Miracle-dz/UniFAR-FTUs huggingface dataset:
Applying Data Mining Techniques for Predicting Prognosis in Patients with Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a systematic chronic inflammatory disease. The disease mechanism remains unclear and may have resulted from autoimmune problems caused by genetic predisposing and pathogen infection. In clinical practice, selection of the initial treatment is based on the degree of disease activity, and treatment plans will be added gradually according to increased severity of the disease. However, treatment results can be unclear and treatment process uncertain and ambiguous, which can cause healthcare quality to become worse. This study attempts to combine expert opinions to construct various classifiers using a number of data mining techniques to analyze the different prognosis of two patient groups, by predicting whether the inflammatory indicator erythrocyte sedimentation rates of these two groups will be within the normal range with different medication strategies. Clinical data were collected for construction of different classifiers and we evaluate the prediction accuracy rate of each classifier afterwards. The optimum prediction model is selected from these classifiers to predict the prognosis of RA within these treatment strategies and analyze various results. The results show the accuracy rate of the prediction model by Logistic, SVM and DT module were 0.7927, 07829 and 0.9094, respectively. In the RA complications dataset, the accuracy rate of were 0.9393, 0.9290 and 0.9812, respectively. Futhermore, gain ratio was used to further analyze the rules and to discover which branch nodes are the most importance factor. The results of this study are helpful for formulation and development of guidelines for clinical RA treatments, and implementation of a decision support system by using the prediction model can assist medical staff to make correct decisions in the disease’s early stage.
Systemic administration of the di-apocarotenoid norbixin (BIO201) is neuroprotective, preserves photoreceptor function and inhibits A2E and lipofuscin accumulation in animal models of age-related macular degeneration and Stargardt disease

Atrophic A\age-related macular degeneration (AMD) and Stargardt disease (STGD) are major blinding diseases affecting millions of patients worldwide, but no treatment is available. In dry AMD and STGD oxidative stress and subretinal accumulation of N-retinylidene-N-retinylethanolamine (A2E), a toxic by-product of the visual cycle, causes retinal pigment epithelium (RPE) and photoreceptor degeneration leading to visual impairment. Acute and chronic retinal degeneration following blue light damage (BLD) in BALB/c mice and aging of Abca4-/- Rdh8-/- mice, respectively, reproduce features of AMD and STGD. Efficacy of systemic administrations of 9'-cis-norbixin (norbixin), a natural di-apocarotenoid, prepared from Bixa orellana seeds with anti-oxidative properties, was evaluated during BLD in BALB/c mice, and in Abca4-/- Rdh8-/- mice of different ages, following three experimental designs: “preventive”, “early curative” and “late curative” supplementations. Norbixin injected intraperitoneally in BALB/c mice, maintained scotopic and photopic electroretinogram amplitude and was neuroprotective. Norbixin chronic oral administration for 6 months in Abca4-/- Rdh8-/- mice following the “early curative” supplementation showed optimal neuroprotection and maintenance of photoreceptor function and reduced ocular A2E accumulation. Thus, norbixin appears promising as a systemic drug candidate for both AMD and STGD treatment.
The Possible Uses and Challenges of Nanomaterials in Mast Cell Research

Mast cells are tissue-resident immune cells that are involved in inflammation and fibrosis but also serve beneficial roles, including tissue maintenance, angiogenesis, pathogen clearance, and immunoregulation. Their multifaceted response and the ability of their mediators to target multiple organs and tissues means that mast cells play important roles in numerous conditions, including asthma, atopic dermatitis, drug sensitivities, ischemic heart disease, Alzheimer disease, arthritis, irritable bowel syndrome, infections (parasites, bacteria and viruses), and cancer. As a result, mast cells have become an important target for drug discovery and diagnostic research. Recent work has focused on applying novel nanotechnologies to explore cell biology. In this brief review, we will highlight the use of nanomaterials to modify mast cell functions and will discuss the potential of these technologies as research tools for understanding mast cell biology.
Chemotactic Responses of Jurkat Cells in Microfluidic Flow-Free Gradient Chambers

Gradients of soluble molecules coordinate cellular communication in a diverse range of multicellular systems. Chemokine-driven chemotaxis is a key orchestrator of cell movement during organ development, immune response and cancer progression. Chemotaxis assays capable of examining cell responses to different chemokines in the context of various extracellular matrices will be crucial to characterize directed cell motion in conditions which mimic whole tissue conditions. Here, a microfluidic device which can generate different chemokine patterns in flow-free gradient chambers while controlling surface extracellular matrix (ECM) to study chemotaxis either at the population level or at the single cell level with high resolution imaging is presented. The device is produced by combining additive manufacturing (AM) and soft lithography. Generation of concentration gradients in the device were simulated and experimentally validated. Then, stable gradients were applied to modulate chemotaxis and chemokinetic response of Jurkat cells as a model for T lymphocyte motility. Live imaging of the gradient chambers allowed to track and quantify Jurkat cell migration patterns. Using this system, it has been found that the strength of the chemotactic response of Jurkat cells to CXCL12 gradient was reduced by increasing surface fibronectin in a dose-dependent manner. The chemotaxis of the Jurkat cells was also found to be governed not only by the CXCL12 gradient but also by the average CXCL12 concentration. Distinct migratory behaviors in response to chemokine gradients in different contexts may be physiologically relevant for shaping the host immune response and may serve to optimize the targeting and accumulation of immune cells to the inflammation site. Our approach demonstrates the feasibility of using a flow-free gradient chamber for evaluating cross-regulation of cell motility by multiple factors in different biologic processes.
Cementless Fixation for Total Knee Arthroplasty in Various Patient Populations: A Literature Review

Abstract The number of total knee arthroplasties (TKAs) performed in the United States has increased considerably in recent years, with a major contribution from younger patients. Maximizing survivorship of these implants has always been a point of emphasis. Early TKA designs with cementless fixation were associated with high rates of complications and implant failures. However, recent advances in cementless designs have shown excellent results. The decision to use cemented or cementless fixation for patients undergoing TKA is typically based on the surgeon's experience and preference. However, several patient characteristics must also be taken into account. The purpose of this review was to describe the clinical outcomes of studies in which a cementless TKA system was utilized for patients who (1) were less than 60 years of age, (2) were greater than 75 years of age, (3) were obese, (4) had rheumatoid arthritis, and (5) had osteonecrosis of the knee. Based on the studies included in this review, it appears that cementless fixation is a viable option for patients who have all of the above demographics.
Cryo-EM, X-ray diffraction, and atomistic simulations reveal determinants for the formation of a supramolecular myelin-like proteolipid lattice

Myelin protein P2 is a peripheral membrane protein of the fatty acid–binding protein family that functions in the formation and maintenance of the peripheral nerve myelin sheath. Several P2 gene mutations cause human Charcot-Marie-Tooth neuropathy, but the mature myelin sheath assembly mechanism is unclear. Here, cryo-EM of myelin-like proteolipid multilayers revealed an ordered three-dimensional (3D) lattice of P2 molecules between stacked lipid bilayers, visualizing supramolecular assembly at the myelin major dense line. The data disclosed that a single P2 layer is inserted between two bilayers in a tight intermembrane space of ∼3 nm, implying direct interactions between P2 and two membrane surfaces. X-ray diffraction from P2-stacked bicelle multilayers revealed lateral protein organization, and surface mutagenesis of P2 coupled with structure-function experiments revealed a role for both the portal region of P2 and its opposite face in membrane interactions. Atomistic molecular dynamics simulations of P2 on model membrane surfaces suggested that Arg-88 is critical for P2-membrane interactions, in addition to the helical lid domain. Negatively charged lipid headgroups stably anchored P2 on the myelin-like bilayer surface. Membrane binding may be accompanied by opening of the P2 β-barrel structure and ligand exchange with the apposing bilayer. Our results provide an unprecedented view into an ordered, multilayered biomolecular membrane system induced by the presence of a peripheral membrane protein from human myelin. This is an important step toward deciphering the 3D assembly of a mature myelin sheath at the molecular level.
Natural limonoids protect mice from alcohol-induced liver injury

Abstract Background Alcoholic liver disease (ALD) is regarded as a global health problem with limited therapeutic options. Previous studies highlighted some anticancer, antiviral, and hepatoprotective activities of limonoids, but the effects of these compounds on ALD remain unknown. The present study aimed to evaluate the effect of some natural limonoids on ethanol-induced liver injury. Methods Thirty-five albino mice (Mus musculus) were administered with 40% ethanol in the presence or absence of the different limonoids [including three havanensin-type limonoids, TS1, TS3, Rubescin D isolated from an African medicinal plant, Trichilia rubescens Oliv. (Meliaceae), and one limonin], or silymarin at 50 mg/kg for 3 days. Thereafter, the effect of the most active compound was evaluated in a chronic model of ALD. For this purpose, 24 mice with each group consisting of six mice were administered orally with 40% ethanol and limonoid at different doses (50, 75, and 100 mg/kg) for 28 days. Finally, biochemical parameters such as alanine aminotransferase (ALT), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), triglyceride (TG), and tumor necrosis factor α (TNF-α) levels were quantified in liver homogenates. Results All tested limonoids significantly (p < 0.01) reduced ALT levels relative to the negative control in the acute model. However, in comparison to other limonoids, limonin at 50 and 75 mg/kg significantly reduced TG, MDA, and TNF-α levels (1.8-fold); alleviated leukocyte infiltration in liver tissue; significantly increased the activity of SOD; and decreased those of CAT better than silymarin used as a positive control at 50 mg/kg. Conclusions These data suggest that limonin possesses protective effects on long-term alcohol poisoning partially due to antioxidant and anti-inflammatory mechanisms.
New Insights on the Emerging Genomic Landscape of CXCR4 in Cancer: A Lesson from WHIM

Deciphering the molecular alterations leading to disease initiation and progression is currently crucial to identify the most relevant targets for precision therapy in cancer patients. Cancers express a complex chemokine network influencing leucocyte infiltration and angiogenesis. Moreover, malignant cells also express a selective repertoire of chemokine receptors that sustain their growth and spread. At present, different cancer types have been shown to overexpress C-X-C chemokine receptor type 4 (CXCR4) and to respond to its ligand C-X-C motif chemokine 12 (CXCL12). The CXCL12/CXCR4 axis influences cancer biology, promoting survival, proliferation, and angiogenesis, and plays a pivotal role in directing migration of cancer cells to sites of metastases, making it a prognostic marker and a therapeutic target. More recently, mutations in the C-terminus of CXCR4 have been identified in the genomic landscape of patients affected by Waldenstrom’s macroglobulinemia, a rare B cell neoplasm. These mutations closely resemble those occurring in Warts, Hypogammaglobulinemia, Immunodeficiency, and Myelokathexis (WHIM) syndrome, an immunodeficiency associated with CXCR4 aberrant expression and activity and with chemotherapy resistance in clinical trials. In this review, we summarize the current knowledge on the relevance of CXCR4 mutations in cancer biology, focusing on its importance as predictors of clinical presentation and response to therapy.
Human cytomegalovirus IE2 drives transcription initiation from a select subset of late infection viral promoters by host RNA polymerase II

Herpesvirus late promoters activate gene expression after viral DNA synthesis has begun. Alphaherpesviruses utilize a viral immediate-early protein to do this, whereas beta- and gammaherpesviruses primarily use a 6-member set of viral late-acting transcription factors (LTF) that are drawn to a TATT sequence in the late promoter. The betaherpesvirus, human cytomegalovirus (HCMV), produces three immediate-early 2 protein isoforms, IE2-86, IE2-60, IE2-40, late in infection, but whether they activate late viral promoters is unknown. Here, we quickly degrade the IE2 proteins in late infection using dTag methodology and analyze effects on transcription using customized PRO-Seq and computational methods combined with multiple validation methods. We discover that the IE2 proteins selectively drive RNA Pol II transcription initiation at a subset of viral early-late and late promoters common to different HCMV strains, but do not substantially affect Pol II transcription of the 9,942 expressed host genes. Most of the IE2-activated viral late infection promoters lack the TATT sequence bound by the HCMV UL87-encoded LTF. The HCMV TATT-binding protein is not mechanistically involved in late RNA expression from the IE2-activated TATT-less UL83 (pp65) promoter, as it is for the TATT-containing UL82 (pp71) promoter. While antecedent viral DNA synthesis is necessary for transcription from the late infection viral promoters, continued viral DNA synthesis is unnecessary. We conclude that in late infection the IE2 proteins target a distinct subset of HCMV early-late and late promoters for transcription initiation by RNA Pol II. Commencement of viral DNA replication renders the HCMV genome late promoters susceptible to late-acting viral transcription factors.
The nature of the purine at position 34 in tRNAs of 4-codon boxes is correlated with nucleotides at positions 32 and 38 to maintain decoding fidelity

Abstract Translation fidelity relies essentially on the ability of ribosomes to accurately recognize triplet interactions between codons on mRNAs and anticodons of tRNAs. To determine the codon-anticodon pairs that are efficiently accepted by the eukaryotic ribosome, we took advantage of the IRES from the intergenic region (IGR) of the Cricket Paralysis Virus. It contains an essential pseudoknot PKI that structurally and functionally mimics a codon-anticodon helix. We screened the entire set of 4096 possible combinations using ultrahigh-throughput screenings combining coupled transcription/translation and droplet-based microfluidics. Only 97 combinations are efficiently accepted and accommodated for translocation and further elongation: 38 combinations involve cognate recognition with Watson-Crick pairs and 59 involve near-cognate recognition pairs with at least one mismatch. More than half of the near-cognate combinations (36/59) contain a G at the first position of the anticodon (numbered 34 of tRNA). G34-containing tRNAs decoding 4-codon boxes are almost absent from eukaryotic genomes in contrast to bacterial genomes. We reconstructed these missing tRNAs and could demonstrate that these tRNAs are toxic to cells due to their miscoding capacity in eukaryotic translation systems. We also show that the nature of the purine at position 34 is correlated with the nucleotides present at 32 and 38.
Modulation of Natural HLA-B*27:05 Ligandome by Ankylosing Spondylitis-associated Endoplasmic Reticulum Aminopeptidase 2 (ERAP2)*

HLA-B*27:05 and ERAP2 are associated with ankylosing spondylitis, a chronic inflammatory spondyloarthropathy. ERAP2 trims N-terminally extended residues of peptide precursors to their final length. The HLA-B*27:05 ligandomes from unedited and edited-ERAP2 isogenic cell clones were compared, which demonstrated alterations at P1, P2, P3, P7, and P9 peptide positions with enrichment of N-terminal basic residues and minority canonical P2 residues in the natural ligandome from edited-ERAP2 cells. Several ERAP2-dependent cellular peptides were highly homologous to multiple arthritogenic bacteria sequences. We propose that these findings highlight the pathogenic role of this aminopeptidase in the triggering of the autoimmune disease. Graphical Abstract Highlights HLA-B*27:05 and ERAP2 are risk factors for ankylosing spondylitis. The effects of ERAP2 on the B*27:05 ligandome are defined. P1, P2, P3, P7, and PΩ peptide positions are influenced by ERAP2. These effects provide a basis for the association of ERAP2 with the autoimmune disease. The HLA-B*27:05 allele and the endoplasmic reticulum-resident aminopeptidases are strongly associated with AS, a chronic inflammatory spondyloarthropathy. This study examined the effect of ERAP2 in the generation of the natural HLA-B*27:05 ligandome in live cells. Complexes of HLA-B*27:05-bound peptide pools were isolated from human ERAP2-edited cell clones, and the peptides were identified using high-throughput mass spectrometry analyses. The relative abundance of a thousand ligands was established by quantitative tandem mass spectrometry and bioinformatics analysis. The residue frequencies at different peptide position, identified in the presence or absence of ERAP2, determined structural features of ligands and their interactions with specific pockets of the antigen-binding site of the HLA-B*27:05 molecule. Sequence alignment of ligands identified with species of bacteria associated with HLA-B*27-dependent reactive arthritis was performed. In the absence of ERAP2, peptides with N-terminal basic residues and minority canonical P2 residues are enriched in the natural ligandome. Further, alterations of residue frequencies and hydrophobicity profile at P3, P7, and PΩ positions were detected. In addition, several ERAP2-dependent cellular peptides were highly similar to protein sequences of arthritogenic bacteria, including one human HLA-B*27:05 ligand fully conserved in a protein from Campylobacter jejuni. These findings highlight the pathogenic role of this aminopeptidase in the triggering of AS autoimmune disease.
Short‐Term Effects of Media Reports on Terrorism That Are Consistent vs. Not Consistent with Media Recommendations on Mass Shootings: A Randomized Controlled Trial

Objective Media recommendations for the reporting of events where one person or a small group kills multiple others in public settings have been developed recently by suicide prevention experts. Evidence on the effects of reports that are compliant or noncompliant with these recommendations is lacking. Methods We conducted a randomized controlled trial with n = 148 participants who were randomly assigned to read newspaper articles (A) on acts of terrorism assumed to be conducted by Islamist terrorists and not consistent with media recommendations, (B) the same articles differing only in their compliance with recommendations, or (C) articles of similar style that were about homicide. Islamophobia as well as suicidal ideation, stress, and mood were measured before reading the article (T1), immediately afterwards (T2), and one week later (T3). The primary hypothesis was that there is an increase in islamophobia after exposure to media portrayals not consistent with media recommendations. Results Compared to the control group, only participants reading media reports that were not consistent with media recommendations showed a short‐term increase in islamophobia. Conclusion These findings suggest that reporting on terrorism that is not consistent with media recommendations appears to increase islamophobia. In the context of reporting on Islamist terrorism, consistency with recommendations might help reduce negative attitudes toward Muslim minorities.
Mucoadhesive Vaginal Discs based on Cyclodextrin and Surfactants for the Controlled Release of Antiretroviral Drugs to Prevent the Sexual Transmission of HIV

The strategies for developing vaginal microbicides to protect women against human immunodeficiency virus (HIV) sexual transmission are constantly changing. Although the initial dosage forms required daily administration to offer effective protection, the trend then moved towards sustained-release dosage forms that require less frequency of administration in order to improve women’s compliance with the treatment. Nevertheless, another possible strategy is to design on-demand products that can be used in a coitally-dependent manner and only need to be administered immediately before intercourse to offer protection. Vaginal discs based on freeze-dried hydroxypropylmethyl cellulose gels have been developed for this purpose, containing two surfactants, i.e., sodium dodecyl sulphate and polysorbate 60, alone or in combination with 2-hydroxypropyl-β-cyclodextrin, to achieve a formulation capable of incorporating both hydrophilic and lipophilic drugs. Several studies have been carried out to evaluate how the inclusion of these substances modifies the structure of gels (viscosity and consistency studies) and the porosimetry of the freeze-dried discs (scanning electron microscopy micrographs, mechanical properties, swelling behaviour). The drug release and mucoadhesive properties of the discs have also been evaluated with a view to their clinical application. The systems combining sodium dodecyl sulphate and 2-hydroxypropyl-β-cyclodextrin were found to be adequate for the vaginal administration of both Tenofovir and Dapivirine and also offer excellent mucoadhesion to vaginal tissue; these discs could therefore be an interesting option for a coitally-dependent administration to protect women against HIV transmission.