tbuckley/cabot-search huggingface dataset:
An engineered cell-laden adhesive hydrogel promotes craniofacial bone tissue regeneration in rats
Authors: Mohammad Mahdi Hasani-Sadrabadi, Patricia Sarrion, Sevda Pouraghaei, Yee Chau, Sahar Ansari, Song Li, Tara Aghaloo, Alireza Moshaverinia
Journal: Science Translational Medicine (2020)

Cell-laden hydrogels are widely used in tissue engineering and regenerative medicine. However, many of these hydrogels are not optimized for use in the oral environment, where they are exposed to blood and saliva. To address these challenges, we engineered an alginate-based adhesive, photocrosslinkable, and osteoconductive hydrogel biomaterial (AdhHG) with tunable mechanical properties. The engineered hydrogel was used as an injectable mesenchymal stem cell (MSC) delivery vehicle for craniofacial bone tissue engineering applications. Subcutaneous implantation in mice confirmed the biodegradability, biocompatibility, and osteoconductivity of the hydrogel. In a well-established rat peri-implantitis model, application of the adhesive hydrogel encapsulating gingival mesenchymal stem cells (GMSCs) resulted in complete bone regeneration around ailing dental implants with peri-implant bone loss. Together, we have developed a distinct bioinspired adhesive hydrogel with tunable mechanical properties and biodegradability that effectively delivers patient-derived dental-derived MSCs. The hydrogel is photocrosslinkable and, due to the presence of MSC aggregates and hydroxyapatite microparticles, promotes bone regeneration for craniofacial tissue engineering applications.
Assessment of a novel immunological biomarker SNP panel from a phase III trial of Bacillus Calmette-Guérin (BCG) adjuvant treatment in stage III melanoma patients.
Authors: Connie Ging Ting Chiu, Donald L. Morton, Kelly Chong, Mirei Hoshino, Sharon Huang, Michael Bruce Nicholl, David Elashoff, Dave S. B. Hoon
Journal: Journal of Clinical Oncology (2012)

2519 Background: Melanoma is an immunogenic cancer, whereby immunotherapy in stage III patients has shown some success. However, there are no effective immune biomarker tests to identify patients most likely to benefit from immunotherapy. BCG (Bacillus Calmette-Guérin) therapy is a form of immunomodulation. The objective was to assess the predictive clinical effect of a single nucleotide polymorphism(SNP) immune biomarker panel in stage III resected melanoma patients treated with BCG. Methods: MMAIT-III was a phase III prospective randomized international multicenter trial of BCG+melanoma vaccine vs BCG+placebo after complete resection of stage III melanoma patients (NIH #NCT00052130). 120/292 patients with palpable disease treated with resection and BCG+placebo had lymphocytes(PBL) from USA sites available for analysis. Endpoints were overall survival(OS) and disease-free survival(DFS), with a 10-yr follow-up. PBL DNA was assessed by MassARRAY MALDI-TOF for 28 SNPs associated with macrophage/monocyte-related immune response pathways to BCG/tuberculosis. A pilot study(n=34) from phase II BCG trial confirmed presence of the SNPs. A logistic regression determined a SNP score, and a cutoff was identified by ROC and used as a predictor in a Cox proportional hazard model in a verification study(n=120). Results: 9 SNPs in 6 genes had prognostic value: NRAMP1 and CD14, 18, 195, 209, 282. The 9-SNP panel distinguished patients in 2 survival groups(OS median 4.9-yrs vs 1.5-yrs, p=0.0008), AUC=0.77. SNP biomarker positivity demonstrates significant association with 10-yr OS (59.7% vs 15.7%; HR 1.97, CI 1.11-3.50, p=0.018) and DFS (47.2% vs 12.3%; HR 2.35, CI 1.43-3.92, p=0.0007). In Cox model, the SNP panel was a significant predictor of OS(HR 2.69, CI 1.56-9.00, p=0.0052) and DFS(HR 2.33, CI 1.49-5.16, p=0.0003) independent of known melanoma prognostic factors. Conclusions: The 9-SNP panel identified patients with an exceptionally favourable disease outcome, and may represent a stratifying predictive SNP panel for identifying patients that are inherently responsive to BCG therapy and potentially other immunomodulating agents in melanoma.
Autism-Associated Shank3 Is Essential for Homeostatic Compensation in Rodent V1
Authors: Vedakumar Tatavarty, Alejandro Torrado Pacheco, Chelsea Groves Kuhnle, Heather Lin, Priya Koundinya, Nathaniel J. Miska, Keith B. Hengen, Florence F. Wagner, Stephen D. Van Hooser, Gina G. Turrigiano
Journal: Neuron (2020)
Quality assurance in surgical trials of new techniques
Authors: R. E. Mansel, F. McNeill
Journal: Journal of Clinical Oncology (2006)

10584 Most surgical trials include quality assurance for data and documentation, but the variable of surgical performance is often ignored, even when new techniques form one arm of the trial. Recent trials of sentinel node biopsy (NSABP-B32, ALMANAC, and AMAROS) have have attempted to control this variable by pre randomisation audit of surgical performance, but logistics and cost have limited this approach. The B-32 and ALMANAC trials did show that defined and validated pre trial audits produced high rates for localisation of the sentinel node (&gt;95%) and false negative rates of &lt;10%. However these results from motivated trial surgeons/teams may not be reproduced when the techniques are rolled out for general use. In the UK participation in the NEW START national training programme has been endorsed by the Health Department as evidence of satisfactory training in sentinel node biopsy. Surgeons and their teams attend a standardised theory session backed up with detailed training material on DVD. Then a training team visits with the surgical team and supervises the first 5 procedures performed by the surgeon in his own OR, after which a further 25 procedures with completion ALND are performed. All these data are evaluated prospectively centrally. A performance standard of &gt;90% localisation rate and &lt;10% false negative was set prospectively to determine if the surgeon is eligible for certification. The programme is currently achieving 98% localisation and &lt;5% false negative rates in surgeons who have never performed the procedure previously, and 50% of breast surgeons in England have attended the theoretical module of the training. These data suggest that surgical trials involving new techniques should be preceeded by training and individual surgeon audit prior to randomising patients. Abbreviations OR = Operating Room ALND = Axillary Lymph Node Dissection. No significant financial relationships to disclose.
ELEVATED AORTIC GRADIENTS AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT IN BICUSPID AORTIC VALVES
Authors: Adamantios Tsangaris, Chris Reiff, Alexandra Hall, Ganesh Raveendran, Rosemary Kelly, Demetris Yannopoulos, Sergey Gurevich
Journal: Journal of the American College of Cardiology (2020)
Benchmarking population-based EGFR mutation testing in nonsquamous non-small cell lung cancer.
Authors: Carolyn Jane Shiau, Jesse Paul Babwah, Gilda Da Cunha Santos, Jenna R Sykes, Scott L. Boerner, William R. Geddie, Cuihong Wei, Suzanne Kamel-Reid, David M Hwang, Ming Sound Tsao
Journal: Journal of Clinical Oncology (2013)

e19032 Background: Epidermal growth factor receptor (EGFR) mutation testing has become critical in the treatment of advanced non-small cell lung cancer (NSCLC) patients. This study involves a large cohort and epidemiologically unselected series of EGFR mutation testing for non-squamous NSCLC patients in a North American population, to determine mutation rates and define factors that influence success in routine clinical EGFR testing. Methods: Data from consecutive cases of Canadian province-wide testing during a 24-month period at a centralized diagnostic laboratory were reviewed. Samples were tested for exon 19 deletion and exon 21 L858R mutations using a validated PCR method with 1-5% detection sensitivity. Results: From 2,651 samples submitted, 2,404 samples were tested with 2,293 samples eligible for analysis. These included 1,780 histology and 513 cytology specimens. The overall test failure rate was 5.4%. Among successfully tested samples, the overall mutation rate was 20.6%. There were no significant differences in the failure rate, mutation rate, or mutation type found between histology and cytology samples. While tumor cellularity was significantly associated with test success or mutation rates in histology and cytology specimens respectively, mutations could be detected in all specimen types. Optimal histology samples contained ≥2 mm 2 of tumor tissue and ≥30% tumor cellularity. Optimal cytology cell-block samples have at least a few groups of nucleated cells dispersed throughout the block, regardless of tumor cellularity. Samples from metastatic deposits in bone, distant lymph nodes, and pleura showed higher mutation rates than primary lesions. Conclusions: Our current method for EGFR mutation testing is able to detect mutations in small tumor volume biopsies, typical of tissue obtained for initial diagnosis. EGFR mutation testing should be attempted in any type of specimen, histology or cytology. Cases that are suboptimal with a negative EGFR mutation result should be considered for repeat testing with an alternate tumor sample.
SOLUBLE FMS-LIKE TYROSINE KINASE-1 (SFLT-1) IS ASSOCIATED WITH SUBCLINICAL AND CLINICAL ASCVD: THE DALLAS HEART STUDY
Authors: Rina Mauricio, Kavisha Singh, Monika Sanghavi, Colby Ayers, Anand Rohatgi, Wanpen Vongpatanasin, James de Lemos, Amit Khera
Journal: Journal of the American College of Cardiology (2020)
GENETIC EVALUATION OF CARDIOMYOPATHIES IN QATAR IDENTIFIES NOVEL SARCOMERE GENE VARIANTS AND FOUNDER ARABIC MUTATIONS FOR THE DISEASE
Authors: Mohammed Alhashemi, Kholoud Al Shafai, Chidambaram Manickam, Rania Musa, Najeeb Syed, Senthli Selvaraj, Fazulur Vempalli, Magdi Yacoub, Xavier Estivill
Journal: Journal of the American College of Cardiology (2020)
THE INFLUENCE OF ANATOMICAL AND GENETIC FACTORS ON LONG-TERM OUTCOMES IN TETRALOGY OF FALLOT: A 35-YEAR POPULATION-BASED COHORT
Authors: Samuel Blais, Ariane Marelli, Alain Vanasse, Christian Drolet, Adrian Dancea, Nagib Dahdah, Frederic Dallaire
Journal: Journal of the American College of Cardiology (2020)
THE BET PROTEIN INHIBITOR APABETALONE REDUCES CONGESTIVE HEART FAILURE INCIDENCE IN PATIENTS WITH ACUTE CORONARY SYNDROME AND DIABETES: RESULTS FROM THE BETONMACE TRIAL
Authors: Michael Sweeney, Stephen J. Nicholls, Kausik Kumar Ray, Kevin Buhr, Henry Ginsberg, Jan Johansson, Kamyar Kalantar-Zadeh, Ewelina Kulikowski, Peter Toth, Norman Wong, Gregory G. Schwartz
Journal: Journal of the American College of Cardiology (2020)
Abstract 10399: New Definition of Hypertension and Lifestyle Modification Treatment Recommendations From the 2017 U.S. Guideline for High Blood Pressure (BP) in Adults: Implications From a Sample of Family Medicine Clinics
Authors: Gregory Wozniak, Michael Rakotz, Jianing Yang, Susan Sutherland, R. Bruce Hanlin, Robert Davis, Brent Egan
Journal: Circulation (2018)

Introduction: The 2017 AHA/ACC Hypertension Guideline (HGL) lowers the threshold for defining hypertension (HTN) to BP ≥ 130/80 mmHg and sets treatment targets for most patients to <130/80 mmHg. Th...
ASSOCIATION OF HEALTH STATUS WITH LONG-TERM SURVIVAL IN PERIPHERAL ARTERY DISEASE
Authors: Andy Tran, John A. Spertus, Herbert D. Aronow, Carlos I. Mena-Hurtado, Ali Malik, Mehdi Shishehbor, Philip Jones, David Safley, Yuanyuan Tang, Clementine Labrosciano, Kim Smolderen
Journal: Journal of the American College of Cardiology (2020)
Using blended learning to improve education on clinical pathways for breast cancer management in Nigeria: Preliminary results.
Authors: Kelechi Ngozi Eguzo, Nofisat Ismaila, Usenime Akpanudo, Oluoha Chukwuemeka, Aniekan Jacob, Mfonobong Udoekong, Charles Adeyinka Adisa
Journal: Journal of Clinical Oncology (2019)

10539 Background: Most Nigerian clinicians lack adequate skills and resources in screening, diagnosis, and managing women with breast cancer. The absence of locally-sensitive clinical pathways in hospitals in Abia State impact patient outcomes and clinicians job satisfaction. Blended learning (BL), a combination of online and face-to-face teaching methods, has been used in other settings to improve the competencies of clinicians. Research seeks to develop and evaluate a BL course that will train clinicians in Abia State on using NCCN breast cancer management guidelines, and to develop and implement locally-sensitive clinical pathways. Methods: The course is divided into four online modules delivered via Google Classroom and a workshop module to be delivered in 3 cities. Course evaluation involves an objective-focused method, following a mixed-methods design. Data collection includes pre-and-post-tests, course evaluation and focus group discussions. Data analysis involved descriptive statistics and t-test. Comments deductively analyzed to identify common themes. A sample size of 107 individuals is required to identify a moderate effect size for the BL course. Results: Forty-three participants (physicians=15, Nurses=28) have been recruited for cohort 1, with average age of 44 (±9.9) years. Most participants have never taken an online class (65%) but use mobile phones (60%) to access the course. With a maximum of 20 points in each test, there is a pattern of improvement in the post-tests performance compared with the pre-tests. Table shows mean scores. Most participants have expressed satisfaction with the course. Conclusions: Results show improvement in learning. More participants are being recruited. The workshops will hold at after the online modules.[Table: see text]
Glioma stem-like cells evade interferon suppression through MBD3/NuRD complex–mediated STAT1 downregulation
Authors: Xiaoyan Zhan, Saisai Guo, Yuanyuan Li, Haowen Ran, Haohao Huang, Lanjuan Mi, Jin Wu, Xinzheng Wang, Dake Xiao, Lishu Chen, Da Li, Songyang Zhang, Xu Yan, Yu Yu, Tingting Li, Qiuying Han, Kun He, Jiuwei Cui, Tao Li, Tao Zhou, Jeremy N. Rich, Shideng Bao, Xuemin Zhang, Ailing Li, Jianghong Man
Journal: The Journal of Experimental Medicine (2020)

Type I interferons (IFNs) are known to mediate antineoplastic effects during tumor progression. Type I IFNs can be produced by multiple cell types in the tumor microenvironment; however, the molecular mechanisms by which tumor cells evade the inhibition of immune microenvironment remain unknown. Here we demonstrate that glioma stem-like cells (GSCs) evade type I IFN suppression through downregulation of STAT1 to initiate tumor growth under inhospitable conditions. The downregulation of STAT1 is mediated by MBD3, an epigenetic regulator. MBD3 is preferentially expressed in GSCs and recruits NuRD complex to STAT1 promoter to suppress STAT1 expression by histone deacetylation. Importantly, STAT1 overexpression or MBD3 depletion induces p21 transcription, resensitizes GSCs to IFN suppression, attenuates GSC tumor growth, and prolongs animal survival. Our findings demonstrate that inactivation of STAT1 signaling by MBD3/NuRD provides GSCs with a survival advantage to escape type I IFN suppression, suggesting that targeting MBD3 may represent a promising therapeutic opportunity to compromise GSC tumorigenic potential.
A Phase I/II Study of Neoadjuvant Cisplatin, Docetaxel, and Nintedanib for Resectable Non–Small Cell Lung Cancer
Authors: Tina Cascone, Boris Sepesi, Heather Y. Lin, Neda Kalhor, Edwin R. Parra, Mei Jiang, Myrna C.B. Godoy, Jianjun Zhang, Frank V. Fossella, Anne S. Tsao, Vincent K. Lam, Charles Lu, Frank E. Mott, George R. Simon, Mara B. Antonoff, Reza J. Mehran, David C. Rice, Carmen Behrens, Annikka Weissferdt, Cesar Moran, Ara A. Vaporciyan, J. Jack Lee, Stephen G. Swisher, Don L. Gibbons, Ignacio I. Wistuba, William N. William, John V. Heymach
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Nintedanib enhances the activity of chemotherapy in metastatic non–small cell lung cancer (NSCLC). In this phase I/II study, we assessed safety and efficacy of nintedanib plus neoadjuvant chemotherapy, using major pathologic response (MPR) as primary endpoint. Patients and Methods: Eligible patients had stage IB (≥4 cm)–IIIA resectable NSCLC. A safety run-in phase was followed by an expansion phase with nintedanib 200 mg orally twice a day (28 days), followed by three cycles of cisplatin (75 mg/m2), docetaxel (75 mg/m2) every 21 days plus nintedanib, followed by surgery. With 33 planned patients, the study had 90% power to detect an MPR increase from 15% to 35%. Results: Twenty-one patients (stages I/II/III, N = 1/8/12) were treated. One of 15 patients treated with nintedanib 200 mg achieved MPR [7%, 95% confidence interval (CI), 0.2%–32%]. Best ORR in 20 evaluable patients was 30% (6/20, 95% CI, 12%–54%). Twelve-month recurrence-free survival and overall survival were 66% (95% CI, 47%–93%) and 91% (95% CI, 79%–100%), respectively. Most frequent treatment-related grade 3–4 toxicities were transaminitis and electrolyte abnormalities. On the basis of an interim analysis the study was discontinued for futility. Higher levels of CD3+ and cytotoxic CD3+CD8+ T cells were found in treated tumors of patients who were alive than in those who died (652.8 vs. 213.4 cells/mm2, P = 0.048; 142.3 vs. 35.6 cells/mm2, P = 0.018). Conclusions: Although tolerated, neoadjuvant nintedanib plus chemotherapy did not increase MPR rate compared with chemotherapy historical controls. Additional studies of the combination in this setting are not recommended. Posttreatment levels of tumor-infiltrating T cells were associated with patient survival. Use of MPR facilitates the rapid evaluation of neoadjuvant therapies. See related commentary by Blakely and McCoach, p. 3499
COX2 inhibits TGFβ signaling through GSK3β mediated Smad3 inhibition
Authors: Jason Neil, William Schiemann
Journal: Cancer Research (2008)

5111  Introduction: Cycloxygenase 2 (COX2) expression is often increased in breast cancer and is regulated by Transforming Growth Factor β (TGFβ), whose tumor suppressing function typically becomes deregulated in cancer progression. Normal Murine Mammary Gland (NMuMG) epithelial cells do not express COX2, while metastatic murine breast cancer (4T1) cells express high levels of COX2 and are highly tumorigenic. The purpose of the present study was to determine the effect of COX2 overexpression on TGFβ mediated signaling, and to determine whether targeting COX2 effectors could restore the tumor suppressing properties of TGFβ. Experimental procedures: Transient and stable expression of COX2, GSK3β, and Smad3 cDNA constructs were performed in NMuMG and 4T1 cells. Assessment of TGFβ function and alter gene expression was measured using luciferase reporter and real time PCR analyses. PGE2 production was determined by ELISA analysis. Altered protein expression and activation of GSK3β and MAP kinase signaling was determined by western blot analyses. Results: Upon induction of EMT by TGFβ, NMuMG cells significantly increased their expression of COX2 mRNA and protein as measured by COX2 promoter driven luciferase reporter (5.21±0.48 fold increase), real time PCR (66±30 relative copy numbers), and western blot analyses. Coupled with this EMT driven change was a 5 fold increase in protaglandin E2 (PGE2) production. Overexpression of COX2 inhibited TGFβ signaling in NMuMG cells, as measured by Smad3 driven luciferase reporter activity (20±10% of control). Likewise, treatment of NMuMG cells with PGE2 activated GSK3β and Erk1/2 MAP kinase, and inhibited Smad3 driven luciferase reporter activity. Treatment of 4T1 cells with the GSK3β inhibitor XIII (50nM) significantly increased TGFβ mediated Smad3 driven luciferase activity. Expression of constitutively active GSK3β in NMuMG cells and dominant negative GSK3β in 4T1 cells confirmed the inhibitory activity of GSK3β on Smad3 activity. Expression of a T66A Smad3 mutant, which contains a mutation of a potential phosphorylation site, only altered Smad3 signaling in metastatic 4T1 cells, not in normal NMuMG cells. Conclusion: Our findings indicate that the loss of tumor suppression mediated by TGFβ can be attributed to the overexpression of COX2 and its consequential production of PGE2, which activates GSK3β. Therefore pharmacological targeting COX2 and/or GSK3β may help in restoring the tumor suppressing properties of TGFβ in malignant, metastatic breast cancer cells.
Bevacizumab (BEV) plus capecitabine as maintenance therapy after initial treatment with BEV plus XELOX in previously untreated patients (pts) with metastatic colorectal cancer (mCRC): Mature data from STOP and GO, a phase III, randomized, multicenter study.
Authors: Suayib Yalcin, Ruchan Uslu, Faysal Dane, Ugur Yilmaz, Nurullah Zengin, Evin Buyukunal, Suleyman Buyukberber, Celalettin Camci, Orhan Sencan, Saadettin Kilickap, Fatih Ozdener, Duygu Cevik
Journal: Journal of Clinical Oncology (2012)

3565 Background: Colorectal cancer is one of the most frequent malignancies, second after breast cancer in women and third after lung cancer and prostate cancer in men. The aim of this study was to evaluate and compare the progression-free survival (PFS) between two arms: Arm A is a combination of BEV + XELOX; Arm B is a combination of BEV + XELOX for 6 cycles followed by maintenance BEV + capecitabine as first-line therapy in mCRC. Methods: BEV (7.5 mg/kg) + XELOX (capecitabine 1000 mg/m 2 bid d1–14 + oxaliplatin 130 mg/m 2 d1 q3w) were administered until progression (Arm A) or 6 cycles of BEV + XELOX followed by BEV + capecitabine were administered until progression (Arm B). PFS was the primary endpoint; secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. A sample size of 118 pts was required to detect with 80% power an increase of 1.5 months in median PFS between two arms with a standard deviation of 3.9 months and significance level of 0.05 (10% drop-out rate). Results: A total of 123 pts were randomized. Demographic characteristics were balanced between the arms. Median treatment period was 7.5 (range 0.5–13.9) and 8.1 (range 0.1–20.7) months in Arms A and B, respectively. There was a statistically significant difference in median PFS between arms, although there was no significant difference in ORR and OS (see table). Tolerability was acceptable in both arms with the following grade 3/4 adverse events (AEs): Arm A 48.4%; Arm B 34.4% (p=0.116). Grade 3/4 diarrhoea occurred in 9.7% vs. 3.3%, weakness in 8.1% vs. 8.2%, hand-foot syndrome in 3.2% vs. 1.6%, and neuropathy in 4.8% vs. 3.3% of pts in Arms A and B, respectively. Conclusions: These findings suggest that maintenance therapy with BEV + capecitabine following induction with 6 cycles of BEV + XELOX may be superior to continuous BEV + XELOX until progression inpts with previously untreated mCRC. [Table: see text]
VENTRICULAR ARRHYTHMIAS AND CLINICAL OUTCOMES IN PATIENTS WITH LEFT MAIN DISEASE TREATED WITH PCI OR CABG: THE EXCEL TRIAL
Authors: Ioanna Kosmidou, Bahira Shahim, Manel Sabate, José L. Pomar, Anthony Gershlick, Pawel Buszman, Andrej Bochenek, Aaron Crowley, Patrick Serruys, Joseph Sabik, A. Kappetein, Gregg Stone
Journal: Journal of the American College of Cardiology (2020)
FEATURE TRACKING MULTI-DETECTOR ROW COMPUTED TOMOGRAPHY-DERIVED LEFT VENTRICULAR GLOBAL LONGITUDINAL STRAIN IN A LARGE COHORT OF TAVR PATIENTS AND ASSOCIATION WITH ALL-CAUSE MORTALITY
Authors: Tea Gegenava, Pieter van der Bijl, Elise Mara Vollema, Frank Kley, Arend de Weger, David Hautemann, Johan H.C. Reiber, Nina Ajmone Marsan, Jeroen Bax, Victoria Delgado
Journal: Journal of the American College of Cardiology (2020)