tbuckley/cabot-search huggingface dataset:
Abstract 2994: A new ER+Her2- Palbociclib resistant breast cancer PDX model
Authors: Michele Melton, Emma M. Hyddmark, Hongmei Jiang, Athena Bast, Nicole Semanik, Stacy Deeds, Andrew Brown
Journal: Cancer Research (2021)

Abstract One out of eight women will get breast cancer during their lifetime with over 250000 new cases of invasive breast cancer diagnosed yearly. The majority of breast cancer medicines (94%) were initially approved in the metastatic setting for patients that have been heavily pre-treated and resistant to the standard of care1. Thus, it is crucial that pre-clinical models are representative of this patient population in order for results to be translational. One recently approved class of drugs are the CDK4/6i which increase progression free survival for many patients. However, some tumors are intrinsically resistant, and others develop resistance over time. Hence, there is a need for new pre-clinical models that mimic these resistance features to test new therapies. WHIM81 and WHIM84 are two new ER+Her2- breast cancer PDX models from the Washington University Human in Mouse collection derived from heavily pretreated tumors. WHIM81 was derived from a patient with liver metastasis consistent with breast primary after she received treatment with Palbociclib, first as a monotherapy for 20 days and later in combination with letrozole for 2 months. During treatment, the patient developed the liver metastasis, whereas the WHIM84 model was grafted from a second patient with a bone metastasis prior to the patient seeing Palbociclib, but once she did, the tumor was unresponsive. In this PDX study, athymic nude mice bearing either WHIM81 or WHIM84 tumors were treated with 3 different concentrations of Palbociclib (10 mg/kg, 25 mg/kg and 75 mg/kg) administered daily for the duration of the experiment and also included an arm with Fulvestrant administered once weekly through a subcutaneous injection of 3 mg/dose. Our results showed that although WHIM81 tumors were responsive to a very high dose of Palbociclib (75 mg/kg), those tumors showed resistance to Palbociclib doses of 10 mg/kg and Palbociclib 25 mg/kg group as well as Fulvestrant, consistent with what was seen in the clinic for the tumor from which this PDX is derived. On the contrary WHIM84, while still showing resistance at the 10 mg/kg dose, was sensitive to treatment with Palbociclib at a dose of 25 mg/kg. Loss of pRb is an unlikely driver of resistance as WHIM81 retains pRb expression based on the presence of both pRb and phospo-pRb in the tumor. Thus, we believe that WHIM81 will provide a valuable new model to test novel therapies aimed to treat patients with CDK4/6i resistant cancers. 1. Leo and Szucs. (2020). Nature Reviews Drug Discovery. 19, 10. Citation Format: Michele Melton, Emma M. Hyddmark, Hongmei Jiang, Athena Bast, Nicole Semanik, Stacy Deeds, Andrew Brown. A new ER+Her2- Palbociclib resistant breast cancer PDX model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2994.
Covid-19: “Freedom day” in England could lead to “significant third wave of hospitalisations and deaths,” modelling predicts
Authors: Gareth Iacobucci
Journal: BMJ (2021)

Covid-19: "Freedom day" in England could lead to "significant third wave of hospitalisations and deaths," modelling predicts Gareth IacobucciThe government's decision to lift all covid restrictions in England on 19 July could lead to "a significant third wave of hospitalisations and deaths," modellers have projected.
Effectiveness of an Inactivated SARS-CoV-2 Vaccine in Chile
Authors: Alejandro Jara, Eduardo A Undurraga, Cecilia González, Fabio Paredes, Tomás Fontecilla, Gonzalo Jara, Alejandra Pizarro, Johanna Acevedo, Katherinne Leo, Francisco Leon, Carlos Sans, Paulina Leighton, Pamela Suárez, Heriberto García-Escorza, Rafael Araos
Journal: New England Journal of Medicine (2021)

Mass vaccination campaigns to prevent coronavirus disease 2019 (Covid-19) are occurring in many countries; estimates of vaccine effectiveness are urgently needed to support decision making. A countrywide mass vaccination campaign with the use of an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine (CoronaVac) was conducted in Chile starting on February 2, 2021. We used a prospective national cohort, including participants 16 years of age or older who were affiliated with the public national health care system, to assess the effectiveness of the inactivated SARS-CoV-2 vaccine with regard to preventing Covid-19 and related hospitalization, admission to the intensive care unit (ICU), and death. We estimated hazard ratios using the extension of the Cox proportional-hazards model, accounting for time-varying vaccination status. We estimated the change in the hazard ratio associated with partial immunization (≥14 days after receipt of the first dose and before receipt of the second dose) and full immunization (≥14 days after receipt of the second dose). Vaccine effectiveness was estimated with adjustment for individual demographic and clinical characteristics. The study was conducted from February 2 through May 1, 2021, and the cohort included approximately 10.2 million persons. Among persons who were fully immunized, the adjusted vaccine effectiveness was 65.9% (95% confidence interval [CI], 65.2 to 66.6) for the prevention of Covid-19 and 87.5% (95% CI, 86.7 to 88.2) for the prevention of hospitalization, 90.3% (95% CI, 89.1 to 91.4) for the prevention of ICU admission, and 86.3% (95% CI, 84.5 to 87.9) for the prevention of Covid-19-related death. Our results suggest that the inactivated SARS-CoV-2 vaccine effectively prevented Covid-19, including severe disease and death, a finding that is consistent with results of phase 2 trials of the vaccine. (Funded by Agencia Nacional de Investigación y Desarrollo and others.).
Correspondence on ‘SARS-CoV-2 vaccination in rituximab-treated patients: evidence for impaired humoral but inducible cellular immune response’
Authors: Timm H Westhoff, Felix S Seibert, Moritz Anft, Arturo Blazquez-Navarro, Sarah Skrzypczyk, Adrian Doevelaar, Bodo Hölzer, Krystallenia Paniskaki, Sebastian Dolff, Benjamin Wilde, Oliver Witzke, Juergen Braun, Ulrik Stervbo, Nina Babel
Journal: Annals of the Rheumatic Diseases (2021)

We read with a great interest the article published by Bonelli et al suggesting an inducible cellular immune response in rituximab (Rtx) treated patients.1 The CD20-antibody Rtx is one of the most widespread biologicals worldwide with a broad spectrum of oncological and rheumatological indications. Due to its depleting effect on circulating B cells, the generation of antibodies against novel pathogens is impaired in Rtx-treated patients.2 3 Accordingly, the last EULAR recommendations on vaccination advised that ‘vaccination should be provided at least 6 months after the last administration and 4 weeks before the next course of B cell-depleting therapy’.4 To ensure appropriate SARS-CoV-2 vaccination, the last EULAR advise was to refer to a rheumatologist.5 The American College of Rheumatology (ACR) has recommended to vaccinate Rtx-treated patients not earlier than 5 months after the last administration with the next cycle given not earlier than 2–4 weeks thereafter.6 In any case, the combination of B cell-depleting therapy with vaccination has been quite a challenge for patients and physicians—especially since it became clear that Rtx therapy may be associated with unfavourable outcomes in B cell-depleted patients.7 Fortunately, very recent data by Bonelli et al have now suggested that a cellular response is mounted after SARS-CoV-2 vaccination in Rtx-treated patients despite a failed humoral immune response.1 The authors demonstrated that peripheral blood cells of vaccinated patients do produce Interferon γ (IFNγ) after stimulation with SARS-CoV-2 spike (S) protein-derived overlapping peptides.1 These results increase the scientific interest into a more detailed characterisation of vaccine-reactive T-cell immunity, which has recently been in the focus of our group as well due to a frequent Rtx application in our settings.

Applying multiparameter flow cytometry, we explored the …
Diagnostic value, oncological outcomes and safety profile of image-guided surgery technologies during robot-assisted lymph node dissection with sentinel node biopsy for prostate cancer
Authors: P. Dell’Oglio, E. Mazzone, N. Grivas, E. Wit, M. Donswijk, A. Briganti, F. Van Leeuwen, H. Van Der Poel
Journal: European Urology (2021)
Abstract 1981: TGF-β induced PLEK2 promotes metastasis and chemoresistance in ESCC by up-regulation of LCN2
Authors: Feng Wang, Chaoqi Zhang, Chengming Liu, Hong Cheng, Nan Sun, Jie He
Journal: Cancer Research (2021)

Abstract Background: Esophageal squamous cell carcinoma (ESCC) patients suffer from poor prognosis in general. Novel molecular markers to predict prognosis and serve as potential therapy target are much needed. Our previous research has established a comprehensive database of ESCC (GSE53625). Combined with data from TCGA, we found Pleckstrin 2 (PLEK2) predicts poor prognosis in ESCC. Meanwhile, its role in ESCC progression remains unknown. Methods: The TCGA database and GSE53625 are used to establish the expression profiles of PLEK2 and overall survival rates. Loss-of-function assays were performed to examine the effect of PLEK2 on proliferation, migration and invasion of ESCC cells in vitro and in vivo. ChIP assay was used to detect the relationship between TGF-β and PLEK2. Western blot and quantitative real time PCR (qRT-PCR) were carried out to reveal the interrelation between PLEK2 and LCN2. Results: PLEK2 had a higher expression in ESCCs and predicted poor overall survival (OS). PLEK2 attenuation by shRNA was sufficient to decrease ESCC cells proliferation, clonogenicity, migration and invasion in vitro and tumorigenicity and distant metastasis in vivo. Conversely, elevating PLEK2 levels performed opposite effects. Downregulation of PLEK2 led to higher proportions of apoptotic ESCC cells when induced by Cisplatin. The high expression of PLEK2 in ESCC patients also linked to shorter OS of patients who received adjuvant chemotherapy. TGF-β could increase the expression of PLEK2 by stimulation of Smad2/3 which can bind directly with the promoter sequences of PLEK2. Analyses of transcriptome profiling suggested LCN2 as the downstream of PLEK2. Overexpression LCN2 in PLEK2 stable knockdown ESCC cells can reverse the decreased migration and invasion, but not the proliferation of ESCC cells. TGF-β increased the expression of LCN2, but the effect disappeared when PLEK2 was knockdown. We also find that AKT pathway is involved in the whole regulatory processes. Conclusion: Our results revealed the significance of PLEK2 in driving oncogenesis and metastasis in ESCC by regulating LCN2 which activates AKT pathway. We also indicated that PLEK2 was associated with chemo-resistance. Our findings indicates the potential use of PLEK2 as a prognostic biomarker and a candidate therapeutic target in ESCC. Keywords: PLEK2; ESCC; TGF-β; chemo-resistance Citation Format: Feng Wang, Chaoqi Zhang, Chengming Liu, Hong Cheng, Nan Sun, Jie He. TGF-β induced PLEK2 promotes metastasis and chemoresistance in ESCC by up-regulation of LCN2 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1981.
A deep neural network-based transfer learning to enhance the performance and learning speed of BCI systems
Authors: Maryam Dehghani, Ali Mobaien, Reza Boostani
Journal: Brain-Computer Interfaces (2021)

Brain–computer interfaces (BCIs) suffer from a lack of classification accuracy when the number of electroencephalography (EEG) trials is low. This is therefore during the learning of a BCI for a subject, there is no clear protocol to use the captured knowledge of other trained BCIs. To overcome this, we have proposed a new parallel deep neural structure containing long short-term memory and multi-layer perception. Furthermore, a subject-to-subject transfer learning is exploited to improve both performance and learning speed. First, the proposed combinatorial classifier is trained over different subjects, then for each new case, a copy of this learned network is adopted to be fine-tuned by the EEG features of the new subject. The proposed method is assessed on an EEG dataset of motor imagery movements and compared to the support vector machines. The proposed method provides superior classification results and significantly speed up the learning process of the deep network.
Abstract 541: Liquid biopsy for molecular characterization and monitoring in patients with metastatic colorectal cancer
Authors: Milena Urbini, Giorgia Marisi, Alessandro Passardi, Chiara Molinari, Matteo Canale, Laura Matteucci, Gianluca Tedaldi, Giovanni Martinelli, Giovanni L. Frassineti, Ulivi Paola
Journal: Cancer Research (2021)

Abstract The use of liquid biopsy in the clinical management of colorectal cancer (CRC) patients is not yet a routine clinical practice, although it could give important information for tumor baseline characterization and for monitoring during treatment. In this retrospective exploratory study, we examined plasma-circulating tumor DNA (ctDNA) in a series of 27 metastatic CRC patients receiving chemotherapy plus bevacizumab as firstline treatment, both at baseline and at progression. All patients were characterized for RAS and BRAF status on tumor tissue before the start of treatment: 70% of patients were RAS-mutated(16 KRAS, 3 NRAS),15% were BRAF mutated and 15% were RAS/BRAF wild-type. Detection of ctDNA mutations were performed using Oncomine™Colon cfDNA Assay on Ion GeneStudio™ S5 System (Thermofisher). All mutations observed in the tissue were identified also in the baseline ctDNA, excluding one BRAF mutated case that was not detected in the ctDNA. Additional mutations on TP53, APC, PIK3CA, FBXW7 were detected respectively in 11, 12, 3 and 2 cases. TP53 mutations were identified also in 3 RAS/BRAF wild-type cases. Baseline RAS/BRAF variant allele frequency (VAF) lower than 10% was found associated with longer progression free survival (PFS) (log-rank p-value=0.027) (Table 1). At progression, 80% of patients carried the same mutations identified at baseline, and 7 cases carried additional mutations of TP53. Predominantly mutations has a lower VAF at progression with respect to baseline, however RAS/BRAF VAF at progression was found not associated with PFS. In conclusion, we report a concordance-rate &amp;gt;96% between ctDNA and tissue demonstrating the high sensibility of liquid biopsy for detection of mutations in metastatic CRC. Thus, ctDNA could be useful for monitoring of minimal residual disease and tumor heterogeneity during therapeutic treatment. These data, if confirmed in a larger cohort, might support the use of liquid biopsy in the clinical management of CRC patients. Table 1.Relationships between RAS/BRAF mutation VAF and progression free survival during treatmentTimeConditionN. of casesMedian PFS (range), daysχ2p-valueBaselineVAF&amp;lt;10%11504 (244-843)4,8960,0269VAF&amp;gt;10%11373 (41-719)ProgressionVAF&amp;lt;10%14414 (110-763)0,32390,5693VAF&amp;gt;10%8412 (41-843) Citation Format: Milena Urbini, Giorgia Marisi, Alessandro Passardi, Chiara Molinari, Matteo Canale, Laura Matteucci, Gianluca Tedaldi, Giovanni Martinelli, Giovanni L. Frassineti, Ulivi Paola. Liquid biopsy for molecular characterization and monitoring in patients with metastatic colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 541.
Problems in Colon Cancer and a Child With Renal Lymphoma
Authors: W. Charles, G. Joseph, B. Hunis, L. Rankin
Journal: Journal of Clinical Oncology (2005)

5% of all ovarian neoplasms. [4]5][6][7] Although the primary site of the metastatic tumor is classically gastric cancer, primary sites such as colon, breast, and biliary tract have been reported.The diagnosis of a primary gastrointestinal malignancy predates development of ovarian metastases in more than 25% of patients. 8In most other patients, the primary malignancy is identified at the time of oophorectomy or during the postoperative period.In our experience, ovarian metastases show less chemotherapy responsiveness than other sites of metastasis.Independent of chemotherapy sensitivity, patients with this pattern of metastasis may fare worse than patients with other sites of metastatic disease.Five-year overall survival after resection of Krukenberg tumors is 19%, in contrast to 5-year overall survival for resected liver metastases from colorectal carcinoma of 37% in one large series. 9,10Krukenberg tumors should be distinguished from primary ovarian neoplasms, such as primary mucinous adenocarcinoma of the ovary, or the benign signet cell stromal tumor of the ovary, since management of these clinical situations is so different.
Efficacy of short‐term intravenous clindamycin prior to oral clindamycin–rifampicin treatment in hidradenitis suppurativa: a retrospective case series
Authors: G. Nikolakis, A. Kristandt, M. Hauptmann, M. Becker, C.C. Zouboulis
Journal: British Journal of Dermatology (2021)

antibiotics represent the first-line hidradenitis suppurativa (HS) treatment, although HS is not an infectious disease1 . Prolonged antibiotic courses exhibit an anti-inflammatory effect, utilized for treating follicular/inflammatory skin diseases, e.g. acne and rosacea. Clindamycin/rifampicin or tetracyclines are usually administered for 10 to 12 weeks in moderate-to-severe HS treatment1 , mostly based on retrospective studies using non-validated severity scoring systems.
Comparison of Outcomes of Elderly Patients with Acute Myeloid Leukemia (AML) in CR1 Receiving Reduced Intensity Allogeneic Stem Cell Transplantation (RICT) from Matched Sibling (MSD) or Unrelated Donors (URD)
Authors: Thomas L Kiss, Elisabeth Wallhult, Harald Anderson, Robert Delage, Jürgen Finke, Tobias Gedde-Dahl, Vladimir Lj Lazarevic, Kari Remes, David Ritchie, Mitchell Sabloff, Alexandros Spyridonidis, Per Ljungman, Mats Brune
Journal: Blood (2017)
Hepatitis B virus evades immune recognition via RNA adenosine deaminase ADAR1-mediated viral RNA editing in hepatocytes
Authors: Liyuan Wang, Yang Sun, Xiaojia Song, Zehua Wang, Yankun Zhang, Ying Zhao, Xueqi Peng, Xiaodong Zhang, Chunyang Li, Chengjiang Gao, Nailin Li, Lifen Gao, Xiaohong Liang, Zhuanchang Wu, Chunhong Ma
Journal: Cellular and Molecular Immunology (2021)
The genomic landscape of unsuspected, incidentally detected Gleason 7 prostate cancer found on autopsy
Authors: A. Foucal, J. Livingstone, A. Salcedo, C. Kuk, M. Fraser, D. Pushkar, A. Govorov, M. Kovylina, R. Bristow, N.E. Fleshner, T.H. Van Der Kwast, A.R. Zlotta, P. Boutros
Journal: European Urology (2021)
Do Tunisians have a European ancestry?
Authors: Helmi Ben Saad
Journal: European Respiratory Journal (2021)

I read with great interest the recent official European Respiratory Society technical standard entitled "Global Lung Function Initiative reference values for static lung volumes in individuals of European ancestry" [1]. The manuscript is very interesting, and certainly it will mark the "history" of pulmonary function reference equations [2]. In the aforementioned study, 7190 observations from 17 centres were submitted and reference equations were derived for individuals aged 5 to 80 years [1]. The centres were based in 11 countries localised in four continents (Europe, Ocean, America and Africa). Since the vast majority (97.2%) of data came from individuals having a "European ancestry", this expression was used to "describe" the included individuals [1]. The statement that Tunisians have a 100% "European ancestry" is a source of ethnic and historical confusion <https://bit.ly/3v3AY5T>
Effect of Cytisine vs Varenicline on Smoking Cessation
Authors: Ryan J. Courtney, Hayden McRobbie, Piotr Tutka, Natasha A. Weaver, Dennis Petrie, Colin P. Mendelsohn, Anthony Shakeshaft, Saki Talukder, Christel Macdonald, Dennis Thomas, Benjamin C. H. Kwan, Natalie Walker, Coral Gartner, Richard P. Mattick, Christine Paul, Stuart G. Ferguson, Nicholas A. Zwar, Robyn L. Richmond, Christopher M. Doran, Veronica C. Boland, Wayne Hall, Robert West, Michael Farrell
Journal: JAMA (2021)

<h3>Importance</h3> Cytisine is more effective than placebo and nicotine replacement therapy for smoking cessation. However, cytisine has not been tested against the most effective smoking cessation medication, varenicline, which is associated with adverse events known to lead to discontinuation of therapy. <h3>Objective</h3> To examine whether standard cytisine treatment (25 days) was at least as effective as standard varenicline treatment (84 days) for smoking cessation. <h3>Design, Setting, and Participants</h3> This noninferiority, open-label randomized clinical trial with allocation concealment and blinded outcome assessment was undertaken in Australia from November 2017 through May 2019; follow-up was completed in January 2020. A total of 1452 Australian adult daily smokers willing to make a quit attempt were included. Data collection was conducted primarily by computer-assisted telephone interview, but there was an in-person visit to validate the primary outcome. <h3>Interventions</h3> Treatments were provided in accordance with the manufacturers' recommended dosage: cytisine (n = 725), 1.5-mg capsules taken 6 times daily initially then gradually reduced over the 25-day course; varenicline (n = 727), 0.5-mg tablets titrated to 1 mg twice daily for 84 days (12 weeks). All participants were offered referral to standard telephone behavioral support. <h3>Main Outcomes and Measures</h3> The primary outcome was 6-month continuous abstinence verified using a carbon monoxide breath test at 7-month follow-up. The noninferiority margin was set at 5% and the 1-sided significance threshold was set at .025. <h3>Results</h3> Among 1452 participants who were randomized (mean [SD] age, 42.9 [12.7] years; 742 [51.1%] women), 1108 (76.3%) completed the trial. Verified 6-month continuous abstinence rates were 11.7% for the cytisine group and 13.3% for the varenicline group (risk difference, −1.62% [1-sided 97.5% CI, −5.02% to ∞];<i>P</i> = .03 for noninferiority). Self-reported adverse events occurred less frequently in the cytisine group (997 events among 482 participants) compared with the varenicline group (1206 events among 510 participants) and the incident rate ratio was 0.88 (95% CI, 0.81 to 0.95;<i>P</i> = .002). <h3>Conclusions and Relevance</h3> Among daily smokers willing to quit, cytisine treatment for 25 days, compared with varenicline treatment for 84 days, failed to demonstrate noninferiority regarding smoking cessation. <h3>Trial Registration</h3> anzctr.org.au Identifier:ACTRN12616001654448
Impact of Endothelial Dysfunction on Residual Platelet Aggregability after Dual Antiplatelet Therapy in Stable Patients with Coronary Artery Disease
Authors: Fujisue Koichiro, Sugiyama Seigo, Ono Takamichi, Mizobe Michio, Yamamoto Koichiro, Akiyama Eiichi, Matsuzawa Yasushi, Kurokawa Hirofumi, Maeda Hirofumi, Matsubara Junichi, Iwashita Satomi, Yamamoto Eiichiro, Kaikita Koichi, Hokimoto Seiji, Nakagawa Kazuko, Ogawa Hisao
Journal: Circulation (2013)