tbuckley/cabot-search huggingface dataset:
Long Noncoding RNA VESTAR Regulates Lymphangiogenesis and Lymph Node Metastasis of Esophageal Squamous Cell Carcinoma by Enhancing VEGFC mRNA Stability
Authors: Yali Wang, Weimin Zhang, Wenzhong Liu, Lijie Huang, Yan Wang, Dan Li, Guangchao Wang, Zitong Zhao, Xinming Chi, Yu Xue, Yongmei Song, Xuefeng Liu, Qimin Zhan
Journal: Cancer Research (2021)

Abstract Lymph node metastasis is one of the most malignant clinical features in patients with esophageal squamous cell carcinoma (ESCC). Understanding the mechanism of lymph node metastasis will provide treatment strategies for patients with ESCC. Long noncoding RNAs (lncRNA) play a critical role in the development and progression of human cancers. However, the role and mechanism of lncRNAs in lymph node metastasis remain largely unknown. Here we show that VEGFC mRNA stability–associated long noncoding RNA (VESTAR) is involved in lymph node metastasis of ESCC. VESTAR was overexpressed in ESCC tissues and was predictive of poor prognosis in patients with ESCC. In ESCC, NXF1 and SRSF3 facilitated nuclear export of VESTAR to the cytoplasm, which was associated with lymph node metastasis. Depletion of VESTAR inhibited ESCC-associated lymphangiogenesis and lymphatic metastasis. Mechanistically, VESTAR directly bound and stabilized VEGFC mRNA. VESTAR also interacted with HuR, a positive regulator of VEGFC mRNA stability, and increased HuR binding to VEGFC mRNA. Our study reveals a novel lncRNA-guided mechanism of lymph node metastasis in ESCC and may provide a potential target for treatment of ESCC lymphatic metastasis. Significance: These findings illustrate the lncRNA-guided regulation of VEGFC mRNA stability via direct RNA–RNA interactions, highlighting a therapeutic target for patients with ESCC with lymphatic metastasis.
MA08.06 Stratifying PD-L1 Expression Level Based on Multimodal Genomic Features for the Prediction of Immunotherapy Benefit in NSCLC
Authors: Y. Wang, Y. Li, C. Li, Y. Jiang, X. Han, S. Liu, X. Xu, W. Tang, Q. Ou, H. Bao, X. Wu, Y. Shao, M. Xing, Y. Zhang
Journal: Journal of Thoracic Oncology (2021)
FP01.02 The Efficacy of Postoperative Radiotherapy in IIIA-N2 Non-Squamous NSCLC with Different EGFR Mutation Status: A Retrospective Analysis
Authors: F. Wu, C. Hu, Y. Huang, X. Pu, C. Liu, X. Liu, F. Ma, L. Zhao, L. Shu, Y. Pan, Y. Zeng
Journal: Journal of Thoracic Oncology (2021)
Surgery compared with cast immobilization for adults with a bi-cortical fracture of the scaphoid waist (SWIFFT): a multicentre, pragmatic, open-label, parallel-group, two-arm randomised clinical trial
Authors: J Dias, S Brealey, C Fairhurst, R Amirfeyz, B Bhowal, N Blewitt, M Brewster, D Brown, S Choudhary, C Coapes, L Cook, M Costa, T Davis, L Dismascio, G Giddins, H Hedley, C Hewitt, S Hinde, J Hobby, S Hodgson, L Jefferson, K Jeyapalan, P Johnston, J Jones, A Keding, P Leighton, A Logan, W Mason, A Mcandrew, I Mcnab, L Muir, J Nicholl, M Northgraves, J Palmer, R Poulter, Z Rahimtoola, A Rangan, S Richards, G Richardson, P Stuart, N Taub, A Tavakkolizadeh, G Tew, J Thompson, D Torgerson, D Warwick
Journal: The Lancet (2020)
Abstract 10675: Arm Exercise ECG is Equivalent to Regadenoson Stress for Detection of Obstructive Coronary Artery Disease
Authors: Anandita Agarwala, Clarence Balke, Divya Kapoor, Jiafu Ou, Hong Xian, Medhat Osman, Jeffrey Chenoweth, Wade H Martin
Journal: Circulation (2019)

Arm exercise ECG stress testing (ARM) is much less expensive and may be a valuable alternative to regadenoson myocardial perfusion imaging (RMPI) in patients unable to perform leg exercise. ARM pro...
P76.60 FLAIR: Phase II Study of Osimertinib plus Bevacizumab versus Osimertinib in Advanced NSCLC Patients with EGFR L858R Mutation
Authors: Q. Zhou, C. Xu, H. Chen, H. Tu, B. Wang, H. Yan, X. Zhang, J. Yang, W. Zhong, S. Liu, Y. Wu
Journal: Journal of Thoracic Oncology (2021)
Comment on: Survival and course of lung function in the presence or absence of antifibrotic treatment in patients with idiopathic pulmonary fibrosis
Authors: Jakob Borchardt
Journal: European Respiratory Journal (2021)

With great interest I recently read the observations of the INSIGHTS-IPF registry published in the August 2020 issue of the European Respiratory Journal [1]. However, the paper represents an instructive example of how peer review occasionally may fail to prevent publication of unfounded conclusions. Though lead-time bias is mentioned as a potential limitation of the study in the discussion (possibly following peer review) and though lead-time bias is evident looking at the published data, the authors conclude that their study shows a significantly lower all-cause mortality in IPF patients with antifibrotic therapy, and that withholding antifibrotic therapy from stable IPF patients may set these patients on a path of increased risk of dying. This is an audacious conclusion given the fact that their data do not show any benefit of antifibrotic therapy, to begin with no slower forced vital capacity decline. Table 1 of the article, which lacks a column showing the statistical significance of differences between untreated and treated patients, demonstrates that while age at diagnosis was similar between the groups (68.1 and 68.0 years, respectively), age at inclusion was different (70.3 and 69.2 years, respectively). That is, patients treated with antifibrotics were included about 1 year earlier than untreated patients. In figure 2, consequently, the part of the Kaplan–Meier survival curve for patients with antifibrotic therapy to be compared with the survival curve of patients without antifibrotic therapy starts at about 1 year of follow-up. To the naked eye it seems that the slope of this part of the curve is not less steep than the curve of the untreated patients. Contrary to the claim of the authors, the observations of this large registry do not argue for immediate antifibrotic treatment of patients with newly diagnosed IPF with few symptoms, minor functional impairment, and, most importantly, no evidence of progression from history, functional studies, or imaging. These patients do exist and the best therapeutic approach to them must be established in a prospective clinical trial. It might well be that the concept of progressive fibrosing interstitial lung disease, now largely accepted for non-IPF interstitial lung disease, may apply to IPF too [2]. The surprising mortality benefit with antifibrotic therapy in the INSIGHTS-IPF registry is explained by lead-time bias <https://bit.ly/3a03Fbh>
Low-Dose Tamoxifen for Mammographic Density Reduction: A Randomized Controlled Trial
Authors: Mikael Eriksson, Martin Eklund, Signe Borgquist, Roxanna Hellgren, Sara Margolin, Linda Thoren, Ann Rosendahl, Kristina Lång, José Tapia, Magnus Bäcklund, Andrea Discacciati, Alessio Crippa, Marike Gabrielson, Mattias Hammarström, Yvonne Wengström, Kamila Czene, Per Hall
Journal: Journal of Clinical Oncology (2021)

Tamoxifen prevents breast cancer in high-risk women and reduces mortality in the adjuvant setting. Mammographic density change is a proxy for tamoxifen therapy response. We tested whether lower doses of tamoxifen were noninferior to reduce mammographic density and associated with fewer symptoms.Women, 40-74 years of age, participating in the Swedish mammography screening program were invited to the 6-month double-blind six-arm randomized placebo-controlled noninferiority dose-determination KARISMA phase II trial stratified by menopausal status (EudraCT 2016-000882-22). In all, 1,439 women were accrued with 1,230 participants accessible for intention-to-treat analysis. The primary outcome was proportion of women treated with placebo, 1, 2.5, 5, and 10 mg whose mammographic density decreased at least as much as the median reduction in the 20 mg arm. The noninferior margin was 17%. Secondary outcome was reduction of symptoms. Post hoc analyses were performed by menopausal status. Per-protocol population and full population were analyzed in sensitivity analysis.The 1,439 participants, 566 and 873 pre- and postmenopausal women, respectively, were recruited between October 1, 2016, and September 30, 2019. The participants had noninferior mammographic density reduction following 2.5, 5, and 10 mg tamoxifen compared with the median 10.1% decrease observed in the 20 mg group, a reduction confined to premenopausal women. Severe vasomotor symptoms (hot flashes, cold sweats, and night sweats) were reduced by approximately 50% in the 2.5, 5, and 10 mg groups compared with the 20 mg group.Premenopausal women showed noninferior magnitude of breast density decrease at 2.5 mg of tamoxifen, but fewer side effects compared with the standard dose of 20 mg. Future studies should test whether 2.5 mg of tamoxifen reduces the risk of primary breast cancer.
Exhaled SARS-CoV-2 quantified by face-mask sampling in hospitalised patients with COVID-19
Authors: Caroline M. Williams, Daniel Pan, Jonathan Decker, Anika Wisniewska, Eve Fletcher, Shirley Sze, Sara Assadi, Richard Haigh, Mohamad Abdulwhhab, Paul Bird, Christopher W Holmes, Alaa Al-Taie, Baber Saleem, Jingzhe Pan, Natalie J Garton, Manish Pareek, Michael R Barer
Journal: Journal of Infection (2021)

Human to human transmission of SARS-CoV-2 is driven by the respiratory route but little is known about the pattern and quantity of virus output from exhaled breath. We have previously shown that face-mask sampling (FMS) can detect exhaled tubercle bacilli and have adapted its use to quantify exhaled SARS-CoV-2 RNA in patients admitted to hospital with Coronavirus Disease-2019 (COVID-19).Between May and December 2020, we took two concomitant FMS and nasopharyngeal samples (NPS) over two days, starting within 24 h of a routine virus positive NPS in patients hospitalised with COVID-19, at University Hospitals of Leicester NHS Trust, UK. Participants were asked to wear a modified duckbilled facemask for 30 min, followed by a nasopharyngeal swab. Demographic, clinical, and radiological data, as well as International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) mortality and deterioration scores were obtained. Exposed masks were processed by removal, dissolution and analysis of sampling matrix strips fixed within the mask by RT-qPCR. Viral genome copy numbers were determined and results classified as Negative; Low: ≤999 copies; Medium: 1000-99,999 copies and High ≥ 100,000 copies per strip for FMS or per 100 µl for NPS.102 FMS and NPS were collected from 66 routinely positive patients; median age: 61 (IQR 49 - 77), of which FMS was positive in 38% of individuals and concomitant NPS was positive in 50%. Positive FMS viral loads varied over five orders of magnitude (<10-3.3 x 106 genome copies/strip); 21 (32%) patients were asymptomatic at the time of sampling. High FMS viral load was associated with respiratory symptoms at time of sampling and shorter interval between sampling and symptom onset (FMS High: median (IQR) 2 days (2-3) vs FMS Negative: 7 days (7-10), p = 0.002). On multivariable linear regression analysis, higher FMS viral loads were associated with higher ISARIC mortality (Medium FMS vs Negative FMS gave an adjusted coefficient of 15.7, 95% CI 3.7-27.7, p = 0.01) and deterioration scores (High FMS vs Negative FMS gave an adjusted coefficient of 37.6, 95% CI 14.0 to 61.3, p = 0.002), while NPS viral loads showed no significant association.We demonstrate a simple and effective method for detecting and quantifying exhaled SARS-CoV-2 in hospitalised patients with COVID-19. Higher FMS viral loads were more likely to be associated with developing severe disease compared to NPS viral loads. Similar to NPS, FMS viral load was highest in early disease and in those with active respiratory symptoms, highlighting the potential role of FMS in understanding infectivity.
FP07.02 Deep Learning Based Analysis of Multiplex IHC Accurately Interprets PD-L1 and Provides Prognostic Information in NSCLC
Authors: A. Haragan, K. Nekolla, A. Kapil, N. Brieu, M. Widmaier, A. Budco, I. Kanchev, M.T. Testori, J. Chan, K. Schneider, A. Hidalgo Sastre, M. Baehner, G. Schmidt, J. Field, M. Davies, J. Gosney
Journal: Journal of Thoracic Oncology (2021)
Red light photodynamic therapy with BF-200 ALA showed superior efficacy in the treatment of actinic keratosis on the extremities, trunk, and neck in a vehicle-controlled phase III study
Authors: Martina Ulrich, Uwe Reinhold, Rolf Dominicus, Roland Aschoff, Rolf-Markus Szeimies, Thomas Dirschka
Journal: Journal of the American Academy of Dermatology (2021)

Actinic keratoses (AK) may occur in all sun-exposed skin areas. Those occurring outside the head area are generally more resistant to treatment than those on the face.To determine efficacy and safety of BF-200 ALA versus vehicle in the treatment of mild-to-severe AK located on extremities, trunk, and neck with red light photodynamic therapy (PDT).This phase III study had an intra-individual design with 50 patients in 6 centers in Germany. Each patient received a maximum of 2 field-directed PDTs. Clinical end points and 1-year follow-up results were recorded.BF-200 ALA was superior to the vehicle with respect to total lesion clearance rates (86.0% vs 32.9%; P < .0001) and patient complete clearance per patient's side (67.3% vs 12.2%, P < .0001). One-year overall lesion recurrence rate was 14.1% versus 27.4% (BF-200 ALA vs vehicle; P = .0068). Patients were more satisfied by the cosmetic outcome of BF-200 ALA/PDT than the vehicle/PDT. Adverse events were consistent with the known safety profile of BF-200 ALA/PDT.Small number of severe lesions; limited sample size; unbalanced but representative distribution of AK.BF-200 ALA showed significantly higher AK clearance rates on extremities, trunk, and neck than the vehicle and was well tolerated.
P62.08 Expression Pattern and Prognostic Significance of Gluconeogenesis Enzymes in Lung Cancer.
Authors: E. Smolle, P. Leko, E. Stacher-Priehse, L. Brcic, A. El-Heliebi, L. Hofmann, F. Quehenberger, A. Hrzenjak, H. Popper, H. Olschewski, K. Leithner
Journal: Journal of Thoracic Oncology (2021)
HSR21-061: Frequency of Oncologists (ONC) Office Visit and Caregiver Burden With Poly(ADP-ribose) Polymerase Inhibitor (PARPi) Versus Chemotherapy (CTX) Among Adult Patients (pts) With Germline BRCA1/2 Mutated (gBRCA1/2mut) HER2- Advanced Breast Cancer (ABC): Results From a Multi-Country Real-World (RW) Study
Authors: Michael Lux, Alex Niyazov, Katie Lewis, Lucy Massey, Alex Rider, Bhakti Arondekar, Reshma Mahtani
Journal: Journal of the National Comprehensive Cancer Network (2021)

"HSR21-061: Frequency of Oncologists (ONC) Office Visit and Caregiver Burden With Poly(ADP-ribose) Polymerase Inhibitor (PARPi) Versus Chemotherapy (CTX) Among Adult Patients (pts) With Germline BRCA1/2 Mutated (gBRCA1/2mut) HER2- Advanced Breast Cancer (ABC): Results From a Multi-Country Real-World (RW) Study" published on 17 Mar 2021 by National Comprehensive Cancer Network.
The Spectrum of Benefit from Checkpoint Blockade in Hypermutated Tumors
Authors: Benoit Rousseau, Michael B. Foote, Steven B. Maron, Bill H. Diplas, Steve Lu, Guillem Argilés, Andrea Cercek, Luis A. Diaz
Journal: New England Journal of Medicine (2021)

Immune Checkpoint Inhibitors and Tumor Mutational Burden The FDA has approved immune checkpoint inhibitors for solid tumors of any histologic origin with more than 10 mutations per megabase of DNA....
Abstract 12808: Mechanism of Chronic Ranolazine Caused Regression of Cardiac Dysfunction in a Murine of Diabetic Cardiomyopathy: Beneficial Effects on Cardiomyocyte Contractile Function, [Ca <sup>2+</sup> ] <sub>i</sub> Regulation and Beta-Adrenergic Modulation
Authors: Xiaoqiang Sun, Jing Cao, Heng-Jie Cheng, Yixi Liu, Zhe Chen, Dalane Kitzman, David Zhao, Donald A McClain, Che Cheng
Journal: Circulation (2020)

Background: Diabetic cardiomyopathy (DCM) increases the risk of heart failure. As yet, no effective therapeutic strategies exist. Recent evidence indicates that intracellular Na + concentration ([Na + ] i ) is augmented in the myocytes from diabetic hearts, where it causes oxidative stress, augments the sarcoplasmic reticulum Ca 2+ leak and contributes to electrical, structural and functional remodeling. Ranolazine (RAN), inhibiting persistent or late inward Na + current has been proposed to be a therapeutic choice for DCM. However, the role and mechanism of chronic RAN in DCM are unclear. We assessed the hypothesis that RAN improves myocyte function, [Ca 2+ ] i regulation, and β-adrenergic receptor (AR) signaling effectiveness, thus limiting DCM. Methods: We compared LV myocyte function, [Ca 2+ ] i transient ([Ca 2+ ] iT ) and responses to the stimulation of β-AR in 3 groups wild-type (WT) female mice over 10 weeks (W):1) DM (n=8), 10 W after receiving streptozotocin (STZ, 200 mg/kg, ip); 2) DM/RAN (n=6), 6 W after STZ, RAN (10 -5 M/kg/day, mini-pump) was initiated and was given for 4 W; and 3) Sham controls (C) (n=8). Results: Versus control, STZ-treated WT mice had DM with significantly elevated blood glucose levels (410 vs 128mg/dl) followed by LV myocyte dysfunction with decreases in myocyte contractility (dL/dt max ) (75.0 vs 140.1 μm/s), relengthening (dR/dt max ) (62.5 vs 116.6 μm/s) and [Ca 2+ ] iT (0.15 vs 0.22). In DM myocytes, the ability of β-AR agonist, isoproterenol (ISO, 10 -8 M) to increase cell contractility was blunted. Versus control, in DM myocytes, ISO-induced increases in dL/dt max (31% vs 60%), dR/dt max (23% vs 50%) and [Ca 2+ ] iT (15% vs 30%) were significantly reduced. By contrary, versus DM alone, DM/RAN myocytes showed normal basal cell contraction (137.8 μm/s), relaxation (117.2 μm/s) and [Ca 2+ ] iT (0.22) with preserved ISO-stimulated positive inotropic effect. Compared control, in DM/RAN, ISO caused similar increases in dL/dt max (62% vs 60%), dR/dt max (52% vs 50%) and [Ca 2+ ] iT (32% vs 30%). Conclusion: Chronic ranolazine leads to the preservation of myocyte function, [Ca 2+ ] iT and β-AR responsiveness in DCM. Thus, antagonizing myocyte [Na + ] i dysregulation might provide a new therapeutic strategy for DM-related decline in myocardial function.
Tissue-resident memory T cells in tumor immunity and immunotherapy
Authors: Karolina Okła, Donna L. Farber, Weiping Zou
Journal: The Journal of Experimental Medicine (2021)

Tissue-resident memory T cells (TRM) represent a heterogeneous T cell population with the functionality of both effector and memory T cells. TRM express residence gene signatures. This feature allows them to traffic to, reside in, and potentially patrol peripheral tissues, thereby enforcing an efficient long-term immune-protective role. Recent studies have revealed TRM involvement in tumor immune responses. TRM tumor infiltration correlates with enhanced response to current immunotherapy and is often associated with favorable clinical outcome in patients with cancer. Thus, targeting TRM may lead to enhanced cancer immunotherapy efficacy. Here, we review and discuss recent advances on the nature of TRM in the context of tumor immunity and immunotherapy.
Procedural Telementoring in Rural, Underdeveloped, and Austere Settings: Origins, Present Challenges, and Future Perspectives
Authors: Juan P. Wachs, Andrew W. Kirkpatrick, Samuel A. Tisherman
Journal: Annual Review of Biomedical Engineering (2021)

Telemedicine is perhaps the most rapidly growing area in health care. Approximately 15 million Americans receive medical assistance remotely every year. Yet rural communities face significant challenges in securing subspecialist care. In the United States, 25% of the population resides in rural areas, where less than 15% of physicians work. Current surgery residency programs do not adequately prepare surgeons for rural practice. Telementoring, wherein a remote expert guides a less experienced caregiver, has been proposed to address this challenge. Nonetheless, existing mentoring technologies are not widely available to rural communities, due to a lack of infrastructure and mentor availability. For this reason, some clinicians prefer simpler and more reliable technologies. This article presents past and current telementoring systems, with a focus on rural settings, and proposes aset of requirements for such systems. We conclude with a perspective on the future of telementoring systems and the integration of artificial intelligence within those systems.
Prevalence of Chlamydial and Gonococcal Infections Among Young Adults—Reply
Authors: William C. Miller, Carol A. Ford, Marcia M. Hobbs, Myron S. Cohen, John L. Schmitz, Kathleen Mullan Harris, Mark S. Handcock, Martina Morris
Journal: JAMA (2004)

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FP12.11 Single-Cell RNA Sequencing Analyses Distinguishes Transcriptional Activity of c-Myc and L-Myc in Small Cell Lung Cancer
Authors: A. Patel, R. Kong, T. Sato, S. Yoo, A. Sinha, C. Powell, J. Zhu, H. Watanabe
Journal: Journal of Thoracic Oncology (2021)