tbuckley/cabot-search huggingface dataset:
Abstract PO004: Enhancer-promoter chromatin looping is enriched for endometrial cancer GWAS risk variation and reveals biologically relevant candidate susceptibility genes
Authors: Dylan M. Glubb, Pamela Pollock, Amanda Spurdle, Tracy A. O'Mara
Journal: Clinical Cancer Research (2021)

Abstract Large-scale genome-wide association studies (GWAS) conducted by the Endometrial Cancer Association Consortium have identified candidate endometrial cancer risk variants at 16 loci. The vast majority of these candidate endometrial cancer risk variants are located in non-coding genomic regions. Studies of other GWAS have shown enrichment of trait-associated variants in enhancer elements suggesting that they may regulate gene expression through chromatin looping. In the current study, we analysed chromatin looping to identify the genes that may mediate the effects of these variants. We used a modified HiChIP technique to capture chromatin loops associated with H3K27Ac (characteristic of active enhancers and promoters) in a normal immortalized and three tumoral endometrial cell lines. Duplicate HiChIP libraries were analysed using paired-end sequencing and bioinformatic pipelines (HiC-Pro, hichipper and IDR2D) to identify replicating cis chromatin loops. The replicating loops were intersected with gene promoter regions to identify promoter-associated chromatin loops and we found significant enrichment of endometrial cancer risk variation in these loops. We identified 74 candidate target genes at 13 endometrial cancer risk loci by intersecting promoter-associated loops with candidate risk variants and prioritising genes with matching RNA-seq expression. The candidate target genes were more conserved than other genes on average, nearly three times more likely to be differentially regulated in endometrial tumours and their encoded proteins interacted more amongst themselves than would be expected by chance. Moreover, functional prioritisation of the wider protein-protein interaction network revealed a set of interacting proteins that was 9-fold enriched for somatic endometrial cancer drivers. In summary, our findings indicate that endometrial cancer risk variation at least partly mediates its effects through enhancer-promoter chromatin looping and corresponding data reveal a set of biologically relevant candidate target genes. Citation Format: Dylan M. Glubb, Pamela Pollock, Amanda Spurdle, Tracy A. O'Mara. Enhancer-promoter chromatin looping is enriched for endometrial cancer GWAS risk variation and reveals biologically relevant candidate susceptibility genes [abstract]. In: Proceedings of the AACR Virtual Special Conference: Endometrial Cancer: New Biology Driving Research and Treatment; 2020 Nov 9-10. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(3_Suppl):Abstract nr PO004.
A Novel Assessment Using Projected Transmitral Gradient Improves Diagnostic Yield of Doppler Hemodynamics in Rheumatic and Calcific Mitral Stenosis
Authors: Nahoko Kato, Sorin V. Pislaru, Ratnasari Padang, Cristina Pislaru, Christopher G. Scott, Vuyisile T. Nkomo, Patricia A. Pellikka
Journal: JACC. Cardiovascular imaging (2021)
A Case of Mild COVID-19 in a Teenager with Common Variable Immunodeficiency and Granulomatous Interstitial Lung Disease on Replacement Immunoglobulin and Infliximab
Authors: Yatyng Chang, Daniel Urschel, Vivian Hernandez-Trujillo, Jose Calderon
Journal: Journal of Allergy and Clinical Immunology (2021)

Common variable immunodeficiency (CVID) is a disorder of the immune system. Patients are generally diagnosed in their adolescence and require regular immunoglobulin replacement. Due to their immune dysregulation, they are at increased risk of infections, autoimmune disease, and cancer. To describe a case of mild COVID-19 in a patient with CVID and granulomatous interstitial lung disease on replacement immunoglobulin and infliximab. The patient is a 15 year old female with CVID, granulomatous interstitial lung disease, and hepatosplenomegaly with pancytopenia and portal hypertension. She receives weekly SCIG and monthly infliximab. In July, an uncle who visits frequently tested positive for COVID-19. Mother, father, and brother subsequently had mild nasal congestion and tested positive for COVID-19. Our patient developed symptoms of headache and nasal congestion, for which Azithromycin was prescribed and symptoms resolved. No fever, cough, shortness of breath, or loss of sense of smell or taste was reported. No hospitalization was required. Her most recent labs with lymphocyte subsets revealed normal CD4 and CD8 T cell levels, low CD19 B cell levels, and normal immunoglobulins. Follow up COVID-19 PCR testing 1 month later remains positive. There are concerns regarding persons with immunodeficiency being at higher risk of serious illness from COVID-19. However, our patient's clinical course suggests that certain types of immunodeficiency or immunomodulators may potentially limit the cytokine storm which causes some COVID-19 complications. Further studies are needed.
Abstract 15198: Predictors of Adverse Cardiovascular Outcomes in Patients With Atrial Fibrillation and Heart Failure With Preserved Systolic Function: A Topcat Americas Post Hoc Analysis
Authors: Sanjeev Saksena, April Slee, Dhanunjaya Lakkireddy, Dipen Shah, Luigi Di Biase, Thorsten Lewalter, Andrea Natale
Journal: Circulation (2020)

Introduction: Presence of atrial fibrillation (AF) is known to increase mortality and impact cardiovascular(CV) outcomes in heart failure (HF) patients (pts) with preserved systolic function (pEF) but its causes are unknown Hypothesis: We hypothesized that AF presentation &amp; clinical factors impact mode of death &amp; CV outcomes of HFpEF pts in the TOPCAT AMERICAS trial. Methods: We analyzed demographic, clinical, ECG and AF presentation as predictors of CV mortality, sudden death( SCD) and pump failure death(PFD). We examined two AF presentations 1. Pts in sinus rhythm (SR, n=1319) compared to pts in AF (n=446) on ECG at study entry or 2. Pts with no AF event by history or ECG ( n=1007 ) compared to those with any AF event (n=760 ) during a mean follow up period of 2.9 years(yrs). Results: AF pts when compared to the rest of the study population were more likely to be older, male, Caucasian origin, have more alcohol use, diabetes, percutaneous coronary interventions. 5 yr CV mortality was higher in pts with AF on ECG (30%) than those in sinus rhythm (18%, p=0.014) but 5 yr SCD was lower (10% in AF on ECG &amp; 7% in any AF) &amp; comparable to SR (7% &amp; 9% respectively, p=ns). 5 yr PFD was higher (13%) than SR (5%, p=0.007. )Table shows Cox proportional hazards analysis of covariates associated with time to CV death, time to SCD &amp; time to PFD adjusted for baseline imbalances. Conclusions:: 1. CV death risk in HFpEF pts increased with age, in minorities, smokers, diabetics, with lower systolic bp, elevated heart rate &amp; AF on ECG.. 2. SCD was more frequent in males, African Americans &amp; diabetics but was low in both AF &amp; SR, perhaps due to a dominant atrial &amp; limited ventricular arrhythmogenic substrate in HFpEF. 3. PFD in HFpEF increased with age, ECG recorded AF &amp; elevated heart rate.This may reflect importance of atrioventricular synchrony in HFpEF. 4. The recording of AF on ECG at study entry was more strongly associated with CV death &amp; PFD, possibly due to greater AF burden in this group compared to those with any AF even..
Artificial Intelligence–Enabled Assessment of the Heart Rate Corrected QT Interval Using a Mobile Electrocardiogram Device
Authors: John R. Giudicessi, Matthew Schram, J. Martijn Bos, Conner D. Galloway, Jacqueline B. Shreibati, Patrick W. Johnson, Rickey E. Carter, Levi W. Disrud, Robert Kleiman, Zachi I. Attia, Peter A. Noseworthy, Paul A. Friedman, David E. Albert, Michael J. Ackerman
Journal: Circulation (2021)

Heart rate-corrected QT interval (QTc) prolongation, whether secondary to drugs, genetics including congenital long QT syndrome, and/or systemic diseases including SARS-CoV-2-mediated coronavirus disease 2019 (COVID-19), can predispose to ventricular arrhythmias and sudden cardiac death. Currently, QTc assessment and monitoring relies largely on 12-lead electrocardiography. As such, we sought to train and validate an artificial intelligence (AI)-enabled 12-lead ECG algorithm to determine the QTc, and then prospectively test this algorithm on tracings acquired from a mobile ECG (mECG) device in a population enriched for repolarization abnormalities.Using >1.6 million 12-lead ECGs from 538 200 patients, a deep neural network (DNN) was derived (patients for training, n = 250 767; patients for testing, n = 107 920) and validated (n = 179 513 patients) to predict the QTc using cardiologist-overread QTc values as the "gold standard". The ability of this DNN to detect clinically-relevant QTc prolongation (eg, QTc ≥500 ms) was then tested prospectively on 686 patients with genetic heart disease (50% with long QT syndrome) with QTc values obtained from both a 12-lead ECG and a prototype mECG device equivalent to the commercially-available AliveCor KardiaMobile 6L.In the validation sample, strong agreement was observed between human over-read and DNN-predicted QTc values (-1.76±23.14 ms). Similarly, within the prospective, genetic heart disease-enriched dataset, the difference between DNN-predicted QTc values derived from mECG tracings and those annotated from 12-lead ECGs by a QT expert (-0.45±24.73 ms) and a commercial core ECG laboratory [10.52±25.64 ms] was nominal. When applied to mECG tracings, the DNN's ability to detect a QTc value ≥500 ms yielded an area under the curve, sensitivity, and specificity of 0.97, 80.0%, and 94.4%, respectively.Using smartphone-enabled electrodes, an AI DNN can predict accurately the QTc of a standard 12-lead ECG. QTc estimation from an AI-enabled mECG device may provide a cost-effective means of screening for both acquired and congenital long QT syndrome in a variety of clinical settings where standard 12-lead electrocardiography is not accessible or cost-effective.
Non-specific Lipid Transfer Protein (Can s 3) Is a Relevant Cannabis Allergen in North America
Authors: Henry Morelli, Cathy Thorpe, Ine Decuyper, Cali Loblundo, Khaldon Abbas, Didier Ebo, Gordon Sussman, Martin Chapman, Ajay Nayak
Journal: Journal of Allergy and Clinical Immunology (2021)
Abstract 123: Long term Prognosis After Methylprednisolon pulse Combination Therapy For Refractory Kawasaki Disease
Authors: Takasuke Ebato, Yoshihito Ogihara, Manabu Takanashi, Takashi Honda, Sumito Kimura, Shohei Ogata, Masahiro Ishii
Journal: Circulation (2015)

Background: We previously investigated the molecular mechanism and the clinical utility of intravenous methylprednisolone-pulse(IVMP) plus intravenous immunoglobulin (IVIG) combination therapy (IVMP+IVIG) for patients with Kawasaki disease (KD) in the acute phase (Pediatr Res 2009, Pediatrics 2012). However, the long-term prognosis after IVMP+IVIG still remains unclear. Objective: To examine the long-term prognosis after IVIG+IVMP. Methods: Forty-six patients (Age: 5-70 months, male: 27) who were enrolled in this study were treated with IVMP+IVIG during the period from 2007 to 2014 at Kitasato University Hospital who were all predicted to show resistance to initial IVIG according to their Egami score (J Pediatr 2006). The IVMP therapy (30mg/kg, 1dose) was administered for 2 hours before starting the IVIG therapy. Heparin (10U/kg/h, continuous infusion) was used concomitantly from 2 hours before the start of IVMP therapy and it was thereafter continued for 24 hours. The long-term prognosis of coronary artery lesions (CALs) and adverse events between the time of diagnosis and 5 years after IVMP +IVIG were determined. The “Z-score2.5-5” and “Z–score&gt;5” were defined as dilatation and an aneurysm, respectively, according to the AHA guidelines. Results: Dilatation cases based on the Z-score2.5-5, were identified in 15 of 46 patients (32.6%) at diagnosis, in 15 of 46 patients (32.6%) after 1 month, and in 3 of 36 patients (8.3%) after 1 year. All patients in whom coronary artery abnormalities were observed at 1 year later demonstrated regression.No patients showed a Z-score≧5 in all phases. Thirty-six patients (78.2%) showed prompt defervescence owing to the combination therapy. The patients had adverse event at acute phase, 16 of 46 patients (34.7%) for hypothermia, 5 patients (10.8%) for hypertension, 2 patients (4.3%) for bradycardia, and 4 patients (8.6%) for recurrent fever. No patients experienced any serious adverse events (short stature, hyperlipidemia, abnormal glucose tolerance) after IVMP +IVIG during the long-term follow-up. Conclusions: This study showed IVMP+IVIG combination therapy to therefore effectively prevent CALs in KD patients that are predicted to be resistant to intial IVIG according to their Egami score.
Tapering infliximab dosages after temporary dose increase does not affect treatment survival in an established RA population.
Authors: B. Vander Cruyssen, R. Westhovens, R. Durez, F. Van Den Bosch, H. Mielants, L. De Clerck, A. Peretz, M. Malaise, Leon Verbruggen, L. Dewulf, N. Vastesaeger, F. De Keyser
Journal: Annals of the Rheumatic Diseases (2007)
“Sleep apnoea and visceral adiposity in middle-aged male and female subjects.” Ilia Kritikou, Maria Basta, Rafel Tappouni, Slobodanha Pejovic, Julio Fernandez-Mendoza, Racha Nazir, Michelle L. Shaffer, Duanping Liao, Edward O. Bixler, George P. Chrousos and Alexandros N. Vgontzas. <i>Eur Respir J</i> 2013; 41: 601–609.
Authors: Ilia Kritikou, Maria Basta, Rafel Tappouni, Slobodanha Pejovic, Julio Fernandez-Mendoza, Racha Nazir, Michelle Shaffer, Duanping Liao, Edward Bixler, George Chrousos, Alexandros Vgontzas
Journal: European Respiratory Journal (2020)
The Ins and Outs of Central Nervous System Inflammation—Lessons Learned from Multiple Sclerosis
Authors: Valeria Ramaglia, Olga Rojas, Ikbel Naouar, Jennifer L. Gommerman
Journal: Annual Review of Immunology (2021)

Multiple sclerosis (MS) is a chronic disease that is characterized by the inappropriate invasion of lymphocytes and monocytes into the central nervous system (CNS), where they orchestrate the demyelination of axons, leading to physical and cognitive disability. There are many reasons immunologists should be interested in MS. Aside from the fact that there is still significant unmet need for patients living with the progressive form of the disease, MS is a case study for how immune cells cross CNS barriers and subsequently interact with specialized tissue parenchymal cells. In this review, we describe the types of immune cells that infiltrate the CNS and then describe interactions between immune cells and glial cells in different types of lesions. Lastly, we provide evidence for CNS-compartmentalized immune cells and speculate on how this impacts disease progression for MS patients.
New human immunoglobulin in Brazil: should we use?
Authors: Caroline Ferreira, Nathalia Vital, Pedro Henrique Bubach, Raissa Roque, Fernanda Pires Cecchetti Vaz, Rafael Saldanha, Barbara Cristina Ramos, Maria Gabriela Viana de Sá, Luana Medeiros, Luiza Salvador Schmid, Rafaela Guimarães, Ligia Maria O. Machado, Mariana Pimentel, Candida Rizzo, Carolina Aranda, Dirceu Sole
Journal: Journal of Allergy and Clinical Immunology (2021)
Evolution of Conserved Noncoding Sequences in<i>Arabidopsis thaliana</i>
Authors: Alan E. Yocca, Zefu Lu, Robert J. Schmitz, Michael Freeling, Patrick P. Edger
Journal: Molecular Biology and Evolution (2021)

Abstract Recent pangenome studies have revealed a large fraction of the gene content within a species exhibits presence–absence variation (PAV). However, coding regions alone provide an incomplete assessment of functional genomic sequence variation at the species level. Little to no attention has been paid to noncoding regulatory regions in pangenome studies, though these sequences directly modulate gene expression and phenotype. To uncover regulatory genetic variation, we generated chromosome-scale genome assemblies for thirty Arabidopsis thaliana accessions from multiple distinct habitats and characterized species level variation in Conserved Noncoding Sequences (CNS). Our analyses uncovered not only PAV and positional variation (PosV) but that diversity in CNS is nonrandom, with variants shared across different accessions. Using evolutionary analyses and chromatin accessibility data, we provide further evidence supporting roles for conserved and variable CNS in gene regulation. Additionally, our data suggests that transposable elements contribute to CNS variation. Characterizing species-level diversity in all functional genomic sequences may later uncover previously unknown mechanistic links between genotype and phenotype.
Redefining outcomes in immune TTP: an international working group consensus report
Authors: Adam Cuker, Spero R. Cataland, Paul Coppo, Javier de la Rubia, Kenneth D. Friedman, James N. George, Paul N. Knoebl, Johanna A. Kremer Hovinga, Bernhard Lӓmmle, Masanori Matsumoto, Katerina Pavenski, Flora Peyvandi, Kazuya Sakai, Ravi Sarode, Mari R. Thomas, Yoshiaki Tomiyama, Agnès Veyradier, John-Paul Westwood, Marie Scully
Journal: Blood (2021)
Wildfire Smoke Exposure Activates Circulating Innate Immune Cells
Authors: Melissa Teuber, Cameron Flayer, Angela Linderholm, Lisa Franzi, Tina Tham, Karla Ramirez, Maya Juarez, Willis Bowman, Michael Schivo, Brooks Kuhn, Amir Zeki, Nicholas Kenyon, Angela Haczku
Journal: Journal of Allergy and Clinical Immunology (2021)
In Opposition to Woman Doctors in Insane Asylums.
Authors: None Richmond
Journal: JAMA (1894)

Richmond, Va., March 19, 1894. <h3>To the Editor:</h3> —You refer in a late issue to the contest in our late Legislature on the "Woman Doctor Bill." Two years ago the lower House passed a bill unanimously compelling the Board of Directors of each insane asylum to put one woman doctor in office for each institution. This bill was defeated in the Senate, though every newspaper in this city and many in the country were heartily in favor of it. We had it " hot and heavy" in the newspapers. Men and women abused me pretty roundly for my opposition. I think I wrote a dozen letters in the papers against it. The asylum influence was very great against it, and but for this help I would have been badly whipped. In the last two years I have given this subject a great deal of thought and observation, wrote my pamphlet on
IL-5 Receptor Subunit Alpha Expression As A Possible Biomarker In Asthma
Authors: Sandra Elena Pérez, David Heredero Jung, Asunción García Sánchez, Miguel Estravís, María Martín, Francisco Muñoz Bellido, María Isidoro García, Catalina Sanz, Ignacio Dávila
Journal: Journal of Allergy and Clinical Immunology (2021)
Imaging the Respiratory Transition at Birth: Unraveling the Complexities of the First Breaths of Life
Authors: David G. Tingay, Olivia Farrell, Jessica Thomson, Elizabeth J. Perkins, Prue M. Pereira-Fantini, Andreas D. Waldmann, Christoph Rüegger, Andy Adler, Peter G. Davis, Inéz Frerichs
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: The transition to air breathing at birth is a seminal respiratory event common to all humans, but the intrathoracic processes remain poorly understood. Objectives: The objectives of this prospective, observational study were to describe the spatiotemporal gas flow, aeration, and ventilation patterns within the lung in term neonates undergoing successful respiratory transition. Methods: Electrical impedance tomography was used to image intrathoracic volume patterns for every breath until 6 minutes from birth in neonates born by elective cesearean section and not needing resuscitation. Breaths were classified by video data, and measures of lung aeration, tidal flow conditions, and intrathoracic volume distribution calculated for each inflation. Measurements and Main Results: A total of 1,401 breaths from 17 neonates met all eligibility and data analysis criteria. Stable FRC was obtained by median (interquartile range) 43 (21-77) breaths. Breathing patterns changed from predominantly crying (80.9% first min) to tidal breathing (65.3% sixth min). From birth, tidal ventilation was not uniform within the lung, favoring the right and nondependent regions; P < 0.001 versus left and dependent regions (mixed-effects model). Initial crying created a unique volumetric pattern with delayed midexpiratory gas flow associated with intrathoracic volume redistribution (pendelluft flow) within the lung. This preserved FRC, especially within the dorsal and right regions. Conclusions: The commencement of air breathing at birth generates unique flow and volume states associated with marked spatiotemporal ventilation inhomogeneity not seen elsewhere in respiratory physiology. At birth, neonates innately brake expiratory flow to defend FRC gains and redistribute gas to less aerated regions.
Author Correction to: Endemic Burkitt lymphoma in second-degree relatives in Northern Uganda: in-depth genome-wide analysis suggests clues about genetic susceptibility
Authors: Mateus H. Gouveia, Isaac Otim, Martin D. Ogwang, Mingyi Wang, Bin Zhu, Nathan Cole, Wen Luo, Belynda Hicks, Kristine Jones, Kathrin Oehl-Huber, Leona W. Ayers, Stefania Pittaluga, Ismail D. Legason, Hadijah Nabalende, Patrick Kerchan, Tobias Kinyera, Esther Kawira, Glen Brubaker, Arthur G. Levin, Lutz Guertler, Jung Kim, Douglas R. Stewart, Melissa Adde, Ian Magrath, Andrew W. Bergen, Steven J. Reynolds, Meredith Yeager, Kishor Bhatia, Adebowale A. Adeyemo, Ludmila Prokunina-Olsson, Michael Dean, Daniel Shriner, Charles N. Rotimi, Stephen Chanock, Reiner Siebert, Sam M. Mbulaiteye
Journal: Leukemia (2021)
Homeless man should have double leg amputation to save his life, says judge
Authors: Clare Dyer
Journal: BMJ (2021)

A High Court judge has ruled that it would be in a homeless man’s best interests to have both legs amputated below the knee after he was found in a bus shelter with severely frostbitten feet and diagnosed with acute limb ischaemia.1

Mr Justice Hayden, vice president of the court of protection, said he found it “deeply shocking to hear how it is possible in modern Britain for a relatively young man living on the streets of a major city, in the enhanced visibility of our present public health crisis, to have suffered in the way that he obviously has.”

The man, referred to as TM and thought to be aged about 42, is …
Prognosis of young patients with monoclonal gammopathy of undetermined significance (MGUS)
Authors: Li Pang, S. Vincent Rajkumar, Prashant Kapoor, Francis Buadi, Angela Dispenzieri, Morie Gertz, Martha Lacy, Robert Kyle, Shaji Kumar
Journal: Blood Cancer Journal (2021)

Monoclonal gammopathy of undetermined significance (MGUS) is rare in young patients (age <40 years at diagnosis), with a prevalence of <0.3%, representing ~2% of all patients with MGUS. We hypothesized that MGUS detected in young patients may be associated with a higher risk of progression. We examined 249 patients with MGUS < 40 years old. Among these, 135 patients had immune-related conditions, including infections, autoimmune and inflammatory disorders at the time of diagnosis of MGUS. The risk of progression to multiple myeloma or a related disorder at 5 years and 10 years was 6.0% and 13.8%, respectively. The size of M protein was a significant risk factor for progression (HR 4.2, 95% CI 2.2-7.9). There was a trend that the risk of progression was higher in patients without immune-related conditions (HR 2.36, 95% CI 0.85-6.52, p = 0.088). The M protein resolved in 36 (14%) patients, with a greater likelihood of resolution in patients with immune-related conditions (RR 1.9, 95% CI 1.02-3.6). Young patients with MGUS have a similar risk of progression as older patients, 1.4% per year. Over 50% are diagnosed in the setting of immune-related disorders. Patients with immune-related disorders may have a lower risk of progression.