tbuckley/cabot-search huggingface dataset:
Abstract EP58: Getting Personal: Improved Statin Adherence Through Individualized Communication
Authors: Amir Khan, Kevin Desai, Avi Aronov, Bradley Recht
Journal: Circulation (2022)

Background: Statin adherence remains suboptimal for primary prevention despite its proven benefits in reducing the risk of future adverse atherosclerotic cardiovascular disease (ASCVD). We aim to determine the effectiveness of personalized communication in improving adherence rates for the primary prevention of ASCVD. Methods: This was a quality improvement initiative involving three primary care clinics at the Jesse Brown Veteran Affairs Medical Center in Chicago, Illinois. Patients were ages 40-79, without a history of ASCVD and prescribed a statin within the past year. Those with a refill rate &lt; 80% were mailed a letter educating them on their individualized 10-year ASCVD risk and statins’ utility in reducing this risk. Statin adherence data were obtained prior to and 90 days following the intervention to assess for an improvement in composite statin refill rate. A control chart was used before sending the mailed letters to determine if special causes of variation existed prior to intervention. A 2-sample t-test was used to compare the mean daily adherence rates pre- and post-intervention. Results: There was a statistically significant improvement in daily average statin adherence in the 90-day post-intervention period (84.88 ± 0.39 vs 83.40 ± 0.09; p &lt; 0.001). Conclusion: Mailed letters that include individualized ASCVD risk scores may be an effective way of improving adherence to statins among patients with no prior history of ASCVD.
Abstract P091: Performance Of Glycated Albumin As A Marker Of Hyperglycemia During Pregnancy: Results From The National Health And Nutrition Examination 1999-2004
Authors: Mary R Rooney, Sui Zhang, Anum A Minhas, Michael Fang, Justin Echouffo Tcheugui, Morgan Grams, Robert H Christenson, Elizabeth Selvin
Journal: Circulation (2022)

Background: Glycated albumin (GA) is FDA-cleared for use as a short-term (2-3 week) marker of glycemia. HbA1c is not recommended for use during pregnancy due to its lack of sensitivity and suboptimal performance due to alterations in blood volume and decreases in hemoglobin. It is unclear if GA has a role for monitoring hyperglycemia in pregnancy. Objective: We evaluated the performance of GA as a measure of hyperglycemia in pregnant women without pre-gestational diabetes and compared our results to those in a sample of similarly-aged non-pregnant women. Methods: We used data from 555 pregnant women aged 20-40 years with measurements of glycemic markers (GA, HbA1c, glucose) without pre-gestational diabetes who participated in the 1999-2004 NHANES. We used Pearson’s correlations and linear regression and evaluated the area under the curve (AUC) for GA to detect elevated glucose or HbA1c. Results were compared to 1607 NHANES women aged 20-40 who were not pregnant. Results: In pregnant women in the US, 1.9% had elevated HbA1c (≥5.7%), 4.4% had elevated glucose (≥100 mg/dL) and 1.9% had elevated GA (≥16.5%). The correlation of HbA1c and glucose was 0.21 in pregnant women and was 0.62 in the non-pregnant women. GA was poorly correlated with HbA1c (r=0.08) and glucose (r=0.17) in pregnant women and modestly associated with HbA1c (r=0.31) and glucose (r=0.35). In pregnancy, BMI was positively associated with HbA1c (r=0.33) and glucose (r=0.25) but was inversely associated with GA (r=-0.27). GA had poor discrimination for detecting mild hyperglycemia in pregnant women, defined as either HbA1c ≥5.7% (AUC=0.538) or glucose ≥100 mg/dL (AUC=0.499) ( Figure ). Similar patterns were observed in women who were not pregnant. Conclusions: Our results suggest that GA is not a useful marker to identify or monitor mild hyperglycemia in pregnancy. GA appears to be strongly affected by adiposity. Weight gain during pregnancy may explain the poor concordance of GA with traditional measures of glycemia in pregnant women.
Early-Onset Colorectal Adenocarcinoma in the IDEA Database: Treatment Adherence, Toxicities, and Outcomes With 3 and 6 Months of Adjuvant Fluoropyrimidine and Oxaliplatin
Authors: Elisa Fontana, Jeff Meyers, Alberto Sobrero, Timothy Iveson, Anthony F. Shields, Julien Taieb, Takayuki Yoshino, Ioannis Souglakos, Elizabeth C. Smyth, Florian Lordick, Markus Moehler, Anne Giraut, Andrea Harkin, Roberto Labianca, Jeffrey Meyerhardt, Thierry André, Ioannis Boukovinas, Sara Lonardi, Mark Saunders, Dewi Vernerey, Eiji Oki, Vassilis Georgoulias, Irit Ben-Aharon, Qian Shi
Journal: Journal of Clinical Oncology (2021)

PURPOSE Early-onset (EO) colorectal cancer (CRC, age &lt; 50 years) incidence is increasing. Decisions on optimal adjuvant therapy should consider treatment adherence, adverse events, and expected outcomes in a population with life expectancy longer than later-onset (LO) CRC (age ≥ 50 years). MATERIALS AND METHODS Individual patient data from six trials in the International Duration Evaluation of Adjuvant Chemotherapy database were analyzed. Characteristics, treatment adherence, and adverse events in stage II or III EO-CRC and LO-CRC were compared. To reduce confounders of non–cancer-related deaths because of age or comorbidities, time to recurrence (3-year relapse-free rate) and cancer-specific survival (5-year cancer-specific mortality rate) were considered. RESULTS Out of 16,349 patients, 1,564 (9.6%) had EO-CRC. Compared with LO-CRC, EO-CRC had better performance status (86% v 80%, P &lt; .01), similar T stage (% T1-3/T4: 76/24 v 77/23, P = .97), higher N2 disease rate (24% v 22%, P &lt; .01), more likely to complete the planned treatment duration (83.2% v 78.2%, P &lt; .01), and received a higher treatment dose intensity, especially with 6-month regimens. Gastrointestinal toxicity was more common in EO-CRC; hematologic toxicity was more frequent in LO-CRC. Compared with LO-CRC, significantly worse cancer-specific outcomes were demonstrated especially in high-risk stage III EO-CRC: lower 3-year relapse-free rate (54% v 65%; hazard ratio [HR] 1.33; 95% CI, 1.14 to 1.55; P value &lt; .001) and higher 5-year cancer-specific mortality rate (24% v 20%; HR 1.21; 95% CI, 1.00 to 1.47; P value &lt; .06). In this subgroup, no difference was observed with 3 or 6 months of therapy, with equally poor disease-free survival rates (57% v 56%; HR 0.97; 95% CI, 0.73 to 1.29; P value = .85). CONCLUSION Young age is negatively prognostic in high-risk stage III CRC and associated with significantly higher relapse rate; this is despite better treatment adherence and higher administered treatment intensity, suggesting more aggressive disease biology.
Targeting HER2 May Overtake Chemo, Immunotherapy in NSCLC
Journal: Cancer Discovery (2021)

Results from phase II trials of two HER2-targeting agents, the antibody-drug conjugate trastuzumab deruxtecan and the HER2-targeting tyrosine kinase inhibitor poziotinib, indicate promising efficacy that could lead to new standards of care for HER2-mutant non-small cell lung cancer.
Acute Gastrointestinal Bleeding
Authors: Jeffrey L. Tokar, Jennifer T. Higa
Journal: Annals of Internal Medicine (2022)

Acute gastrointestinal bleeding (GIB) is a common clinical entity. Expert management of acute GIB requires collaborative care between internists and other specialists. This article reviews the presentation, treatment, and prevention of acute GIB using recommendations from recent guidelines and expert panel reviews. The article acknowledges the pivotal role played by primary care providers in the inpatient and outpatient management of acute GIB.
Common genetic variation in alcohol-related hepatocellular carcinoma: a case-control genome-wide association study
Authors: Eric Trépo, Stefano Caruso, Jie Yang, Sandrine Imbeaud, Gabrielle Couchy, Quentin Bayard, Eric Letouzé, Nathalie Ganne-Carrié, Christophe Moreno, Abderrahim Oussalah, Cyrille Féray, Jean Frédéric Blanc, Bruno Clément, Patrick Hillon, Jérôme Boursier, Valérie Paradis, Julien Calderaro, Viviane Gnemmi, Jean-Charles Nault, Jean-Louis Guéant, Jacques Devière, Isabelle Archambeaud, Carole Vitellius, Bruno Turlin, Jean-Pierre Bronowicki, Thierry Gustot, Angela Sutton, Marianne Ziol, Pierre Nahon, Jessica Zucman-Rossi, Clément Meiller, Qian Cao, Théo Z. Hirsch, Sandra Rebouissou, Delphine Degré, Lukas Otero Sanchez, Nicolas Rosewick, Eric Quertinmont, Mireille Desille-Dugast, Muriel François-Vié, Cécile Moins, Emmanuelle Leteurtre, Guillaume Lassailly, Massih Ningarhari, Emmanuel Boleslawski, Vanessa Cottet
Journal: The Lancet Oncology (2021)
Raman Spectroscopy and Machine Learning Reveals Early Tumor Microenvironmental Changes Induced by Immunotherapy
Authors: Santosh Kumar Paidi, Joel Rodriguez Troncoso, Piyush Raj, Paola Monterroso Diaz, Jesse D. Ivers, David E. Lee, Nathan L. Avaritt, Allen J. Gies, Charles M. Quick, Stephanie D. Byrum, Alan J. Tackett, Narasimhan Rajaram, Ishan Barman
Journal: Cancer Research (2021)

Abstract Cancer immunotherapy provides durable clinical benefit in only a small fraction of patients, and identifying these patients is difficult due to a lack of reliable biomarkers for prediction and evaluation of treatment response. Here, we demonstrate the first application of label-free Raman spectroscopy for elucidating biomolecular changes induced by anti–CTLA4 and anti–PD-L1 immune checkpoint inhibitors (ICI) in the tumor microenvironment (TME) of colorectal tumor xenografts. Multivariate curve resolution–alternating least squares (MCR-ALS) decomposition of Raman spectral datasets revealed early changes in lipid, nucleic acid, and collagen content following therapy. Support vector machine classifiers and random forests analysis provided excellent prediction accuracies for response to both ICIs and delineated spectral markers specific to each therapy, consistent with their differential mechanisms of action. Corroborated by proteomics analysis, our observation of biomolecular changes in the TME should catalyze detailed investigations for translating such markers and label-free Raman spectroscopy for clinical monitoring of immunotherapy response in cancer patients. Significance: This study provides first-in-class evidence that optical spectroscopy allows sensitive detection of early changes in the biomolecular composition of tumors that predict response to immunotherapy with immune checkpoint inhibitors.
5-Aminolevulinate improves metabolic recovery and cell survival of the liver following cold preservation
Authors: Xiaomei Zhang, Liang Chen, Wei Liu, Juan Shen, Haobin Sun, Jinliang Liang, Guo Lv, Guihua Chen, Yang Yang, Jingxing Ou
Journal: Theranostics (2022)

Rationale: Hibernating thirteen-lined ground squirrels (GS; Ictidomys tridecemlineatus) are naturally adapted to prolonged periods of ultraprofound hypothermia (body temperature < 5 °C) during torpor, and drastic oscillations of body temperature and ischemia/reperfusion-like stress during their short euthermic interbout arousals.Thus, their superior adaptability may hold tremendous promise for the advancement of donor organ cold preservation and subsequent organ transplantation.However, bridging hibernation research and translational medicine has been impeded by a dearth of in vitro research tools, till the recent establishment of the GS induced pluripotent stem cells (iPSCs).In this study, we reported the generation of functional hepatocyte-like cells (HLCs) from GS iPSCs.As temperature and oxygen supply affect cellular metabolism, we hypothesized that the GS HLCs can metabolically counter drastic temperature and oxygen supply changes.Differentially regulated metabolites can be evaluated and included into the preservation solution to mitigate temperature and ischemia/reperfusion-associated damage to donor livers.Methods: A protocol has been developed to produce GS iPSCs-derived HLCs.Comparative metabolomic analysis on GS HLCs and human donor liver samples revealed changes in metabolites caused by cold storage and rewarming.Human embryonic stem cell (ESC)-derived HLCs and ex vivo cold preservation and reperfusion of isolated rat livers were used to assess candidate metabolites that may have protective effects against preservation-related injuries.Results: GS iPSCs were efficiently differentiated into expandable, cryopreservation-compatible and functional HLCs.Metabolomic analysis unveiled distinct changes of mitochondrial metabolites between GS and human cells following cold storage and rewarming.GS and human HLC-based experiments indicated that the metabolism of 5-aminolevulinate (5-ALA) is key to restricting free radical production during rewarming.Survival of human HLCs was significantly increased following cold exposure and rewarming, as supplemented 5-ALA enhanced Complex III activity and improved mitochondrial respiration.Further, 5-ALA mitigated damage in rat livers following 48-h cold preservation and ex vivo reperfusion.Metabolomic and transcriptomic analyses revealed that supplemented 5-ALA promoted both anabolic and catabolic activities while alleviating cell death, inflammation, hypoxia and other stress responses in isolated perfused rat livers. Conclusion:In the liver, rewarming from ultraprofound hypothermia imposes complex metabolic challenges and stresses on the mitochondria.Metabolites such as 5-ALA can help alleviate mitochondrial stress.Supplementing 5-ALA to the liver preservation solution can substantially improve the functional recovery of rat livers following prolonged cold preservation, rewarming and reperfusion.
DevKidCC allows for robust classification and direct comparisons of kidney organoid datasets
Authors: Sean B. Wilson, Sara E. Howden, Jessica M. Vanslambrouck, Aude Dorison, Jose Alquicira-Hernandez, Joseph E. Powell, Melissa H. Little
Journal: Genome Medicine (2022)

Abstract Background While single-cell transcriptional profiling has greatly increased our capacity to interrogate biology, accurate cell classification within and between datasets is a key challenge. This is particularly so in pluripotent stem cell-derived organoids which represent a model of a developmental system. Here, clustering algorithms and selected marker genes can fail to accurately classify cellular identity while variation in analyses makes it difficult to meaningfully compare datasets. Kidney organoids provide a valuable resource to understand kidney development and disease. However, direct comparison of relative cellular composition between protocols has proved challenging. Hence, an unbiased approach for classifying cell identity is required. Methods The R package, scPred , was trained on multiple single cell RNA-seq datasets of human fetal kidney. A hierarchical model classified cellular subtypes into nephron, stroma and ureteric epithelial elements. This model, provided in the R package DevKidCC ( github.com/KidneyRegeneration/DevKidCC ), was then used to predict relative cell identity within published kidney organoid datasets generated using distinct cell lines and differentiation protocols, interrogating the impact of such variations. The package contains custom functions for the display of differential gene expression within cellular subtypes. Results DevKidCC was used to directly compare between distinct kidney organoid protocols, identifying differences in relative proportions of cell types at all hierarchical levels of the model and highlighting variations in stromal and unassigned cell types, nephron progenitor prevalence and relative maturation of individual epithelial segments. Of note, DevKidCC was able to distinguish distal nephron from ureteric epithelium, cell types with overlapping profiles that have previously confounded analyses. When applied to a variation in protocol via the addition of retinoic acid, DevKidCC identified a consequential depletion of nephron progenitors. Conclusions The application of DevKidCC to kidney organoids reproducibly classifies component cellular identity within distinct single-cell datasets. The application of the tool is summarised in an interactive Shiny application, as are examples of the utility of in-built functions for data presentation. This tool will enable the consistent and rapid comparison of kidney organoid protocols, driving improvements in patterning to kidney endpoints and validating new approaches.
Micro-elimination of hepatitis C in people who use injectable drugs along the USA–Mexico border: a modelling study
Authors: Lara K Marquez, Clara Fleiz, Carlos Magis-Rodriguez, Natasha K Martin
Journal: The Lancet Global Health (2022)

The prevalence of hepatitis C in people who use injectable drugs along the USA-Mexico border is very high (>90%). In 2019, the Mexican government committed to providing hepatitis C treatment with priority for people who use injectable drugs, people living with HIV, and people living in prison or jail, yet the immediate plan for prioritized treatment allocation and rollout remained unclear prior to the COVID-19 pandemic. Understanding which prevention and intervention strategies and at what level of scale-up can achieve the WHO goal of 80% incidence reduction by 2030 along the border is needed.We adapted our previously published dynamic, deterministic model of hepatitis C transmission among people who use injectable drugs to determine the direct-acting antiviral treatment allocations in combination with harm-reduction interventions (opiate agonist therapy and needle and syringe programmes) needed to achieve the WHO elimination goal between 2021 and 2030. Our model is calibrated and parameterised to epidemiological data from Ciudad Juarez (where approximately 10 000 people who use injectable drugs reside and the seroprevalence of hepatitis C among people who use injectable drugs is 92%) and minimal harm reduction.To reduce hepatitis C incidence by 80% between 2021 and 2030, 910 direct-acting antiviral treatments per 10 000 people who use injectable drugs in Ciudad Juarez per year are needed. Overall, fewer treatments are required if combined with harm reduction. If opiate agonist therapy and needle and syringe programmes are scaled-up to 50%, approximately 30-40% fewer people who use injectable drugs would need to be treated each year (650 direct-acting antiviral treatments per 10 000 people who use injectable drugs per year). Between 2021 and 2030, using direct-acting antivirals alone, an estimated total of 8190 people who use injectable drugs in Ciudad Juarez would need to be treated, compared with 6255 (nearly 25%) fewer people who use injectable drugs overall if treatment is scaled-up alongside 50% of opiate agonist therapy and needle and syringe programmes combination intervention coverage.Hepatitis C treatment with direct-acting antivirals should be prioritised for people who use injectable drugs along the USA-Mexico border and progress towards hepatitis C elimination should be monitored. Regional hepatitis C micro-elimination among people who use injectable drugs could be possible if national treatment allocations are prioritised and distributed to people who use injectable drugs as planned and in the presence of essential harm-reduction programmes.National Institutes of Health; Fogarty International Center grant D43TW009343; and National Institute of Allergy and Infectious Diseases and National Institute on Drug Abuse grant R01AI147490.
From engineered heart tissue to cardiac organoid
Authors: Jaeyeaon Cho, Hyein Lee, Woongchan Rah, Hyuk Jae Chang, Young-Sup Yoon
Journal: Theranostics (2022)

The advent of human pluripotent stem cells (hPSCs) presented a new paradigm to employ hPSC-derived cardiomyocytes (hPSC-CMs) in drug screening and disease modeling. However, hPSC-CMs differentiated in conventional two-dimensional systems are structurally and functionally immature. Moreover, these differentiation systems generate predominantly one type of cell. Since the heart includes not only CMs but other cell types, such monolayer cultures have limitations in simulating the native heart. Accordingly, three-dimensional (3D) cardiac tissues have been developed as a better platform by including various cardiac cell types and extracellular matrices. Two advances were made for 3D cardiac tissue generation. One type is engineered heart tissues (EHTs), which are constructed by 3D cell culture of cardiac cells using an engineering technology. This system provides a convenient real-time analysis of cardiac function, as well as a precise control of the input/output flow and mechanical/electrical stimulation. The other type is cardiac organoids, which are formed through self-organization of differentiating cardiac lineage cells from hPSCs. While mature cardiac organoids are more desirable, at present only primitive forms of organoids are available. In this review, we discuss various models of hEHTs and cardiac organoids emulating the human heart, focusing on their unique features, utility, and limitations.
Abstract P075: An Innovative Statistical Approach To Investigate The Association Of Movement Behaviors On High-sensitivity C-reactive Protein: The Jackson Heart Study
Authors: Robert Booker, Robert L Newton, Keith C Norris, Roland J Thorpe, Mercedes R Carnethon, Megan E Holmes
Journal: Circulation (2022)

Introduction: Over the course of 24 hours, humans engage in multiple movement behaviors including sleep, physical activity (PA), and sedentary behavior (SB) that are each associated with high-sensitivity C-reactive protein (hs-CRP). Traditional regression models do not allow for the estimation of the relative contributions of each of these behaviors on hs-CRP as they are correlated and sum to 100% of the whole day. Compositional and isotemporal substitution analyses will allow us to estimate how exchanging one behavior for another influences hs-CRP. We hypothesize an equal time amount substitution of PA (subtraction) with SB will be associated with higher hs-CRP, while substitution of sleep or SB with PA will be associated with lower hs-CRP. Methods: The Jackson Heart Study (JHS) was designed to investigate cardiovascular disease risk factors among African Americans in the Jackson, MS area. PA was self-reported via the JHS PA Cohort survey and used to calculate minutes per day of total PA. Usual nightly hours of sleep was self-reported using the JHS Sleep History Form. As compositional analysis examines proportions of a whole, SB was calculated as remaining time during the day after PA and sleep. Blood samples of hs-CRP (mg·dl -1 ) were measured by the immunoturbidimetric CRP-latex assay method. Due to being skewed right, hs-CRP was natural logarithmic transformed. Iso-temporal substitutions were calculated as a substitution in one movement behavior of 15 minutes for another while maintaining the third. Models adjusted for age, sex, smoking status, education, body mass index, and metabolic syndrome criteria. Results: The mean age of the 3,716 participants was 61.94 years (SD; 12.06) and the majority of participants were female (63.5%). The median hs-CRP concentration was 0.29 mg·dl -1 (IQR; 0.12, 0.65). Most of daily minutes was spent in SB (72.12%), followed by sleep (26.30%), and PA (1.58%). When replacing 15 minutes of PA for SB or sleep, the predicted hs-CRP was 0.03 mg·dl -1 (95% CIs; -0.00, 0.06) greater than the hs-CRP of the average participant. Substituting 15 minutes of SB for PA was associated with a predicted lowering of hs-CRP of 0.01 mg·dl -1 (-0.02, 0.00) and was similar for substituting 15 minutes of sleep for PA 0.01 mg·dl -1 (-0.03, 0.00). Substituting 15 minutes of SB for sleep, or sleep for SB was associated with no predicted change in hs-CRP (0.00 mg·dl -1 ). Conclusions: Efforts should strive to increase, or at the very least, maintain PA levels to improve measures of systemic inflammation. Future research could aim to tie the proportion of time each day spent in each movement activity to cardiovascular disease risk factors and subclinical or clinical cardiovascular disease.