tbuckley/cabot-search huggingface dataset:
Respiratory impairment and COPD hospitalisation in older persons: a competing risk analysis
Authors: Carlos A. Vaz Fragoso, John Concato, Gail McAvay, Peter H. Van Ness, Thomas M. Gill
Journal: European Respiratory Journal (2012)

The aim of the present study was to evaluate, among older persons, the association between respiratory impairment and hospitalisation for chronic obstructive pulmonary disease (COPD), based on spirometric Z-scores, i.e. the LMS (lambda, mu, sigma) method, and a competing risk approach. Using data on 3,563 white participants aged 65–80 yrs (from the Cardiovascular Health Study) we evaluated the association of LMS-defined respiratory impairment with the incident of COPD hospitalisation and the competing outcome of death without COPD hospitalisation, over a 5-yr period. Respiratory impairment included airflow limitation (mild, moderate or severe) and restrictive pattern. Over a 5-yr period, 276 (7.7%) participants had a COPD hospitalisation incident, whereas 296 (8.3%) died without COPD hospitalisation. The risk of COPD hospitalisation was elevated more than two-fold in LMS-defined mild and moderate airflow limitation and restrictive pattern (adjusted HR (95% CI): 2.25 (1.25–4.05), 2.54 (1.53– 4.22) and 2.65 (1.82–3.86), respectively), and more than eight-fold in LMS-defined severe airflow limitation (adjusted HR (95% CI) 8.33 (6.24–11.12)). Conversely, only LMS-defined restrictive-pattern was associated with the competing outcome of death without COPD hospitalisation (adjusted HR (95% CI) 1.68 (1.22–2.32)). In older white persons, LMS-defined respiratory impairment is strongly associated with an increased risk of COPD hospitalisation. These results support the LMS method as a basis for defining respiratory impairment in older persons.
Assessment by MRI of inflammation and damage in rheumatoid arthritis patients with methotrexate inadequate response receiving golimumab: results of the GO-FORWARD trial
Authors: P. G. Conaghan, P. Emery, M. Ostergaard, E. C. Keystone, M. C. Genovese, E. C. Hsia, W. Xu, M. U. Rahman
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objective</h3> To evaluate golimumab9s effect on MRI-detected inflammation and structural damage in patients with active rheumatoid arthritis (RA) despite methotrexate (MTX). <h3>Methods</h3> Patients (n=444) were randomly assigned to placebo plus MTX, golimumab 100 mg plus placebo, golimumab 50 mg plus MTX, or golimumab 100 mg plus MTX (subcutaneous injections every 4 weeks). A subset of 240 patients participated in an MRI substudy. MRIs (1.5T+contrast enhancement) of the dominant wrist and metacarpophalangeal (MCP) joints were obtained at baseline and weeks 12 and 24. Images were scored by two independent, blinded readers for synovitis (0–9 wrist only (n=240), 0–21 wrist+MCP (n=223)), bone oedema (osteitis) (0–69) and bone erosions (0–230) using the OMERACT Rheumatoid Arthritis MRI Scoring system. <h3>Results</h3> Significant improvements in synovitis and bone oedema (osteitis) were observed in the combined golimumab plus MTX groups versus placebo plus MTX at week 12 (−1.77 vs −0.15, p&lt;0.001 wrist+MCP and −2.00 vs 0.19, p=0.003, respectively) and week 24 (−1.91 vs −0.38, p&lt;0.001 wrist+MCP and −1.74 vs 0.71, p=0.004, respectively). Fewer than 10% of patients had a substantial degree of erosive progression (most showed no progression) across all treatment groups (including the control group), precluding adequate evaluation of golimumab9s effect on bone erosions. <h3>Conclusion</h3> Golimumab plus MTX significantly improved MRI-detected synovitis and osteitis (prognosticators of future structural damage) versus placebo plus MTX at weeks 12 and 24. The effect of golimumab on bone erosions could not be determined by semi-quantitative scoring in these RA patients with minimal progression of bone erosions.
The Evolution of Transcriptional Regulation in Eukaryotes
Authors: G. A. Wray
Journal: Molecular Biology and Evolution (2003)

Gene expression is central to the genotype-phenotype relationship in all organisms, and it is an important component of the genetic basis for evolutionary change in diverse aspects of phenotype. However, the evolution of transcriptional regulation remains understudied and poorly understood. Here we review the evolutionary dynamics of promoter, or cis-regulatory, sequences and the evolutionary mechanisms that shape them. Existing evidence indicates that populations harbor extensive genetic variation in promoter sequences, that a substantial fraction of this variation has consequences for both biochemical and organismal phenotype, and that some of this functional variation is sorted by selection. As with protein-coding sequences, rates and patterns of promoter sequence evolution differ considerably among loci and among clades for reasons that are not well understood. Studying the evolution of transcriptional regulation poses empirical and conceptual challenges beyond those typically encountered in analyses of coding sequence evolution: promoter organization is much less regular than that of coding sequences, and sequences required for the transcription of each locus reside at multiple other loci in the genome. Because of the strong context-dependence of transcriptional regulation, sequence inspection alone provides limited information about promoter function. Understanding the functional consequences of sequence differences among promoters generally requires biochemical and in vivo functional assays. Despite these challenges, important insights have already been gained into the evolution of transcriptional regulation, and the pace of discovery is accelerating.
Authors' reply: Feedback from modelling to surveillance of Ebola virus disease
Authors: H Nishiura, G Chowell
Journal: Eurosurveillance (2014)

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Diaphragm plication following phrenic nerve injury: a comparison of paediatric and adult patients
Authors: D A Simansky
Journal: Thorax (2002)

<b>Background:</b> A study was undertaken to evaluate whether adults differ from children in the indications and outcome of diaphragmatic plication following phrenic nerve injury. <b>Methods:</b> A retrospective study was performed of 21 patients, 10 below the age of 5 and 11 older than 37 years. The indication for surgery for all the children was failure to wean from ventilatory support. The indications for surgery in the adult group were ventilator dependency (n=4) and symptomatic dyspnoea (n=7). All patients had at least one imaging study confirming diaphragmatic paralysis. The American Thoracic Society (ATS) dyspnoea scale, pulmonary function tests, and quantitative pulmonary perfusion scans were used as evaluation parameters. At surgery the diaphragm was centrally plicated. <b>Results:</b> One child died immediately after surgery due to irreversible heart failure and two children died within 2 months of surgery from ongoing complications of their original condition. These three patients were considered as selection failures. Seven children were weaned from ventilatory support within a median of 4 days (range 2–140). Only one of four ventilated adults was successfully weaned. Seven adults who underwent surgery for chronic symptoms had a marked subjective improvement of 2–3 levels in the ATS dyspnoea scale. Pulmonary function studies in the seven symptomatic adults showed a 40% improvement above baseline. Severely asymmetrical perfusion scans reverted to a normal pattern after plication. <b>Conclusions:</b> Diaphragmatic plication offers a significant benefit to children with diaphragmatic paralysis and should be performed early to facilitate weaning from mechanical ventilation. While plication is of limited benefit in weaning ventilated adults, it results in significant subjective and objective lifetime improvement in non-ventilated symptomatic adults.
Low-Calcium Serum-Free Defined Medium Selects for Growth of Normal Prostatic Epithelial Stem Cells
Authors: Ivan V. Litvinov, Donald J. Vander Griend, Yi Xu, Lizamma Antony, Susan L. Dalrymple, John T. Isaacs
Journal: Cancer Research (2006)

Abstract Stage-specific differentiation markers were used to evaluate the cellular composition and the origin of nonimmortalized (PrEC) and immortalized (PZ-HPV7, CA-HPV10, RWPE-1, and 957E/hTERT) human prostate cell lines. These studies documented that immortalized and nonimmortalized prostate epithelial cells established and maintained in low (i.e., &amp;lt;300 μmol/L) Ca2+ serum-free defined (SFD) medium were all derived from normal nonmalignant prostate tissues and contain CD133+/ABCG2+/α2β1Hi/p63−/PSCA−/AR−/PSA− prostate stem cells. In these cultures, prostate stem cells are able to self-renew and generate two distinct cell lineages: the minor proliferatively quiescent neuroendocrine lineage and the major transit-amplifying cell lineage. Subsequently, CD133−/ABCG2−/α2β1Hi/p63+/PSCA−/AR−/PSA− transit-amplifying cells proliferate frequently and eventually mature into proliferatively quiescent CD133−/ABCG2−/α2β1Lo/p63−/PSCA+/AR−/PSA− intermediate cells. Such proliferatively quiescent intermediate cells, however, do not complete their full maturation into CD133−/ABCG2−/α2β1Lo/p63−/PSCA−/AR+/PSA+ luminal-secretory cells in low Ca2+ SFD medium. Addition of universal type I IFN and synthetic androgen (R1881) to culture medium resulted in up-regulation of androgen receptor protein expression. However, it failed to induce full differentiation of intermediate cells into AR+/PSA+ luminal-secretory cells. Our results indicate that such inability of prostate epithelial cells to complete their differentiation is due to continuous expression of Notch-1 receptor and its downstream effector, Hey-1 protein, which actively suppresses differentiation via its ability to transcriptionally repress a series of genes, including the GATA family of transcription factors. (Cancer Res 2006; 66(17): 8598-607)
INFECTIVE ENDOCARDITIS TREATED WITH ANTIDIPHTHERIAL SERUM
Authors: W. R. Judd
Journal: BMJ (1910)

Two previous attacks of rheumatic fever.Admitted with all the signs of failing compensationgeneral oedema, ascites, orthopnoea, and cyanosis.She com- plained of sharp pain in the chest and left upper arm as far as the elbow.Physical Signs in Heart.-H.A.B. fifth space, 51 in.from the middle line.Impulse irregular and not very forcible.At apex both sounds heard, and, in addition, there is a loud, rough, systolic murmur conducted outwards to the axilla.At the base both sounds are heard and the second sound is accentuated at the pulmonary cartilage.There is no murmur at the base.CASE III.M. G., female.Aged 31.Four attacks of rheumatic fever.Complains of shortness of breath, palpitation, and pain.The latter is in various parts of the chest, but especially in the precordium, and often radiates down the left arm.Physical Signs.-H.A.B. in fifth space, 31 in.from the middle line.The impulse is slapping in character, and preceded by a well-marked presystolic thrill.At the apex a rough pre- systolic murmur is heard, followed by a short first sound.The second sound at the pulmonary cartilage is accentuated.The pulse is irregular, and the liver cannot be felt.
First-line erlotinib versus gemcitabine/cisplatin in patients with advanced EGFR mutation-positive non-small-cell lung cancer: analyses from the phase III, randomized, open-label, ENSURE study
Authors: Y.-L. Wu, C. Zhou, C.-K. Liam, G. Wu, X. Liu, Z. Zhong, S. Lu, Y. Cheng, B. Han, L. Chen, C. Huang, S. Qin, Y. Zhu, H. Pan, H. Liang, E. Li, G. Jiang, S.H. How, M.C.L. Fernando, Y. Zhang, F. Xia, Y. Zuo
Journal: Annals of Oncology (2015)
Filtration Markers May Have Prognostic Value Independent of Glomerular Filtration Rate
Authors: Navdeep Tangri, Lesley A. Inker, Hocine Tighiouart, Eric Sorensen, Vandana Menon, Gerald Beck, Michael Shlipak, Josef Coresh, Andrew S. Levey, Mark J. Sarnak
Journal: Journal of the American Society of Nephrology (2011)

Serum levels of creatinine, cystatin C, or β trace protein allow estimation of GFR, but whether these markers contribute additional prognostic information beyond that reflected in GFR is unknown. Here, we analyzed data from the Modification of Diet in Renal Disease study, which provided baseline levels of these markers for 816 participants with a median follow-up of 16.6 years. We examined associations between the reciprocals of these filtration markers and 125I iothalamate GFR, expressed per SD, with kidney failure and mortality. In univariate analysis, lower GFR and higher levels of each filtration marker associated with a higher risk for all outcomes. After adjustment for GFR in a Cox proportional hazards model, higher creatinine associated with a higher risk for kidney failure but a lower risk for all-cause mortality. Higher cystatin C and β trace protein associated with a higher risk for both kidney failure and all-cause mortality. In models including either cystatin C or β trace protein, the association of GFR with all-cause mortality was no longer significant after the addition of the filtration marker, suggesting the possibility of multicollinearity. In summary, after adjustment for GFR, levels of creatinine, cystatin C, and β trace protein, each remained directly associated with kidney failure but differed with respect to their associations with mortality. These differences may be a result of non-GFR–related associations of filtration markers, residual confounding by GFR, or collinearity between the filtration markers and GFR. β trace protein and cystatin C seem to provide more consistent prognostic information than creatinine.
Telomere Length and Telomerase Activity Impact the UV Sensitivity Syndrome Xeroderma Pigmentosum C
Authors: Gerdine J. Stout, Maria A. Blasco
Journal: Cancer Research (2013)

Xeroderma pigmentosum (XP), a UV-sensitivity syndrome characterized by skin hyperpigmentation, premature aging, and increased skin cancer, is caused by defects in the nucleotide excision repair (NER) pathway. XP shares phenotypical characteristics with telomere-associated diseases like Dyskeratosis congenita and mouse models with dysfunctional telomeres, including mice deficient for telomerase (Terc(-/-) mice). Thus, we investigated a hypothesized role for telomerase and telomere dysfunction in the pathobiology of XP by comparing Xpc(-/-)-mutant mice and Xpc(-/-)G1-G3Terc(-/-) double-mutant mice and exposed them to UV radiation. Chronically UV-exposed Xpc(-/-) skin displayed shorter telomeres on an average compared with wild-type skin. Strikingly, this effect was reversed by an additional deficiency in the telomerase. Moreover, aberrantly long telomeres were observed in the double-mutant mice. Telomere lengthening in the absence of telomerase suggested activation of the alternative lengthening of telomeres (ALT) in the UV-exposed skin of the double mutants. Mechanistic investigations revealed an elevated susceptibility for UV-induced p53 patches, known to represent precursor lesions of carcinomas, in Xpc(-/-)G1-G3Terc(-/-) mice where a high number of UV-induced skin tumors occurred that were characterized by aggressive growth. Taken together, our results establish a role for xeroderma pigmentosum, complementation group C (XPC) in telomere stability, particularly upon UV exposure. In absence of telomerase, critically short telomeres in XP mutants seem to aggravate this pathology, associated with an increased tumor incidence, by activating the ALT pathway of telomere lengthening.
Screening for Chronic Obstructive Pulmonary Disease Using Spirometry: Summary of the Evidence for the U.S. Preventive Services Task Force
Authors: Kenneth Lin, Bradley Watkins, Tamara Johnson, Joy Anne Rodriguez, Mary B. Barton
Journal: Annals of Internal Medicine (2008)

Background: Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States. Fewer than half of the estimated 24 million Americans with airflow obstruction have received a COPD diagnosis, and diagnosis often occurs in advanced stages of the disease. Purpose: To summarize the evidence on screening for COPD using spirometry for the U.S. Preventive Services Task Force (USPSTF). Data Sources: English-language articles identified in PubMed and the Cochrane Library through January 2007, recent systematic reviews, expert suggestions, and reference lists of retrieved articles. Study Selection: Explicit inclusion and exclusion criteria were used for each of the 8 key questions on benefits and harms of screening. Eligible study types varied by question. Data Extraction: Studies were reviewed, abstracted, and rated for quality by using predefined USPSTF criteria. Data Synthesis: Pharmacologic treatments for COPD reduce acute exacerbations in patients with severe disease. However, severe COPD is uncommon in the general U.S. population. Spirometry has not been shown to independently increase smoking cessation rates. Potential harms from screening include false-positive results and adverse effects from subsequent unnecessary therapy. Data on the prevalence of airflow obstruction in the U.S. population were used to calculate projected outcomes from screening groups defined by age and smoking status. Limitation: No studies provide direct evidence on health outcomes associated with screening for COPD. Conclusion: Screening for COPD using spirometry is likely to identify a predominance of patients with mild to moderate airflow obstruction who would not experience additional health benefits if labeled as having COPD. Hundreds of patients would need to undergo spirometry to defer a single exacerbation.
Angiotensin II Stimulation of NAD(P)H Oxidase Activity
Authors: Puvi N. Seshiah, David S. Weber, Petra Rocic, Liisa Valppu, Yoshihiro Taniyama, Kathy K. Griendling
Journal: Circulation Research (2002)

Angiotensin II (Ang II)-stimulated hypertrophy of vascular smooth muscle cells is mediated by reactive oxygen species (ROS) derived from NAD(P)H oxidases. The upstream signaling mechanisms by which Ang II activates these oxidases are unclear but may include protein kinase C, tyrosine kinases, phosphatidylinositol-3-kinase, and Rac, a small molecular weight G protein. We found that Ang II-stimulated ROS production is biphasic. The first phase occurs rapidly (peak at 30 seconds) and is dependent on protein kinase C activation. The larger second phase of ROS generation (peak at 30 minutes) requires Rac activation, because inhibition of Rac by either Clostridium difficile toxin A or dominant-negative Rac significantly inhibits Ang II-induced ROS production. Phosphatidylinositol-3-kinase inhibitors (wortmannin or LY294002) and the epidermal growth factor (EGF) receptor kinase blocker AG1478 attenuate both Rac activation and ROS generation. The upstream activator of EGF receptor transactivation, c-Src, is also required for ROS generation, because PP1, an Src kinase inhibitor, abrogates the Ang II stimulation of both responses. These results suggest that c-Src, EGF receptor transactivation, phosphatidylinositol-3-kinase, and Rac play important roles in the sustained Ang II-mediated activation of vascular smooth muscle cell NAD(P)H oxidases and provide insight into the integrated signaling mechanisms whereby Ang II stimulation leads to activation of the growth-related NAD(P)H oxidases.
The Role of Post–Acute Care in Variation in the Medicare Program
Authors: Rita F. Redberg
Journal: JAMA Internal Medicine (2015)

Hospital and Regional Variation in Medicare Payment for Inpatient Episodes of CareHealth care spending varies widely between geographic regions, but there is disagreement regarding the appropriate policy response. 1Regional policies include reducing Medicare payment rates in high-spending regions, 2 limiting the supply of health care facilities using certificate-of-need criteria, and implementing care-improvement collaboratives.The Institute of Medicine opposed regional policies in favor of hospital-and health care professional-focused policies, such as bundled payments, accountable-care organizations, and value-based payments. 3heir concern was that substantial variation in Medicare spending occurs within geographic regions 3-5 and highperforming hospitals and health care professionals in lowperforming regions would be unfairly penalized by regional policies.To further inform this debate, we compared the amount of spending variation that occurs between regions vs between hospitals.Methods | Using claims for all Medicare fee-for-service beneficiaries from January 1, 2008, through December 31, 2008, we summed Medicare payments for hospital and post-acute care services (skilled nursing facilities, home health, and inpatient rehabilitation) for episodes spanning from inpatient admission to 30 days after discharge.Physician payments-a small proportion of both the total episode payments and the variation in episode payments-were not included.
Modulating effects of age and gender on the clinical course of long QT syndrome by genotype
Authors: Wojciech Zareba, Arthur J Moss, Emanuela H Locati, Michael H Lehmann, Derick R Peterson, W.Jackson Hall, Peter J Schwartz, G.Michael Vincent, Silvia G Priori, Jesaia Benhorin, Jeffrey A Towbin, Jennifer L Robinson, Mark L Andrews, Carlo Napolitano, Katherine Timothy, Li Zhang, Aharon Medina
Journal: Journal of the American College of Cardiology (2003)
The Symptomatic Os Trigonum
Authors: Malcolm L. Ecker
Journal: JAMA (1967)

Two patients presented with painful heels. The first was relieved by excision of the os trigonum from each heel. The second was relieved by local steroid injection. The os trigonum is not always an insignificant roentgenographic finding, and fracture of the posterior process of the talus does occur and may in time resemble an os trigonum.
Dual Neofunctionalization of a Rapidly Evolving Aquaporin-1 Paralog Resulted in Constrained and Relaxed Traits Controlling Channel Function during Meiosis Resumption in Teleosts
Authors: C. Zapater, F. Chauvigne, B. Norberg, R. N. Finn, J. Cerda
Journal: Molecular Biology and Evolution (2011)

The preovulatory hydration of teleost oocytes is a unique process among vertebrates. The hydration mechanism is most pronounced in marine acanthomorph teleosts that spawn pelagic (floating) eggs; however, the molecular pathway for water influx remains poorly understood. Recently, we revealed that whole-genome duplication (WGD) resulted in teleosts harboring the largest repertoire of molecular water channels in the vertebrate lineage and that a duplicated aquaporin-1 paralog is implicated in the oocyte hydration process. However, the origin and function of the aquaporin-1 paralogs remain equivocal. By integrating the molecular phylogeny with synteny and structural analyses, we show here that the teleost aqp1aa and -1ab paralogs (previously annotated as aqp1a and -1b, respectively) arose by tandem duplication rather than WGD and that the Aqp1ab C-terminus is the most rapidly evolving subdomain within the vertebrate aquaporin superfamily. The functional role of Aqp1ab was investigated in Atlantic halibut, a marine acanthomorph teleost that spawns one of the largest pelagic eggs known. We demonstrate that Aqp1ab is required for full hydration of oocytes undergoing meiotic maturation. We further show that the rapid structural divergence of the C-terminal regulatory domain causes ex vivo loss of function of halibut Aqp1ab when expressed in amphibian oocytes but not in zebrafish or native oocytes. However, by using chimeric constructs of halibut Aqp1aa and -1ab and antisera specifically raised against the C-terminus of Aqp1ab, we found that this cytoplasmic domain regulates in vivo trafficking to the microvillar portion of the oocyte plasma membrane when intraoocytic osmotic pressure is at a maximum. Interestingly, by coinjecting polyA(+) mRNA from postvitellogenic halibut follicles, ex vivo intracellular trafficking of Aqp1ab is rescued in amphibian oocytes. These data reveal that the physiological role of Aqp1ab during meiosis resumption is conserved in teleosts, but the remarkable degeneracy of the cytoplasmic domain has resulted in alternative regulation of the trafficking mechanism.