Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression of Myoepithelial Markers in Mammary Carcinomas of 119 Pet Rabbits

Simple Summary Mammary cancer is a serious health issue in pet rabbits; prognostic factors are unknown. In a normal mammary gland, glandular secretory cells are surrounded by a single continuous layer of myoepithelial cells. In non-invasive mammary carcinomas, tumor cells are delineated by an intact myoepithelial layer, which is gradually lost to invasive carcinomas. The main aim of this study was to determine in rabbit mammary carcinomas (n = 119) the expression of myoepithelial markers that have prognostic significance in human cancer. Results show that all cases contained some retained myoepithelial cells. In 93% of the tumors, neoplastic cells expressed the myoepithelial marker calponin. There was a statistically significant association between higher percentages of calponin-containing cancer cells and histological features indicative of a better tumor differentiation, i.e., a lower proliferation of tumor cells, an increased percentage of tubular growth within the tumor, and a lower tumor grade, respectively. These results suggest that rabbit mammary carcinomas develop from progression of non-invasive cancer forms, and that calponin expression in cancer cells likely represents a favorable prognostic factor. The latter hypothesis has to be confirmed in long-term follow-up studies. Abstract Most mammary tumors in pet rabbits are carcinomas; prognostic factors are unknown. The aim of this study on rabbit mammary carcinomas was to determine the expression of myoepithelial markers that have a prognostic relevance in human cancers. Mammary carcinomas (n = 119) of female or female-spayed pet rabbits were immunostained for cytokeratin AE1/AE3, vimentin, smooth muscle actin (SMA), and calponin; and percentages of non-neoplastic myoepithelial cells (ME cells) and calponin-positive neoplastic cells were determined. Using statistical analysis, data were correlated with the age of the rabbits and histological tumor characteristics. All carcinomas contained retained spindle-shaped ME, while 115 also contained hypertrophic ME (HME). A statistically significant relationship existed between a higher age and an increase in HME. In 111 carcinomas (93%), tumor cells expressed calponin. There was a significant correlation between higher percentages of calponin-positive tumor cells and a lower mitotic count, an increased percentage of tubular growth, and a lower grading score, respectively. Data suggest that pet rabbit mammary carcinomas develop from progression of in situ cancer and that the extent of calponin expression in tumor cells influences their biological behavior. These results provide the basis for a long-term follow-up on the prognostic significance of calponin expression in mammary cancer cells.
Dual-satellite integrated intelligent reconnaissance autonomous decision-making model

Aiming at aerospace remote sensing technology, this paper proposes a dualsatellite integrated intelligent reconnaissance decision-making model, and establishes a doublesatellite system. One satellite is used for “general investigation” and one satellite is used for “detailed investigation”. The target is carried out by general investigation load. Track identification provides guidance for detailed inspection loads, thereby improving the accuracy, real-time, flexibility and intelligence of space remote sensing. The focus is on three aspects: investigation model design, key algorithm research and semi-physical simulation verification. The reconnaissance model design completes the conceptual design and process demonstration of the model. The key algorithm research part completes the research of the fast detection based on deep learning and the key algorithm of load imaging strategy decision in the system. The satellite semi-physical simulation verification is carried out by constructing the semi-physical simulation verification
Extrapituitary prolactin promotes generation of Eomes-positive helper T cells mediating neuroinflammation

Significance We have previously demonstrated that induction of pathogenic eomesodermin-positive CD4+ T cells (Eomes+ T helper [Th] cells) is associated with transition from an acute stage to a later stage of experimental autoimmune encephalomyelitis (EAE). In the late phase of EAE, B cells and non-B cell antigen-presenting cells (APCs) recruited to the central nervous system strikingly up-regulate prolactin (PRL). The PRL-producing APCs have the potential to promote generation of Eomes+ Th cells from naïve T cells in an MHC class II-restricted manner, and therapies inhibitory for PRL production suppress the induction of Eomes+ Th cells and ameliorate clinical signs of EAE. Our study highlights the unexpected role of extrapituitary PRL in the development of persistent neuroinflammation. Induction of eomesodermin-positive CD4+ T cells (Eomes+ T helper [Th] cells) has recently been correlated with the transition from an acute stage to a later stage of experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. Moreover, these cells’ pathogenic role has been experimentally proven in EAE. While exploring how the pathogenic Eomes+ Th cells are generated during the course of EAE, we unexpectedly found that B cells and MHC class II+ myeloid cells isolated from the late EAE lesions strikingly up-regulated the expression of prolactin (PRL). We demonstrate that such PRL-producing cells have a unique potential to induce Eomes+ Th cells from naïve T cells ex vivo, and that anti-MHC class II antibody could block this process. Furthermore, PRL levels in the cerebrospinal fluid were significantly increased in the late phase of EAE, and blocking the production of PRL by bromocriptine or Zbtb20-specific siRNA significantly reduced the numbers of Eomes+ Th cells in the central nervous system (CNS) and ameliorated clinical signs in the later phase of EAE. The PRL dependency of Eomes+ Th cells was confirmed in a series of in vitro and ex vivo experiments. Collectively, these results indicate that extrapituitary PRL plays a crucial role in the CNS inflammation mediated by pathogenic Eomes+ Th cells. Cellular interactions involving PRL-producing immune cells could be considered as a therapeutic target for the prevention of chronic neuroinflammation.
Plastination—A scientific method for teaching and research

Over the last four decades, plastination has been one of the best processes of preservation for organic tissue. In this process, water and lipids in biological tissues are replaced by polymers (silicone, epoxy, polyester) which are hardened, resulting in dry, odourless and durable specimens. Nowadays, after more than 40 years of its development, plastination is applied in more than 400 departments of anatomy, pathology, forensic sciences and biology all over the world. The most known polymers used in plastination are silicone (S10), epoxy (E12) and polyester (P40). The key element in plastination is the impregnation stage, and therefore depending on the polymer that is used, the optical quality of specimens differs. The S10 silicone technique is the most common technique used in plastination. Specimens can be used, especially in teaching, as they are easy to handle and display a realistic topography. Plastinated silicone specimens are used for displaying whole bodies, or body parts for exhibition. Transparent tissue sections, with a thickness between 1 and 4 mm, are usually produced by using epoxy (E12) or polyester (P40) polymer. These sections can be used to study both macroscopic and microscopic structures. Compared with the usual methods of dissection or corrosion, plastinated slices have the advantage of not destroying or altering the spatial relationships of structures. Plastination can be used as a teaching and research tool. Besides the teaching and scientific sector, plastination becomes a common resource for exhibitions, as worldwide more and more exhibitions use plastinated specimens.
Mitochondrial Calcium Uniporter Structure and Function in Different Types of Muscle Tissues in Health and Disease

Calcium ions (Ca2+) influx to mitochondrial matrix is crucial for the life of a cell. Mitochondrial calcium uniporter (mtCU) is a protein complex which consists of the pore-forming subunit (MCU) and several regulatory subunits. MtCU is the main contributor to inward Ca2+ currents through the inner mitochondrial membrane. Extensive investigations of mtCU involvement into normal and pathological molecular pathways started from the moment of discovery of its molecular components. A crucial role of mtCU in the control of these pathways is now recognized in both health and disease. In particular, impairments of mtCU function have been demonstrated for cardiovascular and skeletal muscle-associated pathologies. This review summarizes the current state of knowledge on mtCU structure, regulation, and function in different types of muscle tissues in health and disease.
Efficacy of methotrexate in management of peripheral psoriatic arthritis - a systematic review.

INTRODUCTION Psoriatic arthritis (PsA) is a chronic inflammatory joint disease associated with psoriasis. Treatment consists of disease-modifying antirheumatic drugs with methotrexate (MTX) as first choice, yet documentation of the efficacy of this treatment is limited. The objective of this review is to make an accessible overview of the existing evidence on the clinical effect of MTX in the treatment of peripheral PsA. METHODS A systematic search for randomised controlled trials was conducted using the PubMed, Embase and Cochrane Library databases. Studies examining the effect of MTX on peripheral arthritis in adult patients with PsA were included. Only trials published in English were considered and for each study, the methodological quality was assessed. RESULTS Seven studies qualified given the selected criteria. None of the two placebo-controlled trials included found a significant reduction in tender and swollen joint counts. Trials comparing MTX to combination therapy with TNF-alpha inhibitor or ciclosporin A demonstrated some clinical benefits of MTX; however, combination therapy was superior to MTX monotherapy. In a strategy trial, patients were able to reach minimal disease activity with MTX treatment alone, pointing towards some efficacy of MTX on clinical manifestations. CONCLUSIONS Clinical benefits have been found in the treatment of PsA with MTX. MTX has demonstrated clinical efficacy in the treatment of psoriasis; however, the treatment of peripheral arthritis still lacks supportive evidence. More controlled trials need to be conducted to underpin evidence-based use of MTX.
Pooled Subject-Reported Outcomes From 2 Phase 3 Studies of OnabotulinumtoxinA for Simultaneous Treatment of Forehead and Glabellar Lines.

BACKGROUND Understanding the subjects' perspective is critical for successfully treating upper facial lines. OBJECTIVE To understand subjects' self-perception and overall satisfaction after onabotulinumtoxinA treatment for forehead and glabellar lines. METHODS This analysis pooled data from two 12-month, pivotal phase 3 studies in which toxin-naive subjects received onabotulinumtoxinA 40 U or placebo for treatment of upper facial lines. OnabotulinumtoxinA was administered as 0.1-mL injections at 10 prespecified sites (frontalis: 20 U; glabellar complex: 20 U). Each study used 3 reliable and validated patient-reported outcome instruments to evaluate subject satisfaction and appearance-related psychological effects: the Facial Line Satisfaction Questionnaire (FLSQ), the Facial Line Outcomes (FLO-11) Questionnaire, and the Self-Perception of Age (SPA) Questionnaire. In total, data for 865 subjects (608, onabotulinumtoxinA 40 U; 257, placebo) were analyzed. RESULTS Treatment with onabotulinumtoxinA 40 U resulted in significant and sustained improvements across all pooled FLO-11 items and FLSQ items compared with placebo. SPA results demonstrated that a significant proportion of subjects in the pooled analysis felt they looked younger after treatment than at baseline (all, p < .0001 vs placebo). CONCLUSION This study demonstrates a high level of treatment satisfaction and significantly improved appearance-related psychological outcomes among toxin-naive subjects after onabotulinumtoxinA 40 U treatment.
Human papillomavirus infection and cervical dysplasia in HIV-positive women: potential role of the vaginal microbiota.

OBJECTIVES To assess the associations between microbiological markers of vaginal dysbiosis and 1) incident/cleared/type-swap/persistent high-risk human papillomavirus (hrHPV) infection; and 2) incident/cured/cleared/persistent high-grade cervical intraepithelial neoplasia (CIN2+) while controlling for persistent hrHPV infection. DESIGN Two nested case-control studies (N = 304 and 236) within a prospective cohort of HIV-positive women in Johannesburg, South Africa. METHODS Participants were examined for hrHPV type (InnoLipA), cervical dysplasia (histology), and vaginal microbiota (VMB) composition (V3-V4 Illumina HiSeq 2x300 bp) at baseline and endline, a median of 16 months later. RESULTS Women with incident hrHPV compared to those who remained hrHPV-negative were less likely to have an optimal Lactobacillus crispatus/jensenii-dominated VMB type at endline (relative risk ratio (RRR) = 0.125, p = 0.019) but not at baseline. Having different hrHPV types at both visits was associated with multiple anaerobic dysbiosis markers at baseline (e.g. increased BV-anaerobes relative abundance: RRR = 3.246, p = 0.026). Compared to women without CIN2+ but with hrHPV at both visits, women with incident CIN2+ had increased Simpson diversity (RRR = 7.352, p = 0.028) and non-significant trends in other anaerobic dysbiosis markers at endline but not baseline. These associations persisted after controlling for age, hormonal contraception, and CD4+ count. Current hormonal contraceptive use (predominantly progestin-only injectables) was associated with increased CIN2+ risk over-and-above persistent hrHPV infection and independent of VMB composition. CONCLUSIONS hrHPV infection (and/or increased sexual risk-taking) may cause anaerobic vaginal dysbiosis, but a bidirectional relationship is also possible. In this population, dysbiosis did not increase CIN2+ risk, but CIN2+ increased dysbiosis risk. The CIN2+ risk associated with progestin-only injectable use requires further evaluation.
Tissue Engineered Soft Tissue Reconstruction Using Non-invasive Mechanical Preconditioning and a Shelf-ready Allograft Adipose Matrix.

BACKGROUND Adipose tissue defects leading to severe functional (disability) and morphological (disfigurement) morbidity are often treated in plastic surgery with fat grafting, which can be limited by resorption, necrosis, and cyst formation. Our study aimed to assess whether adipose scaffolds could provide an environment for in situ autologous fat grafting, and to study whether adipose cell migration and proliferation (adipogenesis) within scaffolds could be enhanced by preliminarily increasing the vascularity (preconditioning) of the surrounding tissues recipient of the scaffolds. METHODS Using an established rodent model of subcutaneous tissue/scaffold grafting, we tested the potential of a human-derived, shelf-ready, injectable, decellularized allograft adipose matrix (AAM) to reconstruct soft tissue defects when used in combination with non-invasive mechanical (suction-induced) skin preconditioning. RESULTS Combined use of the AAM and non-invasive skin preconditioning significantly improved long-term volume retention (50-80% higher at a 12-week follow-up) and histological quality of reconstructed tissues compared to standard of care (autologous adipose grafts). The components of the AAM supported adipogenesis and angiogenesis. Combining the AAM to living adipose grafts mitigated negative outcomes (lower long-term volume retention, higher presence of cystic-like areas). CONCLUSIONS Our study suggests that the synergistic use of the AAM and non-invasive tissue preconditioning provides an effective solution to improve fat grafting. These strategies can easily be tested in clinical trials and could establish the basis for a novel therapeutic paradigm in reconstructive surgery.
Metallacarborane sulfamides: unconventional, specific, and highly selective inhibitors of carbonic anhydrase IX.

Carbonic anhydrase IX (CAIX) is a transmembrane enzyme that regulates pH in hypoxic tumors and promotes tumor cell survival. Its expression is associated with the occurrence of metastases and poor prognosis. Here, we present nine derivatives of the cobalt bis(dicarbollide)(1-) anion substituted at the boron or carbon sites by alkysulfamide group(s) as highly specific and selective inhibitors of CAIX. Interactions of these compounds with the active site of CAIX were explored on the atomic level using protein crystallography. Two selected derivatives displaying subnanomolar or picomolar inhibition constants and high selectivity for the tumor-specific CAIX over cytosolic isoform CAII. Both derivatives had a time-dependent effect on the growth of multicellular spheroids of HT-29 and HCT116 colorectal cancer cells, facilitated penetration and/or accumulation of doxorubicin into spheroids and displayed low toxicity and showed promising pharmacokinetics and a significant inhibitory effect on tumor growth in syngenic breast 4T1 and colorectal HT-29 cancer xenotransplants.
Surface Inhomogeneity of Graphene Oxide Influences Dissociation of Aβ16-21 Peptide Assembly.

Abnormal peptide assembly and aggregation is associated with an array of neurodegenerative diseases including Alzheimer's disease (AD). A detailed understanding of how nanostructured materials such as oxidized graphene perturb the peptide assembly and subsequently induce fibril dissociation may open new directions for the development of potential AD treatments. Here, we investigate the impact of surface inhomogeneity of graphene oxide (GO) on the assembly of amyloid-beta Aβ16-21 peptides on GO surfaces with different degrees of oxidation using molecular dynamics (MD) simulations. Interestingly, nonuniform GO nanosheets (in terms of oxidation sites) have a much stronger perturbation effect on the structure of Aβ16-21 assembly. The Aβ peptides exhibit a remarkable tendency in binding to the scattered interfaces between unoxidized and oxidized regions, which induces the dissociation of Aβ amyloid fibril. These findings should deepen our understanding of surface-induced peptide dissociation and stimulate discovery of alternative AD treatments.
Disease Severity and Quality of Life Outcome Measurements in Patients With Keloids: A Systematic Review.

BACKGROUND Keloids have been assessed by numerous methods and severity indices resulting in a lack of standardization across published research. OBJECTIVE This study aims to evaluate published keloid randomized controlled trials (RCTs) and identify the need for a gold standard of assessment. METHODS AND MATERIALS PubMed, MEDLINE, and Embase were searched for human RCTs on keloid treatment during a 10-year period. Eligible studies were English language RCTs reporting disease severity outcome measures after keloid treatments. RESULTS A total of 40 disease outcome measures were used in 41 included RCTs. Twenty-four (59%) of the included studies used more than one disease severity scale. The most frequently used outcome measures were the Vancouver Scar Scale (34%) (n = 14), followed by serial photography (24%) (n = 10). These were followed by adverse events and complications (20%) (n = 8), Visual Analogue Scale (12%) (n = 5), keloid dimensions (12%) (n = 5), and Patient and Observer Scar Assessment Scale (10%) (n = 4). Only one study reported quality of life outcomes. CONCLUSION There is wide variation in keloid outcome measures in the published literature. A standardized method of assessment should be implemented to reduce the disparities between studies and to better be able to compare the numerous treatment modalities.
Antifungal effects of a 1,3,4-thiadiazole derivative determined by cytochemical and vibrational spectroscopic studies

Compounds belonging to the group of 5-substituted 4-(1,3,4-thiadiazol-2-yl) benzene-1,3-diols exhibit a broad spectrum of biological activity, including antibacterial, antifungal, and anticancer properties. The mechanism of the antifungal activity of compounds from this group has not been described to date. Among the large group of 5-substituted 4-(1,3,4-thiadiazol-2-yl) benzene-1,3-diol derivatives, the compound 4-(5-methyl-1,3,4-thiadiazole-2-yl) benzene-1,3-diol, abbreviated as C1, was revealed to be one of the most active agents against pathogenic fungi, simultaneously with the lowest toxicity to human cells. The C1 compound is a potent antifungal agent against different Candida species, including isolates resistant to azoles, and molds, with MIC100 values ranging from 8 to 96 μg/ml. The antifungal activity of the C1 compound involves disruption of the cell wall biogenesis, as evidenced by the inability of cells treated with C1 to maintain their characteristic cell shape, increase in size, form giant cells and flocculate. C1-treated cells were also unable to withstand internal turgor pressure causing protoplast material to leak out, exhibited reduced osmotic resistance and formed buds that were not covered with chitin. Disturbances in the chitin septum in the neck region of budding cells was observed, as well as an uneven distribution of chitin and β(1→3) glucan, and increased sensitivity to substances interacting with wall polymerization. The ATR-FTIR spectral shifts in cell walls extracted from C. albicans cells treated with the C1 compound suggested weakened interactions between the molecules of β(1→3) glucans and β(1→6) glucans, which may be the cause of impaired cell wall integrity. Significant spectral changes in the C1-treated cells were also observed in bands characteristic for chitin. The C1 compound did not affect the ergosterol content in Candida cells. Given the low cytotoxicity of the C1 compound to normal human dermal fibroblasts (NHDF), it is possible to use this compound as a therapeutic agent in the treatment of surface and gastrointestinal tract mycoses.
The influence of interleukin 28B polymorphisms on the risk of hepatocellular carcinoma among patients with HBV or HCV infection

Abstract Single nucleotide polymorphisms (SNPs) of the interleukin 28B (IL28B) gene has proven to be associated with the clinical outcome of patients with chronic hepatitis virus B or C (HBV or HCV) infections. However, whether IL28B SNPs have an influence on the risk of hepatocellular carcinoma (HCC) among patients with HBV or HCV infection remains controversial. Therefore, this study aims to determine the association between IL28B polymorphisms and the risk of HCC in individuals with HBV or HCV infection. PubMed, EMBASE, and Chinese National Knowledge Infrastructure (CNKI) databases were used to identify studies meeting the selection requirements using the terms “interleukin 28B”, “IFN-lambda-3”, “IFNL3”, “single nucleotide polymorphisms”, “SNPs”, “hepatocellular carcinoma”, “HCC”, “liver cancer”. A total of 24 eligible original studies (1 cohort study and 23 case-control studies) involved 20238 individuals (HCC group = 8725 vs control group = 11,513) were included. Both IL28B rs12979860 CC and rs8099917 TT genotypes were significantly associated with a decreased risk of HCC among patients with HBV or HCV infection (OR = 0.71, 95% CI = 0.57–0.88; OR = 0.82, 95% CI = 0.72–0.94, respectively). Egger test and Begg test revealed no‘ publication bias (P > .05). Sensitivity analyses suggested the robustness of the results in this meta-analysis. Both IL28B rs12979860 CC and rs8099917 TT genotypes are protective factors for the development of HCC among patients with HBV or HCV infection. Future prospective studies examining the impact of IL28B polymorphisms on the risk of HCC and investigating the underlying mechanism for the protective role of IL28B polymorphisms in HCC development are warranted.