tbuckley/cabot-search huggingface dataset:
A large-scale genome-wide association analysis of lung function in the Chinese population identifies novel loci and highlights shared genetic aetiology with obesity
Authors: Zhaozhong Zhu, Jiachen Li, Jiahui Si, Baoshan Ma, Huwenbo Shi, Jun Lv, Weihua Cao, Yu Guo, Iona Y. Millwood, Robin G. Walters, Kuang Lin, Ling Yang, Yiping Chen, Huaidong Du, Bo Yu, Kohei Hasegawa, Carlos A. Camargo, Miriam F. Moffatt, William O.C. Cookson, Junshi Chen, Zhengming Chen, Liming Li, Canqing Yu, Liming Liang
Journal: European Respiratory Journal (2021)

Background Lung function is a heritable complex phenotype with obesity being one of its important risk factors. However, knowledge of their shared genetic basis is limited. Most genome-wide association studies (GWASs) for lung function have been based on European populations, limiting the generalisability across populations. Large-scale lung function GWASs in other populations are lacking. Methods We included 100 285 subjects from the China Kadoorie Biobank (CKB). To identify novel loci for lung function, single-trait GWAS analyses were performed on forced expiratory volume in 1 s (FEV 1 ), forced vital capacity (FVC) and FEV 1 /FVC in the CKB. We then performed genome-wide cross-trait analysis between lung function and obesity traits (body mass index (BMI), BMI-adjusted waist-to-hip ratio and BMI-adjusted waist circumference) to investigate the shared genetic effects in the CKB. Finally, polygenic risk scores (PRSs) of lung function were developed in the CKB and their interaction with BMI's association on lung function were examined. We also conducted cross-trait analysis in parallel with the CKB using up to 457 756 subjects from the UK Biobank (UKB) for replication and investigation of ancestry-specific effects. Results We identified nine genome-wide significant novel loci for FEV 1 , six for FVC and three for FEV 1 /FVC in the CKB. FEV 1 and FVC showed significant negative genetic correlation with obesity traits in both the CKB and UKB. Genetic loci shared between lung function and obesity traits highlighted important biological pathways, including cell proliferation, embryo, skeletal and tissue development, and regulation of gene expression. Mendelian randomisation analysis suggested significant negative causal effects of BMI on FEV 1 and on FVC in both the CKB and UKB. Lung function PRSs significantly modified the effect of change in BMI on change in lung function during an average follow-up of 8 years. Conclusion This large-scale GWAS of lung function identified novel loci and shared genetic aetiology between lung function and obesity. Change in BMI might affect change in lung function differently according to a subject's polygenic background. These findings may open new avenues for the development of molecular-targeted therapies for obesity and lung function improvement.
Cytotoxic lymphocytes target characteristic biophysical vulnerabilities in cancer
Authors: Maria Tello-Lafoz, Katja Srpan, Elisa E. Sanchez, Jing Hu, Jan Remsik, Yevgeniy Romin, Annalisa Calò, Douglas Hoen, Umeshkumar Bhanot, Luc Morris, Adrienne Boire, Katharine C. Hsu, Joan Massagué, Morgan Huse, Ekrem Emrah Er
Journal: Immunity (2021)
P14.03 Increased Tumor-Associated LAG-3+ Lymphocytes Correlate with Aggressive Tumor Behavior and Worse Prognosis in Lung Adenocarcinoma
Authors: D. Shepherd, E. Tabb, M.L. Zhang, M. Kem, Y. Hung, M. Mino-Kenudson
Journal: Journal of Thoracic Oncology (2021)
Vascular smooth muscle cell phenotypic switching and plaque stability: a role for CHI3L1
Authors: Jordi Lambert, Helle F Jørgensen
Journal: Cardiovascular Research (2021)

Corrected proof Vascular smooth muscle cell phenotypic switching and plaque stability: a role for CHI3L1 Jordi Lambert, Jordi Lambert Cardiovascular Medicine Division, Department of Medicine, University of Cambridge, Box 110, ACCI, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK https://orcid.org/0000-0003-4724-5200 Search for other works by this author on: Oxford Academic PubMed Google Scholar Helle F Jørgensen Helle F Jørgensen Cardiovascular Medicine Division, Department of Medicine, University of Cambridge, Box 110, ACCI, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK Corresponding author. Tel: +441223762581, E-mail: hfj22@cam.ac.uk https://orcid.org/0000-0002-7909-2977 Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, cvab099, https://doi.org/10.1093/cvr/cvab099 Published: 11 April 2021
P04.01 Adjuvant Chemotherapy is not Associated with Worse Disease-Free Survival in the Elderly Population.
Authors: L.B. Mendes Gomes, M.D. Spina Donadio, D. Maciel Santana, M.F. Evangelista Simões, M.F. Barbosa De Medeiros, C.I. De Andrade Souza, M. Petrocchi Corassa, H. De Freitas, V.C. De Lima
Journal: Journal of Thoracic Oncology (2021)
Randomized multi-reader evaluation of automated detection and segmentation of brain tumors in stereotactic radiosurgery with deep neural networks
Authors: Shao-Lun Lu, Fu-Ren Xiao, Jason Chia-Hsien Cheng, Wen-Chi Yang, Yueh-Hung Cheng, Yu-Cheng Chang, Jhih-Yuan Lin, Chih-Hung Liang, Jen-Tang Lu, Ya-Fang Chen, Feng-Ming Hsu
Journal: Neuro-Oncology (2021)

Abstract Background Stereotactic radiosurgery (SRS), a validated treatment for brain tumors, requires accurate tumor contouring. This manual segmentation process is time-consuming and prone to substantial inter-practitioner variability. Artificial intelligence (AI) with deep neural networks have increasingly been proposed for use in lesion detection and segmentation but have seldom been validated in a clinical setting. Methods We conducted a randomized, cross-modal, multi-reader, multispecialty, multi-case study to evaluate the impact of AI assistance on brain tumor SRS. A state-of-the-art auto-contouring algorithm built on multi-modality imaging and ensemble neural networks was integrated into the clinical workflow. Nine medical professionals contoured the same case series in two reader modes (assisted or unassisted) with a memory washout period of 6 weeks between each section. The case series consisted of 10 algorithm-unseen cases, including five cases of brain metastases, three of meningiomas, and two of acoustic neuromas. Among the nine readers, three experienced experts determined the ground truths of tumor contours. Results With the AI assistance, the inter-reader agreement significantly increased (Dice similarity coefficient [DSC] from 0.86 to 0.90, P &amp;lt; 0.001). Algorithm-assisted physicians demonstrated a higher sensitivity for lesion detection than unassisted physicians (91.3% vs 82.6%, P = .030). AI assistance improved contouring accuracy, with an average increase in DSC of 0.028, especially for physicians with less SRS experience (average DSC from 0.847 to 0.865, P = .002). In addition, AI assistance improved efficiency with a median of 30.8% time-saving. Less-experienced clinicians gained prominent improvement on contouring accuracy but less benefit in reduction of working hours. By contrast, SRS specialists had a relatively minor advantage in DSC, but greater time-saving with the aid of AI. Conclusions Deep learning neural networks can be optimally utilized to improve accuracy and efﬁciency for the clinical workflow in brain tumor SRS.
Camrelizumab in combination with apatinib in second-line or above therapy for advanced primary liver cancer: cohort A report in a multicenter phase Ib/II trial
Authors: Kuimin Mei, Shukui Qin, Zhendong Chen, Ying Liu, Linna Wang, Jianjun Zou
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Emerging clinical data suggest that an immune checkpoint inhibitor in combination with an antiangiogenic agent is a reasonable strategy for multiple malignancies. We assessed the combination of camrelizumab with apatinib in pretreated advanced primary liver cancer (PLC, cohort A) from a multicohort phase Ib/II trial. Methods Patients with PLC after prior systemic treatment(s) were administered camrelizumab (3 mg/kg, once every 2 weeks) plus apatinib (125, 250, 375, or 500 mg; once per day) in a 3+3 dose-escalation stage and subsequent expansion stage. The primary endpoints were tolerability and safety of study treatment. Results From April 2017 to July 2019, 28 patients (21 with hepatocellular carcinoma and 7 with intrahepatic cholangiocarcinoma) received camrelizumab plus apatinib. Two dose-limiting toxicities (both grade 3 diarrhea) were reported in the 500 mg cohort. Therefore, the 375 mg cohort was expanded. Of the 19 patients in the 375 mg cohort, dose reduction to 250 mg occurred in 8 patients within 2 months after treatment initiation. Of the 28 patients with PLC, 26 had grade ≥3 treatment-related adverse events, with hypertension being the most common (9/28). One treatment-related death occurred. The objective response rate was 10.7% (95% CI 2.3% to 28.2%). Median progression-free survival and overall survival were 3.7 months (95% CI 2.0 to 5.8) and 13.2 months (95% CI 8.9 to not reached), respectively. Conclusion The combination of camrelizumab with apatinib had a manageable toxicity and promising antitumor activity in patients with advanced PLC. Apatinib at a dose of 250 mg is recommended as a combination therapy for further studies of advanced PLC treatment. Trial registration numbers NCT03092895 .
P76.63 Dacomitinib Induces a Drastic Response in Metastatic Brain Lesions of Patients with EGFR-mutant Non-small-cell Lung Cancer: A Brief Report
Authors: L. Wu, W. Peng, X. Pu, M. Jiang, J. Wang, J. Li, K. Li, Y. Xu, F. Xu, B. Chen, Q. Wang, J. Cao, Y. Chen
Journal: Journal of Thoracic Oncology (2021)
Current paradigms in epigenetic anticancer therapeutics and future challenges
Authors: Manoj Singh, Vikas Kumar, Nirmala Sehrawat, Mukesh Yadav, Mayank Chaudhary, Sushil K. Upadhyay, Sunil Kumar, Varruchi Sharma, Sandeep Kumar, Neeraj Dilbaghi, Anil K. Sharma
Journal: Seminars in Cancer Biology (2021)
P10.04 A Budget Impact Analysis for Treatment with Ramucirumab Plus Erlotinib in Metastatic EGFR-Mutated NSCLC in the US
Authors: J. Nilsson, K. Winfree, C. Molife, D. Bhattacharyya, Y. D'Yachova, X. Wang, M. Malmenäs, K. Taipale
Journal: Journal of Thoracic Oncology (2021)
Abstract 3072: Beneficial Effects of Cardiac Resynchronization Therapy in Patients with Class Two Heart Failure
Authors: Kristin E Ellison, Brad J Mikaelian, Karin F Hoth, Fausto G Devecchi, Athena Poppas, Malcolm M Kirk, Alfred E Buxton
Journal: Circulation (2007)

Cardiac resynchronization therapy (CRT) improves heart failure (HF) symptoms in patients (pts) with EF &lt;35%, QRS &gt;120ms, and NYHA class 3 and 4 HF. The aim of this study was to compare the effects of CRT in pts with EF &lt;35%, QRS &gt;130, and class 2 vs 3/4 HF. We enrolled 25 patients. All received ECGs, transthoracic echocardiograms, 6 minute walk tests, and Minnesota quality of life questionnaires pre-op and three months post-op. Fourteen pts were class 2, 10 patients were class 3, and 1 class 4. Ischemic cardiomyopathy accounted for 7 out of the 14 class 2 pts and 5 out of the 11 class 3/4 pts. As a group, all patients had a significant increase in 6 minute walk (1150 vs 1249, p=0.02), increase in EF (30% vs 39%, p&lt;0.01), decreased QRS duration (162 vs 143, p=0.001), and improved quality of life scores (31.1 vs 21.7, p=0.03), comparing pre and post-op measurements. There was no significant difference in response of class 2 versus class 3/4 pts (see table ). Nonischemic pts had greater response than ischemic pts. Class 2 HF pts reported greater improvement in mental health than class 3 and 4. Younger patients reported greater functional improvement, while pts with higher BMI reported less physical benefit. Summary: Pts with NYHA class 2 symptoms derive similar hemodynamic benefit from CRT as pts with class 3/4 symptoms and may derive greater mental health benefits than class 3/4 pts. Comparison of Pre and Post-Implant Parameters Between Class 2 and 3/4 Patients
Identification of the canonical and noncanonical role of miR-143/145 in estrogen-deficient bone loss
Authors: Rongyao Xu, Xin Shen, Hanyu Xie, Hengguo Zhang, Dingshan Liu, Xin Chen, Yu Fu, Ping Zhang, Yi Yang, Jie Cheng, Hongbing Jiang
Journal: Theranostics (2021)

Rationale: Postmenopausal-induced bone loss is mainly caused by declining core transcription factors (TFs) of bone mesenchymal stem cells (BMSCs), but little is known about how miRNAs regulate chromatin structure remodeling of TFs gene to maintain BMSCs function in bone homeostasis. Methods: We examined the serum, salivary and bone samples from Pre- and Post-menopause women by paired analysis and confirmed canonical ceRNA role of MIR143HG and miR-143/145 complexes in cytoplasm and noncanonical role for SOX2 transcription in nucleus (FISH, qRT-PCR, immunostaining, Luciferase assays and ChIP). Moreover, we took advantage of transgenic mice under OVX-induced osteoporosis, studying the in vitro and in vivo effect of miR-143/145 deletion on BMSCs function and bone homeostasis. Last, using miRNA antagonism, antagomiR-143/145 were delivered into bone marrow to treat estrogen-deficient bone loss. Results: Here, we identified miR-143/145 as potential diagnostic candidates for postmenopausal osteoporosis, and miR-143/145 overexpression impaired BMSCs self-renewing and differentiation function. Mechanistically, we confirmed that cytoplasmic miR-143/145 and LncRNA MIR143HG, that controlled by ERβ, cooperatively regulated pluripotency genes translation via canonical ceRNA pathway, and MIR143HG cooperates with miR‑143 to nuclear translocation for co-activation of SOX2 transcription via opening promoter chromatin. Meanwhile, miR‑143/145 were shuttled into osteoclasts in extracellular vesicles and triggered osteoclastic activity by targeting Cd226 and Srgap2. Furthermore, miR-143/145-/- mice or using chemically‑modified antagomiR-143/145 significantly alleviated estrogen-deficient osteoporosis. Conclusions: Our findings reveal a canonical and noncanonical role of miR-143/145 in controlling BMSCs pluripotency and unfold their dual effect on bone formation and bone resorption, suggesting miR-143/145 as promising therapeutic targets for treating estrogen-deficient bone loss.
The histone acetyltransferase HBO1 functions as a novel oncogenic gene in osteosarcoma
Authors: Yan-yang Gao, Zhuo-yan Ling, Yun-Rong Zhu, Ce Shi, Yin Wang, Xiang-yang Zhang, Zhi-qing Zhang, Qin Jiang, Min-Bin Chen, Shuofei Yang, Cong Cao
Journal: Theranostics (2021)

HBO1 (KAT7 or MYST2) is a histone acetyltransferase that acetylates H3 and H4 histones. Methods: HBO1 expression was tested in human OS tissues and cells. Genetic strategies, including shRNA, CRISPR/Cas9 and overexpression constructs, were applied to exogenously alter HBO1 expression in OS cells. The HBO1 inhibitor WM-3835 was utilized to block HBO1 activation. Results:HBO1 mRNA and protein expression is significantly elevated in OS tissues and cells. In established (MG63/U2OS lines) and primary human OS cells, shRNA-mediated HBO1 silencing and CRISPR/Cas9-induced HBO1 knockout were able to potently inhibit cell viability, growth, proliferation, as well as cell migration and invasion. Significant increase of apoptosis was detected in HBO1-silenced/knockout OS cells. Conversely, ectopic HBO1 overexpression promoted OS cell proliferation and migration. We identified ZNF384 (zinc finger protein 384) as a potential transcription factor of HBO1. Increased binding between ZNF384 and HBO1 promoter was detected in OS cell and tissues, whereas ZNF384 silencing via shRNA downregulated HBO1 and produced significant anti-OS cell activity. In vivo, intratumoral injection of HBO1 shRNA lentivirus silenced HBO1 and inhibited OS xenograft growth in mice. Furthermore, growth of HBO1-knockout OS xenografts was significantly slower than the control xenografts. WM-3835, a novel and high-specific small molecule HBO1 inhibitor, was able to potently suppressed OS cell proliferation and migration, and led to apoptosis activation. Furthermore, intraperitoneal injection of a single dose of WM-3835 potently inhibited OS xenograft growth in SCID mice. Conclusion: HBO1 overexpression promotes OS cell growth in vitro and in vivo.
P07.07 Computed Tomography of Lymph Nodes to Predict Occult pN2 Disease in Non-Small-Cell Lung Cancer
Authors: H. Onozawa, D. Nemoto, J. Miura, D. Eriguchi, H. Adachi, T. Nagashima, H. Ito, H. Saito, T. Yokose, H. Nakayama, M. Iwazaki
Journal: Journal of Thoracic Oncology (2021)
Covid-19: Underfunding of health workforce left many European nations vulnerable, says commission
Authors: Gareth Iacobucci
Journal: BMJ (2021)

Many health systems in Europe have suffered “chronic underfunding and underinvestment in the health workforce,” which left them struggling to cope with the covid-19 pandemic, an independent commission has concluded.

In a report published on Tuesday 16 March1 the Pan-European Commission on Health and Sustainable Development, convened by the World Health Organization, urged European leaders to “learn the lessons from this crisis” and implement change accordingly.

“We cannot achieve a sustainable future for health and development in Europe if we fail to address the conditions that allowed the covid-19 pandemic to inflict unprecedented damage on lives and economies,” it said.

In its report the commission, chaired by Italy’s former prime minister Mario Monti, …
MA06.06 Intracavitary Cisplatin-Fibrin followed by Irradiation after Lung Sparing Surgery in a Rat Model of Malignant Mesothelioma
Authors: M. Kirschner, M. Meerang, O. Lauk, K. Furrer, I. Grgic, V. Orlowski, F. Tschanz, M. Guckenberger, M. Pruschy, W. Weder, I. Opitz
Journal: Journal of Thoracic Oncology (2021)
OncoGEMINI: software for investigating tumor variants from multiple biopsies with integrated cancer annotations
Authors: Thomas J. Nicholas, Michael J. Cormier, Xiaomeng Huang, Yi Qiao, Gabor T. Marth, Aaron R. Quinlan
Journal: Genome Medicine (2021)

DNA sequencing has unveiled extensive tumor heterogeneity in several different cancer types, with many exhibiting diverse subclonal populations. Identifying and tracing mutations throughout the expansion and progression of a tumor represents a significant challenge. Furthermore, prioritizing the subset of such mutations most likely to contribute to tumor evolution or that could serve as potential therapeutic targets represents an ongoing problem. Here, we describe OncoGEMINI, a new tool designed for exploring the complex patterns and trajectory of somatic and inherited variation observed in heterogeneous tumors biopsied over the course of treatment. This is accomplished by creating a searchable database of variants that includes tumor sampling time points and allows for filtering methods that reflect specific changes in variant allele frequencies over time. Additionally, by incorporating existing annotations and resources that facilitate the interpretation of cancer mutations (e.g., CIViC, DGIdb), OncoGEMINI enables rapid searches for, and potential identification of, mutations that may be driving subclonal evolution. By combining relevant genomic annotations alongside specific filtering tools, OncoGEMINI provides powerful and customizable approaches that enable the quick identification of individual tumor variants that meet specified criteria. It can be applied to a wide range of tumor-derived sequence data, but is especially designed for studies with multiple samples, including longitudinal datasets. It is available under an MIT license at github.com/fakedrtom/oncogemini .
Abstract 14887: Microhemorrhages in Myocardium and Kidneys Provoked by Amylin-Loaded Erythrocytes
Authors: Miao Liu, Nirmal Verma, Analia Loria, Sanda Despa, Florin Despa
Journal: Circulation (2017)

Introduction: Vascular damage begins years before the development of type-2 diabetes, indicating a contribution of insulin resistance. Individuals with insulin resistance have hypersecretion of ins...
Comparison of 1-Year Health Care Costs and Use Associated With Open vs Robotic-Assisted Radical Prostatectomy
Authors: Kennedy E. Okhawere, I-Fan Shih, Shih-Hao Lee, Yanli Li, Jaime A. Wong, Ketan K. Badani
Journal: JAMA Network Open (2021)

With the current patterns of adoption and use of robotic surgery and improvement in the overall survival of patients with prostate cancer, it is important to evaluate the immediate and long-term cost implications of treatments for patients with prostate cancer.To compare health care costs and use 1 year after open radical prostatectomy (ORP) vs robotic-assisted radical prostatectomy (RARP).This retrospective cohort study used a US commercial claims database from January 1, 2013, to December 31, 2018. A total of 11 457 men aged 18 to 64 years who underwent inpatient radical prostatectomy for prostate cancer and were continuously enrolled with medical and prescription drug coverage from 180 days before to 365 days after inpatient prostatectomy were identified. An inverse probability of treatment weighting analysis was performed to examine the differences in costs and use of health care services by surgical modality. Data analysis was conducted from September 2019 to July 2020.Type of surgical procedure: ORP vs RARP.Three outcomes within 1 year after the inpatient prostatectomy were investigated: (1) total health care costs, including reimbursement paid by insurers and out of pocket by patients; (2) health care use, including inpatient readmission, emergency department, hospital outpatient, and office visits; and (3) estimated days missed from work due to health care use.Of the 11 457 patients who underwent inpatient prostatectomy, 1604 (14.0%) had ORP and 9853 (86.0%) had RARP and most patients (8467 [73.9%]) were aged 55 to 64 years. Compared with patients who underwent ORP, those who received RARP had a higher cost at the index hospitalization (mean difference, $2367; 95% CI, $1821-$2914; P < .001), but similar total cumulative costs were observed within 180 days (mean difference, $397; 95% CI, -$582 to $1375; P = .43) and 1 year after discharge (-$383; 95% CI, -$1802 to $1037; P = .60). One-year postdischarge health care use was significantly lower in the RARP compared with ORP group for mean numbers of emergency department visits (-0.09 visits; 95% CI, -0.11 to -0.07 visits; P < .001) and hospital outpatient visits (-1.5 visits; -1.63 to -1.36 visits; P < .001). The reduction in use of health care services among patients who underwent RARP translated into additional savings of $2929 (95% CI, $1600-$4257; P < .001) and approximately 1.69 fewer days (95% CI, 1.49-1.89 days; P < .001) missed from work for health care visits.Total cumulative cost in this study was similar between ORP and RARP 1 year post discharge; this finding suggests that lower postdischarge health care use after RARP may offset the higher costs during the index hospitalization.