tbuckley/cabot-search huggingface dataset:
lncRNA ZNF649-AS1 Induces Trastuzumab Resistance by Promoting ATG5 Expression and Autophagy
Authors: Mingli Han, Xueke Qian, Hui Cao, Fang Wang, Xiangke Li, Na Han, Xue Yang, Yunqing Yang, Dongwei Dou, Jianguo Hu, Wei Wang, Jing Han, Fan Zhang, Huaying Dong
Journal: Molecular Therapy (2020)

The regulatory mechanism of long non-coding RNAs (lncRNAs) in trastuzumab resistance is not well established to date. In this research, we identified differentially expressed lncRNA and investigated its regulatory role in trastuzumab resistance of breast cancer. HiSeq sequencing and quantitative real-time PCR were performed to identify the dysregulated lncRNAs. Mass spectrometry, RNA fluorescence in situ hybridization (RNA-FISH), and immunoprecipitation assays were performed to identify the direct interactions between ZNF649-AS1 and other associated targets, such as polypyrimidine tract binding protein 1 (PTBP1) and autophagy related 5 (ATG5). Our results showed that ZNF649-AS1 was more highly expressed in trastuzumab-resistant cells compared to sensitive cells. Increased expression of ZNF649-AS1 was associated with a poorer response and shorter survival time of breast cancer patients. ZNF649-AS1 was upregulated by H3K27ac modification at the presence of trastuzumab treatment, and knockdown of ZNF649-AS1 reversed trastuzumab resistance via modulating ATG5 expression and autophagy. Mechanically, ZNF649-AS1 was associated with PTBP1 protein, which further promoted the transcription activity of the ATG5 gene. In conclusion, we demonstrated that H3K27ac modification-induced upregulation of ZNF649-AS1 could cause autophagy and trastuzumab resistance through associating with PTBP1 and promoting ATG5 transcription. The regulatory mechanism of long non-coding RNAs (lncRNAs) in trastuzumab resistance is not well established to date. In this research, we identified differentially expressed lncRNA and investigated its regulatory role in trastuzumab resistance of breast cancer. HiSeq sequencing and quantitative real-time PCR were performed to identify the dysregulated lncRNAs. Mass spectrometry, RNA fluorescence in situ hybridization (RNA-FISH), and immunoprecipitation assays were performed to identify the direct interactions between ZNF649-AS1 and other associated targets, such as polypyrimidine tract binding protein 1 (PTBP1) and autophagy related 5 (ATG5). Our results showed that ZNF649-AS1 was more highly expressed in trastuzumab-resistant cells compared to sensitive cells. Increased expression of ZNF649-AS1 was associated with a poorer response and shorter survival time of breast cancer patients. ZNF649-AS1 was upregulated by H3K27ac modification at the presence of trastuzumab treatment, and knockdown of ZNF649-AS1 reversed trastuzumab resistance via modulating ATG5 expression and autophagy. Mechanically, ZNF649-AS1 was associated with PTBP1 protein, which further promoted the transcription activity of the ATG5 gene. In conclusion, we demonstrated that H3K27ac modification-induced upregulation of ZNF649-AS1 could cause autophagy and trastuzumab resistance through associating with PTBP1 and promoting ATG5 transcription.
THU0203 Incidence of chloroquine retinopahy in rheumatoid arthritis patients
Authors: J Gonzalez-Dominguez, M Santos, A Escudero, A Cisnal, M Romero, V Perez, MD Lopez, MA Caracuel, FG Martinez, JM Gallardo, E Collantes
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To evaluate risk of chloroquine (CQ) retinal toxicity in rheumatoid arthritis (RA) patients. <h3>Methods</h3> Retrospective case-control study of RA patients attended from 1987 to 1999 in our Rheumatology Service. One hundred and fifty RA patients (120 females (F) and 30 males (M) with a mean age of 64 ± 40 years, who lives in the same geographical area, received daily CQ dosage of 250 mg. Ophthalmologic examination was carried out exam previous CQ treatment and toxicity routine ophthalmic screening every 6 months include fundus, central campimetry and tests of colours Farnsworth D-28. After identification of central visual field alteration and/or fundus CQ treatment was stopped. <h3>Results</h3> Eight patients (5.3%), 8 females with mean age of 63.6 ± 11.4 years were identify with CQ retinopathy. Six patients (5F and 1 M) 4% with visual colour defects without CQ retinopathy were detected. Rheumatoid factor (RF) was present in 75% of retinopathy CQ patients (group A) vs. 72.6% in the patients without retinopathy (group B). The duration of treatment and cumulative total dose of CQ was in group A 3.4 ± 2.1 yrs. and 193.7 ± 104.4 gm vs. 3.3 ± 2.6 yrs. and 184 ± 125.9 gm in group B group. <h3>Conclusion</h3> The CQ retinal toxicity was of 5.3%, not related with age, rheumatoid factor, duration of treatment and cumulative total dose.
THU0046 Serum soluble selectins levels in patients with rheumatoid arthritis and systemic sclerosis
Authors: A Ates, G Kinikli, M Turgay, M Duman
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Soluble forms of adhesion molecules may be found in the circulation, and increased levels of selectins have been reported in some connective tissue diseases. It was suggested that the measurement of levels of circulating soluble selectins is useful as an indicator of inflammatory disease. <h3>Objectives</h3> To determine serum levels of soluble (s) E-, L-, and P-selectin in patients with rheumatoid arthritis (RA) and systemic sclerosis (SSc), and to determine whether levels of these molecules correlate with measures of disease activity and pulmonary involvement. <h3>Methods</h3> Serum levels of sE-, L-, and P-selectin were determined by sandwich ELISA in 34 patients with RA, 30 patients with SSc and 15 healthy subjects. The patients with RA were classified according to disease activity, functional status, Larsen score reflecting anatomical joint damage, and the presence of pulmonary involvement. The presence of pulmonary fibrosis and DLCO were determined in patients with SSc. <h3>Results</h3> The mean soluble selectin levels are shown in Table 1. sE- and sL-selectin levels were significantly higher in patients with active RA compared to inactive patients (respectively p &lt; 0.05 and p &lt; 0.05). Although sP-selectin level was higher in active RA patients than those in inactive patients, the difference did not reach statistically significant (p = 0.06). Significant correlations were found between sL-selectin and CRP (p &lt; 0.05), and white blood cell count (p &lt; 0.01) and between sP-selectin and CRP (p &lt; 0.01), and erythrocyte sedimentation rate (p &lt; 0.01). There were no correlations between selectin levels and Larsen score. sE-selectin level was increased in RA patients with advanced functional impairment (56.0 ± 39.8 in stage III-IV vs. 32.7 ± 13.6 ng/ml in stage I-II, p &lt; 0.05). The presence of pulmonary involvement in patients with RA was not correlated with soluble selectin levels. sE-selectin levels was significantly higher in SSc patients with pulmonary fibrosis compared to other SSc patients (p &lt; 0.05). There was a significant correlation between sE-selectin level and DLCO (r = -0.536, p &lt; 0.01). <h3>Conclusion</h3> These results suggest that the measurement of levels of serum soluble selectins may provide a useful additional marker for disease activity in RA patients and for pulmonary involvement, especially sE-selectin, in SSc patients.
Creación de una red Europea para el diagnóstico de enfermedades víricas "importadas" (REDEVI)
Authors: M Niedrig, B Niklasson, G Lloyd, H Schmitz, B LeGuenno
Journal: Eurosurveillance (1998)

La aparicion de epidemias de fiebre hemorragica de Ebola, que en los ultimos anos han tenido lugar en Zaire y Gabon, nos han recordado que infecciones graves pueden importarse a Europa con gran rapidez. Las reuniones convocadas por la Organizacion Mundial de la Salud (OMS) sobre patogenos emergentes y reemergentes, celebradas en 1993 y 1994 (1,2), se centraron en los problemas que presentan los arbovirus y los virus de la fiebre hemorragica, asi como en la necesidad de formar una red mundial de intercambio de informacion, reactivos y metodologias.
The origins and genomic diversity of American Civil War Era smallpox vaccine strains
Authors: Ana T. Duggan, Jennifer Klunk, Ashleigh F. Porter, Anna N. Dhody, Robert Hicks, Geoffrey L. Smith, Margaret Humphreys, Andrea M. McCollum, Whitni B. Davidson, Kimberly Wilkins, Yu Li, Amanda Burke, Hanna Polasky, Lowell Flanders, Debi Poinar, Amogelang R. Raphenya, Tammy T. Y. Lau, Brian Alcock, Andrew G. McArthur, G. Brian Golding, Edward C. Holmes, Hendrik N. Poinar
Journal: Genome biology (2020)

Abstract Vaccination has transformed public health, most notably including the eradication of smallpox. Despite its profound historical importance, little is known of the origins and diversity of the viruses used in smallpox vaccination. Prior to the twentieth century, the method, source and origin of smallpox vaccinations remained unstandardised and opaque. We reconstruct and analyse viral vaccine genomes associated with smallpox vaccination from historical artefacts. Significantly, we recover viral molecules through non-destructive sampling of historical materials lacking signs of biological residues. We use the authenticated ancient genomes to reveal the evolutionary relationships of smallpox vaccination viruses within the poxviruses as a whole.
THU0083 Bone mineral density measurements are suitable for rapid quantification of skeletal destruction in rats with adjuvant arthritis
Authors: U Feige, A Koch, B Bolon
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Reduced bone mineral density [BMD] is one of the major features of arthritis in both humans and animals. In a previous study, we showed that BMD was significantly decreased in both the femorotibial (knee) and tibiotarsal (ankle) joints of male Lewis rats with mycobacteria-induced adjuvant arthritis (AdA) even though clinical inflammation was most pronounced in the ankle.<sup>1</sup> <h3>Objectives</h3> The present experiment measured BMD in the ankles and knees of male Lewis rats with AdA to (1) define which region provides the greatest sensitivity as a rapid screen for anti-arthritic efficacy and to (2) determine the progression of chronic bone loss at these sites. <h3>Methods</h3> AdA was induced on day 0 (body weight of rats, ~100 g) by subcutaneous injection of heat-killed mycobacteria in oil; the day of AdA onset (as defined by paw swelling) was day 9. BMD was assessed in knees and ankles on days 12, 13, 14, 15, 16, 17, 18, 25 or 35 (6 normal and 6 arthritic rats/day) using dual energy x-ray absorptiometry (DEXA; Model 4500A, Hologic, Waltham, MA). <h3>Results</h3> In control rats, mean BMD for both sites increased by 20% between days 0 to 12, remained constant between days 12 to 18, and then increased again by 10% (ankle) or 25% (knee) by day 35. In AdA rats, hind paw volume relative to baseline values doubled between days 9 to 11 and then increased by another 1.5- to 2-fold to plateau on day 15. Mean knee BMD in AdA animals was 85% of control levels on day 12, fell to 75% by day 15, and ended at 55% on day 35. In contrast, mean BMD in ankles of AdA rats was comparable to control values through day 14, was 85% of controls on days 15 to 18, and decreased to 60% on days 25 and 35. <h3>Conclusion</h3> Our data indicate that BMD loss occurs earlier and to a greater degree in the knee of rats with AdA, suggesting that this joint could be a useful site for rapid quantitative screening for skeletal destruction. <h3>Reference</h3> Feige, <i>et al</i>. Ann Rheum Dis. 2000;59(Suppl I):148
Comprehensive mapping of immune perturbations associated with severe COVID-19
Authors: Leticia Kuri-Cervantes, Maria Betina Pampena, Wenzhao Meng, Aaron M. Rosenfeld, Caroline A. G. Ittner, Ariel R. Weisman, Roseline S. Agyekum, Divij Mathew, Amy E. Baxter, Laura A. Vella, Oliva Kuthuru, Sokratis A. Apostolidis, Luanne Bershaw, Jeanette Dougherty, Allison R. Greenplate, Ajinkya Pattekar, Justin Kim, Nicholas Han, Sigrid Gouma, Madison E. Weirick, Claudia P. Arevalo, Marcus J. Bolton, Eileen C. Goodwin, Elizabeth M. Anderson, Scott E. Hensley, Tiffanie K. Jones, Nilam S. Mangalmurti, Eline T. Luning Prak, E. John Wherry, Nuala J. Meyer, Michael R. Betts
Journal: Science Immunology (2020)

Although critical illness has been associated with SARS-CoV-2-induced hyperinflammation, the immune correlates of severe COVID-19 remain unclear. Here, we comprehensively analyzed peripheral blood immune perturbations in 42 SARS-CoV-2 infected and recovered individuals. We identified extensive induction and activation of multiple immune lineages, including T cell activation, oligoclonal plasmablast expansion, and Fc and trafficking receptor modulation on innate lymphocytes and granulocytes, that distinguished severe COVID-19 cases from healthy donors or SARS-CoV-2-recovered or moderate severity patients. We found the neutrophil to lymphocyte ratio to be a prognostic biomarker of disease severity and organ failure. Our findings demonstrate broad innate and adaptive leukocyte perturbations that distinguish dysregulated host responses in severe SARS-CoV-2 infection and warrant therapeutic investigation.
Dexmedetomidine for reduction of atrial fibrillation and delirium after cardiac surgery (DECADE): a randomised placebo-controlled trial
Authors: Alparslan Turan, Andra Duncan, Steve Leung, Nika Karimi, Jonathan Fang, Guangmei Mao, Jennifer Hargrave, Marc Gillinov, Carlos Trombetta, Sabry Ayad, Manal Hassan, Andrew Feider, Kimberly Howard-Quijano, Kurt Ruetzler, Daniel I Sessler, Sergio Bergese, Gildasio De Oliveira, Hooman Honar, Azfar Niazi, Kavita Elliott, Hassan Hamadnalla, Praneeta Chodavarapu, Gausan Bajracharya, Paul Fitzgerald, Evis Cuko, Zohaib Akhtar, Chetan Lokhande, Mohammad Zafeer Khan, Dilara Khoshknabi, Quinton Riter, Matthew Hutcherson, Seyhan Yagar, Logan Glosse, Partha Saha, Syed Raza
Journal: The Lancet (2020)
Rationally designed redirection of natural killer cells anchoring a cytotoxic ligand for pancreatic cancer treatment
Authors: Young Eun Lee, Anna Ju, Hwi Wan Choi, Jin-Chul Kim, Eunice EunKyeong Kim, Tae Sung Kim, Hyo Jeong Kang, Sang-Yeob Kim, Jin-Young Jang, Ja-Lok Ku, Song Cheol Kim, Eunsung Jun, Mihue Jang
Journal: Journal of Controlled Release (2020)
18F-THK5351 PET Can Identify Lesions of Acute Traumatic Brain Injury
Authors: Yasukage Takami, Yuka Yamamoto, Takashi Norikane, Katsuya Mitamura, Tetsuhiro Hatakeyama, Yoshihiro Nishiyama
Journal: Clinical Nuclear Medicine (2020)

Abstract A 67-year-old woman sustained a mild traumatic brain injury (TBI) in a traffic accident and had an initial Glasgow Coma Scale score of 13. She underwent 18 F-THK5351 PET 18 days after TBI. Fused 18 F-THK5351 PET/MRI showed that the location of 18 F-THK5351 accumulations corresponded anatomically to intraparenchymal lesions of acute TBI on MRI. 18 F-THK5351 reportedly binds to monoamine oxidase B highly expressed in astrocytes. Furthermore, TBI induces reactive astrogliosis or blood-brain barrier breakdown included in primary brain injury. Therefore, 18 F-THK5351 uptake may represent primary brain injury in acute TBI lesions.
AB0905 THE PREVALENCE AND RISK FACTORS OF OSTEOPOROSIS IN PATIENTS WITH INFLAMMATORY BOWEL DISEASES: A TUNISIAN STUDY
Authors: L. Mnif, H. Gdoura, L. Chtourou, A. Amouri, M. Boudabbous, N. Tahri
Journal: Annals of the Rheumatic Diseases (2020)

Background: Osteoporosis is as known a chronic complication of inflammatory bowel diseases (IBD). Its etiopathogenesis is often multifactorial. Objectives: The aim of our study was to describe the prevalence of reduced bone mineral density and to identify risk factors of osteoporosis in patients with inflammatory bowel diseases. Methods: This is a retrospective study over three years, collecting patients suffering from IBD and having benefited from a bone densitometry. We have specified for each patient the clinical data and the IBD characteristics. Bone mineral density (BMD, g/ cm) was assessed by dual X-ray absorptiometry. Osteoporosis was diagnosed when BMD was 2.5 standard deviations below the mean peak value in young adults (T score,22.5 SD). Patients with other pathology that may change the bone metabolism were excluded. Results: sixty-one patients were included with an average age of 38 ± 13 years [16-73]. The sex ratio M / F was 1.25. 69% of patients had ulcerative colitis. The bone density profile was normal in 49.2% of the cases. Osteoporosis and osteopenia were noted in 13.1% and 37.7% of patients, respectively. Osteoporosis was associated with advanced age (50.5 ± 16.5 years vs 36.26 ± 12.93 years; p = 0.007) and longer course disease (6.75 ± 7, 4 years vs 2.5 ± 4 years; p = 0.015). The cumulative dose of prednisone equivalent used in patients with osteoporosis was significantly higher than the other patients (2775 ± 3338 mg vs 706 ± 1449 mg; p = 0.003). Osteopenia was more frequently associated with crohn’s disease (58% vs 28.6% p = 0.0029). There was no significant difference between the group with osteoporosis or osteopenia and the group with normal bone densitometry for sex and body mass index. Conclusion: Osteoporosis during IBD is associated with advanced age, longer duration of illness and administration of high doses of corticosteroids. The high proportion of osteoporosis and osteopenia in our study underlines the importance of systematic BMD measurement in all IBD patients as a base for initiating the appropriate treatment. References: [1]The prevalence and risk factors for osteoporosis in patients with inflammatory bowel disease. Miznerova E et al. Bratisl Lek Listy. 2013;114(8):439-45. [2]Osteoporosis and inflammatory bowel disease: prevalence and risk factors in Tunisian patients. Boubaker J et al. Gastroenterol Clin Biol. 2003 Oct;27(10):901-7. Disclosure of Interests: None declared
Sex is associated with differences in gut microbial composition and function in hepatic encephalopathy
Authors: Krishnakant Saboo, Amirhossein Shamsaddini, Mihir V. Iyer, Chang Hu, Andrew Fagan, Edith A. Gavis, Melanie B. White, Michael Fuchs, Douglas M. Heuman, Masoumeh Sikaroodi, Ravishankar K. Iyer, Patrick M. Gillevet, Jasmohan S. Bajaj
Journal: Journal of Hepatology (2020)
AB0155 Chronic tophaceous gout in a premenopausal patient with familial nephropathy
Authors: R Guzel, T Sarpel, E Kozanoglu, S Paydas
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Only 5% of gouty patients are women and 90% of them are postmenopausal at the time of onset. <h3>Objectives</h3> To describe a delayed diagnosis in a young female patient with gouty arthritis and familial nephropathy, to mention about approach to allopurinol cutaneous hypersensitivity. <h3>Methods</h3> A 35-year-old woman presented with a 8 year history of arthritis that became crippling in the last year. Initially she was misdiagnosed as acute rheumatic fever, and later she was treated as rheumatoid arthritis. She denied any usage of diuretics or alcohol. Pedigree evaluation revealed five cases of chronic renal failure in the family, some with gouty complaints. On presentation; blood pressure was 120/70 mmHg, she was Steinbrocker functional class IV. She had large, tophi over metatarsophalangeal joints and tenderness with motion of ankles, wrists and right elbow. Monosodium urate crystals were demonstrated in synovial fluid. Serum urate level was 14 mg/dl, uric acid excretion and creatinine clearance was low, being 290 mg/day and 37 mL/min respectively. Additional abnormal investigations included a haematocrit of 27.3%, urea of 30 mg/dl, ESR of 78 mm/h. Serum trigliceride and total lipid were elevated being 291 mg/dl and 1281 mg/dl respectively. On USG bilateral soft tissue swelling in the axillar region were found to be compatible with lipomatosis. Urolithiasis was not observed. With these findings and family history she was suspected to have hereditary familial hyperuricemic nephropathy. After resolution of the acute attack with indomethacin, allopurinol treatment was started but had to be discontinued upon occurrence of widespread erythematous rash. She was hospitalised and desensitisation regime lasting 10 days was commenced. After desensitisation, she was free of symptoms with 300 mg/day allopurinol and 0.5 mg/day colchicine. Four months later, she developed oral ulcers. Since there was a doubtful genital ulcer history she was examined for Behçet's disease. Pathergy test was negative and unexpectedly she was HLA B27 positive but no other signs suggesting spondyloartropathy was present. Oral ulcers disappeared after allopurinol dosage has been lowered to 150 mg/day, the rash or ulcers has not recurred. The tophii were dissolved, renal functions and blood pressure have not deteriorated over time, there has been dramatic improvement of her symptoms with normalisation of serum urate levels, she is now Steinbrocker class II. <h3>Results</h3> <h3>Conclusion</h3> Hyperuricemia or gout appearing at an early age in a female is usually associated with progressive renal failure. Early recognition of this disorder is important since allopurinol therapy may ameliorate the progression of the renal lesion. In cases of hypersensitivity to allopurinol oral desensitisation is a feasible approach.
Salmonella - un "viejo" organismo, un desafío constante
Authors: S O’Brien, H de Valk
Journal: Eurosurveillance (2003)

Tras los eventos del 11 de septiembre de 2001, el fantasma del bioterrorismo subsiguiente y el considerable esfuerzo destinado a planificar lo impensable (1), en esta edicion de Eurosurveillance recordamos que algunos de los patogenos mas conocidos siguen suponiendo una amenaza constante para la salud publica y que, a veces, se consideran erroneamente bajo control. Recientemente, la incidencia de salmonelosis ha disminuido radicalmente en la Union Europea, habiendo bajado el numero de casos declarados a Enter-net (2) de 100.267 en 1997, el ano de maxima incidencia, a 73.006 en 2001 (I.S.T. Fisher - comunicacion personal). Sin embargo, los ultimos acontecimientos y los articulos siguientes ilustran el reto constante que representa el control de las salmonelas.