Miracle-dz/UniFAR-FTUs huggingface dataset:
Association between IgG responses against the nucleocapsid proteins of alphacoronaviruses and COVID-19 severity

Understanding immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial to contain the COVID-19 pandemic. Using a multiplex approach, serum IgG responses against the whole SARS-CoV-2 proteome and the nucleocapsid proteins of endemic human coronaviruses (HCoVs) were measured in SARS-CoV-2-infected donors and healthy controls. COVID-19 severity strongly correlated with IgG responses against the nucleocapsid (N) of SARS-CoV-2 and possibly with the number of viral antigens targeted. Furthermore, a strong correlation between COVID-19 severity and serum responses against N of endemic alpha- but not betacoronaviruses was detected. This correlation was neither caused by cross-reactivity of antibodies, nor by a general boosting effect of SARS-CoV-2 infection on pre-existing humoral immunity. These findings raise the prospect of a potential disease progression marker for COVID-19 severity that allows for early stratification of infected individuals.
Attenuation of the dynamic pupil light response during screen viewing for arousal assessment

Studies on the psychosensory pupil response often carefully control the lighting conditions in the experiment or require a calibration procedure for each subject under different light conditions for a baseline which is later used to attenuate the pupil light response (PLR) effects from the pupil using steady state models, disregarding the dynamic nature of the pupil. Such approaches are not feasible “in the wild” since they require carefully controlled experimental conditions. We address these shortcomings in the context of screen viewing in a dataset containing 140 subjects playing a first person shooter video game and use an existing dynamic PLR model to attenuate the effects of luminance. We compute the perceived luminance using the pixel values of the screen and show that using the dynamic PLR model is more effective in attenuating the effects of luminance compared to steady state models. Subsequently, we show that attenuating the PLR from the pupil size data improves the performance of machine learning models trained to predict arousing game events compared to using the pupil size without attenuating the PLR. The implications are that our approach for estimating the perceived luminance and attenuating its effects from the pupil data can be applied to screen viewing (including VR) to unobtrusively and continuously monitor users’ emotional arousal via the pupil size.
EMG-driven musculoskeletal model calibration with estimation of unmeasured muscle excitations via synergy extrapolation

Subject-specific electromyography (EMG)-driven musculoskeletal models that predict muscle forces have the potential to enhance our knowledge of internal biomechanics and neural control of normal and pathological movements. However, technical gaps in experimental EMG measurement, such as inaccessibility of deep muscles using surface electrodes or an insufficient number of EMG channels, can cause difficulties in collecting EMG data from muscles that contribute substantially to joint moments, thereby hindering the ability of EMG-driven models to predict muscle forces and joint moments reliably. This study presents a novel computational approach to address the problem of a small number of missing EMG signals during EMG-driven model calibration. The approach (henceforth called “synergy extrapolation” or SynX) linearly combines time-varying synergy excitations extracted from measured muscle excitations to estimate 1) unmeasured muscle excitations and 2) residual muscle excitations added to measured muscle excitations. Time-invariant synergy vector weights defining the contribution of each measured synergy excitation to all unmeasured and residual muscle excitations were calibrated simultaneously with EMG-driven model parameters through a multi-objective optimization. The cost function was formulated as a trade-off between minimizing joint moment tracking errors and minimizing unmeasured and residual muscle activation magnitudes. We developed and evaluated the approach by treating a measured fine wire EMG signal (iliopsoas) as though it were “unmeasured” for walking datasets collected from two individuals post-stroke–one high functioning and one low functioning. How well unmeasured muscle excitations and activations could be predicted with SynX was assessed quantitatively for different combinations of SynX methodological choices, including the number of synergies and categories of variability in unmeasured and residual synergy vector weights across trials. The two best methodological combinations were identified, one for analyzing experimental walking trials used for calibration and another for analyzing experimental walking trials not used for calibration or for predicting new walking motions computationally. Both methodological combinations consistently provided reliable and efficient estimates of unmeasured muscle excitations and activations, muscle forces, and joint moments across both subjects. This approach broadens the possibilities for EMG-driven calibration of muscle-tendon properties in personalized neuromusculoskeletal models and may eventually contribute to the design of personalized treatments for mobility impairments.
COVID-19 and related social distancing measures induce significant metabolic complications without prominent weight gain in Korean adults

Background This study using multi-center health examination data from Korean adults was conducted to confirm changes in weight, and their related cardiometabolic parameters, before and after strengthening of social distancing regulations. Methods A retrospective cohort study was conducted using health check-up data from 13 university hospitals. The study period was from January 2018 to July 2020. To examine the effect of systematic social distancing measures, participants who underwent a health check-up (Visit 3) between July 2020 and July 2021 (during full scale social distancing), and had undergone two previous health check-ups (Visits 1 and 2) between January 2018 and June 2020 (before social distancing), were selected. In total, data from 7,875 participants were analyzed. Linear mixed-effect models were used to calculate estimates of anthropometric indices and metabolic markers measured on Visits 2 and 3, compared with measurements from Visit 1. Results There were no significant differences in body weight, body mass index, waist circumference, and body composition on Visit 3 than on Visits 1 and 2. However, the odds of metabolic syndrome and its components, including hypertension, high glucose, diabetes, hypercholesterolemia, hypertriglyceridemia, hyper-non-high-density lipoprotein cholesterolemia, and dyslipidemia were significantly higher on Visit 3 than on Visits 1 and 2. The increase in metabolic complications was marked, particularly in relatively young adults who visited health check-up centers located in the capital area. Conclusion Metabolic syndrome and its components were significantly worse after high level social distancing, although there were no significant increases in anthropometric indices and body fat levels. Healthcare providers need to prevent and manage worsening of metabolic parameters in subpopulations prone to be more sedentary and eat unhealthy food during the COVID-19 pandemic and associated social distancing measures.
Effect of 9p21.3 (lncRNA and CDKN2A/2B) variant on lipid profile

Background Several 9p21.3 variants, such as rs1333049, rs4977574, rs10757274, rs10757278, and rs10811661, identified from recent genome-wide association studies (GWASs) are reported to be associated with coronary artery disease (CAD) susceptibility but independent of dyslipidemia. This study investigated whether these 9p21.3 variants influenced lipid profiles. Methods and results By searching the PubMed and Cochrane databases, 101,099 individuals were included in the analysis. The consistent finding for the rs1333049 C allele on lipid profiles increased the triglyceride (TG) levels. Moreover, the rs4977574 G allele and the rs10757274 G allele, respectively, increased low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels. However, the rs10811661 C allele largely reduced LDL-C levels. Subgroup analyses indicated that the effects of the rs1333049 C allele, rs4977574 G allele, and rs10757274 G allele on lipid profiles were stronger in Whites compared with Asians. In contrast, the effect of the rs10811661 C allele on lipid profiles was stronger in Asians compared with Whites. Conclusion The rs1333049 C allele, rs4977574 G allele, and rs10757274 G allele of lncRNA, and the rs10811661 G allele of CDKN2A/2B had a significant influence on lipid levels, which may help the understanding of the underlying mechanisms between 9p21.3 variants and CAD.
COVID-19 and arrhythmia: The factors associated and the role of myocardial electrical impulse propagation. An observational study based on cardiac telemetric monitoring

Background The heart is commonly involved in COVID-19, and rhythm disorders have been largely reported. Objective To evaluate the association of some non-cardiac and cardiac comorbidities and QT dispersion with arrhythmias and their impact on outcomes in hospitalized patients with COVID-19. Methods Each patient underwent cardiac telemetry monitoring through the entire hospitalization period, laboratory analyses, 12-lead ECG, and lung imaging examination. Patients with arrhythmia were divided into three groups (bradyarrhythmias, tachyarrhythmias, and tachy- and bradyarrhythmias). Results Two-hundred patients completed the study (males, 123; mean age, 70.1 years); of these, 80 patients (40%) exhibited rhythm disorders on telemetry. Patients with arrhythmia were older (p < 0.0001), had a greater number of comorbidities (p < 0.0001), higher values of creatinine (p = 0.007), B-type natriuretic peptide (p < 0.0001), troponin (p < 0.0001), C-reactive protein (p = 0.01), ferritin (p = 0.001), D-dimer (p < 0.0001), procalcitonin (p = 0.0008), QT interval (p = 0.002), QTc interval (p = 0.04), and QTc dispersion (p = 0.01), and lower values of sodium (p = 0.03), magnesium (p = 0.04), glomerular filtration rate (p < 0.0001), and hemoglobin (p = 0.008) as compared to patients without arrhythmia. By comparing the three subgroups of patients, no significant differences were found. At multivariate analysis, age [odds ratio (OR) = 1.14 (95% CI: 1.07–1.22); p = 0.0004], coronary artery disease [OR = 12.7 (95% CI: 2.38–68.01); p = 0.005], and circulating troponin [OR = 1.05 (95% CI: 1.003–1.10); p = 0.04] represented risk factors independently associated with arrhythmia. All-cause in-hospital mortality was ∼40-fold higher among patients with arrhythmia [OR = 39.66 (95% CI: 5.20–302.51); p = 0.0004]. Conclusion Arrhythmias are associated with aging, coronary artery disease, subtle myocardial injury, hyperinflammatory status, coagulative unbalance, and prolonged QTc dispersion in patients with COVID-19, and confer a worse in-hospital prognosis. Given its usefulness, routinary use of cardiac telemetry should be encouraged in COVID wards.
Integrative bioinformatics analysis to identify the effects of circadian rhythm on Crohn’s disease

Background: Crohn’s disease (CD) is a multifactorial inflammatory bowel disease characterized by complex aberrant autoimmune disorders. Currently, the involvement of the circadian rhythm in the pathogenesis of CD is unknown. Methods: Bulk and single-cell RNA-seq data and associated clinical data from patients with CD were downloaded from the Gene Expression Omnibus (GEO). Single-sample gene set enrichment analysis was performed to calculate the enrichment score (ES) of circadian rhythm-related genes. Differential expression analysis was used to identify differentially expressed genes. Functional enrichment analysis was used to explore potential disease mechanisms. CIBERSORT was used to estimate immune cell abundance. Single-cell RNA-seq data were analyzed using the R package “Seurat. ” Results: The ES of circadian rhythm-related genes was lower in the CD tissue than in the normal tissue. Ubiquitin-specific protease 2 (USP2), a circadian rhythm-related gene, was identified as a potential modulator of CD pathogenesis. USP2 expression was reduced in CD and was associated with disease severity. Moreover, the analysis of bulk RNA-seq and single-cell RNA-seq data showed that monocyte and neutrophil abundance was elevated in CD and was negatively correlated with USP2 expression. It should be noted that USP2 expression in acinar cells was negatively correlated with monocyte and neutrophil abundance. Functional enrichment analysis revealed several canonical pathways to be enriched in CD, including the interleukin-17 signaling pathway, tumor necrosis factor signaling pathway, cytokine–cytokine receptor interaction, toll-like receptor signaling pathway, and nod-like receptor signaling pathway. Conclusion: Aberrant expression of circadian rhythm-related genes is correlated with CD pathogenesis. USP2 might be related to crosstalk among the different cell types in CD. These findings provide insights into future chronotherapy for CD.
Backward-propagating source as a component of rising tone whistler-mode chorus generation

Whistler-mode chorus waves in the magnetosphere play a crucial role in space weather via wave–particle interactions. The past two decades have observed tremendous advances in theory and simulations of chorus generation; however, several details of the generation mechanism are still actively contended. To simulate chorus generation, a new envelope particle-in-cell code is introduced. The model produces a rising tone chorus element in a parabolic geomagnetic field. The initial chorus element “embryo” frequency is shown to initialize near the equator at the frequency of maximum linear growth. A backward resonant current is then observed to propagate upstream of the equator. The trajectory of the backward current follows that of a freely falling electron that has been de-trapped at the equator superimposed with forward motion at the group velocity. The backward current iteratively radiates a rising tone element where the highest frequency components are generated furthest upstream. The work provides new advancements in modeling chorus and corroborates other recent work that has also demonstrated a backward-moving source during the generation of coherent whistler-mode waves.
Potential gene identification and pathway crosstalk analysis of age-related macular degeneration

Age-related macular degeneration (AMD), the most prevalent visual disorder among the elderly, is confirmed as a multifactorial disease. Studies demonstrated that genetic factors play an essential role in its pathogenesis. Our study aimed to make a relatively comprehensive study about biological functions of AMD related genes and crosstalk of their enriched pathways. 1691 AMD genetic studies were reviewed, GO enrichment and pathway crosstalk analyses were conducted to elucidate the biological features of these genes and to demonstrate the pathways that these genes participate. Moreover, we identified novel AMD-specific genes using shortest path algorithm in the context of human interactome. We retrieved 176 significantly AMD-related genes. GO results showed that the most significant term in each of these three GO categories was: signaling receptor binding (PBH = 4.835 × 10−7), response to oxygen-containing compound (PBH = 2.764 × 10−21), and extracellular space (PBH = 2.081 × 10−19). The pathway enrichment analysis showed that complement pathway is the most enriched. The pathway crosstalk study showed that the pathways could be divided into two main modules. These two modules were connected by cytokine-cytokine receptor interaction pathway. 42 unique genes potentially participating AMD development were obtained. The aberrant expression of the mRNA of FASN and LRP1 were validated in AMD cell and mouse models. Collectively, our study carried out a comprehensive analysis based on genetic association study of AMD and put forward several evidence-based genes for future study of AMD.
Chaotic Dynamics in Two-Dimensional Noninvertible Maps

Part 1: Generalities and definition one-dimensional endomorphisms the simplest type of two-dimensional endomorphisms. Part 2: Properties of the phase plane simplest type of two-dimensional endomorphisms. Part 3: Bifurcations more complex types of two-dimensional endomorphisms generalizations to higher dimensions.
The serial changes of Neutrophile-Lymphocyte Ratio and correlation to weight loss after Laparoscopic Sleeve Gastrectomy

Purpose This study aims to identify the pre- and postoperative changes in the neutrophil-lymphocyte ratio (NLR) and its correlations to clinical characteristics in obese patients who underwent laparoscopic sleeve gastrectomy (LSG). Method Retrospectively, we included patients who has undergone LSG in our institution between January 2019 and April 2021. A total of 100 patients whose body mass index over 32.5 and received primary laparoscopic sleeve gastrectomy without infectious condition were included. Results There was a significant decline in NLR (T0 vs. POM3 2.21 vs. 1.78, p = 0.005), neutrophil (T0 vs. POM3 5369 vs. 4050, p < 0.001) and lymphocyte count (T0 vs. POM3 2440: 2100, p < 0.001, respectively) at postoperative 3 months (POM3) compared to preoperative (T0) levels, but similar between POM3 and POM6. The declined counts (Neutrophile vs. Lymphocyte 1445.5/µl vs. 323.5/µl, p < 0.001) and percentage (Neutrophile vs. Lymphocyte 25.11% vs. 13.07%, p < 0.001) of neutrophile are higher than lymphocyte from T0 to POM3, but similar in POM3 and POM6. Preoperative NLR has a significant correlation with the preoperative body weight, preoperative insulin level, and excessive body weight loss (EBWL) at POM3. Preoperative NLR <2.36 had a sensitivity of 67.6% and a specificity of 62.5% in predicting successful weight loss (EBWL > 37.7%) at POM3 (AUC = 0.635, p = 0.032). Conclusion There was a significant decline in NLR, neutrophil, and lymphocyte count from T0 to POM3, but similar between POM3 and POM6. The declined counts and percentage of neutrophile are higher than lymphocyte. Preoperative NLR shows the potential to be used as a prognostic biomarker for predicting successful weight loss at POM3 after LSG. Further studies could be designed to evaluate the value of prediction in successful outcome after LSG and figure out the relationship between the changes of neutrophil function and oncogenesis.
Current trends in regenerative liver surgery: Novel clinical strategies and experimental approaches

Liver resections are performed to cure patients with hepatobiliary malignancies and metastases to the liver. However, only a small proportion of patients is resectable, largely because only up to 70% of liver tissue is expendable in a resection. If larger resections are performed, there is a risk of post-hepatectomy liver failure. Regenerative liver surgery addresses this limitation by increasing the future liver remnant to an appropriate size before resection. Since the 1980s, this surgery has evolved from portal vein embolization (PVE) to a multiplicity of methods. This review presents an overview of the available methods and their advantages and disadvantages. The first use of PVE was in patients with large hepatocellular carcinomas. The increase in liver volume induced by PVE equals that of portal vein ligation, but both result only in a moderate volume increase. While awaiting sufficient liver growth, 20%–40% of patients fail to achieve resection, mostly due to the progression of disease. The MD Anderson Cancer Centre group improved the PVE methodology by adding segment 4 embolization (“high-quality PVE”) and demonstrated that oncological results were better than non-surgical approaches in this previously unresectable patient population. In 2012, a novel method of liver regeneration was proposed and called Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS). ALPPS accelerated liver regeneration by a factor of 2–3 and increased the resection rate to 95%–100%. However, ALPPS fell short of expectations due to a high mortality rate and a limited utility only in highly selected patients. Accelerated liver regeneration, however, was there to stay. This is evident in the multiplicity of ALPPS modifications like radiofrequency or partial ALPPS. Overall, rapid liver regeneration allowed an expansion of resectability with increased perioperative risk. But, a standardized low-risk approach to rapid hypertrophy has been missing and the techniques used and in use depend on local expertise and preference. Recently, however, simultaneous portal and hepatic vein embolization (PVE/HVE) appears to offer both rapid hypertrophy and no increased clinical risk. While prospective randomized comparisons are underway, PVE/HVE has the potential to become the future gold standard.
Pyrancoumarin derivative LP4C targeting of pyrimidine de novo synthesis pathway inhibits MRSA biofilm and virulence

Staphylococcus aureus poses a serious public health threat because of its multidrug resistance and biofilm formation ability. Hence, developing novel anti-biofilm agents and finding targets are needed to mitigate the proliferation of drug-resistant pathogens. In our previous study, we showed that the pyrancoumarin derivative 2-amino-4-(2,6-dichlorophenyl)-3-cyano-5-oxo-4H, 5H- pyrano [3,2c] chromene (LP4C) can destroy the biofilm of methicillin-resistant S. aureus (MRSA) in vitro and in vivo. Here, we further explored the possible mechanism of LP4C as a potential anti-biofilm drug. We found that LP4C inhibits the expression of enzymes involved in the de novo pyrimidine pathway and attenuates the virulence of MRSA USA300 strain without affecting the agr or luxS quorum sensing system. The molecular docking results indicated that LP4C forms interactions with the key amino acid residues of pyrR protein, which functions as the important regulator of bacterial pyrimidine synthesis. These findings reveal that pyrancoumarin derivative LP4C inhibits MRSA biofilm formation and targeting pyrimidine de novo synthesis pathway.
Cytokine competent gut-joint migratory T Cells contribute to inflammation in the joint

Although studies have identified the presence of gut-associated cells in the enthesis of joints affected by spondylarthritis (SpA), a direct link through cellular transit between the gut and joint has yet to be formally demonstrated. Using KikGR transgenic mice to label in situ and track cellular trafficking from the distal colon to the joint under inflammatory conditions of both the gut and joint, we demonstrate bona-fide gut-joint trafficking of T cells from the colon epithelium, also called intraepithelial lymphocytes (IELs), to distal sites including joint enthesis, the pathogenic site of SpA. Similar to patients with SpA, colon IELs from the TNFΔARE/+ mouse model of inflammatory bowel disease and SpA display heightened TNF production upon stimulation. Using ex vivo stimulation of photo-labeled gut-joint trafficked T cells from the popliteal lymph nodes of KikGR and KikGR TNFΔARE/+ we saw that the CD4+ photo-labeled population was highly enriched for IL-17 competence in healthy as well as arthritic mice, however in the TNFΔARE/+ mice these cells were additionally enriched for TNF. Using transfer of magnetically isolated IELs from TNF+/+ and TNFΔARE/+ donors into Rag1 -/- hosts, we confirmed that IELs can exacerbate inflammatory processes in the joint. Finally, we blocked IEL recruitment to the colon epithelium using broad spectrum antibiotics in TNFΔARE/+ mice. Antibiotic-treated mice had reduced gut-joint IEL migration, contained fewer Il-17A and TNF competent CD4+ T cells, and lessened joint pathology compared to untreated littermate controls. Together these results demonstrate that pro-inflammatory colon-derived IELs can exacerbate inflammatory responses in the joint through systemic trafficking, and that interference with this process through gut-targeted approaches has therapeutic potential in SpA.