tbuckley/cabot-search huggingface dataset:
Neural Mechanisms of Frustration in Chronically Irritable Children
Authors: Christen M. Deveney, Megan E. Connolly, Catherine T. Haring, Brian L. Bones, Richard C. Reynolds, Pilyoung Kim, Daniel S. Pine, Ellen Leibenluft
Journal: American Journal of Psychiatry (2013)

Irritability is common in children and adolescents and is the cardinal symptom of disruptive mood dysregulation disorder, a new DSM-5 disorder, yet its neural correlates remain largely unexplored. The authors conducted a functional MRI study to examine neural responses to frustration in children with severe mood dysregulation.The authors compared emotional responses, behavior, and neural activity between 19 severely irritable children (operationalized using criteria for severe mood dysregulation) and 23 healthy comparison children during a cued-attention task completed under nonfrustrating and frustrating conditions.Children in both the severe mood dysregulation and the healthy comparison groups reported increased frustration and exhibited decreased ability to shift spatial attention during the frustration condition relative to the nonfrustration condition. However, these effects of frustration were more marked in the severe mood dysregulation group than in the comparison group. During the frustration condition, participants in the severe mood dysregulation group exhibited deactivation of the left amygdala, the left and right striatum, the parietal cortex, and the posterior cingulate on negative feedback trials, relative to the comparison group (i.e., between-group effect) and to the severe mood dysregulation group's responses on positive feedback trials (i.e., within-group effect). In contrast, neural response to positive feedback during the frustration condition did not differ between groups.In response to negative feedback received in the context of frustration, children with severe, chronic irritability showed abnormally reduced activation in regions implicated in emotion, attention, and reward processing. Frustration appears to reduce attention flexibility, particularly in severely irritable children, which may contribute to emotion regulation deficits in this population. Further research is needed to relate these findings to irritability specifically, rather than to other clinical features of severe mood dysregulation.
Comparing quality measures during hospitalization for chronic obstructive pulmonary disease in 2005-06 and 2010
Authors: Carrie P. Aaron, Natalie H. Yip, Marcia D. Brinson, Eliot Lazar, Brian Regan, Liziamma George, Marc S. Melamed, Paul Sachs, Maryanne Daley, Byron M. Thomashow
Journal: European Respiratory Journal (2014)

Rationale  Admissions for chronic obstructive pulmonary disease (COPD) are frequent and associated with high costs. In recent years initiatives in our Healthcare System have advanced the quality of care. We hypothesized that there would be improvement in care provided during admission for COPD in 2010 compared to 2005-06.   Methods  We performed a chart review of hospitalizations for exacerbation of COPD in 2005-06 and 2010 at five hospitals. Admissions were identified by ICD9 diagnosis code (COPD, emphysema, chronic bronchitis and chronic obstructive asthma). Demographics, medications, vaccinations and smoking cessation were recorded. Chi-squared tests compared rates among the groups.   Results  There were 989 unique patients admitted in 2005-06 and 1,261 in 2010. Patients were 73±12 years old, 42% male, 60% Caucasian, 17% African American and 18% Hispanic. In 2010, hospitalized patients were more likely to be treated with steroids (89.7% vs. 81.5% in 2005-06, P   Conclusions  During admissions for exacerbation of COPD at 5 hospitals in our Healthcare System, there were significant improvements from 2005-06 to 2010 in quality of care; however, there continues to be room for improvement.
Health-financing reforms in southeast Asia: challenges in achieving universal coverage
Authors: Viroj Tangcharoensathien, Walaiporn Patcharanarumol, Por Ir, Syed Mohamed Aljunid, Ali Ghufron Mukti, Kongsap Akkhavong, Eduardo Banzon, Dang Boi Huong, Hasbullah Thabrany, Anne Mills
Journal: The Lancet (2011)
Validation of automated sleep stage and apnoea analysis in suspected obstructive sleep apnoea
Authors: S Andreas, B von Breska, K Magnusson, H Kreuzer
Journal: European Respiratory Journal (1993)

Full-night polysomnography is necessary for the diagnosis of obstructive sleep apnoea (OSA). However, analysis of the sleep stages and apnoeas is time-consuming. Computer systems for automated analysis have, thus, been developed to alleviate this task. We investigated 27 consecutive patients referred to our sleep laboratory with suspected OSA. The analysis of sleep stages and apnoeas was performed by visual scoring, according to Rechtschaffen and Kales, and by commercially available automated analysis device. The mean difference between visual scoring and automated analysis was -1, 111, -140, -3, 1 and 27 min, for sleep stages awake, I, II, III, IV and rapid eye movement (REM) respectively. For the apnoea index, the automated analysis rated a lower figure (mean difference 7.h-1, 95% confidence interval 2-12.h-1). The diagnosis of OSA was performed with a sensitivity of 85% and a specificity of 93% by automated analysis. Comparison of two independent handscores showed good agreement, with a mean difference of 6, 4, 3, -7, 1 and -1 min, for sleep stages awake, I, II, III, IV and REM, respectively. In conclusion, the automated analysis underestimates stage I sleep and the apnoea index. Visual scoring is advisable for control of the results. Automated analysis should only be used by those who are able to perform a visual analysis.
TALEN-mediated targeting of HPV oncogenes ameliorates HPV-related cervical malignancy
Authors: Zheng Hu, Wencheng Ding, Da Zhu, Lan Yu, Xiaohui Jiang, Xiaoli Wang, Changlin Zhang, Liming Wang, Teng Ji, Dan Liu, Dan He, Xi Xia, Tao Zhu, Juncheng Wei, Peng Wu, Changyu Wang, Ling Xi, Qinglei Gao, Gang Chen, Rong Liu, Kezhen Li, Shuang Li, Shixuan Wang, Jianfeng Zhou, Ding Ma, Hui Wang
Journal: Journal of Clinical Investigation (2014)

Persistent HPV infection is recognized as the main etiologic factor for cervical cancer. HPV expresses the oncoproteins E6 and E7, both of which play key roles in maintaining viral infection and promoting carcinogenesis. While siRNA-mediated targeting of E6 and E7 transcripts temporarily induces apoptosis in HPV-positive cells, it does not eliminate viral DNA within the host genome, which can harbor escape mutants. Here, we demonstrated that specifically targeting E6 and E7 within host DNA with transcription activator-like effector nucleases (TALENs) induces apoptosis, inhibits growth, and reduces tumorigenicity in HPV-positive cell lines. TALEN treatment efficiently disrupted E6 and E7 oncogenes, leading to the restoration of host tumor suppressors p53 and retinoblastoma 1 (RB1), which are targeted by E6 and E7, respectively. In the K14-HPV16 transgenic mouse model of HPV-driven neoplasms, direct cervical application of HPV16-E7-targeted TALENs effectively mutated the E7 oncogene, reduced viral DNA load, and restored RB1 function and downstream targets transcription factor E2F1 and cycling-dependent kinase 2 (CDK2), thereby reversing the malignant phenotype. Together, the results from our study suggest that TALENs have potential as a therapeutic strategy for HPV infection and related cervical malignancy.
An Introduction to Clinical Emergency Medicine: Guide for Practitioners in the Emergency Department
Authors: Mike Aisbitt, John Bache
Journal: Journal of the Royal Society of Medicine (2006)

The `4-hour target', and the difficulty experienced by many patients in seeing a GP, has increased workload in UK emergency departments. Why bother telephoning a permanently engaged number when you can attend the nearest emergency department at your convenience and be sorted within 4 hours? And the time will be filled with the excitement normally reserved for a night in front of the television. If you are really lucky, the media may be in the department and you are famous for 15 minutes. And it's all available 24/7, free!

The variety of work is a great attraction. Most departments see adults and children and a typical day may involve treating patients with problems as diverse as dyspnoea, major trauma, lacerations, psychoses, fractures, arrest, intoxication, earache, toothache, backache and heartache. Recently we have seen an escalation in the presentation of acute-on-chronic and extremely chronic conditions.

Will this book help the staff? It is attractively presented with clear illustrations. But the intended readership is unclear. In the UK it would probably be most relevant for senior house officers, emergency nurse practitioners and medical students. There is generally insufficient detail for more senior staff.

Practitioners need instant information, but this book is too bulky for any pocket—unlike the Oxford handbooks. It would have to be kept in a central area, for consultation as required. Even then it is often difficult to glean important information. For example, the many references to meningococcal septicaemia/meningitis in the index failed to provide the essential information needed by practitioners faced with a seriously ill child. Surely such an important condition warrants its own specific text? If you need to look something up quickly, you do not want to navigate your way through eight tables, many repeating each other. Too many tables can make it difficult to find the information required, even if available.

Perhaps the book is intended for reference or in preparation for examinations? The 25 mnemonics (many very contrived) and 228 tables (ranging in length from four lines to four and a half pages) suggest that this may be the case. Although some topics are covered in depth, others are dealt with superficially.

All but one of the 72 contributors is from America. UK readers will thus experience occasional difficulties and some sections are not fully relevant to UK practice.

This book is superficially attractive but will not seriously compete against more established texts.
Effectiveness of switching between TNF inhibitors in ankylosing spondylitis: data from the NOR-DMARD register
Authors: E. Lie, D. van der Heijde, T. Uhlig, K. Mikkelsen, E. Rodevand, W. Koldingsnes, C. Kaufmann, T. K. Kvien
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Objective</h3> To assess the effectiveness of switching to a second tumour necrosis factor inhibitor (TNFi) in patients with ankylosing spondylitis (AS). <h3>Methods</h3> Data were extracted from an ongoing longitudinal observational multicentre study in Norway. This study included anti-TNF naïve patients with AS starting treatment with a TNFi as well as treatment with a second TNFi in these same patients. Effectiveness data and 2-year drug survival were compared between switchers and non-switchers and within switchers (first and second TNFi). <h3>Results</h3> 514 anti-TNF naïve patients with AS were included; 77 patients switched to a second TNFi while 437 patients did not switch. The percentages of non-switchers using etanercept, infliximab or adalimumab were 53%, 32% and 15%, and the percentages of first and second TNFi in the switchers were 42%, 53% and 5% and 40%, 23% and 36%, respectively. The reason for switching was insufficient response (IR) in 30, adverse events (AEs) in 44 and not reported in 3 patients. Baseline disease activity was similar between the groups. Three-month BASDAI 50 and ASAS 40 responses were achieved by 49% and 38% of non-switchers, by 25% and 30% of switchers after the first TNFi and by 28% and 31% after the second TNFi. The 3-month disease activity level was higher for switchers on the second TNFi than for non-switchers. Drug withdrawal rate was higher during the second TNFi among switchers than for non-switchers (p=0.001). No difference was found in the effectiveness of the second TNFi between switchers due to IR and AE. <h3>Conclusion</h3> This study confirms that switching to a second TNFi can be effective in AS and can be as useful as in rheumatoid arthritis, although overall effectiveness seems to be somewhat lower than in non-switchers.
On the Mechanism of Alcohol-Induced Pseudo-Cushing's Syndrome
Authors: R. GROOTE VELDMAN, A. E. MEINDERS
Journal: Endocrine Reviews (1996)

I. IntroductionCushing's syndrome is clinically characterized by truncal obesity, moon face, supraclavicular fat pads, buffalo hump, hirsutism, blue-red striae, easy bruisability, osteoporosis, hypertension, and proximal myopathy. Biochemically, impaired glucose tolerance and hypokalemic alkalosis can be present. Leukocytosis with lymphocytopenia and decreased numbers of eosinophils are often found. Hormonal testing shows an increased secretion of cortisol, which is not suppressed by the overnight dexamethasone test (1 mg). Depending on the etiology of the syndrome, decreased or increased secretion of ACTH is found. In patients with chronic alcohol abuse, clinical or biochemical features or both of Cushing's syndrome can be found. Because both the physical and the hormonal abnormalities disappear after discontinuation of alcohol this phenomenon was called alcohol-induced pseudo-Cushing's syndrome (1, 2). Alcohol-induced pseudo-Cushing's syndrome is indistinguishable from true Cushing's syndrome, although in the former less signs and symptoms seem to be present (3). Yanovski et al. (4) suggest the CRH test after administration of low-dose dexamethasone (2 mg/day for 2 days) to separate these two syndromes: a serum cortisol level above 38 nmol/liter (1.4μg/dl) 15 min after the injection of CRH was found in all subjects with true Cushing's syndrome. The ultimate test, however, is to abstain from alcohol and to wait for the signs and symptoms to disappear. Despite many studies of this subject, the pathogenesis of this syndrome has not been elucidated.
Testing for linkage and association with rheumatoid arthritis a ptpn22 promoter polymorphism reported to be associated and linked with type 1 diabetes in the Caucasian population
Authors: P DieudÃ©, V H Teixeira, C Pierlot, F CornÃ©lis, E Petit-Teixeira
Journal: Annals of the Rheumatic Diseases (2008)

The PTPN22 single nucleotide polymorphism (SNP) +1858 C/T (rs2476601) was found to be linked and associated with rheumatoid arthritis (RA).1 However, the frequency of the susceptibility +1858T allele range from 2% to 15% of south to north Europeans, and is not observed in an Asian population, suggesting the involvement of other disease-associated PTPN22 polymorphisms.2–4 A study performed in the type 1 diabetes (T1D) Japanese population led to the identification of the PTPN22 – 1123 G/C SNP (rs2488457), for which the –1123G allele was found to be associated with T1D.5 This allele in linkage disequilibrium with +1858T was also tested in a familial T1D UK Caucasian sample. The transmission disequilibrium test (TDT) showed a significant excess of transmission of the –1123G allele compared with that …
Differential Distribution of Cardiac Ion Channel Expression as a Basis for Regional Specialization in Electrical Function
Authors: Gernot Schram, Marc Pourrier, Peter Melnyk, Stanley Nattel
Journal: Circulation Research (2002)

The cardiac electrical system is designed to ensure the appropriate rate and timing of contraction in all regions of the heart, which are essential for effective cardiac function. Well-controlled cardiac electrical activity depends on specialized properties of various components of the system, including the sinoatrial node, atria, atrioventricular node, His-Purkinje system, and ventricles. Cardiac electrical specialization was first recognized in the mid 1800s, but over the past 15 years, an enormous amount has been learned about how specialization is achieved by differential expression of cardiac ion channels. More recently, many aspects of the molecular basis have been revealed. Although the field is potentially vast, an appreciation of key elements is essential for any clinician or researcher wishing to understand modern cardiac electrophysiology. This article reviews the major regionally determined features of cardiac electrical function, discusses underlying ionic bases, and summarizes present knowledge of ion channel subunit distribution in relation to functional specialization.
Long-term fenofibrate treatment impairs endothelium-dependent dilation to acetylcholine by altering the cyclooxygenase pathway
Authors: J BLANCORIVERO, I MARQUEZRODAS, F XAVIER, R ARASLOPEZ, I ARROYOVILLA, M FERRER, G BALFAGON
Journal: Cardiovascular Research (2007)

Experimental studies and opinion articles emphasize that cardiovascular alterations associated with ageing can be improved by the long-term use of fenofibrates. We analyzed the effect of fenofibrate treatment on the acetylcholine-induced relaxation in rat aorta and the participation of nitric oxide (NO) and cyclooxygenase (COX)-derived factors in this effect.Acetylcholine relaxation in untreated and 6-week fenofibrate-treated Wistar rats was analyzed in the absence and presence of the NO synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME), the specific inducible NO (iNOS) synthase inhibitor 1400W, the nonspecific COX inhibitor indomethacin, the specific COX-2 inhibitor NS-398, the specific thromboxane receptor antagonist SQ-29548, the thromboxane synthesis inhibitor furegrelate, the prostacyclin synthesis inhibitor tranylcypromine, or the 20-HETES synthesis inhibitor formamidine. eNOS, iNOS, COX-1, and COX-2 expression was studied by Western blotting. In addition, production of prostaglandin F(2alpha) (PGF(2alpha)), thromboxane A(2) (TxA(2)), prostaglandin E(2) (PGE(2)), isoprostanes, and prostacyclin (PGI(2)) was also measured.Fenofibrate treatment reduced acetylcholine relaxation. Indomethacin, NS-398, and tranylcypromine decreased acetylcholine relaxation in untreated rats but enhanced relaxation in treated rats. SQ-29548 increased acetylcholine responses in segments from treated rats but not in segments from untreated rats. L-NAME decreased vasodilator response to acetylcholine in both groups while furegrelate, NS-398, 1400W, and formamidine did not affect acetylcholine responses in either group. eNOS and COX-2 expression was higher in aorta from treated rats while COX-1 and iNOS remained unmodified. Basal and acetylcholine-stimulated NO and PGE(2) release were increased, and that of PGI(2) decreased in treated rats. TxA(2) release was similar, but PGF(2alpha) release was undetectable in both groups.Although it increases NO production through increases in eNOS expression, fenofibrate treatment induces endothelial dysfunction. This effect seems to be mediated by decreased PGI(2) and increased PGE(2) release, and it may help to explain the rise in thromboembolic events observed after long-term fenofibrate treatment in humans.
Differential Contextual Responses of Normal Human Breast Epithelium to Ionizing Radiation in a Mouse Xenograft Model
Authors: Philip J. Coates, M. Virginia, C.L. Appleyard, Karen Murray, Caroline Ackland, June Gardner, Douglas C. Brown, Dougal J.A. Adamson, Lee B. Jordan, Colin A. Purdie, Alastair J. Munro, Eric G. Wright, John A. Dewar, Alastair M. Thompson
Journal: Cancer Research (2010)

Radiotherapy is a key treatment option for breast cancer, yet the molecular responses of normal human breast epithelial cells to ionizing radiation are unclear. A murine subcutaneous xenograft model was developed in which nonneoplastic human breast tissue was maintained with the preservation of normal tissue architecture, allowing us to study for the first time the radiation response of normal human breast tissue in situ. Ionizing radiation induced dose-dependent p53 stabilization and p53 phosphorylation, together with the induction of p21(CDKN1A) and apoptosis of normal breast epithelium. Although p53 was stabilized in both luminal and basal cells, induction of Ser392-phosphorylated p53 and p21 was higher in basal cells and varied along the length of the ductal system. Basal breast epithelial cells expressed ΔNp63, which was unchanged on irradiation. Although stromal responses themselves were minimal, the response of normal breast epithelium to ionizing radiation differed according to the stromal setting. We also demonstrated a dose-dependent induction of γ-H2AX foci in epithelial cells that was similarly dependent on the stromal environment and differed between basal and luminal epithelial cells. The intrinsic differences between human mammary cell types in response to in vivo irradiation are consistent with clinical observation that therapeutic ionizing radiation is associated with the development of basal-type breast carcinomas. Furthermore, there may be clinically important stromal-epithelial interactions that influence DNA damage responses in the normal breast. These findings demonstrate highly complex responses of normal human breast epithelium following ionizing radiation exposure and emphasize the importance of studying whole-tissue effects rather than single-cell systems.
Sites of B Lymphocyte Selection, Activation, and Tolerance in Spleen
Authors: Yong-Jun Liu
Journal: The Journal of Experimental Medicine (1997)

The immune system appears to be rigid, restricting one lymphocyte to make one antibody (([1][1])) and the peripheral B cell pool to a constant number (108 in mice) (2– 4). To make a rapid immune response to an unlimited number of antigens at any anatomical site, it has developed at least three
Ten-Year Mortality after Community-acquired Pneumonia. A Prospective Cohort
Authors: Dean T. Eurich, Thomas J. Marrie, Jasjeet K. Minhas-Sandhu, Sumit R. Majumdar
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Information on the long-term prognosis after community-acquired pneumonia (CAP) is limited.To determine if CAP increases adverse long-term outcomes relative to a control population.Between 2000 and 2002, 6,078 adults with CAP from six hospitals and seven emergency departments in Edmonton (AB, Canada) were prospectively recruited and matched on age, sex, and site of treatment with five control subjects without pneumonia (n = 29,402). Mortality, hospitalizations, and emergency department admissions through 2012 were evaluated using multivariable Cox proportional hazards analyses adjusted for socioeconomic status and comorbidities.Average age was 59 years (2,682 [44%] ≥ 65 yr), 3,214 (53%) were men, and 3,425 (56%) were managed as outpatients. Over a median of 9.8 years, 2,858 patients with CAP died compared with 9,399 control subjects (absolute risk difference, 30 per 1,000 patient years [py]; adjusted hazard ratio [aHR], 1.65; 95% confidence interval, 1.57-1.73; P < 0.001). Patients with CAP who were younger than 25 years old had the lowest absolute rate difference for mortality (4 per 1,000 py; aHR, 2.40), and patients older than 80 years old had the highest absolute rate difference (92 per 1,000 py; aHR, 1.42). Absolute rates of all-cause hospitalization, emergency department visits, and CAP-related visits were all significantly higher in patients with CAP compared with control subjects (P < 0.001 for all comparisons).Our results indicate that an episode of CAP confers a high risk of long-term adverse events compared with the general population who have not experienced CAP, and this is irrespective of age.
Antibody-CD20-interferon-alpha fusion protein has superior in vivo activity against human B cell lymphomas compared to Rituximab, and enhanced complement-dependent cytotoxicity in vitro
Authors: Reiko Yamada, Kristopher Steward, Gataree Ngarmchamnanrith, Ryan Trinh, Sanjay Khare, Raj Sachdev, Iqbal Grewal, Sherie Morrison, John Timmerman
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts We previously reported an anti-CD20-interferon-alpha (IFNα) fusion protein able to induce apoptosis and promote in vivo eradication of a human CD20-expressing mouse B cell lymphoma [Xuan et al, Blood 2010]. We now report the activity of a recombinant anti-CD20-human IFNα fusion