tbuckley/cabot-search huggingface dataset:
Comment on Cundy et al. Early Worsening of Diabetic Nephropathy in Type 2 Diabetes After Rapid Improvement in Chronic Severe Hyperglycemia. Diabetes Care 2021;44:e55–e56
Authors: Alice Larroumet, Oceane Molina, Ninon Foussard, Marie Monlun, Laurence Blanco, Kamel Mohammedi, Vincent Rigalleau
Journal: Diabetes Care (2020)

We were interested in the recent article by Cundy et al. (1), who described a rapid and durable decline of estimated glomerular filtration rate (eGFR) in four subjects with type 2 diabetes after their HbA1c had fallen from 118 mmol/mol (12.9%) to 48 mmol/mol (5.5%). Fifteen years ago, we reported that GFR and its estimations correlated with HbA1c, each +1% (+9 mmol/mol) HbA1c being associated with +5–6 mL/min/1.73 m2 GFR (2). One could then fear a –35 mL/min/1.73 m2 GFR reduction after a rapid –7% reduction of HbA1c.

We have recently shown that a dramatic reduction of HbA1c, by more than 27 mmol/mol (–3%), could be detected during the years preceding admission in 13.5% of 680 patients hospitalized …
Rationalizing constraints on the capacity for cognitive control
Authors: Sebastian Musslick, Jonathan D Cohen
Journal: Trends in Cognitive Sciences (2021)

Humans are remarkably limited in: (i) how many control-dependent tasks they can execute simultaneously, and (ii) how intensely they can focus on a single task. These limitations are universal assumptions of most theories of cognition. Yet, a rationale for why humans are subject to these constraints remains elusive. This feature review draws on recent insights from psychology, neuroscience, and machine learning, to suggest that constraints on cognitive control may result from a rational adaptation to fundamental, computational dilemmas in neural architectures. The reviewed literature implies that limitations in multitasking may result from a trade-off between learning efficacy and processing efficiency and that limitations in the intensity of commitment to a single task may reflect a trade-off between cognitive stability and flexibility.
Abstract P161: Tai Chi Movements Bring On Parasympathetic Nerve Output As Indicated By Audible Bowel Sounds
Authors: Desuo Wang
Journal: Circulation (2021)

Tai Chi movements are unique exercise that can improve cognition, strength somatomotor coordination, and enhance autonomic nerve regulation on internal organ function. The mild increase in heart rate and/or slight sweat during and after practicing Tai Chi indicates the activation of the sympathetic nervous system. There is lack of evidence to show that Tai Chi exercise enhances the activity of parasympathetic nervous system though it has been claimed that practicing Tai Chi could do so. The author tested the hypothesis that Tai Chi exercise brings on an increase in parasympathetic nerve outputs (PNO). The PNO is evaluated by recording the bowel sounds using an audio recorder (Sony digital voice recorder ICD-PX Series) and the data analyses were done using NCH software (WavePad audio editor). The heart rate was simultaneously recorded using a fingertip pulse oximeter (Zacurate Pro Series 500DL) during Tai Chi exercise. All the data was repeatedly collected from a Tai Chi Master in a study period of 6 months. A total of 30 recordings were used to carry out the analysis. The audible bowel sounds occurred when the performer started to do the Ready-Movement of Yang-style Tai Chi. These Tai Chi induced-bowel sounds lasted from the beginning to the end of a set of movements (3-5 min for 24-moves style). The frequency of bowel sounds was in a range of 0.2 to 3.5 Hz. The average number of bowel sounds was approximately 2.5 sounds per Tai Chi Move. The intensity and frequency of the bowel sounds are not related to the change of the performer’s heart rate. In comparison, meditation or deep squat exercise performed by the Tai Chi master did not cause any changes in the bowel sounds. According to the autonomic innervation of the GI tract, increase of bowel movements is mediated by PNO. In conclusion, Tai Chi movements can simultaneously exercise skeletal muscles, sympathetic nervous system and parasympathetic nervous system. The enhancement of parasympathetic nervous system output by Tai Chi exercise is a valuable modality of physical exercise for wellness.
Abstract 12594: Pharmacodynamic Effect of ARO-APOC3, an Investigational Hepatocyte-targeted RNA Interference Therapeutic Targeting Apolipoprotein C3, in Patients With Hypertriglyceridemia and Multifactorial Chylomicronemia
Authors: Peter Clifton, David Sullivan, John Baker, Christian Schwabe, Susan Thackwray, Russell Scott, James Hamilton, Ting Chang, Bruce Given, Javier San Martin, Stacey Melquist, Natasa Rajicic, Gerald F Watts, Ira J Goldberg, Daniel Gaudet, Josh W Knowles, Robert A Hegele, Christie M Ballantyne
Journal: Circulation (2020)

Background: Hypertriglyceridemia (HTG) increases the risk of acute pancreatitis and atherosclerosis. In a Phase 1 study (NCT03783377), single subcutaneous doses of investigational RNA interference (RNAi) therapeutic ARO-APOC3 (10, 25, 50, and 100 mg; N=24) demonstrated deep and prolonged reductions in apolipoprotein C3 (APOC3) and triglycerides (TG) and increases in HDL-C in healthy volunteers with good tolerability, compared with placebo (N=16). Purpose: We report initial results of the effects of ARO-APOC3 in patients with HTG (fasting TG ≥ 300 mg/dL) or multifactorial chylomicronemia (MCM; fasting TG ≥ 880 mg/dL). Methods: Up to 40 subjects with HTG and 20 subjects with MCM will receive ARO-APOC3 or placebo on days 1 and 29. Pharmacodynamic responses include serum APOC3, TG, and other lipid parameters reported up to week 4 prior to the 2 nd dose. Results: At the data cutoff (16 March 2020), the first 4 enrolled patients with HTG and 6 enrolled patients with MCM were administered ARO-APOC3 50 mg. ARO-APOC3 substantially reduced mean (range) APOC3 levels by 96% (88-99%) in both patient groups at Week 4 (Table). ARO-APOC3 substantially reduced mean (range) TG by 78% (67-87%) in HTG patients and by 92% (90-95%) in MCM patients at Week 4. Three of 4 HTG patients and 3 of 6 MCM patients had TG levels below 150 mg/dL. All MCM patients had TG ≤ 500 mg/dL. To date, ARO-APOC3 has been generally well tolerated with no reports of treatment-related serious or severe adverse events. Two of the 6 unblinded MCM patients experienced a transient ALT elevation to &gt;3X ULN that returned to approximate pre-dose baseline by Day 113. Conclusions: Preliminary results indicate that a single dose of ARO-APOC3 reduces APOC3 levels by &gt;90% and TG by ~80% 4 weeks after treatment in patients with HTG and MCM. The magnitude of treatment effect was similar in both populations and ARO-APOC3 had a favorable safety profile. Using RNAi to silence expression of APOC3 appears promising for treating patients with HTG and MCM.
Abstract 15663: Prediction of 5-year Cardiovascular and All-cause Mortality After Myocardial Infarction in United States Veterans
Authors: Bing Lu, Daniel Posner, Jason L Vassy, Yuk-lam Ho, Ashley Galloway, SRIDHARAN RAGHAVAN, Jacqueline P Honerlaw, Laura Tarko, John Russo, Saadia Qazi, Ariela R Orkaby, Vidisha Tanukonda, Luc Djousse, Michael Gaziano, David Gagnon, Kelly Cho, PETER WILSON
Journal: Circulation (2020)

Objective: This is a large prospective study aimed to develop risk prediction models of CVD and all-cause mortality in patients who survived MI. Methods: Using 2002-2012 national electronic health record data from the Veterans Health Administration, sex-specific risk prediction models for CVD and all-cause death were developed from the 5-year follow-up data of 100,601 first MI survivors aged &gt;30 years. Model performance was evaluated using a 5-fold cross-validation approach. Results: We followed 98,657 male and 1,944 female MI survivors up to 5 years (407,199 person-years). There were 31,622 deaths (men 31,147, women 475) and 12,901 CVD deaths (men 12,752, women 149) observed during follow up. Among men, greater age, current smoking, diabetes, atrial fibrillation, heart failure, peripheral artery disease, geographic region, and lower BMI (&lt;20kg/m 2 ) were associated with increased risk of subsequent CVD and all-cause-mortality, while statin treatment, hypertension medication, beta-blocker, eGFR level, and high BMI (≥25 kg/m 2 ) were significantly associated with reduced risk of CVD and all-cause-mortality. Similar associations were generally observed among women. We observed U-shaped relations between total cholesterol and outcomes, and HDL cholesterol and outcomes. The prediction models demonstrated good discrimination and calibration. The estimated Harrell’s C-statistics of the final models versus the cross-validation estimates were similar, ranging from 0.75 to 0.81. The predicted risk of death was well-calibrated compared to observed risk. Conclusions: We developed and validated risk prediction models of 5-year risk for CVD and all-cause death for patients following MI. Traditional risk factors, co-morbidity, lack of blood pressure or lipid treatment, and geographic region were all associated with greater risk of CVD and all-cause mortality.
Increased glutathion (GSH), glutathion S-transferase (GST) and macrophage migration inhibitory factor (MIF) in colon 26 cells acquired high ability of proliferation in the liver.
Authors: Kondo M, Shiroto H, Une Y, Nishihira J, Shinohara T, Kohashi S, Ogawa H, Takahashi N, Oshima T, Sato Y
Journal: Hepatology (1996)
Relationship of respiratory symptoms and climatic seasonality at an out-patient primary health unit in Brazil
Authors: José Laerte Rodrigues Silva Júnior, Thiago Fintelman Padilha, Jordana Eduardo Rezende, Eliane Consuelo Alves Rabelo, Anna Carolina Galvão Ferreira, Marcelo Fouad Rabahi
Journal: European Respiratory Journal (2011)

Brazilian studies have documented an association of humidity with an increase in the proportion of respiratory symptoms. However, they were based on secondary data, raising concerns of validity and reliability.  The goal of this study was to evaluate the relationship between the climatic seasonality and the proportion of respiratory symptoms on subjects attending an out-patient primary health unit during each season at a Brazilian city with tropical weather.  It was a cross-sectional study on subjects attending an primary health unit in relation to meteorological data daily collected. During one year, 48 observations divided by season were made.  Among 3409 subjects, 15% presented with respiratory symptoms. This paper identifies the association of low levels of humidity and precipitation coinciding with an increase in the number of subjects with respiratory symptoms on winter.  ANOVA test shows a significant difference between winter and spring (p=0.02).There was significant negative correlation between the number of patients with respiratory symptoms and the mean of previous three days minimum relative humidity (p=0.002). An ARMAX model shows a statistically significant coefficient (p>0.0001).  These findings suggest that at a Brazilian city with tropical weather, the proportion of respiratory symptoms on subjects attending a primary health unit is increased with the reduction of relative air humidity.
Comment on Rhee et al. Association Between Glycemic Status and the Risk of Parkinson Disease: A Nationwide Population-Based Study. Diabetes Care 2020;43:2169–2175
Authors: Itzel Paola Melgoza, Rayman Jilani, Zarrar Shehzad, Anika K. Anam
Journal: Diabetes Care (2020)

Metabolic diseases, such as diabetes and obesity, increase susceptibility for additional long-term complications, including Parkinson disease (PD). Rhee et al. (1) aim to address this issue by using a large data set obtained from the Korean National Health Insurance consisting of a sample of over 15 million individuals aged 40 years and older who had undergone routine checkups between 2009 and 2010. They evaluated diabetes as a risk factor for PD by analyzing how PD risk varies according to baseline glucose tolerance status, diabetes duration, and comorbidities such as obesity, cardiovascular disease, and cerebrovascular disease. The authors demonstrate that the risk of PD is increased in patients with diabetes and that the incidence of PD is proportional to the degree of exposure to hyperglycemia. The finding that the diagnosis of diabetes itself is not enough …
Management of Intraductal Papillary Mucinous Neoplasms—Watch and Wait or Operate?
Authors: Linda Ye, O. Joe Hines
Journal: JAMA Surgery (2021)

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Abstract 13566: Clinical Utility of Noninvasive Assessment of Flow-pressure Relationship in Scleroderma
Authors: Miharu Arase, Kenya Kusunose, sae morita, Natsumi Yamaguchi, Yukina Hirata, Susumu Nishio, Takayuki Ise, Koji Yamaguchi, Daiju Fukuda, Shusuke Yagi, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Masataka Sata
Journal: Circulation (2020)

Introduction: Cardiac involvement in Systemic sclerosis (SSc), especially left ventricular diastolic dysfunction (DD), is high prevalence and associated with high mortality. Thus, the early detection of left ventricular DD might be important to manage SSc. Recent study has shown that exercise stress test may evaluate an early stage of heart failure in patients with normal resting echocardiogram. Hypothesis: We hypothesized that SSc patients with normal resting hemodynamics may present early phase of left ventricular DD by exercise echocardiogram, leading to the model of predicting long-term outcomes. Methods: Between January 2014 and December 2018, we prospectively enrolled 140 SSc patients who underwent 6-minute walk (6MW) stress echocardiographic studies with normal range of estimated mean pulmonary arterial pressure (mPAP) (&lt;25mmHg) and mean pulmonary artery wedge pressure (mPAWP) (&lt;15mmHg) at rest. We used ΔmPAP/Δcardiac output (CO) to assess pulmonary vascular reserve and ΔmPAWP/ΔCO to assess left ventricular (LV) reserve between resting and post-6MW point. Results: During a median period of 3.6 years, 25 patients (18%) reached the composite outcome. Both ΔmPAP/ΔCO and ΔmPAWP/ΔCO in patients with events were significantly higher than in ones without events (8.9±3.8mmHg/l/min vs. 3.0±1.7mmHg/l/min; p=0.002, and 2.2±0.9mmHg/l/min vs. 0.9±0.5mmHg/l/min; p&lt;0.001, respectively). In addition, ΔmPAWP/ΔCO is strongly associated with events (p=0.04) in patients with normal ΔmPAP/ΔCO (≤median value), although ΔmPAWP/ΔCO had weak impact in patients with abnormal ΔmPAP/ΔCO (&gt;median value) (p=0.23). Conclusions: Exercise echocardiography revealed impaired LV functional reserve in SSc patients with normal resting hemodynamics. Furthermore, in the group of normal pulmonary vascular function, the patients with impaired LV functional reserve had significantly shorter event-free survival than the ones with non-impaired LV function. Thus, the evaluation of early left ventricular DD with 6MW may detect high-risk group in SSc patients.
Abstract 12546: Major Adverse Cardiovascular Events and Hospital Readmissions in the 90 Days Following Acute Myocardial Infarction: Redefining the Risk Period
Authors: Keith Allen, Christopher Young, James Alexander, Susan Gabriel
Journal: Circulation (2020)

Introduction: Centers for Medicare &amp; Medicaid Services (CMS) has implemented a voluntary bundled payment program centered on a 90-day period for acute myocardial infarction (AMI) to increase the quality of care and reduce costs. Tying payments and penalties to a 90-day period, versus the current 30-day period for quality metrics, redefines the risk period for recurrent events following AMI. Objective: To quantify the clinical burden of recurrent events in the 30- and 90-day period post AMI. Methods: A retrospective cohort analysis was conducted of 30- and 90-day major adverse cardiovascular events (MACE: mortality, AMI readmission and stroke), all-cause and cardiac rehospitalization among patients with a primary diagnosis of AMI within a Medicare population. Results: This analysis included 125,772 Medicare patients. At 90 days, the overall rate of all-cause and cardiac rehospitalization was 23.7% and 13.2%, respectively. The rate of MACE at 90 days was 10.2%. Rates of all outcomes increased significantly between day 30 and day 90 (p&lt;0.0001, Figure 1). Relative increases were observed in all-cause rehospitalization (82.1%), cardiac rehospitalization (77.8%), MACE (99.8%), AMI readmission (374.3%), mortality (82.2%), and stroke (77.8%). Conclusions: The 90-day period post AMI is associated with significant healthcare burden, with approximately one quarter of AMI episodes associated with hospital readmissions. Rates of outcomes increase substantially between 30 and 90 days post AMI, in particular AMI readmission increases disproportionately relative to the increase in timeframe. These findings represent a significant impact when moving from a 30- to a 90-day payment bundling model.
Long-term outcomes after gene therapy for adenosine deaminase severe combined immune deficiency
Authors: Bryanna Reinhardt, Omar Habib, Kit L. Shaw, Elizabeth Garabedian, Denise A. Carbonaro-Sarracino, Dayna Terrazas, Beatriz Campo Fernandez, Satiro De Oliveira, Theodore B. Moore, Alan K. Ikeda, Barbara C. Engel, Gregory M. Podsakoff, Roger P. Hollis, Augustine Fernandes, Connie Jackson, Sally Shupien, Suparna Mishra, Alejandra Davila, Jack Mottahedeh, Andrej Vitomirov, Wenzhao Meng, Aaron M. Rosenfeld, Aoife M. Roche, Pascha Hokama, Shantan Reddy, John Everett, Xiaoyan Wang, Eline T. Luning Prak, Kenneth Cornetta, Michael S. Hershfield, Robert Sokolic, Suk See De Ravin, Harry L. Malech, Frederic D. Bushman, Fabio Candotti, Donald B. Kohn
Journal: Blood (2021)
Abstract 13122: Sensor-controlled Digital Game May Improve Weight Monitoring Among Older Adults With Heart Failure
Authors: Kavita Radhakrishnan, Christine Julien, Matthew O'Hair, Thomas Baranowski, Grace Lee, Atami Sagna, Catherine Allen, Edison Thomaz, Miyong T Kim
Journal: Circulation (2020)

Introduction: Poor self-management of heart failure (HF) has contributed to poor health outcomes with an annual loss of $32 billion. Our innovative sensor controlled digital game (SCDG) integrates data from weight scale and physical activity sensors to trigger rewards, progress, changes in avatar’s health status and feedback based on HF individuals’ real-time behaviors (Fig1). Hypothesis: Weight monitoring and physical activity by participants receiving both the SCDG app and sensors will be higher than participants receiving only the sensors (CG). Methods: English-speaking HF adults aged &gt;55 years, own a smartphone, and walk unassisted were recruited from cardiac settings in Texas. Both SCDG and CG participants were given ‘Withings’ activity tracker and smart weight scale sensors to track behaviors for 12 weeks. Physical activity goal was tailored to the participant’s ability. Results: In early results over six weeks on 12 participants (58% women, white, and 65+ years age), the mean days with weight monitoring in the SCDG group was 34 and 27 in the CG. Daily average steps were 2195 (53% of goal) in SCDG group and 3187 in CG (75% of goal). 100% of participants found the SCDG easy and enjoyable to play. Study adaptations in response to the COVID19 crisis will allow us to present results on 30 participants at conference time. Conclusion: SCDG had trends of higher weight monitoring but lower physical activity among older adults with HF. Participants in the study continue to engage in weight-monitoring and physical activity even during the COVID19 crisis. This presents opportunities to tailor digital health interventions to remotely motivate self-management behaviors.
Abstract 16635: Enhanced Cardiac Delivery of a Small Soluble Antifibrotic Peptide With Liposomal Encapsulation
Authors: Swati D Sonkawade, Shirley Xu, Saraswati Pokharel, Umesh C Sharma
Journal: Circulation (2020)

Introduction: N-acetyl-ser-asp-lys-pro (Ac-SDKP) is an enodogenous anti-fibrotic peptide with a great potential for use as a “ replacement therapy ” in fibrotic myocardial remodeling. However, its therapeutic use is limited by its short half-life (4.5 mins) and a negligible bioavailibity. Hypothesis: We hypothesize that liposomal encapsulation of Ac-SDKP (L-Ac-SDKP) enhances its stability, and improves delivery into the myocardial target cells at a higher efficiency than free Ac-SDKP. This will maximize retention time, allowing intermittent dosing and minimizing off-target effects. Methods: We synthesized L-Ac-SDKP using zwitterionic lipid formulation for better cell membrane penetration. We used Fluorophore (FITC)-conjugated Ac-SDKP as a tracer, and scrambled peptides and blank liposomes as controls. After confirming an enhanced uptake efficiency of L-Ac-SDKP into the adult cardiac fibroblasts, we performed in vivo L-Ac-SDKP uptake and distribution studies in a model of cardiac fibrosis induced by 30Gy of thoracic ionizing radiation exposure. Results: Confocal microscopy of the cultured cardiac fibroblasts showed L-Ac-SDKP distribution localized to perinuclear areas corroborating its known effects on cell-cycle and nuclear membrane trafficking compared to the free peptide. Along with flow cytometry analysis L-Ac-SDKP uptake was seen in 98% of cells as opposed to 7% when treated with free Ac-SDKP. In vivo, the mouse model of myocardial fibrosis showed significantly increased L-Ac-SDKP uptake (33±3 fold), compared to normal controls (14±3 fold) after 5 daily injections. Quantification of Ac-SDKP in the cardiac homogenate reached a maximum therapeutic concentration of 1.4 pg/mg after 2 doses in irradiated mice, whereas even higher concentration could be achieved after 5 cumulative doses. Conclusion: We conclude that liposomal-conjugation is a highly effective therapeutic approach for targeting cardiac fibrosis using a potent fibroblast inhibitory peptide, Ac-SDKP as a therapeutic agent. Translational studies in large animal models are currently in progress for further testing its therapeutic utility.
遺伝子治療による拡張型心筋症(HDCM)の遺伝救出:組換えアデノ関連性ウイルス(rAAV)媒介遺伝子導入での形態学的代謝および生理的復元および生存延長されるTO-2ハムスター
Authors: Nakauchi S, Kawada T, Nakazawa M, Sakamoto A, Urabe M, Yamazaki K, Shimamoto R, Masui F, Shin Ws, Suzuki Ji, Sato H, Ozawa K, Toyo-Oka T
Journal: Circulation (2001)