Miracle-dz/UniFAR-FTUs huggingface dataset:
Free-Energy Model of Emotion Potential: Modeling Arousal Potential as Information Content Induced by Complexity and Novelty

Appropriate levels of arousal potential induce hedonic responses (i.e., emotional valence). However, the relationship between arousal potential and its factors (e.g., novelty, complexity, and uncertainty) have not been formalized. This paper proposes a mathematical model that explains emotional arousal using minimized free energy to represent information content processed in the brain after sensory stimuli are perceived and recognized (i.e., sensory surprisal). This work mathematically demonstrates that sensory surprisal represents the summation of information from novelty and uncertainty, and that the uncertainty converges to perceived complexity with sufficient sampling from a stimulus source. Novelty, uncertainty, and complexity all act as collative properties that form arousal potential. Analysis using a Gaussian generative model shows that the free energy is formed as a quadratic function of prediction errors based on the difference between prior expectation and peak of likelihood. The model predicts two interaction effects on free energy: that between prediction error and prior uncertainty (i.e., prior variance) and that between prediction error and sensory variance. A discussion on the potential of free energy as a mathematical principle is presented to explain emotion initiators. The model provides a general mathematical framework for understanding and predicting the emotions caused by novelty, uncertainty, and complexity. The mathematical model of arousal can help predict acceptable novelty and complexity based on a target population under different uncertainty levels mitigated by prior knowledge and experience.
COVID-19 and Diabetes: A Comprehensive Review of Angiotensin Converting Enzyme 2, Mutual Effects and Pharmacotherapy

The potential relationship between diabetes and COVID-19 has been evaluated. However, new knowledge is rapidly emerging. In this study, we systematically reviewed the relationship between viral cell surface receptors (ACE2, AXL, CD147, DC-SIGN, L-SIGN and DPP4) and SARS-CoV-2 infection risk, and emphasized the implications of ACE2 on SARS-CoV-2 infection and COVID-19 pathogenesis. Besides, we updated on the two-way interactions between diabetes and COVID-19, as well as the treatment options for COVID-19 comorbid patients from the perspective of ACE2. The efficacies of various clinical chemotherapeutic options, including anti-diabetic drugs, renin-angiotensin-aldosterone system inhibitors, lipid-lowering drugs, anticoagulants, and glucocorticoids for COVID-19 positive diabetic patients were discussed. Moreover, we reviewed the significance of two different forms of ACE2 (mACE2 and sACE2) and gender on COVID-19 susceptibility and severity. This review summarizes COVID-19 pathophysiology and the best strategies for clinical management of diabetes patients with COVID-19.
Hypoxia Induces Renal Epithelial Injury and Activates Fibrotic Signaling Through Up-Regulation of Arginase-II

The ureohydrolase, type-II arginase (Arg-II), is a mitochondrial enzyme metabolizing L-arginine into urea and L-ornithine and is highly expressed in renal proximal tubular cells (PTC) and upregulated by renal ischemia. Recent studies reported contradictory results on the role of Arg-II in renal injury. The aim of our study is to investigate the function of Arg-II in renal epithelial cell damage under hypoxic conditions. Human renal epithelial cell line HK2 was cultured under hypoxic conditions for 12–48 h. Moreover, ex vivo experiments with isolated kidneys from wild-type (WT) and genetic Arg-II deficient mice (Arg-II–/–) were conducted under normoxic and hypoxic conditions. The results show that hypoxia upregulates Arg-II expression in HK2 cells, which is inhibited by silencing both hypoxia-inducible factors (HIFs) HIF1α and HIF2α. Treatment of the cells with dimethyloxaloylglycine (DMOG) to stabilize HIFα also enhances Arg-II. Interestingly, hypoxia or DMOG upregulates transforming growth factor β1 (TGFβ1) levels and collagens Iα1, which is prevented by Arg-II silencing, while TGFβ1-induced collagen Iα1 expression is not affected by Arg-II silencing. Inhibition of mitochondrial complex-I by rotenone abolishes hypoxia-induced reactive oxygen species (mtROS) and TGFβ1 elevation in the cells. Ex vivo experiments show elevated Arg-II and TGFβ1 expression and the injury marker NGAL in the WT mouse kidneys under hypoxic conditions, which is prevented in the Arg-II–/– mice. Taking together, the results demonstrate that hypoxia activates renal epithelial HIFs-Arg-II-mtROS-TGFβ1-cascade, participating in hypoxia-associated renal injury and fibrosis.
Case Report: Fatal Neurotoxicity Following Resmethrin Poisoning in a Child

Resmethrin, a type I pyrethroid insecticide, can activate sodium channels, causing neurotoxicity in both mammals and insects. Possible routes of poisoning include inhalation, dermal contact and ingestion. There are no specific symptoms for resmethrin poisoning. Until now, no antidote has been available for resmethrin. Resmethrin poisoning is rarely reported in children. Here, we report a fatal case of resmethrin poisoning that might have been caused by accidental ingestion by a 26-month-old child. He presented with neurotoxic symptoms that included vomiting, recurrent seizures, and coma. The cranial CT showed extensive lesions of low intensity in the bilateral white matter, thalamus, brainstem, and cerebellum. Lumbar punctures showed increased intracranial pressure (ICP > 25 mmHg). Cerebrospinal fluid (CSF) tests revealed that protein was elevated to 289.2 mg/dL without pleocytosis. Resmethrin was detected in his blood by liquid chromatography-mass spectrometry, which confirmed the diagnosis of resmethrin poisoning. The child developed brain stem herniation and then was declared brain dead at the 77th h after admission. Resmethrin poisoning can be fatal, and it requires immediate diagnosis and treatment. Previous studies reported that cranial CT and CSF analyses were all normal in patients with pyrethroid poisoning. This case might extend the knowledge of neuroimaging and CSF analysis in children with resmethrin poisoning.
Investigating the Validity Evidence of the Swedish TriPM in High Security Prisoners Using the PCL-R and NEO-FFI

The triarchic model of psychopathy was developed to bridge opposing descriptions of psychopathy by separating the core construct in three domains; boldness, meanness, and disinhibition. The Triarchic Psychopathy Measure (TriPM) operationalizes the model through a 58-item self-report questionnaire. The current study examined the psychometric properties of the Swedish translation by investigating intercorrelations and associations to expert-rated psychopathy, general personality and psychopathy-related traits in male high-security prisoners (n = 191). Psychopathy rated with TriPM and the Psychopathy Checklist Revised (PCL-R) demonstrated expected convergence, as did empathy and impulsivity measures. The Disinhibition and Meanness scales were highly correlated, indicating that the scales might not be adequately differentiated. Nevertheless, the divergent association patterns to other important variables, particularly neuroticism and empathy, also points to meaningful differences. However, the lack of association between Disinhibition and Boldness may put into question if these domains are related at all, especially since there was a lack of similarity in the association patterns with other clinical variables. The influence of antisocial behavior in the TriPM operationalization might amplify the similarities of the Meanness and Disinhibition scales, while diluting the associations between Meanness and Boldness. In conclusion, the Swedish TriPM is effective in measuring the domains of triarchic model in forensic settings, even though a revision of the scales might improve the psychometric properties of the instrument.
Chronic Stress: Impacts on Tumor Microenvironment and Implications for Anti-Cancer Treatments

Chronic stress is common among cancer patients due to the psychological, operative, or pharmaceutical stressors at the time of diagnosis or during the treatment of cancers. The continuous activations of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS), as results of chronic stress, have been demonstrated to take part in several cancer-promoting processes, such as tumorigenesis, progression, metastasis, and multi-drug resistance, by altering the tumor microenvironment (TME). Stressed TME is generally characterized by the increased proportion of cancer-promoting cells and cytokines, the reduction and malfunction of immune-supportive cells and cytokines, augmented angiogenesis, enhanced epithelial-mesenchymal transition, and damaged extracellular matrix. For the negative effects that these alterations can cause in terms of the efficacies of anti-cancer treatments and prognosis of patients, supplementary pharmacological or psychotherapeutic strategies targeting HPA, SNS, or psychological stress may be effective in improving the prognosis of cancer patients. Here, we review the characteristics and mechanisms of TME alterations under chronic stress, their influences on anti-cancer therapies, and accessory interventions and therapies for stressed cancer patients.
In Vitro and In Vivo Anti-infective Potential of Thymol Against Early Childhood Caries Causing Dual Species Candida albicans and Streptococcus mutans

Early childhood caries (ECC), a severe form of caries due to cross-kingdom interaction of Candida albicans and Streptococcus mutans, is a serious childhood dental disease that affects majority of the children with poor background. The present study investigated the anti-infective potential of thymol against C. albicans and S. mutans dual species for the management of ECC. Thymol, a plant derivative of the monoterpene group, has been well known for its numerous biological activities. Thymol at 300 μg/ml concentration completely arrested growth and proliferation of dual species of C. albicans and S. mutans. Rapid killing efficacy of pathogens, within a span of 2 min, was observed in the time kill assay. In addition, at sub-inhibitory concentrations, thymol effectively diminished the biofilm formation and virulence of both C. albicans and S. mutans such as yeast-to-hyphal transition, hyphal-to-yeast transition, filamentation, and acidogenicity and acidurity, respectively, in single and dual species state. qPCR analysis was consistent with virulence assays. Also, through the invertebrate model system Galleria mellonella, in vivo toxicity and efficacy of the phytocompound was assessed, and it was found that no significant toxic effect was observed. Moreover, thymol was found to be proficient in diminishing the infection under single and dual state in in vivo condition. Overall, the results from the present study illustrate the anti-infective potential of thymol against the ECC-causing dual species, C. albicans and S. mutans, and the applicability of thymol in medicated dentifrice formulation.
Diverse Roles and Therapeutic Potentials of Circular RNAs in Urological Cancers

Circular RNAs (circRNAs) are a novel class of noncoding RNAs, which are mainly formed as a loop structure at the exons caused by noncanonical splicing; they are much more stable than linear transcripts; recent reports have suggested that the dysregulation of circRNAs is associated with the occurrence and development of diseases, especially various human malignancies. Emerging evidence demonstrated that a large number of circRNAs play a vital role in a series of biological processes such as tumor cell proliferation, migration, drug resistance, and immune escape. Additionally, circRNAs were also reported to be potential prognostic and diagnostic biomarkers in cancers. In this work, we systematically summarize the biogenesis and characteristics of circRNAs, paying special attention to potential mechanisms and clinical applications of circRNAs in urological cancers, which may help develop potential therapy targets for urological cancers in the future.
Rett Syndrome and Fragile X Syndrome: Different Etiology With Common Molecular Dysfunctions

Rett syndrome (RTT) and Fragile X syndrome (FXS) are two monogenetic neurodevelopmental disorders with complex clinical presentations. RTT is caused by mutations in the Methyl-CpG binding protein 2 gene (MECP2) altering the function of its protein product MeCP2. MeCP2 modulates gene expression by binding methylated CpG dinucleotides, and by interacting with transcription factors. FXS is caused by the silencing of the FMR1 gene encoding the Fragile X Mental Retardation Protein (FMRP), a RNA binding protein involved in multiple steps of RNA metabolism, and modulating the translation of thousands of proteins including a large set of synaptic proteins. Despite differences in genetic etiology, there are overlapping features in RTT and FXS, possibly due to interactions between MeCP2 and FMRP, and to the regulation of pathways resulting in dysregulation of common molecular signaling. Furthermore, basic physiological mechanisms are regulated by these proteins and might concur to the pathophysiology of both syndromes. Considering that RTT and FXS are disorders affecting brain development, and that most of the common targets of MeCP2 and FMRP are involved in brain activity, we discuss the mechanisms of synaptic function and plasticity altered in RTT and FXS, and we consider the similarities and the differences between these two disorders.
Input Impedance of Coaxial Line to Circular Waveguide Feed

The expressions for the real, imaginary parts of the input impedance seen by a coaxial line driving a thin cylindrical probe in a dominant TE/sub 11/ mode circular waveguide are derived. The analysis is carried out by assuming that the cylindrical post is replaced by a curvilinear strip having maximum width equal to the diameter of the probe. Theoretical results on input VSWR and input impedance seen by a coaxial line are in close agreement with experimental data.
Haematococcus pluvialis Accumulated Lipid and Astaxanthin in a Moderate and Sustainable Way by the Self-Protection Mechanism of Salicylic Acid Under Sodium Acetate Stress

To elucidate the mechanism underlying increased fatty acid and astaxanthin accumulation in Haematococcus pluvialis, transcriptome analysis was performed to gain insights into the multiple defensive systems elicited by salicylic acid combined with sodium acetate (SAHS) stresses with a time course. Totally, 112,886 unigenes and 61,323 non-repeat genes were identified, and genes involved in carbon metabolism, primary and secondary metabolism, and immune system responses were identified. The results revealed that SA and NaAC provide both energy and precursors to improve cell growth of H. pluvialis and enhance carbon assimilation, astaxanthin, and fatty acids production in this microalga with an effective mechanism. Interestingly, SA was considered to play an important role in lowering transcriptional activity of the fatty acid and astaxanthin biosynthesis genes through self-protection metabolism in H. pluvialis, leading to its adaption to HS stress and finally avoiding massive cell death. Moreover, positive correlations between 15 key genes involved in astaxanthin and fatty acid biosynthesis pathways were found, revealing cooperative relation between these pathways at the transcription level. These results not only enriched our knowledge of the astaxanthin accumulation mechanism in H. pluvialis but also provided a new view on increasing astaxanthin production in H. pluvialis by a moderate and sustainable way in the future.
Case Report: Identification of Germline Chimerism in Monochorionic Dizygotic Twins

Monochorionic twins are generally considered to be monozygotic, as monochorionic dizygotic (MCDZ) twins are extremely rare in natural pregnancies. Several studies have reported this rare occurrence, and most of these pregnancies have been conceived by assisted reproductive technology (ART). These reports mostly focused on MCDZ twin pregnancies and the childhood development of the twins; a follow-up into adulthood and the effect on their reproduction has not been reported. In this case study, we report a case of chimerism in opposite-sex MCDZ twins who were naturally conceived and have reached reproductive maturity. We collected oral mucosal, endometrial, and germ cells from the twins and evaluated their chimerism using single-nucleotide polymorphism (SNP) array and droplet digital PCR (ddPCR). The SNP array showed that they had 4,049 non-allele shared loci, and they inherited nearly 50% informative SNP loci from each parent, confirming that they are dizygotic twins. We found that the female twin had a 46, XX (2)/46, XY (78) karyotype in her peripheral blood. The SNP array confirmed that the female twin and male twin had the same blood haplotype. The ddPCR result showed 92.84 (± 1.80%) chimerism in her blood. In case of chimerism in her germline, the female twin chose preimplantation genetic testing for aneuploidy for her blastocysts. Fortunately, the patient only had blood chimerism. A healthy boy was born at 39 weeks of gestation.
Establishment of Novel Genotoxicity Assay System Using Murine Normal Epithelial Tissue-Derived Organoids

Short-/middle-term and simple prediction studies for carcinogenesis are needed for the safety assessment of chemical substances. To establish a novel genotoxicity assay with an in vivo mimicking system, we prepared murine colonic/pulmonary organoids from gpt delta mice according to the general procedure using collagenase/dispase and cultured them in a 3D environment. When the organoids were exposed to foodborne carcinogens—2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) and acrylamide (AA)—in the presence of metabolic activation systems, mutation frequencies (MFs) occurring in the gpt gene dose-dependently increased. Moreover, the mutation spectrum analysis indicated predominant G:C to T:A transversion with PhIP, and A:T to C:G and A:T to T:A transversion with AA. These data correspond to those of a previous study describing in vivo mutagenicity in gpt delta mice. However, organoids derived from the liver, a non-target tissue of PhIP-carcinogenesis, also demonstrated genotoxicity with a potency comparable to colonic organoids. Organoids and PhIP were directly incubated in the presence of metabolic activation systems; therefore, there was a lack of organ specificity, as observed in vivo. Additionally, PhIP-DNA adduct levels were comparable in hepatic and colonic organoids after PhIP exposure. Taken together, the organoids prepared in the present study may be helpful to predict chemical carcinogenesis.
Prison Unhealthy Lifestyle and Poor Mental Health of Older Persons—A Qualitative Study

Background: Mental healthcare and lifestyle habits in prison, especially for older individuals, has been shown to be suboptimal. Most psychiatric conditions left untreated worsen food choices, physical inactivity, and substance abuse. In turn, bad habits lead to poorer mental health. Methods: To comprehensively illustrate this downward spiraling, we completed a thorough analysis of data obtained through semi-structured qualitative interviews. There were 50 interviews of aging incarcerated people included in this article. They were analyzed following a classical six-stepped thematic analysis. Results: According to our participants, sports are not well-adapted to aging individuals, nor to people with medical conditions. Prison is even more unadapted for those who both are aging and have medical conditions. Also, food served is less than optimal. According to our interviews, the older imprisoned individual often does not have access to food adapted to his or her medical conditions. Sport is maladapted for older incarcerated individuals and mostly tailored for younger ones. Finally, boredom and lack of responsibility hinder change toward a better lifestyle for older adults in prison. Conclusion: Our paper shows why prison environmental modifications are needed to help older adults with their lifestyle habits. It also exposes an original way to see the relationship between mental health and lifestyle habits.
Evaluation of Blood Glial Fibrillary Acidic Protein as a Potential Marker in Huntington's Disease

Objective: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder. Neurofilament light protein (NfL) is correlated with clinical severity of HD but relative data are the lack in the Chinese population. Reactive astrocytes are related to HD pathology, which predicts their potential to be a biomarker in HD progression. Our aim was to discuss the role of blood glial fibrillary acidic protein (GFAP) to evaluate clinical severity in patients with HD. Methods: Fifty-seven HD mutation carriers (15 premanifest HD, preHD, and 42 manifest HD) and 26 healthy controls were recruited. Demographic data and clinical severity assessed with the internationally Unified Huntington's Disease Rating Scale (UHDRS) were retrospectively analyzed. Plasma NfL and GFAP were quantified with an ultra-sensitive single-molecule (Simoa, Norcross, GA, USA) technology. We explored their consistency and their correlation with clinical severity. Results: Compared with healthy controls, plasma NfL (p < 0.0001) and GFAP (p < 0.001) were increased in Chinese HD mutation carriers, and they were linearly correlated with each other (r = 0.612, p < 0.001). They were also significantly correlated with disease burden, Total Motor Score (TMS) and Total Functional Capacity (TFC). The scores of Stroop word reading, symbol digit modalities tests, and short version of the Problem Behaviors Assessments (PBAs) for HD were correlated with plasma NfL but not GFAP. Compared with healthy controls, plasma NfL has been increased since stage 1 but plasma GFAP began to increase statistically in stage 2. Conclusions: Plasma GFAP was correlated with plasma NfL, disease burden, TMS, and TFC in HD mutation carriers. Plasma GFAP may have potential to be a sensitive biomarker for evaluating HD progression.
Aging in the Digital Age: Using Technology to Increase the Reach of the Clinician Expert and Close the Gap Between Health Span and Life Span

Age-related cognitive impairment (ARCI) has a profound impact on individuals, families, health care systems, and societies at large. Evidence suggests that ARCI is the consequence of underlying brain pathology. Therefore, efforts to minimize the impact of ARCI and thus closing the gap between health span and life span, which has widened in recent years, requires early detection and timely deployment of targeted, personalized interventions. Access to clinical experts is limited and technology screening and assessment methods are thus appealing. However, as traditionally implemented patients were deprived of the benefit of personalized connection with a clinician, which is particularly critical for the prescription and to ensure the adherence to and ultimate success of therapeutic interventions. We present the concept of Intelligent Technology Therapy Assistant (ITA) as a scalable solution that increases the reach of clinical experts while sustaining the personal connection between each patient and their clinician. We illustrate ITA with the “Guttman Neuro Personal Trainer”®, a tele-rehabilitation platform that provides neuropsychological evaluation and care, and the Barcelona Brain Health Initiative (BBHI) multimodal intervention coaching app, a mobile-based platform that provides lifestyle coaching support in domains related to brain health. In addition, we discuss the translation of these models to a large-scale enterprise with Linus Health. To this end, we conclude with a discussion of challenges and opportunities to move the field forward.