tbuckley/cabot-search huggingface dataset:
AB1276 NON-INTERFERON THERAPY OF CHRONIC HEPATITIS C IN A PATIENT WITH SYSTEMIC LUPUS ERYTHEMATOSUS AND SECONDARY SJÖGREN SYNDROME - CASE REPORT
Authors: I. Menshikova, Y. Pak, A. Rybaulina
Journal: Annals of the Rheumatic Diseases (2020)

Background: Hepatitis C virus infection is one of the most significant public health problems in the world. To date, the problem of selection of therapy is very relevant for patients with autoimmune diseases and chronic hepatitis C [1]. Patients with systemic lupus erythematosus (SLE) are forced to take different doses of steroids, often in combination with immunosuppressants (mycophenolate mofetil, azathioprine, etc.) even in the case of long-term remission. Such therapy for many years can contribute to the reactivation of hepatitis C. Objectives: To describe a clinical case of the effectiveness of the combined use of interferon-free therapy and therapy of steroids in a patient with SLE, secondary Sjogren syndrome and chronic hepatitis C. Methods: 56 years-old woman was admitted to the rheumatology department of Clinical Hospital No. 1 in December 2018 with the debut of SLE: photosensitivity, aphthous stomatitis, arthritis, pleurisy, sicca syndrome, leukopenia, ANA 1: 2560, antibodies to dsDNA 55.95 IU / ml, positive antiSS-A (Ro). At the same time, it became known that she was infected with hepatitis C virus in 1985 presumably. At the time of hospitalization, anti-HCV was positive, the virus genotype was 1b, the activity of the process was low (HCV RNA 6.6x10 4 , AST 33 U/L and ALT 25 U/L). The patient was prescribed corticosteroids (methylprednisolone 16 mg/day) and hydroxychloroquine 400 mg/day. In January 2019, after gastroenterologist, hematologist and infectious disease specialist advise, it was decided to conduct the patient a specific interferon-free antiviral therapy for chronic hepatitis C (a 24-week course with asunaprevir and daclatasvir), given the potential long-term glucocorticoid therapy, with the prospect of treating the patient with cytotoxic drugs, and the possibility of reactivation of chronic hepatitis C amid of immunosuppressive therapy for SLE and Sjogren syndrome. Results: Low-disease activity of SLE was achieved in a month, and after 24-week course of antiviral therapy, there was no increase in SLE activity, and positive laboratory and clinical dynamics were noted. Conclusion: Thus, the use of interferon-free therapy of chronic hepatitis C in patients with systemic lupus erythematosus and secondary Sjogren syndrome shows possible ways to safe treatment of this disease in patients with diffuse connective tissue diseases. References: [1]Xiaobo Zhu, Mingqi Wang, Mei Liu, Xinghao Yu &amp; Peng Huang. Efficacy and safety of direct-acting antivirals for treatment-naive patients with genotype 1 hepatitis C virus infection. Per Med. October 2019. 16 (5): 421 doi: 10.2217/pme-2018-0121. Acknowledgments: Supported by the “Russian Academic Excellence Project 5-100” Disclosure of Interests: None declared
Evidence for multiple cases of recurrent<i>Legionella</i>infection: a Danish national surveillance study
Authors: Kelsie Cassell, Charlotte Kjelsø, Daniel M Weinberger, Søren A Uldum
Journal: Thorax (2021)

While case reports have documented recurrence of Legionnaires’ disease, the frequency of recurrent infections has not been systematically examined at a national level over multiple decades. Between 2000 and 2020 in Denmark, 21 individuals had repeat laboratory-identified Legionella infection, totalling 48 episodes of hospitalisation. The majority of these individuals had underlying comorbidities. In at least 3 of the 21 cases, a different Legionella serogroup was detected during the second episode of infection, which could indicate reinfection from a new source. These results emphasise that Legionella can, and does, reinfect high-risk individuals causing multiple hospitalisations.
Long-read transcriptome sequencing reveals abundant promoter diversity in distinct molecular subtypes of gastric cancer
Authors: Kie Kyon Huang, Jiawen Huang, Jeanie Kar Leng Wu, Minghui Lee, Su Ting Tay, Vikrant Kumar, Kalpana Ramnarayanan, Nisha Padmanabhan, Chang Xu, Angie Lay Keng Tan, Charlene Chan, Dennis Kappei, Jonathan Göke, Patrick Tan
Journal: Genome biology (2021)

Abstract Background Deregulated gene expression is a hallmark of cancer; however, most studies to date have analyzed short-read RNA sequencing data with inherent limitations. Here, we combine PacBio long-read isoform sequencing (Iso-Seq) and Illumina paired-end short-read RNA sequencing to comprehensively survey the transcriptome of gastric cancer (GC), a leading cause of global cancer mortality. Results We performed full-length transcriptome analysis across 10 GC cell lines covering four major GC molecular subtypes (chromosomal unstable, Epstein-Barr positive, genome stable and microsatellite unstable). We identify 60,239 non-redundant full-length transcripts, of which &gt; 66% are novel compared to current transcriptome databases. Novel isoforms are more likely to be cell line and subtype specific, expressed at lower levels with larger number of exons, with longer isoform/coding sequence lengths. Most novel isoforms utilize an alternate first exon, and compared to other alternative splicing categories, are expressed at higher levels and exhibit higher variability. Collectively, we observe alternate promoter usage in 25% of detected genes, with the majority (84.2%) of known/novel promoter pairs exhibiting potential changes in their coding sequences. Mapping these alternate promoters to TCGA GC samples, we identify several cancer-associated isoforms, including novel variants of oncogenes. Tumor-specific transcript isoforms tend to alter protein coding sequences to a larger extent than other isoforms. Analysis of outcome data suggests that novel isoforms may impart additional prognostic information. Conclusions Our results provide a rich resource of full-length transcriptome data for deeper studies of GC and other gastrointestinal malignancies.
SARS-CoV-2 vaccination for patients with inflammatory bowel disease: a British Society of Gastroenterology Inflammatory Bowel Disease section and IBD Clinical Research Group position statement
Authors: James L Alexander, Gordon W Moran, Daniel R Gaya, Tim Raine, Ailsa Hart, Nicholas A Kennedy, James O Lindsay, Jonathan MacDonald, Jonathan P Segal, Shaji Sebastian, Christian P Selinger, Miles Parkes, Philip J Smith, Anjan Dhar, Sreedhar Subramanian, Ramesh Arasaradnam, Christopher A Lamb, Tariq Ahmad, Charlie W Lees, Liz Dobson, Ruth Wakeman, Tariq H Iqbal, Ian Arnott, Nick Powell, Christine Norton, Shahida Din, Jackie Glatter, Jochen Kammermeier, Madhoor Ramdeen, Nabil Quraishi, Peter Sagar, Shellie Radford, R. Alexander Speight, Helen Steed, Michael Mcfarlane, A. Barney Hawthorne
Journal: The Lancet. Gastroenterology & hepatology (2021)
Parallel in vivo analysis of large-effect autism genes implicates cortical neurogenesis and estrogen in risk and resilience
Authors: Helen Rankin Willsey, Cameron R.T. Exner, Yuxiao Xu, Amanda Everitt, Nawei Sun, Belinda Wang, Jeanselle Dea, Galina Schmunk, Yefim Zaltsman, Nia Teerikorpi, Albert Kim, Aoife S. Anderson, David Shin, Meghan Seyler, Tomasz J. Nowakowski, Richard M. Harland, A. Jeremy Willsey, Matthew W. State
Journal: Neuron (2021)
Prognostic Implications of Declining Hemoglobin Content in Patients Hospitalized With Acute Coronary Syndromes
Authors: Sergio Leonardi, Felice Gragnano, Greta Carrara, Giuseppe Gargiulo, Enrico Frigoli, Pascal Vranckx, Dario Di Maio, Vanessa Spedicato, Emanuele Monda, Luigi Fimiani, Vincenzo Fioretti, Fabrizio Esposito, Marisa Avvedimento, Fabio Magliulo, Attilio Leone, Salvatore Chianese, Michele Franzese, Martina Scalise, Alessandra Schiavo, Paolo Mazzone, Giovanni Esposito, Giuseppe Andò, Paolo Calabrò, Stephan Windecker, Marco Valgimigli
Journal: Journal of the American College of Cardiology (2021)
Radiotherapy Delivered before CDK4/6 Inhibitors Mediates Superior Therapeutic Effects in ER+ Breast Cancer
Authors: Giulia Petroni, Aitziber Buqué, Takahiro Yamazaki, Norma Bloy, Maurizio Di Liberto, Selina Chen-Kiang, Silvia C. Formenti, Lorenzo Galluzzi
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Recent preclinical data suggest that cyclin-dependent kinase 4/6 (CDK4/6) inhibition may be harnessed to sensitize estrogen receptor–positive (ER+) breast cancer to radiotherapy. However, these findings were obtained in human ER+ breast cancer cell lines exposed to subclinical doses of CDK4/6 inhibitors with limited attention to treatment schedule. We investigated the activity of radiotherapy combined with the prototypic CDK4/6 inhibitor palbociclib placing emphasis on therapeutic schedule. Experimental Design: We combined radiotherapy and palbociclib in various doses and therapeutic schedules in human and mouse models of ER+ and ER-negative (ER−) breast cancer, including an immunocompetent mouse model that recapitulates key features of human luminal B breast cancer in women. We assessed proliferation, cell death, cell-cycle control, and clonogenic survival in vitro, as well as tumor growth, overall survival, and metastatic dissemination in vivo. Results: Radiotherapy and palbociclib employed as standalone agents had partial cytostatic effects in vitro, correlating with suboptimal tumor control in vivo. However, while palbociclib delivered before focal radiotherapy provided minimal benefits as compared with either treatment alone, delivering focal radiotherapy before palbociclib mediated superior therapeutic effects, even in the absence of p53. Such superiority manifested in vitro with enhanced cytostasis and loss of clonogenic potential, as well as in vivo with improved local and systemic tumor control. Conclusions: Our preclinical findings demonstrate that radiotherapy delivered before CDK4/6 inhibitors mediates superior antineoplastic effects compared with alternative treatment schedules, calling into question the design of clinical trials administering CDK4/6 inhibitors before radiotherapy in women with ER+ breast cancer.
Type I Interferon–Activated STAT4 Regulation of Follicular Helper T Cell–Dependent Cytokine and Immunoglobulin Production in Lupus
Authors: Xuemei Dong, Olivia Q. Antao, Wenzhi Song, Gina M. Sanchez, Krzysztof Zembrzuski, Fotios Koumpouras, Alexander Lemenze, Joe Craft, Jason S. Weinstein
Journal: Arthritis & Rheumatology (2021)

Objective To assess the role of STAT4 activation in driving pathogenic follicular helper T (Tfh) cell secretion of the cytokines interleukin‐21 (IL‐21) and interferon‐γ (IFNγ) in murine and human lupus. Methods The effect of STAT4‐dependent Tfh cell signaling on cytokine production and autoreactive B cell maturation was assessed temporally during the course of lupus in a murine model, with further assessment of Tfh cell gene transcription performed using RNA‐Seq technology. STAT4‐dependent signaling and cytokine production were also determined in circulating Tfh‐like cells in patients with systemic lupus erythematosus (SLE), as compared to cells from healthy control subjects, and correlations with disease activity were assessed in the Tfh‐like cells from SLE patients. Results IL‐21– and IFNγ‐coproducing Tfh cells expanded prior to the detection of potentially pathogenic IgG2c autoantibodies in lupus‐prone mice. Tfh cells transcriptionally evolved during the course of disease with acquisition of a STAT4‐dependent gene signature. Maintenance of Tfh cell cytokine synthesis was dependent upon STAT4 signaling, driven by type I IFNs. Circulating Tfh‐like cells from patients with SLE also secreted IL‐21 and IFNγ, with STAT4 phosphorylation enhanced by IFNβ, in association with the extent of clinical disease activity. Conclusion We identified a role for type I IFN signaling in driving STAT4 activation and production of IL‐21 and IFNγ by Tfh cells in murine and human lupus. Enhanced STAT4 activation in Tfh cells may underlie pathogenic B cell responses in both murine and human lupus. These data indicate that STAT4 guides pathogenic cytokine and immunoglobulin production in SLE, demonstrating a potential therapeutic target to modulate autoimmunity.
Associations between pre-pregnancy psychosocial risk factors and infant outcomes: a population-based cohort study in England
Authors: Katie Harron, Ruth Gilbert, Jamie Fagg, Astrid Guttmann, Jan van der Meulen
Journal: The Lancet Public Health (2021)

Existing studies evaluating the association between maternal risk factors and specific infant outcomes such as birthweight, injury admissions, and mortality have mostly focused on single risk factors. We aimed to identify routinely recorded psychosocial characteristics of pregnant women most at risk of adverse infant outcomes to inform targeting of early intervention.We created a cohort using administrative hospital data (Hospital Episode Statistics) for all births to mothers aged 15-44 years in England, UK, who gave birth on or after April 1, 2010, and who were discharged before or on March 31, 2015. We used generalised linear models to evaluate associations between psychosocial risk factors recorded in hospital records in the 2 years before the 20th week of pregnancy (ie, teenage motherhood, deprivation, pre-pregnancy hospital admissions for mental health or behavioural conditions, and pre-pregnancy hospital admissions for adversity, including drug or alcohol abuse, violence, and self-harm) and infant outcomes (ie, birthweight, unplanned admission for injury, or death from any cause, within 12 months from postnatal discharge).Of 2 520 501 births initially assessed, 2 137 103 were eligible and were included in the birth outcome analysis. Among the eligible births, 93 279 (4·4%) were births to teenage mothers (age <20 years), 168 186 (7·9%) were births to previous teenage mothers, 51 312 (2·4%) were births to mothers who had a history of hospital admissions for mental health or behavioural conditions, 58 107 (2·7%) were births to mothers who had a history of hospital admissions for adversity, and 580 631 (27·2%) were births to mothers living in areas of high deprivation. 1 377 706 (64·5%) of births were to mothers with none of the above risk factors. Infants born to mothers with any of these risk factors had poorer outcomes than those born to mothers without these risk factors. Those born to mothers with a history of mental health or behavioural conditions were 124 g lighter (95% CI 114-134 g) than those born to mothers without these conditions. For teenage mothers compared with older mothers, 3·6% (95% CI 3·3-3·9%) more infants had an unplanned admission for injury, and there were 10·2 (95% CI 7·5-12·9) more deaths per 10 000 infants.Health-care services should respond proactively to pre-pregnancy psychosocial risk factors. Our study demonstrates a need for effective interventions before, during, and after pregnancy to reduce the downstream burden on health services and prevent long-term adverse effects for children.Wellcome Trust.
Resumption of Cardiac Activity after Withdrawal of Life-Sustaining Measures
Authors: Sonny Dhanani, Laura Hornby, Amanda van Beinum, Nathan B. Scales, Melanie Hogue, Andrew Baker, Stephen Beed, J. Gordon Boyd, Jennifer A. Chandler, Michaël Chassé, Frederick D’Aragon, Cameron Dezfulian, Christopher J. Doig, Frantisek Duska, Jan O. Friedrich, Dale Gardiner, Teneille Gofton, Dan Harvey, Christophe Herry, George Isac, Andreas H. Kramer, Demetrios J. Kutsogiannis, David M. Maslove, Maureen Meade, Sangeeta Mehta, Laveena Munshi, Loretta Norton, Giuseppe Pagliarello, Tim Ramsay, Katerina Rusinova, Damon Scales, Matous Schmidt, Andrew Seely, Jason Shahin, Marat Slessarev, Derek So, Heather Talbot, Walther N.K.A. van Mook, Petr Waldauf, Matthew Weiss, Jentina T. Wind, Sam D. Shemie
Journal: New England Journal of Medicine (2021)

The minimum duration of pulselessness required before organ donation after circulatory determination of death has not been well studied.
A woman with headache, hemiplegia, and recent toothache
Authors: Jason Yuen, Samiul Muquit
Journal: BMJ (2021)

A woman in her 60s presented to the emergency department with a two week history of headache and progressive left sided weakness over the previous 72 hours. She also had a two week history of toothache and was due to have an extraction procedure for a probable dental infection. She was otherwise well with no relevant medical history. She was alert and oriented but had a dense left sided hemiplegia (0 out of 5 on the Medical Research Council scale). She was afebrile. Table 1 shows the results of relevant blood tests.

View this table:

Table 1 
Relevant blood test results



Computed tomography with contrast and magnetic resonance imaging (MRI) of the brain showed a ring-enhancing lesion in the right frontal area, with an irregular enhancing rim (fig 1). MRI with apparent diffusion coefficient map, calculated using diffusion weighted imaging, …
The complex network of mTOR signalling in the heart
Authors: Sebastiano Sciarretta, Maurizio Forte, Giacomo Frati, Junichi Sadoshima
Journal: Cardiovascular Research (2021)

Abstract The mechanistic target of rapamycin (mTOR) integrates several intracellular and extracellular signals involved in the regulation of anabolic and catabolic processes. mTOR assembles into two macromolecular complexes, named mTORC1 and mTORC2, which have different regulators, substrates and functions. Studies of gain- and loss-of-function animal models of mTOR signalling revealed that mTORC1/2 elicits both adaptive and maladaptive functions in the cardiovascular system. Both mTORC1 and mTORC2 are indispensable for driving cardiac development and cardiac adaption to stress, such as pressure overload. However, persistent and deregulated mTORC1 activation in the heart is detrimental during stress and contributes to the development and progression of cardiac remodelling and genetic and metabolic cardiomyopathies. In this review, we discuss the latest findings regarding the role of mTOR in the cardiovascular system, both under basal conditions and during stress, such as pressure overload, ischemia, and metabolic stress. Current data suggest that mTOR modulation may represent a potential therapeutic strategy for the treatment of cardiac diseases.
AB0994 NEW ALTERNATIVE IN THE TREATMENT OF PATIENT WITH MUTATION OF GEN LACC1
Authors: R. M. Alcobendas, C. Quintana, J. Arostegui, C. Udaondo, S. Murias Loza, A. Remesal
Journal: Annals of the Rheumatic Diseases (2020)

Background: Few patients have been described in the literature with mutations in the Lacasa Domain containing one (LACC1) gene. Its clinical presentation usually associates sustained systemic inflammation associated with chronic polyarticular erosive arthritis. Until now, there have been multiple treatments described to try to control the disease, however, they are generally unsuccessful in the long term. Objectives: Describe the clinical course of a patient as well as the different treatments used Methods: Clinical chart review Results: Female 18-year-old born from a consanguineous Moroccan couple. Mother, brother and sister with similar conditions. She started at 3 years with fever, anemia, intense elevation of acute phase reactants and symmetric polyarthritis (knees, elbows, carps, shoulders, hands and ankles). Subsequent whole exome sequencing identified c.128_129delGT mutation in the LACC1/FAMIN gene. During the course of her illness, she has received treatment with oral, intravenous and infiltrated corticosteroid, methotrexate and etanercept, without getting adequate control of the disease. In 2016, she started treatment with tocilizumab (8 mg / kg every two weeks), obtaining an acceptable control of the disease (requiring periodic infiltrations every 2-3 months due to persistent arthritis). Nonetheless, in April 2019, she consulted for clinical worsening of the arthritis and laboratory test (C reactive protein 99.7 mg / L, erythrosedimentation rate 53 mm / h, leukocytes 13,500/µL and neutrophils 10,930/µL). At that time, she discontinued therapy with tocilizumab and started tofacitinib 5 mg every 12 hours with good evolution. Since its introduction, it has not required joint infiltration again and the inflammatory parameters (persistently elevated previously) have normalized. Conclusion: The jak kinasa inhibitors may be a treatment option in those patients with bad response to conventional therapy. References: [1]Rabionet R, Remesal A, Mensa-Vilaró A, Murías S, Alcobendas R, González-Roca E, Ruiz-Ortiz E, Antón J, Iglesias E, Modesto C, Comas D, Puig A, Drechsel O, Ossowski S, Yagüe J, Merino R, Estivill X, Arostegui JI. Biallelic loss-of-function LACC1/FAMIN Mutations Presenting as Rheumatoid Factor-Negative Polyarticular Juvenile Idiopathic Arthritis. Sci Rep. 2019 Mar 14;9(1):4579 Disclosure of Interests: None declared
A Pulsating Leg
Authors: Moran S. Gal, Shoshana Greenberger
Journal: New England Journal of Medicine (2021)

A 21-month-old boy presented with a pruritic rash on his left leg that was thought to be at the site of a recent insect bite. A video shows a pulsating erythematous plaque, referred to as Quincke’s sign, that was found on his leg.
SAT0192 Relationship between clinically detected joint swelling and effusion diagnosed by ultrasonogrpahy in talocrural joints in patients with rheumatoid arthritis
Authors: RK Luukkainen, H Huhtala, JM KoskiHuhtala
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> In clinical investigation it is often difficult to know if there is effusion in talocrural (TC) joint or not. <h3>Objectives</h3> To compare the relationship between clinically detected swelling and effusion diagnosed by ultrasonography (US) in TC joints in patients with rheumatoid arthritis (RA). <h3>Methods</h3> Thirty-one consecutive patients with RA entered the study. Twenty healthy persons formed a control group. In clinical assessment the TC joint was evaluated on the scale: normal or swelling. The US of the same joints was carried out. Altogether 62 TC joints of the RA patients and 40 of those of the controls were studied. All the clinical assessments were performed by one doctor and the US investigations by another and they were blinded of one others results. <h3>Results</h3> Normal upper limit of the measurement between the talus and the joint capsule was evaluated from the control group. It was 3.1 mm (mean + 2 SD) and only two TC joints of the normal persons had a value above it (4.1 and 5.4 mm). So, if the noechogenic space between the talus and the joint capsule was 3.1 mm or less, it was regarded as normal and if it was 3.2 mm or more, it was regarded as effusion. The clinical assessment and the US gave similar results in 35 TC joints, whereas they differed in the remaining 27 joints. The kappa coefficient between these investigations was 0.039 showing extremely poor agreement. <h3>Conclusion</h3> These preliminary results indicate that clinical evaluation is not adequate in diagnosis of effusion and synovitis of TC joints in patients with RA. It is probable that the main source of error in this respect is tenosynovitis in the region of ankle. So, US may significantly mprove the accuracy of diagnosis of effusion and synovitis in these patients.
Microneedle patch for the ultrasensitive quantification of protein biomarkers in interstitial fluid
Authors: Zheyu Wang, Jingyi Luan, Anushree Seth, Lin Liu, Minli You, Prashant Gupta, Priya Rathi, Yixuan Wang, Sisi Cao, Qisheng Jiang, Xiao Zhang, Rohit Gupta, Qingjun Zhou, Jeremiah J. Morrissey, Erica L. Scheller, Jai S. Rudra, Srikanth Singamaneni
Journal: Nature Biomedical Engineering (2021)