tbuckley/cabot-search huggingface dataset:
A randomised multicentre trial of integrated versus standard treatment for patients with a first episode of psychotic illness
Authors: Lone Petersen, Pia Jeppesen, Anne Thorup, Maj-Britt Abel, Johan Øhlenschlæger, Torben Østergaard Christensen, Gertrud Krarup, Per Jørgensen, Merete Nordentoft
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objectives</b> To evaluate the effects of integrated treatment for patients with a first episode of psychotic illness. <b>Design</b> Randomised clinical trial. <b>Setting</b> Copenhagen Hospital Corporation and Psychiatric Hospital Aarhus, Denmark. <b>Participants</b> 547 patients with first episode of schizophrenia spectrum disorder. <b>Interventions</b> Integrated treatment and standard treatment. The integrated treatment lasted for two years and consisted of assertive community treatment with programmes for family involvement and social skills training. Standard treatment offered contact with a community mental health centre. <b>Main outcome measures</b> Psychotic and negative symptoms (each scored from 0 to a maximum of 5) at one and two years9 follow-up. <b>Results</b> At one year9s follow-up, psychotic symptoms changed favourably to a mean of 1.09 (standard deviation 1.27) with an estimated mean difference between groups of −0.31 (95% confidence interval −0.55 to −0.07, P = 0.02) in favour of integrated treatment. Negative symptoms changed favourably with an estimated difference between groups of −0.36 (−0.54 to −0.17, P &lt; 0.001) in favour of integrated treatment. At two years9 follow-up the estimated mean difference between groups in psychotic symptoms was −0.32 (−0.58 to −0.06, P = 0.02) and in negative symptoms was −0.45 (−0.67 to −0.22, P &lt; 0.001), both in favour of integrated treatment. Patients who received integrated treatment had significantly less comorbid substance misuse, better adherence to treatment, and more satisfaction with treatment. <b>Conclusion</b> Integrated treatment improved clinical outcome and adherence to treatment. The improvement in clinical outcome was consistent at one year and two year follow-ups.
IMPACT OF NEOATHEROSCLEROSIS ASSESSED BY OPTICAL COHERENCE TOMOGRAPHY ON CARDIAC TROPONIN ELEVATION AFTER ELECTIVE PCI
Authors: Tetsumin Lee, Tadashi Murai, Toshiyuki Iwai, Takamitsu Takagi, Ryo Masuda, Yoshito Iesaka, Tsunekazu Kakuta
Journal: Journal of the American College of Cardiology (2013)
Simultaneous presentation of 2 rare hereditary immunodeficiencies: IL-12 receptor β1 deficiency and ataxia-telangiectasia
Authors: Mohammad Ehlayel, Ludovic de Beaucoudrey, Francesca Fike, Shareef A. Nahas, Jacqueline Feinberg, Jean-Laurent Casanova, Richard A. Gatti
Journal: Journal of Allergy and Clinical Immunology (2008)
CHMP5 controls bone turnover rates by dampening NF-κB activity in osteoclasts
Authors: Matthew B. Greenblatt, Kwang Hwan Park, Hwanhee Oh, Jung-Min Kim, Dong Yeon Shin, Jae Myun Lee, Jin Woo Lee, Anju Singh, Ki-young Lee, Dorothy Hu, Changchun Xiao, Julia F. Charles, Josef M. Penninger, Sutada Lotinun, Roland Baron, Sankar Ghosh, Jae-Hyuck Shim
Journal: The Journal of Experimental Medicine (2015)

Physiological bone remodeling requires that bone formation by osteoblasts be tightly coupled to bone resorption by osteoclasts. However, relatively little is understood about how this coupling is regulated. Here, we demonstrate that modulation of NF-κB signaling in osteoclasts via a novel activity of charged multivesicular body protein 5 (CHMP5) is a key determinant of systemic rates of bone turnover. A conditional deletion of CHMP5 in osteoclasts leads to increased bone resorption by osteoclasts coupled with exuberant bone formation by osteoblasts, resembling an early onset, polyostotic form of human Paget’s disease of bone (PDB). These phenotypes are reversed by haploinsufficiency for Rank, as well as by antiresorptive treatments, including alendronate, zolendronate, and OPG-Fc. Accordingly, CHMP5-deficient osteoclasts display increased RANKL-induced NF-κB activation and osteoclast differentiation. Biochemical analysis demonstrated that CHMP5 cooperates with the PDB genetic risk factor valosin-containing protein (VCP/p97) to stabilize the inhibitor of NF-κBα (IκBα), down-regulating ubiquitination of IκBα via the deubiquitinating enzyme USP15. Thus, CHMP5 tunes NF-κB signaling downstream of RANK in osteoclasts to dampen osteoclast differentiation, osteoblast coupling and bone turnover rates, and disruption of CHMP5 activity results in a PDB-like skeletal disorder.
Inhibition of Natural Killer Cells through Engagement of CD81 by the Major Hepatitis C Virus Envelope Protein
Authors: Stefania Crotta, Annalisa Stilla, Andreas Wack, Annalisa D'Andrea, Sandra Nuti, Ugo D'Oro, Marta Mosca, Franco Filliponi, R. Maurizia Brunetto, Ferruccio Bonino, Sergio Abrignani, Nicholas M. Valiante
Journal: The Journal of Experimental Medicine (2001)

The immune response against hepatitis C virus (HCV) is rarely effective at clearing the virus, resulting in ∼170 million chronic HCV infections worldwide. Here we report that ligation of an HCV receptor (CD81) inhibits natural killer (NK) cells. Cross-linking of CD81 by the major envelope protein of HCV (HCV-E2) or anti-CD81 antibodies blocks NK cell activation, cytokine production, cytotoxic granule release, and proliferation. This inhibitory effect was observed using both activated and resting NK cells. Conversely, on NK-like T cell clones, including those expressing NK cell inhibitory receptors, CD81 ligation delivered a costimulatory signal. Engagement of CD81 on NK cells blocks tyrosine phosphorylation through a mechanism which is distinct from the negative signaling pathways associated with NK cell inhibitory receptors for major histocompatibility complex class I. These results implicate HCV-E2–mediated inhibition of NK cells as an efficient HCV evasion strategy targeting the early antiviral activities of NK cells and allowing the virus to establish itself as a chronic infection.
Separating homeologs by phasing in the tetraploid wheat transcriptome
Authors: Ksenia V Krasileva, Vince Buffalo, Paul Bailey, Stephen Pearce, Sarah Ayling, Facundo Tabbita, Marcelo Soria, Shichen Wang, Eduard Akhunov, Cristobal Uauy, Jorge Dubcovsky
Journal: Genome biology (2013)

The high level of identity among duplicated homoeologous genomes in tetraploid pasta wheat presents substantial challenges for de novo transcriptome assembly. To solve this problem, we develop a specialized bioinformatics workflow that optimizes transcriptome assembly and separation of merged homoeologs. To evaluate our strategy, we sequence and assemble the transcriptome of one of the diploid ancestors of pasta wheat, and compare both assemblies with a benchmark set of 13,472 full-length, non-redundant bread wheat cDNAs. A total of 489 million 100 bp paired-end reads from tetraploid wheat assemble in 140,118 contigs, including 96% of the benchmark cDNAs. We used a comparative genomics approach to annotate 66,633 open reading frames. The multiple k-mer assembly strategy increases the proportion of cDNAs assembled full-length in a single contig by 22% relative to the best single k-mer size. Homoeologs are separated using a post-assembly pipeline that includes polymorphism identification, phasing of SNPs, read sorting, and re-assembly of phased reads. Using a reference set of genes, we determine that 98.7% of SNPs analyzed are correctly separated by phasing. Our study shows that de novo transcriptome assembly of tetraploid wheat benefit from multiple k-mer assembly strategies more than diploid wheat. Our results also demonstrate that phasing approaches originally designed for heterozygous diploid organisms can be used to separate the close homoeologous genomes of tetraploid wheat. The predicted tetraploid wheat proteome and gene models provide a valuable tool for the wheat research community and for those interested in comparative genomic studies.
Association of sister chromatid exchange frequencies in patients with ankylosing spondylitis with and without HLA-B27
Authors: M Ikbal
Journal: Annals of the Rheumatic Diseases (2003)

The analysis of sister chromatid exchange (SCE) is a cytogenetic technique used to show DNA damage due to an exchange of DNA fragments between sister chromatids.To determine whether HLA-B27 positive patients with ankylosing spondylitis (AS) were associated with higher SCE frequencies than patients without B27.Lymphocytes from 38 patients with AS (15 women, 23 men) and 34 control subjects were examined. Peripheral lymphocytes were cultured in darkness for 72 hours in BrdU added culture. Metaphase chromosomes were stained with a fluorescence and a Giemsa stain after a standard harvest procedure.The frequency of SCE was significantly increased in patients with AS compared with controls (p<0.001). Furthermore, the SCE frequencies in patients with positive HLA-B27 was much higher than in patients with negative HLA-B27 (p<0.001). The difference between SCE frequencies in the control groups with and without HLA-B27 was not significant.There is a strong association between HLA-B27 and the frequencies of SCE in patients with AS.
Reduced Renal Calcium Excretion in the Absence of Sclerostin Expression
Authors: Rajiv Kumar, Volker Vallon
Journal: Journal of the American Society of Nephrology (2014)

The kidneys contribute to calcium homeostasis by adjusting the reabsorption and excretion of filtered calcium through processes that are regulated by parathyroid hormone (PTH) and 1α,25-dihydroxyvitamin D3 (1α,25[OH]2D3). Most of the filtered calcium is reabsorbed in the proximal tubule, primarily by paracellular mechanisms that are not sensitive to calcium-regulating hormones in physiologically relevant ways. In the distal tubule, however, calcium is reabsorbed by channels and transporters, the activity or expression of which is highly regulated and increased by PTH and 1α,25(OH)2D3. Recent research suggests that other, heretofore unrecognized factors, such as the osteocyte-specific protein sclerostin, also regulate renal calcium excretion. Clues in this regard have come from the study of humans and mice with inactivating mutations of the sclerostin gene that both have increased skeletal density, which would necessitate an increase in intestinal absorption and/or renal reabsorption of calcium. Deletion of the sclerostin gene in mice significantly diminishes urinary calcium excretion and increases fractional renal calcium reabsorption. This is associated with increased circulating 1α,25(OH)2D3 levels, whereas sclerostin directly suppresses 1α-hydroxylase in immortalized proximal tubular cells. Thus, evidence is accumulating that sclerostin directly or indirectly reduces renal calcium reabsorption, suggesting the presence of a novel calcium-excreting bone-kidney axis.
A Comparison of Short-term and Long-term Air Pollution Exposure Associations with Mortality in Two Cohorts in Scotland
Authors: Iain J. Beverland, Geoffrey R. Cohen, Mathew R. Heal, Melanie Carder, Christina Yap, Chris Robertson, Carole L. Hart, Raymond M. Agius
Journal: Environmental Health Perspectives (2012)

Air pollution-mortality risk estimates are generally larger at longer-term, compared with short-term, exposure time scales.We compared associations between short-term exposure to black smoke (BS) and mortality with long-term exposure-mortality associations in cohort participants and with short-term exposure-mortality associations in the general population from which the cohorts were selected.We assessed short-to-medium-term exposure-mortality associations in the Renfrew-Paisley and Collaborative cohorts (using nested case-control data sets), and compared them with long-term exposure-mortality associations (using a multilevel spatiotemporal exposure model and survival analyses) and short-to-medium-term exposure-mortality associations in the general population (using time-series analyses).For the Renfrew-Paisley cohort (15,331 participants), BS exposure-mortality associations were observed in nested case-control analyses that accounted for spatial variations in pollution exposure and individual-level risk factors. These cohort-based associations were consistently greater than associations estimated in time-series analyses using a single monitoring site to represent general population exposure {e.g., 1.8% [95% confidence interval (CI): 0.1, 3.4%] vs. 0.2% (95% CI: 0.0, 0.4%) increases in mortality associated with 10-μg/m³ increases in 3-day lag BS, respectively}. Exposure-mortality associations were of larger magnitude for longer exposure periods [e.g., 3.4% (95% CI: -0.7, 7.7%) and 0.9% (95% CI: 0.3, 1.5%) increases in all-cause mortality associated with 10-μg/m³ increases in 31-day BS in case-control and time-series analyses, respectively; and 10% (95% CI: 4, 17%) increase in all-cause mortality associated with a 10-μg/m³ increase in geometic mean BS for 1970-1979, in survival analysis].After adjusting for individual-level exposure and potential confounders, short-term exposure-mortality associations in cohort participants were of greater magnitude than in comparable general population time-series study analyses. However, short-term exposure-mortality associations were substantially lower than equivalent long-term associations, which is consistent with the possibility of larger, more persistent cumulative effects from long-term exposures.
LSC 2011 Abstract: The influence of glucocorticoid therapy on trancription factor balance in asthma patients
Authors: Roxana Bumbacea, Stephen Durham, Carsten Scmidt Weber
Journal: European Respiratory Journal (2011)

Background:  Transcription factors are important in T-cell subset differentiation as well as clonal expansion and determine the polarization process towards different T cell phenotypes. Glucocorticoids are important for asthma treatment, potentially by modulating T cell differentiation. We hypothesize that the transcription factor balance could be of predictive value in the treatment of asthma. Our study aimed to profile T-cell transcription factors after 8 week GC-treatment of steroid naive asthmatic patients and to test the steroid sensitivity of Th2 versus Th1 and Treg transcription factors (TF) after a treatment period, which is known to control Th2-cell activity and improve clinical symptoms.   Methods:  Human CD4 +  T-cells were isolated from steroid naive atopic asthmatics, prior and 8 weeks after successful inhalative GC-treatment. TF mRNA levels were determined using realtime RT-PCR. Additionally, CD4 +  T-cells from healthy donors were exposed to a serial dilution of GC in the presence of Th1, Th2 or T reg –driving conditions and analyzed for gene expression after 48h.   Results:  After 8 week GC-treatment, RORC2, T-Bet and GATA-3 did not show significant changes, FOXP3 was slightly higher. In contrast the Th2-gene Gfi-1was significantly more highly expressed in asthma patients compared to healthy individuals and decreased significantly following GC treatment.  In vitro  analysis revealed that Gfi-1 is abundantly expressed in Th2-polarizing conditions in asthma and displays dose-dependent sensitivity to GCs.   Conclusion:  The current study shows for the first time that Gfi-1 is involved in allergic asthma and may represent a biomarker for assessing Th2-dependent disease and GC-responsiveness.
Effects of selective endothelin antagonists on the hemodynamic response to cyclosporin A.
Authors: L S Davis, S J Haleen, A M Doherty, W L Cody, J A Keiser
Journal: Journal of the American Society of Nephrology (1994)

Cyclosporin A (CsA) treatment is associated with hypertension and renal dysfunction. Increased circulating endothelin (ET) has been implicated in this renal dysfunction, which is secondary to renal vasoconstriction and decreases in RBF. The effects of the selective blockade of ETA receptors or the combined blockade of ETA and ETB receptors on the acute hemodynamic response to CsA in anesthetized rats were examined. Rats were pretreated with vehicle, BQ-123 (selective ETA receptor antagonist; 0.6 micron/kg per minute), or BQ-123 and PD 142893 (combined ETA/ETB receptor antagonist; 0.6 micron/kg per minute) to achieve both ETA and ETB receptor blockade. After a 10-min pretreatment, CsA (20 mg/kg over 10 min) was administered; mean arterial blood pressure, RBF, and iliac blood flow were monitored continuously. Hemodynamic responses to exogenous endothelin-1 (ET-1, 0.3 and 1 nmol/kg) with and without antagonist pretreatment were measured in separate groups to demonstrate effective receptor blockade. CsA elevated blood pressure 17 to 20% in all three groups; renal resistance maximally increased 23, 20, and 23% in vehicle, BQ-123, and BQ-123 and PD 142893 pretreated groups, respectively. In contrast, the combination of BQ-123 and PD 142893 blocked systemic pressor responses to 0.3 and 1 nmol of ET-1 approximately 50 and 37%, respectively; changes in renal resistance were blocked 81 and 89%, respectively. In conclusion, the elevation in systemic blood pressure and the renal vasoconstrictor activity of CsA do not appear to be mediated through ETA or ETB receptors.
A simple device to subject cells to intermittent hypoxia mimicking obstructive sleep apnea
Authors: Noelia Campillo, Blai Casals, Ramón Farré, Daniel Navajas
Journal: European Respiratory Journal (2013)

Obstructive Sleep Apnea (OSA) is characterized by hypoxia/reoxygenation at the tissue level. Subjecting cultured cells to the fast O2 partial pressure (PO2) changes mimicking those experienced by the tissues in OSA patients is useful to study the mechanisms determining different consequences of the disease. However, modifying PO2 in the gas phase of the cell culture medium results in too slow PO2 changes at the cell level. The aim of this work was to design a simple device to subject cultured cells to intermittent hypoxia mimicking OSA. The device is based on a PDMS well (4 mm diameter) covered with a 10µm thin PDMS membrane. Cells are cultured on top of the membrane. Lateral holes in the block allow circulation of different gas mixtures below the membrane to modify the PO2 applied to cells. The actual PO2 at the upper surface of the membrane was measured by a fast-response O2 microsensor (Unisense, OX-50).The time constant of PO2 changes achieved at the upper surface of the PDMS membrane in response to a step change in PO2 in the well was ∼5 s. The figure shows an example of the changes in PO2 on top of the membrane when PO2 patterns mimicking OSA were applied in the well. In conclusion, the system designed is a useful tool for investigating the consequences of OSA at the cellular level. Supported by the Spanish Ministry of Economy and Competitiveness (SAF2011-22576, FIS-PI11/00089).
Outcomes of transplantation using various hematopoietic cell sources in children with Hurler syndrome after myeloablative conditioning
Authors: Jaap Jan Boelens, Mieke Aldenhoven, Duncan Purtill, Annalisa Ruggeri, Todd DeFor, Robert Wynn, Ed Wraith, Marina Cavazzana-Calvo, Attilio Rovelli, Alain Fischer, Jakub Tolar, Vinod K. Prasad, Maria Escolar, Eliane Gluckman, Anne O’Meara, Paul J. Orchard, Paul Veys, Mary Eapen, Joanne Kurtzberg, Vanderson Rocha, Timothy A. Driscoll, Joanne Kurtzberg, Daniel B. Landi, Paul L. Martin, Kristin M. Page, Suhag H Parikh, Vinod K. Prasad
Journal: Blood (2013)
Effect of Left Ventricular Outflow Tract Obstruction on Clinical Outcome in Hypertrophic Cardiomyopathy
Authors: Martin S. Maron, Iacopo Olivotto, Sandro Betocchi, Susan A. Casey, John R. Lesser, Maria A. Losi, Franco Cecchi, Barry J. Maron
Journal: New England Journal of Medicine (2003)

The influence of left ventricular outflow tract obstruction on the clinical outcome of hypertrophic cardiomyopathy remains unresolved.
The association between serum osmolality and lung function among adults
Authors: Z. E. K. Pogson, T. M. McKeever, A. Fogarty
Journal: European Respiratory Journal (2008)

The extensive pulmonary vasculature results in the lungs being intimately exposed to circulating blood. As increased serum osmolality may be associated with an increase in pro-inflammatory activity, this has the potential to result in damage to the lungs and reduced lung function. The objective of the present study was to test the hypothesis that increased serum osmolality is associated with a lower forced expiratory volume in one second (FEV 1 ) and forced vital capacity (FVC). The present study was a cross-sectional study of 10,602 participants in the Third National Health and Nutrition Examination Survey aged ≥17 yrs for whom there were adequate data on all outcomes and exposures. After adjustment for age, smoking and other confounding factors, increased serum osmolality was inversely associated with both FEV 1 and FVC. An increase of 1 sd in serum osmolality was associated with a decrease in both FEV 1 of 19.8 mL and FVC of 35.3 mL. The constituent assays demonstrated a complex relationship with both FEV 1 and FVC. Increased serum osmolality was associated with decreased forced expiratory volume in one second and forced vital capacity. If causal, this may have implications for the understanding of the processes that are involved in the pathophysiology of decline in lung function.
Cruelty's rewards: The gratifications of perpetrators and spectators
Authors: Victor Nell
Journal: Behavioral and Brain Sciences (2006)

Cruelty is the deliberate infliction of physical or psychological pain on other living creatures, sometimes indifferently, but often with delight. Though cruelty is an overwhelming presence in the world, there is no neurobiological or psychological explanation for its ubiquity and reward value. This target article attempts to provide such explanations by describing three stages in the development of cruelty. Stage 1 is the development of the predatory adaptation from the Palaeozoic to the ethology of predation in canids, felids, and primates. Stage 2 , through palaeontological and anthropological evidence, traces the emergence of the hunting adaptation in the Pliocene, its development in early hominids, and its emotional loading in surviving forager societies. This adaptation provides an explanation for the powerful emotions – high arousal and strong affect – evoked by the pain-blood-death complex. Stage 3 is the emergence of cruelty about 1.5 million years ago as a hominid behavioural repertoire that promoted fitness through the maintenance of personal and social power. The resulting cultural elaborations of cruelty in war, in sacrificial rites, and as entertainment are examined to show the historical and cross-cultural stability of the uses of cruelty for punishment, amusement, and social control. Effective violence prevention must begin with perpetrators, not victims. If the upstream approaches to violence prevention advocated by the public-health model are to be effective, psychologists must be able to provide violence prevention workers with a fine-grained understanding of perpetrator gratifications. This is a distasteful task that will compel researchers to interact with torturers and abusers, and to acknowledge that their gratifications are rooted in a common human past. It is nonetheless an essential step in developing effective strategies for the primary prevention of violence.