Miracle-dz/UniFAR-FTUs huggingface dataset:
Specific Ablation of Antiviral Gene Expression in Macrophages by Antibody-Dependent Enhancement of Ross River Virus Infection

ABSTRACT Ross River virus (RRV) is an indigenous Australian arthropod-borne alphavirus responsible for epidemic polyarthritis (EPA), myalgia, and lethargy in humans. Macrophages and monocytes have been associated with human RRV disease, and previous studies have shown that RRV is capable of infecting macrophages via both a natural virus receptor and by Fc receptor-mediated antibody-dependent enhancement (ADE). Similar to other viruses, such as human immunodeficiency virus and dengue virus, ADE infection results in dramatic RRV growth increases for in vitro macrophage cultures. This study demonstrates that RRV could resist lipopolysaccharide (LPS)-induced antiviral activity in macrophage cultures when infection was via the ADE pathway. Investigation of this infection pathway found that RRV was able to suppress the transcription and translation of key antiviral genes (tumor necrosis factor and inducible nitric oxide synthase) in LPS-stimulated macrophages by disrupting the transcription into mRNA of the genes coding for the associated transcription factors IRF-1 and NF-κB. The transcription of non-antiviral control genes was not perturbed by RRV-ADE infection, and de novo protein synthesis also was not significantly affected in RRV-ADE infected cells. The ADE pathway of infection allowed RRV to specifically target antiviral genes in macrophages, resulting in unrestricted virus replication. As ADE has been observed for several virus families and associated with disease and adverse vaccination outcomes, these findings may have broad relevance to viral disease formation and antiviral vaccination strategies.
Minimum sum-squared residue for fuzzy co-clustering

Clustering is often seen as a more practical but very challenging answer to the task of categorizing objects. Minimum Sum-squared Residue for Fuzzy Co-Clustering (MSR-FCC) is proposed to address two issues faced by many existing clustering algorithms, namely the high-dimensionality and the inherent fuzziness found in most real-world data. MSR-FCC is able to simultaneously cluster data and features using fuzzy techniques. It suggests a new partitioning fuzzy co-clustering algorithm based on the mean squared residue approach. Besides handling overlap clusters, MSR-FCC offers the flexibility that allows the number of data clusters to be different from the number of feature clusters, which reflects the distribution characteristic inherited in real-world data. In this paper, mathematical formulation of MSR-FCC is derived and explained. Experiments were conducted on standard datasets to demonstrate that the proposed algorithm is able to cluster high-dimensional data with overlaps feasibly and at the same time, it provides a new and promising mechanism for improving the interpretability of the co-clusters through the fuzzy membership function.
Is there a relationship between rheumatoid arthritis and periodontal disease?

AIM The aim of this study was to determine whether there is a relationship between disease experience of rheumatoid arthritis and periodontal disease. METHODS 1,412 individuals attending the University of Queensland's School of Dentistry were assessed for the prevalence of periodontal disease and rheumatoid arthritis. Analysis of data obtained from a self-reported health questionnaire and dental records was carried out and included: number of individuals referred for advanced periodontal care (test group); number of individuals attending for routine dentistry; determination of rheumatoid arthritis, cardiovascular disease and diabetes mellitus through self-reporting and assessment of prescription medications; assessment of periodontal disease through assessment of existing oral radiographs. RESULTS In patients referred for periodontal treatment, the prevalence of self-reported rheumatoid arthritis was 3.95% which is significantly higher than that seen in patients not referred for periodontal treatment (0.66%) and also that reported in the general population (1%). Of those referred patients with rheumatoid arthritis, 62.5% had advanced forms of periodontal disease. These results were mirrored in the results of the self-reported prevalence of cardiovascular disease and diabetes mellitus which was consistent with the published higher prevalence in periodontal patients. CONCLUSIONS Based on data derived from self-reported health conditions, and not withstanding the limitations of such a study, we conclude that there is good evidence to suggest that individuals with moderate to severe periodontal disease are at higher risk of suffering from rheumatoid arthritis and vice versa.
A Believer’s Overview of Cancer Immunosurveillance and Immunotherapy

The field of tumor immunology has grown around the idea that one of the important roles of the immune system is to eliminate cancer. This idea was difficult to reconcile with the accepted notion that the immune system evolved to distinguish self from nonself and therefore tumors derived from self-tissues would not be recognized. Lack of appropriate animal models prevented experimental testing of cancer immunosurveillance. This changed with the realization that the immune system evolved to recognize danger and with the advent of mouse models deficient in one or more immune function, which showed predicted increases in susceptibility to cancer. Simultaneously, technical advances that enabled the study of the human immune system provided data for the existence of tumor-specific T cells and Abs and led to molecular identification of tumor Ags, fully validating the cancer immunosurveillance hypothesis. Immunotherapy designed to strengthen cancer immunosurveillance has achieved unprecedented clinical successes.
Lysophosphatidic Acid Induces Interleukin-13 (IL-13) Receptor α2 Expression and Inhibits IL-13 Signaling in Primary Human Bronchial Epithelial Cells*

Interleukin-13 (IL-13), a Th2 cytokine, plays a pivotal role in pathogenesis of bronchial asthma via IL-13 receptor α1 (IL-13Rα1) and IL-4 receptor α (IL-4Rα). Recent studies show that a decoy receptor for IL-13, namely IL-13Rα2, mitigates IL-13 signaling and function. This study provides evidence for regulation of IL-13Rα2 production and release and IL-13-dependent signaling by lysophosphatidic acid (LPA) in primary cultures of human bronchial epithelial cells (HBEpCs). LPA treatment of HBEpCs in at imedependent fashion increased IL-13Rα2 gene expression without altering the mRNA levels of IL-13Rα1 and IL-4Rα. Pretreatment with pertussis toxin (100 ng/ml, 4 h) or transfection of c-Jun small interference RNA or an inhibitor of JNK attenuated LPA-induced IL-13Rα2 gene expression and secretion of soluble IL-13Rα2. Overexpression of catalytically inactive mutants of phospholipase D (PLD) 1 or 2 attenuated LPA-induced IL-13Rα2 gene expression and protein secretion as well as phosphorylation of JNK. Pretreatment of HBEpCs with 1 μm LPA for 6 h attenuated IL-13-but not IL-4-induced phosphorylation of STAT6. Transfection of HBEpCs with IL-13Rα2 small interference RNA blocked the effect of LPA on IL-13-induced phosphorylation of STAT6. Furthermore, pretreatment with LPA (1 μm, 6 h) attenuated IL-13-induced eotaxin-1 and SOCS-1 gene expression. These results demonstrate that LPA induces IL-13Rα2 expression and release via PLD and JNK/AP-1 signal transduction and that pretreatment with LPA down-regulates IL-13 signaling in HBEpCs. Our data suggest a novel mechanism of regulation of IL-13Rα2 and IL-13 signaling that may be of physiological relevance to airway inflammation and remodeling.
Binding of a Sialic Acid-recognizing Lectin Siglec-9 Modulates Adhesion Dynamics of Cancer Cells via Calpain-mediated Protein Degradation*

Background: Siglec-9 binds sialylglycoconjugates on target cells probably causing signals in both sides of cells. Results: Co-culture with Siglec-9-expressing U937 caused degradation of focal adhesion kinase and related proteins in an astrocytoma cell line. Conclusion: Interaction between Siglec-9 and its counterreceptor triggered activation signals in cancer cells via calpain. Significance: Cancer cells may utilize sialylglycoconjugates recognized by Siglec-9 to escape from immunosurveillance. Although regulatory mechanisms for immune cells with inhibitory signals via immunoreceptor tyrosine-based inhibitory motifs are well known, signals transduced via interaction between Siglecs and sialyl compounds on their counterreceptors into target cells have not been reported to date. In this study, we found that an astrocytoma cell line, AS, showed detachment from culture plates when co-cultured with Siglec-9-expressing cells and/or soluble Siglec-9. Moreover, detached AS cells regrew as co-cultured cells with Siglec-9-deficient cells. They also showed increased motility and invasiveness upon Siglec-9 binding. In immunoblotting, rapid degradation of focal adhesion kinase (FAK) and related signaling molecules such as Akt, paxillin, and p130Cas was observed immediately after the co-culture. Despite degradation of these molecules, increased p-Akt was found at the front region of the cytoplasm, probably reflecting increased cell motility. Calpain was considered to be a responsible protease for the protein degradation by the inhibition experiments. These results suggest that protein degradation of FAK and related molecules was induced by Siglec-9 binding to its counterreceptors via sialylglycoconjugates, leading to the modulation of adhesion kinetics of cancer cells. Thus, this might be a mechanism by which cancer cells utilize Siglec-9-derived signals to escape from immunosurveillance.
Overview of the TREC 2016 LiveQA Track

The LiveQA track, now in its second year, is focused on real-time question answering for real-user questions. During the test period, real user questions are drawn from those newly submitted on a popular community question answering site, Yahoo Answers (YA), that have not yet been answered. These questions are sent to the participating systems, who provide an answer in real time. Returned answers are judged by the NIST assessors on a 4-level Likert scale. The most challenging aspects of this task are that the questions can be on any one of many popular topics, are informally stated, and are often complex and at least partly subjective. Furthermore, the participant systems must return an answer in under 60 seconds, which places additional, and realistic, constraints on the kind of processing that a system can do. In addition to the main real-time question answering task, this year we introduced a pilot task aimed at identifying the question intent. As human questions submitted on forums and CQA sites are verbose in nature and contain many redundant or unnecessary terms, participants were challenged to identify the significant parts of the question. The main theme of the question is marked by the systems by specifying a list of spans that capture its main intent. This automatic “summary” of the question was evaluated by measuring its ROUGEand METEOR-based similarity to a succinct rephrase of the question, manually provided by NIST assessors.
e-Cigarette awareness, use, and harm perceptions in US adults.

OBJECTIVES We estimated e-cigarette (electronic nicotine delivery system) awareness, use, and harm perceptions among US adults. METHODS We drew data from 2 surveys conducted in 2010: a national online study (n = 2649) and the Legacy Longitudinal Smoker Cohort (n = 3658). We used multivariable models to examine e-cigarette awareness, use, and harm perceptions. RESULTS In the online survey, 40.2% (95% confidence interval [CI] = 37.3, 43.1) had heard of e-cigarettes, with awareness highest among current smokers. Utilization was higher among current smokers (11.4%; 95% CI = 9.3, 14.0) than in the total population (3.4%; 95% CI = 2.6, 4.2), with 2.0% (95% CI = 1.0, 3.8) of former smokers and 0.8% (95% CI = 0.35, 1.7) of never-smokers ever using e-cigarettes. In both surveys, non-Hispanic Whites, current smokers, young adults, and those with at least a high-school diploma were most likely to perceive e-cigarettes as less harmful than regular cigarettes. CONCLUSIONS Awareness of e-cigarettes is high, and use among current and former smokers is evident. We recommend product regulation and careful surveillance to monitor public health impact and emerging utilization patterns, and to ascertain why, how, and under what conditions e-cigarettes are being used.
Wnt5a regulates the cell proliferation and adipogenesis via MAPK‐independent pathway in early stage of obesity

The early stage of obesity is an important stage in the development of obesity. However, there are few studies which explored the property or changes in obesity at early stage especially involving Wnt5a. The associated gene expression of Wnt5a on cell regeneration and the effect of Wnt5a on rat adipose‐derived stem cell (rASC) proliferation and adipogenesis need additional study. Here, we investigated the changes in obesity at early stage and how Wnt5a regulates rASC regeneration, proliferation, and adipogenesis. Our data revealed that obesity at early stage measured by Lee index presented a state with impaired adipogenesis and more infiltrated inflammatory cells but without significant changes in adipocyte sizes and inflammatory factors. The process might be associated with anti‐canonical Wnt pathway and a reciprocal Wnt5a/JNK pathway. Besides the gene expression of Wnt5a decreased from cell passage 1 to passage 3. The cell proliferation was regulated by increasing dose of Wnt5a with the maximal effect at 50 ng/mL and 50 ng/mL Wnt5a suppressed adipogenic differentiation at middle‐late stage of adipogenesis via anti‐β‐catenin and a mitogen‐activated protein kinase (MAPK) signaling‐independent manner. Accordingly, the research helps to gain further insights into the early stage of obesity and its associated changes on a cellular and molecular level.
Lymphomas occurring late after solid-organ transplantation: Influence of treatment on the clinical outcome

Background. Posttransplant lymphoproliferative disorders (PTLDs) that occur late after solid-organ transplantation are usually a monoclonal proliferation frequently characterized by the lack of the Epstein-Barr virus genome in tumor cells. The clinical outcome and the best management for patients who present with late PTLDs still remain unclear. Patients and Methods. Thirty patients who developed PTLDs more than 12 months (range 13–156) after heart, kidney, or liver transplantation were retrospectively evaluated. Median age was 36.7 years (range 1–70). Fifty-five percent of patients presented with advanced-stage (III–IV) lymphoma, 43% of patients presented with B symptoms, and 40% of patients showed extranodal involvement. Twenty-four cases (75%) were categorized as monoclonal monomorphic PTLD. Results. Three patients died of progressive multiorgan failure before any treatment was initiated. Overall, 17 (63%) patients obtained a clinical response (14 patients had complete remission [CR] and 3 patients had partial remission [PR]). Eight (47%) patients are still alive and in CR, two (12%) patients died in CR, and seven (41%) patients relapsed. With a median follow-up of 6 months (range 0.5–42.8), the median overall survival was 6.2 months. Both clinical response and survival were significantly influenced by the treatment. Indeed, all patients treated for limited disease with surgery or radiotherapy in combination with modulation of immunosuppression obtained CR and are still alive and in CR. On the contrary, 33% of patients who received chemotherapy obtained a clinical response, whereas 15% of patients who received chemotherapy showed progressive disease and 50% of patients who received chemotherapy died of toxicity (infectious or multiorgan failure). Conclusions. We suggest that patients with late PTLDs and limited disease may benefit from local treatment. For patients who require chemotherapy, we suggest that it should be administered to minimize the risk of infection complications.
Screening for distress can predict loss of follow‐up and treatment in cancer patients: results of development and validation of the Distress Inventory for Cancer Version 2

Introduction: The evidence suggests that in most instances distress from cancer goes unrecognised. There has been substantial work in screening for distress leading to development in practice guidelines recommending screening for distress. There is a need to identify distress early in the continuum, where suitable and timely interventions will benefit the patient. The Distress Inventory for Cancer (DIC) was designed for this.
Cyclooxygenase‐2 (Cox‐2) expression and angiogenesis in glioblastoma

Cyclooxygenase‐2 (Cox‐2), the key enzyme that catalyzes the first steps in the biosynthesis of the prostaglandins from arachidonic acid, appears to play a role in the regulation of progression, invasiveness and angiogenesis of various neoplasms. We analyzed the immunohistochemical expression of Cox‐2 and angiogenic parameters (microvessel density (MVD) and vascular patterns) in 54 glioblastomas. We also examined their relation with prognosis. Cox‐2 immunohistochemical expression was observed in 48 tumors (89%). There was no staining in six tumors (11%). On univariate analysis, MVD was correlated with a poor outcome (MVD > 70; hazard ratio, 0.441; 95% confidence interval, 0.200–0.975, P = 0.041). But MVD showed no prognostic impact on multivariate analysis. Neither Cox‐2 expression nor vascular pattern showed prognostic value. The difference in Cox‐2 expression between the classical and bizarre vascular pattern in glioblastomas was statistically significant (P = 0.047). However, no correlation was found between Cox‐2 expression and MVD. These findings suggest that Cox‐2 is heterogeneously expressed in glioblastomas without a significant association with MVD. However, Cox‐2 expression may be related to vascular pattern in glioblastomas.
Increasing Body Mass Index is Associated With Worse Perioperative Outcomes and Higher Costs in Adult Spinal Deformity Surgery

Study Design. Retrospective review. Objective. To investigate associations of obesity with outcomes and costs of adult spinal deformity (ASD) surgery. Summary of Background Data. Increasing body mass index (BMI) is a risk factor for complications after nondeformity spine surgery, but its effect on ASD surgery is unknown. Methods. We reviewed records of 244 ASD patients who underwent spinal arthrodesis of ≥5 levels from 2010 to 2014 and categorized them by World Health Organization BMI groups: BMI < 30, nonobese (64%); BMI = 30–34.99, class-I obese (21%); and BMI ≥ 35, class-II/III obese (15%). We used multivariate logistical regression to determine odds of transfusion, inpatient complications, prolonged intensive care unit (ICU) stay (>2 days), prolonged total length of hospital stay (LOS) (>1 week), and high episode-of-care costs (>$80,000). Results. Preoperative characteristics were similar among groups, except sex, preoperative hemoglobin concentration, and performance/type of osteotomy (all, P = 0.01). On univariate analysis, the groups differed in rates of prolonged ICU stay (P < 0.001), prolonged total LOS (P = 0.016), and high episode-of-care costs (P = 0.013). Inpatient complication rates were similar among groups (P = 0.218). On multivariate analysis, compared with nonobese patients, class I obese patients had greater odds of prolonged ICU stay (odds ratio [OR] = 2.24, 95% confidence interval [CI]: 1.06, 4.71). Class II/III obese patients also had greater odds of prolonged total LOS (OR = 2.21, 95% CI: 1.03, 4.71), and high episode-of-care costs (OR = 2.91, 95% CI: 1.31, 6.50). Conclusion. In ASD surgery, BMI ≥35 is associated with significantly worse perioperative outcomes and higher costs compared with those of nonobese patients. Level of Evidence: 3
An open study of pamidronate in the treatment of refractory ankylosing spondylitis.

OBJECTIVE Bisphosphonates inhibit the development of delayed type hypersensitivity chronic inflammation and suppress inflammation and cartilage/bone erosion in diverse murine arthritis models. We evaluated antiinflammatory properties of the bisphosphonate pamidronate in patients with ankylosing spondylitis (AS) refractory to nonsteroidal antiinflammatory drugs. METHODS Patients included 14 men and 2 women. The first group of 8 patients (Group 1) received pamidronate as a 30 mg intravenous infusion once a month for 3 months, followed by a 60 mg dose once a month for an additional 3 months. Eight additional patients (Group 2) received only the 60 mg dose once a month for 3 months. Clinical assessments included the BASDAI (Bath AS Disease Activity Index), BASFI (Functional Index), and BASMI (Metrology Index), and laboratory assessments hemoglobin and erythrocyte sedimentation rate (ESR) at baseline and one month after final 60 mg dose of pamidronate. Mean BASDAI score at study entry was 6.7 for both groups. RESULTS A significant improvement was observed in disease activity score in Group 1 after 6 monthly infusions of pamidronate (mean BASDAI 4.21; p = 0.03), in the BASMI score (p = 0.01), and the ESR (p = 0.009). A significant improvement in the BASMI was noted in Group 2 patients (p = 0.007) after 3 monthly infusions of pamidronate, but not in the BASDAI score (mean 5.01; p = 0.07) or the ESR (p = 0.12). CONCLUSION Preliminary data suggest pamidronate may possess antiinflammatory activity in patients with AS, particularly with prolonged administration; this agent deserves further evaluation in a controlled trial.
Vascular System: Role of Nitric Oxide in Cardiovascular Diseases

In contrast with the short research history of the enzymatic synthesis of nitric oxide (NO), the introduction of nitrate‐containing compounds for medicinal purposes marked its 150th anniversary in 1997. Glyceryl trinitrate (nitroglycerin) is the first compound of this category. On October 12, 1998, the Nobel Assembly awarded the Nobel Prize in Medicine or Physiology to scientists Robert Furchgott, Louis Ignarro, and Ferid Murad for their discoveries concerning NO as a signaling molecule in the cardiovascular system. NO‐mediated signaling is a recognized component in various physiologic processes (eg, smooth muscle relaxation, inhibition of platelet and leukocyte aggregation, attenuation of vascular smooth muscle cell proliferation, neurotransmission, and immune defense), to name only a few. NO has also been implicated in the pathology of many inflammatory diseases, including arthritis, myocarditis, colitis, and nephritis and a large number of pathologic conditions such as amyotrophic lateral sclerosis, cancer, diabetes, and neurodegenerative diseases. Some of these processes (eg, smooth muscle relaxation, platelet aggregation, and neurotransmission) require only a brief production of NO at low nanomolar concentrations and are dependent on the recruitment of cyclic guanosine monophosphate (cGMP)‐dependent signaling. Other processes are associated with direct interaction of NO or reactive nitrogen species derived from it with target proteins and requires a more sustained production of NO at higher concentrations but do not involve the cGMP pathway.