tbuckley/cabot-search huggingface dataset:
Using lifestyle factors to identify individuals at higher risk of inflammatory polyarthritis (results from the European Prospective Investigation of Cancer-Norfolk and the Norfolk Arthritis Register—the EPIC-2-NOAR Study)
Authors: Manjari Lahiri, Robert N Luben, Catharine Morgan, Diane K Bunn, Tarnya Marshall, Mark Lunt, Suzanne M M Verstappen, Deborah P M Symmons, Kay-Tee Khaw, Nick Wareham, Ian N Bruce
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To investigate the association of lifestyle factors with risk of inflammatory polyarthritis (IP) and rheumatoid arthritis (RA). <h3>Methods</h3> The European Prospective Investigation of Cancer, Norfolk, UK (EPIC-Norfolk) gathered lifestyle data from participants aged 40–79 years from 1993 to 1997. Individuals who subsequently developed IP were identified by linkage with the Norfolk Arthritis Register. A Cox proportional hazard model was developed, and a score assigned to each risk factor to calculate the odds of developing IP. <h3>Results</h3> 25 455 EPIC participants were followed for a median (IQR) of 14.2 (12.9, 15.3) years; 184 developed incident IP (138 cumulatively fulfilled criteria for RA; 107 were seropositive). Pack-years of smoking were associated with increased risk of IP and RA in men (HR 1.21 (95% CI 1.08 to 1.37) per 10-pack-years) and seropositive IP (HR 1.24 (95% CI 1.10 to 1.41)) for all. Diabetes mellitus was associated with increased risk of IP (HR 2.54 (95% CI 1.26 to 5.09)), while alcohol (HR 0.86 (95% CI 0.74 to 0.99) per unit/day) and higher social class (HR 0.36 (95% CI 0.15 to 0.89) for professionals vs manual workers) were associated with reduced risk. Body mass index was associated with seronegative IP (HR 2.75 (95% CI 1.39 to 5.46) for obese vs normal-weight participants). In women, parity (HR 2.81 (95% CI 1.37 to 5.76) for ≥2 vs no children) was associated with increased risk, and breast feeding (HR 0.66 (95% CI 0.46 to 0.94) for every 52 weeks of breast feeding) was inversely associated with risk. Risk factors from the model were used to generate a 'risk score'. A total of 1159 (8.4%) women had scores reflecting a &gt;3-fold increased risk of IP over those with a score of 0. <h3>Conclusions</h3> Several easily ascertained clinical and lifestyle factors can be used to stratify populations for risk of IP.
Ethics in sports medicine--the sports physician.
Authors: P. N. Sperryn
Journal: British Journal of Sports Medicine (1980)

In sports, where there is a major aim to defy nature, the doctor faces an inevitable risk of ethical dilemmas.If he assumes, rightly or wrongly, that rest and conservative management will probably cure everything in due course then, whatever else he does with a sportsman is, by definition, an experiment or a controlled risk in attempting to cut corners or accelerate healing.In the broader picture, there are difficulties of public policy.There is some danger of spending more money on prohibitions and controlling illegalities than in actually preparing positive athletic and sports performance.Dope control has almost become synonymous with sports medicine and is a major preoccupation of many of the International Governing Bodies.In order to serve sports medicine reasonably, the doctor must be acceptable to everyone.It is very easy for the team doctor to be regarded as hostile by management if he takes the side of the sportsman and even easier to be regarded as a hostile member of the "Establishment" by the sportsman if there is any suggestion that he shares the team management's attitude.There are problems about the limitations of medical skills, both generally and in the individual case.In sport every coach and athlete is almost uninterested in present knowledge and its limits.The coach only starts looking for new aids at the borders of the present knowledge.Therefore, the doctor is in the land of speculation, risk, research and new ground, new theory and new fact.In practice, doctors are fairly rigidly educated, rigidly controlled, governed by rigid codes and are, therefore, not very well equipped to meet the attitudes that rule in sport and certainly coaching.Doctors are easily at a disadvantage.They do not really know the language of the trainer and coach.It is no consolation to say that the coach's mythology is not scientific because it is nevertheless the lingua franca of the sport.Anyone can be manipulated.Coaches are experts at manipulating a team manager, a doctor or a physiotherapist and they are constantly trying to make them operate on the coaches' own ground.The biggest danger in clinical practice is for the doctor to be lured out of his own grounds of confidence into somebody else's and so begin to feel insecure in clinical knowledge.The doctor must resist this manipulation and ensure that he conducts his clinical practice on his own ground without biased interference.Specialists, too, can be manipulated, as in the case of a surgeon who operates beyond his skill or takes risks.84a
Burden of community-acquired pneumonia in Italian general practice: Table 1–
Authors: Carmelo Sterrantino, Gianluca Trifirò, Francesco Lapi, Alessandro Pasqua, Giampiero Mazzaglia, Carlo Piccinni, Claudio Cricelli, Alessandro Rossi, Francesco Blasi
Journal: European Respiratory Journal (2013)

To the Editor: 

Community-acquired pneumonia (CAP) is a major respiratory health disease with high prevalence in the general population, clinical heterogeneity and different degrees of severity. In both the USA and Europe, CAP is the most frequent cause of infection-related death. Its incidence varies from country to country and from study to study, and it is higher in very young children and elderly persons [1]. A recent UK study documented an increase of 34% in hospital admissions due to CAP over the past decade [2].

Despite the importance of its social impact, actual incidence of CAP in different settings is still under scrutiny. Thus, we aimed to explore the epidemiology of CAP in Italian general practice.

We collected data from the Health Search - CSD Patient Database (HSD), an electronic general practice database, representative of the Italian general population, which was set up in 1998 by the Italian College of General Practitioners (Florence, Italy). The HSD contains data from approximately 1.2 million inhabitants under the care of 800 general practitioners (GPs), homogenously distributed across Italy. All clinical diagnoses are coded according to the International Classification of Diseases 9th Revision (ICD-9). Drugs are coded according to the Anatomical Therapeutic and Chemical classification system. The HSD has been extensively used for pharmaco-epidemiologic research [3].

Patients recruited between January 1, 2005 and December 31, 2009 were eligible if aged ≥15 years with clinical records in the database spanning a minimum duration of 2 years and an ICD-9-based incident diagnosis of CAP. The first date of CAP diagnosis was defined as …
Optimal Effector Functions in Human Natural Killer Cells Rely upon Autocrine Bone Morphogenetic Protein Signaling
Authors: Neil C. Robson, Laura Hidalgo, Tristan McAlpine, Heng Wei, Víctor G. Martínez, Ana Entrena, Gustavo J. Melen, Andrew S. MacDonald, Alexander Phythian-Adams, Rosa Sacedón, Eugene Maraskovsky, Jonathan Cebon, Manuel Ramírez, Angeles Vicente, Alberto Varas
Journal: Cancer Research (2014)

Abstract Natural killer (NK) cells are critical for innate tumor immunity due to their specialized ability to recognize and kill neoplastically transformed cells. However, NK cells require a specific set of cytokine-mediated signals to achieve optimal effector function. Th1-associated cytokines promote effector functions that are inhibited by the prototypic Th2 cytokine IL4 and the TGFβ superfamily members TGFβ1 and activin-A. Interestingly, the largest subgroup of the TGFβ superfamily are the bone morphogenetic proteins (BMP), but the effects of BMP signaling on NK cell effector functions have not been evaluated. Here, we demonstrate that blood-circulating NK cells express type I and II BMP receptors, BMP-2 and BMP-6 ligands, and phosphorylated isoforms of Smad-1/-5/-8, which mediate BMP family member signaling. In opposition to the inhibitory effects of TGFβ1 or activin-A, autocrine BMP signaling was supportive to NK cell function. Mechanistic investigations in cytokine and TLR-L–activated NK cells revealed that BMP signaling optimized IFNγ and global cytokine and chemokine production, phenotypic activation and proliferation, and autologous dendritic cell activation and target cytotoxicity. Collectively, our findings identify a novel auto-activatory pathway that is essential for optimal NK cell effector function, one that might be therapeutically manipulated to help eradicate tumors. Cancer Res; 74(18); 5019–31. ©2014 AACR.
Telecare Collaborative Management of Chronic Pain in Primary Care
Authors: Kurt Kroenke, Erin E. Krebs, Jingwei Wu, Zhangsheng Yu, Neale R. Chumbler, Matthew J. Bair
Journal: JAMA (2014)

IMPORTANCE Chronic musculoskeletal pain is among the most prevalent, costly, and disabling medical disorders.However, few clinical trials have examined interventions to improve chronic pain in primary care.OBJECTIVE To determine the effectiveness of a telecare intervention for chronic pain. DESIGN, SETTING, AND PARTICIPANTSThe Stepped Care to Optimize Pain Care Effectiveness (SCOPE) study was a randomized trial comparing a telephone-delivered collaborative care management intervention vs usual care in 250 patients with chronic (Ն3 months) musculoskeletal pain of at least moderate intensity (Brief Pain Inventory [BPI] score Ն5).Patients were enrolled from 5 primary care clinics in a single Veterans Affairs medical center from June 2010 through May 2012, with 12-month follow-up completed by June 2013.INTERVENTIONS Patients were randomized either to an intervention group (n = 124) or to a usual care group whose members received all pain care as usual from their primary care physicians (n = 126).The intervention group received 12 months of telecare management that coupled automated symptom monitoring with an algorithm-guided stepped care approach to optimizing analgesics. MAIN OUTCOMES AND MEASURESPrimary outcome was the BPI total score, which ranges from 0 ("no pain") to 10 ("pain as bad as you can imagine") and for which a 1-point change is considered clinically important.Secondary pain outcomes included BPI interference and severity, global pain improvement, treatment satisfaction, and use of opioids and other analgesics.RESULTS Overall, mean (SD) baseline BPI scores in the intervention and control groups were 5.31 (1.81) and 5.12 (1.80), respectively.Compared with usual care, the intervention group had a 1.02-point lower (95% CI, -1.58 to -0.47) BPI score at 12 months (3.57vs 4.59).Patients in the intervention group were nearly twice as likely to report at least a 30% improvement in their pain score by 12 months (51.7% vs 27.1%; relative risk, 1.9 [95% CI, 1.4 to 2.7]), with a number needed to treat of 4.1 (95% CI, 3.0 to 6.4) for a 30% improvement.Secondary pain outcomes also improved.Few patients in either group required opioid initiation or dose escalation.CONCLUSIONS AND RELEVANCE Telecare collaborative management increased the proportion of primary care patients with improved chronic musculoskeletal pain.This was accomplished by optimizing nonopioid analgesic medications using a stepped care algorithm and monitoring.
Is it time to ban dogs as household pets?
Authors: Trevor Jackson
Journal: BMJ (2005)

A fter tobacco, alcohol, and sports utility vehicles, how long will it be before public health experts get serious about the menace of widespread dog ownership? Despite ongoing research into dog bites and zoonoses, the occasional media outcry about pit bull terrier and rottweiler maulings, and legislation such as the United Kingdom's Dangerous Dogs Act of 1991, pet dogs and their owners have mostly been given a rather long leash. And yet it increasingly seems extraordinary to me—considering all the things that the law prevents us from doing—that it is legal for people to keep a potentially dangerous wild animal in their home. Or even, as many postmen and postwomen have discovered to their cost, in their front gardens.

In 2003 the UK had about 6.5 million dogs, estimates the Pet Food Manufacturers' Association (www.pfma.com/public/petownership_stats.htm), although the abolition of the dog licence under Mrs Thatcher's government in 1987 has hampered the collection of data on ownership. That is roughly one dog for every 10 people. (A crude survey among my BMJ colleagues found that, of 35 who replied to an email question, seven were dog owners, double the proportion in the country as a whole.) The only requirement by law in England and Wales is that dogs must wear a collar in public bearing its owner's name and address, although bylaws …
Chlorine-induced Injury to the Airways in Mice
Authors: James G. Martin, Holly R. Campbell, Hiroaki Iijima, Denyse Gautrin, Jean-Luc Malo, David H. Eidelman, Qutayba Hamid, Karim Maghni
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Exposure to chlorine gas (Cl2) causes occupational asthma that we hypothesized occurs through the induction of airway inflammation and airway hyperresponsiveness by oxidative damage. Respiratory mechanics and airway responsiveness to methacholine were assessed in A/J mice 24 hours after a 5-minute exposure to 100, 200, 400, or 800 ppm Cl2 and 2 and 7 days after inhalation of 400 ppm Cl2. Airway responsiveness was higher 24 hours after 400 and 800 ppm Cl2. Responsiveness after inhalation of 400 ppm Cl2 returned to normal by 2 days but was again elevated at 7 days. Airway epithelial loss, patchy alveolar damage, proteinaceous exudates, and inflammatory cells within alveolar walls were observed in animals exposed to 800 ppm Cl2. Macrophages, granulocytes, epithelial cells, and nitrate/nitrite levels increased in lung lavage fluid. Increased inducible nitric oxide synthase expression and oxidation of lung proteins were observed. Epithelial cells and alveolar macrophages from mice exposed to 800 ppm Cl2 stained for 3-nitrotyrosine residues. Inhibition of inducible nitric oxide synthase with 1400W (1 mg/kg) abrogated the Cl2-induced changes in responsiveness. We conclude that chlorine exposure causes functional and pathological changes in the airways associated with oxidative stress. Inducible nitric oxide synthase is involved in the induction of changes in responsiveness to methacholine.
Inherited Metabolic Storage Disorders
Authors: R O Brady
Journal: Annual Review of Neuroscience (1982)

A critical review of recent developments in our understanding of the herita­ ble storage disorders that involve the nervous system is highly appropriate at this time, since a number of new topics that deserve inclusion in this category have not been previously covered by a comprehensive overview. For many years when one considered storage disorders involving the brain, one dealt primarily with the sphingolipidoses, for the following reasons:
Context-Dependent Regulation of Wnt Signaling through the Primary Cilium
Authors: Edwin C. Oh, Nicholas Katsanis
Journal: Journal of the American Society of Nephrology (2012)

The primary cilium is a highly conserved environmental sensor and modulator of fluid movement in tubular structures. The growing recognition of mutations among its many components has led to the discovery of new disorders collectively called ciliopathies. Ciliary dysfunction disturbs a variety of signaling pathways along its basal body and axoneme that are critical for embryonic development and cell and organ homeostasis. Among the many pathways, here we discuss the emerging role of Wnt proteins in morphogenic signaling and ciliary biology during health and disease.
Trastuzumab in the Treatment of Advanced Non-Small-Cell Lung Cancer: Is There a Role? Focus on Eastern Cooperative Oncology Group Study 2598
Authors: Corey J. Langer, Patricia Stephenson, Ann Thor, Mark Vangel, David H. Johnson
Journal: Journal of Clinical Oncology (2004)

Purpose Multiple non–small-cell lung cancer (NSCLC) cell lines and 20% to 50% of pathologic specimens express HER-2/neu, the target of trastuzumab, and HER-2/neu expression has proven to be an independent, unfavorable prognostic factor in resected patients with NSCLC. Trastuzumab, in vitro, has demonstrated growth-inhibiting synergy with platinating agents, and additivity with paclitaxel. The Eastern Cooperative Oncology Group therefore launched a phase II study evaluating combination carboplatin, paclitaxel, and trastuzumab in patients with advanced NSCLC. Materials and Methods Eligibility stipulated the following: measurable tumor, HER-2/neu positivity (1+ to 3+ by Herceptest [Dako Corp, Carpinteria, CA], confirmed by central review), Eastern Cooperative Oncology Group PS 0 to 1, adequate marrow, hepatic and renal function, and left ventricular ejection fraction ≥ 45%. Patients received paclitaxel 225 mg/m 2 /3 hours, and carboplatin (area under the curve, 6) every 3 weeks, and trastuzumab 4 mg/kg intravenously on day 1, then 2 mg/kg weekly for ≤ 1 year. Results Between August 1999 and May 2000, 139 patients were screened; seven specimens (5%) were indeterminate. Fifty patients (36%) were HER-2/neu negative, 38 (27%) were HER-2/neu 1+, 31 (22%) were 2+, and 13 (9%) were 3+. Fifty-six patients were enrolled; 53 were eligible (22 [42%] were 1+, 23 (43%) were 2+, and eight (15%) were 3+). Thirteen (24.5%) of 52 assessable patients (95% CI, 13.8 to 38.3) responded. The incidence of grade ≥ 3 neutropenia and thrombocytopenia was 57% (34%) and 16% (2%), respectively. Asymptomatic grade ≤ 2 reduction in left ventricular ejection fraction occurred in 7%. Other nonhematologic toxicities, including nausea, fatigue, arthralgias, and peripheral sensory neuropathy, were mild to moderate and matched those expected with carboplatin and paclitaxel alone. Eighteen patients (35%) received maintenance trastuzumab. Median progression-free survival was 3.3 months; median survival was 10.1 months, and 1-year survival rate was 42%. Conclusion Combination paclitaxel, carboplatin, and trastuzumab is feasible. Toxicity appears no worse than cytotoxic therapy alone. Overall survival is similar to historical data using carboplatin and paclitaxel alone. However, patients with 3+ HER-2/neu expression did well in contrast to historical data suggesting potential benefit for trastuzumab in this rare subset of NSCLC. Critical assessment of trastuzumab's role in advanced NSCLC will require phase III trials.
Cloning and Characterization of a Novel Subunit of Protein Serine/Threonine Phosphatase 4 from Mesangial Cells
Authors: Takehiko Wada, Toshio Miyata, Reiko Inagi, Masaomi Nangaku, Masako Wagatsuma, Daisuke Suzuki, Brian E. Wadzinski, Kousaku Okubo, Kiyoshi Kurokawa
Journal: Journal of the American Society of Nephrology (2001)

ABSTRACT. Mesangial cells play an important role in maintaining glomeruli structure and function and in the pathogenesis of glomerular diseases. With a novel approach using a rapid large-scale DNA sequencing strategy and computerized data processing, a new human gene, PP4Rmeg was cloned. The full-length cDNA clone of human PP4Rmeg coded for a novel 950-amino acid protein, which was similar to a subunit of protein serine/threonine phosphatase 4 (PP4). Recombinant PP4Rmeg produced in COS-7 cells bound to the catalytic subunit of PP4. PP4Rmeg is therefore structurally and functionally related to the recently reported regulatory subunit of PP4, PP4R1. Amino acid sequence analysis of rat PP4Rmeg homologue revealed that the sequences were well conserved between human and rat (86.3% identity). Northern blot analyses of human tissues and cultured cells demonstrated that the regulatory subunits were expressed abundantly in human cultured mesangial cells, although their expression was relatively ubiquitous. In situ hybridization studies in normal human renal tissues confirmed their expression in glomeruli in vivo. The expression was upregulated in glomeruli of anti-Thy1 glomerulonephritis rats before mesangial proliferation. These data demonstrate that PP4Rmeg is a novel regulatory subunit of PP4, which is expressed ubiquitously but abundantly in mesangial cells. Its pathophysiologic role in mesangial cells and glomerulus remains unknown. As PP4 is an essential protein for nucleation, growth, and stabilization of microtubules at centrosomes/spindle pole bodies during cell division, PP4Rmeg may play a role in regulation of mitosis in mesangial cells.
Structure and expression of endogenous ecotropic murine leukemia viruses in RF/J mice.
Authors: J McCubrey, J M Horowitz, R Risser
Journal: The Journal of Experimental Medicine (1982)

High leukemic mouse strains possess proviral genomes that are more inducible for virus expression by halogenated pyrimidines than the proviral genomes harbored by low leukemic mice. We investigated the induction and arrangement of ecotropic proviruses in RF mice, a strain of mouse that develops a moderate incidence of leukemia late in life. We found that RF mice, unlike either high or low leukemic inbred strains, carried both a gene for high efficiency virus induction (Rjv-1) and a gene for low efficiency virus induction (Rjv-2). Virus induction from mice that contained Rjf-2 alone was observed only in crosses with two other strains that carried ecotropic proviruses, i.e., DBA/2 and C57BL/6, and not in crosses performed with mice that lacked ecotropic proviruses, i.e., 129, SWR, and NFS. Inheritance of the Rjv-1 gene frequently resulted in viremia when a virus-suppressive gene(s) of RF (most likely Fv-1) was not present in the same individual. Rjv-1 and Rjv-2 virus induction genes co-segregated with ecotropic proviruses integrated in different cellular DNA sequences. Rjv-2, the less inducible ecotropic provirus in RF mice, is located in cellular DNA sequences very similar to those found adjacent to the ecotropic provirus of BALB/c. These results document a second system of virus interaction or complementation and demonstrate that ecotropic proviruses of different phenotypes can be found within an individual mouse strain.
Gene Delivery: Synthesis of Tunable Theranostic Fe<sub>3</sub>O<sub>4</sub>@Mesoporous Silica Nanospheres for Biomedical Applications (Adv. Healthcare Mater. 3/2012)
Authors: Yang Zhao, Li‐Ning Lin, Yang Lu, Huai‐Ling Gao, Shao‐Feng Chen, Ping Yang, Shu‐Hong Yu
Journal: Advanced Healthcare Materials (2012)

A system of tunable theranostic Fe3O4@mesoporous silica nanospheres for diagnosis and gene therapy has been designed by Shu-Hong Yu and co-workers on page 327. Tunable delivery of imaging probe and gene can be realized by the tunable magnetic cores and modification of surface charges. These silica nanospheres may act as a theranostic nanosystem due to good biocompatibility, effective MRI diagnosis and gene delivery capabilities.