Miracle-dz/UniFAR-FTUs huggingface dataset:
Requirements for Automating Moderation in Community Question-Answering Websites

In recent years, community Q&A websites have attracted many users and have become reliable sources among experts from various fields. These platforms have specific rules to maintain their content quality in addition to general user agreements. Due to the vast expanse of these systems in terms of the number of users and posts, manual checking and verification of new contents by the administrators and official moderators are not feasible, and these systems require scalable solutions. In major Q&A networks, the current strategy is to use crowdsourcing with reliance on reporting systems. This strategy has serious problems, including the slow handling of violations, the loss of new and experienced users’ time, the low quality of user reports, and discouraging feedback to new users. While this is a great opportunity to utilize machine-learning approaches to provide automated recommender systems and classification models, there are specific non-functional requirements or aspects related to these software systems that need to be introduced and incorporated in the design of a new system. In this short paper, I pinpoint three key aspects: (1) Any good approach should consider specific attributes and features related to context, (2) Automated mechanisms should be proposed according to the highly evolving content of Q&A websites, and (3) Decisions are best to accompany clear and justifiable explanations. Furthermore, a technical conceptual model is proposed by considering these aspects and related approaches. This is a part of a research project where the final goal is to provide accurate, adaptable, efficient, and explainable solutions for automating moderation actions in Q&A websites.
Distinctiveness and continuity in transcriptome and connectivity in the anterior-posterior axis of the paraventricular nucleus of thalamus

The paraventricular nucleus of the thalamus (PVT) projects axons to multiple areas and mediates a wide range of behaviors. Heterogeneity of functions and axonal projections in PVT have been reported, but what cell types exist in PVT and how different they are have not been addressed. We applied single-cell RNA sequencing to depict transcriptomic characteristics of mouse PVT neurons. The transcriptome of PVT neurons had a continuous distribution with the largest variance corresponding to the anterior-posterior axis. Although the single-cell transcriptome classified PVT neurons into four types, transcriptomic and histological analyses showed their continuity. Similarly, anterior and posterior subpopulations had nearly non-overlapping axon projection patterns, while another population showed intermediate patterns. In addition, they responded differently to appetite-related neuropeptides, and their chemogenetic activation showed opposing effects in food consumption. Our studies showed contrasts and continuity of PVT neurons underlying their function as a behavior-modulating hub.
Polymorphic ribonucleoprotein folding as a basis for translational regulation

The widely occurring bacterial RNA chaperone Hfq is a key factor in the post-transcriptional control of hundreds of genes in Pseudomonas aeruginosa. How this broadly acting protein can contribute to the regulation requirements of so many different genes remains puzzling. Here, we describe the structures of higher-order assemblies formed on control regions of different P. aeruginosa target mRNAs by Hfq and its partner protein Crc. Our results show that these assemblies have mRNA-specific quaternary architectures resulting from the combination of multivalent protein-protein interfaces and recognition of patterns in the RNA sequence. The structural polymorphism of the ribonucleoprotein assemblies enables selective translational repression of many different target mRNAs. This system suggests how highly complex regulatory pathways can evolve and be rewired with a simple economy of proteinogenic components. Graphical Abstract The RNA chaperone Hfq, in conjunction with the co-repressor Crc, forms higher order assemblies on nascent mRNAs. These complexes impact on translation of hundreds of transcripts in the pathogen Pseudomonas aeruginosa. Assemblies with different quaternary structures result from the interactions of the proteins with sequence motifs and structural elements in different mRNA targets, as well as from a repertoire of protein-to-protein interfaces. In this way, the combination of RNA sequence and two proteins can generate the diversity required to regulate many genes. It is proposed that the multi-step assembly process is highly cooperative and most likely competes kinetically with translation initiation to silence the targeted transcripts.
Metagenomes of Red Sea subpopulations challenge the use of morphology and marker genes to assess Trichodesmium diversity

The bloom forming Trichodesmium are filamentous cyanobacteria of key interest due to their ability to fix carbon and nitrogen within an oligotrophic marine environment. Trichodesmium blooms typically comprise a complex assemblage of subpopulations and colony-morphologies that are predicted to exhibit distinct ecological lifestyles. Here, we assessed the poorly studied diversity of Trichodesmium in the Red Sea, based on metagenome-assembled genomes (MAGs) and hetR gene-based phylotyping. We assembled four non-redundant MAGs from morphologically distinct Trichodesmium colonies (tufts, dense and thin puffs). T. thiebautii (puffs) and T. erythraeum (tufts) were the dominant species within these morphotypes. While subspecies diversity is present for both T. thiebautii and T. erythraeum, a single T. thiebautii genotype comprised both thin and dense puff morphotypes, and we therefore hypothesize that the phenotypic variation between these morphologies is likely attributed to gene regulation. Additionally, we found the rare non-diazotrophic clade IV and V genotypes, related to T. nobis and T. miru respectively, that likely occurred as single filaments. HetR gene phylogeny indicates that the genotype in clade IV could represent the species T. contortum. We further show that hetR phylotyping can overestimate the taxonomic diversity of Trichodesmium, as two copies of the hetR gene were present within T. thiebautii genomes, one of which misidentified this lineage as T. aureum. Taken together, our results highlight the importance of re-assessing Trichodesmium taxonomy while showing the ability of genomics to capture the complex diversity and distribution of Trichodesmium populations.
Multidimensional single-cell analysis identifies a role for CD2-CD58 interactions in clinical antitumor T cell responses

The in vivo persistence of adoptively transferred T cells is predictive of anti-tumor response. Identifying functional properties of infused T cells that lead to in vivo persistence and tumor eradication has remained elusive. We profiled CD19-specific CAR T cells that comprise the infusion products used to treat large B cell lymphomas using high-throughput single-cell technologies based on Timelapse Imaging Microscopy In Nanowell Grids (TIMING) that integrates killing, cytokine secretion, and transcriptional profiling. Our results show that the directional migration of CD19-specific CAR T cells is correlated with polyfunctionality. We identified that CD2 on T cells is associated with directional migration and that the interaction between CD2 on T cells and CD58 on lymphoma cells accelerates killing and serial killing. Consistent with this, we observed elevated CD58 expression on pre-treatment tumor samples in patients with relapsed or refractory large B cell lymphomas treated with CD19-specific CAR T cell therapy was associated with complete clinical response and survival. These results highlight the importance of studying dynamic T-cell tumor cell interactions in identifying optimal antitumor responses. KEY POINTS - Profiling patient infusion products revealed that polyfunctional CAR T cells show directional migration, which is associated with higher CD2 expression - The ligand for CD2, CD58 is expressed at higher levels in the tumors of lymphoma patients who respond better to CAR T cell treatment
Metagenomic and metabolomic analyses reveal synergistic effects of fecal microbiota transplantation and anti-PD-1 therapy on treating colorectal cancer

Anti-PD-1 immunotherapy has saved numerous lives of cancer patients; however, it only exerts efficacy in 10-15% of patients with colorectal cancer. Fecal microbiota transplantation (FMT) is a potential approach to improving the efficacy of anti-PD-1 therapy, whereas the detailed mechanisms and the applicability of this combination therapy remain unclear. In this study, we evaluated the synergistic effect of FMT with anti-PD-1 in curing colorectal tumor-bearing mice using a multi-omics approach. Mice treated with the combination therapy showed superior survival rate and tumor control, compared to the mice received anti-PD-1 therapy or FMT alone. Metagenomic analysis showed that composition of gut microbiota in tumor-bearing mice treated with anti-PD-1 therapy was remarkably altered through receiving FMT. Particularly, Bacteroides genus, including FMT-increased B. thetaiotaomicron, B. fragilis, and FMT-decreased B. ovatus might contribute to the enhanced efficacy of anti-PD-1 therapy. Furthermore, metabolomic analysis upon mouse plasma revealed several potential metabolites that upregulated after FMT, including punicic acid and aspirin, might promote the response to anti-PD-1 therapy via their immunomodulatory functions. This work broadens our understanding of the mechanism by which FMT improves the efficacy of anti-PD-1 therapy, which may contribute to the development of novel microbiota-based anti-cancer therapies.
Establishment of a Live-Imaging Analysis for Polarized Growth of Conchocelis in the Multicellular Red Alga Neopyropia yezoensis

A wide range of tip-growing cells in plants display polarized cell growth, which is an essential cellular process for the form and function of individual cells. Understanding of the regulatory mechanisms underlying tip growth in terrestrial plants has improved. Cellular processes involved in tip growth have also been investigated in some algae species that form filamentous cells, but their regulatory mechanisms remain unclear. In the macro red alga Neopyropia yezoensis, for which genome information has recently been released, the conchocelis apical cell exhibits tip growth and forms a filamentous structure. Here, we report a live-imaging technique using high-resolution microscopy to analyze the tip growth and cell division of N. yezoensis conchocelis. This imaging analysis addressed tip growth dynamics and cell division in conchocelis apical cells. The directionality and tip growth expansion were disrupted by the application of cytoskeletal drugs, suggesting the involvement of microtubules (MTs) and actin filaments (AFs) in these processes. A growing apical cell mostly contained a single chloroplast that moved toward the expanding part of the apical cell. Drug application also inhibited chloroplast movement, implying that the movement may be dependent on the cytoskeleton. The study determined that live-imaging analysis is a versatile approach for exploring the dynamics of tip growth and cell division in N. yezoensis conchocelis, which provides insights into the regulatory mechanisms underlying cellular growth in multicellular red algae.
Combined Use of Bicyclol and Berberine Alleviates Mouse Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD), ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), is a liver disease worldwide without approved therapeutic drugs. Anti-inflammatory and hepatoprotective drug bicyclol and multi-pharmacological active drug berberine, respectively, have shown beneficial effects on NAFLD in murine nutritional models and patients, though the therapeutic mechanisms remain to be illustrated. Here, we investigated the combined effects of bicyclol and berberine on mouse steatosis induced by Western diet (WD), and NASH induced by WD/CCl4. The combined use of these was rather safe and better reduced the levels of transaminase in serum and triglycerides and cholesterol in the liver than their respective monotherapy, accompanied with more significantly attenuating hepatic inflammation, steatosis, and ballooning in mice with steatosis and NASH. The combined therapy also significantly inhibited fibrogenesis, characterized by the decreased hepatic collagen deposition and fibrotic surface. As per mechanism, bicyclol enhanced lipolysis and β-oxidation through restoring the p62-Nrf2-CES2 signaling axis and p62-Nrf2-PPARα signaling axis, respectively, while berberine suppressed de novo lipogenesis through downregulating the expression of acetyl-CoA carboxylase and fatty acid synthetase, along with enrichment of lipid metabolism-related Bacteroidaceae (family) and Bacteroides (genus). Of note, the combined use of bicyclol and berberine did not influence each other but enhanced the overall therapeutic role in the amelioration of NAFLD. Conclusion: Combined use of bicyclol and berberine might be a new available strategy to treat NAFLD.
Integrating lncRNAs and mRNAs Expression Profiles in Penicillin-Induced Persistent Chlamydial Infection in HeLa Cells

Chlamydia trachomatis (C. trachomatis) is a major etiological agent of sexually transmitted infection. Some stressing conditions can result in persistent chlamydial infection, which is thought to be associated with severe complications including ectopic pregnancy and tubal factor infertility. Long noncoding RNAs (lncRNAs) have been identified as key modulators in many biological processes. Nevertheless, the role of lncRNAs in persistent chlamydial infection is still unclear. In this study, we used lncRNA and mRNA microarray to identify the global lncRNAs and mRNAs expression in penicillin-induced persistent chlamydial infection in HeLa cells as well as the control group (HeLa cells without C. trachomatis infection). Among 1005 differentially expressed lncRNAs, 585 lncRNAs were upregulated and 420 downregulated in persistent chlamydial infection, while 410 mRNAs were identified to express differentially, of which 113 mRNAs were upregulated and 297 downregulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis with differentially expressed genes were performed. We then constructed the lncRNA-miRNA-mRNA competing endogenous RNAs (ceRNAs) network. Four mRNAs were validated to be changed by quantitative real-time PCR which were correlated with the microarray result. Integration of protein-protein interaction network was constructed and hub genes were identified. These findings provide a new perspective on the molecular mechanisms of penicillin-induced persistent chlamydial infection.
Predicting HER2 Status in Breast Cancer on Ultrasound Images Using Deep Learning Method

Purpose The expression of human epidermal growth factor receptor 2 (HER2) in breast cancer is critical in the treatment with targeted therapy. A 3-block-DenseNet-based deep learning model was developed to predict the expression of HER2 in breast cancer by ultrasound images. Methods The data from 144 breast cancer patients with preoperative ultrasound images and clinical information were retrospectively collected from the Shandong Province Tumor Hospital. An end-to-end 3-block-DenseNet deep learning classifier was built to predict the expression of human epidermal growth factor receptor 2 by ultrasound images. The patients were randomly divided into a training (n = 108) and a validation set (n = 36). Results Our proposed deep learning model achieved an encouraging predictive performance in the training set (accuracy = 85.79%, AUC = 0.87) and the validation set (accuracy = 80.56%, AUC = 0.84). The effectiveness of our model significantly exceeded the clinical model and the radiomics model. The score of the proposed model showed significant differences between HER2-positive and -negative expression (p < 0.001). Conclusions These results demonstrate that ultrasound images are predictive of HER2 expression through a deep learning classifier. Our method provides a non-invasive, simple, and feasible method for the prediction of HER2 expression without the manual delineation of the regions of interest (ROI). The performance of our deep learning model significantly exceeded the traditional texture analysis based on the radiomics model.
The Dual Regulation Effects of ESR1/NEDD4L on SLC7A11 in Breast Cancer Under Ionizing Radiation

Radiotherapy is one of the most important treatments for breast cancer. Ferroptosis is a recently recognized form of regulated cell death that is characterized by lipid peroxidation. However, whether ionizing radiation (IR) could induce ferroptosis in breast cancer and how it works remain unknown. Bioinformatics analysis were performed to screen ferroptosis-related genes differentially expressed in breast tumor tissue and normal tissue. Then, breast cancer cell lines with different estrogen receptor (ER) phenotypes were used for studies in vitro, including ER-positive (MCF-7 and ZR-75-1) and ER-negative (MDA-MB-231) cells. The dynamic changes of mRNA and protein levels were examined after x-ray of 8 Gy by qRT-PCR and Western blotting, respectively. Immunoprecipitation (IP) was used to explore the interaction between proteins. Luciferase assay was used to analyze the transcriptional regulation effect of ESR1 on SLC7A11. BODIPY C11 and trypan blue dyes were used to determine lipid peroxidation and cell death, respectively. The result showed that the ferroptosis-related gene SLC7A11 was higher in breast cancer tissues compared with normal tissues and associated with poor survival. A positive correlation exists between ESR1 and SLC7A11 expression. ESR1 promoted SLC7A11 expression at the early stage after IR. ESR1/SLC7A11 knockdown significantly enhanced IR-induced ferroptosis in ER-positive cells. At 12 h after IR, the IP data showed the interaction between E3 ubiquitin ligase NEDD4L and SLC7A11 increased, followed by the ubiquitylation and degradation of SLC7A11. Thus, SLC7A11 expression was regulated by both ESR1 and NEDD4L, in opposite ways. For the first time, we elucidated that ESR1 and NEDD4L functioned together after radiation treatment and finally induced ferroptosis in breast cancer cells, which provides novel insight into the guidance of clinical treatment of breast cancer.
Using CRISPR-Cas9 Technology to Eliminate Xyloglucan in Tobacco Cell Walls and Change the Uptake and Translocation of Inorganic Arsenic

Xyloglucan is a quantitatively major polysaccharide in the primary cell walls of flowering plants and has been reported to affect plants’ ability to tolerate toxic elements. However, it is not known if altering the amounts of xyloglucan in the wall influences the uptake and translocation of inorganic arsenic (As). Here, we identified two Nicotiana tabacum genes that encode xyloglucan-specific xylosyltransferases (XXT), which we named NtXXT1 and NtXXT2. We used CRISPR-Cas9 technology to generate ntxxt1, ntxxt2, and ntxxt1/2 mutant tobacco plants to determine if preventing xyloglucan synthesis affects plant growth and their ability to accumulate As. We show that NtXXT1 and NtXXT2 are required for xyloglucan biosynthesis because no discernible amounts of xyloglucan were present in the cell walls of the ntxxt1/2 double mutant. The tobacco double mutant (ntxxt1/2) and the corresponding Arabidopsis mutant (atxxt1/2) do not have severe growth defects but do have a short root hair phenotype and a slow growth rate. This phenotype is rescued by overexpressing NtXXT1 or NtXXT2 in atxxt1/2. Growing ntxxt mutants in the presence of AsIII or AsV showed that the absence of cell wall xyloglucan affects the accumulation and translocation of As. Most notably, root retention of As increased substantially and the amounts of As translocated to the shoots decreased in ntxxt1/2. Our results suggest that xyloglucan-deficient plants provide a strategy for the phytoremediation of As contaminated soils.
COVID-19 and Chagas Disease in Buenos Aires, Argentina

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2. COVID-19 leads, in most patients, to mild-to-moderate symptoms, but some develop severe disease and succumbed to death. People with medical conditions have a higher risk of death than those without them. Chagas disease (CD) can cause cardiac diseases in approximately one-third of affected people. The aim of this study is to find out if there is any clinical association between Chagas disease and COVID-19 severity. This is a cohort study of 29 patients who were hospitalized with COVID-19 and had a diagnosis of chronic Trypanosoma cruzi infection. This coinfected cohort was matched by sex, age, presence of comorbidities, and requirement of hospitalization on intensive care unit (ICU) at admission with a control cohort of patients hospitalized due to COVID-19 without CD in a 3:1 ratio (n = 87). The clinical outcomes evaluated were as follows: days of hospitalization, death, and requirement of ICU and mechanical respiratory assistance (MV). The study protocol was approved by the Institutional Ethics in Research Committee. The Chagas disease/COVID-19 coinfected cohort had a median age of 55 years old (49.0, 66.0); 17 (59%) were male. All patients survived the acute COVID-19. Three of them were admitted to the ICU, and two required MV. Twenty-two (75.8%) required supplemental oxygen. There were no statistical differences in any laboratory parameters between the groups except for lactic acid dehydrogenase, which showed higher levels in the coinfected cohort, with a median of 573 U/L (interquartile range: 486.00, 771.00) vs. 476 U/L (346.00, 641.00) in the control group (p = 0.007). There were no differences in clinical outcomes between both groups. On the cohort with Chagas disease, there were zero deaths, three (10.3%) were admitted in the ICU, and two (6.9%) required MV, while for the control group there were six deaths (6.6%), 13 required ICU (14.9%), and 11 required MV (12.6%), without a statistically significant difference. This small series of coinfected Chagas disease and COVID-19 does not suggest differences in clinical evolution compared to non-Chagas patients. This data is similar to a Brazilian cohort. More data of this population with and without cardiomyopathy is needed to optimize the follow-up and recommendation for the population affected by this neglected tropical disease about COVID-19.