tbuckley/cabot-search huggingface dataset:
Transposon Insertion Drove the Loss of Natural Seed Shattering during Foxtail Millet Domestication
Authors: Hangqin Liu, Xiaojian Fang, Leina Zhou, Yan Li, Can Zhu, Jiacheng Liu, Yang Song, Xing Jian, Min Xu, Li Dong, Zhongwei Lin
Journal: Molecular Biology and Evolution (2022)

Abstract Loss of seed shattering was a key step during cereal domestication, and it greatly facilitated seed harvest of the staple cereal foxtail millet (Setaria italica) because the cereal has very small seeds. However, the genetic basis for this loss has been largely unknown. Here, we combined comparative and association mapping to identify an 855-bp Harbinger transposable element insertion in the second exon of the foxtail millet gene shattering1 (sh1) that was responsible for the loss of seed shattering. The sh1 gene encodes zinc finger and YABBY domains. The insert prevents transcription of the second exon, causing partial loss of the zinc finger domain and then loss of natural seed shattering. Specifically, sh1 functions as a transcription repressor and represses the transcription of genes associated with lignin synthesis in the abscission zone, including CAD2. The diversity of sh1 is highly reduced in foxtail millet, consistent with either a severe domestication bottleneck or a selective sweep. Phylogenetic analysis of sh1 further revealed a single origin of foxtail millet in China. Our results support the theories that transposons were the most active factors in genome evolution driving loss of natural seed shattering during foxtail millet domestication and that sh1 underwent parallel selection during domestication across different cereal species.
Abstract P111: Differentially Methylated DNA Regions In Left Ventricular Hypertrophy: A HyperGEN Study
Authors: Alana C Jones, Amit Patki, Hemant K Tiwari, Ninad S Chaudhary, Steven Claas, Donna K Arnett, Marguerite M Irvin
Journal: Circulation (2022)

Left ventricular (LV) hypertrophy (LVH) is an independent risk factor for cardiovascular morbidity and mortality that is commonly associated with hypertension. African Americans (AAs) experience an especially high risk of LVH. Genomic studies have identified potential candidate genes associated with LVH, but more research is needed to further explain the high estimated heritability for these traits in AAs. Epigenetic modifications, such as DNA methylation, may account for the unexplained heritability in LVH in AAs. In this study, we used epigenotype and echocardiography data from 636 African Americans selected from the Hypertension Genetic Epidemiology Network (HyperGEN) to identify differentially methylated regions (DMRs) of DNA in association with LV related traits. DNA was isolated from participants’ whole blood, and more than 485,000 CpGs were assayed on Illumina Methyl450K arrays. Linear mixed models were used to test the association between a DMR and LV trait using the coMethDMR package in R. We identified several DMRs associated with LV traits in HyperGEN. There was an association between methylation of XKR6 and ejection fraction (β[SE]:0.005[0.001], FDR: 0.056), as well as TRAK1 and LV internal diastolic dimension (β[SE]:0.113[0.027], FDR: 0.042). There was also an inverse relationship between LV mass indexed to height and methylation of GSE1 (β[SE]:-0.002[0.001], FDR: 0.085), RPS15A (β[SE]:-0.002[0.001], FDR: 0.085), and PSMD7 (β[SE]:-0.003[0.001], FDR: 0.085). Additionally, relative wall thickness was inversely associated with a DMR annotated to DNHD1 (β[SE]:-1.269[0.275], FDR: 0.008). Methylation variations of GSE1 , PSMD7 , and DNHD1 have previously been linked to cardiac structural function, and external validation of these findings is in progress. In summary, differentially methylated regions of DNA may help explain additional variation in LVH-related traits and heritability in AAs. Future studies should evaluate potential relationships between regional DNA methylation patterns and the development and progression of LVH.
Family matters for coronavirus disease and vaccines
Authors: David J. Bean, Manish Sagar
Journal: Journal of Clinical Investigation (2021)

The increasing frequency of pathogenic coronaviruses in the human population has raised public health concerns about possible future pandemics. It is critical to understand whether immune responses to the current circulating coronaviruses provide protection against related viruses or those that may emerge in the future. In this issue of the JCI, Dangi, Palacio, and co-authors detail the extent of coronavirus cross-protection following both vaccination and natural infection and ultimately used murine models to highlight the mechanism behind this heterotypic immunity. This study provides insight into the possibility of a pan-coronavirus vaccine that could protect humans against future coronavirus outbreaks.
Unexpected Retrosternal Goiter Interpreted as Hyperfunctioning Metastasis on the Posttherapeutic 131I SPECT/CT
Authors: Li-ying Hou, Quan-yong Luo, Zhong-ling Qiu
Journal: Clinical Nuclear Medicine (2021)

Abstract We present a 38-year-old man who underwent total thyroidectomy with radical right neck dissection due to papillary thyroid cancer was referred for 131 I treatment. The patient was in subclinical hypothyroidism with remarkable stimulated Tg level after 4 weeks of l -thyroxine withdrawal before 131 I treatment, which indicated hyperfunctioning metastasis. Posttherapeutic 131 I whole-body scan combined with 131 I SPECT/CT performed on day 3 after 131 I administration revealed an elevated 131 I uptake mass in cervicothoracic region. To our surprise, the mass was histologically confirmed to be a retrosternal goiter.
Abstract EP43: Obesity And Incident Cardiovascular Disease (CVD): The Jackson Heart Study
Authors: Yan Gao, Jeannette M Simino, Chiu-hsieh Hsu, Adolfo Correa, Nancy Min
Journal: Circulation (2022)

Background: Although obesity is a well-established risk factor for the development of cardiovascular disease (CVD), it is unclear which anthropometric measure(s) of obesity are the best predictors of CVD. Methods: Using data from 3491 African Americans (mean age: 58.3±12.1; 65.2% women) in the Jackson Heart Study, we examined the associations of incident CVD and its individual components (Coronary heart disease (CHD), heart failure, and stroke) with time-dependent obesity measures (body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR) and waist-to-hip ratio (WHR)). Time-to-event analyses were conducted using time-dependent Cox regression models. Obesity measures were analyzed both as dichotomous (obese vs. non-obese) and standardized continuous predictors. Covariates included age, sex, systolic blood pressure, diastolic blood pressure, and smoking status. Results: There were 331 incident CVD events, including 122 CHD, 192 heart failure, and 95 stroke events. The median follow-up time is 9.04 (Quartile Range: 1.83) years. Comparing obese to non-obese participants, adjusted hazard ratios (aHR) (95% CI) for CVD were 1.38 (1.10, 1.72), 1.36 (1.05, 1.76), 1.23 (0.80, 1.89), and 1.38 (1.04, 1.82) for BMI, WC, WHtR and WHR, respectively. The corresponding aHRs (95% CI) using standardized continuous BMI, WC, WHtR and WHR measures were 1.27 (1.14, 1.43), 1.32 (1.18, 1.47), 1.31 (1.18, 1.46), and 1.24 (1.12 1.39). The significant associations between CVD and obesity measures were largely driven by heart failure. The associations in younger age group (&lt; 60 yrs) were more significant than those in older age group (&gt;= 60 yrs). Conclusions: Dichotomous and standardized continuous BMI, WC and WHR measures were all associated with incident CVD. For WHtR, only the standardized continuous measure was significantly associated with incident CVD. The risk of CVD associated with obesity is not evident in the elderly.
Cancer Relevance of Human Genes
Authors: Tao Qing, Hussein Mohsen, Vincent L Cannataro, Michal Marczyk, Mariya Rozenblit, Julia Foldi, Michael Murray, Jeffrey P Townsend, Yuval Kluger, Mark Gerstein, Lajos Pusztai
Journal: JNCI Journal of the National Cancer Institute (2022)

Abstract Background We hypothesize that genes that directly or indirectly interact with core cancer genes (CCGs) in a comprehensive gene-gene interaction network may have functional importance in cancer. Methods We categorized 12 767 human genes into CCGs (n = 468), 1 (n = 5467), 2 (n = 5573), 3 (n = 915), and more than 3 steps (n = 416) removed from the nearest CCG in the Search Tool for the Retrieval of Interacting Genes/Proteins network. We estimated cancer-relevant functional importance in these neighborhood categories using 1) gene dependency score, which reflects the effect of a gene on cell viability after knockdown; 2) somatic mutation frequency in The Cancer Genome Atlas; 3) effect size that estimates to what extent a mutation in a gene enhances cell survival; and 4) negative selection pressure of germline protein-truncating variants in healthy populations. Results Cancer biology–related functional importance of genes decreases as their distance from the CCGs increases. Genes closer to cancer genes show greater connectedness in the network, have greater importance in maintaining cancer cell viability, are under greater negative germline selection pressure, and have higher somatic mutation frequency in cancer. Based on these 4 metrics, we provide cancer relevance annotation to known human genes. Conclusions A large number of human genes are connected to CCGs and could influence cancer biology to various extent when dysregulated; any given mutation may be functionally important in one but not in another individual depending on genomic context.
Focal psychodynamic therapy, cognitive behaviour therapy, and optimised treatment as usual in female outpatients with anorexia nervosa (ANTOP study): 5-year follow-up of a randomised controlled trial in Germany
Authors: Wolfgang Herzog, Beate Wild, Katrin E Giel, Florian Junne, Hans-Christoph Friederich, Gaby Resmark, Martin Teufel, Dieter Schellberg, Martina de Zwaan, Andreas Dinkel, Stephan Herpertz, Markus Burgmer, Bernd Löwe, Almut Zeeck, Jörn von Wietersheim, Sefik Tagay, Carmen Schade-Brittinger, Henning Schauenburg, Ulrike Schmidt, Stephan Zipfel
Journal: The Lancet Psychiatry (2022)
Systematic Review of the Incidence of and Risk Factors for Urothelial Cancers and Renal Cell Carcinoma Among Patients with Haematuria
Authors: Bhavan P. Rai, José Luis Dominguez Escrig, Luís Vale, Teele Kuusk, Otakar Capoun, Viktor Soukup, Harman M. Bruins, Yuhong Yuan, Philippe D. Violette, Nancy Santesso, Bas W.G. van Rhijn, A. Hugh Mostafid, Muhammad Imran Omar
Journal: European Urology (2022)
Variability in detection of SARS-CoV-2-specific antibody responses following mild infection: a prospective multicentre cross-sectional study, London, United Kingdom, 17 April to 17 July 2020
Authors: Scott JC Pallett, Rachael Jones, Ahmed Abdulaal, Mitchell A Pallett, Michael Rayment, Aatish Patel, Sarah J Denny, Nabeela Mughal, Maryam Khan, Carolina Rosadas de Oliveira, Panagiotis Pantelidis, Paul Randell, Christofer Toumazou, Matthew K O’Shea, Richard Tedder, Myra O McClure, Gary W Davies, Luke SP Moore
Journal: Eurosurveillance (2022)

Introduction Immunoassays targeting different SARS-CoV-2-specific antibodies are employed for seroprevalence studies. The degree of variability between immunoassays targeting anti-nucleocapsid (anti-NP; the majority) vs the potentially neutralising anti-spike antibodies (including anti-receptor-binding domain; anti-RBD), particularly in mild or asymptomatic disease, remains unclear. Aims We aimed to explore variability in anti-NP and anti-RBD antibody detectability following mild symptomatic or asymptomatic SARS-CoV-2 infection and analyse antibody response for correlation with symptomatology. Methods A multicentre prospective cross-sectional study was undertaken (April–July 2020). Paired serum samples were tested for anti-NP and anti-RBD IgG antibodies and reactivity expressed as binding ratios (BR). Multivariate linear regression was performed analysing age, sex, time since onset, symptomatology, anti-NP and anti-RBD antibody BR. Results We included 906 adults. Antibody results (793/906; 87.5%; 95% confidence interval: 85.2–89.6) and BR strongly correlated (ρ = 0.75). PCR-confirmed cases were more frequently identified by anti-RBD (129/130) than anti-NP (123/130). Anti-RBD testing identified 83 of 325 (25.5%) cases otherwise reported as negative for anti-NP. Anti-NP presence (+1.75/unit increase; p &lt; 0.001), fever (≥ 38°C; +1.81; p &lt; 0.001) or anosmia (+1.91; p &lt; 0.001) were significantly associated with increased anti-RBD BR. Age (p = 0.85), sex (p = 0.28) and cough (p = 0.35) were not. When time since symptom onset was considered, we did not observe a significant change in anti-RBD BR (p = 0.95) but did note decreasing anti-NP BR (p &lt; 0.001). Conclusion SARS-CoV-2 anti-RBD IgG showed significant correlation with anti-NP IgG for absolute seroconversion and BR. Higher BR were seen in symptomatic individuals, particularly those with fever. Inter-assay variability (12.5%) was evident and raises considerations for optimising seroprevalence testing strategies/studies.
Prognostic Relevance of Pancreatic Adenocarcinoma Whole-Tumor Transcriptomic Subtypes and Components
Authors: Shulin Zhao, Rémy Nicolle, Jérémy Augustin, Magali Svrcek, Louis de Mestier, Delphine Le Corre, Daniel Pietrasz, Olivier Caliez, Jérôme Cros, Pierre Laurent-Puig, Jean-Baptiste Bachet
Journal: Clinical Cancer Research (2021)

Our team previously defined six quantitative transcriptomic components, and a classification in five subtypes by association of these components. In this study, we compared the robustness of quantitative components and qualitative classifications from different transcriptomic profiling techniques, investigated their clinical relevance, and proposed a new prognostic model.A total of 210 patients from a multicentric cohort and 149 patients from a monocentric cohort were included in this study. RNA microarray profiles were obtained from 165 patients of the multicentric cohort. RNA sequencing (RNA-seq) profiles were obtained from all the patients.For the patients with both RNA microarray and RNA-seq profiles, the concordance in subtype assignment was partial with an 82.4% coherence rate. The correlation between the two technique projections of the six components ranged from 0.85 to 0.95, demonstrating an advantage of robustness. On the basis of the Akaike information criterion, the RNA components showed more prognostic value in univariate or multivariate models than the subtypes. Using the monocentric cohort for training, we developed a multivariate Cox regression model using all six components and clinicopathologic characteristics (node invasion and resection margins) on disease-free survival (DFS). This prognostic model was highly associated with DFS (P < 0.001). The evaluation of the model in the multicentric cohort showed significant association with DFS and overall survival (P < 0.001).We described the advantage of the prognostic value and robustness of the whole-tumor transcriptomic components than subtypes. We created and validated a new DFS-based multivariate Cox regression prognostic model, including six pancreatic adenocarcinoma transcriptomic component levels and pathologic characteristics.
Immunotherapy for Nonmelanoma Skin Cancer: Facts and Hopes
Authors: Sophia Z. Shalhout, Howard L. Kaufman, Kevin S. Emerick, David M. Miller
Journal: Clinical Cancer Research (2022)

Abstract Nonmelanoma skin cancer (NMSC) is the most frequently diagnosed malignancy in humans, representing a broad range of cutaneous tumors. Keratinocyte carcinomas, including basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (CSCC), are the most common NMSCs. The incidence of BCC and CSCC is steadily increasing due to a progressively aging population, chronic exposure to ultraviolet radiation, and increased awareness with earlier diagnosis. Rarer NMSCs, such as Merkel cell carcinoma (MCC) and cutaneous adnexal carcinomas, are also on the rise. Although the majority of NMSC tumors are localized at diagnosis and managed effectively with curative surgery and radiation, in rare cases with nodal and distant metastases, systemic therapy is often required. As our understanding of the immunologic characteristics of NMSCs has improved, effective treatment options have expanded with the development of immunotherapy. The FDA recently approved several immune checkpoint inhibitors for the treatment of locally advanced and metastatic MCC, CSCC, and BCC. We review the emerging role of immunotherapy as the standard of care for several advanced NMSCs not amenable to surgery and/or radiation and underscore the need for considering clinical trials of novel strategies in patients when immunotherapy does not provide durable benefit. Finally, we explore the potential of neoadjuvant and adjuvant immunotherapy.
111P Entrectinib in Chinese (mainland China, Hong Kong, Taiwan) patients (pts) with locally advanced/metastatic ROS1 fusion-positive (fp) NSCLC and NTRK-fp solid tumours
Authors: S. Lu, C-H. Chiu, Y. Yu, H.H.F. Loong, C.C. Lin, X. Hu, X. Dong, J. Li, J. Zhao, S. Ye-Hui, Z. Zhang, N. Zhao, J. Xia, D. Wang, Y. Fan
Journal: Annals of Oncology (2022)
DEEP LEARNING FROM CORONARY COMPUTED TOMOGRAPHY ANGIOGRAPHY FOR ATHEROSCLEROTIC PLAQUE AND STENOSIS QUANTIFICATION AND CARDIAC RISK PREDICTION
Authors: Andrew Lin, Nipun Manral, Priscilla McElhinney, Aditya Killekar, Hidenari Matsumoto, Jacek Kwiecinski, Konrad Pieszko, Kajetan Grodecki, Yuka Otaki, Donghee Han, Evangelos Tzolos, Aakash Shanbhag, Markus Goeller, Mohamed Marwan, Heidi Gransar, Sebastien Cadet, Stephan Achenbach, Stephen J. Nicholls, Dennis TL Wong, Daniel S. Berman, Marc Dweck, David E. Newby, Michelle C. Williams, Piotr Slomka, Damini Dey
Journal: Journal of the American College of Cardiology (2022)
Engineering of donor-acceptor-donor curcumin analogues as near-infrared fluorescent probes for <i>in vivo</i> imaging of amyloid-β species
Authors: Daqing Fang, Xidan Wen, Yuqi Wang, Yidan Sun, Ruibing An, Yu Zhou, Deju Ye, Hong Liu
Journal: Theranostics (2022)

Near-infrared (NIR) fluorescent imaging of both soluble and insoluble Aβ species in the brain of Alzheimer's disease (AD) is crucial for the early diagnosis and intervention of AD.To date, a variety of NIR fluorescent probes have been reported for the detection of Aβ species.Among these probes, CRANAD-58 was reported to have the capability to detect both soluble and insoluble Aβ species, which is vital to monitor the changes of Aβ species during the pathological course of the disease.Though CRANAD-58 has shown promise to noninvasively detect Aβ species in transgenic AD mice, the emission wavelength (~670 nm) is still too short for further applications.Therefore, new probes with longer emission wavelength and improved physiological properties are in highly demand.Herein, we report the design and engineering of nine donor-acceptor-donor molecules as "off-on" near-infrared fluorescent probes for in vivo imaging of both soluble and insoluble Aβ species in living AD mice owing to its improved in vitro properties and in vivo performance.Methods: We report a two-round strategy to develop nine "off-on" NIR fluorescence probes via structural modification of a curcumin analogue-based donor-acceptor-donor architecture.In round one, probes 1 and 2 were synthesized, and probe 2 was identified to be an optimum probe as it showed distinct "off-on" NIR fluorescence at > 690 nm upon binding to Aβ monomers, oligomers and aggregates.To further improve the in vivo performance, further structural modification of probe 2 into probes 3-9 was then conducted.The fluorescence response with Aβ species and histological staining in vitro and in vivo imaging of Aβ species in APP/PS1 transgenic AD mice and age-matched wild-type mice were performed. Results:We demonstrate that, compared to probe 2, probe 9 with improved physiological properties hold the fastest kinetics (~10 min) to produce not only higher brain fluorescence intensity in 10-month-old APP/PS1 transgenic AD mice, but also afford a higher discrepancy in brain fluorescence to discriminate AD mice from wild-type (WT) mice.Probe 9 also hold the ability to detect soluble Aβ species in 6-month-old APP/PS1 transgenic mice.Probe 9 was further applied for dynamic visualization of Aβ plaques in a skull-thinning 14-month-old APP/PS1 mouse, which revealed its immediate penetration into brain parenchyma and selective labeling of both parenchymal and angiopathic Aβ plaques.In addition, probe 9 possessed significantly high attenuation effect on the aggregation of Aβ monomers. Conclusion:Our results demonstrate the good potential of probe 9 for longitudinal NIR fluorescence imaging of soluble and insoluble Aβ species in APP/PS1 transgenic AD mice, which may act as a useful tool for early diagnosis and intervention of AD.
People carrying excess weight have an increased risk of severe covid-19
Authors: Helen Saul, Deniz Gursul, Carmen Piernas
Journal: BMJ (2022)

The study Gao M, Piernas C, Astbury NM, et al. Associations between body-mass index and COVID-19 severity in 6.9 million people in England: a prospective, community-based cohort study. Lancet Diabetes Endocrinol 2021;9:6. To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/excess-weight-increases-risks-of-severe-covid-19/
Steatotic Hepatitis Presenting as a Huge Hypermetabolic Liver Mass
Authors: Abtin Doroudinia, Mehrdad Bakhshayesh Karam, Niloufar Ghadimi, Farhad Yousefi
Journal: Clinical Nuclear Medicine (2022)

FDG PET/CT scan is a diagnostic imaging modality for oncologic patients, but with false-positive findings in inflammatory diseases. In this interesting case, we present a 24-year-old woman with history of giant cell tumor of the bone (lumbar vertebrae) who underwent whole-body FDG PET/CT scan for treatment response evaluation. FDG PET/CT scan demonstrated a large hypermetabolic tumoral mass lesion in segment VI/VII of the right hepatic lobe. A range of malignant versus benign lesions should be considered as differential diagnoses, including metastasis, primary cholangiocarcinoma, hepatocellular carcinoma, focal nodular hyperplasia, and infection. Final diagnosis of "steatotic hepatitis" after CT-guided biopsy was established.