tbuckley/cabot-search huggingface dataset:
THU0212 Imbalance between synovial il-1 activity/il-1ra production and disease course in rheumatoid arthritis
Authors: H Fenner, S Zueger, M Schattenkirchner
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To evaluate in a cross-sectional study the relationship between the clinical/radiological disease outcome, the presence or absence of RA-associated HLA-DRB1* alleles and circulating levels of IL-1ra in patients with rheumatoid arthritis. <h3>Methods</h3> 120 patients, stratified in sub-groups defined by disease duration, RF status and HLA-DRB1* typing were analysed for an association between disease course and circulating levels of IL-1ra. HLA-DRB1* allele typing was performed by standard methods, IL-1ra and other cytokines (IL-6, IL-8, sTNFR55/75) were measured using commercially available ELISA reagents. Patient's characteristics assessed included inflammatory disease activity by clinical and standard laboratory measures. Radiographic disease progression was determined by the Steinbrocker method. <h3>Results</h3> There was inverse correlation between circulating IL-1ra levels and radiographic outcome in the patient population with a disease duration &lt; 5 years (Pearson correlation coefficient: – 0.23; p &lt; 0.03). In most of the sub-populations analysed IL-1ra correlated strongly with the levels of IL-6, IL-8, and sTNFR 55/sTNFR75s. In Subgroups of patients defined by HLA-DRB1* typing, patients (n = 30) with clinical and radiographic evidence for a more severe disease course were positive for a double-dose of HLA-DRB1* 0404/0401 or positive for a combination of a HLA-DRB1* 040x allele with the HLA-DRB1* 0101 allele. These patients presented with significantly (p = 0.01) lower IL-1ra levels (mean: 384 pg/ml) than patients (n = 37) bearing none the RA-linked HLA-DRB1* alleles (mean: 1197 pg/ml). IL-1ra levels in healthy controls (n = 22; mean: 337 pg/ml) were comparable with IL-1ra deficient patients bearing a double gene dose. When only one of the suspected HLA-DRB1* alleles was present, IL-1ra levels were in the intermediate range (n = 42; mean: 626 pg/ml). <h3>Conclusion</h3> IL-1ra deficiency appears to predispose patients to a more aggressive disease course of rheumatoid arthritis, whereas in other patients synovial IL-1ra production in response to increased IL-1 activity represents a physiological mechanism to restore the balance between pro-inflammatory and anti-inflammatory activity.
Therapeutic potential of targeting G protein-gated inwardly rectifying potassium (GIRK) channels in the central nervous system
Authors: Danko Jeremic, Irene Sanchez-Rodriguez, Lydia Jimenez-Diaz, Juan D. Navarro-Lopez
Journal: Pharmacology & Therapeutics (2021)

G protein-gated inwardly rectifying potassium channels (Kir3/GirK) are important for maintaining resting membrane potential, cell excitability and inhibitory neurotransmission. Coupled to numerous G protein-coupled receptors (GPCRs), they mediate the effects of many neurotransmitters, neuromodulators and hormones contributing to the general homeostasis and particular synaptic plasticity processes, learning, memory and pain signaling. A growing number of behavioral and genetic studies suggest a critical role for the appropriate functioning of the central nervous system, as well as their involvement in many neurologic and psychiatric conditions, such as neurodegenerative diseases, mood disorders, attention deficit hyperactivity disorder, schizophrenia, epilepsy, alcoholism and drug addiction. Hence, GirK channels emerge as a very promising tool to be targeted in the current scenario where these conditions already are or will become a global public health problem. This review examines recent findings on the physiology, function, dysfunction, and pharmacology of GirK channels in the central nervous system and highlights the relevance of GirK channels as a worthful potential target to improve therapies for related diseases.
Association of Lymphangiogenic Factors With Pulmonary Arterial Hypertension in Systemic Sclerosis
Authors: Henriette Didriksen, Øyvind Molberg, Håvard Fretheim, Einar Gude, Suzana Jordan, Cathrine Brunborg, Vyacheslav Palchevskiy, Torhild Garen, Øyvind Midtvedt, Arne K. Andreassen, Oliver Distler, John Belperio, Anna‐Maria Hoffmann‐Vold
Journal: Arthritis & Rheumatology (2021)

Objective Pulmonary arterial hypertension (PAH) is a major complication in systemic sclerosis (SSc), a disease marked by vascular and lymphatic vessel abnormalities. This study was undertaken to assess the role of the lymphangiogenic factors vascular endothelial growth factor C (VEGF‐C) and angiopoietin 2 (Ang‐2) and the soluble forms of their respective cognate receptors, soluble VEGF receptor 3 (sVEGFR‐3) and soluble TIE‐2, in patients with SSc, and to evaluate their predictive ability as markers for PAH development in SSc. Methods In this cohort study, we used multiplex bead assays to assess serum levels of lymphangiogenic factors in 2 well‐characterized SSc cohorts: an unselected identification cohort of SSc patients from Oslo University Hospital (n = 371), and a PAH‐enriched validation cohort of SSc patients from Zurich University Hospital and Oslo University Hospital (n = 149). As controls for the identification and validation cohorts, we obtained serum samples from 100 healthy individuals and 68 healthy individuals, respectively. Patients in whom SSc‐related PAH was identified by right‐sided heart catheterization (RHC) in both cohorts were studied in prediction analyses. PAH was defined according to the European Society of Cardiology/European Respiratory Society 2015 guidelines for the diagnosis and treatment of PAH. Associations of serum levels of lymphangiogenic factors with the risk of PAH development were assessed in logistic regression and Cox regression analyses. Associations in Cox regression analyses were expressed as the hazard ratio (HR) with 95% confidence interval (95% CI). Results In the identification cohort, SSc patients had lower mean serum levels of VEGF‐C and higher mean serum levels of Ang‐2 compared to healthy controls (for VEGF‐C, mean ± SD 2.1 ± 0.5 ng/ml in patients versus 2.5 ± 0.4 ng/ml in controls; for Ang‐2, mean ± SD 6.1 ± 7.6 ng/ml in patients versus 2.8 ± 1.8 ng/ml in controls; each P &lt; 0.001); these same trends were observed in SSc patients with PAH compared to those without PAH. The association of serum VEGF‐C levels with SSc‐PAH was confirmed in the PAH‐enriched RHC validation cohort. For prediction analyses, we assembled all 251 cases of SSc‐PAH identified by RHC from the identification and validation cohorts. In multivariable Cox regression analyses adjusted for age and sex, the mean serum levels of VEGF‐C and sVEGFR‐3 were predictive of PAH development in patients with SSc (for VEGF‐C, HR 0.53 [95% CI 0.29–0.97], P = 0.04; for sVEGFR‐3, HR 1.21 [95% CI 1.01–1.45], P = 0.042). Conclusion These findings support the notion that lymphangiogenesis is deregulated during PAH development in SSc, and indicate that VEGF‐C could be a promising marker for early PAH detection in patients with SSc.
Globally diverse Mycobacterium tuberculosis resistance acquisition: a retrospective geographical and temporal analysis of whole genome sequences
Authors: Yasha Ektefaie, Avika Dixit, Luca Freschi, Maha R Farhat
Journal: The Lancet Microbe (2021)

Mycobacterium tuberculosis whole genome sequencing (WGS) data can provide insights into temporal and geographical trends in resistance acquisition and inform public health interventions. We aimed to use a large clinical collection of M tuberculosis WGS and resistance phenotype data to study how, when, and where resistance was acquired on a global scale.We did a retrospective analysis of WGS data. We curated a set of clinical M tuberculosis isolates with high-quality sequencing and culture-based drug susceptibility data (spanning four lineages and 52 countries in Africa, Asia, the Americas, and Europe) using public databases and literature curation. For inclusion, sequence quality criteria and country of origin data were required. We constructed geographical and lineage specific M tuberculosis phylogenies and used Bayesian molecular dating with BEAST, version 1.10.4, to infer the most recent common susceptible ancestor age for 4869 instances of resistance to ten drugs.Between Jan 1, 1987, and Sept 12, 2014, of 10 299 M tuberculosis clinical isolates, 8550 were curated, of which 6099 (71%) from 15 countries met criteria for molecular dating. The number of independent resistance acquisition events was lower than the number of resistant isolates across all countries, suggesting ongoing transmission of drug resistance. Ancestral age distributions supported the presence of old resistance, 20 years or more before, in most countries. A consistent order of resistance acquisition was observed globally starting with resistance to isoniazid, but resistance ancestral age varied by country. We found a direct correlation between gross domestic product per capita and resistance age (r2=0·47; p=0·014). Amplification of fluoroquinolone and second-line injectable resistance among multidrug-resistant isolates is estimated to have occurred very recently (median ancestral age 4·7 years [IQR 1·9-9·8] before sample collection). We found the sensitivity of commercial molecular diagnostics for second-line resistance to vary significantly by country (p<0·0003).Our results highlight that both resistance transmission and amplification are contributing to disease burden globally but vary by country. The observation that wealthier nations are more likely to have old resistance (most recent common susceptible ancestor >20 years before isolation) suggests that programmatic improvements can reduce resistance amplification, but that fit resistant strains can circulate for decades subsequently implies the need for continued surveillance.
Author Correction: AgRP neurons control compulsive exercise and survival in an activity-based anorexia model
Authors: Maria Consolata Miletta, Onur Iyilikci, Marya Shanabrough, Matija Šestan-Peša, Allison Cammisa, Caroline J. Zeiss, Marcelo O. Dietrich, Tamas L. Horvath
Journal: Nature Metabolism (2021)
Blood‐Compatible Materials: Vascular Endothelium‐Mimetic Surfaces that Mitigate Multiple Cell‐Material Interactions
Authors: Jessica R. Vlcek, Mohammadhasan Hedayati, Alyssa C. Melvin, Melissa M. Reynolds, Matt J. Kipper
Journal: Advanced Healthcare Materials (2021)

Abstract When flowing whole blood contacts medical device surfaces, the most common blood–material interactions result in coagulation, inflammation, and infection. Many new blood‐contacting biomaterials have been proposed based on strategies that address just one of these common modes of failure. This study proposes to mitigate unfavorable biological reactions that occur with blood‐contacting medical devices by designing multifunctional surfaces, with features optimized to meet multiple performance criteria. These multifunctional surfaces incorporate the release of the small molecule hormone nitric oxide (NO) with surface chemistry and nanotopography that mimic features of the vascular endothelial glycocalyx. These multifunctional surfaces have features that interact with coagulation components, inflammatory cells, and bacterial cells. While a single surface feature alone may not be sufficient to achieve multiple functions, the release of NO from the surfaces along with their modification to mimic the endothelial glycocalyx synergistically improves platelet‐, leukocyte‐, and bacteria‐surface interactions. This work demonstrates that new blood‐compatible materials should be designed with multiple features, to better address the multiple modes of failure of blood‐contacting medical devices.
SETD1A to induce epithelial-mesenchymal transition to promote invasion and metastasis through epigenetic reprogramming of snail in gastric cancer.
Authors: Jugang Wu, Jiwei Yu, Yan Gu
Journal: Journal of Clinical Oncology (2021)

241 Background: Aberrant epigenetic modification induces oncogenes expression and promotes cancer development. The histone lysine methyltransferase SETD1A, which specifically methylates H3K4, is involved in tumor growth and metastasis, and its ectopic expression has been detected in aggressive malignancies. Our previous study had reported that SETD1A promoted gastric cancer (GC) proliferation and tumorigenesis. However, the function and molecular mechanisms of SETD1A in GC metastasis remain to be elucidated. Methods: Transwell migration and invasion assay were performed to determine GC cell migration and invasion. Lung metastasis assay was used to detect GC cell metastasis. Western Blot and Real-time qPCR were performed to measure the protein and mRNA levels, respectively. ChIP assay was performed to investigate the methylation of H3K4. The correlation between SETD1A and EMT associated key genes in GC were performed by bioinformatic analysis. Results: In this study, we found that overexpression of SETD1A promotes GC migration and invasion, whereas knockdown of SETD1A suppressed GC migration, invasion and metastasis. Furthermore, knockdown of SETD1A suppressed GC epithelial-mesenchymal transition (EMT) by increasing the expression of epithelial marker E-cadherin, and decreasing the expression of mesenchymal markers, including N-cadherin, Fibronectin and Vimentin. Mechanistically, knockdown of SETD1A reduced the EMT key transcriptional factors snail. SETD1A was recruited to the promoter of snail, where SETD1A could methylate H3K4. However, knockdown of SETD1A decreased the methylation of H3K4 on snail promoter. Rescue of snail restored SETD1A knockdown-induced GC migration and invasion inhibition. In addition, linear correlation between SETD1A and several key EMT genes, including E-cadherin, Fibronectin and snail, in GC specimens obtained from TCGA dataset. Conclusions: In summary, our data reveals that SETD1A mediated EMT process and induced metastasis through epigenetic reprogramming of snail.
The kinase AKT1 potentiates the suppressive functions of myeloid-derived suppressor cells in inflammation and cancer
Authors: Anna Jia, Yuexin Wang, Yufei Wang, Yan Li, Qiuli Yang, Yejin Cao, Ying He, Lin Dong, Yingjie Dong, Yueru Hou, Ruoning Wang, Yujing Bi, Guangwei Liu
Journal: Cellular and Molecular Immunology (2021)
Intracellular delivery of nuclearlocalization signal suppresses COVID-19 mediatedinflammation by regulating expression ofcytokines/chemokines
Authors: D. Lee, S. Yu, M. Baek, J. Kim, M. Kang, H. Park, J. Lee, S. Lee, J. Kwak, H. Yu, S. Kim, H. Lee, D. Shin, B. Kim, M. Jung, Y. Choi, D. Jo, G. Kim, D. Kim
Journal: Clinical Cancer Research (2020)

The outbreak of coronavirus disease 19 (COVID-19), caused by the recently identified coronavirus named SARS-CoV-2, is leading patients to death (mortality: ∼7%) because of cytokine storm  COVID-19 induces excessivesecretion of proinflammatory cytokines and chemokines accompanied by the disruption of the bronchi and alveoli, which could ultimately develop into permanent lung impairments such as pulmonary fibrosis  To regulate theuncontrolled expression of proinflammatory cytokines/chemokines, improved cell-permeable nuclear import inhibitor(iCP-NI) has been developed by fusing sequence-optimized hydrophobic cell-penetrating peptide (CPP), namelyadvanced macromolecule transduction domain (aMTD) with nuclear localization signal (NLS) of stress responsivetranscription factors (SRTFs: NF-κB, STAT1/3, AP-1, and NFAT)  Intracellularly delivered NLS is supposed tosuppress expression of proinflammatory cytokines/chemokines by inhibiting transport of SRTFs from cytoplasm intonucleus  iCP-NI regulated expression of cytokines (TNF-α: -79%, IL-6: -91%, IL-12: -110% and IL-10: +574%) andchemokines (MCP-1: -89%) in bronchoalveolar lavage fluids (BALFs) from RNA virus infection mimetic pneumonitisanimals that were induced with inhalation of RNA structure molecule, poly I:C  iCP-NI also significantly decreasedpulmonary fibrosis (-61%) in bleomycin-induced pulmonary fibrosis animals  Moreover, iCP-NI protected leukocytes(CD3+ T cell: 100%, CD4+/CD3+ T cell: 96%, B220+ B cell: 85%, CD45+ macrophage: 100%) and reducedapoptotic splenocytes (-97%) in staphylococcal enterotoxin B (SEB) and poly I:C-induced acute pneumonitisanimals  These results suggest that iCP-NI has potential as a novel therapeutic measurement for inflammationcaused by various infectious diseases including COVID-19 accompanied with cytokine storm and severe sepsis
AB0216 Transformation of primary hypertrophic osteoarthropathy into secondary caused by bronchogenic carcionoma
Authors: Z Jajic, I Jajic
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> This paper reports on the two cases of PHO that transformed into SHO under the influence of bronchogenic carcinoma. <h3>Methods</h3> <h3>Results</h3> The patients had not have any sign of PHO activity until the last 3 and 4 months, when a malignant process of the lungs developed and reactivated all symptoms of the disease (joint swelling, moist palms and soles, unpleasant odour of perspiration, deeper folds on the forehead and deeper nasolabial furrow, enlarged fingers, erythema around the nails). Scintigraphy showed increased radioisotopes accumulation in particular regions of the skeleton. <h3>Conclusion</h3> To our knowledge, similar cases have not been described in literature.
Simplified Regimen Expands Options for Dual-Therapy HIV Maintenance
Authors: Anita Slomski
Journal: JAMA (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
OP0106 Epidemiology of hip fracture in age groups of high osteoporosis risk on the ural, russia
Authors: LI Kuzmina, OM Lesnyak
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> The epidemiology of hip fractures in Eastern parts of Russia has not yet been studied. <h3>Objectives</h3> The aim of this retrospective study was to analyse the incidence of hip fracture in subjects over 50. <h3>Methods</h3> The total population of the city is 1,5 million population in the city of Yekaterinburg. The medical records of four city hospitals where patients with hip fractures were admitted as well as from outpatient emergency units were analysed for 1992–1997. The city administration provided statistical data on relevant population number and age distribution. Hip fracture has been defined as a fracture of the femoral neck or intertrochanteric region fracture (ICD IX code 820.0 and 820.2). There were no exclusion criteria other then the hip fracture occurring as a result of major trauma. <h3>Results</h3> In the health care areas studied there were 2 777 hip fractures: 599 males and 2 178 females. The mean age of males was 69,0 ± 11,2 years of age and females – 76,5 ± 9,3 respectively (p &lt; 0,0001). The incidence of hip fracture for the examined period made up 132,3/100 000 population in those over 50 years (76,9/100 000 for males and 164,8/100 000 for females). The ratio of male to females cases was 1:2. The incidence of hip fracture rose exponentially with age in both genders. The occurrence of hip fracture was maximal in subjects over 80 years old and made up 744,1/100 000 (476,9/100 000 males and 818,2/100 000 females). Male/female ratio was 1:1,7. The incidence of hip fracture in our population has not seasonal variation. <h3>Conclusion</h3> More recent data showed significant differences in the incidence of hip fractures between Russian regions. The lowest rate of hip fracture was found in the western part of Russia and the highest in the Ural (Yekaterinburg). There was a large difference in incidence between regions, which suggests important environmental factors in the causation of hip fracture.
Spontaneous or Deliberate: Effects of Acute Variations in Glycemia on Gastric Emptying in Type 1 Diabetes
Authors: Michael Horowitz, Tongzhi Wu, Christopher K. Rayner, Chinmay S. Marathe, Karen L. Jones
Journal: Diabetes Care (2021)

During the last 30 years, there has been a paradigm shift in knowledge relating to gastric emptying in diabetes, reflecting the application of novel investigative techniques. Scintigraphy, which utilizes radiolabeled solid and/or liquid meals and a γ-camera, remains the gold standard for quantifying gastric emptying (1,2). More recently, stable isotope breath tests, involving measurement of 13CO2 in breath samples after ingestion of a 13C-labeled meal, have been validated against scintigraphy with inherent advantages of simplicity, point-of-care sampling, and avoidance of radiation exposure (1). Key insights in diabetes include the recognition that solids and liquids empty from the stomach differentially and that interindividual variation—already substantial in health (1–4 kcal/min) (2)—is increased in diabetes because emptying is delayed in ∼30–40% of complicated, suboptimally controlled patients attending tertiary centers (2–4), while often modestly accelerated in well-controlled patients with type 1 or type 2 diabetes (2). Upper gastrointestinal symptoms, such as nausea and fullness, occur frequently and impact quality of life adversely, but their relationship to gastric emptying is weak (1–3). Rather than simply being a manifestation of autonomic neuropathy, the pathogenesis of gastroparesis is heterogeneous, involving loss of interstitial cells of Cajal (“pacemaker” cells), an immune infiltrate, and muscle atrophy in addition to changes in intrinsic and extrinsic (vagal) innervation (1). There is a relatively weak relationship between gastroparesis and autonomic dysfunction, as assessed by standardized cardiovascular reflexes (3). Finally, and perhaps most importantly, gastric emptying influences postprandial glycemic excursions, the dominant determinant of HbA1c when the latter is less than ∼64 mmol/mol (8.0%) (5), and emptying can be modulated by dietary or pharmacological approaches (e.g., short-acting glucagon-like peptide 1 receptor agonists or pramlintide) for therapeutic gain (2). Accordingly, gastric emptying is central to the pathogenesis and personalized management of diabetes (6). …