tbuckley/cabot-search huggingface dataset:
Abstract P4-02-14: Digitalizing immunohistochemistry analysis (IHC) with quantitative dot blot analysis (QDB) by absolute quantification of biomarkers in FFPE specimens
Authors: J Zhang, W Zhang, G Yu, F Tang, J Lv
Journal: Cancer Research (2019)

Abstract Purpose: The feasibility of Quantitative Dot Blot (QDB) method for absolute quantification of diagnostic biomarkers was investigated here using diagnostic antibodies for biomarkers in breast cancer tissues, including 4B5 and EP3 for Her2, MIB1 for Ki67. SP2 for Estrogen Receptor and SP1 for progesterone receptor (PR) in more than 300 FFPE specimens. The specificity and accuracy of this method, and the inter-relationship among biomarkers were explored by the absolute expression levels of these biomarkers. Methods: FFPE specimens of 332 breast cancer patients were provided by local hospital, tissue slices of 2X15 um was de-paraffined and total protein was extracted for QDB analysis, with each sample measured in triplicate in three indepedent experiments. Purified protein standards were included to convert the measurement into absolute levels. IHC and FISH results from local hospital were used to validate the sensitivity and specificity of QDB method. Results: The results show high consistency with intra-cv less than 7% and inter-cv less than 14%. With Her2, 99.5% concordance was achieved with IHC method, and 92 to 94% concordance with FISH analysis. Both Her2 level and Ki67 levels were significantly increased in patients at grade III based on Nottingham histologic scores. Conclusion: The QDB method was used here to achieve digitalization of biomarkersl in breast cancer tissue with existing diagnostic antibodies for IHC analysis. The method is simple, objective, consistent, comprehensive and suitable for high throughput analysis. We expect this method to be extended to other diagnostic IHCs with existing diagnostic antibodies, and the easy adoption of this method in clinical practice should have instant impact on pathological practice. Citation Format: Zhang J, Zhang W, Yu G, Tang F, Lv J. Digitalizing immunohistochemistry analysis (IHC) with quantitative dot blot analysis (QDB) by absolute quantification of biomarkers in FFPE specimens [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 P4-02-14.
Mental illness and well‐being: an affect regulation perspective
Authors: James J. Gross, Helen Uusberg, Andero Uusberg
Journal: World Psychiatry (2019)

Mental health crucially depends upon affective states such as emotions, stress responses, impulses and moods. These states shape how we think, feel and behave. Often, they support adaptive functioning. At other times, however, they can become detrimental to mental health via maladaptive affect generation processes and/or maladaptive affect regulation processes. Here, we present an integrative framework for considering the role of affect generation and regulation in mental illness and well-being. Our model views affect generation as an iterative cycle of attending to, appraising and responding to situations. It views affect regulation as an iterative series of decisions aimed at altering affect generation. Affect regulation decisions include identifying what, if anything, should be changed about affect, selecting where to intervene in the affect generation cycle, choosing how to implement this intervention, and monitoring the regulation attempt to decide whether to maintain, switch or stop it. Difficulties with these decisions, often arising from biased inputs to them, can contribute to manifestations of mental illness such as clinical symptoms, syndromes and disorders. The model has a number of implications for clinical assessment and treatment. Specifically, it offers a common set of concepts for characterizing different affective states; it highlights interactions between affect generation and affect regulation; it identifies assessment and treatment targets among the component processes of affect regulation; and it is applicable to prevention and treatment of mental illness as well as to promotion and restoration of psychological well-being.
Interferon‐Induced Transmembrane Proteins Mediate Viral Evasion in Acute and Chronic Hepatitis C Virus Infection
Authors: Florian Wrensch, Gaëtan Ligat, Laura Heydmann, Catherine Schuster, Mirjam B. Zeisel, Patrick Pessaux, François Habersetzer, Barnabas J. King, Alexander W. Tarr, Jonathan K. Ball, Michael Winkler, Stefan Pöhlmann, Zhen‐yong Keck, Steven K.H. Foung, Thomas F. Baumert
Journal: Hepatology (2019)

Although adaptive immune responses against hepatitis C virus (HCV) infection have been studied in great detail, the role of innate immunity in protection against HCV infection and immune evasion is only partially understood. Interferon‐induced transmembrane proteins (IFITMs) are innate effector proteins restricting host cell entry of many enveloped viruses, including HCV. However, the clinical impact of IFITMs on HCV immune escape remains to be determined. Here, we show that IFITMs promote viral escape from the neutralizing antibody (nAb) response in clinical cohorts of HCV‐infected patients. Using pseudoparticles bearing HCV envelope proteins from acutely infected patients, we show that HCV variants isolated preseroconversion are more sensitive to the antiviral activity of IFITMs than variants from patients isolated during chronic infection postseroconversion. Furthermore, HCV variants escaping nAb responses during liver transplantation exhibited a significantly higher resistance to IFITMs than variants that were eliminated posttransplantation. Gain‐of‐function and mechanistic studies revealed that IFITMs markedly enhance the antiviral activity of nAbs and suggest a cooperative effect of human monoclonal antibodies and IFITMs for antibody‐mediated neutralization driving the selection pressure in viral evasion. Perturbation studies with the IFITM antagonist amphotericin B revealed that modulation of membrane properties by IFITM proteins is responsible for the IFITM‐mediated blockade of viral entry and enhancement of antibody‐mediated neutralization. Conclusion: Our results indicate IFITM proteins as drivers of viral immune escape and antibody‐mediated HCV neutralization in acute and chronic HCV infection. These findings are of clinical relevance for the design of urgently needed HCV B‐cell vaccines and might help to increase the efficacy of future vaccine candidates.
Abstract OT3-02-01: RIBANNA — Real-world evidence of ribociclib plus aromatase inhibitor, or endocrine monotherapy, or chemotherapy as first-line therapy for postmenopausal women with HR+, HER2– advanced breast cancer (aBC)
Authors: A Wöckel, PA Fasching, G Guderian, J Heim, C Jackisch, H-J Lück, D Lüftner, F Marmé, T Reimer, T Decker
Journal: Cancer Research (2019)

Abstract Background: In the pivotal phase 3 MONALEESA-2 trial, ribociclib, a highly selective oral CDK4/6 inhibitor in combination with letrozole significantly prolonged progression-free survival (PFS) compared to letrozole alone. In the year 2017, based on the results of MONALEESA-2, ribociclib in combination with an aromatase inhibitor (AI) was approved for the treatment of HR+, HER2– aBC in postmenopausal women with no prior therapy for their advanced disease (first-line treatment). Beyond phase 3 trials, further data for ribociclib are now becoming available from the phase 3b trials, RIBECCA and COMPLEEMENT-1, involving approximately 500 and 3000 patients with aBC, respectively. However, real-world evidence for the effectiveness, safety, and tolerability of ribociclib + AI in the routine clinical practice is needed to further support the use of this combination in the first-line therapy. Methods: RIBANNA is a non-interventional study, which started in October 2017 and plans to enroll 3020 patients across ˜400 sites in Germany. Postmenopausal women diagnosed with aBC will be enrolled into 3 cohorts (cohort 1: ribociclib + AI; cohort 2: endocrine monotherapy; and cohort 3: chemotherapy). Across all cohorts, patients will be treated in accordance with the respective German-prescribing guidelines. Data related to efficacy (with PFS as the primary efficacy criterion), safety, tolerability, duration of therapy, and impact on quality of life (QoL) will be collected. QoL will be assessed using the validated patient questionnaires. This study was especially designed to analyze the patient data from sequential lines of therapy in all three cohorts over a period of up to 7 years. For this purpose, RIBANNA will collect the data on each line of treatment and the reason for changing treatment in all 3 cohorts. The same accounts for QoL, which will also be assessed periodically, regardless of disease progression and initiation of subsequent therapies. RIBANNA is the first study to provide the real-world evidence regarding treatment of HR+, HER2− aBC with the CDK4/6 inhibitor, ribociclib. This study includes 3 treatment cohorts (ribociclib + AI, endocrine monotherapy, and chemotherapy) with subsequent treatment algorithms and assessment of QoL over the entire study period. Citation Format: Wöckel A, Fasching PA, Guderian G, Heim J, Jackisch C, Lück H-J, Lüftner D, Marmé F, Reimer T, Decker T. RIBANNA — Real-world evidence of ribociclib plus aromatase inhibitor, or endocrine monotherapy, or chemotherapy as first-line therapy for postmenopausal women with HR+, HER2– advanced breast cancer (aBC) [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 OT3-02-01.
Enough nudges—time for a shove
Authors: Clemency Nye
Journal: BMJ (2012)

Recently, Denmark introduced the world’s first “fat tax”—a tax on the purchase of foods high in saturated fats. So will the UK, Europe’s fattest country, be introducing a similar tax? Andrew Lansley, the health secretary, claims we will not follow suit because “nudges are very important” and “tax is not a nudge, tax is a shove.” Yet when we look at the obesity statistics, we can conclude that the time for nudges has passed. The percentage of men classified as clinically obese in the UK has risen from 13.2% in 1993 to 22% in 2009, and from 16.4% to 24% for women over the same time.1 This rise requires decisive action.

The government is keen on nudges—using positive influence to alter …
Abstract P2-06-20: CDC20 is a novel therapeutic target in triple negative breast cancer
Authors: J Sharma, I Raicu, J Nguyen, N Udden, Q Wang, P Alluri
Journal: Cancer Research (2019)

Abstract Background: Approximately 15% of breast cancers lack expression of Estrogen Receptor (ER), Progesterone Receptor (PR) and Human Epidermal Growth Factor Receptor 2 (HER-2), and are referred to as Triple Negative Breast Cancer (TNBC). Clinical outcomes in patients with TNBC continue to be poor due to inherently aggressive biology of the disease and paucity of targeted therapies. In this study, we identified Cell Division Cycle protein 20 (CDC20), a key regulatory protein that mediates sister chromatid separation in mitosis, as a novel therapeutic target in TNBC. Methods: To uncover new drivers of TNBC, we nominated genes that are significantly overexpressed in patients with TNBC, compared to non-TNBCs. After identifying CDC20 as a top hit in this analysis, we used expression microarrays, RNA-seq analyses and Western blotting to assess CDC20 expression levels in breast cancer patients and cell lines. Kaplan-Meier analyses were performed to study the correlation between CDC20 expression levels and clinical outcomes, including recurrence-free survival, metastasis-free survival and overall survival. shRNA-mediated knockdown of CDC20 in TNBC cell lines was employed to study the role of CDC20 in TNBC proliferation, invasion, migration and xenograft growth in mice. Results: CDC20 was significantly overexpressed in TNBCs (compared to non-TNBCs) in The Cancer Genome Atlas (TCGA) breast dataset, and in several other independent breast cancer datasets, including Curtis, Stickeler and Kao. CDC20 expression was also significantly higher in TNBC cell lines compared to non-TNBC cell lines. Furthermore, expression levels of CDC20 were highly significantly correlated with clinical outcomes, including recurrence-free survival, metastasis-free survival and overall survival. shRNA-mediated knockdown of CDC20 expression in TNBC cell lines, MDA-MB-231 and MDA-MB-468, resulted in decreased proliferation, invasion and migration. Our preliminary findings suggest that CDC20 knockdown also results in inhibition of cell line-derived xenograft growth in mice. Conclusion: We identified CDC20 is a novel therapeutic target in TNBC. Our findings support development of pharmacologic strategies to inhibit CDC20 function as a potential targeted therapy against TNBC. Citation Format: Sharma J, Raicu I, Nguyen J, Udden N, Wang Q, Alluri P. CDC20 is a novel therapeutic target in 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 P2-06-20.
Abstract P2-06-18: Withdrawn
Authors: R Kunder, S Fernandez Dunne, M Clutter, M Cristofanilli, M Mendillo, A Vasilopoulos, D Horiuchi
Journal: Cancer Research (2019)

Abstract This abstract was withdrawn by the authors. Citation Format: Kunder R, Fernandez Dunne S, Clutter M, Cristofanilli M, Mendillo M, Vasilopoulos A, Horiuchi D. 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 P2-06-18.
Challenging the Pessimism in Providing Critical Care for Elderly Patients
Authors: Robert A. Fowler, Christopher J. Yarnell, Ayah Nayfeh, Peter Kiiza
Journal: JAMA Network Open (2019)

Alice Atramont, MD, MSc; Valérie Lindecker-Cournil, MD, MSc; Jérémie Rudant, MD, PhD; Ayden Tajahmady, MD, MSc; Nicolas Drewniak, MSc; Annie Fouard, MD; Mervyn Singer, MD; Marc Leone, MD, PhD; Matthieu Legrand, MD, PhD
Safety and immunogenicity of a vaccine for extra-intestinal pathogenic Escherichia coli (ESTELLA): a phase 2 randomised controlled trial
Authors: Robert W Frenck, John Ervin, Laurence Chu, Darren Abbanat, Bart Spiessens, Oscar Go, Wouter Haazen, Germie van den Dobbelsteen, Jan Poolman, Stefan Thoelen, Patricia Ibarra de Palacios
Journal: The Lancet Infectious Diseases (2019)
How can I stop falling ill during the holidays?
Authors: Caroline Elton
Journal: BMJ (2015)

Dear Caroline,

Medical school can be full on, and often when it gets to Christmas or summer holidays I fall ill, probably through exhaustion. Can you advise on how I can pace myself and avoid being ill when I manage to get a short break?

anon, fourth year medical school, King’s College London

A first question to ask yourself is whether you seem to be working much harder than your peers. If this is the case, then it might be worth approaching your medical school learning centre for help with study skills, or to rule out whether any additional issues—such as …
Necrotizing Soft Tissue Infections
Authors: Ioana Baiu, Kristan Staudenmayer
Journal: JAMA (2019)

Necrotizing Soft Tissue InfectionsNecrotizing soft tissue infections (NSTIs) are serious, life-threatening infections of the soft tissues.Soft tissues are the skin, its layers, and the muscle underneath.These infections are associated with cellulitis, an inflammation of the superficial layers of the skin (dermis and epidermis) or myositis, in which the muscle is inflamed.Sometimes the thin white layer covering the muscle is involved, a condition called fasciitis.When the tissues die, it is referred to as necrotizing.Necrotizing fasciitis is a type of NSTI that is caused by several different types of bacteria and is particularly dangerous.An NSTI is an infection that can start in one location and spread to large areas of the body within just a few hours.Conditions that increase the risk of these infections include an untreated perirectal abscess, trauma resulting in skin cuts, any weakness in the immune system, diabetes, cancer, smoking, autoimmune diseases, and obesity.However, young and healthy people with no other medical problems can get NSTIs.
Videogame assisted exercise training in patients with chronic obstructive pulmonary disease: A preliminary study
Authors: Y.S. Sutanto, D.N. Makhabah, J. Aphridasari, M. Doewes, None Suradi, N. Ambrosino
Journal: Pulmonology (2019)

Exercise training is key to the comprehensive management of patients with chronic obstructive pulmonary disease (COPD). Interactive game-based systems have been proposed to improve effectiveness and compliance with exercise training.To evaluate the effectiveness of Wii Fit balance board as an additional tool for exercise training in patients with COPD. As a secondary aim we will evaluate the costs.In a randomized controlled trial, patients were divided into experimental (EG) and control (CG) groups. The CG performed exercise training on a cycle ergometer three times a week for 6 weeks. The EG also followed a program (yoga, strength training, aerobic exercise) using the Wii Fit system. Pre and post treatment six-minute walking distance (6MWD) test, transitional dyspnea index (TDI), the Medical Research Council (MRC) score the Saint George's Respiratory Questionnaire (SGRQ), the body max index, airflow obstruction, dyspnea, and exercise capacity index (BODE) were assessed.The 6MWD increased from 410.7 (105.3) to 477.5 (122.4) and from 376.6 (81.0) to 420 (77.6) meters, in CG and EG respectively, p=0.0001 without any difference between groups. Both groups experienced significant improvements in TDI and SGRQ, but not in MRC and BODE, without any significant difference between groups.A Wii Fit balance board based video game program was feasible but did not add any benefit to a well conducted standard exercise training program in patients with COPD.
Abstract P4-03-11: Fibroblasts isolated from the “normal-like” tissue adjacent to breast tumours suppress healthy epithelial progenitor cell proliferation while supporting tumour cell growth
Authors: S Chatterjee, A Berdnikov, V Lee-Wing, J Safneck, E Buchel, A Raouf
Journal: Cancer Research (2017)

Abstract The tissue adjacent to breast tumors has been referred to as “normal-like” tissue despite exhibiting many alterations at epigenetic and gene expression levels consistent with enhanced proliferation and wound healing signatures. However, the influence of such alterations on the proliferation and differentiation of healthy breast progenitors is currently unknown. Fibroblasts are a major component of microenvironment for the healthy and malignant breast cells. We therefore, isolate fibroblast from primary breast tumors, tissue adjacent to tumors (TAT) and the healthy breast tissue and examine their ability to support proliferation of healthy and malignant breast cells. To characterize the TAT samples we first utilized clonal co-culture assays using breast cells obtained from the healthy breast tissue (reduction mammoplasty sample, RM) and the healthy fibroblasts. Our results suggested that the TAT samples surprisingly contained significantly decreased pool of progenitors compared to the RM samples. In order to study the underlying mechanism, we characterized fibroblasts derived from either the breast tumours (TAFs) or the TAT samples (TATF) or the RM normal samples (NAFs) and assessed their role on breast progenitor cell functions. Fibroblasts were isolated from the ER+ and ER- breast tumours and their adjacent breast tissue. We observed that matrigel co-cultures consisting of RM samples and NAFs led to a 5.5-fold expansion of the progenitors, whereas the co-cultures of TAT or the RM samples with either TAFs or TATFs failed to show expansion of epithelial progenitors. The comparative secretome analysis of the NAFs and the TATFs identified TGFβ as a candidate molecule primarily secreted only by the TATFs and not by NAFs. Interestingly, blocking TGFβ signaling restored both TAFs' and TATFs' ability to support the expansion of healthy progenitors in matrigel cultures. Lastly, we found that TAFs were able to enhanced breast cancer cell proliferation in vivo and in vitro but to a lesser extent than the TAFs. Our observations suggest that the tissues adjacent to breast tumours are transformed into a TGFβ-enriched environment that is supportive of breast tumour growth while suppressing the proliferation and differentiation potentials of the healthy breast progenitors. Our data also suggest that the use of TGFβ blockers may be important in reducing risk of local breast tumour recurrence. Citation Format: Chatterjee S, Berdnikov A, Lee-Wing V, Safneck J, Buchel E, Raouf A. Fibroblasts isolated from the “normal-like” tissue adjacent to breast tumours suppress healthy epithelial progenitor cell proliferation while supporting tumour cell growth [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 P4-03-11.
Abstract P4-21-40: <i>In vitro</i> and <i>in vivo</i> activity of HER2-targeted antibody-liposomal doxorubicin conjugate MM-302 in HER2-intermediate tumors
Authors: E Geretti, C Espelin, B Adiwijaya, S Coma, Z Koncki, P Sumner, N Dumont, G Garcia, T Bloom, J Janovsky, J Reynolds, K Campbell, V Moyo, I Molnar, P LoRusso, I Krop, K Miller, C Ma, P Munster, T Wickham
Journal: Cancer Research (2017)

Abstract This abstract was withdrawn by the authors.
Abstract P6-08-01: Not presented
Authors: I Guimarães, E Gimba, M Castelo-Branco, C Sternberg, I Silva, L Rangel
Journal: Cancer Research (2019)

Abstract This abstract was not presented at the conference. Citation Format: Guimarães I, Gimba E, Castelo-Branco M, Sternberg C, Silva I, Rangel L. 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 P6-08-01.
Atypical IgM on T cells predict relapse and steroid dependence in idiopathic nephrotic syndrome
Authors: Manuela Colucci, Rita Carsetti, Maria Manuela Rosado, Simona Cascioli, Maurizio Bruschi, Giovanni Candiano, Giorgia Corpetti, Laura Giardino, Jessica Serafinelli, Chiara Giannone, Gian Marco Ghiggeri, Maria Pia Rastaldi, Roberto Sitia, Francesco Emma, Marina Vivarelli
Journal: Kidney International (2019)