Miracle-dz/UniFAR-FTUs huggingface dataset:
Psychophysiology in Studying VR-Mediated Interactions: Panacea or a Trick? Valuable Applications, Limitations, and Future Directions

Over the last 10 years, we have seen a growing interest in the usage of psychophysiology–i.e., examining physiological signals, such as electrodermal activity, heart rate, and electroencephalography, to study psychological phenomena–in Virtual Reality (VR) psychological research. The change is reflected in a rise in Google Scholar query results—from 811 in 2009 to 2,500 in 2019. This increase reveals a significant shift in the methodology of this field where both direct (e.g., questionnaires) and indirect measures of users’ experience (e.g., psychophysiology) are used. At the same time, research interest in the social applications of VR technology (i.e., using VR to communicate, interact, and stay in presence of agents/avatars) has been consistently growing (discussion: Churchill et al., 2012). The opinions on the usage of psychophysiology in VR research vary from enthusiastic (e.g., Blascovich et al., 2002; Meehan et al., 2002; Wiederhold and Rizzo, 2005; Bombari et al., 2015; Kisker et al., 2019) to reserved (e.g., Slater, 2004; Friedman et al., 2005; Llobera et al., 2010, p. 11). In this paper, we reflect on this polarization, discussing the possible advantages, limitations, and future directions of this methodology in the context of building impactful VR communication platforms.
Case Report: Efficacy of Ninjin'yoeito Treatment for Idiopathic Pulmonary Fibrosis

Ninjin'yoeito, a Kampo prescription, was administered to two patients with idiopathic pulmonary fibrosis (IPF) over a period of 12 weeks to improve loss of appetite and lassitude. In Case 1, improvements were observed in appetite, lassitude, and breathlessness, as well as increases or increasing tendencies in body weight, blood albumin level, and hemoglobin (Hb) level. Case 2 showed no changes in appetite but improvements in lassitude and no deterioration of breathlessness. His body weight and his blood albumin and Hb levels increased or showed increasing trends. In both cases, a trend for improvement of respiratory function was observed. In summary, ninjin'yoeito trended to improve the subjective symptoms and nutritional status of a patient with pulmonary fibrosis.
Effect of Huang-Lian Jie-Du Decoction on Glucose and Lipid Metabolism in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis

Background: Type 2 diabetes mellitus (T2DM) is a heterogeneous disease characterized by persistent hyperglycemia. Huang-Lian Jie-Du decoction (HLJDD) is a traditional Chinese medicine formula which is widely used in treating T2DM in China. A thorough understanding of current body of evidence is needed. Objective: this study aims to summarize the clinical evidence of HLJDD for T2DM to provide an up-to-date and accurate understanding of this issue for research and clinical practice. Methods: Six databases were searched from inception to June 27, 2020 without language and publication status restrictions and randomized controlled trials about HLJDD on T2DM were included. Two evaluators searched and screened citations independently. Risk of bias was assessed by 2019 version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB2). Risk ratio (RR) with 95% confidence interval (CI) was used as an effect measure for dichotomous outcomes and mean difference (MD) with 95% CI was used for continuous outcomes. Subgroup analyses and sensitivity analyses were carried out. Results: Nine studies including 811 participants were included in this study. The overall risk of bias was high risk. Compared with metformin alone, combination treatment of HLJDD and metformin may result in a reduction in HbA1c, FBG, 2hPG, HOMA-IR and an improved lipid metabolism. Evidence comparing HLJDD and metformin or no intervention or placebo was insufficient. The quality of evidence was low. Conclusions: Current evidence about HLJDD on T2DM is still uncertain and more high-quality studies are needed to firmly establish the clinical efficacy and safety of HLJJD.
The HCN Channel Blocker ZD7288 Induces Emesis in the Least Shrew (Cryptotis parva)

Subtypes (1–4) of the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are widely expressed in the central and peripheral nervous systems, as well as the cells of smooth muscles in many organs. They mainly serve to regulate cellular excitability in these tissues. The HCN channel blocker ZD7288 has been shown to reduce apomorphine-induced conditioned taste aversion on saccharin preference in rats suggesting potential antinausea/antiemetic effects. Currently, in the least shew model of emesis we find that ZD7288 induces vomiting in a dose-dependent manner, with maximal efficacies of 100% at 1 mg/kg (i.p.) and 83.3% at 10 µg (i.c.v.). HCN channel subtype (1–4) expression was assessed using immunohistochemistry in the least shrew brainstem dorsal vagal complex (DVC) containing the emetic nuclei (area postrema (AP), nucleus tractus solitarius and dorsal motor nucleus of the vagus). Highly enriched HCN1 and HCN4 subtypes are present in the AP. A 1 mg/kg (i.p.) dose of ZD7288 strongly evoked c-Fos expression and ERK1/2 phosphorylation in the shrew brainstem DVC, but not in the in the enteric nervous system in the jejunum, suggesting a central contribution to the evoked vomiting. The ZD7288-evoked c-Fos expression exclusively occurred in tryptophan hydroxylase 2-positive serotonin neurons of the dorsal vagal complex, indicating activation of serotonin neurons may contribute to ZD7288-induced vomiting. To reveal its mechanism(s) of emetic action, we evaluated the efficacy of diverse antiemetics against ZD7288-evoked vomiting including the antagonists/inhibitors of: ERK1/2 (U0126), L-type Ca2+ channel (nifedipine); store-operated Ca2+ entry (MRS 1845); T-type Ca2+ channel (Z944), IP3R (2-APB), RyR receptor (dantrolene); the serotoninergic type 3 receptor (palonosetron); neurokinin 1 receptor (netupitant), dopamine type 2 receptor (sulpride), and the transient receptor potential vanilloid 1 receptor agonist, resiniferatoxin. All tested antiemetics except sulpride attenuated ZD7288-evoked vomiting to varying degrees. In sum, ZD7288 has emetic potential mainly via central mechanisms, a process which involves Ca2+ signaling and several emetic receptors. HCN channel blockers have been reported to have emetic potential in the clinic since they are currently used/investigated as therapeutic candidates for cancer therapy related- or unrelated-heart failure, pain, and cognitive impairment.
The Chromatin Regulator Ankrd11 Controls Palate and Cranial Bone Development

Epigenetic and chromatin regulation of craniofacial development remains poorly understood. Ankyrin Repeat Domain 11 (ANKRD11) is a chromatin regulator that has previously been shown to control neural stem cell fates via modulation of histone acetylation. ANKRD11 gene variants, or microdeletions of the 16q24.3 chromosomal region encompassing the ANKRD11 gene, cause KBG syndrome, a rare autosomal dominant congenital disorder with variable neurodevelopmental and craniofacial involvement. Craniofacial abnormalities include a distinct facial gestalt, delayed bone age, tooth abnormalities, delayed fontanelle closure, and frequently cleft or submucosal palate. Despite this, the dramatic phenotype and precise role of ANKRD11 in embryonic craniofacial development remain unexplored. Quantitative analysis of 3D images of KBG syndromic subjects shows an overall reduction in the size of the middle and lower face. Here, we report that mice with heterozygous deletion of Ankrd11 in neural crest cells (Ankrd11nchet) display a mild midfacial hypoplasia including reduced midfacial width and a persistent open fontanelle, both of which mirror KBG syndrome patient facial phenotypes. Mice with a homozygous Ankrd11 deletion in neural crest cells (Ankrd11ncko) die at birth. They show increased severity of several clinical manifestations described for KBG syndrome, such as cleft palate, retrognathia, midfacial hypoplasia, and reduced calvarial growth. At E14.5, Ankrd11 expression in the craniofacial complex is closely associated with developing bony structures, while expression at birth is markedly decreased. Conditional deletion of Ankrd11 leads to a reduction in ossification of midfacial bones, with several ossification centers failing to expand and/or fuse. Intramembranous bones show features of delayed maturation, with bone remodeling severely curtailed at birth. Palatal shelves remain hypoplastic at all developmental stages, with a local reduction in proliferation at E13.5. Our study identifies Ankrd11 as a critical regulator of intramembranous ossification and palate development and suggests that Ankrd11nchet and Ankrd11ncko mice may serve as pre-clinical models for KBG syndrome in humans.
Protein Truncating Variants of colA in Clostridium perfringens Type G Strains

Extracellular matrix (ECM) degrading enzymes produced by Clostridium perfringens may play an important role during the initial phases of avian necrotic enteritis by facilitating toxin entry in the intestinal mucosa and destruction of the tissue. C. perfringens is known to produce several ECM-degrading proteases, such as kappa toxin, an extracellular collagenase that is encoded by the colA gene. In this study, the colA gene sequence of a collection of 48 C. perfringens strains, including pathogenic (i.e. toxinotype G) and commensal (i.e. toxinotype A) chicken derived strains and strains originating from other host species, was analyzed. Although the colA gene showed a high level of conservation (>96% nucleotide sequence identity), several gene variants carrying different nonsense mutations in the colA gene were identified, leading to the definition of four truncated collagenase variant types (I-IV). Collagenase variant types I, III and IV have a (nearly) complete collagenase unit but lack parts of the C-terminal recruitment domains, whereas collagenase variant types II misses the N-terminal part of collagenase unit. Gene fragments encoding a truncated collagenase were mainly linked with necrotic enteritis associated C. perfringens type G strains with collagenase variant types I and II being the most prevalent types. Gelatin zymography revealed that both recombinant full-length and variant type I collagenase have active auto-cleavage products. Moreover, both recombinant fragments were capable of degrading type I as well as type IV collagen, although variant type I collagenase showed a higher relative activity against collagen type IV as compared to full-length collagenase. Consequently, these smaller truncated collagenases might be able to break down collagen type IV in the epithelial basement membrane of the intestinal villi and so contribute to the initiation of the pathological process leading to necrotic enteritis.
Ultrasound-Based Radiomics Analysis for Predicting Disease-Free Survival of Invasive Breast Cancer

Background Accurate prediction of recurrence is crucial for personalized treatment in breast cancer, and whether the radiomics features of ultrasound (US) could be used to predict recurrence of breast cancer is still uncertain. Here, we developed a radiomics signature based on preoperative US to predict disease-free survival (DFS) in patients with invasive breast cancer and assess its additional value to the clinicopathological predictors for individualized DFS prediction. Methods We identified 620 patients with invasive breast cancer and randomly divided them into the training (n = 372) and validation (n = 248) cohorts. A radiomics signature was constructed using least absolute shrinkage and selection operator (LASSO) Cox regression in the training cohort and validated in the validation cohort. Univariate and multivariate Cox proportional hazards model and Kaplan–Meier survival analysis were used to determine the association of the radiomics signature and clinicopathological variables with DFS. To evaluate the additional value of the radiomics signature for DFS prediction, a radiomics nomogram combining the radiomics signature and clinicopathological predictors was constructed and assessed in terms of discrimination, calibration, reclassification, and clinical usefulness. Results The radiomics signature was significantly associated with DFS, independent of the clinicopathological predictors. The radiomics nomogram performed better than the clinicopathological nomogram (C-index, 0.796 vs. 0.761) and provided better calibration and positive net reclassification improvement (0.147, P = 0.035) in the validation cohort. Decision curve analysis also demonstrated that the radiomics nomogram was clinically useful. Conclusion US radiomics signature is a potential imaging biomarker for risk stratification of DFS in invasive breast cancer, and US-based radiomics nomogram improved accuracy of DFS prediction.
The Role of Iconic Gestures in Speech Comprehension: An Overview of Various Methodologies

Iconic gesture-speech integration is a relatively recent field of investigation with numerous researchers studying its various aspects. The results obtained are just as diverse. The definition of iconic gestures is often overlooked in the interpretations of results. Furthermore, while most behavioral studies have demonstrated an advantage of bimodal presentation, brain activity studies show a diversity of results regarding the brain regions involved in the processing of this integration. Clinical studies also yield mixed results, some suggesting parallel processing channels, others a unique and integrated channel. This review aims to draw attention to the methodological variations in research on iconic gesture-speech integration and how they impact conclusions regarding the underlying phenomena. It will also attempt to draw together the findings from other relevant research and suggest potential areas for further investigation in order to better understand processes at play during speech integration process.
Health-Related Quality of Life in Italian Adolescents During Covid-19 Outbreak

Coronavirus disease 2019 (COVID-19) outbreak represented an experience of social isolation potentially leading to changes in the health quality of life. The aim of this study is to investigate the health-related quality of life during quarantine in early adolescents. Data were collected from 1,289 adolescents (mean age, 12.5; male, 622), at the beginning of the school year (September 2019, Standard Condition, SC) as part of the AVATAR project and during Phase 1 of the Italian lockdown (mid-late April 2020) (COVID-19 Quarantine, CQ) using an online questionnaire. In the CQ period, with respect to SC, adolescents showed lower perception in the dimensions, such as psychological (p = 0.001), physical well-being (p = 0.001), mood/emotion (p = 0.008), autonomy (p = 0.001), and financial resources (p = 0.018). Relationship with the family (p = 0.021) and peers (p = 0.001), as well as the perception of bullying (p = 0.001) were reduced. In lifestyle, adolescents developed higher adherence to the Mediterranean diet (p = 0.001). Adolescents living in the village had greater reduction in both autonomy (p = 0.002) and peer relationships (p = 0.002). Moreover, the perception of physical well-being was lower in those living in the city instead of those living in the countryside (p = 0.03), in an apartment instead of a detached house (p = 0.002), and in those who did not have green space (p = 0.001). Gender effect emerged for the psychological (p = 0.007) and physical well-being (p = 0.001), mood/emotion (p = 0.001), and self-perception (p = 0.001). The study showed that health-related quality of life during quarantine changed in its psychosocial dimensions, from mood and self-esteem to social relationships, helping to define the educational policies at multiple points in the promotion process of health.
Exploitation of Novel Bt ICPs for the Management of Helicoverpa armigera (Hübner) in Cotton (Gossypium hirsutum L.): A Transgenic Approach

Cotton is a commercial crop of global importance. The major threat challenging the productivity in cotton has been the lepidopteron insect pest Helicoverpa armigera or cotton bollworm which voraciously feeds on various plant parts. Biotechnological interventions to manage this herbivore have been a universally inevitable option. The advent of plant genetic engineering and exploitation of Bacillus thuringiensis (Bt) insecticidal crystal proteins (ICPs) marked the beginning of plant protection in cotton through transgenic technology. Despite phenomenal success and widespread acceptance, the fear of resistance development in insects has been a perennial concern. To address this issue, alternate strategies like introgression of a combination of cry protein genes and protein-engineered chimeric toxin genes came into practice. The utility of chimeric toxins produced by domain swapping, rearrangement of domains, and other strategies aid in toxins emerging with broad spectrum efficacy that facilitate the avoidance of resistance in insects toward cry toxins. The present study demonstrates the utility of two Bt ICPs, cry1AcF (produced by domain swapping) and cry2Aa (produced by codon modification) in transgenic cotton for the mitigation of H. armigera. Transgenics were developed in cotton cv. Pusa 8–6 by the exploitation of an apical meristem-targeted in planta transformation protocol. Stringent trait efficacy-based selective screening of T1 and T2 generation transgenic plants enabled the identification of plants resistant to H. armigera upon deliberate challenging. Evaluation of shortlisted events in T3 generation identified a total of nine superior transgenic events with both the genes (six with cry1AcF and three with cry2Aa). The transgenic plants depicted 80–100% larval mortality of H. armigera and 10–30% leaf damage. Molecular characterization of the shortlisted transgenics demonstrated stable integration, inheritance and expression of transgenes. The study is the first of its kind to utilise a non-tissue culture-based transformation strategy for the development of stable transgenics in cotton harbouring two novel genes, cry1AcF and cry2Aa for insect resistance. The identified transgenic events can be potential options toward the exploitation of unique cry genes for the management of the polyphagous insect pest H. armigera.
Coping Strategies in the Spanish Population: The Role in Consequences of COVID-19 on Mental Health

The worldwide health emergency caused by COVID-19 is a new challenge for humanity which individuals respond to in a diversity of ways. The type of coping people use in such a situation could lead to positive or negative consequences to their health. Our objective was to analyze the use of coping strategies in the general population with attention to sociodemographic variables, and to test the capacity of these strategies for mediating in repercussions on mental health. The 1,160 adults who participated in this study answered the Cognitive Emotion Regulation Questionnaire (CERQ-S) and General Health Questionnaire (GHQ-28). The data were collected in a CAWI (Computer Aided Web Interviewing). The results suggest that the coping strategies they used the most differed depending on sociodemographic characteristics, such as age, sex and education. Furthermore, two mediation models were estimated for positive and negative coping strategies in the relationship between the presence of COVID-19 near them and mental health. The “negative” coping strategies were found to exert an indirect effect as mediators in the impact that COVID-19 positive cases near them had on their health. The consequences to mental health of the impact of coping with adverse situations should not be underestimated and it is important to design programs to educate the population in coping strategies that promote their health.
Co-Occurrence of NDM-5 and RmtB in a Clinical Isolate of Escherichia coli Belonging to CC354 in Latin America

New Delhi metallo-β-lactamase (NDM)-producing isolates are usually resistant to most β-lactams and other antibiotics as a result of the coexistence of several resistance markers, and they cause a variety of infections associated to high mortality rates. Although NDM-1 is the most prevalent one, other variants are increasing their frequency worldwide. In this study we describe the first clinical isolate of NDM-5- and RmtB-producing Escherichia coli in Latin America. E. coli (Ec265) was recovered from a urine sample of a female outpatient. Phenotypical and genotypical characterization of resistance markers and conjugation assays were performed. Genetic analysis of Ec265 was achieved by whole genome sequencing. Ec265 belonging to ST9693 (CC354), displayed resistance to most β-lactams (including carbapenems), aminoglycosides (gentamicin and amikacin), and quinolones. Several resistance genes were found, including bla NDM-5 and rmtB, located on a conjugative plasmid. bla NDM-5 genetic context is similar to others found around the world. Co-transfer of multiple antimicrobial resistance genes represents a particular challenge for treatment in clinical settings, whereas the spread of pathogens resistant to last resort antibiotics should raise an alarm in the healthcare system worldwide.
Novel Small Molecule Glucagon-Like Peptide-1 Receptor Agonist S6 Stimulates Insulin Secretion From Rat Islets

Glucagon-like peptide-1 receptor (GLP-1R) agonist-based therapeutics for type 2 diabetes mellitus have attracted worldwide attention. However, there are challenges in the development of small molecule GLP-1R agonists owing to the complexity of ligand recognition and signal induction mechanisms. Here, we attained S6 using virtual screening and fluorescent imaging plate reader (FLIPR)-based calcium assays. The purpose of this study was to identify and characterize S6, a novel small molecule GLP-1R agonist. Data from cellular thermal shift assay (CETSA) and Bio-Layer Interferometry (BLI) indicated that S6 could bind potently with GLP-1R. Radioimmunoassay data showed that S6 potentiated insulin secretion in a glucose-dependent manner and the insulinotropic effect was mediated by GLP-1R. Calcium imaging techniques suggested that S6 elevated the intracellular calcium concentration [(Ca2+)i] by activating GLP-1R. In patch-clamp experiments, we demonstrated that S6 inhibited voltage-dependent K+ (Kv) channels in a GLP-1R-dependent fashion. Besides, S6 significantly prolonged action potential duration but had no effect on voltage-dependent Ca2+ channels. In summary, these findings indicate that S6 stimulates glucose-dependent insulin secretion mainly by acting on GLP-1R, inhibiting Kv channels, increasing (Ca2+)i. This study will provide direction for the screening and development of novel small-molecule agents targeting GLP-1R in the future.