tbuckley/cabot-search huggingface dataset:
Abstract P1-06-10: Combined tandem affinity purification mass-spectrometry technique with genome-editing CRISPR-Cas9 knockout screening to identify potential subunits in the BRCA1 complex
Authors: H Zhao, H Jiang, W Sun, Z Shao, X Hu
Journal: Cancer Research (2019)

Abstract Background: Genomic instability is one of tumor characteristics. Enhancing the DNA damage load or impairing the ability of DNA damage repair has been therapeutics of cancer. Breast cancer type 1 susceptibility gene (BRCA1) has been studied a lot about the DNA damage and repair in breast cancer and ovarian cancer. BRCA1 mutation increases the risk of developing breast cancer by an eighth to tenth. The C terminal domain of BRCA1 can associates with three proteins Abraxas, Bach1 and CtIP in a phosphorylation-dependent manner forming mutually exclusive complexes, namely BRCA1-A, B, and C complexes. The BRCA1-A complex is necessary in DNA damage repair, and study implicates the complex play roles in chemotherapy resistance. Methods: We explored tandem affinity purification mass-spectrometry (TAP-MAS) technique to identify potential subunits associated with NBA1(one component of BRCA1-A complex). Then we made the genome-editing CRISPR-Cas9 sgRNA library into lentivirus to infect U2OS cells. And 5 Gy dose of Ionizing radiation (IR) was used to induce DNA damage on the cell. After 14 days cultivation, we extracted the DNA from the cells, performed polymerase chain reaction (PCR) and analyzed the correlation between potential genes and DNA damage-repair passage by bioinformatics methods. We generated 200 breast cancer patient tissue samples in our cancer center and performed immunostaining assay. Results: By the TAP-MAS technique of NBA1 tagged with HA and Flag, we found 93 potential subunits except those known subunits in BRCA1-A complex. Combined with CRISPR-Cas9 sgRNA library screening, we scored the relativity of DNA damage and repair passageway of identified 93 potential subunits. We found that nucleoside-triphosphatase, cancer-related (NTPCR) as a new potential subunit of BRCA1-A complex (P value=0.0034) had the highest score. Endogenous and exogenous co-IP validated NTPCR physically associates with subunits within BRCA1-A complex. Besides, we found that NTPCR associated with the same domain of NBA1 as the other subunits in BRCA1-A complex. Immunohistochemistry of patient tissue samples indicated that high levels of NTPCR expression was correlated with poor prognosis in multivariate analysis (HR: 4.990; 95%CI: 1.433-17.378; p value: 0.012). Conclusion: NTPCR is a new subunit in BRCA1-A complex. And high expression of NTPCR is a negative prognostic factor in breast cancer patients. Citation Format: Zhao H, Jiang H, Sun W, Shao Z, Hu X. Combined tandem affinity purification mass-spectrometry technique with genome-editing CRISPR-Cas9 knockout screening to identify potential subunits in the BRCA1 complex [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 P1-06-10.
Abstract P1-11-05: Withdrawn
Authors: NJ Bundred, P Foden, K Riches, J Morris, A Evans, C Todd, M Bramley, A Skene, D Watterson, 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, Watterson D, 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 P1-11-05.
Intercalating in healthcare management and leadership
Authors: Lucy Cuckow, Shahin Ghezelayagh
Journal: BMJ (2017)

Opportunities for extending your knowledge and skills in improving how services are run for the benefit of patients and healthcare staff All doctors in the United Kingdom are expected to demonstrate leadership skills by the General Medical Council,1 and should be supported by their postgraduate training institutions to develop and practise these skills.2 For the NHS to continue to deliver high quality care, doctors must be involved in its leadership and management. This is especially important in the context of a growing and ageing population, government efficiency savings, and the findings of reports that highlight failures in the standards of care in the NHS.34 Research has correlated clinical engagement in service provision with improved trust ratings, patient satisfaction, and reduced patient morbidity.5 Despite a drive to encourage doctors to get involved in leading change,6 teaching on service delivery and efficiency at medical school is sparse.78 Many opportunities are available to help you develop your understanding and skills around healthcare management and leadership at medical school (see box 1). One option is to take an intercalated degree in healthcare management and leadership, which involves undertaking an extra year of study to understand how the health service is run and how healthcare staff can bring about positive change. #### Box 1: Healthcare management and leadership resources
Indoor Endotoxin Exposure and Ambient Air Pollutants Interact on Asthma Outcomes
Authors: Michael J. Abramson, Yuming Guo
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

It is then reasonable to speculate that both aspirin and 5-LO inhibitors benefit AERD through the same final common pathway; namely, the blockade of PgD2 production.The LTE4 receptor is highly expressed on epithelial cells and mast cells.Engagement of these receptors on epithelial cells (15), in part through their secretion of IL-25, IL-33, and TSLP (thymic stromal lymphopoietin), can indirectly drive mast cell activation and PgD2 production.But CysLTs, including especially LTE4, also act directly on mast cells to cause PgD2 production (16).Thus, an intriguing solution to the paradox of both 5-LO inhibitors producing decreased CysLT expression and aspirin administration's increased CysLT expression being beneficial in AERD would be that both agents ultimately act to decrease PgD2.In summary, this study points to the central role of the mast cell in the pathogenesis of AERD, with mast cell-derived PgD2 potentially being a central pathogenic mediator.And any mechanism that blocks PgD2 pathways, including CysLT synthesis inhibitors, cyclooxygenase inhibitors, or perhaps in the future, CRTH2 antagonists, can form the basis for clinical improvement.
The hunt for Ebola
Authors: Emma Rourke
Journal: BMJ (2013)

From the comfort of the library, immersed in textbooks on virology, nothing could seem further removed than an adrenaline fuelled pursuit of a rapidly evolving epidemic across Africa. No Time to Lose , however, describes just that—the adventures of a scientist who has dedicated his life to furthering understanding of some of the world’s most fear provoking viruses.

Peter Piot has had an extraordinary career. He is director at the London School of Hygiene and Tropical Medicine. The book charts his work across the globe from Africa to India, Washington to Cuba, and New York to Nairobi. His jobs have been broad and varied—from characterising deadly viruses as a microbiologist to dealing with diplomats, dictators, and AIDS denialists as undersecretary general of the United Nations.

Readers are invited to join the story in 1976, when …
Abstract P5-09-14: Prevalence and type of BRCA mutations in young breast cancer patients undergoing genetic cancer risk assessment in two developing countries: Analysis of two cohorts from Romania and Mexico
Authors: S Campos-Gomez, N Antone, G Pacheco-Cuéllar, L Pop, K Campos  Gomez, A Stoian, R Eniu, J Valdes-Andrade, E Dronca, R Matei, M Ligtenberg, H Ouchene, A Onisim, O Rotaru, AE Eniu
Journal: Cancer Research (2019)

Abstract Background: a previous study found significant clinicopathological differences between young Breast Cancer BrCA patients (pts) from Romania (Ro) and from Mexico (Mx). Here, we provide a molecular and clinical description of pts carrying BRCA mutations of both cohorts. Methods: in this retrospective study, we analyzed 2 cohorts of BRCA1/2 mutations carriers tested in COEI from Mx between 2014-2017 and IOCN from Ro between 2015 to 2016. Ro pts were selected according to NCCN criteria, while Mx pts were selected based on risk evaluation models. NGS analysis and MLPA for BRCA1&amp;2 were performed in all pts. We compared demographic, clinicopathological and molecular data. Results: 65 pts, 21 (32.7%) from Mx and 44(67.7%) from Ro carried a BRCA mutation. 66.7% of Mx pts and 65.9% of Ro pts carried a BRCA1 mutation. We found clinical similarities: Mean age was 44.5y for Mx and 40.59y for Ro pts. IDC was the most frequent type of BrCa in both series (90.5 vs 90.9%). TNBC was seen in 13 Mx vs 27 Ro pts (61.9% vs 61.4%), HR positive was seen in 7 (33.3%) and 12 (27.3%) cases. Grading 3 was more frequently seen in Ro, while grading 2 was mainly noted in MX pts(p=&amp;lt;0.020). BRCA1/2 pathogenic mutations were different between the 2 cohorts and no BRCA 1/2 identical mutation was identified. 15 different mutations in 21 Mx pts, and 16 different mutations in 44 Ro pts were found. Mutations were different between 2 cohorts. Notably for the Ro cohort, 4 founder mutations (c.181T&amp;gt;G, c.3607C&amp;gt;T, c.5266dupC in BRCA1,and c.9928A&amp;gt;G[GPC1] in BRCA2) were found in 31/44 pts, while the Mx cohort, c.5123C&amp;gt;A and del 9-12del ex in BRCA1 were found in 6/21 mutations. Three Large rearrangements (LR) were exclusively seen in the Mx pts (5/21). Conclusions Both cohorts didn't share any mutation, but the clinical features are similar. BRCA1 del 9-12del is a Mexican founder mutation, we found it in 14% of Mx pts, LR have been described more frequently in Latin American Populations, we found it in 30% of the MX cohort, while for Ro cohort four recurrent mutations qualify as founder mutations. Citation Format: Campos-Gomez S, Antone N, Pacheco-Cuéllar G, Pop L, Campos Gomez K, Stoian A, Eniu R, Valdes-Andrade J, Dronca E, Matei R, Ligtenberg M, Ouchene H, Onisim A, Rotaru O, Eniu AE. Prevalence and type of BRCA mutations in young breast cancer patients undergoing genetic cancer risk assessment in two developing countries: Analysis of two cohorts from Romania and Mexico [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 P5-09-14.
Suspected empyema of the gallbladder
Authors: Joanne Summerscales, Muhammad H Shiwani
Journal: BMJ (2011)

A 72 year old man presented with persistent right upper quadrant pain, fever, and lethargy. He had been treated for cholecystitis the previous week with intravenous antibiotics and then oral antibiotics.

On examination, he was pyrexial and had a tender palpable mass in his right upper quadrant. His white cell count was raised, at 20.6 x 109/L, with a predominance of neutrophilia, and liver function tests were normal except gamma-glutamyl tranferase of 154.

He was started on intravenous antibiotics for suspected empyema of the gallbladder. Ultrasound scan of the abdomen showed multiple gallstones and an 8 cm inflammatory mass adjacent to the gallbladder. A contrast enhanced computed tomography scan of the patient’s abdomen was performed, which confirmed a distended gallbladder with an abscess⇓ adjacent to the gallbladder fundus, which was suggestive of a contained gallbladder perforation.



Fig 1



An ultrasound guided drain was inserted to drain the collection and remained …
Abstract 15898: Lognormal Distribution of Sympathetic Nerve Activity in Normotensive and Spontaneously Hypertensive Rats
Authors: Toru Kawada, Shuji Shimizu, Atsunori Kamiya, Kazunori Uemura, Meihua Li, Can Zheng, Masaru Sugimachi
Journal: Circulation (2012)

Purpose: Although multifiber recording of the sympathetic nerve is commonly used to assess sympathetic nerve activity (SNA) in animal studies, little is known as to the nature of its amplitude dist...
Apps to simplify an orthopaedic placement
Authors: Tom Lewis
Journal: BMJ (2012)

Orthopaedics placements can be challenging. Consultants point out invisible fractures and then confidently decide upon the best treatment plan, often without explanation. Medical students can be left confused. Several mobile phone apps can make understanding orthopaedics easier.

Perhaps the most challenging aspect of an orthopaedic rotation for students is learning and recognising the radiographic problems. Gross fractures are easy to pick up, but far more subtle signs show on radiographs. Real World Orthopaedics is one of the best orthopaedic radiology apps on the market. The app contains radiographs of mostly orthopaedic trauma cases, with explanations of radiographic findings and relevant clinical information.

A wide range of conditions, and a wealth of …
A multicenter, randomized, double-blind study of ulimorelin and metoclopramide in the treatment of critically ill patients with enteral feeding intolerance: PROMOTE trial
Authors: Daren K. Heyland, Arthur R. H. van Zanten, Teodoro Grau-Carmona, David Evans, Albertus Beishuizen, Jeroen Schouten, Oscar Hoiting, Maria Luisa Bordejé, Kenneth Krell, David J. Klein, Jesus Gonzalez, Aitor Perez, Randy Brown, Joyce James, M. Scott Harris
Journal: Intensive Care Medicine (2019)
Abstract P1-20-03: Withdrawn
Authors: SR Dillon, LS Evans, E Rickel, KE Lewis, R Swanson, SD Levin, M Wolfson, SL Peng, KM Swiderek
Journal: Cancer Research (2019)

Abstract This abstract was withdrawn by the authors. Citation Format: Dillon SR, Evans LS, Rickel E, Lewis KE, Swanson R, Levin SD, Wolfson M, Peng SL, Swiderek KM. 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 P1-20-03.
Fracture of 19G needle during transrectal endoscopic ultrasound-guided drainage of perirectal collection: an unusual complication
Authors: Gianfranco Donatelli, Fabrizio Cereatti
Journal: Endoscopy (2019)

A 54-year-old woman was referred to our hospital for general sepsis. Computed tomography (CT) scan highlighted a collection of size 7 cm in the pouch of Douglas. The patient had a medical history of previous salpingo-oophorectomy coupled with appendicectomy for pelvic inflammatory disease.
In my day
Authors: Oliver Ellis
Journal: BMJ (2011)

Give an old timey consultant half a chance and they’ll start reminiscing about how things aren’t as good as they used to be.

“It was a proper medical education back then,” they’ll say. “The hours were long, lessons hard, and surgeons were allowed to lob amputated limbs at students. But by god, they made proper doctors of us.”

Press them further though and they’ll tell you that when they were young their seniors were similarly misty eyed about their own good old days.

At any point in history you …
Hepatic leukemia factor is a novel leukemic stem cell regulator in DNMT3A, NPM1, and FLT3-ITD triple-mutated AML
Authors: Swati Garg, Armando Reyes-Palomares, Lixiazi He, Anne Bergeron, Vincent-Philippe Lavallée, Sébastien Lemieux, Patrick Gendron, Christian Rohde, Jianglong Xia, Prarabdha Jagdhane, Carsten Müller-Tidow, Daniel B. Lipka, Suzan Imren, R. Keith Humphries, Claudia Waskow, Binje Vick, Irmela Jeremias, Guillaume Richard-Carpentier, Josée Hébert, Guy Sauvageau, Judith B. Zaugg, Frédéric Barabé, Caroline Pabst
Journal: Blood (2019)
Association of Adult Congenital Heart Disease With Pregnancy, Maternal, and Neonatal Outcomes
Authors: Kaylee Ramage, Kirsten Grabowska, Candice Silversides, Hude Quan, Amy Metcalfe
Journal: JAMA Network Open (2019)

<h3>Importance</h3> With the help of medical advances, more women with adult congenital heart disease (ACHD) are becoming pregnant. Adverse maternal, obstetric, and neonatal events occur more frequently in women with ACHD than in the general obstetric population. Adult congenital heart disease is heterogeneous, yet few studies have assessed whether maternal and neonatal outcomes differ across ACHD subtypes. <h3>Objective</h3> To assess the association of ACHD and its subtypes with pregnancy, maternal, and neonatal outcomes. <h3>Design, Setting, and Participants</h3> This cross-sectional study used data from the Discharge Abstract Database, which contains information on all hospitalizations in Canada (except Quebec) from fiscal years 2001-2002 through 2014-2015. Discharge Abstract Database information was linked with maternal and infant hospital records across Canada. All women who gave birth in hospitals during the study period were included in the study. Data were analyzed from December 18, 2017, to March 22, 2019. <h3>Exposures</h3> Women with ACHD were identified using diagnostic and procedural codes. Subtypes of ACHD were classified using the Anatomic and Clinical Classification of Congenital Heart Defects scheme. <h3>Main Outcomes and Measures</h3> Primary outcomes were defined a priori and included severe maternal morbidity (measured using the Maternal Morbidity Outcomes Indicator), neonatal morbidity and mortality (measured using the Neonatal Adverse Outcomes Indicator), ischemic placental disease, preterm birth, congenital anomalies, and small-for-gestational-age births. Absolute and relative rates of each outcome were calculated overall and by ACHD subtype. Logistic regression using generalized estimating equations assessed crude and adjusted odds ratios (aORs) for each outcome in women with ACHD compared with women without ACHD after adjustment for comorbidities, mode of delivery, and study year. <h3>Results</h3> The 2114 women with ACHD included in the analysis (mean [SD] age, 29.4 [5.7] years) had significantly higher odds of maternal morbidity (aOR, 2.7; 95% CI, 2.2-3.4) and neonatal morbidity and mortality (aOR, 1.8; 95% CI, 1.6-2.1) compared with women without ACHD (n = 2 682 451). Substantial variation was observed between women with different subtypes of ACHD. For example, the aORs of preterm birth (&lt;37 weeks) varied from 0.4 (95% CI, 0.4-0.5) for women with anomalies of atrioventricular junctions and valves to 4.7 (95% CI, 2.9-7.5) for women with complex anomalies of atrioventricular connections. <h3>Conclusions and Relevance</h3> These results suggest that women with different subtypes of ACHD are not uniformly at risk for adverse maternal and neonatal outcomes. Although some women with ACHD can potentially expect healthy pregnancies, it appears that clinical care should be modified to address the heightened risks of certain ACHD subtypes.
Abstract SY24-03: The signaling landscape of oncogenic ras
Authors: Dafna Bar-Sagi
Journal: Cancer Research (2010)

Abstract Ras proteins are highly conserved membrane-bound nucleotide binding proteins. They are essential for the transduction of diverse extracellular signals that control cell growth, and abnormal activation of Ras proteins is implicated in the development of several types of human cancers. It is now well established that Ras proteins control cell growth through the activation of multiple effector pathways. These pathways form a signaling network that enables the cell to interpret biological inputs in a context-dependent manner. I will describe our efforts to define a molecular framework for the regulation of Ras-dependent signal output and to understand how this output is modified in cancer cells. Citation Format: Dafna Bar-Sagi. The signaling landscape of oncogenic ras [abstract]. In: Proceedings of the AACR 101st Annual Meeting 2010; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr SY24-03
Abstract P5-10-05: Not presented
Authors: A Semetei Kyzy, E Makimbetov, I Kudaibergenova, J Isakova
Journal: Cancer Research (2019)

Abstract This abstract was not presented at the conference. Citation Format: Semetei Kyzy A, Makimbetov E, Kudaibergenova I, Isakova J. Not presented [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 P5-10-05.
Abstract P6-09-06: BRCAness as a prognostic marker in triple-negative breast cancer patients treated with neoadjuvant chemotherapy: A multicenter retrospective study
Authors: Y Kosaka, Y Yamamoto, H Nishimiya, M Ibusuki-Yamamoto, Y Hirota, H Tanino, H Iwase, S Nakamura, S Akashi-Tanaka
Journal: Cancer Research (2019)

Abstract Background: Triple negative breast cancer (TNBC) has several subtypes. Identification of markers associated with recurrence and poor prognosis in TNBC patients is critically needed. BRCAness is a set of traits in which BRCA1 dysfunction, arising from gene mutation, methylation or deletion, results in DNA repair deficiency. In the present study we evaluated the clinical significance and prognosis of BRCAness in a multicenter retrospective study. Methods: Ninety-four TNBC patients treated with neoadjuvant chemotherapy (NAC) were enrolled from three hospitals in Japan for this retrospective study. Of these patients, 86 (91.5%) were treated with anthracyclines and taxanes. BRCAness was determined from 94 core needle biopsy (CNB) specimens prior to NAC and 50 surgical specimens without pathological complete response (pCR). The samples were assessed using multiplex ligation-dependent probe amplification (MLPA) and the amplicons were scored. Samples with scores &amp;gt;0.5 were defined as having BRCAness. Results: Of the 94 TNBC patients, 51 (54.3%) had BRCAness in CNB specimens. There were no significant differences in pCR rate or recurrence between the BRCAness and non-BRCAness groups. Among surgical specimens, the BRCAness group (19/50, 38%) had a significantly shorter recurrence-free survival (RFS) and disease-specific survival (DSS) compared with the non-BRCAness group (p &amp;lt; 0.01 and p &amp;lt; 0.05). The BRCAness group had independent prognostic factors for recurrence and survival in multivariate regression analysis. Conclusions: The BRCAness of surgical specimens is a useful marker to predict prognosis in TNBC patients after NAC. A clinical trial to assess the clinical impact of platinum-containing drugs with BRCAness is planned. Citation Format: Kosaka Y, Yamamoto Y, Nishimiya H, Ibusuki-Yamamoto M, Hirota Y, Tanino H, Iwase H, Nakamura S, Akashi-Tanaka S. BRCAness as a prognostic marker in triple-negative breast cancer patients treated with neoadjuvant chemotherapy: A multicenter retrospective study [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 P6-09-06.