Miracle-dz/UniFAR-FTUs huggingface dataset:
Development and Validation of a Diagnostic Model to Predict the Risk of Ischemic Liver Injury After Stanford A Aortic Dissection Surgery

Objective: To define the risk factors of ischemic liver injury (ILI) following Stanford A aortic dissection surgery and to propose a diagnostic model for individual risk prediction. Methods: We reviewed the clinical parameters of ILI patients who underwent cardiac surgery from Beijing Anzhen Hospital, Capital Medical University between January 1, 2015 and October 30, 2020. The data was analyzed by the use of univariable and multivariable logistic regression analysis. A risk prediction model was established and validated, which showed a favorable discriminating ability and might contribute to clinical decision-making for ILI after Stanford A aortic dissection (AAD) surgery. The discriminative ability and calibration of the diagnostic model to predict ILI were tested using C statistics, calibration plots, and clinical usefulness. Results: In total, 1,343 patients who underwent AAD surgery were included in the study. After univariable and multivariable logistic regression analysis, the following variables were incorporated in the prediction of ILI: pre-operative serum creatinine, pre-operative RBC count <3.31 T/L, aortic cross-clamp time >140 min, intraoperative lactic acid level, the transfusion of WRBC, atrial fibrillation within post-operative 24 h. The risk model was validated by internal sets. The model showed a robust discrimination, with an area under the receiver operating characteristic (ROC) curve of 0.718. The calibration plots for the probability of perioperative ischemic liver injury showed coherence between the predictive probability and the actual probability (Hosmer-Lemeshow test, P = 0.637). In the validation cohort, the nomogram still revealed good discrimination (C statistic = 0.727) and good calibration (Hosmer-Lemeshow test, P = 0.872). The 10-fold cross-validation of the nomogram showed that the average misdiagnosis rate was 9.95% and the lowest misdiagnosis rate was 9.81%. Conclusion: Our risk model can be used to predict the probability of ILI after AAD surgery and have the potential to assist clinicians in making treatment recommendations.
Robots Versus Humans: Automated Annotation Accurately Quantifies Essential Ocean Variables of Rocky Intertidal Functional Groups and Habitat State

Standardized methods for effectively and rapidly monitoring changes in the biodiversity of marine ecosystems are critical to assess status and trends in ways that are comparable between locations and over time. In intertidal and subtidal habitats, estimates of fractional cover and abundance of organisms are typically obtained with traditional quadrat-based methods, and collection of photoquadrat imagery is a standard practice. However, visual analysis of quadrats, either in the field or from photographs, can be very time-consuming. Cutting-edge machine learning tools are now being used to annotate species records from photoquadrat imagery automatically, significantly reducing processing time of image collections. However, it is not always clear whether information is lost, and if so to what degree, using automated approaches. In this study, we compared results from visual quadrats versus automated photoquadrat assessments of macroalgae and sessile organisms on rocky shores across the American continent, from Patagonia (Argentina), Galapagos Islands (Ecuador), Gorgona Island (Colombian Pacific), and the northeast coast of the United States (Gulf of Maine) using the automated software CoralNet. Photoquadrat imagery was collected at the same time as visual surveys following a protocol implemented across the Americas by the Marine Biodiversity Observation Network (MBON) Pole to Pole of the Americas program. Our results show that photoquadrat machine learning annotations can estimate percent cover levels of intertidal benthic cover categories and functional groups (algae, bare substrate, and invertebrate cover) nearly identical to those from visual quadrat analysis. We found no statistical differences of cover estimations of dominant groups in photoquadrat images annotated by humans and those processed in CoralNet (binomial generalized linear mixed model or GLMM). Differences between these analyses were not significant, resulting in a Bray-Curtis average distance of 0.13 (sd 0.11) for the full label set, and 0.12 (sd 0.14) for functional groups. This is the first time that CoralNet automated annotation software has been used to monitor “Invertebrate Abundance and Distribution” and “Macroalgal Canopy Cover and Composition” Essential Ocean Variables (EOVs) in intertidal habitats. We recommend its use for rapid, continuous surveys over expanded geographical scales and monitoring of intertidal areas globally.
High-Throughput Genomic Data Reveal Complex Phylogenetic Relationships in Stylosanthes Sw (Leguminosae)

Allopolyploidy is widely present across plant lineages. Though estimating the correct phylogenetic relationships and origin of allopolyploids may sometimes become a hard task. In the genus Stylosanthes Sw. (Leguminosae), an important legume crop, allopolyploidy is a key speciation force. This makes difficult adequate species recognition and breeding efforts on the genus. Based on comparative analysis of nine high-throughput sequencing (HTS) samples, including three allopolyploids (S. capitata Vogel cv. “Campo Grande,” S. capitata “RS024” and S. scabra Vogel) and six diploids (S. hamata Taub, S. viscosa (L.) Sw. , S. macrocephala M. B. Ferreira and Sousa Costa, S. guianensis (Aubl.) Sw. , S. pilosa M. B. Ferreira and Sousa Costa and S. seabrana B. L. Maass & 't Mannetje) we provide a working pipeline to identify organelle and nuclear genome signatures that allowed us to trace the origin and parental genome recognition of allopolyploids. First, organelle genomes were de novo assembled and used to identify maternal genome donors by alignment-based phylogenies and synteny analysis. Second, nuclear-derived reads were subjected to repetitive DNA identification with RepeatExplorer2. Identified repeats were compared based on abundance and presence on diploids in relation to allopolyploids by comparative repeat analysis. Third, reads were extracted and grouped based on the following groups: chloroplast, mitochondrial, satellite DNA, ribosomal DNA, repeat clustered- and total genomic reads. These sets of reads were then subjected to alignment and assembly free phylogenetic analyses and were compared to classical alignment-based phylogenetic methods. Comparative analysis of shared and unique satellite repeats also allowed the tracing of allopolyploid origin in Stylosanthes, especially those with high abundance such as the StyloSat1 in the Scabra complex. This satellite was in situ mapped in the proximal region of the chromosomes and made it possible to identify its previously proposed parents. Hence, with simple genome skimming data we were able to provide evidence for the recognition of parental genomes and understand genome evolution of two Stylosanthes allopolyploids.
Distinct Roles of N-Terminal Fatty Acid Acylation of the Salinity-Sensor Protein SOS3

The Salt-Overly-Sensitive (SOS) pathway controls the net uptake of sodium by roots and the xylematic transfer to shoots in vascular plants. SOS3/CBL4 is a core component of the SOS pathway that senses calcium signaling of salinity stress to activate and recruit the protein kinase SOS2/CIPK24 to the plasma membrane to trigger sodium efflux by the Na/H exchanger SOS1/NHX7. However, despite the well-established function of SOS3 at the plasma membrane, SOS3 displays a nucleo-cytoplasmic distribution whose physiological meaning is not understood. Here, we show that the N-terminal part of SOS3 encodes structural information for dual acylation with myristic and palmitic fatty acids, each of which commands a different location and function of SOS3. N-myristoylation at glycine-2 is essential for plasma membrane association and recruiting SOS2 to activate SOS1, whereas S-acylation at cysteine-3 redirects SOS3 toward the nucleus. Moreover, a poly-lysine track in positions 7–11 that is unique to SOS3 among other Arabidopsis CBLs appears to be essential for the correct positioning of the SOS2-SOS3 complex at the plasma membrane for the activation of SOS1. The nuclear-localized SOS3 protein had limited bearing on the salt tolerance of Arabidopsis. These results are evidence of a novel S-acylation dependent nuclear trafficking mechanism that contrasts with alternative subcellular targeting of other CBLs by S-acylation.
Interplay Between the N-Terminal Domains of Arabidopsis Starch Synthase 3 Determines the Interaction of the Enzyme With the Starch Granule

The elongation of the linear chains of starch is undertaken by starch synthases. class 3 of starch synthase (SS3) has a specific feature: a long N-terminal region containing starch binding domains (SBDs). In this work, we analyze in vivo the contribution of these domains to the localization pattern of the enzyme. For this purpose, we divided the N-terminal region of Arabidopsis SS3 in three domains: D1, D2, and D3 (each of which contains an SBD and a coiled-coil site). Our analyses indicate that the N-terminal region is sufficient to determine the same localization pattern observed with the full-length protein. D2 binds tightly the polypeptide to the polymer and it is necessary the contribution of D1 and D3 to avoid the polypeptide to be trapped in the growing polymer. The localization pattern of Arabidopsis SS3 appears to be the result of the counterbalanced action of the different domains present in its N-terminal region.
Myocardial Expression of Estrogen Receptor-mRNA Is Associated With Lower Markers of Post-operative Organ Damage in Young Patients With Congenital Cardiac Defect

Background: Estrogen receptors (ERs) relate to cardio-protection in adults, but their role in younger patients is not known. We aimed to assess the myocardial expression of ERα- and ERβ- mRNA in young patients with congenital cardiac disease and to analyze their putative protective role. Patients and Methods: Twenty children and young adults (seven females and 13 males) with a median age of 13.8 years (interquartile range: 12.3 years) were enrolled in this prospective study. The myocardial expression of ER-mRNA and genes involved in inflammation, growth, and stress response was assessed by real-time PCR and was correlated to post-operative (po) outcome. Results: ER-mRNA was detected in the myocardium of all patients, independently of gender and age. The expression of ER-mRNA correlated with that of mRNA coding for brain natriuretic peptide and for all cytokines tested. A higher ERα-mRNA expression correlated with lower troponin T concentrations at 24 h po (p = 0.032), higher PaO2/FiO2 ratio at 4 h po (p = 0.059), lower fluid retention at 4 h po (p = 0.048), and lower aspartate aminotransferase (AST) levels at 24 h po (p = 0.047). A higher ERβ-mRNA expression was also correlated with lower fluid retention at 24 h po (p = 0.048). Patients in whom the levels of ERα- and ERβ-mRNA were >P50 had lower troponin T (p = 0.003, respectively) and lower AST concentrations at 24 h po (p = 0.043, respectively) than the others. Conclusions: The expression of ERα- and ERβ-mRNA is present in the myocardium of children and young adults with congenital cardiac defect and is associated with lower markers of po organ damage. This suggests that ERs may provide perioperative organ protection in this population.
Trophic Enrichment Factors of Carbon and Nitrogen Isotopic Ratios (Δ13C and Δ15N) in Four Marine Ciliates

Understanding the magnitude and causes of isotopic fractionation between organisms and their dietary resources is crucial for gaining knowledge on stable isotope ecology. However, little is known regarding the diet-tissue fractionation values of marine ciliates, which play a critical role in the reconstruction of microbial food webs. In the present study, we conducted experiments on two benthic (Pseudokeronopsis pararubra and Protocruzia labiata) and two pelagic (Strombidium sulcatum and Uronemella filificum) marine ciliates, where they were fed with isotopically constant foods (Chaetoceros calcitrans and Isochrysis galbana) under laboratory culture conditions to determine their carbon and nitrogen isotopic fractionation values (Δ13C and Δ15N). The stable isotope values (δ13C and δ15N) of ciliates for all experiments rapidly increased after the initial feeding, with half-lives ranging from 6.1 to 23.0h for δ13C and from 3.1 to 24.9h for δ15N. The Δ13C and Δ15N for all ciliates represented significantly positive enrichments, with overall mean fractionations of 0.6±0.2 and 1.2±0.4, respectively. Irrespective of the dietary type, both Δ13C and Δ15N were very similar for the same ciliate species. These results suggest that Δ13C and Δ15N for marine ciliates are similar to those found in common marine organisms with very little food-dependent variation. Overall, quantifying the specific isotopic fractionation of marine ciliates is expected to provide fundamental information on the trophic transfer of carbon, nitrogen, and energy flow through the microbial pathway in marine ecosystems.
Immune Checkpoint Inhibitor–Associated Tumor Lysis Syndrome: A Real-World Pharmacovigilance Study

Introduction: Immune checkpoint inhibitors (ICIs) have substantially improved the clinical outcomes of various malignancies. However, the adverse event of tumor lysis syndrome (TLS) has not been included in the National Comprehensive Cancer Network guidelines or drug inserts. In this study, we aimed to establish the relationship between ICI therapies and TLS events using data from a real-world pharmacovigilance database. Methods: The MedDRA terms of TLS and both generic and brand names of ICIs were retrieved from the FDA Adverse Event Reporting System. Four frequentist algorithms were employed to confirm the association between the TLS and the ICI regimens, involving anti-cytotoxic T lymphocyte antigen-4 (anti-CTLA-4), anti–programmed death receptor-1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1), and anti-(CTLA-4 + PD-1). A descriptive and statistical analysis was performed according to the case information. Results: One hundred sixty-four TLS cases, where patients underwent anti-CTLA-4 (n = 14), anti-(PD-1)/(PD-L1) (n = 113), or anti-(CTLA-4 + PD-1) (n = 37) therapies, were collected between the first quarter of 2004 and the fourth quarter of 2020. The most coverage-reporting year, age-group, sex, reporter, region, country, and indication were 2020 (n = 62), 60–74 years (n = 65), males (n = 105), physician (n = 66), Asia (n = 80), Japan (n = 67), and lung and thymus malignancies (n = 40), respectively. The median TLS onset time associated with anti-CTLA-4, anti-(PD-1)/(PD-L1), and anti-(CTLA-4 + PD-1) therapies was 6 (IQR: 2–39.5), 9 (IQR: 2–40), and 20 (IQR: 7.5–37.75) days, respectively. Mortality distribution of 71 reported death outcomes among three groups was statistically significant. All four algorithm signal values of anti-(CTLA-4 + PD-1) were higher than those of anti-CTLA-4 and anti-(PD-1)/(PD-L1). Conclusion: Elderly male patients with lung and thymus malignancies are frequently predisposed to TLS. ICI therapies could induce TLS in both solid and hematological malignancies. The rapid onset time and poor outcomes of patients prompt caution from health-care professionals.
A Zebrafish Model of Metastatic Colonization Pinpoints Cellular Mechanisms of Circulating Tumor Cell Extravasation

Metastasis is a multistep process in which cells must detach, migrate/invade local structures, intravasate, circulate, extravasate, and colonize. A full understanding of the complexity of this process has been limited by the lack of ability to study these steps in isolation with detailed molecular analyses. Leveraging a comparative oncology approach, we injected canine osteosarcoma cells into the circulation of transgenic zebrafish with fluorescent blood vessels in a biologically dynamic metastasis extravasation model. Circulating tumor cell clusters that successfully extravasated the vasculature as multicellular units were isolated under intravital imaging (n = 6). These extravasation-positive tumor cell clusters sublines were then molecularly profiled by RNA-Seq. Using a systems-level analysis, we pinpointed the downregulation of KRAS signaling, immune pathways, and extracellular matrix (ECM) organization as enriched in extravasated cells (p < 0.05). Within the extracellular matrix remodeling pathway, we identified versican (VCAN) as consistently upregulated and central to the ECM gene regulatory network (p < 0.05). Versican expression is prognostic for a poorer metastasis-free and overall survival in patients with osteosarcoma. Together, our results provide a novel experimental framework to study discrete steps in the metastatic process. Using this system, we identify the versican/ECM network dysregulation as a potential contributor to osteosarcoma circulating tumor cell metastasis.
Differential Expression of the TLR4 Gene in Pan-Cancer and Its Related Mechanism

Previous studies have revealed the relationship between toll-like receptor 4 (TLR4) polymorphisms and cancer susceptibility. However, the relationship between TLR4 and prognosis and immune cell infiltration in pan-cancer patients is still unclear. Through the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases, the distinct expression of the TLR4 gene in 24 tumors and normal tissues was analyzed. Univariate Cox proportional hazards regression analysis was used to identify the cancer types whose TLR4 gene expression was related to prognosis. The relationship between TLR4 and tumor cell immune invasion was studied. Spearman’s rank correlation coefficient was used to analyze the relationship among TLR4 and immune neoantigens, tumor mutation burden (TMB), microsatellite instability (MSI), DNA repair genes, and DNA methylation. Gene Set Enrichment Analysis (GSEA) was used to identify the tumor-related pathways that the TLR4 gene was highly expressed in; the expression of the TLR4 gene was verified with the Human Protein Atlas (HPA) database. Low expression of TLR4 was associated with an inferior prognosis in kidney renal clear cell carcinoma (KIRC), skin cutaneous melanoma (SKCM), and uterine corpus endometrial carcinoma (UCEC), while high expression was related to a poor prognosis in head and neck squamous cell carcinoma (HNSC), prostate adenocarcinoma (PRAD), stomach adenocarcinoma (STAD), and testicular germ cell tumor (TGCT). The expression of TLR4 was negatively correlated with the expression of B cells in STAD. The expression of TLR4 was positively correlated with the infiltration of B cells, CD4 and CD8 T cells, neutrophils, macrophages, and dendritic cells in STAD, KIRC, UCEC, TGCT, and SKCM. The expression of the TLR4 gene in KIRC, SKCM, STAD, TGCT, and UCEC was highly correlated with inducible T-cell costimulator (ICOS), cytotoxic T lymphocyte-associated molecule 4 (CTLA4), and CD28 immune checkpoints. Spearman’s rank correlation coefficient showed that the expression of TLR4 gene was significantly correlated with TMB in STAD and UCEC and was prominently correlated with MSI in TGCT, STAD, and SKCM. The expression of the TLR4 gene was highly correlated with MLH1, MSH2, and MSH6 in KIRC, SKCM, and STAD. The expression of the TLR4 gene was remarkably correlated with the methyltransferases DNA methyltransferase 2 (DNMT2) and DNA methyltransferase 3-beta (DNMT3B) in SKCM and STAD. Enrichment analysis showed that TLR4 was highly expressed in the chemokine signaling pathway and the cell adhesion molecule and cytokine receptor interaction pathway. In summary, the expression of TLR4 is linked to the prognosis of KIRC, SKCM, STAD, TGCT, and UCEC patients and the level of immune infiltration of CD4, CD8 T cells, macrophages, neutrophils, and dendritic cells.
Systematic Characterization of Novel Immune Gene Signatures Predicts Prognostic Factors in Hepatocellular Carcinoma

Background: The prognosis of patients with hepatocellular carcinoma (HCC) is negatively affected by the lack of effective prognostic indicators. The change of tumor immune microenvironment promotes the development of HCC. This study explored new markers and predicted the prognosis of HCC patients by systematically analyzing immune characteristic genes. Methods: Immune-related genes were obtained, and the differentially expressed immune genes (DEIGs) between tumor and para-cancer samples were identified and analyzed using gene expression profiles from TCGA, HCCDB, and GEO databases. An immune prognosis model was also constructed to evaluate the predictive performance in different cohorts. The high and low groups were divided based on the risk score of the model, and different algorithms were used to evaluate the tumor immune infiltration cell (TIIC). The expression and prognosis of core genes in pan-cancer cohorts were analyzed, and gene enrichment analysis was performed using clusterProfiler. Finally, the expression of the hub genes of the model was validated by clinical samples. Results: Based on the analysis of 730 immune-related genes, we identified 64 common DEIGs. These genes were enriched in the tumor immunologic related signaling pathways. The first 15 genes were selected using RankAggreg analysis, and all the genes showed a consistent expression trend across multi-cohorts. Based on lasso cox regression analysis, a 5-gene signature risk model (ATG10, IL18RAP, PRKCD, SLC11A1, and SPP1) was constructed. The signature has strong robustness and can stabilize different cohorts (TCGA-LIHC, HCCDB18, and GSE14520). Compared with other existing models, our model has better performance. CIBERSORT was used to assess the landscape maps of 22 types of immune cells in TCGA, GSE14520, and HCCDB18 cohorts, and found a consistent trend in the distribution of TIIC. In the high-risk score group, scores of Macrophages M1, Mast cell resting, and T cells CD8 were significantly lower than those of the low-risk score group. Different immune expression characteristics, lead to the different prognosis. Western blot demonstrated that ATG10, PRKCD, and SPP1 were highly expressed in cancer tissues, while IL18RAP and SLC11A1 expression in cancer tissues was lower. In addition, IL18RAP has a highly positive correlation with B cell, macrophage, Neutrophil, Dendritic cell, CD8 cell, and CD4 cell. The SPP1, PRKCD, and SLC11A1 genes have the strongest correlation with macrophages. The expression of ATG10, IL18RAP, PRKCD, SLC11A1, and SPP1 genes varies among different immune subtypes and between different T stages. Conclusion: The 5-immu-gene signature constructed in this study could be utilized as a new prognostic marker for patients with HCC.