Miracle-dz/UniFAR-FTUs huggingface dataset:
Redox-Mediated Regulation of Mitochondrial Biogenesis, Dynamics, and Respiratory Chain Assembly in Yeast and Human Cells

Mitochondria are double-membrane organelles that contain their own genome, the mitochondrial DNA (mtDNA), and reminiscent of its endosymbiotic origin. Mitochondria are responsible for cellular respiration via the function of the electron oxidative phosphorylation system (OXPHOS), located in the mitochondrial inner membrane and composed of the four electron transport chain (ETC) enzymes (complexes I-IV), and the ATP synthase (complex V). Even though the mtDNA encodes essential OXPHOS components, the large majority of the structural subunits and additional biogenetical factors (more than seventy proteins) are encoded in the nucleus and translated in the cytoplasm. To incorporate these proteins and the rest of the mitochondrial proteome, mitochondria have evolved varied, and sophisticated import machineries that specifically target proteins to the different compartments defined by the two membranes. The intermembrane space (IMS) contains a high number of cysteine-rich proteins, which are mostly imported via the MIA40 oxidative folding system, dependent on the reduction, and oxidation of key Cys residues. Several of these proteins are structural components or assembly factors necessary for the correct maturation and function of the ETC complexes. Interestingly, many of these proteins are involved in the metalation of the active redox centers of complex IV, the terminal oxidase of the mitochondrial ETC. Due to their function in oxygen reduction, mitochondria are the main generators of reactive oxygen species (ROS), on both sides of the inner membrane, i.e., in the matrix and the IMS. ROS generation is important due to their role as signaling molecules, but an excessive production is detrimental due to unwanted oxidation reactions that impact on the function of different types of biomolecules contained in mitochondria. Therefore, the maintenance of the redox balance in the IMS is essential for mitochondrial function. In this review, we will discuss the role that redox regulation plays in the maintenance of IMS homeostasis as well as how mitochondrial ROS generation may be a key regulatory factor for ETC biogenesis, especially for complex IV.
Neuroprotective Effects of Deproteinized Calf Serum in Ischemic Stroke

Deproteinized calf serum (DCS) may have neuroprotective effects after ischemic stroke. The aim of this study is to investigate whether and how the DCS inhibits neuronal injury following cerebral ischemia. Rats were subjected to 2 h transient middle cerebral artery occlusion (MCAO). One dose of 0.125 mg/gbw DCS was given immediately after reperfusion. Neurological deficit and infarct volume at 24 h post-MCAO in DCS-treated rats were lower than those in vehicle-treated rats (p < 0.0005). In cultured neurons model, cell viability was decreased, and apoptosis was increased by oxygen-glucose deprivation/reperfusion (OGD/R) (p < 0.0005). These effects of OGD/R were attenuated by 0.4 μg/μl DCS (p < 0.05) that were validated by CCK8 cell viability assay, phycoerythrin–Annexin V Apoptosis Detection assay, and TUNEL assay. Furthermore, the increase of intracellular ROS level in cultured neurons was suppressed by DCS (p < 0.05). Compared with cells subjected to OGD/R, the expression level of Bax protein decreased, and bcl-2 protein increased after DSC treatment (p < 0.05). Overall, the neuroprotective effects of DCS following cerebral ischemia may in part be due to decreased ROS production and inhibition of apoptosis.
Systematic Analysis of the Impact of R-Methylation on RBPs-RNA Interactions: A Proteomic Approach

RNA binding proteins (RBPs) bind RNAs through specific RNA-binding domains, generating multi-molecular complexes known as ribonucleoproteins (RNPs). Various post-translational modifications (PTMs) have been described to regulate RBP structure, subcellular localization, and interactions with other proteins or RNAs. Recent proteome-wide experiments showed that RBPs are the most representative group within the class of arginine (R)-methylated proteins. Moreover, emerging evidence suggests that this modification plays a role in the regulation of RBP-RNA interactions. Nevertheless, a systematic analysis of how changes in protein-R-methylation can affect globally RBPs-RNA interactions is still missing. We describe here a quantitative proteomics approach to profile global changes of RBP-RNA interactions upon the modulation of type I and II protein arginine methyltransferases (PRMTs). By coupling the recently described Orthogonal Organic Phase Separation (OOPS) strategy with the Stable Isotope Labelling with Amino acids in Cell culture (SILAC) and pharmacological modulation of PRMTs, we profiled RNA-protein interaction dynamics in dependence of protein-R-methylation. Data are available via ProteomeXchange with identifier PXD024601.
Morality of the Heart: Heart Rate Variability and Moral Rule Adherence in Men

Moral rules are a cornerstone of many societies. Most moral rules are concerned with the welfare of other individuals, reflecting individuals’ innate aversion against harming other individuals. Harming others is associated with aversive experiences, implying that individuals who are sensitive to the aversiveness of these experiences are more likely to follow moral rules than individuals who are insensitive to the aversiveness of these experiences. Individuals’ sensitivity for aversive experiences depends on individuals’ ability to integrate the underlying neural and physiological processes: Individuals who are more efficient in integrating these processes are more sensitive to the aversiveness that is associated with moral rule violations than individuals who are less efficient in integrating these processes. Individuals who differ in their ability to integrate these processes may, thus, also differ in their inclination to follow moral rules. We tested this assumption in a sample of healthy individuals (67 males) who completed measures of moral rule adherence and integration abilities. Moral rule adherence was assessed with self-report measure and integration abilities were assessed with a resting state measure of heart rate variability (HRV), which reflects prefrontal–(para-)limbic engagement during the integration of physical and neural processes. We found a positive association between individuals’ HRV and individuals’ moral rule adherence, implying that individuals with efficient integration abilities were more inclined to follow moral rules than individuals with inefficient integration abilities. Our findings support the assumption that individuals with different integration abilities also differ in moral rule adherence, presumably because of differences in aversiveness sensitivity.
Effects of 3% Boric Acid Solution on Cutaneous Candida albicans Infection and Microecological Flora Mice

To determine the effect of 3% boric acid solution on cutaneous infections with Candida albicans (CA) in mice and its effect on skin microflora. Female mice were divided into three groups, with 18 mice in each group. Two injection sites were randomly selected, and 0.1 mL of CA mycelium suspension was injected into the epidermis and dermis of the back of mice. Group N was treated with sterile water for injection (SWFI). We observed the clinical manifestations, fungal fluorescence microscopic examination and colony count. Group B were hydropathically compressed with 3% boric acid solution for 30 min every 12 h. Group M was treated with SWFI, and group N was not treated. One week later, each group was observed with naked eyes, and skin samples were collected. The effect of boric acid on skin microflora was measured using Internal Transcribed Spacer Identification (ITS) and 16S rRNA genes. There were no significant changes in group M. In group B, the degree of skin injury was alleviated, the wounds healed markedly, and the exudate amount decreased. The effective rate of group B (83%) was significantly higher than that of group M (25%) (P < 0.05). The relative average abundance of Candida (P < 0.0001) and CA (P < 0.05) in group B was significantly lower than that in group M. Compared with group M, the microbial richness of group B changed little, but the diversity decreased. The flora structure of group B was significantly different from that of group M, but like that of group N. In group B, the abundance of Proteobacteria (P < 0.001), Enterobacteriaceae (P < 0.001), and Escherichia-Shigella (P < 0.001) was significantly greater, and the abundance of Firmicutes (P < 0.001), Staphylococcaceae (P < 0.001), and Staphylococcus (P < 0.001) were significantly lower. The 3% boric acid solution significantly reduced the symptoms of skin infection with Candida albicans. It inhibited the growth of Candida albicans and CA, reduced the diversity of skin microorganisms, increased the abundance of Proteobacteria, Enterobacteriaceae, Escherichia-Shigella, and reduced the abundance of Firmicutes, Staphylococcaceae, Staphylococcus.
Measuring the Value of a Practical Text Mining Approach to Identify Patients With Housing Issues in the Free-Text Notes in Electronic Health Record: Findings of a Retrospective Cohort Study

Introduction: Despite the growing efforts to standardize coding for social determinants of health (SDOH), they are infrequently captured in electronic health records (EHRs). Most SDOH variables are still captured in the unstructured fields (i.e., free-text) of EHRs. In this study we attempt to evaluate a practical text mining approach (i.e., advanced pattern matching techniques) in identifying phrases referring to housing issues, an important SDOH domain affecting value-based healthcare providers, using EHR of a large multispecialty medical group in the New England region, United States. To present how this approach would help the health systems to address the SDOH challenges of their patients we assess the demographic and clinical characteristics of patients with and without housing issues and briefly look into the patterns of healthcare utilization among the study population and for those with and without housing challenges. Methods: We identified five categories of housing issues [i.e., homelessness current (HC), homelessness history (HH), homelessness addressed (HA), housing instability (HI), and building quality (BQ)] and developed several phrases addressing each one through collaboration with SDOH experts, consulting the literature, and reviewing existing coding standards. We developed pattern-matching algorithms (i.e., advanced regular expressions), and then applied them in the selected EHR. We assessed the text mining approach for recall (sensitivity) and precision (positive predictive value) after comparing the identified phrases with manually annotated free-text for different housing issues. Results: The study dataset included EHR structured data for a total of 20,342 patients and 2,564,344 free-text clinical notes. The mean (SD) age in the study population was 75.96 (7.51). Additionally, 58.78% of the cohort were female. BQ and HI were the most frequent housing issues documented in EHR free-text notes and HH was the least frequent one. The regular expression methodology, when compared to manual annotation, had a high level of precision (positive predictive value) at phrase, note, and patient levels (96.36, 95.00, and 94.44%, respectively) across different categories of housing issues, but the recall (sensitivity) rate was relatively low (30.11, 32.20, and 41.46%, respectively). Conclusion: Results of this study can be used to advance the research in this domain, to assess the potential value of EHR's free-text in identifying patients with a high risk of housing issues, to improve patient care and outcomes, and to eventually mitigate socioeconomic disparities across individuals and communities.
Long-Term Clinical Outcomes in Patients With an Acute ST-Segment-Elevation Myocardial Infarction Stratified by Angiography-Derived Index of Microcirculatory Resistance

Aims: Despite the prognostic value of coronary microvascular dysfunction (CMD) in patients with ST-segment-elevation myocardial infarction (STEMI), its assessment with pressure-wire-based methods remains limited due to cost, technical and procedural complexities. The non-hyperaemic angiography-derived index of microcirculatory resistance (NH IMRangio) has been shown to reliably predict microvascular injury in patients with STEMI. We investigated the prognostic potential of NH IMRangio as a pressure-wire and adenosine-free tool. Methods and Results: NH IMRangio was retrospectively derived on the infarct-related artery at completion of primary percutaneous coronary intervention (pPCI) in 262 prospectively recruited STEMI patients. Invasive pressure-wire-based assessment of the index of microcirculatory resistance (IMR) was performed. The combination of all-cause mortality, resuscitated cardiac arrest and new heart failure was the primary endpoint. NH IMRangio showed good diagnostic performance in identifying CMD (IMR > 40U); AUC 0.78 (95%CI: 0.72–0.84, p < 0.0001) with an optimal cut-off at 43U. The primary endpoint occurred in 38 (16%) patients at a median follow-up of 4.2 (2.0–6.5) years. On survival analysis, NH IMRangio > 43U (log-rank test, p < 0.001) was equivalent to an IMR > 40U(log-rank test, p = 0.02) in predicting the primary endpoint (hazard ratio comparison p = 0.91). NH IMRangio > 43U was an independent predictor of the primary endpoint (adjusted HR 2.13, 95% CI: 1.01–4.48, p = 0.047). Conclusion: NH IMRangio is prognostically equivalent to invasively measured IMR and can be a feasible alternative to IMR for risk stratification in patients presenting with STEMI.
Electrochemical and Computational Study of Oxygen Reduction Reaction on Non-Precious Transition Metal/Nitrogen Doped Carbon Materials

An important challenge in low temperature fuel cell development is to find high performance non-precious catalysts replacing expensive platinum cathode catalysts for oxygen reduction reaction (ORR). The recently developed transition metal/nitrogen doped carbon-based materials (TM-N-C) exhibited catalytic activity close to that of platinum, but there are still many questions under debate. In this thesis, electrochemical and computational methods were employed to reveal the ORR mechanism on TM-N-C catalysts. In the experimental aspect, a cost-effective two-step process, electrospinning and pyrolysis, was developed to produce the TM-N-C catalysts. The electrochemical techniques were applied to the catalytic property characterization of the synthesized catalysts, showing that the Fe-N-C catalyst possesses higher activity than the Co-N-C catalyst and could promote 4e- pathway, while O2 electroreduction was found to proceed mainly with 2e- pathway yielding hydrogen peroxide on the Co-N-C catalyst. In the computational aspect, the first-principles density functional theory (DFT) was employed to calculate the adsorption energies and activation energies, elucidating the ORR mechanism on TM-N4 type active sites. Based upon the calculation results, the linear correlation between the O2 adsorption energy and the non-bonding d orbitals center in the transition metal macrocyclic complexes was established. The free energy diagram extracted from the calculation results uncovered that the ORR could happen through 4e- associative pathway on the FeN4 site, whereas might end with a 2e- pathway on the CoN4 site due to high energy barrier for O-O bond splitting, supporting the experimental observations. The superior activity of TM-N-C catalysts in alkaline than in acid was well-explained by the activity loss of the coexisted metal-free active sites induced by pyridinic nitrogen protonation in acid. Moreover, the microkinetic analysis was demonstrated to interpret DFT calculated energy parameters as polarization curves. With this tool, the study of the local carbon structures in the Fe-N-C catalysts directly revealed that the introduction of micropores could enhance their catalytic activity through facilitating the formation of FeN4-C8 active sites with high specific activity.
MOTIF: A Large Malware Reference Dataset with Ground Truth Family Labels

Malware family classification is a significant issue with public safety and research implications that has been hindered by the high cost of expert labels. The vast majority of corpora use noisy labeling approaches that obstruct definitive quantification of results and study of deeper interactions. In order to provide the data needed to advance further, we have created the Malware Open-source Threat Intelligence Family (MOTIF) dataset. MOTIF contains 3,095 malware samples from 454 families, making it the largest and most diverse public malware dataset with ground truth family labels to date, nearly 3x larger than any prior expert-labeled corpus and 36x larger than the prior Windows malware corpus. MOTIF also comes with a mapping from malware samples to threat reports published by reputable industry sources, which both validates the labels and opens new research opportunities in connecting opaque malware samples to human-readable descriptions. This enables important evaluations that are normally infeasible due to non-standardized reporting in industry. For example, we provide aliases of the different names used to describe the same malware family, allowing us to benchmark for the first time accuracy of existing tools when names are obtained from differing sources. Evaluation results obtained using the MOTIF dataset indicate that existing tasks have significant room for improvement, with accuracy of antivirus majority voting measured at only 62.10% and the well-known AVClass tool having just 46.78% accuracy. Our findings indicate that malware family classification suffers a type of labeling noise unlike that studied in most ML literature, due to the large open set of classes that may not be known from the sample under consideration
Suppression, Maintenance, and Surprise: Neuronal Correlates of Predictive Processing Specialization for Musical Rhythm

Auditory repetition suppression and omission activation are opposite neural phenomena and manifestations of principles of predictive processing. Repetition suppression describes the temporal decrease in neural activity when a stimulus is constant or repeated in an expected temporal fashion; omission activity is the transient increase in neural activity when a stimulus is temporarily and unexpectedly absent. The temporal, repetitive nature of musical rhythms is ideal for investigating these phenomena. During an fMRI session, 10 healthy participants underwent scanning while listening to musical rhythms with two levels of metric complexity, and with beat omissions with different positional complexity. Participants first listened to 16-s-long presentations of continuous rhythms, before listening to a longer continuous presentation with beat omissions quasi-randomly introduced. We found deactivation in bilateral superior temporal gyri during the repeated presentation of the normal, unaltered rhythmic stimulus, with more suppression of activity in the left hemisphere. Omission activation of bilateral middle temporal gyri was right lateralized. Persistent activity was found in areas including the supplementary motor area, caudate nucleus, anterior insula, frontal areas, and middle and posterior cingulate cortex, not overlapping with either listening, suppression, or omission activation. This suggests that the areas are perhaps specialized for working memory maintenance. We found no effect of metric complexity for either the normal presentation or omissions, but we found evidence for a small effect of omission position—at an uncorrected threshold—where omissions in the more metrical salient position, i.e., the first position in the bar, showed higher activation in anterior cingulate/medial superior frontal gyrus, compared to omissions in the less salient position, in line with the role of the anterior cingulate cortex for saliency detection. The results are consistent with findings in our previous studies on Parkinson’s disease, but are put into a bigger theoretical frameset.
Power Dispatching of Transportable Energy Storage System for Post-disaster Restoration Scheme of Port: The AES-Based Joint Restoration Scheme

In recent years, the rapid development of artificial intelligence, Big Data, Cloud Computing, etc., rapidly develops, synergy development of the transportation-energy-information based triple play has been accelerated. The all-electric ship (AES) is satisfied with the demand for both the unreasonable resource configuration of port energy system and low energy efficiency caused by sudden disasters. As a power carrier unit, AES has great potential in improving the resistance of port power distribution network for large-area blackout. Therefore, in this paper, a joint post-disaster restoration scheme for AESs and distribution generation scheduling in ports’ microgrid (MG) is proposed to minimize the cost of post-disaster restoration including customer interruption cost and AES operation cost. The time-space network (TSN) model which describes the scheduling of AESs is applied to compare the grid resilience and flexibility of AES-based joint dispatching and only relying on distributed generation equipment in post-disaster restoration. The joint scheduling problem is formulated as a mixed-integer linear programming. The proposed model and scheme are tested in a system with 3 ports and 4 AESs verified the resilience of the port power distribution network with AESs.
Integrative Analysis of DNA Methylation and microRNA Expression Reveals Mechanisms of Racial Heterogeneity in Hepatocellular Carcinoma

Pathologic alterations in epigenetic regulation have long been considered a hallmark of many cancers, including hepatocellular carcinoma (HCC). In a healthy individual, the relationship between DNA methylation and microRNA (miRNA) expression maintains a fine balance; however, disruptions in this harmony can aid in the genesis of cancer or the propagation of existing cancers. The balance between DNA methylation and microRNA expression and its potential disturbance in HCC can vary by race. There is emerging evidence linking epigenetic events including DNA methylation and miRNA expression to cancer disparities. In this paper, we evaluate the epigenetic mechanisms of racial heterogenity in HCC through an integrated analysis of DNA methylation, miRNA, and combined regulation of gene expression. Specifically, we generated DNA methylation, mRNA-seq, and miRNA-seq data through the analysis of tumor and adjacent non-tumor liver tissues from African Americans (AA) and European Americans (EA) with HCC. Using mixed ANOVA, we identified cytosine-phosphate-guanine (CpG) sites, mRNAs, and miRNAs that are significantly altered in HCC vs. adjacent non-tumor tissue in a race-specific manner. We observed that the methylome was drastically changed in EA with a significantly larger number of differentially methylated and differentially expressed genes than in AA. On the other hand, the miRNA expression was altered to a larger extent in AA than in EA. Pathway analysis functionally linked epigenetic regulation in EA to processes involved in immune cell maturation, inflammation, and vascular remodeling. In contrast, cellular proliferation, metabolism, and growth pathways are found to predominate in AA as a result of this epigenetic analysis. Furthermore, through integrative analysis, we identified significantly differentially expressed genes in HCC with disparate epigenetic regulation, associated with changes in miRNA expression for AA and DNA methylation for EA.