Miracle-dz/UniFAR-FTUs huggingface dataset:
Perceived Self-Control Effort, Subjective Vitality, and General Affect in an Associative Structure

A crucial assumption of the recently developed schema model of self-control is that people’s perceived self-control efforts are related to the experience of lowered subjective vitality. In the present study, this assumption was tested. It was also examined whether perceived self-control effort is related to a diffuse affective experience (i.e., subjective vitality, general positive affect, and general negative affect as a combined factor) or is discretely related to subjective vitality, general positive affect, and general negative affect. Based on the previous literature, it was expected that the latter would better fit the data. In a survey study, university students (N = 501) completed standardized measures of their perceived self-control effort, subjective vitality, general positive affect, and general negative affect with regard to a specific frame of reference (i.e., during the current day and the last 2 days). Bivariate correlations and confirmatory factor analyses revealed the expected relationships, meaning that perceived self-control effort was negatively related to subjective vitality and that the statistical model with three distinct affective variables fit the data better than the model with subjective vitality, positive affect, and negative affect incorporated into one common factor. It was concluded that the findings are in line with the schema model of self-control.
AHL-Lactonase Producing Psychrobacter sp. From Palk Bay Sediment Mitigates Quorum Sensing-Mediated Virulence Production in Gram Negative Bacterial Pathogens

Quorum sensing (QS) is a signaling mechanism governed by bacteria used to converse at inter- and intra-species levels through small self-produced chemicals called N-acylhomoserine lactones (AHLs). Through QS, bacteria regulate and organize the virulence factors’ production, including biofilm formation. AHLs can be degraded by an action called quorum quenching (QQ) and hence QQ strategy can effectively be employed to combat biofilm-associated bacterial pathogenesis. The present study aimed to identify novel bacterial species with QQ potential. Screening of Palk Bay marine sediment bacteria for QQ activity ended up with the identification of marine bacterial isolate 28 (MSB-28), which exhibited a profound QQ activity against QS biomarker strain Chromobacterium violaceum ATCC 12472. The isolate MSB-28 was identified as Psychrobacter sp. through 16S-rRNA sequencing. Psychrobacter sp. also demonstrated a pronounced activity in controlling the biofilm formation in different bacteria and biofilm-associated virulence factors’ production in P. aeruginosa PAO1. Solvent extraction, heat inactivation, and proteinase K treatment assays clearly evidence the enzymatic nature of the bioactive lead. Furthermore, AHL’s lactone ring cleavage was confirmed with experiments including ring closure assay and chromatographic analysis, and thus the AHL-lactonase enzyme production in Psychrobacter sp. To conclude, this is the first report stating the AHL-lactonase mediated QQ activity from marine sediment bacteria Psychrobacter sp. Future work deals with the characterization, purification, and mass cultivation of the purified protein and should pave the way to assessing the feasibility of the identified protein in controlling QS and biofilm-mediated multidrug resistant bacterial infections in mono or multi-species conditions.
Brief Research Report Regional Difference in TRAF2 and TRAF3 Gene Mutations in Colon Cancers

TRAF2 and TRAF3 genes of tumor necrosis factor receptor (TNF-R)-associated factor (TRAF) family are involved in diverse cell signaling, and function as both tumor suppressor gene and oncogene. Alterations of TRAF2 and TRAF3 in colon cancer (CC) along with their regional difference and microsatellite instability (MSI) are largely unknown. In the present study, we analyzed TRAF2 and TRAF3 frameshift mutations in 168 sporadic CCs (100 high MSI (MSI-H) and 68 microsatellite-stable (MSS) CCs). We identified TRAF2 and TRAF3 frameshift mutations in 4 (4%) and 3 CCs (3%) with MSI-H, respectively, but none in 68 cases of MSS CCs. Of the 168 CCs, we analyzed the mutations in multi-regions for 39 CCs (16 MSI-H and 23 MSS CCs), and discovered that 12.5% (2/16) and 6.3% (1/16) of MSI-H CCs exhibited regional difference in TRAF2 and TRAF3 mutations, respectively. In the multi-region samples of 23 MSS CCs, neither TRAF2 nor TRAF3 frameshift mutation was found. In 40% of CCs, both TRAF2 and TRAF3 expressions were increased compared to normal colon cells. Our data indicate that TRAF2 and TRAF3 frameshift mutations and their regional difference as well as altered expressions are present in MSI-H CCs, which could contribute to MSI-H cancer development.
ATP2C2 Has Potential to Define Tumor Microenvironment in Breast Cancer

Tumor microenvironment (TME) is vital for the occurrence and development of breast cancer (BRCA). However, it remains challenging to understand the dynamic modulation of the stromal and immune components comprehensively in TME. Herein, we used ESTIMATE and CIBERSORT algorithm to estimate the number of stromal and immune components and the abundance of tumor-infiltrating immune cells (TICs) in 582 BRCA cases from gene expression omnibus (GEO) database. We employed three regression models including univariable Cox proportion, LASSO regression model and multivariate Cox regression, and identified 7 immune-specific genes related to BRCA survival. Of 7 genes, ATPase Secretory Pathway Ca2+ Transporting 2 (ATP2C2) attracts our attention for significantly predicting prognosis of BRCA patients. Further analysis indicated that ATP2C2 expression was closely related to the clinicopathological features (age, T- and N-staging) and negatively correlated with patients’ survival in BRCA. Gene Set Enrichment Analysis (GSEA) was performed to reveal pathway enrichment between ATP2C2high and ATP2C2low groups. The low ATP2C2 expression groups’ genes were mainly enriched for immune-related activities, while those in the ATP2C2 high-expression group were largely enriched in metabolic-related pathways. Notably, Pearson’s correlation analysis identified that ATP2C2 expression was positively correlated with T follicular helper (Tfh) cells, and negatively correlated with gamma delta (γδ) T cell, suggesting that ATP2C2 might be accountable for the maintenance of immune-dominant status for TME. To sum up, this study comprehensively analyzed the TME and shed light on prognostic immune-related biomarkers for BRCA. In particular, ATP2C2 might be helpful for predicting the prognosis of BRCA patients, which provided an extra insight for BRCA treatment.
Detection of EGFR Mutations From Plasma of NSCLC Patients Using an Automatic Cartridge-Based PCR System

The introduction of liquid biopsies for the detection of EGFR mutations in non-small cell lung cancer patients (NSCLC) has revolutionized the clinical care. However, liquid biopsies are technically challenging and require specifically trained personnel. To facilitate the implementation of liquid biopsies for the detection of EGFR mutations from plasma, we have assessed a fully automated cartridge-based qPCR test that allows the automatic detection of EGFR mutations directly from plasma. We have analyzed 54 NSCLC patients and compared the results of the cartridge-base device to an FDA-approved assay. Detection of EGFR mutations was comparable but slightly lower in the cartridge-based device for L858R mutations (14/15 detected, 93%) and exon 19 deletions (18/20 detected, 90%). Unfortunately, 8/54 (15%) tests failed but increasing the proteinase K volume helped to recover 3/4 (75%) unsuccessful samples. In summary, the fully automated cartridge-based device allowed the detection of EGFR mutations directly from plasma in NSCLC patients with promising accuracy. However, protocol adjustments are necessary to reduce a high test failure rate.
Predicting Metabolite–Disease Associations Based on LightGBM Model

Metabolites have been shown to be closely related to the occurrence and development of many complex human diseases by a large number of biological experiments; investigating their correlation mechanisms is thus an important topic, which attracts many researchers. In this work, we propose a computational method named LGBMMDA, which is based on the Light Gradient Boosting Machine (LightGBM) to predict potential metabolite–disease associations. This method extracts the features from statistical measures, graph theoretical measures, and matrix factorization results, utilizing the principal component analysis (PCA) process to remove noise or redundancy. We evaluated our method compared with other used methods and demonstrated the better areas under the curve (AUCs) of LGBMMDA. Additionally, three case studies deeply confirmed that LGBMMDA has obvious superiority in predicting metabolite–disease pairs and represents a powerful bioinformatics tool.
Fat oxidation during exercise: significance, determinants and response to nutrition

There is a large inter-subject variability in the capacity to oxidise fat (MFO) during exercise and this could have important implications for metabolic health. Chapter 3 of this thesis was designed to explore the relationship between MFO with 24-h fat oxidation and insulin sensitivity. This study showed that MFO during exercise is significantly and positively associated with 24-h fat oxidation and insulin sensitivity. Chapter 4 investigated relationships between selected plasma metabolites, hormones and overnight-fasted resting fat oxidation rates, with MFO. Plasma lipolytic markers, plasma insulin, resting fat oxidation and aerobic capacity were important modulators of the inter-subject variability in MFO. Chapter 5 explored the influence of meal timing around exercise on substrate utilisation, lipolytic markers and insulin, and intra-muscular triglyceride (IMTG) use in obesity. This study found that Fasted- as compared with Fed-state exercise augments exercise fat oxidation, and the circulating concentration of plasma glycerol and NEFA during exercise. This thesis generates new data that contributes to our understanding of the links between MFO and metabolic risk, as well as the factors that influence the inter-subject variability in MFO during exercise. It also shows that fasted exercise augments exercise fat oxidation, which could have meaningful implications for optimising metabolic health.
Independent Measures of Utricular Function: Ocular Vestibular Evoked Myogenic Potentials Do Not Correlate With Subjective Visual Vertical or Fundus Photographic Binocular Cyclorotation

Ocular vestibular evoked myogenic potentials (oVEMPs), subjective visual vertical (SVV), and fundus photographically measured binocular cyclorotation (BCR) are diagnostic tests to assess utricular function in patients with vertigo or dizziness. In 138 patients with chronic vertigo or dizziness, we asked whether the asymmetry ratio of oVEMP (normal, right side pathological, left side pathological) could predict the SVV deviation (normal, rightward deviation, leftward deviation) or BCR (normal, cyclorotation to the right, cyclorotation to the left). There was no correlation between oVEMP and SVV and between oVEMP and BCR, while SVV and BCR correlated highly. Although both oVEMP and SVV measure aspects of utricular function, our findings demonstrate that oVEMP and SVV are not redundant and may reflect different utricular pathologies. The role of fundus photographic BCR may be relegated to only confirm unclear SVV results in vestibular diagnostic workup.
The Value of Companion Dogs as a Source of Social Support for Their Owners: Findings From a Pre-pandemic Representative Sample and a Convenience Sample Obtained During the COVID-19 Lockdown in Spain

Dogs are a source of companionship and comfort for their owners, but the degree to which this might translate into real emotional and social support has not been quantified. Emotional and social support are essential to help people to get through personal crises such as bereavement. In this study we characterize the social support owners obtain from their dogs, provide evidence of how widespread this social support is amongst dog-owners, and show how social support from dogs can increase during a crisis (using the COVID-19 pandemic as an example). We collected data from a representative population-based sample of Spanish dog-owners and found that most respondents said that their dogs helped them to get through tough times. They got comfort from physical contact with their dogs, shared activities with them and treated them as confidants in a similar way to friends and family. These are all key aspects of social support, and dogs offer the advantage of being more available than human sources of support. It would be expected that the support that dogs provide would be increased during a time of personal crisis and when we looked at data collected from a convenience sample of Spanish dog-owners during the COVID-19 confinement that is what we found; during the confinement owners engaged in more shared activities with their dogs, hugged them more often and turned to them more as a source of companionship and comfort (p < 0.0001 in all cases). However, although owners did confide more in their dogs (p < 0.0001), the effect was not as great as for other aspects of social support. We suspect that this is because people were able to use telecommunications such as video conferencing to maintain their human confidant relationships. Our findings indicate that dogs can substitute for humans as sources of some kinds of social support when conventional sources are unavailable. Our conclusion is that where a dog is present in a household, it should be regarded as an important resource for social support. This should be considered when designing clinical interventions and when public health decisions are being made.
Brain Oscillation Entrainment by Perceptible and Non-perceptible Rhythmic Light Stimulation

Objective and Background: Decades of research in the field of steady-state visual evoked potentials (SSVEPs) have revealed great potential of rhythmic light stimulation for brain–computer interfaces. Additionally, rhythmic light stimulation provides a non-invasive method for entrainment of oscillatory activity in the brain. Especially effective protocols enabling non-perceptible rhythmic stimulation and, thereby, reducing eye fatigue and user discomfort are favorable. Here, we investigate effects of (1) perceptible and (2) non-perceptible rhythmic light stimulation as well as attention-based effects of the stimulation by asking participants to focus (a) on the stimulation source directly in an overt attention condition or (b) on a cross-hair below the stimulation source in a covert attention condition. Method: SSVEPs at 10 Hz were evoked with a light-emitting diode (LED) driven by frequency-modulated signals and amplitudes of the current intensity either below or above a previously estimated individual threshold. Furthermore, we explored the effect of attention by asking participants to fixate on the LED directly in the overt attention condition and indirectly attend it in the covert attention condition. By measuring electroencephalography, we analyzed differences between conditions regarding the detection of reliable SSVEPs via the signal-to-noise ratio (SNR) and functional connectivity in occipito-frontal(-central) regions. Results: We could observe SSVEPs at 10 Hz for the perceptible and non-perceptible rhythmic light stimulation not only in the overt but also in the covert attention condition. The SNR and SSVEP amplitudes did not differ between the conditions and SNR values were in all except one participant above significance thresholds suggested by previous literature indicating reliable SSVEP responses. No difference between the conditions could be observed in the functional connectivity in occipito-frontal(-central) regions. Conclusion: The finding of robust SSVEPs even for non-intrusive rhythmic stimulation protocols below an individual perceptibility threshold and without direct fixation on the stimulation source reveals strong potential as a safe stimulation method for oscillatory entrainment in naturalistic applications.
Utility of Multi-Modal MRI for Differentiating of Parkinson's Disease and Progressive Supranuclear Palsy Using Machine Learning

Background: Patients with Parkinson's disease (PD) and progressive supranuclear palsy Richardson's syndrome (PSP-RS) often show overlapping clinical features, leading to misdiagnoses. The objective of this study was to investigate the feasibility and utility of using multi-modal MRI datasets for an automatic differentiation of PD patients, PSP-RS patients, and healthy control (HC) subjects. Material and Methods: T1-weighted, T2-weighted, and diffusion-tensor (DTI) MRI datasets from 45 PD patients, 20 PSP-RS patients, and 38 HC subjects were available for this study. Using an atlas-based approach, regional values of brain morphology (T1-weighted), brain iron metabolism (T2-weighted), and microstructural integrity (DTI) were measured and employed for feature selection and subsequent classification using combinations of various established machine learning methods. Results: The optimal machine learning model using regional morphology features only achieved a classification accuracy of 65% (67/103 correct classifications) differentiating PD patients, PSP-RS patients, and HC subjects. The optimal machine learning model using only quantitative T2 values performed slightly better and achieved an accuracy of 75.7% (78/103). The optimal classifier using DTI features alone performed considerably better with 95.1% accuracy (98/103). The optimal multi-modal classifier using all features also achieved an accuracy of 95.1% but required more features and achieved a slightly lower F1-score compared to the optimal model using DTI features alone. Conclusion: Machine learning models using multi-modal MRI perform significantly better than uni-modal machine learning models using morphological parameters based on T1-weighted MRI datasets alone or brain iron metabolism markers based on T2-weighted MRI datasets alone. However, machine learnig models using regional brain microstructural integrity metrics computed from DTI datasets perform similar to the optimal multi-modal machine learning model. Thus, given the results from this study cohort, it appears that morphology and brain iron metabolism markers may not provide additional value for classification compared to using DTI metrics alone.
Independent Associations of Tumor Necrosis Factor-Alpha and Interleukin-1 Beta With Radiographic Emphysema in People Living With HIV

Background People living with HIV (PLWH) have increased systemic inflammation, and inflammation has been suggested to contribute to the pathogenesis of emphysema. We investigated whether elevated cytokine concentrations (interleukin (IL)-1β, IL-1 receptor antagonist (IL-1RA), IL-2, IL-4, IL-6, IL-10, IL-17A, tumor necrosis factor-alpha (TNFα), interferon-gamma (IFNγ), soluble CD14 (sCD14) and sCD163 were independently associated with radiographic emphysema in PLWH. Methods We included PLWH from the Copenhagen Comorbidity in HIV Infection (COCOMO) Study without hepatitis B and C co-infection and with a plasma sample and a chest computed tomography scan available. Emphysema plus trace emphysema was defined as the percentage of low attenuation area under −950 Houndsfield Unit (%LAA-950) using a cut-off at 5%. Cytokine concentrations were measured by ELISA or Luminex immunoassays. An elevated cytokine concentration was defined as above the 75th percentile. Results Of 783 PLWH, 147 (18.8%) had emphysema. PLWH were predominantly male (86.0%) and 743 (94.9%) had undetectable viral replication. PLWH with emphysema had higher concentrations of TNFα (median (IQR): 8.2 (6.4-9.8) versus 7.1 (5.7-8.6) pg/ml, p<0.001), IL-1β (0.21 (0.1-0.4) versus 0.17 (0.1-0.3) pg/ml, p=0.004) and IL-6 (3.6 (2.6-4.9) versus 3.1 (2.0-4.3) pg/ml, p=0.023) than PLWH without. In a logistic regression model adjusted for age, sex, ethnicity, smoking status, BMI and CD4 nadir, elevated TNFα (adjusted odds ratio (aOR): 1.78 [95%CI: 1.14-2.76], p=0.011) and IL-1β (aOR: 1.81 [95%CI: 1.16-2.81], p=0.009) were independently associated with emphysema. The association between IL-1β and emphysema was modified by smoking (p-interaction=0.020) with a more pronounced association in never-smokers (aOR: 4.53 [95%CI: 2.05-9.98], p<0.001). Conclusion Two markers of systemic inflammation, TNFα and IL-1β, were independently associated with emphysema in PLWH and may contribute to the pathogenesis of emphysema. Importantly, the effect of IL-1β seems to be mediated through pathways that are independent of excessive smoking. Clinical Trial Registration clinicaltrials.gov, identifier NCT02382822.
High-Yield Human Induced Pluripotent Stem Cell-Derived Monocytes and Macrophages Are Functionally Comparable With Primary Cells

Macrophages are pivotal effectors of host immunity and regulators of tissue homeostasis. Understanding of human macrophage biology has been hampered by the lack of reliable and scalable models for cellular and genetic studies. Human induced pluripotent stem cell (hiPSC)-derived monocytes and macrophages, as an unlimited source of subject genotype-specific cells, will undoubtedly play an important role in advancing our understanding of macrophage biology and implication in human diseases. In this study, we present a fully optimized differentiation protocol of hiPSC-derived monocytes and granulocyte-macrophage colony-stimulating factor (GM-CSF) or macrophage colony-stimulating factor (M-CSF). We present characterization of iPSC-derived myeloid lineage cells at phenotypic, functional, and transcriptomic levels, in comparison with corresponding subsets of peripheral blood-derived cells. We also highlight the application of hiPSC-derived monocytes and macrophages as a gene-editing platform for functional validation in research and drug screening, and the study also provides a reference for cell therapies.