tbuckley/cabot-search huggingface dataset:
Beat-to-Beat Variation in QRS Morphology Following Transcatheter Aortic Valve Replacement
Authors: Natee Sirinvaravong, Datun Qi, Gan-Xin Yan
Journal: JAMA Internal Medicine (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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Internal Medicine journal
N-acetyl-l-cysteine protects against lead nitrate-induced oxidative stress and genotoxicity in HepG2 cells
Authors: Clement Yedjou, Paul Tchounwou
Journal: Cancer Research (2007)

1570  Human cells are particularly susceptible to oxidative damage, and it is therefore important to find agents that protect them against this process. N-acetyl-cysteine (NAC) is the acetylated form of L-cysteine. It has an impressive list of protective effects including: antioxidant activity, decrease of the biologically effective dose of carcinogens, anti-inflammatory activity, immunological effects, inhibition of progression to malignancy and metastasis, and protection from the adverse effects of chemopreventive and chemotherapeutic agents. In this research, we hypothesized that the antioxidant, n-acetyl-l-cysteine could attenuateoxidative stress and genotoxicity, and thereby providing cellular protectionto HepG2 cells when exposed to heavy metal such as lead nitrate. To achieve this goal, we performed the thiobarbituric acid test for lipid peroxidation and the microgel electrophoresis (comet) assay for genotoxicity. The results generated from the thiobarbituric acid test showed a significant reduction of lipid peroxidation by-product (malondialdehyde) in HepG2 cells co-exposed to NAC and lead nitrate compared to lead nitrate alone. Incubation of HepG2 cells with increasing concentrations of NAC decreased the amount of MDA formation progressively in lead nitrate-treated HepG2 cells. Data obtained from the comet assay indicated a strong dose-response relationship with regard to lead nitrate-induced genotoxic damage in HepG2 cells. However, the addition of NAC in vitro showed a significant (p   Acknowledgements: This research was financially supported by a grant from the National Institutes of Health (Grant No. 1G12RR13459), through the RCMI-Center for Environmental Health at Jackson State University.
Cartilage Regeneration: Encapsulated Mesenchymal Stromal Cell Microbeads Promote Endogenous Regeneration of Osteoarthritic Cartilage Ex Vivo (Adv. Healthcare Mater. 8/2021)
Authors: Neety Sahu, Pranay Agarwal, Fiorella Grandi, Michela Bruschi, Stuart Goodman, Derek Amanatullah, Nidhi Bhutani
Journal: Advanced Healthcare Materials (2021)

In article number 2002118, Nidhi Bhutani and co-workers employ microencapsulation of mesenchymal stromal cells (MSCs) in alginate hydrogels to sequester MSCs and study their specific paracrine effects in response to patient-derived osteoarthritic (OA) cartilage. The secretome of microencapsulated MSCs, primed to OA cartilage, is able to promote endogenous regeneration in OA cartilage ex vivo by orchestrating a proliferative and anti-apoptotic microenvironment.
AB0567 USING Q-RISK SCALE FOR CHECKING CARDIOVASCULAR RISK IN PATIENTS WITH PSORIATIC ARTHRITIS
Authors: S. Smiyan, A. Bilukha
Journal: Annals of the Rheumatic Diseases (2021)

Background: Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis. In addition to skin and joint involvement, there is a growing evidence suggesting that patients with PsA also have increased risk of clinical and subclinical cardiovascular disease (CVD), mostly due to endothelial dysfunction and accelerated atherosclerosis, which are the main causes of elevated mortality rate among patients with PsA. For prevention and monitoring progression of CVD in clinical practice scale SCORE usually used, but it isn’t adapted for checking in patients with autoimmune diseases and can be used only for patients after forty years old. Objectives: To check a cardiovascular risk in patient with PsA using Q-risk scale. Methods: In total, ninety-four patients with PsA, who fulfilled the disease criteria (CASPAR) were examined using standard diagnostic methods (including C-reactive protein, lipid profile). The QRISK-3 and SCORE scales were used to assess the 10-year risk of CVD. Results: Intermediate (12.4 ± 0,75 %) risk of adverse cardiovascular events within the next 10 years was estimated for PsA patients and it was 7 to 8 – fold higher than the Q - score of a healthy age, sex, and ethnicity – matched subjects. Using classical SCORE, the risk was estimated as low (1,9±0.24 %). Healthy Heart Age was about 25 % higher than predicted as assessed by QRISK. Conclusion: The Q-risk Scale considers not only classical of such risk factors as age, sex, smoking, systolic blood pressure, total cholesterol (which used SCORE) but also index of atherogenity, BMI, family history of coronary artery disease, treatment with antihypertensive drugs and glucocorticosteroids, comorbidity, systemic inflammatory disease and can be used for different age groups and ethnicity. Q-risk scale appears to be adaptive and informative in patients with chronic inflammatory and autoimmune diseases as compared with SCORE, because it uses mostly all important etiological and trigger factors of CVD especially presence autoimmune inflammatory process in our case. References: [1]Abrar Ahmed Wagan. Cardiovascular risk score in Rheumatoid Arthritis. Pak J Med Sci, Vol. 32, Issue 3, 2016, P.534-538; [2]Frank Verhoeven, Clément Prati. Cardiovascular risk in psoriatic arthritis, a narrative review. Joint Bone Spine, Vol. 87, Issue 5, 2020, P.413-418; [3]Julia Hippisley-Cox, Carol Coupland. Development and validation of QRISK3 risk prediction algorithms to estimate future risk of cardiovascular disease: prospective cohort study. BMJ, Vol. 23, 2017, P.357; [4]Naveen Garg, Subrat K. Muduli. Comparison of different cardiovascular risk score calculators for cardiovascular risk prediction and guideline recommended statin uses. Indian Heart J, Vol. 69, Issue 4, 2017, P.458-463; Disclosure of Interests: None declared.
Antibody response after one and two jabs of the BNT162b2 vaccine in nursing home residents: The CONsort‐19 study
Authors: Hubert Blain, Edouard Tuaillon, Lucie Gamon, Amandine Pisoni, Stéphanie Miot, Yves Rolland, Marie‐Christine Picot, Jean Bousquet
Journal: Allergy (2021)

The humoral immune response following COVID-19 vaccination in nursing home residents is poorly known. A longitudinal study compared levels of IgG antibodies against the spike protein (S-RBD IgG) (S-RDB protein IgG) after one and two BNT162b2/Pfizer jabs in residents with and without prior COVID-19.In 22 French nursing homes, COVID-19 was diagnosed with real-time reverse-transcriptase polymerase chain reaction (RT-PCR) for SARS-CoV-2. Blood S-RDB-protein IgG and nucleocapsid (N) IgG protein (N-protein IgG) were measured 21-24 days after the first jab (1,004 residents) and 6 weeks after the second (820 residents).In 735 residents without prior COVID-19, 41.7% remained seronegative for S-RDB-protein IgG after the first jab vs. 2.1% of the 270 RT-PCR-positive residents (p < 0.001). After the second jab, 3% of the 586 residents without prior COVID-19 remained seronegative. However, 26.5% had low S-RDB-protein IgG levels (50-1050 UA/ml) vs. 6.4% of the 222 residents with prior COVID-19. Residents with an older infection (first wave), or with N-protein IgG at the time of vaccination, had the highest S-RDB-protein IgG levels. Residents with a prior COVID-19 infection had higher S-RDB-protein IgG levels after one jab than those without after two jabs.A single vaccine jab is sufficient to reach a high humoral immune response in residents with prior COVID-19. Most residents without prior COVID-19 are seropositive for S-RDB-protein IgG after the second jab, but around 30% have low levels. Whether residents with no or low post-vaccine S-RDB protein IgG are at higher risk of symptomatic COVID-19 requires further analysis.
An ex vivo lung organ culture assay to study pulmonary metastases
Authors: Mohammed Khan, Arnulfo Mendoza, Sung-Hyeok Hong, Ling Ren, Kent Hunter, Lalage Wakefield, Chand Khanna
Journal: Cancer Research (2008)

394  Pulmonary metastasis remains a significant problem for many cancer patients. To improve our understanding of metastasis biology and evaluate new therapies, we sought to develop an ex vivo lung culture assay amenable for the study of metastasis in a microenvironment that mimics in vivo conditions. Such an assay would serve as a needed intermediary between currently available in vitro and in vivo metastasis assays and allow the study of metastasis as both an active process (verb) as well as a physical entity (noun). Distinct mice were injected intravenously with fluorescently labeled tumor cells. The mice were then euthanized, and the lungs extracted, fixed in agar, and sectioned for culture in supplemented serum-free conditions resting on sterile gel-foam at an air-culture interface. Sections were imaged at day 0, 7, 14, and 28 using an inverted fluorescent video-microscope, and software was used to determine the number and size of cellular events. Routine histology of sections showed maintenance of the lung architecture, though at reduced cellularity. Fluorescent imaging at day 0 revealed single tumor cells within the lung parenchyma. Most single tumor cells disappeared over the 28 day observation, while occasional cells proliferated into distinct metastatic clusters. Comparison of high versus low metastatic cell line variants (Parent cell lines: HOS, human osteosarcoma; K7M2, murine osteosarcoma; 4T07, murine breast cancer) suggested the ability of the lung culture assay to predict metastatic phenotype observed in vivo. Interestingly conventional in vitro culture was not able to yield or identify metastatic versus non-metastatic cells. These preliminary studies support the lung culture assay as tool for the study of metastatic phenotype, and potentially to evaluate therapeutic strategies directed against metastases and metastatic progression.
Hydroxyapatite reinforced inorganic-organic hybrid nanocomposite as high-performance adsorbents for bilirubin removal in vitro and in pig models
Authors: Yamin Chai, Zhuang Liu, Yunzheng Du, Lichun Wang, Jinyan Lu, Qian Zhang, Wenyan Han, Tingting Wang, Yameng Yu, Lisha Sun, Lailiang Ou
Journal: Bioactive Materials (2021)

Highly efficient removal of bilirubin from whole blood directly by hemoperfusion for liver failure therapy remains a challenge in the clinical field due to the low adsorption capacity, poor mechanical strength and low biocompatibility of adsorbents. In this work, a new class of nanocomposite adsorbents was constructed through an inorganic-organic co-crosslinked nanocomposite network between vinyltriethoxysilane (VTES)-functionalized hydroxyapatite nanoparticles (V-Hap) and non-ionic styrene-divinylbenzene (PS-DVB) resins (PS-DVB/V-Hap) using suspension polymerization. Notably, our adsorbent demonstrated substantially improved mechanical performance compared to the pure polymer, with the hardness and modulus increasing by nearly 3 and 2.5 times, respectively. Moreover, due to the development of a mesoporous structure, the prepared PS-DVB/V-Hap3 exhibited an ideal adsorption capacity of 40.27 mg g−1. More importantly, the obtained adsorbent beads showed outstanding blood compatibility and biocompatibility. Furthermore, in vivo extracorporeal hemoperfusion verified the efficacy and biosafety of the adsorbent for directly removing bilirubin from whole blood in pig models, and this material could potentially prevent liver damage and improve clinical outcomes. Taken together, the results suggest that PS-DVB/V-Hap3 beads can be used in commercial adsorption columns to threat hyperbilirubinemia patients through hemoperfusion, thus replacing the existing techniques where plasma separation is initially required.
AB0245 ANALYSIS OF THE CLINICAL AND ANTIDESTRUCTIVE EFFECTS OF RITUXIMAB DEPENDING ON GENDER IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: A. Kudryavtseva, G. Lukina, E. Aronova, G. Gridneva, S. Glukhova, A. Smirnov
Journal: Annals of the Rheumatic Diseases (2021)

Background: Rheumatoid arthritis is a chronic autoimmune disease characterized by inflammation of the synovial tissue and destruction of the underlying cartilage and bones. It was found that RA more often affects women than men, with a sex ratio of 3: 1. And the question of the influence of gender on the outcomes and course of RA remains controversial, there is no consensus on whether RA is worse in women or men. Recent reports indicate that women are less likely to achieve remission than men. Women suffer from RA at an earlier age and have higher markers of disease activity such as DAS28 and HAQ. Rituximab is a chimeric monoclonal antibody that targets the CD20 molecule expressed on the surface of B cells, it has been successfully and widely used for the treatment of rheumatoid arthritis, so it is of interest to assess whether gender influences the therapeutic and radiological effects of RTX. Objectives: The aim of this study was to analyze the impact of gender on the response to rituximab (RTX) in patients with RA. Methods: Initially, 221 women(w), 27 men(m), were examined to assess the clinical and X-ray effect (88w/6m), who received RTX treatment (1000 mgx2 or 500 mgx2). Both groups were comparable in terms of the main clinical and laboratory characteristics (age, duration of the disease, the number of preceding DMARDs, in both groups most patients were RF + and ACCP +, a high degree of activity according to DAS 8 - men - 5.6 [4.6-6.7], women - 6.04 [5.2-6.63] Initially, the degree of radiological changes in men is slightly higher than in women (p&gt; 0.05). Clinical effect was scored by EULAR criteria, radiographic progression was assessed using Sharp/van der Heijde modified scoring method. Results: When assessing the clinical effect after 48 weeks in men, a significantly better effect of RTX treatment was noted in comparison with women (Δ DAS28, a significantly better effect was noted in men - Δ DAS28 =3.75[2.8-4.14], and Δ DAS28=1.3[0.37-2.72] in women, (p=0.04). Analyzing the X-ray effect after 48 weeks of RTM treatment: the absence of progression in terms of the total score in 83.33% of men and 60.98% of women; there was no progression in narrowing of the joint space in 83.33% of men and 65.85% of women, noteworthy that the account of erosion practically reaches statistical significance - inhibition of destruction in 100% of men and 74.31% of women (p = 0.06). Conclusion: Thus, having analyzed the clinical and antidestructive effects of RTM therapy depending on gender, we can conclude that the effect is significantly higher in the male group. Also, there is a tendency towards more effective inhibition of radiographic progression in men. Disclosure of Interests: None declared
Ligand-based substituent-anchoring design of selective receptor-interacting protein kinase 1 necroptosis inhibitors for ulcerative colitis therapy
Authors: Jing Zhu, Meng Xin, Congcong Xu, Yuan He, Wannian Zhang, Zhibin Wang, Chunlin Zhuang
Journal: Acta Pharmaceutica Sinica B (2021)

Receptor-interacting protein (RIP) kinase 1 is involved in immune-mediated inflammatory diseases including ulcerative colitis (UC) by regulating necroptosis and inflammation. Our group previously identified TAK-632 (5) as an effective necroptosis inhibitor by dual-targeting RIP1 and RIP3. In this study, using ligand-based substituent-anchoring design strategy, we focused on the benzothiazole ring to obtain a series of TAK-632 analogues showing significantly improving on the anti-necroptosis activity and RIP1 selectivity over RIP3. Among them, a conformational constrained fluorine-substituted derivative (25) exhibited 333-fold selectivity for RIP1 (Kd = 15 nmol/L) than RIP3 (Kd > 5000 nmol/L). This compound showed highly potent activity against cell necroptosis (EC50 = 8 nmol/L) and systemic inflammatory response syndrome (SIRS) induced by TNF-α in vivo. Especially, it was able to exhibit remarkable anti-inflammatory treatment efficacy in a DSS-induced mouse model of UC. Taken together, the highly potent, selective, orally active anti-necroptosis inhibitor represents promising candidate for clinical treatment of UC.
Excess Death Estimates in Patients with End-Stage Renal Disease — United States, February–August 2020
Authors: Robert Ziemba, Kyle N. Campbell, Tsu-Hsuan Yang, Sara Eve Schaeffer, Kelly M. Mayo, Paul McGann, Shalon Quinn, Jesse Roach, Edwin D. Huff
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

Based on the national trend in ESRD deaths during the first 7 months of the U.S. COVID-19 pandemic (FebruaryâAugust 2020), an estimated 8.7â12.9 excess deaths per 1,000 patients or 6,953â10,316 excess deaths in a population of 798,611 U.S. ESRD patients occurred.
POS0005 THE EFFECT OF LKB1 INHIBITION IN RA PATHOGENESIS
Authors: H. R. Lee, J. Kim, S. J. Yoo, J. A. Park, S. W. Kang
Journal: Annals of the Rheumatic Diseases (2021)

Background: Liver kinase B1 (LKB1) is known as a tumor suppressor gene and also inhibits reactive oxygen species (ROS) levels. Intracellular ROS are catalyzed by the enzyme complex nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX). We previously reported that NOX4 induced the migration and invasion of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA). Although LKB1 is expected to alleviate synovial inflammation through ROS regulation, the role of LKB1 in RA has not been examined. Objectives: To explore whether LKB1 affects RA inflammation, we transfected LKB1 siRNA and analyzed related gene expressions in RA FLS. Methods: Synovial tissues were obtained from RA patients who were undergoing synovectomy or joint replacement. The isolated cells were cultured in Dulbecco’s modified Eagle’s medium (DMEM) supplemented with 10% fetal bovine serum, 100 U/ml penicillin and 100 mg/ml streptomycin and maintained in a 5% CO 2 incubator at 37 °C. FLS were used for experiments after four to six passages. Cells were transfected with lipofectamine transfection reagent and LKB1 siRNA duplex targeting constructs. After incubation for 24 h, downregulation of target expression was evaluated by real-time PCR and western blot analysis. Results: RA FLS was transfected with LKB1 siRNA and 90% of LKB1 mRNA expression was decreased. LKB1 knock-down also caused the decreased expression of mechanistic target of rapamycin (mTOR; 0.38 fold) and serine/threonine kinase (AKT) 2 (0.40 fold), which are downstream targets of LKB1. NOX4 was significantly increased (4.94 fold) by LKB1 inhibition. On the other side, the down regulated NOX4 induced significantly elevated LKB1 mRNA expression in RA FLS. When the expressions of proinflammatory cytokines were examined, IL-1β, IL-6, TNF-α were highly increased by LKB1 deficiency. FLS migration-related chemokines, IL-8 and MMP-3 were also enhanced compared to control. Conclusion: There was a negative correlation between NOX4 and LKB1 in RA FLS. As LKB1 deficiency induced the expression of proinflammatory cytokines and migration related chemokines, LKB1 could play a critical role in RA pathogenesis. References: [1]Bartok B, Firestein GS. Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis. Immunol Rev. 2010;233(1):233–55. [2]Mateen S, Moin S, Khan AQ, Zafar A, Fatima N. Increased reactive oxygen species formation and oxidative stress in rheumatoid arthritis. PLoS One. 2016;11(4):e0152925. Disclosure of Interests: None declared.
AB0010 ASSOCIATION OF SAA1 GENE POLYMORPHISM -13T/C (RS12218) WITH ANKYLOSING SPONDYLITIS IN RUSSIAN POPULATION
Authors: I. Guseva, K. Sakharova, M. Krylov, E. Samarkina, S. Erdes
Journal: Annals of the Rheumatic Diseases (2021)

Background: Ankylosing spondylitis is a chronic systemic inflammatory disease. Inflammation and high levels of serum amyloid A (SAA) protein are predisposing factors for secondary AA amyloidosis. The role of SAA1 gene polymorphisms in AS is not well understood. Objectives: To investigate the association of SAA1 gene polymorphism -13T/C (rs12218) with ankylosing spondylitis and to evaluate the influence of this polymorphism on SAA protein concentration. Methods: 123 AS patients (72 males, 51 females; age - M (SD) 37.51 (12.77) years; disease duration - 14.28 (11.22) years; BASDAI – 5.59 (1.13); B27-positive - 111 (90.2%) pts) and 95 gender, age matched healthy individuals (control group) were included in this study. SAA1 gene polymorphism -13T/C was genotyped using allele-specific RT-PCR assay. SAA protein concentration was measured using nephelometry in AS patients. Results: The distribution of genotypes TT, TC and CC differed statistically between AS and control groups (24.4%, 56.1%, 19.5% and 41.1%, 44.2%, 14.7% respectively, χ 2 =6.9, p=0.03). The presence of the C allele was associated with the development of AS (OR=1.55 [CI 1.04-2.33], p=0.03). The SAA1 -13T/C polymorphism tended to be associated with SAA protein value in AS patients: TT+TC genotypes -13.8 mg/l [4.2; 91.0], CC genotype -7.8 mg/l [1.6; 29.6], p=0.07. ESR, CRP and BASDAI values did not correlated with SAA1 - 13T/C polymorphism (p=0.6, p=0.4, p=0.4 respectively). Conclusion: The results of our study demonstrated for the first time that SAA1 gene polymorphism -13T/C (rs12218) is associated with susceptibility to AS. It is also shown that this polymorphism can affect the SAA protein level. Our findings need to be verified in AS patients with high levels of SAA protein in various ethnic and population groups. Disclosure of Interests: None declared
Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) activity is required for V(D)J recombination
Authors: Chun-Chin Chen, Bo-Ruei Chen, Yinan Wang, Philip Curman, Helen A. Beilinson, Ryan M. Brecht, Catherine C. Liu, Ryan J. Farrell, Jaime de Juan-Sanz, Louis-Marie Charbonnier, Shingo Kajimura, Timothy A. Ryan, David G. Schatz, Talal A. Chatila, Jakob D. Wikstrom, Jessica K. Tyler, Barry P. Sleckman
Journal: The Journal of Experimental Medicine (2021)

A whole-genome CRISPR/Cas9 screen identified ATP2A2, the gene encoding the Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) 2 protein, as being important for V(D)J recombination. SERCAs are ER transmembrane proteins that pump Ca2+ from the cytosol into the ER lumen to maintain the ER Ca2+ reservoir and regulate cytosolic Ca2+-dependent processes. In preB cells, loss of SERCA2 leads to reduced V(D)J recombination kinetics due to diminished RAG-mediated DNA cleavage. SERCA2 deficiency in B cells leads to increased expression of SERCA3, and combined loss of SERCA2 and SERCA3 results in decreased ER Ca2+ levels, increased cytosolic Ca2+ levels, reduction in RAG1 and RAG2 gene expression, and a profound block in V(D)J recombination. Mice with B cells deficient in SERCA2 and humans with Darier disease, caused by heterozygous ATP2A2 mutations, have reduced numbers of mature B cells. We conclude that SERCA proteins modulate intracellular Ca2+ levels to regulate RAG1 and RAG2 gene expression and V(D)J recombination and that defects in SERCA functions cause lymphopenia.