bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA damage and brain trauma: a clue to pathophysiology and biomarker development
Authors: Hazrati LN 
Published: September 2019

Mild traumatic brain injury (mTBI) or concussion is a very common occurrence in contact sports, and can cause brain damage with long-term symptoms, including depression, aggression, memory loss, and an increased risk of neurodegeneration later in life. Recently, there has been increased attention towards concussion in sport both in research and media, however the nature and pathophysiology of mTBI-induced neurodegeneration remain unknown. The objective of this study is to identify early pathophysiological markers of TBI. This study used a collection of donated postmortem brains with a history of repetitive mTBI in contact sports and non-TBI control brains. Nanostring ncounter’s immune panel was used to evaluate gene expression, and results showed that brains with a history of TBI tended to group with significantly older brains with no history of TBI in regards to their immune profile. Further analysis of this expression panel revealed that genes associated with senescence and secretory phenotype were upregulated in brains with a history of mTBI. Additionally, immunohistochemistry for γ-H2AX (a marker for double stranded DNA breaks) showed that brains with a history of repetitive TBI accumulated a spectrum of DNA damages not present in controls. This damage was widespread and involved mainly glial cells including oligodendrocytes, and astrocytes. The latter showed morphological changes reminiscent of senescence, including soma swelling and beading of processes. Further, these changes were accompanied by translocation of structural nuclear proteins. These changes preceded the appearance of abnormal protein deposition in the brain. Overall, these results suggest that DNA damage and cellular senescence are upstream events in the manifestation of post-mTBI symptoms and pathology, and represent promising opportunities for discovery of biomarkers for early TBI detection and follow-up of progression.LEARNING OBJECTIVESThe presentation will enable the learner to:1.Explore the relationship between trauma and DNA structural changes2.Explore the relationship between trauma and senescence
Epilepsy Related Death: the London Health Sciences Center Experience
Authors: Zhang Q , Ang LC 
Published: September 2019

Premature mortality among epilepsy patients is well recognized. Except a few identifiable causes of unnatural death, more than half of the epilepsy related death remains unexplained after extensive workup. These cases are classified as sudden unexpected death in epilepsy (SUDEP). SUDEP incidence varies significantly depending on the population, the methods documenting cause of death and the availability of Neuropathological examination. An accurate diagnosis of the cause of death is needed for epilepsy related death. The goal of this study is to present the relevant clinical data, the general autopsy and Neuropathology findings of epilepsy related death investigated in London Health Sciences Center during the period of 2000 to 2011. We identified 71 cases with known history of chronic epilepsy. In the 29 cases of epilepsy associated death, the causes of death have been classified as cardiac, pulmonary, accidental (e.g. drowning), toxic (e.g. drug overdose) and non-related causes. Forty two cases are considered to be SUDEP, and were categorized according to the recently proposed SUDEP Definition and Classification. Half of the SUDEP cases have no specific Neuropathological findings. The most common identifiable lesions in SUDEP cases are perinatal/neonatal destructive lesions (29%), hippocampal sclerosis (24%), and focal cortical dysplasia (20%). These are followed by neuronal heterotopia (9%), previous head trauma (9%), and cavernoma (5%).LEARNING OBJECTIVESThis presentation will enable the learner to:1.Review cause of death in epilepsy related deaths2.Discuss the practice guideline in neuropathology autopsy of epilepsy related deaths
Area postrema: fetal maturation, tumours, vomiting centre, somatic growth and role in neuromyelitis optica
Authors: Sarnat HB , Flores-Sarnat L , Boltshauser E 
Published: September 2019

The area postrema (AP) in the caudal 4th ventricular floor is unique, highly vascular without blood/brain or /CSF barrier. In addition to its function as the vomiting centre, several other important functions are: part of the circumventricular organs for vasomotor and angiotensin II regulation; a role in neuromyelitis optica related to aquaporin-4; contributor to fetal and postnatal somatic growth. Functions are immature at birth.The purpose of this study was to demonstrate AP neuronal/synaptic/glial maturation in normal fetuses and 3 AP tumours. Transverse sections of the caudal 4th ventricle of 18 normal human fetal brains at autopsy, 6 to 40 weeks were examined; also 3 infants 3-18mos; 2 children. A battery of immunocytochemical neuronal and glial markers: MAP2; calretinin; synaptophysin; vimentin; nestin; GFAP; S-100β protein; were applied to paraffin sections. Two children with AP tumours and one with neurocutaneous melanocytosis, all with pernicious vomiting, were studied. In normal fetuses, AP neurons exhibited cytological maturity and well-formed synaptic circuitry by 14wk gestation. Size/volume increase was disproportionately greater than brainstem growth in 2nd and 3rd trimesters and postnatally. Astrocytes co-expressed vimentin/GFAP but glia were best demonstrated by S-100β protein. Ependyma over the AP in fetuses is simple cuboidal, adjacent to pseudostratified columnar of the 4th ventricular floor. Melanocytes infiltrated AP in the toddler with pernicious vomiting; 2 children had primary AP pilocytic astrocytomas. Though AP is cytologically mature by 14wk, growth increases and functions mature into the postnatal months. We recommend that AP neuropathology include synaptophysin and S-100β at autopsy if AP dysfunction suspected.LEARNING OBJECTIVESThis presentation will enable the learner to:1.Explain the maturation of neurons, synaptic circuits and glial elements of the AP2.List and recognize tumours that can affect the area postrema3.Describe functions of the area postrema
Clinical, neuropathological and molecular features of fatal human pegivirus-associated encephalitis
Authors: Schmitt LM , Balcom E , Doan M , Branton WG , Jovel J , Blevins G , Edguer B , Hobman TC , Yacyshyn E , Emery D , Box A , Power C , van Landeghem FKH 
Published: September 2019

Flaviviruses include many viruses causing encephalitis, including West Nile encephalitis, St. Louis encephalitis, tick-borne encephalitis and Japanese encephalitis. Human pegivirus genotype-1 (HPgV-1) is a lesser known member of the Flaviviridae family and has been identified in human serum, cerebrospinal fluid and brain tissue. Here, we describe two adult patients with fatal HPgV-1-associated encephalitis. Neuroimaging revealed multifocal lesions, initially present in the periventricular and brain stem white matter, then one year later throughout the corona radiata bilaterally with marked involvement of the brainstem and cervical spinal cord. Phylogenetic analyses of HPgV-1 showed clustering of brain-derived sequences from both patients with other human pegiviruses. In both patients, a novel 87-nucleotide deletion in the viral NS2 gene was detected. The presence of positive and negative strand HPgV-1 RNA and viral antigens in both patients indicated viral persistence and replication in the CNS. Autopsy showed lymphocyte infiltration and gliosis predominantly in white matter of the brain and brain stem but, to a lesser extent, also in grey matter. Immunofluorescence revealed HPgV-1 NS5A antigen in lymphocytes as well as in astrocytes and oligodendrocytes. Thus, we hypothesize that the novel deletion in the NS2 coding region may have caused HPgV-1 neuroadaptation or might represent a yet unrecognized genotype of human pegivirus.LEARNING OBJECTIVESThis presentation will enable the learner to:1.Describe the clinical and neuropathological features of fatal human pegivirus-associated encephalitis2.Recognize the importance of molecular analysis in encephalitis cases with unknown etiology
Evaluation of the effectiveness of eight screening tools in detecting risk of malnutrition in cirrhotic patients: the KIRRHOS study
Authors: Georgiou Alexandra , Papatheodoridis Georgios V. , Alexopoulou Alexandra , Deutsch Melanie , Vlachogiannakos Ioannis , Ioannidou Panagiota , Papageorgiou Maria-Vasiliki , Papadopoulos Nikolaos , Tsibouris Panagiotis , Prapa Adamantia , Yannakoulia Mary , Kontogianni Meropi D. 
Published: September 2019

AbstractMalnutrition risk screening in cirrhotic patients is crucial, as poor nutritional status negatively affects disease prognosis and survival. Given that a variety of malnutrition screening tools is usually used in routine clinical practice, the effectiveness of eight screening tools in detecting malnutrition risk in cirrhotic patients was sought. A total of 170 patients (57·1 % male, 59·4 (sd 10·5) years, 50·6 % decompensated ones) with cirrhosis of various aetiologies were enrolled. Nutritional screening was performed using the Malnutrition Universal Screening Tool, Nutritional Risk Index, Malnutrition Screening Tool, Nutritional Risk Screening (NRS-2002), Birmingham Nutritional Risk Score, Short Nutritional Assessment Questionnaire, Royal Free Hospital Nutritional Prioritizing Tool (RFH-NPT) and Liver Disease Undernutrition Screening Tool (LDUST). Malnutrition diagnosis was defined using the Subjective Global Assessment (SGA). Data on 1-year survival were available for 145 patients. The prevalence of malnutrition risk varied according to the screening tools used, with a range of 13·5–54·1 %. RFH-NPT and LDUST were the most accurate in detecting malnutrition (AUC = 0·885 and 0·892, respectively) with a high sensitivity (97·4 and 94·9 %, respectively) and fair specificity (73·3 and 58 %, respectively). Malnutrition according to SGA was an independent prognostic factor of within 1-year mortality (relative risk was 2·17 (95 % CI 1·0, 4·7), P = 0·049) after adjustment for sex, age, disease aetiology and Model for End-stage Liver Disease score, whereas nutrition risk according to RFH-NPT, LDUST and NRS-2002 showed no association. RFH-NPT and LDUST were the only screening tools that proved to be accurate in detecting malnutrition in cirrhotic patients.
Gandhi's Newspaperman: T. G. Narayanan and the quest for an independent India, 1938–46
Authors: PAUL SUBIN , DOWLING DAVID 
Published: September 2019

AbstractThe expansion of the colonial public sphere in India during the 1930s and 1940s saw the nation's English-language press increasingly serve as a key site in the struggle for freedom despite British censorship. This article examines the journalistic career of T. G. Narayanan, the first Indian war correspondent and investigative reporter, to understand the role of English-language newspapers in India's quest for independence. Narayanan reported on two major events leading to independence: the Bengal famine of 1943 and the Second World War. Drawing on Michael Walzer's concept of the ‘connected critic’, this research demonstrates that Narayanan's journalism fuelled the Indian nationalist movement by manoeuvring around British censors to publicize and expand Mahatma Gandhi's criticism of British rule, especially in light of the famine and war. His one departure from the pacifist leader, however, was his support of Indian soldiers serving in the Indian National Army and British Army.
Salusin-α levels are negatively correlated with diastolic blood pressure in children with obesity
Authors: Dervişoğlu Pınar , Elmas Bahri , Kösecik Mustafa , İşgüven Şükriye P. , Büyükavcı Mustafa , Köroğlu Mehmet 
Published: September 2019

AbstractSalusins have emerged as a new biomarker that reflects an increased inflammatory state, which is associated with cardiovascular risk. We investigated the predictive value and usefulness of salusins as an inflammatory biomarker in obese children. This prospective cohort study included 75 obese children and 101 healthy children (as a control group). Salusin-α, Salusin-β, and various cardiovascular parameters were assessed in both groups. Correlation analyses of Salusin-α and Salusin-β with body mass index standard deviation scores and inflammatory and cardiovascular markers were performed. The mean patient age was 11.9±2.4 years for the obese group and 12.5±2.1 years for the control group. The obese children had a significantly higher heart rate, systolic blood pressure, diastolic blood pressure, epicardial adipose tissue thickness, and left ventricular mass than did the children in the control group. There was no significant correlation between Salusin-α and Salusin-β and body mass index; however, there was a negative correlation between Salusin- α and diastolic blood pressure (r = 0.277, p = 0.004). Overall, there was no significant difference in the Salusin-α and Salusin-β levels between obese and healthy children. However, a negative correlation was found between Salusin-α and diastolic blood pressure. Although this result suggests that Salusin-α might be an early marker of cardiovascular involvement in obese children, further studies are needed to demonstrate the predictive value of salusins.
Key Uncertainties in the Recent Air‐Sea Flux of CO2
Authors: Woolf D.K. , Shutler J.D. , Goddijn‐Murphy L. , Watson A.J. , Chapron B. , Nightingale P.D. , Donlon C.J. , Piskozub J. , Yelland M.J. , Ashton I. , Holding T. , Schuster U. , Girard‐Ardhuin F. , Grouazel A. , Piolle J.‐F. , Warren M. , Wrobel‐Niedzwiecka I. , Land P.E. , Torres R. , Prytherch J. , Moat B. , Hanafin J. , Ardhuin F. , Paul F. 
Published: September 2019

AbstractThe contemporary air‐sea flux of CO2 is investigated by the use of an air‐sea flux equation, with particular attention to the uncertainties in global values and their origin with respect to that equation. In particular, uncertainties deriving from the transfer velocity and from sparse upper ocean sampling are investigated. Eight formulations of air‐sea gas transfer velocity are used to evaluate the combined standard uncertainty resulting from several sources of error. Depending on expert opinion, a standard uncertainty in transfer velocity of either ~5% or ~10% can be argued and that will contribute a proportional error in air‐sea flux. The limited sampling of upper ocean fCO2 is readily apparent in the Surface Ocean CO2 Atlas databases. The effect of sparse sampling on the calculated fluxes was investigated by a bootstrap method, that is, treating each ship cruise to an oceanic region as a random episode and creating 10 synthetic data sets by randomly selecting episodes with replacement. Convincing values of global net air‐sea flux can only be achieved using upper ocean data collected over several decades but referenced to a standard year. The global annual referenced values are robust to sparse sampling, but seasonal and regional values exhibit more sampling uncertainty. Additional uncertainties are related to thermal and haline effects and to aspects of air‐sea gas exchange not captured by standard models. An estimate of global net CO2 exchange referenced to 2010 of −3.0 ± 0.6 Pg C/year is proposed, where the uncertainty derives primarily from uncertainty in the transfer velocity.
Dinitrogen Fixation Across Physico‐Chemical Gradients of the Eastern Tropical North Pacific Oxygen Deficient Zone
Authors: Selden C. R. , Mulholland M. R. , Bernhardt P. W. , Widner B. , Macías‐Tapia A. , Ji Q. , Jayakumar A. 
Published: September 2019

AbstractThe Eastern Tropical North Pacific Ocean hosts one of the world's largest oceanic oxygen deficient zones (ODZs). Hot spots for reactive nitrogen (Nr) removal processes, ODZs generate conditions proposed to promote Nr inputs via dinitrogen (N2) fixation. In this study, we quantified N2 fixation rates by 15N tracer bioassay across oxygen, nutrient, and light gradients within and adjacent to the ODZ. Within subeuphotic oxygen‐deplete waters, N2 fixation was largely undetectable; however, addition of dissolved organic carbon stimulated N2 fixation in suboxic (<20 μmol/kg O2) waters, suggesting that diazotroph communities are likely energy limited or carbon limited and able to fix N2 despite high ambient concentrations of dissolved inorganic nitrogen. Elevated rates (>9 nmol N·L−1·day−1) were also observed in suboxic waters near volcanic islands where N2 fixation was quantifiable to 3,000 m. Within the overlying euphotic waters, N2 fixation rates were highest near the continent, exceeding 500 μmol N·m−2·day−1 at one third of inshore stations. These findings support the expansion of the known range of diazotrophs to deep, cold, and dissolved inorganic nitrogen‐replete waters. Additionally, this work bolsters calls for the reconsideration of ocean margins as important sources of Nr. Despite high rates at some inshore stations, regional N2 fixation appears insufficient to compensate for Nr loss locally as observed previously in the Eastern Tropical South Pacific ODZ.
Mantle Structure in the Central Mediterranean Region From P and S Receiver Functions
Authors: Monna S. , Montuori C. , Piromallo C. , Vinnik L. 
Published: September 2019

AbstractWe investigate the upper mantle discontinuities in the central Mediterranean region by applying the P and S receiver function techniques on waveforms recorded at broadband stations located around the Tyrrhenian basin. P and S wave velocity profiles (down to 300‐km depth) are calculated with joint inversion of P and S receiver functions. We could identify the Moho, lithosphere‐asthenosphere boundary, and an underlying low‐velocity layer between ~60‐ and ~200‐km depth. The low‐velocity layer is interpreted as asthenospheric material, and its lower boundary is identified below the western Ionian and Tyrrhenian basins as a sharp Lehmann discontinuity. Although the stations are located on different lithospheric domains we find a strong correlation between Moho and the lithosphere‐asthenosphere boundary depths, which suggests ubiquitous coupling of the crust and lithospheric mantle, consistently with the southward opening of the Tyrrhenian basin. The Tyrrhenian and western Ionian basins present thinning of the transition zone of ~14 km, as inferred from a reduced P660s‐P410s differential time. Below the southern Apennines we observe a standard differential time that implies an average mantle transition zone thickness. We explain these mantle transition zone thickness variations as due to temperature heterogeneity linked to the area's subduction history. Finally, under central Europe (the location of the deep S‐to‐P conversion points) two strong signals from nonstandard discontinuities within the mantle transition zone are observed. These signals can be explained as being generated at the boundaries of high seismic velocity layers that are spatially correlated with stagnant slabs in the transition zone detected by seismic tomography.
Structure‐Coupled 3‐D Imaging of Magnetotelluric and Wide‐Angle Seismic Reflection/Refraction Data With Interfaces
Authors: Peng Miao , Tan Handong , Moorkamp Max 
Published: September 2019

AbstractMagnetotelluric (MT) and wide‐angle seismic reflection/refraction surveys play a fundamental role in understanding the crustal rheology and lithospheric structure of the Earth. In recent years, the integration of the two methods in order to improve the robustness of the inversion has started to gain attention. We present a new approach for joint 3‐D inversion of MT and wide‐angle seismic reflection/refraction data to accurately determine crustal structures and Moho depth. Based on H‐κ stacking of teleseismic receiver functions, we estimate an initial reference Moho. This is used as input for the subsequent MT/seismic joint inversion, where the Moho interface is updated and crustal structures are added to the model. During the joint inversion process, structural similarity is facilitated through the cross‐gradient constraint. Synthetic model tests show an improvement of the inversion results over separate inversions. In particular, the tests based on two geologically realistic models demonstrate that the crustal structure and even the trade‐off between velocity and Moho interface can be sufficiently resolved by combined MT and seismic data sets when using the estimates from analysis of receiver functions. These results show that the new method can provide useful constraints on crustal structures including their geophysical properties and discontinuities.
Infrasonic Wave‐Induced Variations of Ionospheric HF Sounding Echoes
Authors: Mabie Justin , Bullett Terence 
Published: September 2019

AbstractWe conducted ionospheric observations during several Orbital Corporation International Space Station Resupply missions from the Mid‐Atlantic Regional Spaceport at National Aeronautics and Space Administration Wallops Flight Facility in Virginia. These observations were made under different ionospheric and thermospheric conditions using different variations of an experimental sounding mode of the Wallops Vertical Incidence Pulsed Ionospheric Radar. We present an analysis of variations in signal strength (fading), range (signal delay), and echo arrival angle as the rocket‐generated High Altitude Acoustic Waves propagate in the thermosphere and through the plasma layers being observed. The results improve our understanding of the effects of infrasonic waves on remote sensing of the ionosphere and on radio wave propagation through the ionosphere and thermosphere.
History and progress of hypotheses and clinical trials for Alzheimer’s disease
Authors: Liu Pei-Pei , Xie Yi , Meng Xiao-Yan , Kang Jian-Sheng 
Published: September 2019

AbstractAlzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive memory loss along with neuropsychiatric symptoms and a decline in activities of daily life. Its main pathological features are cerebral atrophy, amyloid plaques, and neurofibrillary tangles in the brains of patients. There are various descriptive hypotheses regarding the causes of AD, including the cholinergic hypothesis, amyloid hypothesis, tau propagation hypothesis, mitochondrial cascade hypothesis, calcium homeostasis hypothesis, neurovascular hypothesis, inflammatory hypothesis, metal ion hypothesis, and lymphatic system hypothesis. However, the ultimate etiology of AD remains obscure. In this review, we discuss the main hypotheses of AD and related clinical trials. Wealthy puzzles and lessons have made it possible to develop explanatory theories and identify potential strategies for therapeutic interventions for AD. The combination of hypometabolism and autophagy deficiency is likely to be a causative factor for AD. We further propose that fluoxetine, a selective serotonin reuptake inhibitor, has the potential to treat AD.
Multilevel structure–activity profiling reveals multiple green tea compound families that each modulate ubiquitin-activating enzyme and ubiquitination by a distinct mechanism
Authors: Fenteany Gabriel , Gaur Paras , Hegedűs Lili , Dudás Kata , Kiss Ernő , Wéber Edit , Hackler László , Martinek Tamás , Puskás László G. , Haracska Lajos 
Published: September 2019

AbstractWe developed and implemented a reconstituted system to screen for modulators of the ubiquitination of proliferating cell nuclear antigen, a process that activates pathways of DNA damage tolerance and drug resistance. We identified the primary putatively health-beneficial green tea polyphenol epigallocatechin gallate (EGCG) and certain related small molecules as potent inhibitors of ubiquitination. EGCG directly and reversibly targets the ubiquitin-activating enzyme Uba1, blocking formation of the Uba1~ubiquitin thioester conjugate and thus ubiquitination and in the cell. Structure–activity relationship profiles across multiple biochemical and cellular assays for a battery of EGCG analogues revealed distinct chemical and mechanism-of-action clusters of molecules, with catechin gallates, alkyl gallates, and myricetin potently inhibiting ubiquitination. This study defines a number of related though distinct first-in-class inhibitors of ubiquitination, each series with its own unique activity pattern and mechanistic signature.