tbuckley/cabot-search huggingface dataset:
Abstract P3-03-42: Withdrawn
Authors: NJ Bundred, P Foden, K Riches, J Morris, A Evans, C Todd, M Bramley, A Skene, A Purushotham, V Keeley
Journal: Cancer Research (2019)

Abstract This abstract was withdrawn by the authors. Citation Format: Bundred NJ, Foden P, Riches K, Morris J, Evans A, Todd C, Bramley M, Skene A, Purushotham A, Keeley V. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-03-42.
Abstract P1-06-03: A selective Cdk12/13 non-covalent inhibitor with potent anti-breast cancer activity
Authors: V Quereda, S Bayle, V Francesca, M Andrii, R William, D Derek
Journal: Cancer Research (2019)

Abstract Cyclin-dependent kinases 12 and 13 (CDK12 and CDK13) are Ser/Thr protein kinase members of the CDK family. CDKs are regulated by cyclins and members of the family are key regulators of the cell cycle. Other members of this family—CDK7, CDK8, CDK9, CDK12 and CDK13—have been described as transcription-regulating kinases. CDK12 and CDK13 phosphorylate the C-terminal domain (CTD) of rpb1 the largest subunit of RNA polymerase II and interact with RNA processing factors, playing pivotal roles controlling transcription initiation and elongation, as well as posttranscriptional RNA processing. Specifically, CDK12 acts as the limiting factor for the transcription of a small subset of genes that are involved in the DNA damage response pathway and CDK13 affects expression of genes involved in growth signaling pathways. Importantly, like their cell cycle family members CDK12 and CDK13 have also been shown to be promising therapeutic targets for several cancer types. We have generated a novel, selective, and orally bioavailable, small molecule inhibitor of CDK12 and CDK13. Our lead molecule downregulates key DNA damage repair proteins including ATM, ATR, Brca1 and Rad51 leading to induction of apoptotic cell death in all triple negative breast cancer (TNBC) cell lines tested. We have confirmed the selectivity of our compound by kinase profiling and by comparing the gene expression profile by RNA-seq of cells treated with compound or infected with CRISPR sgRNA targeting Cdk12 and/or Cdk13. Importantly, our compound acts in synergy with the chemotherapeutic agents Cisplatin, Irinotecan and Olaparib. Finally, in preclinical efficacy studies, our lead compound blocked tumor progression in two different PDX models of TNBC and demonstrated tumor regression and enhanced efficacy over single treatment when dosed in combination with selected chemotherapeutic agents. Citation Format: Quereda V, Bayle S, Francesca V, Andrii M, William R, Derek D. A selective Cdk12/13 non-covalent inhibitor with potent anti-breast cancer activity [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-06-03.
Abstract 19730: Temporal Trends in the Incidence and Outcomes of Acute Ischemic Stroke in the United States
Authors: Fahad Alqahtani, Sami Aljohani, Tatiana Busu, Ahmad Almustafa, Abdulrahman Tarabishy, Abdelrahman Beltagy, Mohamad Adnan Alkhouli
Journal: Circulation (2017)

Introduction: Significant advances have been made in the prevention and treatment of acute ischemic stroke (AIS) in the last decade. Hypothesis: The incidence of AIS, its management patterns are ch...
UKCAT does not predict medical school performance, study finds
Authors: Chris Thomas
Journal: BMJ (2013)

Scores in the UK clinical aptitude test (UKCAT) do not accurately predict subsequent performance at medical school, indicate the results of a study from the University of Nottingham.1

UKCAT was designed to help medical schools distinguish between the large number of candidates with top grades, but the ability of the UKCAT to select the students best suited to studying medicine has been questioned since its launch.

The research aimed to assess whether UKCAT scores accurately predicted student performance in the latter part of the medical course, which is mainly delivered on …
The Importance of Outcome and Precise Evaluation in Economic Analysis of Cancer Drugs—Reply
Authors: Abdulaali R. Almutairi, Nimer S. Alkhatib, Ivo Abraham
Journal: JAMA Dermatology (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Abstract IA21: PARP trapping and Schlafen 11 to kill cancer cells
Authors: Yves G. Pommier, Junko Murai
Journal: Clinical Cancer Research (2018)

Abstract Poly(ADP-ribose) polymerase inhibitors (PARPIs) kill cancer cells by trapping PARP1 and PARP2. Talazoparib, the most potent PARP inhibitor (PARPI), exhibits remarkable selectivity among the NCI-60 cancer cell lines beyond BRCA inactivation. Our genomic analyses reveal high correlation between response to talazoparib and Schlafen 11 (SLFN11) expression. Causality was established in four isogenic SLFN11-positive and -negative cell lines and extended to olaparib. Response to the talazoparib-temozolomide combination was also driven by SLFN11 and validated in 36 small-cell lung cancer cell lines, and in xenograft models. Resistance in SLFN11-deficient cells was caused neither by impaired drug penetration nor by activation of homologous recombination. Rather, SLFN11 induced irreversible and lethal replication inhibition, which was independent of ATR-mediated S-phase checkpoint. The resistance to PARPIs by SLFN11 inactivation was overcome by ATR inhibition, mechanistically because SLFN11-deficient cells solely rely on ATR activation for their survival under PARPI treatment. Our study reveals that SLFN11 inactivation, which is common (~45%) in cancer cells, is a novel and dominant resistance determinant to PARPIs. Citation Format: Yves G. Pommier, Junko Murai. PARP trapping and Schlafen 11 to kill cancer cells [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr IA21.
Mutational landscape of the transcriptome offers putative targets for immunotherapy of myeloproliferative neoplasms
Authors: Fiorella Schischlik, Roland Jäger, Felix Rosebrock, Eva Hug, Michael Schuster, Raimund Holly, Elisabeth Fuchs, Jelena D. Milosevic Feenstra, Edith Bogner, Bettina Gisslinger, Martin Schalling, Elisa Rumi, Daniela Pietra, Gottfried Fischer, Ingrid Faé, Loan Vulliard, Jörg Menche, Torsten Haferlach, Manja Meggendorfer, Anna Stengel, Christoph Bock, Mario Cazzola, Heinz Gisslinger, Robert Kralovics
Journal: Blood (2019)
Abstract 3: Loss of Type 9 Adenylyl Cyclase Triggers Reduced Phosphorylation of Hsp20 and Diastolic Dysfunction
Authors: Tanya A Baldwin, Yong Li, Yan Wang, Cameron S Brand, Carmen W Dessauer
Journal: Circulation Research (2017)

Adenylyl cyclase type 9 (AC9) is found tightly associated with the scaffolding protein Yotiao and the I Ks ion channel in heart. But apart from potential I Ks regulation, physiological roles for AC9 are unknown. Utilizing a gene-trap mouse line that disrupts expression of AC9, we show that loss of AC9 reduces less than 2% of total AC activity in heart but eliminates Yotiao-associated AC activity. AC9 -/- mice exhibit no structural abnormalities but show a significant bradycardia. Global changes in PKA phosphorylation patters are not altered in AC9 -/- heart, however basal phosphorylation of heat shock protein 20 (Hsp20) is significantly decreased. AC9 binds Hsp20 in a Yotiao-independent manner, while deletion of AC9 decreases Hsp20-associated AC activity in heart, consistent with and an AC9-Hsp20 complex. Phosphorylation of Hsp20 occurs largely in ventricles and is vital for the cardioprotective effects of Hsp20. Decreased Hsp20 phosphorylation suggests a potential baseline ventricular defect for AC9 -/- . Doppler echocardiography of AC9 -/- mice displays a decrease in the early ventricular filling velocity and ventricular filling ratio (E/A), indicative of grade 1 diastolic dysfunction. Our findings unveil potential new roles for AC9 in cardiac function and emphasize the importance of local cAMP production in the context of macromolecular complexes.
Abstract P4-02-15: The effect of the 2013 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines in HER2 positivity rates among women with breast cancer in SEER registries
Authors: XK Wang, N Hu, K Herget, BR Cinbis, EH Gulbahce
Journal: Cancer Research (2019)

Abstract Introduction: The American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) revised the HER2 testing guidelines in breast cancer (BC) which was published in December 2013, practically becoming effective in 2014. Since then, many studies reported a significant increase in HER2 positivity rate in BC. Although HER2 has been routinely evaluated in BC for over a decade, HER2 status was not included in SEER registries until 2010. The aim of this study is to look at the effect of the 2013 ASCO/CAP guidelines on HER2 status in the SEER database that captures approximately 28% of all cancers in the US. Material and Methods. Using data from 18 SEER cancer registries between the years of 2010-2015 when HER2 status for breast cancers was available, women with invasive BC were identified and their HER2 status and race was recorded. The Chi-square test was used to test the significance between positive proportions before and after the new ASCO/CAP guidelines were effective. Logistic regression was used to test if the changes in positivity rate were the same among different races. All calculations were made after excluding cases with unknown/missing HER2 status. Results: We identified 376,278 women diagnosed with invasive BC between the years 2010-2015. HER2 positivity before 2014 (2010-2013) was 14.4% compared to 15.6% after 2013 (2014-2015) (p&amp;lt;0.001). HER2 positivity increased in all races after 2013. There was no significant difference in the increase of HER2 positivity between whites and blacks after the new guidelines went into effect. Unknown/missing HER2 status continually decreased over the study period from 7.4% in 2010 to 5.3% in 2015. Overall unknown/missing HER2 was significantly different among races: 6.5% in whites; 7.1% in blacks; and 6.2% in other races (p&amp;lt;0.01). Conclusion: Revised ASCO/CAP HER2 guidelines significantly increased HER2 positivity rates in SEER registries from 14.4% to 15.6% after implementation started in 2014. HER2 positivity increased in all races after 2013. Unknown/missing HER2 status is significantly different among different races. Blacks have highest unknown/ missing HER2 status in SEER registries. Citation Format: Wang XK, Hu N, Herget K, Cinbis BR, Gulbahce EH. The effect of the 2013 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines in HER2 positivity rates among women with breast cancer in SEER registries [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-02-15.
Modified action as a determinant of adult and age-related sensorimotor integration: Where does it begin?
Authors: Hubert R. Dinse
Journal: Behavioral and Brain Sciences (2001)

Modified action, either artificially induced or occurring naturally during life-span, alters organization and processing of primary somatosensory cortex, thereby serving as a predictor of age-related changes. These findings, together with the interconnectedness between motor-sensory systems and temporally-distributed processing across hierarchical levels, throws into question a sharp division between early perception and cognition, and suggest that composite codes of perception and action might not be limited to higher areas.
Abstract P2-14-05: Can an internal surgical adhesive facilitate drain-free mastectomy and reduce overall invasiveness?-A prospective, randomized, controlled, multicenter non-inferiority trial
Authors: C Eichler, S Paepke, R Ohlinger, W Mathias, I Scheffen, M Lux, S Hadad, T Kiernan, L Whisker, M Kaushik, P King
Journal: Cancer Research (2019)

Abstract Introduction: Mastectomy closure without drains has many potential advantages. Flap fixation techniques have shown to be an effective alternative to drains. This study tested the non-inferiority of a surgical adhesive in overall invasiveness compared to standard wound closure with drains. Methods: This trial (ClinicalTrials.gov Identifier: NCT02958449) recruited seventy-seven patients undergoing eighty-four mastectomies +/- SLNB (n=84) at eleven international centers. Procedures were prospectively randomized to standard wound closure with drains (SWC; n=41) or wound closure without drains using a high strength lysine-based adhesive named TissuGlu® (TG; n= 43). The primary outcome measured assessed overall invasiveness using the number of post-operative clinical interventions, including drain removals and needle aspirations. Secondary endpoints included total wound drainage, cumulative days of treatment, days to drain removal and wound healing related complications. A patient questionnaire evaluating quality of life measures was also administered. Results: Subjects in the TissuGlu® group required significantly fewer post-operative clinical interventions (1.25 ± 1.39 TG vs. 2.03 ± 1.45 SWC, p = &amp;lt;.0001) compared to the Control group and had fewer cumulative days of treatment (defined as days of drains being in place and / or days on which an aspiration occurred; 2.14 ± 4.15 TG vs. 5.76 ± 4.02 SWC, p = &amp;lt;0.0001). Presence of a drain was associated with significantly higher pain and lower mobility scores. Conclusion: The study demonstrates that flap fixation with this adhesive can permit drain-free mastectomy closure, reducing overall invasiveness and patient morbidity. Citation Format: Eichler C, Paepke S, Ohlinger R, Mathias W, Scheffen I, Lux M, Hadad S, Kiernan T, Whisker L, Kaushik M, King P. Can an internal surgical adhesive facilitate drain-free mastectomy and reduce overall invasiveness?-A prospective, randomized, controlled, multicenter non-inferiority trial [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-14-05.
A Study of Magnetic Resonance Imaging Assessment of Cardiac and Liver Iron Load in Patients with Haemoglobinopathies, Myelodysplastic Syndromes or Other Anaemias Treated with Deferasirox (the MILE study CICL670AAU01) - Results of An Interim Analysis At a
Authors: P. Joy Ho, Lay Tay, Juliana Teo, Paula Marlton, Andrew Grigg, Tim St Pierre, Greg Brown, Othon L. Gervasio, Donald K. Bowden
Journal: Blood (2011)
Government is “losing its grip” of cancer screening services, say MPs
Authors: Jacqui Thornton
Journal: BMJ (2019)

A damning report into health screening has accused the government of “losing its grip” as it revealed that the number of women accessing the cervical cancer programme has dropped to a 21 year low.

The report by the Public Accounts Committee1 (PAC) covers the management of four of the 11 health screening programmes operating in England: bowel, breast and cervical cancers, and abdominal aortic aneurysm.

None of them met targets for ensuring the eligible population was screened in 2017-18.

The House of Commons Committee said that national bodies are not doing enough to make sure that everyone who is eligible to take part in screening is doing so, and do not know if everyone who should be invited for screening has been.

Just 71.7% of the eligible population, or 3.2 million women, …
How should I go about finding a mentor?
Authors: Sophia Bourne
Journal: BMJ (2019)

Dear Sophia,

How should I go about finding a mentor?

Rosie Bate, fourth year medical student, University of Leicester

Mentoring is a supportive professional relationship, where a more experienced colleague (mentor) advises and guides someone who is less experienced (mentee). An effective mentoring relationship is based on trust, and provides a means to explore career pathways, clarify goals, and broaden your knowledge and skills. Mentees also report that having a mentor has helped them grow in confidence and feel more inspired about their career, …
Abstract 1795: Noninvasive genetic detection of head and neck squamous cell carcinoma
Authors: Seema Sethi, Michael S Benninger, Mei Lu, Shaleta Havard, Maria J Worsham
Journal: Cancer Research (2008)

Abstract Purpose of the study: To develop and evaluate a noninvasive approach for head and neck squamous cell carcinoma (HNSCC) based on genomic alterations of loss and gain of gene copy number. Experimental Procedures: The study cohort comprised 37 subjects, 27 HNSCC patients and 10 healthy controls. DNA extracted from saliva of the study subjects was interrogated by multiplex ligation-dependent probe amplification (MLPA) assay for gene copy number alterations (losses and gains) using two panels of 82 gene probes with known associations to HNSCC. MLPA permits evaluation of 41 different genes in one PCR reaction using scant amounts of DNA. The data were analyzed using the Classification and Regression Tree (CART) to determine whether gene alterations detected in saliva DNA discriminated HNSCC patients from normal controls. Results were validated using the leave-one-out validation approach. Results: Of the 82 genes analyzed, 11 genes, ERBB2, ABCC4, UTY, DNMT1, PMAIP1, CDKN2B, CDKN2D, NFKB1, TP53, PTPN1, DCC, had the highest individual predictive ability for HNSCC. CART analysis revealed gain of PMAIP1 (18q21.31) solely or in conjunction with gain of PTPN1 (20q13.13) genes classified all 27 HNSCC patients with 100% sensitivity and 100% specificity. Validation results showed a sensitivity and specificity of 96% and 90% respectively. Conclusions: Gain of PMAIP1 (18q21.31) and PTPN1 (20q13.13) genes definitively separated HNSCC patients from normal controls, providing proof of concept that saliva based gene algorithms may have clinical utility for noninvasive HNSCC detection. Keywords: Genetic alterations; Head and neck squamous cell carcinoma (HNSCC); Multiplex Ligation-dependent Probe Amplification Assay (MLPA); Classification and Regression Tree (CART). Support: HFHS Dev Grant 06 (SS), R01 NIH DE 15990 (MJW).
A swollen leg
Authors: Rebecca Dicks, Stephen Sandys, CJL Hetherington
Journal: BMJ (2011)

This 81 year old man presented to the emergency department with a 24 hour history of increasing pain and swelling of his left leg. His medical history includes atrial fibrillation and advanced prostate cancer, for which he is being treated with diethylstilbestrol, an oestrogen hormone. On examination his left leg had a mottled dusky blue appearance and was markedly swollen, with the left and right calf circumferences measuring 43 cm and 38 cm respectively. On palpation the leg was cool to touch, tender, and blanched to pressure. Examination with a handheld Doppler ultrasound indicated good arterial flow in the posterior tibial artery bilaterally.

(1) What is the likely diagnosis in this man, and what differentials would you consider?

(2) What are the risk factors for this condition?

(3) How would you confirm the diagnosis?

(4) How would you treat this man?

(5) What are the potential complications of this condition?

(1) This man has a large deep vein thrombosis (DVT) in his left leg. It is likely that he also has a …
Talking to seriously ill patients, knowing what I know now
Authors: Angus Radford
Journal: BMJ (2014)

In early 2012, aged 53, my father was diagnosed with advanced metastatic prostate carcinoma. At the time I was struck by a multitude of thoughts and feelings, some of which were identical to those I had experienced towards other cancer patients. What do I say? How do I behave? Will the subject be uncomfortable?

Since my father’s diagnosis I have observed a tangible feeling of awkwardness around the subject of cancer; friends are left tongue tied; family members stand back unsure what to do; others want to help but few seem to know how. In my experience most people with cancer do not want to be defined by their disease—they want to be treated normally, but with a degree of sensitivity. There is no right answer or magical …
A useful evidence based medicine resource
Authors: Alex Romain
Journal: BMJ (2011)

Webliography of resources for evidence-based health care

The Cochrane Collaboration.

www.cochrane.org/about-us/evidence-based-health-care/webliography

Rating: \***|

Students usually visit the Cochrane Library to browse meta-analyses when they are writing a literature review. This uninspiring website does not encourage casual exploration. So it is easy to miss the webliography, a one stop reference list for all your evidence based medicine needs.

Click on the webliography and you will find a list of subcategories like “databases.” Your initial disinterest is compounded by each subsequent click. The webliography churns out titles of books and papers that …