tbuckley/cabot-search huggingface dataset:
KMT9 Controls Stemness and Growth of Colorectal Cancer
Authors: Christopher Berlin, Félicie Cottard, Dominica Willmann, Sylvia Urban, Stephan M. Tirier, Lisa Marx, Karsten Rippe, Mark Schmitt, Valentina Petrocelli, Florian R. Greten, Stefan Fichtner-Feigl, Rebecca Kesselring, Eric Metzger, Roland Schüle
Journal: Cancer Research (2021)

Abstract Colorectal cancer is among the leading causes of cancer-associated deaths worldwide. Treatment failure and tumor recurrence due to survival of therapy-resistant cancer stem/initiating cells represent major clinical issues to overcome. In this study, we identified lysine methyltransferase 9 (KMT9), an obligate heterodimer composed of KMT9α and KMT9β that monomethylates histone H4 at lysine 12 (H4K12me1), as an important regulator in colorectal tumorigenesis. KMT9α and KMT9β were overexpressed in colorectal cancer and colocalized with H4K12me1 at promoters of target genes involved in the regulation of proliferation. Ablation of KMT9α drastically reduced colorectal tumorigenesis in mice and prevented the growth of murine as well as human patient-derived tumor organoids. Moreover, loss of KMT9α impaired the maintenance and function of colorectal cancer stem/initiating cells and induced apoptosis specifically in this cellular compartment. Together, these data suggest that KMT9 is an important regulator of colorectal carcinogenesis, identifying KMT9 as a promising therapeutic target for the treatment of colorectal cancer. Significance: The H4K12 methyltransferase KMT9 regulates tumor cell proliferation and stemness in colorectal cancer, indicating that targeting KMT9 could be a useful approach for preventing and treating this disease.
Abstract P139: Changes In Sex Hormones In Premenopausal Black And White Women Associated With Childbearing: The Cardia Women’s Study.
Authors: Sadaf Dabeer, Katherine H Ingram, Duke Appiah, Melissa Wellons, Catherine Kim, Dhananjay Vaidya, David S Siscovick, Cora E Lewis, Charles Quesenberry, Pamela Schreiner, Ronit Calderon-Margalit, Monika Sarkar, Erica P Gunderson
Journal: Circulation (2022)

Introduction: Sex hormone binding globulin (SHBG) levels in blood are associated with bioavailability of sex hormones, glucose metabolism, and cardiometabolic health of premenopausal women. Low SHBG levels are associated with insulin resistance in women. Pregnancy is characterized by 6-10-fold increase in SHBG levels. This study is designed to evaluate the long-term associations among pregnancy, and SHBG, free and total testosterone levels in premenopausal women. Methods: Premenopausal women, aged 20-32 years, from the CARDIA Women’s Study cohort were tested for levels of serum SHBG, free testosterone, and total testosterone. Hormonal, anthropometric, socio-demographic, and behavioral data, along with self-reported pregnancy and birth data, were collected at baseline (1987-88 [Y0]; n=1,191) and after eight years (Y8; n=809) and 14 years (Y14; n=474) for follow-up. Participants who were pregnant, breastfeeding, had diabetes, hysterectomy, or were using oral contraceptive at any time point were excluded. Participants were divided in parity groups of 0, 1, and 2+births for analyses. Eight-year decrements of SHBG, free and total testosterone were used for primary analyses and 14-year decrements were used for secondary analyses Results: SHBG levels decreased more in parous than nulliparous women in a fully adjusted model including race, CARDIA field center, age, education, alcohol, smoking status, baseline BMI, weight gain and change in waist girth. Total testosterone decreased more in parous women between Y0-Y10 but not thereafter. No significant differences in free testosterone levels were observed among parity change groups in fully adjusted models. Hormone decrement analyses from fully adjusted model Conclusion: Childbearing is associated with a more pronounced long term decrease in SHBG but not with free testosterone levels in premenopausal women. A strong association was observed among parity and total testosterone decrements at 8-year but not 14-year follow-up.
Prevalence of sexually transmitted infections with Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium and Trichomonas vaginalis: findings from the National Survey of Sexual Lifestyles, Attitudes and Health, Slovenia, 2016 to 2017
Authors: Irena Klavs, Maja Milavec, Lina Berlot, Tanja Kustec, Marta Grgič-Vitek, Darja Lavtar, Metka Zaletel, Andrej Golle, Darja Duh, Tjaša Žohar Čretnik
Journal: Eurosurveillance (2022)

BackgroundTo inform prevention and control of sexually transmitted infections (STIs), we need reliable prevalence estimates.AimOne objective of the Slovenian National Survey of Sexual Lifestyles, Attitudes and Health was to estimate the prevalence of STIs with Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium and Trichomonas vaginalis.MethodsData were collected between October 2016 and July 2017 in a probability sample of the general population aged 18-49 years. Computer-assisted face-to-face interviewing and self-completion of questionnaires were used. Respondents were invited to provide urine samples to be tested for STIs.ResultsOf 1,929 survey participants, 1,087 individuals provided urine samples which were tested confidentially for C. trachomatis and a subset (n = 1,023) were tested anonymously for the other STIs. The prevalence of C. trachomatis was 0.5% (95% confidence interval (CI): 0.1-1.8) in men and 1.7% (95% CI: 0.9-3.2) in women. Age-specific prevalence was the highest among individuals aged 18-24 years, 2.8% (95% CI: 0.7-10.6) in men and 4.7% (95% CI: 1.7-12.3) in women. N. gonorrhoea was not detected. Prevalence of M. genitalium was 0.5% (95% CI: 0.1-2.2) in men and 0.3% (95% CI: 0.1-1.1) in women; the highest prevalence was among men aged 25-34 years (1.1%; 95% CI: 0.2-7.5) and women aged 35-49 years (0.5%; 95% CI: 0.1-2.0). T. vaginalis was detected in the sample from one woman (0.2%; 95% CI: 0.1-1.2).ConclusionThe substantial prevalence of C. trachomatis among young adults suggests gaps in testing, diagnosis and treatment.
Letter by Belmadani and Matrougui Regarding Article, “Integrated Stress Response Couples Mitochondrial Protein Translation With Oxidative Stress Control”
Authors: Souad Belmadani, Khalid Matrougui
Journal: Circulation (2022)

Despite available therapies and interventional coronary reperfusion approaches, acute myocardial infarction (MI)-induced morbidity and mortality remains substantial.Therefore, there is a critical unmet need to delineate mechanisms, identify treatable targets to improve cardiac function and structure, and limit the progression of acute MI.Zhang et al 1 documented the effect of the integrated stress response (PERK [PKR-like endoplasmic reticulum resident kinase]/eIF2α [α subunit of eukaryotic initiation factor 2]) dictating protein translation in combination with mitochondrial reactive oxidative stress in acute MI induced by cardiac ischemia/reperfusion (I/R).It is well established that the endoplasmic reticulum (ER) stress PERK and eIF2α pathway induces C/EBP homologous protein (CHOP) induction. 2Previous studies reported the role of ER stress-induced CHOP in cardiac damage induced by I/R injury. 3The inhibition of ER stress-induced CHOP pharmacologically or genetically protects the heart from damage. 3,4The study by Zhang et al 1 reported that acute PERK activation protects against acute I/R injury, whereas chronic PERK activation damages the heart. 5 It would be interesting to determine the concept and delineate the mechanism by which acute PERK activation could favor the cardioprotective pathway through the mitochondria versus the detrimental pathway of chronic PERK activation through CHOP induction.Moreover, the overexpression of ER stress-induced ATF6 (activating transcription factor 6) has been documented to protect the heart against I/R.These complex ER stress pathways in the context of cardiac damage are not clearly understood and future studies are needed to delineate their interaction within the cardiomyocytes in the setting of acute and chronic I/R injury.Another aspect to take into consideration is the fact that the majority of cells in the heart are nonmyocytes.
Abstract 062: Racial And Ethnic Differences In The Population Burden Of Dementia Attributable To Modifiable Risk Factors In The United States
Authors: Mark Lee, Eric A Whitsel, Christy L Avery, Timothy M Hughes, Michael Griswold, Sanaz Sedaghat, Rebecca F Gottesman, Thomas Mosley, Gerardo M Heiss, Pamela L Lutsey
Journal: Circulation (2022)

Introduction: Modifiable risk factors (including cardiovascular traits) are associated with dementia risk. However, it is unknown which risk factors have the greatest influence on dementia rates in the United States, or how that varies by race/ethnicity. Objective: For all Americans and separately by race and ethnicity, we calculated population attributable fractions (PAFs) of dementia for 12 potentially modifiable risk factors: low education, hearing loss, traumatic brain injury, hypertension, excessive alcohol consumption, obesity, smoking, depression, social isolation, physical inactivity, diabetes, and air pollution. Methods: Assuming a causal relationship between risk factors and dementia, we calculated PAFs for dementia using relative risks and prevalence estimates for each risk factor. We used relative risks from recent meta-analyses and prevalence estimates from nationally representative cross-sectional survey data (e.g., NHANES). We estimated prevalence separately by race/ethnicity. We calculated the PAF (for all Americans and separately by race and ethnicity) for each dementia risk factor and a combined PAF accounting for correlations between exposures. Results: In the total population, 42.6% of dementia cases were attributable to the 12 risk factors we considered. The estimated PAF of these risk factors was greater for Black and Hispanic Americans (47.5% and 47.3%, respectively) than it was for White and Asian Americans (41.3% and 37.8%, respectively). The greatest fractions of dementia cases were attributable to key cardiovascular traits: hypertension (20.2%), obesity (20.9%), and physical inactivity (20.1%). These factors were highest within each racial and ethnic group, though the proportions varied (Figure 1). Conclusions: A large fraction of dementia cases are attributable to potentially modifiable factors, especially for Black and Hispanic Americans. Further research is needed to test whether intervening on these factors reduces dementia risk.
Abstract EP18: Cardiopulmonary Testing In Long Covid Versus Non-CovidPatients With Undifferentiated Dyspnea On Exertion
Authors: Alejandra Meza, Darrell B Newman, Alexander S Niven, Michael R Mueller, Nina M Schwenk, Ravindra Ganesh, Ray W Squires, Amanda Bonikowske, Lucio Cappelloni, Thomas G Allison
Journal: Circulation (2022)

Background: COVID-19 reveals new manifestations not only in the acute phase but also in the long term. The latter is what has been termed as ‘post acute sequelae of SARS-CoV-2 infection’ (PASC) — or “long COVID”— with dyspnea as one of its hallmarks. Cardiopulmonary stress testing (CPET) is increasingly being used to better evaluate such patients. Objective: To compare CPET findings of long COVID patients versus non-COVID patients with undifferentiated dyspnea on exertion seen at Mayo Clinic. Methods: A cohort study was carried out using Mayo Clinic’s exercise testing database. The study group included 77 PASC patients confirmed by a positive antigen or PCR test with no prior history of heart or lung disease. PASC patients were compared to 766 non-COVID patients with unspecified dyspnea without known diagnosis of cardiac or pulmonary disease. ANOVA according to the general linear model and Pearson’s Chi square were used for the bivariate analysis of the quantitative and categorical variables, respectively. Analyses were controlled for age, sex, and beta blocker use as appropriate. Both HR and SBP at rest and peak exercise were significantly different between groups, although the absolute differences were small. Results: Compared with the control group, the post-COVID patients were younger (mean age 47 SD ±14.9 years versus 50.5 SD ±10.1 years) and more likely to be female (70.1% (54 of 77) vs 57.6% (441 of 766)). Although there were many significant differences in the CPET results, the most outstanding were a lower FAC (73 SD ±19.4% vs 85.2 SD ±20.8%) and peak VO2 (22 SD ±6.4 ml/kg/min vs 25.8 SD ±7.37 ml/kg/min) in the study group (p&lt;.0001). Also, CNS changes during CPET were reported at higher rates (19.5% (15 of 77) vs 11.4% (87 of 766)) while dyspnea at lower rates (55.8% (43 of 77) vs 65.7% (503 of 766)) in post-COVID patients (p=0.02). When adjusting for age and sex, weight was significantly higher in the study group (p=0.03) although the absolute difference was modest and BMI remained not significant. PFTs did not suggest any pulmonary abnormalities. Conclusions: We identified a high rate of severe exercise limitation among long COVID patients. Young women may be at higher risk for these complications. Pre-exercise PFTs and absence of objective respiratory limitation during CPET argue against a primary pulmonary cause of the observed limitations, though evaluation of cardiac, autonomic, and muscular impairment is pending. Further studies are warranted to untangle the physiologic abnormalities responsible for these observations.
Abstract 042: Trends In Hypertensive Disorders Of Pregnancy Among Nulliparous Individuals With Singleton Live Births In The United States: An Age-period-cohort Analysis Between 1995-2019
Authors: Natalie A Cameron, Lucia Petito, Nilay Shah, Amanda M Perak, Janet M Catov, Natalie A Bello, Simon CAPEWELL, Martin E Oflaherty, Don M Lloyd-jones, Philip Greenland, William GROBMAN, Sadiya Khan
Journal: Circulation (2022)

Introduction: Incidence of hypertensive disorders of pregnancy (HDP) has increased concurrently with maternal age at first birth. To better understand the contributions of age, delivery year (period), and maternal birth year (birth cohort) to HDP rates, we performed an age-period-cohort analysis. Methods: We included data from the National Center for Health Statistics for nulliparous individuals without pre-pregnancy hypertension who were 15-44 years with singleton live births from 1995-2019. We defined HDP as gestational hypertension, preeclampsia or eclampsia. We determined age effects by calculating HDP incidence adjusted separately for period and cohort in each 5-year age group. Period and cohort effects were quantified as rate ratios (RR) comparing age-adjusted HDP incidence to the median period (2005-2009) and cohort (1980-1984), respectively. Age, period, and cohort effects were summarized as the age-standardized estimated annual percent change (EAPC) in HDP rates adjusted for cohort and stratified by self-reported maternal race and ethnicity group (Hispanic, non-Hispanic American Indian/Alaskan Native [AIAN], non-Hispanic Asian-Pacific Islander [API], non-Hispanic Black [NHB], non-Hispanic White [NHW]). Results: Of 38,141,561 individuals included, 0.8% were AIAN, 6.5% API, 20.2% Hispanic, 13.9% NHB, and 57.8% NHW. Mean maternal age increased from 1995-2019 (24.5-26.9). Age, period and cohort were each significantly associated with HDP rates overall and in each race and ethnicity group. Incidence was higher with older maternal age. Age-standardized incidence increased from 1995-2019 (EAPC 2.1%/year [2.1-2.2]). RR of HDP in pregnant individuals born 2000-2004 versus 1980-1984 was 1.5 (1.4-1.5). Differences in RRs among racial and ethnic groups were observed with the largest cohort effects among API and NHB individuals born 2000-2004. ( FIGURE ). Conclusions: More recent generations have experienced substantially higher rates of HDP, even with adjustment for maternal age and delivery year.
Abstract EP24: Menu Calorie Label Use Is Associated With Healthier Diet Quality In Americans
Authors: Jenny Jia, Matthew J O'Brien
Journal: Circulation (2022)

Background: Unhealthy diet quality is a risk factor for cardiometabolic diseases. The Affordable Care Act mandated menu calorie labeling in many food service businesses to promote healthy food choices, but evidence is limited on whether label use affects dietary intake. Hypothesis: We studied the hypothesis that menu calorie label use is associated with healthier diet quality in a nationally representative dataset. Methods: We included individuals age≥16 years from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 who reported buying food from a fast food, sit-down, or buffet restaurant or coffee shop in the past year (n=3,823). The exposure, menu calorie label use, was dichotomized to participants who used labels vs. those who did not use labels at any of the mentioned food service sites using the Consumer Behavior Phone Follow-up Module survey data. The primary outcome was diet quality measured by the Healthy Eating Index 2015 (HEI-2015; range 0-100) using two days of 24-hour diet recall data (n=3,809). Secondary outcomes included certain HEI components (added sugars, saturated fats, fruits, vegetables) and total daily calories. We used multiple linear regression to measure the association between label use and outcomes, accounting for the complex survey design of NHANES and adjusting for demographic, socioeconomic, and comorbidity factors. Results: Of 3,806 participants (representing 224,305,985 Americans), 903 (26.9 weighted %) used menu calorie labels. Those who used menu calorie labels were more likely to be younger (μ=43.3 years, SE 0.58), female (60.8%), and with higher educational attainment (college degree or higher 44.6%), and less likely to be low-income (≤200% of federal poverty level 19.5%) compared to those who did not use them (age μ=47.1 years, SE 0.79; female 49.7%; college degree or higher 26.9%; ≤200% FPL 33.6%). Compared to participants who did not use calorie labels, those who used menu calorie labels had HEI-2015 scores that were 3.95 points (95% CI 2.28, 5.63) higher and consumed less calories (β=-240.4 kcal, 95% CI -384.3, -96.5). Of the HEI-2015 components, participants who used menu calorie labels ate more vegetables (β=0.41 points, 95% CI 0.20, 0.62) and less added sugars (β=0.74 points, 95% CI 0.24, 1.24). No differences were seen in saturated fat or fruit intake. Conclusions: Individuals who used menu calorie labels had significantly healthier dietary intake and consumed less calories compared to those who did not use labels, suggesting that providing caloric information may influence healthy food decisions. Those who did not use labels had lower education level and family income. Further research is needed to explore how people use label information to make food choices and why individuals may not use calorie labels to improve utility and effectiveness of point-of-purchase nutrition information without amplifying health disparities.
Appropriate management of polycythaemia vera with cytoreductive drug therapy: European LeukemiaNet 2021 recommendations
Authors: Monia Marchetti, Alessandro Maria Vannucchi, Martin Griesshammer, Claire Harrison, Steffen Koschmieder, Heinz Gisslinger, Alberto Álvarez-Larrán, Valerio De Stefano, Paola Guglielmelli, Francesca Palandri, Francesco Passamonti, Giovanni Barosi, Richard T Silver, Rüdiger Hehlmann, Jean-Jacques Kiladjian, Tiziano Barbui
Journal: The Lancet Haematology (2022)
“Did You Leave the Wire in?” A Striking Case of Linear Pulmonary Cement Embolism
Authors: Shishir Rao, Madhav Chopra, Swathy Puthalapattu
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

"“Did You Leave the Wire in?” A Striking Case of Linear Pulmonary Cement Embolism." American Journal of Respiratory and Critical Care Medicine, 204(10), pp. e110–e112
Telehealth for Substance Use Disorders: A Rapid Review for the 2021 U.S. Department of Veterans Affairs and U.S. Department of Defense Guidelines for Management of Substance Use Disorders
Authors: Stacey Uhl, Aaron Bloschichak, Amber Moran, Kristina McShea, Megan S. Nunemaker, James R. McKay, Kristen E. D’Anci
Journal: Annals of Internal Medicine (2022)

Approximately 20.4 million Americans met criteria for a substance use disorder (SUD) in 2019; however, only about 12.2% of persons with an SUD receive specialty care. Telehealth offers alternatives to traditional forms of substance use treatment.To synthesize recent findings on the efficacy of telehealth for SUDs.MEDLINE, Embase, PubMed, and the Cochrane Library from January 2015 through August 2021 (English language only).Randomized controlled trials (RCTs) of adults with a diagnosis of SUD based on the Diagnostic and Statistical Manual of Mental Disorders or International Classification of Diseases.One investigator abstracted data and assessed study quality, and a second checked for accuracy.This rapid review synthesized evidence from 17 RCTs. Evidence is very uncertain that telehealth provided as videoconference therapy (1 RCT) or web-based cognitive behavioral therapy (CBT) (3 RCTs) has similar effects to in-person therapy for improving abstinence from alcohol or cannabis. Low-strength evidence suggests that web-based CBT has similar effects for improving abstinence in multiple SUDs (2 RCTs). Low-strength evidence suggests that adding supportive text messaging to follow-up care improves abstinence and amount of alcohol per day (2 RCTs) but does not improve emergency department visits or frequency of consumption (2 RCTs). Enhanced telephone monitoring likely reduces readmissions for SUD detoxification compared with usual follow-up alone (1 RCT) but does not reduce days of substance use (low-strength evidence).Narrative synthesis, heterogeneity of telehealth interventions, no assessment of publication bias, and study methodology.Evidence is very uncertain that telehealth is similar to in-person care for SUD outcomes. Limited evidence suggests some benefit of adding telehealth to usual SUD care.U.S. Department of Veterans Affairs Veterans Health Administration.