tbuckley/cabot-search huggingface dataset:
FRI0154 Leflunomide in a patient with glucocorticoid- and methotrexat- resistant takayasu?s arteritis
Authors: G Haberhauer, J Feyertag, EM Kittl, K Bauer, A Dunky
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Takayasu's arteritis (TA) is a chronic inflammatory large-vessel vasculitis of unknown cause, which involves the aorta and its major branches. Glucocorticosteroids (GC) and methotrexat (MTX) are the primary treatment to reduce the activity of vascular inflammation in TA. A subset of TA patients (&lt;15%) has chronic, unremittive disease and is unresponsive to GC + MTX therapy. Herein we describe our benefit experience with Leflunomide (LEFLU) therapy in patient with GC- and MTX-resistant TA. <h3>Objectives</h3> Case Report: A 28-year old Turkish female with (biopsy proved) TA, markedly elevated ESR of 96 mm/h, and elevated C-reactive protein (CRP) 73 mg/dl (normal Postoperative, after 6 month, MTX therapy was withdrawn and replaced by LEFLU (30 mg/day). Within the next 2 month GC was slowly tappered to 2 mg/day and then withdrawn. Six month after initiating LEFLU therapy, ESR (22 mm/h), CRP (12 mg/dl), SAA (8 mg/dl) and IL-6 (16 pg/ml) significantly decreased near to normal ranges. Even sCD44v5 decreased to 9 ng/ml. Blood pressure measurements were now 110/70 mmHg in the right arm, 90/55 mmHg in the left arm and radial pulses were palpable in both arms. The patient reported no syncopes, headache or any limitations of activities of daily living. ESR, CRP, SAA, IL-6 and sCD44v5 still remained in the last mentioned low ranges during the next two month of observation. <h3>Methods</h3> "*" <h3>Results</h3> "*" <h3>Conclusion</h3> In this case of GC+MTX resistant TA, LEFLU appears to be an effective (slow acting) and well tolerated agent to reduce the activity of inflammation. Extensive and long-term studies will be required to assess our single observation.
Using Functionality Rather than Elective Nature to Characterize Neurosurgeries During Pandemic Triage
Authors: Nathan A. Shlobin, Joshua M. Rosenow, Paul J. Ford
Journal: The American Journal of Bioethics (2020)

This article refers to:Ethical Challenges Arising in the COVID-19 Pandemic: An Overview from the Association of Bioethics Program Directors (ABPD) Task Force
Treatment-related changes in bone mineral density as a surrogate biomarker for fracture risk reduction: meta-regression analyses of individual patient data from multiple randomised controlled trials
Authors: Dennis M Black, Douglas C Bauer, Eric Vittinghoff, Li-Yung Lui, Andreas Grauer, Fernando Marin, Sundeep Khosla, Anne de Papp, Bruce Mitlak, Jane A Cauley, Charles E McCulloch, Richard Eastell, Mary L Bouxsein
Journal: The Lancet Diabetes & Endocrinology (2020)
Non-specific orbital inflammation: Current understanding and unmet needs
Authors: Min Joung Lee, Stephen R. Planck, Dongseok Choi, Christina A. Harrington, David J. Wilson, Roger A. Dailey, John D. Ng, Eric A. Steele, Bronwyn E. Hamilton, Sang In Khwarg, James T. Rosenbaum
Journal: Progress in Retinal and Eye Research (2020)
The Contribution of the Age Distribution of Cases to COVID-19 Case Fatality Across Countries
Authors: Nikkil Sudharsanan, Oliver Didzun, Till Bärnighausen, Pascal Geldsetzer
Journal: Annals of Internal Medicine (2020)

There is wide variation in coronavirus disease 2019 (COVID-19) case-fatality rates (CFRs) across countries, leading to uncertainty about the true lethality of the disease. A large part of this variation may be due to the ages of individuals who are tested and identified.
Abstract IA02: Novel strategies for early cancer detection and prevention: The Li-Fraumeni syndrome story
Authors: David Malkin, Nicholas Light, Valli Subrasi, Benjamin Brew, Sangeetha Paramathas, Arash Nabbi, Sergei Prykhozhij, Trevor Pugh, Jason Berman, Anna Goldenberg, Adam Shlien
Journal: Cancer Research (2020)

Abstract More than 85% of patients with Li-Fraumeni syndrome harbor germline TP53 mutations. The spectrum of mutations and the heterogeneity of tumor presentation (age of onset and type) within and between families is remarkable and indicates that modifiers must play an important role in defining the phenotype of each patient and each family. We recently reported the feasibility and utility of a clinical surveillance protocol for early detection of tumors in TP53 mutation carriers (Villani et al., Lancet Oncol 2016). Results from deep sequencing of the genome and epigenome of germline and tumor tissues of TP53 mutation carriers provide exciting new insight into the role of modifiers on both the functional activity of p53 in the germline as well as their influence on tumor onset, tumor spectrum, and clinical outcome/response to therapy. Data will be presented to support the creation of molecular algorithms that may be used in a precise manner to predict cancer onset, as well as to better define the molecular landscape of cancers that arise in TP53 mutation carriers. It is anticipated that the combined use of this germline and somatic landscape data can more effectively refine and guide the creation of personalized surveillance and chemoprevention strategies for these patients. Citation Format: David Malkin, Nicholas Light, Valli Subrasi, Benjamin Brew, Sangeetha Paramathas, Arash Nabbi, Sergei Prykhozhij, Trevor Pugh, Jason Berman, Anna Goldenberg, Adam Shlien. Novel strategies for early cancer detection and prevention: The Li-Fraumeni syndrome story [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr IA02.
Potential Elimination of Active <i>Taenia solium</i> Transmission in Africa
Authors: Sarah Gabriël, Kabemba E. Mwape, Emma C. Hobbs, Brecht Devleesschauwer, Inge Van Damme, Gideon Zulu, Chembensofu Mwelwa, Chishimba Mubanga, Maxwell Masuku, Moses Mambwe, Tine De Coster, Isaac K. Phiri, Dirk L. Berkvens, Angie Colston, Emmanuel Bottieau, Niko Speybroeck, Jennifer K. Ketzis, A. Lee Willingham, Chiara Trevisan, Pierre Dorny
Journal: New England Journal of Medicine (2020)

Potential Elimination of Active Taenia solium Transmission in AfricaTo the Editor: Taeniasis and cysticercosis due to Taenia solium are major foodborne parasitic zoonoses that severely affect public health, social, and economic sectors, with the burden of neurocysticercosis estimated at 2,788,426 disabilityadjusted life-years. 1 A study involving an integrated intervention program in humans and pigs showed elimination of transmission of T. solium in Peru. 2 This study provided important proof of concept; however, similar studies of T. solium elimination have not been completed in sub-Saharan Africa, where the prevalence of this infection and the level of poverty are higher than in Peru. 3 We conducted the CYSTISTOP study (Clinical Trials.govnumber, NCT02612896), which involved a 2-year integrated intervention in humans and pigs in eastern Zambia, where taeniasis and cysticercosis are hyperendemic, to evaluate the feasibility of eliminating T. solium in sub-Saharan Africa.The prevalence of porcine cysticercosis (the primary outcome measure, as determined by carcass dissection) and the prevalence of hu-
Transmission of viral hepatitis through blood transfusion in Sweden, 1968 to 2012
Authors: Viktor Dahl, Ammar Majeed, Agneta Wikman, Rut Norda, Gustaf Edgren
Journal: Eurosurveillance (2020)

Introduction Viral hepatitis remains a significant threat to transfusion safety, although largely mitigated by donor screening. Aim Our objective was to estimate the past and present burden of transfusion transmission of all types of viral hepatitis (A to E) and to find undiagnosed infections with hepatitis C virus (HCV). Method We performed a retrospective cohort study using a database of the entire computerised transfusion experience of Sweden from 1968 to 2012 and linking it to a nationwide database of notifiable infections. We then used two independent statistical approaches. Firstly, we tracked recipients of blood from donors with confirmed viral hepatitis. Secondly, we computed a donor-specific risk score, defined as the difference between the observed and the expected number of HCV infections among all previous recipients of all donors, where thresholds were determined using simulation. Results Among 1,146,307 transfused patients, more than 5,000 were infected with HCV. Transfusion transmission only occurred before 1992 when donor screening had been completely implemented. Overall, we found 44 donors and 1,180 recipients likely to be infected with HCV who were still alive but who remained undiagnosed. Conclusion There is still a substantial number of individuals in Sweden who have probably been infected with HCV through blood transfusion and who are still unaware of their infection. We recommend that a follow-up study should be conducted to validate the method we used by approaching these individuals and offer testing. This would also serve as an opportunity to offer treatment to those who remain infected.
Response to: ‘Should patients starting biologics be screened for COVID-19?’ by Cardenas-de la Garza<i>et al</i>
Authors: Robert B M Landewé, Hendrik Schulze-Koops
Journal: Annals of the Rheumatic Diseases (2020)

<h3>BACKGROUND AND PURPOSE:</h3> Treatment-related changes and recurrent tumors often have overlapping features on conventional MR imaging. The purpose of this study was to assess the utility of DWI and DSC perfusion imaging alone and in combination to differentiate treatment-related effects and recurrent high-grade gliomas. <h3>MATERIALS AND METHODS:</h3> We retrospectively identified 68 consecutive patients with high-grade gliomas treated by surgical resection followed by radiation therapy and temozolomide, who then developed increasing enhancing mass lesions indeterminate for treatment-related changes versus recurrent tumor. All lesions were diagnosed by histopathology at repeat surgical resection. ROI analysis was performed of the enhancing lesion on the ADC and DSC maps. Measurements made by a 2D ROI of the enhancing lesion on a single slice were recorded as ADC<sub>Lesion</sub> and rCBV<sub>Lesion</sub>, and measurements made by the most abnormal small fixed diameter ROI as ADC<sub>ROI</sub> and rCBV<sub>ROI</sub>. Statistical analysis was performed with Wilcoxon rank sum tests with <i>P</i> = .05. <h3>RESULTS:</h3> Ten of the 68 patients (14.7%) had treatment-related changes, while 58 patients (85.3%) had recurrent tumor only (<i>n</i> = 19) or recurrent tumor mixed with treatment effect (<i>n</i> = 39). DWI analysis showed higher ADC<sub>Lesion</sub> in treatment-related changes than in recurrent tumor (<i>P</i> = .003). DSC analysis revealed lower relative cerebral blood volume (rCBV)<sub>Lesion</sub> and rCBV<sub>ROI</sub> in treatment-related changes (<i>P</i> = .003 and <i>P</i> = .011, respectively). Subanalysis of patients with suspected pseudoprogression also revealed higher ADC<sub>Lesion</sub> (<i>P</i> = .001) and lower rCBV<sub>Lesion</sub> (<i>P</i> = .028) and rCBV<sub>ROI</sub> (<i>P</i> = .032) in treatment-related changes. Applying a combined ADC<sub>Lesion</sub> and rCBV<sub>Lesion</sub> model did not outperform either the ADC or rCBV metric alone. <h3>CONCLUSIONS:</h3> Treatment-related changes showed higher diffusion and lower perfusion than recurrent tumor. Similar correlations were found for patients with suspected pseudoprogression.
Overexpression of arylsulfatase B or of galactose-6-sulfatase leads to increased expression of syndecan-1 and decorin and increased chondroitin sulfate in MCF-7 cells
Authors: Sumit Bhattacharyya, Kumar Kotlo, Nitika Pant, Sagar Shukla, Robert Danziger, Joanne Tobacman
Journal: Cancer Research (2007)

2812  Arylsulfatase B (ASB) and galactose-6-sulfatase (GALNS) are human lysosomal enzymes that can modify the glycosaminoglycans (GAGs) chondroitin 4-sulfate (C4S;CSA) and chondroitin 6-sulfate (C6S;CSC), by removing sulfate groups of the target disaccharide at the non-reducing end. This function has clinical significance in the genetic diseases MPS VI and MPS IVA, associated with deficient ASB or GALNS activity, respectively. Previously, we reported that activity of GALNS and ASB in MCF-7 cells is 2-8 fold less than in normal primary mammary epithelial and myoepithelial cells. To determine whether these enzymes may have a role in modification of the GAGs on vital cell surface proteoglycans in malignant cells, we overexpressed these enzymes in MCF-7 cells and determined the impact on expression of syndecan and decorin by QRT-PCR, and on C4S and C6S by Western blot. Since proteoglycans, such as syndecan and decorin, are characterized and differentiated by their GAG side chains, changes in sulfatase function may have relevance for altered cell-cell interactions of malignant cells. MCF-7 cells, grown in phenol-red free RPMI with 10% FBS and Pen-Strep antibiotics, were transiently transfected with full-length ASB (OriGene; NM_000046) or GALNS (Origene; NM_00512.3) in pCMV6-XL4 vector with LipofectamineTM 2000 (Invitrogen). Cell lysate was harvested for RNA extraction or enzyme activity assay at 72 hours. Baseline ASB activity rose from 53.4 (±1.2) to 100.5 (±4.8) nmol/hr/mg protein, an 88% increase. Baseline GALNS activity increased from 3.6 to 8.2 nmol/hr/mg protein, a 228% increase. Quantitative PCR demonstrated 2.2-fold increase in transcript abundance of syndecan-1 and 5.2-fold increase in expression of decorin following overexpression of ASB. Following overexpression of GALNS, there was 3.0-fold increase in syndecan-1 and 2.3-fold increase in decorin transcript expression, compared to control vector transfections. Changes are statistically significant (p
The Burden and Trends of Primary Liver Cancer Caused by Specific Etiologies from 1990 to 2017 at the Global, Regional, National, Age, and Sex Level Results from the Global Burden of Disease Study 2017
Authors: Longfei Lin, Lei Yan, Yuling Liu, Changhai Qu, Jian Ni, Hui Li
Journal: Liver Cancer (2020)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Liver cancer is one of the leading causes of cancer-related deaths worldwide. The primary causes of liver cancer include hepatitis B virus (HBV), hepatitis C virus (HCV), alcohol consumption, nonalcoholic fatty liver disease, and other factors. &lt;b&gt;&lt;i&gt;Aims:&lt;/i&gt;&lt;/b&gt; The objective of this study was to evaluate the global and sex-, age-, region-, country-, and etiology-related liver cancer burden, as well as the trends in liver cancer caused by different etiologies. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; The causes of liver cancer from 1990 to 2017, including global, regional, and national liver cancer incidence, mortality, and etiology, were collected from the Global Burden of Disease study 2017, and the time-dependent change in the trends of liver cancer burden was evaluated by annual percentage change. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; The global liver cancer incidence and mortality have been increasing. There were 950,000 newly-diagnosed liver cancer cases and over 800,000 deaths in 2017, which is more than twice the numbers recorded in 1990. HBV and HCV are the major causes of liver cancer. HBV is the major risk factor of liver cancer in Asia, while HCV and alcohol abuse are the major risk factors in the high sociodemographic index and high human development index regions. The mean onset age and incidence of liver cancer with different etiologies have gradually increased in the past 30 years. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; The global incidence is still rising and the causes have national, regional, or population specificities. More targeted prevention strategies must be developed for the different etiologic types in order to reduce liver cancer burden.
SP0177 Partnership in action – how patient and professional organisations are working together in the uk
Authors: S Edwards
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> With the advent of patient empowerment and self-management, it is more important than ever that people with arthritis/rheumatism and those who treat them understand each others' needs and are able to work together. National organisations of patients and professionals have an important role to play in promoting partnership and mutual understanding. BLAR is an umbrella group which brings patient and professional organisations together to work for better services for people with arthritis/rheumatism in the UK. We have 23 Member organisations. We promote partnership and communication at a local and national level through a number of ways, for example: A multi-disciplinary project to agree and audit patient-centred standards of care. Establishing local networks of service users, health professionals and patient groups. Joint parliamentary lobbying for higher priority for arthritis/rheumatism. Joint policy development on issues of mutual concern. Workshops and meetings for service users and professionals to exchange information and best practice. <h3>Results</h3> These projects have been very successful, and have demonstrated that partnership can be beneficial to both patient and professional organisations. We have also learned that by working together, we strengthen our voice. Partnership is not possible on every issue, and there will always be differences of opinion. However, we have succeeded in building lasting partnerships on key issues.
Early Features of Progressive Hemifacial Atrophy—Clinical and Imaging Findings
Authors: Krystal M. Jones, Jennifer K. Tan, Ahmad I. Alomari, Mary Beth Son, Ruth Ann Vleugels, John B. Mulliken, Marilyn G. Liang
Journal: JAMA Dermatology (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Targeting NFATc4 attenuates non-alcoholic steatohepatitis in mice
Authors: Meng Du, Xiaojing Wang, Lin Yuan, Bing Liu, Xiaoxiang Mao, Dandan Huang, Liu Yang, Kun Huang, Fengxiao Zhang, Yan Wang, Xi Luo, Cheng Wang, Jiangtong Peng, Minglu Liang, Dan Huang, Kai Huang
Journal: Journal of Hepatology (2020)
Clinical <i>BRCA1/2</i> Reversion Analysis Identifies Hotspot Mutations and Predicted Neoantigens Associated with Therapy Resistance
Authors: Stephen J. Pettitt, Jessica R. Frankum, Marco Punta, Stefano Lise, John Alexander, Yi Chen, Timothy A. Yap, Syed Haider, Andrew N.J. Tutt, Christopher J. Lord
Journal: Cancer Discovery (2020)

Abstract Reversion mutations in BRCA1 or BRCA2 are associated with resistance to PARP inhibitors and platinum. To better understand the nature of these mutations, we collated, codified, and analyzed more than 300 reversions. This identified reversion “hotspots” and “deserts” in regions encoding the N and C terminus, respectively, of BRCA2, suggesting that pathogenic mutations in these regions may be at higher or lower risk of reversion. Missense and splice-site pathogenic mutations in BRCA1/2 also appeared less likely to revert than truncating mutations. Most reversions were &amp;lt;100 bp deletions. Although many deletions exhibited microhomology, this was not universal, suggesting that multiple DNA-repair processes cause reversion. Finally, we found that many reversions were predicted to encode immunogenic neopeptides, suggesting a route to the treatment of reverted disease. As well as providing a freely available database for the collation of future reversion cases, these observations have implications for how drug resistance might be managed in BRCA-mutant cancers. Significance: Reversion mutations in BRCA genes are a major cause of clinical platinum and PARP inhibitor resistance. This analysis of all reported clinical reversions suggests that the position of BRCA2 mutations affects the risk of reversion. Many reversions are also predicted to encode tumor neoantigens, providing a potential route to targeting resistance. This article is highlighted in the In This Issue feature, p. 1426
Effect of a quality improvement package for intrapartum and immediate newborn care on fresh stillbirth and neonatal mortality among preterm and low-birthweight babies in Kenya and Uganda: a cluster-randomised facility-based trial
Authors: Dilys Walker, Phelgona Otieno, Elizabeth Butrick, Gertrude Namazzi, Kevin Achola, Rikita Merai, Christopher Otare, Paul Mubiri, Rakesh Ghosh, Nicole Santos, Lara Miller, Nancy L Sloan, Peter Waiswa
Journal: The Lancet Global Health (2020)

Although gains in newborn survival have been achieved in many low-income and middle-income countries, reductions in stillbirth and neonatal mortality have been slow. Prematurity complications are a major driver of stillbirth and neonatal mortality. We aimed to assess the effect of a quality improvement package for intrapartum and immediate newborn care on stillbirth and preterm neonatal survival in Kenya and Uganda, where evidence-based practices are often underutilised.This unblinded cluster-randomised controlled trial was done in western Kenya and eastern Uganda at facilities that provide 24-h maternity care with at least 200 births per year. The study assessed outcomes of low-birthweight and preterm babies. Eligible facilities were pair-matched and randomly assigned (1:1) into either the intervention group or the control group. All facilities received maternity register data strengthening and a modified WHO Safe Childbirth Checklist; facilities in the intervention group additionally received provider mentoring using PRONTO simulation and team training as well as quality improvement collaboratives. Liveborn or fresh stillborn babies who weighed between 1000 g and 2500 g, or less than 3000 g with a recorded gestational age of less than 37 weeks, were included in the analysis. We abstracted data from maternity registers for maternal and birth outcomes. Follow-up was done by phone or in person to identify the status of the infant at 28 days. The primary outcome was fresh stillbirth and 28-day neonatal mortality. This trial is registered with ClinicalTrials.gov, NCT03112018.Between Oct 1, 2016, and April 30, 2019, 20 facilities were randomly assigned to either the intervention group (n=10) or the control group (n=10). Among 5343 eligible babies in these facilities, we assessed outcomes of 2938 newborn and fresh stillborn babies (1447 in the intervention and 1491 in the control group). 347 (23%) of 1491 infants in the control group were stillborn or died in the neonatal period compared with 221 (15%) of 1447 infants in the intervention group at 28 days (odds ratio 0·66, 95% CI 0·54-0·81). No harm or adverse effects were found.Fresh stillbirth and neonatal mortality among low-birthweight and preterm babies can be decreased using a package of interventions that reinforces evidence-based practices and invests in health system strengthening.Bill & Melinda Gates Foundation.