tbuckley/cabot-search huggingface dataset:
AB1206 OCULAR SARCOIDOSIS AND CLUSTERS OF CLINICAL ASSOCIATIONS. STUDY OF A SERIES OF 383 PATIENTS WITH SYSTEMIC SARCOIDOSIS FROM A SINGLE UNIVERSITY HOSPITAL
Authors: C. Alvarez Reguera, J. J. Gaitán-Valdizán, R. Fernández-Ramón, R. Demetrio-Pablo, R. Blanco
Journal: Annals of the Rheumatic Diseases (2020)

Background: Sarcoidosis is an inflammatory disease which can affect multiple organs. The most frequent affected organs are lungs, skin and eyes (1-5). Ocular involvement is a severe complication. Objectives: To assess the association of ocular sarcoidosis with other clinical domains. Methods: Study of a large cohort of systemic sarcoidosis from a single tertiary university hospital. All consecutive patients were diagnosed with systemic sarcoidosis from January 1, 1999 to January 1, 2019 according the ATS/ERS/WASOG criteria (6). Results: 41 (22 women/19 men) of 383 (10.7%) patients had ocular involvement, mean age 44.8±16 years. Lung was the most common affected organ associated with ocular sarcoidosis (n=36; 87.8%) followed by skin (n=14; 34.1%), joints (n=12; 29.3%) and neurological affection (n=8; 19.5%). Ocular sarcoidosis presents a higher percentage of renal and neurological affection compared to organs affected in general sarcoidosis of our larger cohort (12% vs 6% and 19.5 vs 7%; respectively) (FIGURE). Conclusion: The proportion of clinical domains affected in ocular sarcoidosis is mostly similar to global sarcoidosis, except the neurological (which almost is threefold) and renal (which doubles) affection. Hence, the importance of being aware of neurological and renal complications when ocular affection is present. References: [1]Riancho-Zarrabeitia L, et al. Semin Arthritis Rheum. 2015; 45:361-8. [2]Calvo-Río V, et al. Clin Exp Rheumatol. 2014; 32:864-8. [3]Riancho-Zarrabeitia L, et al. Clin Exp Rheumatol. 2014; 32:275-84. [4]Vegas-Revenga N, et al. Am J Ophthalmol. 2019; 200:85-94. [5]Calvo-Río V, et al. Clin Exp Rheumatol. 2014;32 (4 Suppl 84): S54-7. [6]Costabel U, Hunninghake GW. Eur Respir J 1999; 14: 735-737 FIGURE. Comparison between distribution of organs affected in ocular sarcoidosis (left) and distribution of organs affected in general sarcoidosis (right) Disclosure of Interests: Carmen Alvarez Reguera: None declared, Jorge Javier Gaitán-Valdizán: None declared, Raúl Fernández-Ramón: None declared, Rosalía Demetrio-Pablo: None declared, Ricardo Blanco Grant/research support from: Abbvie, MSD and Roche, Consultant of: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Lilly and MSD
Hiatus hernia and interstitial lung abnormalities
Authors: Peter M. George, Tomoyuki Hida, Rachel K. Putman, Takuya Hino, Sujal R. Desai, Anand Devaraj, Sacheen Kumar, John A. Mackintosh, Vilmundur Gudnason, Hiroto Hatabu, Gunnar Gudmundsson, Gary M. Hunninghake
Journal: European Respiratory Journal (2020)

<b>Hiatus hernia is not associated with ILA or its progression, but is twice as prevalent in those with UIP than other subtypes and those without ILA. Moderate to large hiatus hernia is strongly linked to an increased risk of mortality across 4885 participants</b>https://bit.ly/3gy7yq7
Immunotherapy of Ipilimumab and Nivolumab in Patients with Advanced Neuroendocrine Tumors: A Subgroup Analysis of the CA209-538 Clinical Trial for Rare Cancers
Authors: Oliver Klein, Damien Kee, Ben Markman, Michael Michael, Craig Underhill, Matteo S. Carlino, Louise Jackett, Caroline Lum, Clare Scott, Adnan Nagrial, Andreas Behren, Jane Y. So, Jodie Palmer, Jonathan Cebon
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Combination immunotherapy with anti–CTLA-4 and anti–PD-1 blockade has demonstrated significant clinical activity across several tumor types. Neuroendocrine tumors (NET) are a heterogeneous group of rare tumors with limited treatment options. CA209-538 is a clinical trial of combination immunotherapy with ipilimumab and nivolumab in rare cancers, including advanced NETs. Patients and Methods: CA209-538 is a prospective multicenter clinical trial in patients with advanced rare cancers. Patients received treatment with nivolumab at a dose of 3 mg/kg and ipilimumab at 1 mg/kg every three weeks for four doses, followed by nivolumab 3 mg/kg every two weeks and continued for up to 96 weeks, until disease progression or the development of unacceptable toxicity. Response was assessed every 12 weeks by RECIST 1.1. The primary endpoint was clinical benefit rate (CBR; complete remission + partial remission + stable disease). Results: Twenty-nine patients with advanced NETs received treatment. Three (10%) patients had low-, 13 (45%) had intermediate-, and 13 (45%) had high-grade tumors; lung was the most common primary site (39%). The objective response rate was 24% with a CBR of 72%; 43% of patients with pancreatic neuroendocrine neoplasms (NEN), and 33% of patients with atypical bronchial carcinoid achieved an objective response. The median progression-free survival was 4.8 months [95% confidence interval (CI): 2.7–10.5] and overall survival was 14.8 months (95% CI: 4.1–21.3). Immune-related toxicity was reported in 66% of patients with 34% experiencing grade 3/4 events. Conclusions: Combination immunotherapy with ipilimumab and nivolumab demonstrated significant clinical activity in subgroups of patients with advanced NETs including patients with atypical bronchial carcinoid and high-grade pancreatic NENs.
Detection of SARS-CoV-2 RNA in fecal specimens of patients with confirmed COVID-19: A meta-analysis
Authors: Martin CS Wong, Junjie Huang, Christopher Lai, Rita Ng, Francis K.L. Chan, Paul K.S. Chan
Journal: Journal of Infection (2020)

Recent studies showed that SARS-CoV-2 RNA may be found in fecal specimens of COVID-19 patients, but the sample size is limited. This systematic review and meta-analysis examined the detection rate of SARS-CoV-2 RNA in fecal specimens of these patients according to their clinical characteristics.
Spatially regularized parametric map reconstruction for fast magnetic resonance fingerprinting
Authors: Fabian Balsiger, Alain Jungo, Olivier Scheidegger, Pierre G. Carlier, Mauricio Reyes, Benjamin Marty
Journal: Medical Image Analysis (2020)

Magnetic resonance fingerprinting (MRF) provides a unique concept for simultaneous and fast acquisition of multiple quantitative MR parameters. Despite acquisition efficiency, adoption of MRF into the clinics is hindered by its dictionary matching-based reconstruction, which is computationally demanding and lacks scalability. Here, we propose a convolutional neural network-based reconstruction, which enables both accurate and fast reconstruction of parametric maps, and is adaptable based on the needs of spatial regularization and the capacity for the reconstruction. We evaluated the method using MRF T1-FF, an MRF sequence for T1 relaxation time of water (T1H2O) and fat fraction (FF) mapping. We demonstrate the method's performance on a highly heterogeneous dataset consisting of 164 patients with various neuromuscular diseases imaged at thighs and legs. We empirically show the benefit of incorporating spatial regularization during the reconstruction and demonstrate that the method learns meaningful features from MR physics perspective. Further, we investigate the ability of the method to handle highly heterogeneous morphometric variations and its generalization to anatomical regions unseen during training. The obtained results outperform the state-of-the-art in deep learning-based MRF reconstruction. The method achieved normalized root mean squared errors of 0.048 $\pm$ 0.011 for T1H2O maps and 0.027 $\pm$ 0.004 for FF maps when compared to the dictionary matching in a test set of 50 patients. Coupled with fast MRF sequences, the proposed method has the potential of enabling multiparametric MR imaging in clinically feasible time.
Clostridioides difficile Senses and Hijacks Host Heme for Incorporation into an Oxidative Stress Defense System
Authors: Reece J. Knippel, Aaron G. Wexler, Jeanette M. Miller, William N. Beavers, Andy Weiss, Valérie de Crécy-Lagard, Katherine A. Edmonds, David P. Giedroc, Eric P. Skaar
Journal: Cell Host & Microbe (2020)
SAT0541 THE SEVERITY OF FMF MAY BE ASSOCIATED WITH CO-MORBIDITIES
Authors: M. E. Tezcan, N. Şen, M. Yilmaz, Ö. Volkan, E. Tükel, S. Yilmaz-Oner
Journal: Annals of the Rheumatic Diseases (2020)

Background: Familial Mediterranean fever (FMF) is an auto inflammatory disease with recurrent attacks of serositis. Frequent attacks and disease related sequels may be associated with co-morbidities in FMF patients. Objectives: One of the tools for evaluating the FMF severity is the international severity scoring system for FMF (ISSF) 1 . This score includes disease related sequels, acute phase measurements, attack features and exertional leg pain. Therefore, more severe disease may be link with subclinical inflammation, amyloidosis and frequent, prolonged and widespread attacks. All these components may augment the frequency of non-disease related co-morbidities. Methods: We enrolled 158 FMF patients who fulfilled modified Tel - Hashomer Diagnosis Criteria2. The patients dichotomized based upon disease severity (mild disease or severe disease). Patients with ISSF scores lower or equal to 2 were accepted to have mild disease. Then, we compared frequency of non-disease related co-morbidities between the groups. These co-morbidities are hypertension, hypothyroidism, hyperthyroidism cardiovascular diseases, coronary artery diseases, cerebrovascular diseases, chronic renal disease (non-FMF related), chronic obstructive pulmonary diseases, and diabetes mellitus. This study was approved by the Local Research Ethics Committee and carried out in compliance with the Helsinki Declaration. All the patients gave written informed consent. P-value lower than 0.05 was considered as statistically significant. Results: Demographic features, disease duration, smoking history and body mass index (BMI) were similar between the groups. Frequency of co-morbidity in severe disease group was statistically higher than mild disease group (p=0.02). Most frequent co-morbidity was hypertension in both groups. Table. Features of mild and severe FMF groups Mild (n=135) Severe (n=23) p Gender (M/F) 47/88 11/12 0.23 Age 36.4±11.3 36.5±14.3 0.68 Smoking (%) 38 (28.1) 5 (21.7) 0.52 BMI (kg/m 2 ) 24.3±9.2 24.0±8.9 0.34 Disease duration (year) 7.7±11.3 8.6±14.3 0.09 Amyloidosis (%) 2 (1.4) 3 (13.0) 0.02 Exon 10 homozygote (%) 35 (25.9) 9 (39.1) 0.19 Colchicine dosage (mg/day) 1.2±0.4 1.4±0.5 0.02 ISSF scores 0.7 ±0.7 3.4±0.5 &lt;0.001 Co-morbidity (%) 25 (18.5) 9 (39.1) 0.02 Conclusion: In our FMF patient cohort, we found that severity of the disease may be associated with higher frequency of co-morbidities. Therefore, clinicians should be aware of the high possibility of co-morbidities in patients with more severe FMF and addressed these co-morbidities timely and properly. References: [1]Demirkaya E, et al. Development and initial validation of international severity scoring system for familial Mediterranean fever (ISSF). Ann Rheum Dis 2016; 75 :1051-6. [2]Berkun Y, et al. Diagnostic criteria of familial Mediterranean fever. Autoimmun Rev 2014; 13 :388-90. Acknowledgments: None Disclosure of Interests: None declared
Engineering Mono‐Chalcogen Nanomaterials for Omnipotent Anticancer Applications: Progress and Challenges
Authors: Chenyang Xing, Peng Yin, Zhengchun Peng, Han Zhang
Journal: Advanced Healthcare Materials (2020)

Abstract Belonging to the chalcogen group, the elements selenium (Se) and tellurium (Te) are located in Group VI‐A of the periodic table. Zero‐valent nanodimensioned Se (nano‐Se) and Te (nano‐Te) have displayed important biomedical applications in recent years. The past two decades have witnessed an explosion in novel cancer treatment strategies using nano‐Se and nano‐Te as aggressive weapons against tumors. Indeed, they are both inorganic nanomedicines that suppress tumor cell proliferation, diffusion, and metastasis. Abundant synthesis strategies for rational and precise surface decoration of nano‐Se and nano‐Te make them significant players in resisting cancers by means of powerful multi‐modal treatment methods. This review focuses on the design and engineering of nano‐Se‐ and nano‐Te‐based nanodelivery systems and their precise uses in cancer treatment. The corresponding anticancer molecular mechanisms of nano‐Se and nano‐Te are discussed in detail. Given their different photo‐induced behaviors, the presence or absence of near infrared illumination is used as a defining characteristic when describing the anticancer applications of nano‐Se and nano‐Te. Finally, the challenges and future prospects of nano‐Se and nano‐Te are summarized and highlighted.
Complementary autophagy inhibition and glucose metabolism with rattle-structured polydopamine@mesoporous silica nanoparticles for augmented low-temperature photothermal therapy and<i> in vivo</i> photoacoustic imaging
Authors: Leihou Shao, Yunhao Li, Feifei Huang, Xuan Wang, Jianqing Lu, Fan Jia, Zian Pan, Xinyue Cui, Guanglu Ge, Xiongwei Deng, Yan Wu
Journal: Theranostics (2020)

Rattle-structured nanoparticles with movable cores, porous shells and hollow interiors have shown great effectiveness in drug delivery and cancer theranostics.Targeting autophagy and glucose have provided alternative strategies for cancer intervention therapy.Herein, rattle-structured polydopamine@mesoporous silica nanoparticles were prepared for in vivo photoacoustic (PA) imaging and augmented low-temperature photothermal therapy (PTT) via complementary autophagy inhibition and glucose metabolism.Methods: The multifunctional rattle-structured nanoparticles were designed with the nanocore of PDA and the nanoshell of hollow mesoporous silica (PDA@hm) via a four-step process.PDA@hm was then loaded with autophagy inhibitor chloroquine (CQ) and conjugated with glucose consumer glucose oxidase (GOx) (PDA@hm@CQ@GOx), forming a corona-like structure nanoparticle.Results: The CQ and GOx were loaded into the cavity and decorated onto the surface of PDA@hm, respectively.The GOx-mediated tumor starvation strategy would directly suppress the expression of HSP70 and HSP90, resulting in an enhanced low-temperature PTT induced by PDA nanocore.In addition, autophagy inhibition by the released CQ made up for the loss of low-temperature PTT and starvation efficiencies by PTT-and starvation-activated autophagy, realizing augmented therapy efficacy.Furthermore, the PDA nanocore in the PDA@hm@CQ@GOx could be also used for PA imaging.Conclusion: Such a "drugs" loaded rattle-structured nanoparticle could be used for augmented low-temperature PTT through complementarily regulating glucose metabolism and inhibiting autophagy and in vivo photoacoustic imaging.
Covid-19: Low dose steroid cuts death in ventilated patients by one third, trial finds
Authors: Elisabeth Mahase
Journal: BMJ (2020)

Covid-19: Low dose steroid cuts death in ventilated patients by one third, trial finds Elisabeth MahaseLow dose dexamethasone reduces deaths in patients hospitalised with covid-19 who need ventilation, according to preliminary results from the RECOVERY trial.The drug was also found to reduce deaths by one fifth in other hospitalised patients receiving oxygen only, but no benefit was seen among covid-19 patients who did not need respiratory support.1
Abstract B10: Manipulating translesion synthesis proteins MAGE-A4 and RAD18 in a murine model of oral cancer
Authors: Bethany L. Wagner, Jason Guo, Yanzhe Gao, Cyrus Vaziri, Scott E. Williams
Journal: Clinical Cancer Research (2020)

Abstract Head and neck squamous cell carcinomas (HNSCCs) account for 6% of cancers worldwide. Because of their link to carcinogens such as alcohol and tobacco, HNSCCs are characterized by a high mutational burden and genome instability. Cancer recurrence due to chemoresistance, or a tolerance of chemotherapy-induced mutations, is the major cause of mortality in HNSCCs. DNA damage response pathways, such as translesion synthesis (TLS), are activated in response to genotoxic stress, including from conventional chemotherapy. The TLS pathway facilitates repair of certain types of mutations and thus is important for DNA damage tolerance. However, TLS polymerases are error-prone and therefore, paradoxically, may promote genome instability. In this way, elevated or “pathologic” TLS in the context of a cancer cell may be a “double-edged sword,” conferring damage tolerance but at the expense of introducing additional mutations that could fuel tumor growth. We have previously shown that melanoma antigen A4 (MAGE-A4) recruits the E3 ubiquitin ligase Rad18 to stalled replication forks where it monoubiquitinates PCNA to recruit TLS polymerases to bypass the lesion. In HNSCC, MAGE-A4 overexpression correlates with both increased mutational burden and worse prognosis. We hypothesize that aberrant high MAGE-A4 expression tolerizes cancer cells to excessive mutations, making them invulnerable to the DNA-damaging effects of traditional chemotherapies. In order to gain a better understanding of the consequences of MAGE-A4 overexpression and TLS activation in oral tumors in vivo, we created a genetically engineered mouse model that expresses MAGE-A4 under the control of an epithelial-specific Cre driver. When treated with the potent mutagen 4NQO in their drinking water, both transgenic and control mice developed oral tumors. The collected squamous cell carcinomas were analyzed using whole-exome sequencing and immunofluorescence to examine whether MAGE-A4+ tumors gained more mutations and were more invasive than MAGE-A4- or RAD18 KO tumors. Together, these data provide a greater understanding of MAGE-A4 and RAD18 biology and TLS in oral cancers. Citation Format: Bethany L. Wagner, Jason Guo, Yanzhe Gao, Cyrus Vaziri, Scott E. Williams. Manipulating translesion synthesis proteins MAGE-A4 and RAD18 in a murine model of oral cancer [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr B10.
Pain and analgesic use in men with metastatic prostate cancer
Authors: E. M. Basch, L. Sit, M. Fruscione, L. Burke, R. Kane, D. George, M. A. Carducci, P. Matthew, T. M. Beer, H. I. Scher
Journal: Journal of Clinical Oncology (2009)

e20515 Background: Pain is an important endpoint in metastatic prostate cancer and was the basis for the 1996 FDA approval of mitoxantrone. Standards for pain assessment have evolved, and a 2006 draft FDA guidance provides new recommendations for patient- reported outcomes. Contemporary palliation models generally require pain reduction starting from baseline worst pain scores of ≥4/10, and progression models require a sufficient proportion of patients’ pain scores to worsen in order to assure an adequate effect size. The prevalence and distribution of pain severity at specific points in the prostate cancer disease continuum are not well defined. Consequently, it is unclear if sufficient numbers of patients are available to conduct prospective studies using pain palliation or prevention as primary endpoints. Methods: A questionnaire that includes the Brief Pain Inventory and additional pain/analgesia items was developed as a collaboration between the DOD/PCF-supported Prostate Cancer Clinical Trials Consortium (PCCTC) and FDA Study Endpoints and Labeling Design (SEALD) team. IRB waivers were obtained for anonymous administration at 5 PCCTC institutions (Sloan-Kettering, Duke, Johns Hopkins, Anderson, OHSU). Administration is ongoing. Results: Between August-December 2008, 325 men with prostate cancers representing different disease states being seen in outpatient clinics of participating centers were each queried once. Median age was 70 (range 49–87). More than half (n=175) self-reported metastatic disease, including 129 with bone metastases. Among those with bone metastases, 76 (59%) reported experiencing any level of pain in the last week; 49 (38%) reported a worst pain score ≥4/10 of which 38 (78%) used analgesics over the past week and 31 (63%) used daily analgesia. In addition, 70 of the 76 (92%) noted that their pain interfered with work, sleep, or enjoyment of life, with 25 (33%) noting severe interference. Among the 49 patients with pain scores ≥4/10, current or past docetaxel use was reported by 32 (65%), androgen deprivation therapy by 47 (96%), and 28 (57%) had been or were currently enrolled in a clinical trial. Conclusions: Pain is sufficiently prevalent in men with metastatic prostate cancer to enable prospective assessment of palliation endpoints in clinical trials. No significant financial relationships to disclose.
THU0226 MESENCHYMAL STEM CELL TRANSPLANTATION AMELIORATES EXPERIMENTAL SJÖGREN’S SYNDROME BY DOWNREGUALTING MDSCS VIA COX2/PGE2 PATHWAY
Authors: G. Yao, S. Wang, L. Sun
Journal: Annals of the Rheumatic Diseases (2020)

Background: Although mesenchymal stem cells (MSCs) transplantation have been demonstrated to be an effective therapeutic approach to treat experimental Sjögren’s syndrome (ESS) 1 , the specific underlying mechanisms remain to be elucidated. Myeloid-derived suppressor cells (MDSCs) were significantly increased with decreased suppressive capacity during disease development in ESS 2-3 . However, the therapeutic effects and mechanisms by which MSCs regulating MDSCs in SS still remain unknown. Objectives: Here we aim to explore whether regulation of MDSCs was responsible for the beneficial effects of MSC transplantation on SS. Methods: The MSCs were infused intonon-obese diabetic (NOD) mice via the tail vein. The histological features of submandibular glands, lung, saliva flow rate were evaluated. The number and immune-suppressive activity of MDSCs, the subsets of MDSCs, polymorphonuclear MDSCs (PMN-MDSCs) and monocytic-MDSCs (M-MDSCs) in NOD mice were determined. The bone marrow cells under MDSCs differentiation conditions were co-cultured with or without MSCs. The COX2 inhibitor NS-398, anti-TGF-β1, or anti-IFN-β antibodies were added to coculture medium of MSCs and MDSCs induced from bone marrow cells respectively. Results: We found that MDSCs in bone marrow and peripheral blood increased in ESS mice. MSC transplantation ameliorated SS-like syndrome and down-regulated the percentages of MDSCs, PMN-MDSCs and M-MDSCs and promoted their suppressive ability in ESS mice significantly (Figure 1). In vitro, MSCs could down-regulate the differentiation and up-regulate the suppressive ability of MDSCs. Mechanistically, MSCs inhibited the differentiation of MDSCs and PMN-MDSCs via secreting prostaglandin E2, and inhibited the differentiation of M-MDSCs by secreting interferon-β (Figure 2). Figure 1. MSCs ameliorated SS symptoms and decreased MDSCs in NOD mice. Figure 2. MSCs inhibited the differentiation of PMN-MDSCs and M-MDSCs by COX2/PGE2 and IFN-β respectively. Conclusion: Our findings suggested that MSCs alleviated SS-like symptoms by suppressing the aberrant accumulation and improving the suppressive function of MDSCs in ESS mice via COX2/PGE2 pathway. References: [1]Shi B, Qi J, Yao G, et al. Mesenchymal stem cell transplantation ameliorates Sjögren’s syndrome via suppressing IL-12 production by dendritic cells. Stem Cell Res Ther, 2018; 9(1):308. [2]Qi J, Li D, Shi G, et al. Myeloid-derived suppressor cells exacerbates Sjögren’s syndrome by inhibiting Th2 immune responses. Mol Immunol, 2018; 101:251-258. [3]Tian J, Rui K, Hong Y, et al. Increased GITRL impairs the function of myeloid-derived suppressor cells and exacerbates primary Sjögren’s syndrome. J Immunol, 2019; 202(6):1693-1703. Disclosure of Interests: None declared