bluuebunny/crossref_metadata_2025 huggingface dataset:
Perampanel Add-on to Standard Radiochemotherapy in vivo Promotes Neuroprotection in a Rodent F98 Glioma Model
Authors: Lange Falko , Hartung Jens , Liebelt Clara , Boisserée Julius , Resch Tobias , Porath Katrin , Hörnschemeyer Max Frederik , Reichart Gesine , Sellmann Tina , Neubert Valentin , Kriesen Stephan , Hildebrandt Guido , Schültke Elisabeth , Köhling Rüdiger , Kirschstein Timo
Published: November 2020

An abnormal glutamate signaling of glioblastoma may contribute to both tumor progression and the generation of glioma-associated epileptic seizures. We hypothesized that the AMPA receptor antagonist perampanel (PER) could attenuate tumor growth and epileptic events. F98 glioma cells, grown orthotopically in Fischer rats, were employed as a model of glioma to investigate the therapeutic efficiency of PER (15 mg/kg) as adjuvant to standard radiochemotherapy (RCT). The epileptiform phenotype was investigated by video-EEG analysis and field potential recordings. Effects on glioma progression were estimated by tumor size quantification, survival analysis and immunohistological staining. Our data revealed that orthotopically-growing F98 glioma promote an epileptiform phenotype in rats. RCT reduced the tumor size and prolonged the survival of the animals. The adjuvant administration of PER had no effect on tumor progression. The tumor-associated epileptic events were abolished by PER application or RCT respectively, to initial baseline levels. Remarkably, PER preserved the glutamatergic network activity on healthy peritumoral tissue in RCT-treated animals. F98 tumors are not only a robust model to investigate glioma progression, but also a viable model to simulate a glioma-associated epileptiform phenotype. Furthermore, our data indicate that PER acts as a potent anticonvulsant and may protect the tumor-surrounding tissue as adjuvant to RCT, but failed to attenuate tumor growth or promote animal survival.
Characterization of the Meal-Stimulated Incretin Response and Relationship With Structural Brain Outcomes in Aging and Alzheimer’s Disease
Authors: Morris Jill K. , John Casey S. , Green Zachary D. , Wilkins Heather M. , Wang Xiaowan , Kamat Ashwini , Swerdlow Russell S. , Vidoni Eric D. , Petersen Melissa E. , O’Bryant Sid E. , Honea Robyn A. , Burns Jeffrey M.
Published: November 2020

Background

Individuals with Alzheimer’s Disease (AD) are often characterized by systemic markers of insulin resistance; however, the broader effects of AD on other relevant metabolic hormones, such as incretins that affect insulin secretion and food intake, remains less clear.

Methods

Here, we leveraged a physiologically relevant meal tolerance test to assess diagnostic differences in these metabolic responses in cognitively healthy older adults (CH; n = 32) and AD (n = 23) participants. All individuals also underwent a comprehensive clinical examination, cognitive evaluation, and structural magnetic resonance imaging.

Results

The meal-stimulated response of glucose, insulin, and peptide tyrosine tyrosine (PYY) was significantly greater in individuals with AD as compared to CH. Voxel-based morphometry revealed negative relationships between brain volume and the meal-stimulated response of insulin, C-Peptide, and glucose-dependent insulinotropic polypeptide (GIP) in primarily parietal brain regions.

Conclusion

Our findings are consistent with prior work that shows differences in metabolic regulation in AD and relationships with cognition and brain structure.
Antioxidant and Anti-Inflammatory Effects of Genus Gynura: A Systematic Review
Authors: Tan Jiah Ning , Mohd Saffian Shamin , Buang Fhataheya , Jubri Zakiah , Jantan Ibrahim , Husain Khairana , Mohd Fauzi Norsyahida
Published: November 2020

Background:Gynura species have been used traditionally to treat various ailments, such as fever, pain, and to control blood glucose level. This systematic review critically discusses studies regarding Gynura species that exhibited antioxidant and anti-inflammatory effects, thus providing perspectives and instructions for future research of the plants as a potential source of new dietary supplements or medicinal agents.

Methods: A literature search from internet databases of PubMed, Scopus, Science Direct, e-theses Online Service, and ProQuest was carried out using a combination of keywords such as “Gynura,” “antioxidant,” “anti-inflammatory,” or other related words. Research articles were included in this study if they were experimental (in vitro and in vivo) or clinical studies on the antioxidant or anti-inflammatory effects of Gynura species and if they were articles published in English.

Results: Altogether, 27 studies on antioxidant and anti-inflammatory effects of Gynura species were selected. The antioxidant effects of Gynura species were manifested by inhibition of reactive oxygen species production and lipid peroxidation, modulation of glutathione-related parameters, and enzymatic antioxidant production or activities. The anti-inflammatory effects of Gynura species were through the modulation of inflammatory cytokine production, inhibition of prostaglandin E2 and nitric oxide production, cellular inflammatory-related parameters, and inflammation in animal models. The potential anti-inflammatory signaling pathways modulated by Gynura species are glycogen synthase kinase-3, nuclear factor erythroid 2-related factor 2, PPARγ, MAPK, NF-κB, and PI3K/Akt. However, most reports on antioxidant and anti-inflammatory effects of the plants were on crude extracts, and the chemical constituents contributing to bioactivities were not clearly understood. There is a variation in quality of studies in terms of design, conduct, and interpretation, and in-depth studies on the underlying mechanisms involved in antioxidant and anti-inflammatory effects of the plants are in demand. Moreover, there is limited clinical study on antioxidant and anti-inflammatory effects of Gynura species.

Conclusion: This review highlighted antioxidant and anti-inflammatory effects of genus Gynura and supported their traditional uses to treat oxidative stress and inflammatory-related diseases. This review is expected to catalyze further studies on genus Gynura. However, extensive preclinical data need to be generated from toxicity and pharmacokinetic studies before clinical studies can be pursued for their development into clinical medicines to treat oxidative stress and inflammatory conditions.
Weichang’an Formula Inhibits Tumor Growth in Combination with Bevacizumab in a Murine Model of Colon Cancer—Making up for the Deficiency of Bevacizumab by inhibiting VEGFR-1
Authors: Pan Chuan-Fang , Zhang Xi , Wang Jing-Wen , Yang Tao , Zhong Linda L. D. , Shen Ke-Ping
Published: November 2020

Aim: Angiogenesis plays an important role in the initiation, development, and metastasis of malignant tumors. Antiangiogenic drugs combined with immune therapy are considered to have a synergistic effect on anti-tumor strategy. Weichang’an formula (WCAF) is a prescription of traditional Chinese medicine (TCM) based on pharmaceutical screening and clinical experience. The aim of this study is to examine the effect of WCAF and its combined action with Bevacizumab (BEV) in colorectal cancer, and to identify the possible mechanism of action.

Methods: A human colon cancer cell (HCT 116) subcutaneous xenograft model was established in BALB/c-nu/nu mice. Tumor-bearing mice were randomized into each of four groups: control, WCAF treated, BEV treated, and WCAF plus BEV treated. Apoptosis was detected by TUNEL assay. Western blot was used to assess the protein levels of Leptin-R, STAT3, p-STAT3, BCL-2, and VEGFR-1. Immunohistochemistry was used to detect the micro-vessel density (MVD) and AKT1. Leptin and Vascular endothelial growth factor A (VEGF-A) mRNA expression were detected by Real-time PCR (RT-PCR). A network pharmacology study and validation assay were carried out to find the underlying molecular targets of WCAF related to immune regulation.

Results: Compared with the control group, WCAF reduced tumor weight and volume, as well as promoted tumor cell apoptosis. WCAF treatment decreased the mRNA expression of Leptin and VEGF-A, while the protein levels of CD31, LEP-R, VEGFR-1, STAT3, and p-STAT3 were decreased in tumor tissues. In addition, VEGFR-1 protein expression was decreased in the WCAF group and the WCAF plus BEV group but not in the BEV group. The combination of WCAF and BEV demonstrated a partial additive anti-tumor effect in vivo. The pharmacological network also found there are 26 WCAF target proteins related to cancer immune and 12 cancer immune related pathways. The AKT1 protein expression in the WCAF and WCAF + BEV groups were significantly lower than the that in the control group (p < 0.01).

Conclusion: WCAF can inhibit tumor growth and promote apoptosis and inhibit tumor angiogenesis in subcutaneous xenografts of human colon cancer HCT-116 in nude mice. WCAF also makes up for the deficiency of BEV by inhibiting VEGFR-1. The VEGFR-1 expression between the combination group and BEV alone achieved statistically significant difference (p < 0.01). Combined with BEV, WCAF showed a partial additive anti-tumor effect. The mechanism may be related to Leptin/STAT3 signal transduction, VEGF-A, VEGFR-1 and WCAF target proteins related to cancer immune such as leptin and AKT1.
Chemoresistance in Breast Cancer Patients Associated With Changes in P2X7 and A2A Purinergic Receptors in CD8+ T Lymphocytes
Authors: Ruiz-Rodríguez Victor Manuel , Turiján-Espinoza Eneida , Guel-Pañola Jaime Arturo , García-Hernández Mariana Haydee , Zermeño-Nava José de Jesús , López-López Nallely , Bernal-Silva Sofia , Layseca-Espinosa Esther , Fuentes-Pananá Ezequiel M. , Estrada-Sánchez Ana María , Portales-Pérez Diana Patricia
Published: November 2020

Breast cancer (BRCA) is the most frequent cancer type that afflicts women. Unfortunately, despite all the current therapeutic strategies, many patients develop chemoresistance hampering the efficacy of treatment. Hence, an early indicator of therapy efficacy might aid in the search for better treatment and patient survival. Although emerging evidence indicates a key role of the purinergic receptors P2X7 and A2A in cancer, less is known about their involvement in BRCA chemoresistance. In this sense, as the chemotherapeutic treatment stimulates immune system response, we evaluated the expression and function of P2X7 and A2A receptors in CD8+ T cells before and four months after BRCA patients received neoadjuvant chemotherapy. The results showed an increase in the levels of expression of P2X7 and a decrease in the expression of A2A in CD8+ T cells in non-chemoresistant (N-CHR) patients, compared to chemoresistant (CHR) patients. Interestingly, in CHR patients, reduced expression of P2X7 occurs along with a decrease in the CD62L shedding and the production of IFN-γ. In the case of the A2A function, the inhibition of IFN-γ production was not observed after chemotherapy in CHR patients. A possible relationship between the modulation of the expression and function of the P2X7 and A2A receptors was found, according to the molecular subtypes, where the patients that were triple-negative and human epidermal growth factor receptor 2 (HER2)-enriched presented more alterations. Comorbidities such as overweight/obesity and type 2 diabetes mellitus (T2DM) participate in the abnormalities detected. Our results demonstrate the importance of purinergic signaling in CD8+ T cells during chemoresistance, and it could be considered to implement personalized therapeutic strategies.
Analgesic Effect of Acetaminophen: A Review of Known and Novel Mechanisms of Action
Authors: Ohashi Nobuko , Kohno Tatsuro
Published: November 2020

Acetaminophen is one of the most commonly used analgesic agents for treating acute and chronic pain. However, its metabolism is complex, and its analgesic mechanisms have not been completely understood. Previously, it was believed that acetaminophen induces analgesia by inhibiting cyclooxygenase enzymes; however, it has been considered recently that the main analgesic mechanism of acetaminophen is its metabolization toN-acylphenolamine (AM404), which then acts on the transient receptor potential vanilloid 1 (TRPV1) and cannabinoid 1 receptors in the brain. We also recently revealed that the acetaminophen metabolite AM404 directly induces analgesia via TRPV1 receptors on terminals of C-fibers in the spinal dorsal horn. It is known that, similar to the brain, the spinal dorsal horn is critical to pain pathways and modulates nociceptive transmission. Therefore, acetaminophen induces analgesia by acting not only on the brain but also the spinal cord. In addition, acetaminophen is not considered to possess any anti-inflammatory activity because of its weak inhibition of cyclooxygenase (COX). However, we also revealed that AM404 induces analgesia via TRPV1 receptors on the spinal dorsal horn in an inflammatory pain rat model, and these analgesic effects were stronger in the model than in naïve rats. The purpose of this review was to summarize the previous and new issues related to the analgesic mechanisms of acetaminophen. We believe that it will allow clinicians to consider new pain management techniques involving acetaminophen.
Linagliptin Regulates the Mitochondrial Respiratory Reserve to Alter Platelet Activation and Arterial Thrombosis
Authors: Li Yi , Li Rong , Feng Ziqian , Wan Qin , Wu Jianbo
Published: November 2020

Background: The pharmacological inhibition of dipeptidyl peptidase-4 (DPP-4) potentiates incretin action, and DPP-4 is a drug target for type 2 diabetes and reducing cardiovascular risk. However, little is known about the non-enteroendocrine pathways by which DPP-4 might contribute to ischaemic cardiovascular events.

Methods: We tested the hypothesis that inhibition of DPP-4 can inhibit platelet activation and arterial thrombosis by preventing platelet mitochondrial dysfunction and release. The effects of pharmacological DPP-4 inhibition on carotid artery thrombosis, platelet aggregation, and platelet mitochondrial respiration signaling pathways were studied in mice.

Results: Platelet-dependent arterial thrombosis was significantly delayed in mice treated with high dose of linagliptin, a potent DPP-4 inhibitor, and fed normal chow diet compared to vehicle-treated mice. Thrombin induced DPP-4 expression and activity, and platelets pretreated with linagliptin exhibited reduced thrombin-induced aggregation. Linagliptin blocked phosphodiesterase activity and contrained cyclic AMP reduction when thrombin stimulates platelets. Linagliptin increases the inhibition of platelet aggregation by nitric oxide. The bioenergetics profile revealed that platelets pretreated with linagliptin exhibited decreased oxygen consumption rates in response to thrombin. In transmission electron microscopy, platelets pretreated with linagliptin showed markedly reversed morphological changes in thrombin-activated platelets, including the secretion of α-granules and fewer mitochondria.

Conclusion: Collectively, these findings identify distinct roles for DPP-4 in platelet function and arterial thrombosis.
Comorbidity in an Older Population with Type-2 Diabetes Mellitus: Identification of the Characteristics and Healthcare Utilization of High-Cost Patients
Authors: Guerrero-Fernández de Alba Inmaculada , Orlando Valentina , Monetti Valeria M. , Mucherino Sara , Gimeno-Miguel Antonio , Vaccaro Olga , Forjaz Maria João , Poblador Plou Beatriz , Prados-Torres Alexandra , Riccardi Gabriele , Menditto Enrica
Published: November 2020

Objectives: Little is known about the specific comorbidities contributing to higher costs in patients with type-2 diabetes mellitus (T2DM), particularly in older cases. We aimed to evaluate the prevalence, type, and cost of comorbidities occurring in older T2DM patients versus older non-T2DM patients, and the factors associated with high cost (HC) T2DM patients.

Methods: Retrospective cohort study using information from the Campania Region healthcare database. People aged ≥65 years who received ≥2 prescriptions for antidiabetic drugs were identified as “T2DM patients.” Comorbidities among T2DM and non-T2DM groups were assessed through the RxRiskV Index (modified version). T2DM individuals were classified according to the total cost distribution as HC or “non-high cost.” Two sub-cohorts of HC T2DM patients were assessed: above 90th and 80th percentile of the total cost. Age- and sex-adjusted logistic regression models were created.

Results: Among the T2DM cohort, concordant and discordant comorbidities occurred significantly more frequently than in the non-T2DM cohort. Total mean annual cost per T2DM patient due to comorbidities was €7,627 versus €4,401 per non-T2DM patient. Among T2DM patients identified as being above 90th and 80th percentiles of cost distribution, the total annual costs were >€19,577 and >€2,563, respectively. The hospitalization cost was higher for T2DM cases. Strongest predictors of being a HC T2DM patient were having ≥5 comorbidities and renal impairment.

Conclusion: HC patients accrued >80% of the total comorbidities cost in older T2DM patients. Integrated care models, with holistic and patient-tailored foci, could achieve more effective T2DM care.
Erythrocytes Induce Endothelial Injury in Type 2 Diabetes Through Alteration of Vascular Purinergic Signaling
Authors: Mahdi Ali , Tratsiakovich Yahor , Tengbom John , Jiao Tong , Garib Lara , Alvarsson Michael , Yang Jiangning , Pernow John , Zhou Zhichao
Published: November 2020

It is well established that altered purinergic signaling contributes to vascular dysfunction in type 2 diabetes (T2D). Red blood cells (RBCs) serve as an important pool for circulating ATP and the release of ATP from RBCs in response to physiological stimuli is impaired in T2D. We recently demonstrated that RBCs from patients with T2D (T2D RBC) serve as key mediators of endothelial dysfunction. However, it remains unknown whether altered vascular purinergic signaling is involved in the endothelial dysfunction induced by dysfunctional RBCs in T2D. Here, we evaluated acetylcholine-induced endothelium-dependent relaxation (EDR) of isolated rat aortas after 18 h ex vivo co-incubation with human RBCs, and aortas of healthy recipient rats 4 h after in vivo transfusion with RBCs from T2D Goto-Kakizaki (GK) rats. Purinergic receptor (PR) antagonists were applied in isolated aortas to study the involvement of PRs. EDR was impaired in aortas incubated with T2D RBC but not with RBCs from healthy subjects ex vivo, and in aortas of healthy rats after transfusion with GK RBCs in vivo. The impairment in EDR by T2D RBC was attenuated by non-selective P1R and P2R antagonism, and specific A1R, P2X7R but not P2Y6R antagonism. Transfusion with GK RBCs in vivo impaired EDR in aortas of recipient rats, an effect that was attenuated by A1R, P2X7R but not P2Y6R antagonism. In conclusion, RBCs induce endothelial dysfunction in T2D via vascular A1R and P2X7R but not P2Y6R. Targeting vascular purinergic singling may serve as a potential therapy to prevent endothelial dysfunction induced by RBCs in T2D.
Characterization of Three Fusarium graminearum Effectors and Their Roles During Fusarium Head Blight
Authors: Hao Guixia , McCormick Susan , Usgaard Thomas , Tiley Helene , Vaughan Martha M.
Published: November 2020

Fusarium graminearum causes Fusarium head blight (FHB) on wheat, barley, and other grains. During infection, F. graminearum produces deoxynivalenol (DON), which contaminates grain and functions as a virulence factor to promote FHB spread throughout the wheat head. F. graminearum secretes hundreds of putative effectors, which can interfere with plant immunity to promote disease development. However, the function of most of these putative effectors remains unknown. In this study, we investigated the expression profiles of 23 F. graminearum effector-coding genes during the early stage of wheat head infection. Gene expression analyses revealed that three effectors, FGSG_01831, FGSG_03599, and FGSG_12160, respectively, were highly induced in both a FHB susceptible and a moderately resistant variety. We generated deletion mutants for these effector genes and performed FHB virulence assays on wheat head using point and dip inoculations to evaluate FHB spread and initial infection. No statistically significant difference in FHB spread was observed in the deletion mutants. However, deletion mutants Δ01831 displayed a significant reduction in initial infection, and thus resulted in less DON contamination. To investigate the potential mechanisms involved, these three effectors were transiently expressed in Nicotiana benthamiana leaves. N. benthamiana leaves expressing these individual effectors had significantly reduced production of reactive oxygen species induced by chitin, but not by flg22. Furthermore, FGSG_01831 and FGSG_03599 markedly suppressed Bax-induced cell death when co-expressed with Bax in N. benthamiana leaves. Our study provides new insights into the functions of these effectors and suggests they play collective or redundant roles that likely ensure the successful plant infection.
Perceived Threat of the Coronavirus and the Role of Trust in Safeguards: A Case Study in Slovakia
Authors: Kanovsky Martin , Halamová Júlia
Published: November 2020

In this exploratory research study, we developed an instrument to investigate people’s confidence in safeguarding measures [Confidence in Safeguards Scale (CSS)] and we adapted an instrument measuring perceived risk of coronavirus [perceived risk of coronavirus scale (PRCS)] that was originally based on a perceived risk of HIV measure. We then explored the effect of public confidence in safeguarding measures designed to halt the spread of the coronavirus on perceived risk, controlling for related covariates. The sample consisted of N = 565 respondents; 119 were males (21.1%) and 446 were females (78.9%). Mean age was 35.42 (SD = 13.11), range was 18–77 years. We used convenience sampling to gather the data at the end of March 2020 via social media in Slovakia. The CSS showed good reliability levels and a three-factor structure: Confidence in Institutions, Confidence in Personal and Family Behaviors, and Confidence in Others’ Behaviors. The PRCS showed good reliability levels and a two-factor structure: Fear of Contraction and Perceived Likelihood of Contraction. Participants with higher levels of Confidence in Others’ Behaviors perceived the spread of the coronavirus to be less threatening, both cognitively (less perceived likelihood of contraction) and affectively (less fear of contraction). This finding could be used when designing public health policy and emergency communication. Enhancing confidence in others’ behaviors could encourage individual responsibility, social responsibility, and solidarity through social bonds extending beyond the family. In future research we plan to replicate the data collection using the same instruments in different countries so the results are comparable across cultures and can be used to improve emergency communication.
Common Ground Information Affects Reference Resolution: Evidence From Behavioral Data, ERPs, and Eye-Tracking
Authors: Richter Maria , Paul Mariella , Höhle Barbara , Wartenburger Isabell
Published: November 2020

One of the most important social cognitive skills in humans is the ability to “put oneself in someone else’s shoes,” that is, to take another person’s perspective. In socially situated communication, perspective taking enables the listener to arrive at a meaningful interpretation of what is said (sentence meaning) and what is meant (speaker’s meaning) by the speaker. To successfully decode the speaker’s meaning, the listener has to take into account which information he/she and the speaker share in their common ground (CG). We here further investigated competing accounts about when and how CG information affects language comprehension by means of reaction time (RT) measures, accuracy data, event-related potentials (ERPs), and eye-tracking. Early integration accounts would predict that CG information is considered immediately and would hence not expect to find costs of CG integration. Late integration accounts would predict a rather late and effortful integration of CG information during the parsing process that might be reflected in integration or updating costs. Other accounts predict the simultaneous integration of privileged ground (PG) and CG perspectives. We used a computerized version of the referential communication game with object triplets of different sizes presented visually in CG or PG. In critical trials (i.e., conflict trials), CG information had to be integrated while privileged information had to be suppressed. Listeners mastered the integration of CG (response accuracy 99.8%). Yet, slower RTs, and enhanced late positivities in the ERPs showed that CG integration had its costs. Moreover, eye-tracking data indicated an early anticipation of referents in CG but an inability to suppress looks to the privileged competitor, resulting in later and longer looks to targets in those trials, in which CG information had to be considered. Our data therefore support accounts that foresee an early anticipation of referents to be in CG but a rather late and effortful integration if conflicting information has to be processed. We show that both perspectives, PG and CG, contribute to socially situated language processing and discuss the data with reference to theoretical accounts and recent findings on the use of CG information for reference resolution.
Introversion and Social Engagement: Scale Validation, Their Interaction, and Positive Association With Self-Esteem
Authors: Tuovinen Sanna , Tang Xin , Salmela-Aro Katariina
Published: November 2020

Learning through social interaction has been documented widely; however, how introverted people are socially engaged in learning is largely unknown. The aim of this study was, first, to examine the reliability and validity of the social engagement scale among students at Finnish comprehensive schools. Then, we aimed to examine the interaction effect of introversion and social engagement on self-esteem, schoolwork engagement, and school burnout. Based on a sample of 862 ninth grade students in Finland, we found that a two-factor model best fitted the social engagement scale (i.e., social engagement and social disengagement). Further, we found that introverts with high social engagement have higher self-esteem than introverts with low social engagement. Our results implied that introverts should be given extra support when they encounter group work in school.
Perceived Teacher Responses to Bullying Influence Students’ Social Cognitions
Authors: Demol Karlien , Verschueren Karine , Salmivalli Christina , Colpin Hilde
Published: November 2020

Teachers’ responses to bullying incidents are key in bullying intervention at school. Scholars have suggested that teacher responses can predict student cognitions that are associated with their bullying behaviors. However, little is known about whether and how teacher responses affect these cognitions. Therefore, the current study investigated the effects of four immediate teacher responses on four bullying-related student cognitions, using an experimental vignette design. Additionally, it was examined whether students’ own participant role behaviors in actual bullying moderated these effects. The investigated teacher responses were non-response, comforting the victim, correcting the bully, and a combination of comforting the victim and correcting the bully. The investigated student cognitions were perceived teacher attitudes toward bullying, perceived teacher moral disengagement regarding bullying, student willingness to report bullying to the teacher and student expectations regarding bullying participant role behaviors in the classroom. Fourth-to-sixth grade students (N = 910; 47% boys; Mage = 11.04 years, SD = 0.91) read a vignette describing a hypothetical teacher’s response to a same bullying incident, following random assignment to one of eight conditions (i.e., four teacher responses × two genders of bully and victim in the vignette). Afterward, students completed questionnaires about their social cognitions and manipulation checks. ANOVA demonstrated that students perceived stronger teacher anti-bullying attitudes and less teacher moral disengagement when the hypothetical teacher displayed an active response. These effects were even stronger when the teacher corrected the bully compared to when only the victim was comforted. Further, students were more willing to report bullying when the teacher corrected the bully than when the teacher only comforted the victim. Finally, students expected less pro-bullying behaviors, more defending and less victimization in the vignette’s classroom following active teacher response compared to non-response. The effects of teacher responses on student cognitions were not moderated by students’ own participant roles in bullying. Taken together, these findings emphasize the importance of active teacher responses to bullying, and especially, responses that clearly show that bullying is not tolerated. Teachers are encouraged to be aware that students can deduce beliefs from teacher responses which can, in turn, affect bullying processes in the classroom.
Adverse Mental Health Impact of the COVID-19 Lockdown in Individuals With Tourette Syndrome in Italy: An Online Survey
Authors: Conte Giulia , Baglioni Valentina , Valente Francesca , Chiarotti Flavia , Cardona Francesco
Published: November 2020

During the early stages of the coronavirus disease 2019 (COVID-19) pandemic in Italy, an online survey was launched via a local patient advocacy website to investigate mental health issues in children and adolescents with Tourette syndrome (TS). Respondents were parents, who were asked to report on their child's general health, tics, comorbidities/problems, pharmacological treatment/psychotherapy, symptom variations, and daily routine, as well as on their family's health and work experiences during the pandemic. Two hundred thirty-eight people participated in the survey, 203 females and 35 males. Our findings indicate that, in the time window of 4–6 weeks after the beginning of the COVID-19-related lockdown, 67% of individuals with TS developed a relevant worsening of the overall clinical condition as rated by their parents. An improvement or no variation of the clinical picture was reported in 20.5 and 6.7% of cases, respectively. Most worsened symptoms included tics, hyperactivity, rage attacks, obsessions/compulsions, and anxiety. Of the subjects experiencing a clinical worsening, the majority (51.76%) showed variations across two to five symptom domains. No association was found between symptom variation and family demographics or health and economic issues specifically related to the lockdown. The current COVID-19 pandemic is exerting a considerable impact on the mental health of young individuals with TS by worsening both tics and emotional and behavioral symptoms.
Retrospective Assessment of Risk Factors for Head and Neck Cancer Among World Trade Center General Responders
Authors: Bover Manderski Michelle T. , Black Kathleen , Udasin Iris G. , Black Taylor M. , Steinberg Michael B. , Giuliano Anna R. , Luft Benjamin J. , Harrison Denise , Crane Michael A. , Moline Jacqueline , Passannante Marian R. , Ohman Strickland Pamela , Dasaro Christopher R. , Lucchini Roberto G. , Todd Andrew C. , Graber Judith M.
Published: November 2020

Objective: To assess the reliability of a questionnaire designed to reconstruct risk factors for head and neck cancer relative to the 9/11 World Trade Center (WTC) response and over the lifetime.

Methods: As part of a nested case-control study, 200 WTC Health Program (WTCHP) General Responder Cohort (GRC) members completed a newly-developed study questionnaire via telephone (with a trained interviewer) or online (self-administered). We assessed agreement between measures of tobacco and alcohol use in our questionnaire results and data collected previously during WTCHP-GRC monitoring visits using Cohens Kappa (κ) and intraclass correlation coefficient (ICC) for categorical and continuous measures, respectively. We compared agreement by disease status, survey mode, and year of WTCHP enrollment.

Results: We observed high agreement between measures of lifetime, pre-WTC, and post-WTC smoking prevalence (all κ > 0.85) and smoking duration (all ICC > 0.84). There was moderate agreement between measures of smoking frequency (ICC: 0.61–0.73). Agreement between measures of smoking frequency, but not duration, differed by disease status, and agreement between smoking measures was higher for participants who completed our survey by phone than by web. Among cases, there were no differences based on enrollment in the WTCHP before or after diagnosis.

Conclusion: Agreement between measures was generally high, although potential reporting bias and a mode effect that should be considered when interpreting analyses of self-reported data in this population; however differential misclassification appears to be minimal. Our questionnaire may be useful for future studies examining similar behavioral risk factors among disaster-exposed populations.
A Comparison of Artificial Intelligence and Human Doctors for the Purpose of Triage and Diagnosis
Authors: Baker Adam , Perov Yura , Middleton Katherine , Baxter Janie , Mullarkey Daniel , Sangar Davinder , Butt Mobasher , DoRosario Arnold , Johri Saurabh
Published: November 2020

AI virtual assistants have significant potential to alleviate the pressure on overly burdened healthcare systems by enabling patients to self-assess their symptoms and to seek further care when appropriate. For these systems to make a meaningful contribution to healthcare globally, they must be trusted by patients and healthcare professionals alike, and service the needs of patients in diverse regions and segments of the population. We developed an AI virtual assistant which provides patients with triage and diagnostic information. Crucially, the system is based on a generative model, which allows for relatively straightforward re-parameterization to reflect local disease and risk factor burden in diverse regions and population segments. This is an appealing property, particularly when considering the potential of AI systems to improve the provision of healthcare on a global scale in many regions and for both developing and developed countries. We performed a prospective validation study of the accuracy and safety of the AI system and human doctors. Importantly, we assessed the accuracy and safety of both the AI and human doctors independently against identical clinical cases and, unlike previous studies, also accounted for the information gathering process of both agents. Overall, we found that the AI system is able to provide patients with triage and diagnostic information with a level of clinical accuracy and safety comparable to that of human doctors. Through this approach and study, we hope to start building trust in AI-powered systems by directly comparing their performance to human doctors, who do not always agree with each other on the cause of patients’ symptoms or the most appropriate triage recommendation.
Social License and Animal Welfare: Developments from the Past Decade in Australia
Authors: Hampton Jordan O. , Jones Bidda , McGreevy Paul D.
Published: November 2020

“Social license to operate” (SLO) refers to the implicit process by which a community gives an industry approval to conduct its current business activities. It has become an important focus for many natural resource management fields (especially mining), but there is less awareness of its role in animal use industries. This article describes how animal welfare has recently become arguably the most crucial consideration underpinning the SLO for Australian animal use industries. It describes several industries in Australia that have faced animal welfare scrutiny in the past decade (2010–2020) to illustrate how persistent issues can erode SLO, lead to regulatory bans, and decimate previously profitable industries. Industries described include the live export of livestock, greyhound and horse racing, kangaroo harvesting, and dairy and sheep farming. In these cases, there has been intense public discourse but little scholarly progress. This article examines factors that may have contributed to these developments and suggests approaches that may assist these industries in maintaining their SLO. Animal welfare has become a mainstream societal concern in Australia, and effective management of the community’s expectations will be essential for the maintenance of SLO for many animal use industries.
Escherichia coli as Commensal and Pathogenic Bacteria among Food-Producing Animals: Health Implications of Extended Spectrum β-Lactamase (ESBL) Production
Authors: Ramos Sónia , Silva Vanessa , Dapkevicius Maria de Lurdes Enes , Caniça Manuela , Tejedor-Junco María Teresa , Igrejas Gilberto , Poeta Patrícia
Published: November 2020

Escherichia coli are facultative, anaerobic Gram-negative rods with many facets. Within resistant bacterial populations, they play an important ecological role and can be used as a bioindicator of antimicrobial resistance. All animal species used for food production, as well as humans, carry E. coli in their intestinal tracts; plus, the genetic flexibility and adaptability of this bacteria to constantly changing environments allows it to acquire a great number of antimicrobial resistance mechanisms. Thus, the prevalence of antimicrobial resistance in these commensal bacteria (or others, such as enterococci) can be a good indicator for the selective pressure caused by the use of antimicrobial agents, providing an early warning of the emergence of antimicrobial resistance in pathogens. As many as 90% of E. coli strains are commensals inhabiting the intestinal tracts of humans and warm-blooded animals. As a commensal, it lives in a mutually beneficial association with its hosts and rarely causes diseases. However, E. coli also remains as one of the most frequent causes of several common bacterial infections in humans and animals. In humans, it is the prominent cause of enteritis, community- and hospital-acquired urinary tract infection (UTI), septicemia, postsurgical peritonitis, and other clinical infections, such as neonatal meningitis, while, in farm animals, it is more prominently associated with diarrhea. On a global scale, E. coli can be considered the most important human pathogen, causing severe infection along with other major bacterial foodborne agents, such as Salmonella spp. and Campylobacter. Thus, the importance of resistance in E. coli, typically considered a benign commensal, should not be underestimated.
Recovery from Hypersaline-Stress-Induced Immunity Damage and Intestinal-Microbiota Changes through Dietary β-glucan Supplementation in Nile tilapia (Oreochromis niloticus)
Authors: Xu Chang , Suo Yantong , Wang Xiaodan , Qin Jian G , Chen Liqiao , Li Erchao
Published: November 2020

Long-term exposure to hyperosmotic environments can induce severe immune damage and increase risk in tilapia breeding. As an effective immunoregulator, β-glucan has attracted extensive attention in nutritional research and given rise to high expectations of improving health status and alleviating organismal damage in tilapia, Oreochromis niloticus, in brackish water. In this study, an 8-week cultivation experiment was conducted on tilapia fed a basal diet or diets with β-glucan supplementation in freshwater (control) and brackish water. Growth performance, hematological aspects, immune cytokine expression, and the intestinal microbiota of tilapia were analyzed. The results indicated that supplementation with β-glucan significantly reduced the enlarged spleen of tilapia resulting from hypersaline stress. Tilapia fed β-glucan showed significantly-greater decreases in the red blood cell count, hematocrit, red cell distribution width, platelet count, and plateletcrit than those fed the basal diet. β-glucan significantly decreased the high expression of immune-related genes in the spleen induced by hyperosmotic stress. In the intestine, the high migration inhibitory factor-2 (MIF-2) and IL-1β gene expression induced by hypersaline stress was significantly reduced. β-glucan supplementation also significantly increased the abundance of beneficial microbiota such as Lactobacillus, Phycicoccus, and Rikenellaceae. Therefore, dietary β-glucan supplementation can significantly reduce spleen enlargement and improve immune function in tilapia in brackish water. β-glucan intake can also optimize the intestinal microbiota of tilapia in brackish water and improve fish health.
Effect of Dietary Flaxseed Oil Supplementation on the Redox Status, Haematological and Biochemical Parameters of Horses’ Blood
Authors: Sembratowicz Iwona , Zięba Grzegorz , Cholewinska Ewelina , Czech Anna
Published: November 2020

This study compared the effect of two dietary vegetable oils on plasma biochemical indices, haematological parameters, and redox status of horses. Forty riding horses (20 mares and 20 stallions) of the Malopolski breed were divided equally into two groups that were similar in terms of age, sex, and body weight (on average 530 ± 30 kg). The horses received soybean oil (SO) or flaxseed oil (FO) in the amount of 25 mL per 100 kg BW/day. After 60 days, blood was collected for biochemical and haematological analyses. The results show that horses receiving FO as compared to the SO group had significantly lower plasma levels of glucose, low density lipoprotein cholesterol, total cholesterol/high-density lipoprotein (HDL) ratio and triacylglycerols, as well as the activities of alanine aminotransferase and alkaline phosphatase. In turn, %HDL-TC and lactate dehydrogenase activity were significantly higher in the FO group. The inclusion of FO in the diet contributed to an increase in antioxidant indices: creatinine, vitamin C, copper, and zinc contents and also superoxide dismutase and catalase activities. The level of the end product of lipid peroxidation, i.e., malonyl dialdehyde, in the FO group as compared to the SO group was significantly lower. Moreover, FO caused an elevation in red blood cell indicators, lymphocyte count and lysozymes. In conclusion, FO exerts a beneficial effect by stimulating antioxidant defence mechanisms of horses and reducing the severity of oxidative stress. FO also improved the lipid profile and haematological parameters of the blood. The replacement of SO by FO is recommended based on these findings.
Subsistence Agriculture Productivity and Climate Extreme Events
Authors: Moura Cardoso do Vale Tásia , Helena Constantino Spyrides Maria , De Melo Barbosa Andrade Lara , Guedes Bezerra Bergson , Evangelista da Silva Pollyanne
Published: November 2020

The occurrence of rainfall extreme events leads to several environmental, social, cultural, and economic consequences, heavily impacting agriculture. The analysis of climate extreme indices at the municipal level is of the uttermost importance to the overall study of climate variability and regional food security. Corn, bean, and cassava are among the most cultivated temporary subsistence crops. Thus, the objective of this study was to analyze the relationship between subsistence agriculture productivity and the behavior of rainfall extreme indices in the Rio Grande do Norte state in the period from 1980 to 2013. We used the dataset provided by Xavier (2016) and the climate extreme indices obtained through the Expert Team on Climate Change Detection and Indices. Crop productivity data were retrieved from the Municipal Agriculture Survey from the Brazilian Institute of Geography and Statistics system. The methodology evaluated the behavior and the relationship between agricultural productivity time series and extreme precipitation indicators. We applied the following statistical techniques: descriptive analysis, time series trend analysis by the Mann-Kendall test, cluster analysis, and analysis of variance to check for equal means between identified groups. Cluster analysis was considered an adequate tool for the comprehension of data spatial distribution, allowing the identification of five homogenous subregions with different precipitation patterns. Rainfall extreme indices allowed the analysis of regional conditions regarding consecutive dry days, annual precipitation in wet days, and heavy rainfall. Trends were identified in these indices and they were significantly correlated with dryland crops productivity, indicating a direct relationship between water availability and regional agroclimatic stress.
A Transient Stochastic Rainfall Generator for Climate Changes Analysis at Hydrological Scales in Central Italy
Authors: De Luca Davide Luciano , Petroselli Andrea , Galasso Luciano
Published: November 2020

In this work, a comprehensive methodology for trend investigation in rainfall time series, in a climate-change context, is proposed. The crucial role played by a Stochastic Rainfall Generator (SRG) is highlighted. Indeed, SRG application is particularly suitable to obtain rainfall series that are representative of future rainfall series at hydrological scales. Moreover, the methodology investigates the climate change effects on several timescales, considering the well-known Mann–Kendall test and analyzing the variation of probability distributions of extremes and hazard. The hypothesis is that the effects of climate changes could be more evident only for specific time resolutions, and only for some considered aspects. Applications regarded the rainfall time series of the Viterbo rain gauge in Central Italy.
Lag Variables in Nitrogen Oxide Concentration Modelling: A Case Study in Wrocław, Poland
Authors: Kamińska Joanna A. , Jiménez Fernando , Lucena-Sánchez Estrella , Sciavicco Guido , Turek Tomasz
Published: November 2020

Due to the unwavering interest of both residents and authorities in the air quality of urban agglomerations, we pose the following question in this paper: What impact do current and past meteorological factors and traffic flow intensity have on air quality? What is the impact of lagged variables on the fit of an explanation model, and how do they affect its ability to predict? We focused on NO2 and NOx concentrations, and conducted this research using hourly data from the city of Wrocław (western Poland) from 2015 to 2017; we used multi-objective optimization to determine the optimal delays. It turned out that for both NO2 and NOx, the past values for traffic flow, wind speed, and sunshine duration are more important than the current ones. We built random forest models on each of the pollutants for both the current and past values and discovered that including a lagged variable increases the resulting R2 from 0.51 to 0.56 for NO2 and from 0.46 to 0.52 for NOx. We also analyzed the feature importance in each model, and found that for NO2, a wind speed delay of more than three hours causes a significant decrease, while the importance of relative humidity increases with a seven-hour delay; likewise, wind speed increases the importance for NOx prediction with a two-hour delay. We concluded that, in pollutant concentration modeling, the possibility of a delayed effect of the independent variables should always be considered, because it can significantly increase the performance of the model and suggest unexpected relationships or dependencies.