tbuckley/cabot-search huggingface dataset:
Spontaneous reversal of stenosis in tissue-engineered vascular grafts
Authors: Joseph D. Drews, Victoria K. Pepper, Cameron A. Best, Jason M. Szafron, John P. Cheatham, Andrew R. Yates, Kan N. Hor, Jacob C. Zbinden, Yu-Chun Chang, Gabriel J. M. Mirhaidari, Abhay B. Ramachandra, Shinka Miyamoto, Kevin M. Blum, Ekene A. Onwuka, Jason Zakko, John Kelly, Sharon L. Cheatham, Nakesha King, James W. Reinhardt, Tadahisa Sugiura, Hideki Miyachi, Yuichi Matsuzaki, Julie Breuer, Eric D. Heuer, T. Aaron West, Toshihiro Shoji, Darren Berman, Brian A. Boe, Jeremy Asnes, Mark Galantowicz, Goki Matsumura, Narutoshi Hibino, Alison L. Marsden, Jordan S. Pober, Jay D. Humphrey, Toshiharu Shinoka, Christopher K. Breuer
Journal: Science Translational Medicine (2020)

We developed a tissue-engineered vascular graft (TEVG) for use in children and present results of a U.S. Food and Drug Administration (FDA)-approved clinical trial evaluating this graft in patients with single-ventricle cardiac anomalies. The TEVG was used as a Fontan conduit to connect the inferior vena cava and pulmonary artery, but a high incidence of graft narrowing manifested within the first 6 months, which was treated successfully with angioplasty. To elucidate mechanisms underlying this early stenosis, we used a data-informed, computational model to perform in silico parametric studies of TEVG development. The simulations predicted early stenosis as observed in our clinical trial but suggested further that such narrowing could reverse spontaneously through an inflammation-driven, mechano-mediated mechanism. We tested this unexpected, model-generated hypothesis by implanting TEVGs in an ovine inferior vena cava interposition graft model, which confirmed the prediction that TEVG stenosis resolved spontaneously and was typically well tolerated. These findings have important implications for our translational research because they suggest that angioplasty may be safely avoided in patients with asymptomatic early stenosis, although there will remain a need for appropriate medical monitoring. The simulations further predicted that the degree of reversible narrowing can be mitigated by altering the scaffold design to attenuate early inflammation and increase mechano-sensing by the synthetic cells, thus suggesting a new paradigm for optimizing next-generation TEVGs. We submit that there is considerable translational advantage to combined computational-experimental studies when designing cutting-edge technologies and their clinical management.
Abstract 18008: Trends and Outcomes of Outpatient Management of Pulmonary Embolism in a Real World Setting
Authors: Adi J Klil-Drori, Janie Coulombe, Samy Suissa, Andrew Hirsch, Vicky Tagalakis
Journal: Circulation (2016)

Introduction: Outpatient management of low-risk pulmonary embolism (PE) is recommended in guidelines. However, no studies have reported on population-based outcomes of outpatient management of PE. ...
US Public Concerns About the COVID-19 Pandemic From Results of a Survey Given via Social Media
Authors: Lorene M. Nelson, Julia F. Simard, Abiodun Oluyomi, Vanessa Nava, Lisa G. Rosas, Melissa Bondy, Eleni Linos
Journal: JAMA Internal Medicine (2020)

increasing from 18.6% to 23.6% of total expenditures and accounting for 28.6% of the increased spending.Specialty care was the third largest category, accounting for 17.9% of the increase in spending.In contrast, primary care spending accounted for 6.5% of total expenditures in 2002 and 5.4% in 2016 (Table).As a proportion of total expenditures, primary care spending was similar throughout the study period (Figure).On average, office and outpatient visits to primary care physicians accounted for 6.6% of total health care expenditures from 2002 through 2016.Even when all nurse, nurse practitioner, and physician assistant expenditures were added to primary care spending-an overestimate given that a majority of this care is provided in specialty settings-there was no upward or downward trend (data not shown).Discussion | Using MEPS data, we found that spending on inpatient services, specialty care, and prescriptions combined accounted for about two-thirds of the increase in total US health care expenditures from 2002 to 2016.In contrast, primary care accounted for 4.2% of the total increase in health care expenditures, while declining as a proportion of all expenditures.There are many reasons to increase investment in primary care, including its beneficial effects on quality of care, access to care, and mortality.
Parental metabolic syndrome epigenetically reprograms offspring hepatic lipid metabolism in mice
Authors: Dario F. De Jesus, Kazuki Orime, Dorota Kaminska, Tomohiko Kimura, Giorgio Basile, Chih-Hao Wang, Larissa Haertle, Renzo Riemens, Natalie K. Brown, Jiang Hu, Ville Männistö, Amélia M. Silva, Ercument Dirice, Yu-Hua Tseng, Thomas Haaf, Jussi Pihlajamäki, Rohit N. Kulkarni
Journal: Journal of Clinical Investigation (2020)

The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide. Although gene-environment interactions have been implicated in the etiology of several disorders, the impact of paternal and/or maternal metabolic syndrome on the clinical phenotypes of offspring and the underlying genetic and epigenetic contributors of NAFLD have not been fully explored. To this end, we used the liver-specific insulin receptor knockout (LIRKO) mouse, a unique nondietary model manifesting 3 hallmarks that confer high risk for the development of NAFLD: hyperglycemia, insulin resistance, and dyslipidemia. We report that parental metabolic syndrome epigenetically reprograms members of the TGF-β pathway, including neuronal regeneration–related protein (NREP) and growth differentiation factor 15 (GDF15). NREP and GDF15 modulate the expression of several genes involved in the regulation of hepatic lipid metabolism. In particular, NREP downregulation increases the protein abundance of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and ATP-citrate lyase (ACLY) in a TGF-β receptor/PI3K/protein kinase B–dependent manner, to regulate hepatic acetyl-CoA and cholesterol synthesis. Reduced hepatic expression of NREP in patients with NAFLD and substantial correlations between low serum NREP levels and the presence of steatosis and nonalcoholic steatohepatitis highlight the clinical translational relevance of our findings in the context of recent preclinical trials implicating ACLY in NAFLD progression.
EGFR inhibition triggers an adaptive response by co-opting antiviral signaling pathways in lung cancer
Authors: Ke Gong, Gao Guo, Nishah Panchani, Matthew E. Bender, David E. Gerber, John D. Minna, Farjana Fattah, Boning Gao, Michael Peyton, Kemp Kernstine, Bipasha Mukherjee, Sandeep Burma, Cheng-Ming Chiang, Shanrong Zhang, Adwait Amod Sathe, Chao Xing, Kathryn H. Dao, Dawen Zhao, Esra A. Akbay, Amyn A. Habib
Journal: Nature Cancer (2020)
Human liver CD8+ MAIT cells exert TCR/MR1-independent innate-like cytotoxicity in response to IL-15
Authors: Min-Seok Rha, Ji Won Han, Jong Hoon Kim, June-Young Koh, Hye Jung Park, Soon Il Kim, Myoung Soo Kim, Jae Geun Lee, Hyun Woong Lee, Dong Hyeon Lee, Won Kim, Jun Yong Park, Dong Jin Joo, Su-Hyung Park, Eui-Cheol Shin
Journal: Journal of Hepatology (2020)
John Thompson Rowling
Authors: Lionello D Coen
Journal: BMJ (2020)

John Thompson Rowling (“JTR”) was a retired consultant surgeon. He worked in Sheffield at the Royal Hospital and later at the Royal Hallamshire Hospital. He was born in Leeds to a family whose medical connections dated back to Elizabethan times. His father, Herbert Samuel Thompson Rowling, was one of the old school family doctors with a special interest in anaesthesia. He was a pioneer in his specialty and worked with Lord Moynihan. His elder sister, Dorothy, was an orthopaedic surgeon.

Before entering medical school, Rowling obtained a bachelor of arts degree in natural sciences from the University of Cambridge. He undertook his clinical training in Leeds, taking his finals in Cambridge in 1946, graduating MA MB BChir.

His first jobs after qualifying were in the Leeds area. Subsequently he decided to enrol for national service. He writes “this could have been postponed or avoided, but having had a relatively safe war, it was just to accept it.”

He served valiantly in the Royal Army Medical Corps, reaching the …
Targeting epigenetics in sarcomas through EZH2 inhibition
Authors: Antoine Italiano
Journal: Journal of Hematology & Oncology (2020)

Abstract Soft-tissue sarcomas represent a heterogeneous group of diseases with distinct genetic and clinical features accounting for up to 1% of cancer in adults and 15% of cancer in children. Epithelioid sarcoma is an extremely rare and aggressive tumor affecting young adults that is characterized by loss of INI1 expression. INI1 (SMARCB1, SNF5, BAF47) is a subunit of the SWI/SNF chromatin remodeling complex that opposes the enzymatic function of EZH2. When INI1 loses its regulatory function, EZH2 activity is de-regulated, allowing EZH2 to play a driving, oncogenic role. Tazemetostat, a specific EZH2 inhibitor, has just been approved for patients with advanced epithelioid sarcoma and represents a new therapeutic option in this devastating disease.
Angiotensin converting enzyme 2 and angiotensin (1–7) axis in pulmonary arterial hypertension
Authors: Julio Sandoval, Leonardo Del Valle-Mondragón, Felipe Masso, Nayeli Zayas, Tomás Pulido, Ricardo Teijeiro, Hector Gonzalez-Pacheco, Rossana Olmedo-Ocampo, Carlos Sisniega, Araceli Paez-Arenas, Gustavo Pastelin-Hernandez, Jose Gomez-Arroyo, Norbert F. Voelkel
Journal: European Respiratory Journal (2020)

Background In animal models of pulmonary arterial hypertension (PAH), angiotensin-converting enzyme (ACE)2 and angiotensin (Ang)-(1–7) have been shown to have vasodilatory, antiproliferative, antifibrotic and antihypertrophic properties. However, the status and role of the ACE2-Ang(1–7) axis in human PAH is incompletely understood. Methods We studied 85 patients with a diagnosis of PAH of distinct aetiologies. 55 healthy blood donors paired for age and sex served as controls. Blood samples were obtained from the pulmonary artery in patients with PAH during right heart catheterisation. Peripheral blood was obtained for both groups. Ang(1–7) and -II were measured using zone capillary electrophoresis. Aldosterone, Ang(1–9), AngA and ACE2 were measured using ELISA, and ACE2 activity was determined enzymatically. Results Of the 85 patients, 47 had idiopathic PAH, 25 had PAH associated with congenital heart disease and 13 had PAH associated with collagen vascular disease. Compared to controls, patients with PAH had a higher concentration of AngII (median 1.03, interquartile range 0.72–1.88 pmol·mL −1 versus 0.19, 0.10–0.37 pmol·mL −1 ; p&lt;0.001) and of aldosterone (88.7, 58.7–132 ng·dL −1 versus 12.9, 9.55–19.9 ng·dL −1 ; p&lt;0.001). Conversely, PAH patients had a lower concentration of Ang(1–7) than controls (0.69, 0.474–0.91 pmol·mL −1 versus 4.07, 2.82–6.73 pmol·mL −1 ; p&lt;0.001), and a lower concentration of Ang(1–9) and AngA. Similarly, the ACE2 concentration was higher than in controls (8.7, 5.35–13.2 ng·mL −1 versus 4.53, 1.47–14.3 ng·mL −1 ; p=0.011), whereas the ACE2 activity was significantly reduced (1.88, 1.08–2.81 nmol·mL −1 versus 5.97, 3.1–17.8 nmol·mL −1 ; p&lt;0.001). No significant differences were found among the three different aetiological forms of PAH. Conclusions The AngII–ACE2–Ang(1–7) axis appears to be altered in human PAH and we propose that this imbalance, in favour of AngII, plays a role in the pathogenesis of the severe PAH. Further mechanistic studies are warranted.
Design and validation of a patient-reported outcome measure scale in acute pancreatitis: the PAN-PROMISE study
Authors: Enrique de-Madaria, Claudia Sánchez-Marin, Irene Carrillo, Santhi Swaroop Vege, Serge Chooklin, Andriy Bilyak, Rafael Mejuto, Violeta Mauriz, Peter Hegyi, Katalin Márta, Ayesha Kamal, Eugenia Lauret-Braña, Sorin T Barbu, Vitor Nunes, M Lourdes Ruiz-Rebollo, Guillermo García-Rayado, Edgard E Lozada-Hernandez, Jorge Pereira, Ionut Negoi, Silvia Espina, Marcus Hollenbach, Andrey Litvin, Federico Bolado-Concejo, Rómulo D Vargas, Isabel Pascual-Moreno, Vikesh K Singh, José J Mira
Journal: Gut (2020)

Objective This study aimed to develop and validate a patient-reported outcome measure (PROM) in acute pancreatitis (AP) as an endpoint centred on the patient. Design A PROM instrument (PAtieNt-rePoRted OutcoMe scale in acute pancreatItis, an international proSpEctive cohort study, PAN-PROMISE scale) was designed based on the opinion of patients, professionals and an expert panel. The scale was validated in an international multicentre prospective cohort study, describing the severity of AP and quality of life at 15 days after discharge as the main variables for validation. The COSMIN (COnsensus-based Standards for the selection of health status Measurement INstruments) methodology was applied. Both the design and validation stages considered the content and face validity of this new instrument; the metric properties of the different items, reliability (reproducibility and internal consistence), the construct, structural and criterion validity, responsiveness and interpretability of this scale. Results PAN-PROMISE consists of a seven-item scale based on the symptoms that cause the most discomfort and concern to patients with AP. The validation cohort involved 15 countries, 524 patients. The intensity of symptoms changed from higher values during the first 24 hours to lower values at discharge and 15 days thereafter. Items converged into a unidimensional ordinal scale with good fit indices. Internal consistency and split-half reliability at discharge were adequate. Reproducibility was confirmed using test–retest reliability and comparing the PAN-PROMISE score at discharge and 15 days after discharge. Evidence is also provided for the convergent-discriminant and empirical validity of the scale. Conclusion The PAN-PROMISE scale is a useful tool to be used as an endpoint in clinical trials, and to quantify patient well-being during the hospital admission and follow-up. Trial registration number NCT03650062
Intravenous Iron Dosing and Infection Risk in Patients on Hemodialysis: A Prespecified Secondary Analysis of the PIVOTAL Trial
Authors: Iain C. Macdougall, Sunil Bhandari, Claire White, Stefan D. Anker, Kenneth Farrington, Philip A. Kalra, Patrick B. Mark, John J. V. McMurray, Chante Reid, Michele Robertson, Charles R.V. Tomson, David C. Wheeler, Christopher G. Winearls, Ian Ford
Journal: Journal of the American Society of Nephrology (2020)

Experimental and observational studies have raised concerns that giving intravenous (IV) iron to patients, such as individuals receiving maintenance hemodialysis, might increase the risk of infections. The Proactive IV Iron Therapy in Haemodialysis Patients (PIVOTAL) trial randomized 2141 patients undergoing maintenance hemodialysis for ESKD to a high-dose or a low-dose IV iron regimen, with a primary composite outcome of all-cause death, heart attack, stroke, or hospitalization for heart failure. Comparison of infection rates between the two groups was a prespecified secondary analysis.Secondary end points included any infection, hospitalization for infection, and death from infection; we calculated cumulative event rates for these end points. We also interrogated the interaction between iron dose and vascular access (fistula versus catheter).We found no significant difference between the high-dose IV iron group compared with the lose-dose group in event rates for all infections (46.5% versus 45.5%, respectively, which represented incidences of 63.3 versus 69.4 per 100 patient years, respectively); rates of hospitalization for infection (29.6% versus 29.3%, respectively) also did not differ. We did find a significant association between risk of a first cardiovascular event and any infection in the previous 30 days. Compared with patients undergoing dialysis with an arteriovenous fistula, those doing so via a catheter had a higher incidence of having any infection, hospitalization for infection, or fatal infection, but IV iron dosing had no effect on these outcomes.The high-dose and low-dose IV iron groups exhibited identical infection rates. Risk of a first cardiovascular event strongly associated with a recent infection.
Strengthening the Public Health Impacts of the Supplemental Nutrition Assistance Program Through Policy
Authors: Sara N. Bleich, Alyssa J. Moran, Kelsey A. Vercammen, Johannah M. Frelier, Caroline G. Dunn, Anthony Zhong, Sheila E. Fleischhacker
Journal: Annual Review of Public Health (2020)

The US Department of Agriculture (USDA) Supplemental Nutrition Assistance Program (SNAP) is the cornerstone of the US nutrition safety net. Each month, SNAP provides assistance to 40 million low-income Americans—nearly half of them children. A number of changes could strengthen the public health impacts of SNAP. This review first presents a framework describing the mechanisms through which SNAP policy can influence public health, particularly by affecting the food security, the diet quality, and, subsequently, the health of SNAP participants. We then discusspolicy opportunities with the greatest potential to strengthen the public health impacts of SNAP, organized into three areas: ( a) food production and distribution, ( b) benefit allocation, and ( c) eligibility and enrollment. For each section, we describe current policy and limitations of the status quo, suggest evidence-based opportunities for policy change to improve public health, and identify important areas for future research.
Abstract 174: Effects of Melatonin (N-Acetyl-5-Methoxytryptamine) on Inflammation and Cerebral Microcirculation After Cardiopulmonary Resuscitation in a Rat Model of Cardiac Arrest
Authors: Juntao Hu, Guanghui Zheng, Fenglian He, Weiwei Ge, Jing Xu, Xianfei Ji, Jennifer Bradley, Mary Ann A Peberdy, Joseph P Ornato, Wanchun Tang
Journal: Circulation (2019)

Introduction: Cerebral ischemia-reperfusion injury produces inflammation and cerebral microcirculatory dysfunction after cardiopulmonary resuscitation (CPR). Melatonin (N-acetyl-5-methoxytryptamine) has both anti-inflammatory and anti-oxidative properties. In this study, we investigated the effects of melatonin on inflammation and cerebral microcirculation after cardiopulmonary resuscitation in a rat model of cardiac arrest. Hypothesis: Melatonin decreases the systemic inflammatory response after cardiopulmonary resuscitation and will preserve cerebral microcirculation in a rat model of cardiac arrest. Method: Eighteen male Sprague Dawley rats weighing between 450-550 g were randomized into three groups: 1) sham: no ventricular fibrillation (VF) and CPR; 2) CPR control: untreated VF for 6 min followed by 8 min CPR; 3) CPR+melatonin: untreated VF for 6 min followed by 8 min CPR. Melatonin (10 mg/kg) was administered intraperitoneal (IP) in line with hypoxia-ischemia animal studies after return of spontaneous circulation (ROSC). Serum TNF- α, IL-1 β and cerebral microcirculation were measured at baseline and 6 h following ROSC. Result: Serum TNF-α and IL-1β were significantly lower in the CPR+melatonin group at 6h after ROSC compared to CPR controls ( p &lt;0.01, Fig. 1). Animals treated with melatonin had improved cerebral microcirculation including perfused vessel density (PVD), proportion of perfused vessels (PPV) and microvascular flow index (MFI) compared to control animals ( p &lt;0.05, Fig. 2). Conclusion: In a rat model of cardiac arrest, melatonin reduced systemic inflammation and preserved cerebral microcirculation following resuscitation.
表皮坏死松解症幸存者的健康相关生活质量和长期相关疾病:一项针对 57 例患者的研究
Authors: S. Ingen‐Housz‐Oro, A. Alves, A. Colin, R. Ouedraogo, R. Layese, F. Canoui‐Poitrine, O. Chosidow, A. Mekontso‐Dessap, P. Wolkenstein, N. Prost
Journal: British Journal of Dermatology (2020)

表皮坏死松解症 (EN),包括史蒂芬斯‐强森症候群和中毒性表皮坏死松解症(或 Lyell 综合征),是危及生命的药物反应,可导致皮肤和粘膜水疱和脱落。它们代表具有一系列严重程度的单一疾病。急性期(意味着更严重)的死亡率(死亡发生率)从 15% 到 30% 不等。 支持性治疗是治疗的基石。一些患者需要在重症监护室 (ICU) 或烧伤病房接受诊疗护理。本研究旨在研究 EN 生存者的长期健康相关生活质量 (HR‐QoL),以及他们后来因 EN 发生的其他疾病(称为后遗症)。 我们对 2010 年至 2017 年间因 EN 入住医院的患者进行了一项研究。在电话访谈期间,通过使用不同的生活质量测量方法评估 HR‐QoL:SF‐36 问卷、医院焦虑抑郁 (HAD) 量表、事件影响量表‐修订版 (IES‐R) 和一般 QoL 结局,包括特定后遗症。 主要(重要)结局指标为 SF‐36 的身体组分总评分 (PCS)。其中,评分越高表明生活质量越高(或更好),而评分越低表明生活质量越差。 共有 57 例 EN 存活者(包括 19 例入住 ICU 的患者)在出院后 3.6 年(中位数)接受了电话采访。中位 SF36 身体组分评分 (PCS) 低于年龄‐性别匹配的参考人群(指相同年龄和性别但未接受 EN 的人群),并且与未入住 ICU 的 EN 存活者相比,入住 ICU 的 EN 存活者的 PCS 显著较低。 焦虑和抑郁评分高的患者比例分别为 54% 和 21%。报告的特定后遗症为皮肤相关的,这意味着其影响皮肤 (77%)、眼部(眼睛,70%)、心理 (60%)、牙齿/口腔 (49%)、生殖器 (30%) 和呼吸(呼吸/肺,18%)。 我们的研究证实了 EN 对生存者生活质量的主要负担和长期影响,并强调了在 EN 急性期后需要长期密切随访。 本摘要涉及研究:表皮坏死松解症幸存者的健康相关生活质量和长期后遗症:一项针对 57 例患者的观察性研究
E2F7 Is a Potent Inhibitor of Liver Tumor Growth in Adult Mice
Authors: Eva Moreno, Mathilda J.M. Toussaint, Saskia C. van Essen, Laura Bongiovanni, Elsbeth A. van Liere, Mirjam H. Koster, Ruixue Yuan, Jan M. van Deursen, Bart Westendorp, Alain de Bruin
Journal: Hepatology (2020)

Background and Aims Up‐regulation of the E2F‐dependent transcriptional network has been identified in nearly every human malignancy and is an important driver of tumorigenesis. Two members of the E2F family, E2F7 and E2F8, are potent repressors of E2F‐dependent transcription. They are atypical in that they do not bind to dimerization partner proteins and are not controlled by retinoblastoma protein. The physiological relevance of E2F7 and E2F8 remains incompletely understood, largely because tools to manipulate their activity in vivo have been lacking. Approach and Results Here, we generated transgenic mice with doxycycline‐controlled transcriptional activation of E2f7 and E2f8 and induced their expression during postnatal development, in adulthood, and in the context of cancer. Systemic induction of E2f7 and, to lesser extent, E2f8 transgenes in juvenile mice impaired cell proliferation, caused replication stress, DNA damage, and apoptosis, and inhibited animal growth. In adult mice, however, E2F7 and E2F8 induction was well tolerated, yet profoundly interfered with DNA replication, DNA integrity, and cell proliferation in diethylnitrosamine‐induced liver tumors. Conclusion Collectively, our findings demonstrate that atypical E2Fs can override cell‐cycle entry and progression governed by other E2F family members and suggest that this property can be exploited to inhibit proliferation of neoplastic hepatocytes when growth and development have subsided during adulthood.