tbuckley/cabot-search huggingface dataset:
RESVERATROL COUNTERS ATHEROGENIC EFFECTS OF INTERFERON-GAMMA ON CHOLESTEROL EFFLUX IN THP-1 HUMAN MONOCYTES/MACROPHAGES
Authors: Ofek Y. Hai, Kamran Anwar, Peter A. Wirkowski, Iryna Voloshyna, Steven E. Carsons, Allison B. Reiss
Journal: Journal of the American College of Cardiology (2010)
Quantitative Microscopy Comparison of Peroxisome Proliferation by the Lipid-Regulating Agent Gemfibrozil in Several Species
Authors: Robert H. Gray, Felix A. La De Iglesia
Journal: Hepatology (1984)

Peroxisome proliferation, a well-documented subcellular reaction which follows the administration of hypolipidemic agents, has been well studied in rodents. However, quantitative studies of this phenomenon in other species of laboratory animals are not readily available even though these species are commonly used as predictors of tolerance or safety in humans. The quantitative stereologic studies reported here compared the effects of the new hypolipidemic agent gemfibrozil on hepatic peroxisomes of monkeys, dogs, hamsters and rats of both sexes under several treatment schedules. Gemfibrozil was administered to rats at 300 mg per kg per day for 1 year in the diet; to hamsters at 400 mg per kg per day for 2 weeks by diet admixture; to dogs at 300 mg per kg per day in gelatin capsules for 1 year; and to monkeys at 300 mg per kg day for 3 months by gavage. These dose levels were selected on the basis of tolerance from preliminary studies in each species. At the end of each experimental interval, liver samples were processed for quantitative microscopy. Peroxisomes from male rats were enlarged and the number of peroxisomes per cell were increased 7-fold over controls, resulting in a 20-fold increased peroxisome volume per cell. Statistically, significant increases also occurred in female rats and the difference between treated and controls was 3-fold for both number and volume of peroxisomes per cytoplasmic unit volume. In hamsters, peroxisomes were proliferated and were of significantly smaller size to the extent that the volume of cytoplasm occupied by peroxisomes was not significantly changed. In dogs, the number of peroxisomes per cell was increased and the volume fraction was significantly increased in females only. The number of peroxisomes in young monkeys did not change after treatment, and the peroxisome volume was decreased in males and increased in females. Aged monkeys had increased number of peroxisomes per hepatocyte with increased volume fraction. These results indicate significant differences in the magnitude and direction of peroxisome changes, reflecting species-dependent organelle response to hypolipidemic agents. The order of susceptibility of peroxisome proliferation in laboratory animals is dog &lt; monkey &lt; hamster &lt; rat.
Zinc finger transcription factor zDC is a negative regulator required to prevent activation of classical dendritic cells in the steady state
Authors: Matthew M. Meredith, Kang Liu, Alice O. Kamphorst, Juliana Idoyaga, Arito Yamane, Pierre Guermonprez, Suzannah Rihn, Kai-Hui Yao, Israel T. Silva, Thiago Y. Oliveira, Dimitris Skokos, Rafael Casellas, Michel C. Nussenzweig
Journal: The Journal of Experimental Medicine (2012)

Classical dendritic cells (cDCs) process and present antigens to T cells. Under steady-state conditions, antigen presentation by cDCs induces tolerance. In contrast, during infection or inflammation, cDCs become activated, express higher levels of cell surface MHC molecules, and induce strong adaptive immune responses. We recently identified a cDC-restricted zinc finger transcription factor, zDC (also known as Zbtb46 or Btbd4), that is not expressed by other immune cell populations, including plasmacytoid DCs, monocytes, or macrophages. We define the zDC consensus DNA binding motif and the genes regulated by zDC using chromatin immunoprecipitation and deep sequencing. By deleting zDC from the mouse genome, we show that zDC is primarily a negative regulator of cDC gene expression. zDC deficiency alters the cDC subset composition in the spleen in favor of CD8+ DCs, up-regulates activation pathways in steady-state cDCs, including elevated MHC II expression, and enhances cDC production of vascular endothelial growth factor leading to increased vascularization of skin-draining lymph nodes. Consistent with these observations, zDC protein expression is rapidly down-regulated after TLR stimulation. Thus, zDC is a TLR-responsive, cDC-specific transcriptional repressor that is in part responsible for preventing cDC maturation in the steady state.
Handgun Violence, Public Health, and the Law
Authors: Gregory D. Curfman, Stephen Morrissey, Jeffrey M. Drazen
Journal: New England Journal of Medicine (2008)

Firearms were used to kill 30,143 people in the United States in 2005, the most recent year with complete data from the Centers for Disease Control and Prevention.1 A total of 17,002 of these were suicides, 12,352 homicides, and 789 accidental firearm deaths. Nearly half of these deaths occurred in people under the age of 35. When we consider that there were also nearly 70,000 nonfatal injuries from firearms, we are left with the staggering fact that 100,000 men, women, and children were killed or wounded by firearms in the span of just one year. This translates into one death . . .
Contribution of lung ventilation and perfusion distributions to the phase III slope of exhaled CO2 during acute bronchoconstriction studied by synchrotron imaging in rabbit
Authors: Sam Bayat, Mathieu Guilbart, Liisa Porra, Loïc Dégrugilliers, Satu Strengell, Pekka Suortti, Anssi Sovijärvi
Journal: European Respiratory Journal (2013)

We studied the relation between the phase III slope of the volumetric capnogram (S3v) and the regional distributions of ventilation and blood volume (as a surrogate of perfusion) in 5 anesthetized and ventilated rabbits (Wt=2.9±0.1 kg). We used K-edge subtraction synchrotron imaging to quantify the regional distribution of ventilation (V’), blood volume (VB), the area of ventilated regions (VAA), at baseline, after inhaled methacholine (Mch, 125 mg/ml×1 min), and after salbutamol inhalation (2 mg/ml×5 min). Capnograms were recorded during tidal breathing. S3v was automatically computed and averaged using custom software. Respiratory mechanics were measured using multiple linear regression.  The heterogeneity of V9 increased more than that of VB after Mch (Figure). We found a significant relation between S3v and V’/VB (R=-0.65, p=0,0004), whereas the relation was weaker with VAA (R=-0.51, p=0.009) and V9 (R=-0.49, p=0.014), and insignificant with VB (R=0.26, p=0.211).  CONCLUSIONS: Direct measurements of regional lung V9 and VB distributions during bronchoconstriction suggest that S3v is primarily determined by the V9/VB ratio.
Enhanced top-down characterization of histone post-translational modifications
Authors: Zhixin Tian, Nikola Tolić, Rui Zhao, Ronald J Moore, Shawna M Hengel, Errol W Robinson, David L Stenoien, Si Wu, Richard D Smith, Ljiljana Paša-Tolić
Journal: Genome biology (2012)

Abstract Post-translational modifications (PTMs) of core histones work synergistically to fine tune chromatin structure and function, generating a so-called histone code that can be interpreted by a variety of chromatin interacting proteins. We report a novel online two-dimensional liquid chromatography-tandem mass spectrometry (2D LC-MS/MS) platform for high-throughput and sensitive characterization of histone PTMs at the intact protein level. The platform enables unambiguous identification of 708 histone isoforms from a single 2D LC-MS/MS analysis of 7.5 µg purified core histones. The throughput and sensitivity of comprehensive histone modification characterization is dramatically improved compared with more traditional platforms.
Major histocompatibility complex (MHC) class II alleles, haplotypes and epitopes which confer susceptibility or protection in systemic sclerosis: analyses in 1300 Caucasian, African-American and Hispanic cases and 1000 controls
Authors: F. C. Arnett, P. Gourh, S. Shete, C. W. Ahn, R. E. Honey, S. K. Agarwal, F. K. Tan, T. McNearney, M. Fischbach, M. J. Fritzler, M. D. Mayes, J. D. Reveille
Journal: Annals of the Rheumatic Diseases (2009)

<h3>Objective</h3> To determine human leucocyte antigen-class II (HLA-class II) (DRB1, DQB1, DQA1 and DPB1) alleles, haplotypes and shared epitopes associated with scleroderma (systemic sclerosis (SSc)) and its subphenotypes in a large multi-ethnic US cohort by a case–control association study. <h3>Patients and methods</h3> 1300 SSc cases (961 white, 178 black and 161 Hispanic subjects) characterised for clinical skin forms (limited vs diffuse), SSc-specific autoantibodies (anticentromere (ACA), anti-topoisomerase I (ATA), anti-RNA polymerase III (ARA), anti-U3 ribonucleoprotein (fibrillarin)) and others were studied using molecular genotyping. Statistical analyses in SSc itself by ethnicity, gender, skin type and autoantibodies were performed using exact logistic regression modelling for dominant, additive and recessive effects from HLA. <h3>Results</h3> The strongest positive class II associations with SSc in white and Hispanic subjects were the <i>DRB1*1104, DQA1*0501, DQB1*0301</i> haplotype and <i>DQB1</i> alleles encoding a non-leucine residue at position 26 (<i>DQB1</i> 26 epi), while the <i>DRB1*0701, DQA1*0201, DQB1*0202</i> haplotype and <i>DRB1*1501</i> haplotype were negatively correlated and possibly protective in dominant and recessive models, respectively. These associations did not discriminate between limited and diffuse SSc. SSc in black subjects was associated with <i>DRB1*0804, DQA1*0501, DQB1*0301</i> alleles. <i>DPB1*1301</i> showed the highest odds ratio for ATA (OR = 14). Moreover, it showed no linkage disequilibrium or gene interaction with DR/DQ. ACA was best explained by <i>DQB1*0501</i> and <i>DQB1*26</i> epi alleles and ARA by <i>DRB1*0404, DRB1*11</i> and <i>DQB1*03</i> alleles in white and Hispanic subjects but <i>DRB1*08</i> in black subjects. <h3>Conclusion</h3> These data indicate unique and multiple HLA-class II effects in SSc, especially on autoantibody markers of different subphenotypes.
Paternal age and schizophrenia: a population based cohort study
Authors: Attila Sipos, Finn Rasmussen, Glynn Harrison, Per Tynelius, Glyn Lewis, David A Leon, David Gunnell
Journal: BMJ (2004)

<h3>Abstract</h3> The topology of endoplasmic reticulum (ER) network is highly regulated by various cellular and environmental stimuli and affects major functions such as protein quality control and the cell's response to metabolic changes. The ability to quantify the dynamical changes of the ER structures in response to cellular perturbations is crucial for the development of novel therapeutic approaches against ER associated diseases, such as hereditary spastic paraplegias and Niemann Pick Disease type C. However, the rapid movement and small spatial dimension of ER networks make this task challenging. Here, we combine video-rate super-resolution imaging with a state-of-the-art semantic segmentation method capable of automatically classifying sheet and tubular ER domains inside individual cells. Data are skeletonised and represented by connectivity graphs to enable the precise and efficient quantification and comparison of the network connectivity from different complex ER phenotypes. The method, called ERnet, is powered by a Vision Transformer architecture, and integrates multi-head self-attention and channel attention into the model for adaptive weighting of frames in the time domain. We validated the performance of ERnet by measuring different ER morphology changes in response to genetic or metabolic manipulations. Finally, as a means to test the applicability and versatility of ERnet, we showed that ERnet can be applied to images from different cell types and also taken from different imaging setups. Our method can be deployed in an automatic, high-throughput, and unbiased fashion to identify subtle changes in cellular phenotypes that can be used as potential diagnostics for propensity to ER mediated disease, for disease progression, and for response to therapy.
Employment After Therapy for Localized Prostate Cancer: Widening the Perspective
Authors: James A. Talcott
Journal: JNCI Journal of the National Cancer Institute (2005)

From the traditional biological perspective, medical therapy is judged by its effects on survival or other indicators related to pathophysiology, such as growth or shrinkage of cancer masses. More recently, investigators have broadened their assessments of medical interventions (and conditions). So-called outcomes research explicitly recognizes that chronic diseases and their treatments may affect patients’ lives in ways other than causing symptoms, organ dysfunction, and death. They may also impair patients’ ability to perform activities of daily living, continue their usual social roles and interactions, and preserve their economic condition — each a plausible aspect of health-related quality of life. A rapidly progressing cancer’s ability to wreak havoc on virtually all aspects of patients’ lives is widely appreciated. However, although measuring these consequences might infl uence public policy choices, the results would rarely affect clinical decisions. Patients with advanced, aggressive cancers have two basic choices: either pursue the treatment their oncologists identify as most likely to postpone death from cancer or — if deterred by brief anticipated survival, frail health, or the expected toxicity of treatment — submit to their cancer, focusing on symptom palliation. However, for cancer patients who can anticipate prolonged survival and have two or more treatment alternatives, neither of which is decisively more effi cacious or less toxic, a fuller appreciation of the manifold consequences of each treatment may help them identify the better choice, given their own circumstances, goals, and preferences. Clinically localized prostate cancer meets these conditions. Nearly all patients survive a decade or more; competing treatments do not differ demonstrably in effi cacy but produce various combinations of permanent urinary, bowel, or sexual dysfunction in most men; and observation alone would not affect most men’s life expectancy [although evidence that a small group of men live longer after active therapy is now appearing ( 1 , 2 ) ] but would produce anxiety in many men and their families. Although we have at best a rough idea how men choose between alternatives with consequences that diverge in so many ways, a reasonable model is that they compare treatments by what matters most to them fi rst, proceeding through progressively less important characteristics until they reach a crucial, “ deal-breaker ” difference ( 3 ) . In the past decade, outcomes researchers have documented the phys
Evaluation of MicroRNA Expression Profiles That May Predict Recurrence of Localized Stage I Non–Small Cell Lung Cancer after Surgical Resection
Authors: Santosh K. Patnaik, Eric Kannisto, Steen Knudsen, Sai Yendamuri
Journal: Cancer Research (2009)

Prognostic markers that can predict the relapse of localized non-small cell lung cancer (NSCLC) have yet to be defined. We surveyed expression profiles of microRNA (miRNA) in stage I NSCLC to identify patterns that might predict recurrence after surgical resection of this common deadly cancer. Small RNAs extracted from formalin-fixed and paraffin-embedded tissues were hybridized to locked nucleic acid probes against 752 human miRNAs (representing 82% of the miRNAs in the miRBase 13.0 database) to obtain expression profiles for 37 cases with recurrence and 40 cases without recurrence (with clinical follow-up for at least 32 months). Differential expression between the two case groups was detected for 49% of the miRNAs (Wilcoxon rank sum test; P<0.01). The performance of expression profiles at differentiating the two case groups was assessed by leave-one-out and Monte Carlo cross-validations. In leave-one-out cross-validation using support vector machines- or top-scoring gene pair classifier methods, which looked for six- or two-miRNA-based classifiers, the identified miRNA expression pattern predicted recurrence with an accuracy of 70% and 83%, and hazard ratio of 3.6 [95% confidence interval (95% CI), 1.8-7.1] and 9.0 (95% CI, 4.4-18.2), respectively. Mean accuracy in Monte Carlo cross-validation using 1,000 random 60-17 splits was 69% (95% CI, 68-70) and 72% (95% CI, 71-72), respectively. The specific miRNAs mir-200b*, mir-30c-1*, mir-510, mir-630, mir-657, and mir-146b-3p and mir-124*, mir-585, and mir-708, respectively, represented most commonly among the 1,000 classifiers identified in Monte Carlo cross-validation by the two methods. MiRNAs mir-488, mir-503, and mir-647 were identified as potential reference miRNAs for future studies, based on the stability of their expression patterns across the 77 cases and the two case-groups. Our findings reinforce efforts to profile miRNA expression patterns for better prognostication of stage I NSCLC.
ZX8I epilepsy-a case for lumping.
Authors: P Sandercock, C Warlow
Journal: BMJ (1982)

here.Not only does insulin treatment present problems, but most patients also have con- siderable emotional problems related to chronic ill-health, fear of dying, loss of employment, inability to keep up at school, conflict with the family, and so on.Although brittle diabetes unresponsive to continuous subcutanecus insulin infusion is rare, we feel that it is a definite and important entity with enormous impact on the life of the patient and on health service resources.Study of its pathophysiological basis may also help us understand the lesser degrees of unexplained instability which trouble many insulindependent diabetics.
PRICE OF PETROL ON THE CONTINENT
Authors: H. M. Buist
Journal: BMJ (1920)

TMu BiLiJou 53 I -tlle country.My midwife also lhas learnt the advantage of having all lacerations sutured, and always sclnds for me after the birtlh for this purpose.This may seem a small tliing to write about, but it may lhelp to explain whiy sepsis only rarely follows extensive instru- mental manipulation, as in these cases the lacerations are evident and are immediately attended to.We often arrive at a case wlhen all is over, and may not take the trouble to look for lacerations, but if we do and attend to them we slhall be well repaid.-I am, etc.,
ACL injury incidence in female handball 10 years after the Norwegian ACL prevention study: important lessons learned
Authors: Grethe Myklebust, Arnhild Skjølberg, Roald Bahr
Journal: British Journal of Sports Medicine (2013)

Success in injury prevention in the short run is possible. Several studies have documented that injuries can be prevented if programme compliance is sufficient.1–6 However, the efficacy of an intervention is in a controlled trial does not mean that it will be widely adopted and sustained and have an impact on public health.7–9 Finch9 outlined the Translating Research into Injury Prevention Practice framework, emphasising that only research that can and will be adopted by the participants, the coaches and sporting bodies will succeed in the long run.

Anterior cruciate ligament (ACL) injuries is an example where there are controlled studies showing promising efficacy (that the intervention is capable of producing the desired effect);5 ,10–13 however, their efficiency (whether the desired effect occurs under real-life conditions) is not known. We wanted to know ‘Have ACL injury prevention initiatives taken in Norway during the last decade been successful in the long run?’ We report our experience with Norwegian handball as an example, as this is an area where several initiatives (table 1) building on prevention trials have coincided with an ongoing surveillance programme.

View this table:

Table 1 
Prevention initiatives from 1998 through 2011



### ACL Injury Prevention Study

The 1998–1999 season served as the baseline for the ACL Injury Prevention Study; during the 1999–2000 season, an injury prevention programme was introduced in the top three divisions in female handball in Norway.10 The intervention consisted of a neuromuscular training programme with exercises on a wobble board, a balance mat and handball-specific exercises. In the first season (1999–2000), the intervention was based on coaches delivering the programme after being instructed by the investigators. However, as compliance was low, physical therapists were engaged to take charge of delivery of the programme during the second intervention season (2000–2001). Compared with a baseline rate of 0.48 ACL injuries per team, …
Central Vagotonic Effects of Atropine Modulate Spectral Oscillations of Sympathetic Nerve Activity
Authors: Nicola Montano, Chiara Cogliati, Alberto Porta, Massimo Pagani, Alberto Malliani, Krzysztof Narkiewicz, Francois M. Abboud, Clay Birkett, Virend K. Somers
Journal: Circulation (1998)

Background —Low-dose atropine causes bradycardia either by acting on the sinoatrial node or by its effects on central muscarinic receptors increasing vagal activity. Any central muscarinic effects of high-dose atropine on RR interval are masked by peripheral muscarinic blockade at the sinoatrial node, which causes tachycardia. Effects of central parasympathetic activation on sympathetic activity are not known. Methods and Results —Using power spectral analysis of RR interval, intra-arterial blood pressure, respiration, and muscle sympathetic nerve activity (MSNA), we examined the effects of both low (2 μg/kg IV) and high (15 μg/kg IV) doses of atropine. After low-dose atropine, RR increased by 9±1% ( P &lt;0.0001), the low-frequency (LF) component (in normalized units, NU) of RR variability decreased by −32±8%, and the high-frequency (HF) NU component increased (+74±19%); hence, LF/HF of RR variability fell by 52±10% (all P &lt;0.01). Although overall MSNA did not change, LF NU of MSNA decreased (−15±5%), HF NU of MSNA increased (+31±3%), and LF/HF of MSNA fell (−41±8%) (all P &lt;0.01). After high-dose atropine, LF NU of MSNA decreased (−17±12%), HF NU of MSNA increased (+22±3%), and LF/HF of MSNA fell (−51±21%) (all P &lt;0.02). Conclusions —Increasing central parasympathetic activity with low-dose atropine is associated with an increase in the HF and a decrease in the LF oscillations of both RR interval and MSNA variability. High-dose atropine similarly induces an increase in the HF and a decrease in the LF components of MSNA variability. Thus, central parasympathetic activation is able to modulate the oscillatory characteristics of sympathetic nerve traffic to peripheral blood vessels.