bluuebunny/crossref_metadata_2025_split huggingface dataset:
EEG-based measurement system for monitoring student engagement in learning 4.0
Authors: Apicella Andrea , Arpaia Pasquale , Frosolone Mirco , Improta Giovanni , Moccaldi Nicola , Pollastro Andrea 
Published: April 2022

AbstractA wearable system for the personalized EEG-based detection of engagement in learning 4.0 is proposed. In particular, the effectiveness of the proposed solution is assessed by means of the classification accuracy in predicting engagement. The system can be used to make an automated teaching platform adaptable to the user, by managing eventual drops in the cognitive and emotional engagement. The effectiveness of the learning process mainly depends on the engagement level of the learner. In case of distraction, lack of interest or superficial participation, the teaching strategy could be personalized by an automatic modulation of contents and communication strategies. The system is validated by an experimental case study on twenty-one students. The experimental task was to learn how a specific human-machine interface works. Both the cognitive and motor skills of participants were involved. De facto standard stimuli, namely (1) cognitive task (Continuous Performance Test), (2) music background (Music Emotion Recognition—MER database), and (3) social feedback (Hermans and De Houwer database), were employed to guarantee a metrologically founded reference. In within-subject approach, the proposed signal processing pipeline (Filter bank, Common Spatial Pattern, and Support Vector Machine), reaches almost 77% average accuracy, in detecting both cognitive and emotional engagement.
SH3-domain mutations selectively disrupt Csk homodimerization or PTPN22 binding
Authors: Brian Ben F. , Sjaastad Frances V. , Freedman Tanya S. 
Published: April 2022

AbstractThe kinase Csk is the primary negative regulator of the Src-family kinases (SFKs, e.g., Lck, Fyn, Lyn, Hck, Fgr, Blk, Yes), phosphorylating a tyrosine on the SFK C-terminal tail that mediates autoinhibition. Csk also binds phosphatases, including PTPN12 (PTP-PEST) and immune-cell PTPN22 (LYP/Pep), which dephosphorylate the SFK activation loop to promote autoinhibition. Csk-binding proteins (e.g., CBP/PAG1) oligomerize within membrane microdomains, and high local concentration promotes Csk function. Purified Csk homodimerizes in solution through an interface that overlaps the phosphatase binding footprint. Here we demonstrate that Csk can homodimerize in Jurkat T cells, in competition with PTPN22 binding. We designed SH3-domain mutations in Csk that selectively impair homodimerization (H21I) or PTPN22 binding (K43D) and verified their kinase activity in solution. Disruption of either interaction in cells, however, decreased the negative-regulatory function of Csk. Csk W47A, a substitution previously reported to block PTPN22 binding, had a secondary effect of impairing homodimerization. Csk H21I and K43D will be useful tools for dissecting the protein-specific drivers of autoimmunity mediated by the human polymorphism PTPN22 R620W, which impairs interaction with Csk and with the E3 ubiquitin ligase TRAF3. Future investigations of Csk homodimer activity and phosphatase interactions may reveal new facets of SFK regulation in hematopoietic and non-hematopoietic cells.
Rare species disproportionally contribute to functional diversity in managed forests
Authors: Basile Marco 
Published: April 2022

AbstractFunctional diversity is linked with critical ecosystem functions, yet its relationship with numerical diversity, e.g. species richness, is not fully understood. The mechanisms linking changes of species richness, e.g. random and non-random species losses and gains, with changes of functional diversity become more relevant in the face of rapid environmental changes. In particular, non-random species changes including rare species may affect functional diversity, and the overall ecosystem function, disproportionately compared to random species changes including common species. In this study, I investigated how changes in numerical diversity of bird assemblages are related to functional diversity, and how the environment, and in particular forest management, influences such a relationship. I collected bird count data in the extensively-managed forest landscape of the Black Forest (Germany), at 82 sampling sites over three years. Data included species richness and abundance per site, and functional traits related to diet and habitat type for each species to compute functional diversity. By partitioning numerical diversity changes into five components using Price Equations, I calculated the contribution of random and non-random species losses and gains, and the abundance of common species, to functional diversity. Then I modelled these contributions as a function of several environmental variables describing broad forest conditions, and including forest management intensity. I found that, beside the major contribution of random species losses to functional diversity, non-random species losses also play a role, indicating that rare species that contribute more to functional diversity are often lost earlier than common species. The overall contribution to functional diversity of species losses is larger than that of species gains, pointing toward an ongoing simplification of the forest bird assemblage. Among all Price components, random species gains were influenced by management intensity, while other components were not influenced by any management variable. This highlight that potential conservation actions may not be effective in halting ecosystem functioning decline, as species gains do not result in increased functional diversity.
Quantum spinning photonic circulator
Authors: Jing Yu-Wei 
Published: April 2022

AbstractWe propose a scheme to realize a four-port quantum optical circulator for critical coupling of a spinning Kerr resonator to two tapered fibers. Its nonreciprocal effect arises from the Fizeau drag induced splitting of the resonance frequencies of the two counter-travelling optical modes. The transmitted photons exhibit direction dependent quantum correlations and nonreciprocal photon blockade occurs for photons transferred between the two fibers. Moreover, the quantum optical circulator is robust against the back scattering induced by intermodal coupling between counter-travelling optical modes. The present quantum optical circulator has significant potential as an elementary cell in chiral quantum information processing without magnetic field.
The CMS19 disease model specifies a pivotal role for collagen XIII in bone homeostasis
Authors: Kemppainen A. V. , Finnilä M. A. , Heikkinen A. , Härönen H. , Izzi V. , Kauppinen S. , Saarakkala S. , Pihlajaniemi T. , Koivunen J. 
Published: April 2022

AbstractMutations in theCOL13A1gene result in congenital myasthenic syndrome type 19 (CMS19), a disease of neuromuscular synapses and including various skeletal manifestations, particularly facial dysmorphisms. The phenotypic consequences inCol13a1null mice (Col13a1−/−) recapitulate the muscle findings of the CMS19 patients. Collagen XIII (ColXIII) is exists as two forms, a transmembrane protein and a soluble molecule. While theCol13a1−/−mice have poorly formed neuromuscular junctions, the prevention of shedding of the ColXIII ectodomain in theCol13a1tm/tmmice results in acetylcholine receptor clusters of increased size and complexity. In view of the bone abnormalities in CMS19, we here studied the tubular and calvarial bone morphology of theCol13a1−/−mice. We discovered several craniofacial malformations, albeit less pronounced ones than in the human disease, and a reduction of cortical bone mass in aged mice. In theCol13a1tm/tmmice, where ColXIII is synthesized but the ectodomain shedding is prevented due to a mutation in a protease recognition sequence, the cortical bone mass decreased as well with age and the cephalometric analyses revealed significant craniofacial abnormalities but no clear phenotypical pattern. To conclude, our data indicates an intrinsic role for ColXIII, particularly the soluble form, in the upkeep of bone with aging and suggests the possibility of previously undiscovered bone pathologies in patients with CMS19.
Affective response to physical activity as a deep phenotype in a non-randomized pilot study
Authors: Lee Harold H. , McGeary John E. , Dunsiger Shira , Emerson Jessica A. , Bock Beth , McCaffery Jeanne , Dwyer Kayla , Bryan Angela D. , Williams David M. 
Published: April 2022

AbstractLarge-scale genomic studies are beginning to identify genetic predictors of physical activity (PA). For those genetically predisposed to engage in low PA, a behavioral intervention may target a malleable factor that mediates genetic predisposition to low PA (i.e., intermediate phenotype) to mitigate the genetic influences. In a non-randomized exercise promotion pilot study, we test the feasibility of examining affective response to PA (how one feels during PA) as an intermediate phenotype between genetic variation and PA adherence. We hypothesized that three single nucleotide polymorphisms (SNPs; rs8044769 and rs3751812 in FTO; rs6265 in BDNF), identified from a prior systematic review, would be predictive of affective response to PA, and that affective response to PA would mediate the SNP-PA link. Forty five healthy, low-active adults received a 12-week print-based PA promotion program. Baseline affective response to PA was assessed using the Feeling Scale, a single-item measure of affective valence. Moderate to vigorous PA (MVPA) was assessed using accelerometers pre- and post-intervention. We examined the three SNPs in a weighted genetic score. Age, sex, body mass index, race, and neighborhood walkability were potential covariates. Affective response to PA and MVPA at follow-up (minutes/day over 4–7 days) were regressed on variation in SNPs, controlling for covariates. One unit increase in genetic score was associated with a 0.14 higher mean Feeling Scale, though was not statistically significant (p = 0.13). Among individual SNPs, having an additional FTO rs8044769 C allele was associated with a mean Feeling Scale score of 0.53 units higher (p = 0.015), which was statistically significant after applying the corrected p-value of 0.016. The genetic score or individual SNPs were not predictive of MVPA 12 weeks later, thereby mediation analyses were not performed. The preliminary findings demonstrate the promise of the intermediate phenotype approach.
Spatial frequency domain imaging for monitoring immune-mediated chemotherapy treatment response and resistance in a murine breast cancer model
Authors: Tank Anup , Vergato Cameron , Waxman David J. , Roblyer Darren 
Published: April 2022

AbstractSpatial Frequency Domain Imaging (SFDI) can provide longitudinal, label-free, and widefield hemodynamic and scattering measurements of murine tumors in vivo. Our previous work has shown that the reduced scattering coefficient (μ′s) at 800 nm, as well as the wavelength dependence of scattering, both have prognostic value in tracking apoptosis and proliferation during treatment with anti-cancer therapies. However, there is limited work in validating these optical biomarkers in clinically relevant tumor models that manifest specific treatment resistance mechanisms that mimic the clinical setting. It was recently demonstrated that metronomic dosing of cyclophosphamide induces a strong anti-tumor immune response and tumor volume reduction in the E0771 murine breast cancer model. This immune activation mechanism can be blocked with an IFNAR-1 antibody, leading to treatment resistance. Here we present a longitudinal study utilizing SFDI to monitor this paired responsive-resistant model for up to 30 days of drug treatment. Mice receiving the immune modulatory metronomic cyclophosphamide schedule had a significant increase in tumor optical scattering compared to mice receiving cyclophosphamide in combination with the IFNAR-1 antibody (9% increase vs 10% decrease on day 5 of treatment, p < 0.001). The magnitude of these differences increased throughout the duration of treatment. Additionally, scattering changes on day 4 of treatment could discriminate responsive versus resistant tumors with an accuracy of 78%, while tumor volume had an accuracy of only 52%. These results validate optical scattering as a promising prognostic biomarker that can discriminate between treatment responsive and resistant tumor models.
Usp5, Usp34, and Otu1 deubiquitylases mediate DNA repair in Drosophila melanogaster
Authors: Páhi Zoltán G. , Kovács Levente , Szűcs Diána , Borsos Barbara N. , Deák Péter , Pankotai Tibor 
Published: April 2022

AbstractUbiquitylation is critical for preventing aberrant DNA repair and for efficient maintenance of genome stability. As deubiquitylases (DUBs) counteract ubiquitylation, they must have a great influence on many biological processes, including DNA damage response. To elucidate the role of DUBs in DNA repair in Drosophila melanogaster, systematic siRNA screening was applied to identify DUBs with a reduced survival rate following exposure to ultraviolet and X-ray radiations. As a secondary validation, we applied the direct repeat (DR)-white reporter system with which we induced site-specific DSBs and affirmed the importance of the DUBs Ovarian tumor domain-containing deubiquitinating enzyme 1 (Otu1), Ubiquitin carboxyl-terminal hydrolase 5 (Usp5), and Ubiquitin carboxyl-terminal hydrolase 34 (Usp34) in DSB repair pathways using Drosophila. Our results indicate that the loss of Otu1 and Usp5 induces strong position effect variegation in Drosophila eye following I-SceI-induced DSB deployment. Otu1 and Usp5 are essential in DNA damage-induced cellular response, and both DUBs are required for the fine-tuned regulation of the non-homologous end joining pathway. Furthermore, the Drosophila DR-white assay demonstrated that homologous recombination does not occur in the absence of Usp34, indicating an indispensable role of Usp34 in this process.
Better, worse, or different than expected: on the role of value and identity prediction errors in fear memory reactivation
Authors: Gerlicher A. M. V. , Verweij S. A. , Kindt M. 
Published: April 2022

AbstractAlthough reconsolidation-based interventions constitute a promising new avenue to treating fear and anxieties disorders, the success of the intervention is not guaranteed. The initiation of memory reconsolidation is dependent on whether a mismatch between the experienced and predicted outcome-a prediction error (PE)-occurs during fear memory reactivation. It remains, however, elusive whether any type of PE renders fear memories susceptible to reconsolidation disruption. Here, we investigated whether a value PE, elicited by an outcome that is better or worse than expected, is necessary to make fear memories susceptible to reconsolidation disruption or whether a model-based identity PE, i.e., a PE elicited by an outcome equally aversive but different than expected, would be sufficient. Blocking beta-adrenergic receptors with propranolol HCl after reactivation did, however, not reduce the expression of fear after either type of PE. Instead, we observed intact fear memory expression 24 h after reactivation in the value-, identity- and a no-PE control group. The present results do not corroborate our earlier findings of reconsolidation disruption and point towards challenges that the field is currently facing in observing evidence for memory reconsolidation at all. We provide potential explanations for the unexpected failure of replicating reconsolidation disruption and discuss future directions.
Spontaneous regression rates of actinic keratosis: a systematic review and pooled analysis of randomized controlled trials
Authors: Steeb Theresa , Petzold Anne , Hornung Annkathrin , Wessely Anja , Berking Carola , Heppt Markus V. 
Published: April 2022

AbstractActinic keratosis (AK) are precancerous lesions of the skin which may progress to invasive squamous cell carcinoma. However, single lesions may also persist or even regress and heal spontaneously. Until now, evidence on the natural course of AK including spontaneous regression is limited. We aimed to synthesize regression rates of AK. We performed a systematic literature research in Medline, Embase, and CENTRAL for eligible trials until 3rd March 2020. Spontaneous regression rates were pooled using a random-effects model to calculate pooled proportions of participant-specific and lesion-specific complete clearance rates reported for the placebo arms of randomized controlled trials. Subgroup analyses were performed to dissect differences according to the type of placebo, immunocompetence of the participants, and localization of the lesions. Data from 38 records was included. The pooled participant-specific clearance rate was 8% (95% CI 6–10%, I2 = 71%) while the lesion-specific clearance rate was 23% (95% CI 16–31%, I2 = 97%). The highest participant- and lesion-specific clearance rates were achieved 12 weeks after the end of treatment (12% and 33%, respectively). Subgroup analysis revealed participant- as well as lesion-specific clearance rates of 0% for organ transplant recipients (OTR). We conclude that only a few participants achieve complete regression of their AK without any active treatment. Besides, the results underline that lesion clearance without active treatment is unlikely in OTR. Thus, early and consequent treatment of AK is recommended. Special attention should be paid when treating AK of OTR.
Adherence to a western dietary pattern and risk of invasive ductal and lobular breast carcinomas: a case–control study
Authors: Foroozani Elahe , Akbari Ali , Amanat Sasan , Rashidi Nastaran , Bastam Dariush , Ataee Shima , Sharifnia Golnaz , Faraouei Mohammad , Dianatinasab Mostafa , Safdari Hassan 
Published: April 2022

AbstractLittle is known about the role of diet in the risk of invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) of the breast, the most common histological subtypes of breast cancer (BC). This is because, the majority of studies on the association of diet and the risk of BC are focused on single food items, and studies considering the overall diet in terms of dietary patterns are limited. Also, the potential heterogeneity in the impact of Western diet (WD) on histological subtypes of BC is not established. This, the age-frequency-matched case–control study included 1009 incident BC cases and 1009 healthy controls. The required data was obtained from the patients’ medical files and interviews using a previously validated researcher-designed questionnaire for collecting data on socio-economic and anthropometric statuses and a valid food frequency questionnaire (FFQ) to measure the participants’ dietary intake. We used multinomial logistic regression, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. A positive and significant association was observed between higher adherence to a WD and risk of IDC (OR comparing highest with the lowest tertile: 2.45, 95% CI 1.88, 3.17; p-trend < 0.001), whereas no significant association was observed between adherence to the WD and the risk of ILC (OR comparing highest with the lowest tertile: 1.63, 95% CI 0.63, 3.25) (p for heterogeneity = 0.03). The results of an analysis stratified by menopausal status suggested a similar pattern. We provided evidence that adherence to a WD raises the risk of IDC, but not ILC, suggesting different etiological mechanisms for IDC and ILC.
Altered hypoxia inducible factor regulation in hereditary haemorrhagic telangiectasia
Authors: Wrobeln Anna , Leu Tristan , Jablonska Jadwiga , Geisthoff Urban , Lang Stephan , Fandrey Joachim , Droege Freya 
Published: April 2022

AbstractPatients with hereditary haemorrhagic telangiectasia (HHT), also known as Rendu–Osler–Weber syndrome, suffer from the consequences of abnormal vessel structures. These structures can lead to haemorrhages or shunt effects in liver, lungs and brain. This inherited and rare disease is characterized by mutations affecting the transforming growth factor-β (TGF-β)/Bone Morphogenetic Protein (BMP) pathway that results in arteriovenous malformations and studies indicate an impaired immune response. The mechanism underlying this altered immune response in HHT patients is still unknown. TGF-β interacts with hypoxia inducible factors (HIF), which both orchestrate inflammatory and angiogenic processes. Therefore, we analysed the expression of HIF and related genes in whole blood samples from HHT patients. We could show significantly decreased expression of HIF-1α on the mRNA and protein level. However, commonly known upstream regulators of HIF-1α in inflammatory responses were not affected, whereas HIF-1α target genes were significantly downregulated. There was no correlation between HIF1A or HIF2A gene expression and the severity of HHT detected. Our results represent a rare case of HIF-1α downregulation in a human disease, which underlines the relevance of HIFs in HHT. The study indicates an interaction of the known mutation in HHT and the dysregulation of HIF-1α in HHT patients, which might contribute to the clinical phenotype.
Hypothermia differentially modulates the formation and decay of NBS1, γH2AX and 53BP1 foci in U2OS cells exposed to gamma radiation
Authors: Płódowska Magdalena , Krakowiak Wiktoria , Węgierek-Ciuk Aneta , Lankoff Anna , Szary Karol , Lis Krzysztof , Wojcik Andrzej , Lisowska Halina 
Published: April 2022

AbstractIn studies on the mechanism of DNA damage response where ionizing radiation is used as the DNA damaging agent, cells are often exposed to ionizing radiation on melting ice (corresponding to 0.8 °C). The purpose of this procedure is to inhibit cellular processes i.e. DNA repair. Low temperature at exposure has been shown to act in a radioprotective manner at the level of cytogenetic damage, but its mechanisms of action are poorly understood. The aim of the study was to analyze the effect of hypothermia at the level of formation and decay of NBS1, γH2AX, and 53BP1 foci, micronuclei, survival, cell cycle progression and oxidative stress in U2OS cells. The results show that hypothermia alone induced oxidative stress and foci. When applied in combination with radiation but only during the exposure time, it potentiated the formation of γH2AX and 53BP1 but not of NBS1 foci. When applied during irradiation and subsequent repair time, 53BP1 and NBS1 foci formed and decayed, but the levels were markedly lower than when repair was carried out at 37 °C. The frequency of micronuclei was elevated in cells irradiated at 0.8 °C, but only when analysed 20 h after irradiation which is likely due to a reduced G2 cell cycle block. Hypothermia reduced cell survival, both with and without radiation exposure. The temperature effect should be considered when cooling cells on melting ice to inhibit DNA repair in the induction of DNA damage.