tbuckley/cabot-search huggingface dataset:
Abstract 19017: Sex Differences in Severe Pulmonary Arterial Hypertension Produced by SU5416 in a Colony of “Hyper-responsive” Sprague Dawley Rats
Authors: Ketul R Chaudhary, Yupu Deng, Kurt Tyson, Anli Yang, Duncan J Stewart
Journal: Circulation (2015)

Introduction: Our lab has identified a sub-strain of Sprague Dawley (SD) rats from Charles River Labs, obtained from a specific colony housed at a Canadian facility (Sherbrooke, Quebec), which develop severe progressive PAH in response to single injection of SU5416 (SU), a VEGFR2 antagonist, even in absence of chronic hypoxia (CH). This trait appears to due to the presence of unique genetic modifiers found only in this colony. Interestingly, there was a strong sex difference with &gt;70% of males and only &lt;30% of females showing the SU hyper-responsive (HR) phenotype. The purpose of the project was to explore the mechanisms contributing to sex related differences in response to SU alone in a hyper-responsive sub-strain of SD rats. Hypothesis: Sex dependent differences in the HR phenotype are due to the protective effects of female sex hormones, reducing the susceptibility to PAH in response to VEGFR2 inhibition. Methods and Results: Male and female rats were injected with SU (20mg/kg, sc) or vehicle. Right ventricular systolic pressure (RVSP) was measured at four and seven weeks after SU injection. In male SD rats, 72% (13 of 18) of rats exhibited an HR phenotype in response to SU with mean RVSP of 97±18 mmHg in absence of CH; whereas only 27% (7 of 26) of the female rats were responsive to SU alone. We studied the SU responsiveness in the oophorectomized female rats to investigate the role of female sex hormones in the sex-specific HR phenotype. Interestingly, the proportion of HR animals increased drastically in oophorectomized female rats to 71% (10 of 14), compared to non-operated female rats (33%, 4 of 12). Moreover, estradiol replacement completely abrogated the HR phenotype in both male rats and oophorectomized female rats. Conclusion: These data support a role of female sex hormones in modulating the development of severe PAH in response to SU alone in a unique colony of SD rats that exhibit increased sensitivity to VEGFR2 blockade. The HR SD rat colony model exhibits exquisite sensitivity to estrogen and thus provides a unique opportunity to further define the complex interactions between hormonal and genetic modifiers in the development of PAH.
P12.07 Radiation Mediated Down-Regulation of Indoleamine 2,3-dioxygenase 1 (IDO1) Expression in Lung Cancer Cells is Associated with iNOS-NO Pathway
Authors: W. Pi, Y. Lan, X. Xia, W. Wang, Y. Meng, H. Yang, F.M. Kong
Journal: Journal of Thoracic Oncology (2021)
FP07.04 Effect of Tumor Treating Fields (TTFields) on DNA Damage and The FA-BRCA DNA Repair Pathway in Mesothelioma
Authors: H. Mumblat, A. Martinez-Conde, O. Braten, M. Munster, E. Dor-On, R. Schneiderman, Y. Porat, T. Voloshin, S. Davidi, R. Blatt, A. Shteingauz, C. Tempel-Brami, E. Zeevi, C. Lajterer, Y. Shmueli, S. Danilov, A. Haber, M. Giladi, A. Kinzel, U. Weinberg, Y. Palti
Journal: Journal of Thoracic Oncology (2021)
Annals Graphic Medicine - Not Unreasonable
Authors: Lauren Scanlon
Journal: Annals of Internal Medicine (2021)

Web ExclusivesOctober 2021Annals Graphic Medicine - Not UnreasonableFREELauren Scanlon, BA, MFA, MLISLauren Scanlon, BA, MFA, MLISUniversity of Wisconsin–Madison, Madison, Wisconsin (L.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G20-0120 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Katie ZamanUtah State University, Tribal and Rural Opioid Initiative20 October 2021 Professor Freaky Friday! Thank you for sharing this. I am grateful for the inside look at the complexity of what you experienced. I could see Professor Freaky Friday's influence through the whole piece - isn't she amazing?! Author, Article, and Disclosure InformationAffiliations: University of Wisconsin–Madison, Madison, Wisconsin (L.S.)Disclosures: The author has reported no disclosures of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G20-0120.Author/Illustrator Information: Lauren Scanlon, BA, MFA, MLIS, is a visual artist and PhD student in the iSchool at the University of Wisconsin-Madison (e-mail, [email protected]com; website, www.laurenscanlon.com).This article was published at Annals.org on 12 October 2021. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics October 2021Volume 174, Issue 10Page: W96-W104 ePublished: 12 October 2021 Issue Published: October 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
David Oliver:<i>Daily Mail</i>’s campaign on general practice won’t help GPs or their patients
Authors: David Oliver
Journal: BMJ (2021)

For months several UK national newspaper titles have been carrying exhortations for GPs to return to seeing more patients in their consulting rooms and scale back their online and telephone consultations.12 I have often found the papers’ tone to be unpleasant, highly critical, or downright hostile. Any attempt to understand or explain is often buried in the prose well below the inflammatory headlines.

The Daily Mail ’s recent campaign for a “right” for all patients who want face-to-face GP appointments to get them exemplifies the problems with this combative approach. This week the Mail claimed a “win” in its campaign, with England’s health and social care secretary, Sajid Javid, announcing that GPs will be incentivised to …
Endocrine Manifestations and New Developments in Mitochondrial Disease
Authors: Yi Shiau Ng, Albert Zishen Lim, Grigorios Panagiotou, Doug M Turnbull, Mark Walker
Journal: Endocrine Reviews (2021)

Mitochondrial diseases are a group of common inherited diseases causing disruption of oxidative phosphorylation. Some patients with mitochondrial disease have endocrine manifestations, with diabetes being predominant but also include hypogonadism, hypoadrenalism and hypoparathyroidism. There have been major developments in mitochondrial disease over the last decade that have major implications for all patients. The collection of large cohorts of patients has better defined the phenotype of mitochondrial diseases and the majority of patients with endocrine abnormalities have involvement of several other systems. This means that patients with mitochondrial disease and endocrine manifestations need specialist follow up because some of the other manifestations, such as stroke-like episodes and cardiomyopathy, are potentially life threatening. Also, the development and follow up of large cohorts of patients means that there are clinical guidelines for the management of patients with mitochondrial disease. There is also considerable research activity to identify novel therapies for the treatment of mitochondrial disease. The revolution in genetics, with the introduction of next generation sequencing, has made genetic testing more available and establishing a precise genetic diagnosis is important since it will affect the risk for involvement for different organ systems. Establishing a genetic diagnosis is also crucial since there are important reproductive options have been developed which will prevent the transmission of mitochondrial disease due to mitochondrial DNA variants to the next generation.
P66.07 ASCL1 and DLL3 Expression and Their Clinicopathological Implications in Surgically Resected Pure Small Cell Lung Cancer
Authors: J. Dong, C. Hu, L. Liu, Y. Guo, J. Zhang, F. Teng, X. Sun, X. Wang, J. Ying, J. Li, P. Xing, L. Yang
Journal: Journal of Thoracic Oncology (2021)
Temporal trends in pulmonary arterial hypertension: results from the COMPERA registry
Authors: Marius M. Hoeper, Christine Pausch, Ekkehard Grünig, Gerd Staehler, Doerte Huscher, David Pittrow, Karen M. Olsson, Carmine Dario Vizza, Henning Gall, Oliver Distler, Christian Opitz, J. Simon R. Gibbs, Marion Delcroix, H. Ardeschir Ghofrani, Stephan Rosenkranz, Da-Hee Park, Ralf Ewert, Harald Kaemmerer, Tobias J. Lange, Hans-Joachim Kabitz, Dirk Skowasch, Andris Skride, Martin Claussen, Juergen Behr, Katrin Milger, Michael Halank, Heinrike Wilkens, Hans-Jürgen Seyfarth, Matthias Held, Daniel Dumitrescu, Iraklis Tsangaris, Anton Vonk-Noordegraaf, Silvia Ulrich, Hans Klose
Journal: European Respiratory Journal (2021)

Since 2015, the European pulmonary hypertension guidelines recommend the use of combination therapy in most patients with pulmonary arterial hypertension (PAH). However, it is unclear to what extent this treatment strategy is adopted in clinical practice and if it is associated with improved long-term survival.We analysed data from COMPERA, a large European pulmonary hypertension registry, to assess temporal trends in the use of combination therapy and survival of patients with newly diagnosed PAH between 2010 and 2019. For survival analyses, we looked at annualised data and at cumulated data comparing the periods 2010-2014 and 2015-2019.A total of 2531 patients were included. The use of early combination therapy (within 3 months after diagnosis) increased from 10.0% in patients diagnosed with PAH in 2010 to 25.0% in patients diagnosed with PAH in 2019. The proportion of patients receiving combination therapy 1 year after diagnosis increased from 27.7% to 46.3%. When comparing the 2010-2014 and 2015-2019 periods, 1-year survival estimates were similar (89.0% (95% CI 87.2-90.9%) and 90.8% (95% CI 89.3-92.4%), respectively), whereas there was a slight but nonsignificant improvement in 3-year survival estimates (67.8% (95% CI 65.0-70.8%) and 70.5% (95% CI 67.8-73.4%), respectively).The use of combination therapy increased from 2010 to 2019, but most patients still received monotherapy. Survival rates at 1 year after diagnosis did not change over time. Future studies need to determine if the observed trend suggesting improved 3-year survival rates can be confirmed.
Assisted dying: medical professionals’ freedom of opinion must endure
Authors: Anne Williams
Journal: BMJ (2021)

Hurley and colleagues say it is a question of when, not if, assisted dying will be legalised in the UK.1 The legalisation of assisted suicide would be the death knell not only for many vulnerable patients but also for freedom of the medical profession because of the campaign for restrictions on conscientious objection.

Respect for others’ freedom was reflected in the recent BMA poll on assisted dying.2 Although 50% of …
Saúde no Brasil 4: Doenças crônicas não transmissíveis no Brasil: carga e desafios atuais
Authors: Maria Inês Schmidt, Bruce Bartholow Duncan, Gulnar Azevedo e Silva, Ana Maria Menezes, Carlos Augusto Monteiro, Sandhi Maria Barreto, Dora Chor, Paulo Rossi Menezes
Journal: The Lancet (2015)
Circular RNA circIPO11 drives self-renewal of liver cancer initiating cells via Hedgehog signaling
Authors: Yang Gu, Yanying Wang, Luyun He, Jiahang Zhang, Xiaoxiao Zhu, Nian Liu, Jianyi Wang, Tiankun Lu, Lei He, Yong Tian, Zusen Fan
Journal: Molecular Cancer (2021)

Abstract Background Hepatocellular carcinoma (HCC) is one of the most intractable tumors in the world due to its high rate of recurrence and heterogeneity. Liver cancer initiating cells also called cancer stem cells (CSCs) play a critical role in resistance against typical therapy and high tumor-initiating potential. However, the role of the novel circular RNA (circRNA) circIPO11 in the maintenance of liver cancer initiating cells remains elusive. Methods CircRNAs highly conserved in humans and mice were identified from 3 primary HCC samples by circRNA array. The expression and function of circIPO11 were further evaluated by Northern blot, limiting dilution xenograft analysis, chromatin isolation by RNA purification-PCR assay (ChIRP) and HCC patient-derived tumor cells (PDC) models. CircIpo11 knockout (KO) mice were generated by a CRISPR/Cas9 technology. Results CircIPO11 is highly expressed in HCC tumor tissues and liver CSCs. CircIPO11 is required for the self-renewal maintenance of liver CSCs to initiate HCC development. Mechanistically, circIPO11 recruits TOP1 to GLI1 promoter to trigger its transcription, leading to the activation of Hedgehog signaling. Moreover, GLI1 is also highly expressed in HCC tumor tissues and liver CSCs, and TOP1 expression levels positively correlate with the metastasis, recurrence and survival of HCC patients. Additionally, circIPO11 knockout in mice suppresses the progression of chemically induced liver cancer development. Conclusion Our findings reveal that circIPO11 drives the self-renewal of liver CSCs and promotes the propagation of HCC via activating Hedgehog signaling pathway. Antisense oligonucleotides (ASOs) against circIPO11 combined with TOP1 inhibitor camptothecin (CPT) exert synergistic antitumor effect. Therefore, circIPO11 and the Hedgehog signaling pathway may provide new potential targets for the treatment of HCC patients.
Characteristics and outcome of acute myeloid leukemia with uncommon retinoic acid receptor-alpha (RARA) fusion variants
Authors: Laura Cicconi, Anna Maria Testi, Pau Montesinos, Eduardo Rego, Hong Hu Zhu, Hiroyuki Takahashi, Michael Dworzak, Elihu Estey, Anthony Schwarer, Jordi Esteve, Ombretta Annibali, Roberto Castelli, Milena Mirabile, Mario Angelini, Vladimir Lazarevic, Jeevan Kumar, Giuseppe Avvisati, Carmelo Gurnari, Franco Locatelli, Maria Teresa Voso, Miguel Angel Sanz, Francesco Lo-Coco, Oussama Abla
Journal: Blood Cancer Journal (2021)

Acute promyelocytic leukemia (APL) is characterized by the reciprocal balanced translocation t(15;17)(q24.1;q21.2),which fuses the promyelocytic leukemia (PML) and retinoic acid receptor-α (RARA) genes, responsible for inhibition of cellular differentiation and proliferation of undifferentiated elements [1].RARA can be fused to partners other than PML in rare cases of acute myeloid leukemia (AML), presenting with features suggestive of APL.At least 14 variant translocations have been identified, including ZBTB16-RARA [2], the most frequent one, followed byand the more recentThese cases display limited sensitivity to molecularly targeted therapies active in PML-RARA-positive APL, with the majority (i.e., ZTBTB16-RARA, STAT5B-RARA) showing in vitro and/or in vivo resistance to all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) [1,2].Given their rarity, data on the clinical characteristics and outcomes of these patients are limited to small case series with the largest including 11 ZBBTB16-RARA and 2 NPM1-RARA leukemias [1].Herein we report the clinico-biological features, treatment strategies, and outcomes of 24 cases of AML with rare RARA rearrangements diagnosed between 2005 and 2017, collected from 16 study groups/institutions in Europe (Italy, Spain, Austria, Sweden), China, Brazil, Japan, India, Australia, and United States.Common case report forms were sent to all participating centers and laboratory data including flow cytometry, cytogenetics, and molecular biology were centrally reviewed.Four cases had been previously reported [11][12][13].The study was approved by the research ethics boards of all participating centers.Thirty-eight consecutive PML-RARA-positive APLs diagnosed at the Policlinico Tor Vergata University in Rome from 2005 and 2019 were selected as controls.Statistical analyses were performed using the SPSS software and the distributions of time-to-event variables were estimated by the Kaplan-Meier method.As to therapy outcomes, complete remission (CR), partial remission (PR), molecular remission, and primary refractory disease were defined according to the European Leukemia-Net AML guidelines [14].Induction death was defined as occurring after the start of therapy and before achievement of CR while overall survival (OS) and event-free survival (EFS) were calculated from diagnosis until death and until failure to enter CR, relapse, second malignancy, or death, respectively.Twenty-four patients with a median age of 47 years (range, 2-83 years) were included in this study, with 4 pediatric patients (age range, 2-17 years).Three cases (12.5%) were
FP04.02 RATIONALE-307: Updated Biomarker Analysis of Phase 3 Study of Tislelizumab Plus Chemo vs Chemo Alone For 1L Advanced Sq-NSCLC
Authors: J. Wang, S. Lu, Z. Wang, C. Hu, Y. Sun, K. Yang, M. Chen, J. Zhao, L. Liang, Y. Huo, Y. Zhang, R. Huang, X. Wu, X. Ma, S.J. Leaw, F. Bai, Z. Shen
Journal: Journal of Thoracic Oncology (2021)
Serial assessment of measurable residual disease in medulloblastoma liquid biopsies
Authors: Anthony P Y Liu, Kyle S Smith, Rahul Kumar, Leena Paul, Laure Bihannic, Tong Lin, Kendra K Maass, Kristian W Pajtler, Murali Chintagumpala, Jack M Su, Eric Bouffet, Michael J Fisher, Sridharan Gururangan, Richard Cohn, Tim Hassall, Jordan R Hansford, Paul Klimo, Frederick A Boop, Clinton F Stewart, Julie H Harreld, Thomas E Merchant, Ruth G Tatevossian, Geoffrey Neale, Matthew Lear, Jeffery M Klco, Brent A Orr, David W Ellison, Richard J Gilbertson, Arzu Onar-Thomas, Amar Gajjar, Giles W Robinson, Paul A Northcott
Journal: Cancer Cell (2021)
P50.01 RELAY, Erlotinib Plus Ramucirumab in Untreated, EGFR-Mutated, Metastatic NSCLC: Outcomes by EGFR Exon 19-del Variants
Authors: K. Nishino, J. Shih, C. Lovly, K. Nakagawa, M. Reck, E. Garon, M. Ceccarelli, S. Wijayawardana, C. Visseren-Grul, E. Nadal
Journal: Journal of Thoracic Oncology (2021)
P19.01 RATIONALE-303 Phase 3 Tislelizumab vs Docetaxel in Previously Treated Advanced NSCLC: China Subgroup Analysis
Authors: Y. Fan, D. Huang, Z. Ma, X. Yu, Y. Cheng, Y. Ma, Y. Wang, Z. Pan, C. Yu, C. Zhou
Journal: Journal of Thoracic Oncology (2021)
mRNA Vaccines in the COVID-19 Pandemic and Beyond
Authors: Michael J. Hogan, Norbert Pardi
Journal: Annual Review of Medicine (2021)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. This extraordinary situation prompted entities in government, industry, and academia to work together at unprecedented speed to develop safe and effective vaccines. Indeed, vaccines of multiple types have been generated in record time, and many have been evaluated in clinical trials. Of these, messenger RNA (mRNA) vaccines have emerged as lead candidates due to their speed of development and high degree of safety and efficacy. To date, two mRNA vaccines have received approval for human use, providing proof of the feasibility of this next-generation vaccine modality. This review gives a detailed overview about the types of mRNA vaccines developed for SARS-CoV-2, discusses and compares preclinical and clinical data, gives a mechanistic overview about immune responses generated by mRNA vaccination, and speculates on the challenges and promising future of this emergent vaccine platform.
Abstract 19246: The Impact of CT Coronary Angiography on the Business of Acute Chest Pain: Resource Utilization, Cost and Length of Stay
Authors: Srija Bhattacharyya, Jonathan Christiansen, Zina Ayar, Colin Edwards, Hamish Hart, Andrew To
Journal: Circulation (2015)

Introduction: Chest pain is one of the most frequent presentations to the emergency department, resulting in a large number of hospital admissions and diagnostic tests. CT coronary angiography (CTCA) has been shown to provide accurate information, without necessarily resorting to invasive, costly tests, such as coronary angiography. Managers and funders are often concerned that CTCA availability may lead to over-investigation and impact unfavorably on hospital budgets. Here, we report on the impact of CTCA on hospital services, with an emphasis on resource utilization, using individual patient data. Methods: We compare a cohort of patients presenting with chest pain to the emergency department before and after implementation of the CTCA program at Waitemata District Health Board (WDHB), in August 2011. Information on LOS, investigations performed, demographic/comorbidity details and cost related to the admission were obtained from clinical coding information, existing databases and the accounts department (using a schedule that breaks cost into resource pools). Follow up was 1 year. WDHB provides hospital services for ~600,000 people. Initial Results: 25,199 patients were admitted with the presenting complaint of chest pain between February 2008 and August 2011, aged 18yrs-106 yrs. The mean LOS was 3.056 days. A total of 2,087 angiograms (8.3%) were performed in this cohort. Between August 2011 and February 2014, 20,642 patients presented with chest pain, aged 18yrs-102yrs. The mean LOS was 2.727 days (p&lt;0.001). A total of 1,442 angiograms (7.0%, p&lt;0.05) were performed in this cohort. A total of 1,246 inpatient CTCA scans were done during this period. There was no significant difference in readmission rate or other non-invasive testing. There was a trend toward lower costs associated with chest pain admissions, without adjusting for inflation. Conclusion: The CTCA program appears to have been beneficial in decreasing LOS and the total number of angiograms performed. CTCA availability has not led to uncontrolled service growth. Savings made from decreased resource utilization may justify the capital/staff expenditure required to implement the program. Further research to understand the economics of CTCA would be beneficial.
P59.01 Clinical Characteristics of Patients With MET Amplification-Positive NSCLC After EGFR-TKI Therapy
Authors: J.H. Lee, B. Ahn, M.H. Kim, K. Pyo, C. Lee, S.M. Lim, M.H. Hong, H.R. Kim, B.C. Cho
Journal: Journal of Thoracic Oncology (2021)