tbuckley/cabot-search huggingface dataset:
Validation of Postoperative Angiofibroma Radionuclide Imaging Study (PARIS) Protocol Using PSMA PET/CT—A Proof of Concept Study
Authors: Alok Thakar, Pirabu Sakthivel, Sreedharan Thankarajan Arunraj, Ashu Seith Bhalla, Arun Prashanth, Rakesh Kumar, Suresh Chandra Sharma, Rakesh Kumar
Journal: Clinical Nuclear Medicine (2021)

Juvenile nasopharyngeal angiofibroma (JNA) expresses prostate-specific membrane antigen (PSMA), and PSMA PET/CT scan may be used for its imaging. Also, the precise diagnosis of residual/recurrent JNA after surgical treatment remains difficult with conventional contrast MRI and/or CT; functional imaging with PSMA PET/CT promises greater accuracy in the detection or exclusion of recurrent/residual JNA.In this prospective study, 22 postoperative JNA patients who underwent a PSMA PET/CT scan both preoperatively and postoperatively from January 2018 to September 2020 were included. All patients underwent a low-dose head and neck spot PET/CT imaging. Abnormal postcontrast enhancement of a definite lesion was considered residual/recurrent tumor in contrast-enhanced MRI (CEMRI). In PSMA PET/CT, any abnormal uptake apart from physiological sites in the head and neck was considered as residual lesions. Radiological results were categorized as negative, suspicious for residual lesions, or definite residual/recurrent tumors. PSMA PET/CT findings were considered as the radiological standard, and patients were managed accordingly. The sensitivity, specificity, positive predictive value, and negative predictive value were separately calculated for CEMRI and PSMA PET/CT for diagnosing residual lesions.On postoperative CEMRI evaluation, 12 patients had residual tumors, 2 had normal suspicious scans, and 8 had normal postoperative scans. On PSMA PET/CT, only 7 patients had residual tumors and 15 had normal postoperative scans. In 1 patient with a residual tumor on both scans, a discrepancy was noted concerning tumor extent, and PSMA PET/CT accurately mapped the tumor. The sensitivity, specificity, positive predictive value, and negative predictive value of CEMRI were 100%, 53.33%, 41.67%, and 100%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of PSMA PET/CT were 100% for all parameters.Because CEMRI is oversensitive and less specific compared with PSMA PET/CT, Postoperative Angiofibroma Radionuclide Imaging Study (PARIS) protocol should be used always. In residual tumors, PSMA PET/CT has an outright advantage over CEMRI in the diagnosis, tumor mapping, decision making, planning stereotactic radiation, and aiding in future follow-ups.
Sorafenib or placebo in patients with newly diagnosed acute myeloid leukaemia: long-term follow-up of the randomized controlled SORAML trial
Authors: Christoph Röllig, Hubert Serve, Richard Noppeney, Maher Hanoun, Utz Krug, Claudia D. Baldus, Christian H. Brandts, Volker Kunzmann, Hermann Einsele, Alwin Krämer, Carsten Müller-Tidow, Kerstin Schäfer-Eckart, Andreas Neubauer, Andreas Burchert, Aristoteles Giagounidis, Stefan W. Krause, Andreas Mackensen, Walter Aulitzky, Regina Herbst, Mathias Hänel, Norbert Frickhofen, Johannes Kullmer, Ulrich Kaiser, Alexander Kiani, Hartmut Link, Thomas Geer, Albrecht Reichle, Christian Junghanß, Roland Repp, Achim Meinhardt, Heinz Dürk, Ina-Maria Klut, Martin Bornhäuser, Markus Schaich, Stefani Parmentier, Martin Görner, Christian Thiede, Malte von Bonin, Uwe Platzbecker, Johannes Schetelig, Michael Kramer, Wolfgang E. Berdel, Gerhard Ehninger
Journal: Leukemia (2021)

Abstract Early results of the randomized placebo-controlled SORAML trial showed that, in patients with newly diagnosed acute myeloid leukaemia (AML), sorafenib led to a significant improvement in event-free (EFS) and relapse-free survival (RFS). In order to describe second-line treatments and their implications on overall survival (OS), we performed a study after a median follow-up time of 78 months. Newly diagnosed fit AML patients aged ≤60 years received sorafenib ( n = 134) or placebo ( n = 133) in addition to standard chemotherapy and as maintenance treatment. The 5-year EFS was 41 versus 27% (HR 0.68; p = 0.011) and 5-year RFS was 53 versus 36% (HR 0.64; p = 0.035). Allogeneic stem cell transplantation (allo SCT) was performed in 88% of the relapsed patients. Four years after salvage allo SCT, the cumulative incidence of relapse was 54 versus 35%, and OS was 32 versus 50%. The 5-year OS from randomization in all study patients was 61 versus 53% (HR 0.82; p = 0.282). In conclusion, the addition of sorafenib to chemotherapy led to a significant prolongation of EFS and RFS. Although the OS benefit did not reach statistical significance, these results confirm the antileukaemic activity of sorafenib.
Abstract SP125: Rescue DNA repair pathway and tumor immunity
Authors: M Rao
Journal: Cancer Research (2021)

Abstract Defects in DNA damage response (DDR) is a major factor that predispose normal cells to acquire oncogenic mutations. However, after a tumor develops, cancer cells manage their survival by repairing DNA damage resulting from unchecked DNA replication. Cancer cells can use the alternative or backup (rescue) DNA repair programs to overcome their DDR defects and cope with genotoxic lesions. For example, breast cancer cells with deficiency in homologous recombination (HR) can repair their DNA by either relying on other highly expressed HR-related proteins (such as RAD51 or PARP1), or by using other DNA repair mechanisms such as break-induced replication, alternative nonhomologous end joining (ALT-NHEJ) and basal excision repair (BER). Since DNA repair pathways operate in related networks in cancers in general and breast cancers in particular, it is likely that factor/s that play important roles in multiple DNA repair pathways may serve as a critical component of backup DNA repair pathways that breast cancer cells get addicted to survive and to become therapy resistant. One way these rescue DNA repair pathway factor/s may promote breast cancer progression is by shaping tumor immune microenvironment. Consistent with that, DNA damage and DNA repair pathways in general have been shown to regulate multiple arms of the immune response including antigenicity or tumor mutational burden (TMB) and regulation of immune checkpoint protein levels. Our studies suggest that rescue DNA repair pathways may support tumor progression and therapy response by promoting tumor cell intrinsic and extrinsic mechanisms of immunosuppression. Our results reveal that factors associated with backup DNA repair pathwaysmay promote immunosuppression by altering cGAS-STING and Type I Interferon (IFN) signaling pathways. Furthermore, using a specific inhibitor that targets rescue DNA repair pathway signaling, we show altered levels of several proteins involved in antigen processing and presentation, including proteasome/Immunoproteasome subunits and MHC I protein subunits, which are essential for the detection of cancer cells by cytotoxic T cells. Importantly, our pre-clinical and clinical data suggest that approaches aimed at successfully targeting rescue DNA repair factor(s) may promote anti-tumor immunity and will have promising clinical outcomes for treating breast cancer patients. Citation Format: M Rao. Rescue DNA repair pathway and tumor immunity [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 SP125.
Hyper-Functional Synthetic Transgenes Improve the Efficiency of Lentiviral and AAV- Based Liver-Directed Gene Therapy and Induce Immune Tolerance: Conference: 16th Annual Meeting of the ASGCT, Location: Salt Lake City, UT, Date: MAY 15-18, 2013, By: Nisha Nair, Alessio Cantore, Mario Di Matteo, Patrizia Della Valle, Jessica Willems, Hanneke Evens, Armando D Angelo, Janka Matrai, Luigi Naldini, Marinee Chuah, Thierry VandenDriessche.
Authors: Nisha Nair Shivsankaran Nair
Journal: Molecular Therapy (2013)
Abstract PS9-63: Real world data on the adoption of trastuzumab biosimilars in the treatment of HER2-positive breast cancer
Authors: William A Flood, Tiffany Avery, Vlad Kozlovsky, Neil Margolis, Sandeep Reddy
Journal: Cancer Research (2021)

Abstract Background: Biosimilars for trastuzumab were introduced into the US market for the treatment of HER2-positive breast cancer in 2019, with the goal of providing the clinical benefit of the brand product at a lower price (increased value). Adoption of trastuzumab biosimilars may be affected by multiple factors, including physician confidence in biosimilar efficacy and efficacy across stages, practice reimbursement, payer medical policy/redirection. To look at the adoption of trastuzumab biosimilars in the US medical oncology community, we queried a database of submitted treatment plans for patients with breast cancer. Methods: Data from a pre-authorization platform used by multiple commercial insurance companies in the US (NantHealth Eviti) was analyzed. Cases were identified from approved treatment plans for patients with breast cancer by inclusion of brand trastuzumab or trastuzumab + hyaluronidase-oysk, or trastuzumab biosimilars. Results: As of July 1, 2020, 10,557 treatment plans trastuzumab-based therapy were submitted, 1740 (16.5%) of which used a trastuzumab biosimilar. Adoption of trastuzumab biosimilars increased over time, from 1.6% (27/1676) treatment plans in Q3-2109 to 43.3% (753/1736) in Q2-2020. No clear differences were observed between use in stage 0-IIIc disease (17.4%) vs stage IV/recurrent disease (14.5%). Using the July 1, 2020 CMS pricing for these drugs at normalized dose of 440 mg for trastuzumab/trastuzumab biosimilars or 600 mg of trastuzumab + hyaluronidase, the average cost/cycle/patient for brand therapy and biosimilar therapy is $4502 and $3618, respectfully, representing a savings of $1,374,620/cycle across the biosimilar-treated population. Additional analyses to be presented will include Q3 2020 utilization and patterns of utilization across payers with/without medical policy favoring biosimilars. Conclusions: Adoption of trastuzumab biosimilars in this commercial population has been rapid since their introduction. Use of these drugs provides a substantial opportunity for societal savings in the treatment of HER2-positive breast cancer. Citation Format: William A Flood, Tiffany Avery, Vlad Kozlovsky, Neil Margolis, Sandeep Reddy. Real world data on the adoption of trastuzumab biosimilars in the treatment of HER2-positive 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 PS9-63.
Real-world disease burden and comorbidities of pediatric prurigo nodularis
Authors: Amy H. Huang, Youkyung Sophie Roh, Nishadh Sutaria, Justin Choi, Kyle A. Williams, Thomas Pritchard, Martin Prince Alphonse, Joseph K. Canner, Anna L. Grossberg, Shawn G. Kwatra
Journal: Journal of the American Academy of Dermatology (2021)
Abstract PS1-26: Sentinel lymph node biopsy alone in locally advanced breast cancer after neoadjuvant chemotherapy: Turkish multicentric neosenti-turk MF-18-02-study
Authors: Neslihan Cabioglu, Hasan Karanlık, Mahmut Muslumanoglu, Guldeniz Karadeniz Çakmak, Didem Can Trablus, Mustafa Tukenmez, Yeliz E. Ersoy, Cihan Uras, Baha Zengel, Selman Emiroğlu, Ayfer Kamalı Polat, Levent Yeniay, Enver Ozkurt, Halil Kara, Kamuran Ibis, Adnan Aydiner, Vahit Ozmen, Abdullah Igci
Journal: Cancer Research (2021)

Abstract BACKGROUND: Omitting axillary lymph node dissection (ALND) following sentinel lymph node biopsy (SLNB) in patients with locally advanced breast cancer (LABC) after neoadjuvant chemotherapy (NAC) is still controversial. In this study, we evaluated factors affecting local recurrence and outcome in patients with LABC, who underwent SLNB alone after NAC. METHODS: Between 2004 to 2018, 320 patients with clinically node-positive LABC who received NAC and underwent SLNB alone after negative axillary staging were analyzed. All patients had breast and/or regional nodal irradiation. RESULTS: Median age was 46 (23-70). Of those, 228 patients had ypN0 disease (71.25%), whereas 92 patients had ypN(+) disease including 19 (20.6%) isolated tumor cells (ITC), 33 micrometastasis (35.9%) and 40 macrometastases (43.5%). At a median follow-up of 37 months (24-172), one patient (0.3%) with macrometastatic SLN having extracapsular extension was found to have locoregional recurrence at the 60th month. Five-year disease-free survival (DFS) and disease specific survival (DSS) rates were found as 87% and 95%, respectively. Patients with cT3&amp;4 (HR=2.22, 95% CI; 1.07-4.62), non-luminal molecular pathology (HR=2.71, 95% CI, 1.23-5.97), and non-pCR in the breast (HR=2.21, 95% CI, 0.94-5.17) were found to have an increased HR compared to others in 5-year DFS. However, no significant differences could be found between patients ypN0, ypN-ITC&amp;micrometastasis and ypN-macrometastasis regarding 5-year DFS and DSS rates. CONCLUSIONS: ALND could be safely avoided in selected patients with LABC who underwent SLNB after NAC having cT1-2, luminal pathology, breast and/or nodal pCR or low volume nodal disease, as long as axillary radiotherapy is provided. Citation Format: Neslihan Cabioglu, Hasan Karanlık, Mahmut Muslumanoglu, Guldeniz Karadeniz Çakmak, Didem Can Trablus, Mustafa Tukenmez, Yeliz E. Ersoy, Cihan Uras, Baha Zengel, Selman Emiroğlu, Ayfer Kamalı Polat, Levent Yeniay, Enver Ozkurt, Halil Kara, Kamuran Ibis, Adnan Aydiner, Vahit Ozmen, Abdullah Igci. Sentinel lymph node biopsy alone in locally advanced breast cancer after neoadjuvant chemotherapy: Turkish multicentric neosenti-turk MF-18-02-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 PS1-26.
Endoscopic full-thickness resection in the rectum closed with PolyLoop-and-clips method using single-channel endoscope
Authors: Edgar Castillo-Regalado, Carlos Huertas, Leyanira Torrealba, Manuela Hombrados, Montserrat Figa, David Busquets, Hugo Uchima
Journal: Endoscopy (2021)

Endoscopic submucosal dissection (ESD) allows en bloc resection regardless of tumor size. It is an effective but technically demanding procedure, with perforation rates of about 5 % [1]. Nevertheless, the safety profile is adequate, because almost all ESD complications can be managed endoscopically and the risk of surgery related to post-ESD complications (1 %) is low [2]. The European Society of Gastrointestinal Endoscopy recommends the use of through-the-scope clips for iatrogenic perforations < 10 mm and consideration of the use of the over-the-scope clip for defects > 10 mm, nonetheless larger iatrogenic perforations or failed closure may require surgical repair [3]. Another purse-string suture technique to close the perforations using a dual-channel endoscope with a PolyLoop (Olympus, Tokyo, Japan) and clips has been described [4].
Interleukin-6 Receptor Inhibition in Covid-19 — Cooling the Inflammatory Soup
Authors: Eric J. Rubin, Dan L. Longo, Lindsey R. Baden
Journal: New England Journal of Medicine (2021)

Viruses cannot replicate by themselves. Instead, they rely on the host for almost all their replicative functions. Similarly, many viruses are unable to cause damage without the host immune system....
Abstract 394: Medium Chain Acyl-Coenzyme a Dehydrogenase Gene Therapy Induces Physiological Cardiac Hypertrophy and Protects Against Pathological Remodeling
Authors: Bianca C Bernardo, Kate L Weeks, Thawin Pongsukwechkul, Xiaoming Gao, Helen Kiriazis, Yow Keat Tham, Xiao-Jun Du, Paul Gregorevic, Julie R McMullen
Journal: Circulation Research (2017)

Introduction: Gene-based therapies represent a realistic and feasible avenue for the treatment of cardiac disease. We previously demonstrated that activation of phosphoinositide 3-kinase [P13K(p110α)] was beneficial in heart failure mouse models and identified PI3K(p110α)-regulated mRNAs. We found that gene expression of medium chain acyl-coenzyme A dehydrogenase (MCAD) to be i) elevated in hearts with increased PI3K activity, ii) reduced in hearts with decreased PI3K activity, iii) reduced in settings of cardiac injury, and iv) positively correlated with cardiac function. Aim: The aim of this study was to determine whether gene delivery of MCAD could attenuate pressure overload-induced pathological remodeling. Methods: Recombinant adeno-associated viral vectors (rAAV) encoding MCAD or a control (2x10 11 vector genomes) were delivered to normal adult mice (n=9) and mice with pre-existing pathological hypertrophy and cardiac dysfunction due to pressure overload, induced by transverse aortic constriction (TAC, n=16). Cardiac function was assessed by echocardiography. Molecular/histological analyses were performed on heart tissue. Results: rAAV6:MCAD delivery promoted physiological growth of the heart in normal mice. Treated mice had larger hearts (Heart weight/tibia length [HW/TL] of rAAV6:control 8.3±0.5 mg/mm vs. HW/TL of rAAV6:MCAD 10.1±0.5 mg/mm, n=4-5/group, P&lt;0.05), thicker left ventricular walls (rAAV6:control 0.82±0.03mm vs. rAAV6:MCAD 1.00±0.05mm, n=3-4/group, P&lt;0.05), preserved systolic function, and no evidence of cardiac fibrosis, lung congestion or re-expression of the fetal genes atrial- and B- type natriuretic peptides. In a setting of pressure overload, mice that received rAAV:MCAD had less left ventricular fibrosis (3.4-fold lower vs. control, n=6-10/group, P&lt;0.05), higher levels of SERCA2a gene expression, and a more favorable metabolic gene expression profile (increased gene expression of Pgc1α , Cpt1b and Glut4 , n=6-10/group, P&lt;0.05) than control mice at the end of the treatment period. Conclusion: In summary, we show that MCAD can promote physiological cardiac hypertrophy in normal mice, and can attenuate fibrosis in a mouse model of cardiac injury.
Going beyond elementary mechanisms: the strategic interplay between grounded procedures
Authors: Peter Kardos
Journal: Behavioral and Brain Sciences (2021)

Abstract The model presented by Lee and Schwarz provides a novel explanation for the elementary mechanisms of psychological cleansing. I argue that the model could be extended to account for complex instances of psychological cleansing where the grounded procedures are not isolated and the opposing motives of separation and connection are entangled in a strategic interplay.
Letter to the Editor: Acute Liver Injury Due to Therapeutic Doses of Acetaminophen—Confounders Must Be Ruled Out!
Authors: Nikhil Vojjala, Rohit Mehtani, Virendra Singh
Journal: Hepatology (2021)

We read the study by Louvet et al (1) describing risk factors and outcomes associated with acute liver injury due to therapeutic doses of acetaminophen (ALITD) with great interest. They conclude that ALITD is associated with severe liver injury and occurs in patients with excess alcohol consumption or fasting. This makes us ponder the mechanisms behind ALITD to prospectively modify host risk factors associated with therapeutic misadventure of acetaminophen. However, certain issues warrant further clarification.
Single Nuclei Sequencing Reveals Novel Insights Into the Regulation of Cellular Signatures in Children With Dilated Cardiomyopathy
Authors: Luka Nicin, Wesley T. Abplanalp, Anne Schänzer, Anke Sprengel, David John, Hannah Mellentin, Lukas Tombor, Matthias Keuper, Evelyn Ullrich, Karin Klingel, Reinhard B. Dettmeyer, Jedrzej Hoffmann, Hakan Akintuerk, Christian Jux, Dietmar Schranz, Andreas M. Zeiher, Stefan Rupp, Stefanie Dimmeler
Journal: Circulation (2021)

Dilated cardiomyopathy (DCM) is a leading cause of death in children with heart failure. The outcome of pediatric heart failure treatment is inconsistent, and large cohort studies are lacking. Progress may be achieved through personalized therapy that takes age- and disease-related pathophysiology, pathology, and molecular fingerprints into account. We present single nuclei RNA sequencing from pediatric patients with DCM as the next step in identifying cellular signatures. We performed single nuclei RNA sequencing with heart tissues from 6 children with DCM with an age of 0.5, 0.75, 5, 6, 12, and 13 years. Unsupervised clustering of 18 211 nuclei led to the identification of 14 distinct clusters with 6 major cell types. The number of nuclei in fibroblast clusters increased with age in patients with DCM, a finding that was confirmed by histological analysis and was consistent with an age-related increase in cardiac fibrosis quantified by cardiac magnetic resonance imaging. Fibroblasts of patients with DCM >6 years of age showed a profoundly altered gene expression pattern with enrichment of genes encoding fibrillary collagens, modulation of proteoglycans, switch in thrombospondin isoforms, and signatures of fibroblast activation. In addition, a population of cardiomyocytes with a high proregenerative profile was identified in infant patients with DCM but was absent in children >6 years of age. This cluster showed high expression of cell cycle activators such as cyclin D family members, increased glycolytic metabolism and antioxidative genes, and alterations in ß-adrenergic signaling genes. Novel insights into the cellular transcriptomes of hearts from pediatric patients with DCM provide remarkable age-dependent changes in the expression patterns of fibroblast and cardiomyocyte genes with less fibrotic but enriched proregenerative signatures in infants.
Junction plakoglobin regulates and destabilizes HIF2α to inhibit tumorigenesis of renal cell carcinoma
Authors: Ke Chen, Jin Zeng, Yi Sun, Wei Ouyang, Gan Yu, Hui Zhou, Yangjun Zhang, Weimin Yao, Wei Xiao, Junhui Hu, Jinchun Xing, Kefeng Xiao, Lily Wu, Zhiqiang Chen, Zhangqun Ye, Hua Xu
Journal: Cancer Communications (2021)

Abstract Background Increased hypoxia‐inducible factor 2α (HIF2α) activation is a common event in clear cell renal cell carcinoma (ccRCC) progression. However, the function and underlying mechanism of HIF2α in ccRCC remains uninvestigated. We conducted this study to access the potential link between junction plakoglobin (JUP) and HIF2α in ccRCC. Methods Affinity purification and mass spectrometry (AP‐MS) screening, glutathione‐s‐transferase (GST) pull‐down and co‐immunoprecipitation (Co‐IP) assays were performed to detect the interacting proteins of HIF2α. Quantitative PCR (qPCR) and Western blotting were used to detect the expression of JUP in human ccRCC samples. Luciferase reporter assays, chromatin immunoprecipitation (ChIP), cycloheximide chase assays, and ubiquitination assays were conducted to explore the regulation of JUP on the activity of HIF2α. Cell Counting Kit‐8 (CCK‐8) assays, colony formation assays, transwell assays, and xenograft tumor assays were performed to investigate the effect of JUP knockdown or overexpression on the tumorigenicity of renal cancer cells. Results We identified JUP as a novel HIF2α‐binding partner and revealed an important role of JUP in recruiting von Hippel‐Lindau (VHL) and histone deacetylases 1/2 (HDAC1/2) to HIF2α to regulate its stability and transactivation. JUP knockdown promoted and overexpression suppressed the tumorigenicity of renal cell carcinoma in vitro and in vivo. Importantly, the low expression of JUP was found in clinical ccRCC samples and correlated with enhanced hypoxia scores and poor treatment outcomes. Conclusion Taken together, these data support a role of JUP in modulating HIF2α signaling during ccRCC progression and identify JUP as a potential therapeutic target.