tbuckley/cabot-search huggingface dataset:
THU0163 Cortisol and prolactin levels in rheumatoid arthritis and systemic lupus erythematosus
Authors: E Grabocka, A Tafaj, A Këlliçi
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Accumulated evidence suggests the existence of bidirectional communication between the neuroendocrine and immune systems. The pituitary gland can regulate the immune response secreting both immunostimulatory [e.g. prolactin (PRL)] and immunosupressive (cortisol via ACTH) hormones. A disorder of the immunoregulatory circuit between these systems could potentially result in the development of immune mediated diseases. Hiperprolactinemia has been implicated in the pathogenesis of systemic lupus erythematosus (SLE), Reiter’s Syndrome and psoriatic arthritis. Elevated PRL levels have been described in patients with rheumatoid arthritis (RA). However, clinical studies regarding the PRL level and disease activity have yielded contradictory results. <h3>Objectives</h3> In this study our aim was to assess prolactin and cortisol plasma levels in patients with RA and SLE and to evaluate their correlation with disease activity. <h3>Methods</h3> PRL and cortisol plasma levels were measured in 40 female patients aged (24 RA patients and 16 SLE patients) 38.88 ± 14.44 and 40 age-matched healthy controls. Pregnant patients, patients taking drugs that could increase PRL or cortisol levels and those with renal and/or hepatic failure, were excluded from the study. All subjects were premenopausal women with regular menstrual cycles. Plasma concentrations of prolactin and cortisol were determined by radioimmunoassay under standardised conditions in venous blood drawn through an indwelling cannula. Disease activity was assessed using the Disease Activity Score (DAS) for the RA patients SLEDAI for SLE patients. <h3>Results</h3> The mean PRL plasma level was higher in RA and SLE than in the control group (13.8 ± 6.1; 15.6 ± 4.2 vs. 8.78 ± 2.43, respectively, p &lt; 0.05). Cortisol plasma levels were found to be higher in the RA and SLE patients than in controls, but there were not significantly different (14.2 ± 3.6; 16.3 ± 3.3 vs. 13.1 ± 2.8 respectively, p &gt; 0.05). <h3>Conclusion</h3> No difference was found in prolactin and cortisol levels between RA and SLE patients. A correlation between prolactin and cortisol levels was found only in SLE patients (p &lt; 0.05). No correlation was found between PRL or cortisol levels and disease activity in RA and SLE subjects.
Direct targeting of <i>β</i>‐catenin in the Wnt signaling pathway: Current progress and perspectives
Authors: Zhen Wang, Zilu Li, Haitao Ji
Journal: Medicinal Research Reviews (2021)

Abstract Aberrant activation of the Wnt/ β ‐catenin signaling circuit is associated with cancer recurrence and relapse, cancer invasion and metastasis, and cancer immune evasion. Direct targeting of β ‐catenin, the central hub in this signaling pathway, is a promising strategy to suppress the hyperactive β ‐catenin signaling but has proven to be highly challenging. Substantial efforts have been made to discover compounds that bind with β ‐catenin, block β ‐catenin‐mediated protein–protein interactions, and suppress β ‐catenin signaling. Herein, we characterize potential small‐molecule binding sites in β ‐catenin, summarize bioactive small molecules that directly target β ‐catenin, and review structure‐based inhibitor optimization, structure–activity relationship, and biological activities of reported inhibitors. This knowledge will benefit future inhibitor development and β ‐catenin‐related drug discovery.
Abstract 18203: Argon Ventilation Improves Circulation During Cardiopulmonary Resuscitation in a Porcine Model of Cardiac Arrest
Authors: Claudius Balzer, Hunter F Douglas, Kadambari Chandra Shekar, Michele M Salzman, Demetris Yannopoulos, Tom P Aufderheide, Matthias L Riess
Journal: Circulation (2017)

Introduction: Following cardiac arrest (CA), ventilation with the noble gas Argon after ROSC has been shown to improve hemodynamic and neurologic outcome in rats and pigs. We recently found a prono...
The expressive rationality of inaccurate perceptions
Authors: Dan M. Kahan
Journal: Behavioral and Brain Sciences (2017)

Abstract This commentary uses the dynamic of identity-protective cognition to pose a friendly challenge to Jussim (2012). Like other forms of information processing, this one is too readily characterized as a bias. It is no mistake, however, to view identity-protective cognition as generating inaccurate perceptions. The “bounded rationality” paradigm incorrectly equates rationality with forming accurate beliefs. But so does Jussim's critique.
心不全JACCにおけるカリウムの異常-最新のレビュー【JST・京大機械翻訳】
Authors: Ferreira Joao Pedro, Butler Javed, Rossignol Patrick, Pitt Bertram, D Anker Stefan, Kosiborod Mikhail, H Lund Lars, L Bakris George, R Weir Matthew, Zannad Faiez
Journal: Journal of the American College of Cardiology (2020)
AB1051 KIKUCHI FUJIMOTO DISEASE, IS IT SLE?
Authors: J. Camins-Fàbregas, V. Ortiz-Santamaria, N. Busquets-Pérez, A. Cuervo, I. Cañas Alcántara, R. Acal, E. Hadad-Casorelli, A. Guilabert, J. Sola
Journal: Annals of the Rheumatic Diseases (2020)

Background: Kikuchi-Fujimoto disease (KFD) is a rare entity characterized by adenopathies and fever. It raises a broad differential diagnosis that includes lymphoproliferative disorders, infections and systemic autoimmune diseases, and diagnostic confirmation is always by histology, which shows histiocytic necrotizing lymphadenitis. Although its course is generally benign and self-limited, it can be associated both at the time of diagnosis and during follow-up with systemic autoimmune diseases, the most frequent of which is systemic lupus erythematosus (SLE). Objectives: To describre the clinical and analytical characteristics of patients diagnosed with KFD and the development of systemic autoimmune disease. Methods: Patients diagnosed with KFD during the 1990s and 2020s are collected in a regional hospital (Granollers General Hospital). The clinic is documented at the diagnosis of EKF, the appearance of systemic autoimmune disease during follow-up and its clinical and analytical characteristics. Results: A total of 7 patients with EKF were diagnosed. All of them women with a mean age at diagnosis of 30 years. Diagnosis was made in all cases with compatible clinical symptoms, fever and lymphadenopathy, and lymph node biopsy confirming histiocytic necrotizing lymphadenitis. At the time of diagnosis, a patient was also diagnosed with SLE. During the follow-up, 4 of the 6 remaining patients developed clinical manifestations compatible with SLE (3 of them with systemic manifestations and a case of subacute cutaneous lupus. The mean time of onset of SLE was 34 months (between 6 months and 5 years). All of them received treatment with hydroxychloroquine, with good response to treatment. The clinical and analytical characteristics are presented in Table 1 below. Conclusion: In our center, 5 of the 7 patients (71%) diagnosed with EKF developed manifestations compatible with SLE. The importance of the diagnosis of EKF lies precisely in the possible association with systemic autoimmune disease, the most common being SLE, so it is recommended that patients be monitored to identify those who develop associated autoimmune disease. Disclosure of Interests: None declared
Epitope-resolved profiling of the SARS-CoV-2 antibody response identifies cross-reactivity with endemic human coronaviruses
Authors: Jason T. Ladner, Sierra N. Henson, Annalee S. Boyle, Anna L. Engelbrektson, Zane W. Fink, Fatima Rahee, Jonathan D’ambrozio, Kurt E. Schaecher, Mars Stone, Wenjuan Dong, Sanjeet Dadwal, Jianhua Yu, Michael A. Caligiuri, Piotr Cieplak, Magnar Bjørås, Mona H. Fenstad, Svein A. Nordbø, Denis E. Kainov, Norihito Muranaka, Mark S. Chee, Sergey A. Shiryaev, John A. Altin
Journal: Cell Reports Medicine (2021)

The SARS-CoV-2 proteome shares regions of conservation with endemic human coronaviruses (CoVs), but it remains unknown to what extent these may be cross-recognized by the antibody response. Here, we study cross-reactivity using a highly multiplexed peptide assay (PepSeq) to generate an epitope-resolved view of IgG reactivity across all human CoVs in both COVID-19 convalescent and negative donors. PepSeq resolves epitopes across the SARS-CoV-2 Spike and Nucleocapsid proteins that are commonly targeted in convalescent donors, including several sites also recognized in some uninfected controls. By comparing patterns of homologous reactivity between CoVs and using targeted antibody-depletion experiments, we demonstrate that SARS-CoV-2 elicits antibodies that cross-recognize pandemic and endemic CoV antigens at two Spike S2 subunit epitopes. We further show that these cross-reactive antibodies preferentially bind endemic homologs. Our findings highlight sites at which the SARS-CoV-2 response appears to be shaped by previous CoV exposures and which have the potential to raise broadly neutralizing responses.
<i>JEM</i> career launchpad
Authors: Anna Bigas, Ivan Zanoni, Matthew R. Hepworth, Stephanie C. Eisenbarth, Seth Lucian Masters, Jonathan Kipnis, Carola G. Vinuesa, Kim L. Good-Jacobson, Stuart G. Tangye, Sayuri Yamazaki, Claire Hivroz, Elia Tait Wojno, Ziv Shulman, Marco Colonna
Journal: The Journal of Experimental Medicine (2021)

JEM has been a launching pad for scientific careers since its inception. Here is a collection of testimonials attesting to the diversity of the scientific community it serves.
FRI0025 The rheumatoid arthritis patient in the clinic: comparing 1319 consecutive dmard therapies
Authors: D Aletaha, JS Smolen
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> Rheumatoid arthritis (RA) patients are prone to receive a series of consecutive disease modifying antirheumatic drugs (DMARDs). This study was performed to reveal possible strategies and treatment patterns with traditional DMARDs in the 1980s and 1990s to serve as a basis for improvement of treatment strategies. <h3>Methods</h3> 593 RA outpatients (80.4% women) from two hospitals who received 1319 consecutive courses of DMARDs (2376 patient years of therapy) were followed from their first presentation throughout the whole course of their disease. Data were collected as dosage, duration of therapy, reason for discontinuation and all adverse effects that had emerged during DMARD treatment. Furthermore, efficacy of individual DMARDs (using CRP and ESR as surrogates) and survival (applying Kaplan-Meier-estimates) of drug therapy were assessed. <h3>Results</h3> Chloroquine (CQ), sulfasalazine (SSZ), and gold compounds (OG, PG) were typical first DMARDs, while penicillamine (DPA), methotrexate (MTX), azathioprine (AZP), cyclosporine (CyA), and combinations were usually used later in the disease course. MTX, SSZ and CQ were the most commonly employed DMARDs throughout the years,<sup>1</sup> however, SSZ and CQ therapies were mostly followed by MTX. Disease characteristics did not differ between patients with longstanding therapy and those with therapies terminated early. For consecutive DMARDs, there was a decreasing tendency of efficacy (reduction of acute phase response) and of treatment duration (Table 1). <h3>Conclusion</h3> MTX is the most commonly employed DMARD therapy for RA and is increasingly used as first therapy in newly diagnosed RA. Patients with high disease activity are more often subjected to MTX therapy than to other DMARDs, while those with low activity were more likely to receive SSZ or CQ. There is a loss of efficacy with increasing number of subsequent therapies. Thus, treatment duration decreases with increasing number of consecutive DMARD therapies. <h3>Reference</h3> Felson DT, Anderson JJ, Meenan RF. Use of short-term efficacy/toxicity tradeoffs to select second-line drugs in rheumatoid arthritis. A metaanalysis of published clinical trials. Arthritis Rheum. 1992;35:1117–25
THU0187 Quality of life im rheumatoid arthritis: adaptation of raqol for use in turkey
Authors: S Kutlay, D Gonul, A Kucukdeveci
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Traditionally, the primary focus of medical research is the measurement of mortality and morbidity. During the past decade however interest is increasing in measurement of quality of life, health status, and functional status in the field of rheumatology. <h3>Objectives</h3> The purpose of this study was to adapt the RAQoL for Turkish population and to test the new version's reliability and validity. <h3>Methods</h3> After the translation process, 61 patients with rheumatoid arthritis (mean age 49, 82% female) were recruited for validation study. All the patients were evaluated by the disease activity scale (DAS), Nottingham health Profile (NHP), and Stanford Health Assessment Questionnaire. Patients were interviewed twice with a week interval. <h3>Results</h3> The test-retest reliability of Turkish version of RAQoL was good (Spearman correlation coefficient for total RAQoL was 0,913). The internal consistency of RAQoL was satisfactory (Cronbach alpha: 0,95). It was found high correlation between the RAQoL and NHP subscores and low correlations between the RAQoL and DAS, HAQ. <h3>Conclusion</h3> The results of this study are the indicator of the validity and reliability of the RAQoL as an important additional measurement which reflects the impact of RA from the patient perspective in Turkey.
Pros and cons: Is faecal microbiota transplantation a safe and efficient treatment option for gut dysbiosis?
Authors: Tom Marrs, Jens Walter
Journal: Allergy (2021)

Faecal Microbiota Transplantation (FMT) is well established as an effective treatment for Clostridioides difficile infection (CDI), restoring gut microbiome diversity and function. The utility of FMT is currently being explored in relation to other immune-mediated pathologies, such as allergic disease, inflammatory bowel diseases and autoimmune diseases. Clinical trials in these areas are ongoing, and the altered gut microbiota (dysbiosis) that is often observed in these pathologies provides a rationale for the application of FMT to restore the microbiome. However, there is controversy on the risk-benefit ratio as it relates to the use of FMTs in pathologies other than CDI. In this Pro and Con article, we present the arguments for and against the use of FMT in immune-mediated pathologies, such as allergic disease. We further identify research gaps and recommend how these may be addressed in future studies.
Real-world outcomes of esophagectomy versus chemoradiotherapy for clinical stage I esophageal squamous cell carcinoma.
Authors: Hiroki Yukami, Kentaro Sawada, Hisashi Fujiwara, Saori Mishima, Daisuke Kotani, Tomohiro Kadota, Atsushi Inaba, Keiichiro Nishihara, Daiki Sato, Keiichiro Nakajo, Yusuke Yoda, Masaki Nakamura, Hidehiro Hojo, Tomonori Yano, Takeo Fujita, Takashi Kojima
Journal: Journal of Clinical Oncology (2021)

178 Background: Recently, JCOG0502 trial have shown a comparable efficacy with chemoradiotherapy (CRT) and esophagectomy as standard treatment in patients with clinical stage (cStage) I esophageal squamous cell carcinoma (ESCC), showing the standard treatment option of CRT. However, there is few reports for comparison of clinical outcomes with these treatments in real-world. The aim of this study was to clarify the real-world outcomes in cStage I ESCC who performed with CRT or esophagectomy. Methods: This retrospective study included patients with clinical stage I ESCC who received thoracoscopic or open esophagectomy with three-field lymph node dissection or CRT mainly consisted of 5-fluorouracil and platinum with concurrent radiotherapy (50.4 Gy/28Fr or 60 Gy/30Fr) between 2009 and 2017 at National Cancer Center Hospital East. Survival outcomes were calculated using the Kaplan-Meier method, and the differences were evaluated using the log-rank test. Results: Among a total of 156 patients, 128 were male and median age was 68 years old. 120 and 36 patients underwent esophagectomy and CRT, respectively. ECOG performance status 0/1/2 were 138/12/6 patients. Tumor location was Ut/Mt/Lt in 16/87/53 patients. Clinical tumor depth (MM-SM1/SM2-SM3) were 33/123 patients. Patients’ characteristics were similar among treatment groups, except clinical tumor depth (SM2-3; 84.2% in esophagectomy group vs. 61.1% in CRT group, p = 0.005). All patients underwent radical surgery in esophagectomy group, while three patients (8.3%) in CRT group were received additional esophagectomy or endoscopic resection due to residual disease. With a median follow-up of 72 months, 5-year overall survival (OS) and progression-free survival rate were 81.5%/77.0% in esophagectomy group and 82.6/74.4% in CRT group (p = 0.89 and p = 0.48). In safety profile, grade 3 or higher stenosis was observed in 21.7% of esophagectomy group. There was no treatment-related death in both groups. In subgroup analysis for OS, elderly patients (75 years and older) tended to have better 5-year OS rate in CRT group (76.9% in esophagectomy group vs. 81.8% in CRT group), while younger patients ( &lt; 75 years) showed comparable 5-year OS rate in both groups (82.4% in esophagectomy group vs. 82.9% in CRT group). Conclusions: Real-world data reproduced the results of clinical trial, supporting CRT as one of the standard treatment options in patients with cStage I ESCC.
Transcatheter Edge-to-Edge Repair for Treatment of Tricuspid Regurgitation
Authors: Philipp Lurz, Ralph Stephan von Bardeleben, Marcel Weber, Marta Sitges, Paul Sorajja, Jörg Hausleiter, Paolo Denti, Jean-Noël Trochu, Michael Nabauer, Gilbert H.L. Tang, Patric Biaggi, Shih-Wa Ying, Phillip M. Trusty, Abdellaziz Dahou, Rebecca T. Hahn, Georg Nickenig
Journal: Journal of the American College of Cardiology (2021)
Thrombin or glue – you decide
Authors: Gaurav Kumar Singh, Shamshersingh G. Chauhan, Pratik Sethiya, Vikas Pandey
Journal: Endoscopy (2021)

See also: A prospective, randomized trial of thrombin versus cyanoacrylate injection in the control of acute gastric variceal hemorrhageEndoscopy 2020; 52(07): 548-555DOI: 10.1055/a-1127-3170 See also: Reply to Singh et al.Endoscopy 2021; 53(02): 211-211DOI: 10.1055/a-1243-0660
Covid-19: Biden buys 200 million doses of vaccines to tackle supply shortages across US
Authors: Janice Hopkins Tanne
Journal: BMJ (2021)

President Joe Biden announced on 26 January that he had purchased 200 million more doses of the two authorised vaccines-100 million doses of the Pfizer BioNTech vaccine and 100 million doses of the Moderna vaccine-for what he called a "wartime effort to tackle the supply shortages we inherited from the previous administration." 1 At the same time he warned that the death toll from the virus might be half a million by the end of February.
NRG-GI004/SWOG-S1610: Colorectal Cancer Metastatic dMMR Immuno-Therapy (COMMIT) Study—A randomized phase III study of atezolizumab (atezo) monotherapy versus mFOLFOX6/bevacizumab/atezo in the first-line treatment of patients (pts) with deficient DNA mismatch repair (dMMR) or microsatellite instability high (MSI-H) metastatic colorectal cancer (mCRC).
Authors: Michael J. Overman, Greg Yothers, Samuel A. Jacobs, Hanna Kelly Sanoff, Deirdre Jill Cohen, Katherine A Guthrie, Norah Lynn Henry, Patricia A. Ganz, Scott Kopetz, Peter C. Lucas, Charles David Blanke, Norman Wolmark, Howard S. Hochster, Thomas J. George, Caio Max Sao Pedro Rocha Lima
Journal: Journal of Clinical Oncology (2021)

TPS158 Background: Despite activity of programmed cell death-1 (PD-1) pathway inhibition in dMMR/MSI-H mCRC, approximately one-third of patients demonstrate progressive disease as best response to anti-PD1 monotherapy. Preclinical models have demonstrated synergistic interactions between FOLFOX, anti-VEGF, and anti-PD-1. We hypothesize that the dMMR/MSI-H mCRC subset may be more effectively targeted by the combination of PD-1 pathway blockade and mFOLFOX6/bevacizumab (bev) rather than with anti-PD-1 therapy (atezo) alone. Methods: Initially a three-arm study, the mFOLFOX6/bev arm was closed to new enrollment on 6-4-20 due to emerging data; the redesigned COMMIT is a prospective phase III open-label trial that will randomize (1:1) mCRC dMMR/MSI-H pts (N=211) to either atezo monotherapy or mFOLFOX6/bev+atezo combination. Stratification factors include BRAFV600E status, metastatic site, and prior adjuvant CRC therapy. Primary endpoint is progression-free survival (PFS) as assessed by site investigator. Secondary endpoints include OS, objective response rate, safety profile, disease control rate, duration of response, and centrally-reviewed PFS. Health-related quality of life is an exploratory objective. Archived tumor tissue and blood samples will be collected for correlative studies. Key inclusion criteria are: mCRC without prior chemotherapy for advanced disease; dMMR tumor determined by local CLIA-certified IHC assay (MLH1/MSH2/MSH6/PMS2) or MSI-H by local CLIA-certified PCR or NGS panel; and measurable disease per RECIST. Support: U10CA180868, -180822, -180888, -180819, UG1CA189867, U24CA196067; Genentech, Inc. Clinical trial information: NCT02997228.
SAT0058 The novel cox-2 specific inhibitor, valdecoxib, does not affect platelet function in healthy adults
Authors: PT Leese, D Recker, ME Kuss
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Conventional NSAIDs have traditionally been used to manage pain and inflammation; however, as nonspecific inhibitors of cyclooxygenase (COX-1 and COX-2), they are associated with significant adverse events, including impaired platelet function. <h3>Objectives</h3> The purpose of this study was to compare the effect of valdecoxib, a new COX-2 specific inhibitor, on platelet aggregation and bleeding time to that of the conventional NSAIDs, naproxen and diclofenac. <h3>Methods</h3> This was a single-centre, double-blind, randomised comparison of valdecoxib 40 mg BID, naproxen 500 mg BID, diclofenac 75 mg BID, and placebo in healthy adult subjects. Sixty-two subjects received active medication or placebo for 7.5 days. Platelet aggregation responses to arachidonate (AA), collagen, and adenosine diphosphate (ADP); Simplate II bleeding times; and serum thromboxane (Tx) B<sub>2</sub> concentrations were measured at baseline; 30 min predose, 2, 4, and 8 h postdose on Day 1; and 2, 4, and 8 h after the final dose on Day 8. <h3>Results</h3> Valdecoxib produced no observable effects on Days 1 and 8 on platelet aggregation responses to AA, collagen, or ADP. Compared to placebo, valdecoxib produced no significant differences at any assessment. In contrast, naproxen significantly reduced all three platelet aggregation responses compared to placebo at most assessment times. The diclofenac group experienced significant reductions in AA-induced platelet aggregation compared to placebo at most assessment times, with fewer significant changes observed in response to collagen and ADP. Valdecoxib also had no effect on bleeding time compared to placebo (p &gt; = 0.136). Serum TxB<sub>2</sub> was not significantly altered from baseline for either valdecoxib or placebo at any assessment time (p &gt; = 0.267), while significant differences from baseline were seen for naproxen at all assessment times when compared to placebo (p &lt; = 0.002). <h3>Conclusion</h3> The lack of effect on platelet aggregation and bleeding time would suggest that valdecoxib will have an improved clinical safety profile over conventional NSAIDs, particularly in patients for whom bleeding complications are a concern. Sponsored by Pharmacia Corporation and Pfizer, Inc.