tbuckley/cabot-search huggingface dataset:
Abstract P5-16-18: Oncologic outcomes and reconstruction quality of immediate autologous breast reconstruction in intermediate and locally advanced breast cancer
Authors: WS Yoon, DS Yang, GS Son, SU Woo, D-W Kim, E-S Dhong, YW Chang
Journal: Cancer Research (2019)

Abstract Purpose: We analyzed oncologic outcomes and reconstruction quality in locally advanced stage breast cancer after performing immediate autologous breast reconstruction (IABR). Methods: From 2007 to 2014, data of patients with stage II-III breast cancer of ≤ 70-years-old who received total mastectomy (TM) from two institutions were extracted. Exclusion criteria were: previous contralateral breast cancer, follow-up loss before adjuvant therapy completion, and artificial reconstruction. Patients were divided into two groups; 1) TM alone and 2) TM+IABR. Overall survival (OS) and loco-regional recurrence free survival (LRRFS) were calculated and minor revision, abnormal volume on CT, and breast height change were observed. Results: Sixty-one of 188 patients received IABR after TM. Neoadjuvant chemotherapy and postoperative radiotherapy was done in 27 and 80 patients, respectively. Fifty-nine percent, 19.2%, and 21.8% of patients were in stage II, IIIA, and IIIB-C, respectively. Stage IIIB-C was the most important prognostic factor for OS and LRRFS. In a median of 56.8 follow-up months, 5-year TM and TM+IABR OS rate were 96.8% and 100% for stage II (P=0.324) and 57.6%, 95.5% and 91.7% for stage IIIA (P=0.698), and 62.5% for stage IIIB-C (P=0.544), respectively. Five-year TM and TM+IABR LRRFS were 98.1% and 95.7% for stage II (P=0.998)91.1% and 100% for stage IIIA (P=0.277), and 70.8% and 62.5% for stage IIIB-C (P=0.378), respectively. However, two locoregional failures after 5-years were developed in stage IIIB-C of TM+IABR at 71 and 94 months. Minor revisions 3 months of IABR, including two major complications, were done in 49.2%. The reduction of breast height was 21.2% (11/52) and 31.9% (15/47) in about 18 months and about 42 months observations after IABR, respectively. The volume of abnormal imaging was over 10 cc in 27.3% (15/55) on CT of 6 months after IABR. Although minor revisions, abnormal volume on CT, and breast height change were common, they were not related to therapeutic methods, including radiotherapy and tumor stage. Conclusions: In about 5-years follow-up, IABR did not aggravate oncologic outcomes, and adjuvant radiotherapy was not closely related with quality of reconstruction. It must be considered, however, that absolute oncologic outcomes of advanced stage were not sufficient, and minor problems post-IABR were commonly developed. Citation Format: Yoon WS, Yang DS, Son GS, Woo SU, Kim D-W, Dhong E-S, Chang YW. Oncologic outcomes and reconstruction quality of immediate autologous breast reconstruction in intermediate and locally advanced 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 P5-16-18.
The dietary transition and its association with cardiometabolic mortality among Chinese adults, 1982–2012: a cross-sectional population-based study
Authors: Yuna He, Yanping Li, Xiaoguang Yang, Elena C Hemler, Yuehui Fang, Liyun Zhao, Jian Zhang, Zhenyu Yang, Zhu Wang, Li He, Jing Sun, Dong D Wang, Jingzhong Wang, Jianhua Piao, Xiaofeng Liang, Gangqiang Ding, Frank B Hu
Journal: The Lancet Diabetes & Endocrinology (2019)
A phase III, randomized, open-label study of ASP8273 versus erlotinib or gefitinib in patients with advanced stage IIIB/IV non-small-cell lung cancer
Authors: R.J. Kelly, F.A. Shepherd, A. Krivoshik, F. Jie, L. Horn
Journal: Annals of Oncology (2019)

ASP8273, a novel, small molecule, irreversible tyrosine kinase inhibitor (TKI) specifically inhibits the epidermal growth factor receptor (EGFR) in patients with activating mutations or EGFR T790M resistance mutations. The current study examines the efficacy, safety, and tolerability of ASP8273 versus erlotinib or gefitinib in patients with non-small-cell lung cancer (NSCLC) with activating EGFR mutations not previously treated with an EGFR inhibitor.
Social media: concerns over effects on teenagers are overblown and lack evidence
Authors: Elisabeth Mahase
Journal: BMJ (2019)

Concerns over how social media impacts teenagers’ wellbeing and quality of life have been overblown and are not supported by solid evidence, according to researchers from the University of Oxford.1

The research team from the Oxford Internet Institute analysed data from 12 672 children aged 10 to 15 years between 2009 and 2017 and found the effects of social media were “small at best,” concluding usage is not a strong predictor of life satisfaction.

The authors warned that the fearful headlines about social media are not supported by significant evidence and that policy based on these fears will be “garbage.”

Last October, health secretary Matt Hancock gave an urgent warning …
The Facebook friend finder
Authors: Sky KH Chew, Art Chew
Journal: BMJ (2013)

Riveted to my seat, I listen intently to the latest advancements in diagnostic techniques for prostate cancer. The lecturer then starts to explain the qualities of the tests—sensitivity, specificity, positive predictive value, negative predictive value . . . and I start to doze off. As a medical student, these terms often made me switch off my attention. I would just give up on understanding concepts, and merely learn definitions by rote and equations before exams, which of course were promptly forgotten afterwards.

In addition to being so abstract, terms such as false positives and negatives made it hard to get a grip on things. Sure, they made sense after I had thought it through, but the effort needed to understand them was galling. Even Wikipedia fails in this respect and just provides dry definitions.

Using examples that students can relate to would make things clearer and allow them to remember not just formulas but concepts that can be applied throughout their medical practice. One example is Facebook.

Remember the first time you set up your Facebook account? After the initial profiling, Facebook comes up with a list of suggested “friends” whom you might know. Although almost accurate to the point of creepiness, it isn’t perfect, excluding that hot acquaintance you wanted to know better and suggesting some people you wouldn’t be seen dead with. This concept of the friend finder identifying your real friends and excluding others is similar to a screening test, which detects disease (your friends in this case) and excludes those without disease.

### The ideal friend finder—sensitivity and specificity

Ideally, a perfect friend finder would be one that fulfils two criteria—it includes all your friends and excludes everyone else.

Criterion one is referred to as sensitivity. When a high proportion of your friends are identified, the friend finder is considered to have a …
Abstract P4-06-30: Adipose PD-L1 modulates checkpoint blockade immunotherapy efficacy in breast cancer
Authors: B Wu, X Sun, HB Gupta, B Yuan, F Ge, J Li, Y Hu, TJ Curiel, R Li
Journal: Cancer Research (2019)

Abstract Programmed death-ligand 1 (PD-L1) and its receptor programmed cell death protein 1 (PD-1) play important roles in modulating antitumor immune response and are targeted by checkpoint blockade immunotherapy. While PD-L1 expression in both tumor and host cells is associated with antitumor therapeutic efficacy, the exact contribution of PD-L1 in various tissue and cell compartments to antitumor immune response remains to be elucidated. Here we show that PD-L1 expression is markedly elevated in human and mouse mature adipocytes compared to their preadipocyte counterparts. When co-cultured with mouse splenocytes in vitro, adipocytes prevent anti-PD-L1 antibody from activating CD8+T cells. Genetic ablation of adipose PD-L1 obliterates the inhibitory effect of adipocytes on anti-PD-L1 antibody. Conversely, enforced PD-L1 expression in preadipocytes confers the antibody-inhibitory activity. GW9662, a pharmacologic inhibitor of peroxisome proliferator-activated receptor γ (PPARγ) in adipogenesis, selectively reduces PD-L1 expression in mouse adipose tissue. The same PPARγ antagonist also enhances the antitumor efficacy of checkpoint blockade antibodies for treating multiple mammary tumors. Our findings provide a previously unappreciated approach to bolster anticancer immunotherapy efficacy and suggest a mechanism for the role of adipose tissue in breast cancer progression. Citation Format: Wu B, Sun X, Gupta HB, Yuan B, Ge F, Li J, Hu Y, Curiel TJ, Li R. Adipose PD-L1 modulates checkpoint blockade immunotherapy efficacy 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 P4-06-30.
Assisted dying: the APM should embrace diversity of opinion and encourage sociable debate
Authors: Andrew N Davies
Journal: BMJ (2019)

The Personal View from five anonymous consultants in palliative medicine is an “inconvenient truth” for the Association for Palliative Medicine and should be a further wake-up call for the officers of the APM (and its membership).1 As immediate past president of the association, I can attest to the validity of the concerns, as I have been personally ostracised over my support for a neutral …
Abstract P6-20-12: FGFR1β is a driver isoform of FGFR1 alternative splicing in breast cancer cells
Authors: M Zhao, M-L Zhuo, X Zheng, X Su, F Meric-Bernstam
Journal: Cancer Research (2019)

Abstract Background:Abnormal FGFR1 alternative splicing is correlated with tumorigenicity and poor prognosis in several tumor types. We sought to determine the roles of FGFR1α and FGFR1β variants in breast cancer. Methods: TCGA breast cancer samples and cell lines were analyzed for FGFR1α and FGFR1β expression. MCF-10A cells were used to overexpress these variants. Cell growth was assessed by SRB and colony formation assays. Cell transformation was assessed by 3D-Matrigel, soft agar, cell motility assays. Cell survival assay was used to determine drug IC50. Results: In the TCGA, compared to FGFR1 non-amplified samples, FGFR1-amplified samples had significantly higher FGFR1α, but not FGR1β levels. FGFR1β expression levels and FGFR1β/FGFR1α ratio were higher in basal subtype samples than in luminal samples in both the TCGA and in a panel of breast cancer cell lines. Both FGFR1α and FGFR1b induced transformation of MCF-10A cells. However, only FGFR1β-expressing cells, not FGFR1α, enhanced cell growth, cell motility, and FGFR signaling. Cells with higher FGFR1β levels and FGFR1β/FGFR1α ratio were more sensitive to FGFR inhibitor BGJ-398. Interestingly, in ER-negative cells, BGJ-398 decreased FGFR1β levels, likely by increasing expression of splicing repressor PTBP1. In ER-positive cells, estrogen treatment increased FGFR1β levels by decreasing PTBP1 expression, which was blocked by 4-OHT. Lastly, combination treatment with BGJ-398 and 4-OHT synergistically inhibited cell survival. Conclusions: These findings suggest that FGFR1 alternative splicing plays an important role in breast cancer, where FGFR1β functions as a driver isoform. Further work is needed to assess FGFR1β prognostic and predictive role. Citation Format: Zhao M, Zhuo M-L, Zheng X, Su X, Meric-Bernstam F. FGFR1β is a driver isoform of FGFR1 alternative splicing in breast cancer cells [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 P6-20-12.
The Morphology of Tumor Progression in Melanoma In Situ
Authors: Philip E. LeBoit
Journal: JAMA Dermatology (2019)

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Abstract P3-10-22: BluePrint molecular subtyping versus HER2 assessment by immunohistochemistry and FISH in the real-world diagnostic setting
Authors: T Treece, W Audeh, F Navarro, J Wei
Journal: Cancer Research (2019)

Abstract Background: Both the Aphinity and ExteNET trials for anti-HER2 targeted agents were challenged in showing significant benefit of added HER2-targeted treatment. The findings suggested biological heterogeneity in HER2+ cancers, not entirely identified by IHC/FISH, requiring more nuanced biomarkers to clearly identify patient subsets who may derive benefit from new HER2-targeted agents. We have previously shown that BluePrint (80-gene) molecular subtyping reclassifies nearly half of HER2+/ER+ patients to Luminal-type with differential neoadjuvant treatment response (Whitworth, Ann Surg Oncol 2014; Whitworth, ASCO 2018). Here, we evaluated the reclassification rate in the real-world diagnostic setting. Methods: Physicians regularly provide pathology reports to Agendia, Inc for samples which are processed for MammaPrint (70-gene signature) and BluePrint molecular assays as part of routine diagnostic care. For this analysis, 4986 sequentially available pathology reports (submitted between October 2016 to October 2017) were reviewed; HER2 and ER IHC results were captured. The molecular subtype was compared to IHC/FISH status. Results: HER2 IHC/FISH results were available for 1568 samples. Of those, 85% (1330/1568) were HER2-nonamplified, 10% (153/1568) were HER2-equivocal, and 5% (85/1568) were HER2-amplified by IHC/FISH. Of the HER2-nonamplified tumors, BluePrint reclassified 0.1% (2/1330) as HER2-type. Of the HER2-equivocal tumors, none were HER2-type by BluePrint; 91% (139/153) were Luminal-type and 9% (14/153) were Basal-type. Of the HER2-amplified tumors, 15% (13/85) were dominant HER2-type, 79% (67/85) were dominant Luminal-type, and 6% (5/85) were Basal-type. Conclusions: In this set of tumors identified as HER2-amplified by IHC/FISH, BluePrint reclassified 85% of tumors to non-HER2 molecular subtypes, mostly Luminal-type for ER-positive tumors and Basal-type for ER-negative tumors. Moreover, BluePrint gave clarity where IHC/FISH could not, classifying all HER2-equivocal tumors to non-HER2 subtypes. Additional therapeutic options should be explored for HER2+/ER+ BluePrint Luminal-type patients who have observed much lower pCR rates versus BluePrint HER2-type patients (12% vs. 51%, respectively; Lee, AACR 2018). HER2 IHC/FISH vs BluePrint SubtypeHER2 IHC/FISH StatusHER2-type Luminal-type Basal-type Total IHC ER-IHC ER+IHC ER-IHC ER+IHC ER-IHC ER+ Nonamplified (ER-Unknown, n=28)118120353361330Equivocal (ER-Unknown, n=6) 2131104153Amplified (ER-Unknown, n=2)112 664 85Total21310140067401568 Citation Format: Treece T, Audeh W, Navarro F, Wei J. BluePrint molecular subtyping versus HER2 assessment by immunohistochemistry and FISH in the real-world diagnostic setting [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 P3-10-22.
Abstract LB-248: A single-institution prospective study evaluating the functional diffusion map (fDM) as an early imaging biomarker for overall survival in high-grade glioma
Authors: Brian D Ross, Daniel A Hamstra, Craig J Galban, Charles R Meyer, Timothy D Johnson, Pia C Sundgren, Christina Tsien, Larry Junck, David J Ross, Alnawaz Rehemtulla, Thomas L Chenevert, Theodore S Lawrence
Journal: Cancer Research (2008)

Abstract Introduction: Standard assessment of radiologic response in patients with malignant glioma is traditionally carried out using T1 gadolinium-enhanced MRI at approximately 10 weeks following treatment initiation. Diffusion-weighted MRI of gliomas, analyzed by the functional diffusion map (fDM), may provide an early measure of response during treatment to predict patient survival (OS). Tumor cells restrict the random diffusion of water molecules within a tumor; therefore, diffusion will increase during successful therapy. The fDM imaging biomarker is a voxel-wise method for analysis of DW-MRI data providing for quantification of treatment-associated spatial alterations in tumor diffusion values earlier than radiologic response. Methods: A prospective single-institution trial of early assessment of brain tumor response by MRI was performed early during radiation therapy. Sixty patients with high grade glioma undergoing radiation therapy were enrolled in an IRB-approved study of intra-treatment MRI 1, 3, and 10 weeks after the initiation of treatment. Receiver operating characteristic curve analysis was used to evaluate imaging parameters as a function of patient survival at one-year. Log Rank and Cox Proportional Hazards models were utilized to assess OS. Results: Measurable changes in diffusion MRI were observed as early as one week into treatment. The volume of tumor with increased diffusion as assessed by fDM 3 weeks after the start of therapy was the strongest predictor of patient survival at one year, with larger fDM predicting longer median survival [52.6 vs. 10.9 months, log-rank, P&amp;lt;0.003, HR 2.7 (95% CI: 1.5-5.9)]. Radiologic response at 10 weeks was of similar prognostic value [log-rank, P&amp;lt;0.0007, HR 2.9 (95% CI: 1.7-7.2)]. Pre-treatment age (&amp;lt;50 vs. 50+, P&amp;lt;0.007), pathologic grade (III vs. IV, P&amp;lt;0.05), and the use of concurrent temozolomide (yes vs. no, P&amp;lt;0.05) all predicted for increased survival on univariate analysis. On multivariate analysis only age (P&amp;lt;0.03) and fDM (P&amp;lt;0.04) retained prognostic significance for overall survival. Radiologic response and fDM agreed in their stratification for 75% of patients. However, a composite index of response including both fDM at 3 weeks and RR at 10 weeks provided a more robust predictor of patient survival and may help identify patients where RR does not correlate with clinical outcome. Conclusions: Compared to conventional neuro-imaging, fDM provided an earlier assessment of equal predictive value during the course of treatment, providing the opportunity to individualize therapy. The combination of fDM and RR provided a more accurate prediction of patient survival than either metric alone.
Breast milk alkylglycerols sustain beige adipocytes through adipose tissue macrophages
Authors: Haidong Yu, Sedat Dilbaz, Jonas Coßmann, Anh Cuong Hoang, Victoria Diedrich, Annika Herwig, Akiko Harauma, Yukino Hoshi, Toru Moriguchi, Kathrin Landgraf, Antje Körner, Christina Lucas, Susanne Brodesser, Lajos Balogh, Julianna Thuróczy, Gopal Karemore, Michael Scott Kuefner, Edwards A. Park, Christine Rapp, Jeffrey Bryant Travers, Tamás Röszer
Journal: Journal of Clinical Investigation (2019)

Prevalence of obesity among infants and children below 5 years of age is rising dramatically, and early childhood obesity is a forerunner of obesity and obesity-associated diseases in adulthood. Childhood obesity is hence one of the most serious public health challenges today. Here, we have identified a mother-to-child lipid signaling that protects from obesity. We have found that breast milk-specific lipid species, so-called alkylglycerol-type (AKG-type) ether lipids, which are absent from infant formula and adult-type diets, maintain beige adipose tissue (BeAT) in the infant and impede the transformation of BeAT into lipid-storing white adipose tissue (WAT). Breast milk AKGs are metabolized by adipose tissue macrophages (ATMs) to platelet-activating factor (PAF), which ultimately activates IL-6/STAT3 signaling in adipocytes and triggers BeAT development in the infant. Accordingly, lack of AKG intake in infancy leads to a premature loss of BeAT and increases fat accumulation. AKG signaling is specific for infants and is inactivated in adulthood. However, in obese adipose tissue, ATMs regain their ability to metabolize AKGs, which reduces obesity. In summary, AKGs are specific lipid signals of breast milk that are essential for healthy adipose tissue development.
Evidence, autonomy, and male circumcision
Authors: Lloyd D Hughes
Journal: BMJ (2012)

Religion has been an integral part of the fabric of ancient and modern society. However, we must finely balance how much influence faith should have in medicine, and I feel that we have got this balance wrong. I was glad to see that, in Germany, progress has been made to try to distinguish what is and is not acceptable medical practice under the guise of religious and cultural norms.

In June, a court in Cologne ruled in favour of banning male circumcision, labelling it a form of grievous bodily harm, after a botched operation on a 4 year old child led to urological complications and hospitalisation. The court noted evidence from New York, where two children have died and one has experienced brain damage in the past 10 years, as a result of …
Abstract B55: Targeting indoleamine 2,3 dioxygenase to improve the efficacy of a therapeutic vaccine against human papillomaviruses-associated tumors
Authors: Ana Carolina Ramos Moreno, Bruna F. M. M. Porchia, Patrícia da Cruz Souza, Roberta Liberato Pagni, Rafael Pegoraro, Luís Carlos de Souza Ferreira
Journal: Clinical Cancer Research (2018)

Abstract The activity of the enzyme indoleamine 2,3 dioxygenase-1 (IDO) has been associated with the maintenance of the immunosuppressive microenvironment in many types of cancers. IDO catalyzes the degradation of tryptophan via the kynurenine pathway, which impacts on the effector activity of immune cells. The role of IDO in immune tolerance observed in human papillomaviruses-associated tumors is poor understood. Here, we targeted IDO to improve the efficacy of a therapeutic protein vaccine against HPV-16-associated tumors. The combination of IDO inhibitors with immunotherapy showed evidence that can support a new antitumor therapeutic approach. In the murine model C57BL/6, different biologic parameters were evaluated in order to determine the activation of the protective immunity obtained by the combined immunotherapy. We observed that isoforms of 1-methyl tryptophan, combined with our therapeutic vaccine, led to an activation of cytotoxic CD8 (+) T cells in mice grafted with tumor cells expressing the HPV-16 oncoproteins. In addition, the combination of melatonin enhanced the efficacy of the immunotherapeutic approach, resulting in the complete eradication of tumor masses. Altogether, our results indicate that blocking the immunosuppressive mechanisms mediated by IDO may improve the antitumor response induced by immunotherapies. Citation Format: Ana Carolina Ramos Moreno, Bruna F. M. M. Porchia, Patrícia da Cruz Souza, Roberta Liberato Pagni, Rafael Pegoraro, Luís Carlos de Souza Ferreira. Targeting indoleamine 2,3 dioxygenase to improve the efficacy of a therapeutic vaccine against human papillomaviruses-associated tumors [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr B55.