bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ketogenic Diet in Established Epilepsy Indications
Authors: Bergin Ann M. 
Published: November 2017

Abstract
The ketogenic diet is a metabolic therapy that provides an alternative strategy for seizure control in medication-resistant epilepsy. Many decades of continued use of diet therapy, amassing consistent observational evidence, was recently supported by a randomized, controlled study indicating benefit of diet treatment in children with refractory epilepsy as compared with a control group who continued with standard of care and delayed diet treatment for three months. Well-established uses include children with refractory, nonsurgical epilepsies and epileptic encephalopathies including infantile spasms and West syndrome, Lennox Gastaut syndrome, and Dravet and Doose syndromes. Current knowledge on the efficacy and role of diet therapy in these conditions are discussed.
The Ketogenic Diet and Related Therapies in “Novel” Situations
Authors: Kessler Sudha Kilaru 
Published: November 2017

Abstract
The ketogenic diet (KD) is often considered as a treatment option for medication-resistant focal epilepsies and symptomatic generalized epilepsies, but is perhaps less commonly considered for idiopathic generalized epilepsies. The evidence for the use of the KD in two common idiopathic generalized epilepsy syndromes, childhood absence epilepsy and juvenile myoclonic epilepsy, is presented here.
Ketogenic Diet in Status Epilepticus
Authors: Nabbout Rima 
Published: November 2017

Abstract
Refractory status epilepticus (RSE) is associated with a significant risk of death or neurological morbidity. The ketogenic diet (KD) is a dietary therapy that succeeds in controlling seizures in otherwise RSE in children and adult patients. Inflammatory etiologies might be a particular target, but KD has reported efficacy in other etiologies. KD is well tolerated, and the effect is seen within days. Randomized and controlled studies are lacking in this area, and studies are needed to prove the efficacy of KD in RSE and to identify specific indications. This would help to increase its use and to implement it in intensive care units to resolve severe epileptic conditions quickly.
Metabolism-Based Treatments to Counter Cancer
Authors: Seyfried Thomas N. , Shelton Laura M. 
Published: November 2017

AbstractAccumulating evidence indicates that cancer is a type of mitochondrial metabolic disease. Chronic damage to mitochondria causes a gradual shift in cellular energy metabolism from respiration to fermentation. Consequently, fermentable metabolites become the drivers of cancer. Mitochondrial injury can explain the long-standing “oncogenic paradox,” and all major hallmarks of cancer including genomic instability. Restriction of fermentable fuels therefore becomes a viable therapeutic strategy for cancer management. The ketogenic diet (KD) is a metabolic therapy that lowers blood glucose and elevates blood ketone bodies. Ketone bodies are a “super fuel” for functional mitochondria, but cannot be metabolized efficiently by tumor mitochondria. The efficacy of KDs for cancer management can be enhanced when used together with drugs and procedures (such as hyperbaric oxygen therapy) (that further target fermentation. Therapeutic ketosis can represent an alternative, nontoxic strategy for managing and preventing a broad range of cancers while reducing healthcare costs.
Ketogenic Diet as Adjunctive Therapy for Malignant Brain Cancer
Authors: Woolf Eric C. , Scheck Adrienne C. 
Published: November 2017

Abstract
Malignant brain tumors are devastating, and increased survival requires new therapeutic modalities. Metabolic dysregulation results in an increased need for glucose in tumor cells, suggesting that reduced tumor growth could be achieved with decreased glucose availability either through pharmacological means or use of a high-fat, low-carbohydrate ketogenic diet (KD). KD provides increased blood ketones to support energy needs of normal tissues and has been shown to reduce tumor growth, angiogenesis, inflammation, peritumoral edema, migration, and invasion. Furthermore, this diet can enhance the activity of radiation and chemotherapy in a mouse model of glioma, thus increasing survival. In vitro studies indicate that increasing ketones in the absence of glucose reduction can also inhibit cell growth and potentiate the effects of radiation. Thus, emerging data provide strong support for the use of KD in the treatment of malignant gliomas and thus far has led to a limited number of clinical trials.
Metabolic Therapy for Autism Spectrum Disorder and Comorbidities
Authors: Cheng Ning , Masino Susan A. , Rho Jong M. 
Published: November 2017

AbstractAutism spectrum disorder (ASD) is a heretogenous developmental disorder characterized by deficits in sociability and communication and by repetitive and/or restrictive behaviors. Currently, only comorbid manifestations can be alleviated (such as seizures and sleep disturbance) not core behavioral symptoms. Recent studies have increasingly implicated mitochondrial dysfunction as a cause of ASD. Mitochondria play an integral role in many cellular functions and are susceptible to many pathophysiological insults. Derangements in mitochondrial structure and function provide a scientific rationale for experimental therapeutics. Meanwhile, the high-fat, low-carbohydrate ketogenic diet (KD) has been shown to enhance mitochondrial function through a multiplicity of mechanisms. Reviewed herein is clinical and basic laboratory evidence for the use of metabolism-based therapies such as the KD in the treatment of ASD, as well as emerging comorbid models of epilepsy and autism. Future research directions aimed at validating such therapeutic approaches and identifying novel mechanistic targets are discussed.
Dietary Therapy for Neurological Disorders
Authors: Stafstrom Carl E. 
Published: November 2017

Abstract
Dietary and metabolic therapies such as the high-fat, low-carbohydrate ketogenic diet (KD) are best known for the treatment of intractable epilepsy. Yet, dietary and metabolic approaches have also found some efficacy in a wide variety of other neurological diseases, including autism spectrum disorder, brain trauma, Alzheimer’s disease, sleep disorders, brain tumors, pain, and multiple sclerosis, as discussed in other chapters of this volume. This chapter provides an overview of clinical and experimental studies using the KD in an array of other neurologic disorders: amyotrophic lateral sclerosis, Parkinson’s disease, mood disorders, and migraine. Despite the wide spectrum of pathophysiological mechanisms underlying these disorders, it is possible that one or more final common metabolic pathways might be influenced by dietary intervention. There is compelling albeit preliminary evidence that correction of aberrant energy metabolism through dietary manipulation could favorably influence diverse neurological diseases.
Ketogenic Diet in a Hippocampal Slice
Authors: Kawamura Masahito 
Published: November 2017

AbstractThe hippocampus is thought to be a good experimental model for investigating epileptogenesis in and/or antiepileptic therapy for temporal lobe epilepsy. The hippocampus is also a useful target for researching the ketogenic diet. This chapter focuses on electrophysiological recordings using hippocampal slices and introduces their use for studying the anticonvulsant effects underlying ketogenic diets. The major difficulty in using hippocampal slices is the inability to precisely reproduce the in vivo condition of ketogenic diet feeding in this in vitro preparation. Three different approaches are reported to reproduce diet effects in the hippocampal slices: (1) direct application of ketone bodies, (2) mimicking the ketogenic diet condition with whole-cell patch-clamp technique, and (3) hippocampal slices from ketogenic diet–fed animals. Significant results have been found with each of these methods. These three approaches are useful tools to elucidate the underlying anticonvulsant mechanisms of the ketogenic diet.
Ketogenic Diet, Adenosine, Epigenetics, and Antiepileptogenesis
Authors: Lusardi Theresa A. , Boison Detlev 
Published: November 2017

AbstractEpilepsy is common, affecting about 1% of the population. Conventional treatments are ineffective in about one third of patients, and current therapies do not prevent epilepsy or its progression. For individuals with drug-refractory epilepsy the ketogenic diet (KD) can provide seizure relief in approximately fifty percent of patients, with complete and permanent remission in some cases, suggesting possible antiepileptogenic effects of the diet. Whereas mechanisms underlying antiseizure effects of KD have been identified, mechanistic links between KD therapy and antiepileptogenesis constitute a novel area of research. An adenosine receptor-mediated role of KD therapy in seizure suppression is well established, and recent evidence demonstrates that the KD regulates adenosine homeostasis in the brain. Adenosine in turn has previously unappreciated epigenetic functions as a regulator of DNA methylation. This chapter discusses recent evidence that KD influences the epigenome through modulation of adenosine metabolism as a plausible antiepileptogenic mechanism of the diet.
Alzheimer’s Disease
Authors: Veech Richard L. , King M. Todd 
Published: November 2017

Abstract
Deficits in cerebral glucose utilization in Alzheimer’s disease (AD) arise decades before cognitive impairment and accumulation of amyloid plaques and neurofibrillary tangles in brain. Addressing this metabolic deficit has greater potential in treating AD than targeting later disease processes – an approach that has failed consistently in the clinic. Cerebral glucose utilization requires numerous enzymes, many of which have been shown to decline in AD. Perhaps the most important is pyruvate dehydrogenase (PDH), which links glycolysis with the Krebs cycle and aerobic metabolism, and whose activity is greatly suppressed in AD. The unique metabolism of ketone bodies allows them to bypass the block at pyruvate dehydrogenase and restore brain metabolism. Recent studies in mouse genetic models of AD and in a human Alzheimer’s patient showed the potential of ketones in maintaining brain energetics and function. Oral ketone bodies might be a promising avenue for treatment of Alzheimer’s disease.
Mitigation of Damage from Reactive Oxygen Species and Ionizing Radiation by Ketone Body Esters
Authors: Curtis William , Kemper Martin , Miller Alexandra , Pawlosky Robert , King M. Todd , Veech Richard L. 
Published: November 2017

AbstractReactive oxygen and nitrogen species, ROS and RNS, are ubiquitous in living cells. They have beneficial effects but are also the cause of a wide variety of diseases. However adding excessive amounts of reducing agents has a long history of clinical failure. This problem can be overcome by providing a novel ester of D-beta-hydroxybutyrate–R-1,3-butanediol, which is rapidly hydrolyzed to ketone bodies, the metabolism of which leads to the production of NADPH. The free cytosolic [NADP+]/[NADPH] redox potential is the most negative in the cell and sets the potential of the glutathione and ascorbic acid couples. Ketone bodies also act by inhibiting histone deacetylases, activating the transcription factor FOXO3 and increasing the transcription of enzymes involved in the destruction of ROS. Ketone esters would be effective in the treatment of a variety of disparate diseases where ROS play a role, ranging from Parkinson’s disease to radiation sickness and aging.
Effects of the Ketogenic Diet on the Blood-Brain Barrier
Authors: Banjara Manoj , Janigro Damir 
Published: November 2017

AbstractKetone bodies (KBs) are always present in the blood, and their levels increase after high-fat diet intake, prolonged exercise, or extended fasting. Thus, one can predict effects on the brain capillary endothelium from high levels of ketones in the blood. Prolonged exposure of blood-brain barrier (BBB) endothelial cells to KBs induces expression of monocarboxylate transporters and enhances brain uptake of KBs. In addition, cell migration and expression of gap junction proteins are up-regulated by KBs. Thus, beneficial effects of the ketogenic diet may depend on increased brain uptake of KBs to match metabolic demand and repair of a disrupted BBB. As the effects of KBs on the BBB and their transport mechanisms across the BBB are better understood, it will be possible to develop alternative strategies to optimize the therapeutic benefits of KBs for brain disorders where the BBB is compromised.
Ketone Supplementation for Health and Disease
Authors: Poff Angela M. , Kesl Shannon L. , D’Agostino Dominic P. 
Published: November 2017

Abstract
Exogenous ketone supplements rapidly elevate blood ketones in a dose-dependent manner regardless of dietary intake, making them a practical method of inducing therapeutic ketosis for medical use. It is thought that ketone supplementation could be used as a stand-alone therapy, or as a way to further augment the therapeutic efficacy of the ketogenic diet. Ketone supplementation could increase treatment compliance by allowing many patients to maintain a more normal lifestyle with a less restrictive diet. The therapeutic effects of ketone supplementation are likely mediated in part by a stabilization of blood glucose and insulin levels, an increase in metabolic efficiency, and an inhibition of oxidative stress and inflammation. Ketone supplements may also serve as an effective preventative medicine due to their potential ability to protect and enhance mitochondrial health and function. Indeed, preliminary evidence suggests there are a number of conditions for which exogenous ketone supplementation may be beneficial.
2-Deoxyglucose
Authors: Stafstrom Carl E. , Sutula Thomas P. 
Published: November 2017

Abstract
Metabolic regulation of excitability is increasingly appreciated as a strategy to control seizures and reduce pathogenesis. Inhibiting or bypassing glycolysis may be one way in which the ketogenic diet suppresses seizures. 2-deoxy-D-glucose (2DG) is a glucose analog that partially inhibits glycolysis and has antiseizure effects in several acute and chronic seizure models. The mechanisms underlying the acute and chronic effects of 2DG are being investigated. Preliminary studies provide evidence that the acute anticonvulsant actions of 2DG involve activity-dependent presynaptic suppression of excitatory synaptic transmission during network synchronization. The chronic effects of 2DG entail reduction of the expression of brain-derived neurotrophic factor and its receptor, tyrosine kinase B. Preclinical toxicology studies demonstrate that 2DG has a favorable toxicity profile at doses effective for seizure protection. Currently available preclinical studies support 2DG as a novel first-in-class metabolic treatment for epilepsy with an antiglycolytic mechanism distinct from all other anticonvulsants.
Error, bias, and confounding in epidemiology
Authors: Bhopal Raj S. 
Published: November 2017

Abstract
Epidemiological studies are prone to error, because they usually study complex matters in human populations in natural settings and not in laboratory conditions. Bias may be thought of as error which affects comparison groups unequally or leads to inappropriate inferences about one group compared with another. Three broad problems confront epidemiologists: selection of study populations, quality of information, and confounding. Selection and imperfect information cause biases. Confounding is not an error or bias as normally understood, but it leads to errors of data interpretation. The different epidemiological research designs have similar problems with error and bias, which are mostly inherent in the survey and disease registration methods. Principles which apply to all studies and help to minimize these errors are also similar. The chronology and structure of a research project offers a pragmatic framework for the systematic analysis of error bias and confounding.
Cause and effect: The epidemiological approach
Authors: Bhopal Raj S. 
Published: November 2017

Abstract
Cause and effect understanding is the highest form of scientific knowledge. In epidemiology, demonstrating causality is difficult because of the long and complex natural history of many human diseases and because of ethical restraints. Epidemiologists should: hold the attitude that all judgements of cause and effect are tentative; understand that causal thinking demands a judgement; be alert for the play of chance, error, and bias; always consider reverse causality and confounding, utilize the power of causal models that broaden causal perspectives; apply guidelines for causality as an aid to thinking and not as a checklist; and look for corroboration of causality from other scientific frameworks for assessment of cause and effect. The ultimate aim of epidemiology is to use knowledge of cause and effect to break links between disease and its causes and to improve health. The application of erroneous knowledge has serious repercussions.
The concept of risk and fundamental measures of disease frequency: Incidence and prevalence
Authors: Bhopal Raj S. 
Published: November 2017

Abstract
In epidemiology, risk refers to the likelihood, or in statistical language probability, of an individual in a defined population developing a disease or other adverse health problem. The prime measures of disease frequency, including probability of outcomes, in epidemiology are incidence rates and prevalence proportions. The incidence rate is the number of new cases in relation to a population, time, and place. Prevalence proportion measures all disease or a risk factor in a population, either at a particular time (point prevalence) or over a time period (period prevalence, lifetime prevalence). Rates and proportions are most accurately presented by age and sex groups (‘specific’ rates and proportions), but for ease of interpretation they may be grouped as overall, actual (crude) rates. The collection of both disease, risk factor and population data to achieve accurate figures of incidence rates and prevalence proportions is problematic, and remains a major challenge.
Summarizing, presenting, and interpreting epidemiological data: Building on incidence and prevalence
Authors: Bhopal Raj S. 
Published: November 2017

Abstract
Basic epidemiological data on disease occurrence and population structure can be manipulated and presented in many ways. Epidemiological summary measures, broadly, estimate absolute or relative frequency of outcomes. Usually, relative measures are more useful in causal enquiry while absolute measures are better in health planning and policy. These measures, usually in association with risk factor prevalence data, allow estimation of the risk attributable to a risk factor in those exposed and in the entire population. Avoidable mortality (and morbidity) refers to the potential to avoid death (or morbidity) from a number of specified causes if the best possible health care actions were taken. Years of life saved measures help to measure the impact of avoidable mortality in the population. Epidemiological data on diseases can be combined with other information, such as socio-economic circumstances, social values and attitudes, and behaviours relevant to health, to build up a community health profile.
Working with vulnerable populations
Authors: Betancourt Theresa S. , Beardslee William , Kirk Catherine , Hann Katrina , Zombo Moses , Mushashi Christine , Kanyanganzi Fredrick , Munyana Morris , Bizimana Justin I. 
Published: November 2017

We discuss key issues to consider when conducting clinical trials with vulnerable children, youths, and families, with particular attention to groups affected by communal violence/war and families affected by HIV/AIDS. Across these settings, there is an overlap of several forms of adversity and vulnerability which require careful research attention. We also discuss ethical practices with vulnerable groups, including the use of qualitative methods to enhance understanding of local perspectives and language around mental health problems and resilience, planning for risk of harm referral networks, and applications of community-based participatory research (CBPR) techniques. Such approaches can raise community awareness and increase engagement for addressing mental health in vulnerable populations while also informing and promoting practice and policy change. Drawing from examples of work in Sub-Saharan Africa and with refugees in the US, we conclude with a series of recommendations for advancing sensitive research practices with vulnerable populations.
GW170817: a neutron star merger in a mass-transferring triple system
Authors: Chang Philip , Murray Norman 
Published: November 2017

Abstract
The light curve of GW170817 is surprisingly blue and bright. Assuming that the event is a binary neutron star merger, we argue that blueness and brightness of the light curve is the result of ejecta that contains an substantial amount of thermal energy. To achieve this, the ejecta must be reheated at a substantial distance (1–2000 solar radii) from the merger to avoid losing the energy to adiabatic cooling. We show that this reheating can occur if the merger occurs in a hierarchical triple system where the outer star has evolved and filled its Roche lobe. The outer star feeds mass to the inner binary, forming a circumbinary disc, driving the inner binary to merge. Because the outer star fills its Roche lobe, a substantial fraction of the dynamical ejecta collides with the evolved star, reheating the ejecta in the process. We suggest that the process of mass transfer in hierarchical triples tends to form coplanar triple systems such as PSR J0337+1715, and may provide electromagnetic counterparts to binary black hole mergers.
Antiplatelet Premedication for Stent-Assisted Coil Embolization of Intracranial Aneurysms: Low-Dose Prasugrel vs Clopidogrel
Authors: Choi Hyun Ho , Lee Jung Jun , Cho Young Dae , Han Moon Hee , Cho Won-Sang , Kim Jeong Eun , An Sang Joon , Mun Jong Hyeon , Yoo Dong Hyun , Kang Hyun-Seung 
Published: November 2017

Abstract

BACKGROUND
The use of antiplatelet medications to prevent thrombosis in the treatment of cerebral aneurysms with stents has become widely emphasized.

OBJECTIVE
To compare low-dose prasugrel with clopidogrel in stent-assisted coil embolization of intracranial aneurysms.

METHODS
This is a retrospective review of 311 aneurysms from 297 patients who underwent stent-assisted endovascular coil embolization of unruptured intracranial aneurysm between November 2014 and March 2017. Thromboembolic and hemorrhagic adverse events were compared between 207 patients who received low-dose prasugrel (PSG group) and 90 patients who received clopidogrel (CPG group).

RESULTS
P2Y12 reaction unit (PRU) values were significantly lower in the PSG group (PSG group vs CPG group, 132.3 ± 76.9 vs 238.1 ± 69.1; P < .001); the percentage of inhibition was also statistically higher in the PSG group (54.0 ± 26.0% vs 20.8 ± 18.6%; P < .001). Thromboembolic events occurred less frequently in the PSG group than in the CPG group (0.9% vs 6.4%; P = .01), whereas there was no significant difference in the percentage of hemorrhagic complications (0.5% vs 2.2%; P = .22). In the multivariate analysis, clopidogrel as the antiplatelet medication was the sole significant risk factor for thromboembolism in this series of patients undergoing stent-assisted coil embolization.

CONCLUSION
Use of low-dose PSG as an antiplatelet premedication is quick, effective, and safe for stent-assisted coil embolization of unruptured intracranial aneurysms. Prasugrel premedication significantly lowered the frequency of thromboembolic events without increasing the risk of hemorrhage.