tbuckley/cabot-search huggingface dataset:
Where there’s smoke
Authors: Isobel Weinberg
Journal: BMJ (2013)

Why do some medical students smoke? After seeing smoking appear in list after list of risk factors for a whole heap of diseases, they certainly can’t plead ignorance. At least, that’s true for cigarettes. But have students grasped the harms of shisha smoking? Alexander Isted’s article on p 10 (doi:10.1136/sbmj.f2327). suggests not. Misconceptions abound: cold water in the shisha pipe filters toxins from the smoke (wrong), shisha is less harmful than cigarettes (wrong), shisha isn’t harmful (definitely wrong). A survey asked young people to guess what the “cigarette equivalent” of an hour’s shisha smoking is. Most guess 10 or fewer cigarettes; the true figure is 50-100. …
Normal Versus Pathological Mood: Implications for Diagnosis
Authors: Ayelet Meron Ruscio
Journal: Annual Review of Clinical Psychology (2019)

Is there a clear line between normal and abnormal mood? Studies of manifest and latent structure provide strong support for a continuum that extends from asymptomatic to subsyndromal to syndromal cases of increasing severity. Subsyndromal symptoms are impairing, predict syndrome onset and relapse, and account for more doctor's visits and suicide attempts than the full syndromes, yet they are not recognized in the current classification. For most research and some clinical activities, dimensional diagnoses are recommended, and examples are offered for how such diagnoses could be made. For clinical activities requiring decisions, a multithreshold model is proposed in which both lower (e.g., mild depression, capturing subsyndromal cases) and upper (e.g., major depression, capturing clinically significant cases) diagnostic categories are used to inform clinical care. Beyond its implications for diagnosis, the dimensionality of depression and anxiety has implications for etiology and for research aimed at understanding how emotions become disrupted in psychopathology.
Catheter Ablation of Atrial Fibrillation With and Without On-Site Cardiothoracic Surgery
Authors: Daniel J. Friedman, Sean D. Pokorney, Rahul Khanna, Laura Goldstein, Brett D. Atwater, Tristram D. Bahnson, James P. Daubert, Kevin P. Jackson, E. Kevin Heist, Jagmeet P. Singh, Hugh Calkins, Jonathan P. Piccini
Journal: Journal of the American College of Cardiology (2019)
Volunteering for a non-governmental organisation
Authors: Sophia Bourne
Journal: BMJ (2017)

Dear Sophia

I want to volunteer for Medicins Sans Frontieres in the future. What can I do to prepare?

Laura Nunez-Mulder, fourth year medical student, University of Cambridge

Voluntary medical work can benefit you, your patients, and ultimately the NHS when you return. You will grow professionally and personally from working across different healthcare systems, where you will enhance valuable communication and leadership skills as you face different challenges and resource constraints.

You can practise medicine on a …
Abstract 4188: Dietary energy balance impacts spontaneous pancreatic lesions in the K5.COX-2 transgenic model of pancreatic cancer
Authors: Laura M Lashinger, Lauren Malone, Elizabeth Daniels, Nicole C. Smith, Amy Pavone, Jennifer L. Colby, Susan M. Fischer, Stephen D. Hursting
Journal: Cancer Research (2008)

Abstract Pancreatic cancer is the fourth leading cause of cancer death in both men and women in the United States. Obesity, which has increased dramatically over the past 40 years, has emerged as an important risk factor for pancreatic cancer, although the mechanisms underlying the obesity-pancreatic cancer association have not been identified. Calorie restriction (CR), a dietary strategy for inducing negative energy balance and preventing or reversing obesity, has significant anti-cancer effects in several species, for a variety of tumor types, and for both spontaneous and chemically-induced tumors. However, the effects of dietary energy balance modulation on pancreatic tumor formation have not been well studied. We hypothesized that spontaneous tumor development in the K5.COX-2 transgenic mouse model of pancreatitis-driven pancreatic cancer would be reduced in lean mice, relative to overweight or diet-induced obese (DIO) mice. In order to test this hypothesis, we placed 6-8 week old K5.COX-2 transgenic mice on one of three diets for 14 weeks (n=12/group): lean (30% CR), overweight (AIN-76A diet fed ad libitum), or a high calorie/high fat DIO regimen. K5.COX-2 transgenic mice develop spontaneous pancreatic lesions as early as 4 weeks with 100% becoming moribund within 6-8 months. Based on histologic analysis of the percentage of pancreas that is comprised of enlarged and dilated ductal lesions, the CR animals were significantly protected from spontaneous pancreatic lesion formation (7.5%±1.44) as compared to the overweight (45%±10.5) and DIO (57.5%±9.46) groups. Furthermore, CR mice had smaller lesions at time of harvest with none exhibiting signs of moribundity. Conversely, the DIO group generally had the largest lesions, although there was no statistical difference between the overweight and DIO groups. In addition, several mice in the overweight and DIO groups had to be sacrificed early due to extensive abdominal distention, morbidity from enlarged cystic lesions, and other signs of distress. Further investigation is needed to discern how CR exerts its effects. Preliminary analyses suggest that IGF-1 may be playing a significant role. Moreover, pro-inflammatory cytokines were shown to be significantly reduced in sera of CR-animals as compared to the other two groups. In conclusion, using a model of pancreatitis-induced pancreatic tumorigenesis, our findings indicate that dietary energy balance modulation can alter the development of pancreatic cancer. This could have direct implications for the prevention and control of pancreatic tumors due to chronic inflammation and/or obesity.
Doctors should not be legally obliged to report youths at risk of knife crime
Authors: Sophie Timmis
Journal: BMJ (2019)

The Home Office has proposed legislation that doctors, nurses, and teachers should be legally obliged to report concerns about young people at risk of becoming involved in knife crime.1 The surge in violent youth crime is a tragedy, and frontline staff across the public sector should undeniably be working together to tackle this. But I am concerned about …
Abstract P1-05-03: Isoform specific targeting of insulin receptor
Authors: K LaPara, JY Chan, A Zdechlik, K Ljunggren, D Schmidt, B Hackel, D Yee
Journal: Cancer Research (2019)

Abstract The insulin receptor (InsR) exists in both an A and B isoform. InsR-B differs from InsR-A by the inclusion of exon 11, which encodes 12 amino acid residues at the C-terminus of the InsR alpha-subunit. Increased InsR-A expression is associated with mitogenic signaling pathways while InsR-B is linked to insulin-mediated metabolic functions. Predominant InsR-A expression may therefore be important in growth and fetal development of embryos, whereas predominant InsR-B expression has a role in metabolic insulin action in adult life. Increased InsR-A expression is seen in breast cancer. In endocrine resistant breast cancer, InsR-A is expressed at high levels (Gradishar, et al. Clin Cancer Res 22:301 2016 PMID: 26324738). Thus, developing InsR-A specific inhibitors could be a useful therapy for breast cancer. We have previously published InsR specific binders using a T7 phage gene 2 protein (Gp2), a small protein scaffold (Chan, et al. Mol Cancer Ther 16:1324 2017 PMID: 28468775), with the long-term goal of creating effective InsR inhibitors and diagnostics. Using yeast display and directed evolution, we identified three Gp2 variants (Gp2 #1, #5, and #10) with low nanomolar affinity and specific binding to cell surface InsR. We have shown that these Gp2 variants inhibited insulin-mediated monolayer proliferation in both endocrine-sensitive and resistant breast cancer, but did not downregulate InsR expression. To further characterize the specificity of Gp2 variants, we used two techniques. HEK293T cells were infected with lentiviral vectors expressing either InsR-A tagged with mCherry or InsR-B tagged with eGFP. Using these cells, we performed “mock panning” and showed the Gp2 #5 variant bound both InsR-A and InsR-B, but had higher affinity for InsR-B. We also incorporated Gp2 #5 into the capsid of a tropism-null adeno-associated virus (AAV). Using this Gp2-AAV, we infected HEK293T-InsR-A or InsR-B cells at a number of different multiplicities of infection. These data were consistent with panning data and showed specific Gp2-AAV infection of cells expressing high levels of InsR-B, but not InsR-A. Thus, our data show that Gp2 variants we created have a higher affinity for InsR-B than InsR-A. Despite this preferred affinity, these Gp2 binders have sufficient binding to InsR-A to disrupt the biological effects of insulin in breast cancer cells. Thus, even relatively low affinity binding to InsR-A can disrupt its function. Further development of InsR-A Gp2 binders may be developed and provide more specific targeting of the breast cancer specific isoform of InsR. Citation Format: LaPara K, Chan JY, Zdechlik A, Ljunggren K, Schmidt D, Hackel B, Yee D. Isoform specific targeting of insulin receptor [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 P1-05-03.
The Effect of <i>Wolffia globosa</i> Mankai, a Green Aquatic Plant, on Postprandial Glycemic Response: A Randomized Crossover Controlled Trial
Authors: Hila Zelicha, Alon Kaplan, Anat Yaskolka Meir, Gal Tsaban, Ehud Rinott, Ilan Shelef, Amir Tirosh, Dov Brikner, Efrat Pupkin, Lu Qi, Joachim Thiery, Michael Stumvoll, Nora Kloting, Martin von Bergen, Uta Ceglarek, Matthias Blüher, Meir J. Stampfer, Iris Shai
Journal: Diabetes Care (2019)

To compare the postprandial and overnight glycemic response using a novel green aquatic plant thought to provide a dietary source for high-quality protein, with an iso-carbohydrate/protein/caloric dairy shake.This is a randomized controlled crossover trial among 20 abdominally obese participants (age 51.4 years; fasting plasma glucose 110.9 mg/dL), who were allocated to replace dinner with either, first, a green shake containing Wolffia globosa duckweed (Mankai: specific-strain) or an iso-carbohydrate/protein/calorie yogurt shake. A 2-week flash glucose-monitoring system was used to assess postmeal glucose dynamics (6 net administration days; 97 observation days in total). We further obtained from each participant dietary/daily activity/satiety scale/sleep logs. Participants were recruited from the green-Mediterranean diet arm of the 18-month Dietary Intervention Randomized Controlled Trial-Polyphenols Unprocessed (DIRECT-PLUS) study.Wolffia globosa Mankai elicited a lower postprandial glucose peak compared with yogurt (∆peak = 13.4 ± 9.2 vs. 19.3 ± 15.1 mg/dL; P = 0.044), which occurred later (77.5 ± 29.2 vs. 59.2 ± 28.4 min; P = 0.037) and returned faster to baseline glucose levels (135.8 ± 53.1 vs. 197.5 ± 70.2 min; P = 0.012). The mean post-net incremental area under the curve (netAUC) was lower with Wolffia globosa up to 60 and 180 min (netAUC 60 min: 185.1 ± 340.1 vs. 441.4 ± 336.5 mg/dL/min, P = 0.005; netAUC 180 min: 707.9 ± 1,428.5 vs. 1,576.6 ± 1,810.1 mg/dL/min, P = 0.037). A Wolffia globosa-based shake replacing dinner resulted in lower next-morning fasting glucose levels (83.2 ± 0.8 vs. 86.6 ± 13 mg/dL; P = 0.041). Overall, postprandial glucose levels from the shake administration until the next morning were lower in the Wolffia globosa Mankai green shake compared with the yogurt shake (P < 0.001). Overnight sleep duration was similar (378.2 ± 22.4 vs. 375.9 ± 28.4 min; P = 0.72), and satiety rank was slightly higher for the Wolffia globosa shake compared with the yogurt shake (7.5 vs. 6.5; P = 0.035).Wolffia globosa Mankai duckweed may serve as an emerging alternative plant protein source with potential beneficial postprandial glycemic effects.
Abstract P2-05-32: Tissue kallikrein-related peptidase 4, a novel biomarker in triple-negative breast cancer
Authors: J Dorn, F Yang, M Aubele, M Kiechle, M Schmitt
Journal: Cancer Research (2017)

Abstract Triple-negative breast cancer (TNBC), lacking the steroid hormone receptors estrogen receptor and progesterone receptor and not overexpressing the oncoprotein HER2, is characterized by its aggressive pattern and insensitivity to endocrine and HER2-directed therapy. Human kallikrein-related peptidases KLK1-15 provide a rich source of serine protease-type biomarkers associated with tumor growth and cancer progression for a variety of malignant diseases. In this study, recombinant KLK4 protein was generated and affinity-purified KLK4-directed polyclonal antibody pAb587 established to allow localization of KLK4 protein expression in tumor cell lines and archived formalin-fixed, paraffin-embedded triple-negative breast cancer (TNBC) tumor tissue specimens. For this, KLK4 protein expression was assessed by immunohistochemistry in primary tumor tissue sections (tissue microarrays) of 188 TNBC patients, mainly treated with anthracycline- or CMF-based polychemotherapy. KLK4 protein is localized in the cytoplasm of tumor cells and that of accessory stroma cells. In this patient cohort, elevated stroma KLK4 expression, but not tumor cell expression, is predictive for poor disease-free survival by univariate analysis (hazard ratio: 2.26, p=0.001) and multivariable analysis (hazard ratio: 2.12, p&amp;lt;0.01). Likewise, univariate analysis revealed a trend for statistical significance of elevated KLK4 stroma cell expression for overall survival of TNBC patients as well. Citation Format: Dorn J, Yang F, Aubele M, Kiechle M, Schmitt M. Tissue kallikrein-related peptidase 4, a novel biomarker in triple-negative 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 P2-05-32.
<i>Vital Signs:</i> Pregnancy-Related Deaths, United States, 2011–2015, and Strategies for Prevention, 13 States, 2013–2017
Authors: Emily E. Petersen, Nicole L. Davis, David Goodman, Shanna Cox, Nikki Mayes, Emily Johnston, Carla Syverson, Kristi Seed, Carrie K. Shapiro-Mendoza, William M. Callaghan, Wanda Barfield
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

Background: Approximately 700 women die from pregnancy-related complications in the United States every year.Methods: Data from CDC's national Pregnancy Mortality Surveillance System (PMSS) for 2011-2015 were analyzed.Pregnancy-related mortality ratios (pregnancy-related deaths per 100,000 live births; PRMRs) were calculated overall and by sociodemographic characteristics.The distribution of pregnancy-related deaths by timing relative to the end of pregnancy and leading causes of death were calculated.Detailed data on pregnancy-related deaths during 2013-2017 from 13 state maternal mortality review committees (MMRCs) were analyzed for preventability, factors that contributed to pregnancy-related deaths, and MMRC-identified prevention strategies to address contributing factors.Results: For 2011-2015, the national PRMR was 17.2 per 100,000 live births.Non-Hispanic black (black) women and American Indian/Alaska Native women had the highest PRMRs (42.8 and 32.5, respectively), 3.3 and 2.5 times as high, respectively, as the PRMR for non-Hispanic white (white) women (13.0).Timing of death was known for 87.7% (2,990) of pregnancy-related deaths.Among these deaths, 31.3%occurred during pregnancy, 16.9% on the day of delivery, 18.6% 1-6 days postpartum, 21.4% 7-42 days postpartum, and 11.7% 43-365 days postpartum.Leading causes of death included cardiovascular conditions, infection, and hemorrhage, and varied by timing.Approximately sixty percent of pregnancy-related deaths from state MMRCs were determined to be preventable and did not differ significantly by race/ethnicity or timing of death.MMRC data indicated that multiple factors contributed to pregnancy-related deaths.Contributing factors and prevention strategies can be categorized at the community, health facility, patient, provider, and system levels and include improving access to, and coordination and delivery of, quality care.Conclusions: Pregnancy-related deaths occurred during pregnancy, around the time of delivery, and up to 1 year postpartum; leading causes varied by timing of death.Approximately three in five pregnancy-related deaths were preventable.
Abstract P4-02-04: Tumor-infiltrating lymphocytes in invasive lobular breast cancer identify a poor prognostic sub-group
Authors: J-C Tille, C Saint Martin, L Fuhrmann, L De Koning, F Reyal, M Piccart, Y Kirova, P Cottu, M Carton, A Vincent Salomon
Journal: Cancer Research (2019)

Abstract Background: Tumor infiltrating lymphocytes (TILs) are associated with an improved outcome in triple negative and HER2 breast cancers. Conversely, a recent pioneer study showed that TILs in infiltrating lobular carcinoma (ILC) were associated with a worse prognosis. We aimed at assessing the prognostic impact of TILs in a large cohort of primary surgically treated ILC with a long follow-up in a single institution. Methods: We retrospectively reviewed 459 ILC treated at the Curie Institute between 2005 and 2008. Clinico-pathological patients' characteristics were collected and all archived tumor slides were centrally reviewed for TILs quantification. We analyzed stromal TILs scored as a continuous variable. Cox analyses were performed for relapse free survival (RFS) and for overall survival (OS), and chi-square and Fisher test were performed to evaluate the correlation between TILs and other clinico-pathological variables. For statistical analyses, presence or absence of TILs was considered. Results: Patients had a mean age of 60.3 years and a median follow-up of 8.8 years, during which 74 local and/or distant relapse events occurred, among which 37 deaths due to the disease. The presence of TILs were significantly associated with greater tumor size (pT), positive nodal status (pN), molecular class (HER2 amplified), and specific morphological nuclear features such as high nuclear grade, multinucleation, macronucleoli and high Nottingham Prognostic Index class. Presence of intra-tumoral lymphocytes is significantly associated with a worse RFS (HR: 2.07 p=0.003) and OS (HR: 4.58 p&amp;lt;0.001) in a multivariate analysis, independently of chemotherapy. Relapse Free Survival TILs% (IC 95%)% (IC 95%)No95.3 (92.5-98.2)89.0 (84.3-94.0)Yes89.3 (85.1-93.6)74.0 (67.5-81-1) Overall Survival OS at 5 yearsOS at 10 yearsTILs% (IC 95%)% (IC 95%)No99.5 (97.8-100)95.8 (92.3-99.4)Yes95.3 (92.3-98.1)83.5 (77.8-89.7) Conclusion: TILs are an independent prognostic factor associated with a poor outcome in ILC that are easy to assess on diagnostic biopsies. In order to elucidate the role of TILs in ILC, we will further characterize the immune infiltrate and integrate these results with DNA, RNA and protein analyses of the same carcinomas, in order to gain insight into their molecular features and to facilitate the identification of new therapeutic strategies for these ILC with TILs. Citation Format: Tille J-C, Saint Martin C, Fuhrmann L, De Koning L, Reyal F, Piccart M, Kirova Y, Cottu P, Carton M, Vincent Salomon A. Tumor-infiltrating lymphocytes in invasive lobular breast cancer identify a poor prognostic sub-group [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 P4-02-04.
Abstract GS6-06: Local therapy and quality of life outcomes in young women with breast cancer
Authors: LS Dominici, J Hu, TA King, KJ Ruddy, RM Tamimi, J Peppercorn, L Schapira, VF Borges, SE Come, E Warner, AH Partridge, SM Rosenberg
Journal: Cancer Research (2019)

Abstract Background: Increasing rates of mastectomy, primarily bilateral mastectomy (BMx), have been most dramatic in young women with breast cancer (BC). Impact on long-term quality of life (QOL) is largely unknown. Methods: Between 10/2016-11/2017, we administered the BREAST-Q, a validated patient-reported outcomes measure, to women dx with BC at age ≤40 in a large prospective cohort study. Demographic and treatment information was obtained by surveys and chart review. Mean BREAST-Q scores for each domain (breast satisfaction, physical, psychosocial, and sexual) were compared by surgery types; higher BREAST-Q scores (range: 0-100) indicate better QOL. Linear regression was used to identify predictors of BREAST-Q domain scores. Results: 581 women with stage 0-3 BC completed the BREAST-Q a median of 5.8 years from dx. Median age at dx was 37 (range: 26-40) years; 86% had stage 0, 1 or 2 disease; 28% had breast-conserving surgery (BCS); 72% had mastectomy (Mx), among whom 72% underwent BMx and 89% had reconstruction. Mean BREAST-Q scores (unadjusted) for breast satisfaction, psychosocial, and sexual well-being were lower for patients having unilateral mastectomy (UMx) or BMx compared to BCS; physical function was similar among groups. In multivariate analysis, lower BREAST-Q psychosocial scores were associated with radiation and Mx (UMx or BMx). Lower sexual well-being scores were also associated with Mx. Lower satisfaction with breast scores following radiation were of a clinically significant magnitude (β -8.1 95% CI -11.9- -4.3, p-value 0.03). Lower scores for physical well-being were seen for patients reporting lymphedema and higher for those who had undergone surgery more than 5 years prior. Lower scores across all 4 domains were associated with reported financial distress. BREAST-Q domain mean scores (SD) BMxUMxBCSp-valueBreast satisfaction60.3 (18.9)59.5 (21.3)65.9 (20.7)0.008Physical well-being78.6 (14.9)79.7 (15.1)78.9 (15.5)0.8Psychosocial well-being68.1 (20.8)70.5 (21.2)76.1 (20.5)&amp;lt;0.001Sexual well-being48.6 (21.3)53.2 (21.7)57.5 (18.7)&amp;lt;0.001SD Standard deviation Conclusion: Local therapy in young breast cancer survivors may have a persistent impact on their breast satisfaction, psychosocial, and sexual outcomes, with particular effects from UMx or BMx. Socio-economic stressors also appear to play a role. When counseling young women about their surgical decisions, knowledge of potential long-term QOL impact is of critical importance. Citation Format: Dominici LS, Hu J, King TA, Ruddy KJ, Tamimi RM, Peppercorn J, Schapira L, Borges VF, Come SE, Warner E, Partridge AH, Rosenberg SM. Local therapy and quality of life outcomes in young women with 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 GS6-06.