Miracle-dz/UniFAR-FTUs huggingface dataset:
A Novel Computed Tomography-Based Imaging Approach for Etiology Evaluation in Patients With Acute Coronary Syndrome and Non-obstructive Coronary Angiography

Objective: This study sought to investigate the diagnostic value of dynamic CT myocardial perfusion imaging (CT-MPI) combined with coronary CT angiography (CCTA) in acute coronary syndrome (ACS) patients without obstructive coronary angiography. Methods: Consecutive ACS patients with normal or non-obstructive coronary angiography findings who had cardiac magnetic resonance (CMR) contraindications or inability to cooperate with CMR examinations were prospectively enrolled and referred for dynamic CT-MPI + CCTA + late iodine enhancement (LIE). ACS etiology was determined according to combined assessment of coronary vasculature by CCTA, quantified myocardial blood flow (MBF) and presence of LIE. Results: Twenty two patients were included in the final analysis. CCTA revealed two cases of side branch occlusion and one case of intramural hematoma which were overlooked by invasive angiography. High risk plaques were observed in 6 (27.3%) patients whereas myocardial ischemia was presented in 19 (86.4%) patients with varied extent and severity. LIE was positive in 13 (59.1%) patients and microvascular obstruction was presented in three cases with side branch occlusion or spontaneous intramural hematoma. The specific etiology was identified in 20 (90.9%) patients, of which the most common cause was cardiomyopathies (41%), followed by microvascular dysfunction (14%) and plaque disruption (14%). Conclusion: Dynamic CT-MPI + CCTA was able to reveal the potential etiologies in majority of patients with ACS and non-obstructive coronary angiography. It may be a useful alternative to CMR for accurate etiology evaluation.
Prediction of Minimal Inhibitory Concentration of Meropenem Against Klebsiella pneumoniae Using Metagenomic Data

Minimal inhibitory concentration (MIC) is defined as the lowest concentration of an antimicrobial agent that can inhibit the visible growth of a particular microorganism after overnight incubation. Clinically, antibiotic doses for specific infections are determined according to the fraction of MIC. Therefore, credible assessment of MICs will provide a physician valuable information on the choice of therapeutic strategy. Early and precise usage of antibiotics is the key to an infection therapy. Compared with the traditional culture-based method, the approach of whole genome sequencing to identify MICs can shorten the experimental time, thereby improving clinical efficacy. Klebsiella pneumoniae is one of the most significant members of the genus Klebsiella in the Enterobacteriaceae family and also a common non-social pathogen. Meropenem is a broad-spectrum antibacterial agent of the carbapenem family, which can produce antibacterial effects of most Gram-positive and -negative bacteria. In this study, we used single-nucleotide polymorphism (SNP) information and nucleotide k-mers count based on metagenomic data to predict MICs of meropenem against K. pneumoniae. Then, features of 110 sequenced K. pneumoniae genome data were combined and modeled with XGBoost algorithm and deep neural network (DNN) algorithm to predict MICs. We first use the XGBoost classification model and the XGBoost regression model. After five runs, the average accuracy of the test set was calculated. The accuracy of using nucleotide k-mers to predict MICs of the XGBoost classification model and XGBoost regression model was 84.5 and 89.1%. The accuracy of SNP in predicting MIC was 80 and 81.8%, respectively. The results show that XGBoost regression is better than XGBoost classification in both nucleotide k-mers and SNPs to predict MICs. We further selected 40 nucleotide k-mers and 40 SNPs with the highest correlation with MIC values as features to retrain the XGBoost regression model and DNN regression model. After 100 and 1,000 runs, the results show that the accuracy of the two models was improved. The accuracy of the XGBoost regression model for k-mers, SNPs, and k-mers & SNPs was 91.1, 85.2, and 91.3%, respectively. The accuracy of the DNN regression model was 91.9, 87.1, and 91.8%, respectively. Through external verification, some of the selected features were found to be related to drug resistance.
Interactive 3D Brain Helps You Learn How the Brain is Organized

Which parts of your brain help you to talk to and understand others? How about recognizing your friends by their faces? Or remembering the last time you ate your favorite dessert? In this article we describe EduCortex, a free educational tool that allows you to play with a 3D brain, to discover how different parts of the brain work together to help you do things. By clicking on the brain, you will see words that are most associated with the selected brain region. For example, by entering a word like “language,” you can see the parts of the brain related to language. EduCortex works by using an online collection of information that automatically checks over 14,000 scientific papers, to see how the content of each paper relates to different brain parts.
Effect of Gender to Fat Deposition in Yaks Based on Transcriptomic and Metabolomics Analysis

Fat deposition in yaks plays an important part in survival, multiplication, and meat quality. In this work, the characteristic of fat deposition in male yaks (MYs) and female yaks (FYs) and the regulations of gender to yak fat deposition were explored by mRNA-Seq and non-targeted metabolomics analyses. FYs possessed a higher body fat rate (BFR) of visceral fat, fat content in longissimus dorsi (LD) and liver, and subcutaneous fat thickness (p < 0.05). The fat and cholesterol synthesis in liver and the fat transport in FY blood increased. The fat metabolism in yaks is the combined effect of carbohydrate, fatty acid, and amino acid metabolism by tricarboxylic acid (TCA) cycle, and an increase of triglyceride (TG) synthesis was accompanied by an increase of steroid synthesis. The high levels of myo-inositol and cortisol (COR) (p < 0.01) activated the calcium signaling in FY subcutaneous fat, followed by the increase of adipocyte secretion, and resulted in more leptin (LEP) secretion (p < 0.01). Then peroxisome proliferator-activated receptor (PPAR) signaling was activated by the focal adhesions and ECM–receptor interaction. Finally, the TG and steroid synthesis increased by the expression regulation of ME1, SCD, ELOVL6, DGAT2, DBI, LPL, CPT1, PLIN1, LIPA, DHCR24, and SQLE gene. The above genes can be considered as the candidate genes for yak with higher fat amount in molecular breeding in the future. This study can provide a theoretical basis for improving the meat quality and breeding of yaks.
Alexithymia Is a Key Mediator of the Relationship Between Magical Thinking and Empathy

Thought action fusion (TAF), whereby internal thoughts are perceived to exert equivalent effects to external actions, is a form of magical thinking. Psychiatric disorders associated with TAF (e.g. schizophrenia; obsessive compulsive disorder) can feature atypical social cognition. We explored relationships between TAF and empathy in 273 healthy young adults. TAF was directly correlated with higher personal distress, but not perspective taking, fantasy or empathic concern. TAF moral (the belief that thinking about an action/behaviour is morally equivalent to actually performing that behaviour) was predicted by emotion contagion, alexithymia and need for closure. TAF likelihood (the belief that simply having a thought about an event makes that event more likely to occur) was predicted by personal distress, sense of agency and alexithymia. Both cognitive (TAF and negative sense of agency) and emotional (emotion contagion, alexithymia) factors contributed to personal distress. TAF, negative sense of agency and personal distress mediated the effect of emotion contagion on alexithymia. Our findings reveal complex relationships between emotional processes and TAF, shedding further light on the social cognitive profile of disorders associated with magical thinking. Furthermore, they emphasise the potential importance of alexithymia and emotion contagion as mediators or potential risk factors in the development of psychiatric symptoms linked to TAF, such as intrusive thoughts about harm to others.
The Role of Hemoglobin Subunit Delta in the Immunopathy of Multiple Sclerosis: Mitochondria Matters

Background Although the exact pathophysiology of MS has not been identified, mitochondrial stress can be one of the culprits in MS development. Herein, we have applied microarray analysis, single-cell sequencing analysis, and ex vivo study to elucidate the role of mitochondrial stress in PBMCs of MS patients. Methods For this purpose, we analyzed the GSE21942 and GSE138266 datasets to identify the DEGs and hub genes in the PBMCS of MS patients and describe the expression of shared genes in the different immune cells. The GO pathway analysis of DEGs and turquoise module genes were conducted to shed light on their biological significance. To validate the obtained results, the gene expression of HBD, as the most remarkable DEG in the PBMCS of affected patients, was measured in the PBMCS of healthy donors, treatment-naïve MS patients, and MS patients treated with GA, fingolimod, DMF, and IFNβ-1α. Results Based on WGCNA and DEGs analysis, HBD, HBM, SLC4A1, LILRA5, SLC25A37, SELENBP1, ALYREF, SNRNP40, and HINT3 are the identified common genes in the PMBCS. Using single-cell sequencing analysis on PBMCS, we have characterized various cell populations in MS and illustrated the common gene expression on the different immune cells. Furthermore, GO pathway analysis of DEGs, and turquoise module genes have indicated that these genes are involved in immune responses, myeloid cell activation, leukocyte activation, oxygen carrier activity, and replication fork processing bicarbonate transport pathways. Our ex vivo investigation has shown that HBD expression in the treatment-naïve RRMS patients is significantly increased compared to healthy donors. Of interest, immunomodulatory therapies with fingolimod, DMF, and IFNβ-1α have significantly decreased HBD expression. Conclusion HBD is one of the remarkably up-regulated genes in the PBMCS of MS patients. HBD is substantially up-regulated in treatment-naïve MS patients, and immunomodulatory therapies with fingolimod, DMF, and IFNβ-1α can remarkably down-regulate HBD expression. Based on the currently available evidence, the cytoprotective nature of HBD against oxidative stress can be the underlying reason for HBD up-regulation in MS. Nevertheless, further investigations are needed to shed light on the molecular mechanisms of HBD in the oxidative stress of MS patients.
Traumatic Brain Injury Induces cGAS Activation and Type I Interferon Signaling in Aged Mice

Aging adversely affects inflammatory processes in the brain, which has important implications in the progression of neurodegenerative disease. Following traumatic brain injury (TBI), aged animals exhibit worsened neurological function and exacerbated microglial-associated neuroinflammation. Type I Interferons (IFN-I) contribute to the development of TBI neuropathology. Further, the Cyclic GMP-AMP Synthase (cGAS) and Stimulator of Interferon Genes (STING) pathway, a key inducer of IFN-I responses, has been implicated in neuroinflammatory activity in several age-related neurodegenerative diseases. Here, we set out to investigate the effects of TBI on cGAS/STING activation, IFN-I signaling and neuroinflammation in young and aged C57Bl/6 male mice. Using a controlled cortical impact model, we evaluated transcriptomic changes in the injured cortex at 24 hours post-injury, and confirmed activation of key neuroinflammatory pathways in biochemical studies. TBI induced changes were highly enriched for transcripts that were involved in inflammatory responses to stress and host defense. Deeper analysis revealed that TBI increased expression of IFN-I related genes (e.g. Ifnb1, Irf7, Ifi204, Isg15) and IFN-I signaling in the injured cortex of aged compared to young mice. There was also a significant age-related increase in the activation of the DNA-recognition pathway, cGAS, which is a key mechanism to propagate IFN-I responses. Finally, enhanced IFN-I signaling in the aged TBI brain was confirmed by increased phosphorylation of STAT1, an important IFN-I effector molecule. This age-related activation of cGAS and IFN-I signaling may prove to be a mechanistic link between microglial-associated neuroinflammation and neurodegeneration in the aged TBI brain.
RanBP3 Regulates Proliferation, Apoptosis and Chemosensitivity of Chronic Myeloid Leukemia Cells via Mediating SMAD2/3 and ERK1/2 Nuclear Transport

Abnormal subcellular localization of proteins is an important cause of tumorigenesis and drug resistance. Chromosome region maintenance 1 (CRM1), the nuclear export regulator of most proteins, has been confirmed to be over-expressed in various malignancies and is regarded as an efficient target. But the potential role of the CRM1 cofactor RanBP3 (Ran Binding Protein 3) is left unrevealed in chronic myeloid leukemia (CML). Here, we first detected the level of RanBP3 in CML and found an elevated RanBP3 expression in CML compared with control. Then we used shRNA lentivirus to down-regulated RanBP3 in imatinib sensitive K562 cells and resistant K562/G01 cells and found RanBP3 silencing inhibited cell proliferation by up-regulating p21, induced caspase3-related cell apoptosis, and enhanced the drug sensitivity of IM in vitro. Notably, we observed that RanBP3 silencing restored imatinib sensitivity of K562 cells in NOD/SCID mice. Mechanistically, the nuclear aggregation of SMAD2/3 revealed that tumor suppressor axis (TGF-β)-SMAD2/3-p21 was the anti-proliferation program related to RanBP3 knockdown, and the decrease of cytoplasmic ERK1/2 caused by RanBP3 interference leaded to the down-regulation of anti-apoptosis protein p(Ser112)-BAD, which was the mechanism of increased cell apoptosis and enhanced chemosensitivity to imatinib in CML. In summary, this study revealed the expression and potential role of RanBP3 in CML, suggesting that targeting RanBP3 alone or combined with TKIs could improve the clinical response of CML.
Tumor Infiltrating Lymphocytes Target HLA-I Phosphopeptides Derived From Cancer Signaling in Colorectal Cancer

There is a pressing need for novel immunotherapeutic targets in colorectal cancer (CRC). Cytotoxic T cell infiltration is well established as a key prognostic indicator in CRC, and it is known that these tumor infiltrating lymphocytes (TILs) target and kill tumor cells. However, the specific antigens that drive these CD8+ T cell responses have not been well characterized. Recently, phosphopeptides have emerged as strong candidates for tumor-specific antigens, as dysregulated signaling in cancer leads to increased and aberrant protein phosphorylation. Here, we identify 120 HLA-I phosphopeptides from primary CRC tumors, CRC liver metastases and CRC cell lines using mass spectrometry and assess the tumor-resident immunity against these posttranslationally modified tumor antigens. Several CRC tumor-specific phosphopeptides were presented by multiple patients’ tumors in our cohort (21% to 40%), and many have previously been identified on other malignancies (58% of HLA-A*02 CRC phosphopeptides). These shared antigens derived from mitogenic signaling pathways, including p53, Wnt and MAPK, and are therefore markers of malignancy. The identification of public tumor antigens will allow for the development of broadly applicable targeted therapeutics. Through analysis of TIL cytokine responses to these phosphopeptides, we have established that they are already playing a key role in tumor-resident immunity. Multifunctional CD8+ TILs from primary and metastatic tumors recognized the HLA-I phosphopeptides presented by their originating tumor. Furthermore, TILs taken from other CRC patients’ tumors targeted two of these phosphopeptides. In another cohort of CRC patients, the same HLA-I phosphopeptides induced higher peripheral T cell responses than they did in healthy donors, suggesting that these immune responses are specifically activated in CRC patients. Collectively, these results establish HLA-I phosphopeptides as targets of the tumor-resident immunity in CRC, and highlight their potential as candidates for future immunotherapeutic strategies.
Tracing Nutrients and Organic Matter Changes in Eutrophic Wenchang (China) and Oligotrophic Krka (Croatia) Estuaries: A Comparative Study

Estuaries modify the concentration and composition of riverine nutrients and organic matter (OM), which eventually determine the riverine flux effect to coasts. Nutrients, organic carbon (OC), pigments, and amino acids (AAs) from the samples collected in the eutrophic Wenchang River Estuary (WRE) in China and the oligotrophic Krka River Estuary (KRE) in Croatia were analyzed in order to have a better understanding of how estuaries regulate terrestrial materials. We found a clear increase of dissolved inorganic nitrogen (DIN) concentration and its subsequent decrease due to the removal of DIN (over 100 μM) in the WRE, whereas DIN showed minor variation lengthwise in the KRE, i.e., with the salinity changes, ranging between 1.0 and 5.8 μM. The elevated algae-derived OC, dissolved organic nitrogen, and particulate AAs nitrogen suggest that the OM assimilation may explain approximately one-third of the DIN removal in the WRE, whereas in the oligotrophic KRE, such inorganic to organic transformation is not likely to be significant. Due to the prominent estuarine nitrogen removal/assimilation process, DIN/dissolved inorganic phosphorus (DIP) ratio was as high as 425 in the upper WRE under strong riverine influence, but it declined to as low as 5.4 at the mouth of WRE, that is even lower than DIN/DIP ratio at the mouth of oligotrophic KRE (12). When compared with other rivers worldwide, the Wenchang River showed high nutrients and organic carbon yields. Given the contrasting estuarine process (e.g., DIN removal) between the KRE and the WRE, apparent high nutrient yield from eutrophic rivers should be viewed with caution in ocean studies as the final impact to coastal zone could be similar to the oligotrophic rivers like the KRE.
Evolutionary Diversity Peaks at Mid-Elevations Along an Amazon-to-Andes Elevation Gradient

Elevation gradients present enigmatic diversity patterns, with trends often dependent on the dimension of diversity considered. However, focus is often on patterns of taxonomic diversity and interactions between diversity gradients and evolutionary factors, such as lineage age, are poorly understood. We combine forest census data with a genus level phylogeny representing tree ferns, gymnosperms, angiosperms, and an evolutionary depth of 382 million years, to investigate taxonomic and evolutionary diversity patterns across a long tropical montane forest elevation gradient on the Amazonian flank of the Peruvian Andes. We find that evolutionary diversity peaks at mid-elevations and contrasts with taxonomic richness, which is invariant from low to mid-elevation, but then decreases with elevation. We suggest that this trend interacts with variation in the evolutionary ages of lineages across elevation, with contrasting distribution trends between younger and older lineages. For example, while 53% of young lineages (originated by 10 million years ago) occur only below ∼1,750 m asl, just 13% of old lineages (originated by 110 million years ago) are restricted to below ∼1,750 m asl. Overall our results support an Environmental Crossroads hypothesis, whereby a mid-gradient mingling of distinct floras creates an evolutionary diversity in mid-elevation Andean forests that rivals that of the Amazonian lowlands.
Urban Ecological Restoration: Setting Priorities for Restoring Native Vegetation in Lava Field Remnants in Mexico City

As cities overgrow, the need for ecological restoration is becoming increasingly urgent, especially in densely populated areas. Urban ecological restoration represents the best approach to undertake damages to restore native ecosystem remnants fulfilling biodiversity but also social goals in dense urban settings such as Mexico City. The feasibility of restoring unique xerophytic scrub vegetation in lava field remnants was evaluated in a portion of a university campus in Mexico City. Here we present an index (Need and Feasibility of Restoration Index, NFRI) for such purpose. The NFRI was designed through multicriteria analysis and considered ecological, economic, and social indicators. Cluster and principal components analysis were carried out to identify different groups of lava field remnants with similar characteristics and to point out critical variables that in turn would support management strategies. The outcomes made evident the necessity of restoring native vegetation for all of the evaluated remnants; however, the group containing the largest ones obtained the highest values for restoration feasibility and NFRI. The recovery of the rest of the remnants is critical to support the ecological restoration of the area as this may provide connectivity with better-preserved ecosystem remnants. When the restoration is unaffordable due to financial constraints, it is highly recommended to direct efforts towards ecological rehabilitation actions. The establishment of native xerophytic gardens is promoted when remnants cannot support a self-sustainable plant community. It is crucial to include the diversity of views and values of the community and the economic and ecological aspects to guarantee the sustainability of the landscape, especially in the urban context. The latter can provide better planning and design processes, ensuring benefits for humans and nature.