tbuckley/cabot-search huggingface dataset:
The functions and clinical significance of circRNAs in hematological malignancies
Authors: Xiangxiang Zhou, Linquan Zhan, Kai Huang, Xin Wang
Journal: Journal of Hematology & Oncology (2020)

Abstract With covalently closed circular structures, circular RNAs (circRNAs) were once misinterpreted as by-products of mRNA splicing. Being abundant, stable, highly conserved, and tissue-specific, circRNAs are recently identified as a type of regulatory RNAs. CircRNAs bind to certain miRNAs or proteins to participate in gene transcription and translation. Emerging evidence has indicated that the dysregulation of circRNAs is closely linked to the tumorigenesis and treatment response of hematological malignancies. CircRNAs play critical roles in various biological processes, including tumorigenesis, drug resistance, tumor metabolism, autophagy, pyroptosis, and ferroptosis. The N6-methyladenosine modification of circRNAs and discovery of fusion-circRNAs provide novel insights into the functions of circRNAs. Targeting circRNAs in hematological malignancies will be an attractive treatment strategy. In this review, we systematically summarize recent advances toward the novel functions and molecular mechanisms of circRNAs in hematological malignancies, and highlight the potential clinical applications of circRNAs as novel biomarkers and therapeutic targets for future exploration.
Covid-19 exposes NHS fault lines in England
Authors: Chris Ham
Journal: BMJ (2020)

Covid-19 exposes NHS fault lines in EnglandLegislation is needed to ensure collaboration between organisations Chris Ham chairEverything in the NHS changed in March when national and local leaders acted to prepare for the rapid increase in demand for care foreshadowed by experience in countries affected earlier in the covid-19 pandemic.Hospitals reorganised their services to increase intensive care capacity, discharge patients to free up beds, and redeploy staff to support the treatment of patients with covid-19.National leaders commissioned additional capacity in the Nightingale hospitals to avoid patients being denied care at the peak of the pandemic.General practices collaborated by designating some surgeries for the assessment of patients with covid-19 and others for the treatment of non-covid problems.
Interventional Radiology and Pulmonology in Life-Threatening Aneurysm of the Left Pulmonary Artery
Authors: Stephan Eisenmann, Franz Stangl, Nina Lambrecht, Bettina Wollschläger, Sebastian Böhm, Richard Brill, Iris Vogt, Henning Baust, Michael Bucher, Walter A. Wohlgemuth
Journal: American Journal of Respiratory and Critical Care Medicine (2020)
Development of anticancer agents using bioactive products of marine Bacillus spp. in head and neck cancer
Authors: Chul-Ho Kim, Sung Un Kang, HaNeul Lee, Mi Hye Lee, JungHee Pyun, Hye Sook Hwang
Journal: Cancer Research (2008)

637  Background: H31 is a new anti-tumor material that were originally discovered in marine Bacillus spp. H31 has demonstrated powerful anticancer effect against panel of human hypopharyngeal SCC(FaDu), oral cavity SCC(KB), larynx SCC(SNU1066), gastric cancer(SNU1, 16) at very low concentrations. In this study, we investigated the effect of H31 as a chemopreventative or therapeutic agent in head and neck cancer.  Method: We finally found 5(/514) candidate materials from marine microbial extracts in anti-cancer drug screening by MTT assay. We investigated the effect of H31(one of the candidates) on HGF-induced proliferation, dispersion, invasion, and expression of MMPs(by RT-PCR, zymogram) and induction of apoptosis(by DNA fragmentation assay, FACScan with Annexin V-FITC) in FaDu cells, a hypopharyngeal cancer cell line. And we analyzed signal pathway of H31 and evaluated neurotoxicity in vivo zebrafish model.  Results: H31 is originated from novel marine Bacillus spp. (similarity 95% with Bacillus spp by gene sequencing). H31 inhibited HGF-induced scattering, migration, invasion and MMP-2 activity of hypopharyngeal cancer cells in dose-dependant. (p
TNAP as a therapeutic target for cardiovascular calcification: a discussion of its pleiotropic functions in the body
Authors: Claudia Goettsch, Agnieszka Strzelecka-Kiliszek, Laurence Bessueille, Thibaut Quillard, Laura Mechtouff, Slawomir Pikula, Emmanuelle Canet-Soulas, Millan Jose Luis, Caroline Fonta, David Magne
Journal: Cardiovascular Research (2020)

Cardiovascular calcification (CVC) is associated with increased morbidity and mortality. It develops in several diseases and locations, such as in the tunica intima in atherosclerosis plaques, in the tunica media in type 2 diabetes and chronic kidney disease, and in aortic valves. In spite of the wide occurrence of CVC and its detrimental effects on cardiovascular diseases (CVD), no treatment is yet available. Most of CVC involve mechanisms similar to those occurring during endochondral and/or intramembranous ossification. Logically, since tissue-nonspecific alkaline phosphatase (TNAP) is the key-enzyme responsible for skeletal/dental mineralization, it is a promising target to limit CVC. Tools have recently been developed to inhibit its activity and preclinical studies conducted in animal models of vascular calcification already provided promising results. Nevertheless, as its name indicates, TNAP is ubiquitous and recent data indicate that it dephosphorylates different substrates in vivo to participate in other important physiological functions besides mineralization. For instance, TNAP is involved in the metabolism of pyridoxal phosphate and the production of neurotransmitters. TNAP has also been described as an anti-inflammatory enzyme able to dephosphorylate adenosine nucleotides and lipopolysaccharide. A better understanding of the full spectrum of TNAP's functions is needed to better characterize the effects of TNAP inhibition in diseases associated with CVC. In this review, after a brief description of the different types of CVC, we describe the newly uncovered additional functions of TNAP and discuss the expected consequences of its systemic inhibition in vivo.
The prognostic value of cardiopulmonary exercise testing in interstitial lung disease: a systematic review
Authors: Shaney L Barratt, Richard J Davis, Charles Sharp, John Pauling
Journal: European Respiratory Journal (2020)

The heterogeneity of interstitial lung disease (ILD) results in prognostic uncertainty concerning end-of-life discussions and optimal timing for transplantation. Effective prognostic markers and prediction models are needed. Cardiopulmonary exercise testing (CPET) provides a comprehensive assessment of the physiological changes in the respiratory, cardiovascular and musculoskeletal systems in a controlled laboratory environment. It has shown promise as a prognostic factor for other chronic respiratory conditions. We sought to evaluate the prognostic value of CPET in predicting outcomes in longitudinal studies of ILD.

MEDLINE, Embase and the Cochrane Database of Systematic Reviews were used to identify studies reporting the prognostic value of CPET in predicting outcomes in longitudinal studies of ILD. Study quality was assessed using the Quality in Prognosis Study risk of bias tool.

Thirteen studies were included that reported the prognostic value of CPET in ILD. All studies reported at least one CPET parameter predicting clinical outcomes in ILD, with survival being the principal outcome assessed. Maximum oxygen consumption, reduced ventilatory efficiency and exercise-induced hypoxaemia were all reported to have prognostic value in ILD. Issues with study design (primarily due to inherent problems of retrospective studies, patient selection and presentation of numerous CPET parameters), insufficient adjustment for important confounders and inadequate statistical analyses limit the strength of the conclusions that can be drawn at this stage.

There is insufficient evidence to confirm the value of CPET in facilitating “real-world” clinical decisions in ILD. Additional prospective studies are required to validate the putative prognostic associations reported in previous studies in carefully phenotyped patient populations.
Prehospital Plasma Resuscitation in Patients With Traumatic Brain Injury
Authors: Robert H. Bonow
Journal: JAMA Network Open (2020)

Danielle S. Gruen, PhD; Francis X. Guyette, MD; Joshua B. Brown, MD; David O. Okonkwo, MD; Ava M. Puccio, PhD; Insiyah K. Campwala, BS; Matthew T. Tessmer, BS; Brian J. Daley, MD; Richard S. Miller, MD; Brian G. Harbrecht, MD; Jeffrey A. Claridge, MD; Herb A. Phelan, MD; Matthew D. Neal, MD; Brian S. Zuckerbraun, MD; Mark H. Yazer, MD; Timothy R. Billiar, MD; Jason L. Sperry, MD
Proteins for increased surface expression of the α6β4 nicotinic acetylcholine receptor: nothing but good news?
Authors: Stephen Grant, Henry A Lester
Journal: Journal of Clinical Investigation (2020)

Useful animal models of disease in neuroscience can make accurate predictions about a therapeutic outcome, a feature known as predictive validity. In this issue of the JCI, Knowland et al. provide an improved model to assess nicotinic acetylcholine receptor (nAChR) ligands for treating chronic pain. The authors identify two proteins, the voltage-dependent calcium channel auxiliary subunit BARP and the unfolded protein response sensor IRE1α, that are required for robust heterologous expression of α6β4, an nAChR subtype in dorsal root ganglia (DRG). This nAChR is a candidate for the analgesic effects of nicotine as well as the frog toxin epibatidine. Now researchers can efficiently screen for α6β4 nAChR-selective agonists using heterologous expression systems. Candidates that emerge will enable researchers to test the predictive validity of mouse models for chronic pain in the nAChR context. If all these steps work, one can envision a class of non-opioid nAChR-targeted analgesics for chronic pain.
Multiple sclerosis: NICE recommends treatment for secondary progressive MS
Authors: Jacqui Wise
Journal: BMJ (2020)

The National Institute for Health and Care Excellence has recommended an oral drug for treating secondary progressive multiple sclerosis, the first new treatment for this group of patients in more than a decade.

The draft guidance recommends siponimod (marketed in the UK by Novartis as Mayzent) for patients with secondary progressive MS with evidence of active disease: those who have relapses or have evidence of inflammatory …
Workforce implications of self-isolation resulting from symptomatic schoolchildren
Authors: Danny J N Wong, Kariem El-Boghdadly
Journal: BMJ (2020)

After a trough in new covid-19 cases in the UK over the summer, case numbers in recent weeks have begun to rise sharply again.1 Either causing this or in spite of this, children have returned to schools2 and the government is actively encouraging people to return to their offices for work.

As Mathew mentions,3 returning to …
Kia ora koutou katoa: Australasian College of Sport and Exercise Physicians (ACSEP) warm up
Authors: Hamish Robert Osborne, Daniel Joseph Exeter
Journal: British Journal of Sports Medicine (2020)

Kia ora koutou katoa. Welcome to the Australasian College of Sport and Exercise Physicians (ACSEP) edition of the BJSM

In June/July 2020 the COVID-19 free land of Aotearoa New Zealand launched the first full return of professional basketball to the world. The national women’s team, the Tall Ferns, played in front of a live audience in Auckland shortly before a small cluster of COVID-19 re-emerged and Auckland went again into lockdown. At the time of writing, New Zealand’s ‘team of 5 million’ were socially isolating and getting used to wearing masks in public. While several parts of Australia are COVID-19 free, millions in Melbourne remain in lockdown. While some sports have managed to play in bubbles, others have had system failures and widespread viral infection involving whole teams.

As clinicians, COVID-19 has meant providing ‘usual’medical care, to support athletes health, well-being and employment in isolation bubbles and then then in a heartbeat caring for whole teams with life threatening virus. Ultimately, there will be much musing over how we best supported athletes through a pandemic. Elimination again appears possible in New Zealand and athletes will again …
A simple way to deliver vacuum therapy: the tube-in-tube endoluminal vacuum therapy modification
Authors: Marcelo Lima, Gustavo Lima, Caterina Pennacchi, Rodrigo Scomparin, Gustavo de Paulo, Bruno Martins, Fauze Maluf-Filho
Journal: Endoscopy (2020)

A patient underwent endoscopic submucosal dissection of the middle esophagus to treat a superficial squamous cell carcinoma (T1a). He was admitted to the emergency room 2 weeks later with signs of sepsis. Computed tomography (CT) scan showed a mediastinal abscess, and an endoscopic evaluation revealed esophageal perforation at the resection site communicating with the mediastinal abscess. We decided to manage this situation with vacuum therapy [1] [2] [3]. However, a small esophageal perforation orifice and a much larger mediastinal abscess raised the question of how to position the sponge into the mediastinum. Inspired by the experience of pediatric surgeons, we assembled an aspiration device using a 12-Fr Levin tube within a 20-Fr Levin tube. The vacuum pump was attached to the inner tube, and the outer tube functioned to prevent aspiration biopsies or clogging. No sponge was used, and the aspiration device was easily positioned inside the mediastinal abscess by sliding it over a guidewire ([Video 1]).
Abstract 11398: Incidence of Takotsubo Cardiomyopathy in a Large Urban Hospital in the USA
Authors: Dinesh Kadariya, Lori Keyser-Marcus, Liangsuo Ma, Tamas S Gal, Rehan Qayyum, Gerry Moeller, Antonio Abbate
Journal: Circulation (2018)

Introduction: Takotsubo cardiomyopathy (TCM) or stress cardiomyopathy is a transient reversible, but potentially life-threatening cardiomyopathy initially described in the Japanese population. An i...
Human Prion Disease Surveillance in Washington State, 2006-2017
Authors: Liliana Sánchez-González, Ryan A. Maddox, Larissa C. Lewis, Janis E. Blevins, Elizabeth J. Harker, Brian S. Appleby, Marissa K. Person, Lawrence B. Schonberger, Ermias D. Belay, Chas DeBolt, Kathryn H. Lofy
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Human prion disease surveillance is critical to detect possible cases of variant Creutzfeldt-Jakob disease and other acquired forms of prion disease in the United States. Results are presented here that describe 12 years of surveillance in Washington, the only US state that has reported the presence of classic bovine spongiform encephalopathy, an animal prion disease that has been shown to transmit to humans. <h3>Objective</h3> To describe the current prion disease surveillance system in Washington and the epidemiological and clinical results of surveillance from 2006 through 2017. <h3>Design, Setting, and Participants</h3> This cross-sectional study reports findings from the human prion disease surveillance system in place in Washington state from January 1, 2006, through December 31, 2017. Participants included Washington residents with a clinical suspicion of human prion disease or suggestive test results from the National Prion Disease Pathology Surveillance Center or with prion disease listed as a cause of death on the death certificate. Data for this report were analyzed from June 1, 2016, to July 1, 2020. <h3>Exposure</h3> Human prion disease diagnosis. <h3>Main Outcomes and Measures</h3> The main outcome was incidence of human prion disease cases, including identification of variant Creutzfeldt-Jakob disease. <h3>Results</h3> A total of 143 human prion disease cases were detected during the study period, none of which met criteria for a variant Creutzfeldt-Jakob disease diagnosis. Among 137 definite or probable cases, 123 (89.8%) occurred in persons aged 55 years or older, with a median age at death of 66 years (range, 38-84 years). Most patients were White (124 [92.5%] among 134 with reported race), and slightly over half were male (70 [51.1%]). The average annual age-adjusted prion disease incidence was 1.5 per million population per year, slightly higher than the national rate of 1.2 per million. A total of 99 cases (69.2%) were confirmed by neuropathology. Sporadic prion disease was the most common diagnosis, in 134 cases (93.7%), followed by familial prion disease in 8 cases (5.6%). One iatrogenic prion disease case (0.7%) was also reported. <h3>Conclusions and Relevance</h3> The findings of this cross-sectional study suggest that demographic characteristics of patients with prion disease in Washington are consistent with national findings. The slightly higher incidence rate may be due to the state’s enhanced surveillance activities, including close collaboration with key partners and educational efforts targeted toward health care providers. Results indicate that surveillance will continue to be beneficial for monitoring epidemiological trends, facilitating accurate diagnoses, and detecting variant Creutzfeldt-Jakob disease or other emerging human prion disease cases.
COVID-19, Social Justice, and Clinical Cancer Research
Authors: James H Doroshow, Sheila Prindiville, Worta McCaskill-Stevens, Margaret Mooney, Patrick J Loehrer
Journal: JNCI Journal of the National Cancer Institute (2020)

The coronavirus disease 2019 (COVID-19) pandemic and related socioeconomic events have markedly changed the environment in which cancer clinical trials are conducted. These events have resulted in a substantial, immediate-term decrease in accrual to both diagnostic and therapeutic cancer investigations as well as substantive alterations in patterns of oncologic care. The sponsors of clinical trials, including the US National Cancer Institute, as well as the cancer centers and community oncology practices that conduct such studies, have all markedly adapted their models of care, usage of healthcare personnel, and regulatory requirements in the attempt to continue clinical cancer investigations while maintaining high levels of patient safety. In doing so, major changes in clinical trials practice have been embraced nationwide. There is a growing consensus that the regulatory and clinical research process alterations that have been adopted in response to the pandemic (such as the use of telemedicine visits to reduce patient travel requirements and the application of remote informed consent procedures) should be implemented long term. The COVID-19 outbreak has also refocused the oncologic clinical trials community on the need to bring clinical trials closer to patients by dramatically enhancing clinical trial access, especially for minority and underserved communities that have been disproportionately affected by the pandemic. In this commentary, changes to the program of clinical trials supported by the National Cancer Institute that could improve clinical trial availability, effectiveness, and diversity are proposed.
46P Gold nanoparticles as radiosensitizers for human colon carcinoma cells
Authors: V. Glazunova, N. Samunashvili, J. Volodina, E. Ivanova, M. Kartseva, O. Dementyeva, V. Karandashev, A. Belousov, V. Rudoy, M. Kolyvanova, A. Shtil, V. Morozov
Journal: Annals of Oncology (2020)
Abstract 10669: Treatment of Acute Cardiac Transplantation Rejection by Fk506-loaded Microbubbles Combined With Ultrasound-targeted Microbubble Destruction (utmd)
Authors: Mingxing Xie, Jie Liu, Yihan Chen, Li Zhang
Journal: Circulation (2019)

Objective: FK506 is an effective immunosuppressant for acute cardiac transplantation rejection. However, its’ therapeutic effect is limited by side effects, poor water solubility, and pharmacokinet...
SP0056 Measurement issues
Authors: A Tennant
Journal: Annals of the Rheumatic Diseases (2001)

<h3></h3> In a recent European survey of outcome measures for rheumatoid arthritis over 60 different instruments were found to be in use. For low back pain, over 100 different instruments were found to be in use. If, for example, measuring disability is considered important, what are the characteristics of a good measure of disability? How do we chose between competing instruments? Recent advances in our understanding of outcome measurement have identified a number of fundamental criteria that should be met, prior to more established tests of reliability, validity and responsiveness. The two most important characteristics are unidimensionality and absence of Differential Item Functioning (DIF). The ICIDH helps us to think conceptually about outcomes, and contributes to measurement by identifying unidimensional constructs. A new mathematical approach (Rasch analysis) then allows for formal tests of unidimensionality in ordinal scales. Questions, or tasks which are summated in some fashion to give an overall score must be unidimensional. Furthermore, at the same level of ability (for example in walking), the probability of a patient doing a task must be the same irrespective of whether they are male or female, young or old, underlying pathology (cross-diagnostic validity) or country of use (cross-cultural validity) – the absence of DIF. Once these fundamental requirements of measurement are met, tests of reliability, validity and responsiveness may proceed. In this way, those working in the field of arthritis can be confident that evaluation of interventions are supported by high quality measurement.
Sequential Stratification Prognostic Score for Patients with Intermediate-Risk Myelodysplastic Syndrome
Authors: Christopher B Benton, Maliha Khan, Graciela Nogueras González, Aziz Nazha, Jin Piao, Jing Ning, Fleur M. Aung, Elias J. Jabbour, Tapan Kadia, Gautam Borthakur, Farhad Ravandi, Rami S. Komrokji, David P. Steensma, Amy E. DeZern, Gail J. Roboz, Mikkael A. Sekeres, Michael Andreeff, Hagop M. Kantarjian, Guillermo Garcia-Manero
Journal: Blood (2017)
Abstract 11757: Prevalence of Hypertension and Cardiovascular Risk According to Blood Pressure Thresholds Used for Diagnosis
Authors: Julio A Lamprea-Montealegre, Ian H de Boer, Leila R Zelnick, Nisha Bansal, Yoshio N Hall
Journal: Circulation (2018)

Background: The recent American College of Cardiology and American Heart Association hypertension guidelines recommend a blood pressure (BP) threshold of 130/80 mmHg or higher for the diagnosis of ...
進行性再発性子宮頚癌患者におけるパゾパニブ+ラパチニブ併用療法と比較した,パゾパニブもしくはラパチニブの単独治療に関する第2相非盲検試験
Authors: J Monk Bradley, Lopez Luis Mas, J Zarba Juan, Oaknin Ana, Tarpin Carole, Termrungruanglert Wichai, A Alber Jacquelyn, Ding Jie, W Stutts Melissa, N Pandite Lini
Journal: Journal of Clinical Oncology (2010)
Clinical decision support systems in low resource settings
Authors: Robert R Korom, Gabriel Njue
Journal: BMJ (2020)

A recent meta-analysis of the impact of clinical decision support systems,1 along with an accompanying editorial,2 suggests that such systems have so far resulted in very modest improvements in healthcare quality. The editorial authors suggest a change of approach.

We work in a low resource ambulatory care setting in Kenya and we are successfully implementing clinical decision support systems …
Prevalence of allergic contact dermatitis to decyl and lauryl glucoside in the UK and Ireland
Authors: L.F. Soriano, C.G. Bertram, M.M.U. Chowdhury, P. Cousen, P. Divekar, S.A. Ghaffar, C. Green, A. Havelin, C.R. Holden, G.A. Johnston, A.A. Mughal, E. Nic Dhonncha, R.A. Sabroe, N.M. Stone, D.A. Thompson, S.M. Wilkinson, D.A. Buckley
Journal: British Journal of Dermatology (2020)