tbuckley/cabot-search huggingface dataset:
The Major Tick Salivary Gland Proteins and Toxins from the Soft Tick, Ornithodoros savignyi, Are Part of the Tick Lipocalin Family: Implications for the Origins of Tick Toxicoses
Authors: B. J. Mans
Journal: Molecular Biology and Evolution (2003)

The origins of tick toxicoses remain a subject of controversy because no molecular data are yet available to study the evolution of tick-derived toxins. In this study we describe the molecular structure of toxins from the soft tick, Ornithodoros savignyi. The tick salivary gland proteins (TSGPs) are four highly abundant proteins proposed to play a role in salivary gland granule biogenesis of the soft tick O. savignyi, of which the toxins TSGP2 and TSGP4 are a part. They were assigned to the lipocalin family based on sequence similarity to known tick lipocalins. Several other tick lipocalins were also identified using Smith-Waterman database searches, bringing the tick lipocalin family up to 20. Phylogenetic analysis showed that most tick lipocalins group within genus-specific clades, suggesting that gene duplication and divergence of tick lipocalin function occurred after tick speciation, most probably during the evolution of a hematophagous lifestyle. TSGP2 and TSGP3 show high sequence identity and group terminal to moubatin, an inhibitor of collagen-induced platelet aggregation from the tick, O. moubata. However, no platelet aggregation inhibitory activity is associated with the TSGPs using ADP or collagen as agonists, suggesting that TSGP2 and TSGP3 duplicated after divergence of O. savignyi and O. moubata. This timing is supported by the absence of TSGP2-4 in the salivary gland extracts of O. moubata. The absence of TSGP2 and TSGP4 in salivary gland extracts from O. moubata correlates with the nontoxicity of this tick species. The implications of this study are that the various forms of tick toxicoses do not have a common origin, but must have evolved independently in those tick species that cause pathogenesis.
Ionic mechanisms and Ca2+ handling in airway smooth muscle
Authors: S. Hirota, P. Helli, L. J. Janssen
Journal: European Respiratory Journal (2007)

Asthma is a disease characterised by reversible contraction of airway smooth muscle. Many signalling pathways are now known to underlie that contraction, almost all of which revolve around Ca<sup>2+</sup> handling. Ca<sup>2+</sup> homeostasis in turn is governed by a wide variety of ionic mechanisms, which are still poorly understood. The present review will briefly summarise those mechanisms that have been recognised for decades, but will then devote considerable attention to several novel ionic signalling mechanisms such as capacitative Ca<sup>2+</sup> entry, the reverse mode of the Na<sup>+</sup>/Ca<sup>2+</sup> exchanger, the role of Cl<sup>-</sup> channels in the release of internal Ca<sup>2+</sup> and that of ryanodine receptors in the refilling of the sarcoplasmic reticulum, as well as the regulation of the monomeric G-protein Rho by ionic mechanisms. Lastly, evidence will be provided that Ca<sup>2+</sup>-dependent contraction may be driven by spatial and temporal heterogeneities in the intracellular Ca<sup>2+</sup> concentration (<i>i.e.</i> Ca<sup>2+</sup> waves/oscillations) rather than by an increase in the global steady state intracellular Ca<sup>2+</sup> concentration.
Beyond DNA Repair: DNA-PK Function in Cancer
Authors: Jonathan F. Goodwin, Karen E. Knudsen
Journal: Cancer Discovery (2014)

Abstract The DNA-dependent protein kinase (DNA-PK) is a pivotal component of the DNA repair machinery that governs the response to DNA damage, serving to maintain genome integrity. However, the DNA-PK kinase component was initially isolated with transcriptional complexes, and recent findings have illuminated the impact of DNA-PK–mediated transcriptional regulation on tumor progression and therapeutic response. DNA-PK expression has also been correlated with poor outcome in selected tumor types, further underscoring the importance of understanding its role in disease. Herein, the molecular and cellular consequences of DNA-PK are considered, with an eye toward discerning the rationale for therapeutic targeting of DNA-PK. Significance: Although DNA-PK is classically considered a component of damage response, recent findings illuminate damage-independent functions of DNA-PK that affect multiple tumor-associated pathways and provide a rationale for the development of novel therapeutic strategies. Cancer Discov; 4(10); 1126–39. ©2014 AACR.
How good are fast and frugal inference heuristics in case of limited knowledge?
Authors: Edgar Erdfelder, Martin Brandt
Journal: Behavioral and Brain Sciences (2000)

Gigerenzer and his collaborators have shown that the Take the Best heuristic (TTB) approximates optimal decision behavior for many inference problems. We studied the effect of incomplete cue knowledge on the quality of this approximation. Bayesian algorithms clearly outperformed TTB in case of partial cue knowledge, especially when the validity of the recognition cue is assumed to be low.
A phase 2 study of idelalisib plus rituximab in treatment-naïve older patients with chronic lymphocytic leukemia
Authors: Susan M. O'Brien, Nicole Lamanna, Thomas J. Kipps, Ian Flinn, Andrew D. Zelenetz, Jan A. Burger, Michael Keating, Siddhartha Mitra, Leanne Holes, Albert S. Yu, David M. Johnson, Langdon L. Miller, Yeonhee Kim, Roger D. Dansey, Ronald L. Dubowy, Steven E. Coutre
Journal: Blood (2015)
Geriatric Psychiatry Versus General Psychiatry Inpatient Treatment of the Elderly
Authors: Izzet Cagri Yazgan, Blaine S. Greenwald, Neil J. Kremen, Joan Strach, Elisse Kramer-Ginsberg
Journal: American Journal of Psychiatry (2004)

The authors compared the clinical treatment given older psychiatric inpatients on a geriatric psychiatry unit and a general psychiatry unit.The charts of 50 randomly selected general psychiatry inpatients over the age of 65 years and 50 inpatients from the geriatric psychiatry unit who were matched for age, gender, and primary diagnosis were reviewed.Significantly greater percentages of older inpatients treated on the geriatric psychiatry unit received complete organic medical workups, structured cognitive assessment, aging-sensitive aftercare referral, and monitoring of psychopharmacological side effects and blood levels than comparable patients on a general psychiatry unit.Geriatric psychiatry subspecialty inpatient care appears to be associated with distinct clinically relevant assessment and treatment advantages. Continuing geropsychiatric education of general psychiatrists is indicated.
The effect of pre-season dance training on physical indices and back pain in elite cross-country skiers: a prospective controlled intervention study
Authors: M Alricsson, S Werner
Journal: British Journal of Sports Medicine (2004)

To evaluate the effect of pre-season dance training on back pain, joint mobility, and muscle flexibility, and on speed and agility in elite cross-country skiers.26 skiers participated (mean (SD) age, 19 (3.9) years). An intervention group (n = 16) had 12 weeks of dance training; a control group (n = 10) did not dance; otherwise both groups followed a similar pre-season physical training programme. Joint mobility and muscle flexibility of the spine, hip, and ankle were measured. Two sports related functional tests (slalom and hurdle) were also done. All measurements/tests were carried out before and after the dancing period.Four (of six) subjects from the intervention group who initially complained of ski related back pain did not report back pain after the dance training; the three subjects with back pain from the control group were unchanged. At study onset the intervention group had a slightly impaired range of motion in the spine compared with the control group. After dance training, there was a better relation between kyphosis of the thoracic spine and lordosis of the lumbar spine, and a 7.1 degrees increase in hip flexion with the knee extended (p = 0.02). In the control group hip extension decreased by 0.08 m on average (p = 0.01). No positive effects of dance training on sports related functional tests were observed.Preseason dance training improved the range of hip motion and joint mobility and the flexibility of the spine. These improvements might explain the reduction in ski related back pain in the intervention group.
Two Rotavirus Outbreaks Caused by Genotype G2P[4] at Large Retirement Communities
Authors: Cristina V. Cardemil
Journal: Annals of Internal Medicine (2012)

Background: Outbreaks of rotavirus gastroenteritis in elderly adults are reported infrequently but are often caused by G2P[4] strains. In 2011, outbreaks were reported in 2 Illinois retirement facilities. Objective: To implement control measures, determine the extent and severity of illness, and assess risk factors for disease among residents and employees. Design: Cohort studies using surveys and medical chart abstraction. Setting: Two large retirement facilities in Cook County, Illinois. Patients: Residents and employees at both facilities and community residents with rotavirus disease. Measurements: Attack rates, hospitalization rates, and rotavirus genotype. Results: At facility A, 84 of 324 residents (26%) were identified with clinical or laboratory-confirmed rotavirus gastroenteritis (median age, 84 years) and 11 (13%) were hospitalized. The outbreak lasted 7 weeks. At facility B, 90 case patients among 855 residents (11%) were identified (median age, 88 years) and 19 (21%) were hospitalized. The facility B outbreak lasted 9.3 weeks. Ill employees were identified at both locations. In each facility, attack rates seemed to differ by residential setting, with the lowest rates among those in more separated settings or with high baseline level of infection control measures. The causative genotype for both outbreaks was G2P[4]. Some individuals shed virus detected by enzyme immunoassay or genotyping reverse transcription polymerase chain reaction for at least 35 days. G2P[4] was also identified in 17 of 19 (89%) samples from the older adult community but only 15 of 40 (38%) pediatric samples. Limitation: Medical or cognitive impairment among residents limited the success of some interviews. Conclusion: Rotavirus outbreaks can occur among elderly adults in residential facilities and can result in considerable morbidity. Among older adults, G2P[4] may be of unique importance. Health professionals should consider rotavirus as a cause of acute gastroenteritis in adults. Primary Funding Source: None.
Psephology and pulmonology
Authors: M. Barry
Journal: European Respiratory Journal (2014)

Science and politics can't be viewed in isolation: ERS brings both together through ongoing advocacy activities http://ow.ly/yUrHn''Just because you do not take an interest in politics does not mean politics won't take an interest in you'' PericlesEurope, in its various forms, has been voting since antiquity.From the golden Athenian age of Pericles to the austerity age of modern Europe, elections and their results continue to be anticipated, scrutinised and debated.This editorial focuses on the recent exercise from May22-25, 2014, when citizens of the European Union (EU) voted to elect the 8th legislature of the European Parliament.Psephology is the ''the statistical study of elections and trends in voting'' as defined by the Oxford English Dictionary (www.oed.com).These trends show that in May 2014, 43% of EU voters turned out to ''act, react, and impact'' [1].Although there was an improvement compared with previous turnouts, it seems Pericles' warning has still not been heeded by the majority of EU voters.By contrast, those who did vote have already shaped the policies of the European Parliament for the coming years, which include those that affect pulmonology.According to the European Parliamentary Research Service, in the Parliament's last term (2009)(2010)(2011)(2012)(2013)(2014), it held 2821 meetings, conducted more than 23 500 votes, and adopted more than 19 000 amendments whilst rejecting even more [2].Hardly surprising, therefore, that the European Parliament is one of three main institutions within the EU that is involved in EU legislation.It has been directly elected since 1979, and on this occasion 751 Members of the European Parliament (MEPs) were elected.These MEPs will, by now, have organised themselves according to political groups, rather than by country or by national party.Well established political groups include (from right to left): European Conservatives and Reformists (ECR), the European Peoples' Party (EPP), Alliance of Liberals and Democrats for Europe (ALDE), Socialists and Democrats (S&D) and the Greens [3].During this term, these MEPs will join specific committees such as the Environment, Public Health and Food Safety committee or the Industry, Research and Energy committee.There are 20 such Committees preparing, debating, and negotiating legislation on topics from agriculture to employment law to development assistance.The main powers of the European Parliament can be summed up as the ability to accept, reject or amend draft legislation, budgetary oversight, and approval of the appointment of European Commissioners [4].This, in a nutshell, is the task of those elected to represent the interests of 500 million citizens for the next 5 years.While the election results make interesting reading, they may not be as dramatic as reported.Despite anticipated disarray, the largest parties remain the centre-right EPP followed by the centre-left S&D.
Environmental urban factors (air pollution and allergens) and the rising trends in allergic respiratory diseases
Authors: Gennaro D'Amato
Journal: Allergy (2002)

Respiratory allergic diseases such as rhinitis and bronchial asthma appear to be increasing worldwide, affecting in particular subjects living in urban areas, and the reasons for this increase are still largely unknown. Although the role played by air pollution has yet to be clarified, a body of evidence suggests that urbanization, with its high levels of vehicle emissions and a westernised lifestyle are linked to the rising frequency of these diseases observed in most industrialized countries. Laboratory studies confirm the epidemiological evidence that inhalation of some pollutants, either individually or in combination, adversely affect lung function in asthmatics. Air pollutants may not only increase the frequency and intensity of symptoms in already allergic patients but may promote airway sensitization to airborne allergens in predisposed subjects. By attaching to the surface of pollen grains and of plant-derived paucimicronic particles, pollutants can modify the morphology of these antigen-carrying agents and alter their allergenic potential. In addition, by inducing airway inflammation, pollutants may overcome the mucosal barrier and so "prime" allergen-induced responses. In other words airway mucosal damage and impaired mucociliary clearance induced by air pollution may facilitate the access of inhaled allergens to the cells of the immune system.
Autofluorescence bronchoscopy for lung cancer surveillance based on risk assessment
Authors: G. Loewen, N. Natarajan, D. Tan, E. Nava, D. Klippenstein, M. Mahoney, M. Cummings, M. Reid
Journal: Thorax (2006)

<b>Background:</b> This is a preliminary report of an ongoing prospective bimodality lung cancer surveillance trial for high-risk patients. Bimodality surveillance incorporates autofluorescence bronchoscopy (AFB) and spiral CT (SCT) scanning in high-risk patients as a primary lung cancer surveillance strategy, based entirely on risk factors. AFB was used for surveillance and findings were compared with conventional sputum cytology for the detection of malignancy and pre-malignant central airway lesions. <b>Methods:</b> 402 patients registering at Roswell Park Cancer Institute were evaluated with spirometric testing, chest radiography, history and physical examination, of which 207 were deemed eligible for the study. For eligibility, patients were required to have at least two of the following risk factors: (1) ⩾20 pack year history of tobacco use, (2) asbestos-related lung disease on the chest radiograph, (3) chronic obstructive pulmonary disease with a forced expiratory volume in 1 s (FEV<sub>1</sub>) &lt;70% of predicted, and (4) prior aerodigestive cancer treated with curative intent, with no evidence of disease for &gt;2 years. All eligible patients underwent AFB, a low-dose SCT scan of the chest without contrast, and a sputum sample was collected for cytological examination. Bronchoscopic biopsy findings were correlated with sputum cytology results, SCT-detected pulmonary nodules and surveillance-detected cancers. To date, 186 have been enrolled with 169 completing the surveillance procedures. <b>Results:</b> Thirteen lung cancers (7%) were detected in the 169 subjects who have completed all three surveillance studies to date. Pre-malignant changes were common and 66% of patients had squamous metaplasia or worse. Conventional sputum cytology missed 100% of the dysplasias and 68% of the metaplasias detected by AFB, and failed to detect any cases of carcinoma or carcinoma-in-situ in this patient cohort. Sputum cytology exhibited 33% sensitivity and 64% specificity for the presence of metaplasia. Seven of 13 lung cancers (58%) were stage Ia or less, including three patients with squamous cell carcinoma. Patients with peripheral pulmonary nodules identified by SCT scanning of the chest were 3.16 times more likely to exhibit pre-malignant changes on AFB (p&lt;0.001). <b>Conclusion:</b> Bimodality surveillance will detect central lung cancer and pre-malignancy in patients with multiple lung cancer risk factors, even when conventional sputum cytology is negative. AFB should be considered in high-risk patients, regardless of sputum cytology findings.
Pilot Study of Oral Silibinin, a Putative Chemopreventive Agent, in Colorectal Cancer Patients: Silibinin Levels in Plasma, Colorectum, and Liver and Their Pharmacodynamic Consequences
Authors: Carmen Hoh, David Boocock, Tim Marczylo, Rajinder Singh, David P. Berry, Ashley R. Dennison, David Hemingway, Andrew Miller, Kevin West, Stephanie Euden, Giuseppe Garcea, Peter B. Farmer, William P. Steward, Andreas J. Gescher
Journal: Clinical Cancer Research (2006)

Silibinin, a flavonolignan from milk thistle, has intestinal cancer chemopreventive efficacy in rodents. It is a strong antioxidant and modulates the insulin-like growth factor (IGF) system by increasing circulating levels of IGF-binding protein 3 (IGFBP-3) and decreasing levels of IGF-I. Here, the hypothesis was tested that administration of oral silibinin generates agent levels in human blood and colorectal and hepatic tissues consistent with pharmacologic activity. Patients with confirmed colorectal adenocarcinoma received silibinin formulated with phosphatidylcholine (silipide) at dosages of 360, 720, or 1,440 mg silibinin daily for 7 days. Blood and biopsy samples of normal and malignant colorectum or liver were obtained before dosing, and blood and colorectal or hepatic tissues were collected at resection surgery after the final silipide dose. Levels of silibinin were quantified by high-pressure liquid chromatography-UV, and plasma metabolites were identified by liquid chromatography-mass spectrometry. Blood levels of IGFBP-3, IGF-I, and the oxidative DNA damage pyrimidopurinone adduct of deoxyguanosine (M1dG) were determined. Repeated administration of silipide was safe and achieved levels of silibinin of 0.3 to 4 micromol/L in the plasma, 0.3 to 2.5 nmol/g tissue in the liver, and 20 to 141 nmol/g tissue in colorectal tissue. Silibinin monoglucuronide, silibinin diglucuronide, silibinin monosulfate, and silibinin glucuronide sulfate were identified in the plasma. Intervention with silipide did not affect circulating levels of IGFBP-3, IGF-I, or M1dG. The high silibinin levels achieved in the human colorectal mucosa after consumption of safe silibinin doses support its further exploration as a potential human colorectal cancer chemopreventive agent.
Intestinal crypt cell apoptosis in murine acute graft versus host disease is mediated by tumour necrosis factor α and not by the FasL-Fas interaction: effect of pentoxifylline on the development of mucosal atrophy
Authors: E Stüber, A Büschenfeld, A von Freier, T Arendt, U R Fölsch
Journal: Gut (1999)

BACKGROUND Murine T cell mediated acute semiallogeneic graft versus host disease (GVHD) is characterised by lymphocytic infiltrates, crypt hyperplasia, and villous atrophy. It has been shown that programmed cell death (apoptosis) of the crypt epithelium takes place during the intestinal manifestation of acute GVHD. AIMS To investigate which of the two most investigated inductors of apoptosis (Fas ligand (FasL) and tumour necrosis factor α (TNF-α)) is responsible for the induction of apoptosis in this animal model. METHODS Animals undergoing acute semiallogeneic GvH reaction were treated with neutralising anti-TNF-α, two different anti-FasL antibodies, or pentoxifylline. RESULTS Anti-TNF-α application inhibited the appearance of apoptotic cells in the intestinal mucosa, whereas anti-FasL antibodies had no influence on mucosal apoptosis. In addition, the transfer of FasL deficient (gld) donor lymphocytes still induced crypt cell apoptosis, villous atrophy, and crypt hyperplasia. Furthermore, when the animals were treated with pentoxifylline, a known inhibitor of TNF-α secretion in vitro and in vivo, there was significant normalisation of the intestinal morphology accompanied by inhibition of epithelial apoptosis. CONCLUSIONS The FasL-Fas interaction is not involved in the induction of apoptosis during acute GVHD. However, neutralisation of TNF-α by an antibody or by pentoxifylline inhibits the occurrence of apoptosis and of mucosal atrophy in this animal model. These results have implications for the treatment of immunologically mediated human atrophic gut diseases—for example, diet refractory cases of coeliac disease.
Aberrant activation of AMP-activated protein kinase remodels metabolic network in favor of cardiac glycogen storage
Authors: Ivan Luptak, Mei Shen, Huamei He, Michael F. Hirshman, Nicolas Musi, Laurie J. Goodyear, Jie Yan, Hiroko Wakimoto, Hiroyuki Morita, Michael Arad, Christine E. Seidman, J.G. Seidman, Joanne S. Ingwall, James A. Balschi, Rong Tian
Journal: Journal of Clinical Investigation (2007)

AMP-activated protein kinase (AMPK) responds to impaired cellular energy status by stimulating substrate metabolism for ATP generation. Mutation of the gamma2 regulatory subunit of AMPK in humans renders the kinase insensitive to energy status and causes glycogen storage cardiomyopathy via unknown mechanisms. Using transgenic mice expressing one of the mutant gamma2 subunits (N488I) in the heart, we found that aberrant high activity of AMPK in the absence of energy deficit caused extensive remodeling of the substrate metabolism pathways to accommodate increases in both glucose uptake and fatty acid oxidation in the hearts of gamma2 mutant mice via distinct, yet synergistic mechanisms resulting in selective fuel storage as glycogen. Increased glucose entry in the gamma2 mutant mouse hearts was directed through the remodeled metabolic network toward glycogen synthesis and, at a substantially higher glycogen level, recycled through the glycogen pool to enter glycolysis. Thus, the metabolic consequences of chronic activation of AMPK in the absence of energy deficiency is distinct from those previously reported during stress conditions. These findings are of particular importance in considering AMPK as a target for the treatment of metabolic diseases.