tbuckley/cabot-search huggingface dataset:
Pembrolizumab in MSI-H–dMMR Advanced Colorectal Cancer — A New Standard of Care
Authors: Axel Grothey
Journal: New England Journal of Medicine (2020)

Nothing has changed cancer therapy more in the past 5 to 10 years than the introduction of immune checkpoint inhibitors. In solid tumors, the activity of these agents is commonly linked to the presence of a hypermutated phenotype with the expression of tumor-specific neoantigens at the surface of cancer cells that can serve as targets for T cells. A higher tumor mutation burden can be the result of exogenous, DNA-damaging carcinogens, such as ultraviolet light and smoking, or linked to cell-intrinsic deficiencies in DNA repair mechanisms. Germline mutations in genes encoding mismatch repair proteins are the hallmarks of the Lynch . . .
239MO NUWA project: The first national real-world gynaecological oncology research and patient management platform in China
Authors: Q. Gao, D. Ma, Q. Zhou, L. Wang, Q. Li, L. Chen, J. Wang, B. Xia, W. Jiang, S. Yao, Y. Chen, X. Xie, S. Zeng, X. Peng
Journal: Annals of Oncology (2020)
Ultrasound Mediated Destruction of DNA-Loaded Microbubbles for Enhancement of Cell-Based Therapies: New Promise Amidst a Confluence of Uncertainties?⁎⁎Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology.
Authors: Flordeliza S. Villanueva
Journal: JACC. Cardiovascular imaging (2009)
50P Efficacy and safety analysis of pyrotinib in lapatinib resistant HER2-positive metastatic breast cancer: A retrospective study
Authors: Y. Hua, F. Yang, Y. Yang, S. Bao, C. Sun, X. Yan, T. Zeng, M. Jiang, X. Huang, H. Wu, J. Li, W. Li, Y. Yin
Journal: Annals of Oncology (2020)
Channeling Post-Infarction Ventricular Tachycardia Ablation: “Electroanatomy” Versus Electrophysiology⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Haris M. Haqqani, Joseph B. Morton, Jonathan M. Kalman
Journal: Journal of the American College of Cardiology (2013)
Molecular characterization and natural history of linear porokeratosis: A case series
Authors: Mina Saleva-Stateva, Maria Hess, Kristin Technau-Hafsi, Lisa Weibel, Mihai-Alexandru Badea, Maria del Carmen Boente, Martin Theiler, Maria Jose Fiandrino, Peter Hoeger, Andreas Zimmer, David Rafei-Shamsabadi, Maria Balabanova, Judith Fischer, Melanie Boerries, Cristina Has
Journal: Journal of the American Academy of Dermatology (2020)
341P Relationship between muscle mass and quality of life in breast cancer patients who underwent chemotherapy
Authors: A. Kurniawan, D.A. Halim, R.D. Hatma, A. Adisasmita, N. Sutandyo, S.S. Panigoro, F.I. Witjaksono, D.S. Rivami, T.Z. Tamin, R. Sumantri, C. Jodhinata, W. Raffaelo, F. Wijovi, H. Putri, O.A. Saroso, F. Dharmaraja, N.P.H. Lugito, C. Cindy, A. Tancherla
Journal: Annals of Oncology (2020)
The disruption of protein−protein interactions with co-chaperones and client substrates as a strategy towards Hsp90 inhibition
Authors: Michael A. Serwetnyk, Brian S.J. Blagg
Journal: Acta Pharmaceutica Sinica B (2020)

The 90-kiloDalton (kD) heat shock protein (Hsp90) is a ubiquitous, ATP-dependent molecular chaperone whose primary function is to ensure the proper folding of several hundred client protein substrates. Because many of these clients are overexpressed or become mutated during cancer progression, Hsp90 inhibition has been pursued as a potential strategy for cancer as one can target multiple oncoproteins and signaling pathways simultaneously. The first discovered Hsp90 inhibitors, geldanamycin and radicicol, function by competitively binding to Hsp90's N-terminal binding site and inhibiting its ATPase activity. However, most of these N-terminal inhibitors exhibited detrimental activities during clinical evaluation due to induction of the pro-survival heat shock response as well as poor selectivity amongst the four isoforms. Consequently, alternative approaches to Hsp90 inhibition have been pursued and include C-terminal inhibition, isoform-selective inhibition, and the disruption of Hsp90 protein-protein interactions. Since the Hsp90 protein folding cycle requires the assembly of Hsp90 into a large heteroprotein complex, along with various co-chaperones and immunophilins, the development of small molecules that prevent assembly of the complex offers an alternative method of Hsp90 inhibition.
Personalized B cell response to the <i>Lactobacillus rhamnosus GG</i> probiotic in healthy human subjects: a randomized trial
Authors: Jette Bornholdt, Christa Broholm, Yun Chen, Alfredo Rago, Stine Sloth, Jakob Hendel, Cathrine Melsæther, Christina V. Müller, Maria Juul Nielsen, Jesper Strickertsson, Lars Engelholm, Kristoffer Vitting-Seerup, Kim B. Jensen, Adam Baker, Albin Sandelin
Journal: Gut Microbes (2020)

The specific effects of administering live probiotics in the human gut are not well characterized. To this end, we investigated the immediate effect of Lactobacillus rhamnosus GG (LGG) in the jejunum of 27 healthy volunteers 2 h after ingestion using a combination of global RNA sequencing of human biopsies and bacterial DNA sequencing in a multi-visit, randomized, cross-over design (ClinicalTrials.gov number NCT03140878). While LGG was detectable in jejunum after 2 h in treated subjects, the gene expression response vs. placebo was subtle if assessed across all subjects. However, clustering analysis revealed that one-third of subjects exhibited a strong and consistent LGG response involving hundreds of genes, where genes related to B cell activation were upregulated, consistent with prior results in mice. Immunohistochemistry and single cell-based deconvolution analyses showed that this B cell signature likely is due to activation and proliferation of existing B cells rather than B cell immigration to the tissue. Our results indicate that the LGG strain has an immediate effect in the human gut in a subpopulation of individuals. In extension, our data strongly suggest that studies on in vivo probiotic effects in humans require large cohorts and must take individual variation into account.
15169 Impact of guselkumab on quality of life and work productivity outcomes among patients with plaque psoriasis in the Corrona Psoriasis Registry
Authors: April W. Armstrong, Kristina Callis-Duffin, Jonathan Uy Janssen, Tania C. Gonzalez-Rivera, Timothy Fitzgerald, Amanda Teeple, Katelyn Rowland, Robert R. McLean, Lin Guo, Ying Shan, Abby S. Van Voorhees
Journal: Journal of the American Academy of Dermatology (2020)
The SPPL3-Defined Glycosphingolipid Repertoire Orchestrates HLA Class I-Mediated Immune Responses
Authors: Marlieke L.M. Jongsma, Antonius A. de Waard, Matthijs Raaben, Tao Zhang, Birol Cabukusta, René Platzer, Vincent A. Blomen, Anastasia Xagara, Tamara Verkerk, Sophie Bliss, Xiangrui Kong, Carolin Gerke, Lennert Janssen, Elmer Stickel, Stephanie Holst, Rosina Plomp, Arend Mulder, Soldano Ferrone, Frans H.J. Claas, Mirjam H.M. Heemskerk, Marieke Griffioen, Anne Halenius, Hermen Overkleeft, Johannes B. Huppa, Manfred Wuhrer, Thijn R. Brummelkamp, Jacques Neefjes, Robbert M. Spaapen
Journal: Immunity (2020)
Controlled release of etoricoxib from poly(ester urea) films for post-operative pain management
Authors: Natasha C. Brigham, Rebecca Nofsinger, Xin Luo, Nathan Z. Dreger, Alexandra K. Abel, Tiffany P. Gustafson, Seth P. Forster, Andre Hermans, Ru-Rong Ji, Matthew L. Becker
Journal: Journal of Controlled Release (2020)
Scotland becomes first country to provide free period products
Authors: Elisabeth Mahase
Journal: BMJ (2020)

Period products will be obtainable free of charge in Scotland for every person who needs to use them, after the country became the first in the world to pass legislation on the issue.

A bill passed unanimously in the Scottish parliament on 24 November1 requires all local authorities in Scotland to ensure that period products are freely available. Schools, colleges, and universities must also make them available free of charge in their toilets, and …
Abstract 17379: Relationship Between Myocyte Branching and Location Within Myocardial Sheetlet
Authors: Alexander J Wilson, Gregory B Sands, Daniel B Ennis
Journal: Circulation (2020)

Introduction: Cardiomyocytes form a continuously branching syncytium that also form sheetlets four to six cells thick. Myocytes and sheetlets have essential structural and functional roles, but descriptions of their complex branching structure are limited. Herein, we characterize the branching structure of cardiomyocytes within a myocardial sheetlet segment. Hypothesis: Due to topological constraints, cardiomyocytes on the sheetlet surfaces branch within the fiber-sheetlet plane more than myocytes on the interior of the sheetlet. Methods: Rodent myocardium was stained for collagen and the left ventricular free wall was imaged using extended volume confocal microscopy (0.4 μm 3 voxel size), a and sheetlet portion segmented (146 х 214 х 339 μm 3 , approx. 5 by 10 by 3 cells). The centerline of each myocyte was tracked, with branch-points identified where the cell bodies of adjacent cardiomyocytes merge. This produced a connected network (Figure) with five cell-layers along the normal axis: lower surface, lower interior, middle interior, upper interior, and upper surface. Results: The cardiomyocyte branching frequency varied between cell-layers (Figure); the sheetlet-surface cell-layers branched within their own cell-layer more frequently than myocytes in the sheetlet interior (0.28 vs 0.11 branches per 100 μm). Cardiomyocytes on the sheetlet surface also branched less frequently with cardiomyocytes of a different cell-layer, compared with cardiomyocytes in the sheetlet interior (0.31 vs 0.67 branches per 100 μm). Cardiomyocytes in the middle interior cell-layer had the highest number of branches between cell-layers (0.86 per 100 μm), and the lowest number of branches within their own cell-layer (0.03 per 100 μm). Conclusion: Analysis of confocal images revealed differences in cardiomyocyte branching between cell-layers of a sheetlet segment, and confirmed that sheetlet boundaries provide a topological constraint for cardiomyocyte branching.
LBA4 GEMSTONE-302: A phase III study of platinum-based chemotherapy (chemo) with placebo or CS1001, an anti-PDL1 antibody, for first-line (1L) advanced non-small cell lung cancer (NSCLC)
Authors: C. Zhou, Z. Wang, Y. Sun, L. Cao, Z. Ma, R. Wu, Y. Yu, W. Yao, J. Chang, J. Chen, W. Zhuang, J. Cui, X. Chen, Y. Lu, H. Shen, P. Li, J. Wang, B. Sun, D. Lu, J. Yang
Journal: Annals of Oncology (2020)
Comparative Performance of 99mTc-TRODAT-1 SPECT/CT and 18F-FDOPA PET/CT Imaging in Patients With Parkinson’s Disease, Parkinson-Plus Syndrome, and Essential Tremor
Authors: Apurva Sood, Jaya Shukla, Ritu Shree, Rakhee Vatsa, Manish Modi, Bhagwant Rai Mittal
Journal: Clinical Nuclear Medicine (2020)

Purpose The aim of this study was to assess the utility of presynaptic dopaminergic imaging using 99m Tc-TRODAT-1 SPECT/CT and 18 F-FDOPA PET/CT and compare their performance in Parkinson’s disease (PD), Parkinson-plus syndrome (PPS), and essential tremor (ET). Patients and Methods A total of 103 patients (PD = 48, PPS = 19, and ET = 36) were enrolled prospectively. Hoehn and Yahr (H&amp;Y) staging and MDS-UPDRS (Movement Disorder Society–Sponsored Revision of Unified Parkinson’s Disease Rating Scale) were done for PD and PPS cases. All the patients underwent 99m Tc-TRODAT-1 SPECT/CT and 18 F-FDOPA PET/CT brain scan. The scans were analyzed visually and semiquantitatively. Average pixel count and SUV mean of the striatum were calculated in SPECT and PET images, respectively, to calculate the specific uptake ratio of striatum (SUR). Comparison of scan findings and SURs among different groups and correlation with clinical characteristics was done. Results Symmetrical comma-shaped uptake was seen in bilateral striatum in ET cases with mean SURs significantly higher than in cases of early PD (H&amp;Y stage I and II, n = 37), PD and PPS both on SPECT and PET images ( P ≤ 0.001). The mean SURs between PD and PPS showed no significant difference (SPECT, P = 0.17; PET, P = 0.61). Substantial agreement (weighted κ = 0.659) was found between 99m Tc-TRODAT-1 and 18 F-FDOPA for the detection of presynaptic dopaminergic dysfunction. Specific uptake ratio of striatum correlation between SPECT and PET was statistically significant ( r = 0.67; P &lt; 0.01). A negative but nonsignificant correlation was found between the SURs and H&amp;Y staging/MDS-UPDRS. Conclusions Both 99m Tc-TRODAT-1 SPECT/CT and 18 F-FDOPA PET/CT showed substantial agreement and proved to be potential imaging biomarker for the detection of dopaminergic dysfunction, thus assisting in differentiating early PD/PD and PPS from ET cases.
Pervasive generation of non-canonical subgenomic RNAs by SARS-CoV-2
Authors: Jason Nomburg, Matthew Meyerson, James A. DeCaprio
Journal: Genome Medicine (2020)

Abstract Background SARS-CoV-2, a positive-sense RNA virus in the family Coronaviridae , has caused a worldwide pandemic of coronavirus disease 2019 or COVID-19. Coronaviruses generate a tiered series of subgenomic RNAs (sgRNAs) through a process involving homology between transcriptional regulatory sequences (TRS) located after the leader sequence in the 5′ UTR (the TRS-L) and TRS located near the start of ORFs encoding structural and accessory proteins (TRS-B) near the 3′ end of the genome. In addition to the canonical sgRNAs generated by SARS-CoV-2, non-canonical sgRNAs (nc-sgRNAs) have been reported. However, the consistency of these nc-sgRNAs across viral isolates and infection conditions is unknown. The comprehensive definition of SARS-CoV-2 RNA products is a key step in understanding SARS-CoV-2 pathogenesis. Methods Here, we report an integrative analysis of eight independent SARS-CoV-2 transcriptomes generated using three sequencing strategies, five host systems, and seven viral isolates. Read-mapping to the SARS-CoV-2 genome was used to determine the 5′ and 3′ coordinates of all junctions in viral RNAs identified in these samples. Results Using junctional abundances, we show nc-sgRNAs make up as much as 33% of total sgRNAs in cell culture models of infection, are largely consistent in abundance across independent transcriptomes, and increase in abundance over time during infection. By assessing the homology between sequences flanking the 5′ and 3′ junction points, we show that nc-sgRNAs are not associated with TRS-like homology. By incorporating read coverage information, we find strong evidence for subgenomic RNAs that contain only 5′ regions of ORF1a. Finally, we show that non-canonical junctions change the landscape of viral open reading frames. Conclusions We identify canonical and non-canonical junctions in SARS-CoV-2 sgRNAs and show that these RNA products are consistently generated by many independent viral isolates and sequencing approaches. These analyses highlight the diverse transcriptional activity of SARS-CoV-2 and offer important insights into SARS-CoV-2 biology.
15792 β3-Tubulin knockdown impairs microtubule dynamics, induces cell cycle arrest, and decreases the spontaneous release of microvesicles in human skin malignant melanoma cells (A375)
Authors: Philip Surmanowicz, Mohammed Omar Altonsy, Anutosh Ganguly, Gilles J. Lauzon, P. Régine Mydlarski
Journal: Journal of the American Academy of Dermatology (2020)
16232 Analysis of androgen excess and association with polycystic ovary syndrome in female-pattern hair loss before 30 years of age
Authors: Gyeong Je Cho, Seong Min Hong, Jong Uk Kim, Woo Jung Jin, So Hee Park, In Ho Park, Jung Eun Seol, So Young Jung, Hyojin Kim
Journal: Journal of the American Academy of Dermatology (2020)
TUG1 long non‐coding RNA enlists the USF1 transcription factor to overexpress ROMO1 leading to hepatocellular carcinoma growth and metastasis
Authors: Shihai Liu, Jing Qiu, Weitai He, Chao Geng, Guifang He, Changchang Liu, Duo Cai, Xiangping Liu, Ben Tian, Huazheng Pan
Journal: MedComm (2020)

Hepatocellular carcinoma (HCC) is a prevalent and highly aggressive cancer. Long non-coding RNAs (lncRNAs) are recognized as potential molecular targets for HCC and are currently under increased research focus. Here, we investigate the regulatory processes underlying the axis of the lncRNA taurine upregulated gene 1 (TUG1), Upstream Transcription Factor 1 (USF1), and reactive oxygen species modulator 1 (ROMO1) in the propagation and metastasis of HCC cells. Distribution of lncRNA TUG1 was found to be prominent in HCC cell cytoplasm and nuclei. LncRNA TUG1 conscripted the USF1 transcription factor to enhance the promoter function of ROMO1. Enlisting the USF1 transcription factor to increase ROMO1 expression following upregulation of TUG1 lncRNA enhanced HCC Huh7 cell proliferation, motility, and metastasis. Rapid tumor proliferation in nude mice provided in vivo verification. The importance of the lncRNA TUG1/USF1/ROMO1 complex as a target for HCC therapy is a key result of this investigation which is exemplified by its role in regulating the proliferation, motility, and metastasis of HCC cells.
Brain Injury After Transcatheter Replacement of Bicuspid Versus Tricuspid Aortic Valves
Authors: Jiaqi Fan, Xian Fang, Chunhui Liu, Gangjie Zhu, Cody R. Hou, Jubo Jiang, Xinping Lin, Lihan Wang, Yuxin He, Qifeng Zhu, Stella Ng, Zexin Chen, Haitao Hu, Xianbao Liu, Jian’an Wang, Martin B. Leon
Journal: Journal of the American College of Cardiology (2020)

An increasing number of bicuspid aortic valve (BAV) patients are undergoing transcatheter aortic valve replacement (TAVR), but the risk of brain injury in diffusion-weighted magnetic resonance imaging (DW-MRI) is currently unknown.This study sought to evaluate the risk of brain injury in BAV patients following TAVR.A total of 204 consecutive severe aortic stenosis patients who underwent TAVR were enrolled. A total of 83 (40.7%) patients were BAV patients, and the other 121 patients were tricuspid aortic valve (TAV) patients. All patients received DW-MRI at baseline, and after TAVR.Median ages (76 years [interquartile range (IQR): 71 to 81 years] vs. 79 years [IQR: 74 to 83 years]; p = 0.004) and Society of Thoracic Surgeons scores (4.87 [IQR: 3.72 to 8.54] vs. 6.38 [IQR: 3.96 to 9.50]; p = 0.044) of the BAV and TAV patients were significantly different, while the overt stroke rates (2.4% vs. 1.7%; p = 0.704) were comparable between the 2 groups. BAV patients were associated with higher number of new lesions (4.0 [IQR: 1.0 to 8.0] vs. 2.0 [IQR: 1.0 to 5.0]; p = 0.008), total lesion volume (290 mm3 [IQR: 70 to 930 mm3] vs. 140 mm3 [IQR: 35 to 480 mm3]; p = 0.008), and the volume per lesion (70.0 mm3 [IQR: 45.0 to 115.0 mm3] vs. 57.5 mm3 [IQR: 24.5 to 93.0 mm3]; p = 0.037) in DW-MRI. Moreover, the proportion of patients with lesions larger than 1 cm3 (28.6% vs. 10.9%; p = 0.005) was higher in BAV patients than in TAV patients.BAV patients may encounter more severe brain injuries not only due to greater number of lesions, but also due to larger lesion size in the early phase after TAVR. (Transcatheter Aortic Valve Replacement Single Center Registry in Chinese Population [TORCH]; NCT02803294).
Abstract 15426: Is Cessation of Anticoagulation Safe Post Successful AF Ablation: Late Occurrence of Thromboembolic Events
Authors: Melissa E Middeldorp, Adrian Elliott, Dennis H Lau, Prashanthan Sanders
Journal: Circulation (2019)

Introduction: Whether elimination of atrial fibrillation (AF) by catheter ablation reduces this risk of stroke is not known. Thromboembolic stroke remains the most devastating complication of AF. A...
16321 Investigator assessment of the efficacy of sonidegib 200 mg once daily and concordance rates with assessments by central review in patients with locally advanced basal cell carcinoma: Results of the 42-month randomized double-blind BOLT study
Authors: Michael Migden, Reinhard Dummer, Nicholas A. Squittieri, Li Liu, Alexander Guminski, John Lear
Journal: Journal of the American Academy of Dermatology (2020)
Abstract PO-36: Functional bypass of cell cycle entry checkpoints by MYC T58A mutation in germinal center-derived lymphomas
Authors: Jongkuen Lee, David Dominguez-Sola
Journal: Blood Cancer Discovery (2020)

Abstract Somatic missense mutations targeting MYC's coding sequence are found in &amp;gt;50% of Burkitt lymphomas and in a small fraction of diffuse large B-cell lymphomas. These mutations typically arise in translocated MYC alleles and cluster at specific protein residues, particularly Threonine 58 (T58). Previous studies in non-B cell models suggested that MYC mutations enhance oncogenic properties by escaping MYC-induced apoptosis. However, the functional impact of these mutations on the biology of germinal center (GC) B cells, where these mutations arise, has never been investigated. In GC B cells, MYC expression is induced by positive selection signals during cognate interactions with T follicular helper cells, concurrent with activation of PI3K and mTOR signaling. PI3K and mTOR are activated upon CD40 and B-cell receptor co-engagement and are critically required for positive selection and clonal expansion of GC B cells. Using newly generated MYC T58A knock-in mouse models, we found that MYC T58A mutation allows B cells to bypass a cell cycle entry checkpoint dependent on PI3K and mTOR activities. Exposure of wild-type (WT) B cells to rapamycin or, less markedly, to PI3K inhibitors, prevented the proliferation upon CD40 and IL4 stimulation ex vivo (a cytokine combination mimicking T-cell help) whereas MYC T58A mutant B cells divided multiple times and maintained adequate rates of active biosynthesis. Similarly, administration of rapamycin to immunized WT mice collapsed formed GCs while MYC T58A GCs maintained normal size and proliferation rates in vivo. These phenotypes were in part explained by the effects of PI3K/mTOR signaling on GSK3-beta, a kinase that normally phosphorylates MYC T58 to control protein turnover. Differences in metabolic and gene expression profiles between MYC WT and T58A cells offered additional insights into the mechanisms by which this mutation bypasses PI3K/mTOR checkpoint. Finally, we found that GC B cell-specific overexpression of MYC T58A, resulted in abnormally enlarged GCs upon immunization, a phenotype common to lymphoma models. Altogether, these results indicate that MYC somatic mutations confer competitive advantages to B cells by bypassing a strict requirement for upstream signals during cell cycle entry, which may support the clonal expansion of MYC mutant B cells during GC responses. These results have important translational implications, particularly given the increasing interest in the potential use of PI3K and/or mTOR inhibitors in the treatment of lymphomas. Citation Format: Jongkuen Lee, David Dominguez-Sola. Functional bypass of cell cycle entry checkpoints by MYC T58A mutation in germinal center-derived lymphomas [abstract]. In: Proceedings of the AACR Virtual Meeting: Advances in Malignant Lymphoma; 2020 Aug 17-19. Philadelphia (PA): AACR; Blood Cancer Discov 2020;1(3_Suppl):Abstract nr PO-36.
Implementation of Hospital Practices Supportive of Breastfeeding in the Context of COVID-19 — United States, July 15–August 20, 2020
Authors: Cria G. Perrine, Katelyn V. Chiang, Erica H. Anstey, Daurice A. Grossniklaus, Ellen O. Boundy, Erin K. Sauber-Schatz, Jennifer M. Nelson
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Breastfeeding has health benefits for both infants and mothers and is recommended by numerous health and medical organizations*