tbuckley/cabot-search huggingface dataset:
Abstract PS6-26: Recurindex® predicts local regional recurrence for n1 breast cancer after mastectomy
Authors: Li-Na Zhang, Yue-Ping Liu, Chun-Xiao Li, Chao Song, Ning Wang, Ji-Yu Tang, Meng-Li Zhou, Ting-Hao Chen, Ming-Shuo Chen, Skye Hung-Chun Cheng, Cui-Zhi Geng
Journal: Cancer Research (2021)

Abstract Background: Post-mastectomy radiation therapy (PMRT) is part of standard regimen in the management of breast cancer. It has been shown to decrease the incidence of local regional recurrence (LRR) and improve breast cancer survival. Yet, its role in patients with 1-3 positive lymph nodes (N1) remains unclear. The lack of biological markers to evaluate the efficacy of PMRT for N1 patients leads to excessive treatment of low-risk patients and ignore of those at high risk. A clinical-genomic model RecurIndex® (RI-LR), based on a genomic database from mRNA expression as well as clinical factors (lymph node involvement, ER status,age at diagnosis, and lymphovascular invasion), is mainly developed for predicting the LRR in early stage breast cancer patients. Method: The preliminary result enrolled 107 breast cancer patients with N1 involvement in a retrospective study atthe fourth hospital of Hebei Medical University. Kaplan Meier method is used to calculate the survival rates in terms of LRR-free interval (LRFI). The log rank test and cox regression model are applied for the survival difference between two independent groups, and for investigating prognostic factors related to high-risk patients. The primary endpoint is LRFI. Results: With a median follow-up of 84 [IQR 64-84] months, RI-LR partitioned these N1 patients into 70% high-risk group and 30% low-risk group. LRR rate was 14.7% in the high-risk group whereas only 3.1% in the low-risk group. The survival curve clearly showed a partitioned trend of two groups (5-year LRFI 87.5%vs 100%, p = 0.085). Patients identified in the RI-LR high-risk group showed significantly higher LRFI if they had PMRT compared to those without PMRT (5-year LRFI 94% vs 70%, p =0.043), suggesting that higher radiosensitive patients could be identified by RI-LR. Multivariate analysis revealed that high-risk patients treated with PMRT has a 71 % reduction of LRR compared to those without PMRT (HR 0.29, 95%CI: 0.08-1.00, p = 0.051). Conclusions:The present study provided robust evidence that RI-LR could partition N1 breast cancer patients into good and poor prognosis of LRR. RI-LR is capable of identifying high-risk patients who would benefit from PMRT. This observation warrants to validate in a larger cohort. Key words: Early breast cancer, genomic assay, recurrence index (RI), local-regional recurrence (LRR), post mastectomy radiotherapy (PMRT) Citation Format: Li-Na Zhang, Yue-Ping Liu, Chun-Xiao Li, Chao Song, Ning Wang, Ji-Yu Tang, Meng-Li Zhou, Ting-Hao Chen, Ming-Shuo Chen, Skye Hung-Chun Cheng, Cui-Zhi Geng. Recurindex® predicts local regional recurrence for n1 breast cancer after mastectomy [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 PS6-26.
Current challenges and future perspectives in oral absorption research: An opinion of the UNGAP network
Authors: Zahari Vinarov, Bertil Abrahamsson, Per Artursson, Hannah Batchelor, Philippe Berben, Andreas Bernkop-Schnürch, James Butler, Jens Ceulemans, Nigel Davies, Didier Dupont, Gøril Eide Flaten, Nikoletta Fotaki, Brendan T. Griffin, Vincent Jannin, Janneke Keemink, Filippos Kesisoglou, Mirko Koziolek, Martin Kuentz, Alan Mackie, Antonio J. Meléndez-Martínez, Mark McAllister, Anette Müllertz, Caitriona M. O'Driscoll, Neil Parrott, Jadwiga Paszkowska, Petr Pavek, Christopher J.H. Porter, Christos Reppas, Cordula Stillhart, Kiyohiko Sugano, Elena Toader, Kateřina Valentová, Maria Vertzoni, Saskia N. De Wildt, Clive G. Wilson, Patrick Augustijns
Journal: Advanced Drug Delivery Reviews (2021)

Although oral drug delivery is the preferred administration route and has been used for centuries, modern drug discovery and development pipelines challenge conventional formulation approaches and highlight the insufficient mechanistic understanding of processes critical to oral drug absorption. This review presents the opinion of UNGAP scientists on four key themes across the oral absorption landscape: (1) specific patient populations, (2) regional differences in the gastrointestinal tract, (3) advanced formulations and (4) food-drug interactions. The differences of oral absorption in pediatric and geriatric populations, the specific issues in colonic absorption, the formulation approaches for poorly water-soluble (small molecules) and poorly permeable (peptides, RNA etc.) drugs, as well as the vast realm of food effects, are some of the topics discussed in detail. The identified controversies and gaps in the current understanding of gastrointestinal absorption-related processes are used to create a roadmap for the future of oral drug absorption research.
Hepatobiliary Organoids and Their Applications for Studies of Liver Health and Disease: Are We There Yet?
Authors: Junya Shiota, Linda C. Samuelson, Nataliya Razumilava
Journal: Hepatology (2021)

Organoid culture systems have emerged as a frontier technology in liver and biliary research. These three‐dimensional (3D) cell cultures derived from pluripotent and adult hepatobiliary cells model organ structure and function. Building on gastrointestinal organoid establishment, hepatobiliary organoid cultures were generated from mouse leucine‐rich repeat–containing G‐protein–coupled receptor 5–positive liver progenitor cells. Subsequently, 3D hepatobiliary organoid cultures were developed from hepatocytes and cholangiocytes to model human and animal hepatobiliary health and disease. Hepatocyte organoids have been used to study Alagille syndrome, fatty liver disease, Wilson disease, hepatitis B viral infection, and cystic fibrosis. Cholangiocyte organoids have been established to study normal cholangiocyte biology and primary sclerosing cholangitis and to test organoid potential to form bile ducts and gallbladder tissue in vitro . Hepatobiliary cancer organoids, termed tumoroids, have been established from frozen and fresh human tissues and used as a drug‐testing platform and for biobanking of cancer samples. CRISPR‐based gene modifications and organoid exposure to infectious agents have permitted the generation of organoid models of carcinogenesis. This review summarizes currently available adult cell–derived hepatobiliary organoid models and their applications. Challenges faced by this young technology will be discussed, including the cellular immaturity of organoid‐derived hepatocytes, co‐culture development to better model complex tissue structure, the imperfection of extracellular matrices, and the absence of standardized protocols and model validation.
Clinical Impact of Contralateral Carotid Occlusion in Patients Undergoing Carotid Artery Revascularization
Authors: Anna K. Krawisz, Kenneth Rosenfield, Christopher J. White, Michael R. Jaff, Joseph Campbell, Kevin Kennedy, Thomas Tsai, Beau Hawkins, Schuyler Jones, Eric A. Secemsky
Journal: Journal of the American College of Cardiology (2021)
Endoscopic septotomy for fistula after bariatric surgery
Authors: Mateus Bond Boghossian, Mateus Pereira Funari, Epifanio Silvino do Monte Junior, Rodrigo Silva de Paula Rocha, Diogo Turiani Hourneaux de Moura, Thiago Ferreira de Souza, Eduardo Guimarães Hourneaux de Moura
Journal: Endoscopy (2021)

Gastric fistula following bariatric surgery is a complication with considerable morbidity and mortality [1] [2]. After Roux-en-Y gastric bypass (RYGB), the gastric pouch may develop a chronic fistula and the formation of a perigastric cavity bounded by a septum. The altered anatomy chronically elevates the intraluminal pressure, impairing emptying of the perigastric cavity and perpetuating the fistula [3].
The Impact of Purifying and Background Selection on the Inference of Population History: Problems and Prospects
Authors: Parul Johri, Kellen Riall, Hannes Becher, Laurent Excoffier, Brian Charlesworth, Jeffrey D. Jensen
Journal: Molecular Biology and Evolution (2021)

Current procedures for inferring population history generally assume complete neutrality-that is, they neglect both direct selection and the effects of selection on linked sites. We here examine how the presence of direct purifying selection and background selection may bias demographic inference by evaluating two commonly-used methods (MSMC and fastsimcoal2), specifically studying how the underlying shape of the distribution of fitness effects and the fraction of directly selected sites interact with demographic parameter estimation. The results show that, even after masking functional genomic regions, background selection may cause the mis-inference of population growth under models of both constant population size and decline. This effect is amplified as the strength of purifying selection and the density of directly selected sites increases, as indicated by the distortion of the site frequency spectrum and levels of nucleotide diversity at linked neutral sites. We also show how simulated changes in background selection effects caused by population size changes can be predicted analytically. We propose a potential method for correcting for the mis-inference of population growth caused by selection. By treating the distribution of fitness effect as a nuisance parameter and averaging across all potential realizations, we demonstrate that even directly selected sites can be used to infer demographic histories with reasonable accuracy.
Statins have no overall effect on frequency or severity of muscle symptoms, study finds
Authors: Elisabeth Mahase
Journal: BMJ (2021)

Statins have no overall effect on the frequency or severity of muscle symptoms compared with placebo, according to a study published in The BMJ .1

The trial involved 200 people from 50 general practices in England and Wales who had recently stopped taking statins because of muscle symptoms (75.5%) or were considering stopping (24.5%). Each person was randomised to a sequence of six double blinded treatment periods (two months each) in which they received either 20 mg of atorvastatin daily or placebo.

Following the study, 66% (74 people) of those who attended the end of trial discussion (113) had already restarted taking statins or intended to resume the treatment.

Despite severe side effects being rare with the use of statins, many people think they cause …
Predicted sensitivity to endocrine therapy for stage II-III hormone receptor-positive and HER2-negative (HR+/HER2−) breast cancer before chemo-endocrine therapy
Authors: L. Du, C. Yau, L. Brown-Swigart, R. Gould, G. Krings, G.L. Hirst, I. Bedrosian, R.M. Layman, J.M. Carter, M. Klein, S. Venters, S. Shad, M. van der Noordaa, A.J. Chien, T. Haddad, C. Isaacs, L. Pusztai, K. Albain, R. Nanda, D. Tripathy, M.C. Liu, J. Boughey, R. Schwab, N. Hylton, A. DeMichele, J. Perlmutter, D. Yee, D. Berry, L. van't Veer, V. Valero, L.J. Esserman, W.F. Symmans
Journal: Annals of Oncology (2021)
68Ga-DOTATATE PET/CT Findings of Cervical Esophageal Neuroendocrine Tumor
Authors: Nuh Filizoglu, Salih Ozguven
Journal: Clinical Nuclear Medicine (2021)

Neuroendocrine tumors (NETs) of the esophagus are extremely rare and aggressive and have a poor prognosis. Because most esophageal cancers occur in the middle and lower parts of the esophagus, cervical esophageal NETs are even rarer. Herein, we present 68Ga-DOTATATE PET/CT findings in a 37-year-old woman who was diagnosed with cervical esophageal NET.
Response to Comment on Herring et al. Metabolic Effects of an SGLT2 Inhibitor (Dapagliflozin) During a Period of Acute Insulin Withdrawal and Development of Ketoacidosis in People With Type 1 Diabetes. Diabetes Care 2020;43:2128–2136
Authors: Roselle A. Herring, Fariba Shojaee-Moradie, Robert Garesse, Mary Stevenage, Nicola Jackson, Barbara A. Fielding, Agampodi Mendis, Sigurd Johnsen, A. Margot Umpleby, Melanie Davies, David L. Russell-Jones
Journal: Diabetes Care (2021)

Using the power of stable isotope techniques, our study explored the physiological effects of the SGLT2 inhibitor dapagliflozin on glucose flux, lipolysis, and ketone body concentration in people with acute absolute insulin withdrawal (1). The power of our study from the clinical perspective was the crossover design with each individual undergoing an identical insulin withdrawal protocol with the only difference being the presence or absence of an SGLT2 inhibitor.

Bolli et al. (2) argue that we would have seen a greater effect on nonesterified fatty acids (NEFAs) and ketones at baseline (prior to withdrawal of insulin) if the insulin dose had been adjusted in the SGLT2 arm during the 7 days preceding …
Abstract 10625: Inhibition of Fatty Acid Synthase in Vascular Smooth Muscle Cell Ameliorates Abnormal Cell Proliferation and Experimental Pulmonary Arterial Hypertension in Mice
Authors: Hiroki Matsui, Hiroaki Sunaga, Satoko Furukawa, Nozomi Furukawa, Norimichi Koitabashi, Tatsuya Iso, Tomoyuki Yokoyama, Masahiko Kurabayashi
Journal: Circulation (2019)

Introduction: Pulmonary arterial hypertension (PAH) is characterized by a progressive increase in pulmonary arterial smooth muscle cell (PASMC) proliferation resulting in chronic obstruction of sma...
Methodologic Concerns With Concluding a Link Between Epidural and Autism Spectrum Disorder—Reply
Authors: Chunyuan Qiu, Vimal Desai, Anny H. Xiang
Journal: JAMA Pediatrics (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Abstract PS17-38: Comprehensive association analysis of 21-gene recurrence score and overweight in breast cancer patients
Authors: Yiwei Tong, Weiqi Gao, Jiayi Wu, Siji Zhu, Ou Huang, Jianrong He, Li Zhu, Weiguo Chen, Yafen Li, Kunwei Shen, Xiaosong Chen
Journal: Cancer Research (2021)

Abstract Background: The association between 21-gene recurrence score (RS) and host factors such as overweight remains unclear for breast cancer patients. The objectives of the current study are to comprehensively analyze the distribution, single gene expression, and prognostic predictive value of RS between overweight or non-overweight patients.Patients and methods: Luminal-like patients receiving surgery between January 2009 and December 2018 in the Comprehensive Breast Health Center, Shanghai Ruijin Hospital, with 21-gene RS results were retrospectively retrieved. Association and subgroup analysis between BMI and 21-gene RS were conducted. Single-gene expression in 21-gene RS panel was compared between overweight and non-overweight groups. Recurrence-free survival (RFS) and overall survival (OS) were calculated according to RS category and BMI status.Results: Among 1876 patients included, 442 (23.56%), 995 (53.04%) and 439 (23.40%) were classified into low, intermediate and high risk groups. RS category was significantly differently distributed between overweight and non-overweight patients (P=0.035). Overweight patients had a trend of lower RS score than patients with normal weight (25.13 vs 26.17, P=0.080). The effect of BMI on RS significantly varied according to age (P=0.012) and menstruation status (P&amp;lt;0.001). Compared to non-overweight patients, overweight ones presented with higher ER (P&amp;lt;0.001), PR (P&amp;lt;0.001), CEGP1 (P=0.017), Ki67 (P=0.020) and STMY3 (P=0.026) mRNA expression levels. Regarding menstrual status, postmenopausal women with BMI≥24 kg/m2 were associated with higher ER group score (P&amp;lt;0.001), with higher ER (P=0.041), PR (P&amp;lt;0.001), CEGP1 (P=0.005), as well as GRB7 (P=0.015) expression, which was not significant in premenopausal women. After a median follow-up of 39.40 months (range 1.67-119.53), overweight patients had similar RFS (P=0.670) and OS (P=0.077) to non-overweight ones. Moreover, RS category could significantly predict RFS in the whole population (P&amp;lt;0.001), in either those overweight (P=0.003) or non-overweight (P=0.019).Conclusion: 21-gene RS was differently distributed between overweight and non-overweight patients, which interacted with age and menopausal status. ER, PR, CEGP1, Ki67 and STMY3 genes were more expressed in overweight patients. RS category could predict RFS regardless of BMI status, which warranted further validation. Citation Format: Yiwei Tong, Weiqi Gao, Jiayi Wu, Siji Zhu, Ou Huang, Jianrong He, Li Zhu, Weiguo Chen, Yafen Li, Kunwei Shen, Xiaosong Chen. Comprehensive association analysis of 21-gene recurrence score and overweight in breast cancer patients [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 PS17-38.
uFLIM — Unsupervised analysis of FLIM-FRET microscopy data
Authors: Francesco Masia, Walter Dewitte, Paola Borri, Wolfgang Langbein
Journal: Medical Image Analysis (2022)

Despite their widespread use in cell biology, fluorescence lifetime imaging microscopy (FLIM) data-sets are challenging to analyse, because each spatial position can contain a superposition of multiple fluorescent components. Here, we present a data analysis method employing all information in the available photon budget, as well as being fast. The method, called uFLIM, determines spatial distributions and temporal dynamics of multiple fluorescent components with no prior knowledge. It goes significantly beyond current approaches which either assume the functional dependence of the dynamics, e.g. an exponential decay, or require dynamics to be known, or calibrated. Its efficient non-negative matrix factorization algorithm allows for real-time data processing. We validate in silico that uFLIM is capable to disentangle the spatial distribution and spectral properties of five fluorescing probes, from only two excitation and detection channels and a photon budget of 100 detected photons per pixel. By adapting the method to data exhibiting Forster resonant energy transfer (FRET), we retrieve the spatial and transfer rate distribution of the bound species, without constrains on donor and acceptor dynamics.
Therapeutic options in VEXAS syndrome: insights from a retrospective series
Authors: Estelle Bourbon, Maël Heiblig, Mathieu Gerfaud Valentin, Thomas Barba, Cécile-Audrey Durel, Jean Christophe Lega, Fiorenza Barraco, Pascal Sève, Yvan Jamilloux, Pierre Sujobert
Journal: Blood (2021)
Abstract PS18-49: A transcriptome approach to reveal CTDP1 knockdown induced G1 cell cycle arrest in triple negative breast cancer cells
Authors: Henry Chun Hin Law, Nicholas Woods
Journal: Cancer Research (2021)

Abstract CTDP1 (C-terminal domain phosphatase 1) is the only phosphatase domain with a BRCT-domain and known to be associated with transcription and mitosis in eukaryotic systems. Our previous research showed that CTDP1 participates in the DNA damage response by mediating interstrand DNA repair through the Fanconi anemia pathway. This study also revealed that CTDP1 is an essential gene in breast cancer cell lines but not in normal breast derived epithelial MCF10A cells. This project aims to identify the changes in transcripts, kinases and interactors leading to the cell death induced by CTDP1 knockdown in the triple-negative breast cancer cell lines. Since RNA Pol II is one of the major targets of CTDP1 phosphatase activity, we initially hypothesized that the cellular changes were mediated by transcriptional regulation. The global transcriptomic profiling of shCTDP1 MDA-MB-231 cells detected more than 29000 gene products, where 1000 and 616 genes were found consistently up- and down-regulated, respectively. The downregulation of cell cycle-associated genes CCNA2, TOP2A and POLA1 in the MDA-MB-231 cells were confirmed with q-RT-PCR. While the upregulated genes did not show enrichment in the Reactome pathway database, the downregulated genes were significantly associated with DNA damage response, mitosis and transcription, which is consistent with the known functions of CTDP1. The transcription factor binding motifs analysis with iRegulon reveals that the E2F1 transcription activity decreased as CTDP1 was knocked down in MDA-MB-231. The subsequent cell cycle analysis supports this prediction and showed G1 arrest as CTDP1 is knocked down in MDA-MB-231 and MDA-MB-453, but not in MCF10A. A kinase array analysis was also conducted to further identify kinases activated or deactivated as CTDP1 is knocked down. A nested network analysis of the predicted transcription factors, kinases and CTDP1 interactors is used to identify potential pathways contributing to cell death of the triple-negative breast cancer cells upon loss of CTDP1 expression. Citation Format: Henry Chun Hin Law, Nicholas Woods. A transcriptome approach to reveal CTDP1 knockdown induced G1 cell cycle arrest in triple negative breast cancer cells [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 PS18-49.
Homozygous BCMA gene deletion in response to anti-BCMA CAR T cells in a patient with multiple myeloma
Authors: Matteo C. Da Vià, Oliver Dietrich, Marietta Truger, Panagiota Arampatzi, Johannes Duell, Anke Heidemeier, Xiang Zhou, Sophia Danhof, Sabrina Kraus, Manik Chatterjee, Manja Meggendorfer, Sven Twardziok, Maria-Elisabeth Goebeler, Max S. Topp, Michael Hudecek, Sabrina Prommersberger, Kristen Hege, Shari Kaiser, Viktoria Fuhr, Niels Weinhold, Andreas Rosenwald, Florian Erhard, Claudia Haferlach, Hermann Einsele, K. Martin Kortüm, Antoine-Emmanuel Saliba, Leo Rasche
Journal: Nature Medicine (2021)