tbuckley/cabot-search huggingface dataset:
Abstract 14816: Twelve-month Outcomes of Stenting versus Standard Balloon Angioplasty for the Below-the-Knee Arterial Disease Patients Underwent Percutaneous Transluminal Angioplasty
Authors: Seung Woon Rha, Byoung Geol Choi, Se Yeon Choi, Jae Kyeong Byun, Jin Oh Na, Cheol Ung Choi, Hong Euy Lim, Jin Won Kim, Eung Ju Kim, Chang Gyu Park, Hong Seog Seo, Dong Joo Oh
Journal: Circulation (2015)

Background: Although percutaneous transluminal angioplasty (PTA) is considered as an effective treatment strategy in patients (pts) with critical limb ischemia (CLI), below-the-knee (BTK) lesions with CLI is particularly challenging. This study sought to compare the 12-month outcomes following stenting versus standard plain old balloon angioplasty (POBA) alone in BTK lesions. Method: This study consisted of 339 consecutive lower extremity arterial disease pts (394 limbs, 1026 lesions included 716 BTK lesions) with BTK lesions from Sep 2004 to Dec 2013. All the enrolled pts were treated by stenting (bare metal stents, primary or provisional, 78 limbs in 73 pts) or POBA (316 limbs in 266 pts) with PTA. Procedural success, complications and clinical outcomes were compared between the two groups up to 12 months. To adjust potential confounders, a propensity score matched (PSM) analysis was performed using the logistic regression model. Results: After PSM analysis, 2 propensity-matched groups (56 pairs in pts, n= 112; 61 pairs in limbs, n=122, C-statistic=0.808) were generated, and the baseline &amp; angiographic characteristics of the two groups were balanced. Procedural success, complication incidences were similar between the two groups. Six to 9-month CT or angiographic follow-up, there were similar incidence of binary restenosis, primary, and secondary patency. At 12 months, there were similar incidence of individual hard endpoints including mortality, myocardial infarction, limb salvage, and any extremity amputations except the target lesion and extremity revascularization. Repeat PTA incidence was higher in the stenting group than POBA group (table). Conclusion: Although the repeat PTA risk was increased with BTK stenting, other major individual clinical outcomes and limb salvage rates were similar between the POBA and stenting for the BTK lesions.
MINTIE: identifying novel structural and splice variants in transcriptomes using RNA-seq data
Authors: Marek Cmero, Breon Schmidt, Ian J. Majewski, Paul G. Ekert, Alicia Oshlack, Nadia M. Davidson
Journal: Genome biology (2021)

Calling fusion genes from RNA-seq data is well established, but other transcriptional variants are difficult to detect using existing approaches. To identify all types of variants in transcriptomes we developed MINTIE, an integrated pipeline for RNA-seq data. We take a reference-free approach, combining de novo assembly of transcripts with differential expression analysis to identify up-regulated novel variants in a case sample. We compare MINTIE with eight other approaches, detecting > 85% of variants while no other method is able to achieve this. We posit that MINTIE will be able to identify new disease variants across a range of disease types.
MA03.02 TROPION-PanTumor01: Updated Results From the NSCLC Cohort of the Phase 1 Study of Datopotamab Deruxtecan in Solid Tumors
Authors: E. Garon, M. Johnson, A. Lisberg, A. Spira, N. Yamamoto, R. Heist, J. Sands, K. Yoh, F. Meric-Bernstam, S. Kitazono, J. Greenberg, F. Kobayashi, F. Guevara, Y. Kawasaki, T. Shimizu
Journal: Journal of Thoracic Oncology (2021)
SR-Mitochondria Crosstalk Shapes Ca Signalling to Impact Pathophenotype in Disease Models Marked by Dysregulated Intracellular Ca Release
Authors: Brian D Tow, Arpita Deb, Shraddha Neupane, Shuchi M Patel, Meagan Reed, Anna-Beth Loper, Roman A Eliseev, Björn C Knollmann, Sándor Györke, Bin Liu
Journal: Cardiovascular Research (2021)

Diastolic Ca release (DCR) from sarcoplasmic reticulum (SR) Ca release channel ryanodine receptor (RyR2) has been linked to multiple cardiac pathologies, but its exact role in shaping divergent cardiac pathologies remains unclear. We hypothesize that the SR-mitochondria interplay contributes to disease phenotypes by shaping Ca signalling.
Abstract 13282: Prioritization of Post-Myocardial Infarction Heart Failure Targets Using Large-Scale Plasma Proteomics and Genome-Wide Single-Cardiac Cell Transcriptomics
Authors: Mark Y Chan, Motakis Efthymios, Sock-hwee Tan, Matthew A Johnson, Kelvin See, John Pickering, Richard Troughton, Chris J Pemberton, Hee Hwa Ho, Lieng Ling, Wern Miin Soo, Chester L Drum, Siang Chew Chai, Alan Fong, Joshua Loh, Chi Hang Lee, Roger Foo, Anna P Pilbrow, Arthur M Richards
Journal: Circulation (2019)

Introduction: Heart failure (HF) is the commonest complication of myocardial infarction (MI). Hypothesis: Large-scale plasma proteomics cross-referenced to unbiased single-cell transcriptomics can ...
Risks of Multiple Skin Cancers in Organ Transplant Recipients
Authors: Mackenzie R. Wehner, Jiangong Niu, Lee Wheless, Laura X. Baker, Olivia G. Cohen, David J. Margolis, Sharon H. Giordano, Thuzar M. Shin
Journal: JAMA Dermatology (2021)

<h3>Importance</h3> There are limited reports on the risks of multiple primary skin cancers in organ transplant recipients (OTRs). <h3>Objective</h3> To determine the risks over time and risk factors for OTRs developing (1) any skin cancer posttransplant, (2) a subsequent skin cancer after the first posttransplant skin cancer in the data sets used in the study, and (3) 10 or more skin cancers. <h3>Design, Setting, and Participants</h3> This retrospective cohort study used data from Optum deidentified electronic health record data set (7.7 million patients) and Truven Health MarketScan insurance claims data set (161 million patients) from 2007 to 2017. Skin cancers were identified using diagnosis plus treatment codes for basal cell carcinoma, squamous cell carcinoma, and melanoma; OTRs were identified using 4 or more diagnosis codes for organ transplant. Data analysis took place from January 1, 2007, to December 31, 2017. <h3>Main Outcomes and Measures</h3> Cumulative risks of (1) any skin cancer treatment posttransplant, (2) a subsequent skin cancer treatment after the first posttransplant skin cancer treatment in our data, and (3) 10 or more skin cancer treatments in OTRs. A Wei-Lin-Weissfeld marginal model was used to evaluate risk factors for any skin cancer. <h3>Results</h3> A total of 7390 OTRs in Optum and 133 651 in MarketScan were identified, 4.5% and 13.3% of which had had at least 1 skin cancer treatment, respectively. At 2 years after the initial posttransplant skin cancer in the data sets, OTRs had a 44.0% to 57.0% risk of a subsequent skin cancer treatment and a 3.7% to 6.6% risk of having 10 or more skin cancer treatments. Statistically significant risk factors for any skin cancer included age, history of skin cancer, and history of actinic keratosis in both data sets, and male sex and thoracic transplant in MarketScan. <h3>Conclusions and Relevance</h3> In this retrospective cohort study, approximately half of the OTRs who developed at least 1 posttransplant skin cancer developed a subsequent skin cancer within 2 years, and approximately 1 in 20 developed 10 or more skin cancers. Identifying OTRs at highest risk for multiple primary skin cancers may help target strategies for prevention and early detection.
Heatwave-associated Vibrio infections in Germany, 2018 and 2019
Authors: Thomas Theo Brehm, Laura Berneking, Meike Sena Martins, Susann Dupke, Daniela Jacob, Oliver Drechsel, Jürgen Bohnert, Karsten Becker, Axel Kramer, Martin Christner, Martin Aepfelbacher, Stefan Schmiedel, Holger Rohde
Journal: Eurosurveillance (2021)

BackgroundVibrio spp. are aquatic bacteria that prefer warm seawater with moderate salinity. In humans, they can cause gastroenteritis, wound infections, and ear infections. During the summers of 2018 and 2019, unprecedented high sea surface temperatures were recorded in the German Baltic Sea.AimWe aimed to describe the clinical course and microbiological characteristics of Vibrio infections in Germany in 2018 and 2019.MethodsWe performed an observational retrospective multi-centre cohort study of patients diagnosed with domestically-acquired Vibrio infections in Germany in 2018 and 2019. Demographic, clinical, and microbiological data were assessed, and isolates were subjected to whole genome sequencing and antimicrobial susceptibility testing.ResultsOf the 63 patients with Vibrio infections, most contracted the virus between June and September, primarily in the Baltic Sea: 44 (70%) were male and the median age was 65 years (range: 2-93 years). Thirty-eight patients presented with wound infections, 16 with ear infections, six with gastroenteritis, two with pneumonia (after seawater aspiration) and one with primary septicaemia. The majority of infections were attributed to V. cholerae (non-O1/non-O139) (n = 30; 48%) or V. vulnificus (n = 22; 38%). Phylogenetic analyses of 12 available isolates showed clusters of three identical strains of V. vulnificus, which caused wound infections, suggesting that some clonal lines can spread across the Baltic Sea.ConclusionsDuring the summers of 2018 and 2019, severe heatwaves facilitated increased numbers of Vibrio infections in Germany. Since climate change is likely to favour the proliferation of these bacteria, a further increase in Vibrio-associated diseases is expected.
Uncovering the Immunoregulatory Function and Therapeutic Potential of the PD-1/PD-L1 Axis in Cancer
Authors: Michael R. Pitter, Weiping Zou
Journal: Cancer Research (2021)

Abstract Immune checkpoint blockade involves the targeted antagonism of immunosuppressive interactions between antigen-presenting cells and/or tumor cells and effector T cells. Blockade of B7-H1, also known as programmed death-ligand 1 (PD-L1), prevents the ligation of inhibitory PD-L1 molecules to programmed cell death receptor 1 (PD-1) on T cells, engendering a potentiated response of tumor-specific T cells against tumor cells. In a Cancer Research article, Hirano and colleagues showed that T-cell–mediated tumor immunity becomes impaired when tumor cells interact with T cells via PD-L1 in the mouse tumor microenvironment. They showed that targeting PD-L1 or PD-1 with mAbs increased tumor cell lysis by T cells and suggested that tumor PD-L1 forms a “shield” preventing tumor cell lysis. Alongside other original mouse and human studies, this work generated scientific rationales for a new generation of cancer treatment focused on targeting the inhibitory PD-1/PD-L1 signaling pathway in the tumor microenvironment. See related article by Hirano and colleagues, Cancer Res 2005;65:1089–1096.
A Tale of Two Checkpoints: ATR Inhibition and PD-(L)1 Blockade
Authors: Natalie Y.L. Ngoi, Guang Peng, Timothy A. Yap
Journal: Annual Review of Medicine (2021)

Innate immunity and the DNA damage response (DDR) pathway are inextricably linked. Within the DDR, ataxia telangiectasia and Rad3-related (ATR) is a key kinase responsible for sensing replication stress and facilitating DNA repair through checkpoint activation, cell cycle arrest, and promotion of fork recovery. Recent studies have shed light on the immunomodulatory role of the ATR-CHK1 pathway in the tumor microenvironment and the specific effects of ATR inhibition in stimulating an innate immune response. With several potent and selective ATR inhibitors in developmental pipelines, the combination of dual ATR and PD-(L)1 blockade has attracted increasing interest in cancer therapy. In this review, we summarize the clinical and preclinical data supporting the combined inhibition of ATR and PD-(L)1, discuss the potential challenges surrounding this approach, and highlight biomarkers relevant for selected patients who are most likely to benefit from the blockade of these two checkpoints.
P60.05 Radiomic Signature to Predict Outcomes in EGFR-Mutant Non-Small Cell Lung Cancer
Authors: J.N. Minatta, D. Deza, M. Aineseder, M. Mestas Nuñez, C. Mosquera, L. Lupinacci, S. Benitez, A. Seehaus, D. Luna, A. Beresñak, F. Diaz
Journal: Journal of Thoracic Oncology (2021)
Conjugate Electrospun 3D Gelatin Nanofiber Sponge for Rapid Hemostasis (Adv. Healthcare Mater. 20/2021)
Authors: Xianrui Xie, Dan Li, Yujie Chen, Yihong Shen, Fan Yu, Wei Wang, Zhengchao Yuan, Yosry Morsi, Jinglei Wu, Xiumei Mo
Journal: Advanced Healthcare Materials (2021)
FP12.03 Associations of Urinary Biomarkers of Tobacco Toxicants With Lung Cancer Incidence in Smokers: The Multiethnic Cohort Study
Authors: S. Cigan, S. Murphy, Y. Patel, D. Stram, L. Le Marchand, S. Hecht, I. Stepanov, S. Park
Journal: Journal of Thoracic Oncology (2021)
L-Type Calcium Channel Blockers: A Potential Novel Therapeutic Approach to Drug Dependence
Authors: Hilary J. Little
Journal: Pharmacological Reviews (2021)

This review describes interactions between compounds, primarily dihydropyridines, that block L-type calcium channels and drugs that cause dependence, and the potential importance of these interactions. The main dependence-inducing drugs covered are alcohol, psychostimulants, opioids, and nicotine. In preclinical studies, L-type calcium channel blockers prevent or reduce important components of dependence on these drugs, particularly their reinforcing actions and the withdrawal syndromes. The channel blockers also reduce the development of tolerance and/or sensitization, and they have no intrinsic dependence liability. In some instances, their effects include reversal of brain changes established during drug dependence. Prolonged treatment with alcohol, opioids, psychostimulant drugs, or nicotine causes upregulation of dihydropyridine binding sites. Few clinical studies have been carried out so far, and reports are conflicting, although there is some evidence of effectiveness of L-channel blockers in opioid withdrawal. However, the doses of L-type channel blockers used clinically so far have necessarily been limited by potential cardiovascular problems and may not have provided sufficient central levels of the drugs to affect neuronal dihydropyridine binding sites. New L-type calcium channel blocking compounds are being developed with more selective actions on subtypes of L-channel. The preclinical evidence suggests that L-type calcium channels may play a crucial role in the development of dependence to different types of drugs. Mechanisms for this are proposed, including changes in the activity of mesolimbic dopamine neurons, genomic effects, and alterations in synaptic plasticity. Newly developed, more selective L-type calcium channel blockers could be of considerable value in the treatment of drug dependence. <h3>Significance Statement</h3> Dependence on drugs is a very serious health problem with little effective treatment. Preclinical evidence shows drugs that block particular calcium channels, the L-type, reduce dependence-related effects of alcohol, opioids, psychostimulants, and nicotine. Clinical studies have been restricted by potential cardiovascular side effects, but new, more selective L-channel blockers are becoming available. L-channel blockers have no intrinsic dependence liability, and laboratory evidence suggests they reverse previously developed effects of dependence-inducing drugs. They could provide a novel approach to addiction treatment.
Abstract 17855: Prognostic Impact of Coronary Revascularization in Acute Coronary Syndrome Patients With Cardiogenic Shock
Authors: Kazuo Sakamoto, Tetsuya Matoba, Masahiro Mohri, Nobuhiro Tanaka, Yohei Hokama, Motoki Fukutomi, Katsutaka Hashiba, Rei Fukuhara, Yasushi Ueki, Satoru Suwa, Hirohide Matsuura, Eizo Tachibana, Naohiro Yonemoto, Ken Nagao
Journal: Circulation (2015)

Background: Randomized trials have shown that coronary revascularization benefits patients with acute coronary syndrome (ACS). Furthermore, recent studies reported that revascularization could improve the outcome even in high-risk patients. We investigated the prognostic impact of revascularization and the factors that abandon the invasive strategy in patients with ACS complicated with cardiogenic shock. Methods and results: The Japanese Circulation Society Cardiovascular Shock registry (JCS-Shock registry) was a prospective, observational, multi-center, cohort study. Between May, 2012 and June, 2014, a total of 980 patients with cardiovascular shock were enrolled from 82 centers in Japan. We assessed the prognostic impact of coronary revascularization in ACS patients in JCS-Shock registry. The primary endpoint was all cause mortality at 30 days after administration. Among 495 subjects with ACS (ST-segment elevation acute myocardial infarction (STEMI) 408, Non-ST-segment elevation ACS (NSTEACS) 87), emergent coronary angiography was carried out in 448 (90.9%) subjects and any revascularization (percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG)) was performed in 411 (83.0%) subjects. Thirty-day mortality in subjects treated with PCI and/or CABG (Revasc group) was 29.8% and neither PCI nor CABG (Non-Revasc group) was 51.2% (n=84, 17.0%) (P=0.0015 by Chi-square test), suggesting a beneficial effect of revascularization. Baseline characteristics of subgroups in Revasc or Non-Revasc were significantly different in age (71.0 vs. 76.5, P&lt;0.0037), female gender (23.2% vs. 40.5%, P=0.0016), previous PCI (66.7% vs. 39.1%, P&lt;0.0276), STEACS (86.8% vs. 60.7%, P&lt;0.0001). Conclusions: In the JCS Shock registry that observed contemporary emergency cardiovascular care in Japan, 30-day mortality of ACS complicated with cardiogenic shock was lower in patients underwent coronary revascularization compared with patients without any revascularization. Revascularization was less performed in elderly, female, patients without previous PCI and NSTEACS patients, associated with unfavorable outcomes. We may reconsider the therapeutic strategy to benefit patients by coronary revascularization.
Electrophysiological Manifestations of Cardiac Amyloidosis
Authors: Jack Hartnett, Wael Jaber, Mathew Maurer, Brett Sperry, Mazen Hanna, Patrick Collier, Divyang R. Patel, Oussama M. Wazni, Eoin Donnellan
Journal: JACC CardioOncology (2021)

Cardiac amyloidosis (CA) is an infiltrative cardiomyopathy caused by the extracellular deposition of amyloid fibrils in the myocardium. Although cardiac amyloidosis patients primarily present with heart failure symptoms, arrhythmias and conduction system disease are frequently encountered. Atrial fibrillation (AF) is observed in up to 70% of patients at the time of diagnosis, and patients typically have controlled ventricular rates caused by concomitant conduction system disease. Thromboembolic risk is particularly high in patients with CA and AF, and left atrial thrombi have been observed even in the absence of clinically diagnosed AF. Atrioventricular nodal and infra-Hisian disease are common, and permanent pacemakers are frequently required. The use of implantable cardioverter-defibrillators in this population is controversial. This review summarizes the published data and therapeutic strategies surrounding arrhythmias and conduction system disease with the goal of aiding clinicians managing the clinical complexities of CA.
Development of Nickel Selenide@polydopamine Nanocomposites for Magnetic Resonance Imaging Guided NIR‐II Photothermal Therapy
Authors: Wenxue Hu, Wenyao Zhen, Mengchao Zhang, Wei Wang, Xiaodan Jia, Shangjie An, Yue Wang, Zhuo Guo, Xiue Jiang
Journal: Advanced Healthcare Materials (2021)

The penetration depth of near-infrared laser has greatly restricted the development of most photothermal agents. Recently, photothermal agents in the second near-infrared (NIR-II) window have drawn great attention as they can overcome above barrier. Herein, a novel "all in one" NIR-II responsive nanoplatform (nickel selenide @polydopamine nanocomposites, NiSe@PDA NCs) based on in situ coating the polydopamine (PDA) on the surface of biomineralized nickel selenide nanoparticles (NiSe NPs) for dual-model imaging-guided photothermal therapy is reported. Under the illumination of NIR-II laser (1064 nm), the photothermal conversion efficiency of NiSe@PDA NCs can reach 48.4%, which is higher than that of single NiSe NPs due to the enhanced molar extinction coefficient. In addition, because of the paramagnetic effect of NiSe NPs, the constructed NiSe@PDA NCs can be acted as T1 contrast agent for magnetic resonance imaging (MRI). Most importantly, the MRI contrast effect is enhanced with the coating of PDA layer due to the loose structure of PDA. Ultimately, both in vitro and in vivo experiments demonstrate that the developed NCs can achieve efficient MRI-guided photothermal therapy for treating malignant tumor. Therefore, the designed NiSe@PDA NCs with excellent features show great potential for clinical MRI-guided cancer therapy.
Integrative epigenomic and high-throughput functional enhancer profiling reveals determinants of enhancer heterogeneity in gastric cancer
Authors: Taotao Sheng, Shamaine Wei Ting Ho, Wen Fong Ooi, Chang Xu, Manjie Xing, Nisha Padmanabhan, Kie Kyon Huang, Lijia Ma, Mohana Ray, Yu Amanda Guo, Ngak Leng Sim, Chukwuemeka George Anene-Nzelu, Mei Mei Chang, Milad Razavi-Mohseni, Michael A. Beer, Roger Sik Yin Foo, Raghav Sundar, Yiong Huak Chan, Angie Lay Keng Tan, Xuewen Ong, Anders Jacobsen Skanderup, Kevin P. White, Sudhakar Jha, Patrick Tan
Journal: Genome Medicine (2021)

Abstract Background Enhancers are distal cis -regulatory elements required for cell-specific gene expression and cell fate determination. In cancer, enhancer variation has been proposed as a major cause of inter-patient heterogeneity—however, most predicted enhancer regions remain to be functionally tested. Methods We analyzed 132 epigenomic histone modification profiles of 18 primary gastric cancer (GC) samples, 18 normal gastric tissues, and 28 GC cell lines using Nano-ChIP-seq technology. We applied Capture-based Self-Transcribing Active Regulatory Region sequencing (CapSTARR-seq) to assess functional enhancer activity. An Activity-by-contact (ABC) model was employed to explore the effects of histone acetylation and CapSTARR-seq levels on enhancer-promoter interactions. Results We report a comprehensive catalog of 75,730 recurrent predicted enhancers, the majority of which are GC-associated in vivo (&gt; 50,000) and associated with lower somatic mutation rates inferred by whole-genome sequencing. Applying CapSTARR-seq to the enhancer catalog, we observed significant correlations between CapSTARR-seq functional activity and H3K27ac/H3K4me1 levels. Super-enhancer regions exhibited increased CapSTARR-seq signals compared to regular enhancers, even when decoupled from native chromatin contexture. We show that combining histone modification and CapSTARR-seq functional enhancer data improves the prediction of enhancer-promoter interactions and pinpointing of germline single nucleotide polymorphisms (SNPs), somatic copy number alterations (SCNAs), and trans -acting TFs involved in GC expression. We identified cancer-relevant genes ( ING1 , ARL4C ) whose expression between patients is influenced by enhancer differences in genomic copy number and germline SNPs, and HNF4α as a master trans -acting factor associated with GC enhancer heterogeneity. Conclusions Our results indicate that combining histone modification and functional assay data may provide a more accurate metric to assess enhancer activity than either platform individually, providing insights into the relative contribution of genetic ( cis ) and regulatory ( trans ) mechanisms to GC enhancer functional heterogeneity.