tbuckley/cabot-search huggingface dataset:
Risk of Serious Infection With Biologic and Systemic Treatment of Psoriasis
Authors: Robert E. Kalb, David F. Fiorentino, Mark G. Lebwohl, John Toole, Yves Poulin, Arnon D. Cohen, Kavitha Goyal, Steven Fakharzadeh, Stephen Calabro, Marc Chevrier, Wayne Langholff, Yin You, Craig L. Leonardi
Journal: JAMA Dermatology (2015)

IMPORTANCEThe efficacy of treatment for psoriasis must be balanced against potential adverse events.OBJECTIVE To determine the effect of treatment on the risk of serious infections in patients with psoriasis.A multicenter, longitudinal, disease-based registry (Psoriasis Longitudinal Assessment and Registry [PSOLAR]) at dermatology centers.Participants were adult patients with psoriasis who were receiving or were eligible to receive conventional systemic or biologic agents.The registry opened on June 20, 2007, and data included herein were collected through August 23, 2013. DESIGN, SETTING, AND PARTICIPANTSEXPOSURES Patients were prescribed psoriasis therapies as in standard clinical practice.Patients will be followed for up to 8 years.Data were collected and serious adverse events (including serious infections) were assessed at regular intervals.MAIN OUTCOMES AND MEASURES Cohort characteristics are described based on evaluation at entry into the registry.The cumulative incidence rates of serious infections are reported across treatment cohorts, including ustekinumab, infliximab, adalimumab, etanercept, and nonbiologics (with or without methotrexate).A multivariate analysis using a Cox proportional hazards regression model was used to identify predictors of the time to the first serious infection using the nonmethotrexate/nonbiologics cohort as the reference.RESULTS Data were analyzed from 11 466 patients with psoriasis (22 311 patient-years).Differences in patient characteristics were found between the biologics and nonmethotrexate/ nonbiologics cohorts (eg, age, sex, body mass index, and disease characteristics), as well as among the individual biologic groups (eg, a higher prevalence of psoriatic arthritis in the infliximab cohort).The cumulative incidence rate of serious infections was 1.45 per 100 patient-years (n = 323) across treatment cohorts, and the rates were 0.83, 1.47, 1.97, and 2.49 per 100 patient-years in the ustekinumab, etanercept, adalimumab, and infliximab cohorts, respectively, and 1.05 and 1.28 per 100 patient-years in the nonmethotrexate/nonbiologics and methotrexate/nonbiologics cohorts, respectively.The most commonly reported types of serious infections across the registry were pneumonia and cellulitis.Increasing age, diabetes mellitus, smoking, significant infection history, infliximab exposure, and adalimumab exposure were each associated with an increased risk of serious infection.CONCLUSIONS AND RELEVANCE Results from PSOLAR suggest a higher risk of serious infections with adalimumab and infliximab compared with nonmethotrexate and nonbiologic therapies.No increased risk was observed with ustekinumab or etanercept.
Attentional functioning in schizotypal personality disorder [published erratum appears in Am J Psychiatry 1997 Aug;154(8):1180]
Authors: S E Roitman, B A Cornblatt, A Bergman, M Obuchowski, V Mitropoulou, R S Keefe, J M Silverman, L J Siever
Journal: American Journal of Psychiatry (1997)

Previous research has shown biological, phenomenological, and cognitive similarities between schizophrenic patients and individuals with schizophrenia-related personality disorders and features. Evidence further suggests that of these common dysfunctions, abnormal attention is one of the most promising indicators of a biological susceptibility to schizophrenia-related disorders. Although attentional dysfunctions have been reliably detected in schizophrenic patients as well as in a variety of populations at risk for schizophrenia, few studies have investigated attention in clinical patients with schizotypal personality disorder. In this study, the extent of attentional impairment was assessed in subjects with schizotypal personality disorder, normal comparison subjects, patients with other personality disorders, and schizophrenic patients.Thirty subjects with schizotypal personality disorder, 35 subjects with other personality disorders (i.e., clinic patients with non-odd cluster personality disorders), 36 subjects with schizophrenia, and 20 comparison subjects who did not meet criteria for any axis I or axis II disorder participated in this study. All subjects were diagnosed according to DSM-III criteria. Attention was assessed by using the Continuous Performance Test, Identical Pairs Version.Analyses indicated that subjects with schizotypal personality disorder, like schizophrenic subjects, performed significantly worse than comparison subjects on both the verbal and spatial tasks of the Continuous Performance Test, Identical Pairs Version. In contrast, patients with other personality disorders performed similarly to comparison subjects across conditions.These results suggest that patients with schizotypal personality disorder are impaired in their attentional functioning relative to normal comparison subjects and that they display deficits that are similar to the pattern characterizing schizophrenic patients.
Sex: when less means more
Authors: Roger Dobson
Journal: BMJ (2000)

Absence really may make the heart grow fonder, according to a report on short term human mating. The more time couples spend apart, the more sperm the husbands inseminate in their wives, says the report in Personality and Individual Differences (2000;28:929-63).

When couples spend 100% of their time together, men inseminate 389 million sperm per ejaculate, but when only 5% of their time is in each other's company, the figure almost doubles to 712 million.

The report says that …
Abstract 18248: Apolipoprotein E Gene Mutations in Subjects with Mixed Hyperlipoproteinemia and a Clinical Diagnosis of Familial Combined Hyperlipidemia
Authors: María Solanas-Barca, Isabel de Castro-Orós, Ana M. Bea, Montserrat Cofán, Nuria Plana, Emilio Ros, Luis Masana, José Puzo, Miguel Pocoví, Fernando Civeira, Ana Cenarro
Journal: Circulation (2011)

Introduction Familial combined hyperlipidemia (FCH) is characterized by elevated levels of total cholesterol (TC) and triglycerides (TG), vertical transmission of a variable hyperlipidemic phenotype, and high risk of premature cardiovascular disease. FCH is the most common cause of primary mixed hyperlipoproteinemia (MHLP). An APOE E2/E2 genotype in the presence of MHLP is diagnostic of familial dysbetalipoproteinemia. However, rare dominant mutations in APOE , which go undetected with the usual genotyping procedure, may also cause dysbetalipoproteinemia. Uncovering such rare APOE variants may change the diagnosis from FCH to dysbetalipoproteinemia. Objectives To identify APOE mutations associated with dominant MHLP and to establish their frequency in subjects with a clinical diagnosis of FCH. Methods We examined 472 unrelated subjects with dominant MHLP and a clinical diagnosis of FCH and 264 unrelated normolipidemic subjects (control group). Clinical and analytical determinations were done in all of them. Screening of LDLR and APOB gene mutations was performed with Lipochip, version 4 (Progenika, Derio, Spain). Entire APOE gene (4 exons and intron-flanking sequences) was sequenced. Results In the MHLP group, 10 subjects had the E2/E2 genotype, and then, were diagnosed as dysbetalipoproteinemia. Twenty three subjects were carriers of a functional mutation in the LDLR gene. In the left 439 subjects with MHLP, two rare functional APOE variants, R136S and DeltaL149, were identified. Nine subjects (2.0%) were carriers of the R136S mutation and 6 subjects (1.4%) were carriers of the DeltaL149 mutation. In the control group, no rare APOE mutation was identified. Subjects with R136S mutation had higher VLDL-cholesterol/TG ratio and lower apoB/TC ratio, similar to those of E2/E2 subjects, suggesting a diagnosis of dysbetalipoproteinemia. However, subjects carrying the DeltaL149 mutation did not show this pattern, being their VLDL-cholesterol/TG and apoB/TC ratios similar to those of E3/E3 subjects. Conclusion Rare mutations in the APOE gene, R136S and DeltaL149, were identified in subjects with mixed hyperlipoproteinemia and a clinical diagnosis of FCH, indicating that the APOE gene contributes to this phenotype.
Winterfreude (Pleasures of Winter)
Authors: M. Therese Southgate
Journal: JAMA (1998)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 9634: Luteolin Inhibits the Wall Expansion of Aortic Anuerysm in Mice Model
Authors: Atsuko Nakayama, Hiroyuki Morita, Ryozo Nagai
Journal: Circulation (2011)

Background: Luteolin is a food-derived flavonoid and its antioxidant, anti-inflammatory, and antiallergic functions are reported. Abdominal aortic aneurysm (AAA) is well-known disease that needs surgical repair before rupture of aortic wall. But little is known about the nonsurgical treatment for AAA. Method: Female ApoE-/- mice at age 9 weeks were fed with chow containing 0.5% luteolin for 3 weeks and then were infused with angiotensin II (Ang II; 1.0 μ g/kg/min) for 4 weeks by an osmotic mini-pump. Control ApoE-/- mice and Ang II infused ApoE-/- mice with normal chow were also prepared for comparison. Their body weight, blood pressure and ultrasonographic diameter of abdominal aorta were measured every week until sacrifice at age 16 weeks. Result: The body weight was similar in three groups (control 22.8±1.0 g, Ang ll with normal food group [Ang II +Luteolin-] 23.0±1.5 g, Ang II with luteolin food group [Ang II +Luteolin+] 23.4±1.7 g). Systolic blood pressure at sacrifice was extremely high in Ang II infused mice, but no difference between Ang II +Luteolin- and Ang II +Luteolin+ (control 94±4 mmHg, Ang II +Luteolin- 159±39 mmHg, Ang II +Luteolin+ 168±48 mmHg). The diameter of abdominal aorta at first was similar in three groups, and gradually increased with Ang II infusion. The max diameter at sacrifice was significantly smaller in Ang II +Luteolin+ than in Ang II +Luteolin- (1.1±0.2 mm vs. 1.9±0.5 mm, P&lt;0.01). Histopathologic studies showed less frequent disruption of elastic media in Ang II +Luteolin+ than in Ang II +Luteolin-. Conclusion: Luteolin inhibits the wall expansion of aorta in Ang ll-infused ApoE-/- mice model.
Abstract 2529: Optimization of small molecules targeting BMI1 protein expression. Part 1. Amino-thiazoles: the first-in-class highly potent inhibitors of BMI1 protein
Authors: Nadiya Sydorenko, Ramil Baiazitov, Soongyu Choi, Chang-Sun Lee, Liangxian Cao, Thomas W. Davis, Neil G. Almstead, Young-Choon Moon
Journal: Cancer Research (2014)

Abstract BMI1 (B-cell specific Moloney Murine Leukemia Virus Insertion 1) is a gene predominantly expressed in stem cells. A deficiency of BMI1 protein leads to a reduction in the adult stem cell population. Decreasing of BMI1 protein levels by siRNA causes apoptosis and/or senescence in tumor cells in vitro and increases susceptibility to cytotoxic agents. In tumors, the level of BMI1 protein is often elevated. Consequently, the expression level of BMI1 is highly prognostic in many types of cancers. Since BMI1 is non-enzymatic, targeting this protein by traditional drug discovery approaches has not met with success. PTC Therapeutics has developed a novel screening technology referred to as GEMSTM (Gene Expression Modulation by Small molecules) to identify small molecules that modulate the levels of a protein of interest by targeting post-transcriptional regulatory processes. Using this screening technology, we have identified a number of compounds that can selectively reduce levels of BMI1 protein. Schematically, the lead scaffold could be represented by four key components: a bicyclic right core, a heterocyclic middle ring (thiazole), a linking group and a left aryl region. Structure-activity relationships associated with this series have been investigated through medicinal chemistry efforts. Incorporation of a small electron-donating para- substituent at the left part of the molecule is highly effective in decreasing levels of BMI1, indicating the strong influence of both steric and electronic effects on activity. An amino (linking group) moiety was found to be essential for activity. Variation at the right-hand moiety appears to be more tolerated, allowing improvements in both pharmacokinetic and activity profiles. These SAR findings have revealed important pharmacophoric and structural features required for the desired biological activity with this series, and provide a foundation for further lead optimization efforts. Citation Format: Nadiya Sydorenko, Ramil Baiazitov, Soongyu Choi, Chang-Sun Lee, Liangxian Cao, Thomas W. Davis, Neil G. Almstead, Young-Choon Moon. Optimization of small molecules targeting BMI1 protein expression. Part 1. Amino-thiazoles: the first-in-class highly potent inhibitors of BMI1 protein. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2529. doi:10.1158/1538-7445.AM2014-2529
524. Adenovirus-Mediated Silencing of Huntingtin Expression by hsiRNA
Authors: Bin Huang, Stefan Kochanek
Journal: Molecular Therapy (2004)

Huntington disease (HD) is an autosomal dominant inherited neurodegenerative disease that is caused by a gain of function mutation due to the expansion of an unstable CAG trinucleotide repeat in exon 1 of the huntingtin (htt) gene. Using an inducible mouse model of HD it has previously been demonstrated that abolishment of the expression of the mutant protein not only halted progression of the disease but also reversed aggregate formation and neuronal degeneration. Therefore, blocking the expression of mutant htt might be a promising therapeutic strategy for HD. Small interference RNA (siRNA) has been shown to be a potent tool to inhibit specific gene expression in vitro and more recently also in vivo. We elected to adapt the siRNA technology for adenovirus-mediated inhibition of htt expression as a new treatment strategy for HD.
Abstract 15907: Disruption of HCN2 Leads to Laterality Defects and Cardiac Arrhythmia
Authors: Bin Ye, Greg Taycher, Tim Hacker, Leslie Chan, Nian-Qing Shi
Journal: Circulation (2014)

Background: Congenital heart defects (CHDs) encompass a large numbers of cardiovascular malformations, and remain the major cause of infant mortality among all types of birth defects. However, molecular mechanisms underlying CHDs remain elusive, largely owning to the complexity of the diseases and lack of animal models that can reproduce the pathophysiological conditions in a laboratory setting. The hyperpolarization-activated, cyclic nucleotide-gated cation channels (HCN) are responsible for generating spontaneous pacemaker activities in cardiac and central nervous systems. These channels are also detected in other cell types such as ventricular myocytes. HCN currents recorded from neonatal cells have an activation threshold of -70 mV while those recorded from adult cells are activated at -110 mV. This difference indicates that HCN activity might be important in early development. However, roles of HCN channels in cardiogenesis and development are not fully understood. Methods and Results: We created a HCN2 conditional knockout (HCN2KO) model in which the full-length HCN2 was disrupted. Two KO lines were subsequently derived from this model. The first line was weaned by 21 days and they all died by 4-5 wks of age. Maternal ultrasound study revealed that these KO mice developed fetal arrhythmia and had an underdeveloped left side in their hearts. The second line was able to live on under our special diet/care. These mice displayed a slower growth rate (1.1±0.2 g/wk) and lower body weight (15.1±2.0 g) relative to their age-matched WT controls (2.2±0.1 g/wk and 27.5±1.5 g; n=9-10, p&lt;0.05). Echocardiography and tissue staining data suggested that KO hearts had laterality defects compared to their size-matched WT controls. The survived KO mice were able to maintain cardiac function by developing much thicker anterior and posterior walls to sustain blood-pumping (n=6, p&lt;0.05). Electrocardiographic results indicated that the average heart rate recorded from KO mice was ~100 bpm slower than their age-matched WT controls (n=5-6, p&lt;0.05). Conclusions: These novel findings indicate that HCN2 is indispensable in mouse cardiogenesis and development. Our KO models are therefore innovative platforms for future CHD research.
Abstract 1616: Phosphoprotein enrichment pathway analysis tools for studying cancer signaling
Authors: Danica Wiredja, Yu Liu, Daniela Schlatzer, Giridharan Gokulrangan, Goutham Narla, Mark Chance
Journal: Cancer Research (2014)

Abstract Cancer development and progression is driven by dysregulated signaling transduction, which is predominantly regulated by serine, threonine, and tyrosine phosphorylation. Consequently, MS-based phosphoproteomics, which can identify and quantitate thousands of phosphopeptides, provides a powerful quantitative tool to detect and comprehensively catalog alterations in cancer signaling cascades that cannot be captured by analysis of DNA or RNA alone. Unfortunately, the complexity of the datasets generated by these advanced proteomic methodologies are still not matched with well-established or fully tested bioinformatics tools to extract critical pathways from these high-dimensional phosphoprotein data. Here, we present two approaches for identifying pathways with altered phosphorylation patterns: Protein Set Enrichment Analysis (PSEA) and Protein Interaction Enrichment Network Analysis (PIENA). Development of these tools was inspired by two published methods utilizing gene expression datasets to identify disrupted gene sets: Gene Set Enrichment Analysis (GSEA) and Gene Interaction Enrichment Network Analysis (GIENA), respectively. PSEA, through pathway scoring, extracts pathways that show a uniform directional phosphorylation change through all protein members of that set. As in the traditional GSEA method, an enrichment score is calculated for each pathway based on intensity values from all detected phosphopeptides. The second method, PIENA, looks for notable differences in phosphorylation between phosphopeptide pairs. Ultimately, this approach identifies pathways enriched with altered phosphoprotein interactions. Both methods have been used to identify changes in signaling states for two lung adenocarcinoma cell lines, A549 and H358, treated with either control or a novel phosphatase activator with anti-cancer properties. Both PSEA and PIENA identify pathways classically implicated in cancer, including p53, mitosis and cell cycle progression, insulin secretion, immune regulation, and RAS signaling cascades. Furthermore, the ERK pathway is consistently found to be significantly disrupted in both A549 and H358. This corroborates biological findings that this novel drug has activity against KRAS mutated cell lines. Although future cellular experiments will help to confirm the detailed mechanism of this drug's effects, our current results demonstrate the advantage of these new pathway identification tools in providing unbiased and global identification of key drivers of signaling. Citation Format: Danica Wiredja, Yu Liu, Daniela Schlatzer, Giridharan Gokulrangan, Goutham Narla, Mark Chance. Phosphoprotein enrichment pathway analysis tools for studying cancer signaling. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1616. doi:10.1158/1538-7445.AM2014-1616
Does Video Game Violence Sow Aggression?
Authors: Brian Vastag
Journal: JAMA (2004)

Puskas estimates that 95% of his CABG surgeries are performed off-pump. John Pepper, MChir, a cardiothoracic surgeon at Royal Brompton Hospital in London and coauthor of the English article, agreed that physician experience may have been a factor in the lower graft-patency rate in study participants who underwent offpump CABG. “It may reflect that we were still on a learning curve, despite more than 2 years of experience,” Pepper said. “The point of our study was to sound a word of caution against the wholesale abandonment of cardiopulmonary bypass for isolated coronary artery surgery, which has been advocated in some quarters.” Surgeon experience may also be a factor in results from a recent observational study, in which researchers followed shortand long-term outcomes for 59 044 patients undergoing onpump CABG and 9135 undergoing offpump between 1997 and 2000 in New York State ( J Am Coll Cardiol . 2004;43:557-564). Edward L. Hannan, PhD, a study coauthor, said the investigators concluded that on-pump patients had better long-term survival (at 3 years) and freedom from revascularization compared with off-pump patients. But the survival difference disappeared when looking only at patients undergoing the procedures in the last 2 years of the study. “The differences in the last 2 years disappeared possibly because the education curve had improved,” said Hannan, a distinguished professor and chair of the Department of Health Policy Management and Behavior at the University of Albany School of Public Health, in New York. However, when the researchers assessed the need for revascularization in patients who underwent the procedures during the last 2 years of the study, they found that those in the on-pump CABG group still fared better than those who had the offpump surgery, Hannan said.