tbuckley/cabot-search huggingface dataset:
Development of a Framework and Tool to Facilitate Cost-of-Care Conversations With Patients During Prenatal Care
Authors: Kim Erwin, Veronica Fitzpatrick, Sarah Norell, Melissa Gilliam
Journal: Annals of Internal Medicine (2019)

Background: Studies show that patients want to engage in cost-of-care conversations and factor costs into the formulation of care plans. Low-income patients are particularly likely to defer care because of costs, suggesting that cost-of-care conversations may be an important factor in health equity. Little guidance is available to clinicians and health systems for how to integrate effective cost-of-care conversations into clinical practice or to address specific cost needs of low-income patients. Objective: To develop a framework and tool to assist cost-of-care conversations with low-income patients during prenatal care. Design: A qualitative study using human-centered design methods. Setting: University medical center–based obstetrics-gynecology (ob-gyn) practice. Participants: 20 pregnant or recently postpartum women, 16 clinicians, and 8 support and executive staff. Results: Pregnant women accumulate substantial indirect costs that interfere with treatment adherence and stress patients and their relationships. Frequency and duration of appointments are primary drivers of indirect costs; the burden is exacerbated by not knowing these costs in advance and disproportionately affects low-income patients. Working with ob-gyn clinicians, staff, and patients, a paper-based tool was developed to help patients forecast treatment demands and indirect costs, and to help clinicians introduce and standardize cost conversations. Limitations: Data were collected from a small number of stakeholders in a single clinical setting that may not be generalizable to other settings. The tool has not been tested for effects on adherence or clinical outcomes. Conclusion: A communication tool that helps pregnant patients understand their care plan and anticipate indirect costs can promote cost-of-care conversations between clinicians and low-income patients. Primary Funding Source: Robert Wood Johnson Foundation.
A microfluidic assay for the quantification of the metastatic propensity of breast cancer specimens
Authors: Christopher L. Yankaskas, Keyata N. Thompson, Colin D. Paul, Michele I. Vitolo, Panagiotis Mistriotis, Ankit Mahendra, Vivek K. Bajpai, Daniel J. Shea, Kristen M. Manto, Andreas C. Chai, Navin Varadarajan, Aikaterini Kontrogianni-Konstantopoulos, Stuart S. Martin, Konstantinos Konstantopoulos
Journal: Nature Biomedical Engineering (2019)
HER2-Enriched Subtype and ERBB2 Expression in HER2-Positive Breast Cancer Treated with Dual HER2 Blockade
Authors: Aleix Prat, Tomás Pascual, Carmine De Angelis, Carolina Gutierrez, Antonio Llombart-Cussac, Tao Wang, Javier Cortés, Brent Rexer, Laia Paré, Andres Forero, Antonio C Wolff, Serafín Morales, Barbara Adamo, Fara Brasó-Maristany, Maria Vidal, Jamunarani Veeraraghavan, Ian Krop, Patricia Galván, Anne C Pavlick, Begoña Bermejo, Miguel Izquierdo, Vanessa Rodrik-Outmezguine, Jorge S Reis-Filho, Susan G Hilsenbeck, Mafalda Oliveira, Maria Vittoria Dieci, Gaia Griguolo, Roberta Fasani, Paolo Nuciforo, Joel S Parker, PierFranco Conte, Rachel Schiff, Valentina Guarneri, C Kent Osborne, Mothaffar F Rimawi
Journal: JNCI Journal of the National Cancer Institute (2019)

Abstract Background Identification of HER2-positive breast cancers with high anti-HER2 sensitivity could help de-escalate chemotherapy. Here, we tested a clinically applicable RNA-based assay that combines ERBB2 and the HER2-enriched (HER2-E) intrinsic subtype in HER2-positive disease treated with dual HER2-blockade without chemotherapy. Methods A research-based PAM50 assay was applied in 422 HER2-positive tumors from five II–III clinical trials (SOLTI-PAMELA, TBCRC023, TBCRC006, PER-ELISA, EGF104090). In SOLTI-PAMELA, TBCRC023, TBCRC006, and PER-ELISA, all patients had early disease and were treated with neoadjuvant lapatinib or pertuzumab plus trastuzumab for 12–24 weeks. Primary outcome was pathological complete response (pCR). In EGF104900, 296 women with advanced disease were randomized to receive either lapatinib alone or lapatinib plus trastuzumab. Progression-free survival (PFS), overall response rate (ORR), and overall survival (OS) were evaluated. Results A total of 305 patients with early and 117 patients with advanced HER2-positive disease were analyzed. In early disease, HER2-E represented 83.8% and 44.7% of ERBB2-high and ERBB2-low tumors, respectively. Following lapatinib and trastuzumab, the HER2-E and ERBB2 (HER2-E/ERBB2)-high group showed a higher pCR rate compared to the rest (44.5%, 95% confidence interval [CI] = 35.4% to 53.9% vs 11.6%, 95% CI = 6.9% to 18.0%; adjusted odds ratio [OR] = 6.05, 95% CI = 3.10 to 11.80, P &amp;lt; .001). Similar findings were observed with neoadjuvant trastuzumab and pertuzumab (pCR rate of 66.7% in HER2-E/ERBB2-high, 95% CI = 22.3% to 95.7% vs 14.7% in others, 95% CI = 4.9% to 31.1%; adjusted OR = 11.60, 95% CI = 1.66 to 81.10, P = .01). In the advanced setting, the HER2-E/ERBB2-high group was independently associated with longer PFS (hazard ratio [HR] = 0.52, 95% CI = 0.35 to 0.79, P &amp;lt; .001); higher ORR (16.3%, 95% CI = 8.9% to 26.2% vs 3.7%, 95% CI = 0.8% to 10.3%, P = .02); and longer OS (HR = 0.66, 95% CI = 0.44 to 0.97, P = .01). Conclusions Combining HER2-E subtype and ERBB2 mRNA into a single assay identifies tumors with high responsiveness to HER2-targeted therapy. This biomarker could help de-escalate chemotherapy in approximately 40% of patients with HER2-positive breast cancer.
A FATal Combination: Fibroblast-Derived Lipids and Cancer-Derived Autotaxin Promote Pancreatic Cancer Growth
Authors: Giulia Biffi, David A. Tuveson
Journal: Cancer Discovery (2019)

In this issue of Cancer Discovery, Auciello and colleagues find that in the pancreatic cancer microenvironment activated fibroblasts secrete specific lipids that provide a source of biomass production and signaling molecules for cancer cells, fueling their proliferation and migration. Targeting of this stromal-tumor metabolic cross-talk impairs pancreatic cancer progression and represents a new potential therapeutic opportunity.See related article by Auciello et al., p. 617.
Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive breast cancer previously treated with trastuzumab emtansine: a dose-expansion, phase 1 study
Authors: Kenji Tamura, Junji Tsurutani, Shunji Takahashi, Hiroji Iwata, Ian E Krop, Charles Redfern, Yasuaki Sagara, Toshihiko Doi, Haeseong Park, Rashmi K Murthy, Rebecca A Redman, Takahiro Jikoh, Caleb Lee, Masahiro Sugihara, Javad Shahidi, Antoine Yver, Shanu Modi
Journal: The Lancet Oncology (2019)
Notable Names in Anaesthesia
Authors: Andrew Papanikitas
Journal: BMJ (2002)

At first glance, an uncharitable observer may wonder whether historical figures from anaesthesia are notable. But some of the names do ring bells immediately: Apgar, Ringer, and Trendelenberg are names that should have meaning for most clinical students.

Why should this not just be yet another exercise in train spotting? You may disagree, but many find that a knowledge of the …
Cosy up with any good books lately?
Authors: Teresa Pun
Journal: BMJ (2006)

I participated in medical school interviews last year and quickly learnt how informative a question like “What do you read for fun?” can be. One candidate mentioned Vanity Fair and when asked his opinion of Becky Sharp, he blurted out a disbelieving “She's terrible!” The smile on my face was from ear to ear. Something about the protagonist had struck a chord with him, and when he spoke out against her, she seemed almost real. What I found particularly interesting was that she made him seem more real as well.

Novels and non-fiction can be found popping out of backpacks all along the aisle, and many of us are just as eager about reading our books as sharing them with our friends.

At the San Luigi Medical School in Italy, researchers found that medical students do read (68% of 34 students had read at least one book in the preceding month) and that the texts of choice were novels and short stories.1 The preference for fiction may be its appeal to the imagination. We live and breathe medicine for quite a few hours each day and when left to our own devices, Sherlock Holmes or Dracula may provide the rest our brains need from the healthcare world. One medical student wrote that she reads Anne of Green Gables because these are stories she “read as a girl. It's funny, tragic at times and ever so romantic. And everything is too pretty in there; sometimes you just need that to feel better about things.”

People read the newspaper to find out about the world outside. Novels and short stories, in contrast, provide a little something more. A study of medical students at Newcastle University in England showed that medical students read for a variety of reasons. Extracurricular material can lead …
Human 3D cellular model of hypoxic brain injury of prematurity
Authors: Anca M. Pașca, Jin-Young Park, Hyun-Woo Shin, Qihao Qi, Omer Revah, Rebecca Krasnoff, Ruth O’Hara, A. Jeremy Willsey, Theo D. Palmer, Sergiu P. Pașca
Journal: Nature Medicine (2019)
Accelerating Biomarker Discovery Through Electronic Health Records, Automated Biobanking, and Proteomics
Authors: Quinn S. Wells, Deepak K. Gupta, J. Gustav Smith, Sean P. Collins, Alan B. Storrow, Jane Ferguson, Maya Landenhed Smith, Jill M. Pulley, Sarah Collier, Xiaoming Wang, Dan M. Roden, Robert E. Gerszten, Thomas J. Wang
Journal: Journal of the American College of Cardiology (2019)
Effect of Vein-First vs Artery-First Surgical Technique on Circulating Tumor Cells and Survival in Patients With Non–Small Cell Lung Cancer
Authors: Shiyou Wei, Chenglin Guo, Jintao He, Qunyou Tan, Jiandong Mei, Zhenyu Yang, Chengwu Liu, Qiang Pu, Lin Ma, Yong Yuan, Feng Lin, Yunke Zhu, Hu Liao, Wenping Wang, Zheng Liu, Qiang Li, Bin Jiang, Chuan Li, Liang Xia, Kejia Zhao, Fanyi Gan, Jiahan Cheng, Zhu Wu, Yun Wang, Yidan Lin, Yingli Kou, Guowei Che, Longqi Chen, Jing Li, Lunxu Liu
Journal: JAMA Surgery (2019)

It is important to develop a surgical technique to reduce dissemination of tumor cells into the blood during surgery.To compare the outcomes of different sequences of vessel ligation during surgery on the dissemination of tumor cells and survival in patients with non-small cell lung cancer.This multicenter, randomized clinical trial was conducted from December 2016 to March 2018 with patients with non-small cell lung cancer who received thoracoscopic lobectomy in West China Hospital, Daping Hospital, and Sichuan Cancer Hospital. To further compare survival outcomes of the 2 procedures, we reviewed the Western China Lung Cancer database (2005-2017) using the same inclusion criteria.Vein-first procedure vs artery-first procedure.Changes in folate receptor-positive circulating tumor cells (FR+CTCs) after surgery and 5-year overall, disease-free, and lung cancer-specific survival.A total of 86 individuals were randomized; 22 patients (25.6%) were younger and 64 (74.4%) older than 60 years. Of these, 78 patients were analyzed. After surgery, an incremental change in FR+CTCs was observed in 26 of 40 patients (65.0%) in the artery-first group and 12 of 38 (31.6%) in the vein-first group (P = .003) (median change, 0.73 [interquartile range (IQR), -0.86 to 1.58] FU per 3 mL vs -0.50 [IQR, -2.53 to 0.79] FU per 3 mL; P = .006). Multivariate analysis confirmed that the artery-first procedure was a risk factor for FR+CTC increase during surgery (hazard ratio [HR], 4.03 [95% CI, 1.53-10.63]; P = .005). The propensity-matched analysis included 420 patients (210 with vein-first procedures and 210 with artery-first procedures). The vein-first group had significantly better outcomes than the artery-first group for 5-year overall survival (73.6% [95% CI, 64.4%-82.8%] vs 57.6% [95% CI, 48.4%-66.8%]; P = .002), disease-free survival (63.6% [95% CI, 55.4%-73.8%] vs 48.4% [95% CI, 40.0%-56.8%]; P = .001), and lung cancer-specific survival (76.4% [95% CI, 67.6%-85.2%] vs 59.9% [95% CI, 50.5%-69.3%]; P = .002). Multivariate analyses revealed that the artery-first procedure was a prognostic factor of poorer 5-year overall survival (HR, 1.65 [95% CI, 1.07-2.56]; P = .03), disease-free survival (HR, 1.43 [95% CI, 1.01-2.04]; P = .05) and lung cancer-specific survival (HR = 1.65 [95% CI, 1.04-2.61]; P = .03).Ligating effluent veins first during surgery may reduce tumor cell dissemination and improve survival outcomes in patients with non-small cell lung cancer.ClinicalTrials.gov identifier: NCT03436329.
Circular RNA circTADA2A promotes osteosarcoma progression and metastasis by sponging miR-203a-3p and regulating CREB3 expression
Authors: Yizheng Wu, Ziang Xie, Junxin Chen, Jiaxin Chen, Weiyu Ni, Yan Ma, Kangmao Huang, Gangliang Wang, Jiying Wang, Jianjun Ma, Shuying Shen, Shunwu Fan
Journal: Molecular Cancer (2019)

As a subclass of noncoding RNAs, circular RNAs (circRNAs) have been demonstrated to play a critical role in regulating gene expression in eukaryotes. Recent studies have revealed the pivotal functions of circRNAs in cancer progression. However, little is known about the role of circTADA2A, also named hsa_circ_0043278, in osteosarcoma (OS).CircTADA2A was selected from a previously reported circRNA microarray comparing OS cell lines and normal bone cells. QRT-PCR was used to detect the expression of circTADA2A in OS tissue and cell lines. Luciferase reporter, RNA immunoprecipitation (RIP), RNA pull-down and fluorescence in situ hybridization (FISH) assays were performed to confirm the binding of circTADA2A with miR-203a-3p. OS cells were stably transfected with lentiviruses, and Transwell migration, Matrigel invasion, colony formation, proliferation, apoptosis, Western blotting, and in vivo tumorigenesis and metastasis assays were employed to evaluate the roles of circTADA2A, miR-203a-3p and CREB3.Our findings demonstrated that circTADA2A was highly expressed in both OS tissue and cell lines, and circTADA2A inhibition attenuated the migration, invasion and proliferation of OS cells in vitro as well as tumorigenesis and metastasis in vivo. A mechanistic study revealed that circTADA2A could readily sponge miR-203a-3p to upregulate the expression of CREB3, which was identified as a driver gene in OS. Furthermore, miR-203a-3p inhibition or CREB3 overexpression could reverse the circTADA2A silencing-induced impairment of malignant tumor behavior.CircTADA2A functions as a tumor promoter in OS to increase malignant tumor behavior through the miR-203a-3p/CREB3 axis, which could be a novel target for OS therapy.
The English- Asian divide: does it exist?
Authors: Abarna Ratnarajah, Nithya Sukumar
Journal: BMJ (2006)

All medical students want to be good doctors, right? And we must have all had it hammered into us the importance of good communication skills to achieve this. The doctor of tomorrow should be able to “communicate effectively with individuals regardless of their social, cultural or ethnic backgrounds, or their disabilities,” according to the General Medical Council.1 What better place to do this than in our own medical school? With an increasing number of medical undergraduates coming from a range of ethnic groups, we are finding ourselves studying in a multicultural society. But do we actually use the opportunity we are given to integrate?

We all wish for our distinctive identities to be acknowledged and respected and therefore naturally form friendships with people similar to ourselves to whom we can relate. However, by possibly not interacting with all students, are we missing out? Also, as it is human nature to “go where our friends go” and “do what our friends do,” some subgroups of students may be poorly represented in certain committees and societies, which can be a worrying consequence of this trend.

Anyway, whether (or not) you think a divide between English and Asian students exists, and if so that this is important, may well be personal opinion. However, have you ever wondered whether anything could unintentionally promote a divide? The first year is a good time at university to form close friendships. In our university, where the intake of students is large, students are assigned to a particular teaching group in the first year and can easily find themselves completing the year without really getting to know anyone from other groups. Well, grouping is alphabetical, and as most Asian surnames begin with later letters of the alphabet, the mix of Asians and English in groups is not …
Students should understand gay health needs
Authors: Andrew Iles
Journal: BMJ (2003)

Gay men, lesbians, and bisexuals who are open about their sexuality report prejudice from health professionals, a new study has found. The questionnaire, done at University College, London, also found that gay men and lesbians saw many advantages in being able to choose a lesbian, gay, or bisexual clinician.

But Jolyon Oxley, co-chair of the Gay and Lesbian …
Inflammatory Breast Cancer Promotes Development of M2 Tumor-Associated Macrophages and Cancer Mesenchymal Cells through a Complex Chemokine Network
Authors: Amanda Valeta-Magara, Abhilash Gadi, Viviana Volta, Beth Walters, Rezina Arju, Shah Giashuddin, Hua Zhong, Robert J. Schneider
Journal: Cancer Research (2019)

Inflammatory breast cancer (IBC) is a highly aggressive form of breast cancer that displays profound cancer stem cell (CSC) and mesenchymal features that promote rapid metastasis. Another hallmark of IBC is high infiltration of M2 tumor-associated (immune-suppressing) macrophages. The molecular mechanism that drives these IBC phenotypes is not well understood. Using patient breast tumor specimens, breast cancer cell lines, and a patient-derived xenograft model of IBC, we demonstrate that IBC strongly expresses IL8 and growth-regulated oncogene (GRO) chemokines that activate STAT3, which promotes development of high levels of CSC-like cells and a mesenchymal phenotype. We also show that IBC expresses high levels of many monocyte recruitment and macrophage polarization factors that attract and differentiate monocytes into tumor-promoting, immune-suppressing M2-like macrophages. The M2 macrophages in turn were found to secrete high levels of IL8 and GRO chemokines, thereby creating a feed-forward chemokine loop that further drives an IBC epithelial-to-mesenchymal transition. Our study uncovers an intricate IBC-initiated autocrine-paracrine signaling network between IBC cells and monocytes that facilitates development of this highly aggressive form of breast cancer. SIGNIFICANCE: This study uncovers a signaling network in which IBC cells commandeer macrophages to become tumor-promoting, and they in turn drive IBC cells to be more cancer stem-like, mesenchymal, and aggressive.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/79/13/3360/F1.large.jpg.
High-Quality Food Combined With Organic Food Consumption and the Risk of Cancer
Authors: Ian Jun Yan Wee, Nicholas Li-Xun Syn
Journal: JAMA Internal Medicine (2019)

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Altered Localization of Hybrid Incompatibility Proteins in Drosophila
Authors: Jacob Carter Cooper, Andrea Lukacs, Shelley Reich, Tamas Schauer, Axel Imhof, Nitin Phadnis
Journal: Molecular Biology and Evolution (2019)

Understanding the molecular basis of hybrid incompatibilities is a fundamental pursuit in evolutionary genetics. In crosses between Drosophila melanogaster females and Drosophila simulans males, an interaction between at least three genes is necessary for hybrid male lethality: Hmr mel, Lhr sim, and gfzf sim. Although HMR and LHR physically bind each other and function together in a single complex, the connection between gfzf and either of these proteins remains mysterious. Here, we show that GFZF localizes to many regions of the genome in both D. melanogaster and D. simulans, including at telomeric retrotransposon repeats. We find that GFZF localization at telomeres is significantly different between these two species, reflecting the rapid evolution of telomeric retrotransposon copy number composition between the two species. Next, we show that GFZF and HMR normally do not colocalize in D. melanogaster. In interspecies hybrids, however, HMR shows extensive mis-localization to GFZF sites, thus uncovering a new molecular interaction between these hybrid incompatibility factors. We find that spreading of HMR to GFZF sites requires gfzf sim but not Lhr sim, suggesting distinct roles for these factors in the hybrid incompatibility. Finally, we find that overexpression of HMR and LHR within species is sufficient to mis-localize HMR to GFZF binding sites, indicating that HMR has a natural low affinity for GFZF sites. Together, these studies provide the first insights into the different properties of gfzf between D. melanogaster and D. simulans, and uncover a molecular interaction between gfzf and Hmr in the form of altered protein localization.
Circulating levels of the anti-oxidant indoleproprionic acid are associated with higher gut microbiome diversity
Authors: Cristina Menni, Marisa Matey Hernandez, Marius Vital, Robert P. Mohney, Tim D. Spector, Ana M. Valdes
Journal: Gut Microbes (2019)

The gut microbiome has recently emerged as an important regulator of insulin resistance and abdominal obesity. The tryptophan metabolite generated by the gut microbiome, indoleproprionic acid (IPA) has been shown to predict the onset of type 2 diabetes. IPA is a metabolite produced by gut microbes from dietary tryptophan that exhibits a high degree of inter-individual variation. The microbiome composition parameters that are associated with circulating levels of this potent anti-oxidant have however not been investigated to date in human populations. In 1018 middle-aged women from the TwinsUK cohort, we assessed the relationship between serum IPA levels and gut microbiome composition targeting the 16S rRNA gene. Microbiome alpha-diversity was positively correlated with serum indoleproprionic acid levels (Shannon Diversity: Beta[95%CI] = 0.19[0.13;0.25], P = 6.41 × 10−10) after adjustment for covariates. Sixteen taxa and 12 operational taxonomic units (OTUs) associated with IPA serum levels. Among these are positive correlations with the butyrate-producing Faecalibacterium prausnitzii, the class Mollicutes and the order RF39 of the Tenericutes, and Coprococcus Negative correlations instead were observed with Eubacterium dolichum previously shown to correlate with visceral fat mass and several genera in the Lachnospiraceae family such as Blautia and Ruminococcus previously shown to correlate with obesity. Microbiome composition parameters explained ~20% of the variation in circulating levels of IPA, whereas nutritional and host genetic parameters explained only ~4%. Our data confirm an association between IPA circulating levels and metabolic syndrome parameters and indicate that gut microbiome composition influences IPA levels.