bluuebunny/crossref_metadata_2025_split huggingface dataset:
Absence of Gliosis in the Brains of Epileptic Fowl
Authors: Munoz D.G. , McNab B. , George D.H. , Johnson D. 
Published: May 2019

ABSTRACT:Chickens homozygous for the epi gene (epileptics) suffer from spontaneous seizures throughout their life, whereas heterozygous (carriers) are phenotypically normal. Seizures can also be evoked in epileptics by photic stimulation. In addition, epileptic chickens' brains are 25% heavier than those of carriers. We have investigated whether hyperplasia or hypertrophy of astrocytes or increased numbers of astrocytic processes are involved in the development of seizures and the megalencephaly in this model by quantitative comparison of sections immunocytochemically stained for glial fibrillary acidic protein (GFAP). No statistically significant differences between epileptics and controls were found in any of seven areas selected for comparison. In this model gliosis is not involved in the development of epilepsy, nor does it result from repeated seizures.
Subarachnoid Hemorrhage and Normal Angiography: Should the Angiogram be Reviewed by a Second Neuroradiologist?
Authors: Shuaib Ashfaq , Lee Mary Anne , Johns Robert D. , Swanson Harold A. 
Published: May 2019

ABSTRACT:In recent years there has been a tendency to abandon repeat cerebral angiography in patients with subarachnoid hemorrhage (SAH) if the initial angiogram is normal because prognosis is said to be excellent. Our experience does not support such a conclusion. We report our experiences in 25 patients with SAH, who had a normal initial angiogram. Aneurysms were seen in five of 20 cases when angiography was repeated. On subsequent review of the initial angiograms, the aneurysm was apparent in four of the five cases. When these four initial angiograms were shown to a second observer, unaware of the results of the second study, three of the four aneurysms were correctly identified. We suggest that if, under strong clinical suspicion of SAH, the angiogram is reported as normal the study should be reviewed by a second neuro-radiologist before proceeding to repeat angiography.
Basilar Artery Blood Flow in Subclavian Steal
Authors: Bornstein Natan M. , Krajewski Adam , Norris John W. 
Published: May 2019

ABSTRACT:Subclavian “steal”, when blood siphons from one vertebral artery to the other, has been suggested as a cause of brain stem ischaemia and stroke. We investigated 33 patients using transcranial Doppler to determine the direction and velocity of basilar blood flow. All patients had severe subclavian stenosis with reversed vertebral blood flow in the ipsilateral artery previously demonstrated by extracranial Doppler. Basilar flow was normal in direction in all cases, but its velocity was significantly increased (p<0.0008) compared to age- and sex-matched controls. These findings, in conjunction with previous observations using extracranial Doppler techniques, suggest that subclavian steal is little more than a harmless haemodynamic phenomenon.
Lupus Anticoagulant, Antiphospholipid Antibodies and Migraine
Authors: Hogan M.J. , Brunet D.G. , Ford P.M. , Lillicrap D. 
Published: May 2019

ABSTRACT:The records of fifteen patients referred for neurological assessment and found to have lupus anticoagulant or elevated anticardiolipin antibodies were reviewed. The mean age for females in the group was 29.4 years and for males was 35. A diagnosis of migraine, either as an acute or chronic problem, was made in 10 (66%) of these patients. Seven of the 15 patients had ischemic stroke and two patients had other thrombotic complications associated with lupus anticoagulant. Three of the nine female patients with migraine had histories of spontaneous abortions. All migraine patients experienced transient or more prolonged neurological deficits with their headaches. An association between lupus anticoagulant and migraine can only be suggested. Data on the incidence of migraine in patients with lupus anticoagulant in the general medical population does not exist. Furthermore the prevalence of lupus anticoagulant in migraine sufferers is unknown. Therefore further studies are required to investigate this possible association.
Dermatomyositis and Granulomatous Myopathy Associated with Sarcoidosis
Authors: Lipton Jeffrey H. , McLeod B. Daniel , Brownell A. Keith W. 
Published: May 2019

ABSTRACT:A previously healthy, 21-year-old female presented with acute dermatomyositis. Chest X-ray revealed bilateral hilar adenopathy, and mediastinal lymph node biopsy demonstrated noncaseating granulomata compatible with sarcoidosis. The patient improved spontaneously. The significance of bilateral hilar adenopathy in association with dermatomyositis and implications for management are discussed.
Recurrent Intracranial Hemorrhage in an Adult with Moyamoya Disease: Case Report, Radiographic Studies and Pathology
Authors: Kaufman Mark , Little Brian W. , Berkowitz Bernard W. 
Published: May 2019

ABSTRACT:Moyamoya disease is an unusual vascular disorder highlighted by progressive bilateral internal carotid artery occlusion and collateralization of intracranial blood flow. Recurrent multifocal cerebral ischemic events and isolated intracerebral hemorrhage are known to occur in this disorder. We report a 52 year old man who over a nine year period had four apparent intracranial hemorrhages. Serial angiograms demonstrated the evolution of moyamoya disease. Pathologic examination confirmed multiple vascular lesions, including two that were clinically silent.
Gender's Role in Manuscript Acceptance: Sex in the Journal
Authors: Harper Carolyn R. , Willis Cleve E. 
Published: May 2019

Women authors fare poorly at the hands of referees in some economics journals, especially when the review process is not blind. Using data on the 155 manuscripts submitted to the NJARE for publication during the period 1984–88, we found no evidence of differential referee acceptance rates for manuscripts with female and male lead authors.Thus it is quite possible that the name “Miss” transmits through the board or division some vibration which is not registered in the examination room.Virginia WoolfThree Guineas
Toward a Development Policy for Rural America: Discussion
Authors: Smith Stephen M. 
Published: May 2019

The issue of a rural policy—whether or not we have one, what one should look like, should we have one—has been discussed more specifically in the mid-1980s. This is a result of the general economic crisis that has affected rural areas, and the realization that agricultural policy has only a limited impact. Professor Barkley has provided us with a valuable and interesting context within which to examine the need for and content of a rural development policy. His paper should force us to raise such questions as:1.Have the ways we dealt with rural problems, i.e., our rural policy, changed in any substantial way?2.Have we had any successes, and substantially affected rural problems?3.Or, do we continue to propose the same solutions to the same problems?
The Saturday Leisure Club: A Means of Facilitating the Integration of the Disabled
Authors: Gow Lyn , Balla John 
Published: May 2019

AbstractProviding out-of-school recreation programs for the disabled enables them to use their free time productively and provides a means by which they can be integrated into the community. Although the need to foster integration of the disabled is internationally acknowledged, in Australia there is a dearth of out-of-school recreation programs for the disabled in Australia where such integration can be promoted. To remediate this deficiency in the Illawarra Region, “The Saturday Leisure Club” was piloted to ascertain its feasibility and suitability. Non-disabled siblings of the disabled were included in this program, in order to achieve a first stage of integration, and to provide them with an opportunity to meet other siblings of the disabled so that they might discuss their socio-emotional difficulties with one another. Questionnaires were completed by parents of participants and the co-ordinators of the program after a 4-week pilot run in order to evaluate the aims of the Club and to assess the success of this pilot project. In addition, time samples of the pilot run were recorded on videotape so that a more objective evaluation of the success of integration of the disabled with their non-disabled peers could be obtained. To do this “integrative” and “isolative” behaviours and “positive enotional experiences” were measured by a specially designed checklist. Results of the questionnaires showed that, according to the parents and co-ordinators, the aims of the pilot run were achieved and the program was a success. Further, the analysis of the videotapes showed that there was an increase in “integrative” behaviour over the four weeks of the pilot run. As a consequence, the program was continued and the ultimate aim, of providing a permanent leisure program for under 18 year olds in the Illawarra Region, N.S. W., where integration of the disabled could be fostered, was fulfilled.
INCOMPLETENESS VIA PARADOX AND COMPLETENESS
Authors: DEAN WALTER 
Published: May 2019

AbstractThis paper explores the relationship borne by the traditional paradoxes of set theory and semantics to formal incompleteness phenomena. A central tool is the application of the Arithmetized Completeness Theorem to systems of second-order arithmetic and set theory in which various “paradoxical notions” for first-order languages can be formalized. I will first discuss the setting in which this result was originally presented by Hilbert & Bernays (1939) and also how it was later adapted by Kreisel (1950) and Wang (1955) in order to obtain formal undecidability results. A generalization of this method will then be presented whereby Russell’s paradox, a variant of Mirimanoff’s paradox, the Liar, and the Grelling–Nelson paradox may be uniformly transformed into incompleteness theorems. Some additional observations are then framed relating these results to the unification of the set theoretic and semantic paradoxes, the intensionality of arithmetization (in the sense of Feferman, 1960), and axiomatic theories of truth.
Characterization of a waterhemp (Amaranthus tuberculatus) population from Illinois resistant to herbicides from five site-of-action groups
Authors: Evans Cody M. , Strom Seth A. , Riechers Dean E. , Davis Adam S. , Tranel Patrick J. , Hager Aaron G. 
Published: May 2019

AbstractExperiments were initiated to characterize a waterhemp population (CHR) discovered in a central Illinois corn field after it was not controlled by the 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor topramezone. Field experiments conducted during 2014–2015 indicated that acetolactate synthase (ALS)-, protoporphyrinogen oxidase (PPO)-, photosystem II (PSII)-, and HPPD-inhibiting herbicides and the synthetic auxin 2,4-D did not control the CHR population. Laboratory experiments confirmed target site–based resistance mechanisms to ALS- and PPO-inhibiting herbicides. Herbicide doses required to reduce dry biomass 50% (GR50) were determined in greenhouse dose–response experiments, and indicated 16-fold resistance to the HPPD inhibitor mesotrione, 9.5-fold resistance to the synthetic auxin 2,4-D, and 252-fold resistance to the PSII inhibitor atrazine. Complementary results from field, laboratory, and greenhouse investigations indicate that the CHR population has evolved resistance to herbicides from five sites of action (SOAs): ALS-, PPO-, PSII-, and HPPD-inhibiting herbicides and 2,4-D. Herbicide use history for the field in which CHR was discovered indicates no previous use of 2,4-D.
A genome-wide association meta-analysis of prognostic outcomes following cognitive behavioural therapy in individuals with anxiety and depressive disorders
Authors: Rayner Christopher , Coleman Jonathan R. I. , Purves Kirstin L. , Hodsoll John , Goldsmith Kimberley , Alpers Georg W. , Andersson Evelyn , Arolt Volker , Boberg Julia , Bögels Susan , Creswell Cathy , Cooper Peter , Curtis Charles , Deckert Jürgen , Domschke Katharina , El Alaoui Samir , Fehm Lydia , Fydrich Thomas , Gerlach Alexander L. , Grocholewski Anja , Hahlweg Kurt , Hamm Alfons , Hedman Erik , Heiervang Einar R. , Hudson Jennifer L. , Jöhren Peter , Keers Robert , Kircher Tilo , Lang Thomas , Lavebratt Catharina , Lee Sang-hyuck , Lester Kathryn J. , Lindefors Nils , Margraf Jürgen , Nauta Maaike , Pané-Farré Christiane A. , Pauli Paul , Rapee Ronald M , Reif Andreas , Rief Winfried , Roberts Susanna , Schalling Martin , Schneider Silvia , Silverman Wendy K. , Ströhle Andreas , Teismann Tobias , Thastum Mikael , Wannemüller Andre , Weber Heike , Wittchen Hans-Ulrich , Wolf Christiane , Rück Christian , Breen Gerome , Eley Thalia C. 
Published: May 2019

AbstractMajor depressive disorder and the anxiety disorders are highly prevalent, disabling and moderately heritable. Depression and anxiety are also highly comorbid and have a strong genetic correlation (rg ≈ 1). Cognitive behavioural therapy is a leading evidence-based treatment but has variable outcomes. Currently, there are no strong predictors of outcome. Therapygenetics research aims to identify genetic predictors of prognosis following therapy. We performed genome-wide association meta-analyses of symptoms following cognitive behavioural therapy in adults with anxiety disorders (n = 972), adults with major depressive disorder (n = 832) and children with anxiety disorders (n = 920; meta-analysis n = 2724). We estimated the variance in therapy outcomes that could be explained by common genetic variants (h2SNP) and polygenic scoring was used to examine genetic associations between therapy outcomes and psychopathology, personality and learning. No single nucleotide polymorphisms were strongly associated with treatment outcomes. No significant estimate of h2SNP could be obtained, suggesting the heritability of therapy outcome is smaller than our analysis was powered to detect. Polygenic scoring failed to detect genetic overlap between therapy outcome and psychopathology, personality or learning. This study is the largest therapygenetics study to date. Results are consistent with previous, similarly powered genome-wide association studies of complex traits.
Postmortem transcriptional profiling reveals widespread increase in inflammation in schizophrenia: a comparison of prefrontal cortex, striatum, and hippocampus among matched tetrads of controls with subjects diagnosed with schizophrenia, bipolar or major depressive disorder
Authors: Lanz Thomas A. , Reinhart Veronica , Sheehan Mark J. , Rizzo Stacey J. Sukoff , Bove Susan E. , James Larry C. , Volfson Dmitri , Lewis David A. , Kleiman Robin J. 
Published: May 2019

AbstractPsychiatric disorders such as schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD) arise from complex interactions between genetic and environmental factors. Common genetic variants associated with multiple psychiatric disorders suggest that shared genetic architecture could contribute to divergent clinical syndromes. To evaluate shared transcriptional alterations across connected brain regions, Affymetrix microarrays were used to profile postmortem dorsolateral prefrontal cortex (DLPFC), hippocampus, and associative striatum from 19 well-matched tetrads of subjects with SCZ, BD, MDD, or unaffected controls. SCZ subjects showed a substantial burden of differentially expressed genes across all examined brain regions with the greatest effects in hippocampus, whereas BD and MDD showed less robust alterations. Pathway analysis of transcriptional profiles compared across diagnoses demonstrated commonly enriched pathways between all three disorders in hippocampus, significant overlap between SCZ and BD in DLPFC, but no significant overlap of enriched pathways between disorders in striatum. SCZ samples showed increased expression of transcripts associated with inflammation across all brain regions examined, which was not evident in BD or MDD, or in rat brain following chronic dosing with antipsychotic drugs. Several markers of inflammation were confirmed by RT-PCR in hippocampus, including S100A8/9, IL-6, MAFF, APOLD1, IFITM3, and BAG3. A cytokine ELISA panel showed significant increases in IL-2 and IL-12p70 protein content in hippocampal tissue collected from same SCZ subjects when compared to matched control subjects. These data suggest an overlapping subset of dysregulated pathways across psychiatric disorders; however, a widespread increase in inflammation appears to be a specific feature of the SCZ brain and is not likely to be attributable to chronic antipsychotic drug treatment.
Optimization of 4-1BB antibody for cancer immunotherapy by balancing agonistic strength with FcγR affinity
Authors: Qi Xinyue , Li Fanlin , Wu Yi , Cheng Chen , Han Ping , Wang Jieyi , Yang Xuanming 
Published: May 2019

AbstractCostimulation of T cell responses with monoclonal antibody agonists (mAb-AG) targeting 4-1BB showed robust anti-tumor activity in preclinical models, but their clinical development was hampered by low efficacy (Utomilumab) or severe liver toxicity (Urelumab). Here we show that isotype and intrinsic agonistic strength co-determine the efficacy and toxicity of anti-4-1BB mAb-AG. While intrinsically strong agonistic anti-4-1BB can activate 4-1BB in the absence of FcγRs, weak agonistic antibodies rely on FcγRs to activate 4-1BB. All FcγRs can crosslink anti-41BB antibodies to strengthen co-stimulation, but activating FcγR-induced antibody-dependent cell-mediated cytotoxicity compromises anti-tumor immunity by deleting 4-1BB+cells. This suggests balancing agonistic activity with the strength of FcγR interaction as a strategy to engineer 4-1BB mAb-AG with optimal therapeutic performance. As a proof of this concept, we have developed LVGN6051, a humanized 4-1BB mAb-AG that shows high anti-tumor efficacy in the absence of liver toxicity in a mouse model of cancer immunotherapy.
BRAF inhibition sensitizes melanoma cells to α-amanitin via decreased RNA polymerase II assembly
Authors: Frischknecht Lukas , Britschgi Christian , Galliker Patricia , Christinat Yann , Vichalkovski Anton , Gstaiger Matthias , Kovacs Werner J. , Krek Wilhelm 
Published: May 2019

AbstractDespite the great success of small molecule inhibitors in the treatment of patients with BRAFV600E mutated melanoma, the response to these drugs remains transient and patients eventually relapse within a few months, highlighting the need to develop novel combination therapies based on the understanding of the molecular changes induced by BRAFV600E inhibitors. The acute inhibition of oncogenic signaling can rewire entire cellular signaling pathways and thereby create novel cancer cell vulnerabilities. Here, we demonstrate that inhibition of BRAFV600E oncogenic signaling in melanoma cell lines leads to destabilization of the large subunit of RNA polymerase II POLR2A (polymerase RNA II DNA-directed polypeptide A), thereby preventing its binding to the unconventional prefoldin RPB5 interactor (URI1) chaperone complex and the successful assembly of RNA polymerase II holoenzymes. Furthermore, in melanoma cell lines treated with mitogen-activated protein kinase (MAPK) inhibitors, α-amanitin, a specific and irreversible inhibitor of RNA polymerase II, induced massive apoptosis. Pre-treatment of melanoma cell lines with MAPK inhibitors significantly reduced IC50 values to α-amanitin, creating a state of collateral vulnerability similar to POLR2A hemizygous deletions. Thus, the development of melanoma specific α-amanitin antibody-drug conjugates could represent an interesting therapeutic approach for combination therapies with BRAFV600E inhibitors.
Vesicular Stomatitis Virus-Based Vaccine Protects Mice against Crimean-Congo Hemorrhagic Fever
Authors: Rodriguez Sergio E. , Cross Robert W. , Fenton Karla A. , Bente Dennis A. , Mire Chad E. , Geisbert Thomas W. 
Published: May 2019

AbstractCrimean-Congo hemorrhagic fever virus (CCHFV), a tick-borne bunyavirus, can cause a life-threatening hemorrhagic syndrome in humans but not in its animal host. The virus is widely distributed throughout southeastern Europe, the Middle East, Africa, and Asia. Disease management has proven difficult and there are no broadly licensed vaccines or therapeutics. Recombinant vesicular stomatitis viruses (rVSV) expressing foreign glycoproteins (GP) have shown promise as experimental vaccines for several viral hemorrhagic fevers. Here, we developed and assessed a replication competent rVSV vector expressing the CCHFV glycoprotein precursor (GPC), which encodes CCHFV structural glycoproteins. This construct drives strong expression of CCHFV-GP, in vitro. Using these vectors, we vaccinated STAT-1 knock-out mice, an animal model for CCHFV. The vector was tolerated and 100% efficacious against challenge from a clinical strain of CCHFV. Anti-CCHFV-GP IgG and neutralizing antibody titers were observed in surviving animals. This study demonstrates that a rVSV expressing only the CCHFV-GP has the potential to serve as a replication competent vaccine platform against CCHF infections.
Increased prefrontal cortex interleukin-2 protein levels and shift in the peripheral T cell population in progressive supranuclear palsy patients
Authors: Rydbirk Rasmus , Elfving Betina , Folke Jonas , Pakkenberg Bente , Winge Kristian , Brudek Tomasz , Aznar Susana 
Published: May 2019

AbstractAccumulating evidence suggests neuroinflammation to be an integrated feature of neurodegeneration. Profiling inflammatory mediators across diseases may reveal common and disease-specific signatures. Here, we focused on progressive supranuclear palsy (PSP), a tauopathy presenting motor and cognitive dysfunction. We screened for 21 cytokines and growth factors in the dorsomedial prefrontal cortex of 16 PSP and 16 control brains using different quantitative techniques. We found and validated increased interleukin (IL)-2 protein levels in the PSP group expressed locally by neurons and glia cells. We further investigated central players in neuroinflammatory pathways and found increased mRNA expression of glycogen synthase kinase 3 beta (GSK3B). IL-2 and GSK3B proteins are T and natural killer (NK) cell regulators and have previously been associated with other neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease and multiple system atrophy. In addition, we identified a shift in peripheral CD4+ and CD8+ T cell populations toward increased numbers of memory and reduced numbers of naive T cells. We also observed increased numbers of CD56+ NK cells, but not of CD56+CD57+ or CD57+ NK cells. Our findings suggest a role for IL-2 in PSP disease processes and point toward active and possibly dysfunctional peripheral immune responses in these patients.