tbuckley/cabot-search huggingface dataset:
Comment on Vistisen et al. A Validated Prediction Model for End-Stage Kidney Disease in Type 1 Diabetes. Diabetes Care 2021;44:901–907
Authors: Helena Bleken Østergaard, Joep van der Leeuw, Frank L.J. Visseren, Jan Westerink
Journal: Diabetes Care (2021)

With great interest we read the recent study by Vistisen et al. (1) wherein a prediction model for end-stage kidney disease (ESKD) in patients with type 1 diabetes was derived and validated. The model is intended to inform clinical decision-making by predicting 5-year risk of ESKD using routinely available clinical measurements. The model accounts for all-cause mortality as competing risk and performed very well in discrimination, although it was less robust regarding calibration. Furthermore, the authors provide a user-friendly online calculator …
Shared inflammatory pathways and therapeutic strategies in COVID-19 and cancer immunotherapy
Authors: Lorenzo Iovino, Laurel A Thur, Sacha Gnjatic, Aude Chapuis, Filippo Milano, Joshua A Hill
Journal: Journal for ImmunoTherapy of Cancer (2021)

COVID-19, the syndrome caused by the infection with SARS-CoV-2 coronavirus, is characterized, in its severe form, by interstitial diffuse pneumonitis and acute respiratory distress syndrome (ARDS). ARDS and systemic manifestations of COVID-19 are mainly due to an exaggerated immune response triggered by the viral infection. Cytokine release syndrome (CRS), an inflammatory syndrome characterized by elevated levels of circulating cytokines, and endothelial dysfunction are systemic manifestations of COVID-19. CRS is also an adverse event of immunotherapy (IMTX), the treatment of diseases using drugs, cells, and antibodies to stimulate or suppress the immune system. Graft-versus-host disease complications after an allogeneic stem cell transplant, toxicity after the infusion of chimeric antigen receptor-T cell therapy and monoclonal antibodies can all lead to CRS. It is hypothesized that anti-inflammatory drugs used for treatment of CRS in IMTX may be useful in reducing the mortality in COVID-19, whereas IMTX itself may help in ameliorating effects of SARS-CoV-2 infection. In this paper, we focused on the potential shared mechanisms and differences between COVID-19 and IMTX-related toxicities. We performed a systematic review of the clinical trials testing anti-inflammatory therapies and of the data published from prospective trials. Preliminary evidence suggests there might be a benefit in targeting the cytokines involved in the pathogenesis of COVID-19, especially by inhibiting the interleukin-6 pathway. Many other approaches based on novel drugs and cell therapies are currently under investigation and may lead to a reduction in hospitalization and mortality due to COVID-19.
Shrinkage-based Random Local Clocks with Scalable Inference
Authors: Alexander A Fisher, Xiang Ji, Akihiko Nishimura, Guy Baele, Philippe Lemey, Marc A Suchard
Journal: Molecular Biology and Evolution (2023)

Abstract Molecular clock models undergird modern methods of divergence-time estimation. Local clock models propose that the rate of molecular evolution is constant within phylogenetic subtrees. Current local clock inference procedures exhibit one or more weaknesses, namely they achieve limited scalability to trees with large numbers of taxa, impose model misspecification, or require a priori knowledge of the existence and location of clocks. To overcome these challenges, we present an autocorrelated, Bayesian model of heritable clock rate evolution that leverages heavy-tailed priors with mean zero to shrink increments of change between branch-specific clocks. We further develop an efficient Hamiltonian Monte Carlo sampler that exploits closed form gradient computations to scale our model to large trees. Inference under our shrinkage clock exhibits a speed-up compared to the popular random local clock when estimating branch-specific clock rates on a variety of simulated datasets. This speed-up increases with the size of the problem. We further show our shrinkage clock recovers known local clocks within a rodent and mammalian phylogeny. Finally, in a problem that once appeared computationally impractical, we investigate the heritable clock structure of various surface glycoproteins of influenza A virus in the absence of prior knowledge about clock placement. We implement our shrinkage clock and make it publicly available in the BEAST software package.
Abstract P212: Comparison Of Vascular Risk Factors And Serum Fatty Acids At Admission Between Intracerebral Hemorrhage And Acute Ischemic Stroke
Authors: Takahisa Mori, Kazuhiro Yoshioka, Yuichi Miyazaki
Journal: Circulation (2021)

Introduction: Dietary triglycerides influence fatty acid (FA) serum concentrations and weight percentages (wt%), which may be associated with the onset of intracerebral hemorrhage (ICH) or acute ischemic stroke (AIS). Hypothesis: There are significant differences between FAs at the admission of ICH and AIS. Methods: We included patients admitted between 2016 and 2019 within 24 h of ICH or AIS onset and calculated correlation coefficients between their ages, serum FA concentrations, and FA wt% values. We evaluated differences in age, average blood pressure (ABP), glucose, A1c, serum lipids, and FAs between two groups. Excluding variables with multicollinearity, we performed multiple logistic regression (MLR) analysis to identify independent variables distinguishing ICH from AIS. We estimated the threshold values of independent variables using the area under the curve values derived from the receiver operating characteristic (ROC) curves. Results: Our inclusion criteria were met by 141 of ICH patients and 525 of AIS patients. In the ICH group, age, A1c, and eicosapentaenoic acid (EPA) levels were smaller than those in the AIS group. ABP, high-density lipoprotein cholesterol (HDL-C), myristic acid (MyA), linoleic acid (LiA) concentrations, and MyA wt% were higher than those in the AIS group. MLR analysis between two groups indicated that age, ABP, A1c, HDL-C were independent variables. Serum FA levels were not independent. ROC curves showed that the threshold values of age, ABP, A1c, and HDL-C for ICH onset were ≤ 69 years, ≥ 126.6 mmHg, ≤ 6.0%, and ≥ 1.62 mmol/L, respectively. In 27 patients with age ≤ 69 , ABP ≥ 126.6, A1c ≤ 6.0%, and HDL-C ≥ 1.62 and 87 patients with age &gt; 69 , ABP&lt; 126.6, A1c &gt; 6.0, and HDL-C &lt; 1.62, there were 19 (70.4%) and 9 (10.3%) patients with ICH, the MyA concentrations were 108 and 73 μmol/L (p &lt; 0.001), the LiA concentration were 2,900 and 2,410μmol/L (p &lt; 0.001), and the EPA wt% were 1.4 and 2.0% (p=0.059), respectively. Conclusions: Younger patients with higher ABP, lower A1c, and higher HDL-C suffered from not AIS but ICH, and their MyA and LiA concentrations were higher than older patients without them.
Dealing With Death as an Outcome in Supportive Care Clinical Trials
Authors: Scott D. Halpern, Jennifer S. Temel, Katherine R. Courtright
Journal: JAMA Internal Medicine (2021)

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Item-Level Genome-Wide Association Study of the Alcohol Use Disorders Identification Test in Three Population-Based Cohorts
Authors: Travis T. Mallard, Jeanne E. Savage, Emma C. Johnson, Yuye Huang, Alexis C. Edwards, Jouke J. Hottenga, Andrew D. Grotzinger, Daniel E. Gustavson, Mariela V. Jennings, Andrey Anokhin, Danielle M. Dick, Howard J. Edenberg, John R. Kramer, Dongbing Lai, Jacquelyn L. Meyers, Ashwini K. Pandey, Kathryn Paige Harden, Michel G. Nivard, Eco J.C. de Geus, Dorret I. Boomsma, Arpana Agrawal, Lea K. Davis, Toni-Kim Clarke, Abraham A. Palmer, Sandra Sanchez-Roige
Journal: American Journal of Psychiatry (2021)

Genome-wide association studies (GWASs) of the Alcohol Use Disorders Identification Test (AUDIT), a 10-item screen for alcohol use disorder (AUD), have elucidated novel loci for alcohol consumption and misuse. However, these studies also revealed that GWASs can be influenced by numerous biases (e.g., measurement error, selection bias), which may have led to inconsistent genetic correlations between alcohol involvement and AUD, as well as paradoxically negative genetic correlations between alcohol involvement and psychiatric disorders and/or medical conditions. The authors used genomic structural equation modeling to elucidate the genetics of alcohol consumption and problematic consequences of alcohol use as measured by AUDIT.
Abstract 15685: Multicenter Analysis of Advanced Heart Failure Referral Outcomes by Race
Authors: Jared J Herr, Farooq Sheikh, Parin Patel, Anuradha Lala, Christopher Chien, Ajay Srivastava, Stephen J Forest, Michael Tong, Benjamin DSouza, Ashwin Ravichandran
Journal: Circulation (2020)

Background: Advanced heart failure (AHF) therapies can improve survival in Stage D HF patients. We sought to evaluate racial differences in AHF therapy referrals and decision-making across a multicenter survey. Methods/Results: We performed a retrospective analysis of patients referred for evaluation for AHF therapies at 9 centers (N=515) across the country. Data included: demographics, clinical/referring physician characteristics and evaluation outcomes. By identified racial/ethnic groups, referrals comprised of 55.7% Caucasian, 29.9% African American, 9.1% Hispanic, and 4.7% Asian. Univariate analysis was performed between Caucasian and a combined non-Caucasian group. Most patients were advanced in their disease state, with 47.7% of Caucasian and 55.7% of non-Caucasian patients having EF&lt;20% with a high risk INTERMACS profiles (1-3), 77% and 71.1% respectively. Non-ischemic etiology was more common in non-Caucasians (66.6% vs. 47.4% p=0.001), ischemic etiology more common in Caucasians (41.1% vs. 23.2% p=0.001). The primary reasons for Caucasians to be referred were ventricular arrhythmias (7.6% vs. 3%, p=0.024) and pulmonary hypertension (3.4% vs 0.4% p=0.018), while non-Caucasians were referred most for worsening heart failure (35.9% vs. 25.4% p=0.009). Non-Caucasians were more likely to be declined/deferred for LVAD (45.9% vs. 39.7% p=0.014) or transplantation (48.2% vs. 66.9% p=0.002). Patient preference to not pursue LVAD therapy differed significantly between the groups (Non-Caucasians 17.6% vs. Caucasians 9.6% p=0.022). Conclusions: In this multicenter analysis of referrals for AHF therapies, significant differences exist in referral characteristics and evaluation outcomes between Caucasian and non-Caucasians. The driving factor for not offering LVAD therapy in non-Caucasians was patient preference, raising concerns for potential differences in patient education surrounding AHF therapies between racial groups. Further investigation is needed to explore these differences and why non-Caucasians were more likely to be declined or deferred for LVAD and transplantation.
Abstract 16838: Lipoprotein(a) is Weakly Associated With Coronary Artery Calcification in Molecularly Defined Heterozygous FH Subjects
Authors: Marcio H Miname, Betina Novaes, Bruna Remedio, Raul D Santos
Journal: Circulation (2020)

Introduction: Familial hypercholesterolemia (FH) is characterized by premature atherosclerosis (ATH). Coronary calcium score (CAC) reflects coronary plaque burden. Lipoprotein(a) [Lp(a)] increases ATH risk in FH. Little is known about the association of CAC and Lp(a) in heterozygous FH. Hypothesis: Lp(a) could be associated with CAC presence in HeFH independently of LDL-c and age. Methods: Molecularly confirmed primary prevention FH individuals that were submitted to CAC and Lp(a) evaluation were included. LDL-c was corrected by Lp(a)-cholesterol. Binary logistic regression analysis with CAC presence as dependent variable was used to evaluate determinants of CAC. Spearman correlation and area under ROC curve (AUC) were calculated for Lp(a) discrimination of CAC presence. Results: We included 217 FH [65.4% female, 43.9±13.6 years, LDL-c 237±76 mg/dL, median Lp(a) 29 mg/dL (interquartile range: 53)]. CAC was present in 98 (45.1%) individuals. In univariate analysis CAC associated with (OR, 95%CI): age (1.09, 1.062-1.120, p&lt;0.001), LDL-c (1.005, 1.001-1.009, p=0.017), Lp(a) (1.010, 1.003-1.017, p=0.007), hypertension (3.99, 2.202-7.868, p&lt;0.001), BMI (1.096, 1.030-1.166, p=0.004) and corneal arcus (3.20, 1.509-6.790, p=0.002). After multivariate logistic regression only age (OR: 1.086, 95%CI 1.052-1.121, p&lt;0.001) and LDL-c (OR: 1.005, 95% CI 1.001-1.010, p=0.024) persisted associated with CAC. LDL-c was associated with CAC for those with Lp(a) below the median (OR=1.007, 95% CI 1.001-1.013, p=0.019) and this association persisted even including Lp(a) in the model (p=0.022). However, LDL-c was not associated with CAC for those with Lp(a) above the median (OR=1.003, 95%CI 0.997-1.008) and persisted not associated when including Lp(a) in the model (p=0.208). The reverse occurred with Lp(a), which was not associated with CAC for those with Lp(a) below the median (p=0.534) and was associated to CAC for those above median (p=0.013). Lp(a) correlation with CAC was weak (r=0.175, p=0.010) and the AUC was 0.581 (95% CI 0.503-0.659, p=0.040). Conclusions: Lp(a) is weakly correlated to CAC in FH and the association of LDL-c and Lp(a) with CAC is different according to Lp(a) levels. This suggests that Lp(a) may not be associated with plaque burden in FH.
PRICESステートメント:クリティカルケア心エコー研究を実施し報告するための方法論に関するESICM専門家コンセンサス【JST・京大機械翻訳】
Authors: Sanfilippo Filippo, Huang Stephen, Herpain Antoine, Balik Martin, S Chew Michelle, Clau-Terre Fernando, Corredor Carlos, De Backer Daniel, Fletcher Nick, Geri Guillaume, Mekontso-Dessap Armand, McLean Anthony, Morelli Andrea, Orde Sam, Petrinic Tatjana, Slama Michel, C C van der Horst Iwan, Vignon Philippe, Mayo Paul, Vieillard-Baron Antoine
Journal: Intensive Care Medicine (2021)
National Survey Demonstrates Practice Gaps in Cytogenetic and Molecular Testing in Acute Myeloid Leukemia
Authors: Jessica K. Altman, Ellen Denzen, AnneMarie W. Block, Robert P. Hasserjian, Heidi Klepin, Bruno C Medeiros, Amanda Noe, Wendy E Scales, Martin S. Tallman, Kathleen Wiley, Linda J. Burns
Journal: Blood (2017)
Abstract 13024: Cardiovascular Disease Beyond the Aorta in Marfan Syndrome
Authors: Niels H Andersen, Kristian A Groth, Agnete Berglund, Claus H Gravholt, Kirstine Stochholm
Journal: Circulation (2020)

Introduction: Aortic disease is the major cardiovascular disease in Marfan syndrome (MFS), however numerous studies indicate that other heart conditions may also be a major disease burden for patients with MFS Hypothesis: We hypothesized that the burden of non-aortic cardiovascular disease in MFS is considerable and the aim of the study is therefore to assess the extent of this issue in Danish patient with MFS. Methods: A register-based population study of Danish patients with a Ghent II verified Marfan Syndrome diagnosis. All patients were alive January 1st 1994, at the beginning of the ICD-10 system. Each patient was age-matched with up to 100 controls with the same sex. Results: We identified 407 MFS patients from the Danish healthcare system (1977-2014) and compared our findings with 40,700 persons from the background population. We found the following hazard ratios and confidence intervals: Mitral valve disease HR: 60.8 [39.5-93.5], p&lt;0.0001. Cardiomyopathy HR:12.7 [5.8-28.0], p&lt;0.0001. Heart failure HR 8.2 [5.2-12.9], p &lt;0.0001. Tachyarrhythmia HR: 9.7 [7.5-12.6], p &lt;0.0001. AV-Block HR: 4.7 [1.5-15.1], p&lt;0.01. Sudden cardiac death HR: 8.3 [3.8-18.0], p&lt;0.0001. Discussion: The registration of mitral valve disease occurred earlier and more often in women with MFS compared to men with MFS (age at registration: 22 vs. 38 years, HR: 2.2 (1.1-4.6) Among patients with arrhythmia 20 % had ventricular ectopics or tachycardia. Forty percent of the cases with tachyarrhythmia were unrelated to heart surgery and 37 % of the total cohort had tachyarrhythmia without having any surgery done. AV-block was in all cases related to heart surgery. Twenty patients with MFS had a registration with heart failure, whereof 9 were diagnosed unrelated to heart surgery. Looking only at registrations unrelated to heart surgery the HR was 4.8 (2.5-9.5). There was no difference in registration of heart failure between men and women. The sudden cardiac death etiology was unclear due to lack of autopsies. Conclusion: The burden of non-aortic cardiovascular disease is massive in patients with MFS and this must be in focus in the caretaking of patients with MFS
TVT登録からのバルーン拡張可能な補綴物洞察によるTAVR後の症例容積と転帰【JST・京大機械翻訳】
Authors: J Russo Mark, M McCabe James, H Thourani Vinod, Guerrero Mayra, Genereux Philippe, Nguyen Tom, N Hong Kimberly, Kodali Susheel, B Leon Martin
Journal: Journal of the American College of Cardiology (2019)
Abstract P208: The Differential Impact Of Residential Segregation On Gestational Hypertension Development Among Minority Women
Authors: Mary D Schiff, Anthony Fabio, Tiffany Gary-Webb, Dara Mendez
Journal: Circulation (2021)

Introduction: Higher levels of residential segregation have been associated with poorer cardiometabolic health profiles among women. Still, it remains unclear whether segregation may differentially impact the development of gestational hypertension (gHTN) among an ethnically-diverse cohort of pregnant women. We used birth record data from 2003-2009 and data from the 2000 US Census to determine whether racial and economic segregation are associated with gHTN among a diverse cohort of child-bearing women in the greater Philadelphia area. Methods: We quantified racial and economic segregation using sociodemographic data from the US Census and the local Getis-Ord (Gi*) spatial statistic. The Gi* produces a spatially-weighted z-score for each census tract reflecting the degree of clustering of racially-similar neighborhoods in an area relative to the surrounding Philadelphia region. We categorized each type of segregation as low (Gi*&lt;0), moderate (Gi*0-1.96), or high (Gi*&gt;1.96), and assigned these to each woman by her census tract of residence. Gestational hypertension was defined in the birth record data as the development of pregnancy-induced hypertension or preeclampsia. We used hierarchical generalized linear mixed effect models to obtain risk ratios and differences (per 1000 women) for the relationships between each form of residential segregation and gHTN. All models were stratified by maternal race/ethnicity, and sequentially adjusted for maternal sociodemographics, health behaviors, medical histories, and neighborhood-level characteristics. Results: Our sample consisted of 220,897 Non-Hispanic (NH) Black (26%), NH White (64%), and Hispanic (10%) women, of whom 4% developed gHTN. However, a much greater proportion of NH Black women both developed gHTN and lived in high segregation neighborhoods compared to NH Whites and Hispanics. After adjustment, NH Black women in moderate and high economic segregation areas had 16% higher risk (RR=1.16, 95% CI: 1.03-1.31) and 23% higher risk (RR=1.23, 95% CI: 1.08-1.39) of gHTN, respectively, compared to NH Black women living in low segregation areas. NH Black women in highly racially segregated neighborhoods saw an additional 9 cases of gHTN (per 1000 women) compared to NH Black women living in more racially integrated neighborhoods (RD=8.47, 95% CI: 3.14-13.80). Among NH White and Hispanic women, economic segregation was not associated with gHTN, and only marginally significant findings were observed for racial segregation. Conclusions: In our diverse sample of child-bearing women from the greater Philadelphia area, higher levels of racial and economic segregation were associated with greater risk of gHTN among NH Black women. Future work should seek to delineate the specific pathways by which neighborhoods differentially impact individual level cardiovascular health based upon race.
Abstract 16447: Exercise Predicted Peak Oxygen Uptake and Definition of Gas Exchange Phenotypes in an Apparently Healthy Population: An Analysis of the Euroex Trial
Authors: jessica zannoni, ANTONIO SISINNI, omar alessandro oliva, Mattia Mazzucca, enrico poletti, Marco Guazzi
Journal: Circulation (2020)

Aims: We aimed at identifying how exercise performance by percent of predicted oxygen uptake defines the exercise gas exchange phenotypes in a population of apparently healthy individuals enrolled in the Euro-Ex population-based trial. Methods: 782 healthy subjects (age 63 ± 12 years; male 45 %; BMI 28.95 ± 5.2 kg/m 2 ) enrolled in the EURO-EX prevention trial with at least one major cardiovascular risk factor (hypertension, diabetes, tabagism, dyslipidaemia, body mass index &gt; 25), but no previous CV events, underwent cardiopulmonary exercise test (CPET) with personalized incremental ramp protocol. Peak oxygen consumption (VO2), the percent predicted normal value and other main CPET- derived variables were obtained. The population was divided into tertiles groups based on the VO2 predicted (I tertile [21%-60%), II tertile [60%-75%], III tertile [75%- 164%]). Results: Subjects in the tertile 1 compared to the other two groups were younger (age 60 ± 13 years), more frequently females with a higher BMI (31.12 ± 5.83 kg/m 2 ), and smokers in a higher rate (31.89 %). No significant differences in the frequency of diabetes, hypertension and dyslipidemia were observed in the three groups. As reported in the table, the group with lower % predicted peak VO2 showed higher prevalence of exercise oscillatory ventilation, lower exercise tolerance (peak VO2 and VO2 at threshold), peak O2 pulse and VO2/Work slope, higher VE/VCO2 slope. This group showed lower heart rate recovery at first minute and heart rate reserve. Subjects with lower VO2 predicted tertiles had comparatively poorer CPET performance and gas exchange phenotype. Conclusions: The use of % predicted peak VO2 appears helpful to phenotype gas exchange and identify the progressive level of cardiovascular risk of apparently healthy subjects. These findings broaden the constellation of targets that need to be considered in the preventive strategies of individuals at risk for cardiovascular events.
Analysis of the Anatomical Tachycardia Circuit in Verapamilsensitive Atrial Reentrant Tachycardia Originating From the Vicinity of the Atrioventricular Node
Authors: Morishisa Kenji, Yamabe Hiroshige, Uemura Takashi, Tanaka Yasuaki, Morikami Yasuhiro, Kimura Yoshihiro, Hokamura Yoichi, Ogawa Hisao
Journal: Circulation (2006)