tbuckley/cabot-search huggingface dataset:
POS0384 A NOVEL MECHANISM LINKING MUCOSAL BACTERIA WITH AUTOANTIBODY RESPONSES IN RA: ACETYLATED BACTERIAL LYSATE AS A MODEL ANTIGEN
Authors: M. Volkov, A. S. B. Kampstra, K. van Schie, J. Kwekkeboom, T. Huizinga, R. Toes, D. van der Woude
Journal: Annals of the Rheumatic Diseases (2021)

Background: Rheumatoid arthritis (RA) is characterized by autoantibodies against post-translationally modified proteins (AMPA) such as citrullinated, carbamylated and acetylated proteins. Importantly, these antibodies are highly multireactive, as they often recognize more than one of these post-translational modifications. Despite extensive research, the antigens inducing the breach of tolerance remain unknown, although microbial antigens are often suspected. Various bacteria are known to be capable of acetylation, therefore, it is intriguing to know what mechanisms can underlie the breach of tolerance towards acetylated proteins and development of anti-acetylated protein antibodies (AAPA). Objectives: To investigate whether acetylated proteins of bacterial origin (1) are recognized by human derived AMPA and AMPA expressing B cells; and (2) can induce AMPA development when used to immunize mice. Methods: Acetylated E. coli proteins were acquired with two separate methods (Figure 1A): by culturing E. coli in a condition promoting auto-acetylation (intrinsically acetylated bacterial proteins, IABP), or by directly acetylating lysate-derived proteins via a chemical reaction (extrinsically acetylated BP, EABP). Acetylated ovalbumin (AcOVA) served as positive control for AAPA induction in mice, non-acetylated BP (NABP) and phosphate buffer saline (PBS) served as negative control. Mice were immunized with these proteins and the resulting antibody response was studied by ELISA. Furthermore, EABP/IABP/NABP were investigated for recognition by human-derived AAPA with ELISA and AAPA-expressing B cells with spleen tyrosine kinase (Syk) phosphorylation assay; acetylated human fibrinogen and native fibrinogen served as positive and negative control. Results: Repetitive immunization of mice with EABP resulted in an AMPA response recognizing acetylated, carbamylated and citrullinated proteins. AMPA titers in these mice exceeded the titers in the positive control mice immunized with AcOVA and were substantially higher than in the NABP-immunized mice (Figure 1B). Human-derived monoclonal AAPA recognized EABP and IABP (not shown). B cell activation (measured by Syk phosphorylation) assay indicated that AAPA expressing B cells recognized EABP and (to a lesser extent) IABP, but not NABP (Figure 1C). Conclusion: Acetylated bacterial proteins are potent antigens that can induce cross-reactive AMPA responses in mice and they are recognized by human AAPA. This suggests that acetylated bacterial proteins could possibly be involved in the breach of tolerance in RA. Acknowledgements: We thank Dr. Can Araman and Prof. Chunaram Choudhary for their advice regarding optimization of bacterial auto-acetylation. Disclosure of Interests: None declared
Shear-stress sensing by PIEZO1 regulates tendon stiffness in rodents and influences jumping performance in humans
Authors: Fabian S. Passini, Patrick K. Jaeger, Aiman S. Saab, Shawn Hanlon, Nicole A. Chittim, Matthias J. Arlt, Kim David Ferrari, Dominik Haenni, Sebastiano Caprara, Maja Bollhalder, Barbara Niederöst, Aron N. Horvath, Tobias Götschi, Shang Ma, Bettina Passini-Tall, Sandro F. Fucentese, Ulrich Blache, Unai Silván, Bruno Weber, Karin Grävare Silbernagel, Jess G. Snedeker
Journal: Nature Biomedical Engineering (2021)
Multifunctional nanorods based on self-assembly of biomimetic apolipoprotein E peptide for the treatment of Alzheimer's disease
Authors: Shanshan Zhang, Sajid Asghar, Chenqi Zhu, Junxiu Ye, Ling Lin, Liu Xu, Ziyi Hu, Zhipeng Chen, Feng Shao, Yanyu Xiao
Journal: Journal of Controlled Release (2021)
An ex vivo physiologic and hyperplastic vessel culture model to study intra-arterial stent therapies
Authors: Juan Wang, Mehmet H. Kural, Jonathan Wu, Katherine L. Leiby, Vinayak Mishra, Taras Lysyy, Guangxin Li, Jiesi Luo, Allison Greaney, George Tellides, Yibing Qyang, Nan Huang, Laura E. Niklason
Journal: Biomaterials (2021)
A New Wound-Based Severity Score for Diabetic Foot Ulcers
Authors: Stefan Beckert, Maria Witte, Corinna Wicke, Alfred Königsrainer, Stephan Coerper
Journal: Diabetes Care (2006)

OBJECTIVE—Several well-accepted classification systems are available for diabetic foot ulcers. However, there are only a few and scientifically not validated severity scores. The aim of this study was to establish a new wound-based clinical scoring system for diabetic foot ulcers suitable for daily clinical practice anticipating chances for healing and risk of amputation. RESEARCH DESIGN AND METHODS—Four clinically defined parameters, namely palpable pedal pulses, probing to bone, ulcer location, and presence of multiple ulcerations, were prospectively assessed in 1,000 consecutive patients. In the next step, a new diabetic ulcer severity score (DUSS) was created from these parameters. Palpable pedal pulses were categorized by the absence (scored as 1) or presence (scored as 0) of pedal pulses, while probing to bone was defined as yes (scored as 1) or no (scored as 0). The site of ulceration was defined as toe (scored as 0) or foot (scored as 1) ulcer. Patients with multiple ulcerations were graded as 1 compared with those with single ulcers (scored as 0). The DUSS was calculated by adding these separate gradings to a theoretical maximum of 4. Wounds were followed-up for 365 days or until healing or amputation if earlier. Probability of healing and risk of amputation were calculated by the Kaplan-Meier method. RESULTS—Uni- and multivariate analyses showed a significantly higher probability of healing for patients with palpable pulses, no probing to bone, toe ulcers, and absence of multiple ulcerations. When patients were divided into subgroups with the same DUSS, we found significantly different probabilities for healing. We showed a decreasing probability of healing for ulcers with a high DUSS, concurrent with increasing amputation rates. An increase in the DUSS by one score point reduced the chance for healing by 35%. Similarly, the higher the ulcer score, the larger the initial wound area, the longer the wound history, and the more likely the need for surgery or hospitalization. CONCLUSIONS—The DUSS categorizes different ulcers into subgroups with specific severity and similar clinical outcome. Using this score, the probabilities for healing, amputation, need for surgery, and hospitalization are predictable with high accuracy. This might be useful for the anticipation of health care costs and for comparison of subgroups of patients in clinical studies.
OP0088 A COHORT STUDY ON THE BIDIRECTIONAL RELATIONSHIP BETWEEN FIBROMYALGIA AND PERIODONTITIS OVER A 15-YEAR FOLLOW-UP
Authors: K. S. K. MA, T. Van Dyke
Journal: Annals of the Rheumatic Diseases (2021)

Background: Fibromyalgia has been proposed to be driven by chronic inflammation and infections that are associated with early rheumatoid arthritis and inflammatory arthritis. Other than the central sensitization model, our knowledge of fibromyalgia pathogenesis has been expanded with an inflammation-dependent theory, which is stimulated by prolonged spinal cord hyperexcitability. Objectives: To determine the relationship between periodontitis and fibromyalgia. Methods: In this cohort study, 196,428 periodontitis patients and 196,428 propensity score-matched non-periodontitis controls were enrolled. A Cox proportional hazard model was utilized to estimate the risk of fibromyalgia and survival analysis was adopted to assess the time-dependent effect of periodontitis on fibromyalgia. Subgroup analyses stratified by age, gender, and follow-up years were conducted to identify susceptible populations. A symmetrical cohort was designed to ascertain the relationship between fibromyalgia and the risk of periodontitis. Results: Patients with history of periodontitis were more likely to develop fibromyalgia than non-periodontitis controls (HR =1.42, 95% CI =1.39–1.44, P &lt; 0.001), which persisted in the survival analysis (log-rank test P &lt; 0.0001). This effect was significant in both genders and all age subgroups, and was particularly evident in males (HR=1.52, 95% CI = 1.48–1.56, P &lt; 0.001) and younger periodontitis patients (HR= 1.55, 95% CI =1.50-1.60, P &lt; 0.001). Fibromyalgia patients who never had periodontitis presented with higher risk for periodontitis over time (HR = 1.43, 95% CI = 1.40 - 1.45, P &lt; 0.001). Conclusion: This is the first longitudinal study that addresses the bidirectional relationship between fibromyalgia and periodontitis, in which periodontitis may serve as a risk factor or early sign of fibromyalgia. Based on the observed relationship between fibromyalgia and periodontitis, regular follow-ups and patient education are recommended for patients with either disease. Disclosure of Interests: None declared
Effects of Diet and Sodium Reduction on Cardiac Injury, Strain, and Inflammation
Authors: Stephen P. Juraschek, Lara C. Kovell, Lawrence J. Appel, Edgar R. Miller, Frank M. Sacks, Alex R. Chang, Robert H. Christenson, Heather Rebuck, Kenneth J. Mukamal
Journal: Journal of the American College of Cardiology (2021)
Comparing the cost-effectiveness of two screening strategies for latent tuberculosis infection in Portugal
Authors: Sofia Sousa, Diogo Rocha, Joelma C. Silva, Ana Isabel Ribeiro, Guilherme Gonçalves, Álvaro Almeida, Ana Maria Correia, Raquel Duarte, Carlos Carvalho
Journal: Pulmonology (2021)

Screening for latent tuberculosis infection (LTBI) in close contacts of infectious TB cases might include Tuberculin Skin Test (TST) and Interferon-Gamma Release Assays (IGRA), in combination or as single-tests. In Portugal, the screening strategy changed from TST followed by IGRA to IGRA-only testing in 2016. Our objective was to compare the cost-effectiveness of two-step TST/IGRA with the current IGRA-only screening strategy in immunocompetent individuals exposed to individuals with respiratory TB.We reviewed clinical records of individuals exposed to infectious TB cases diagnosed in 2015 and 2016, in two TB outpatient centers in the district of Porto. We estimated medical, non-medical and indirect costs for each screening strategy, taking into account costs of tests and health care personnel, travel distance from place of residence to screening site and employment status. We calculated the incremental cost-effectiveness ratio (ICER) as the cost difference between the two screening strategies with the difference number of LTBI diagnosis as a measure of cost-effectiveness, assuming that treating LTBI is a cost-effective intervention. We also calculated adjusted odds-ratios to test the association between diagnosis of LTBI and screening strategy and estimated the total cost for averting a potential TB case.We compared 499 contacts TST/IGRA screened with 547 IGRA-only. IGRA-only strategy yielded a higher screening effectiveness for diagnosing latent tuberculosis infection (aOR 2.12, 95%CI: 1.53 - 2.94). ICER was €106 per LTBI diagnosis, representing increased effectiveness with a slightly increased cost of IGRA-only screening strategy.Our data suggests that in Portugal LTBI screening with IGRA-only is more cost-effective than the two-step TST/IGRA testing strategy, preventing a higher number of cases of TB cases.
Gut Akkermansia muciniphila ameliorates metabolic dysfunction-associated fatty liver disease by regulating the metabolism of L-aspartate via gut-liver axis
Authors: Yong Rao, Zhiqi Kuang, Chan Li, Shiyao Guo, Yaohao Xu, Dandan Zhao, Yutao Hu, Bingbing Song, Zhi Jiang, Zhenhuang Ge, Xiyuan Liu, Chengdao Li, Shuobin Chen, Jiming Ye, Zhishu Huang, Yongjun Lu
Journal: Gut Microbes (2021)

The gut bacterium
Diagnosing muscle disease in a cohort of classic dermatomyositis patients seen at a rheumatologic dermatology outpatient clinic
Authors: Sarah Ahmed, Josef Symon Salgado Concha, Srita Chakka, Rebecca Louise Krain, Danielle Zamalin, Galen Foulke, Victoria P. Werth
Journal: Journal of the American Academy of Dermatology (2021)
Nontuberculous mycobacterial pulmonary disease and associated risk factors in China: A prospective surveillance study
Authors: Yaoju Tan, Yunfeng Deng, Xiaofeng Yan, Fangchao Liu, Yunhong Tan, Quan Wang, Xundi Bao, Jianhua Pan, Xiaolu Luo, Yanhong Yu, Xiaoli Cui, Guangfu Liao, Chunmei Ke, Ping Xu, Xiaofei Li, Chunlei Zhang, Xiangyang Yao, Ye Xu, Tongxin Li, Biyi Su, Zhenhua Chen, Ruiying Ma, Yue Jiang, Xiaohua Ma, Dewu Bi, Jinghong Ma, Han Yang, Xuezheng Li, Liusheng Tang, Yongmin Yu, Yufeng Wang, Huafeng Song, Hongwei Liu, Meiling Wu, Yinghui Yang, Zhongtan Xue, Liang Li, Qingge Li, Yu Pang
Journal: Journal of Infection (2021)
Impacts of allopolyploidization and structural variation on intraspecific diversification in Brassica rapa
Authors: Xu Cai, Lichun Chang, Tingting Zhang, Haixu Chen, Lei Zhang, Runmao Lin, Jianli Liang, Jian Wu, Michael Freeling, Xiaowu Wang
Journal: Genome biology (2021)

Despite the prevalence and recurrence of polyploidization in the speciation of flowering plants, its impacts on crop intraspecific genome diversification are largely unknown. Brassica rapa is a mesopolyploid species that is domesticated into many subspecies with distinctive morphotypes.Herein, we report the consequences of the whole-genome triplication (WGT) on intraspecific diversification using a pan-genome analysis of 16 de novo assembled and two reported genomes. Among the genes that derive from WGT, 13.42% of polyploidy-derived genes accumulate more transposable elements and non-synonymous mutations than other genes during individual genome evolution. We denote such genes as being "flexible." We construct the Brassica rapa ancestral genome and observe the continuing influence of the dominant subgenome on intraspecific diversification in B. rapa. The gene flexibility is biased to the more fractionated subgenomes (MFs), in contrast to the more intact gene content of the dominant LF (least fractionated) subgenome. Furthermore, polyploidy-derived flexible syntenic genes are implicated in the response to stimulus and the phytohormone auxin; this may reflect adaptation to the environment. Using an integrated graph-based genome, we investigate the structural variation (SV) landscapes in 524 B. rapa genomes. We observe that SVs track morphotype domestication. Four out of 266 candidate genes for Chinese cabbage domestication are speculated to be involved in the leafy head formation.This pan-genome uncovers the possible contributions of allopolyploidization on intraspecific diversification and the possible and underexplored role of SVs in favorable trait domestication. Collectively, our work serves as a rich resource for genome-based B. rapa improvement.
Improving adherence to asthma medications: same-old, same-old?
Authors: Mark Weatherall
Journal: European Respiratory Journal (2021)

The paper by Moore et al. [1] in this issue of the European Respiratory Journal reports on the effect of various forms of feedback on actual use of asthma medications in research participants with moderate asthma. The primary outcome for the trial was actual adherence, assessed as the proportion (reported as a percentage) of doses taken compared to doses prescribed, after both a run-in period and 3 months of the trial, during the second 3-month period of the trial. Other secondary outcome variables included the Asthma Control Test (ACT) and peak expiratory flow rate (PEFR). The number of participants with a severe exacerbation was also recorded. Electronic adherence interventions improve adherence but may still not improve asthma outcomes <https://bit.ly/3ofGi2H>
Nonrandomized Comparison of Adverse Events Following Facility- and Home-Infused Biologics Using Real-World Data
Authors: Gregory S. Calip, Prakirthi Yerram, Mustafa S. Ascha
Journal: JAMA Network Open (2021)

Matthew C. Baker, MD, MS; Yingjie Weng, MHS; Robert Fairchild, MD, PhD; Neera Ahuja, MD; Nidhi Rohatgi, MD, MS
Comparison of Emergency Medical Dispatch Systems for Performance of Telecommunicator-Assisted Cardiopulmonary Resuscitation Among 9-1-1 Callers With Limited English Proficiency
Authors: Stephen Sanko, Siyu Feng, Christianne Lane, Marc Eckstein
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Increasing bystander cardiopulmonary resuscitation (CPR) among racial/ethnic minority groups and culturally underserved populations is a key strategy in improving health care disparities in out-of-hospital cardiac arrest. <h3>Objective</h3> To ascertain whether implementation of the Los Angeles Tiered Dispatch System (LA-TDS) was associated with improved performance of telecommunicator-assisted CPR (T-CPR) among 9-1-1 callers with limited English proficiency in the City of Los Angeles. <h3>Design, Setting, and Participants</h3> This cohort study compared emergency medical services–treated, nontraumatic out-of-hospital cardiac arrest calls using the Medical Priority Dispatch System (MPDS) from January 1 to March 31, 2014, with calls using LA-TDS from January 1 to March 31, 2015. Trained data abstractors evaluated all 9-1-1 audio recordings for the initiation of T-CPR and the elapsed time to predefined events. Data were analyzed between January and December 2017. <h3>Main Outcomes and Measures</h3> The primary outcome was the prevalence of T-CPR among 9-1-1 callers with limited English proficiency for field-confirmed nontraumatic cardiac arrests. Additional outcomes included T-CPR among callers with English proficiency and the elapsed time until key events in the call. <h3>Results</h3> Of the 1027 emergency medical services calls during the study periods, 597 met the inclusion criteria. A total of 289 calls (48%) were made using MPDS (263 callers with English proficiency, and 26 callers with limited English proficiency), and 308 calls (52%) were made using LA-TDS (273 callers with English proficiency, and 35 callers with limited English proficiency). No differences between MPDS and LA-TDS cohorts were found in age, sex, known comorbidities, arrest location (private vs public), or witnessed status. The prevalence of T-CPR among callers with limited English proficiency was significantly greater using LA-TDS (69%) vs MPDS (28%) (odds ratio [OR], 5.66; 95% CI, 1.79-17.85;<i>P</i> = .003). For callers with English proficiency, the prevalence of T-CPR improved from 55% using MPDS to 67% using LA-TDS (OR, 1.66; 95% CI, 1.15-2.41;<i>P</i> = .007). With LA-TDS, callers with limited English proficiency had a significant decrease in time to recognition of cardiac arrest (OR, 0.59; 95% CI, 0.41-0.84;<i>P</i> = .005) and dispatch of resources (OR, 0.71; 95% CI, 0.54-0.94;<i>P</i> = .02). <h3>Conclusions and Relevance</h3> The LA-TDS compared with MPDS was associated with increased performance of T-CPR for out-of-hospital cardiac arrests involving 9-1-1 callers with limited English proficiency. Further studies are needed in communities with a predominance of people with limited English proficiency to characterize bystander response, promote activation of the chain of survival, and clarify the precise elements of LA-TDS that can improve T-CPR performance.
Long-Lasting Dissociation of Esophageal Eosinophilia and Symptoms After Dilation in Adults With Eosinophilic Esophagitis
Authors: Ekaterina Safroneeva, Zhaoxing Pan, Eileen King, Lisa J. Martin, Margaret H. Collins, Guang-Yu Yang, Kelley E. Capocelli, Nicoleta C. Arva, J. Pablo Abonia, Dan Atkins, Peter A. Bonis, Evan S. Dellon, Gary W. Falk, Nirmala Gonsalves, Sandeep K. Gupta, Ikuo Hirano, John Leung, Paul A. Menard-Katcher, Vincent A. Mukkada, Alain M. Schoepfer, Jonathan M. Spergel, Barry K. Wershil, Marc E. Rothenberg, Seema S. Aceves, Glenn T. Furuta
Journal: Clinical Gastroenterology and Hepatology (2021)
Arsenic Combined With All-Trans Retinoic Acid for Pediatric Acute Promyelocytic Leukemia: Report From the CCLG-APL2016 Protocol Study
Authors: Huyong Zheng, Hui Jiang, Shaoyan Hu, Ning Liao, Diying Shen, Xin Tian, Guoping Hao, Runming Jin, Jianxin Li, Yongjun Fang, Xiuli Ju, Ansheng Liu, Ningling Wang, Xiaowen Zhai, Jiashi Zhu, Qun Hu, Limin Li, Wei Liu, Lirong Sun, Li Wang, Yunpeng Dai, Xiaoqin Feng, Fu Li, Hui Liang, Xinhui Luo, Mei Yan, Qingning Yin, Yan Chen, Yueqin Han, Lijun Qu, Yanling Tao, Hui Gao, Zhixu He, Limin Lin, Jixia Luo, Kaili Pan, Jingrong Zhang, Rong Zhang, Min Zhou, Yuanyuan Zhang, Linya Wang, Ruidong Zhang, Peifang Xiao, Yayun Ling, Xiaoxia Peng, Yaguang Peng, Tianyou Wang
Journal: Journal of Clinical Oncology (2021)

Arsenic combined with all-trans retinoic acid (ATRA) is the standard of care for adult acute promyelocytic leukemia (APL). However, the safety and effectiveness of this treatment in pediatric patients with APL have not been reported on the basis of larger sample sizes.We conducted a multicenter trial at 38 hospitals in China. Patients with newly diagnosed APL were stratified into two risk groups according to baseline WBC count and FLT3-ITD mutation. ATRA plus arsenic trioxide or oral arsenic without chemotherapy were administered to the standard-risk group, whereas ATRA, arsenic trioxide, or oral arsenic plus reduced-dose anthracycline were administered to the high-risk group. Primary end points were event-free survival and overall survival at 2 years.We enrolled 193 patients with APL. After a median follow-up of 28.9 months, the 2-year overall survival rate was 99% (95% CI, 97 to 100) in the standard-risk group and 95% (95% CI, 90 to 100) in the high-risk group (P = .088). The 2-year event-free survival was 97% (95% CI, 93 to 100) in the standard-risk group and 90% (95% CI, 83 to 96) in the high-risk group (P = .252). The plasma levels of arsenic were significantly elevated after treatment, with a stable effective level ranging from 42.9 to 63.2 ng/mL during treatment. In addition, plasma, urine, hair, and nail arsenic levels rapidly decreased to normal 6 months after the end of treatment.Arsenic combined with ATRA is effective and safe in pediatric patients with APL, although long-term follow-up is still needed.