tbuckley/cabot-search huggingface dataset:
Thymosin β4 released from functionalized self-assembling peptide activates epicardium and enhances repair of infarcted myocardium
Authors: Yong-li Wang, Shu-na Yu, Hao-ran Shen, Hai-jie Wang, Xue-ping Wu, Qiang-li Wang, Bin Zhou, Yu-zhen Tan
Journal: Theranostics (2021)

The epicardium plays an important role in cardiomyogenesis during development, while it becomes quiescent in adult heart during homeostasis. This study investigates the efficiency of thymosin β4 (Tβ4) release with RPRHQGVM conjugated to the C-terminus of RADA16-I (RADA-RPR), the functionalized self-assembling peptide (SAP), to activate the epicardium and repairing the infarcted myocardium. Methods: The functionalized SAP was constituted with self-assembling motif, Tβ4-binding site, and cell adhesive ligand. Myocardial infarction (MI) models of the transgenic mice were established by ligation of the left anterior descending coronary artery. At one week after intramyocardial injection of Tβ4-conjugated SAP, the activation of the epicardium was assessed. At four weeks after implantation, the migration and differentiation of epicardium-derived cells (EPDCs) as well as angiogenesis, lymphangiogenesis and myocardial regeneration were examined. Results: We found that the designer RADA-RPR bound Tβ4 and adhered to EPDCs and that Tβ4 released from the functionalized SAP could effectively activate the epicardium and induce EPDCs to differentiate towards cardiovascular cells as well as lymphatic endothelial cells. Moreover, SAP-released Tβ4 (SAP-Tβ4) promoted proliferation of cardiomyocytes. Furthermore, angiogenesis, lymphangiogenesis and myocardial regeneration were enhanced in the MI models at 4 weeks after delivery of SAP-Tβ4 along with attenuation of adverse myocardial remodeling and significantly improved cardiac function. Conclusions: These results demonstrate that sustained release of Tβ4 from the functionalized SAP can activate the epicardium and effectively enhance the repair of infarcted myocardium. We believe the delivery of SAP-Tβ4 may be a promising strategy for MI therapy.
P56.01 Postoperative ctDNA Positive Presents the High-risk of Recurrence in Resectable Non-Small Cell Lung Cancers
Authors: J. Zhang, M. Zhang, R. Fu, X. Chu, Z. Wen, Y. Gong, B. Jiang, R. Liao, S. Dong, Q. Nie, R. Chen, X. Xia, X. Yang, W. Zhong, Y. Wu
Journal: Journal of Thoracic Oncology (2021)
Gene therapy companies have an ethical obligation to develop expanded access policies
Authors: Lisa Kearns, Carolyn Riley Chapman, Kenneth I. Moch, Arthur L. Caplan, Tom Watson, Andrew McFadyen, Pat Furlong, Alison Bateman-House
Journal: Molecular Therapy (2021)

In the US, gene therapy companies, as with all biopharmaceutical companies, are not required by law or regulation to provide their investigational products to patients via non-trial preapproval (expanded) access. However, we believe that gene therapy companies, in particular, have a moral obligation to develop policies regarding such access, historically known as "compassionate use." Gene therapies are predominantly intended for patients with serious or life-threatening rare diseases for which there are limited treatments;1 this should compel companies to develop product-specific non-trial preapproval access policies.
FGFR2 fusion proteins drive oncogenic transformation of mouse liver organoids towards cholangiocarcinoma
Authors: Giulia Cristinziano, Manuela Porru, Dante Lamberti, Simonetta Buglioni, Francesca Rollo, Carla Azzurra Amoreo, Isabella Manni, Diana Giannarelli, Cristina Cristofoletti, Giandomenico Russo, Mitesh J. Borad, Gian Luca Grazi, Maria Grazia Diodoro, Silvia Giordano, Andrea Sacconi, Mattia Forcato, Sergio Anastasi, Carlo Leonetti, Oreste Segatto
Journal: Journal of Hepatology (2021)
Single-cell Spatial Proteomic Revelations on the Multiparametric MRI Heterogeneity of Clinically Significant Prostate Cancer
Authors: Russell K. Pachynski, Eric H. Kim, Natalia Miheecheva, Nikita Kotlov, Akshaya Ramachandran, Ekaterina Postovalova, Ilia Galkin, Viktor Svekolkin, Yang Lyu, Qiong Zou, Dengfeng Cao, Joseph Gaut, Joseph E. Ippolito, Alexander Bagaev, Maria Bruttan, Olga Gancharova, Krystle Nomie, Maria Tsiper, Gerald L. Andriole, Ravshan Ataullakhanov, James J. Hsieh
Journal: Clinical Cancer Research (2021)

Multiparametric MRI (mpMRI) has become an indispensable radiographic tool in diagnosing prostate cancer. However, mpMRI fails to visualize approximately 15% of clinically significant prostate cancer (csPCa). The molecular, cellular, and spatial underpinnings of such radiographic heterogeneity in csPCa are unclear.We examined tumor tissues from clinically matched patients with mpMRI-invisible and mpMRI-visible csPCa who underwent radical prostatectomy. Multiplex immunofluorescence single-cell spatial imaging and gene expression profiling were performed. Artificial intelligence-based analytic algorithms were developed to examine the tumor ecosystem and integrate with corresponding transcriptomics.More complex and compact epithelial tumor architectures were found in mpMRI-visible than in mpMRI-invisible prostate cancer tumors. In contrast, similar stromal patterns were detected between mpMRI-invisible prostate cancer and normal prostate tissues. Furthermore, quantification of immune cell composition and tumor-immune interactions demonstrated a lack of immune cell infiltration in the malignant but not in the adjacent nonmalignant tissue compartments, irrespective of mpMRI visibility. No significant difference in immune profiles was detected between mpMRI-visible and mpMRI-invisible prostate cancer within our patient cohort, whereas expression profiling identified a 24-gene stromal signature enriched in mpMRI-invisible prostate cancer. Prostate cancer with strong stromal signature exhibited a favorable survival outcome within The Cancer Genome Atlas prostate cancer cohort. Notably, five recurrences in the 8 mpMRI-visible patients with csPCa and no recurrence in the 8 clinically matched patients with mpMRI-invisible csPCa occurred during the 5-year follow-up post-prostatectomy.Our study identified distinct molecular, cellular, and structural characteristics associated with mpMRI-visible csPCa, whereas mpMRI-invisible tumors were similar to normal prostate tissue, likely contributing to mpMRI invisibility.
Interleukin-10 suppression enhances T-cell antitumor immunity and responses to checkpoint blockade in chronic lymphocytic leukemia
Authors: J. R. Rivas, Y. Liu, S. S. Alhakeem, J. M. Eckenrode, F. Marti, J. P. Collard, Y. Zhang, K. A. Shaaban, N. Muthusamy, G. C. Hildebrandt, R. A. Fleischman, L. Chen, J. S. Thorson, M. Leggas, S. Bondada
Journal: Leukemia (2021)
P52.03 Concordance of PET Scan and EBUS-TBNA for Mediastinal Staging of Stage 3 Non-Small Cell Lung Cancer
Authors: M. Saltiel, N. Malik, A. Singnurkar, C. Mcdonald, H. Wong, A. Louie, M. Doherty
Journal: Journal of Thoracic Oncology (2021)
Routine asymptomatic testing strategies for airline travel during the COVID-19 pandemic: a simulation study
Authors: Mathew V Kiang, Elizabeth T Chin, Benjamin Q Huynh, Lloyd A C Chapman, Isabel Rodríguez-Barraquer, Bryan Greenhouse, George W Rutherford, Kirsten Bibbins-Domingo, Diane Havlir, Sanjay Basu, Nathan C Lo
Journal: The Lancet Infectious Diseases (2021)
Apprenticeships only part of the answer to widening participation in medicine, says BMA
Authors: Abi Rimmer
Journal: BMJ (2021)

The BMA has said that proposals for an apprenticeship model as an alternative to a traditional medical degree will only be one part of a solution to widening participation in the profession.

Earlier this month the HSJ reported1 that Health Education England (HEE) was considering an apprenticeship programme for medical training which would allow trainee doctors to earn while they train. “It is …
Review of Eye Tracking Metrics Involved in Emotional and Cognitive Processes
Authors: Vasileios Skaramagkas, Giorgos Giannakakis, Emmanouil Ktistakis, Dimitris Manousos, Ioannis Karatzanis, Nikolaos Tachos, Evanthia Tripoliti, Kostas Marias, Dimitrios I. Fotiadis, Manolis Tsiknakis
Journal: IEEE Reviews in Biomedical Engineering (2021)

Eye behaviour provides valuable information revealing one's higher cognitive functions and state of affect. Although eye tracking is gaining ground in the research community, it is not yet a popular approach for the detection of emotional and cognitive states. In this paper, we present a review of eye and pupil tracking related metrics (such as gaze, fixations, saccades, blinks, pupil size variation, etc.) utilized towards the detection of emotional and cognitive processes, focusing on visual attention, emotional arousal and cognitive workload. Besides, we investigate their involvement as well as the computational recognition methods employed for the reliable emotional and cognitive assessment. The publicly available datasets employed in relevant research efforts were collected and their specifications and other pertinent details are described. The multimodal approaches which combine eye-tracking features with other modalities (e.g. biosignals), along with artificial intelligence and machine learning techniques were also surveyed in terms of their recognition/classification accuracy. The limitations, current open research problems and prospective future research directions were discussed for the usage of eye-tracking as the primary sensor modality. This study aims to comprehensively present the most robust and significant eye/pupil metrics based on available literature towards the development of a robust emotional or cognitive computational model.
Pulmonary vascular proliferation in patients with severe COVID-19: an autopsy study
Authors: Belén Pérez-Mies, María Gómez-Rojo, Irene Carretero-Barrio, Tommaso Bardi, Amparo Benito, Mónica García-Cosío, Álvaro Caballero, Raul de Pablo, Juan Carlos Galán, David Pestaña, Jose Palacios
Journal: Thorax (2021)

Diffuse alveolar damage and thrombi are the most common lung histopathological lesions reported in patients with severe COVID-19. Although some studies have suggested increased pulmonary angiogenesis, the presence of vascular proliferation in COVID-19 lungs has not been well characterised. Glomeruloid-like microscopic foci and/or coalescent vascular proliferations measuring up to 2 cm were present in the lung of 14 out of 16 autopsied patients. These lesions expressed CD31, CD34 and vascular endothelial cadherin. Platelet-derived growth factor receptor-β immunohistochemistry and dual immunostaining for CD34/smooth muscle actin demonstrated the presence of pericytes. These vascular alterations may contribute to the severe and refractory hypoxaemia that is common in patients with severe COVID-19.
Hospital consultants deserve 5% pay rise, says BMA
Authors: Abi Rimmer
Journal: BMJ (2021)

Gorbenko and Malenko (2014) propose a segmented-market perspective. We extend the literature by directly testing if a segmented-market perspective helps explain the premium difference between private and public acquisitions. Empirically, we follow Fidrmuc et al. (2012) and use a matched sample design. We find that private acquirers do not pay less than public acquirers when controlling for the selling mechanism (which characterizes different corporate control markets) as well as the effects of outliers. Our results suggest that premium differences between private and public acquisitions may be more consistent with a segmented-market perspective as opposed to the agency explanation of Bargeron et al. (2008). <b>TOPICS:</b>Private equity, Performance measurement
Effect of Experimental Manipulation of the Orbitofrontal Cortex on Short-Term Markers of Compulsive Behavior: A Theta Burst Stimulation Study
Authors: Rebecca B. Price, Claire M. Gillan, Colleen Hanlon, Fabio Ferrarelli, Tae Kim, Helmet T. Karim, Marlee Renard, Rachel Kaskie, Michelle Degutis, Anna Wears, Emelina P. Vienneau, Angel V. Peterchev, Vanessa Brown, Greg J. Siegle, Meredith L Wallace, Susanne E. Ahmari
Journal: American Journal of Psychiatry (2021)

Compulsive behaviors are a core feature of obsessive-compulsive spectrum disorders but appear across a broad spectrum of psychological conditions. It is thought that compulsions reflect a failure to override habitual behaviors "stamped in" through repeated practice and short-term distress reduction. Animal models suggest a possible causal role of the orbitofrontal cortex (OFC) in compulsive behaviors, but human studies have largely been limited by correlational designs. The goal of this study was to establish the first experimental evidence in humans for a mechanistic model in order to inform further experimental work and the eventual development of novel mechanistic treatments involving synergistic biological-behavioral pairings.After a baseline assessment, 69 individuals with compulsive behavior disorders were randomly assigned, in a double-blind, between-subjects design, to receive a single session of one of two active stimulation conditions targeting the left OFC: intermittent theta burst stimulation (iTBS), expected to increase OFC activity, or continuous TBS (cTBS), expected to decrease activity (both conditions, 600 pulses at 110% of target resting motor threshold). In both conditions, brain modulation was paired with a subsequent computer task providing practice in overriding a clinically relevant habit (an overlearned shock avoidance behavior), delivered during the expected window of OFC increase or decrease. Pre- and post-TBS functional MRI assessments were conducted of target engagement and compulsive behaviors performed in response to an idiographically designed stressful laboratory probe.cTBS and iTBS modulated OFC activation in the expected directions. cTBS, relative to iTBS, exhibited a beneficial impact on acute laboratory assessments of compulsive behaviors 90 minutes after TBS. These acute behavioral effects persisted 1 week after cTBS.Experimental modulation of the OFC, within the behavioral context of habit override training, affected short-term markers of compulsive behavior vulnerability. The findings help delineate a causal translational model, serving as an initial precursor to mechanistic intervention development.
P54.04 A Study to Determine the Association of Trace Eelments and Heavy Metals with Lung Cancer and their Correlation with Smoking
Authors: I. Vanidassane, P. Malik, P. Gupta, J. Sharma, S. Kumar, S. Gunasekar, D. Jain, S. V, A. Mohan, D. Ramavath
Journal: Journal of Thoracic Oncology (2021)
Tralokinumab does not impact vaccine-induced immune responses: Results from a 30-week, randomized, placebo-controlled trial in adults with moderate-to-severe atopic dermatitis
Authors: Joseph F. Merola, Jerry Bagel, Peter Almgren, Mads A. Røpke, Katja W. Lophaven, Natacha Strange Vest, Parbeer Grewal
Journal: Journal of the American Academy of Dermatology (2021)

Atopic dermatitis (AD) is a chronic inflammatory skin disease. Interleukin (IL) 13 is a type 2 cytokine that is key to the inflammation underlying AD. Tralokinumab is a first-in-class, fully human, monoclonal antibody that specifically binds with high affinity to IL-13, neutralizing it in AD. Immunomodulatory treatments may impair vaccine-induced immune responses.Assess the immune responses to standard vaccines in adults with moderate-to-severe AD who are undergoing treatment with tralokinumab.ECZema TRAlokinumab Trial No. 5 (ECZTRA 5; NCT03562377) was a phase 2, double-blind, randomized, placebo-controlled trial taking place over 30 weeks. Eligible adults were randomized 1:1, with 107 patients receiving tralokinumab 300 mg and 108 patients receiving a placebo every 2 weeks for 16 weeks. All patients received Tdap (tetanus/diphtheria/pertussis) and meningococcal vaccines at week 12. The primary end points were positive antitetanus and antimeningococcal responses between weeks 12 and 16 (noninferiority margin, -25%; responder, >3-fold increase in IgG).The noninferiority of tralokinumab versus placebo for immune response to Tdap (91.9% vs 96.1%) and meningococcal (86.0% vs 84.2%) vaccines was demonstrated at week 16. During treatment, the rates of adverse events were lower for tralokinumab than for the placebo, with most events being mild or moderate.Responses to other vaccines (including influenza) were not examined.Treatment with tralokinumab 300 mg every 2 weeks did not affect immune responses to Tdap and meningococcal vaccines. Treatment was well tolerated when administered concomitantly with the vaccines and demonstrated a safety profile comparable to phase 3 trials.
P68.02 Computer Extracted Morphology Features of Tumor Nuclei Predict Response to Chemotherapy and Prognostic of OS in Small Cell Lung Cancer
Authors: P. Jain, C. Barrera, A. Osme, P.A. Toro, S. Chahar, K. Butler, M. Khorrami, P. Fu, G. Corredor, K. Bera, A. Dowlati, A. Madabhushi
Journal: Journal of Thoracic Oncology (2021)
Many “do not resuscitate” decisions in England during pandemic ignored equality and human rights laws, says CQC
Authors: Clare Dyer
Journal: BMJ (2021)

Equality and human rights laws were flouted when “inappropriate” advance non-resuscitation decisions were taken during the covid-19 pandemic, the Care Quality Commission (CQC) has found in a government commissioned report.1

The Department of Health and Social Care for England asked the CQC to carry out a rapid review after allegations that blanket “do not attempt cardiopulmonary resuscitation” (DNACPR) decisions were imposed on some groups, such as people in care homes, and that some people with DNACPR decisions in their records were unaware of the fact.

Advance decisions not to attempt cardiopulmonary resuscitation should a person’s heart or breathing stop in the future should be made only after discussion with the person involved or the family if the patient lacks capacity, and they should be made on an individual basis, the CQC emphasised. But, amid fears early in …
Abstract 12323: Early Percutaneous Coronary Intervention Does Not Affect 30-Day Readmissions in Patients Admitted With Acute Myocardial Infarction and Cardiogenic Shock
Authors: Karan Sud, Vivek Modi, Dhrubajyoti Bandyopadhyay, Xin Wei, Eyal Herzog
Journal: Circulation (2018)

Introduction: Few studies have looked at the predictors for readmissions in patients with acute myocardial infraction and cardiogenic shock. PCI timing is often determined based on the initial pres...
P76.47 Molecular Characteristics and Response to Diverse EGFR TKIs of NSCLC Patients Harboring EGFR E709-T710delinsX
Authors: W. Fang, C. Xu, X. Li, L. Zeng, X. Wang, J. Li, Y. Sun, Q. Zhang, N. Yang, Y. Huang, S. Li, J. Ye
Journal: Journal of Thoracic Oncology (2021)
A genetic map of the mouse dorsal vagal complex and its role in obesity
Authors: Mette Q. Ludwig, Wenwen Cheng, Desiree Gordian, Julie Lee, Sarah J. Paulsen, Stine N. Hansen, Kristoffer L. Egerod, Pernille Barkholt, Christopher J. Rhodes, Anna Secher, Lotte Bjerre Knudsen, Charles Pyke, Martin G. Myers, Tune H. Pers
Journal: Nature Metabolism (2021)
FP07.04 Predictive Efficacy of Morphological Biomarkers Based on Digital Pathology for ICI Therapy of Non-Small Cell Lung Cancer
Authors: N. Motoi, H. Yoshida, T. Kiyuna, H. Saiga, H. Horinouchi, T. Yoshida, S. Watanabe, Y. Ohe, A. Ochiai
Journal: Journal of Thoracic Oncology (2021)
Regulating Polθ in Breast Cancer
Authors: Denisse Carvajal-Maldonado, Richard D. Wood
Journal: Cancer Research (2021)

Abstract DNA polymerase θ, a protein encoded by the POLQ gene, is the defining factor for the DNA double-strand break repair pathway known as theta-mediated end-joining (TMEJ). Some cancers depend on TMEJ for survival and tumor growth. TMEJ might be useful as a biomarker to guide patient treatment and is now an active target for drug development, making it critical to understand how it is regulated in cells. In a recent article, Prodhomme and colleagues provide the first identification of a transcription regulator of POLQ expression and TMEJ activity: the transcription factor, ZEB1. See related article by Prodhomme et al., p. 1595
I Am Not Burned Out
Authors: Sarah M. Bagley
Journal: JAMA (2021)

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Optimising child and adolescent health and development through an integrated ecological life course approach
Authors: Mark Tomlinson, Xanthe Hunt, Bernadette Daelmans, Nigel Rollins, David Ross, Frank Oberklaid
Journal: BMJ (2021)

Fully realising the potential of children and adolescents will require an ecological life course approach, together with multisectoral, coordinated, integrated action for the provision of care and services for children and adolescents, argue <b>Mark Tomlinson and colleagues</b>
Nursing Home Characteristics Associated With Resident COVID-19 Morbidity in Communities With High Infection Rates
Authors: Angela T. Chen, Hyunkyung Yun, Kira L. Ryskina, Hye-Young Jung
Journal: JAMA Network Open (2021)

This cross-sectional study uses data from the Centers for Medicare and Medicaid Services Nursing Home COVID-19 Public File to assess the characteristics associated with resident morbidity among 3008 nursing homes in US communities with the highest COVID-19 infection prevalence.
FP12.01 Circulating Tumor DNA to the Identification of EGFR Positive NSCLC Long-Term Survivors
Authors: F. Franco, R. Serna-Blasco, A. Sanchez-Hernandez, M. De Julian Campayo, C. Garcia Giron, M. Dómine Gómez, A. Blasco, J.M. Sanchez, J. Oramas, J. Bosch-Barrera, M. Sala, M. Sereno Moyano, A.L. Ortega Granados, L.E. Chara, B. Hernandez, A. Padilla, J. Coves, R. Blanco, J. Balsalobre, X. Mielgo Rubio, C. Bueno, M. Auglyte, V. Calvo, A. Romero, M. Provencio
Journal: Journal of Thoracic Oncology (2021)
Abstract 14567: Percutaneous Coronary Intervention versus Coronary Artery Bypass Grafting in Patients With End-Stage Renal Disease Requiring Dialysis: 5-Year Outcomes of the CREDO-Kyoto PCI/CABG Registry Cohort-2
Authors: Akira Marui, Takeshi Kimura, Hiroki Shiomi, Shiro Tanaka, Michiya Hanyu, Tatsuhiko Komiya, Toru Kita, Ryuzo Sakata, Cabg Registry Cohort Investigators
Journal: Circulation (2013)

Background: Ischemic heart disease is a major risk factor for morbidity and mortality in patients with end-stage renal disease (ESRD). However, long-term benefit of percutaneous coronary interventi...
FP10.02 Investigating the Immunophenotype of Small Cell Lung Cancer to Improve Immunotherapeutic Targeting
Authors: S. Best, J. Hess, F. Souza-Fonseca Guimaraes, J. Cursons, A. Kersbergen, Y. You, J. Ng, M. Davis, T. Leong, L. Irving, M. Ritchie, D. Steinfort, N. Huntington, K. Sutherland
Journal: Journal of Thoracic Oncology (2021)