bluuebunny/crossref_metadata_2025_split huggingface dataset:
Beyond Intravenous Thrombolysis
Authors: Lee Kiwon , Muppidi Srikanth , Siddiq Farhan , Pineda Carissa , Brock David G. , Bell Rodney D. 
Published: August 2016

ABSTRACTThe National Institute of Neurological Disorders and Stroke trial of recombinant tissue plasminogen activator has been considered a landmark study in the acute treatment of ischemic stroke. Unfortunately, only a small percentage of all ischemic stroke patients presents to the hospital in time to receive the drug. Moreover, the recannalization rate of a major artery occlusion, such as the proximal middle cerebral artery or top of the internal carotid artery occlusion, after intravenous (IV) thrombolytic therapy has been disappointingly low. Since the Food and Drug Administration's approval of IV plasminogen activator, there have been numerous randomized clinical trials investigating the safety and efficacy of different thrombolytics administered in various time frames. In addition to the IV administration, efforts have been made in order to study the radiographic as well as clinical effects of intra-arterial (IA) thrombolysis. The combination of IV and IA thrombolysis has been studied. For patients who do not qualify for receiving chemical thrombolysis, new devices have been developed for mechanical thrombectomy.
Anxiety as a Primary Symptom in Cycloid Psychosis
Authors: Strik Werner K. 
Published: August 2016

AbstractPsychotic anxiety has not been systematically included in standard psychopathologic and diagnostic literature, presumably because anxiety is implicitly perceived to be an emphatically comprehensible consequence of the cognitive symptoms of psychosis. This review gives an overview of neurophysiologic studies that indicate different pathogenic mechanisms for different types of psychosis. Convergent and complementary structural and functional imaging findings, biochemical and neuropsychological data allow conjecture as to neurophysiologic-psychopathologic links in cycloid psychosis. Intriguing results suggest that in cycloid psychosis, a generalized hyperasousal related to the tonus of the noradrenergic system may be the basic disturbance causing the delusionary and perceptual psychotic distortions. The findings are specific for cycloid psychoses, which are diagnosed as polymorphous psychosis in the International Classification of Diseases and Related Health Problems, 10th Edition. Furthermore, these findings are consistent with the author's hypothesis that the emotional derailment is the primary disturbance in cycloid psychosis (anxiety-elation). In contrast, cognitive disturbances are secondary and remit after the exceptional emotional state is rebalanced.
Sexual and Other Axis I Diagnoses of 60 Males Arrested for Crimes Against Children Involving the Internet
Authors: Krueger Richard B. , Kaplan Meg S. , First Michael B. 
Published: August 2016

ABSTRACTObjective:This study was conducted to describe Axis I sexual diagnoses of 60 males arrested for possession of child pornography obtained via the Internet and/or attempting to meet children via the Internet.Methods:Data was obtained from a chart review of evaluations conducted on 60 males referred for a psychosexual evaluation following an arrest for possession of child pornography and/or attempting to meet children. All crimes involved use of the Internet. Information obtained from the chart review was entered into SAS. All diagnoses were made according to theDiagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Simple descriptive statistics were computed and cross tabulations were tested for significance using χ2 or Fisher's Exact test.Results:Of the total sample, 40% had at least one paraphilia. Thirty-one percent had a diagnosis of pedophilia and 18% of a paraphilia not otherwise specified (NOS). Thirty-three percent had a sexual disorder NOS, characterized by hypersexuality. Seventy percent of the total sample had an Axis I disorder that antedated and was judged to be contributory to the behavior leading to their arrest.Conclusions:This sample of men arrested for committing crimes against children and adolescents via the Internet has a high incidence of lifetime sexual and other psychopathology.
Cognitive Factors in Schizophrenia: Causes, Impact, and Treatment
Authors: Meltzer Herbert Y. 
Published: August 2016

AbstractGreater attention has been given to the cognitive dimension in schizophrenia in recent years. This has resulted from increased recognition that cognitive impairment and negative symptoms of the disease have a greater impact on quality of life (QOL) compared to positive symptoms. Successful treatment of positive symptoms in patients with schizophrenia has not been shown to robustly translate into improvements in employment status or social relationships, while cognitive improvements are strongly associated with these important aspects of QOL and independence. These findings are based on extensive testing with standard cognitive tests for measuring executive function, verbal learning and memory, word recall, verbal working memory, spatial working memory, attention, and vigilance. Verbal learning and executive function, in particular, have been found to be valid predictors of employment success independent of the degree of severity of positive symptoms.
Clinical Trials of Amyloid-Based Therapies for Alzheimer's Disease
Authors: Tariot Pierre N. 
Published: August 2016

AbstractWe appear to be on the brink of a new epoch of treatment for Alzheimer's disease. Compelling evidence suggests that Aβ42 secretion is the triggering event in the pathogenesis of Alzheimer's disease, and that tau aggregation may be an important secondary event linked to neurodegeneration. Prophylactic administration of anti-amyloid agents designed to prevent Aβ accumulation in persons with subclinical disease is likely to be more effective than therapeutic interventions in established Alzheimer's disease. Drug development programs in Alzheimer's disease focus primarily on agents with anti-amyloid disease-modifying properties, and many different pharmacologic approaches to reducing amyloid pathology and tauopathy are being studied. Classes of therapeutic modalities currently in advanced-stage clinical trial testing include forms of immunotherapy (activeβ-amyloid immunoconjugate and human intravenous immunoglobulin), a γ-secretase inhibitor, the selective Aβ42-lowering agent R-flurbiprofen, and the anti-aggregation agent tramiprosate. Non-traditional dementia therapies such as the HMG-CoA reductase inhibitors (statins), valproate, and lithium are now being assessed for clinical benefit as anti-amyloid disease-modifying treatments. Positive findings of efficacy and safety from clinical studies are necessary but not sufficient to demonstrate that a drug has disease-modifying properties. Definitive proof of disease-modification requires evidence from validated animal models of Alzheimer's disease; rigorously controlled clinical trials showing a significantly improved, stabilized, or slowed rate of decline in cognitive and global function compared to placebo; and prospectively obtained evidence from surrogate biomarkers that the treatment resulted in measurable biological changes associated with the underlying disease process.
Integrating Symptomatic- and Disease-Modifying Treatments
Authors: Cummings Jeffrey L. 
Published: August 2016

Although treatments for Alzheimer’s disease (AD) currently focus on symptomatic therapies, we are entering into an era of disease-modifying therapies. Central to disease modification is early diagnosis; the disease should be slowed as early as possible, maximizing the preservation of cognitive integrity. Ideally, AD should be diagnosed before the onset of dementia, perhaps with the use of biomarkers.Some therapies suggest that cholinesterase inhibitors and memantine have disease-modifying properties, though not all studies agree. Doody and colleagues have produced data suggesting that these agents may modify the course of AD, but it is not clear that they affect the underlying mechanisms that lead to cell death. Rather than being disease-modifying agents, cholinesterase inhibitors and memantine have potential as disease-course-modifying agents. Language precision will be extremely important in describing these therapies. One European consensus conference concluded that affecting disease course is not adequate for disease modification, but this has not been largely endorsed.Symptomatic therapies are those affecting the course of the disease. Their benefits are multidimensional, improving cognition, global assessment, activities of daily living, behavior, and caregiver burden. Symptomatic therapies should defer decline. Clinical trials show that symptomatic therapies produce an initial improvement above baseline. However, some patients experience observable changes and some experience none. These therapies are believed to produce ~1 point improvement on the Mini-Mental State Examination (MMSE) average, and a decline that is otherwise parallel to a placebo group after a period of delayed progression (Slide 1).
The Psychobiology of Resilience
Authors: Stein Dan J. 
Published: August 2016

AbstractAlthough adverse environments are well known to be a risk factor for psychopathology, many individuals respond adaptively to such environments. There is growing interest in the underlying mechanisms involved in such resilience. Several cognitive-affective processes may be involved, and these may be mediated by particular neuronal circuits and neurochemical systems. This article summarizes some of the relevant work on the role of fear conditioning, reward processing, and social behavior in resilience. There is a growing body of data on how particular gene-environment interactions affect these processes, and thus underpin resilience. Ultimately, a better understanding of the mechanisms underpinning resilience may lead to novel interventions.
Update on the Etiology and Treatment of Schizophrenia and Bipolar Disorder
Authors: Buckley Peter F. 
Published: August 2016

AbstractSchizophrenia and bipolar disorder are two debilitating mental health disorders, both of which manifest early in adulthood and are associated with severe impairment as well as increased suicide risk. In addition, factors affecting disease severity, such as substance abuse, are often prevalent in these patient populations. In the United States, the prevalence of bipolar disorder is believed to be ~3.5%, while the rate for schizophrenia is ~1%. Although each disorder presents with its own symptom profile, the approaches to treatment are similar and include early diagnosis and use of psychosocial therapy. Research initiatives, such as genetic studies, are used in both disorders as well. For schizophrenia, treatment typically includes the combination of an antipsychotic and psychosocial intervention. For bipolar disorder, clinicians commonly prescribe mood-stabilizing drugs (eg, lithium, valproic acid) as first-line treatment. Many of the second-generation antipsychotics have been approved by the US Food and Drug Administration for bipolar disorder treatment in the manic phase. Patients who are affected by either disorder also face the challenges of treatment nonadherence, which can be affected by substance abuse and can hinder symptom remission as well as spur unnecessary medication switches due to nonresponse. Family members play a key role in the treatment of either disorder.This expert review supplement focuses on treatment options and research strategies being utilized for the management and advanced understanding of schizophrenia and bipolar disorder. Research examining the pharmacology of commonly used medications for the treatment of both disorders is also presented.
Phos-tag analysis of Rab10 phosphorylation by LRRK2: a powerful assay for assessing kinase function and inhibitors
Authors: Ito Genta , Katsemonova Kristina , Tonelli Francesca , Lis Pawel , Baptista Marco A.S. , Shpiro Natalia , Duddy Graham , Wilson Steve , Ho Philip Wing-Lok , Ho Shu-Leong , Reith Alastair D. , Alessi Dario R. 
Published: July 2016

Autosomal dominant mutations that activate the leucine-rich repeat kinase 2 (LRRK2) cause inherited Parkinson's disease. Recent work has revealed that LRRK2 directly phosphorylates a conserved threonine/serine residue in the effector-binding switch-II motif of a number of Rab GTPase proteins, including Rab10. Here we describe a facile and robust method to assess phosphorylation of endogenous Rab10 in mouse embryonic fibroblasts (MEFs), lung and spleen-derived B-cells, based on the ability of the Phos-tag reagent to retard the electrophoretic mobility of LRRK2-phosphorylated Rab10. We exploit this assay to show that phosphorylation of Rab10 is ablated in kinase-inactive LRRK2[D2017A] knockin MEFs and mouse lung, demonstrating that LRRK2 is the major Rab10 kinase in these cells/tissue. We also establish that the Phos-tag assay can be deployed to monitor the impact that activating LRRK2 pathogenic (G2019S and R1441G) knockin mutations have on stimulating Rab10 phosphorylation. We show that upon addition of LRRK2 inhibitors, Rab10 is dephosphorylated within 1–2 min, markedly more rapidly than the Ser935 and Ser1292 biomarker sites that require 40–80 min. Furthermore, we find that phosphorylation of Rab10 is suppressed in LRRK2[S910A+S935A] knockin MEFs indicating that phosphorylation of Ser910 and Ser935 and potentially 14-3-3 binding play a role in facilitating the phosphorylation of Rab10 by LRRK2 in vivo. The Rab Phos-tag assay has the potential to significantly aid with evaluating the effect that inhibitors, mutations and other factors have on the LRRK2 signalling pathway.
Inhibitory effect of NBL1 on PDGF-BB-induced human PASMC proliferation through blockade of PDGFβ-p38MAPK pathway
Authors: Cui Chuanjue , Zhang Hongliang , Guo Lin-Na , Zhang Xiaoling , Meng Liukun , Pan Xiangbin , Wei Yingjie 
Published: July 2016

Pulmonary artery remodelling is a key feature in the pathological progress of pulmonary arterial hypertension (PAH). Moreover, excessive proliferation of pulmonary arterial smooth muscle cells (PASMCs) plays a critical role in the pathogenesis of pulmonary artery remodelling. Neuroblastoma suppressor of tumorigenicity 1 (NBL1) has been previously shown to induce growth inhibition in tumour cells. However, the effect of NBL1 in the regulation of human PASMC proliferation remains unclear. In cultured human PASMCs, we observed a dose-dependent inhibitory effect of NBL1 on platelet derived growth factor (PDGF)-BB-induced cell growth, DNA synthesis and proliferating cell nuclear antigen (PCNA) expression, as measured by MTS assay, 5-ethynil-2-deoxyuridine (EdU) analysis and western blots respectively. We also detected the expression and activities of cell-cycle positive regulators (cyclin D1, cyclin E, CDK2, CDK4 and CDK6) and negative regulators (p21 and p27) in human PASMCs by western blots and co-immuoprecipitation (IP). Our results show that NBL1-induced growth suppression is associated with the decreased activity of cyclin D1–CDK4 and the decreased phosphorylation of p27 in PDGF-BB-treated human PASMCs. By western blots using the phosphor-specific antibodies, we further demonstrated that NBL1 induced growth suppression is mediated by blockade of the up-stream PDGF-receptor β (PDGFRβ)-p38 mitogen-activated protein kinase (MAPK). In conclusion, our results suggest that NBL1 could inhibit PDGF-BB-induced human PASMC proliferation, and the underlying mechanism is associated with the decreased cyclin D1–CDK4 activity and up-regulated p27 by decreasing the phosphorylation of p27 via blockade of PDGFRβ-p38MAPK signal cascade. Our findings may provide a potential therapeutic target for PAH.
The role of Arabidopsis Actin-Related Protein 3 in amyloplast sedimentation and polar auxin transport in root gravitropism
Authors: Zou Jun-Jie , Zheng Zhong-Yu , Xue Shan , Li Han-Hai , Wang Yu-Ren , Le Jie 
Published: July 2016

Abstract
Gravitropism is vital for shaping directional plant growth in response to the forces of gravity. Signals perceived in the gravity-sensing cells can be converted into biochemical signals and transmitted. Sedimentation of amyloplasts in the columella cells triggers asymmetric auxin redistribution in root tips, leading to downward root growth. The actin cytoskeleton is thought to play an important role in root gravitropism, although the molecular mechanism has not been resolved. DISTORTED1 ( DIS1 ) encodes the ARP3 subunit of the Arabidopsis Actin-Related Protein 2/3 (ARP2/3) complex, and the ARP3/DIS1 mutant dis1-1 showed delayed root curvature after gravity stimulation. Microrheological analysis revealed that the high apparent viscosity within dis1-1 central columella cells is closely associated with abnormal movement trajectories of amyloplasts. Analysis using a sensitive auxin input reporter DII-VENUS showed that asymmetric auxin redistribution was reduced in the root tips of dis1-1 , and the actin-disrupting drug Latrunculin B increased the asymmetric auxin redistribution. An uptake assay using the membrane-selective dye FM4-64 indicated that endocytosis was decelerated in dis1-1 root epidermal cells. Treatment and wash-out with Brefeldin A, which inhibits protein transport from the endoplasmic reticulum to the Golgi apparatus, showed that cycling of the auxin-transporter PIN-FORMED (PIN) proteins to the plasma membrane was also suppressed in dis1-1 roots. The results reveal that ARP3/DIS1 acts in root gravitropism by affecting amyloplast sedimentation and PIN-mediated polar auxin transport through regulation of PIN protein trafficking.
Point-of-Care Viral Load Testing for Sub-Saharan Africa: Informing a Target Product Profile
Authors: Phillips Andrew N. , Cambiano Valentina , Nakagawa Fumiyo , Ford Deborah , Apollo Tsitsi , Murungu Joseph , Rousseau Christine , Garnett Geoff , Ehrenkranz Peter , Bansi-Matharu Loveleen , Vojnov Lara , Katz Zachary , Peeling Rosanna , Revill Paul 
Published: July 2016

Abstract
Point-of-care viral load tests are being developed to monitor patients on antiretroviral therapy (ART) in sub-Saharan Africa. Test design involves trade-offs between test attributes, including accuracy, complexity, robustness, and cost. We used a model of the human immunodeficiency virus epidemic and ART program in Zimbabwe and found that the attributes of a viral load testing approach that are most influential for cost effectiveness are avoidance of a high proportion of failed tests or results not received, use of an approach that best facilitates retention on ART, and the ability to facilitate greater use of differentiated care, including through expanding coverage of testing availability.
Prevalence and Outcomes of Hepatitis B Coinfection and Associated Liver Disease Among Antiretroviral Therapy-Naive Individuals in a Rural Tanzanian Human Immunodeficiency Virus Cohort
Authors: Ramírez-Mena Adrià , Glass Tracy R. , Winter Annja , Kimera Namvua , Ntamatungiro Alex , Hatz Christoph , Tanner Marcel , Battegay Manuel , Furrer Hansjakob , Wandeler Gilles , Letang Emilio ,   The KIULARCO Study Group, Asantiel Aschola , Battegay Manuel , Chale Adolphina , Faini Diana , Felger Ingrid , Francis Gideon , Furrer Hansjakob , Gamell Anna , Glass Tracy , Hatz Christoph , Hwaya Speciosa , Kalinjuma Aneth Vedastus , Kasuga Bryson , Kimera Namvua , Kisunga Yassin , Klimkait Thomas , Letang Emilio , Luhombero Antonia , Luwanda Lameck B , Mapesi Herry , Mbwile Leticia , Mkulila Mengi , Mkumbo Julius , Mkusa Margareth , Mnzava Dorcus K , Mossad Germana , Mpundunga Dolores , Mtandanguo Athumani , Mwamelo Kim , Myeya Selerine , Nahota Sanula , Ndaki Regina , Ngulukila Agatha , Ntamatungiro Alex John , Samson Leila , Sikalengo George , Tanner Marcel , Vanobberghen Fiona , Weisser Maja 
Published: July 2016

Abstract
Background.  We evaluated the prevalence of chronic hepatitis B virus (HBV) infection and liver fibrosis/cirrhosis in human immunodeficiency virus (HIV)-infected individuals enrolled in a rural Tanzanian prospective cohort and assessed hepatic fibrosis progression 12–24 months after antiretroviral treatment (ART) initiation.
Methods.  All ART-naive HIV-infected adults ≥15-year-old enrolled in the Kilombero and Ulanga Antiretroviral Cohort who started ART between 2005 and 2015 were included. Pre-ART factors associated with significant liver fibrosis (aspartate aminotransferase-to-platelet ratio index [APRI] &gt;1.5) and cirrhosis (APRI &gt; 2.0) were identified using logistic regression.
Results.  Of 3097 individuals screened, 227 (7.3%; 95% CI, 6.4–8.2) were hepatitis B surface antigen (HBsAg) positive. Before ART initiation, 9.1% individuals had significant liver fibrosis and 5.3% had cirrhosis. Human immunodeficiency virus/HBV-coinfected individuals were more likely to have an APRI score indicating significant fibrosis (14.2% vs 8.7%, P = .03) and cirrhosis (9.2% vs 4.9%, P = .03) than HBV-uninfected patients. CD4 cell count &lt;200 cell/μL and alcohol consumption were independently associated with pre-ART APRI score, indicating significant fibrosis and cirrhosis in multivariable analyses. Among individuals with elevated APRI measurements pre- and 12–24 months post-ART initiation, 53 of 57 (93.0%) of HIV-monoinfected and 4 of 5 (80.0%) of HIV/HBV-coinfected had a regression to APRI &lt; 1.5.
Conclusions.  Hepatic fibrosis and cirrhosis were common in our cohort, especially among HIV/HBV-coinfected individuals. The APRI improved in most patients. Pre-ART HBsAg screening and early onset of tenofovir-based ART for HIV/HBV-coinfection should be prioritized in sub-Saharan Africa.
Insurance Status and the Risk of Severe Respiratory Syncytial Virus Disease in United States Preterm Infants Born at 32–35 Weeks Gestational Age
Authors: Franklin Jeremy A. , Anderson Evan J. , Wu Xionghua , Ambrose Christopher S. , Simões Eric A. F. 
Published: July 2016

Abstract
Background.  Database studies have identified that public health insurance status is associated with an increased risk of severe respiratory syncytial virus (RSV) disease in US infants. However, these studies did not adjust for the presence of other risk factors and did not evaluate the risk in preterm infants.
Methods.  In this study, we evaluate the independent association between public insurance and severe RSV disease outcomes adjusting for other risk factors. The prospective, observational RSV Respiratory Events among Preterm Infants Outcomes and Risk Tracking (REPORT) study was conducted over 2 consecutive RSV seasons at 188 US clinical sites that enrolled preterm infants born at 32–35 wGA who had not received RSV immunoprophylaxis with palivizumab. Adjusted incidence rates per 100 infant-seasons of the RSV-associated endpoints of outpatient lower respiratory tract infection (LRI), emergency department (ED) visits, RSV hospitalizations (RSVHs), and intensive care unit admissions during peak RSV season (November–March) were compared for infants with private and public insurance.
Results.  Of 1642 evaluable infants enrolled in the REPORT study, 50.1% had private insurance and 49.9% had public health insurance. Adjusted rates of RSV outpatient LRIs were similar; however, rates of ED visits (hazard ratio [HR], 2.04; 95% confidence interval [CI], 1.20–3.45) were higher for subjects with public insurance, with a similar but nonsignificant trend observed for hospitalization (HR, 1.61; 95% CI, .93–2.78).
Conclusions.  Socioeconomic status, as evaluated by public versus private healthcare insurance, is a significant independent risk factor for ED use in US preterm infants and may contribute to increased RSVHs in this population.