tbuckley/cabot-search huggingface dataset:
Abstract 19027: Glycation of ApoA-IV is Associated With the Severity of Coronary Artery Disease in Diabetic Patients and Glycated ApoA-IV Protein Promotes Atherogenesis Through Nuclear Receptor NR4A3 Mediation
Authors: Lin Lu, Yang Dai, Ying Shen, Jia Teng Sun, Xiao Qun Wang, Xiao Xiang Yan, Rui Yan Zhang, Wei Feng Shen
Journal: Circulation (2015)

Background: ApoA-IV is associated with HDL in plasma but a large portion circulates lipid free. It has been shown to possess anti-inflammatory and anti-atherosclerotic effects. Methods and Results: We isolated HDL from plasma of type 2 diabetic patients and healthy controls, and found that apoA-IV of HDL from diabetic patients was significantly glycated by using Western blot and mass spectrometry. The glycation levels of apoA-IV were higher in diabetic patients than in controls, and were associated with the severity of coronary artery disease. Immunohistochemically, glycation sites co-localized with apoA-IV in atherosclerotic plaques from diabetic patients. In cell and animal studies, in vitro glycated apoA-IV protein promoted inflammatory reactions in human aortic endothelial cells and atherogenesis in apoE-KO mice as compared with control, whereas apoA-IV exhibited anti-inflammatory and anti-atherogenic effects. The pro-inflammatory action of glycated apoA-IV was mediated by receptor for glycation end products in endothelial cells. In microarray analysis and verification in endothelial cells, glycated apoA-IV but not apoA-IV, enhanced the expression of nuclear receptor NR4A3 greatly. Glycated apoA-IV-induced inflammatory reaction and atherogenic effect was significantly attenuated in endothelial cell with siRNA-NR4A3, native endothelial cells and macrophages from NR4A3-KO mice and in NR4A3-KO mice. Co-localization of NR4A3 with CD31 was observed in atherosclerotic plaque from diabetic patients. Moreover, glycated apoA-IV but not apoA-IV induced trans-activation of NR4A3 to the promoter of adhesion molecules (VCAM-1, ICAM-1 and E-selectin). ESI-Q-TOF-MS identified several glycation sites including K78, K189 and K328 in apoA-IV from diabetic patients, but not in controls. Mutated apoA-IV proteins (m-apoA-IV-K78A/K189A/K328A) were made. In vitro glycated m-apoA-IV displayed significantly attenuated activation of NR4A3 in endothelial cells and atherogenesis in apoE-KO mice, as compared with glycated apoA-IV. Conclusion: Glycation of apoA-IV is associated with the severity of coronary artery disease in diabetic patients and glycated apoA-IV protein promotes atherogenesis through nuclear receptor NR4A3 mediation.
Palliative care interventions in intensive care unit patients
Authors: Victoria Metaxa, Despina Anagnostou, Savvas Vlachos, Nishkantha Arulkumaran, Sherihane Bensemmane, Ingeborg van Dusseldorp, Rebecca A. Aslakson, Judy E. Davidson, Rik T. Gerritsen, Christiane Hartog, J. Randall Curtis
Journal: Intensive Care Medicine (2021)
P52.01 Understanding Treatment Preferences of Patients With KRAS p.G12C[LC1] [MK2] – Mutated Advanced Non-Small Cell Lung Cancer
Authors: K. Myers, A. Barrett, C. Leach, T. Matsuda, K. Stevinson, C. Lu, C. Fu, M. Bittoni, C. Presley
Journal: Journal of Thoracic Oncology (2021)
P45.03 Tepotinib in Patients with MET exon 14 (METex14) Skipping NSCLC as Identified by Liquid (LBx) or Tissue (TBx) biopsy
Authors: E. Felip, M.C. Garassino, H. Sakai, X. Le, R. Veillon, E. Smit, J. Mazieres, A. Cortot, J. Raskin, M. Thomas, S. Viteri, W. Iams, H.R. Kim, J. Yang, C. Stroh, G. Otto, R. Bruns, P. Paik
Journal: Journal of Thoracic Oncology (2021)
P40.11 Trimodality Therapy Protocol in 144 Superior Sulcus Patients: Good Results Even for Extended Resections and Indications
Authors: M. Paul, J. Winkelman, C. Dickhoff, D. Heineman, S.M.S. Hashemi, M. Dahele, S. Ünal, H. Zandbergen, B. Koolen, J. Braun
Journal: Journal of Thoracic Oncology (2021)
Platelet transcriptome identifies progressive markers and potential therapeutic targets in chronic myeloproliferative neoplasms
Authors: Zhu Shen, Wenfei Du, Cecelia Perkins, Lenn Fechter, Vanita Natu, Holden Maecker, Jesse Rowley, Jason Gotlib, James Zehnder, Anandi Krishnan
Journal: Cell Reports Medicine (2021)

Predicting disease progression remains a particularly challenging endeavor in chronic degenerative disorders and cancer, thus limiting early detection, risk stratification, and preventive interventions. Here, profiling the three chronic subtypes of myeloproliferative neoplasms (MPNs), we identify the blood platelet transcriptome as a proxy strategy for highly sensitive progression biomarkers that also enables prediction of advanced disease via machine-learning algorithms. The MPN platelet transcriptome reveals an incremental molecular reprogramming that is independent of patient driver mutation status or therapy. Subtype-specific markers offer mechanistic and therapeutic insights, and highlight impaired proteostasis and a persistent integrated stress response. Using a LASSO model with validation in two independent cohorts, we identify the advanced subtype MF at high accuracy and offer a robust progression signature toward clinical translation. Our platelet transcriptome snapshot of chronic MPNs demonstrates a proof-of-principle for disease risk stratification and progression beyond genetic data alone, with potential utility in other progressive disorders.
Brain rhythms define distinct interaction networks with differential dependence on anatomy
Authors: Julien Vezoli, Martin Vinck, Conrado Arturo Bosman, André Moraes Bastos, Christopher Murphy Lewis, Henry Kennedy, Pascal Fries
Journal: Neuron (2021)

Cognitive functions are subserved by rhythmic neuronal synchronization across widely distributed brain areas. In 105 area pairs, we investigated functional connectivity (FC) through coherence, power correlation, and Granger causality (GC) in the theta, beta, high-beta, and gamma rhythms. Between rhythms, spatial FC patterns were largely independent. Thus, the rhythms defined distinct interaction networks. Importantly, networks of coherence and GC were not explained by the spatial distributions of the strengths of the rhythms. Those networks, particularly the GC networks, contained clear modules, with typically one dominant rhythm per module. To understand how this distinctiveness and modularity arises on a common anatomical backbone, we correlated, across 91 area pairs, the metrics of functional interaction with those of anatomical projection strength. Anatomy was primarily related to coherence and GC, with the largest effect sizes for GC. The correlation differed markedly between rhythms, being less pronounced for the beta and strongest for the gamma rhythm.
Natural Biomaterials from Biodiversity for Healthcare Applications
Authors: Erick Insuasti‐Cruz, Victoria Suárez‐Jaramillo, Kevin Andres Mena Urresta, Kevin O. Pila‐Varela, Xiomira Fiallos‐Ayala, Si Amar Dahoumane, Frank Alexis
Journal: Advanced Healthcare Materials (2021)

Natural biomaterials originating during the growth cycles of all living organisms have been used for many applications. They span from bioinert to bioactive materials including bioinspired ones. As they exhibit an increasing degree of sophistication, natural biomaterials have proven suitable to address the needs of the healthcare sector. Here the different natural healthcare biomaterials, their biodiversity sources, properties, and promising healthcare applications are reviewed. The variability of their properties as a result of considered species and their habitat is also discussed. Finally, some limitations of natural biomaterials are discussed and possible future developments are provided as more natural biomaterials are yet to be discovered and studied.
Robotic-assisted nipple-sparing mastectomy followed by immediate microsurgical free flap reconstruction: Feasibility and aesthetic results – Case series
Authors: Jung-Ju Huang, Eva Yu-Hsuan Chuang, David Chon-Fok Cheong, Bong-Sung Kim, Frank Chun-Shin Chang, Wen-Ling Kuo
Journal: International Journal of Surgery (2021)
Tunicate‐Inspired Photoactivatable Proteinic Nanobombs for Tumor‐Adhesive Multimodal Therapy
Authors: Yeonsu Jeong, Yun Kee Jo, Mou Seung Kim, Kye Il Joo, Hyung Joon Cha
Journal: Advanced Healthcare Materials (2021)

Abstract Near‐IR (NIR) light‐responsive multimodal nanotherapeutics have been proposed to achieve improved therapeutic efficacy and high specificity in cancer therapy. However, their clinical application is still elusive due to poor biometabolization and short retention at the target site. Here, innovative photoactivatable vanadium‐doped adhesive proteinic nanoparticles (NPs) capable of allowing biological photoabsorption and NIR‐responsive anticancer therapeutic effects to realize trimodal photothermal‐gas‐chemo‐therapy treatments in a highly biocompatible, site‐specific manner are proposed. The photoactivatable tumor‐adhesive proteinic NPs can enable efficient photothermal conversion via tunicate‐inspired catechol–vanadium complexes as well as prolonged tumor retention by virtue of mussel protein‐driven distinctive adhesiveness. The incorporation of a thermo‐sensitive nitric oxide donor and doxorubicin into the photoactivatable adhesive proteinic NPs leads to synergistic anticancer therapeutic effects as a result of photothermal‐triggered “bomb‐like” multimodal actions. Thus, this protein‐based phototherapeutic tumor‐adhesive NPs have great potential as a spatiotemporally controllable therapeutic system to accomplish effective therapeutic implications for the complete ablation of cancer.
Developing guidelines for the management of brain tumour related epilepsy
Authors: Elizabeth Vacher, Miguel Rodriguez Ruiz, Jeremy Rees
Journal: Neuro-Oncology (2021)

Abstract Aims Brain Tumour Related Epilepsy (BTRE) has a significant impact on Quality of Life with implications for driving, employment and social and domestic activities. Management of BTRE is complex due to the higher incidence of pharmacoresistance and the potential for interaction between anti-cancer therapy and anti-epileptic drugs (AEDs). Neurologists, oncologists, palliative care physicians and clinical nurse specialists treating these patients would benefit from up-to-date clinical guidelines. We aim to review the current evidence to adapt current NICE guidelines for Epilepsy and to outline specific recommendations for the optimal treatment of BTRE, encompassing both primary and metastatic brain tumours. Method A comprehensive search of the literature from the past 20 years on BTRE was carried out in three databases: Embase, Medline and EMCARE. A broad search strategy was used and the evidence was evaluated and graded based on the Oxford Centre for Evidence-Based Medicine Levels of Evidence. Results All patients with BTRE should be treated with AEDs. There is no proven benefit for the use of prophylactic AEDs, although there are no randomised trials testing newer agents. Seizure frequency varies between 10-40% (Class 2a evidence) in patients with Brain Metastases (BM) and from 30% (high-grade gliomas) to 90% (low-grade gliomas) (Class 2a evidence) in patients with Primary Brain Tumours (PBT). In patients with BM, risk factors include number of BM and melanoma histology (Class 2b evidence). In patients with PBT, risk factors include frontal and temporal location, oligodendroglial histology, IDH mutation and cortical infiltration (Class 2b evidence). There is a low incidence of seizures (13%) after stereotactic radiosurgery for BM (Class 2b evidence). Non-enzyme inducing AEDs are recommended as first line treatment for BTRE, but up to 50% of patients with BTRE due to PBT remain resistant (Class 2b evidence). Conclusion The review has highlighted the relative dearth of high quality evidence for the management of BTRE, and provides a framework for further studies aiming to improve seizure control, quality of life, and indications for AEDs.
P71.02 Molecular and Cellular Dynamics of Drug-Tolerant Persister (DTP) Cells During Osimertinib Therapy in EGFR Mutant Lung Adenocarcinoma
Authors: M. Mikubo, Q. Li, S. Filho, Y. Inoue, N. Pham, N. Moghal, M. Tsao
Journal: Journal of Thoracic Oncology (2021)
Optimizing drug selection from a prescription trajectory of one patient
Authors: Alejandro Aguayo-Orozco, Amalie Dahl Haue, Isabella Friis Jørgensen, David Westergaard, Pope Lloyd Moseley, Laust Hvas Mortensen, Søren Brunak
Journal: npj Digital Medicine (2021)

It is unknown how sequential drug patterns convey information on a patient's health status and treatment guidelines rarely account for this. Drug-agnostic longitudinal analyses of prescription trajectories in a population-wide setting are needed. In this cohort study, we used 24 years of data (1.1 billion prescriptions) from the Danish prescription registry to model the risk of sequentially redeeming a drug after another. Drug pairs were used to build multistep longitudinal prescription trajectories. These were subsequently used to stratify patients and calculate survival hazard ratios between the stratified groups. The similarity between prescription histories was used to determine individuals' best treatment option. Over the course of 122 million person-years of observation, we identified 9 million common prescription trajectories and demonstrated their predictive power using hypertension as a case. Among patients treated with agents acting on the renin-angiotensin system we identified four groups: patients prescribed angiotensin converting enzyme (ACE) inhibitor without change, angiotensin receptor blockers (ARBs) without change, ACE with posterior change to ARB, and ARB posteriorly changed to ACE. In an adjusted time-to-event analysis, individuals treated with ACE compared to those treated with ARB had lower survival probability (hazard ratio, 0.73 [95% CI, 0.64-0.82]; P < 1 × 10-16). Replication in UK Biobank data showed the same trends. Prescription trajectories can provide novel insights into how individuals' drug use change over time, identify suboptimal or futile prescriptions and suggest initial treatments different from first line therapies. Observations of this kind may also be important when updating treatment guidelines.
OA17.04 The Global Impact of COVID-19 on Telehealth and Care for Persons With Thoracic Cancers
Authors: M. Smeltzer, B. Bunn, Y.S. Choi, L. Coate, J. Corona-Cruz, A. Drilon, N. Duma, M. Edelman, M.J. Fidler, S. Gadgeel, Y. Goto, R. Herbst, M. Hesdorffer, K. Higgins, B. Labdi, T. Leal, S. Liu, J. Mazotti, S. Novello, S. Patel, S. Popat, R. Ramirez, K. Reckamp, N. Reguart, R. Soo, A. Tan, J. Wolf, S. Yano, B. Stiles, A. Baird
Journal: Journal of Thoracic Oncology (2021)
Comment on Choi et al. Alcohol Abstinence and the Risk of Atrial Fibrillation in Patients With Newly Diagnosed Type 2 Diabetes Mellitus: A Nationwide Population-Based Study. Diabetes Care 2021;44:1393–1401
Authors: Tsung-Kun Lin, Ya-Hui Lin, Gwo-Ping Jong
Journal: Diabetes Care (2021)

We read with great interest the article by Choi et al. (1), who investigated the impact of alcohol abstinence on the prevention of new-onset atrial fibrillation (AF) in patients with type 2 diabetes. They reported that alcohol abstinence was associated with a low risk of AF development in patients newly diagnosed with type 2 diabetes. This study is a valuable addition to clinical practice. However, two issues have not been addressed by the authors, preventing the generalization and ultimate application of the study …
A global cancer data integrator reveals principles of synthetic lethality, sex disparity and immunotherapy
Authors: Christopher Yogodzinski, Abolfazl Arab, Justin R. Pritchard, Hani Goodarzi, Luke A. Gilbert
Journal: Genome Medicine (2021)

Advances in cancer biology are increasingly dependent on integration of heterogeneous datasets. Large-scale efforts have systematically mapped many aspects of cancer cell biology; however, it remains challenging for individual scientists to effectively integrate and understand this data. We have developed a new data retrieval and indexing framework that allows us to integrate publicly available data from different sources and to combine publicly available data with new or bespoke datasets. Our approach, which we have named the cancer data integrator (CanDI), is straightforward to implement, is well documented, and is continuously updated which should enable individual users to take full advantage of efforts to map cancer cell biology. We show that CanDI empowered testable hypotheses of new synthetic lethal gene pairs, genes associated with sex disparity, and immunotherapy targets in cancer. CanDI provides a flexible approach for large-scale data integration in cancer research enabling rapid generation of hypotheses. The CanDI data integrator is available at https://github.com/GilbertLabUCSF/CanDI .
Covid-19: Prioritise vulnerable patients to prevent further deterioration, says charity
Authors: Elisabeth Mahase
Journal: BMJ (2021)

Covid-19: Prioritise vulnerable patients to prevent further deterioration, says charity Elisabeth MahaseClinically extremely vulnerable people, who have been asked to shield during the covid pandemic, have been left with "significant unmet health needs and worsening mental health" and should be prioritised by the NHS to ensure their conditions do not deteriorate further, the Health Foundation has said.1
I couldn’t pee when people were around
Authors: Ian Harris
Journal: BMJ (2021)

I couldn't pee when people were around Ian Harris shares how being unable to pee in public toilets was affecting his life, until his GP told him help was available Ian HarrisSomewhere in my late teens I started to have difficulty peeing in public toilets.I would stand there with nothing coming out, willing myself on with no success.As this problem became more frequent, I stopped going to urinals and used cubicles instead.In my mind this wasn't normal, and I started to feel inadequate compared with other men.I would try to make as little noise as possible so people couldn't hear me peeing in the cubicle, as I worried others would think I was weird.
Biomimetic hybrid hydrogel for hemostasis, adhesion prevention and promoting regeneration after partial liver resection
Authors: Zuhong Li, Yalei Zhao, Xiaoxi Ouyang, Ya Yang, Yangjun Chen, Qixia Luo, Yanhong Zhang, Danhua Zhu, Xiaopeng Yu, Lanjuan Li
Journal: Bioactive Materials (2021)

Partial liver resection is an established treatment for hepatic disorders. However, surgical bleeding, intra-abdominal adhesion and rapid liver regeneration are still major challenges after partial liver resection, associated with morbidity and mortality. Herein, a biomimetic hybrid hydrogel, composed of oxidized hyaluronic acid, glycol chitosan and MenSCs-derived conditioned medium (CM), is presented to address these issues. The hybrid hydrogel is formed through reversible Schiff base, and possesses injectability and self-healing capability. Moreover, hybrid hydrogel exhibits the capabilities of hemostasis, anti-infection, tissue adhesion and controllable release of cargoes. Based on in vivo studies of the multifunctional hybrid hydrogel, it is demonstrated that acute bleeding in partial liver resection can be ceased immediately by virtue of the hemostasis features of hybrid hydrogel. Also, a significant reduction of intra-abdominal adhesion is confirmed in hybrid hydrogel-treated resection surface. Furthermore, upon the treatment of hybrid hydrogel, hepatic cell proliferation and tissue regeneration can be significantly improved due to the controllably released cytokines from MenSCs-derived CM, exerting the effects of mitogenesis and anti-inflammation in vivo. Thus, the biomimetic hybrid hydrogel can be a promising candidate with great potential for application in partial liver resection.
CXCR4-Targeted Imaging of Post-Infarct Myocardial Tissue Inflammation
Authors: Rudolf A. Werner, Tobias Koenig, Johanna Diekmann, Arash Haghikia, Thorsten Derlin, James T. Thackeray, L. Christian Napp, Hans-Jürgen Wester, Tobias L. Ross, Andreas Schaefer, Johann Bauersachs, Frank M. Bengel
Journal: JACC. Cardiovascular imaging (2021)
Genomic Screening for Pathogenic Transthyretin Variants Finds Evidence of Underdiagnosed Amyloid Cardiomyopathy From Health Records
Authors: Brendan J. Carry, Katelyn Young, Samuel Fielden, Melissa A. Kelly, Amy C. Sturm, J. David Avila, Christa L. Martin, H. Lester Kirchner, Brandon K. Fornwalt, Christopher M. Haggerty
Journal: JACC CardioOncology (2021)

New treatments for transthyretin amyloidosis improve survival, but diagnosis remains challenging. Pathogenic or likely pathogenic (P/LP) variants in the transthyretin (TTR) gene are one cause of transthyretin amyloidosis, and genomic screening has been proposed to identify at-risk individuals. However, data on disease features and penetrance are lacking to inform the utility of such population-based genomic screening for TTR. This study characterized the prevalence of P/LP variants in TTR identified through exome sequencing and the burden of associated disease from electronic health records for individuals with these variants from a large (N = 134,753), primarily European-ancestry cohort. We compared frequencies of common disease features and cardiac imaging findings between individuals with and without P/LP TTR variants. We identified 157 of 134,753 (0.12%) individuals with P/LP TTR variants (43% male, median age 52 [Q1-Q3: 37–61] years). Seven P/LP variants accounted for all observations, the majority being V122I (p.V142I; 113, 0.08%). Approximately 60% (n = 91) of individuals with P/LP TTR variants (all V122I) had African ancestry. Diagnoses of amyloidosis were limited (2 of 157 patients), although related heart disease diagnoses, including cardiomyopathy and heart failure, were significantly increased in individuals with P/LP TTR variants who were aged >60 years. Fourteen percent (7 of 49) of individuals aged ≥60 or older with a P/LP TTR variant had heart disease and ventricular septal thickness >1.2 cm, only one of whom was diagnosed with amyloidosis. Individuals with P/LP TTR variants identified by genomic screening have increased odds of heart disease after age 60 years, although amyloidosis is likely underdiagnosed without knowledge of the genetic variant.