bluuebunny/crossref_metadata_2025_split huggingface dataset:
Meal-Related Changes in Apolipoprotein Particles After Treatment With an Antisense Oligonucleotide to Apolipoprotein CIII
Authors: Brite Brianna , Lightbourne Marissa , Startzell Megan S , Shamburek Robert , Brown Rebecca J 
Published: May 2021

Abstract
Background: Lipodystrophy (LD) is defined by partial or complete absence of adipose tissue causing metabolic complications such as high triglycerides (TG). Apolipoprotein CIII (ApoCIII) contributes to high TG by inhibiting lipoprotein lipase (LPL). Measurement of lipoprotein particles using NMR can offer insights into lipid metabolism. Hypothesis: We hypothesized that during a mixed meal test (MMT), clearance of TG-rich lipoprotein particles (TRLP) measured by NMR would increase in LD patients given an antisense oligonucleotide (ASO) to lower ApoCIII. Experimental Design: Five adults with partial LD underwent an MMT (with 18g fat) at week 0 and after 16 weeks (wk) of the ApoCIII ASO. Blood samples were obtained at 0, 30, 60, 120, 180, 240, 300, and 360 minutes (min) and assessed using NMR with the LP4 deconvolution algorithm, which separates TRLPs into 5 size categories: very large (VL), large (L), medium (M), small (S), and very small (VS), all expressed as nmol/L. Major Results: At wk 0, patients had high fasting TG (median 523 mg/dL, IQR 335–1060 mg/dL, normal &lt;150), which decreased after 16wk of ASO[BR([1] (196 mg/dL) Mean TRLP over the 360 min of the MMT was lower after ASO (181.6±14.1 at wk 0, 80.4±2.2 at wk 16). At wk 0, mean L_TRLP during the MMT was 26.8 ± 6.9 and decreased to 9.3±1.3 at wk 16. At wk 0, L_TRLP rose during the MMT to a peak at 180min; at wk 16 there was no rise in L_TRLP during the MMT. Mean S_TRLP during the MMT increased from wk 0 (5.4±3.9) to wk 16 (13.4±10.4). At wk 0, S_TRLP increased minimally during the MMT from 5.2±11.7 at 0 min to 10.9±15.2 at 360 min. At wk 16 there was a more notable rise in S_TRLP in the last 3 hrs of the MMT, from 12.2±15.1 at 0 min to 37.6±28.6 at 360 min. Interpretation of Results and Conclusions: As expected, an ApoCIII ASO lowered fasting and postprandial TG and TRLP. There was minimal rise or fall in any subclass of TRLP during the MMT, either before or after ASO, likely due to the small fat load, which was chosen due to concern for triggering pancreatitis in this at-risk group. The greater post-prandial fluctuation of L_TRLP prior to ASO may represent appearance and disappearance of chylomicron remnants; at wk 16 this was not seen, perhaps due to more rapid clearance of chylomicron remnants by LPL. The larger increase in S_TRLP at the end of the MMT at wk 16 may reflect more rapid lipolysis of L_TRLP by LPL during ASO treatment, thus generating S_TRLP. Next steps include measuring apoB48 and apoB100 during the MMT to distinguish VLDL from chylomicrons, accruing a larger sample size, and collecting MMT data in healthy controls.
Muscle Function is Associated With Presence, New-onset, or Worsening of Hepatic Steatosis Assessed by Biochemical Parameters, Independent of Muscle Mass
Authors: Hong Namki , Lee Seunghyun , Kim Kyoungjin , Shim Jee-Seon , Kim Hyeon Chang , Rhee Yumie 
Published: May 2021

Abstract
Non-alcoholic fatty liver disease (NAFLD) becomes a major health problem leading to metabolic complications and end-stage liver disease, lacking effective therapeutic interventions. Skeletal muscle deficit, or sarcopenia, is related to accelerated accumulation of ectopic fat at liver. Skeletal muscle can be a novel intervention target of NAFLD. However, previous studies focused on the association between muscle mass and NAFLD, whereas the association of muscle function with NAFLD, a more clinically relevant assessment regarding skeletal muscle, remains unclear. Among participants enrolled between 2013 to 2014 in cardiovascular and Metabolic Diseases Etiology Research Center (CMERC) study (n=807), a cohort of community-dwelling Korean adults to study cardiovascular risk factors, a total of 500 individuals were recruited for 5-year follow-up. Hepatic steatosis was defined by hepatic steatosis index 36 or higher (HSI=8X(AST/ALT)+BMI+2 [if diabetes]+2 [if female]). New-onset of hepatic steatosis was defined as newly developed hepatic steatosis at current follow-up compared to baseline and worsening of HSI was defined as the highest quartile of HSI changes (2 or higher HSI increase). Muscle function was assessed by peak countermovement jump power relative weight (W/kg), 5 times chair rise test (CRT; in seconds), and grip strength (GS; in kg). Appendicular lean mass (ALM) was measured using bioimpedance analysis (InBody770, Biospace, Seoul, Korea). A total of 439 subjects (women 74%; mean age 57 ± 8 year) were analyzed after excluding those with excessive alcohol intake (n=51) and any missing values (n=10). Hepatic steatosis was present in 40% of subjects, which was increased from baseline period (33%, p&lt;0.001). Low peak jump power (adjusted odds ratio [aOR] 1.14 per 1 W/kg decrease), GS (aOR 1.08 per 1kg decrease), and CRT performance (aOR 1.09 per 1 second increase; p&lt;0.05 for all) were all associated with elevated odds of hepatic steatosis, after adjustment for age, gender, height, ALM, and metabolic syndrome components. Compared to those without hepatic steatosis at baseline and follow-up, those with persistent hepatic steatosis had significantly lower jump power in both men and women (33 vs. 40 W/kg in men, p=0.027; 26 vs. 29 W/kg in women, p&lt;0.001). Jump power remained as robust predictor for new-onset hepatic steatosis or worsening of HSI (aOR 1.05 per 1W/kg decrease, p=0.044), whereas GS, CRT, and ALM were not. Muscle function measured by jump power was associated with presence or worsening of hepatic steatosis assessed by biochemical parameters, independent of muscle mass. Acknowledgement: We thank CMERC participants and all research staffs for this work. Funding: This study was supported by research grants from Hanmi Pharmaceutical Co.,Ltd. (4-2018-0845).
Serum Soluble (Pro)renin Receptor Level as a Prognostic Factor in Patients Undergoing Maintenance Hemodialysis
Authors: Morimoto Satoshi , Amari Yoshifumi , Suda Chikahito , Ichihara Atsuhiro 
Published: May 2021

Abstract
Background: The (pro)renin receptor [(P)RR)] is a multifunctional protein with roles in angiotensin II-dependent and -independent intracellular cell signaling and as an adaptor protein between the Wnt receptor complex and vacuolar proton-translocating adenosine triphosphatase. The (P)RR is cleaved to generate soluble (P)RR [s(P)RR], reflecting the status of the tissue renin-angiotensin system and/or activity of the (P)RR. Patients undergoing hemodialysis (HD) have poor prognosis because of the increased prevalence of cardiovascular and malignant diseases. This study was conducted to investigate whether the s(P)RR level is associated with new onset of cardiovascular events or malignant diseases and prognosis in patients undergoing HD. Methods: A total of 258 patients undergoing maintenance HD who were enrolled in our cohort study investigating the relationships between serum s(P)RR levels and background factors were prospectively followed up for 60 months. We investigated the relationships between s(P)RR levels and new onset of cardiovascular events or malignant diseases and mortality during the follow-up period. Results: The cumulative incidence of new onset of cardiovascular events (P = 0.009) and cardiovascular deaths (P &lt; 0.001), but not of malignant diseases, was significantly greater in patients with higher serum s(P)RR level (≥ 29.8 ng/ml) than in those with lower s(P)RR level (&lt; 29.8 ng/ml). A high serum s(P)RR level was independently correlated with cardiovascular mortality (P = 0.046). Conclusions: These data showed that the serum s(P)RR level is associated with cardiovascular events and mortality, suggesting that the serum s(P)RR level could be used as a biomarker for selecting patients requiring intensive care.
Statin Intolerance: Prevalence and Management in a Specialized Lipid Clinic
Authors: Turdo Yannick , Collet Tinh-Hai 
Published: May 2021

Abstract
Statins are recommended and used as first-line treatment to prevent cardiovascular disease, but high rates of adverse events and subsequent discontinuation can prevent effective treatment in some patients. We aimed to describe the intensity, nature and frequency of adverse effects caused by statins and other lipid-lowering drugs, and to assess their association with clinical predictors and treatment strategies. This is a retrospective study of 121 consecutive unselected patients followed at a specialized lipid referral clinic in Lausanne University Hospital, Switzerland, in 2018. Adverse effects were reported by 58% of patients, causing musculoskeletal (72%), neurologic (40%), gastrointestinal (25%) and other (25%) symptoms. Gastrointestinal symptoms affected 35% of women, but only 12% of men (p=0.06). Statins caused more adverse effects than other drugs, with atorvastatin (63%) and simvastatin (64%) achieving the lowest rates, pravastatin (87%) and fluvastatin (100%) the highest. Fenofibrate was associated with significantly less frequent adverse effects than statins (p=0.006). Either adapting, or terminating the treatment, led to 86% and 88% lower intensity of symptoms, respectively. While the predominance of musculoskeletal symptoms caused by lipid-lowering drugs is known, symptoms affecting other organ systems should not be ignored. Statins were the lipid-lowering drug class with the highest rates of adverse effects. To maintain compliance and cardiovascular prevention, treatment strategies such as a change of dosage, frequency of administration, daily timing, or switching active substance can contribute to better tolerance of statin treatment. Further investigation is needed to establish specific treatment strategies for individual patient profiles.
Total Testosterone Confounds the Association Between Total Bilirubin and Dyslipidemia
Authors: Visaria Aayush , Raju Priyanka , James Joel , Islam Sumaiya , Khangura Karen K , Amanullah Amir , Polamarasetti Pooja 
Published: May 2021

Abstract
Background: The mechanism for the association between total bilirubin (TBili) and dyslipidemia remains unclear. Total testosterone (TT) has been implicated in reducing bilirubin conjugation and decreasing atherogenic lipids. We hypothesized that 1) TBili was inversely associated with dyslipidemia, and 2) TT confounded this association.
Methods: Our study population consisted of 5,878 (2,730 male and 3,148 non-pregnant female) adults aged ≥20 years from the 2011–2016 National Health and Nutrition Examination Survey (NHANES). We excluded those taking self-reported cholesterol medications. Participants with transaminitis (AST or ALT &gt;45 IU/L; AST/ALT &gt;5), excessive alcohol consumption (&gt;20 drinks/week for males; &gt;10 for females), iron overload (transferrin &gt;50%), or positive hepatitis B/C serology were also excluded. We categorized TBili into sex-specific quartiles (Male: &lt;0.5, 0.5–0.6, 0.6–0.8, ≥0.8 mg/dl; Female: &lt;0.4, 0.4–0.5, 0.5–0.6, ≥0.6). Dyslipidemia was defined as elevated TG (≥150 mg/dl) or low HDL (&lt;40 mg/dl for male; &lt;50 for female). We used survey design-adapted multivariable logistic regression, adjusting for TT, demographics, cardiometabolic factors, and liver function. We also stratified by sex-specific median TT levels (386 ng/dl in males; 18.5 ng/dl in females) to determine effect modification. Further, we determined whether the association between TBili and dyslipidemia persisted in males with TT deficiency (&lt;280 ng/dl).
Results: Among the 5,878 adults, 1,013 (38%) males & 958 (30%) females had elevated TG, and 803 (29%) males & 1,146 (33%) females had low HDL. Males in the highest quartile (Q4) of TBili had age-adjusted, mean (SD) 50.1 (3.5) mg/dl lower TG and 4.0 (0.9) mg/dl higher HDL than males in the lowest quartile (Q1; p&lt;0.0001). Females in Q4 had 36.4 (4.9) mg/dl lower TG and 5.1 (1.4) mg/dl higher HDL than Q1 (p&lt;0.0001). Males and females in Q4 had 60% and 59% lower odds, respectively, of elevated TG compared to Q1 (adjusted OR [95% CI]; Male: 0.40 [0.28, 0.57], Female: 0.41 [0.32, 0.52]). Males and females in Q4 had 44% and 39% lower odds, respectively, of low HDL compared to Q1 (Male: 0.56 [0.38, 0.81], Female: 0.61 [0.42, 0.90]). Adjusting for TT increased the parameter estimate for Q4, relative to the univariate estimate, by 21% in both sexes. There was no significant difference in TT-stratified odds of elevated TG or low HDL. Among the 544 (19%) males with TT deficiency, Q4 had 56% lower odds of elevated TG and 46% lower, but insignificant, odds of low HDL (aOR [95% CI]; TG: 0.44 [0.21, 0.89], HDL: 0.54 [0.26, 1.12]).
Conclusion: TBili was inversely associated with elevated TG and low HDL. TT confounded, but did not modify, this association. Future studies examining TBili’s antiatherogenic role should adjust for TT.
ULK1 Regulates Hepatic Lipid Metabolism via Autophagy Independent Mechanisms
Authors: Koo Young Do , Castillo Romilia Tatiana , Hinton Antentor Othrell , Abel Evan Dale 
Published: May 2021

Abstract
Non-alcoholic steatohepatitis (NASH), a major complication of obesity, diabetes, and metabolic syndrome has emerged as a leading cause of chronic liver disease and a risk factor for hepatocellular carcinoma. Autophagy is a critical pathway for the degradation of intracellular components by lysosomes. Established functions for autophagy in hepatic lipid metabolism and insulin sensitivity suggest a mechanistic link between altered autophagy and NASH. However, the interactions between insulin sensitivity, NASH, and autophagy are incompletely understood. The Unc-51 Like Autophagy Activating Kinase 1 (ULK1) is the only serine/threonine kinase in the core autophagy pathway and thus represents an excellent drug target. In this study, we observed that ULK1 may directly regulate insulin signaling and lipid metabolism via mechanisms that might involve modulation of AKT dephosphorylation. Surprisingly, silencing ULK1 did not significantly alter autophagy in hepatocytes despite impairing insulin-stimulated activation of AKT. To further elucidate the autophagy-independent role of ULK1 in hepatic lipid metabolism and insulin action, ULK1 liver-specific knock-out mice were generated. L-ULK1 KO mice exhibited impaired glucose tolerance and insulin resistance on a normal chow diet or 60% high-fat diet (HFD). In young mice (4 weeks after birth), the expression of genes that regulate de novo lipogenesis, such as FAS, SCD1, and SREBP1-c were induced in livers of L-ULK1KO mice even prior to the development of insulin resistance and obesity. Hepatomegaly and lipid accumulation developed in L-ULK1KO on normal chow and was exacerbated relative to wild type mice on a HFD. Serum concentrations of insulin, triglyceride, cholesterol, AST and ALT were significantly increased. In contrast, L-ULK2 KO mice were phenotypically normal. To identify putative novel ULK1 targets, we conducted a phospho-proteomics screen in a ULK1 deficient hepatocyte cell line. We identified a relatively small number of novel proteins whose phosphorylation levels were reduced by ULK1 deficiency. The identification of these targets supports autophagy-independent mechanisms of action of ULK1. Recently, we confirmed that NCOA3, one of the targets regulates hepatic lipid metabolism by interacting directly with ULK1. These data suggest that ULK-1 may regulate cellular targets that regulate hepatic lipid metabolism and insulin sensitivity.
A Case of Primary Hyperaldosteronism Presenting as Hemorrhagic Stroke
Authors: Anjum Azeen , Tumyan Gayane , Tayon Kevin 
Published: May 2021

Abstract
Background: Primary aldosteronism (PA) is the most common form of secondary hypertension. Patients with PA are more likely to suffer from end-organ damage compared to matched controls with essential hypertension. We present a case of PA identified in a patient who presented with hypertensive emergency and hemorrhagic stroke.
Clinical Case: A 52-year-old man with hypertension and chronic kidney disease presented with sudden onset left-sided weakness. He had a ten year history of hypertension and was taking carvedilol, losartan, and hydralazine prior to presentation. On arrival, his blood pressure was 263/142 mmHg. He had 3/5 grade weakness in the left upper and lower extremities. Laboratory analysis showed a potassium level of 2.8 mmol/L (n = 3.5–5 mmol/L) and a bicarbonate level of 33 mmol/L (n = 21–29 mmol/L). Screening labs for PA were drawn after potassium repletion. CT Head without contrast revealed an acute 2.5-centimeter intracerebral hemorrhage of the right basal ganglia. He was admitted to the intensive care unit and was started on a nicardipine drip with an improvement of blood pressure. His weakness improved and he was discharged home on carvedilol, hydralazine, nifedipine, and losartan.
Screening for PA revealed a plasma aldosterone concentration (PAC) of 22.8 ng/dL (n &lt; 16 ng/dL) and a plasma renin activity (PRA) of 0.1 ng/ml/hr (n = 0.2–1.6 ng/ml/hr). The PAC/PRA ratio was therefore extremely elevated at 228. The presence of spontaneous hypokalemia, very low renin, and PAC &gt;20 ng/dL confirmed the diagnosis of primary aldosteronism. He underwent an adrenal MRI which revealed two left adrenal nodules, the largest measuring 10 mm, and a 7.3 mm right adrenal nodule, consistent with bilateral adrenal adenomas. The patient did not desire surgery, therefore adrenal vein sampling was deferred. His hypertension improved with the addition of a mineralocorticoid receptor antagonist. Eight weeks after his stroke the patient was readmitted due to chest pain. He was found to have severe multi-vessel coronary artery disease and underwent a four vessel coronary artery bypass.
Conclusion: Patients with PA have higher rates of adverse cardiovascular events compared to age-, sex-, and blood pressure-matched controls with essential hypertension. Studies demonstrate that aldosterone excess has blood pressure independent proinflammatory and profibrotic effects on the vessel wall which leads to endothelial dysfunction and thus accelerated atherosclerosis. Appropriate treatment can eliminate the excess cardiovascular risk associated with PA. This case highlights the importance of including PA in the differential diagnosis of secondary hypertension, particularly among patients presenting with spontaneous hypokalemia, severe uncontrolled hypertension and early onset cardiovascular or cerebrovascular disease.
Impact of Provider-Directed Plant-Strong Nutrition & Counseling on Cardiometabolic Health: A Case Series at the Michael E. DeBakey VA Medical Center
Authors: Ahmad Sara Miriam , Joad Sabaa Salim , Pham Codey , Vasudevan Madhuri Mukhopadhyay 
Published: May 2021

Abstract
Background:
Cardiometabolic syndrome, Type 2 diabetes mellitus (DM), and non-alcoholic fatty liver disease (NAFLD) share common pathogenic mechanisms including inflammation, insulin resistance, lipid accumulation, and increased oxidation. Diet is an important modifiable determinant in cardio-metabolic diseases (CMD) progression. The clinician/specialist provides pharmacotherapeutic guidance, but often defers nutrition guidance to supportive services. We present the impact of specialist-directed nutrition counseling for 3 patients with various manifestations of CMD.
Clinical Case Series:
A 63-year-old man with Type 1DM, status post coronary artery bypass grafting (CABG), reported high animal fat/protein intake, very low carbohydrate (CHO) intake and soda consumption. The specialist educated the patient on anti-inflammatory benefits of plant-strong nutrition, recommended liberalizing healthy CHO, grains, fruits and vegetable intake, limiting animal products to 1 serving daily and eliminating processed foods and beverages. The patient followed the diet, lost 50 pounds in 7 months with improvement in blood pressure and lipids. Insulin requirements reduced by 50% while maintaining HbA1C 7%.
A 71-year-old man with T2DM, NAFLD, obesity, coronary artery disease status post CABG, HbA1C 9.6% reported increased fatigue, depressive symptoms, and maladaptive coping strategies including excessive alcohol consumption. The endocrinologist recommended plant-strong nutrition for weight loss and glycemic benefits, reduced animal fat/protein consumption and complete elimination of alcohol intake. The patient adopted plant-based nutrition and stopped alcohol consumption. After 18 months, he lost 100 pounds, achieved HbA1C 7.6%, without additional medication.
A 63-year-old man with Crohn’s disease, NAFLD, obesity, referred for NAFLD, reported consuming six servings of soda, unchecked fried foods with limited vegetable intake. Exam was notable for abdominal adiposity. The endocrinologist recommended to eliminate soda and fried foods. The patient initially declined, but after 4 months of continued reinforcement, he adopted a plant-forward diet. After 2 years, the patient lost 160 pounds and transaminitis resolved. All specialist-directed nutrition counseling was in accordance with American Heart Association and American Diabetes Association recommendations for macronutrient and micronutrient nutrition consumption.
Conclusion:
These cases signify how provider-directed nutrition counseling can have an impact on CMD. The first step to integrate nutrition counseling into practice is to become well-versed in basic concepts of nutrition science and develop a broader understanding of nutrient composition. We therefore encourage the integration of nutrition science into medical curricula that could translate into improved cardiometabolic health outcomes.