tbuckley/cabot-search huggingface dataset:
Lung cancer probability and clinical outcomes of baseline and new subsolid nodules detected on low-dose CT screening
Authors: Yeon Wook Kim, Byoung Soo Kwon, Sung Yoon Lim, Yeon Joo Lee, Jong Sun Park, Young-Jae Cho, Ho Il Yoon, Kyung Won Lee, Jae Ho Lee, Jin-Haeng Chung, Eunjeong Ji, Choon-Taek Lee
Journal: Thorax (2021)

Limited data are available regarding the management of subsolid nodules detected on lung cancer screening with low-dose CT (LDCT). We aimed to determine the characteristics of screen-detected subsolid nodules, and to evaluate the probability of lung cancer and the clinical course of subsolid nodules detected at baseline and during follow-up screening.We evaluated 50 132 asymptomatic adults (22 631 never-smokers and 27 501 ever-smokers) who underwent LDCT screening for lung cancer between May 2003 and June 2019 at a tertiary centre in South Korea. The incidence, characteristics and clinical outcomes of the baseline and new screen-detected subsolid nodules were determined.A total of 6725 subsolid nodules (5116 pure ground glass opacity nodules and 1609 part-solid nodules) were detected in 4545 participants (1484 new subsolid nodules detected in 937 (1.9%) participants; the overall incidence of subsolid nodules: 10.7% in never-smokers and 7.7% in ever-smokers, p<0.001). Among 4918 subsolid nodules that underwent follow-up with CT scans (the mean number of CT scans, including the baseline LDCT scan: 4.6), 2116 nodules (30.0% of baseline subsolid nodules and 78.9% of new subsolid nodules) resolved spontaneously. Among 293 biopsied subsolid nodules, 227 (77.5%) nodules were diagnosed as lung cancer, of which 226 (99.6%) were adenocarcinomas. No significant difference was observed in pathological invasiveness or the initial stage between the baseline and new cancerous subsolid nodules. Multivariable analyses revealed that new detection at follow-up screening was significantly associated with a lower probability of lung cancer (OR 0.26, 95% CI 0.14 to 0.49) and overall growth (OR 0.39, 95% CI 0.26 to 0.59), but with a higher probability of resolution (OR 6.30, 95% CI 5.09 to 7.81).LDCT screening led to a considerably high rate of subsolid nodule detection, particularly in never-smokers. Compared with the baseline subsolid nodules, the new subsolid nodules were associated with a lower probability of lung cancer and higher probability of spontaneous resolution, indicating their more inflammatory nature. Less aggressive follow-up may be allowed for new subsolid nodules, particularly in screening programmes for Asian populations.
Oncogenic <i>KRAS</i> Recruits an Expansive Transcriptional Network through Mutant p53 to Drive Pancreatic Cancer Metastasis
Authors: Michael P. Kim, Xinqun Li, Jenying Deng, Yun Zhang, Bingbing Dai, Kendra L. Allton, Tara G. Hughes, Christian Siangco, Jithesh J. Augustine, Ya'an Kang, Joy M. McDaniel, Shunbin Xiong, Eugene J. Koay, Florencia McAllister, Christopher A. Bristow, Timothy P. Heffernan, Anirban Maitra, Bin Liu, Michelle C. Barton, Amanda R. Wasylishen, Jason B. Fleming, Guillermina Lozano
Journal: Cancer Discovery (2021)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is almost uniformly fatal and characterized by early metastasis. Oncogenic KRAS mutations prevail in 95% of PDAC tumors and co-occur with genetic alterations in the TP53 tumor suppressor in nearly 70% of patients. Most TP53 alterations are missense mutations that exhibit gain-of-function phenotypes that include increased invasiveness and metastasis, yet the extent of direct cooperation between KRAS effectors and mutant p53 remains largely undefined. We show that oncogenic KRAS effectors activate CREB1 to allow physical interactions with mutant p53 that hyperactivate multiple prometastatic transcriptional networks. Specifically, mutant p53 and CREB1 upregulate the prometastatic, pioneer transcription factor FOXA1, activating its transcriptional network while promoting WNT/β-catenin signaling, together driving PDAC metastasis. Pharmacologic CREB1 inhibition dramatically reduced FOXA1 and β-catenin expression and dampened PDAC metastasis, identifying a new therapeutic strategy to disrupt cooperation between oncogenic KRAS and mutant p53 to mitigate metastasis. Significance: Oncogenic KRAS and mutant p53 are the most commonly mutated oncogene and tumor suppressor gene in human cancers, yet direct interactions between these genetic drivers remain undefined. We identified a cooperative node between oncogenic KRAS effectors and mutant p53 that can be therapeutically targeted to undermine cooperation and mitigate metastasis. This article is highlighted in the In This Issue feature, p. 1861
Potential Value of Maternal Oxygen Supplementation
Authors: Ola Didrik Saugstad, Maximo Vento
Journal: JAMA Pediatrics (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Unilateral nipple rash in a man
Authors: Hamid Abudhaise, Mohsin Dani, Haresh Devalia
Journal: BMJ (2021)

A man in his 50s was referred to the breast surgery clinic with a one month history of an exudating, oedematous, itchy right nipple-areolar complex. He had experienced hay fever in the past but reported no recent contact with known irritants or allergens. He had not used topical steroids before presentation. On examination, both the right nipple and the areola were erythematous, thickened, and excoriated (fig 1). The left nipple was unaffected, and there were no palpable breast lumps or axillary lymphadenopathy bilaterally. Lesions were not present elsewhere. Mammography and ultrasonography only showed thickened right areolar skin. Right areolar punch biopsy revealed epidermal hyperplasia, hyperkeratosis/parakeratosis, and spongiosis with subepithelial inflammation.



Fig 1 
Right nipple eczema, showing erythema, oedema, and excoriation of …
Validation of a Clinical Decision Rule to Predict Abuse in Young Children Based on Bruising Characteristics
Authors: Mary Clyde Pierce, Kim Kaczor, Douglas J. Lorenz, Gina Bertocci, Amanda K. Fingarson, Kathi Makoroff, Rachel P. Berger, Berkeley Bennett, Julia Magana, Shannon Staley, Veena Ramaiah, Kristine Fortin, Melissa Currie, Bruce E. Herman, Sandra Herr, Kent P. Hymel, Carole Jenny, Karen Sheehan, Noel Zuckerbraun, Sheila Hickey, Gabriel Meyers, John M. Leventhal
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Bruising caused by physical abuse is the most common antecedent injury to be overlooked or misdiagnosed as nonabusive before an abuse-related fatality or near-fatality in a young child. Bruising occurs from both nonabuse and abuse, but differences identified by a clinical decision rule may allow improved and earlier recognition of the abused child. <h3>Objective</h3> To refine and validate a previously derived bruising clinical decision rule (BCDR), the TEN-4 (bruising to torso, ear, or neck or any bruising on an infant &lt;4.99 months of age), for identifying children at risk of having been physically abused. <h3>Design, Setting, and Participants</h3> This prospective cross-sectional study was conducted from December 1, 2011, to March 31, 2016, at emergency departments of 5 urban children's hospitals. Children younger than 4 years with bruising were identified through deliberate examination. Statistical analysis was completed in June 2020. <h3>Exposures</h3> Bruising characteristics in 34 discrete body regions, patterned bruising, cumulative bruise counts, and patient's age. The BCDR was refined and validated based on these variables using binary recursive partitioning analysis. <h3>Main Outcomes and Measures</h3> Injury from abusive vs nonabusive trauma was determined by the consensus judgment of a multidisciplinary expert panel. <h3>Results</h3> A total of 21 123 children were consecutively screened for bruising, and 2161 patients (mean [SD] age, 2.1 [1.1] years; 1296 [60%] male; 1785 [83%] White; 1484 [69%] non-Hispanic/Latino) were enrolled. The expert panel achieved consensus on 2123 patients (98%), classifying 410 (19%) as abuse and 1713 (79%) as nonabuse. A classification tree was fit to refine the rule and validated via bootstrap resampling. The resulting BCDR was 95.6% (95% CI, 93.0%-97.3%) sensitive and 87.1% (95% CI, 85.4%-88.6%) specific for distinguishing abuse from nonabusive trauma based on body region bruised (torso, ear, neck, frenulum, angle of jaw, cheeks [fleshy], eyelids, and subconjunctivae), bruising anywhere on an infant 4.99 months and younger, or patterned bruising (TEN-4-FACESp). <h3>Conclusions and Relevance</h3> In this study, an affirmative finding for any of the 3 BCDR TEN-4-FACESp components in children younger than 4 years indicated a potential risk for abuse; these results warrant further evaluation. Clinical application of this tool has the potential to improve recognition of abuse in young children with bruising.
A report from the European Hyperoxaluria Consortium (OxalEurope) Registry on a large cohort of patients with primary hyperoxaluria type 3
Authors: Cristina Martin-Higueras, Sander F. Garrelfs, Jaap W. Groothoff, Dorrit E. Jacob, Shabbir H. Moochhala, Justine Bacchetta, Cecile Acquaviva, Marcin Zaniew, Przymyslaw Sikora, Bodo B. Beck, Bernd Hoppe
Journal: Kidney International (2021)
Cannabidiol converts NF-κB into a tumor suppressor in glioblastoma with defined antioxidative properties
Authors: Marie N M Volmar, Jiying Cheng, Haitham Alenezi, Sven Richter, Alisha Haug, Zonera Hassan, Maria Goldberg, Yuping Li, Mengzhuo Hou, Christel Herold-Mende, Cecile L Maire, Katrin Lamszus, Charlotte Flüh, Janka Held-Feindt, Gaetano Gargiulo, Geoffrey J Topping, Franz Schilling, Dieter Saur, Günter Schneider, Michael Synowitz, Joel A Schick, Roland E Kälin, Rainer Glass
Journal: Neuro-Oncology (2021)

Abstract Background The transcription factor NF-κB drives neoplastic progression of many cancers including primary brain tumors (glioblastoma [GBM]). Precise therapeutic modulation of NF-κB activity can suppress central oncogenic signaling pathways in GBM, but clinically applicable compounds to achieve this goal have remained elusive. Methods In a pharmacogenomics study with a panel of transgenic glioma cells, we observed that NF-κB can be converted into a tumor suppressor by the non-psychotropic cannabinoid cannabidiol (CBD). Subsequently, we investigated the anti-tumor effects of CBD, which is used as an anticonvulsive drug (Epidiolex) in pediatric neurology, in a larger set of human primary GBM stem-like cells (hGSC). For this study, we performed pharmacological assays, gene expression profiling, biochemical, and cell-biological experiments. We validated our findings using orthotopic in vivo models and bioinformatics analysis of human GBM datasets. Results We found that CBD promotes DNA binding of the NF-κB subunit RELA and simultaneously prevents RELA phosphorylation on serine-311, a key residue that permits genetic transactivation. Strikingly, sustained DNA binding by RELA-lacking phospho-serine 311 was found to mediate hGSC cytotoxicity. Widespread sensitivity to CBD was observed in a cohort of hGSC defined by low levels of reactive oxygen species (ROS), while high ROS content in other tumors blocked CBD-induced hGSC death. Consequently, ROS levels served as a predictive biomarker for CBD-sensitive tumors. Conclusions This evidence demonstrates how a clinically approved drug can convert NF-κB into a tumor suppressor and suggests a promising repurposing option for GBM therapy.
Germline variants at SOHLH2 influence multiple myeloma risk
Authors: Laura Duran-Lozano, Gudmar Thorleifsson, Aitzkoa Lopez de Lapuente Portilla, Abhishek Niroula, Molly Went, Malte Thodberg, Maroulio Pertesi, Ram Ajore, Caterina Cafaro, Pall I. Olason, Lilja Stefansdottir, G. Bragi Walters, Gisli H. Halldorsson, Ingemar Turesson, Martin F. Kaiser, Niels Weinhold, Niels Abildgaard, Niels Frost Andersen, Ulf-Henrik Mellqvist, Anders Waage, Annette Juul-Vangsted, Unnur Thorsteinsdottir, Markus Hansson, Richard Houlston, Thorunn Rafnar, Kari Stefansson, Björn Nilsson
Journal: Blood Cancer Journal (2021)

Multiple myeloma (MM) is caused by the uncontrolled, clonal expansion of plasma cells. While there is epidemiological evidence for inherited susceptibility, the molecular basis remains incompletely understood. We report a genome-wide association study totalling 5,320 cases and 422,289 controls from four Nordic populations, and find a novel MM risk variant at SOHLH2 at 13q13.3 (risk allele frequency = 3.5%; odds ratio = 1.38; P = 2.2 × 10-14). This gene encodes a transcription factor involved in gametogenesis that is normally only weakly expressed in plasma cells. The association is represented by 14 variants in linkage disequilibrium. Among these, rs75712673 maps to a genomic region with open chromatin in plasma cells, and upregulates SOHLH2 in this cell type. Moreover, rs75712673 influences transcriptional activity in luciferase assays, and shows a chromatin looping interaction with the SOHLH2 promoter. Our work provides novel insight into MM susceptibility.
Polygenic Risk Scores have high diagnostic capacity in ankylosing spondylitis
Authors: Zhixiu Li, Xin Wu, Paul J Leo, Erika De Guzman, Nurullah Akkoc, Maxime Breban, Gary J Macfarlane, Mahdi Mahmoudi, Helena Marzo-Ortega, Lisa K Anderson, Lawrie Wheeler, Chung-Tei Chou, Andrew A Harrison, Simon Stebbings, Gareth T Jones, So-Young Bang, Geng Wang, Ahmadreza Jamshidi, Elham Farhadi, Jing Song, Li Lin, Mengmeng Li, James Cheng-Chung Wei, Nicholas G Martin, Margaret J Wright, MinJae Lee, Yuqin Wang, Jian Zhan, Jin-San Zhang, Xiaobing Wang, Zi-Bing Jin, Michael H Weisman, Lianne S Gensler, Michael M Ward, Mohammad Hossein Rahbar, Laura Diekman, Tae-Hwan Kim, John D Reveille, Bryan Paul Wordsworth, Huji Xu, Matthew A Brown
Journal: Annals of the Rheumatic Diseases (2021)

We sought to test the hypothesis that Polygenic Risk Scores (PRSs) have strong capacity to discriminate cases of ankylosing spondylitis (AS) from healthy controls and individuals in the community with chronic back pain.PRSs were developed and validated in individuals of European and East Asian ethnicity, using data from genome-wide association studies in 15 585 AS cases and 20 452 controls. The discriminatory values of PRSs in these populations were compared with other widely used diagnostic tests, including C-reactive protein (CRP), HLA-B27 and sacroiliac MRI.In people of European descent, PRS had high discriminatory capacity with area under the curve (AUC) in receiver operator characteristic analysis of 0.924. This was significantly better than for HLA-B27 testing alone (AUC=0.869), MRI (AUC=0.885) or C-reactive protein (AUC=0.700). PRS developed and validated in individuals of East Asian descent performed similarly (AUC=0.948). Assuming a prior probability of AS of 10% such as in patients with chronic back pain under 45 years of age, compared with HLA-B27 testing alone, PRS provides higher positive values for 35% of patients and negative predictive values for 67.5% of patients. For PRS, in people of European descent, the maximum positive predictive value was 78.2% and negative predictive value was 100%, whereas for HLA-B27, these values were 51.9% and 97.9%, respectively.PRS have higher discriminatory capacity for AS than CRP, sacroiliac MRI or HLA-B27 status alone. For optimal performance, PRS should be developed for use in the specific ethnic groups to which they are to be applied.
Abstract 18373: Investigational RNAI Therapeutic Targeting Angiotensinogen Ameliorates the Preeclamptic Phenotype in Rodent Models of Preeclampsia
Authors: Nadine Haase, Don Foster, Mark W Cunningham, Stuart Milstein, Klaus Charisse, Michaela Golic, Florian Herse, Kristin Kräker, Satya Kuchimanchi, Brian Bettencourt, Greg Hinkle, Babbette LaMarca, Dominik N Müller, Ralf Dechend
Journal: Circulation (2017)

Introduction: Preeclampsia, syndrome with hallmark features of new-onset hypertension and proteinuria after 20 weeks of gestation, affects 5% of pregnancies. It is a major cause of fetal and matern...
Abstract 12192: Prevalence of Cardiac Amyloidosis in Patients Referred for Atrial Fibrillation Ablation by Cardiac MRI
Authors: Christian Ngo, Matthew Cham, Nazem W Akoum, Richard Cheng, Sofia Carolina C Masri
Journal: Circulation (2019)

Introduction: Atrial fibrillation (AF) is the most commonly encountered heart rhythm disorder in patients with cardiac amyloidosis (CA). The prevalence of CA in patients referred to AF ablation wit...
Advanced genetic engineering to achieve in vivo targeting of adenovirus utilizing camelid single domain antibody
Authors: Myungeun Lee, Zhi Hong Lu, Charles B. Shoemaker, Jacqueline M. Tremblay, Bradley St. Croix, Steven Seaman, Rebeca Gonzalez-Pastor, Elena A. Kashentseva, Igor P. Dmitriev, David T. Curiel
Journal: Journal of Controlled Release (2021)

For the developing field of gene therapy the successful address of the basic requirement effective gene delivery has remained a critical barrier. In this regard, the "Holy Grail" vector envisioned by the field's pioneers embodied the ability to achieve efficient and specific in vivo gene delivery. Functional linkage of antibody selectivity with viral vector efficiency represented a logical strategy but has been elusive. Here we have addressed this key issue by developing the technical means to pair antibody-based targeting with adenoviral-mediated gene transfer. Our novel method allows efficient and specific gene delivery. Importantly, our studies validated the achievement of this key vectorology mandate in the context of in vivo gene delivery. Vectors capable of effective in vivo delivery embody the potential to dramatically expand the range of successful gene therapy cures.
Ssu72 is a T-cell receptor-responsive modifier that is indispensable for regulatory T cells
Authors: Jin-Kwan Lee, Seo-Young Koo, Hye-Mi Nam, Jee-Boong Lee, Jiwon Ko, Kyung-Mo Kim, Eun-Ji Park, Tae Jin Kim, Ho Lee, Heounjeong Go, Chang-Woo Lee
Journal: Cellular and Molecular Immunology (2021)
PRMT1-mediated H4R3me2a recruits SMARCA4 to promote colorectal cancer progression by enhancing EGFR signaling
Authors: Bing Yao, Tao Gui, Xiangwei Zeng, Yexuan Deng, Zhi Wang, Ying Wang, Dongjun Yang, Qixiang Li, Peipei Xu, Ruifeng Hu, Xinyu Li, Bing Chen, Jin Wang, Ke Zen, Haitao Li, Melissa J. Davis, Marco J. Herold, Hua-Feng Pan, Zhi-Wei Jiang, David C. S. Huang, Ming Liu, Junyi Ju, Quan Zhao
Journal: Genome Medicine (2021)

Aberrant changes in epigenetic mechanisms such as histone modifications play an important role in cancer progression. PRMT1 which triggers asymmetric dimethylation of histone H4 on arginine 3 (H4R3me2a) is upregulated in human colorectal cancer (CRC) and is essential for cell proliferation. However, how this dysregulated modification might contribute to malignant transitions of CRC remains poorly understood.In this study, we integrated biochemical assays including protein interaction studies and chromatin immunoprecipitation (ChIP), cellular analysis including cell viability, proliferation, colony formation, and migration assays, clinical sample analysis, microarray experiments, and ChIP-Seq data to investigate the potential genomic recognition pattern of H4R3me2s in CRC cells and its effect on CRC progression.We show that PRMT1 and SMARCA4, an ATPase subunit of the SWI/SNF chromatin remodeling complex, act cooperatively to promote colorectal cancer (CRC) progression. We find that SMARCA4 is a novel effector molecule of PRMT1-mediated H4R3me2a. Mechanistically, we show that H4R3me2a directly recruited SMARCA4 to promote the proliferative, colony-formative, and migratory abilities of CRC cells by enhancing EGFR signaling. We found that EGFR and TNS4 were major direct downstream transcriptional targets of PRMT1 and SMARCA4 in colon cells, and acted in a PRMT1 methyltransferase activity-dependent manner to promote CRC cell proliferation. In vivo, knockdown or inhibition of PRMT1 profoundly attenuated the growth of CRC cells in the C57BL/6 J-ApcMin/+ CRC mice model. Importantly, elevated expression of PRMT1 or SMARCA4 in CRC patients were positively correlated with expression of EGFR and TNS4, and CRC patients had shorter overall survival. These findings reveal a critical interplay between epigenetic and transcriptional control during CRC progression, suggesting that SMARCA4 is a novel key epigenetic modulator of CRC. Our findings thus highlight PRMT1/SMARCA4 inhibition as a potential therapeutic intervention strategy for CRC.PRMT1-mediated H4R3me2a recruits SMARCA4, which promotes colorectal cancer progression by enhancing EGFR signaling.
Three Automated Quantitative Cardiac Magnetic Resonance Perfusion Analyses Versus Invasive Fractional Flow Reserve in Swine
Authors: Andrew J. Bradley, Daniel W. Groves, Mitchel Benovoy, Sarah K. Yang, Shawn Kozlov, Joni L. Taylor, Arlene Sirajuddin, Li-Yueh Hsu, Andrew E. Arai
Journal: JACC. Cardiovascular imaging (2021)