tbuckley/cabot-search huggingface dataset:
Causes of Death After Type 2 Myocardial Infarction and Myocardial Injury
Authors: Claire E. Raphael, Véronique L. Roger, Yader Sandoval, Matthew Johnson, Allan Jaffe, Amir Lerman, Charanjit S. Rihal, Malcolm R. Bell, Mandeep Singh, Rajiv Gulati
Journal: Journal of the American College of Cardiology (2021)
Optimisation of the event-based TOF filtered back-projection for online imaging in total-body J-PET
Authors: R.Y. Shopa, K. Klimaszewski, P. Kopka, P. Kowalski, W. Krzemień, L. Raczyński, W. Wiślicki, N. Chug, C. Curceanu, E. Czerwiński, M. Dadgar, K. Dulski, A. Gajos, B.C. Hiesmayr, K. Kacprzak, Ł. Kapłon, D. Kisielewska, G. Korcyl, N. Krawczyk, E. Kubicz, Sz. Niedźwiecki, J. Raj, S. Sharma, None Shivani, E.Ł. Stȩpień, F. Tayefi, P. Moskal
Journal: Medical Image Analysis (2021)

We perform a parametric study of the newly developed time-of-flight (TOF) image reconstruction algorithm, proposed for the real-time imaging in total-body Jagiellonian PET (J-PET) scanners. The asymmetric 3D filtering kernel is applied at each most likely position of electron-positron annihilation, estimated from the emissions of back-to-back $\gamma$-photons. The optimisation of its parameters is studied using Monte Carlo simulations of a 1-mm spherical source, NEMA IEC and XCAT phantoms inside the ideal J-PET scanner. The combination of high-pass filters which included the TOF filtered back-projection (FBP), resulted in spatial resolution, 1.5 $\times$ higher in the axial direction than for the conventional 3D FBP. For realistic $10$-minute scans of NEMA IEC and XCAT, which require a trade-off between the noise and spatial resolution, the need for Gaussian TOF kernel components, coupled with median post-filtering, is demonstrated. The best sets of 3D filter parameters were obtained by the Nelder-Mead minimisation of the mean squared error between the resulting and reference images. The approach allows training the reconstruction algorithm for custom scans, using the IEC phantom, when the temporal resolution is below 50 ps. The image quality parameters, estimated for the best outcomes, were systematically better than for the non-TOF FBP.
P-52 Overall survival with cetuximab every 2 weeks vs standard once-weekly administration schedule for first-line treatment of RAS wild-type metastatic colorectal cancer in patients with left- and right-sided primary tumor location
Authors: S. Kasper, A. Cheng, M. Rouyer, C. Foch, F. Lamy, R. Esser, M. Batech, C. Wong, A. Zhang, T. Brodowicz, C. Zielinski
Journal: Annals of Oncology (2021)
Abstract 17069: Inhibition of Autophagy Attenuates Klotho Gene Deficiency-Induced Arterial Stiffening and Hypertension
Authors: Kai Chen, Zhongjie SUN
Journal: Circulation (2018)

Background and Objective: Klotho is an anti-aging gene which shortens lifespan when disrupted and extends lifespan when overexpressed. The objective of this study is to investigate whether autophagy plays a role in Klotho gene deficiency-induced arterial stiffening and hypertension. Methods and Results: Klotho mutant heterozygous (KL+/–) mice and age- and sex-matched wild-type (WT) mice were used. Pulse wave velocity (PWV), a direct measure of arterial stiffness, and blood pressure (BP) were increased significantly in KL+/– mice. The autophagy level, as measured by LC3II expression and autophagy flux, was increased in aortas of KL+/– mice, indicating that Klotho deficiency upregulated autophagy. Interestingly, chloroquine attenuated Klotho deficiency-induced increases in PWV and BP. Chloroquine abolished the upregulation of autophagic flux in KL+/– mice. Klotho deficiency-induced arterial stiffness was associated with accumulation of stiffer collagen and degeneration of compliant elastin which were accompanied by upregulation of MMP9, TGF-β1, TGF-β3, RUNX2 and ALP. These changes were effectively attenuated by chloroquine. Chloroquine also abolished the increase in scleraxis expression in aortas of Klotho +/– mice. In cultured mouse aortic smooth muscle cells, Klotho deficiency increased autophagy which led to upregulation of scleraxis, a key transcription factor of collagen synthesis. Klotho deficiency failed to upregulate scleraxis expression when autophagy was inhibited, suggesting that autophagy is a critical mediator of Klotho deficiency-induced upregulation of scleraxis. Conclusion: Suppression of autophagy by chloroquine attenuates Klotho gene deficiency-induced arterial stiffening and hypertension by abolishing upregulation of MMP9 and scleraxis. The enhanced autophagic activity plays a critical role in Klotho deficiency-induced arterial stiffening and hypertension.
It’s not ‘just a tube of blood’: principles of protocol development, sample collection, staffing and budget considerations for blood-based biomarkers in immunotherapy studies
Authors: Cindy Y Jiang, Zeqi Niu, Michael D Green, Lili Zhao, Shelby Raupp, Brittany Pannecouk, Dean E Brenner, Sunitha Nagrath, Nithya Ramnath
Journal: Journal for ImmunoTherapy of Cancer (2021)

Immunotherapy for cancer is now a standard pillar in the armamentarium of treatments for many cancers. Immune checkpoint inhibitors, in particular, have resulted in significant therapeutic benefit and prolongation of survival in solid organ cancers, such as melanoma and lung cancer. However, the extent of benefit is not uniform. There are several groups studying predictors of benefit from these therapies. Recently, there has been a burgeoning interest in studying predictive biomarkers from the blood. These markers include circulating tumor DNA, circulating tumor cells, lymphocyte subpopulations, exosomes and metabolites to name a few. The logistics involved in such biomarker work are complex and rigorous with potential to impact a given study. Such pre-analytic components include development of a rigorous protocol, standard operating procedures for collection and storage of various blood components, ethics of patient consent, personnel involved as well as budget considerations. In this primer, we lay out representative aspects of each of the aforementioned components as a guide to blood-based biomarker research for immunotherapy studies in cancer.
MO9-1 Real-world data of multiple diagnostic biomarker testing for lung cancer patients in Japan
Authors: Yasushi Yatabe, Makoto Nishio, Toshiaki Takahashi, Kazumi Nishino, Yasumasa Yoshiki, Kanae Togo, Birol Emir, Laura Iadeluca, Kazuto Nishio
Journal: Annals of Oncology (2021)
Icotinib versus chemotherapy as adjuvant treatment for stage II–IIIA EGFR-mutant non-small-cell lung cancer (EVIDENCE): a randomised, open-label, phase 3 trial
Authors: Jianxing He, Chunxia Su, Wenhua Liang, Shidong Xu, Lin Wu, Xiangning Fu, Xiaodong Zhang, Di Ge, Qun Chen, Weimin Mao, Lin Xu, Chun Chen, Bing Hu, Guoguang Shao, Jian Hu, Jian Zhao, Xiaoqing Liu, Zhidong Liu, Zheng Wang, Zemin Xiao, Taiqian Gong, Wen Lin, Xingya Li, Feng Ye, Yang Liu, Haitao Ma, Yunchao Huang, Jianying Zhou, Zhonglin Wang, Junke Fu, Lieming Ding, Li Mao, Caicun Zhou
Journal: The Lancet Respiratory Medicine (2021)
Genetic Continuity of Bronze Age Ancestry with Increased Steppe-Related Ancestry in Late Iron Age Uzbekistan
Authors: Vikas Kumar, E Andrew Bennett, Dongyue Zhao, Yun Liang, Yunpeng Tang, Meng Ren, Qinyan Dai, Xiaotian Feng, Peng Cao, Ruowei Yang, Feng Liu, Wanjing Ping, Ming Zhang, Manyu Ding, Melinda A Yang, Berdimurodov Amridin, Hasanov Muttalib, Jianxin Wang, Qiaomei Fu
Journal: Molecular Biology and Evolution (2021)

Although Uzbekistan and Central Asia are known for the well-studied Bronze Age civilization of the Bactria-Margiana Archaeological Complex (BMAC), the lesser-known Iron Age was also a dynamic period that resulted in increased interaction and admixture among different cultures from this region. To broaden our understanding of events that impacted the demography and population structure of this region, we generated 27 genome-wide single-nucleotide polymorphism capture data sets of Late Iron Age individuals around the Historical Kushan time period (∼2100-1500 BP) from three sites in South Uzbekistan. Overall, Bronze Age ancestry persists into the Iron Age in Uzbekistan, with no major replacements of populations with Steppe-related ancestry. However, these individuals suggest diverse ancestries related to Iranian farmers, Anatolian farmers, and Steppe herders, with a small amount of West European Hunter Gatherer, East Asian, and South Asian Hunter Gatherer ancestry as well. Genetic affinity toward the Late Bronze Age Steppe herders and a higher Steppe-related ancestry than that found in BMAC populations suggest an increased mobility and interaction of individuals from the Northern Steppe in a Southward direction. In addition, a decrease of Iranian and an increase of Anatolian farmer-like ancestry in Uzbekistan Iron Age individuals were observed compared with the BMAC populations from Uzbekistan. Thus, despite continuity from the Bronze Age, increased admixture played a major role in the shift from the Bronze to the Iron Age in southern Uzbekistan. This mixed ancestry is also observed in other parts of the Steppe and Central Asia, suggesting more widespread admixture among local populations.
COVID-19, the Built Environment, and Health
Authors: Howard Frumkin
Journal: Environmental Health Perspectives (2021)

Since the dawn of cities, the built environment has both affected infectious disease transmission and evolved in response to infectious diseases. COVID-19 illustrates both dynamics. The pandemic presented an opportunity to implement health promotion and disease prevention strategies in numerous elements of the built environment.This commentary aims to identify features of the built environment that affect the risk of COVID-19 as well as to identify elements of the pandemic response with implications for the built environment (and, therefore, for long-term public health).Built environment risk factors for COVID-19 transmission include crowding, poverty, and racism (as they manifest in housing and neighborhood features), poor indoor air circulation, and ambient air pollution. Potential long-term implications of COVID-19 for the built environment include changes in building design, increased teleworking, reconfigured streets, changing modes of travel, provision of parks and greenspace, and population shifts out of urban centers. Although it is too early to predict with confidence which of these responses may persist, identifying and monitoring them can help health professionals, architects, urban planners, and decision makers, as well as members of the public, optimize healthy built environments during and after recovery from the pandemic. https://doi.org/10.1289/EHP8888.
Haploidentical Hematopoietic Stem Cell Allogeneic Transplantation with High Dose Post Transplantation Cyclophosphamide for Patients over 60 Years of Age
Authors: Samia Harbi, Raynier Devillier, Stefania Bramanti, Thomas Pagliardini, Faezeh Legrand, Maud Cecile, Valerio Maisano, Cecile Braticevic, Angela Granata, Frederique Rousseau, Sabine Furst, Catherine Faucher, Christian Chabannon, pierre Jean Weiller, Luca Castagna, Didier Blaise
Journal: Blood (2017)
Bone Mineral Density and Type 1 Diabetes in Children and Adolescents: A Meta-analysis
Authors: Phoebe Loxton, Kruthika Narayan, Craig F. Munns, Maria E. Craig
Journal: Diabetes Care (2021)

There is substantial evidence that adults with type 1 diabetes have reduced bone mineral density (BMD); however, findings in youth are inconsistent.To perform a systematic review and meta-analysis of BMD in youth with type 1 diabetes using multiple modalities: DXA, peripheral quantitative computed tomography (pQCT), and/or quantitative ultrasound (QUS).PubMed, Embase, Scopus, and Web of Science from 1 January 1990 to 31 December 2020, limited to humans, without language restriction.Inclusion criteria were as follows: cross-sectional or cohort studies that included BMD measured by DXA, pQCT, or QUS in youth (aged <20 years) with type 1 diabetes and matched control subjects.We collected data for total body, lumbar spine, and femoral BMD (DXA); tibia, radius, and lumbar spine (pQCT); and phalanx and calcaneum (QUS). Weighted mean difference (WMD) or standardized mean difference was estimated and meta-regression was performed with age, diabetes duration, and HbA1c as covariates.We identified 1,300 nonduplicate studies; 46 met the inclusion criteria, including 2,617 case and 3,851 control subjects. Mean ± SD age was 12.6 ± 2.3 years. Youth with type 1 diabetes had lower BMD: total body (WMD -0.04 g/cm2, 95% CI -0.06 to -0.02; P = 0.0006), lumbar spine (-0.02 g/cm2, -0.03 to -0.0; P = 0.01), femur (-0.04 g/cm2, -0.05 to -0.03; P < 0.00001), tibial trabecular (-11.32 g/cm3, -17.33 to -5.30; P = 0.0002), radial trabecular (-0.91 g/cm3, -1.55 to -0.27; P = 0.005); phalangeal (-0.32 g/cm3, -0.38 to -0.25; P < 0.00001), and calcaneal (standardized mean difference -0.69 g/cm3, -1.11 to -0.26; P = 0.001). With use of meta-regression, total body BMD was associated with older age (coefficient -0.0063, -0.0095 to -0.0031; P = 0.002) but not with longer diabetes duration or HbA1c.Meta-analysis was limited by the small number of studies with use of QUS and pQCT and by lack of use of BMD z scores in all studies.Bone development is abnormal in youth with type 1 diabetes, assessed by multiple modalities. Routine assessment of BMD should be considered in all youth with type 1 diabetes.
Expression Levels of the TERT Gene Can be Used to Risk Stratify Aplastic Anemia Patients: Study in an Indian Cohort
Authors: Arati Khanna-Gupta, Durga Sarvepalli, Snigdha Majumder, Coral Karunakaran, Malini Manoharan, Shilpa Sudesh, Varun Bafna, Chirantan Bose, Ravi Gupta, K.S. Natraj, Sharat Damodar, Arkasubhra Ghosh
Journal: Blood (2017)
Abstract 9354: Mechanisms of Random Wave Propagation Perpetuated After Pulmonary Vein Isolation: Comparison Between Paroxysmal and Persistent Atrial Fibrillation
Authors: Hiroshige Yamabe, Junjiroh Koyama, Tadashi Hoshiyama, Hisanori Kanazawa, Hisao Ogawa
Journal: Circulation (2011)

Background: The precise mechanisms of random wave propagation perpetuated after pulmonary vein isolation (PVI) in atrial fibrillation (AF) has not been well clarified. Objectives: The purpose of this study was to define the mechanism of random wave propagation perpetuated after PVI in AF. We further clarified the difference in this perpetuating mechanism between paroxysmal and persistent AF. Methods: Endocardial mapping of the left atrium was performed before and after PVI in 7 paroxysmal and 7 persistent AF patients using a three-dimensional non-contact mapping system (EnSite 3000). We analyzed the difference in the left atrial activation sequence between paroxysmal and persistent AF, especially in relation to the complex fractionated electrograms (CFAE) region. Results: Random wave propagation after PVI was maintained by the combination of focal discharge, the activation around the isolated PV and mitral annulus, wave break and pivoting activation anchored around the functional conduction block region. The frequency of pivoting activation, wave break and wave fusion were significantly higher in the persistent AF than in the paroxysmal AF (8.4±10.4 vs. 2.0±3.5 times/sec; p&lt;0.001, 1.9±3.2 vs. 0±0 times/sec; p&lt;0.05, and 12.1±3.3 vs. 6.3±13.4 times/sec; p&lt;0.005). However, the frequency of focal discharge derived from non-PV region in persistent AF was lower than in paroxysmal AF (0.3±0.6 vs. 3.2±8.8 times/sec; p&lt;0.03). The area of CFAE was significantly reduced following PVI both in paroxysmal and persistent AF (18.0±16.9 to 2.2±4.9 cm 2 ; p&lt;0.0001, 26.8±22.3 to 6.6±2.9 cm 2 ; p&lt;0.0001). However, the area of CFAE in persistent AF was significantly larger than that in paroxysmal AF both before (p=0.003) and after PVI (p&lt;0.002). Pivoting activation and wave break were observed on the residual CFAE region which was still observed after PVI. Conclusions: Activation sequence of the wave during ongoing AF perpetuated after PVI was more disorganized in persistent AF than in paroxysmal AF. Disorganized activation after PVI in persistent AF was caused by the pivoting activation and wave break associated with the residual CFAE region.
Abstract P077: Plasma Homocysteine, Dietary B Vitamins, and Risk of Peripheral Artery Disease
Authors: Monica L Bertoia, Jennifer K Pai, Michel M Joosten, Murray A Mittleman, Eric B Rimm, Kenneth J Mukamal
Journal: Circulation (2013)

Background: Clinical trials of vitamin B supplements to lower homocysteine levels have not consistently lowered risk of PAD, but these interventions were typically 1-2 years duration and limited to participants with pre-existing vascular disease. Whether long-term homocysteine levels influence the development of incident PAD remains uncertain. Objective: To examine the association between levels of plasma homocysteine and dietary B vitamins (folate, B6 and B12) and risk of PAD. Methods: We identified 276 cases of PAD in the Nurses’ Health Study (NHS) which followed 121,700 female nurses from 1980-2010, and 406 cases in the Health Professionals Follow-up Study (HPFS) which followed 51,529 male health professionals from 1986 to 2008. B vitamin intake was measured using a FFQ administered every four years. After excluding individuals with a history of CVD at baseline, plasma homocysteine was measured in baseline blood samples in two nested case-control studies with three controls matched to each case: NHS (1989-2010; 144 cases and 432 controls) and HPFS (1994-2008; 143 cases and 429 controls). PAD cases were confirmed by medical record based on at least one of: (1) amputation, bypass, or revascularization procedure, (2) angiogram/ultrasound confirming at least 50% stenosis, (3) ankle-brachial index &lt; 0.9, or (4) documented physician’s diagnosis. We used Cox proportional hazards models to estimate hazard ratios (HR) for PAD in the cohorts and conditional logistic regression to estimate relative risks (RR) for PAD in the nested case-control studies. Results: Men in the highest tertile of plasma homocysteine had more than double the risk of PAD compared to men in the lowest tertile (Table). This association was not replicated in women. Lower folate intake was also associated with an increased risk of PAD in men but not women (Table). Total B6 and B12 intake was not consistently associated with risk of PAD in men or women. Conclusions: Higher plasma homocysteine levels were associated with an increased risk of PAD in men but not women.
Younger age is associated with lower self-reported quality of life among patients with autoimmune disease during Canada's response to the COVID-19 pandemic
Authors: C. Plagiannakos, S. Roberts, M. Saini, C. Vincent, L. Worobetz, A. L. Mason, J. Flemming, C. Tsien, K. Qumosani, G. Hirschfield, H. Janssen, A. Gulamhusein, B. Hansen
Journal: Journal of Hepatology (2021)
Mutant <i>Idh2</i> Cooperates with a <i>NUP98-HOXD13</i> Fusion to Induce Early Immature Thymocyte Precursor ALL
Authors: Liat Goldberg, Vijay Negi, Yang Jo Chung, Masahiro Onozawa, Yuelin J. Zhu, Robert L. Walker, Rachel Pierce, Daxesh P. Patel, Kristopher W. Krausz, Frank J. Gonzalez, Margaret A. Goodell, Benjamin A.T. Rodriguez, Paul S. Meltzer, Peter D. Aplan
Journal: Cancer Research (2021)

Abstract Mutations in the isocitrate dehydrogenase 1 (IDH1) and IDH2 genes are frequently observed in a wide variety of hematologic malignancies, including myeloid and T-cell leukemias. In this study, we generated Idh2R140Q transgenic mice to examine the role of the Idh2R140Q mutation in leukemia. No leukemia developed in Idh2R140Q transgenic mice, suggesting a need for additional genetic events for leukemia development. Because myeloid cells from NUP98-HOXD13 fusion (NHD13) transgenic mice frequently acquire somatic Idh mutations when they transform to acute myeloid leukemia, we generated Idh2R140Q/NHD13 double transgenic mice. Idh2R140Q/NHD13 transgenic mice developed an immature T-cell leukemia with an immunophenotype similar to double-negative 1 (DN1) or DN2 thymocytes. Idh2R140Q/NHD13 leukemic cells were enriched for an early thymic precursor transcriptional signature, and the gene expression profile for Idh2R140Q/NHD13 DN1/DN2 T-ALL closely matched that of human early/immature T-cell precursor (EITP) acute lymphoblastic leukemia (ALL). Moreover, recurrent mutations found in patients with EITP ALL, including KRAS, PTPN11, JAK3, SH2B3, and EZH2 were also found in Idh2R140Q/NHD13 DN1/DN2 T-ALL. In vitro treatment of Idh2R140Q/NHD13 thymocytes with enasidenib, a selective inhibitor of mutant IDH2, led to a marked decrease in leukemic cell proliferation. These findings demonstrate that Idh2R140Q/NHD13 mice can serve as a useful in vivo model for the study of early/immature thymocyte precursor acute lymphoblastic leukemia development and therapy. Significance: T-cell leukemia induced in Idh2R140Q/NUP98-HOXD13 mice is immunophenotypically, transcriptionally, and genetically similar to human EITP ALL, providing a model for studying disease development and treatment.
CoBRA: Containerized Bioinformatics Workflow for Reproducible ChIP/ATAC-Seq Analysis
Authors: Xintao Qiu, Avery S. Feit, Ariel Feiglin, Yingtian Xie, Nikolas Kesten, Len Taing, Joseph Perkins, Shengqing Gu, Yihao Li, Paloma Cejas, Ningxuan Zhou, Rinath Jeselsohn, Myles Brown, X. Shirley Liu, Henry W. Long
Journal: Genomics Proteomics & Bioinformatics (2021)

Chromatin immunoprecipitation sequencing (ChIP-seq) and the Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) have become essential technologies to effectively measure protein-DNA interactions and chromatin accessibility. However, there is a need for a scalable and reproducible pipeline that incorporates proper normalization between samples, correction of copy number variations, and integration of new downstream analysis tools. Here we present Containerized Bioinformatics workflow for Reproducible ChIP/ATAC-seq Analysis (CoBRA), a modularized computational workflow which quantifies ChIP-seq and ATAC-seq peak regions and performs unsupervised and supervised analyses. CoBRA provides a comprehensive state-of-the-art ChIP-seq and ATAC-seq analysis pipeline that can be used by scientists with limited computational experience. This enables researchers to gain rapid insight into protein-DNA interactions and chromatin accessibility through sample clustering, differential peak calling, motif enrichment, comparison of sites to a reference database, and pathway analysis. CoBRA is publicly available online at https://bitbucket.org/cfce/cobra.