tbuckley/cabot-search huggingface dataset:
HP0038 Preferences for improvement in health: a comparison between age, sex and education-matched patients with osteoarthritis (oa) and rheumatoid arthritis (ra)
Authors: T Heiberg, B Slatkowsky-Christensen, TK Kvien
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Awareness of patients' preferences are of salient importance for health professionals in today's health care system. Preferences both on an individual and on a group level form the premises for the provision of an effective and efficient health care service. <h3>Objective</h3> The aim of this study was to examine in which areas of health a group of patients with OA would most like to see improvement, and to compare their preferences with the preferences reported by matched RA patients. <h3>Materials and methods</h3> Fifty-one patients (mean (SD) age 66 (4) years, 4 (8%) males, mean (SD) years of education 12 (3)) with generalised OA including hand OA, previously referred to a rheumatology outpatient department, underwent a comprehensive clinical examination including completion of several self-reported health status questionnaires. Among these were AIMS2, MHAQ, SF36 and joint pain VAS and fatigue VAS. These OA patients were compared with 51 RA patients matched for age, gender and level of education who were recruited from the Oslo RA register and had previously responded to identical questionnaires. All patients were asked to check three out of twelve health areas in which they would most like to see improvement (AIMS2, question 60). Scores of health status were computed from the different scales of health status questionnaires. Comparisons between the two matched patients groups were performed by McNemar tests (categorical variables) and paired analyses (continuous variables). <h3>Results</h3> Out of the OA patients 82.4% reported priority for improvement in pain, compared to 58.8% of the RA patients (p = 0.02, McNemar test). Other health areas had lower priorities in both groups without any significant group difference and were distributed as follows among the OA/RA patients: Mobility level 5.9/17.6%, walking and bending 31.4/25.5%, hand and finger function 45.1/52.9%, arm function 9.8/23.5%, self-care 11.8/21.6%, household tasks 39.2/31.4%, social activity 2.0/11.8%, support from family 3.9/3.9%, work level 3.9/5.9%, tension 11.8/7.8%, mood 25.5/17.6%. Across different instruments OA patients also reported numerically more severe pain and mental health scores than RA patients whereas RA patients had significantly worse scores within the dimension of physical disability. <h3>Conclusion</h3> Although being a preliminary study with only 51 patients in each group, these findings indicate that pain is the area where both OA and RA patients would most like to see improvement, and that patients with OA have pain as an even higher preference for improvement than patients with RA. Consequently, pain is the area of health that deserves increased attention in clinical practice, both for patients with OA and RA.
Comprehensive analysis of T cell immunodominance and immunoprevalence of SARS-CoV-2 epitopes in COVID-19 cases
Authors: Alison Tarke, John Sidney, Conner K. Kidd, Jennifer M. Dan, Sydney I. Ramirez, Esther Dawen Yu, Jose Mateus, Ricardo da Silva Antunes, Erin Moore, Paul Rubiro, Nils Methot, Elizabeth Phillips, Simon Mallal, April Frazier, Stephen A. Rawlings, Jason A. Greenbaum, Bjoern Peters, Davey M. Smith, Shane Crotty, Daniela Weiskopf, Alba Grifoni, Alessandro Sette
Journal: Cell Reports Medicine (2021)
SP0035 Supra-spinal mechanisms of pain and non-invasive imaging in the study of chronic pain in humans
Authors: C Bushnell
Journal: Annals of the Rheumatic Diseases (2001)

<h3></h3> Pain is a complex experience that includes sensory, emotional, autonomic and motoric components, and each of these components can differ among various pain states. Despite the many qualitative differences of clinical and experimental pain states, they all share a common aversive nature, leading us to characterise each as "pain." This talk will present evidence showing a common cortical network that, when activated, leads to the perception of pain. Activation of this circuit can result from direct stimulation of peripheral nociceptors or from the disruption of endogenous modulatory circuits in the CNS that allows normally nonpainful stimuli to access the cortical pain system. Using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), we find that a network of cortical regions is reliably activated by experimental pain and chronic clinical pain states, including the primary and secondary somatosensory cortices (S1 and S2), the anterior cingulate cortex (ACC) and the insular cortex (IC). This network is activated during pain produced by stimuli as divergent as cutaneous heat, visceral pain produced by esophageal distension, or tactile allodynia produced by capsaicin application. Our imaging data show that allodynia related to peripheral or CNS damage activates the same cortical pain system as that activated during acute pain states. Other experiments suggest that these various cortical regions have a differential role in processing the sensory and affective dimensions of pain. Experimental manipulations that selectively alter the affective component of pain predominantly modulate activity in ACC, whereas those that alter the sensory component of pain modulate activity in the other cortical regions, particularly S1 cortex. Finally, whether the cortical areas are activated by experimental pain or by aberrant chronic pain states, the pain-evoked activation can be modulated by cognitive factors, such as direction of attention.
Cardiac efficacy and toxicity of aconitine: A new frontier for the ancient poison
Authors: Wei Zhou, Hong Liu, Li‐Zhen Qiu, Lan‐Xin Yue, Guang‐Jie Zhang, Hui‐Fang Deng, Yu‐Hao Ni, Yue Gao
Journal: Medicinal Research Reviews (2021)

Aconitine (AC) is well-known as the main toxic ingredient and active compound of Aconitum species, of which several aconites are essential herbal medicines of Traditional Chinese Medicine (TCM) and widely applied to treat diverse diseases for their excellent anti-inflammatory, analgesic, and cardiotonic effects. However, the cardiotoxicity and neurotoxicity of AC attracted a lot of attention and made it a favorite botanic poison in history. Nowadays, the narrow therapeutic window of AC limits the clinical application of AC-containing herbal medicines; overdosing on AC always induces ventricular tachyarrhythmia and heart arrest, both of which are potentially lethal. But the underlying cardiotoxic mechanisms remained chaos. Recently, beyond its cardiotoxic effects, emerging evidence shows that low doses of AC or its metabolites could generate cardioprotective effects and are necessary to aconite's clinical efficacy. Consistent with TCM's theory that even toxic substances are powerful medicines, AC thus could not be simply identified as a toxicant or a drug. To prevent cardiotoxicity while digging the unique value of AC in cardiac pharmacology, there exists a huge urge to better know the characteristic of AC being a cardiotoxic agent or a potential heart drug. Here, this article reviews the advances of AC metabolism and focuses on the latest mechanistic findings of cardiac efficacy and toxicity of this aconite alkaloid or its metabolites. We also discuss how to prevent AC-related cardiotoxicity, as well as the issues before the development of AC-based medicines that should be solved, to provide new insight into the paradoxical nature of this ancient poison.
Anti–Cytosolic 5′‐Nucleotidase 1A Autoantibodies Are Absent in Juvenile Dermatomyositis
Authors: Anke Rietveld, Judith Wienke, Eline Visser, Wilma Vree Egberts, Wolfgang Schlumberger, Baziel van Engelen, Annet van Royen‐Kerkhof, Hui Lu, Lucy Wedderburn, Christiaan Saris, Sarah Tansley, Ger Pruijn
Journal: Arthritis & Rheumatology (2021)

To assess anti-cytosolic 5'-nucleotidase 1A (anti-cN-1A) autoantibodies in children with juvenile dermatomyositis (DM) and healthy controls, using 3 different methods of antibody detection, as well as verification of the results in an independent cohort.Anti-cN-1A reactivity was assessed in 34 Dutch juvenile DM patients and 20 healthy juvenile controls using the following methods: a commercially available full-length cN-1A enzyme-linked immunosorbent assay (ELISA), a synthetic peptide ELISA, and immunoblotting with a lysate from cN-1A-expressing HEK 293 cells. Sera from juvenile DM patients with active disease and those with disease in remission were analyzed. An independent British cohort of 110 juvenile DM patients and 43 healthy juvenile controls was assessed using an in-house full-length cN-1A ELISA.Anti-cN-1A reactivity was not present in sera from juvenile DM patients or healthy controls when tested with the commercially available full-length cN-1A ELISA or by immunoblotting, in either active disease or disease in remission. Additionally, in the British juvenile DM cohort, anti-cN-1A reactivity was not detected. Three Dutch juvenile DM patients had weakly positive results for 1 of 3 synthetic cN-1A peptides measured by ELISA.Juvenile DM patients and young healthy individuals did not show anti-cN-1A reactivity as assessed by different antibody detection techniques.
RAF1 kinase activity is dispensable for KRAS/p53 mutant lung tumor progression
Authors: Manuel Sanclemente, Patricia Nieto, Sara Garcia-Alonso, Fernando Fernández-García, Laura Esteban-Burgos, Carmen Guerra, Matthias Drosten, Eduardo Caleiras, Jorge Martinez-Torrecuadrada, David Santamaría, Monica Musteanu, Mariano Barbacid
Journal: Cancer Cell (2021)
Assessing Social Risks Prior to Commencement of a Clinical Trial: Due Diligence or Ethical Inflation?
Authors: Scott Burris, Corey Davis
Journal: The American Journal of Bioethics (2009)

Assessing social risks has proven difficult for IRBs. We undertook a novel effort to empirically investigate social risks before an HIV prevention trial among drug users in Thailand and China. The assessment investigated whether law, policies and enforcement strategies would place research subjects at significantly elevated risk of arrest, incarceration, physical harm, breach of confidentiality, or loss of access to health care relative to drug users not participating in the research. The study validated the investigator's concern that drug users were subject to serious social risks in the site localities, but also suggested that participation in research posed little or no marginal increase in risk and might even have a protective effect. Our experience shows that it is feasible to inform IRB deliberations with actual data on social risks, but also raises the question of whether and when such research is an appropriate use of scare research resources.
Neutrophil dysfunction in bronchiectasis: an emerging role for immunometabolism
Authors: Yan Hui Giam, Amelia Shoemark, James D. Chalmers
Journal: European Respiratory Journal (2021)

Bronchiectasis is a heterogenous disease with multiple underlying causes. The pathophysiology is poorly understood but neutrophilic inflammation and dysfunctional killing of pathogens is believed to be key. There are, however, no licensed therapies for bronchiectasis that directly target neutrophilic inflammation. In this review, we discuss our current understanding of neutrophil dysfunction and therapeutic targeting in bronchiectasis. Immunometabolic reprogramming, a process through which inflammation changes inflammatory cell behaviour by altering intracellular metabolic pathways, is increasingly recognised across multiple inflammatory and autoimmune diseases. Here, we show evidence that much of the neutrophil dysfunction observed in bronchiectasis is consistent with immunometabolic reprogramming. Previous attempts at developing therapies targeting neutrophils have focused on reducing neutrophil numbers, resulting in increased frequency of infections. New approaches are needed and we propose that targeting metabolism could theoretically reverse neutrophil dysfunction and dysregulated inflammation. As an exemplar, 5' adenosine monophosphate (AMP)-activated protein kinase (AMPK) activation has already been shown to reverse phagocytic dysfunction and neutrophil extracellular trap (NET) formation in models of pulmonary disease. AMPK modulates multiple metabolic pathways, including glycolysis which is critical for energy generation in neutrophils. AMPK activators can reverse metabolic reprogramming and are already in clinical use and/or development. We propose the need for a new immunomodulatory approach, rather than an anti-inflammatory approach, to enhance bacterial clearance and reduce bronchiectasis disease severity.
Personal neoantigen vaccines induce persistent memory T cell responses and epitope spreading in patients with melanoma
Authors: Zhuting Hu, Donna E. Leet, Rosa L. Allesøe, Giacomo Oliveira, Shuqiang Li, Adrienne M. Luoma, Jinyan Liu, Juliet Forman, Teddy Huang, J. Bryan Iorgulescu, Rebecca Holden, Siranush Sarkizova, Satyen H. Gohil, Robert A. Redd, Jing Sun, Liudmila Elagina, Anita Giobbie-Hurder, Wandi Zhang, Lauren Peter, Zoe Ciantra, Scott Rodig, Oriol Olive, Keerthi Shetty, Jason Pyrdol, Mohamed Uduman, Patrick C. Lee, Pavan Bachireddy, Elizabeth I. Buchbinder, Charles H. Yoon, Donna Neuberg, Bradley L. Pentelute, Nir Hacohen, Kenneth J. Livak, Sachet A. Shukla, Lars Rønn Olsen, Dan H. Barouch, Kai W. Wucherpfennig, Edward F. Fritsch, Derin B. Keskin, Catherine J. Wu, Patrick A. Ott
Journal: Nature Medicine (2021)
AB0183 Correlation between the bone mineral density and the obesity in healthy woman
Authors: NZ Vujasinovic-Stupar, P Vukojevic, NZ Pilipovic
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> <h3>Methods</h3> In 425 randomly chosen women, bone mineral density (BMD) assessment of lumbar spine (region L2-L4) was done using LUNAR DPXL device. All the subjects included were healthy with negative significant risk factors for osteoporosis. The demographic data of included subjects are: Mean age of women was 47.1 (20–78) yrs; menarche mean age was 13.5 (10–19) yrs; average weight 68.8 (45–107) kg and average height 160 (147–183) cm; mean value of BMI was 25.6 (14.8–45.6) kg/m<sup>2</sup>; mean value of BMD was 1.16 (0.701–1.98) g/ccm. According to BMI the subjects were divided in 4 groups (grade 0 = normal, grade 1 = mild obesity, grade 2 = moderate obesity and 3 = severe obesity) and the linear correlation test was done between BMD and BMI. <h3>Results</h3> The results with correlation coefficient (R) and corresponding p values are shown in the Table 1. <h3>Conclusion</h3> The significant positive correlation (p = 0,006) was observed between lumbar spine BMD and BMI in whole group. In subjects with normal BMI (group 0) and mild obesity such correlation was not present. In subjects with moderate obesity significant positive correlation was observed (p = 0,021), while in group representing severe obesity subjects highly significant negative correlation was calculated (p = 0,036).
AB0039 Investigation of intrarenal hemodynamics in patients with rheumatoid arthritis
Authors: BF Nemtsov, GA Postnikova, OV Simonova
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Impairment of the kidneys in case of rheumatoid artritis (RA) is one of the most severe complications and results in unfavourable prognoses. <h3>Objectives</h3> To investigate intrarenal hemodynamics (IRHD) in patients with diverse clinical forms of RA. <h3>Methods</h3> 43 RA patients were studied according to ACR criteria. Of them, there were 36 females and 7 males. The mean age was 47.8 years. The average duration of RA was 7.8 years. Extraarticular symptoms were revealed in 23 patients. 18 patients had arterial hypertension. 14 had steroid dependence. 11 patients had chronic nephropathy without kidney failure. 3 patients had secondary amyloidosis. IRHD was studied by means of renal functional reserve (RFR). RSR was studied by means of dynamic evaluation of glomerulofiltration with oral protein tests (0.7 gr of proteins per 1 kg of weight). <h3>Results</h3> Disorders of IRHD (RFR &lt; 5%) were revealed in 17 RA patients including 3 patients with secondary amyloidosis. Of note are the following clinical features of this group: in 11 patients, duration of RA was more than 12 years; 12 patients had other extra articular symptoms and arterial hypertension; IRHD disorders were revealed in 5 patients who had no clinical and laboratory renal abnormalities. Those 5 patients had pre-existing arterial hypertension, extra articular symptoms and RA duration was more than 10 years. <h3>Conclusion</h3> IRHD disorders were revealed in severe cases of RA with signs of nephropathy. However, our findings of RFR disorders in patients, who had no nephropathy, required evaluation and estimation of IRHD in patients with RA duration over 10 years, associated arterial hypertension and extra articular symptoms.
Familial pancreatic cancer (FPC) status as a clinical biomarker in patients receiving platinum-based systemic therapy: A case-control analysis.
Authors: Deirdre Kelly, Ayelet Borgida, Sheron Perera, Robert Edward Denroche, Spring Holter, Zhihui (Amy) Liu, Zijin Liu, Amy Zhang, Anna Dodd, Stephanie Ramotar, Shawn Hutchinson, Julie Wilson, Faiyaz Notta, Jennifer J. Knox, Steven Gallinger, Robert C Grant, Grainne M. O'Kane
Journal: Journal of Clinical Oncology (2021)

430 Background: Familial pancreatic cancer (FPC) is broadly defined as kindreds with at least a pair of first-degree relatives with pancreatic ductal adenocarcinoma (PDA). The role of DNA damage response agents, including platinum has not been well studied in this patient population. Methods: In this retrospective analysis, treatment details and clinical outcomes were analyzed in pts with FPC with advanced, unresectable or recurrent disease enrolled in the Ontario Pancreatic Cancer Study database. The primary outcome, overall survival (OS) was calculated from the initial diagnosis of advanced disease until death. 179 non-FPC patients from the COMPASS trial [NCT02750657] served as a control cohort all of whom had full molecular profiling and family history documented. OS between pts that received platinum-based therapy, and those that did not was compared using multivariable Cox proportional hazards model adjusting for age, sex, diagnosis year and FPC status. Interaction between FPC status and platinum was evaluated. Results: A total of 205 FPC pts were identified, 71% of pts had full germline testing and 16 (8%) had germline pathogenic variants in BRCA1/2. 104 (51%) were female and 101 (49%) male. Median age was 63 years (20-93) and 58 (28%) received platinum-based chemotherapy. Within the control arm (n=179), 71 (40%) were female, and 108 (60%) male; the median age was 64 years (29-84) and 106 (59%) received platinum-based therapy. In univariable analysis, median OS in pts with FPC was 16.9 months compared to 9.6 months (HR 0.46 [95% CI 0.37-0.58]). FPC patients receiving platinum had a superior median OS of 19 months compared to 15.5 months without platinum. In a multivariable analysis, both FPC (HR 0.33 [95% CI 0.21-0.51]) and receipt of platinum HR 0.53 [95% CI 0.38-0.73]) were prognostic. No interaction was seen with FPC and receipt of platinum (p=0.15). Conclusions: FPC status is prognostic but not predictive of platinum response in this study. Further molecular profiling of this unique cohort of patients will provide insights into putative predisposing germline alterations, and novel treatment strategies.
NRG-GI002: A phase II clinical trial platform using total neoadjuvant therapy (TNT) in locally advanced rectal cancer (LARC)—Pembrolizumab experimental arm (EA) primary results.
Authors: Osama E. Rahma, Greg Yothers, Theodore S. Hong, Marcia McGory Russell, Y. Nancy You, William Parker, Samuel A. Jacobs, Linda H. Colangelo, Peter C. Lucas, Marc J Gollub, William Adrian Hall, Lisa A. Kachnic, Namrata Vijayvergia, Norman Wolmark, Thomas J. George
Journal: Journal of Clinical Oncology (2021)

8 Background: This NCTN multi-arm randomized phase II modular clinical trial platform utilizes TNT with parallel EAs in LARC. EAs are not intended for direct comparison, but rather to test a variety of sensitizers or hypotheses in a consistent and homogenous high-risk pt population with correlative biomarkers. Here we report the primary and available secondary endpoints (EPs). Methods: Stage II/III LARC pts (with ONE or more of the following: distal location [cT3-4 ≤5cm from anal verge, any N]; bulky [any cT4 or tumor within 3mm of mesorectal fascia]; high risk for metastatic disease [cN2]; or not a sphincter-sparing surgery [SSS] candidate) were randomized to neoadjuvant FOLFOX x 4mo → chemoRT (capecitabine with 50.4Gy +/- pembrolizumab 200mg IV Q3 wks x 6 doses) → surgery 8-12 wks following last dose of radiotherapy. Primary EP: Improvement in Neoadjuvant Rectal Cancer (NAR) score for EA v control potentially representing a 3-4% absolute OS improvement. Secondary EPs: Comparisons of OS, DFS, toxicity, pCR, cCR, therapy completion, negative surgical margins, sphincter sparing surgery (SSS), and exploratory assessments of molecular and radiographic predictors of response and distant failure. Binary EPs compared by Fisher’s exact test. Reported p-values are two-sided. Results: From 8/2018-5/2019, 185 pts were randomized to control (n=95) or pembrolizumab (n= 90). Baseline characteristics were relatively well balanced. 137 pts were evaluable for NAR (68 control, 69 pembrolizumab). Mean NAR was 14.08 for control (95% CI: 10.7-17.4) v 11.53 for pembrolizumab (CI: 8.5-14.6) (p=0.26). pCR=29.4% v 31.9% (p=0.75); cCR=13.6% v 13.9% (p=0.95); and SSS=71.0% v 59.4% (p=0.15). The side effects on Arm 3 were consistent with both CRT and pembrolizumab safety profile. Grade 3/4 AEs were slightly increased on the pembrolizumab arm during and after CRT (48.2 v 37.3%). There were 2 deaths during FOLFOX, one on the control arm due to sepsis; the other on the EA due to pneumonia. There were no statistically significant differences in RT (fractions, dose, boost fractions, or boost dose), FOLFOX or capecitabine doses. Conclusions: Pembrolizumab added to chemoRT as part of TNT was safe and without unexpected short-term toxicities but failed to improve the NAR score. The secondary endpoints including PFS and OS have not been reached. Correlative analysis for both T-cell and myeloid cell populations in the tissue and blood in addition to comprehensive cytokine analysis is ongoing. NCT02921256. Support: U10CA180868, -180822; UG1-189867; U24-196067. Clinical trial information: NCT02921256.