tbuckley/cabot-search huggingface dataset:
Abstract P2-05-26: uPA/PAI-1 and adjuvant chemotherapy decision-making in early breast cancer
Authors: E Deluche, L Venat-Bouvet, S Leobon, V Fermeaux, Y Aubard, N Saïdi, I Jammet, N Tubiana-Mathieu
Journal: Cancer Research (2017)

Abstract Background: Adjuvant chemotherapy decisions are relatively simple using clinicopathological parameters (Goldhirsch et al. 2007), some cases require the addition of biomarkers as in patients with node negative or micrometastatic (N0), grade II (GII) breast cancer. The objective of this study was to evaluate the impact of uPA/PAI-1 compared to classical criteria +/- KI67 in adjuvant treatment decision-making in this population. Methods: This retrospective study included patients, treated from March 2008 to May 2016 in the Department of Medical Oncology at Limoges University Hospital (France). Ki67 and uPA/PAI-1 were analyzed on the initial specimen tumor. Optimal cut-off of Ki67 was defined at 20% (Coates et al. 2015). The positivity thresholds of uPA and PAI-1 were 3 ng/mg and 14 ng/mg respectively (Look et al. 2002). A positive uPA/PAI-1 level was defined as the elevation of at least one of these markers above the positivity threshold. All clinicopathological parameters were recorded prospectively. Results: 2364 patients with breast cancer were screened. Among these patients, 256 N0, GII breast cancer patients were included with a median age of 62 years (32-87). Discordance between the two markers uPA/PAI-1 and KI67 was observed in 58% of tumors. Adding KI67 to the other classical clinicopathological parameters, 143 cases were defined as high risk versus 111 cases without KI67; low risk were defined in 113 cases versus 145 cases without KI67. Considering Ki67 status, the indication to perform adjuvant chemotherapy was increased by 29% compared to clinicopathological parameters. uPA/PAI-1 level was positive in these 143 high risk tumors in 93 cases and negative in 50 cases; in the 113 low risk tumors uPA/PAI-1 was positive in 72 cases and negative in 41 cases. uPA/PAI-1 increased indication to perform adjuvant chemotherapy by 15% compared to St Gallen criteria (including KI67) and by 49% compared to St Gallen criteria (excluding KI67). Using these two markers the final decision of chemotherapy by the multidisciplinary board was increased by 3% compared to St Gallen criteria (including KI67). Conclusions: This study highlighted that uPA/PAI-1 and Ki67 assessment provides additional information for adjuvant chemotherapy decision-making. This study confirms the difficulty to assess the level of importance (weighting) of these biomarkers in adjuvant chemotherapy decision-making. The use of uPA/PAI-1 was feasible, cost-effective in N0, GII breast cancer's patients. Citation Format: Deluche E, Venat-Bouvet L, Leobon S, Fermeaux V, Aubard Y, Saïdi N, Jammet I, Tubiana-Mathieu N. uPA/PAI-1 and adjuvant chemotherapy decision-making in early breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-05-26.
Hematopoietic Stem Cell Transplantation in 65 Patients with Leukocyte Adhesion Deficiency Type I and Type III — A Retrospective Multi-Center Study
Authors: Shahrzad Bakhtiar, Dirk-Jan Eikema, Henric-Jan Blok, Mouhab Ayas, Franco Locatelli, Pietro Merli, Amos Toren, Gal Goldstein, Gerard Michel, Gülyüz Öztürk, Ansgar Schulz, Carsten Heilmann, Robert Wynn, Olga Aleinikova, Yves Bertrand, Abdelghani Tbakhi, Ardeshir Ghavamzadeh, Paul Veys, Arjan Lankester, Peter Bader, Andrew Gennery
Journal: Blood (2017)
Make a mental note
Authors: Matthew Billingsley
Journal: BMJ (2017)

Patients who experience mental health disorders in healthcare settings are not always confined to the psychiatric ward. No matter where you are working, you need to be prepared to assess and manage challenging behaviours and presentations that could be the result of an underlying mental health disorder.

The work of the liaison psychiatry team is an example of how mental health issues permeate all hospital departments. On p38, Jessica Scott and Kieron Kumar, foundation year 2 doctors, and Peter Aitken and Thirza Peters, consultant liaison psychiatrists, describe when you might need to call for assistance from this multidisciplinary mental health team, which can advise on and assess patients experiencing mental health problems while in hospital.

Marina Soltan, foundation year 1 doctor, and Joseph Girguis, …
Abstract P6-14-04: Not presented
Authors: NA Mohd Taib, T Islam, TT Su, S Musthaffa, N Abdullah Din, Z Rahman, KNB Mohamed, S Kaur, J Filza, F Shaheera, C Ellsworth Beaumont
Journal: Cancer Research (2019)

Abstract This abstract was not presented at the conference. Citation Format: Mohd Taib NA, Islam T, Su TT, Musthaffa S, Abdullah Din N, Rahman Z, Mohamed KNB, Kaur S, Filza J, Shaheera F, Ellsworth Beaumont C. 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 P6-14-04.
Our resources are strained by recession, say mental health charities
Authors: Tomasz Pierscionek
Journal: BMJ (2012)

The recession is having a negative impact on the mental wellbeing of people in the UK. The mental health charity Mind reported a 28% rise in the number of people phoning its helplines between October 2011 and April 2012, compared with the same period the previous year. It also reported that twice as many people are seeking advice on …
Abstract PL1: Breast Tumor Evolution and Intratumor Heterogeneity - Insights from Single Cell Genomics
Authors: N Navin
Journal: Cancer Research (2019)

Abstract Breast tumors evolve from single cells in the ducts and acquire mutations leading to divergent lineages and intratumor heterogeneity in invasive cancers. To understand the genomic evolution of breast cancers during complex evolutionary processes including initiation, invasion and therapeutic resistance we have developed single cell sequencing (SCS) methods. I will discuss our efforts in applying SCS methods to study invasion in 10 premalignant breast cancer patients with ductal-carcinoma-in-situ (DCIS), which led to a discovery of early punctuated copy number evolution in the ducts and multi-clonal invasion. I will also discuss our work in applying both single cell DNA and RNA sequencing methods to study chemoresistance evolution in 20 triple-negative breast cancer patients using longitudinal samples, which identified an adaptive genomic evolution and acquired transcriptional reprogramming during resistance. Finally I will present unpublished work on our efforts to develop a 'Human Breast Cell Atlas' of cell types and cell states (transcriptional programs) of normal cell types, and recent work on delineating copy number evolution in BRCA-positive breast cancer patients. Citation Format: Navin N. Breast Tumor Evolution and Intratumor Heterogeneity - Insights from Single Cell Genomics [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 PL1.
Response to ‘Antinuclear antibodies by indirect immunofluorescence and solid phase assays’ by Bossuyt<i>et al</i>
Authors: David S Pisetsky, Diane M Spencer, Peter E Lipsky, Brad H Rovin
Journal: Annals of the Rheumatic Diseases (2019)

Response to 'Antinuclear antibodies by indirect immunofluorescence and solid phase assays' by Bossuyt et al We would like to thank Dr Bossuyt and colleagues 1 for their comments on our article on variability in testing for antinuclear antibodies (ANA). 2 This letter, along with previous correspondence, [3][4][5][6][7][8][9] highlights the many issues about ANA testing and the results obtained with different assay platforms.We agree that a combination of different assays can be a valuable approach to assess more completely the serological profile of patients with autoantibody-associated rheumatic disease (AARD).We would note, however, that, just as indirect immunofluorescence assays (IIF) can differ in performance characteristics, so too can solid phase assays (SPA).For SPA, differences can result from the composition of the antigens on the solid phase and the use of mixtures of purified proteins in contrast to a cell extract.It is important, therefore, that studies with SPA indicate antigens present as Bossuyt et al have done in their letter.In our study that was published in Annals of Rheumatic Diseases, we focused on systemic lupus erythematosus (SLE), seeking to understand the high frequency of ANA negativity observed in screening of patients for clinical trials for new agents. 21][12] Since the array of ANA expressed in SLE differs from that of other AARD, testing of a variety of IIF and SPA kits may be necessary to find a combination most applicable to this disease.ANA expression has been viewed as almost invariable in SLE although this conclusion is based on the assays used for these determinations and therefore may be worth revisiting.
Outcomes Associated With Cardiogenic Shock in Takotsubo Syndrome
Authors: Davide Di Vece, Rodolfo Citro, Victoria L. Cammann, Ken Kato, Sebastiano Gili, Konrad A. Szawan, Jozef Micek, Stjepan Jurisic, Katharina J. Ding, Beatrice Bacchi, Moritz Schwyzer, Alessandro Candreva, Eduardo Bossone, Fabrizio D’Ascenzo, Annahita Sarcon, Jennifer Franke, L. Christian Napp, Milosz Jaguszewski, Michel Noutsias, Thomas Münzel, Maike Knorr, Susanne Heiner, Hugo A. Katus, Christof Burgdorf, Heribert Schunkert, Holger Thiele, Johann Bauersachs, Carsten Tschöpe, Burkert M. Pieske, Lawrence Rajan, Guido Michels, Roman Pfister, Alessandro Cuneo, Claudius Jacobshagen, Gerd Hasenfuβ, Mahir Karakas, Wolfgang Koenig, Wolfgang Rottbauer, Samir M. Said, Ruediger C. Braun-Dullaeus, Adrian Banning, Florim Cuculi, Richard Kobza, Thomas A. Fischer, Tuija Vasankari, K.E. Juhani Airaksinen, Grzegorz Opolski, Rafal Dworakowski, Philip MacCarthy, Christoph Kaiser, Stefan Osswald, Leonarda Galiuto, Filippo Crea, Wolfgang Dichtl, Klaus Empen, Stephan B. Felix, Clément Delmas, Olivier Lairez, Ibrahim El-Battrawy, Ibrahim Akin, Martin Borggrefe, Ekaterina Gilyarova, Alexandra Shilova, Mikhail Gilyarov, John Horowitz, Martin Kozel, Petr Tousek, Petr Widimský, David E. Winchester, Christian Ukena, Carlo Di Mario, Abhiram Prasad, Michael Böhm, Jeroen J. Bax, Thomas F. Lüscher, Frank Ruschitzka, Jelena R. Ghadri, Christian Templin
Journal: Circulation (2019)
Dual-Physician Households
Authors: Lauren Ferrante, Lona Mody
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Abstract ES12-1: BRCA2 and control of transcription: R-loop dynamics
Authors: A Venkitaraman
Journal: Cancer Research (2019)

Abstract Pathogenic germline mutations affecting the breast cancer genes, BRCA1 and BRCA2, predispose to cancers of the breast, ovary, and other tissues with a high penetrance. Cancer pathogenesis in mutation carriers has been linked to genomic instability following inactivation of the essential cellular functions of the encoded BRCA1 and BRCA2 proteins in DNA repair and the restoration of stalled DNA replication (reviewed in Venkitaraman, Science 343, 1470-5 (2014)). Here, I will discuss emerging evidence that links previously unrecognized functions of the BRCA proteins to carcinogenesis, focusing on BRCA2. Increasing evidence indicates that heterozygosity for pathogenic BRCA2 mutations suffices for carcinogenesis in experimental models and in human mutation carriers (eg., Skoulidis et al., Cancer Cell 18, 499-509 (2010); Maxwell et al., Nature Commun 8, 319 (2017); Huang et al., Cell 173, 355-370 (2018)). Heterozygous mis-sense mutations in BRCA2 may act trans-dominantly to interfere with the nuclear transport of BRCA2/RAD51 complexes (Jeyasekharan et al., Nature Str Mol Biol 20, 1191-8 (2013)). We have reported recently a gene-environment interaction that may modify carcinogenesis in BRCA2 mutation carriers, wherein exposure to aldehydes, a pervasive class of endogenous and environmental toxins, selectively proteolyzes BRCA2, inducing haploinsufficiency for DNA repair and replication fork stability in cells bearing heterozygous truncating BRCA2 mutations (Tan et al., Cell 169, 1105-18 (2017)). BRCA2-deficient cells accumulate unscheduled RNA-DNA hybrids (R-loops) and genomic damage through an unexpected role of BRCA2 in promoting the switch from promoter-proximal pausing to transcription elongation by RNA polymerase II (Shivji et al., Cell Rep 22, 1031-1039 (2018)). These emerging functions have implications for the pathogenesis and therapy of cancers arising in patients who carry BRCA2 mutations. Citation Format: Venkitaraman A. BRCA2 and control of transcription: R-loop dynamics [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 ES12-1.
Abstract P5-08-05: The interplay between stromal density, epithelial mesenchymal transition and chemoresistance in breast cancer
Authors: V Agarwal, LJ Spalding, T Blick, A Dobrovic, EW Thompson, A Redfern
Journal: Cancer Research (2019)

Abstract Epithelial Mesenchymal Transition (EMT) refers to the transition of cells from a more differentiated epithelial phenotype to a less differentiated mesenchymal phenotype, a process that may be triggered by a range of therapeutic interventions including cytotoxic treatment, and which we have previously linked to poor breast cancer (BrCa) outcome after neoadjuvant chemotherapy (NAC)1. Mammographic breast density (MBD)represents the white radiographic appearance of epithelial and stromal breast tissue on a mammogram. High MBD in patients being treated for BrCa also associates with chemoresistance, correlating with lower pathological complete response rates (pCR)2. Linking these two stimuli, EMT can also be induced by artificial high-density stroma, where it also leads to chemoresistance in vitro3. Here we set out to validate the link between poor outcome after NAC and EMT in a larger validatory patient cohort, and to ascertain the molecular drivers through which EMT is triggered in this setting. Further we look to confirm the association of high MBD with poor chemoresponse in the same cohort, and to assess whether this chemoresistance is mediated through EMT with the same drivers. In a pilot cohort of 50 NAC-treated locally advanced BrCas with a pCR rate of 20%, pre-NAC biopsies and post-NAC surgical specimens were analysed for expression changes in a panel of EMT-related markers across treatment using 230 Nanostring assays. This included the EMT-driving transcription factors TWIST 1 and 2, SNAIL 1, 2 and 3 and ZEB 1 and 2, which were correlated with risk of relapse. Snail-3 showed significantly greater induction in relapsers compared to non-relapsers (OR=1.8, p=0.04) with a borderline significantly greater induction of TWIST-1 (OR=2.4, p=0.08) in relapsers in addition. In a subsequent 240-patient validation cohort with a pCR rate of 18%, contralateral cranio-caudal view mammograms from the time of diagnosis have been collated and digitized with MBD assessment employing Cumulus software ongoing. Percent breast density will be assessed both as a continuous variable and by quartiles. Immunohistochemistry on pre- and post-operative tissue sections with pan-cytokeratin-vimentin co-staining to identify EMT and staining for SNAIL-3 and TWIST-1 is also in progress. Associations between MBD, EMT before and after chemotherapy, pCR and relapse-free survival will be presented. The role of Snail-3 and TWIST-1 in the interplay between MBD, EMT and outcome is being explored and will be reported. Citation Format: Agarwal V, Spalding LJ, Blick T, Dobrovic A, Thompson EW, Redfern A. The interplay between stromal density, epithelial mesenchymal transition and chemoresistance in breast cancer [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 P5-08-05.
Efficacy and clinical significance of omitting blue dye injection during sentinel lymph node biopsy before Mohs micrographic surgery for malignant melanoma of the lower extremities
Authors: T.H. Kim, H.J. Kim, J.W. Seo, K.H. Song
Journal: British Journal of Dermatology (2019)

Sentinel lymph node biopsy (SLNB) is usually performed using a triple technique that includes lymphoscintigraphy (LSG), which involves the injection of a radiolabelled tracer, blue dye injection, and detection of the radioisotope with a gamma probe. However, blue dye injection may cause pathological misinterpretation and obscure clinical margins, especially when combined with Mohs micrographic surgery (MMS) for cutaneous melanoma.To assess the efficacy of SLNB without blue dye injection in patients who subsequently underwent MMS for melanomas of the lower extremities.We evaluated patients who underwent MMS with or without SLNB using preoperative localization of the primary melanoma via LSG and intraoperative confirmation using a gamma probe between 2010 and 2016.Seventy-two patients with melanoma of mean Breslow thickness 3·03 ± 1·44 mm were evaluated. Sixty-five of the 72 patients underwent SLNB, the success rate of which was 98%. The 5-year overall and disease-free survival rates were 78% and 76%, respectively.Blue dye injection can be omitted without compromising the accuracy of standard SLNB. Omitting blue dye injection also has marked advantages in MMS for melanoma. What's already known about this topic? Sentinel lymph node biopsy (SLNB) is usually performed using a triple technique including lymphoscintigraphy, which involves the injection of a radiolabelled tracer, blue dye injection, and radioisotope detection using a gamma probe. Blue dye injection may cause pathological misinterpretation and obscure clinical margins. What does this study add? Omitting the dye does not decrease diagnostic accuracy and is particularly advantageous for Mohs micrographic surgery (MMS) in melanomas with clinically indistinct tumour borders. SLNB without blue dye injection is feasible in MMS for melanoma.
Abstract P5-03-10: Circulating exosomal microRNA profiling to depict mechanisms of chemotherapy resistance among triple negative breast cancer
Authors: Y He, J Tang
Journal: Cancer Research (2019)

Abstract Background: Chemotherapeutic resistance leads to high mortality among triple negative breast cancer (TNBC) and underlying mechanisms are poorly understood. Exosomes have been new member of liquid biophsy. MicroRNAs (miRNAs), as the most important inclusions in exosomes, making them ideal candidate biomarkers and therapeutical targets. Methods: We isolated exosomes and analyzed exosome-carried miRNAs signatures in several TNBC cells lines sensitive or resistant to adariamycin, docetaxel or cisplatin. The resistance transfer capacity was determined by flow cytometry after sensitive cells incubated 48 hours with exosomes from drug resistant cells. Locked nucleic acid probes and enzyme-labeled fluorescence (LNA-ELF-FISH) was performed to detect exosomal miRNA molecules transfer. Animal mode was constructed to evaluate treatment feasibility using miRNA modified exosomes. Serum exosomes from 40 TNBC stage IV patients underwent chemotherapy before or after progress disease (PD) status were isolated to analyze miRNA profiling for potential biomarkers identification. Results: We successfully isolated and identified exosomes from several drug sensitive and resistant TNBC cell lines and patients. Exosomal miR-222, miR-4443, miR-100, miR-17, miR-210 were found significantly upregulated from chemotherapy resistance cells. Incubation of exosomes from the resistant cells with the sensitive cells resulted in increasing resistant capacity among sensitive cells. Exosomal miRNA molecules transfer were detected using LNA-ELF-FISH. Transfection of synthesized miRNAs competitors into exosomes increased drug sensitivity in vivo. Exosomal miR-222, miR-4443, miR-100, miR-17, miR-210 were also found upregulated significantly from serums of patients after PD status. These five miRNAs were able to differentiate patients with PD status from those with CR or PR status with at least 89% accuracy. Conclusion: Exosomes from chemotherapy resistant TNBC cells could transfer drug resistance to sensitive cells via exosomal miRNAs. A circulating exosomal microRNA profiling was estabilished for potential biomarkers and therapeutical targets identification. Citation Format: He Y, Tang J. Circulating exosomal microRNA profiling to depict mechanisms of chemotherapy resistance among triple negative breast cancer [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 P5-03-10.
Bronchiolitis: an infant with a dry cough
Authors: Ally Xiang, Margrid Schindler
Journal: BMJ (2010)

A 25 week old boy with a week’s history of worsening chest infection was brought to the paediatric emergency department by his parents. He had a dry cough and was short of breath and wheezing. His mother had noticed less milk intake, more vomiting after feeds, and subsequent weight loss (from the ninth to the 0.4th centile in two weeks). His general practitioner had prescribed salbutamol inhaler and amoxicillin antibiotics, but symptoms had worsened over the next two days.

The infant was born at 36 weeks by emergency caesarean section. He needed resuscitation with bag and mask for two minutes and was admitted to the neonatal intensive care unit because of respiratory distress. He developed pneumonia at four weeks and pyloric stenosis, for which he underwent a pyloromyotomy at seven weeks. There were no known family congenital defects or consanguinity. Respiratory examination showed subcostal and intercostals recession and decreased air entry bilaterally, with expiratory wheeze.

(1) What are the differential diagnoses for shortness of breath in an infant?

(2) What are the radiological findings …
Abstract P4-06-09: Withdrawn
Authors: F Corsi, F Andreata, M Truffi, L Sorrentino, F D'Addio, M Monieri, A Gambaro, M Bellini, D Prosperi, S Mazzucchelli
Journal: Cancer Research (2019)

Abstract This abstract was withdrawn by the authors. Citation Format: Corsi F, Andreata F, Truffi M, Sorrentino L, D'Addio F, Monieri M, Gambaro A, Bellini M, Prosperi D, Mazzucchelli S. 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 P4-06-09.