tbuckley/cabot-search huggingface dataset:
Pathology of Peripheral Artery Disease in Patients With Critical Limb Ischemia
Authors: Navneet Narula, Andrew J. Dannenberg, Jeffrey W. Olin, Deepak L. Bhatt, Kipp W. Johnson, Girish Nadkarni, James Min, Sho Torii, Priti Poojary, Sonia S. Anand, Jeroen J. Bax, Salim Yusuf, Renu Virmani, Jagat Narula
Journal: Journal of the American College of Cardiology (2018)
NHS chief tells hospitals to send patients to private providers to cut waiting times
Authors: Gareth Iacobucci
Journal: BMJ (2018)

NHS patients could be sent to private providers for routine elective treatment under a plan by healthcare bosses to reduce waiting times.

The NHS has been struggling to meet its target to treat 92% of patients who need elective care within 18 weeks. In June 4.3 million people in England were awaiting treatment, the highest number since data collection began in August 2007.1

In a letter sent to local clinical commissioning groups, NHS England’s national director for operations and information, Matthew Swindells, said that there had been a “significant underdelivery …
Abstract 14658: Accuracy of 3D Printed Models of the Aortic Valve Complex for Transcatheter Aortic Valve Replacement (TAVR) Planning: Comparison to Computed Tomographic Angiography (CTA)
Authors: Tianrun Cai, Michael K Cheezum, Andreas A Giannopoulos, Ron Blankstein, Frank J Rybicki, Michael L Steigner, DImitrios Mitsouras
Journal: Circulation (2015)

Background: TAVR is a safe alternative to surgical valve replacement. 3D printing is an emerging technology transforming 2D medical images to tangible anatomically accurate models. Hypothesis: To determine the accuracy of 3D printed models of the aortic valve (AV) complex for TAVR planning compared to CTA. Methods: 10 pts with pre TAVR contrast enhanced CTA were randomly selected. The blood pool of the AV complex from proximal ascending aorta above the coronary arteries to the AV annulus was automatically segmented. A 3D printable STL model was exported to Computer Aided Design software and further processed. Models were printed with a material extrusion 3D printer. One reader blinded to CTA measured the max and min diameter of the AV annulus and coronary ostia takeoff height of the printed model with a caliper. Two independent CV imagers performed these measurements in double-oblique CTA reformats. Model measurements were compared to CTA findings by Pearson’s correlation and via the mean and 95% confidence interval (CI) of the absolute difference to CTA compared to CTA interobserver differences. Results: 3D printed model measurements had excellent correlation to CTA (r=.86-.97). Mean absolute difference in max diameter between 3D-printed model and CTA was 0.85 mm (CI: [.43, 1.28]), compared to 1.17mm (CI: [.59, 1.75]) between CTA readers; for min diameter it was 0.49mm (CI: [.2, .78]) compared to 0.45mm (CI: [.17, .73]) between CTA readers. Mean absolute difference of height to left main ostium was 1.62mm (CI: [.93, 2.3]) compared to 1.47 mm (CI: [.78, 2.16]) for CTA readers, and to right coronary ostium it was 1.0 mm (CI: [0.53-1.46]) compared to 1.98 mm (CI: [1.38, 2.58]) for CTA readers. Conclusion: CTA-derived 3D printed models of the AV complex provided excellent correlation to CTA measurements of the annulus and ostia height. 3D printing can assist towards planning of TAVR sizing and minimizing procedural complications such as paravalvular leak and coronary occlusion.
Scottish consultants being “singled out” for low pay award, says BMA
Authors: Abi Rimmer
Journal: BMJ (2018)

NHS salaried doctors in Scotland who earn below £80 000 (€88 000; $103 000) will get a 3% increase in pay in 2018-19, backdated to 1 April 2018, the Scottish government has announced. But increases for salaried doctors earning more than £80 000 will be capped at £1600, in line with the Agenda for Change pay deal and the Scottish public sector pay policy.

Independent contractor GPs will also receive a 3% increase in earnings in 2018-19.

The increase is higher than …
Human Leukocyte Antigen Class I-Restricted Activation of CD8+ T Cells Provides the Immunogenetic Basis of a Systemic Drug Hypersensitivity
Authors: Diana Chessman, Lyudmila Kostenko, Tessa Lethborg, Anthony W. Purcell, Nicholas A. Williamson, Zhenjun Chen, Lars Kjer-Nielsen, Nicole A. Mifsud, Brian D. Tait, Rhonda Holdsworth, Coral Ann Almeida, David Nolan, Whitney A. Macdonald, Julia K. Archbold, Anthony D. Kellerher, Debbie Marriott, Simon Mallal, Mandvi Bharadwaj, Jamie Rossjohn, James McCluskey
Journal: Immunity (2008)
Tissue Engineered Constructs for Periodontal Regeneration: Current Status and Future Perspectives
Authors: Cedryck Vaquette, Sophia P. Pilipchuk, P. Mark Bartold, Dietmar W. Hutmacher, William V. Giannobile, Saso Ivanovski
Journal: Advanced Healthcare Materials (2018)

Abstract The periodontium, consisting of gingiva, periodontal ligament, cementum, and alveolar bone, is a hierarchically organized tissue whose primary role is to provide physical and mechanical support to the teeth. Severe cases of periodontitis, an inflammatory condition initiated by an oral bacterial biofilm, can lead to significant destruction of soft and hard tissues of the periodontium and result in compromised dental function and aesthetics. Although current treatment approaches can limit the progression of the disease by controlling the inflammatory aspect, complete periodontal regeneration cannot be predictably achieved. Various tissue engineering approaches are investigated for their ability to control the critical temporo‐spatial wound healing events that are essential for achieving periodontal regeneration. This paper reviews recent progress in the field of periodontal tissue engineering with an emphasis on advanced 3D multiphasic tissue engineering constructs (TECs) and provides a critical analysis of their regenerative potential and limitations. The review also elaborates on the future of periodontal tissue engineering, including scaffold customization for individual periodontal defects, TEC's functionalization strategies for imparting enhanced bioactivity, periodontal ligament fiber guidance, and the utilization of chair‐side regenerative solutions that can facilitate clinical translation.
Managing scarlet fever
Journal: BMJ (2018)

### What you need to know

Scarlet fever is an infection caused by toxin producing strains of Streptococcus pyogenes (also known as group A streptococcus, or GAS). It was associated with high levels of morbidity and mortality when epidemics were common in the 18th and 19th centuries in Europe and the USA.1 Although the disease nearly disappeared during the 20th century, several countries, including the UK, have recently experienced a re-emergence of scarlet fever.123 In this article, we discuss the management of scarlet fever. In the UK, it is a notifiable disease.

In England and Wales, the incidence of scarlet fever reduced from 250 notifications in 100 000 population per year in 1944 to less than 5 in 100 000 in the 2000s.3 In 2013-14, however, there were 25 notifications in 100 000.3 Around 87% of cases were in children under 10.2

In 2014, England experienced the highest number of scarlet fever cases in 45 years (table 1).4 In 2015 and 2016, scarlet fever notifications were elevated in all areas in England compared with the same period in the preceding year.56 In the 2016-17 season, weekly scarlet fever notification rates fell below those seen during the previous three seasons.7

View this table:

Table 1 
Scarlet fever statistics (England)4



Peak season for GAS infections, including scarlet fever, occurs between December and April. …
CIRCpedia v2: An Updated Database for Comprehensive Circular RNA Annotation and Expression Comparison
Authors: Rui Dong, Xu-Kai Ma, Guo-Wei Li, Li Yang
Journal: Genomics Proteomics & Bioinformatics (2018)

Abstract Circular RNAs (circRNAs) from back-splicing of exon(s) have been recently identified to be broadly expressed in eukaryotes, in tissue- and species-specific manners. Although functions of most circRNAs remain elusive, some circRNAs are shown to be functional in gene expression regulation and potentially relate to diseases. Due to their stability, circRNAs can also be used as biomarkers for diagnosis. Profiling circRNAs by integrating their expression among different samples thus provides molecular basis for further functional study of circRNAs and their potential application in clinic. Here, we report CIRCpedia v2, an updated database for comprehensive circRNA annotation from over 180 RNA-seq datasets across six different species. This atlas allows users to search, browse, and download circRNAs with expression features in various cell types/tissues, including disease samples. In addition, the updated database incorporates conservation analysis of circRNAs between humans and mice. Finally, the web interface also contains computational tools to compare circRNA expression among samples. CIRCpedia v2 is accessible at http://www.picb.ac.cn/rnomics/circpedia.
Abstract 20433: Role of Cardiac Implantable Device Therapy in Patients With ATTR Wild Type Amyloidosis : A Retrospective Analysis of Mortality Outcomes
Authors: Deepak Padmanabhan, Anwar Chahal, Jennifer Knight, Nidhhi Tandon, Paul Chacko, Virend K Somers, Angela Dispenzieri, Martha Grogan, Peter Brady, Grace Lin
Journal: Circulation (2016)

Introduction: The role of cardiac implantable electronic device(CIED) therapy in patients with ATTR (senile) amyloid is not very well defined. Methods: We performed a retrospective analysis of a pr...
Comprehensive long‐term safety of adalimumab from 18 clinical trials in adult patients with moderate‐to‐severe plaque psoriasis
Authors: C. Leonardi, K. Papp, B. Strober, D. Thaçi, R.B. Warren, S. Tyring, D. Arikan, M. Karunaratne, W.C. Valdecantos
Journal: British Journal of Dermatology (2018)

Adalimumab (Humira® , AbbVie Inc., North Chicago, IL, U.S.A.) is a fully human monoclonal antibody specific for tumour necrosis factor-α that is approved to treat adults with moderate-to-severe chronic plaque psoriasis.To assess long-term safety for patients with psoriasis receiving adalimumab in clinical studies.Adalimumab safety data from adults with psoriasis who received at least one adalimumab dose in 18 clinical trials were evaluated. Adalimumab was delivered subcutaneously in all treatment regimens. Treatment-emergent adverse events (AEs) were collected from the first dose to 70 days after the last dose or cut-off date (31 December 2015). AE incidence rates were expressed as events per 100 patient-years (E/100 PYs) of adalimumab exposure. Standardized incidence ratios (SIRs) for malignancies and standardized mortality ratios (SMRs) were calculated.Cumulative exposure was 5429·7 PYs in 3727 patients. Overall, there were 16 536 AEs (304·6 E/100 PYs). The most common AEs were nasopharyngitis, upper respiratory infection and headache (23·7, 12·9 and 7·9 E/100 PYs, respectively). Incidence rates for serious infections, tuberculosis and opportunistic infections were 1·8, 0·3 and 0·02 E/100 PYs, respectively. Incidence of malignancy excluding nonmelanoma skin cancer (NMSC) was 0·8 E/100 PYs [SIR 0·86, 95% confidence interval (CI) 0·58-1·23]. Incidences of NMSC and melanoma were 0·6 and 0·2 E/100 PYs, respectively. The SIR was 1·55 (95% CI 1·10-2·13) for NMSC and 3·04 (95% CI 1·11-6·62) for melanoma. The SMR was 0·34 (95% CI 0·16-0·65).AE rates remained stable in this analysis of patients with psoriasis receiving adalimumab; no new safety signals were identified compared with earlier analyses.
포스터 전시 : 간세포암의 분화도와 PIVKA-2의 관계
Authors: 박혜원, 황준영, 서상혁, 장병국, 박경식, 조광범, 황재석, 안성훈, 박승국, 강유나
Journal: Clinical and Molecular Hepatology (2003)

배경/목적: 간암의 예후에 있어 기저 간질환의 상태, 종양의 형태, 간문맥 혈전증이 중요한 영향을 미치는 것으로 알려져 있다. 혈청 알파태아단백(AFP)의 일정 분획과 PIVKA-II (protein induced by vitamin K abscence or antagonist -II)는 간세포암의 종양 표지자로 상호 보완적인 검사법으로 많이 사용되고 있다. 한편 AFP의 수치는 간세포암 조직의 분화도와 상관 관계가 있다는 일부 보고가 있으며, 특히 PIVKA-II가 증가된 경우에는 종양의 진행속도가 비교적 빠른 것으로 알려져 있다. 이에 저자들은 조직학적으로 진단된 간세포암 환자에서 AFP과 PIVKA-II 수치와 간세포암의 분화도와의 상관관계를 알아보기 위해 본 연구를 시행하였다. 대상과 방법: 2002년 1월부터 2003년 4월까지 내과를 방문하여 간조직 검사를 시행하여 원발성 간암으로 진단된 환자 21명을 대상으로 하였다. 간세포암의 분화도는 Edmondson-Steiner의 등급에 따라 최고분화형 I, 고분화형 II, 중등도분화형 III, 저분화형 IV의 4단계로 구분하였으며, 최고분화형 및 고분화형을 1군으로, 중등도 및 저분화형을 2군으로 구분하였다. 결과: 1군은 13명으로 남자가 11명, 여자가 2명이었으며, 평균나이가 54세이고, 원인 간질환은 만성 B형 간염이 11례, 만성 C형 간염이 2례였다. 2군은 8명으로 남자가 6명, 여자가 2명이었으며, 평균 나이가 51세이고, 원인 간질환은 만성 B형 간염이 6명, 알콜성 간질환이 2명이었다. 1군의 AFP은 2.08-5412.01 ng/mL (평균 617.6±426 ng/mL)로 측정되었고, PIVKA-II는 9-2000 ng/mL (평균 586.47±231.78 ng/mL) 이었다. 2군의 AFP은 1.87-332.86 ng/mL (평균 74.67±41.67 ng/mL)로 측정되었고, PIVKA-II는 9.4-2000 ng/mL (평균 665.6±306.12 ng/mL)이었다. 두 군간의 AFP과 PIVKA-II 수치의 차이를 비모수 검증을 통해 분석하였으며 두 군간의 유의한 차이는 없었다. 결론: 본 연구를 종합하여 볼 때 PIVKA-II와 AFP의 수치는 간세포암의 분화정도를 예측할 수 없는 것으로 보이나 세침 흡인 조직검사가 전체 간암의 분화도를 대신 할 수 없으므로 수술절제 표본의 이용과 더 많은 환자를 대상으로 한 연구가 필요할 것으로 생각된다.
PTTG and PBF Functionally Interact with p53 and Predict Overall Survival in Head and Neck Cancer
Authors: Martin L. Read, Bhavika Modasia, Alice Fletcher, Rebecca J. Thompson, Katie Brookes, Peter C. Rae, Hannah R. Nieto, Vikki L. Poole, Sally Roberts, Moray J. Campbell, Kristien Boelaert, Andrew S. Turnell, Vicki E. Smith, Hisham Mehanna, Christopher J. McCabe
Journal: Cancer Research (2018)

Abstract Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide and poses a significant health burden due to its rising incidence. Although the proto-oncogene pituitary tumor–transforming gene 1 (PTTG) predicts poor patient outcome, its mechanisms of action are incompletely understood. We show here that the protein PBF modulates PTTG function, is overexpressed in HNSCC tumors, and correlates with significantly reduced survival. Lentiviral shRNA attenuation of PTTG or PBF expression in HNSCC cells with either wild-type or mutant p53, and with and without HPV infection, led to dysregulated expression of p53 target genes involved in DNA repair and apoptosis. Mechanistically, PTTG and PBF affected each other's interaction with p53 and cooperated to reduce p53 protein stability in HNSCC cells independently of HPV. Depletion of either PTTG or PBF significantly repressed cellular migration and invasion and impaired colony formation in HNSCC cells, implicating both proto-oncogenes in basic mechanisms of tumorigenesis. Patients with HNSCC with high tumoral PBF and PTTG had the poorest overall survival, which reflects a marked impairment of p53-dependent signaling. Significance: These findings reveal a complex and novel interrelationship between the expression and function of PTTG, PBF, and p53 in human HNSCC that significantly influences patient outcome. Cancer Res; 78(20); 5863–76. ©2018 AACR.
Sweden shows how the Nordic model could improve women’s wellbeing and create a better society
Authors: Harriet Evans, Richard Byng, Lynne Callaghan, Anna Fisher
Journal: BMJ (2018)

Proponents of the two main opposing models of legislating sex work (full decriminalisation versus the Nordic model) agree that criminalising sellers of sex is counterproductive, but the overall aims of and evidence for the two models were not fully explored by Howard.1 Our experience is that distress, trauma, substance misuse, poverty, or coercion can lead to prostitution, causing further emotional and physical harm.2

Harriet, survivor and activist, …
Abstract 16084: Progression of Myocardial Dysfunction in Hypertrophic Cardiomyopathy Patients: Association With Heart Failure Outcomes
Authors: Yasmine L Hiemstra, Philippe Debonnaire, Suzanne E van Wijngaarden, Marianne Bootsma, Martin J Schalij, Jeroen J Bax, Victoria Delgado, Nina A Marsan
Journal: Circulation (2016)

Introduction: Serial echocardiographic studies in hypertrophic cardiomyopathy (HCM) are lacking and little is known about the natural progression of left ventricular (LV) structural and functional abnormalities in these patients. Furthermore, whether a worsening in LV function over time is associated with the development of heart failure (HF) has not been explored. Hypothesis: We hypothesized that LV dysfunction is a progressive phenomenon in HCM patients which could be measured by echocardiography and particularly applying more sensitive techniques such as speckle tracking strain imaging. Importantly, a worsening in LV performance could be associated with HF outcomes. Methods: Transthoracic echocardiography was performed in 279 HCM patients (69% male, age 50±14 years) at their initial visit and during follow-up (median time 6.3 (IQR 3.8-9.5) years). Changes in echocardiographic variables, including LV global longitudinal strain (GLS) and left atrial volume index (LAVI) during follow-up were assessed usin...
Oncology trial authors don’t fully disclose financial conflicts of interests, analysis finds
Authors: Ingrid Torjesen
Journal: BMJ (2018)

A substantial proportion of US oncologists involved in clinical trials used to gain marketing authorisation for cancer drugs do not fully disclose financial conflicts of interest when the trial is published, research in JAMA Oncology shows.

The analysis, published as a research letter,1 found that a of third of oncologist authors failed to completely disclose payments from the drug company sponsor of the trial when the trial was published.

The researchers identified cancer drugs approved by the US Food and Drug Administration between January 2016 and August 2017, extracted the clinical trial registry numbers of the …
Approaches to the Pharmacological Management of Jet Lag
Authors: Josephine Arendt
Journal: Drugs (2018)

For many years now a treatment mitigating the debilitating effects of jet lag has been sought. Rapid travel across time zones leads, in most people, to temporary symptoms, in particular poor sleep, daytime alertness and poor performance. Mis-timed circadian rhythms are considered to be the main factor underlying jet-lag symptoms, together with the sleep deprivation from long haul flights. Virtually all aspects of physiology are rhythmic, from cells to systems, and circadian rhythms are coordinated by a central pacemaker or clock in the suprachiasmatic nucleus (SCN) of the hypothalamus. The SCN adapts slowly to changes in time zone, and peripheral clocks or oscillators adapt at different rates, such that the organism is in a state of desynchrony from the external environment and internally. Light exposure is the main factor controlling the circadian system and needs to be considered together with any pharmacological interventions. This review covers the relatively new chronobiotic drugs, which can hasten adaptation of the circadian system, together with drugs directly affecting alertness and sleep propensity. No current treatment can instantly shift circadian phase to a new time zone; however, adaptation can be hastened. The melatoninergic drugs are promising but larger trials in real-life situations are needed. For short stopovers it is recommended to preserve sleep and alertness without necessarily modifying the circadian system. New research suggests that modification of clock function via genetic manipulation may one day have clinical applications.
Abstract 12446: Frequency and Practice Level Variation in Statin Use Among Patients With Diabetes: Insights From the NCDR® PINNACLE Registry
Authors: Yashashwi Pokharel, Kensey Gosch, Anna Grodzinsky, Vijay Nambi, Paul Chan, Mikhail Kosiborod, John Spertus, Christie Ballantyne, Laura Petersen, Salim Virani
Journal: Circulation (2015)

Background: Statins reduce major adverse cardiovascular events and mortality among patients with diabetes and routine use is endorsed by clinical practice guidelines. However, national trends and practice level variation in statin use are not known. Methods: From the American College of Cardiology’s Practice Innovation and Clinical Excellence (PINNACLE) registry, we identified 256,701 patients with diabetes 40-75 years of age from 187 practices with at least 30 diabetic patients between May 1, 2008 and September 31, 2014. Among patients without contraindication to statin therapy, we calculated the percentage of patients receiving statin therapy at each practice. We then examined variation in statin use across practices using multivariable hierarchical regression to determine median rate ratio (MRR), which quantifies the likelihood that 2 randomly chosen practices would differ in treating an identical patient. Results: Overall, 141,900 (55%) diabetic patients were on statins. Those prescribed statins were more likely to be men, of white race, have coexisting dyslipidemia or hypertension, be on non-statin lipid lowering medications and have lower LDL-C levels (91 vs. 103 mg/dL, P&lt;0.001 for all). The median practice level use of statin was 57% (IQR, 48-63%), which remained similar throughout the study period. The adjusted MRR for statin use was 1.62 (95% CI: 1.57-1.67), indicating 62% differences in likelihood of statin treatment between 2 identical patients at 2 random practices (Figure). Conclusion: In a national outpatient registry, just over half of patients with diabetes 40-75 years old were treated with statins, with wide variation across cardiology practices. These results suggest that quality improvement initiatives are needed to support guideline recommended use of statins among patients with diabetes.
Abstract 18709: MicroRNA Target Regulation is Cell Type Specific and is Influenced by Stress Conditions
Authors: Eva-Maria Kremp, Gaspare La Rocca, Angelika Bonauer, Ariane Fischer, Andreas M Zeiher, Stefanie Dimmeler
Journal: Circulation (2016)

MicroRNAs (miRs) modulate gene expression by repressing translation or inducing degradation of targeted mRNAs. Although miRs are currently explored as novel therapeutic targets, the cell type and c...
Abstract 1992: Epigenetic and transcriptomic profiling of mammary gland development and tumor models disclose regulators of cell state plasticity
Authors: Christopher Dravis, Chi-Yeh Chung, Geoff Wahl
Journal: Cancer Research (2018)

Abstract Cell state reprogramming during tumor progression significantly contributes to the genesis of intra-tumoral heterogeneity. Discovering how cell state plasticity is specified during normal mammary development, and how this relates to breast cancer, could provide new treatment approaches. We used chromatin accessibility assays and transcriptional profiling to infer lineage potential within distinct normal mammary cell populations. We show that fetal and adult basal cells exhibit features consistent with multi-lineage differentiation potential. SOX family transcription factor DNA-binding motifs were enriched in the open chromatin of stem/progenitor cells, implicating SOX factors in mammary cell plasticity. We provide evidence that SOX10 expression correlates with multiple indicators of cell state plasticity, and that it directly contributes to tumor development in multiple animal models. Strikingly, we show that SOX10-positive tumor cells uniquely exhibit neural crest cell features, and that SOX10 binds to genes that regulate neural crest cell identity. Collectively, these data help to resolve conflicts concerning cell fate and cell potential in the mammary cell hierarchy, reveal that SOX10 is a plasticity factor driving mammary tumor progression, and demonstrate the remarkable scope of cell state reprogramming that can occur during tumorigenesis. Citation Format: Christopher Dravis, Chi-Yeh Chung, Geoff Wahl. Epigenetic and transcriptomic profiling of mammary gland development and tumor models disclose regulators of cell state plasticity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1992.