tbuckley/cabot-search huggingface dataset:
Abstract PS13-45: Radiological response pattern predicts disease-free survival in breast cancer patients undergoing neoadjuvant chemotherapy
Authors: Juneyoung Ahn, Tae-kyung Yoo, Pill Sun Paik, Min Kyung Cho, Chang Ik Yoon, Woo Chan Park
Journal: Cancer Research (2021)

Abstract Purpose Pathological complete response (pCR) predicts improved survival in breast cancer patients undergoing neoadjuvant chemotherapy (NAC). However, the prognosis of patients with non-pCR remains unclear. The aim of this study was to evaluate the effect of radiological response pattern on breast cancer patients’ outcome. Method A total of 396 breast cancer patients who underwent neoadjuvant chemotherapy between 2010-2017 at Seoul St. Mary’s Hospital were retrospectively reviewed. Among them, patients who underwent 4-6 cycles of neoadjuvant chemotherapy and underwent response evaluation every 2 cycles using breast MRI were included for analysis. Early and late response ratio was calculated from breast MR images using the longest diameter of the main tumor. Early response ratio was calculated as post-2 cycle NAC / pre-NAC ratio. Late response ratio was calculated as post-4 cycle NC / post-2 cycle NAC ratio. Radiological response pattern was divided into three groups; fast-slow responder meaning early response ratio &amp;gt; late response ratio + 20%, slow-fast responder meaning late response ratio &amp;gt; early response ratio + 20% and constant responder meaning the difference between initial response ratio and later response ratio is lower than 20%. Survival analysis was done using the Kaplan-Meier method and multivariate analysis by Cox regression. Disease-free survival (DFS) was defined as locoregional recurrence, contralateral breast recurrence and distant metastasis. Result A total of 177 patients were included for analysis. Among them 19 (10.7%) patients were pCR, 122 (68.9%) patients had partial response, 29 (16.4%) patients had stable disease and 7 (4.0%) patients had progressive disease. Median follow-up period was 50 months (range, 3-112 months). Radiological response pattern was significantly associated with disease-free survival in univariate analysis (p=0.042). Fast-slow responders had significantly worse disease-free survival (DFS) in univariate analysis compared to slow-fast responders and constant responders (p=0.042, 5-year DFS 67.6%, 88.3% 67.6%). Radiological response pattern continued to be statistically significant by multivariable analysis (p=0.037). Conclusion Our results showed that fast-slow responders have worse survival compared to constant or slow-fast responders. Radiological response patterns may be useful to more accurately assess prognosis, especially when considering adjuvant chemotherapy. Citation Format: Juneyoung Ahn, Tae-kyung Yoo, Pill Sun Paik, Min Kyung Cho, Chang Ik Yoon, Woo Chan Park. Radiological response pattern predicts disease-free survival in breast cancer patients undergoing neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-45.
Abstract 989: Transcriptional Analysis of Cardiac Hypoxia Inducible Factor-1
Authors: Chad B Walton, Joel T Outten, Ralph V Shohet
Journal: Circulation (2007)

The response to hypoxia in tissues is regulated by the heterodimeric transcription factor hypoxia inducible factor-1 (HIF-1). It coordinates many downstream processes including angiogenesis and gly...
Biomimetic co-assembled nanodrug of doxorubicin and berberine suppresses chemotherapy-exacerbated breast cancer metastasis
Authors: Xiao Zheng, Yawei Zhao, Yong Jia, Dan Shao, Fan Zhang, Madi Sun, Jianati Dawulieti, Hanze Hu, Lianzhi Cui, Yue Pan, Chao Yang, Wen Sun, Shuang Zhang, Kan He, Jing Li, Jinzhi Du, Ming Zhang, Li Chen
Journal: Biomaterials (2021)
Comparative Genomics Reveals Early Emergence and Biased Spatiotemporal Distribution of SARS-CoV-2
Authors: Matteo Chiara, David S Horner, Carmela Gissi, Graziano Pesole
Journal: Molecular Biology and Evolution (2021)

Effective systems for the analysis of molecular data are fundamental for monitoring the spread of infectious diseases and studying pathogen evolution. The rapid identification of emerging viral strains, and/or genetic variants potentially associated with novel phenotypic features is one of the most important objectives of genomic surveillance of human pathogens and represents one of the first lines of defense for the control of their spread. During the COVID 19 pandemic, several taxonomic frameworks have been proposed for the classification of SARS-Cov-2 isolates. These systems, which are typically based on phylogenetic approaches, represent essential tools for epidemiological studies as well as contributing to the study of the origin of the outbreak. Here, we propose an alternative, reproducible, and transparent phenetic method to study changes in SARS-CoV-2 genomic diversity over time. We suggest that our approach can complement other systems and facilitate the identification of biologically relevant variants in the viral genome. To demonstrate the validity of our approach, we present comparative genomic analyses of more than 175,000 genomes. Our method delineates 22 distinct SARS-CoV-2 haplogroups, which, based on the distribution of high-frequency genetic variants, fall into four major macrohaplogroups. We highlight biased spatiotemporal distributions of SARS-CoV-2 genetic profiles and show that seven of the 22 haplogroups (and of all of the four haplogroup clusters) showed a broad geographic distribution within China by the time the outbreak was widely recognized-suggesting early emergence and widespread cryptic circulation of the virus well before its isolation in January 2020. General patterns of genomic variability are remarkably similar within all major SARS-CoV-2 haplogroups, with UTRs consistently exhibiting the greatest variability, with s2m, a conserved secondary structure element of unknown function in the 3'-UTR of the viral genome showing evidence of a functional shift. Although several polymorphic sites that are specific to one or more haplogroups were predicted to be under positive or negative selection, overall our analyses suggest that the emergence of novel types is unlikely to be driven by convergent evolution and independent fixation of advantageous substitutions, or by selection of recombined strains. In the absence of extensive clinical metadata for most available genome sequences, and in the context of extensive geographic and temporal biases in the sampling, many questions regarding the evolution and clinical characteristics of SARS-CoV-2 isolates remain open. However, our data indicate that the approach outlined here can be usefully employed in the identification of candidate SARS-CoV-2 genetic variants of clinical and epidemiological importance.
Telemedicine and Medical Licensure — Potential Paths for Reform
Authors: Ateev Mehrotra, Alok Nimgaonkar, Barak Richman
Journal: New England Journal of Medicine (2021)

Telemedicine and Medical Licensure The growth of telemedicine is seen by some physicians, academics, and policymakers as a silver lining of the Covid-19 pandemic. Congress is considering bills that...
The impact of grounded procedures can vary as a function of perceived thought validity, meaning, and timing
Authors: Pablo Briñol, Richard E. Petty
Journal: Behavioral and Brain Sciences (2021)

Cleansing (separation) inductions reduce the impact of negative and positive reactions, whereas connection manipulations magnify them. We suggest that grounded procedures can produce these effects by affecting the perceived validity of thoughts. In accord with the self-validation theory, we also note the importance of considering how moderators, such as the meaning of the action and the timing of inductions, affect outcomes.
COVID-19 vaccination: the VOICE for patients with cancer
Authors: Astrid A. M. van der Veldt, Sjoukje F. Oosting, Anne-Marie C. Dingemans, Rudolf S. N. Fehrmann, Corine GeurtsvanKessel, Mathilde Jalving, Guus F. Rimmelzwaan, Pia Kvistborg, Christian U. Blank, Egbert F. Smit, Valery E. E. P. Lemmens, T. Jeroen N. Hiltermann, Marion P. G. Koopmans, Anke L. W. Huckriede, Nynke Y. Rots, Cecile A. C. M. van Els, Debbie van Baarle, John B. A. G. Haanen, Elisabeth G. E. de Vries
Journal: Nature Medicine (2021)
Abstract PS1-65: What lessons can be learned from the poly implant prothese scandal ? A french retrospective study
Authors: Lea Pauly, Benoit Couturaud, Fabien Reyal
Journal: Cancer Research (2021)

Abstract Background : Silicone breast implants from the French manufacturer Poly Implant Prothese (PIP) were recalled from the French market after the use of a non-medical silicone filler has been established. The systematic explantation of the implants had been proposed to women with PIP implants in France, a preventive measure concerning approximately 30,000 patients.Objectives : This study aimed to evaluate the consequences of having at least one PIP breast implant on overall and disease-free survival after breast reconstruction for cancer or prophylactic surgery.Materials and Methods : We performed a multicentric retrospective cohort study on women who underwent immediate or delayed implant-based reconstruction after curative or prophylactic mastectomy between January 01,2002 and March 30,2010 in three French private health institutions of public interest. These dates correspond respectively to the arrival of PIP breast implants on the French market and the decision to withdraw them by the French government. The primary endpoints were disease-free and overall survival, depending on whether or not having a PIP breast implant used during breast reconstruction of prophylactic surgery.Results : We identified 2499 patients with the use of 4106 breast implants between 2002 and 2010.The median age of cancer diagnosis was 47 years (19-77). This patient population selected for breast reconstruction had good prognosis criteria (77% T1 and 68% N0). PIP was the most common brand used between 2002 and 2010 and represented 45% of all breast implants (1764 implants). PIP has been preferentially used in courses with immediate breast reconstruction. On the 1764 PIP, 1408 (80%) were removed, mainly after the preventive measure recommending systematic explantation. Censored data on March 30, 2010, showed that the incidence of PIP implants removal is lower than other brands (Log-rank test : p&amp;lt;0.001). Overall survival of patients who had at least on PIP was no different from that of patients who never had a PIP (Log-rank test : p=0.2). Disease-free survival was also similar between these two populations (Log-rank test : p=0.12).Conclusion : We did not identify any increase in local-regional recurrence or overall mortality associated with the use of PIP. Citation Format: Lea Pauly, Benoit Couturaud, Fabien Reyal. What lessons can be learned from the poly implant prothese scandal ? A french retrospective study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-65.
Controlling COVID-19 Spread in a Confined, High-Risk Population
Authors: Gregory C. Gray
Journal: JAMA Network Open (2021)

Joseph E. Marcus, MD; Dianne N. Frankel, DO, MPH; Mary T. Pawlak, MD, MPH; Theresa M. Casey, DVM; Robert J. Cybulski Jr, PhD; Erin Enriquez, RN; Jason F. Okulicz, MD; Heather C. Yun, MD
Abstract SP022: Special topics in early stage ER+ breast cancer
Authors: D Cameron
Journal: Cancer Research (2021)

Abstract ER+ve HER2-ve breast cancer, also known as luminal breast cancer, is the commonest form of early breast cancer, and the commonest cause of breast cancer death. It is defined pathologically in terms of significant levels of expressesion of hormone receptors without over-amplified HER2: but like all other subtypes of breast cancer is not just one disease. The majority of these tumours are sensitive to endocrine therapy, and also benefit from the other standard interventions, such as chemotherapy, surgery, radiotherapy and the use of bisphosphonates: all of the curative benefits of these treatments (bar surgery) having been confirmed in individual patient meta-analyses. So what is there to say apart from exploring the mechanisms of resistance to therapy and the biologically-driven new therapeutic approaches which will be covered by the two other speakers in this session? Firstly, a review of these important data: exploration of the key questions such as choice of, and duration of, adjuvant endocrine therapy in both pre- and post-menopausal women (and in brief, men); discussion of the pattern of relapse including the almost linear risk of relapse per year for at least 10 years (unlike other subtypes of breast cancer), and the implications of that pattern for patients, clinicians and trialists. In particular the presenter will consider the SOFT/TEXT studies, the data from the meta-analyses of the adjuvant endocrine and bisphosphonate therapy studies and the very significant issues of adherence and toxicity for women. Secondly a brief look at the data on bio-markers used to suggest certain cancers don’t benefit from the use of adjuvant chemotherapy, noting the distinction between prognostic and predictive, and the challenge at times of separating these effects in women with a good prognosis, and can thus be used to offer women the possibility of avoiding chemotherapy. How to approach the pre-menopausal woman to maximise her chance of cure whilst making life tolerable and helping her “normalise” any plans she may have to have children. Third, looking at the newer therapies entering clinical trials, and in particular consideration of the emerging data on the use of CDK 4/6i in early breast cancer and what this may mean for both clinical trial design and clinical practice. But perhaps most importantly, this talk will identify pitfalls in interpretation of data, the need for long-term outcome data to truly understand what trials tell us, and what they don’t: and pointers to the future of where we may be able to further improve the lot of women with the commonest and ultimately most fatal of the main breast cancer subtypes. Citation Format: D Cameron. Special topics in early stage ER+ breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SP022.
Loss-of-function HSD17B13 variants, non-alcoholic steatohepatitis and adverse liver outcomes: Results from a multi-ethnic Asian cohort
Authors: Yi-Wen Ting, Amanda Shen-Yee Kong, Shamsul Mohd Zain, Wah-Kheong Chan, Hwa-Li Tan, Zahurin Mohamed, Yuh-Fen Pung, Rosmawati Mohamed
Journal: Clinical and Molecular Hepatology (2021)

Background/Aims: 17β-hydroxysteroid dehydrogenase 13 (HSD17B13) variants were recently reported to have significantly lower odds of non-alcoholic fatty liver disease (NAFLD). This is a two-part study that aimed to evaluate the association of HSD17B13 variants with NAFLD and its histological severity, and to identify the association of the variants with clinical outcomes in a cohort of biopsy-proven NAFLD patients.Methods: Consecutive biopsy-proven NAFLD patients and controls without fatty liver were recruited for this study between 2009 and 2014. Genotyping for HSD17B13 variants was performed using rhAmp assays. A total of 165 patients with NAFLD were monitored up until August 2019. Clinical outcomes were recorded.Results: HSD17B13 rs72613567 TA allele and rs6834314 G allele were associated with lower odds of non-alcoholic steatohepatitis (NASH) in the overall cohort and among ethnic Chinese, but not among ethnic Malays or Indians (P&lt;0.05). During a mean follow-up of 89 months, 32 patients (19.4%) experienced at least one clinical outcome (cardiovascular events, n=22; liver-related complications, n=6; extra-hepatic malignancy, n=5; and mortality, n=6). The rs72613567 homozygous TA allele and the rs6834314 homozygous G allele were independently associated with a lower incidence of liver-related complications (hazard ratio [HR], 0.004; 95% confidence interval [CI], 0.00–0.64; P=0.033 and HR, 0.01; 95% CI, 0.00–0.97; P=0.048, respectively) and were associated with lower grade of hepatocyte ballooning among the ethnic Chinese.Conclusion: HSD17B13 rs72613567 and rs6834314 variants were inversely associated with NAFLD and NASH, and were associated with lower incidence of adverse liver outcomes in a cohort of multi-ethnic Asian patients with NAFLD.
Abstract 10603: Relation of Left Atrial Volume Index and Cryoballoon Ablation Outcomes for Paroxysmal Atrial Fibrillation
Authors: Abhishek Bose, Parag A Chevli, Ajay K Mishra, Zeba Hashmath, Gregory Berberian, Jerzy Januszkiewicz, Ghasan Ahmad, Douglas Laidlaw
Journal: Circulation (2019)

Background: Cryoballoon ablation (CBA) is the recommended therapy for patients with paroxysmal atrial fibrillation (AF) refractory to anti-arrhythmic drug therapy. In spite of significant procedura...
Regenerative potential of epicardium-derived extracellular vesicles mediated by conserved miRNA transfer
Authors: Cristina Villa del Campo, Norman Y Liaw, Mala Gunadasa-Rohling, Moritz Matthaei, Luca Braga, Tahnee Kennedy, Gabriela Salinas, Niels Voigt, Mauro Giacca, Wolfram-Hubertus Zimmermann, Paul Richard Riley
Journal: Cardiovascular Research (2021)

Abstract Aims After a myocardial infarction, the adult human heart lacks sufficient regenerative capacity to restore lost tissue, leading to heart failure progression. Finding novel ways to reprogram adult cardiomyocytes into a regenerative state is a major therapeutic goal. The epicardium, the outermost layer of the heart, contributes cardiovascular cell types to the forming heart and is a source of trophic signals to promote heart muscle growth during embryonic development. The epicardium is also essential for heart regeneration in zebrafish and neonatal mice and can be reactivated after injury in adult hearts to improve outcome. A recently identified mechanism of cell–cell communication and signalling is that mediated by extracellular vesicles (EVs). Here, we aimed to investigate epicardial signalling via EV release in response to cardiac injury and as a means to optimize cardiac repair and regeneration. Methods and results We isolated epicardial EVs from mouse and human sources and targeted the cardiomyocyte population. Epicardial EVs enhanced proliferation in H9C2 cells and in primary neonatal murine cardiomyocytes in vitro and promoted cell cycle re-entry when injected into the injured area of infarcted neonatal hearts. These EVs also enhanced regeneration in cryoinjured engineered human myocardium (EHM) as a novel model of human myocardial injury. Deep RNA-sequencing of epicardial EV cargo revealed conserved microRNAs (miRs) between human and mouse epicardial-derived exosomes, and the effects on cell cycle re-entry were recapitulated by administration of cargo miR-30a, miR-100, miR-27a, and miR-30e to human stem cell-derived cardiomyocytes and cryoinjured EHM constructs. Conclusion Here, we describe the first characterization of epicardial EV secretion, which can signal to promote proliferation of cardiomyocytes in infarcted mouse hearts and in a human model of myocardial injury, resulting in enhanced contractile function. Analysis of exosome cargo in mouse and human identified conserved pro-regenerative miRs, which in combination recapitulated the therapeutic effects of promoting cardiomyocyte proliferation.
WHSC1/NSD2 regulates immune infiltration in prostate cancer
Authors: Muzamil Y Want, Takemasa Tsuji, Prashant K Singh, James L Thorne, Junko Matsuzaki, Ellen Karasik, Bryan Gillard, Eduardo Cortes Gomez, Richard C. Koya, Amit Lugade, Kunle Odunsi, Sebastiano Battaglia
Journal: Journal for ImmunoTherapy of Cancer (2021)

Immunotherapy in prostate cancer (PCa) lags behind the progresses obtained in other cancer types partially because of its limited immune infiltration. Tumor-resident immune cells have been detected in the prostate, but the regulatory mechanisms that govern tumor infiltration are still poorly understood. To address this gap, we investigated the role of Wolf-Hirschhorn syndrome candidate 1 (WHSC1), a histone methyltransferase enzyme that targets dimethyl and trimethyl H3K36. WHSC1 is known to promote malignant growth and progression in multiple tumors, but its role in the interface between PCa and immune system is unknown. RNA Sequencing (RNASeq) data from patients with PCa from The Cancer Genome Atlas (TCGA) were collected and divided into top/bottom 30% based on the expression of WHSC1 and disease-free survival was calculated. Publicly available chromatin immunoprecipitation (ChIPSeq) data were obtained from Cistrome and integrated with the available RNASeq data. RNASeq, ATACSeq and methylomic were analyzed using R Bioconductor packages comparing C42 cells with or without stable knockdown on WHSC1. Flow cytometry was used to measure Major Histocompatibility complex (MHC) levels, MHC-bound ovalbumin and tumor infiltration. C57B6 and NOD scid gamma (NSG) mice were subcutaneously grafted with TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) C2 cells and treated with MCTP39 (10 mg/kg); tumor size was monitored over time and curves were compared using permutation analyses. All analyses used a significance threshold of 0.05. Leveraging TCGA data, we demonstrated that elevated WHSC1 levels positively correlate with the presence of an immunosuppressive microenvironment. We validated those results in vitro, demonstrating that genetic and pharmacological inhibition of WHSC1 restores antigen presentation. This occurs via an elegant epigenetic regulation of gene expression at the chromatin and DNA methylation levels. In vivo studies in immunocompetent mice also show an increased frequency of CD8+ T cells in tumors from mice treated with WHSC1 inhibitor, supporting the hypothesis that the antitumor effect following WHSC1 inhibition requires a fully functional immune system. This study demonstrates a novel role for WHSC1 in defining immune infiltration in PCa, with significant future implications for the use of immunotherapies in prostate malignancies.
Selective elimination of immunosuppressive T cells in patients with multiple myeloma
Authors: Mohamed H. S. Awwad, Abdelrahman Mahmoud, Heiko Bruns, Hakim Echchannaoui, Katharina Kriegsmann, Raphael Lutz, Marc S. Raab, Uta Bertsch, Markus Munder, Anna Jauch, Katja Weisel, Bettina Maier, Niels Weinhold, Hans Jürgen Salwender, Volker Eckstein, Mathias Hänel, Roland Fenk, Jan Dürig, Benedikt Brors, Axel Benner, Carsten Müller-Tidow, Hartmut Goldschmidt, Michael Hundemer
Journal: Leukemia (2021)

Abstract Elimination of suppressive T cells may enable and enhance cancer immunotherapy. Here, we demonstrate that the cell membrane protein SLAMF7 was highly expressed on immunosuppressive CD8 + CD28 - CD57 + Tregs in multiple myeloma (MM). SLAMF7 expression associated with T cell exhaustion surface markers and exhaustion-related transcription factor signatures. T cells from patients with a high frequency of SLAMF7 + CD8 + T cells exhibited decreased immunoreactivity towards the MART-1 aa26–35*A27L antigen. A monoclonal anti-SLAMF7 antibody (elotuzumab) specifically depleted SLAMF7 + CD8 + T cells in vitro and in vivo via macrophage-mediated antibody-dependent cellular phagocytosis (ADCP). Anti-SLAMF7 treatment of MM patients depleted suppressive T cells in peripheral blood. These data highlight SLAMF7 as a marker for suppressive CD8 + Treg and suggest that anti-SLAMF7 antibodies can be used to boost anti-tumoral immune responses in cancer patients.
Gut microbiome pattern reflects healthy ageing and predicts survival in humans
Authors: Tomasz Wilmanski, Christian Diener, Noa Rappaport, Sushmita Patwardhan, Jack Wiedrick, Jodi Lapidus, John C. Earls, Anat Zimmer, Gustavo Glusman, Max Robinson, James T. Yurkovich, Deborah M. Kado, Jane A. Cauley, Joseph Zmuda, Nancy E. Lane, Andrew T. Magis, Jennifer C. Lovejoy, Leroy Hood, Sean M. Gibbons, Eric S. Orwoll, Nathan D. Price
Journal: Nature Metabolism (2021)