tbuckley/cabot-search huggingface dataset:
Intrahepatic Cholangiocarcinoma with Lymph Node Metastasis: Treatment-Related Outcomes and the Role of Tumor Genomics in Patient Selection
Authors: Joshua S. Jolissaint, Kevin C. Soares, Kenneth P. Seier, Ritika Kundra, Mithat Gönen, Paul J. Shin, Thomas Boerner, Carlie Sigel, Ramyasree Madupuri, Efsevia Vakiani, Andrea Cercek, James J. Harding, Nancy E. Kemeny, Louise C. Connell, Vinod P. Balachandran, Michael I. D'Angelica, Jeffrey A. Drebin, T. Peter Kingham, Alice C. Wei, William R. Jarnagin
Journal: Clinical Cancer Research (2021)

Lymph node metastasis (LNM) drastically reduces survival after resection of intrahepatic cholangiocarcinoma (IHC). Optimal treatment is ill defined, and it is unclear whether tumor mutational profiling can support treatment decisions.Patients with liver-limited IHC with or without LNM treated with resection (N = 237), hepatic arterial infusion chemotherapy (HAIC; N = 196), or systemic chemotherapy alone (SYS; N = 140) at our institution between 2000 and 2018 were included. Genomic sequencing was analyzed to determine whether genetic alterations could stratify outcomes for patients with LNM.For node-negative patients, resection was associated with the longest median overall survival [OS, 59.9 months; 95% confidence interval (CI), 47.2-74.31], followed by HAIC (24.9 months; 95% CI, 20.3-29.6), and SYS (13.7 months; 95% CI, 8.9-15.9; P < 0.001). There was no difference in survival for node-positive patients treated with resection (median OS, 19.7 months; 95% CI, 12.1-27.2) or HAIC (18.1 months; 95% CI, 14.1-26.6; P = 0.560); however, survival in both groups was greater than SYS (11.2 months; 95% CI, 14.1-26.6; P = 0.024). Node-positive patients with at least one high-risk genetic alteration (TP53 mutation, KRAS mutation, CDKN2A/B deletion) had worse survival compared to wild-type patients (median OS, 12.1 months; 95% CI, 5.7-21.5; P = 0.002), regardless of treatment. Conversely, there was no difference in survival for node-positive patients with IDH1/2 mutations compared to wild-type patients.There was no difference in OS for patients with node-positive IHC treated by resection versus HAIC, and both treatments had better survival than SYS alone. The presence of high-risk genetic alterations provides valuable prognostic information that may help guide treatment.
Human cells and networks of pain: Transforming pain target identification and therapeutic development
Authors: William Renthal, Alexander Chamessian, Michele Curatolo, Steve Davidson, Michael Burton, Sulayman Dib-Hajj, Patrick M. Dougherty, Allison D. Ebert, Robert W. Gereau, Andre Ghetti, Michael S. Gold, Gwendolyn Hoben, Daniela Maria Menichella, Philippe Mercier, Wilson Z. Ray, Daniela Salvemini, Rebecca P. Seal, Stephen Waxman, Clifford J. Woolf, Cheryl L. Stucky, Theodore J. Price
Journal: Neuron (2021)
Whole-genome sequencing of phenotypically distinct inflammatory breast cancers reveals similar genomic alterations to non-inflammatory breast cancers
Authors: Xiaotong Li, Sushant Kumar, Arif Harmanci, Shantao Li, Robert R. Kitchen, Yan Zhang, Vikram B. Wali, Sangeetha M. Reddy, Wendy A. Woodward, James M. Reuben, Joel Rozowsky, Christos Hatzis, Naoto T. Ueno, Savitri Krishnamurthy, Lajos Pusztai, Mark Gerstein
Journal: Genome Medicine (2021)

Abstract Background Inflammatory breast cancer (IBC) has a highly invasive and metastatic phenotype. However, little is known about its genetic drivers. To address this, we report the largest cohort of whole-genome sequencing (WGS) of IBC cases. Methods We performed WGS of 20 IBC samples and paired normal blood DNA to identify genomic alterations. For comparison, we used 23 matched non-IBC samples from the Cancer Genome Atlas Program (TCGA). We also validated our findings using WGS data from the International Cancer Genome Consortium (ICGC) and the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We examined a wide selection of genomic features to search for differences between IBC and conventional breast cancer. These include (i) somatic and germline single-nucleotide variants (SNVs), in both coding and non-coding regions; (ii) the mutational signature and the clonal architecture derived from these SNVs; (iii) copy number and structural variants (CNVs and SVs); and (iv) non-human sequence in the tumors (i.e., exogenous sequences of bacterial origin). Results Overall, IBC has similar genomic characteristics to non-IBC, including specific alterations, overall mutational load and signature, and tumor heterogeneity. In particular, we observed similar mutation frequencies between IBC and non-IBC, for each gene and most cancer-related pathways. Moreover, we found no exogenous sequences of infectious agents specific to IBC samples. Even though we could not find any strongly statistically distinguishing genomic features between the two groups, we did find some suggestive differences in IBC: (i) The MAST2 gene was more frequently mutated (20% IBC vs. 0% non-IBC). (ii) The TGF β pathway was more frequently disrupted by germline SNVs (50% vs. 13%). (iii) Different copy number profiles were observed in several genomic regions harboring cancer genes. (iv) Complex SVs were more frequent. (v) The clonal architecture was simpler, suggesting more homogenous tumor-evolutionary lineages. Conclusions Whole-genome sequencing of IBC manifests a similar genomic architecture to non-IBC. We found no unique genomic alterations shared in just IBCs; however, subtle genomic differences were observed including germline alterations in TGFβ pathway genes and somatic mutations in the MAST2 kinase that could represent potential therapeutic targets.
Ten-eleven translocation protein 1 modulates medulloblastoma progression
Authors: Hyerim Kim, Yunhee Kang, Yujing Li, Li Chen, Li Lin, Nicholas D. Johnson, Dan Zhu, M. Hope Robinson, Leon McSwain, Benjamin G. Barwick, Xianrui Yuan, Xinbin Liao, Jie Zhao, Zhiping Zhang, Qiang Shu, Jianjun Chen, Emily G. Allen, Anna M. Kenney, Robert C. Castellino, Erwin G. Van Meir, Karen N. Conneely, Paula M. Vertino, Peng Jin, Jian Li
Journal: Genome biology (2021)

Abstract Background Medulloblastoma (MB) is the most common malignant pediatric brain tumor that originates in the cerebellum and brainstem. Frequent somatic mutations and deregulated expression of epigenetic regulators in MB highlight the substantial role of epigenetic alterations. 5-hydroxymethylcytosine (5hmC) is a highly abundant cytosine modification in the developing cerebellum and is regulated by ten-eleven translocation (TET) enzymes. Results We investigate the alterations of 5hmC and TET enzymes in MB and their significance to cerebellar cancer formation. We show total abundance of 5hmC is reduced in MB, but identify significant enrichment of MB-specific 5hmC marks at regulatory regions of genes implicated in stem-like properties and Nanog-binding motifs. While TET1 and TET2 levels are high in MBs, only knockout of Tet1 in the smoothened ( SmoA1) mouse model attenuates uncontrolled proliferation, leading to a favorable prognosis. The pharmacological Tet1 inhibition reduces cell viability and platelet-derived growth factor signaling pathway-associated genes. Conclusions These results together suggest a potential key role of 5hmC and indicate an oncogenic nature for TET1 in MB tumorigenesis, suggesting it as a potential therapeutic target for MBs.
Association of Rare Genetic Variants and Early-Onset Atrial Fibrillation in Ethnic Minority Individuals
Authors: Brandon Chalazan, Denise Mol, Faisal A. Darbar, Aylin Ornelas-Loredo, Bahaa Al-Azzam, Yining Chen, David Tofovic, Arvind Sridhar, Zain Alzahrani, Patrick Ellinor, Dawood Darbar
Journal: JAMA Cardiology (2021)

<h3>Importance</h3> Although rare variants in cardiac ion channels, transcription factors, and myocardial structural proteins are associated with early-onset atrial fibrillation (AF) in White individuals of European descent, it remains unclear whether genetic variation also contributes to the cause of AF in those of minority ethnicity. <h3>Objectives</h3> To assess the prevalence of rare and novel pathogenic variants in candidate genes in ethnic minority probands with early-onset AF and determine genotype-phenotype associations. <h3>Design, Setting, and Participants</h3> In this cohort, family-based study, probands of African and Hispanic descent with early-onset AF (defined as AF occurring in individuals aged ≤66 years) prospectively enrolled in a clinical and genetic biorepository underwent sequencing of 60 candidate genes. Recruitment took place from July 1, 2015, to June 30, 2019. Data were analyzed from February 1 to February 28, 2020. <h3>Exposures</h3> Rare and novel variants categorized as pathogenic or likely pathogenic. <h3>Main Outcomes and Measures</h3> The prevalence of rare and novel pathogenic variants in African American and Hispanic/Latinx probands with early-onset AF and genotype-phenotype associations. <h3>Results</h3> Among 227 probands with early-onset AF, mean (SD) age at onset of AF was 51.0 (9.9) years, 132 probands (58.1%) were men, 148 (65.2%) were African American, and 79 (34.8%) were Hispanic/Latinx. A family history of AF was verified in 24 probands with early-onset AF (10.6%). Sequencing 60 candidate genes identified 53 (23 rare and 30 novel) variants with 16 of the 227 (7.0%) probands harboring likely pathogenic (43.8%) or pathogenic (56.2%) variants, with most loss-of-function variants in<i>TTN</i>, the gene encoding the sarcomeric protein titin (46.7%). In 6 families with more than 2 affected members, variants of unknown significance in sodium channel (<i>SCN10A</i>), potassium channel (<i>KCNE5</i>), sarcomeric proteins (<i>MYH6</i>and<i>TTN</i>), and atrial natriuretic peptide (<i>NPPA</i>) cosegregated with AF. <h3>Conclusions and Relevance</h3> In this study, likely pathogenic and pathogenic variants were identified, with most loss-of-function variants in<i>TTN</i>, that increase susceptibility to early-onset AF in African American and Hispanic/Latinx individuals. These findings provide further understanding toward molecular phenotyping of AF and suggest novel mechanism-based therapeutic approaches for this common arrhythmia in ethnic minority groups.
Involvement of CFTR in the pathogenesis of pulmonary arterial hypertension
Authors: Hélène Le Ribeuz, Lucie To, Maria-Rosa Ghigna, Clémence Martin, Chandran Nagaraj, Elise Dreano, Catherine Rucker-Martin, Barbara Girerd, Jérôme Bouligand, Christine Pechoux, Mélanie Lambert, Angèle Boet, Justin Issard, Olaf Mercier, Konrad Hoetzenecker, Boris Manoury, Frédéric Becq, Pierre-Régis Burgel, Charles-Henry Cottart, Andrea Olschewski, Isabelle Sermet-Gaudelus, Frédéric Perros, Marc Humbert, David Montani, Fabrice Antigny
Journal: European Respiratory Journal (2021)

Introduction A reduction in pulmonary artery relaxation is a key event in the pathogenesis of pulmonary arterial hypertension (PAH). Cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction in airway epithelial cells plays a central role in cystic fibrosis; CFTR is also expressed in pulmonary arteries and has been shown to control endothelium-independent relaxation. Aim and objectives We aimed to delineate the role of CFTR in PAH pathogenesis through observational and interventional experiments in human tissues and animal models. Methods and results Reverse-transcriptase quantitative PCR, confocal imaging and electron microscopy showed that CFTR expression was reduced in pulmonary arteries from patients with idiopathic PAH (iPAH) and in rats with monocrotaline-induced pulmonary hypertension (PH). Moreover, using myography on human, pig and rat pulmonary arteries, we demonstrated that CFTR activation induces pulmonary artery relaxation. CFTR-mediated pulmonary artery relaxation was reduced in pulmonary arteries from iPAH patients and rats with monocrotaline- or chronic hypoxia-induced PH. Long-term in vivo CFTR inhibition in rats significantly increased right ventricular systolic pressure, which was related to exaggerated pulmonary vascular cell proliferation in situ and vessel neomuscularisation. Pathologic assessment of lungs from patients with severe cystic fibrosis ( F508del-CFTR ) revealed severe pulmonary artery remodelling with intimal fibrosis and medial hypertrophy. Lungs from homozygous F508delCftr rats exhibited pulmonary vessel neomuscularisation. The elevations in right ventricular systolic pressure and end diastolic pressure in monocrotaline-exposed rats with chronic CFTR inhibition were more prominent than those in vehicle-exposed rats. Conclusions CFTR expression is strongly decreased in pulmonary artery smooth muscle and endothelial cells in human and animal models of PH. CFTR inhibition increases vascular cell proliferation and strongly reduces pulmonary artery relaxation.
Combined reflectance confocal microscopy and optical coherence tomography to improve the diagnosis of equivocal lesions for basal cell carcinoma
Authors: Jilliana Monnier, Nathalie De Carvalho, Ucalene Harris, Jason Garfinkel, Aleissa Saud, Cristian Navarrete-Dechent, Konstantinos Liopyris, Ofer Reiter, Gennady Rubinstien, Nicusor Iftimia, Kishwer S. Nehal, Alina Markova, Liang Deng, Anthony M. Rossi, Ashfaq A. Marghoob, Michael A. Marchetti, Veronica Rotemberg, Giovanni Pellacani, Manu Jain
Journal: Journal of the American Academy of Dermatology (2021)
CONTINUOUS INFUSION VERSUS INTERMITTENT BOLUS FUROSEMIDE FOR ACUTE DECOMPENSATED HEART FAILURE: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Pinang Shastri, Cameron Burmeister, Jeremy Tomcho, Mitra Patel, Ahmed Elzanaty, Sapan Bhuta, Neha Patel, Omar Sajdeya, Mohammed Mhanna, Sami Ghazaleh, Azizullah Beran
Journal: Journal of the American College of Cardiology (2021)
Questions Regarding Patient-Reported Symptom Burden as a Predictor of Emergency Department Use and Unplanned Hospitalization in Head and Neck Cancer
Authors: Kazuki Yokoyama, Hiroto Ishiki
Journal: Journal of Clinical Oncology (2021)

Noel et al 1 have presented valuable real-world data that showed the potential of the Edmonton Symptom Assessment System (ESAS) as a screening tool to avoid emergency department visits and unplanned hospitalization (ED/Hosp) in patients with head and neck cancer.We read this article with great interest and would like the authors to provide some additional data and discuss the interpretation of the results involving the use of the ESAS as a screening tool.
만성 C형간염에서 삶의 질
Authors: 서정일
Journal: Clinical and Molecular Hepatology (2010)

Chronic infection with the hepatitis C virus (HCV) reduces the health-related quality of life (HRQoL). The most common complaints such as fatigue, depression and neurocognitive dysfunction in chronic hepatitis C have the potential to impair HRQoL. Treatment of chronic HCV infection may temporarily worsen HRQoL due to common adverse effects such as fatigue, muscle aches, depression and cognitive deficits. Although treatment- related adverse effects may prevent patient from starting therapy and reduce compliance with associated reductions in sustained viral clearance (SVR), SVR improves not only long-term prognosis but also HRQoL. HCV self-management program, regular psychological support and counselling, and new oral antiviral agents including HCV protease and polymerase inhibitors appear to offer improved SVR and potentially leading to improvements in HRQoL in patients with chronic hepatitis C.
Automated Explainable Multidimensional Deep Learning Platform of Retinal Images for Retinopathy of Prematurity Screening
Authors: Ji Wang, Jie Ji, Mingzhi Zhang, Jian-Wei Lin, Guihua Zhang, Weifen Gong, Ling-Ping Cen, Yamei Lu, Xuelin Huang, Dingguo Huang, Taiping Li, Tsz Kin Ng, Chi Pui Pang
Journal: JAMA Network Open (2021)

<h3>Importance</h3> A retinopathy of prematurity (ROP) diagnosis currently relies on indirect ophthalmoscopy assessed by experienced ophthalmologists. A deep learning algorithm based on retinal images may facilitate early detection and timely treatment of ROP to improve visual outcomes. <h3>Objective</h3> To develop a retinal image–based, multidimensional, automated, deep learning platform for ROP screening and validate its performance accuracy. <h3>Design, Setting, and Participants</h3> A total of 14 108 eyes of 8652 preterm infants who received ROP screening from 4 centers from November 4, 2010, to November 14, 2019, were included, and a total of 52 249 retinal images were randomly split into training, validation, and test sets. Four main dimensional independent classifiers were developed, including image quality, any stage of ROP, intraocular hemorrhage, and preplus/plus disease. Referral-warranted ROP was automatically generated by integrating the results of 4 classifiers at the image, eye, and patient levels. DeepSHAP, a method based on DeepLIFT and Shapley values (solution concepts in cooperative game theory), was adopted as the heat map technology to explain the predictions. The performance of the platform was further validated as compared with that of the experienced ROP experts. Data were analyzed from February 12, 2020, to June 24, 2020. <h3>Exposure</h3> A deep learning algorithm. <h3>Main Outcomes and Measures</h3> The performance of each classifier included true negative, false positive, false negative, true positive, F1 score, sensitivity, specificity, receiver operating characteristic, area under curve (AUC), and Cohen unweighted κ. <h3>Results</h3> A total of 14 108 eyes of 8652 preterm infants (mean [SD] gestational age, 32.9 [3.1] weeks; 4818 boys [60.4%] of 7973 with known sex) received ROP screening. The performance of all classifiers achieved an F1 score of 0.718 to 0.981, a sensitivity of 0.918 to 0.982, a specificity of 0.949 to 0.992, and an AUC of 0.983 to 0.998, whereas that of the referral system achieved an F1 score of 0.898 to 0.956, a sensitivity of 0.981 to 0.986, a specificity of 0.939 to 0.974, and an AUC of 0.9901 to 0.9956. Fine-grained and class-discriminative heat maps were generated by DeepSHAP in real time. The platform achieved a Cohen unweighted κ of 0.86 to 0.98 compared with a Cohen κ of 0.93 to 0.98 by the ROP experts. <h3>Conclusions and Relevance</h3> In this diagnostic study, an automated ROP screening platform was able to identify and classify multidimensional pathologic lesions in the retinal images. This platform may be able to assist routine ROP screening in general and children hospitals.
Single-Cell Multiplex Proteomics Reveals Synergistic Impact of Antigen and Rimiducid-Dependent Stimulatory Signals on Promoting Polyfunctional GoCAR-T Cells Targeting Prostate Stem Cell Antigen (PSCA)
Authors: Sean Mackay, Brianna Flynn, Kevin Morse, Colin Ng, Kyle Gallatin, Patrick Paczkowski, Aruna Mahendravada, Nicholas Shinners, David M. Spencer, Aaron Foster, Jing Zhou
Journal: Blood (2017)
Effect of Continuous Positive Airway Pressure on Arrhythmia in Atrial Fibrillation and Sleep Apnea: A Randomized Controlled Trial
Authors: Gunn Marit Traaen, Lars Aakerøy, Tove-Elizabeth Hunt, Britt Øverland, Christina Bendz, Lars Øivind Sande, Svend Aakhus, Morten Wang Fagerland, Sigurd Steinshamn, Ole-Gunnar Anfinsen, Richard John Massey, Kaspar Broch, Thor Ueland, Harriet Akre, Jan Pål Loennechen, Lars Gullestad
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: Sleep apnea (SA) is highly prevalent in patients with atrial fibrillation (AF), and both conditions are associated with adverse cardiovascular outcomes.Objectives: To determine the effect of continuous positive airway pressure (CPAP) on AF burden.Methods: This open-label, parallel-group, randomized controlled trial included patients with paroxysmal AF and moderate to severe SA (apnea-hypopnea index ⩾15). A computerized system randomized eligible patients (1:1) to 5 months' treatment with CPAP plus usual care (CPAP, n = 55) or usual care alone (control, n = 54). The outcome assessment was blinded. The planned primary outcome was the difference between CPAP treatment and control groups in change of AF burden (percentage of time in AF) as measured by implantable loop recorder.Measurements and Main Results: A total of 579 patients with paroxysmal AF had respiratory polygraphy, of whom 244 (42%) had moderate to severe SA. Of these, 158 (65%) participated in the CPAP run-in period, of whom 39 (25%) patients did not tolerate the treatment. A total of 108 patients were available for the primary analysis. The mean time in AF decreased from 5.6% at baseline to 4.1% during the last 3 months of CPAP intervention and from 5.0% to 4.3% in the control group. The adjusted between-group difference at follow-up was -0.63 (95% confidence interval, -2.55 to 1.30) percentage points (P = 0.52). Seven serious adverse events (13%) occurred in the CPAP group, and two (4%) occurred in the control group.Conclusions: In patients with paroxysmal AF and SA, treatment with CPAP did not result in a statistically significant reduction in the burden of AF.Clinical trial registered with www.clinicaltrials.gov (NCT02727192).
ANTIDEPRESSANTS AND RISK OF SUDDEN CARDIAC DEATH: A NETWORK META-ANALYSIS AND SYSTEMATIC REVIEW
Authors: Narut Prasitlumkum, Wisit Cheungpasitporn, Kimberly Ding, Nithi Tokavanich, Ronpichai Chokesuwattanaskul
Journal: Journal of the American College of Cardiology (2021)
COMPLICATED VENTRICULAR SEPTAL RUPTURE REQUIRING MECHANICAL CIRCULATORY SUPPORT BRIDGE TO HEART TRANSPLANT: A CONSEQUENCE OF LATE PRESENTING MYOCARDIAL INFARCTION IN THE ERA OF COVID-19
Authors: Raghav Gattani, Hooman Bakhshi, Emmanuel Ekanem, Mehul Desai, Shashank Sinha, Alan Speir, Ramesh Singh, Matthew Sherwood, Behnam Tehrani, Wayne Batchelor
Journal: Journal of the American College of Cardiology (2021)
Pulse oximetry gives artificially high readings in presence of carboxyhaemoglobin
Authors: John Moyle
Journal: BMJ (2021)

Greenhalgh and colleagues omit a serious limitation of two wavelength pulse oximetry.1 They mention “falsely low readings with certain haemoglobinopathies,” but a much more important danger is that standard two wavelength pulse oximeters give artificially high readings in the presence of circulating carboxyhaemoglobin to …
IMPACT OF ANNULAR OVERSIZING ON PARAVALVULAR REGURGITATION AND VALVE HEMODYNAMICS: NEW INSIGHTS FROM THE PARTNER 3 TRIAL
Authors: Abdul Rahman Ihdayhid, Jonathon Leipsic, Rebecca Hahn, Philippe Pibarot, Vinod Thourani, Raj Makkar, Susheel Kodali, Mark Russo, Samir Kapadia, Michael Lu, Michael Mack, John Webb, Jeroen Bax, Martin Leon, Philipp Blanke
Journal: Journal of the American College of Cardiology (2021)
Abstract 14421: Temporal Changes in Sensing and Pacing Parameters in Individuals With Cardiac Amyloidosis and Cardiac Implantable Electronic Devices
Authors: Benjamin B Holmes, Eun Jong Kim, Jay Montgomery, Greg Michaud, Roy John
Journal: Circulation (2018)

Introduction: The need for cardiac implantable electronic devices (CIEDs) in patients with cardiac amyloidosis (CA) is frequent. Little is known about the temporal changes in device pacing and sens...
FAMILIAL HYPERCHOLESTEROLEMIA AND ABDOMINAL AORTIC OBSTRUCTION IN A YOUNG WOMAN: A CASE REPORT
Authors: Vinícius Machado Correia, Viviane Rocha, Pamela Maciel, Ana Paula Chacra, Cinthia Elim Jannes Lapski, Raul Dias Santos, Marcio Miname, Wilson Salgado
Journal: Journal of the American College of Cardiology (2021)