Miracle-dz/UniFAR-FTUs huggingface dataset:
IL-27 overexpression alleviates inflammatory response in allergic asthma by inhibiting Th9 differentiation and regulating Th1/Th2 balance

Abstract Objective To investigate the effect of IL-27 on Th9 differentiation and Th1/Th2 balance. Methods C57BL/6 (B6) mice were treated with ovalbumin to establish an allergic asthma (AA) model and subjected to IL-27 overexpression (OV) and empty vector (EV). Hematoxylin-eosin (HE) staining was performed to observe lung tissue inflammation. Flow cytometry was carried out to evaluate the percentage of Th9, Th1, and Th2 cells. The expression of IL-27, IL-27R, IL-9, T-bet, IFN-γ, and IgE was evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). Western blot was conducted to observe the expression of pSTAT-1 and pSTAT-3. Results Compared with the Model group, the number of Th1 cells in the Model + OV group increased significantly (p < .05), while those of Th9 and Th2 cells decreased significantly (p < .05). The expression of IL-27, IL-27R, and IFN-γ in blood serum was increased (p < .05), and that of IL-9 and IgE was significantly decreased in the Model + OV group compared to the Model (p < .05). Western blot revealed that Model + OV exhibited lower expression of pSTAT-3 than that in the Model and Model + EV groups (p < .05), while pSTAT-1 expression was significantly increased (p < .05). Inflammatory infiltration in the Model + OV group was significantly reduced, and there was no significant difference between the Model and Model + EV groups. Conclusions IL-27 OV inhibits Th9 differentiation and regulates the imbalance of Th1/Th2, thereby alleviating inflammatory response in AA. The findings suggest that IL-27 OV may be a potential strategy for clinical treatment of AA.
Geometry of the moduli space of Higgs bundles

This thesis contains work which appeared in several papers. Additionally to the results in the papers it contains a detailed introduction and some further proofs and remarks. The dissertation gives a description of the topology and symplectic and algebraic geometry of Hitchin's hyperkaehler moduli space M of rank 2 Higgs bundles with fixed determinant of odd degree over a fixed Riemann surface. After the long introduction it describes a compactification of M in great detail, using symplectic cutting (math.AG/9804083). Examining the downward Morse flow of a natural circle action on M it shows the vanishing of intersection numbers (math.AG/9805071). Examining the upward Morse flow it explains a set of generators of the cohomology ring and a conjectured explicit description of the cohomology ring (which was proven in math.AG/0003094). Then finally it introduces the resolution tower for M, and shows that its direct limit is homotopically equivalent with the classifying space of the gauge group. In turn it yields another proof of the generation theorem (as in math.AG/0003093) and also yields a purely algebraic geometric proof of the Mumford conjecture about the cohomology ring of the moduli space of rank 2 stable bundles on curves. It finishes by proving homotopy stabilizations in the resolution tower analogously to the Atiyah-Jones conjecture.
Celastrol inhibits pathologic neovascularization in oxygen-induced retinopathy by targeting the miR-17-5p/HIF-1α/VEGF pathway

ABSTRACT Retinopathy of prematurity (ROP), which is characterized by retinal neovascularization (RNV), is a major cause of neonatal blindness. The primary treatment for ROP is anti-vascular endothelial growth factor (VEGF) therapy, which is costly and can rapidly lead to desensitization. Celastrol, a bioactive compound extracted from Tripterygium wilfordii Hook F. (“Thunder of God Vine”), has been shown to exert anticancer and anti-inflammatory effects. However, whether celastrol has antiangiogenic activity and can suppress inflammation to inhibit ROP progression is unclear. This was investigated in the present study in vitro as well as in vivo using a mouse model of oxygen-induced retinopathy (OIR). Our results showed that celastrol treatment reduced neovascular and avascular areas in the retina and inhibited microglia activation and inflammation in OIR mice. Celastrol also inhibited proliferation, migration, and tube formation in cultured human retinal microvascular endothelial cells, and reversed the activation of the microRNA (miR)-17-5p/hypoxia-inducible factor (HIF)-1α/VEGF pathway in the retina of OIR mice. These results indicate that celastrol alleviates pathologic RNV in the retina by protecting neuroglia and suppressing inflammation via inhibition of miR-17-5p/HIF-1α/VEGF signaling, and thus has therapeutic potential for the prevention and treatment of ROP. Abbreviations: BSA, bovine serum albumin; COX2, cyclooxygenase 2; ECM, endothelial cell medium; FBS, fetal bovine serum; HDAC, histone deacetylase; HIF-1, hypoxia-inducible factor 1; HRMEC, human retinal microvascular endothelial cell; Hsp70, heat shock protein; IB4, isolectin B4; ICAM-1, intercellular adhesion molecule 1; IL-1β/6, interleukin 1 beta/6; MAPK, mitogen-activated protein kinase; MCP-1, monocyte chemoattractant protein 1; miRNA, microRNA; MMP, matrix metalloproteinase; mTOR, mammalian target of rapamycin; NF-κB, nuclear factor-kappa B; OIR, oxygen-induced retinopathy; PBS, phosphate-buffered saline; PCNA, proliferating cell nuclear antigen; PI3K, phosphatidylinositol-3-kinase; qRT-PCR, quantitative real-time PCR; RNV, retinal neovascularization; ROP, retinopathy of prematurity; RTCA, real-time cell analyzer; RVO, retinal vaso-obliteration; TNF-α, tumor necrosis factor alpha; VCAM-1, vascular cell adhesion molecule 1; VEGF, vascular endothelial growth factor.
Symbiotic microorganisms: prospects for treating atopic dermatitis

ABSTRACT Introduction Atopic dermatitis (AD) is a common chronic recurrent inflammatory skin disease. The pathogenesis is unclear but may be related to genetic, immune, and environmental factors and abnormal skin barrier function. Symbiotic microorganisms in the gut and on the skin are associated with AD occurrence. Areas covered We discuss the metabolism and distribution of intestinal and skin flora and review their relationship with AD, summarizing the recent applications of intestinal and skin flora in AD treatment, and discussing the prospect of research on these two human microbiota systems and their influence on AD treatment. The PubMed database was searched to identify relevant publications from 1949 to 2020 for the bibliometric analysis of atopic dermatitis and symbiotic microorganisms. Expert opinion Many studies have suggested a potential contribution of microbes in the intestine and on the skin to AD. Bacteria living on the skin can aggravate AD by secreting numerous virulence factors. Moreover, the metabolism of intestinal flora can influence AD occurrence and development via the circulatory system. Current evidence suggests that by regulating intestinal and skin flora, AD can be treated and prevented.
Comparison of Crimean-Congo Hemorrhagic Fever Virus and Aigai Virus in Life Cycle Modeling Systems Reveals a Difference in L Protein Activity

Crimean-Congo hemorrhagic fever virus (CCHFV) is the cause of severe hemorrhagic disease, which is often fatal. Present throughout Africa, Asia, and Southeast Europe, a diverse number of viral genotypes exist. ABSTRACT Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne orthonairovirus that causes a severe, often fatal, hemorrhagic disease throughout Africa, Asia, and Southeast Europe. A wide variety of strains are circulating in the field which broadly correlate to their geographic distribution. The viral determinants of pathogenicity remain unclear, as does the contribution of strain-specific differences to pathology. Aigai virus (AIGV) is a closely related virus (formally designated CCHFV genotype VI, Europe II, or AP92-like virus), which has been proposed to be less virulent than CCHFV. However, the molecular details leading to potential differences in virulence are unknown. To explore if differences exist, life cycle modeling systems, including both a minigenome and a transcriptionally competent virus-like particle assay, were developed for AIGV to allow the comparison with the CCHFV reference IbAr10200 strain. Using this approach, we could demonstrate that AIGV exhibits lower viral gene expression than the reference strain of CCHFV. Subsequent systematic exchange of viral components revealed that the L protein is responsible for the observed differences in gene expression and that the interferon (IFN) antagonistic activity of the ovarian tumor-type protease domain is not responsible for this effect. IMPORTANCE Crimean-Congo hemorrhagic fever virus (CCHFV) is the cause of severe hemorrhagic disease, which is often fatal. Present throughout Africa, Asia, and Southeast Europe, a diverse number of viral genotypes exist. However, the viral determinants of pathogenicity remain unclear. It has been proposed that the closely related Aigai virus (AIGV) may be a less virulent virus. Here, using newly developed and improved life cycle modeling systems we have examined potential differences between the CCHFV reference strain, IbAr10200, and AIGV. Using this approach, we identified lower viral gene expression driven by the AIGV viral polymerase as a major difference which may be indicative of lower virulence.
A review of the circumstances and health‐seeking behaviours associated with bat exposures in high‐income countries

Human–bat interactions are now the source of the majority of locally acquired human lyssavirus infections in many high‐income countries without hematophagous or ‘vampire’ bat species. This study aims to identify the most common types and circumstances of bat exposures occurring among members of the general public in high‐income countries with no hematophagous bats, and to describe the health‐seeking behaviours associated with exposures in these settings. We conducted a scoping review of relevant academic and grey literature on bat exposures and confirmed bat lyssavirus infections among members of the general public in Australia, Canada, the United States and high‐income European countries from 1996 to 2019. Case studies and population‐based studies were included for analysis, and findings were extracted and synthesized by the literature type and geographic region. A total of 63 publications were identified, including: 47 case studies and 16 population‐based studies. Overall, most exposures in Australia and Europe were intentionally initiated by humans and involved attempts to handle, touch or help a bat. In North America, however, household exposures were more common and predominantly involved a bat being found in a room or area where a person had slept. Studies also showed that a proportion of bat exposures in high‐income countries go unreported in the absence of a public health investigation and are therefore unlikely to receive prompt treatment. The results of this review suggest that the most effective strategies for preventing bat exposures vary between regions and that health‐seeking behaviours following bat exposures could be improved in high‐income settings.
Electron microscopic study on the effect of chronic fluoxetine treatment on pituitary gland and the possible therapeutic effect of adipose-derived mesenchymal stem cells in adult male albino rats

ABSTRACT Background: Adipose-derived mesenchymal stem cells (ADSCs) have therapeutic potential for the treatment of a variety of disorders due to their self-renewal and multipotential differentiation capabilities. Aim of the work: This study was planned to demonstrate the electron microscopic structure of the pituitary gland after chronic fluoxetine treatment and the possible therapeutic effect of ADSCs. Materials and methods:Thirty healthy male adult albino rats were classified into Control group (Group I). Fluoxetine treated (Group II) received 24 mg/kg/day of fluoxetine dissolved in 1.0 mL of tap water once a day. Fluoxetine group treated with ADSCs (Group III) received fluoxetine as group (II) for 30 days and then was injected once by ADSCs at a dose of 1 × 106 cells/rat in the tail vein suspended in 0.5 ml of phosphate-buffered saline (PBS). Recovery group (Group IV) received fluoxetine for 30 days and then received no treatment till the end of the experiment. Results: The ultrastructural observations of the fluoxetine-treated group revealed major histological changes in both the pars distalis and nervosa. Pars distalis revealed cells with different shapes, sizes, nuclei, and variable profiles of the cytoplasm. Pars nervosa, on the other hand, revealed pituicytes with electron-lucent cytoplasm and small apoptotic nuclei. Administration of ADSCs greatly improved the microscopic appearance of cells, while the recovery group showed similar histological changes as the fluoxetine group. Conclusion: Fluoxetine caused various deleterious changes in the pituitary gland of albino rats, as evidenced by electron microscopy. These changes were almost corrected by the ADSCs treatment.
YouTube as a Source of Patient Information for Ankle Arthroplasty: Quantitative Analysis of Video Reliability, Quality, and Content

Background. There are limited data on the quality and content of videos discussing total ankle arthroplasty (TAA) on the YouTube video platform. Methods. The first 60 unique YouTube videos resulting from the keyword query “ankle arthroplasty” and “ankle replacement” were analyzed for comprehensiveness and quality. Content was assessed using the Journal of American Medical Association (JAMA) benchmark criteria, DISCERN, Global Quality Scale (GQS), and an arthroplasty-specific score. Results. Videos demonstrated low mean DISCERN (49.2/80), GQS (3.2/5), and arthroplasty-specific scores (4.3/12) with substantial variability between videos. Most of the content was produced by nonacademic physicians (46.7%) and academic sources (21.7%). Academic videos saw significantly higher mean JAMA scores (P = .013) but were otherwise comparable to non-academic physicians. Commercial content demonstrated significantly low-quality scores compared to academic (P = .012) and physician (P = .008) sources despite the highest mean viewership. Conclusions. Information on TAA on the YouTube platform is highly variable based on video source, with generally poor quality and content. Level of Evidence: Level V, systemic review of non-peer reviewed resources
Clinical Studies that Initiated the Use of Spinal Opioids for the Treatment of Pain: A New Approach to Historical Review

Opioids administered into the spinal space by intrathecal or epidural routes can provide potent and prolonged selective analgesia. Compared to the systemic administration of opioids, spinal administration can bring about analgesia with fewer central and systemic adverse effects. For the past 40 years, spinal opioid analgesia has achieved great popularity in various fields of pain treatment. The aim of this work is to identify clinical studies that initiated the use of spinal opioids for the treatment of pain. To determine the historical role of each of the review’s studies, we used the combination of two factors: the study priority in terms of the time of its publication and the degree of its acknowledgement in the form of citation impact. The date of publication was regarded as the primary factor, but only if the count of citations indicated a sufficient acknowledgement by the other authors. The citation impact was assessed as the initial citation count – for a period of five years after the year of article publication – and the total count. Analysis of the related data shows that the clinical studies initiating the use of spinal opioids for the treatment of pain belong to two groups of authors – Wang et al. and Behar et al. Both studies were published in 1979 and described delivery of morphine into the spinal space, although the techniques of administration were different: Wang et al. injected morphine intrathecally, Behar et al. administered morphine epidurally. The response to these studies was overwhelming - close to a dozen reports on this topic were published in 1979 and more than a hundred – in 1980-1981. The total citation response to the Wang et al. article reached 699, and that to Behar et al. – 518. Two earlier records (1900-1901) of the use of intrathecal morphine, by Nicolae Racoviceanu-Pitesti and Otojiro Kitagawa, found no following in medical literature for more than three quarters of a century.
The Association of Early Corticosteroid Therapy With Clinical and Health-Related Quality of Life Outcomes in Children With Septic Shock*

OBJECTIVES: Corticosteroids are commonly used in the treatment of pediatric septic shock without clear evidence of the potential benefits or risks. This study examined the association of early corticosteroid therapy with patient-centered clinically meaningful outcomes. DESIGN: Subsequent cohort analysis of data derived from the prospective Life After Pediatric Sepsis Evaluation (LAPSE) investigation. Outcomes among patients receiving hydrocortisone or methylprednisolone on study day 0 or 1 were compared with those who did not use a propensity score–weighted analysis that controlled for age, sex, study site, and measures of first-day illness severity. SETTING: Twelve academic PICUs in the United States. PATIENTS: Children with community-acquired septic shock 1 month to 18 years old enrolled in LAPSE, 2013–2017. Exclusion criteria included a history of chronic corticosteroid administration. INTERVENTIONS: None. MEASUREMENTS and MAIN RESULTS: Among children enrolled in LAPSE, 352 of 392 met analysis inclusion criteria, and 155 of 352 (44%) received early corticosteroid therapy. After weighting corticosteroid therapy administration propensity across potentially confounding baseline characteristics, differences in outcomes associated with treatment were not statistically significant (adjusted effect or odds ratio [95% CI]): vasoactive-inotropic support duration (–0.37 d [–1.47 to 0.72]; p = 0.503), short-term survival without new morbidity (1.37 [0.83–2.28]; p = 0.218), new morbidity among month-1 survivors (0.70 [0.39–1.23]; p = 0.218), and persistent severe deterioration of health-related quality of life or mortality at month 1 (0.70 [0.40–1.23]; p = 0.212). CONCLUSIONS: This study examined the association of early corticosteroid therapy with mortality and morbidity among children encountering septic shock. After adjusting for variables with the potential to confound the relationship between early corticosteroid administration and clinically meaningful end points, there was no improvement in outcomes associated with this therapy. Results from this propensity analysis provide additional justification for equipoise regarding corticosteroid therapy for pediatric septic shock and ascertain the need for a well-designed clinical trial to examine benefit/risk for this intervention.
Basilar artery occlusion: A review of clinicoradiologic features, treatment selection, and endovascular techniques

Basilar artery occlusion (BAO) is an infrequent but often fatal subtype of stroke. Predicting outcomes and selecting patients for endovascular therapy (EVT) remains challenging. Advances in neuroimaging and the development of prognostic scoring systems have augmented clinical decision-making over time. Recent randomized trials, BEST (Basilar Artery Occlusion Endovascular Intervention vs. Standard Medical Treatment), BASICS (Basilar Artery International Cooperation Study), BAOCHE (Basilar Artery Occlusion CHinese Endovascular Trial) and ATTENTION (Endovascular Treatment for Acute Basilar Artery Occlusion), compared EVT and medical management for patients with BAO. These trials yielded mixed results. The former two suggested unclear benefit while the latter two supported a benefit of EVT. While all had limitations, most providers agree caution should be exercised when excluding patients from EVT who may stand to benefit. Further studies are therefore needed to determine the effectiveness, safety, selection criteria, and optimal technical approach for EVT among patients with BAO. Hyperacute-phase advanced imaging can offer several benefits to aid decision making. It is reasonable to exclude patients with low National Institutes of Health Stroke Scale (NIHSS), large imaging-proven cores, and evidence of perforator occlusion by branch atheromatous disease. Herein, we review the clinical presentation, imaging work-up, treatments, and clinical outcomes for BAO, while highlighting knowledge gaps in treatment selection and technique.
Mechanisms and modeling of wound repair in the intestinal epithelium

ABSTRACT The intestinal epithelial barrier is susceptible to injury from insults, such as ischemia or infectious disease. The epithelium’s ability to repair wounded regions is critical to maintaining barrier integrity. Mechanisms of intestinal epithelial repair can be studied with models that recapitulate the in vivo environment. This review focuses on in vitro injury models and intestinal cell lines utilized in such systems. The formation of artificial wounds in a controlled environment allows for the exploration of reparative physiology in cell lines modeling diverse aspects of intestinal physiology. Specifically, the use of intestinal cell lines, IPEC-J2, Caco-2, T-84, HT-29, and IEC-6, to model intestinal epithelium is discussed. Understanding the unique systems available for creating intestinal injury and the differences in monolayers used for in vitro work is essential for designing studies that properly capture relevant physiology for the study of intestinal wound repair.
Whole-genome sequencing as an alternative to analyze copy number abnormalities in acute myeloid leukemia and myelodysplastic syndrome

Abstract Copy number aberrations (CNA) are the core determinants for diagnosis, risk stratification and prognosis in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). In this study, a shallow whole-genome sequencing-based assay, LeukoPrint, was utilized to depict genomic CNA profiles from the bone marrow of 137 newly diagnosed AML/MDS patients. It demonstrated 98.1% concordance of CNA profiles with cytogenetics and/or fluorescence in situ hybridization (FISH). It is advantageous in detecting CNAs of short segments (1 Mb) and from samples with low leukemic cell content, more accurate for describing complex karyotypes and less confounded by subjective bias. LeukoPrint improved the overall diagnostic yield by redefining the risk categories for 16 patients by presenting new information. In summary, LeukoPrint provided an automated, convenient, and cost-effective approach to describe genomic CNA profiles. It brought greater diagnostic yield and risk stratification information by incorporating into the routine cytogenetics based on the CNA-related criteria of standard ELN/IPSS-R guidelines.