tbuckley/cabot-search huggingface dataset:
A young woman with upper lobe predominant bronchiectasis
Authors: Leonard E Riley, Anupa P Nadkarni
Journal: BMJ (2019)

A 26 year old woman presented with a 10 year history of recurrent lower respiratory tract infections, productive cough, progressive dyspnoea on exertion, and difficulty gaining weight. She had no history of loose or frequent bowel movements, or abdominal pain, and did not smoke. She had not been in contact with any sources of tuberculosis and had no family members with chronic pulmonary conditions. Her body mass index was 18.9 kg/m2, lung sounds were clear, and there was no evidence of nail clubbing. Chest radiography and computed tomography revealed upper lobe predominant bronchiectasis (fig 1, arrow) and airways with mucoid impaction (fig 1, arrowhead). …
Minimal Residual Disease Status with Venetoclax Monotherapy Is Associated with Progression-Free Survival in Chronic Lymphocytic Leukemia
Authors: William G. Wierda, Andrew W. Roberts, Paolo Ghia, Jennifer R. Brown, Stephan Stilgenbauer, Florence Cymbalista, Nicole Lamanna, John F. Seymour, Sebastian Böttcher, Madlaina Breuleux, Brenda Chyla, Lang Zhou, Jacqueline Nielsen, Su Young Kim, Jalaja Potluri, Johnathan C. Maher, Peter Hillmen
Journal: Blood (2018)
Comparison between human infections caused by highly and low pathogenic H7N9 avian influenza viruses in Wave Five: Clinical and virological findings
Authors: Yang Yang, Gary Wong, Liuqing Yang, Shuguang Tan, Jianming Li, Bing Bai, Zhixiang Xu, Hong Li, Wen Xu, Xiaonan Zhao, Chuansong Quan, Haixia Zheng, William J. Liu, Wenjun Liu, Lei Liu, Yingxia Liu, Yuhai Bi, George F. Gao
Journal: Journal of Infection (2019)
David Oliver: Money, efficiency, and the NHS plan
Authors: David Oliver
Journal: BMJ (2019)

When the government committed to giving the NHS a 70th birthday present of an extra £20.5bn (€23bn; $26.3bn) a year by 2023-24, it asked in return for a plan showing what the money would be spent on over the next decade.1 The publication of the NHS’s long term plan earlier this month fulfilled that commitment,2 and the government officially expects the NHS to deliver on that plan.

We should be cautious of government and media claims about this “historic funding boost.”3 In reality—as the NHS plan acknowledges—the funding increase (to an average 3.4% a year)4 is merely a return to something near the 3.7% real terms annual increase that was the norm in the years leading up to the 2012 spending review—after which it fell to around 2.2%, leaving services struggling.

Of course, the headline amount is higher …
Elucidating the Molecular Basis for Inhibitory Neurotransmission Regulation by Artemisinins
Authors: Vikram Babu Kasaragod, Torben Johann Hausrat, Natascha Schaefer, Maximilian Kuhn, Nikolaj Riis Christensen, Ingrid Tessmer, Hans Michael Maric, Kenneth Lindegaard Madsen, Christoph Sotriffer, Carmen Villmann, Matthias Kneussel, Hermann Schindelin
Journal: Neuron (2019)
Correcetions to “A standardised, generic, validated approach to stratify the magnitude of clinical benefit that can be anticipated from anti-cancer therapies: the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS)”
Authors: N.I. Cherny, R. Sullivan, U. Dafni, J.M. Kerst, A. Sobrero, C. Zielinski, E.G.E. de Vries, M.J. Piccart
Journal: Annals of Oncology (2016)
AB0086 Type ii collagen and glycosaminoglycan turnover in bovine articular cartilage is modulated by long-term dynamic compression
Authors: A. Engstrøm, A.-C. Bay-Jensen, M.A. Karsdal, C.S. Thudium
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Osteoarthritis (OA) patients suffer from progressive degradation of articular cartilage, to which there is no available treatment to block or reverse the catabolic mechanisms. Articular cartilage confers a biomechanical function in the joints, and in concordance chondrocytes have shown to be mechanosensitive. The effect of dynamic compression on cartilage extracellular matrix (ECM) could prove to be crucial for translational research in development and screening of new OA drug candidates. <h3>Objectives</h3> This study investigates the effect of long-term dynamic compression of a bovine articular cartilage <i>ex vivo</i> model through quantification of cartilage associated biomarkers. <h3>Methods</h3> Full depth bovine cartilage explants were cultured for 2 weeks. The explants were treated 3 times a week with either OSM [10 ng/mL] and TNF-a [2 ng/mL] (O+T), or TGF-B1 [50 ng/mL]. Untreated samples were included as negative controls (w/o). For each condition two groups were established; an unloaded group and a group compressed 3 times a week. Compression was applied using Electroforce 5500 (TA Instruments), in a sine wave with a maximum load per cycle of 1 MPa, at 1 Hz frequency for 1200 cycles. Metabolic activity was measured once a week using AlamarBlue. Biomarkers released to the supernatant were assessed using the following well-described ELISAs: formation of type II collagen was measured by ProC2, and MMP-degradation of type II collagen was measured by C2M. Sulfated glycosaminoglycans (sGAG) released to media, and sGAG extracted from the explants on the last day using a 4 mM GuHCl solution were quantified using a 1.9-dimethylmethylene blue (DMB) assay. <h3>Results</h3> Compression of bovine explants significantly decreased release of C2M compared to unloaded samples in O-T and w/o groups with 42% and 48% respectively. ProC2 release was not affected by compression. Compression of w/o or TGF-b treated explants increased sGAG release with 195% and 152% relative to their unloaded controls. However, the total amount of sGAG extracted from the explants on the last day remained unchanged. Compression of the explants did not affect the metabolic activity. <h3>Conclusions</h3> Compression significantly reduced the degradation of type II collagen, which in combination with unaltered formation as measured by ProC2, may suggest suppression of the involved catabolic processes and increased deposition of type II collagen in the cartilage matrix. Furthermore, compression elevated the sGAG release without reduction in the explant GAG content, indicating an increased turnover of GAG. In conclusion, the cartilage ECM turnover is significantly modulated by dynamic compression. This method adds essential translational value to the continuous research addressing OA. <h3>Disclosure of Interest</h3> None declared
Prospective Validation of the Emergency Heart Failure Mortality Risk Grade for Acute Heart Failure
Authors: Douglas S. Lee, Jacques S. Lee, Michael J. Schull, Bjug Borgundvaag, Marcia L. Edmonds, Maria Ivankovic, Shelley L. McLeod, Jonathan F. Dreyer, Sam Sabbah, Phillip D. Levy, Tara O’Neill, Alice Chong, Therese A. Stukel, Peter C. Austin, Jack V. Tu
Journal: Circulation (2019)

Improved risk stratification of acute heart failure in the emergency department may inform physicians' decisions regarding patient admission or early discharge disposition. We aimed to validate the previously-derived Emergency Heart failure Mortality Risk Grade for 7-day (EHMRG7) and 30-day (EHMRG30-ST) mortality.We conducted a multicenter, prospective validation study of patients with acute heart failure at 9 hospitals. We surveyed physicians for their estimates of 7-day mortality risk, obtained for each patient before knowledge of the model predictions, and compared these with EHMRG7 for discrimination and net reclassification improvement. We also prospectively examined discrimination of the EHMRG30-ST model, which incorporates all components of EHMRG7 as well as the presence of ST-depression on the 12-lead ECG.We recruited 1983 patients seeking emergency department care for acute heart failure. Mortality rates at 7 days in the 5 risk groups (very low, low, intermediate, high, and very high risk) were 0%, 0%, 0.6%, 1.9%, and 3.9%, respectively. At 30 days, the corresponding mortality rates were 0%, 1.9%, 3.9%, 5.9%, and 14.3%. Compared with physician-estimated risk of 7-day mortality (PER7; c-statistic, 0.71; 95% CI, 0.64-0.78) there was improved discrimination with EHMRG7 (c-statistic, 0.81; 95% CI, 0.75-0.87; P=0.022 versus PER7) and with EHMRG7 combined with physicians' estimates (c-statistic, 0.82; 95% CI, 0.76-0.88; P=0.003 versus PER7). Model discrimination increased nonsignificantly by 0.014 (95% CI, -0.009-0.037) when physicians' estimates combined with EHMRG7 were compared with EHMRG7 alone ( P=0.242). The c-statistic for EHMRG30-ST alone was 0.77 (95% CI, 0.73-0.81) and 30-day model discrimination increased nonsignificantly by addition of physician-estimated risk to 0.78 (95% CI, 0.73-0.82; P=0.187). Net reclassification improvement with EHMRG7 was 0.763 (95% CI, 0.465-1.062) when assessed continuously and 0.820 (0.560-1.080) using risk categories compared with PER7.A clinical model allowing simultaneous prediction of mortality at both 7 and 30 days identified acute heart failure patients with a low risk of events. Compared with physicians' estimates, our multivariable model was better able to predict 7-day mortality and may guide clinical decisions.URL: https://www.clinicaltrials.gov . Unique identifier: NCT02634762.
AB0675 Rheumatoid factor positivity is related to clinical and immunological characteristics in patients with eosinophilic granulomatosis with polyangiitis
Authors: J. Inamo, Y. Kaneko, Y. Ohta, T. Takeuchi
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), which is characterised by vasculitis with allergic features such as asthma and eosinophilia. Although rheumatoid factor (RF) positivity is known to be as high as 37%–50% in AAV patients<sup>1</sup> the clinical significance of RF-positivity remains unknown. <h3>Objectives</h3> To investigate clinical features in patients with RF in EGPA. <h3>Methods</h3> Consecutive patients who were diagnosed with EGPA between January 2008 and January 2018 in Keio University Hospital were enrolled. Clinical information were collected from medical records retrospectively. We divided patients into 2 groups according to RF positivity, and compared clinical features. <h3>Results</h3> Seventeen patients were enrolled in the study. The mean age was 57.4 years old, and 82% were female. Among them, 11 patients were RF positive (RF positive group) and 6 patients were negative (RF negative group). The female rate tended to be higher in the RF positive group than the negative group (82% vs 50%, p=0.087). While the Birmingham Vasculitis Activity Score was comparable between the two groups (21.5 vs 17.3, p=0.329), general symptoms (fever and weight loss) and gastrointestinal lesions were more frequent in the RF positive group (55% vs 17%, p=0.072; 45% vs 17%, p=0.137) and central nervous involvement was less frequent (18% vs 67%, p=0.024). No patient with negative RF presented with arthralgia/arthritis. The count of eosinophil and IgA levels at diagnosis were significantly higher in the RF positive group than the RF negative group (15704/μl vs 4751/μl, p=0.009; 238 mg/dL vs 162 mg/dL, p=0.048). Interestingly, ANCA positivity was negatively correlated with RF positivity. MPO-ANCA was positive in 27% of the RF positive group and in 66% of the RF negative group, and PR3-ANCA was positive in none of the RF positive group and 17% of the RF negative group. Double negative was more frequent in RF positive group (73% vs 33%, p=0.060). <h3>Conclusions</h3> RF positivity was associated with clinical and serological characteristics in patients with EGPA, suggesting different pathogenesis or immunological disturbances is related. <h3>Reference</h3> [1] Pagnoux C, Seror R, Bérezné A, Rouabhia S, Goulvestre C, Guillevin L. Remittent non-destructive polysynovitis in P-ANCA-positive vasculitis patients with anti-CCP antibodies. Joint Bone Spine. 2010;77(6):604–7. <h3>Disclosure of Interest</h3> None declared
AB0817 Prominent nailfold capillary avascular area predicts malignancy in progressive systemic sclerosis
Authors: W.-N. Huang, Y.-M. Chen, W.-T. Hung, C.-W. Hsieh, C.-T. Lin, Y.-H. Chen
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Systemic sclerosis (SSc) is an autoimmune disease characterised with proximal scleroderma and internal organ involvement. Observational studies demonstrated increased incidences of cancer in SSc patients<sup>1</sup>. Nailfold capillaroscopy is useful for the diagnosis and disease activity assessment of SSc. However, whether the nailfold capillaroscopy pattern is distinct in SSc patients with malignancy remained unknown. <h3>Objectives</h3> The aim of this study was to investigate the incidence rate of malignancy in SSc patients. Nailfold capillaroscopy morphology patterns in SSc patients with cancer were also compared to those without cancer. <h3>Methods</h3> <sup>During 2004</sup> to 2014, consecutive 310 SSc patients who visited outpatient clinics at Taichung Veterans General Hospital, Taiwan were enrolled. Nailfold capillaroscopy was performed at a magnification of 200x. Abnormal morphology description were analysed and categorised by the scoring system proposed by Dr. Cutolo<sup>2</sup>. SSc with malignancy was defined if the subject had a cancer diagnosis during the follow-up period. <h3>Results</h3> Among 310 SSc patients, 28 (10.9%, 13 males, 25 females) patients had cancer. The mean age of SSc with malignancy is 62±10.9 years. Sixty-four percent SSc patients with cancer is diffuse type, but only 42% of them were tested positive for anti-Scl-70 antibodies. The most common cancer were genitourinary tract and gastrointestinal tract, accounting for almost two-thirds patients. Cancer and SSc were frequently diagnosed at the same year. In SSc patients with cancer, 19 patients received nailfold capillary microscope exams when SSc was diagnosed. The assessment of nailfold capillaroscopy morphology patterns in SSc patients with cancer demonstrated neither enlarged loop, giant loop, microhemorrhage nor angiogenesis. However, prominent avascular areas could be observed universally in SSc patients with malignancy. <h3>Conclusions</h3> Rheumatologists should be aware of malignancy in SSc patients, especially those with diffuse type and within the 1st year of symptoms onset. SSc patients with malignancy tend to present atypical capillaroscopic pattern of prominent avascular area without loop dilatation, microhemorrhage and angiogenesis. <h3>References</h3> [1] Bonifazi M, et al.,Rheumatology (Oxford). 2013Jan;52(1):143–54 [2] Maurizio Cutolo (2010) Atlas of Capillaroscopy in Rheumatic diseases chapter 11 page 77–86 <h3>Disclosure of Interest</h3> None declared
FRI0419 Intravenous immunoglobulins prevents experimental fibrosis in a murine model of systemic sclerosis
Authors: M.-M. Farhat, S. Speca, M. Jendoubi, C. Hauspie, T. Guerrier, V. Sobanski, S. Sanges, E. Hachulla, G. Lefevre, M. Labalette, S. Dubucquoi, D. Launay
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Systemic sclerosis (SSc) is an autoimmune disease characterised by an extensive multi-organs fibrosis. Immunosuppressants are effective in some extent but their incomplete efficacy is hampered by a higher infection risk. Intravenous immunoglobulins (IVIG) have a good safety profile, exhibit immunomodulatory and antifibrotic properties and hence could be a relevant treatment for SSc. <h3>Objectives</h3> The purpose of this study was to investigate the effects of IVIG in an experimental model of SSc. <h3>Methods</h3> SSc was induced in 6 weeks old Balb/c mice by subcutaneous injections of HOCl five days a week during six weeks (n=20), whereas control mice received subcutaneous injections of PBS (n=20). Human IVIG was administrated intravenously by single retro-orbital injection at a dose of 2 g/kg the first day of HOCl administration (n=20). A control group received an injection of 2% Maltose (n=20). Skin thickness was assessed during the protocol until the sacrifice (day 42). Skin tissues were collected in 4% PFA and processed for histological analysis. Dermal thickness was measured by performing a May-Grünwald–Giemsa staining of 4 µm skin sections; collagen deposition was assessed by performing a Picrosirius red-staining and quantified by using a colour deconvolution method. In addition, immunostaining of skin sections was performed in order to evaluate the α-smooth muscle actin (α-SMA) expression. Frozen skin tissues were analysed to also assess the mRNA expression of main inflammatory and pro-fibrotic genes (by quantitative reverse transcription polymerase chain reaction). Collagen deposition was also evaluated by measuring the content of hydroxyproline in 10 mg of frozen tissue. <h3>Results</h3> Mice exposed to HOCl developed a diffuse cutaneous SSc with higher dermal thickness compared to the PBS group. IVIG significantly reduced dermal thickness and collagen deposition in HOCl-receiving mice. The amount of α-SMA positive cells evaluated by immunofluorescence was reduced in the HOCl treated mice receiving IVIG. mRNA expression profile of various markers of fibrosis (fibronectin, TGFβ) or inflammation (TNFα, IL-1β, IL-6) were also significantly decreased in the skin of HOCl mice treated with IVIG compared to HOCl-treated mice receiving 2% maltose. <h3>Conclusions</h3> These results demonstrate the efficacy of IVIG in preventing experimental fibrosis in a HOCl murine model of SSc. <h3>Disclosure of Interest</h3> None declared
Circular RNAs in immune responses and immune diseases
Authors: Xu Chen, Tian Yang, Wei Wang, Wenjin Xi, Tianze Zhang, Qi Li, Angang Yang, Tao Wang
Journal: Theranostics (2019)

Circular RNAs (circRNAs) are novel clusters of endogenous noncoding RNAs (ncRNAs) that are widely expressed in eukaryotic cells. In contrast to the generation of linear RNA transcripts, circRNAs undergo a "back-splicing" process to form a continuous, covalently closed, stable loop structure without 5' or 3' polarities and poly (A) tails during posttranscriptional modification. Due to the widespread availability of several technologies, especially high-throughput RNA sequencing, numerous circRNAs have been discovered not only in mammals but also in plants and insects. Notably, due to their abilities to serve as microRNA (miRNA) "sponges", miRNA "reservoirs", regulate gene expression and encode proteins, circRNAs participate in the development and progression of different immune responses and immune diseases by enriching various forms of epigenetic modification. CircRNAs have been demonstrated to be expressed in a tissue-specific and pathogenesis-related manner during the occurrence of multiple immune diseases. Additionally, because of their circular configurations, expression in blood and peripheral tissues and coexistence with exosomes, circRNAs show inherent conservation along with environmental resistance stability and may be regarded as potential biomarkers or therapeutic targets for some immune diseases. In this review, we summarize the characteristics, functions and mechanisms of circRNAs and their involvement in immune responses and diseases. Although our knowledge of circRNAs remains preliminary, this field is worthy of deeper exploration and greater research efforts.
Fucosylation Enhances the Efficacy of Adoptively Transferred Antigen-Specific Cytotoxic T Lymphocytes
Authors: Gheath Alatrash, Na Qiao, Mao Zhang, Madhushree Zope, Alexander A. Perakis, Pariya Sukhumalchandra, Anne V. Philips, Haven R. Garber, Celine Kerros, Lisa S. St. John, Maria R. Khouri, Hiep Khong, Karen Clise-Dwyer, Leonard P. Miller, Steve Wolpe, Willem W. Overwijk, Jeffrey J. Molldrem, Qing Ma, Elizabeth J. Shpall, Elizabeth A. Mittendorf
Journal: Clinical Cancer Research (2019)

Inefficient homing of adoptively transferred cytotoxic T lymphocytes (CTLs) to tumors is a major limitation to the efficacy of adoptive cellular therapy (ACT) for cancer. However, through fucosylation, a process whereby fucosyltransferases (FT) add fucose groups to cell surface glycoproteins, this challenge may be overcome. Endogenously fucosylated CTLs and ex vivo fucosylated cord blood stem cells and regulatory T cells were shown to preferentially home to inflamed tissues and marrow. Here, we show a novel approach to enhance CTL homing to leukemic marrow and tumor tissue.Using the enzyme FT-VII, we fucosylated CTLs that target the HLA-A2-restricted leukemia antigens CG1 and PR1, the HER2-derived breast cancer antigen E75, and the melanoma antigen gp-100. We performed in vitro homing assays to study the effects of fucosylation on CTL homing and target killing. We used in vivo mouse models to demonstrate the effects of ex vivo fucosylation on CTL antitumor activities against leukemia, breast cancer, and melanoma.Our data show that fucosylation increases in vitro homing and cytotoxicity of antigen-specific CTLs. Furthermore, fucosylation enhances in vivo CTL homing to leukemic bone marrow, breast cancer, and melanoma tissue in NOD/SCID gamma (NSG) and immunocompetent mice, ultimately boosting the antitumor activity of the antigen-specific CTLs. Importantly, our work demonstrates that fucosylation does not interfere with CTL specificity.Together, our data establish ex vivo CTL fucosylation as a novel approach to improving the efficacy of ACT, which may be of great value for the future of ACT for cancer.
THU0116 Lipid profile and cardiovascular risk in subjects at risk for developing rheumatoid arthritis
Authors: L. van Boheemen, M. van Beers-Tas, D. van Schaardenburg, M.T. Nurmohamed
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease associated with an increased cardiovascular (CV) risk that is already present at the time of diagnosis. However, it is unclear at what point in the period before diagnosis of RA the CV risk increases. Therefore, we assessed the 10 year risk of CV morbidity and mortality in a cohort of subjects at risk for RA and analysed associations with anti-citrullinated protein antibody (ACPA) status and arthritis development. <h3>Methods</h3> In a cohort of 594 consecutive arthralgia patients with positivity for rheumatoid factor (RF) and/or ACPA, demographics, medical history, medication use and comorbidities were assessed. Lipid profile was determined and blood pressure was measured in a subset of patients. The 10 year CV risk score according to the Dutch CV risk management guideline (Dutch Systematic Coronary Risk Evaluations (SCORE)) was calculated for patients of whom data were complete. <h3>Results</h3> ACPA positive subjects (n=382) were younger (mean age 48.6 vs 51.6, p=0.003), more often smokers (31.8% vs 23.9%, p=0.045) and had lower cholesterol (mean level 5.2 vs 5.5, p=0.001) and HDL (mean level 1.1 vs 1.2, p=0.004) than ACPA negative subjects. Subjects who developed arthritis (n=205) had lower cholesterol (mean level 5.2 vs 5.4, p=0.008) and HDL levels (mean level 1.0 vs 1.2, p=0.001) and a higher TC/HDL ratio (median ratio 5.2 vs 4.8, p=0.047) compared to subjects who did not develop arthritis. Lower cholesterol (OR 1.24, CI 1.04–1.48), lower HDL (OR 2.01, CI 1.29–3.13) and higher TC/HDL ratio (OR 1.07, CI 1.000–1.138) predicted arthritis development. The Dutch SCORE was calculated in 177 subjects (median 2, IQR 1–9). 76.4% had a low risk (SCORE &lt;10%), 12.5% a medium risk (SCORE 10-&lt;20%) and 11.4% had a high 10 year risk (SCORE &gt;20%) of cardiovascular morbidity and mortality. The score was not associated with ACPA status or arthritis development. <h3>Conclusions</h3> Dyslipidemia as known in RA patients with active disease was also present in seropositive arthralgia patients at risk for RA, and predicted development of RA. However, arthralgia subjects who developed arthritis did not have a higher CV risk score than those who did not develop arthritis. Also, despite differences in lipid profile and smoking, the CV risk score does not differ between ACPA positive and ACPA negative subjects at risk for RA. Overall, differences in lipid profile predict development of RA but were too small to have an effect on the 10 year risk of CV morbidity and mortality as calculated by the Dutch CV risk score. <h3>Disclosure of Interest</h3> None declared