tbuckley/cabot-search huggingface dataset:
CircRNA inhibits DNA damage repair by interacting with host gene
Authors: Xiaolong Xu, Jingwei Zhang, Yihao Tian, Yang Gao, Xin Dong, Wenbo Chen, Xiaoning Yuan, Weinan Yin, Jinjing Xu, Ke Chen, Chunjiang He, Lei Wei
Journal: Molecular Cancer (2020)

Abstract Background Deregulated circular RNAs (circRNAs) are associated with the development of cancer and therapy resistance. However, functional research of circRNAs mostly focus on potential miRNA or protein binding and more potential regulation of circRNA on host gene DNA in cancers are yet to be inspected. Method We performed total RNA sequencing on clinical breast cancer samples and identified the expression patterns of circRNAs and corresponding host genes in patient blood, tumor and adjacent normal tissues. qPCR, northern blot and in situ hybridization were used to validate the dysregulation of circRNA circSMARCA5. A series of procedures including R-loop dot-blotting, DNA-RNA immunoprecipitation and mass spectrum, etc. were conducted to explore the regulation of circSMARCA5 on the transcription of exon 15 of SMARCA5. Moreover, immunofluorescence and in vivo experiments were executed to investigate the overexpression of circSMARCA5 with drug sensitivities. Results We found that circRNAs has average higher expression over its host linear genes in peripheral blood. Compared to adjacent normal tissues, circSMARCA5 is decreased in breast cancer tissues, contrary to host gene SMARCA5. The enforced expression of circSMARCA5 induced drug sensitivity of breast cancer cell lines in vitro and in vivo. Furthermore, we demonstrated that circSMARCA5 can bind to its parent gene locus, forming an R-loop, which results in transcriptional pausing at exon 15 of SMARCA5. CircSMARCA5 expression resulted in the downregulation of SMARCA5 and the production of a truncated nonfunctional protein, and the overexpression of circSMARCA5 was sufficient to improve sensitivity to cytotoxic drugs. Conclusion Our results revealed a new regulatory mechanism for circRNA on its host gene and provided evidence that circSMARCA5 may serve as a therapeutic target for drug-resistant breast cancer patients.
Effect of Remdesivir vs Standard Care on Clinical Status at 11 Days in Patients With Moderate COVID-19
Authors: Christoph D. Spinner, Robert L. Gottlieb, Gerard J. Criner, José Ramón Arribas López, Anna Maria Cattelan, Alex Soriano Viladomiu, Onyema Ogbuagu, Prashant Malhotra, Kathleen M. Mullane, Antonella Castagna, Louis Yi Ann Chai, Meta Roestenberg, Owen Tak Yin Tsang, Enos Bernasconi, Paul Le Turnier, Shan-Chwen Chang, Devi SenGupta, Robert H. Hyland, Anu O. Osinusi, Huyen Cao, Christiana Blair, Hongyuan Wang, Anuj Gaggar, Diana M. Brainard, Mark J. McPhail, Sanjay Bhagani, Mi Young Ahn, Arun J. Sanyal, Gregory Huhn, Francisco M. Marty
Journal: JAMA (2020)

Remdesivir demonstrated clinical benefit in a placebo-controlled trial in patients with severe coronavirus disease 2019 (COVID-19), but its effect in patients with moderate disease is unknown.
Invasive versus non-invasive management of older patients with non-ST elevation myocardial infarction (SENIOR-NSTEMI): a cohort study based on routine clinical data
Authors: Amit Kaura, Jonathan A C Sterne, Adam Trickey, Sam Abbott, Abdulrahim Mulla, Benjamin Glampson, Vasileios Panoulas, Jim Davies, Kerrie Woods, Joe Omigie, Anoop D Shah, Keith M Channon, Jonathan N Weber, Mark R Thursz, Paul Elliott, Harry Hemingway, Bryan Williams, Folkert W Asselbergs, Michael O'Sullivan, Graham M Lord, Narbeh Melikian, Thomas Johnson, Darrel P Francis, Ajay M Shah, Divaka Perera, Rajesh Kharbanda, Riyaz S Patel, Jamil Mayet
Journal: The Lancet (2020)

BackgroundPrevious trials suggest lower long-term risk of mortality after invasive rather than non-invasive management of patients with non-ST elevation myocardial infarction (NSTEMI), but the trials excluded very elderly patients. We aimed to estimate the effect of invasive versus non-invasive management within 3 days of peak troponin concentration on the survival of patients aged 80 years or older with NSTEMI.MethodsRoutine clinical data for this study were obtained from five collaborating hospitals hosting NIHR Biomedical Research Centres in the UK (all tertiary centres with emergency departments). Eligible patients were 80 years old or older when they underwent troponin measurements and were diagnosed with NSTEMI between 2010 (2008 for University College Hospital) and 2017. Propensity scores (patients' estimated probability of receiving invasive management) based on pretreatment variables were derived using logistic regression; patients with high probabilities of non-invasive or invasive management were excluded. Patients who died within 3 days of peak troponin concentration without receiving invasive management were assigned to the invasive or non-invasive management groups based on their propensity scores, to mitigate immortal time bias. We estimated mortality hazard ratios comparing invasive with non-invasive management, and compared the rate of hospital admissions for heart failure.FindingsOf the 1976 patients with NSTEMI, 101 died within 3 days of their peak troponin concentration and 375 were excluded because of extreme propensity scores. The remaining 1500 patients had a median age of 86 (IQR 82–89) years of whom (845 [56%] received non-invasive management. During median follow-up of 3·0 (IQR 1·2–4·8) years, 613 (41%) patients died. The adjusted cumulative 5-year mortality was 36% in the invasive management group and 55% in the non-invasive management group (adjusted hazard ratio 0·68, 95% CI 0·55–0·84). Invasive management was associated with lower incidence of hospital admissions for heart failure (adjusted rate ratio compared with non-invasive management 0·67, 95% CI 0·48–0·93).InterpretationThe survival advantage of invasive compared with non-invasive management appears to extend to patients with NSTEMI who are aged 80 years or older.FundingNIHR Imperial Biomedical Research Centre, as part of the NIHR Health Informatics Collaborative.
Pulmonary artery thrombosis in COVID-19 patients
Authors: A. Graziani, M. Domenicali, G. Zanframundo, F. Palmese, B. Caroli, L. Graziani
Journal: Pulmonology (2020)

distance between people (n = 7); three provided hand sanitizers, only one provided gloves.Regarding employees, in four of the eight stores observed the cashiers wore a visor or mask/glasses and gloves; in seven stores there was an acrylic separator wall between them and the customers.Store operators wore gloves in three out of eight outlets, but in only two cases they used a visor or a mask.Of the 78 customers observed, 47 (60.3%) were women and the majority were between 18 and 65 years old (n = 60; 76.9%).In the total sample, 26.9% (n = 21) used a surgical mask and 0.05% (n = 4) used a handmade mask or scarf.No customer wore a visor.Gloves were the most commonly used equipment by customers (n = 25; 32.1%).To sum up, compliance with prevention measures recommended to avoid COVID-19 contamination in retail food stores in Braga varied widely between outlets in April 2020.There were examples of excellent practice, but also of poor practice.Only one store met all recommended standards.The situation is more worrying in mini markets, where none of the recommendations were being followed.The main shortcomings, in general, were the absence of protective equipment for the employees, and lack of hand sanitizer for customers.According to recent information from the European Centre for Disease Prevention and Control, 4 one of the best preventive practices to reduce the transmission of COVID-19 is the generalized use of face masks as a complementary measure to safety distance, proper education being fundamental for their safe use.
Evaluation of Smad2/3 and Smad4 as inhibitors of estrogens and Ski protein as a predictive factor in T1, T2 N0 breast carcinomas
Authors: D. S. Koumoundourou, T. I. Kassimatis, E. Tzorakoleftherakis
Journal: Journal of Clinical Oncology (2009)

1543 Background: Smad proteins are TGF-β intracellular substrates, and Ski protein is a negative regulator of TGF-pathway. Tamoxifen's inhibition in breast cancer cells is mediated through TGF-β and Smad proteins. The purpose of our study was to investigate the activation of Smad2/3, Smad4, and Ski proteins in breast carcinomas and correlate their expression with each other and with hormonal receptors, as well as with other clinicopathological parameters such as the tumor size and grade, and the Distant Disease Free and the Overall Survival. Methods: One hundred forty-seven paraffin-embedded specimens from 22 in situ and 125 invasive ductal node-negative carcinomas were used, for which we had a mean follow-up time of 96 months. ER and PR status, as well as the expression of Smad2/3, Smad4, and Ski proteins were evaluated using immunohistochemistry. Staining of 5% of the tumor cells was adopted as a threshold. SPSS13 for windows was used for the statistical analysis of the results. Results: Smad2/3 and Smad4 were strongly correlated with each other (p &lt; 0,001) and inversely correlated with patients’ DDFS (Kaplan-Meier plots, p = 0,004 for Smad2/3 and p = 0,026 for Smad4) and OS (Kaplan-Meier plots, p = 0,034 for Smad2/3 and p = 0,017 for Smad4). Smad2/3 was proved to be an independent prognostic factor in grade 1 tumors, while Smad4 was inversely correlated with PR expression (p = 0,028) and had a strong prognostic value in ER+ tumors (p = 0,02). Ski protein had a strong association with tumor grade (p &lt; 0.001) and was found to be an independent prognostic factor in Cox regression analysis (p = 0,006, exp(B) = 4,98). Conclusions: Smad 2/3 and Smad 4 not only are tumor suppressor molecules, but also inhibit ER dependent gene expression. This inhibition is lost when Smad's expression is reduced, and that is a potent explanation for Smad 4 prognostic value in ER positive tumors. Moreover the correlation with PR expression, may be due to the fact that PR is an indicator of ER pathway's integrity and also to PR's enallaktiki activation by ER-β. From the other hand, Ski protein acts as an oncogene in breast carcinogenesis and contributes to the development of a more aggressive tumor phenotype. No significant financial relationships to disclose.
Not just antibodies: B cells and T cells mediate immunity to COVID-19
Authors: Rebecca J. Cox, Karl A. Brokstad
Journal: Nature reviews. Immunology (2020)

Recent reports that antibodies to SARS-CoV-2 are not maintained in the serum following recovery from the virus have caused alarm. However, the absence of specific antibodies in the serum does not necessarily mean an absence of immune memory. Here, we discuss our current understanding of the relative contribution of B cells and T cells to immunity to SARS-CoV-2 and the implications for the development of effective treatments and vaccines for COVID-19. Here, Cox and Brokstad briefly discuss T cell- and B cell-mediated immunity to SARS-CoV-2, stressing that a lack of serum antibodies does not necessarily equate with a lack of immunity to the virus.
Primary Atrial Undifferentiated Sarcoma Found on FDG PET/CT Mimicking Cardiac Myxoma
Authors: Rang Wang, Guohua Shen, Rong Tian
Journal: Clinical Nuclear Medicine (2020)

Abstract A 52-year-old man had shortness of breath and chest discomfort for 2 months. Chest CT and MRI showed a mass in the left atrium attached to the mitral annulus without obvious enhancement. Initial diagnosis was suspected of myxoma. Preoperative FDG PET/CT demonstrated the corresponding lesion with abnormal FDG uptake, indicating a malignancy. Finally, histopathologic examination revealed primary undifferentiated sarcoma.
Neighborhood Environment Has a Profound Association With Refugees’ Health
Authors: Charles Agyemang, Marie Norredam
Journal: JAMA Network Open (2020)

Rita Hamad, MD, PhD; Buket Öztürk, MSc; Else Foverskov, PhD; Lars Pedersen, PhD; Henrik T. Sørensen, MD, PhD; Hans E. Bøtker, MD, PhD; Justin S. White, PhD
On-treatment serum albumin level can guide long-term treatment in patients with cirrhosis and uncomplicated ascites
Authors: Paolo Caraceni, Manuel Tufoni, Giacomo Zaccherini, Oliviero Riggio, Paolo Angeli, Carlo Alessandria, Sergio Neri, Francesco G. Foschi, Fabio Levantesi, Aldo Airoldi, Loredana Simone, Gianluca Svegliati-Baroni, Stefano Fagiuoli, Giacomo Laffi, Raffaele Cozzolongo, Vito Di Marco, Vincenzo Sangiovanni, Filomena Morisco, Pierluigi Toniutto, Antonio Gasbarrini, Rosanna De Marco, Salvatore Piano, Silvia Nardelli, Chiara Elia, Andrea Roncadori, Maurizio Baldassarre, Mauro Bernardi, Marco Domenicali, Ferdinando A. Giannone, Agnese Antognoli, Manuela Merli, Chiara Pasquale, Stefania Gioia, Silvano Fasolato, Antonietta Sticca, Daniela Campion, Alessandro Risso, Giorgio M. Saracco, Loredana Prestianni, Federica Fidone, Daniela Maiorca, Agostino Rizzotto, Federica Mirici Cappa, Arianna Lanzi, Elga Neri, Anna Visani, Antonio Mastroianni, Giovanni Perricone, Alberto B. Alberti, Lucia Cesarini, Chiara Mazzarelli, Marcello Vangeli, Raffaella Viganò, Marco Marzioni, Francesca Capretti, Alba Kostandini, Giulia Magini, Maria Colpani, Tommaso Gabbani, Maria Marsico, Marianna Zappimbulso, Josè Petruzzi, Vincenza Calvaruso, Giovanni Parrella, Nicola Caporaso, Francesco Auriemma, Maria Guarino, Fabio Pugliese, Annalisa Tortora, Pietro Leo, Mario Angelico, Francesco De Leonardis, Alessandra Pecchioli, Piera Rossi, Giovanni Raimondo, Irene Cacciola, Gianfranco Elia, Elisa Negri, Marcello Dallio, Carmelina Loguercio, Alessandro Federico, Dario Conte, Sara Massironi, Giorgio Ballardini Natascia Celli, Maria Rendina, Roberto Bringiotti, Nicola Maurizio Castellaneta, Francesco Salerno, Sergio Boccia, Riccardo Guarisco, Alessandra Galioto, Marta Cavallin, Alida Andrealli
Journal: Journal of Hepatology (2020)
Detection of unknown primary neuroendocrine tumors (CUP-NET) using <sup>68</sup>Ga DOTA-NOC receptor PET/CT
Authors: D. Hörsch, V. Prasad, V. Ambrosini, M. Hommann, S. Fanti, R. P. Baum
Journal: Journal of Clinical Oncology (2009)

4599 Background: This bi-centric study aimed at determining the role of receptor PET/CT using 68 Ga-DOTA-NOC in the detection of undiagnosed primary sites of neuroendocrine tumours (NETs). Methods: Overall 59 patients (M: F 33:26, age 65±9 yr) with documented NET and unknown primary, were enrolled. PET/CT was performed after injection of approximately 100 MBq (46–260 MBq) of 68 Ga-DOTA-NOC. The maximum standardised uptake values (SUVmax) were calculated and compared with SUVmax in known pancreatic NET (pNET) and ileum / jejunum / duodenum (SI-NET). The results of PET/CT were also correlated with CT alone. Results: In 35/59 (59%) of patients, 68 Ga-DOTA-NOC PET/CT localised the site of the primary: ileum/jejunum (14), pancreas (16), rectum (2), lungs (2) and paraganglioma (1). CT alone (on retrospective analyses) confirmed the findings in 12/59 (20%) patients. The mean SUVmax of identified previously unknown pNET and SI-Net were 18.6 ± 9.8 (range 7.8–34.8) and 9.1± 6.0 (range 4.2–27.8), respectively. SUVmax in patients with previously known pNET and SI-NET were 26.1± 14.5 (range 8.7–42.4) and 11.3±3.7 (range 5.6- 17.9). The SUVmax of the unknown pNET and SI-NET were significantly lower (p&lt; 0.05) as compared to the ones with known primary tumour sites. 19% of the patients had high grade, and 81% low grade NET. In 4/59 patients the primary tumour was subsequently resected (2 pancretic, one ileal and one rectal tumour). Conclusions: Our data indicate that 68 Ga- DOTA-NOC PET/CT is highly superior to 111 In Octreoscan (17% detection rate for CUP according to literature) and can play a major role in the management of patients with CUP-NET. No significant financial relationships to disclose.
Reproductive health importance in oncology care
Authors: H. A. Zaren, A. Patel, E. K. Radeke, A. B. Uy
Journal: Journal of Clinical Oncology (2009)

e20744 Background: Based on a case series of patients, we recognized a disparity between patients’ reproductive health goals and conveyed health information by providers on reproductive health issues. The objective of this study was to assess the reproductive health interest amongst cancer care providers. Methods: This observational study was performed using a 13 item questionnaire that was administered to 15 healthcare professionals in oncology and allied health fields. The items in the questionnaire related to information regarding the importance of cancer care, sexuality, fertility preservation and contraception. Results: Of the providers surveyed, 11 were medical doctors, 3 were nurses, and 1 was indicated as other. On a scale of 0 to 10, 86.6% (n=13) rated cancer care as extremely important (10), 33% (n=5) felt the same for fertility preservation, and 46.6% (n=7) for sexuality. In a rank of importance, cancer care was first, followed by sexuality, fertility, and contraception. Only 33% (n=5) of providers always asked patients about interest in fertility preservation and with regards to contraception, only 33% (n=5) offer contraception to reproductive age patients. Conclusions: Although most providers felt that sexuality and fertility are important to women diagnosed with cancer, their practice and information provision does not reflect these findings. This highlights the significance of bringing closer together the goals of the health care providers with their actual practice to improve patient care. No significant financial relationships to disclose.
HP0006 A randomised controlled trial evaluating effectiveness of three hand treatment approaches in rheumatoid arthritis (ra)
Authors: AV Chadwick, C Simpson, K Murray, D Mulherin, PW Jones, K Dziedzic
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Little evidence available about optimum therapy for the rheumatoid hand or its effect on disability. <h3>Objectives</h3> To evaluate the effectiveness of three different therapeutic approaches to the rheumatoid hand. <h3>Methods</h3> 67 Subjects (M = 20), mean age 59.6 yrs (range 24–77 yrs) and disease duration 13.4 yrs (range 1–52 yrs), were randomised to 3 groups. Each subject received written and verbal information about joint protection from an experienced therapist. Group 1 subjects received strengthening and mobilising exercises, Group 2 stretching exercises and Group 3 the joint protection advice alone. Subjects in Groups 1 and 2 undertook a graduated programme of increasing repetitions (up to 20) of the exercises, twice daily over the six month study period. Outcome measures were obtained by two blinded assessors at 1, 3 and 6 months using AIMS II subscales relating to upper limb, hand and finger function; dynamometry; gross and pinch grip measured using the Jamar dynamometer; the Jebson-Taylor Hand Function Test and goniometry including joint ranges for wrist, thumb and individual fingers of each hand. Ethical approval was granted from the Local Research Ethics Committee. <h3>Results</h3> 67 patients with a confirmed diagnosis of RA entered into the study. There were no statistically significant differences in baseline characteristics or demographic data. 52 patients completed all visits for all measurements. 58 attended at their one month measurement and 54 at their 3 month measurement. 15 subjects dropped out of the study. There was no significant difference in drop out rates between the 3 groups. One subject was lost to follow up. Analysis was performed using the SPSS package version 10.0. Differences in change between baseline and follow-up at 6 months were assessed using ANOVA for approximately normal data and Kruskal-Wallis test for non-normal data. At 6 months there was a statistically significant difference in AIMS II Upper limb function (p = 0.007, F-ratio 5.47) in the 3 groups. Comparison of pairs of groups at the 5% level of significance with Bonferroni adjustment showed that Group 1 was significantly different from Groups 2 and 3. In addition there were non-significant differences but improvements noted in AIMS (hand and finger function subscales) and pinch grip for both hands in this group. There were no changes in hand function or impairment measures in Groups 2 or 3. <h3>Conclusions</h3> This study demonstrates a statistically and clinically significant improvement in upper limb function following a programme of home strengthening hand exercises in patients with RA. Further work is recommended to evaluate which specific exercises are most beneficial.
Oral mucositis prevention by low-level laser therapy in head and neck cancer patients submitted to concurrent chemoradiation: A prospective randomized study
Authors: G. Castro, A. G. de Lima, D. R. Lopes, M. V. Ortegosa, M. C. Rosalmeida, E. Gil, A. I. Cavalcanti Leal, M. H. Federico, R. C. Villar, I. Snitcovsky
Journal: Journal of Clinical Oncology (2009)

6019 Background: Oral mucositis is a major treatment-related complication of concurrent chemoradiation (CRT) in head and neck cancer (HNC) patients (pts), affecting nutrition, pain control, quality of life and adequate treatment delivery. Low level laser (LLL) is a promising preventive therapy. We aimed to evaluate the efficacy of LLL to decrease and delay severe oral mucositis and its impact on RT interruptions. Methods: In this prospective, randomized, double-blind, phase III trial, pts were treated with either daily He-Ne LLL 2.5 J/cm 2 , or placebo laser, before RT. Eligible pts had to be diagnosed with SCC or undifferentiated carcinoma of oral cavity, pharynx, larynx, or metastatic to the neck with unknown primary site (UPS); age &gt; 18 y; candidates to adjuvant or definitive CRT; signed informed consent. CRT consisted of conventional RT 60–70 Gy (1.8–2.0 Gy/d, 5 times/wk) + concurrent cisplatin 100 mg/m 2 every 3 wks. Main endpoints were oral mucositis severity in wks 2, 4 and 6 (CTC-NCI v.2.0); RT interruptions due to mucositis; pain intensity (VAS). To detect a decrease in the incidence of grade 3 or 4 oral mucositis from 80 to 50%, we planned to enroll 74 pts, error I/II 5 and 20%, respectively. Results: 73 pts were included (77% male; mean age 53 y); primary site: oropharynx (31 pts), larynx (15), nasopharynx (10), hypopharynx (8), oral cavity (7 pts), UPS (2); 36 pts received prophylactic LLL. Mean delivered RT dose (Gy) was higher in pts treated with LLL (69.3 vs. 67.8, p = 0.04). The number of treatment fields was the same (6 vs. 6, p = 0.50) and the mean cisplatin dose-intensity was 40.9 and 40.1 mg/m 2 /wk (p = 0.3) between pts treated with LLL or placebo, respectively. During CRT, the number of pts diagnosed with grade 3 or 4 oral mucositis treated with LLL/placebo was 4/5 (wk 2, p = 1.0); 4/11 (wk 4, p = 0.08); and 8/9 (wk 6, p = 1.0), respectively. More pts treated with placebo had RT interruptions due to mucositis (6 vs. 0, p =0.02). The occurrence of severe pain did not differ between the study arms in wks 2, 4 and 6 (5/5, 8/8 and 8/8, p = 1.0). Conclusions: LLL therapy was effective in reducing grade 3 or 4 oral mucositis and in reducing RT interruptions in these HNC pts treated with concurrent CRT, which may translate into improved CRT efficacy and tolerance. No significant financial relationships to disclose.