tbuckley/cabot-search huggingface dataset:
Two Trajectories to Melanoma on the Hands and Feet
Authors: A. Hunter Shain
Journal: JAMA Dermatology (2021)

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Abstract P018: Advanced Glycation End Products And And Incident Cardiovascular Disease
Authors: Julio A Lamprea-montealegre, Alice Arnold, Robyn McClelland, Russell P Tracy, Luc Djousse, Kenneth J Mukamal, Bruce M Psaty, David S Siscovick, Susan J Zieman, Michael Brownlee, Mary Lou Biggs, Paul J Beisswenger, Joachim H Ix, Jorge R Kizer
Journal: Circulation (2021)

Background: Advanced glycation end-products (AGEs) have been linked to cardiovascular disease (CVD) in populations with and without diabetes. There are limited data, however, regarding the longitudinal associations of the array of circulating AGE adducts with risk of CVD in the general population. We tested the hypothesis that major plasma AGEs, measured by gold-standard liquid chromatography/tandem mass spectrometry (LC/MS) are associated with incident CVD in subsets of two population-based cohort studies with different demographic and risk factor profiles. Methods: Analyses were performed in a case-cohort study of 2000 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) and in a random cohort of 466 participants in the Cardiovascular Health Study (CHS). Five AGEs were measured by LC/MS: CML, 3DG-H, CEL, G-H1 and MG-H1. Incident CVD was defined as first occurrence of fatal or non-fatal stroke, myocardial infarction, or coronary heart disease death. Cox regression was used to examine associations between AGEs and CVD. Results: Participants in CHS were older than in MESA (median age=74 vs 65), had lower eGFR (67 vs 82 ml/min/1.73m 2 ) but higher CRP (median 2.53 vs 2.06 mg/L), and had substantially higher levels of all AGEs (Table) . During a median follow-up of 11 years in both cohorts, 439 (22%) participants in MESA and 200 (42%) in CHS developed incident CVD. In unadjusted models, all AGEs were strongly and significantly associated with incident CVD in MESA and CHS (Table). In multivariable adjusted models, CML, 3DG-H and a summary variable that accounted for all measured AGEs (PC1) were significantly associated with incident CVD in CHS but not in MESA. Conclusion: We found AGEs to be significantly associated with CVD in an older cohort, but not in a healthier middle-aged to older population that had lower systemic inflammation and lower baseline AGE concentrations. In the general population, AGEs may exert detrimental cardiovascular effects only at higher levels over longer cumulative exposure.
The Nexus of cfDNA and Nuclease Biology
Authors: Diana S.C. Han, Y.M. Dennis Lo
Journal: Trends in Genetics (2021)

Cell-free DNA (cfDNA) is a widely used noninvasive biomarker for diagnosis and prognosis of multiple disease states. Emerging evidence suggests that cfDNA might not just be passive waste products of cell death but could have a physiological and pathological function in inflammation and autoimmunity. The balance of cfDNA generation and clearance may thus be vital in health and disease. In particular, plasma nuclease activity has been linked to multiple pathologies including cancer and systemic lupus erythematosus (SLE) and associated with profound changes in the nonrandom fragmentation of cfDNA. Lastly, in this review, we explore the effects of DNA fragmentation factor B (DFFB), DNASE1L3, and DNASE1 on cfDNA levels and their fragmentomic profiles, and what these recent insights reveal about the biology of cfDNA.
The Multisystem Inflammatory Syndrome in Adults With SARS-CoV-2 Infection—Another Piece of an Expanding Puzzle
Authors: Eric J. Chow
Journal: JAMA Network Open (2021)

Giovanni E. Davogustto, MD; Daniel E. Clark, MD, MPH; Edward Hardison, MD; Ahmad H. Yanis, MD; Brandon D. Lowery, BS; Natasha B. Halasa, MD, MPH; Quinn S. Wells, MD, PharmD, MSCI
Abstract 15661: Discordant LDL-C Estimates and Incident Atherosclerotic Cardiovascular Disease: The Dallas Heart Study
Authors: Nicholas Macpherson, Nestor Vasquez, Amit Khera, Anand Rohatgi, Seth S Martin, Steven R Jones, Colby Ayers, Renato Quispe, Parag H Joshi, Alagarraju Muthukumar
Journal: Circulation (2020)

Introduction: The Friedewald equation (F-LDL-C) and the Martin-Hopkins algorithm (MH-LDL-C) estimate direct LDL-C from a standard lipid panel. Discordant LDL-C estimates by the two methods may carry significant clinical implications. We evaluated the clinical variables associated with discordant LDL-C estimates and the association of discordance with risk of incident atherosclerotic cardiovascular disease (ASCVD) in the Dallas Heart Study (DHS), a multi-ethnic, population based prospective cohort. Methods: We estimated F-LDL-C and MH-LDL-C in 2824 DHS participants (42% male; mean age 43.5 years) with TG ≤ 400 mg/dL, who were not on baseline lipid lowering therapy and were free of prior ASCVD. We divided the cohort into quintiles of LDL-C discordance (MH-LDL-C minus F-LDL-C, in mg/dL) and assessed associations with ASCVD risk factors. We evaluated associations between discordance and incident ASCVD by sequentially adjusted Cox regression models, and we generated restricted cubic spline plots of discordance and hazard for ASCVD. Results: There were 228 ASCVD events over a median of 12.3 years. Clinical characteristics across discordance quintiles are shown in the Table . After adjustment for traditional ASCVD risk factors, there was a linear association between higher LDL-C discordance and increased risk of ASCVD events ( Figure ) with the highest hazard in Quintile 5 (HR 1.5, 95% CI 1.1 - 2.0). Conclusions: Discordant LDL-C estimates were largely associated with male sex, White and Hispanic races, and characteristics of the metabolic syndrome. Individuals in the highest quintile of discordant LDL-C estimates, with MH-LDL-C &gt; F-LDL-C, had greater risk for incident ASCVD.
Heat/pH-boosted release of 5-fluorouracil and albumin-bound paclitaxel from Cu-doped layered double hydroxide nanomedicine for synergistical chemo-photo-therapy of breast cancer
Authors: Jianping Liu, Kai Liu, Liming Zhang, Ming Zhong, Tingliang Hong, Run Zhang, Yufan Gao, Rui Li, Tiefeng Xu, Zhi Ping Xu
Journal: Journal of Controlled Release (2021)
Oncolytic viruses as a promising therapeutic strategy against the detrimental health impacts of air pollution: The case of glioblastoma multiforme
Authors: Hamed Kazemi Shariat Panahi, Mona Dehhaghi, Su Shiung Lam, Wanxi Peng, Mortaza Aghbashlo, Meisam Tabatabaei, Gilles J. Guillemin
Journal: Seminars in Cancer Biology (2021)
Evaluation of the Risk of Stroke Without Anticoagulation Therapy in Men and Women With Atrial Fibrillation Aged 66 to 74 Years Without Other CHA<sub>2</sub>DS<sub>2</sub>-VASc Factors
Authors: Husam Abdel-Qadir, Sheldon M. Singh, Andrea Pang, Peter C. Austin, Cynthia A. Jackevicius, Karen Tu, Paul Dorian, Dennis T. Ko
Journal: JAMA Cardiology (2021)

There are limited clinical trial data and discrepant recommendations regarding use of anticoagulation therapy in patients with atrial fibrillation (AF) aged 65 to 74 years without other stroke risk factors.To evaluate the risk of stroke without anticoagulation therapy in men and women with AF aged 66 to 74 years without other CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes, stroke, vascular disease, age 65-74 years, female sex) risk factors and examine the association of stroke incidence with patient age.A population-based retrospective cohort study was conducted using linked administrative databases. The population included 16 351 individuals aged 66 to 74 years who were newly diagnosed with AF in Ontario, Canada, between April 1, 2007, and March 31, 2017. Exclusion criteria included long-term care residence, prior anticoagulation therapy, valvular disease, heart failure, hypertension, diabetes, stroke, and vascular disease. The cumulative incidence function was used to estimate the 1-year incidence of stroke in patients who did not receive anticoagulation therapy. Fine-Gray regression was used to study the association of patient characteristics with stroke incidence and derive estimates of stroke risk at each age. Death was treated as a competing risk and patients were censored if they initiated anticoagulation therapy. Inverse probability of censoring weights was used to account for patient censoring. Data analysis was performed from May 26, 2019, to December 9, 2020.Atrial fibrillation and age.Hospitalizations for stroke.Of the 16 351 individuals with AF (median [interquartile range] age, 70 [68-72] years), 8352 (51.1%) were men; 6314 individuals (38.6%) started anticoagulation therapy during follow-up. The overall 1-year stroke incidence among patients who did not receive anticoagulation therapy was 1.1% (95% CI, 1.0%-1.3%) and the incidence of death without stroke was 8.1% (95% CI, 7.7%-8.5%). The incidence of stroke was not significantly associated with sex. The estimated 1-year stroke risk increased with patient age from 66 years (0.7%; 95% CI, 0.5%-0.9%) to 74 years (1.7%; 95% CI, 1.3%-2.1%).The risk of stroke more than doubled in this study as men and women with AF but no other CHA2DS2-VASc risk factors aged from 66 to 74 years. These data suggest that anticoagulation therapy is more likely to benefit older individuals within this group of patients, whereas younger individuals are less likely to gain net clinical benefit from anticoagulation therapy.
Impact of genetic background of Salmonella Typhimurium on maturation of human dendritic cells
Authors: Agnieszka Michael, Justin John, Desmond Barton, Hardev Pandha
Journal: Cancer Research (2005)

3380  Live attenuated bacterial vectors such as Salmonella Typhimurium (S T) have shown considerable promise as efficient delivery vehicles for DNA. A lasting immune response is largely dependent on the interaction between S T and dendritic cells (DC), DC maturation pattern, as well as the gene transfer process. S T is known to mature DC, however different attenuated strains appear to have a varying effect on the cells with some inducing more efficient maturation and therefore showing a potential advantage as gene transfer vehicles. We have evaluated two novel strains of S T and their impact on human DC maturation. The WTO5 strain contains defined deletions in two genes, aroC and ssaV and the CD12 strain contains a defined deletion in the aroC gene as well as a second defined deletion in the sifA gene, both strains are on TML background. The maturation of DC was assessed by expression of maturation markers such as MHC Class I, Class II, CD83, CD86 and CD40 as well as cytokine and chemokine production: IL-12, IL-12 p70, TNF alpha, IL10 and IL-1beta, MIP-1alpha, MIP-1beta and RANTES. Following infection of DC by S T and incubation, the cells were stained with antibodies and analysed by flow cytometry. The cytokine concentration was tested from the supernatants by ELISA and cytometric bead array. The gene transfer was evaluated using EGFP as a reporter gene. Following infection of DC with S T carrying EGFP and incubation, the DC were analysed for EGFP expression by flow cytometry. Analysis of maturation markers confirmed that both strains of S T are capable to mature DC with WT05 strain being more efficient. The difference between two strains was very marked when analysing cytokine profile. Infection with the strain WT05 induced DC to produce large amounts of IL-12, IL-12 p70, TNF alpha, IL10 and IL-1beta whereas strain CD12 was significantly less efficient (p=0.05). The chemokine profile followed the pattern but the values were not statistically significant. The cytokine release was compared to the background strain TML which produced very similar amounts to strain WT05. To explain the difference between the CD12 and WT05 induced cytokine profile, a polymyxin B (PMB) assay was performed. PMB is known to block lipid A fraction of the LPS. Addition of PMB to DC infected by ST strongly inhibited the release of cytokines indicating that the likely cause of low cytokine release was the different structure of the lipid A possibly induced by the sif A mutation. The gene transfer process by DCs infected with CD12 and WT05 was comparable, with up to 11% of DCs expressing EGFP. In conclusion ST is capable to mature DCs and to mediate gene transfer in vitro but the efficacy of the process is dependent upon genetic background of the ST. A type of mutation used to attenuate ST can strongly influence cytokine pattern.
My Teacher, My Cadaver
Authors: Stephanie Jillian Handler
Journal: Annals of Internal Medicine (2021)

On Being a DoctorMay 2021My Teacher, My CadaverStephanie Jillian Handler, MDStephanie Jillian Handler, MDLos Angeles County Harbor–UCLA Medical Center Torrance, CaliforniaSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M21-0576 Audio Reading - “My Teacher, My Cadaver” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads “My Teacher, My Cadaver” by Stephanie Jillian Handler, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The night before my first day of human anatomy lab, I assembled my tools: scrubs, dissector, dissection kit, extra-long gloves, and shoes destined to be discarded at the end of the semester because they would be forever impregnated with the experience of the cadaver lab.My team was assigned to cadaver 17, off in the corner of the room. One by one, we opened the shiny metal boxes that contained the cadavers. The bodies. “My body,” we would come to say. “I have a really good sciatic nerve,” or, “My liver is giant and green because my gallbladder ruptured.” I ... Author, Article, and Disclosure InformationAffiliations: Los Angeles County Harbor–UCLA Medical Center Torrance, CaliforniaCorresponding Author: Stephanie Jillian Handler, MD, Division of Female Pelvic Medicine and Reconstructive Surgery, Department of Obstetrics and Gynecology, Harbor–UCLA Medical Center, 1000 West Carson Street, Torrance, CA, 90509; e-mail, stephanie.[email protected]com. PreviousarticleNextarticle Advertisement Audio Reading - “My Teacher, My Cadaver” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads “My Teacher, My Cadaver” by Stephanie Jillian Handler, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics May 2021Volume 174, Issue 5Page: 712 ePublished: 18 May 2021 Issue Published: May 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Abstract 15356: Echocardiographic Features in Neuromuscular Diseases
Authors: Byung-Jun Kim, Jong-Ho Nam, Hun-Tae Kim, Jong-Il Park, Jang-Won Son
Journal: Circulation (2020)

Introductions: Cardiac involvement is a major cause of morbidity and mortality in neuromuscular disease patients. However, echocardiographic features in these patients have not been well evaluated. We aimed this study to analyze echocardiographic features of the patients with neuromuscular disease Methods: We retrospectively enrolled 112 adult patients with neuromuscular disease who performed echocardiography. Patients were divided into two groups according to the main involving site; diseases that invades the nervous system (Group 1, N=51) and diseases that invades muscular system (Group 2, N=62); and echocardiographic features were analyzed. Group 1 was consisted with amyotrophic lateral sclerosis (43 patients), Guillain-Barre’s syndrome (4 patients), and other diseases (4 patients). Group 2 was consisted with Duchenne muscular dystrophy (6 patients), myotonic muscular dystrophy (4 patients), spinal muscle atrophy (2 patients) and unclassified muscular dystrophy (49 patients) Results: Compared with the Group 1, the patients in Group 2 were younger (62.4±11.5 vs. 37.2±14.4, p&lt;0.001), had significantly lower ejection fraction (EF : 52.1±13.7% vs. 62.2±7.7%, p&lt;0.001), had larger left ventricular (LV) size (end systolic LV dimension: 32.7±8.6mm vs. 29.0±4.8mm, p&lt;0.001) and thinner interventricular septum (IVSd: 7.42±1.61mm vs 8.88±1.57mm, p&lt;0.001). Group 2 also showed lower A velocity, higher E/A ratio and shorter deceleration time (DT) compared with Group 1 (A velocity : 0.507±0.147cm/s vs. 0.781±0.219cm/s , p&lt;0.001, E/A ratio : 1.398±0.657 vs. 0.801±0.242, p&lt;0.001 and DT : 191.5±52.6 vs. 219.7±42.9, p=0.004) Conclusions: Patients with neuromuscular disease mainly involving muscular system had lower LV systolic function and impaired diastolic function compared with the patients mainly involving nervous system. More careful cardiac evaluation should be performed in these patients.
Abstract P054: Duration Of Diabetes, Glucose Excursions, Glycemic Control, And Low Heart Rate Variability: The Atherosclerosis Risk In Communities (aric) Study
Authors: Mary R Rooney, Justin B Echouffo Tcheugui, Faye L Norby, Elsayed Z Soliman, Lin Y Chen, Elizabeth Selvin
Journal: Circulation (2021)

Introduction: Individuals with diabetes often have low heart rate variability (HRV)—a marker of autonomic dysfunction. How diabetes duration, glucose excursions, and poor glycemic control relate to HRV is not well characterized. Objectives: To evaluate the associations of diabetes status, duration of diabetes, and biomarkers of glucose excursions (1,5-anhydroglucitol [1,5-AG]—a measure of glycosuria) and glycemic control with HRV. Methods: We conducted a cross-sectional analysis of ARIC Study participants who underwent a 2-minute electrocardiogram at visit 4 (1996-98). We considered root mean square of successive differences in normal-to-normal R-R intervals (rMSSD, measure of parasympathetic activity), standard deviation of normal-to-normal R-R intervals (SDNN, total variability), low frequency (LF, primarily sympathetic activity), high frequency (HF, reflects parasympathetic activity), and LF/HF ratio (sympathetic-parasympathetic balance) as HRV indices. In persons with diabetes, we compared geometric means of HRV indices by diabetes duration (&lt;5 years vs ≥5 years), 1,5-AG (&lt;6 μg/mL vs ≥6 μg/mL), and glucose control (estimated A1C &lt;8% vs ≥8%). We obtained p-values from linear regressions adjusted for age and sex. Results: Among 10169 participants (mean age 63, 57% female, 22% black), participants with diabetes had significantly lower rMSSD, SDNN, LF, HF, and LF/HF ratio compared to those without diabetes ( Table ). Among the 1667 participants with diabetes, longer duration of diabetes, low 1,5-AG, and poor glycemic control were associated with lower rMSSD, SDNN, LF, and HF. No statistically significant associations were found for diabetes duration, 1,5-AG, glycemic control with LF/HF ratio. Discussion: Our results demonstrate that longer duration of diabetes, glucose excursions, and poor glycemic control are associated with some measures of low HRV. This study underscores that cardiac autonomic neuropathy is a common but overlooked complication of long-standing and/or poorly managed diabetes.
The expression of GPRC5A in cultured normal and malignant cells is modulated by endogenous retinoids in serum
Authors: Xiaofeng Ye, Jiong Deng, Dafna Lotan, Reuben Lotan
Journal: Cancer Research (2007)

1652  GPRC5A, a gene that encodes a retinoic acid (RA) inducible G protein coupled receptor (Cheng and Lotan, J Biol Chem, 1998, 273:35008-15), is a candidate tumor suppressor in the mouse lung (Tao et al., Proc. AACR, 2004, 45: 876). The presence of a RA response element in its promoter (Tao et al., Genomics, 2004, 83:270-80) suggests that GPRC5A is a primary target of retinoids and could mediate some of their effects on cell growth, differentiation and apoptosis. Wu et al. reported that the GPRC5A expression is up regulated in several tumor cell lines including non-small cell lung cancer (NSCLC) cell lines than in normal cells (J Biol Chem, 2005, 280: 12935-43). These results contradicted our observation that GPRC5A expression was high in normal lung tissue and decreased in NSCLC cell lines (Cheng and Lotan, 1998). Because primary cultures of normal epithelial cells are usually grown in serum-free medium, whereas tumor cells are cultured in medium supplemented with 10% serum (e.g., fetal bovine), we hypothesized that the differential expression of GPRC5A observed by Wu et al., may have occurred due to the presence of endogenous retinoids in the growth medium of the tumor cells but not of their normal counterparts. To test this hypothesis, we analyzed GPRC5A expression by real-time PCR using RNA isolated from different human primary cell strains and established cancer cell lines that were all cultured without or with 10% fetal bovine serum. The primary and low passage normal cell strains included cells derived from lung (n=9), breast (n=3), prostate (n=2), oral gingiva (n=1), and bladder (n=1). The established cancer cell lines included NSCLC (n=11), breast (n=9), head and neck squamous cell carcinomas (n=6), prostate (n=3), and bladder carcinomas (n=5). We found that GPRC5A was induced to some degree in 44/50 (88%) of these cells, and >2 fold in 34/50 (68%) of these cells when they were cultured with serum compared with serum-free medium. In most cases, the fold induction by serum and the induced levels of GPRC5A in the normal cells was higher than in their corresponding cancer cells. Further studies with 7 normal lung cells and 2 normal breast cell strains revealed that AGN193109, an antagonist of retinoic acid receptors, suppressed the induction of GPRC5A by serum as evident by real time- and reverse-transcription PCR. Our results demonstrate that GPRC5A expression can be induced by endogenous serum retinoids in both normal and malignant human cells and that a comparison of the expression of this and likely other genes between normal and malignant cells should be performed under the same culture conditions and medium supplements (e.g., serum) to avoid reaching potentially erroneous conclusions (e.g., that the expression of certain genes is increased in tumor cells relative to normal cells when such genes may be regulated by serum retinoids). Supported in part by Department of Defense grant DAMD W81XWH-04-1-0142.