tbuckley/cabot-search huggingface dataset:
SAT0609 WOMEN WITH METABOLIC SYNDROME AND GENERAL OBESITY ARE AT HIGHER RISK FOR SIGNIFICANT HYPERURICEMIA THAN MEN: RESULTS FROM THE 2016 KOREA NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEY
Authors: Yeonghee Eun, In-Young Kim, Eun-Jung Park, Ji-Young Chai, Kyung-Do Han, Hoon-Suk Cha, Eun-MI Koh, Hyungjin Kim, Jaejoon Lee
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Hyperuricemia is emerging as a potential biomarker and a predictor for metabolic syndrome (MetS) and its related complications. <h3>Objectives:</h3> We aimed this study to investigate the risk factors of hyperuricemia, particularly, the association of hyperuricemia with MetS and general obesity. <h3>Methods:</h3> We performed multivariate logistic regression analyses using the 2016 Korea National Health and Nutrition Examination Survey (KNHANES) data collected in a representative sample of Korean adults. Hyperuricemia was defined by serum uric acid level ≥7.0 mg/dl for men and ≥6.0 mg/dl for women. General obesity was based on body mass index (BMI) ≥25 kg/m<sup>2</sup>. <h3>Results:</h3> Among a total of 5,591 Korean adult participants, 685 (12.3%) individuals were classified as having hyperuricemia. Hyperuricemia was significantly associated with MetS in men (Odd ratio (OR): 1.74, 95% CI: 1.29-2.34) and women (OR: 2.47, 95% CI: 1.55-3.93) after adjustments for age, sex, smoking, alcohol, exercise, BMI and estimated glomerular filtration rate (eGFR). General obesity was also independently related to hyperuricemia in both sex (OR: 1.70, 95% CI: 1.31-2.19 in men, OR: 3.73, 95% CI: 2.57-5.41 in women). Among the components of MetS, elevated blood pressure, elevated triglyceride and reduced HDL-cholesterol in men, and increased waist circumference, hyperglycemia, elevated triglyceride in women were risk factors for hyperuricemia. In subgroup analyses, the presence of concomitant MetS and general obesity posed strikingly higher risk for hyperuricemia among women (OR: 7.24, 95% CI: 4.56-11.50 in women, versus, OR: 2.90, 95% CI: 2.12-3.96 in men) when compared to individuals free of neither conditions (OR: 1.00, referent). In addition, the risk of hyperuricemia has increased up to 6-fold by the presence of MetS and general obesity among young adults aged less than 40 years old. <h3>Conclusion:</h3> Hyperuricemia was independently associated with MetS and general obesity, regardless of sex. These increases in risk of hyperuricemia were more prominent in women. Among women, those who had both MetS and general obesity were at nearly 7-fold increased risk for hyperuricemia compared to those without both conditions. It may be considered to incorporate hyperuricemia as one of the components of MetS. <h3>References</h3> <h3> Disclosure of Interests:</h3> None declared
“Just stay at home” was lonely and terrifying
Authors: Lisa Jensen
Journal: BMJ (2020)

Just stay at home" was lonely and terrifying Lisa Jensen describes how covid-19 has affected her and how important empathy is as she faces the long term effects. Lisa JensenI became sick with covid-19 on 7 March.I was told to stay at home unless I thought I was dying.Those words might seem straightforward, but following them proved to be terrifying, lonely, and confusing.
Monosomy 7 and Co-Occurrent Genomic Aberrations Determine Chemotherapy Response in Acute Myeloid Leukemia (AML) Patients Using the Cellworks Omics Biology Model (CBM): Mycare-021-04
Authors: Michael Castro, Drew Watson, Ansu Kumar, Prashant Ramachandran Nair, Himanshu Grover, Diwyanshu Sahu, Subrat Mohapatra, Poornachandra G, Ashish Agarwal, Rakhi Purushothaman Suseela, Naga Ganesh, Mohammed Sauban, Chandan Kumar, Rahul K Raman, Divya Singh, Sayani Basu, Neelesh Lunkad, Nirjhar Mundkur, Michele Dundas Macpherson, Shweta Kapoor, Scott Howard
Journal: Blood (2020)
PIPAC-OX: A Phase I Study of Oxaliplatin-Based Pressurized Intraperitoneal Aerosol Chemotherapy in Patients with Peritoneal Metastases
Authors: Guowei Kim, Hon Lyn Tan, Raghav Sundar, Bettina Lieske, Cheng Ean Chee, Jingshan Ho, Asim Shabbir, Maria V. Babak, Wee Han Ang, Boon Cher Goh, Wei Peng Yong, Lingzhi Wang, Jimmy B.Y. So
Journal: Clinical Cancer Research (2020)

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel laparoscopic, intraperitoneal chemotherapy delivery technique aiming to improve drug distribution and tissue penetration to treat peritoneal metastases. Thus far, PIPAC oxaliplatin is conducted at an arbitrary dose of 92 mg/m2. We conducted a phase I study to establish safety and tolerability.We used a 3+3 dose-escalation design of PIPAC oxaliplatin for patients with peritoneal metastases from gastrointestinal tumors, after failure of at least first-line chemotherapy. Dose levels were planned at 45, 60, 90, and 120 mg/m2.This study included 16 patients with 24 PIPAC procedures (8 gastric; 5 colorectal; and 1 gallbladder, pancreas, and appendix cancer each). Median age and peritoneal cancer index (PCI) score were 62 years and 17, respectively. Two patients developed pancreatitis (grade 2 and 3) at 45 mg/m2, necessitating cohort expansion. Another patient developed grade 2 pancreatitis at 90 mg/m2. There were no other dose-limiting toxicities, and the highest-dose cohort (120 mg/m2) tolerated PIPAC well. Pharmacokinetic analyses demonstrated good linearity between dose and maximum concentration (r2 = 0.95) and AUC (r2 = 0.99). On the basis of RECIST, 62.5% and 50% had stable disease after one and two PIPAC procedures, respectively. A total of 8 patients underwent two PIPAC procedures, with improvement of median PCI and peritoneal regression grade score from 15 to 12 and 2.5 to 2.0, respectively.The recommended phase II dose is 120 mg/m2. Future studies should further delineate the efficacy and role of PIPAC oxaliplatin for peritoneal metastases.See related commentary by de Jong et al., p. 1830.
Sebaceous Carcinoma Incidence and Survival Among Solid Organ Transplant Recipients in the United States, 1987-2017
Authors: Michael R. Sargen, Elizabeth K. Cahoon, Charles F. Lynch, Margaret A. Tucker, Alisa M. Goldstein, Eric A. Engels
Journal: JAMA Dermatology (2020)

Risk of sebaceous carcinoma (SC), a rare skin cancer associated with Muir-Torre syndrome, is elevated among solid organ transplant recipients (SOTRs). However, population studies evaluating this association and assessing survival for posttransplant cases are lacking, and further understanding of SC epidemiology in this immunosuppressed population could provide etiologic and clinical insights.
Normal parents: Trans pregnancy and the production of reproducers
Authors: Elizabeth Dietz
Journal: International Journal of Transgender Health (2020)

Background Some trans people want to create families in a variety of ways that include pregnancy, but often face obstacles in doing so.Aims This paper explores how trans pregnancy is treated as exceptional and out of the ordinary by reproductive institutions.Methods Analysis of case studies demonstrates the ubiquity of institutional obstacles to trans pregnancy and how reproductive institutions unnecessarily render trans pregnancy exceptional.Results Reproductive institutions shape the kinds of people for whom achieving pregnancy is made easier, and often fail to imagine the possibility of trans parents. This failure of imagination is not rooted in biological fact, but rather in social logics that ought to be the site for transformations that expand access and shift provider attitudes.Discussion Trans parents are unexceptional in the sense that, even though they may experience relatively more concentrated forms of adversity, they share many reproductive capabilities and obstacles with cis parents. In light of that concentrated adversity and the epistemic insights it might generate, how might prospective trans parents engage with new reproductive technologies? How might these engagements render them moral pioneers called to make decisions about the sorts of people created using reproductive biotechnologies?
Associations Between Intake of Sugar‐Containing Beverages in Infancy With Liver Fat Accumulation at School Age
Authors: Madelon L. Geurtsen, Susana Santos, Romy Gaillard, Janine F. Felix, Vincent W. V. Jaddoe
Journal: Hepatology (2020)

Background and Aims Sugar‐containing beverage intake is a major risk factor for obesity in both children and adults and appears to be associated with NAFLD in adults. The purpose of this study was to examine the associations between sugar‐containing beverage intake in infancy and liver fat accumulation and NAFLD among school‐aged children. Approach and Results In a population‐based prospective cohort study of 1,940 infants, we assessed sugar‐containing beverage intake at 1 year with a validated Food Frequency Questionnaire. Liver fat fraction and NAFLD (liver fat fraction ≥5.0%) were assessed with MR. Higher sugar‐containing beverage intake in infancy was not associated with higher liver fat accumulation at 10 years of age when assessed continuously (SD, 0.03; 95% CI, 0.02, 0.07, per one‐serving/day increase of sugar‐containing beverage intake) or categorically ( P = 0.38). However, compared to infants with &lt;1.0 serving/day, those with &gt;2.0 servings/day had the highest odds of NAFLD at 10 years of age (OR, 3.02; 95% CI, 1.34, 6.83). These associations remained borderline significant after additional adjustment for sugar‐containing beverage intake and body mass index at school age ( P = 0.13). Stratified analyses showed stronger associations between sugar‐containing beverage intake in infancy and NAFLD at 10 years of age among children of mothers with lower educational attainment (OR, 1.48; 95% CI, 1.12, 1.97) and among children with overweight or obesity (OR, 1.47; 95% CI, 1.05, 2.07). Conclusions Higher sugar‐containing beverage intake in infancy was associated with NAFLD in school‐aged children, independent of sugar‐containing beverage intake and body mass index at school age. Limiting the intake of sugar‐containing beverages in infancy may help prevent liver steatosis at school age.
Telomere Length and CD49d Cooperate with IGHV Gene Status As Predictors of Long-Term Progression-Free Survival in CLL Patients Treated with FCR-Based Regimens
Authors: Andrea GS Pepper, Antonella Zucchetto, Kevin Norris, Erika Tissino, Jerry Polesel, Zarni Soe, David Allsup, Anna Hockaday, Pei Loo Ow, Peter Hillmen, Andrew Rawstron, Daniel Catovsky, Riccardo Bomben, Duncan M Baird, Christopher Fegan, Valter Gattei, Chris Pepper
Journal: Blood (2020)
Abstract 508: Nuclear Lamins At Enhancers: A New Hypothesis for Laminopathies
Authors: Kohta Ikegami, Stefano Secchia, Omar Almakki, Alexis V Stutzman, Sachie Ikegami, Natalia Ayres, Sunny Y Liu, Jason D Lieb, Ivan P Moskowitz
Journal: Circulation Research (2020)

The segregation of heterochromatin domains (LADs) at the nuclear periphery by the nuclear lamina, composed by polymerized nuclear Lamin A/C, provides a longstanding paradigm for the control of gene expression and for the mechanisms underlying Lamin-A/C-associated disorders, including progeria and cardiomyopathy. Here, we provide evidence supporting a novel paradigm that Lamin A/C functions as a transcription factor in the nuclear interior. We discovered that Ser22-phosphorylated Lamin A/C (pS22-Lamin A/C), required for lamin depolymerization during mitosis, populated the nuclear interior throughout the cell cycle. pS22-Lamin A/C ChIP-deq demonstrated localization at a large subset of putative active enhancers, not LADs. pS22-Lamin A/C-binding sites were co-occupied by the transcriptional activator c-Jun. In progeria patient-derived fibroblasts, a subset of pS22-Lamin A/C-binding sites were lost whereas new pS22-Lamin A/C-binding sites emerged. New pS22-Lamin A/C binding was accompanied by increased histone acetylation and increased c-Jun binding, whereas loss of pS22-Lamin A/C-binding was accompanied by loss of histone acetylation and c-Jun binding. New pS22-Lamin A/C enhancer binding in progeria was associated with upregulated expression of genes implicated in progeria pathophysiology, including cardiovascular disease. In contrast, alteration of LADs in progeria-patient cells could not explain the observed gene expression changes. These results suggest that Lamin A/C regulates gene expression by enhancer binding in the nuclear interior, independent of its function at the nuclear lamina, providing a new paradigm for the pathogenesis of lamin-associated disorders. pS22-Lamin A/C was also present in the nuclear interior of adult mouse cardiomyocytes. Cardiomyocyte-specific deletion of Lmna encoding Lamin A/C in adult mice caused extensive transcriptional changes in the heart and dilated cardiomyopathy, without apparent reduction of nuclear peripheral Lamin A/C. Disruption of the gene regulatory rather than LAD tethering function of Lamin A/C may underlie the pathogenesis of disorders caused by LMNA mutations, including cardiomyopathy.
New insights from SONAR indicate adding sodium glucose co-transporter 2 inhibitors to an endothelin receptor antagonist mitigates fluid retention and enhances albuminuria reduction
Authors: Hiddo J.L. Heerspink, Donald E. Kohan, Dick de Zeeuw
Journal: Kidney International (2020)

The diuretic effects achieved with sodium glucose co-transporter 2 inhibitors (SGLT2i) may offset fluid retaining effects of the endothelin receptor antagonist (ERA) atrasentan while effects on albuminuria and kidney protection of both drug classes may be complimentary due to distinct mechanisms of action. Here, post-hoc analysis of the SONAR trial, in patients with type 2 diabetes and chronic kidney disease, show that six-weeks treatment with combined SGLT2i/atrasentan versus atrasentan alone decreased body weight, a surrogate for fluid retention, and further decreased albuminuria. Thus, these promising findings support future clinical studies to characterize the long-term efficacy and safety of combined SGLT2i/ERA treatment.
Safety profile of upadacitinib in rheumatoid arthritis: integrated analysis from the SELECT phase III clinical programme
Authors: Stanley B Cohen, Ronald F van Vollenhoven, Kevin L Winthrop, Cristiano A F Zerbini, Yoshiya Tanaka, Louis Bessette, Ying Zhang, Nasser Khan, Barbara Hendrickson, Jeffrey V Enejosa, Gerd R Burmester
Journal: Annals of the Rheumatic Diseases (2020)

This integrated analysis presents the safety profile of upadacitinib, a Janus kinase inhibitor, at 15 mg and 30 mg once daily in patients with moderately to severely active rheumatoid arthritis (RA).
<i>PTG-300 Eliminates the Need for Therapeutic Phlebotomy in Both Low and High-Risk Polycythemia Vera Patients</i>
Authors: Marina Kremyanskaya, Yelena Ginzburg, Andrew T. Kuykendall, Abdulraheem Yacoub, Jay Yang, Suneel K Gupta, Frank Valone, Sarita Khanna, Srdan Verstovsek, Ronald Hoffman
Journal: Blood (2020)
Targeting 1q21 Amplification with APG2575 and Lenalidomide to Sensitize BCL-2 Inhibition with the Decrease of MCL-1 Protein in High Risk MM Models
Authors: Yan Xie, Chengcheng FU, Lingzhi Yan, Song Jin, Jingjing Shang, Xiaolan Shi, Jinlan Pan, Yan Yin, Tingting Mao, Jing Deng, Douglas D. Fang, Dajun Yang, Yifan Zhai, Shuang Yan, Yingying Zhai, Ying Yao, Panfeng Wang, Jing Wang, Depei Wu
Journal: Blood (2020)
AB0167 Efficiency of rehabilitation in the old patients periarthritis
Authors: EL Sidenco
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> We studied a group of 40 old patients with soft tissues sufferings (periarthritis) at the shoulder or hip. Patients accused pain and limited mobility, and at the clinical examination we found muscular hypotrophy and limitation of function in the shoulder or hip. <h3>Methods</h3> We applied an associated kinetic programme of stretching-strengthening- control and co-ordination exercises in two different periods of 15 days, supported by electro-thermo-massotherapy. The valuations were made at the beginning and the end of the programme, on a clinical score of valuation obtained by the clinical parameters; the results were statistically processing. <h3>Results</h3> We find from the beginning a large incidence of the periarthritis at the old patients (25,37%) and the preference for the women, larger in comparison with other ages (27 cases from the group of 40). Application of the kinetic programme, physically supported, significantly improved the pain (completely for the spontaneous and nocturnal pain, and over 70% for the pain at the motion). Limitation of mobility increased over 63,6%, even the functional remaining is limited at the old patient and the real possibilities of the kinetic programme display can be limited by the associated pathologies. Muscular hypotrophy had a medium response (improvement under 33,7%), because of the limited biological capital and also the associated pathologies which imposed the adaptation of the kinetic programme to the real effort?s possibilities. Global function of the upper limb increased over 77,5%. <h3>Conclusion</h3> We consider the soft tissues sufferings of the old patient indicated for the kinetic programme, adequately supported by physical proceedings; the associated cardiovascular diseases do not forbid the rehabilitation, kinetic programme specially, if the patients are well medically treated and the kinetic programme is well adapted at the real effort?s possibilities of the patients.
Abstract 551: Distinct Transcriptional Roles for Wildtype vs. Truncated Nrf2 in the Heart of Transgenic Mice
Authors: sini sunny, David Crossman, Gobinath Shanmugam, Namakkal S. Rajasekaran
Journal: Circulation Research (2020)

Background: Nuclear erythroid-2 like factor-2 (Nrf2), a redox-sensitive transcriptional regulator of cytoprotective and antioxidant genes. Despite the basal transcription of antioxidants/redox genes, forced activation of Nrf2 may lead to “reductive stress” (RS). In this study, we hypothesized that controlled vs. sustained activation of Nrf2 differentially regulates the myocardial transcriptome, which elucidates the transition of a physiological adaptation to pathological process. Methods: Cardiac specific Nrf2 transgenic mice expressing full length Nrf2 (FL-TG) and truncated Nrf2 (TR-TG), and their non-transgenic littermates (NTG) in the C57/BL6J backround at the age of 6-8 months were used for this study. Next generation RNA sequencing was performed using the myocardial mRNA obtained from FL-TG, TR-TG and NTG mice (n=3/group). Validation of the NGS data was carried out by qPCR analysis using specific primers for the targeted genes(n=4 to 6/group). Results: Analysis of the NGS data uncovered eccentric genomic profiles in the myocardium of mice with a 310 differentially regulated genes (DEGs) in FL-TG ( vs. NTG) and 472 DEGs in TR-TG ( vs. NTG). A closer evaluation reveals 397 and 237 DEGs commonly shared between FL-TG and TR-TG, respectively. STRING analysis revealed genomic networks involve in oxidoreductase, antioxidant and glutathione transferase were differentially altered between TL-TG vs. TR-TG groups. For instance, within the glutathione synthesis pathway, Gclm transcript was upregulated 6.0 fold (FL-TG) and 8.0 fold (TR-TG) when compared to NTG. Indeed, a significant douwnregulation of stress response genes Hspa1b (5.0 &amp; 2.0 fold) and Hsph1 (2.0 &amp; 2.2 fold) was apparent in between the groups. An eccentric cytoskeletal disarrangement ( Efnb3, Map1a, Acta ), an impaired protein quality control ( Bin1,Myl4 ) and a reduced cardiac function ( Timp4) were significantly downregulated in both the groups. Conclusion: These findings conclude that transgenic expression of wild-type vs. mutant forms of Nrf2 in the heart uniquely regulate the myocardial transcriptome, which might result in independent pathological processes.
SAT0087 The effect of meloxicam versus usual care nsaids for the treatment of osteoarthritis in a ususal care setting. the results of the improve trial
Authors: P Gagnier, G Singh, JI Reed, M Kobe, P Arnold, E Hwang
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Traditionally, NSAIDs have been the mainstays for managing symptoms of osteoarthritis (OA). While NSAIDs generally are considered to be effective in managing pain and inflammation, they frequently are associated with gastrointestinal side effects or lose their effectiveness leading to discontinuation of therapy or switching to another NSAID. These side effects can add significantly to the direct medical cost of managing the OA patient population. This suggests that there is dissatisfaction with current therapies on the part of the patient, physician or both. The time to discontinuation or change to another NSAID may be used as one measure that can examine the interrelated reasons for discontinuation, mainly efficacy and tolerability. Currently, there are no published randomised prospective studies that have examined the time to NSAID discontinuation; or NSAID switches and <h3>Objectives</h3> The objective of this study was to compare the percentage of treatment successes or failures in patients randomised to meloxicam 7.5 mg vs. usual care prescription NSAIDS in a variety of managed care settings (MCOs). A success was defined as a patient who started on their initially prescribed study NSAID and never received a different prescription NSAID during the trial. During the trial, the patient could have temporarily discontinued the new study prescription NSAID, restart the same drug and be considered a treatment success. A treatment failure was defined as a patient who started on an originally prescribed study NSAID and changed to another NSAID at any point during the trial. <h3>Methods</h3> This was a multicenter, randomised, parallel-group, open-label trial of meloxicam 7.5 mg versus usual care administration of prescription formulary NSAIDs for the treatment of patients with OA in a variety of MCO models. Patients with OA of the hip, knee, hand or spine were randomised to receive either meloxicam 7.5 mg or any other prescription NSAID that they had not previously been treated with for their OA based on the patients formulary. The study was designed to mirror actual MCO practices and not add costly and unnecessary study-driven procedures at enrolment and throughout the observation period. The treatment/observation period was 6 months in duration and assessments were made to determine the reasons for permanent discontinuation from the initial prescription NSAIDs, number of NSAID therapies, as well as the health care utilisation, efficacy and safety. <h3>Results</h3> There were 1,321 patients entered into the trial and approximately 67% of the patients were female and 95% Caucasian. The mean age was approximately 64 years and the mean duration of OA was over 9 years. Rates of NSAID switching and efficacy will be discussed. <h3>Conclusion</h3> The study was well accepted by physicians and patients.
Copy Number Signatures Predict Chromothripsis and Poor Clinical Outcome in Newly Diagnosed Multiple Myeloma Patients
Authors: Kylee H Maclachlan, Binbin Zheng-Lin, Venkata Yellapantula, Andriy Derkach, Even H Rustad, Benjamin Diamond, Malin Hultcrantz, Ahmet Dogan, Yanming Zhang, Gareth Morgan, Ola Landgren, Francesco Maura
Journal: Blood (2020)
Double-Hit Signature with <i>TP53</i> Abnormalities Predicts Poor Survival in Patients with Germinal Center Type Diffuse Large B-Cell Lymphoma Treated with R-CHOP
Authors: Joo Y Song, Anamarija M. Perry, Alex F. Herrera, Lu Chen, Pam Skrabek, Michel Nasr, Rebecca Ottesen, Janet Nikowitz, Victoria Bedell, Joyce Murata-Collins, Yuping Li, Christine McCarthy, Raju Pillai, Jinhui Wang, Xiwei Wu, Jasmine M. Zain, Leslie L. Popplewell, Larry W Kwak, Auayporn P. Nademanee, Joyce Niland, David W. Scott, Qiang Gong, Wing (John) C. Chan, Dennis D. Weisenburger
Journal: Blood (2020)