bluuebunny/crossref_metadata_2025 huggingface dataset:
On Noble and Inherited Virtues: Discussions of the Semitic Race in the Levant and Egypt, 1876–1918
Authors: Bashkin Orit
Published: July 2021

This article examines new notions about race, ethnicity and language current in modern movements of Arabic literary and cultural revival. I argue that the Arab print market before World War I adopted the racial category of the Semite as highly relevant to Arab ethnicity and language, but the philological and literary significations of the term subverted the negative constructions affiliated with the Semitic races in Western race theories. Combining elements from the study of linguistics, religion, and political philosophy, Arabic journals, books, and works of historical fiction, created a Semitic and Arab universe, populated by grand historical figures and mesmerizing literary and cultural artifacts. Such publications advanced the notion that the Arab races belonged to Semitic cultures and civilizations whose achievements should be a source of pride and rejuvenation. These printed products also conveyed the idea that the Arabic language and Arab ethnicity can create ecumenical and pluralistic conversations. Motivated by the desire to find a rational explanation to phenomena they identified with cultural and literary decline, Arab authors also hoped to reconstruct the modes with which their Semitic and Arab ancestors dealt with questions relating to community and civilization. By publishing scientific articles on philology, literature, and linguistics, the print media illustrated that Arabic itself was a language capable of expressing complex scientific concepts and arguments.
The Forerunners on Heritage Stones Investigation: Historical Synthesis and Evolution
Authors: Freire-Lista David M.
Published: July 2021

Human activity has required, since its origins, stones as raw material for carving, construction and rock art. The study, exploration, use and maintenance of building stones is a global phenomenon that has evolved from the first shelters, manufacture of lithic tools, to the construction of houses, infrastructures and monuments. Druids, philosophers, clergymen, quarrymen, master builders, naturalists, travelers, architects, archaeologists, physicists, chemists, curators, restorers, museologists, engineers and geologists, among other professionals, have worked with stones and they have produced the current knowledge in heritage stones. They are stones that have special significance in human culture. In this way, the connotation of heritage in stones has been acquired over the time. That is, the stones at the time of their historical use were simply stones used for a certain purpose. Therefore, the concept of heritage stone is broad, with cultural, historic, artistic, architectural, and scientific implications. A historical synthesis is presented of the main events that marked the use of stones from prehistory, through ancient history, medieval times, and to the modern period. In addition, the main authors who have written about stones are surveyed from Ancient Roman times to the middle of the twentieth century. Subtle properties of stones have been discovered and exploited by artists and artisans long before rigorous science took notice of them and explained them.
Variation in Obsessive-Compulsive Disorder Symptoms and Treatments: A Side Effect of COVID-19
Authors: Liu Wuqianhui , Zhang Haitao , He Yuan
Published: July 2021

The Coronavirus Disease 2019 (COVID-19) exerts variable impact on patients with obsessive compulsive disorders (OCD). There remains a challenge to determine the extent to which OCD is exacerbated due to the pandemic. Therefore, our aim is to explicate the latest researching progress of OCD under COVID-19 based on a review of 15 existing articles. Our review confirms the prevalence of OCD exacerbation in different age groups and particular symptoms. However, it also reveals nonconformity among research, lack of investigation in OCD treatment, and imbalance in OCD symptoms research. Further, we discuss the probable reasons of the exacerbation and current situation of OCD treatments. Finally, based on our discussion, we offer suggestions on how to manage OCD under the new circumstance, including the introduction of new policies, the use of communications technology, the improvement of researching methods, and possible angles for further research.
The Affective Domain—A Program to Foster Social-Emotional Orientation in Novice Physical Education Teachers
Authors: Zach Sima , Rosenblum Hily
Published: July 2021

The present study aimed to assess the influence of an emotional-based program for novice physical education teachers on their perception of the affective domain in teaching, and the influence of the program on their social-emotional orientation. Thirty-two physical educators in their induction year participated. Instrumentations included reflective assignments: individual tasks, a group artwork task, short videos containing student–teacher scenarios, and summary reflections. The study covered tasks that contained a variety of emotional expressions—verbalizing, acting, and art creation. Content analysis was conducted for each of the assignments. The results indicate that the participants felt that they gradually developed an awareness of the role of emotions in their practice. In addition to personal gain, they felt that their empathy for others—especially their students—was enhanced. These results highlight the important influence that an emotional-based program has on physical educators’ social-emotional orientation.
Reciprocal Relationships between Sleep Problems and Problematic Smartphone Use in Taiwan: Cross-Lagged Panel Study
Authors: Chen Ji-Kang , Wu Wen-Chi
Published: July 2021

Prior studies have suggested a link between sleep problems and problematic smartphone use. However, the causal relationships between these two variables have not been identified, particularly in adolescence. Utilizing longitudinal panel data from Taiwan, this report examined the temporal relationships between sleep problems and problematic smartphone use among adolescents. One thousand and thirty-nine students (Grades 7–12) were surveyed at two-time points with a 6-month interval. The results of cross-lagged panel analysis showed that sleep problems at Time 1 significantly predicted problematic smartphone use at Time 2. Problematic smartphone use at Time 1 also significantly predicted sleep problems at Time 2. These findings applied to boys and girls and suggested that temporal relationships between sleep problems and problematic smartphone use among teenagers are reciprocal. Accordingly, increasing sleep quality may prevent future problematic smartphone use, while reducing problematic smartphone use may prevent sleep problems in adolescents.
Effectiveness of Swimming Program in Adolescents with Down Syndrome
Authors: Naczk Alicja , Gajewska Ewa , Naczk Mariusz
Published: July 2021

The aim of this study was to estimate the influence of a 33-week swimming program on aerobic capacity, muscle strength, balance, flexibility, and body composition of adolescents with Down syndrome (DS). Twenty-two adolescents diagnosed with DS were randomly allocated into the training group (T) and the control group (C). The T group participated in 33 weeks of water-based exercise and a swimming program while the control group maintained their normal daily activity. Following thirty-three weeks of swimming program, body mass, body fat, and BMI of the T group decreased significantly (from 56.8 ± 7.97 kg to 55.0 ± 7.11 kg, from 15.1 ± 4.47 kg to 13.2 ± 3.92 kg, and from 25.1 ± 2.37 to 24.0 ± 2.05, respectively) while a significant increase was recorded in C (from 57.3 ± 8.43 kg to 59.7 ± 8.29 kg, from 14.5 ± 2.76 kg to 16.0 ± 3.11 kg, and from 25.4 ± 2.46 to 26.0 ± 2.72, respectively). Moreover, significant improvement in aerobic capacity in the T group was noted; VO2max (mL/kg/min) increased by 16.3% in T and decreased by 4.8% in C. Improvement in static arm strength, trunk strength and endurance/functional strength were noted in T, while the parameters did not change in C. The speed of arm movement, balance and flexibility did not change following the intervention. Also, the aquatic skills improved significantly in the training group. Changes in C were not significant. The results of our study indicate that 33-week swimming program significantly improved health status and swimming skills in adolescents with DS.
In-Treatment Changes in Quality of Life-Related Variables in Therapeutic Communities for Cocaine Abusers: Are These Changes Associated with Clinical Outcomes?
Authors: González-Saiz Francisco , Vergara-Moragues Esperanza
Published: July 2021

Background: Few studies have explored changes in quality of life during the first three months of admission to a therapeutic community for addictions. The objective of this study was to determine the relationship between these changes and treatment outcomes at discharge. Methods: We undertook a prospective longitudinal study of 142 cocaine-dependent patients treated at a therapeutics community. All of these patients reached the 3-month evaluation and were subsequently followed until discharge. All participants completed the following measures: Health-Related Quality of Life for Drug Abusers Test; Beck Depression Inventory; State–Trait Anxiety Inventory; Opiate Treatment Index; Dual Diagnosis and Discharge Checklist. Results: At the 3-month assessment, scores on the Health-Related Quality of Life for Drug Abusers Test had increased significantly (Cohen’s d: 0.92), while scores on the Opiate Treatment Index (Cohen’s d: 0.86) and Beck Depression Inventory (Cohen’s d: 0.20) scales both decreased significantly. A higher proportion of the patients considered to have achieved “clinically relevant” treatment outcomes at discharge versus those without clinically relevant outcomes were considered “recovered” according to the Reliable Change Index. Conclusions: An improvement in quality of life-related variables from baseline to the 3-month assessment was associated with better outcomes at discharge from the therapeutic community. The findings of this study may help us to optimise therapeutic interventions.
The Relationship between Individual and Family Characteristics and Cyberbullying Exposure in a Nationally Representative Sample of School-Aged Children Living in Serbia
Authors: Rakic Ljiljana , Santric-Milicevic Milena , Nikolic Dejan , Vasic Milena , Babic Uros , Todorovic Jovana , Terzic-Supic Zorica , Milenkovic Sanja
Published: July 2021

The study provides evidence on the individual and family factors as potential predictors (odds ratio—OR and 95% CI) of cyber-violence among school-aged children (11–17 years old) from 64 schools participating in the 2017 Serbian Study on health behavior in school-age children (HBSC). The standardized international HBSC research protocol was used. The study population was the nationally representative sample of 3267 students of V and VII grades of primary and I grade of secondary schools in Serbia. Potential predictors for the probability of occurrence vs. non-occurrence of cyberbullying exposure at least once and multiple times were identified among 24 explanatory variables, including the individual characteristics and family context. The cyberbullying exposure was more prevalent among girls than among boys of school-age, i.e., over one in seven girls and one in ten boys were exposed to cyberbullying. Over one in seven students at age 13 years and almost every seventh student at grade I of the gymnasium were exposed to cyberbullying. There were more students exposed to at least one cyberbullying than to multiple cyberbullying. Potential predictors of exposure to cyberbullying are gender, opinion of the family’s affluence status, fathers’ employment, communication with father, and family support. The study compensates for the evidence of cyberbullying in Serbia, which could help raise awareness, inform national and international stakeholders in the region and enable their efforts and strengthen cooperation in ending cyberbullying. This study’s findings could inform the development of an intervention program aimed at families and various professionals involved in protecting and improving school-age children’s health and well-being.
Guided Tissue Regeneration Treatment Yields Better Results in Class II Furcations in the Mandible Than in the Maxilla: A Retrospective Study
Authors: Dorj Odontuya , Lee Wei-Fang , Salamanca Eisner , Pan Yu-Hwa , Wu Yi-Fan , Hsu Yung-Szu , Lin Jerry C. Y. , Lin Yu-De , Choy Cheuk-Sing , Chang Wei-Jen
Published: July 2021

Absorbable porcine collagen membrane with a bovine bone graft can be considered for regenerative treatment in periodontal class II furcation defects. We evaluated the clinical efficacy of guided tissue regeneration (GTR) treatment with bovine bone xenograft and a porcine collagen membrane in molars with class II furcations. Probing depth (PD), clinical attachment level (CAL), and bone level (BL) were recorded at baseline and at 3, 6, and 9 months postoperatively. Thirty class II furcation defects from the lower and upper molars were assessed. Significant improvements in PD and CAL were observed from baseline to 9 months in all groups (p < 0.01). BL improved in all groups except group A in the upper molars in radiographic assessment (p < 0.05). The lower and upper molars showed PD reduction of 50.5% ± 7.44% and 46.2% ± 11.2%, respectively, at 9 months (p = 0.044). In furcations of 1–3 mm, the lower and upper molars showed PD reductions of 51.2% ± 4.49% and 36.5% ± 16.14%, respectively (p = 0.035). The lower and upper molars showed a CAL gain of 51.1% ± 4.64% and 33.6% ± 18.8%, respectively (p = 0.037). Thus, GTR with bovine bone graft and porcine collagen membrane yielded good results in class II furcations, with better results in the lower than in the upper molars.
Candida Chorioamnionitis in Mothers with Gestational Diabetes Mellitus: A Report of Two Cases
Authors: Shazniza Shaaya Elia , Halim Siti Atiqah Abdul , Leong Ka Wen , Ku Kevin Boon Ping , Lim Pei Shan , Tan Geok Chin , Wong Yin Ping
Published: July 2021

Background:Candida chorioamnionitis is rarely encountered, even though vulvovaginal candidiasis incidence is about 15%. Interestingly, it has characteristic gross and histological findings on the umbilical cord that are not to be missed. Case Report: We report two cases of Candida chorioamnionitis with presence of multiple yellowish and red spots of the surface of the umbilical cord. Microscopically, these consist of microabscesses with evidence of fungal yeasts and pseudohyphae. The yeasts and pseudohyphae were highlighted by periodic acid– Schiff and Grocott methenamine silver histochemical stains. Both cases were associated with a history of gestational diabetes mellitus. Discussion: Peripheral funisitis is a characteristic feature of Candida chorioamnionitis. It is associated with high risk of adverse perinatal and neonatal outcomes, such as preterm delivery, stillbirth and neonatal death. We recommend careful examination of the umbilical cord of mothers with gestational diabetes mellitus.
Comparison Study of the Histomorphometric Results after Socket Preservation with PRF and Allograft Used for Socket Preservation—Randomized Controlled Trials
Authors: Ivanova Vasilena , Chenchev Ivan , Zlatev Stefan , Mijiritsky Eitan
Published: July 2021

The aim of the present clinical study was to assess and compare the histomorphometric results and efficacy of freeze-dried bone allograft (FDBA) in combination with platelet-rich fibrin (PRF), and PRF as a sole grafting material for socket preservation. Ninety patients in need of tooth extraction and implant restoration were included in this study. The participants were randomly divided into three groups based on post-extraction clinical protocol: socket preservation procedure with allograft in combination with a PRF membrane (PRFm), PRF as a sole grafting material, and a control group. A total of 90 implants were placed four months post-extraction. During the surgical re-entry a bone biopsy was harvested with a trephine drill. Histological samples were prepared and analyzed for percentage vital bone and connective tissue. One-way ANOVA with Bonferroni post-hoc analysis were used to assess the results. Both test groups revealed a significantly higher percentage of vital bone formation compared to the control group. No statistically significant differences regarding vital bone formation and connective tissue quantity between the tested groups were observed (FDBA + PRFm: 3.29 ± 13.03%; and PRF: 60.79 ± 9.72%). From a clinical and histological point of view, both materials in the test groups are suitable for the filling of post-extraction sockets without bone defects. Both of the tested groups revealed a significantly higher percentage of vital bone formation compared to the control group.
Please Like Me: Ingratiation as a Moderator of the Impact of the Perception of Organizational Politics on Job Satisfaction
Authors: Fitriastuti Triana , Larasatie Pipiet , Vanderstraeten Alex
Published: July 2021

Drawing from the negative impacts of the perception of organizational politics (POP) on the literature on organizational outcomes, the model proposed in this study examines a nonlinear relationship of POP on job satisfaction. In a similar way, ingratiation as a moderator variable is tested. Based on a survey of 240 state-owned enterprise employees in Indonesia, this study finds that POP exhibits an inverted U-shaped relationship with job satisfaction. Low and high levels of POP have a negative impact on job satisfaction. Nevertheless, our most intriguing finding is that ingratiation behavior not only strengthens POP’s effects on job satisfaction, but can also alter the direction of the relationship in which its shape is represented by a U-shape. This shape indicates that the employees who engage in high levels of ingratiation as a coping mechanism and adaptive strategy tend to do so when they perceive high degrees of POP. These results are then discussed from a cross-cultural perspective as an attempt to explain the legitimacy of ingratiation in Indonesia.
Seasoned Equity Offerings and Differences in Share-Price Impact by Firm Categories
Authors: Abdullah Saeed Md. , Zaby Simon
Published: July 2021

The seasoned equity offering (SEO) market plays a significant role in the economic development of a country by providing liquidity for ongoing commercialization and innovation. This study is a comprehensive analysis of 149 SEOs and their effect on share prices in Thailand between 2009 and 2019. SEOs are categorized based on their time categories (early, mid, and grown) and volume categories (small, medium, big, and super). Using the event study methodology (multi-factor model), we find that most SEOs under both categories have a negative cumulative abnormal return (CAR) in the window period. Ranking the types of SEOs reveals that grown SEOs have the highest proportion of negative CAR under the time categories. Under the volume categories, medium SEOs show the largest share. The results were validated by regression assumption tests provided by Gnu Regression, Econometrics and Time-series Library, and correspond to established theories. The paper also contains an extensive literature review of studies examining the link between SEOs and share-price development. Our findings have important implications for corporations, investors, and regulatory bodies and can thus help in increasing market confidence for sustainable corporate funding.
HopA1 Effector from Pseudomonas syringae pv syringae Strain 61 Affects NMD Processes and Elicits Effector-Triggered Immunity
Authors: Dahale Shraddha K. , Ghosh Daipayan , Ingole Kishor D. , Chugani Anup , Kim Sang Hee , Bhattacharjee Saikat
Published: July 2021

Pseudomonas syringae-secreted HopA1 effectors are important determinants in host range expansion and increased pathogenicity. Their recent acquisitions via horizontal gene transfer in several non-pathogenic Pseudomonas strains worldwide have caused alarming increase in their virulence capabilities. In Arabidopsis thaliana, RESISTANCE TO PSEUDOMONAS SYRINGAE 6 (RPS6) gene confers effector-triggered immunity (ETI) against HopA1pss derived from P. syringae pv. syringae strain 61. Surprisingly, a closely related HopA1pst from the tomato pathovar evades immune detection. These responsive differences in planta between the two HopA1s represents a unique system to study pathogen adaptation skills and host-jumps. However, molecular understanding of HopA1′s contribution to overall virulence remain undeciphered. Here, we show that immune-suppressive functions of HopA1pst are more potent than HopA1pss. In the resistance-compromised ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1) null-mutant, transcriptomic changes associated with HopA1pss-elicited ETI are still induced and carry resemblance to PAMP-triggered immunity (PTI) signatures. Enrichment of HopA1pss interactome identifies proteins with regulatory roles in post-transcriptional and translational processes. With our demonstration here that both HopA1 suppress reporter-gene translations in vitro imply that the above effector-associations with plant target carry inhibitory consequences. Overall, with our results here we unravel possible virulence role(s) of HopA1 in suppressing PTI and provide newer insights into its detection in resistant plants.
Antifungal Activity and Biosynthetic Potential of New Streptomyces sp. MW-W600-10 Strain Isolated from Coal Mine Water
Authors: Siupka Piotr , Hansen Frederik Teilfeldt , Schier Aleksandra , Rocco Simone , Sørensen Trine , Piotrowska-Seget Zofia
Published: July 2021

Crop infections by fungi lead to severe losses in food production and pose risks for human health. The increasing resistance of pathogens to fungicides has led to the higher usage of these chemicals, which burdens the environment and highlights the need to find novel natural biocontrol agents. Members of the genus Streptomyces are known to produce a plethora of bioactive compounds. Recently, researchers have turned to extreme and previously unexplored niches in the search for new strains with antimicrobial activities. One such niche are underground coal mine environments. We isolated the new Streptomyces sp. MW-W600-10 strain from coal mine water samples collected at 665 m below ground level. We examined the antifungal activity of the strain against plant pathogens Fusarium culmorum DSM62188 and Nigrospora oryzae roseF7. Furthermore, we analyzed the strain’s biosynthetic potential with the antiSMASH tool. The strain showed inhibitory activity against both fungi strains. Genome mining revealed that it has 39 BGCs, among which 13 did not show similarity to those in databases. Additionally, we examined the activity of the Streptomyces sp. S-2 strain isolated from black soot against F. culmorum DSM62188. These results show that coal-related strains could be a source of novel bioactive compounds. Future studies will elucidate their full biotechnological potential.
Transcriptome Analysis and miRNA Target Profiling at Various Stages of Root-Knot Nematode Meloidogyne incognita Development for Identification of Potential Regulatory Networks
Authors: Mani Vimalraj , Assefa Awraris Derbie , Hahn Bum-Soo
Published: July 2021

Root-knot nematodes (RKNs) are a group of plant-parasitic nematodes that cause damage to various plant species and extensive economical losses. In this study, we performed integrated analysis of miRNA and mRNA expression data to explore the regulation of miRNA and mRNA in RKNs. In particular, we aimed to elucidate the mRNA targets of Meloidogyne incognita miRNAs and variations of the RKN transcriptome during five stages of its life cycle. Stage-wise RNA sequencing of M. incognita resulted in clean read numbers of 56,902,902, 50,762,456, 40,968,532, 47,309,223, and 51,730,234 for the egg, J2, J3, J4, and female stages, respectively. Overall, stage-dependent mRNA sequencing revealed that 17,423 genes were expressed in the transcriptome of M. incognita. The egg stage showed the maximum number of transcripts, and 12,803 gene transcripts were expressed in all stages. Functional Gene Ontology (GO) analysis resulted in three main GO classes: biological process, cellular components, and molecular function; the detected sequences were longer than sequences in the reference genome. Stage-wise selected fragments per kilobase of transcript per million mapped reads (FPKM) values of the top 10 stage-specific and common mRNAs were used to construct expression profiles, and 20 mRNAs were validated through quantitative real-time PCR (qRT-PCR). Next, we used three target prediction programs (miRanda, RNAhybrid, and PITA) to obtain 2431 potential target miRNA genes in RKNs, which regulate 8331 mRNAs. The predicted potential targets of miRNA were generally involved in cellular and metabolic processes, binding of molecules in the cell, membranes, and organelles. Stage-wise miRNA target analysis revealed that the egg stage contains heat shock proteins, transcriptional factors, and DNA repair proteins, whereas J2 includes DNA replication, heat shock, and ubiquitin-conjugating pathway-related proteins; the J3 and J4 stages are represented by the major sperm protein domain and translation-related proteins, respectively. In the female stage, we found proteins related to the maintenance of molybdopterin-binding domain-containing proteins and ubiquitin-mediated protein degradation. In total, 29 highly expressed stage-specific mRNA-targeting miRNAs were analyzed using qRT-PCR to validate the sequence analysis data. Overall, our findings provide new insights into the molecular mechanisms occurring at various developmental stages of the RKN life cycle, thus aiding in the identification of potential control strategies.
Liver Bile Acid Changes in Mouse Models of Alzheimer’s Disease
Authors: Kaur Harpreet , Seeger Drew , Golovko Svetlana , Golovko Mikhail , Combs Colin Kelly
Published: July 2021

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive cognitive impairment. It is hypothesized to develop due to the dysfunction of two major proteins, amyloid-β (Aβ) and microtubule-associated protein, tau. Evidence supports the involvement of cholesterol changes in both the generation and deposition of Aβ. This study was performed to better understand the role of liver cholesterol and bile acid metabolism in the pathophysiology of AD. We used male and female wild-type control (C57BL/6J) mice to compare to two well-characterized amyloidosis models of AD, APP/PS1, and AppNL-G-F. Both conjugated and unconjugated primary and secondary bile acids were quantified using UPLC-MS/MS from livers of control and AD mice. We also measured cholesterol and its metabolites and identified changes in levels of proteins associated with bile acid synthesis and signaling. We observed sex differences in liver cholesterol levels accompanied by differences in levels of synthesis intermediates and conjugated and unconjugated liver primary bile acids in both APP/PS1 and AppNL-G-F mice when compared to controls. Our data revealed fundamental deficiencies in cholesterol metabolism and bile acid synthesis in the livers of two different AD mouse lines. These findings strengthen the involvement of liver metabolism in the pathophysiology of AD.
In Vitro and In Silico Characterization of an Antimalarial Compound with Antitumor Activity Targeting Human DNA Topoisomerase IB
Authors: Soren Bini Chhetri , Babu Dasari Jagadish , Ottaviani Alessio , Messina Beatrice , Andreotti Giada , Romeo Alice , Iacovelli Federico , Falconi Mattia , Desideri Alessandro , Fiorani Paola
Published: July 2021

Human DNA topoisomerase IB controls the topological state of supercoiled DNA through a complex catalytic cycle that consists of cleavage and religation reactions, allowing the progression of fundamental DNA metabolism. The catalytic steps of human DNA topoisomerase IB were analyzed in the presence of a drug, obtained by the open-access drug bank Medicines for Malaria Venture. The experiments indicate that the compound strongly and irreversibly inhibits the cleavage step of the enzyme reaction and reduces the cell viability of three different cancer cell lines. Molecular docking and molecular dynamics simulations suggest that the drug binds to the human DNA topoisomerase IB-DNA complex sitting inside the catalytic site of the enzyme, providing a molecular explanation for the cleavage-inhibition effect. For all these reasons, the aforementioned drug could be a possible lead compound for the development of an efficient anti-tumor molecule targeting human DNA topoisomerase IB.
Oxytocin Signaling Acts as a Marker for Environmental Stressors in Zebrafish
Authors: Chuang Hsin-Ju , Chang Chun-Yung , Ho Huai-Ping , Chou Ming-Yi
Published: July 2021

The oxytocin system plays a role in stress responses and behavior modulation. However, the effects of oxytocin signaling on stress adaptation remain unclear. Here, we demonstrated the roles of oxytocin signaling as a biomarker under stress conditions in the peripheral tissues (the gills) and central nervous system (the brain). All the environmental stressors downregulated the expression of oxytocin receptors in the gills, and the alteration of the expression of oxytocin receptors was also found in the brain after the acidic (AC) and high-ammonia (HA) treatments. The number of oxytocin neurons was increased after double-deionized (DI) treatment. By transgenic line, Tg(oxtl:EGFP), we also investigated the projections of oxytocin neurons and found oxytocin axon innervations in various nuclei that might regulate the anxiety levels and aggressiveness of adult zebrafish under different environmental stresses. The oxytocin system integrates physiological responses and behavioral outcomes to ensure environmental adaptation in adult zebrafish. Our study provides insight into oxytocin signaling as a stress indicator upon environmental stressors.
Oxidative Stress and Inflammatory Biomarkers for the Prediction of Severity and ICU Admission in Unselected Patients Hospitalized with COVID-19
Authors: Ducastel Morgane , Chenevier-Gobeaux Camille , Ballaa Yassine , Meritet Jean-François , Brack Michel , Chapuis Nicolas , Pene Frédéric , Carlier Nicolas , Szwebel Tali-Anne , Roche Nicolas , Terrier Benjamin , Borderie Didier
Published: July 2021

Objective: We aimed to investigate the prognostic performances of oxidative stress (OS), inflammatory and cell activation biomarkers measured at admission in COVID-19 patients. Design: retrospective monocentric study. Setting: patients with suspected SARS-CoV-2 infection (COVID-19) admitted to the hospital. Patients: One hundred and sixty documented and unselected COVID-19-patients. Disease severity (from mild to critical) was scored according to NIH’s classification. Interventions: none. Measurements and main results: We measured OS biomarkers (thiol, advanced oxidation protein products (AOPP), ischemia-modified albumin (IMA)), inflammation biomarkers (interleukin-6 (IL-6), presepsin) and cellular activation biomarkers (calprotectin) in plasma at admission. Thiol concentrations decreased while IMA, IL-6, calprotectin and PSEP increased with disease severity in COVID-19 patients and were associated with increased O2 needs and ICU admission. The best area under the receiver-operating-characteristics curve (AUC) for the prediction of ICU admission was for thiol (AUC = 0.762). A thiol concentration <154 µmol/L was predictive for ICU admission (79.7% sensitivity, 64.6% specificity, 58.8% positive predictive value, 78.9% negative predictive value). In a stepwise logistic regression, we found that being overweight, having dyspnoea, and thiol and IL-6 plasmatic concentrations were independently associated with ICU admission. In contrast, calprotectin was the best biomarker to predict mortality (AUC = 0.792), with an optimal threshold at 24.1 mg/L (94.1% sensitivity, 64.9% specificity, 97.1% positive predictive value and 98.9% negative predictive value), and survival curves indicated that high IL-6 and calprotectin concentrations were associated with a significantly increased risk of mortality. Conclusions: Thiol measurement at admission is a promising tool to predict ICU admission in COVID-19-patients, whereas IL-6 and calprotectin measurements effectively predict mortality.
Elevated Circulating and Placental SPINT2 Is Associated with Placental Dysfunction
Authors: Murphy Ciara N. , Walker Susan P. , MacDonald Teresa M. , Keenan Emerson , Hannan Natalie J. , Wlodek Mary E. , Myers Jenny , Briffa Jessica F. , Romano Tania , Roddy Mitchell Alexandra , Whigham Carole-Anne , Cannon Ping , Nguyen Tuong-Vi , Kandel Manju , Pritchard Natasha , Tong Stephen , Kaitu’u-Lino Tu’uhevaha J.
Published: July 2021

Biomarkers for placental dysfunction are currently lacking. We recently identified SPINT1 as a novel biomarker; SPINT2 is a functionally related placental protease inhibitor. This study aimed to characterise SPINT2 expression in placental insufficiency. Circulating SPINT2 was assessed in three prospective cohorts, collected at the following: (1) term delivery (n = 227), (2) 36 weeks (n = 364), and (3) 24–34 weeks’ (n = 294) gestation. SPINT2 was also measured in the plasma and placentas of women with established placental disease at preterm (<34 weeks) delivery. Using first-trimester human trophoblast stem cells, SPINT2 expression was assessed in hypoxia/normoxia (1% vs. 8% O2), and following inflammatory cytokine treatment (TNFα, IL-6). Placental SPINT2 mRNA was measured in a rat model of late-gestational foetal growth restriction. At 36 weeks, circulating SPINT2 was elevated in patients who later developed preeclampsia (p = 0.028; median = 2233 pg/mL vs. controls, median = 1644 pg/mL), or delivered a small-for-gestational-age infant (p = 0.002; median = 2109 pg/mL vs. controls, median = 1614 pg/mL). SPINT2 was elevated in the placentas of patients who required delivery for preterm preeclampsia (p = 0.025). Though inflammatory cytokines had no effect, hypoxia increased SPINT2 in cytotrophoblast stem cells, and its expression was elevated in the placental labyrinth of growth-restricted rats. These findings suggest elevated SPINT2 is associated with placental insufficiency.
Baricitinib, a JAK-STAT Inhibitor, Reduces the Cellular Toxicity of the Farnesyltransferase Inhibitor Lonafarnib in Progeria Cells
Authors: Arnold Rouven , Vehns Elena , Randl Hannah , Djabali Karima
Published: July 2021

Hutchinson–Gilford progeria syndrome (HGPS) is an ultra-rare multisystem premature aging disorder that leads to early death (mean age of 14.7 years) due to myocardial infarction or stroke. Most cases have a de novo point mutation at position G608G within exon 11 of the LMNA gene. This mutation leads to the production of a permanently farnesylated truncated prelamin A protein called “progerin” that is toxic to the cells. Recently, farnesyltransferase inhibitor (FTI) lonafarnib has been approved by the FDA for the treatment of patients with HGPS. While lonafarnib treatment irrefutably ameliorates HGPS disease, it is however not a cure. FTI has been shown to cause several cellular side effects, including genomic instability as well as binucleated and donut-shaped nuclei. We report that, in addition to these cellular stresses, FTI caused an increased frequency of cytosolic DNA fragment formation. These extranuclear DNA fragments colocalized with cGAs and activated the cGAS-STING-STAT1 signaling axis, upregulating the expression of proinflammatory cytokines in FTI-treated human HGPS fibroblasts. Treatment with lonafarnib and baricitinib, a JAK-STAT inhibitor, not only prevented the activation of the cGAS STING-STAT1 pathway, but also improved the overall HGPS cellular homeostasis. These ameliorations included progerin levels, nuclear shape, proteostasis, cellular ATP, proliferation, and the reduction of cellular inflammation and senescence. Thus, we suggest that combining lonafarnib with baricitinib might provide an opportunity to reduce FTI cellular toxicity and ameliorate HGPS symptoms further than lonafarnib alone.
Autophagy and Tau Protein
Authors: Hamano Tadanori , Enomoto Soichi , Shirafuji Norimichi , Ikawa Masamichi , Yamamura Osamu , Yen Shu-Hui , Nakamoto Yasunari
Published: July 2021

Neurofibrillary tangles, which consist of highly phosphorylated tau protein, and senile plaques (SPs) are pathological hallmarks of Alzheimer’s disease (AD). In swollen axons, many autophagic vacuoles are observed around SP in the AD brain. This suggests that autophagy function is disturbed in AD. We used a neuronal cellular model of tauopathy (M1C cells), which harbors wild type tau (4R0N), to assess the effects of the lysosomotrophic agent NH4Cl, and autophagy inhibitors chloroquine and 3 methyladenine (3MA). It was found that chloroquine, NH4Cl and 3MA markedly increased tau accumulation. Thus, autophagy lysosomal system disturbances disturbed the degradation mechanisms of tau protein. Other studies also revealed that tau protein, including aggregated tau, is degraded via the autophagy lysosome system. Phosphorylated and C terminal truncated tau were also reported to disturb autophagy function. As a therapeutic strategy, autophagy upregulation was suggested. Thus far, as autophagy modulators, rapamycin, mTOCR1 inhibitor and its analogues, lithium, metformin, clonidine, curcumin, nicotinamide, bexaroten, and torehalose have been proposed. As a therapeutic strategy, autophagic modulation may be the next target of AD therapeutics.
The Expression Pattern of Surface Markers in Canine Adipose-Derived Mesenchymal Stem Cells
Authors: Krešić Nina , Prišlin Marina , Vlahović Dunja , Kostešić Petar , Ljolje Ivana , Brnić Dragan , Turk Nenad , Musulin Andrija , Habrun Boris
Published: July 2021

The influence of cultivation on the expression pattern of canine adipose-derived mesenchymal stem cells (cAD-MSCs) surface markers, contributing to, among others, the promotion of growth, proliferation, differentiation and immunomodulatory mechanisms of an excellent therapeutic, is still unknown. To fill the gap, we investigated CD90, CD44, CD73, CD29, CD271, CD105, CD45 and CD14 patterns of expression at the protein level with flow cytometry and mRNA level using a real-time polymerase chain reaction array. Gentle variations of expression occurred during cultivation, along with increased CD90, CD44 and CD29 expression, low and decreasing CD271 and CD73 expression and a decrease of initially high CD105. As expected, CD45 and CD14 were not expressed by cAD-MSCs. Interestingly, we discovered a significant decrease of CD73 expression, compared to early (P1–P3) to late (P4–P6) passages, although the CD73 gene expression was found to be stable. The percentage of positive cells was found to be higher for all positive markers up to P4. As CD73′s one important feature is a modulation from a pro-inflammatory environment to an anti-inflammatory milieu, the expression of CD73 in our conditions indicate the need to consider the time cells spend in vitro before being transplanted into patients, since it could impact their favourable therapeutical properties.
COVID-19 in Children: Expressions of Type I/II/III Interferons, TRIM28, SETDB1, and Endogenous Retroviruses in Mild and Severe Cases
Authors: Tovo Pier-Angelo , Garazzino Silvia , Daprà Valentina , Pruccoli Giulia , Calvi Cristina , Mignone Federica , Alliaudi Carla , Denina Marco , Scolfaro Carlo , Zoppo Marisa , Licciardi Francesco , Ramenghi Ugo , Galliano Ilaria , Bergallo Massimiliano
Published: July 2021

Children with the new coronavirus disease 2019 (COVID-19) have milder symptoms and a better prognosis than adult patients. Several investigations assessed type I, II, and III interferon (IFN) signatures in SARS-CoV-2 infected adults, however no data are available for pediatric patients. TRIM28 and SETDB1 regulate the transcription of multiple genes involved in the immune response as well as of human endogenous retroviruses (HERVs). Exogenous viral infections can trigger the activation of HERVs, which in turn can induce inflammatory and immune reactions. Despite the potential cross-talks between SARS-CoV-2 infection and TRIM28, SETDB1, and HERVs, information on their expressions in COVID-19 patients is lacking. We assessed, through a PCR real time Taqman amplification assay, the transcription levels of six IFN-I stimulated genes, IFN-II and three of its sensitive genes, three IFN-lIIs, as well as of TRIM28, SETDB1, pol genes of HERV-H, -K, and -W families, and of env genes of Syncytin (SYN)1, SYN2, and multiple sclerosis-associated retrovirus (MRSV) in peripheral blood from COVID-19 children and in control uninfected subjects. Higher expression levels of IFN-I and IFN-II inducible genes were observed in 36 COVID-19 children with mild or moderate disease as compared to uninfected controls, whereas their concentrations decreased in 17 children with severe disease and in 11 with multisystem inflammatory syndrome (MIS-C). Similar findings were found for the expression of TRIM-28, SETDB1, and every HERV gene. Positive correlations emerged between the transcriptional levels of type I and II IFNs, TRIM28, SETDB1, and HERVs in COVID-19 patients. IFN-III expressions were comparable in each group of subjects. This preserved induction of IFN-λs could contribute to the better control of the infection in children as compared to adults, in whom IFN-III deficiency has been reported. The upregulation of IFN-I, IFN-II, TRIM28, SETDB1, and HERVs in children with mild symptoms, their declines in severe cases or with MIS-C, and the positive correlations of their transcription in SARS-CoV-2-infected children suggest that they may play important roles in conditioning the evolution of the infection.
The Immune System through the Lens of Alcohol Intake and Gut Microbiota
Authors: Calleja-Conde Javier , Echeverry-Alzate Victor , Bühler Kora-Mareen , Durán-González Pedro , Morales-García Jose , Segovia-Rodríguez Lucía , Rodríguez de Fonseca Fernando , Giné Elena , López-Moreno Jose
Published: July 2021

The human gut is the largest organ with immune function in our body, responsible for regulating the homeostasis of the intestinal barrier. A diverse, complex and dynamic population of microorganisms, called microbiota, which exert a significant impact on the host during homeostasis and disease, supports this role. In fact, intestinal bacteria maintain immune and metabolic homeostasis, protecting our organism against pathogens. The development of numerous inflammatory disorders and infections has been linked to altered gut bacterial composition or dysbiosis. Multiple factors contribute to the establishment of the human gut microbiota. For instance, diet is considered as one of the many drivers in shaping the gut microbiota across the lifetime. By contrast, alcohol is one of the many factors that disrupt the proper functioning of the gut, leading to a disruption of the intestinal barrier integrity that increases the permeability of the mucosa, with the final result of a disrupted mucosal immunity. This damage to the permeability of the intestinal membrane allows bacteria and their components to enter the blood tissue, reaching other organs such as the liver or the brain. Although chronic heavy drinking has harmful effects on the immune system cells at the systemic level, this review focuses on the effect produced on gut, brain and liver, because of their significance in the link between alcohol consumption, gut microbiota and the immune system.
Are Sutureless and Rapid-Deployment Aortic Valves a Serious Alternative to TA-TAVI? A Matched-Pairs Analysis
Authors: Al-Maisary Sameer , Farag Mina , Te Gussinklo Willem Hendrik , Kremer Jamila , Pleger Sven T. , Leuschner Florian , Karck Matthias , Szabo Gabor , Arif Rawa
Published: July 2021

Background: Transcatheter aortic valve implantation is a feasible alternative to conventional aortic valve replacement with expanding indication extending to low-risk patients. Sutureless and rapid-deployment aortic valves were developed to decrease procedural risks in conventional treatment. This paired-match analysis aims to compare patients undergoing surgical transcatheter aortic valve implantation to sutureless and rapid-deployment aortic valve implantation. Methods: Retrospective database analysis between 2010 and 2016 revealed 214 patients undergoing transcatheter aortic valve implantation procedures through surgical access (predominantly transapical) and 62 sutureless and rapid-deployment aortic valve procedures including 26 patients in need of concomitant coronary artery bypass surgery. After matching, 52 pairs of patients were included and analyzed. Results: In-hospital death (5.8% vs. 3.8%; p = 0.308) was comparable between transcatheter aortic valve implantation (mean age 77 ± 4.3 years) and sutureless and rapid-deployment aortic valve implantation groups (mean age 75 ± 4.0 years), including 32 females in each group. The logistic EuroSCORE was similar (19 ± 12 vs. 17 ± 10; p = 0.257). Postoperative renal failure (p = 0.087) and cerebrovascular accidents (p = 0.315) were without significant difference. The incidence of complete heart block requiring permanent pacemaker treatment was relatively low for both groups (1.9% vs. 7.7%; p = 0.169) for TAVI and sutureless and rapid-deployment valves respectively. Intraoperative use of blood transfusion was higher in the sutureless and rapid-deployment aortic valve implantation group (0.72 U vs. 1.46 U, p = 0.014). Estimated survival calculated no significant difference between both groups after 6 months (transcatheter aortic valve implantation: 74 ± 8% vs. sutureless and rapid-deployment aortic valve implantation: 92 ± 5%; log rank p = 0.097). Conclusion: Since sutureless and rapid-deployment aortic valve implantation is as safe and effective as transapical transcatheter aortic valve implantation, combining the advantage of standard diseased-valve removal with shorter procedural times, sutureless and rapid-deployment aortic valve replacement may be considered as an alternative for patients with elevated operative risk considered to be in the “gray zone” between transcatheter aortic valve implantation and conventional surgery, especially if concomitant myocardial revascularization is required.
Static Crow’s Feet Treated with Voltaic Arc Dermabrasion (Atmospheric Plasma): Post-Operative Pain Assessment by Thermal Infrared Imaging
Authors: Scarano Antonio , Inchingolo Francesco , Amuso Domenico , Scogna Giuseppe , Amore Roberto , Lorusso Felice
Published: July 2021

Background: In the literature, several strategies have been described for the treatment of unaesthetic marks on the face resulting from the aging processes. The atmospheric plasma procedure is a non-invasive, inexpensive technique proposed for the rejuvenation of facial tissues. The aim of this study was to evaluate the performance of voltaic arc dermabrasion (VAD) for the treatment of static crow’s feet of the periorbital area. Methods: The crow’s feet of 135 patients (127 female and 8 male) were treated using the VAD technique. The perioperative skin temperature measurement was assessed using an Infrared Temperature sensor. The pain was measured using the Visual Analogic Score (VAS) at 1 week, 1 month and 1 year. The patient’s and surgeon’s satisfaction were assessed using the Global Aesthetic Improvement Scale (GAIS) at 1 month and 1 year from the procedure. The severity of the crow’s feet was rated using the Crow’s Feet Grading Scale (CFGS). Results: A complete epidermal healing of all the subjects treated was evident at 7 days. The atmospheric plasma technique showed an efficient treatment for the removal of the crow’s feet, with a good aesthetic outcome, high surgeon and patient satisfaction, without clinical complications. Conclusions: The atmospheric plasma technique can be a useful modality in the cosmetic as well as therapeutic treatment of crow’s feet.