Miracle-dz/UniFAR-FTUs huggingface dataset:
Exploration of the molecular mechanisms, shared gene signatures, and MicroRNAs between systemic lupus erythematosus and diffuse large B cell lymphoma by bioinformatics analysis

Background Systemic lupus erythematosus (SLE) is a complex heterogeneous systemic autoimmune disease. Previous studies have shown that SLE may be related to diffuse large B cell lymphoma (DLBCL), but the mechanism of their relationship is still unclear. The present study aimed to explore the common genetic molecular mechanisms, core shared genes, and miRNAs between SLE and DLBCL as well as to investigate the diagnostic markers of DLBCL. Methods The SLE and DLBCL microarray data were downloaded from the comprehensive Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was used to identify co-expression modules. Four core shared genes were screened out by various algorithms and validated in other cohorts. Finally, we constructed a common core gene-miRNA network using the human microRNA disease database (HMDD) and TarBase. Results Using WGCNA, four modules were identified as important modules for SLE and DLBCL. Enrichment analysis of the shared genes showed that the highly activated NF-κB pathway was a common feature of the pathophysiology. Four core shared genes, namely, PSMB10, PSMB4, TAF10, and NFΚBIA, were screened out. These core shared genes were significantly upregulated in both diseases, and they may be potential diagnostic markers of DLBCL. The core gene-miRNA network showed that miR-155–5p, regulating the shared NF-κB pathway, may play an important role in the susceptibility of SLE patients to DLBCL. Conclusion The present study revealed that NF-κB pathway in SLE may be a crucial susceptible factor for DLBCL. In addition, we identified PSMB10, PSMB4, TAF10, NFΚBIA and miR-155 involved in the common pathogenesis as potential biomarkers and therapeutic targets for DLBCL.
A deep learning method for predicting metabolite-disease associations via graph neural network

Metabolism is the process by which an organism continuously replaces old substances with new substances. It plays an important role in maintaining human life, body growth and reproduction. More and more researchers have shown that the concentrations of some metabolites in patients are different from those in healthy people. Traditional biological experiments can test some hypotheses and verify their relationships but usually take a considerable amount of time and money. Therefore, it is urgent to develop a new computational method to identify the relationships between metabolites and diseases. In this work, we present a new deep learning algorithm named as graph convolutional network with graph attention network (GCNAT) to predict the potential associations of disease-related metabolites. First, we construct a heterogeneous network based on known metabolite-disease associations, metabolite-metabolite similarities and disease-disease similarities. Metabolite and disease features are encoded and learned through the graph convolutional neural network. Then, a graph attention layer is used to combine the embeddings of multiple convolutional layers, and the corresponding attention coefficients are calculated to assign different weights to the embeddings of each layer. Further, the prediction result is obtained by decoding and scoring the final synthetic embeddings. Finally, GCNAT achieves a reliable area under the receiver operating characteristic curve of 0.95 and the precision-recall curve of 0.405, which are better than the results of existing five state-of-the-art predictive methods in 5-fold cross-validation, and the case studies show that the metabolite-disease correlations predicted by our method can be successfully demonstrated by relevant experiments. We hope that GCNAT could be a useful biomedical research tool for predicting potential metabolite-disease associations in the future.
Whole‐exome sequencing uncovered genetic diagnosis of severe inherited haemolytic anaemia: Correlation with clinical phenotypes

Next‐generation sequencing has shed light on the diagnosis of previously unsolved cases of inherited haemolytic anaemia (IHA). We employed whole‐exome sequencing to explore the molecular diagnostic spectrum of 21 unrelated Thai paediatric patients with non‐thalassemic IHA, presenting hydrops fetalis and/or becoming transfusion‐dependent for 1 year or more or throughout their lifespan. Anaemia was detected prenatally, within the first month and the fifth year of life in three, 12 and six patients respectively. Molecular diagnosis obtained from all patients revealed SPTB as the most frequently mutated gene (four reported, three novel), found in 31 of 42 studied alleles. The other two mutated genes identified were ANK1 (three novel) and KLF1 (two reported). Four recurring mutations within exon 29/30 (NM_001024858.2) accounted for the vast majority (90%) of mutated SPTB alleles, biallelic inheritance of which resulted in the most severe phenotypes: hydrops fetalis and life‐long transfusion dependency. Dominant ANK1 (n = 3) and SPTB (n = 2) mutations and biallelic class 2 KLF1 mutations (n = 1) led to a shorter period of transfusion dependency. Our study demonstrated that mutated SPTB causing red‐cell membranopathy is likely the most common cause of severe non‐thalassemic IHA among Thai patients. This urges carrier screening in the population to prevent subsequent, severely affected births.
R0 resection of vaginal stump recurrence of gynecologic malignancy by bi‐directional endoscopic approach: A case series of four patients

Vaginal stump recurrence post‐hysterectomy for gynecologic malignancies occurs in 2%–3% of cases. Local excision has been recognized as the primary treatment of localized recurrence, in which precise surgical margin is critical. However, R0 resection is not always easy, given the deep and narrow operation field, as well as severe postoperative fibrosis or adhesion of the vaginal stump at times. Here, we report four cases of vaginal stump recurrence of gynecologic malignancies resected by bi‐directional (laparoscopic and pneumovaginoscopic) endoscopy to overcome these difficulties. The primary tumors were uterine cancer in two cases and uterine cervical and ovarian cancer in one case each. The mean operating time was 199 (162–235) minutes, blood loss was minimal, and no perioperative complications were observed. Postoperative follow‐up (7.0–19.4 months) revealed no recurrence. This combined procedure could be a therapeutic option for localized vaginal stump recurrence.
Test of a Retinal Nerve Fiber Bundle Trajectory Model Using Eyes With Glaucomatous Optic Neuropathy

Purpose To test a model of retinal nerve fiber bundle trajectories that predicts the arcuate-shaped patterns seen on optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) probability/deviation maps (p-maps) in glaucomatous eyes. Methods Thirty-one glaucomatous eyes from a database of 250 eyes had clear arcuate-shaped patterns on RNFL p-maps derived from an OCT cube scan. The borders of the arcuate patterns were extracted from the RNFL p-maps. Next, the trajectories from an arcuate model were compared against these borders via a normalized root-mean-square difference analysis. The model's parameter, β, was varied, and the best-fitting, initial clock-hour position of the trajectory to the border was found for each β. Finally, the regions, as determined by the arcuate border's best-fit, initial clock-hour positions, were compared against the abnormal regions on the circumpapillary retinal nerve fiber layer (cpRNFL) profile. Results The arcuate model's mean βSup and βInf parameters minimized large differences between the trajectories and the arcuate borders on the RNFL p-maps. Furthermore, on average, 68% of the cpRNFL regions defined by the arcuate border's best-fit, initial clock-hour positions were abnormal (i.e., below the ≤5% threshold). Conclusions The arcuate model performed well in predicting the borders of arcuate patterns seen on RNFL p-maps. It also predicted the associated abnormal regions of the cpRNFL thickness plots. Translational Relevance This model should prove useful in helping clinicians understand topographical comparisons among different OCT representations and should improve structure-structure, as well as structure-function agreement analyses.
Biogenic and facile synthesis of selenium nanoparticles using Vaccinium arctostaphylos L. fruit extract and anticancer activity against in vitro model of breast cancer

Biogenic synthesis of selenium nanoparticles (SeNPs) using plant extracts has emerged as a promising alternative approach to traditional chemical synthesis. The current study aims to introduce a safe, low‐cost, and green synthesis of SeNPs using fresh fruit extract of Vaccinium arctostaphylos L. The biogenic synthesis of SeNPs was confirmed by different analyses including ultraviolet‐visible spectrophotometry, Fourier transform infrared, and energy‐dispersive X‐ray. Also, the crystalline nature, size, and morphology of the obtained SeNPs were characterized by X‐ray diffraction, dynamic light scattering, field emission scanning electron microscopy, and transmission electron microscopy techniques. The SeNPs were successfully synthesized with fruit extract of V. arctostaphylos L. in a regular spherical form and narrow size distribution with suitable zeta‐potential values and exhibited appropriate biocompatibility. It revealed that the synthesized SeNPs can significantly inhibit the growth of 4T1 breast cancer cells with an IC50 of ∼84.19 ± 25.96 µg/ml after 72 h treatment. Overall, it can be concluded that the green synthesized SeNPs can be attractive, nontoxic, and eco‐friendly candidates for drug delivery or medicinal applications.
Cryo‐EM reveals mechanisms of angiotensin I‐converting enzyme allostery and dimerization

Hypertension (high blood pressure) is a major risk factor for cardiovascular disease, which is the leading cause of death worldwide. The somatic isoform of angiotensin I‐converting enzyme (sACE) plays a critical role in blood pressure regulation, and ACE inhibitors are thus widely used to treat hypertension and cardiovascular disease. Our current understanding of sACE structure, dynamics, function, and inhibition has been limited because truncated, minimally glycosylated forms of sACE are typically used for X‐ray crystallography and molecular dynamics simulations. Here, we report the first cryo‐EM structures of full‐length, glycosylated, soluble sACE (sACES1211). Both monomeric and dimeric forms of the highly flexible apo enzyme were reconstructed from a single dataset. The N‐ and C‐terminal domains of monomeric sACES1211 were resolved at 3.7 and 4.1 Å, respectively, while the interacting N‐terminal domains responsible for dimer formation were resolved at 3.8 Å. Mechanisms are proposed for intradomain hinging, cooperativity, and homodimerization. Furthermore, the observation that both domains were in the open conformation has implications for the design of sACE modulators.
Exploring the importance of a usable and emotional product design from the user’s perspective

Abstract Usability and emotionality are important components of user experience. However, an equal consideration of both constructs in product design is not always possible due to sometimes competitive objectives. In order to foster a user-oriented design decision in such conflicting situations, this paper examines the general importance of both constructs and their dimensions from the user’s perspective while taking into account socio-demographic variables. Examination was realised by conducting a product independent anonymous online survey (n = 130). The findings confirm that both constructs are important, yet in a direct comparison, usability is perceived as more important than emotionality. Taking selected dimensions of both constructs into account, an intuitive, easy and learnable usage, suitability for the user's task and freedom from impairment are particularly important in terms of usability. An aesthetic and pleasurable product design as well as originality is essential in terms of emotionality. Practitioner summary: This paper aims for supporting user-oriented design decisions in the context of conflicting objectives occurring in the consideration of usability and emotionality in product design. The conducted survey (n = 130) revealed usability as perceived more important than emotionality. Usability may thus be prioritised within conflicting design decisions. Abbreviations: DFG: German Research Foundation; e.g.: for example; GESIS: Leibniz Institute for the Social Sciences; m: metric; M: Mean; n: number of participants; n: nominal; o: ordinal; p level: level of statistical significance; RQ: Research question; r: correlation coefficient; V: Cramer’s V; χ2: Chi-square
Impact of greening attitude and buyer power on supplier environmental management strategy

Studies on the appropriate strategies for supplier relationship management vary according to the greening approaches of a ﬁrm. The relative power of greening approaches for suppliers remains untapped. This research aims to ﬁll this gap, arguing that ﬁrm attitudes toward going green and their dominance in supply chains affect their corresponding environmental management practices. The case study method is utilized. The main objects of study include Taiwanese ﬁrms in high-tech industries. Eleven ﬁrms were selected for in-depth investigation. Supplier management approaches are investigated from six different perspectives: supplier policy, information sharing/communication, joint action of supplier/buyer, relationship-handling issues, supplier support, and relationship quality. Results show that each case group emphasizes different perspectives. Thus, this study coined four strategies: strategic alliance, arm’s length relationship, partnership, and ongoing relationship.
The Measurement of Racial Colorblindness

Although there is consensus that the intergroup ideology of multiculturalism is negatively related to prejudice and that assimilation is positively related to prejudice, research regarding the relationship of racial colorblindness to prejudice has produced mixed results. We investigated whether these mixed results might stem from colorblindness being a multifaceted construct despite typically being treated as unidimensional. Exploratory and confirmatory factor analyses of items from existing measures revealed three factors—equality orientation, color evasion, and rejection of racial categorization—from which we created the Multidimensional Assessment of Racial Colorblindness (MARC). Four studies provided evidence for the reliability and construct validity of the MARC and found that its subscales were often differentially related to other variables, including prejudice. We also compared the MARC to another measure of colorblindness, the Color-Blind Racial Attitudes Scale (CoBRAS). We discuss the implications of racial colorblindness as a multifaceted construct.
Phytochemical Screening and Antioxidant Activity of Meyna laxiflora Species Found in Imphal West District of Manipur

Aqueous and methanol extracts of Meyna laxiflora leaf, fruit pulp and seed were screened for the presence of phytochemical constituents. Total phenolic content, total flavonoid content and antioxidant activity in the extracts were also determined. Phytochemicals were extracted using soxhlet extraction method. Phytochemical screening showed the presence of most of the phytoconstituents in aqueous and methanol extracts of various parts of M . laxiflora . Methanol was found to be a better solvent for extraction of phytochemicals from M . laxiflora . Total phenolic content is expressed in terms of gallic acid equivalent (GAE) and was found to be highest in methanolic fruit pulp extract (129.54 ± 0.25mg /g of extract). Total flavonoid content is expressed in terms of quercetin equivalent (QE) and methanolic leaf extract recorded the highest (80.45 µg ± 0.16 /100g of dried extract) followed by fruit pulp and seed extracts. Results indicate that aqueous and methanol extracts of various parts of M . laxiflora were found to possess DPPH scavenging activity, ferric reducing power and total antioxidant activity in dose dependent manner. In the entire antioxidant assay performed methanol extracts were found to have higher activity than aqueous extracts and among the various parts of M . laxiflora used for the study, fruit pulp was showing higher activity than leaf and seed which may be due to higher total phenolic content.
Decomposition of Correlation Integral to Local Functions

We show that the correlation integral can be decomposed into functions each related to a particular point of data space. For these functions, one can use similar polynomial approximations such as the correlation integral. The essential difference is that the value of the exponent, which would correspond to the correlation dimension, differs in accordance to the position of the point in question. Moreover, we show that the multiplicative constant in that polynomial approximation is proportional to the probability density estimation at that point. This finding is used to construct a classifier.
Hematopoietic transcription factor GFI1 promotes anchorage independence by sustaining ERK activity in cancer cells

The switch from anchorage-dependent to anchorage-independent growth is essential for epithelial metastasis. The underlying mechanism, however, is not fully understood. In this study, we identified growth factor independent-1 (GFI1), a transcription factor that drives the transition from adherent endothelial cells to suspended hematopoietic cells during hematopoiesis, as a critical regulator of anchorage independence in lung cancer cells. GFI1 elevated the numbers of circulating and lung-infiltrating tumor cells in xenograft models and predicted poor prognosis of patients with lung cancer. Mechanistically, GFI1 inhibited the expression of multiple adhesion molecules and facilitated substrate detachment. Concomitantly, GFI1 reconfigured the chromatin structure of the RASGRP2 gene and increased its expression, causing Rap1 activation and subsequent sustained ERK activation upon detachment, and this led to ERK signaling dependency in tumor cells. Our studies unveiled a mechanism by which carcinoma cells hijacked a hematopoietic factor to gain anchorage independence and suggested that the intervention of ERK signaling may suppress metastasis and improve the therapeutic outcome of patients with GFI1-positive lung cancer.
9 60 40 07 v 1 3 A pr 1 99 6 Gravitational vacuum polarization I : Energy conditions in the Hartle – Hawking vacuum gr-qc / 9604007

When a quantum field theory is constructed on a curved background spacetime, the gravitationally induced vacuum polarization typically induces a non-zero vacuum expectation value for the quantum stress-energy tensor. It is well-known that this gravitational vacuum polarization often violates the point-wise energy conditions and sometimes violates the averaged energy conditions. In this paper I begin a systematic attack on the question of where and by how much the various energy conditions are violated. To keep the discussion manageable, I work in the test-field limit, and focus on conformally coupled massless scalar fields in Schwarzschild spacetime, using the Hartle–Hawking vacuum. The discussion invokes a mixture of analytical and numerical techniques, and critically compares the qualitative behaviour to be expected from the Page approximation with that adduced from the numerical calculations of Anderson, Hiscock, and Samuel. I show that the various pointwise energy conditions are violated in a series of onion-like layers located between the unstable photon orbit and the event horizon, the sequence of violations being DEC, WEC, and (NEC+SEC). Furthermore the ANEC is violated for some of the null geodesics trapped in this region. Having established the basic machinery in this paper, the Boulware vacuum will be treated in a companion paper, while studies of the Unruh vacuum should be straightforward, as should extensions to nonconformal couplings, massive scalars, and Reissner–Nordström geometries.
Collective Cell Behaviour – a Cell-Based Parallelisation Approach for a Phase Field Active Polar Gel Model

We consider a continuum model for collective cell movement. Each cell is modelled by a phase ﬁeld active polar gel model and the cells interact via steric interactions. We provide a ﬁnite element implementation with a parallel efﬁciency of at least 0.5 in the number of cells. This is achieved by considering each cell on a different processor and various improvements to reduce the communication overhead to deal with the cell-cell interactions. We describe implementation details and demonstrate results for up to 768 cells.
A subpopulation of pulmonary neuroendocrine cells are reserve stem cells regulated by the tumor suppressors Rb, p53, and Notch

Pulmonary neuroendocrine (NE) cells are neurosensory cells sparsely distributed throughout the bronchial epithelium, many in innervated clusters of 20–30 cells. Following lung injury, NE cells proliferate and generate other cell types to promote epithelial repair. Here we show that only a subpopulation of NE cells, typically 2–4 cells per cluster, function as stem cells. These differentiated cells display the key features of classical stem cells. Most proliferate (self-renew) following injury, and some migrate into the injured area. Rare cells, often just one per cluster, lose NE identity, transit amplify, and reprogram to other fates, creating a large clonal patch of regenerated epithelium. Small cell lung cancer (SCLC) tumor suppressors regulate the stem cell program: Rb/p53 suppress self-renewal, whereas Notch initiates deprogramming and transit amplification. We propose that NE stem cells are tumor-initiating cells for SCLC, and transformation results from constitutive activation of stem cell renewal and inhibition of deprogramming. and and NE cell dynamics simulations and analyzed and interpreted data images for and outgrowth quantifications.