of origin; in others, it was not possible to assess an exclusive source for bees to produce honey. Conclusion: The results contributed to place the three varieties of honey investigated among the commercial products available in the market. Many variables determined returned positive indications about quality and safety of these special honeys.
Ex Situ LIBS Analysis of WEST Divertor Wall Tiles after C3 Campaign
Authors: Jõgi Indrek , Paris Peeter , Bernard Elodie , Diez Mathilde , Tsitrone Emmanuelle , Hakola Antti , Likonen Jari , Vuoriheimo Tomi , Grigore Eduard ,   the WEST Team,   EUROfusion WP PFC/PWIE Contributors
Published: January 2023

Fuel retention monitoring in tokamak walls requires the development of remote composition analysis methods such as laser-induced breakdown spectroscopy (LIBS). The present study investigates the feasibility of the LIBS method to analyse the composition and fuel retention in three samples from WEST divertor erosion marker tiles after the experimental campaign C3. The investigated samples originated from tile regions outside of strong erosion and deposition regions, where the variation of thin deposit layers is relatively small and facilitates cross-comparison between different analysis methods. The depth profiles of main constituents W, Mo and C were consistent with depth profiles determined by other composition analysis methods, such as glow-discharge optical emission spectroscopy (GDOES) and secondary ion mass spectrometry (SIMS). The average LIBS depth resolution determined from depth profiles was 100 nm/shot. The averaging of the spectra collected from multiple spots of a same sample allowed us to improve the signal-to-noise ratio, investigate the presence of fuel D and trace impurities such as O and B. In the investigated tile regions with negligible erosion and deposition, these impurities were clearly detectable during the first laser shot, while the signal decreased to noise level after a few subsequent laser shots at the same spot. LIBS investigation of samples originating from the deposition regions of tiles may further clarify LIBS’ ability to investigate trace impurities.
Severe Fungal Asthma: A Role for Biologics and Inhaled Antifungals
Authors: Moss Richard B.
Published: January 2023

Allergic asthma has traditionally been treated with inhaled and systemic glucocorticosteroids. A continuum of allergic fungal airways disease associated with Aspergillus fumigatus colonization and/or atopic immune responses that encompasses fungal asthma, severe asthma with fungal sensitization and allergic bronchopulmonary aspergillosis is now recognized along a phenotypic severity spectrum of T2-high immune deviation lung disease. Oral triazoles have shown clinical, anti-inflammatory and microbiologic efficacy in this setting; in the future inhaled antifungals may improve the therapeutic index. Humanized monoclonal antibody biologic agents targeting T2-high disease also show efficacy and promise of improved control in difficult cases. Developments in these areas are highlighted in this overview.
Ecological Environment Dynamic Monitoring and Driving Force Analysis of Karst World Heritage Sites Based on Remote-Sensing: A Case Study of Shibing Karst
Authors: Zhang Ning , Xiong Kangning , Xiao Hua , Zhang Juan , Shen Chuhong
Published: January 2023

The evaluation and monitoring of the ecological environment quality of heritage sites can help provide sustainable and healthy development strategies for heritage management organizations. In this study, an ecological evaluation model based on the remote sensing ecological index (RSEI) was used to measure the ecological environment of the Shibing Karst World Heritage Site and its buffer zone and the Moran index and geographic probe model were combined to quantify the ecological environment. The results show that, (1) from 2013 to 2020, the ecological environment quality of the heritage site and buffer zone was moderate to high and the mean RSEI values in the three periods studied were 0.720, 0.723 and 0.742, showing an overall upward and improving trend; (2) ecological environment quality grades of moderate and good accounted for more than 70% of the area, the distribution pattern of ecological environment quality is significantly better at the heritage site than in the buffer zone and the southwest is better than the northeast; (3) the Moran index increased from 0.600 in 2013 to 0.661 in 2020, residing in the first and third quadrants, respectively, with significantly spatial aggregation; and (4) greenness and humidity were shown to play a positive feedback role on the ecological environment quality and the spatial influence ability of humidity and dryness was greater. Overall, the RSEI is an effective method of evaluating and monitoring the ecological environment quality of heritage sites, the ecological environment quality of the Karst heritage site in Shibing is in a steady state of improvement and the relevant departments of heritage conservation need to further coordinate the relationship between conservation and development to promote the sustainable development of the heritage site and provide effective solutions for the monitoring of other Karst World Heritage sites.