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The Macrophage Inhibitor Cni-1493 Blocks Metastasis In A Mouse Model Of Ewing Sarcoma Through Inhibition Of Extravasation, A. J. Hesketh, C. Maloney, C. A. Behr, M. C. Edelman, R. D. Glick, Y. Al-Abed, M. Symons, S. Z. Soffer, B. M. Steinberg Jan 2015

The Macrophage Inhibitor Cni-1493 Blocks Metastasis In A Mouse Model Of Ewing Sarcoma Through Inhibition Of Extravasation, A. J. Hesketh, C. Maloney, C. A. Behr, M. C. Edelman, R. D. Glick, Y. Al-Abed, M. Symons, S. Z. Soffer, B. M. Steinberg

Journal Articles

Metastatic Ewing Sarcoma carries a poor prognosis, and novel therapeutics to prevent and treat metastatic disease are greatly needed. Recent evidence demonstrates that tumor-associated macrophages in Ewing Sarcoma are associated with more advanced disease. While some macrophage phenotypes (M1) exhibit anti-tumor activity, distinct phenotypes (M2) may contribute to malignant progression and metastasis. In this study, we show that M2 macrophages promote Ewing Sarcoma invasion and extravasation, pointing to a potential target of anti-metastatic therapy. CNI-1493 is a selective inhibitor of macrophage function and has shown to be safe in clinical trials as an anti-inflammatory agent. In a xenograft mouse model …

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Immune Dysregulation In Patients Persistently Infected With Human Papillomaviruses 6 And 11, A. V. Lucs, J. A. Devoti, L. Hatam, A. Afzal, A. L. Abramson, B. M. Steinberg, V. R. Bonagura Jan 2015

Immune Dysregulation In Patients Persistently Infected With Human Papillomaviruses 6 And 11, A. V. Lucs, J. A. Devoti, L. Hatam, A. Afzal, A. L. Abramson, B. M. Steinberg, V. R. Bonagura

Journal Articles

Human Papillomaviruses (HPVs) 6 and 11 are part of a large family of small DNA viruses, some of which are commensal. Although much of the population can contain or clear infection with these viruses, there is a subset of individuals who develop persistent infection that can cause significant morbidity and on occasion mortality. Depending on the site of infection, patients chronically infected with these viruses develop either recurrent, and on occasion, severe genital warts or recurrent respiratory papillomas that can obstruct the upper airway. The HPV-induced diseases described are likely the result of a complex and localized immune suppressive milieu …

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N-Acetylcysteine Attenuates Tumor Necrosis Factor Alpha Levels In Autoimmune Inner Ear Disease Patients, S. Pathak, C. Stern, A. Vambutas Jan 2015

N-Acetylcysteine Attenuates Tumor Necrosis Factor Alpha Levels In Autoimmune Inner Ear Disease Patients, S. Pathak, C. Stern, A. Vambutas

Journal Articles

Autoimmune inner ear disease (AIED) is a poorly understood disease marked by bilateral, rapidly progressive hearing loss triggered by unknown stimuli, which is corticosteroid responsive in 60 % of patients. Although the mechanism of the disease is not precisely understood, a complex interaction of cytokines is believed to contribute toward the inflammatory disease process and hearing loss. Previously, we showed the role of TNF-alpha in steroid-sensitive and IL-1beta in steroid-resistant immune-mediated hearing loss. N-Acetylcysteine (NAC), a broad spectrum antioxidant, has been effective in other autoimmune disorders. Other studies have shown NAC to have a protective adjunct role in human idiopathic …

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Poly(I:C) Induces Controlled Release Of Il-36gamma From Keratinocytes In The Absence Of Cell Death, A. A. Rana, A. V. Lucs, J. Devoti, L. Blanc, J. Papoin, R. Wu, C. J. Papayannakos, A. Abramson, V. R. Bonagura, B. M. Steinberg Jan 2015

Poly(I:C) Induces Controlled Release Of Il-36gamma From Keratinocytes In The Absence Of Cell Death, A. A. Rana, A. V. Lucs, J. Devoti, L. Blanc, J. Papoin, R. Wu, C. J. Papayannakos, A. Abramson, V. R. Bonagura, B. M. Steinberg

Journal Articles

The epithelium is part of an integrated immune system where cytokines, toll-like receptors and their ligands, and extracellular vesicles play a crucial role in initiating an innate immune response. IL-36gamma is a pro-inflammatory member of the IL-1 family that is mainly expressed by epithelial cells, but regulation of its expression and release are only beginning to be understood. Previous studies reported that IL-36gamma is abundant in recurrent respiratory papillomatosis, a rare but devastating disease caused by human papillomaviruses (HPV) types 6 and 11, in which papillomas recurrently grow in and block the airway. Despite the overexpression of IL-36gamma, papilloma tissues …

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Giant Cell Tumor Of The Larynx Treated By Surgery And Adjuvant Denosumab: Case Report And Review Of The Literature, A. E. Yancoskie, D. K. Frank, J. E. Fantasia, S. Savona, N. Eiseler, I. Reder, L. B. Kahn Jan 2015

Giant Cell Tumor Of The Larynx Treated By Surgery And Adjuvant Denosumab: Case Report And Review Of The Literature, A. E. Yancoskie, D. K. Frank, J. E. Fantasia, S. Savona, N. Eiseler, I. Reder, L. B. Kahn

Journal Articles

Giant cell tumor of the larynx (GCTL) is a rare entity; only 34 cases have been reported in the literature. We report a case of GCTL in a 46 year-old male presenting clinical, radiographic, histological and therapeutic features. Previously reported cases are also reviewed.

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Beta-Human Chorionic Gonadotropin Producing Osteosarcoma Of The Sacrum In A 26-Year-Old Woman: A Case Report And Review Of The Literature, R. Glass, J. R. Asirvatham, L. Kahn, M. Aziz Jan 2015

Beta-Human Chorionic Gonadotropin Producing Osteosarcoma Of The Sacrum In A 26-Year-Old Woman: A Case Report And Review Of The Literature, R. Glass, J. R. Asirvatham, L. Kahn, M. Aziz

Journal Articles

Ectopic secretion of beta-human chorionic gonadotropin is considered a poor prognostic marker in epithelial tumors. However, very few cases have been reported in sarcomas. We present the case of a 26-year-old female who presented with a metastatic osteosarcoma. She underwent usual testing prior to starting treatment and was found to have elevated levels of beta-human chorionic gonadotropin. As the patient was not pregnant, another source of beta-human chorionic gonadotropin secretion had to be considered. The tumor cells demonstrated positive staining for beta-human chorionic gonadotropin by immunohistochemistry, and serum levels of beta-human chorionic gonadotropin were used to monitor tumor progression and …

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Tbl1xr1 In Physiological And Pathological States, J. Y. Li, G. Daniels, J. Wang, X. Zhang Jan 2015

Tbl1xr1 In Physiological And Pathological States, J. Y. Li, G. Daniels, J. Wang, X. Zhang

Journal Articles

Transducin (beta)-like 1X related protein 1 (TBL1XR1/TBLR1) is an integral subunit of the NCoR (nuclear receptor corepressor) and SMRT (silencing mediator of retinoic acid and thyroid hormone receptors) repressor complexes. It is an evolutionally conserved protein that shares high similarity across all species. TBL1XR1 is essential for transcriptional repression mediated by unliganded nuclear receptors (NRs) and othe regulated transcription factors (TFs). However, it can also act as a transcription activator through the recruitment of the ubiquitin-conjugating/19S proteasome complex that mediates the exchange of corepressors for coactivators. TBL1XR1 is required for the activation of multiple intracellular signaling pathways. TBL1XR1 germline mutations …

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High Mobility Group Box Protein 1 (Hmgb1): The Prototypical Endogenous Danger Molecule, Huan Yang, H. Wang, Sangeeta S. Chavan, Ulf Andersson Jan 2015

High Mobility Group Box Protein 1 (Hmgb1): The Prototypical Endogenous Danger Molecule, Huan Yang, H. Wang, Sangeeta S. Chavan, Ulf Andersson

Journal Articles

No abstract provided.

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Milk Fat Globule Epidermal Growth Factor-Factor 8-Derived Peptide Attenuates Organ Injury And Improves Survival In Sepsis, W. L. Yang, A. Sharma, F. Zhang, S. Matsuo, Z. Wang, H. Wang, P. Wang Jan 2015

Milk Fat Globule Epidermal Growth Factor-Factor 8-Derived Peptide Attenuates Organ Injury And Improves Survival In Sepsis, W. L. Yang, A. Sharma, F. Zhang, S. Matsuo, Z. Wang, H. Wang, P. Wang

Journal Articles

INTRODUCTION: Sepsis involves overwhelming inflammatory responses with subsequent immune-suppression that can lead to multiple organ dysfunction and ultimately death. Milk fat globule epidermal growth factor-factor 8 (MFG-E8) is a secretory protein found to have multiple biological activities against autoimmune and inflammatory diseases. MFG-E8 contains an Arg-Gly-Asp (RGD) motif involved in cell-cell and cell-matrix interactions. In sepsis, excessive neutrophils migration through endothelial cells and matrix to sites of inflammation results in organ damage. We hypothesized that MFG-E8-derived short peptides (MSP) flanking its RGD motif could provide protection against organ injury in sepsis. METHODS: The differentiated human neutrophil-like HL-60 cells (dHL60) were …

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Transmucosal Bleomycin For Tongue Lymphatic Malformations, E. W. Cerrati, T. M. O., D. Binetter, Y. Bernstein, M Waner Jan 2015

Transmucosal Bleomycin For Tongue Lymphatic Malformations, E. W. Cerrati, T. M. O., D. Binetter, Y. Bernstein, M Waner

Journal Articles

No abstract provided.

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Diagnosis And Management Of Infantile Hemangioma, D. H. Darrow, A. K. Greene, A. J. Mancini, A. J. Nopper, T. M. O Jan 2015

Diagnosis And Management Of Infantile Hemangioma, D. H. Darrow, A. K. Greene, A. J. Mancini, A. J. Nopper, T. M. O

Journal Articles

Infantile hemangiomas (IHs) are the most common tumors of childhood. Unlike other tumors, they have the unique ability to involute after proliferation, often leading primary care providers to assume they will resolve without intervention or consequence. Unfortunately, a subset of IHs rapidly develop complications, resulting in pain, functional impairment, or permanent disfigurement. As a result, the primary clinician has the task of determining which lesions require early consultation with a specialist. Although several recent reviews have been published, this clinical report is the first based on input from individuals representing the many specialties involved in the treatment of IH. Its …

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Should Sports Drinks Be Given To Children And Adolescents Engaged In Athletics As An Effective Source Of Hydration?, Zeev W. Rubinson Jan 2015

Should Sports Drinks Be Given To Children And Adolescents Engaged In Athletics As An Effective Source Of Hydration?, Zeev W. Rubinson

The Science Journal of the Lander College of Arts and Sciences

Dehydration in children and adolescents is a major concern for caretakers. Often children are not drinking enough, particularly while participating in physical activity. Utilizing data drawn from pediatricians, nutritionists, and bio-scientists, this paper will examine whether sports drinks are a good source of fluids for the exercising child. The results of the research indicate that the advantages generally associated with sports drinks, to achieve higher body water absorption levels, prevent electrolyte deficits, and maintain proper electrolyte/water concentrations, are reserved for unique circumstances. Sports drink intake should be encouraged only when the child is participating in prolonged physical activity, in intense …

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North American Prodrome Longitudinal Study (Napls 2) The Prodromal Symptoms, J. Addington, L. Liu, L. Buchy, K. S. Cadenhead, T. D. Cannon, B. A. Cornblatt, D. O. Perkins, C. E. Bearden, D. H. Mathalon, T. H. Mcglashan, +4 Additional Authors Jan 2015

North American Prodrome Longitudinal Study (Napls 2) The Prodromal Symptoms, J. Addington, L. Liu, L. Buchy, K. S. Cadenhead, T. D. Cannon, B. A. Cornblatt, D. O. Perkins, C. E. Bearden, D. H. Mathalon, T. H. Mcglashan, +4 Additional Authors

Journal Articles

In studies describing the long-term follow-up up of youth at clinical high risk (CHR) of psychosis, little attention has been given to details of specific prodromal symptoms. In this paper, we describe the prodromal symptoms of 764 CHR participants recruited in the multi-site North American Prodrome Longitudinal Study (NAPLS). Symptoms were rated on the Scale of Prodromal Symptoms (SOPS) at baseline and 6-, 12-, 18-, and 24-month follow-ups. Clinical outcome at the 2-year assessment was categorized as psychotic, prodromal progression, symptomatic or in remission. Most of the CHR sample (92%) met criteria for the attenuated positive symptoms syndrome (APSS). Significant …

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Association Of Thalamic Dysconnectivity And Conversion To Psychosis In Youth And Young Adults At Elevated Clinical Risk, A. Anticevic, K. Haut, J. D. Murray, G. Repovs, B. Goodyear, K. S. Cadenhead, H. Mirzakhanian, B. A. Cornblatt, D. Olvet, T. D. Cannon, +16 Additional Authors Jan 2015

Association Of Thalamic Dysconnectivity And Conversion To Psychosis In Youth And Young Adults At Elevated Clinical Risk, A. Anticevic, K. Haut, J. D. Murray, G. Repovs, B. Goodyear, K. S. Cadenhead, H. Mirzakhanian, B. A. Cornblatt, D. Olvet, T. D. Cannon, +16 Additional Authors

Journal Articles

IMPORTANCE: Severe neuropsychiatric conditions, such as schizophrenia, affect distributed neural computations. One candidate system profoundly altered in chronic schizophrenia involves the thalamocortical networks. It is widely acknowledged that schizophrenia is a neurodevelopmental disorder that likely affects the brain before onset of clinical symptoms. However, no investigation has tested whether thalamocortical connectivity is altered in individuals at risk for psychosis or whether this pattern is more severe in individuals who later develop full-blown illness. OBJECTIVES: To determine whether baseline thalamocortical connectivity differs between individuals at clinical high risk for psychosis and healthy controls, whether this pattern is more severe in those …

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Perfectionism Related To Self-Reported Insomnia Severity, But Not When Controlled For Stress And Emotion Regulation, S. Brand, R. Kirov, N. Kalak, M. Gerber, U. Puhse, S. Lemola, Christoph Correll, S. Cortese, T. Meyer, E. Holsboer-Trachsler Jan 2015

Perfectionism Related To Self-Reported Insomnia Severity, But Not When Controlled For Stress And Emotion Regulation, S. Brand, R. Kirov, N. Kalak, M. Gerber, U. Puhse, S. Lemola, Christoph Correll, S. Cortese, T. Meyer, E. Holsboer-Trachsler

Journal Articles

Background: Perfectionism is understood as a set of personality traits such as unrealistically high and rigid standards for performance, fear of failure, and excessive self-criticism. Previous studies showed a direct association between increased perfectionism and poor sleep, though without taking into account possible mediating factors. Here, we tested the hypothesis that perfectionism was directly associated with poor sleep, and that this association collapsed, if mediating factors such as stress and poor emotion regulation were taken into account. Methods: Three hundred and forty six young adult students (M=23.87 years) completed questionnaires relating to perfectionism traits, sleep, and psychological functioning such as …

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Abnormal Movements In First-Episode, Nonaffective Psychosis: Dyskinesias, Stereotypies, And Catatonic-Like Signs, M. T. Compton, F. Fantes, C. R. Wan, S. Johnson, E. F. Walker Jan 2015

Abnormal Movements In First-Episode, Nonaffective Psychosis: Dyskinesias, Stereotypies, And Catatonic-Like Signs, M. T. Compton, F. Fantes, C. R. Wan, S. Johnson, E. F. Walker

Journal Articles

Motor abnormalities represent a neurobehavioral domain of signs intrinsic to schizophrenia-spectrum disorders, though they are commonly attributed to medication side effects and remain understudied. Individuals with first-episode psychosis represent an ideal group to study innate movement disorders due to minimal prior antipsychotic exposure. We measured dyskinesias, stereotypies, and catatonic-like signs and examined their associations with: (1) age at onset of psychotic symptoms and duration of untreated psychosis; (2) positive, negative, and disorganized symptoms; (3) neurocognition; and (4) neurological soft signs. Among 47 predominantly African American first-episode psychosis patients in a public-sector hospital, the presence and severity of dyskinesias, stereotypies, and …

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Memory Systems In Schizophrenia: Modularity Is Preserved But Deficits Are Generalized, K. M. Haut, K. H. Karlsgodt, R. M. Bilder, E. Congdon, N. B. Freimer, E. D. London, F. W. Sabb, J. Ventura, T. D. Cannon Jan 2015

Memory Systems In Schizophrenia: Modularity Is Preserved But Deficits Are Generalized, K. M. Haut, K. H. Karlsgodt, R. M. Bilder, E. Congdon, N. B. Freimer, E. D. London, F. W. Sabb, J. Ventura, T. D. Cannon

Journal Articles

OBJECTIVE: Schizophrenia patients exhibit impaired working and episodic memory, but this may represent generalized impairment across memory modalities or performance deficits restricted to particular memory systems in subgroups of patients. Furthermore, it is unclear whether deficits are unique from those associated with other disorders. METHOD: Healthy controls (n=1101) and patients with schizophrenia (n=58), bipolar disorder (n=49) and attention-deficit-hyperactivity-disorder (n=46) performed 18 tasks addressing primarily verbal and spatial episodic and working memory. Effect sizes for group contrasts were compared across tasks and the consistency of subjects' distributional positions across memory domains was measured. RESULTS: Schizophrenia patients performed poorly relative to the …

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Genome-Wide Autozygosity Is Associated With Lower General Cognitive Ability, D. P. Howrigan, M. A. Simonson, G. Davies, S. E. Harris, A. Tenesa, J. M. Starr, D. C. Liewald, D. I. Boomsma, P. Derosse, M. C. Keller, +37 Additional Authors Jan 2015

Genome-Wide Autozygosity Is Associated With Lower General Cognitive Ability, D. P. Howrigan, M. A. Simonson, G. Davies, S. E. Harris, A. Tenesa, J. M. Starr, D. C. Liewald, D. I. Boomsma, P. Derosse, M. C. Keller, +37 Additional Authors

Journal Articles

Inbreeding depression refers to lower fitness among offspring of genetic relatives. This reduced fitness is caused by the inheritance of two identical chromosomal segments (autozygosity) across the genome, which may expose the effects of (partially) recessive deleterious mutations. Even among outbred populations, autozygosity can occur to varying degrees due to cryptic relatedness between parents. Using dense genome-wide single-nucleotide polymorphism (SNP) data, we examined the degree to which autozygosity associated with measured cognitive ability in an unselected sample of 4854 participants of European ancestry. We used runs of homozygosity-multiple homozygous SNPs in a row-to estimate autozygous tracts across the genome. We …

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New Data And An Old Puzzle: The Negative Association Between Schizophrenia And Rheumatoid Arthritis, S. H. Lee, T. Lencz, A. K. Malhotra, H. Medeiros, V. Milanova, J. Shi, P. Sklar, P. K. Gregersen, M. Van Laar, P. Van Riel, +134 Additional Authors Jan 2015

New Data And An Old Puzzle: The Negative Association Between Schizophrenia And Rheumatoid Arthritis, S. H. Lee, T. Lencz, A. K. Malhotra, H. Medeiros, V. Milanova, J. Shi, P. Sklar, P. K. Gregersen, M. Van Laar, P. Van Riel, +134 Additional Authors

Journal Articles

BACKGROUND: A long-standing epidemiological puzzle is the reduced rate of rheumatoid arthritis (RA) in those with schizophrenia (SZ) and vice versa. Traditional epidemiological approaches to determine if this negative association is underpinned by genetic factors would test for reduced rates of one disorder in relatives of the other, but sufficiently powered data sets are difficult to achieve. The genomics era presents an alternative paradigm for investigating the genetic relationship between two uncommon disorders. METHODS: We use genome-wide common single nucleotide polymorphism (SNP) data from independently collected SZ and RA case-control cohorts to estimate the SNP correlation between the disorders. We …

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Targeting The Schizophrenia Genome: A Fast Track Strategy From Gwas To Clinic, T. Lencz, A. K. Malhotra Jan 2015

Targeting The Schizophrenia Genome: A Fast Track Strategy From Gwas To Clinic, T. Lencz, A. K. Malhotra

Journal Articles

The Psychiatric Genomics Consortium-Schizophrenia Workgroup (PGC-SCZ) has recently published a genomewide association study (GWAS) identifying > 100 genetic loci, encompassing a total of 341 protein-coding genes, attaining genomewide significance for susceptibility to schizophrenia. Given the extremely long time (12-15 years) and expense (>$1 billion) associated with the development of novel drug targets, repurposing of drugs with known and validated targets may be the most expeditious path toward deriving clinical utility from these GWAS findings. In the present study, we examined all genes within loci implicated by the PGC-SCZ GWAS against databases of targets of both approved and registered pharmaceutical compounds. …

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Prognostic Role And Implications Of Mutation Status Of Tumor Suppressor Gene Arid1a In Cancer: A Systematic Review And Meta-Analysis, C. Luchini, N. Veronese, M. Solmi, H. Cho, J. H. Kim, S. Kyo, S. Y. Lee, D. W. Kim, G. M. Yousef, C. U. Correll, +22 Additional Authors Jan 2015

Prognostic Role And Implications Of Mutation Status Of Tumor Suppressor Gene Arid1a In Cancer: A Systematic Review And Meta-Analysis, C. Luchini, N. Veronese, M. Solmi, H. Cho, J. H. Kim, S. Kyo, S. Y. Lee, D. W. Kim, G. M. Yousef, C. U. Correll, +22 Additional Authors

Journal Articles

Loss of the tumor suppressor gene AT-rich interactive domain-containing protein 1A (ARID1A) has been demonstrated in several cancers, but its prognostic role is unknown. We aimed to investigate the risk associated with loss of ARID1A (ARID1A-) for all-cause mortality, cancer-specific mortality and recurrence of disease in subjects with cancer. PubMed and SCOPUS search from database inception until 01/31/2015 without language restriction was conducted, contacting authors for unpublished data. Eligible were prospective studies reporting data on prognostic parameters in subjects with cancer, comparing participants with presence of ARID1A (ARID1A+) vs. ARID1A-, assessed either via immunohistochemistry (loss of expression) or with genetic …

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The Navigate Program For First-Episode Psychosis: Rationale, Overview, And Description Of Psychosocial Components, K. T. Mueser, D. L. Penn, P. Meyer-Kalos, S. R. Mcgurk, C. Cather, S. Saade, D. G. Robinson, N. R. Schooler, R. A. Rosenheck, J. M. Kane, +6 Additional Authors Jan 2015

The Navigate Program For First-Episode Psychosis: Rationale, Overview, And Description Of Psychosocial Components, K. T. Mueser, D. L. Penn, P. Meyer-Kalos, S. R. Mcgurk, C. Cather, S. Saade, D. G. Robinson, N. R. Schooler, R. A. Rosenheck, J. M. Kane, +6 Additional Authors

Journal Articles

Comprehensive coordinated specialty care programs for first-episode psychosis have been widely implemented in other countries but not in the United States. The National Institute of Mental Health's Recovery After an Initial Schizophrenia Episode (RAISE) initiative focused on the development and evaluation of first-episode treatment programs designed for the U.S. health care system. This article describes the background, rationale, and nature of the intervention developed by the RAISE Early Treatment Program project-known as the NAVIGATE program-with a particular focus on its psychosocial components. NAVIGATE is a team-based, multicomponent treatment program designed to be implemented in routine mental health treatment settings and …

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Psychiatric Genome-Wide Association Study Analyses Implicate Neuronal, Immune And Histone Pathways, C. O'Dushlaine, C. Betancur, S. Herms, R. Krasucki, M. Leboyer, D. H. Ledbetter, T. Lencz, A. K. Malhotra, J. W. Smoller, P. A. Holmans, +365 Additional Authors Jan 2015

Psychiatric Genome-Wide Association Study Analyses Implicate Neuronal, Immune And Histone Pathways, C. O'Dushlaine, C. Betancur, S. Herms, R. Krasucki, M. Leboyer, D. H. Ledbetter, T. Lencz, A. K. Malhotra, J. W. Smoller, P. A. Holmans, +365 Additional Authors

Journal Articles

Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple …

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Severity Of Thought Disorder Predicts Psychosis In Persons At Clinical High-Risk, D. O. Perkins, C. D. Jeffries, B. A. Cornblatt, S. W. Woods, J. Addington, D. H. Mathalon, L. J. Seidman, M. T. Tsuang, E. F. Walker, T. H. Mcglashan, +4 Additional Authors Jan 2015

Severity Of Thought Disorder Predicts Psychosis In Persons At Clinical High-Risk, D. O. Perkins, C. D. Jeffries, B. A. Cornblatt, S. W. Woods, J. Addington, D. H. Mathalon, L. J. Seidman, M. T. Tsuang, E. F. Walker, T. H. Mcglashan, +4 Additional Authors

Journal Articles

BACKGROUND: Improving predictive accuracy is of paramount importance for early detection and prevention of psychosis. We sought a symptom severity classifier that would improve psychosis risk prediction. METHODS: Subjects were from two cohorts of the North American Prodrome Longitudinal Study. All subjects met Criteria of Psychosis-Risk States. In Cohort-1 (n=296) we developed a classifier that included those items of the Scale of Psychosis-Risk Symptoms that best distinguished subjects who converted to psychosis from nonconverters, with performance initially validated by randomization tests in Cohort-1. Cohort-2 (n=592) served as an independent test set. RESULTS: We derived 2-Item and 4-Item subscales. Both included …

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Iqgap1 Regulates Actin Cytoskeleton Organization In Podocytes Through Interaction With Nephrin, Y. P. Liu, W. Liang, Y. J. Yang, Y. B. Pan, Q. Yang, X. H. Chen, P. C. Singhal, G. H. Ding Jan 2015

Iqgap1 Regulates Actin Cytoskeleton Organization In Podocytes Through Interaction With Nephrin, Y. P. Liu, W. Liang, Y. J. Yang, Y. B. Pan, Q. Yang, X. H. Chen, P. C. Singhal, G. H. Ding

Journal Articles

Increasing data has shown that the cytoskeletal reorganization of podocytes is involved in the onset of proteinuria and the progression of glomerular disease. Nephrin behaves as a signal sensor of the slit diaphragm to transmit cytoskeletal signals to maintain the unique structure of podocytes. However, the nephrin signaling cascade deserves further study. IQGAP1 is a scaffolding protein with the ability to regulate cytoskeletal organization. It is hypothesized that IQGAP1 contributes to actin reorganization in podocytes through interaction with nephrin. IQGAP1 expression and IQGAP1-nephrin colocalization in glomeruli were progressively decreased and then gradually recovered in line with the development of foot …

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Body Mass Index, Pam50 Subtype, And Outcomes In Node-Positive Breast Cancer: Calgb 9741 (Alliance), J. A. Ligibel, C. T. Cirrincione, M. Liu, M. Citron, J. N. Ingle, W. Gradishar, S. Martino, W. Sikov, R. Michaelson, W. T. Barry, +6 Additional Authors Jan 2015

Body Mass Index, Pam50 Subtype, And Outcomes In Node-Positive Breast Cancer: Calgb 9741 (Alliance), J. A. Ligibel, C. T. Cirrincione, M. Liu, M. Citron, J. N. Ingle, W. Gradishar, S. Martino, W. Sikov, R. Michaelson, W. T. Barry, +6 Additional Authors

Journal Articles

BACKGROUND: Obesity at diagnosis is associated with poor prognosis in women with breast cancer, but few reports have been adjusted for treatment factors. METHODS: CALGB 9741 was a randomized trial of dose density and sequence of chemotherapy for node-positive breast cancer. All patients received doxorubicin, cyclophosphamide, and paclitaxel, dosed by actual body weight. Height and weight at diagnosis were abstracted from patient records, and the PAM50 assay was performed from archived specimens using the NanoString platform. Relationships between body mass index (BMI), PAM50, and recurrence-free and overall survival (RFS and OS) were evaluated using proportional hazards regression, adjusting for number …

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Mitochondrial Dysfunction In Peripheral Blood Mononuclear Cells In Pediatric Septic Shock, S. L. Weiss, M. A. Selak, F. Tuluc, J. Perales Villarroel, V. M. Nadkarni, C. S. Deutschman, L. B. Becker Jan 2015

Mitochondrial Dysfunction In Peripheral Blood Mononuclear Cells In Pediatric Septic Shock, S. L. Weiss, M. A. Selak, F. Tuluc, J. Perales Villarroel, V. M. Nadkarni, C. S. Deutschman, L. B. Becker

Journal Articles

OBJECTIVES: Mitochondrial dysfunction in peripheral blood mononuclear cells has been linked to immune dysregulation and organ failure in adult sepsis, but pediatric data are limited. We hypothesized that pediatric septic shock patients exhibit mitochondrial dysfunction within peripheral blood mononuclear cells which in turn correlates with global organ injury. DESIGN: Prospective observational study. SETTING: Academic PICU. PATIENTS: Thirteen pediatric patients with septic shock and greater than or equal to two organ failures and 11 PICU controls without sepsis or organ failure. INTERVENTIONS: Ex vivo measurements of mitochondrial oxygen consumption and membrane potential (DeltaPsim) were performed in intact peripheral blood mononuclear cells …

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Population Pharmacokinetics Of Darbepoetin Alfa In Conjunction With Hypothermia For The Treatment Of Neonatal Hypoxic-Ischemic Encephalopathy, J. K. Roberts, C. Stockmann, R. M. Ward, J. Beachy, M. C. Baserga, M. G. Spigarelli, C. M. Sherwin Jan 2015

Population Pharmacokinetics Of Darbepoetin Alfa In Conjunction With Hypothermia For The Treatment Of Neonatal Hypoxic-Ischemic Encephalopathy, J. K. Roberts, C. Stockmann, R. M. Ward, J. Beachy, M. C. Baserga, M. G. Spigarelli, C. M. Sherwin

Journal Articles

AIM: The aim of this study was to determine the population pharmacokinetics of darbepoetin alfa in hypothermic neonates with hypoxic-ischemic encephalopathy treated with hypothermia. METHODS: Neonates >/=36 weeks gestation andrandomized, multicenter, investigational, new drug pharmacokinetic study. Two intravenous darbepoetin alfa treatment groups were evaluated: 2 and 10 microg/kg. Serum erythropoietin concentrations were measured using an enzyme-linked immunosorbent assay. Monolix 4.3.1 was used to estimate darbepoetin alfa clearance and volume of distribution. Covariates tested included: birthweight, gestational age, postnatal age, postmenstrual age, sex, Sarnat score, and study site. RESULTS: Darbepoetin alfa pharmacokinetics were well described by a one-compartment model with exponential …

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Use Of Serogroup B Meningococcal Vaccines In Adolescents And Young Adults: Recommendations Of The Advisory Committee On Immunization Practices, 2015, J. R. Macneil, L. Rubin, T. Folaranmi, I. R. Ortega-Sanchez, M. Patel, S. W. Martin Jan 2015

Use Of Serogroup B Meningococcal Vaccines In Adolescents And Young Adults: Recommendations Of The Advisory Committee On Immunization Practices, 2015, J. R. Macneil, L. Rubin, T. Folaranmi, I. R. Ortega-Sanchez, M. Patel, S. W. Martin

Journal Articles

At its June 2015 meeting, the Advisory Committee on Immunization Practices (ACIP) recommended that adolescents and young adults aged 16-23 years may be vaccinated with a serogroup B meningococcal (MenB) vaccine to provide short-term protection against most strains of serogroup B meningococcal disease. This report summarizes the deliberations of ACIP, the rationale for its decision, and recommendations for use of MenB vaccines in adolescents and young adults. Two MenB vaccines have recently been licensed by the Food and Drug Administration (FDA) for use in the United States and approved for use in persons aged 10-25 years: MenB-FHbp (Trumenba, Wyeth Pharmaceuticals, …

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Neutralizing Antibodies Against West Nile Virus Identified Directly From Human B Cells By Single-Cell Analysis And Next Generation Sequencing, K. Tsioris, N. T. Gupta, A. O. Ogunniyi, R. M. Zimnisky, F. Qian, Y. Yao, X. Wang, J. N. Stern, R. Chari, J. C. Love, +8 Additional Authors Jan 2015

Neutralizing Antibodies Against West Nile Virus Identified Directly From Human B Cells By Single-Cell Analysis And Next Generation Sequencing, K. Tsioris, N. T. Gupta, A. O. Ogunniyi, R. M. Zimnisky, F. Qian, Y. Yao, X. Wang, J. N. Stern, R. Chari, J. C. Love, +8 Additional Authors

Journal Articles

West Nile virus (WNV) infection is an emerging mosquito-borne disease that can lead to severe neurological illness and currently has no available treatment or vaccine. Using microengraving, an integrated single-cell analysis method, we analyzed a cohort of subjects infected with WNV - recently infected and post-convalescent subjects - and efficiently identified four novel WNV neutralizing antibodies. We also assessed the humoral response to WNV on a single-cell and repertoire level by integrating next generation sequencing (NGS) into our analysis. The results from single-cell analysis indicate persistence of WNV-specific memory B cells and antibody-secreting cells in post-convalescent subjects. These cells exhibited …

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