tbuckley/cabot-search huggingface dataset:
Error-prone bypass of DNA lesions during lagging-strand replication is a common source of germline and cancer mutations
Authors: Vladimir B. Seplyarskiy, Evgeny E. Akkuratov, Natalia Akkuratova, Maria A. Andrianova, Sergey I. Nikolaev, Georgii A. Bazykin, Igor Adameyko, Shamil R. Sunyaev
Journal: Nature Genetics (2018)
PB2066 DAMAGE OF THE TP53 GENE POLYADENYLATION SIGNAL IN DLBCL
Authors: E. Voropaeva, T. Pospelova, M. Voevoda, V. Maximov, M. Kolesnikova
Journal: HemaSphere (2019)

Background: Single nucleotide replacement rs78378222 lead to change of the normal TP53 gene polyadenylation signal and cause disorders of processing of 3′‐end of mRNA. The experimental data have suggested that rare allele C of the rs78378222 leads to much lower level of TP53 expression and decrease the apoptosis induction level in cells under the influence of genotoxic agents in comparison with allele A. Thus, rs78378222 is thought to be the unique allele variant of TP53 gene with the reduced p53 function. Aims: The purpose of the present study was to reveal the frequency of the rs78378222 of TP53 in tumor tissue of the patients with diffuse large B‐cell lymphoma (DLBCL). Methods Genomic DNA was isolated from formalin‐embedded paraffin blocks of lymph nodes and extranodal tumor lesions biopsies of 92 patients with DLBCL by phenol‐chloroform extraction method using guanidine. The tissue sections containing at least 70‐80% of the tumor cells were taken. Genotyping of the rs78378222 was performed by the PCR‐RFLP method. To confirm the presence of rare allele C of the rs78378222 Sanger's direct sequencing was performed. Results: The frequency of the rs78378222 in DLBCL tumor tissue was 9/92 (9.8%). It was noted that 5 of 9 patients had minor allele C in the homozygous state. Since the detection of cases of the rare homozygous genotype C/C of the rs78378222 in normal tissue has not described previously, the received results indicated a loss of heterozygosity in the TP53 gene in DLBCL tumor tissue of rs78378222 carriers. Only two of these cases were combined with mutations in the gene. In three cases ‐ loss of heterozygosity was the only aberration in TP53 . Summary/Conclusion: Aberrations in 3′‐UTR of TP53 gene may be a universal carcinogenesis mechanism, playing role in pathogenesis of DLBCL as well. The loss of normal allele A rs78378222 stimulates the significant growth of cells malignant potential.
Mode of progression after first line treatment correlates with outcome of chronic lymphocytic leukemia (CLL)
Authors: Othman Al‐Sawaf, Alexandra Bazeos, Sandra Robrecht, Jasmin Bahlo, Craig Gower, Anna‐Maria Fink, Julia Tresckow, Paula Cramer, Petra Langerbeins, Nadine Kutsch, Kathryn Humphrey, Günter Fingerle‐Rowson, Stephan Stilgenbauer, Clemens‐Martin Wendtner, Kirsten Fischer, Barbara Eichhorst, Michael Hallek, Valentin Goede
Journal: American Journal of Hematology (2019)

In CLL, progressive disease (PD) following remission after first line treatment can present with varying phenotypes. We hypothesized that the mode of PD correlates with clinical outcomes. Data from three phase III trials of the German CLL Study Group (GCLLSG) (CLL8, CLL10, CLL11) including a total of 2159 patients receiving first line (immuno)-chemotherapy (FCR, FC, CLB, CLB-R, CLB-Ob) were analyzed. Patients were categorized as "ALC" if PD was due to increasing absolute lymphocyte count, or as "Ly" if due to lymphadenopathy. A group of 241 patients progressed with ALC, and 727 progressed with Ly, including 329 who progressed on both modalities. In fit patients, median TTNT after PD in the Ly group was 12.3 months vs 17.0 months in the ALC group (HR 1.299 [1.036-1.628]; P = .024). Median OS after PD was 45.1 months in the Ly group and 42.4 months in the ALC group (HR=1.023 [0.753-1.389]; P = .885). For unfit patients, median TTNT in the Ly group was 11.7 months vs 21.4 months in the ALC group (HR 1.357 [1.051-1.753]; P = .019). Median OS was 42.8 months in the Ly group and not reached in the ALC group (HR 1.851 [1.280-2.677]; P = .001). Patients in the Ly group more frequently showed impairment of quality of life (QoL). This analysis demonstrates that patients with progressive lymphadenopathy have a significantly shorter TTNT, OS and less favorable QoL. Our findings might help physicians to better estimate the clinical course of a progressing CLL patient.
Abstract 18584: Cardiac Beta-Catenin Deletion Mediated by Alpha-MHC Promoter Causes Ventricular Hypoplasia
Authors: Bo Ye, Haodong Xu, Faqian Li
Journal: Circulation (2010)

Backgrounds: During early cardiogenesis, canonical Wnt signaling appears to have biphasic and antagonistic roles: stimulatory effects before and inhibitory effects during and after gastrulation. Ho...
Apremilast in chronic recalcitrant erythema nodosum leprosum: a report of two cases
Authors: T. Narang, A. Kaushik, S. Dogra
Journal: British Journal of Dermatology (2019)

Erythema nodosum leprosum (ENL) is a severe immune reaction commonly encountered as a complication in patients with multibacillary leprosy. Management of chronic ENL in leprosy is challenging and necessitates the use of systemic immunosuppressants, including corticosteroids and thalidomide. No single drug is universally effective and most current therapeutic agents carry a significant risk of systemic toxicity. Apremilast is an orally effective phosphodiesterase‐4 inhibitor with a potent immunomodulatory action and is clinically effective in inflammatory conditions like chronic plaque psoriasis. We report two patients with poorly controlled chronic ENL, despite the use of multiple therapeutic agents. Both patients demonstrated significant clinical improvement with apremilast, without any adverse effects, thereby suggesting its potential as a novel therapeutic option in chronic ENL. What's already known about this topic? Erythema nodosum leprosum (ENL) is an immune‐mediated reaction in patients with multibacillary leprosy, with chronicity and recurrences frequently reported. Management of chronic ENL requires systemic immunosuppressants like corticosteroids, which may not be universally effective and carry a risk of serious toxicity. Apremilast is an oral immunomodulator with good efficacy in inflammatory conditions like chronic plaque psoriasis. What does this study? Apremilast may be an effective therapeutic agent in patients with chronic ENL.
AB1156 DEFINITION OF TWO NEW ULTRASOUND ENTHESOPHYTES SCORES: APPLICATION IN A CONSECUTIVE SERIES OF IBD PATIENTS
Authors: Pierluigi Macchioni, Federica Martinis, Giorgia Citriniti, Nicolò Girolimetto, Carlo Salvarani
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Recent studies have developped criteria for US definition of entheseal abnomalities [1] however no actual scores are available to determine the extension and severity of enthesophyte growth in clinical practice. <h3>Objectives</h3> To <b>evaluate</b> the faseability of two new scores to quantifie enthesophytes occurence and its dimensional changes with time. <h3>Methods</h3> We have evaluated 816 enthesis two years apart in a consecutive series of 68 IBD patients for the presence and size of enthesopytes. Images were collected at baseline and after 24 months using an Esaote MyLabClass, 18-6 MHz linear multifrequence transducer both in B-mode and PD-mode. The following sites were evaluated bilaterally: lateral epicondyle of the humerus, distal quadricipital insertion at the patella, superior and inferior pole of the patella, Achilles tendon insertion, and plantar aponeurosis insertion. The presence of enthesophyte was scored dichotomously as present (=1) or absent (=0) for each site and summed up to generate the ARE score (ARES). Enthesophytes was also scored semiquantitatively in a 0-3 scale (0 = absent, 1 = minimal, 2 = discrete, 3 = massive) according to Aydin SZ et al. [2] for each site and summed up to generate RES score (RESS). All the stored images were then reviewed and scored by 4 rheumatologists (FM, GC, PM, NG) well trained in US examination of enthesis. ICC inter- and intra-observers was done for each site and for the ARES and RESS. <h3>Results</h3> ICC was exellent for presence or absence of enthsophytes both intra and inter examinator for all the sites. ICC of the ARE score was excellent (Cronbach alfa = 0.930, 95%CI 0.72-0.98). ICC was excellent also for the semiquantitative RESS at all the examined sites and only moderate at the plantar fascia level (Cronbach alfa = 0.571, 95%CI -0.72-0.89). The total RESS have an exellent ICC (Cronbach alfa = 0.963, 95%CI 0.85-0.99). <h3>Conclusion</h3> The two scores are easily feasible and have high reliability and and exellent intra- and inter-obeserver reproducibility. <h3>References</h3> 1. Balint PV, et al. Reliability of a consensus-based ultrasound definition and scoring for enthesitis in spondyloarthritis and psoriatic arthritis: an OMERACT US initiative. Ann Rheum Dis. 2018 Dec;77(12):1730-1735. 2. Aydin SZ, et al. A relationship between spinal new bone formation in ankylosing spondylitis and the sonographically determined Achilles tendon enthesophytes. Rheumatol Int 2016 Mar;36(3):397-404. <h3>Disclosure of Interests</h3> None declared
Abstract 17549: Human Epicardial Fat Shares Molecular and Morphologic Features of Omental Fat
Authors: Rebecca Baumann, Nancy Lee, Sarah Nicoloro, Olga Hardy, Richard Perugini, Juerg Straubhaar, Stanley Tam, Melinda Darrigo, Michael Czech, Timothy Fitzgibbons
Journal: Circulation (2013)

Introduction: Epicardial adipose tissue (EAT) has been postulated to play a direct role in obesity associated cardiovascular disease. However, the majority of observational studies have shown that ...
Patterns of Opioid Administration Among Opioid-Naive Inpatients and Associations With Postdischarge Opioid Use
Authors: Julie M. Donohue, Jason N. Kennedy, Christopher W. Seymour, Timothy D. Girard, Wei-Hsuan Lo-Ciganic, Catherine H. Kim, Oscar C. Marroquin, Patience Moyo, Chung-Chou H. Chang, Derek C. Angus
Journal: Annals of Internal Medicine (2019)

Background: Patterns of inpatient opioid use and their associations with postdischarge opioid use are poorly understood. Objective: To measure patterns in timing, duration, and setting of opioid administration in opioid-naive hospitalized patients and to examine associations with postdischarge use. Design: Retrospective cohort study using electronic health record data from 2010 to 2014. Setting: 12 community and academic hospitals in Pennsylvania. Patients: 148 068 opioid-naive patients (191 249 admissions) with at least 1 outpatient encounter within 12 months before and after admission. Measurements: Number of days and patterns of inpatient opioid use; any outpatient use (self-report and/or prescription orders) 90 and 365 days after discharge. Results: Opioids were administered in 48% of admissions. Patients were given opioids for a mean of 67.9% (SD, 25.0%) of their stay. Location of administration of first opioid on admission, timing of last opioid before discharge, and receipt of nonopioid analgesics varied substantially. After adjustment for potential confounders, 5.9% of inpatients receiving opioids had outpatient use at 90 days compared with 3.0% of those without inpatient use (difference, 3.0 percentage points [95% CI, 2.8 to 3.2 percentage points]). Opioid use at 90 days was higher in inpatients receiving opioids less than 12 hours before discharge than in those with at least 24 opioid-free hours before discharge (7.5% vs. 3.9%; difference, 3.6 percentage points [CI, 3.3 to 3.9 percentage points]). Differences based on proportion of the stay with opioid use were modest (opioid use at 90 days was 6.4% and 5.4%, respectively, for patients with opioid use for ≥75% vs. ≤25% of their stay; difference, 1.0 percentage point [CI, 0.4 to 1.5 percentage points]). Associations were similar for opioid use 365 days after discharge. Limitation: Potential unmeasured confounders related to opioid use. Conclusion: This study found high rates of opioid administration to opioid-naive inpatients and associations between specific patterns of inpatient use and risk for long-term use after discharge. Primary Funding Source: UPMC Health System and University of Pittsburgh.
Invasive ductal breast cancer, tumor size, and its correlation between physical examination, imaging techniques, and pathological anatomy.
Authors: Ana Lopez-Gonzalez, Patricia Ibeas, Maria Soledad Carmona, Elisabeth Rivero, Roberto Lopez, Miriam Huelves, Bernard Gaston Doger de Speville, Blanca Cantos, Miguel Angel Pastrana, Mariano Provencio
Journal: Journal of Clinical Oncology (2012)

e11035 Background: The most frequent indication of magnetic resonance in breast cancer is the evaluation of tumoral extension. Several studies suggest that mammography and ultrasound underestimate tumor size. We try to analize the correlation between the tumor size of invasive ductal carcinomas in physical examination, mammography, magnetic resonance and pathological anatomy. Methods: We review the 290 magnetic resonance made in our Radiology Department from 1 st January 2009 to 1 st September 2010. 56 of them were applied as complementary study before surgery of suspected lesions of breast cancer. We made an analysis of paired test, and then a hypothesis test for equal sample testing, supported by an analysis of power curves. The paired test analysed were physical examination (PE)- mammography - magnetic resonance (MR) - pathological anatomy (PA). Results: A 100% were women; average of age of 54.1 years old. A 42.8% were premenopausal. Averages of tumor size: 18.3mm in PE; 18.8mm in mammography; 25.3mm in MR and 24.8mm in PA. The correlation between the tumor size in PE and PA is not statistically significant (p=0.05, 95% CI 11.07; 1.93), and also between the mammography and the PA (p=0.05, 95% CI 10.69; 1.47). The correlation between tumor size in mammography and MR is statistically significant (p=0.05, 95% CI -9.83; -3.26), and also between MR and PA (p=0.05, 95% CI -3.31; 4.25). We analysed the relation between clinical tumor size by MR and PA size, and in a 25% of the cases, the clinical and the pathological stage were different. The pathological was more advance in a 57.1% of them. Conclusions: Mammography underestimate the tumor size, with no correlation with the pathological tumor size. However, there is a good correlation between the tumor size in MR and the pathological size. The MR is the most reliable imaging technique to optimize the surgical and oncological treatment in patients with breast cancer.
Abstract 12200: Blood Pressure Control in Diabetic Patients is Most Effective Between Ages 65 to 75 for Prevention of Atherosclerotic Events
Authors: Hirofumi Soejima, Takeshi Morimoto, Sadanori Okada, Mio Sakuma, Masafumi Nakayama, Shiro Uemura, Kanauchi Masao, Naofumi Doi, Hideaki Jinnouchi, Seigo Sugiyama, Masako Waki, Yoshihiko Saito, Hisao Ogawa
Journal: Circulation (2015)

Background: In 2013, the blood pressure (BP) control target for diabetic patients was changed in both Europe and USA; however, there was a paucity of supporting evidence. We investigated whether BP control&lt;140/90 mmHg was effective in any age group in diabetic patients for preventing atherosclerotic events. Methods: We performed the Japanese primary prevention of atherosclerosis with aspirin for diabetes (JPAD) trial to examine the efficacy of low-dose aspirin therapy in 2536 type 2 diabetes patients. After completion of the JPAD trial in 2008, we followed up the same subjects until 2013, the JPAD2 cohort. Primary end points were a composite of ischemic heart disease, stroke, peripheral arterial disease, and sudden death. We divided the patients into either a high age 65 (H65) group (n=1360; age≥65 years) or a low age 65 (L65) group (n=1176; age&lt;65 years). We then re-divided the patients into a high age 75 (H75) group (n=412; age≥75 years) or a low age 75 (L75) group (n=2124; age&lt;75 years). Results: Systolic BP was unchanged 131 mmHg in 2009 and 130 mmHg in 2013 in each JPAD patients. Diastolic BP decreased from 73 mmHg in 2009 to 71 mmHg in 2013. The difference of incidence of atherosclerotic events between BP≥140/90 patients and BP&lt;140/90 patients was significant in H65 group (P=0.0026, Figure). During a median of 8.1 years, the difference of incidence of the events between the patient groups was not significant in the L65 group (P=0.4515, Figure). The difference of incidence of the events was not significant in H75 group (P=0.8050, Figure). The difference of incidence of the events was significant in the L75 group (P=0.0034, Figure). Conclusions: The difference of incidence of atherosclerotic events between BP≥140/90 patients and BP&lt;140/90 patients was significant only when patients aged 65 to 75 years is included in the analysis. This study then supports a recommendation of the guidelines that better BP control target of age≥75 years patients is not necessary to be BP&lt;140/90 mmHg.
Finding Answers for Enlarged Hearts, Communication Disorders, and How to Swallow Insulin
Authors: Rebecca Voelker
Journal: JAMA (2019)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Chaperone protein HSC70 regulates intercellular transfer of Y chromosome antigen DBY
Authors: Sascha Kretschmann, Stefanie Herda, Heiko Bruns, Josefine Russ, Edith D. van der Meijden, Ursula Schlötzer-Schrehardt, Marieke Griffioen, Il-Kang Na, Andreas Mackensen, Anita N. Kremer
Journal: Journal of Clinical Investigation (2019)

Recent studies have demonstrated that CD4+ T cells can efficiently reject MHC-II-negative tumors. This requires indirect presentation of tumor-associated antigens on surrounding antigen-presenting cells. We hypothesized that intercellular transfer of proteins is not the sole consequence of cell death-mediated protein release, but depends on heat-shock cognate protein 70 (HSC70) and its KFERQ-like binding motif on substrate proteins. Using human Y chromosome antigen DBY, we showed that mutation of one of its 2 putative binding motifs markedly diminished T cell activation after indirect presentation and reduced protein-protein interaction with HSC70. Intercellular antigen transfer was shown to be independent of cell-cell contact, but relied on engulfment within secreted microvesicles. In vivo, alterations of the homologous KFERQ-like motif in murine DBY hampered tumor rejection, T cell activation, and migration into the tumor and substantially impaired survival. Collectively, we show that intercellular antigen transfer of DBY is tightly regulated via binding to HSC70 and that this mechanism influences recognition and rejection of MHC-II-negative tumors in vivo.
Abstract 13250: Gender Differences in Asymptomatic Carotid Artery Stenosis; the Association of Age and Smoking With Disease Progression in Males
Authors: Hartaj Girn, Han Tun, David Wee, Leonardo Clavijo, David Shavelle, Parveen Garg
Journal: Circulation (2015)

Background: A direct relationship exists between internal carotid artery (ICA) disease progression and stroke incidence. For asymptomatic patients with known ICA disease, there is no proven surveillance strategy. It remains unclear which individuals are at greater risk for disease progression, and whether there are gender-specific risk factors. We examined clinical characteristics associated with ICA disease progression in men and women undergoing carotid duplex ultrasound (CDU) surveillance. Methods: We retrospectively studied 289 patients with known ICA stenosis at baseline who underwent CDU from 2008-2014 and had at least one other CDU ≥11 months later. Categories of stenosis included minimal (0-15%), mild (16-49%), moderate (50-79%), and severe (80-99%). Symptomatic patients (stroke or TIA within 6 months), those with severe baseline stenosis, and arteries with prior interventions were excluded. The primary outcome was progression of stenosis to a level of moderate or higher. Baseline clinical data was recorded, and logistic regression analysis was performed. Results: Twenty-seven (23%) of 116 females and 30 (17%) of 173 males had progression of ICA stenosis (p=0.21). Females with disease progression were more likely to have moderate baseline stenosis (52% vs 26%, p = 0.01) compared to mild or minimal. Males with disease progression were older (74y vs 70y, p &lt; 0.04), more likely to be current or past smokers (66% vs 44%, p = 0.03), and more likely to have moderate baseline stenosis (50% vs 23 %, p&lt;0.003). Multivariate analysis in males showed age, smoking, and moderate baseline stenosis to be independent predictors of disease progression. Conclusion: There was no significant difference in proportion of disease progression between genders. In addition to relying on baseline stenosis for both genders, our findings suggest a role for age and smoking history to help determine effective surveillance protocols for monitoring ICA disease progression in males.
Abstract 18590: Heart Rate Score and Outcomes in ICD Patients: Insights From the Prospective Randomized INTRINSIC RV Trial
Authors: Rakesh Gopinathannair, Arjun Sharma, Paul Jones, Connor English, Stephen Furmanek, Brian Olshansky
Journal: Circulation (2017)

Introduction: Heart rate score (HRS), the percentage of all atrial sensed and paced beats in the largest 10 beats/min bin on a device histogram, a marker of chronotropic incompetence, predicts surv...