tbuckley/cabot-search huggingface dataset:
Development and Validation of a Dementia Risk Prediction Model in the General Population: An Analysis of Three Longitudinal Studies
Authors: Silvan Licher, Maarten J.G. Leening, Pinar Yilmaz, Frank J. Wolters, Jan Heeringa, Patrick J.E. Bindels, Meike W. Vernooij, Blossom C.M. Stephan, Ewout W. Steyerberg, M. Kamran Ikram, M. Arfan Ikram
Journal: American Journal of Psychiatry (2018)

Identification of individuals at high risk of dementia is essential for development of prevention strategies, but reliable tools are lacking for risk stratification in the population. The authors developed and validated a prediction model to calculate the 10-year absolute risk of developing dementia in an aging population.In a large, prospective population-based cohort, data were collected on demographic, clinical, neuropsychological, genetic, and neuroimaging parameters from 2,710 nondemented individuals age 60 or older, examined between 1995 and 2011. A basic and an extended model were derived to predict 10-year risk of dementia while taking into account competing risks from death due to other causes. Model performance was assessed using optimism-corrected C-statistics and calibration plots, and the models were externally validated in the Dutch population-based Epidemiological Prevention Study of Zoetermeer and in the Alzheimer's Disease Neuroimaging Initiative cohort 1 (ADNI-1).During a follow-up of 20,324 person-years, 181 participants developed dementia. A basic dementia risk model using age, history of stroke, subjective memory decline, and need for assistance with finances or medication yielded a C-statistic of 0.78 (95% CI=0.75, 0.81). Subsequently, an extended model incorporating the basic model and additional cognitive, genetic, and imaging predictors yielded a C-statistic of 0.86 (95% CI=0.83, 0.88). The models performed well in external validation cohorts from Europe and the United States.In community-dwelling individuals, 10-year dementia risk can be accurately predicted by combining information on readily available predictors in the primary care setting. Dementia prediction can be further improved by using data on cognitive performance, genotyping, and brain imaging. These models can be used to identify individuals at high risk of dementia in the population and are able to inform trial design.
Dual delivery nanoscale device for miR-345 and gemcitabine co-delivery to treat pancreatic cancer
Authors: Metin Uz, Manisha Kalaga, Ramesh Pothuraju, Juhyung Ju, Wade M. Junker, Surinder K. Batra, Surya Mallapragada, Satyanarayana Rachagani
Journal: Journal of Controlled Release (2018)
Near-infrared light control of bone regeneration with biodegradable photothermal osteoimplant
Authors: Liping Tong, Qing Liao, Yuetao Zhao, Hao Huang, Ang Gao, Wei Zhang, Xiaoyong Gao, Wei Wei, Min Guan, Paul K. Chu, Huaiyu Wang
Journal: Biomaterials (2018)
Defining a ‘frequent admitter’ phenotype among patients with repeat heart failure admissions
Authors: Yun Yun Go, Reinhard Sellmair, John C. Allen, Anders Sahlén, Heerajnarain Bulluck, David Sim, Fazlur R. Jaufeerally, Michael R. MacDonald, Zhan Yun Lim, Ping Chai, Seet Yoong Loh, Jonathan Yap, Carolyn S.P. Lam
Journal: European Journal of Heart Failure (2018)
Abstract 12151: Contrast-Enhanced Carotid Plaque for Detection of Myocardial Damage Risks After PCI in ST-segment Elevation Myocardial Infarction
Authors: Juntaro Deyama, Takamitsu Nakamura, Jun Nakamura, Takehusa Horikoshi, Mika Futamata, Satoshi Matsuoka, Takuya Shimizu, Manabu Uematsu, Tsuyoshi Kobayashi, Daisuke Fujioka, Yukio Saito, Kazuto Nakamura, Ken-ichi Kawabata, Jun-ei Obata, Kiyotaka Kugiyama
Journal: Circulation (2015)

Background: The presence of coronary vulnerable plaque has been shown to increase the risk of myocardial damage after percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI) patients. It is possible that coronary plaque vulnerability may be assessed by evaluating plaque characteristics in other vessels such as the carotid arteries. Contrast-enhanced ultrasound (CEUS) of carotid plaque has been shown to detect the plaque neovascularization of carotid plaques, which is a feature of vulnerable plaque. Thus, in this study we examined whether CEUS of the carotid artery may provide information for myocardial damage risks after PCI in STEMI patients. Methods and Results: CEUS of the carotid plaques using perfluorobutane microbubbles as an ultrasound contrast agent were performed in consecutive 95 STEMI patients treated with emergent PCI. Intraplaque neovascularization was identified on the basis of microbubbles within the carotid plaque and graded as: G0, not visible; G1, moderate; or G2, extensive microbubbles. Obtained coronary flow and myocardial damage after PCI were estimated by corrected TIMI frame count (cTFC), Myocardial Blush Grade (MBG), peak CK-MB and Troponin T. The presence of G2 in the carotid arteries was associated with higher levels of cTFC (G0, 34±19 frames; G1, 41±21 frames; 43±24 frames,ρ=0.005) , lower levels of MBG (G0, 2.3±0.7; G1, 1.7±0.9; G2, 1.5±0.9,ρ=0.013), and higher levels of carotid IMT, fast blood glucose, hemoglobin A1c, hsCRP, and troponin T (ρ=0.049, 0.042, 0.046, 0.048, 0.01, and 0.02). Conclusion: The presence of carotid plaque neovascularization was related with myocardial damage after PCI in STEMI patients. Measurement of CEUS of Carotid Plaque is useful for risk stratification of STEMI patients underwent emergent PCI.
Optimal concentration range of ustekinumab in patients with plaque-type psoriasis
Authors: Sergio Martín-González, Peru Urigoitia-Ugalde, Jesús Careaga, Daniel Nagore, Rosaura Navarro, Rosa Izu-Belloso, Laura Blanch, Jaime González del Tánago, Antonio Martínez, Ainhoa Ruiz del Agua
Journal: Journal of the American Academy of Dermatology (2018)
Tumor-derived IFN triggers chronic pathway agonism and sensitivity to ADAR loss
Authors: Huayang Liu, Javad Golji, Lauren K. Brodeur, Franklin S. Chung, Julie T. Chen, Rosalie S. deBeaumont, Caroline P. Bullock, Michael D. Jones, Grainne Kerr, Li Li, Daniel P. Rakiec, Michael R. Schlabach, Sosathya Sovath, Joseph D. Growney, Raymond A. Pagliarini, David A. Ruddy, Kenzie D. MacIsaac, Joshua M. Korn, E. Robert McDonald
Journal: Nature Medicine (2018)
Targeting Lymphomas Using Non-Engineered, Multi-Antigen Specific T Cells
Authors: George Carrum, Premal Lulla, Ifigeneia Tzannou, Ayumi Watanabe, Manik Kuvalekar, Mrinalini Bilgi, Rammurti Kamble, Carlos A. Ramos, Rayne Rouce, Bambi J. Grilley, Adrian P. Gee, Malcolm K. Brenner, Helen E. Heslop, Cliona M. Rooney, Juan F. Vera, Ann M. Leen
Journal: Blood (2018)
Sirtuin 4 Depletion Promotes Hepatocellular Carcinoma Tumorigenesis Through Regulating Adenosine‐Monophosphate–Activated Protein Kinase Alpha/Mammalian Target of Rapamycin Axis in Mice
Authors: Yun‐Shan Wang, Lutao Du, Xingsi Liang, Peng Meng, Lei Bi, Yu‐li Wang, Chuanxin Wang, Bo Tang
Journal: Hepatology (2018)

Sirtuin 4 (SIRT4) has been reported to play a vital role in the maintenance of glutamine catabolism and adenosine triphosphate (ATP) homeostasis, but its character in hepatocellular carcinomas (HCCs) remains obscure. In this study, we observed low expression of SIRT4 in both HCC cell lines and HCCs from patients. Decreased disease‐free survival time is associated with low tumor levels of SIRT4 in patients. Deficiency of SIRT4 facilitated liver tumor development and lung metastasis in xenografts and knockout (KO) mice by promoting colony formation and migration of hepatoma cells and enhancing sphere formation of HCCs. Mechanistically, SIRT4 deletion augmented mammalian target of rapamycin (mTOR) signaling by inactivating adenosine‐monophosphate (AMP)‐activated protein kinase alpha (AMPKα) through regulation of glutamine catabolism and subsequent AM)/liver kinase B1 (LKB1) axis. Blockage of mTOR by rapamycin or inhibition of glutaminolysis abolished the discrepancy in tumorigenic capacity between SIRT4‐depleted hepatoma cells and control cells. Suppression of LKB1 or promotion of AMP by metformin also abrogated the hyperproliferative phenotype caused by SIRT4 loss, which further confirmed that the LKB1/AMPKα/mTOR axis is required in SIRT4‐deficiency–promoted HCC tumorigenesis. Conclusion: SIRT4 could exert its tumor suppressive function in HCC by inhibiting glutamine metabolism and thereby increasing the adenosine diphosphate (ADP)/AMP levels to phosphorylate AMPKα by LKB1, which blocks the mTOR signaling pathway.
Do All Patients With Polycythemia Vera or Essential Thrombocythemia Need Cytoreduction?
Authors: Kamya Sankar, Brady L. Stein
Journal: Journal of the National Comprehensive Cancer Network (2018)

Polycythemia vera (PV) and essential thrombocythemia (ET) are Philadelphia chromosome–negative chronic myeloproliferative neoplasms (MPNs), characterized by expansion of normal blood counts, bleeding, thrombosis, and the potential for transformation to myelofibrosis (MF) or acute myeloid leukemia (AML). The primary goals of treatment for MPNs are to reduce the risk of thrombosis, alleviate systemic symptom burden (eg, fatigue, pruritus, microvascular symptoms, and symptomatic splenomegaly), and to prevent transformation to MF/AML. Preventing transformation is clearly important, but not expected with current therapies. Currently, cytoreduction is advised based on vascular risk assessments, which include age and thrombosis history, as well as molecular profile in ET. Traditionally, cytoreduction has been advised only in patients with high vascular risk. Recently, a large prospective study evaluated the safety and efficacy of cytoreduction in patients with ET with less-than-high-risk vascular profiles. A larger question in the MPN field is whether cytoreduction is advisable for all patients with ET and PV, regardless of risk. This article reviews existing data on cytoreduction, evaluating hydroxyurea, interferons, and ruxolitinib in ET and PV. This review evaluates whether evidence supports a more liberal strategy of cytoreduction for all patients with ET and PV.
Investigating the Relationship between Cerebral Blood Flow and Cognitive Function in Hemodialysis Patients
Authors: Mark Duncan Findlay, Jesse Dawson, David Alexander Dickie, Kirsten P. Forbes, Deborah McGlynn, Terry Quinn, Patrick B. Mark
Journal: Journal of the American Society of Nephrology (2018)

The immediate and longer-term effects of hemodialysis on cerebral circulation, cerebral structure, and cognitive function are poorly understood.In a prospective observational cohort study of 97 adults (median age 59 years) receiving chronic hemodialysis, we used transcranial Doppler ultrasound to measure cerebral arterial mean flow velocity (MFV) throughout dialysis. Using a well validated neuropsychological protocol, we assessed cognitive function during and off dialysis and after 12 months of treatment. We also used brain magnetic resonance imaging (MRI) to assess atrophy, white matter hyperintensities (WMHs), and diffusion parameters, and tested correlations between MFV, cognitive scores, and changes on MRI.MFV declined significantly during dialysis, correlating with ultrafiltrate volumes. Percentage of decline in MFV correlated with intradialytic decline in cognitive function, including global function, executive function, and verbal fluency. At follow-up, 73 patients were available for repeat testing, 34 of whom underwent repeat MRI. In a subgroup of patients followed for 12 months of continued dialysis, percentage of decline in MFV correlated significantly with lower global and executive function and with progression of WMH burden (a marker of small vessel disease). Twelve of 15 patients who received renal transplants during follow-up had both early and follow-up off-dialysis assessments. After transplant, patients' memory (on a delayed recall test) improved significantly; increased fractional anisotropy of white matter (a measure of cerebral diffusion) in these patients correlated with improving executive function.Patients undergoing hemodialysis experience transient decline in cerebral blood flow, correlating with intradialytic cognitive dysfunction. Progressive cerebrovascular disease occurred in those continuing dialysis, but not in transplanted patients. Cognitive function and cerebral diffusion improved after transplant.
Abstract 15721: Long-term Therapy With Elamipretide Normalizes BNIP3 Protein Levels in Left Ventricular Myocardium of Dogs With Advanced Heart Failure
Authors: Hani N Sabbah, Ramesh C Gupta, Vinita Singh-Gupta, Kefei Zhang, Jiang Xu
Journal: Circulation (2017)

Introduction: BNIP3 is a hypoxia responsive protein localized to the outer mitochondrial (MITO) membrane and involved in key cellular processes such as autophagy, mitophagy, apoptosis and necrotic-...
Spliceosome Mutations Are Common in MPN-Associated Myelofibrosis with RBC-Transfusion-Dependence and Correlate with Response to Pomalidomide
Authors: Onima Chowdhury, Jennifer O'Sullivan, Nikolas Barkas, Gemma Buck, Angela Hamblin, Ayalew Tefferi, Haifa Al-Ali, Giovanni Barosi, Timothy Devos, Heinz Gisslinger, Qian Jiang, Jean-Jacques Kiladjian, Ruben A. Mesa, Francesco Passamonti, Vincent Ribrag, Gary J. Schiller, Alessandro M. Vannucchi, Daobin Zhou, Mary Frances McMullin, David Reiser, Jim Zhong, Robert Peter Gale, Adam J. Mead
Journal: Blood (2018)
Post-progression evaluation of patients treated with nivolumab for advanced non-small cell lung cancer: A prospective cohort analysis
Authors: E. Quaquarini, L. Gervaso, F. Sottotetti, A. Bernardo, R. Palumbo, A. Gambaro, M. Frascaroli, B. Tagliaferri, C.M. Teragni, D. Presti, C. Porta
Journal: Annals of Oncology (2018)

Background: The aim of the present study is to investigate the efficacy of first treatment received after nivolumab in a cohort of patients affected by advanced non-small cell lung cancer (NSCLC). Methods: This is a prospective, multicentre trial conducted between September 2015 and August 2018 at ICS Maugeri Hospital of Pavia (Italy) and Luigi Sacco Hospital in Milan (Italy) on patients who discontinued nivolumab due to disease progression or adverse events. The primary end-point was progression-free survival (PFS) to the first treatment given after nivolumab. Secondary endpoints were response rate (RR) to post–progression therapy and overall survival (OS). Results: Eighty-four patients have been evaluated with the following baseline characteristics: median age 69 years (range 54 – 83); 66% males; 74% had an ECOG performance status (PS) 0-1; 82% had a metastatic disease; 45% received nivolumab as second–line treatment. Among the 38 patients eligible for post-nivolumab treatment analysis, 75% had and ECOG PS of 0-1; 75% had a metastatic disease; all patients received single agent chemotherapy (CT) (43% docetaxel, 27% vinorelbine, 30% gemcitabine). Median PFS of first-line post-nivolumab treatment was 4.5 months (range 3–16); RR was 33% and OS was 8 months (range 2-17). Patients who received nivolumab in earlier line, had higher PFS and RR to post–nivolumab treatments than patients who received nivolumab as > = 3 line (6 vs 3.5 months, 38% vs 28%, respectively, p < 0.05); OS was 9.5 vs 5.8 months, respectively. Moreover, patients who had a PFS > = 6 months to nivolumab treatment, had a better PFS and RR to the subsequent treatment than patients with shorter benefit to nivolumab (8.1 vs 3.3 months and 45% vs 26%, respectively, p < 0.05). This data is irrespective of the type of CT received. Conclusions: This trial elicits a better performance of post-nivolumab treatments in patients who received nivolumab in earlier line and who get greater benefit to nivolumab. Some patients (about 20%) experienced also prolonged survival times under CT. This could be due to a long-term effect of immunotherapy on immune memory cells which might be boosted by the further CT lines. Legal entity responsible for the study: Medical Oncology, ICS Maugeri Pavia. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Native American Perspectives on Health and Traditional Ecological Knowledge
Authors: Gwyneira Isaac, Symma Finn, Jennie R. Joe, Elizabeth Hoover, Joseph P. Gone, Clarita Lefthand-Begay, Stewart Hill
Journal: Environmental Health Perspectives (2018)

Background: Traditional ecological knowledge (TEK) is a conceptual framework that highlights Indigenous knowledge (IK) systems. Although scientific literature has noted the relevance of TEK for environmental research since the 1980s, little attention has been given to how Native American (NA) scholars engage with it to shape tribal-based research on health, nor how non-Native scholars can coordinate their approaches with TEK. This coordination is of particular importance for environmental health sciences (EHS) research exploring interdisciplinary approaches and the integration of environmental and human health. Objective: Our perspective on TEK arose from a series of Health and Culture Research Group (HCRG) workshops that identified gaps in existing EHS methodologies that are based on a reliance on Euro-American concepts for assessing environmental exposures in tribal communities. These prior methods neither take into account cultural behavior nor community responses to these. Our objective is to consider NA perspectives on TEK when analyzing relationships between health and the environment and to look at how these may be applied to address this gap. Discussion: The authors—the majority of whom are NA scholars—highlight two research areas that consider health from a TEK perspective: food systems and knowledge of medicinal plants. This research has yielded data, methods, and knowledge that have helped Indigenous communities better define and reduce health risks and protect local natural food resources, and this TEK approach may prove of value to EHS research. Conclusion: NA perspectives on TEK resulting from the HCRG workshops provide an opportunity for developing more accurate Indigenous health indicators (IHI) reflecting the conceptualizations of health maintained in these communities. This approach has the potential to bridge the scientific study of exposure with methods addressing a tribal perspective on the sociocultural determinants of health, identifying potential new areas of inquiry in EHS that afford nuanced evaluations of exposures and outcomes in tribal communities. https://doi.org/10.1289/EHP1944
The season of giving and sharing
Authors: Navjoyt Ladher
Journal: BMJ (2018)

If 2018 can be summed up by the Oxford Dictionaries word of the year—“toxic”1—we hope that generosity and compassion can serve as an antidote. We have a few ideas for giving and sharing, inspired by the articles in this year’s festive edition of the journal.

Abi Rimmer asked several prominent doctors about moments of compassion that have helped to brighten a busy and stressful day (doi:10.1136/bmj.k5136). We’re asking readers to share their own acts of …
Changing Landscape of Liver Cancer in California: A Glimpse Into the Future of Liver Cancer in the United States
Authors: Summer S Han, Scott P Kelly, Yuqing Li, Baiyu Yang, Mindie Nguyen, Samuel So, Philip S Rosenberg, Ann W Hsing
Journal: JNCI Journal of the National Cancer Institute (2018)

Asians and Hispanics currently have the highest incidence rates of hepatocellular carcinoma (HCC) in the United States. The numbers of these minority populations are rapidly increasing, reshaping the demographic in the United States and particularly California, where approximately one-third of US Asians and Hispanics reside. With the changing demographic and rising incidence of HCC that has tripled during the past three decades, it is important to forecast the future burden of HCC by age, sex, and race/ethnicity to plan prevention and control strategies for HCC.
Orchestration of Tryptophan‐Kynurenine Pathway, Acute Decompensation, and Acute‐on‐Chronic Liver Failure in Cirrhosis
Authors: Joan Clària, Richard Moreau, François Fenaille, Alex Amorós, Christophe Junot, Henning Gronbaek, Minneke J. Coenraad, Alain Pruvost, Aurélie Ghettas, Emeline Chu‐Van, Cristina López‐Vicario, Karl Oettl, Paolo Caraceni, Carlo Alessandria, Jonel Trebicka, Marco Pavesi, Carme Deulofeu, Agustin Albillos, Thierry Gustot, Tania M. Welzel, Javier Fernández, Rudolf E. Stauber, Faouzi Saliba, Noémie Butin, Benoit Colsch, Christophe Moreno, François Durand, Frederik Nevens, Rafael Bañares, Daniel Benten, Pere Ginès, Alexander Gerbes, Rajiv Jalan, Paolo Angeli, Mauro Bernardi, Vicente Arroyo
Journal: Hepatology (2018)

Systemic inflammation (SI) is involved in the pathogenesis of acute decompensation (AD) and acute‐on‐chronic liver failure (ACLF) in cirrhosis. In other diseases, SI activates tryptophan (Trp) degradation through the kynurenine pathway (KP), giving rise to metabolites that contribute to multiorgan/system damage and immunosuppression. In the current study, we aimed to characterize the KP in patients with cirrhosis, in whom this pathway is poorly known. The serum levels of Trp, key KP metabolites (kynurenine and kynurenic and quinolinic acids), and cytokines (SI markers) were measured at enrollment in 40 healthy subjects, 39 patients with compensated cirrhosis, 342 with AD (no ACLF) and 180 with ACLF, and repeated in 258 patients during the 28‐day follow‐up. Urine KP metabolites were measured in 50 patients with ACLF. Serum KP activity was normal in compensated cirrhosis, increased in AD and further increased in ACLF, in parallel with SI; it was remarkably higher in ACLF with kidney failure than in ACLF without kidney failure in the absence of differences in urine KP activity and fractional excretion of KP metabolites. The short‐term course of AD and ACLF (worsening, improvement, stable) correlated closely with follow‐up changes in serum KP activity. Among patients with AD at enrollment, those with the highest baseline KP activity developed ACLF during follow‐up. Among patients who had ACLF at enrollment, those with immune suppression and the highest KP activity, both at baseline, developed nosocomial infections during follow‐up. Finally, higher baseline KP activity independently predicted mortality in patients with AD and ACLF. Conclusion: Features of KP activation appear in patients with AD, culminate in patients with ACLF, and may be involved in the pathogenesis of ACLF, clinical course, and mortality.
p53 Up‐regulated Modulator of Apoptosis Induction Mediates Acetaminophen‐Induced Necrosis and Liver Injury in Mice
Authors: Dongshi Chen, Hong‐Min Ni, Lei Wang, Xiaowen Ma, Jian Yu, Wen‐Xing Ding, Lin Zhang
Journal: Hepatology (2018)

Acetaminophen (APAP) overdose is one of the leading causes of hepatotoxicity and acute liver failure in the United States. Accumulating evidence suggests that hepatocyte necrosis plays a critical role in APAP‐induced liver injury (AILI). However, the mechanisms of APAP‐induced necrosis and liver injury are not fully understood. In this study, we found that p53 up‐regulated modulator of apoptosis (PUMA), a B‐cell lymphoma‐2 (Bcl‐2) homology domain 3 (BH3)‐only Bcl‐2 family member, was markedly induced by APAP in mouse livers and in isolated human and mouse hepatocytes. PUMA deficiency suppressed APAP‐induced mitochondrial dysfunction and release of cell death factors from mitochondria, and protected against APAP‐induced hepatocyte necrosis and liver injury in mice. PUMA induction by APAP was p53 independent, and required receptor‐interacting protein kinase 1 (RIP1) and c‐Jun N‐terminal kinase (JNK) by transcriptional activation. Furthermore, a small‐molecule PUMA inhibitor, administered after APAP treatment, mitigated APAP‐induced hepatocyte necrosis and liver injury. Conclusion: Our results demonstrate that RIP1/JNK‐dependent PUMA induction mediates AILI by promoting hepatocyte mitochondrial dysfunction and necrosis, and suggest that PUMA inhibition is useful for alleviating acute hepatotoxicity attributed to APAP overdose.