tbuckley/cabot-search huggingface dataset:
Attenuation of Obstructive Sleep Apnea by Compression Stockings in Subjects with Venous Insufficiency
Authors: Stefania Redolfi, Isabelle Arnulf, Michel Pottier, Jacques Lajou, Isabelle Koskas, T. Douglas Bradley, Thomas Similowski
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Fluid accumulation in the legs and its overnight redistribution into the neck appears to play a causative role in obstructive sleep apnea (OSA) in sedentary men. Chronic venous insufficiency (CVI) promotes fluid accumulation in the legs that can be counteracted by compression stockings.To test the hypotheses that, in nonobese subjects with CVI and OSA, wearing compression stockings during the day will attenuate OSA by reducing the amount of fluid displaced into the neck overnight.Nonobese subjects with CVI and OSA were randomly assigned to 1 week of wearing compression stockings or to a 1-week control period without compression stockings, after which they crossed over to the other arm. Polysomnography and measurement of overnight changes in leg fluid volume and neck circumference were performed at baseline and at the end of compression stockings and control periods.Twelve subjects participated. Compared with the end of the control period, at the end of the compression stockings period there was a 62% reduction in the overnight leg fluid volume change (P = 0.001) and a 60% reduction in the overnight neck circumference increase (P = 0.001) in association with a 36% reduction in the number of apneas and hypopneas per hour of sleep (from 48.4 ± 26.9 to 31.3 ± 20.2, P = 0.002).Redistribution of fluid from the legs into the neck at night contributes to the pathogenesis of OSA in subjects with CVI. Prevention of fluid accumulation in the legs during the day, and its nocturnal displacement into the neck, attenuates OSA in such subjects.
Comparative Analysis of Metabolic Networks Provides Insight into the Evolution of Plant Pathogenic and Nonpathogenic Lifestyles in Pseudomonas
Authors: A. Mithani, J. Hein, G. M. Preston
Journal: Molecular Biology and Evolution (2010)

Plant pathogenic pseudomonads such as Pseudomonas syringae colonize plant surfaces and tissues and have been reported to be nutritionally specialized relative to nonpathogenic pseudomonads. We performed comparative analyses of metabolic networks reconstructed from genome sequence data in order to investigate the hypothesis that P. syringae has evolved to be metabolically specialized for a plant pathogenic lifestyle. We used the metabolic network comparison tool Rahnuma and complementary bioinformatic analyses to compare the distribution of 1,299 metabolic reactions across nine genome-sequenced strains of Pseudomonas, including three strains of P. syringae. The two pathogenic Pseudomonas species analyzed, P. syringae and the opportunistic human pathogen P. aeruginosa, each displayed a high level of intraspecies metabolic similarity compared with nonpathogenic Pseudomonas. The three P. syringae strains lacked a significant number of reactions predicted to be present in all other Pseudomonas strains analyzed, which is consistent with the hypothesis that P. syringae is adapted for growth in a nutritionally constrained environment. Pathway predictions demonstrated that some of the differences detected in metabolic network comparisons could account for differences in amino acid assimilation ability reported in experimental analyses. Parsimony analysis and reaction neighborhood approaches were used to model the evolution of metabolic networks and amino acid assimilation pathways in pseudomonads. Both methods supported a model of Pseudomonas evolution in which the common ancestor of P. syringae had experienced a significant number of deletion events relative to other nonpathogenic pseudomonads. We discuss how the characteristic metabolic features of P. syringae could reflect adaptation to a pathogenic lifestyle.
Phase II Study of Preoperative Gefitinib in Clinical Stage I Non–Small-Cell Lung Cancer
Authors: Humberto Lara-Guerra, Thomas K. Waddell, Maria A. Salvarrey, Anthony M. Joshua, Catherine T. Chung, Narinder Paul, Scott Boerner, Akira Sakurada, Olga Ludkovski, Clement Ma, Jeremy Squire, Geoffrey Liu, Frances A. Shepherd, Ming-Sound Tsao, Natasha B. Leighl
Journal: Journal of Clinical Oncology (2009)

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have proven efficacy in advanced non-small-cell lung cancer (NSCLC). Their role in early-stage NSCLC has not been established. Our purpose was to explore the use of preoperative gefitinib in clinical stage I NSCLC to assess tumor response, toxicity, and clinical and molecular predictors of response.Patients received gefitinib 250 mg/d for up to 28 days, followed by mediastinoscopy and surgical resection in an open-label, single-arm study. Tumor response was evaluated by Response Evaluation Criteria in Solid Tumors. Blood samples and tumor biopsies were collected and analyzed for transforming growth factor alpha level, EGFR protein expression, EGFR gene copy number, and EGFR (exon 19 to 21) and KRAS mutations.Thirty-six patients completed preoperative treatment (median duration, 28 days; range, 27 to 30 days). Median follow-up time is 2.1 years (range, 0.86 to 3.46 years). Three patients experienced grade 3 toxicities (rash, diarrhea, and elevated ALT). Tumors demonstrated EGFR-positive protein expression in 83%, high gene copy number in 59%, EGFR mutations in 17%, and KRAS mutations in 17%. Tumor shrinkage was more frequent among women and nonsmokers. Partial response was seen in four patients (11%), and disease progression was seen in three patients (9%). The strongest predictor of response was EGFR mutation.Preoperative window therapy with gefitinib is a safe and feasible regimen in early NSCLC and provides a trial design that may better inform predictors of treatment response or sensitivity.
Contrasting Patterns of X/Y Polymorphism Distinguish Carica papaya from Other Sex Chromosome Systems
Authors: L. A. Weingartner, R. C. Moore
Journal: Molecular Biology and Evolution (2012)

The sex chromosomes of the tropical crop papaya (Carica papaya) are evolutionarily young and consequently allow for the examination of evolutionary mechanisms that drive early sex chromosome divergence. We conducted a molecular population genetic analysis of four X/Y gene pairs from a collection of 45 wild papaya accessions. These population genetic analyses reveal striking differences in the patterns of polymorphism between the X and Y chromosomes that distinguish them from other sex chromosome systems. In most sex chromosome systems, the Y chromosome displays significantly reduced polymorphism levels, whereas the X chromosome maintains a level of polymorphism that is comparable to autosomal loci. However, the four papaya sex-linked loci that we examined display diversity patterns that are opposite this trend: the papaya X alleles exhibit significantly reduced polymorphism levels, whereas the papaya Y alleles maintain greater than expected levels of diversity. Our analyses suggest that selective sweeps in the regions of the X have contributed to this pattern while also revealing geographically restricted haplogroups on the Y. We discuss the possible role sexual selection and/or genomic conflict have played in shaping the contrasting patterns of polymorphism found for the papaya X and Y chromosomes.
Giant Cell Interstitial Pneumonia: Report of Two Cases with High Titanium Concentration in the Lung
Authors: C. Paris, J.-C. Pairon, M.-A. Billon-Galland, H. Vanoni-Espiand, B. Godbert, Y. Martinet, F. Chabot, B. Aymard, J.-M. Vignaud
Journal: American Journal of Respiratory and Critical Care Medicine (2011)
Mortality prediction in diabetic patients with myocardial infarction: experiences from the DIGAMI study
Authors: K Malmberg
Journal: Cardiovascular Research (1997)

Objectives: We analysed predictors of 1-year mortality following acute myocardial infarction in patients with diabetes mellitus by applying uni- and multivariate statistics on the DIGAMI cohort. Background: Diabetic patients with acute myocardial infarction have a poor prognosis. This may depend on a poor metabolic control, a hypothesis that was tested in DIGAMI, a prospective randomised study. In this trial institution of immediate intensive insulin treatment reduced 1-year mortality by 30%. Methods: We recruited 620 diabetic patients with acute myocardial infarction, 314 of whom served as controls, while the remaining 306 patients were treated with an acute insulin–glucose infusion followed by multidose subcutaneous insulin. Results: Age, previous myocardial damage, duration of the diabetes and previous insulin therapy were significantly related to 1-year mortality, while conventional risk factors lacked independent prognostic weight. Female sex was not linked to mortality when controlling for the confounding effects of other predictors. One of the strongest predictors of a fatal outcome, in particular during the hospital phase, was blood glucose at hospital admission. Beta-blockade appeared to exert a striking, independent secondary-preventive effect. Conclusions: It seems that good metabolic control and not conventional risk factors is of major importance for diabetic patients sustaining acute myocardial infarction. Also treatment with beta-blockade seems to be of special importance in this category of patients.
Prognostic Value of <b> <i>TP53</i> </b> Codon 72 Polymorphism in Advanced Gastric Adenocarcinoma
Authors: Zun-Wu Zhang, Nicola J. Laurence, Andrew Hollowood, Paul Newcomb, Moganaden Moorghen, Jyoti Gupta, Roger Feakins, Michael J. G. Farthing, Derek Alderson, Jeff Holly
Journal: Clinical Cancer Research (2004)

Abstract Purpose: A common polymorphism of the tumor suppressor gene TP53 at codon 72 has been associated with human cancer susceptibility. The prognostic role of the polymorphism was assessed in 102 patients with advanced gastric adenocarcinoma. Experimental Design: We followed up 102 consecutive Caucasian patients with advanced gastric adenocarcinoma for &amp;gt;5 years and determined the status of the TP53 codon 72 polymorphism in DNA samples extracted from archived gastric tissues. Results: The frequency of the arginine homozygous allele was positively correlated to patient age at baseline (P = 0.002). However, the age-related increase in the percentage of codon 72 arginine p53 was not correlated to the prognosis for gastric cancer patients. Multivariable analysis in patients who had surgery showed that baseline age may be inversely associated with patient survival (odds ratio, 1.1; 95% confidence interval, 1.0–1.2; P = 0.02). Furthermore, alcohol consumption may be associated with reduced survival (P = 0.06). Conclusions: These findings indicate that codon 72 arginine p53 may not be associated with a prolonged survival in patients with advanced gastric adenocarcinoma, but further study is needed to assess whether this polymorphism is associated with a late onset or slow progress of early gastric adenocarcinoma.
Decreased Expression and Androgen Regulation of the Tumor Suppressor Gene INPP4B in Prostate Cancer
Authors: Myles C. Hodgson, Long-jiang Shao, Anna Frolov, Rile Li, Leif E. Peterson, Gustavo Ayala, Michael M. Ittmann, Nancy L. Weigel, Irina U. Agoulnik
Journal: Cancer Research (2011)

Patients with metastatic prostate cancer who undergo androgen-ablation therapy invariably relapse and develop incurable castration-resistant disease. Activation of the prosurvival Akt pathway accompanies androgen ablation. We discovered that the androgen receptor induces the expression of the tumor suppressor inositol polyphosphate 4-phosphatase type II (INPP4B) but not PTEN in prostate cancer cells. Optimal induction of INPP4B by an androgen receptor required the expression of the transcriptional coactivator NCoR. INPP4B dephosphorylates phosphatidylinositol-3, 4-bisphosphate, which leads to reduced phosphorylation and activity of Akt. In support of a key role for INPP4B in Akt control, INPP4B depletion activated Akt and increased cellular proliferation. The clinical significance of INPP4B in androgen-dependent prostate cancers was determined in normal or primary tumor prostate tissues derived from radical prostatectomy specimens. In primary tumors, the expression of both INPP4B and PTEN was substantially reduced compared with normal tissue. Further, the decreased expression of INPP4B reduced the time to biochemical recurrence. Thus, androgen ablation can activate the Akt pathway via INPP4B downregulation, thereby mitigating the antitumor effects of androgen ablation. Our findings reinforce the concept that patients undergoing androgen ablation may benefit from Akt-targeting therapies.
Synthetic MicroRNA Designed to Target Glioma-Associated Antigen 1 Transcription Factor Inhibits Division and Induces Late Apoptosis in Pancreatic Tumor Cells
Authors: Naotake Tsuda, Satoshi Ishiyama, Yufeng Li, Constantin G. Ioannides, James L. Abbruzzese, David Z. Chang
Journal: Clinical Cancer Research (2006)

Abstract Purpose: To determine whether the synthetic microRNAs (miRNA) could effectively target tumor cells we designed several miRNA complementary to glioma-associated antigen-1 (Gli-1) mRNA and investigated their ability to inhibit tumor cell proliferation. The sonic hedgehog pathway is an early and late mediator of tumorigenesis in epithelial cancers. Activation of sonic hedgehog signaling seems to precede transformation of tissue stem cells to cancerous stem cells, with the Gli-1 transcription factor functioning as a mediator of environmental signals. Inhibiting cancer cell proliferation by targeting the Gli-1 effector pathway is difficult to achieve by chemotherapeutic agents or short interfering RNA. Experimental Design: We hypothesized that targeting the 3′-untranslated region of Gli-1 mRNA would effectively inhibit tumor cell proliferation. To test this hypothesis, we used synthetic miRNAs of our own design and corresponding duplex/small temporal RNAs by introducing three-nucleotide loops in the 3′-untranslated region Gli-1 sequence of high GU content. Results: We found that miRNA (Gli-1-miRNA-3548) and its corresponding duplex (Duplex-3548) significantly inhibited proliferation of Gli-1+ ovarian (SK-OV-3) and pancreatic (MiaPaCa-2) tumor cells. The miRNAs mediated delayed cell division and activation of late apoptosis in MiaPaCa-2 cells. This is the first demonstration of inhibition of pancreatic tumor cell division by designed miRNA. Conclusions: Gli-1 miRNAs should significantly add to the general understanding of the mechanisms of metastasis and contribute toward the design of better treatments for epithelial cancers.
Cerebellar Control of the Vestibulo-Ocular Reflex--Around the Flocculus Hypothesis
Authors: M Ito
Journal: Annual Review of Neuroscience (1982)

The vestibulo-ocular reflex (VOR) is an elementary reflex, which attracted the attention of a number of classical neurophysiologists who studied, in particular, the reflexive compensatory eye movements induced by head movements (cfMagnus 1924, Lorente de No 1931). The major pathway for this reflex is the well-defined trineuronal are, composed of primary vestibu­ lar neurons, secondary vestibular neurons, and oculomotor neurons (Ra­ mon y Cajal 1909, Lorente de N6 1931, 1933, Szentagothai 1943, 1950, 1964, Brodal & Pompeiano 1957). The pioneering electrophysiological work by Lorente de N6 (1939) and by subsequent investigators recognized that the vestibulo-ocular reflex involves both excitation and inhibition (Szentllgothai 1950, Cohen et al 1964). More recent data about the VOR have been reviewed by Brodal (1974), Cohen (1974), Precht (1978), and Wilson & Melvill Jones (1979). In recent years, the vestibulo-ocular refiex has been reexamined in detail because of its close relationship with the cerebellum. Supported by remark­ able advances in cerebellar physiology and eye movement studies, the VOR has become an interesting and important subject of neurophysiology, espe­ cially for investigation of cerebellar control mechanisms. This article re­ views the efforts made in the past decade toward understanding the
Demographic histories of four spruce (Picea) species of the Qinghai-Tibetan Plateau and neighboring areas inferred from multiple nuclear loci
Authors: Yuan Li, Michael Stocks, Sofia Hemmilä, Thomas Källman, Hongtao Zhu, Yongfeng Zhou, Jun Chen, Jianquan Liu, Martin Lascoux
Journal: Molecular Biology and Evolution (2009)

Nucleotide variation at 12-16 nuclear loci was studied in three spruce species from the Qinghai-Tibetan Plateau (QTP), Picea likiangensis, P. wilsonii, and P. purpurea, and one species from the Tian Shan mountain range, P. schrenkiana. Silent nucleotide diversity was limited in P. schrenkiana and high in the three species from the QTP, with values higher than in boreal spruce species, despite their much more restricted distributions compared with that of the boreal species. In contrast to European boreal species that have experienced severe bottlenecks in the past, coalescent-based analysis suggests that DNA polymorphism in the species from the QTP and adjacent areas is compatible with the standard neutral model (P. likiangensis, P. wilsonii, and P. schrenkiana) or with population growth (P. purpurea). In order to test if P. purpurea is a diploid hybrid of P. likiangensis and P. wilsonii, we used a combination of approaches, including model-based inference of population structure, isolation-with-migration models, and recent theoretical results on the effect of introgression on the geographic distribution of diversity. In contrast to the three other species, each of which was predominantly assigned to a single cluster in the Structure analysis, P. purpurea individuals were scattered over the three main clusters and not, as we had expected, confined to the P. likiangensis and P. wilsonii clusters. Furthermore, the contribution of P. schrenkiana was by far the largest one. In agreement with this, the divergence between P. purpurea and P. schrenkiana was lower than the divergence of either P. likiangensis or P. wilsonii from P. schrenkiana. These results, together with previous ones showing that P. purpurea and P. wilsonii share the same haplotypes at both chloroplast and mitochondrial markers, suggest that P. purpurea has a complex origin, possibly involving additional species.
Physical Aggression in Dementia Patients and Its Relationship to Depression
Authors: Constantine G. Lyketsos, Cynthia Steele, Elizabeth Galik, Adam Rosenblatt, Martin Steinberg, Andrew Warren, Jeannie-Marie Sheppard
Journal: American Journal of Psychiatry (1999)

The goal of this study was to determine the frequency of physically aggressive behavior in community-residing patients with dementia and its relationship to depression.A consecutive series of 541 patients with DSM-IV-defined dementia underwent comprehensive neuropsychiatric evaluation and were rated on the Cornell Scale for Depression in Dementia, the Mini-Mental State, the Psychogeriatric Dependency Rating Scale, and the General Medical Health Rating.Physically aggressive behavior was exhibited by 79 patients in the 2 weeks before evaluation. Aggressive behavior was closely associated with moderate to severe depression, male gender, and greater impairment in activities of daily living, even after adjustment for delusions, hallucinations, sleep disturbance, and severity of cognitive impairment. After adjustment for depression, gender, and impairment in activities of daily living, there was no association between physically aggressive behavior and the presence of either delusions or hallucinations.A substantial minority of patients with dementia exhibit physically aggressive behavior, and this aggression is strongly linked with the presence of depressive symptoms. It is possible that the identification and treatment of depression in dementia may be a means of preventing and managing physically aggressive behavior.
Outcomes of endoscopic surgery compared with open surgery for carpal tunnel syndrome among employed patients: randomised controlled trial
Authors: Isam Atroshi, Gert-Uno Larsson, Ewald Ornstein, Manfred Hofer, Ragnar Johnsson, Jonas Ranstam
Journal: BMJ (2006)

<h3>Abstract</h3> <b>Objectives</b> To compare endoscopic and open carpal tunnel release surgery among employed patients with carpal tunnel syndrome. <b>Design and setting</b> Randomised controlled trial at a single orthopaedic department. <b>Participants</b> 128 employed patients aged 25-60 years with clinically diagnosed and electrophysiologically confirmed idiopathic carpal tunnel syndrome. <b>Main outcome measures</b> The primary outcome was severity of postoperative pain in the scar or proximal palm and the degree to which pain or tenderness limits activities, each rated on a 4 point scale, transformed into a combined score of 0 (none) to 100 (severe pain or tenderness causing severe activity limitation). The secondary outcomes were length of postoperative work absence, severity of symptoms of carpal tunnel syndrome and functional status scores, SF-12 quality of life score, and hand sensation and strength (blinded examiner); follow-up at three and six weeks and three and 12 months. <b>Results</b> 63 patients were allocated to endoscopic surgery and 65 patients to open surgery, with no withdrawals or dropouts. Pain in the scar or proximal palm was less prevalent or severe after endoscopic surgery than after open surgery but the differences were generally small. At three months, pain in the scar or palm was reported by 33 patients (52%) in the endoscopic group and 53 patients (82%) in the open group (number needed to treat 3.4, 95% confidence interval 2.3 to 7.7) and the mean score difference for severity of pain in scar or palm and limitation of activity was 13.3 (5.3 to 21.3). No differences between the groups were found in the other outcomes. The median length of work absence after surgery was 28 days in both groups. Quality of life measures improved substantially. <b>Conclusions</b> In carpal tunnel syndrome, endoscopic surgery was associated with less postoperative pain than open surgery, but the small size of the benefit and similarity in other outcomes make its cost effectiveness uncertain.
No Evidence for an Effect of COMT Val158Met Genotype on Executive Function in Patients With 22q11 Deletion Syndrome
Authors: Bronwyn Glaser, Martin Debbane, Christine Hinard, Michael A. Morris, Sophie P. Dahoun, Stylianos E. Antonarakis, Stephan Eliez
Journal: American Journal of Psychiatry (2006)

OBJECTIVE: Previous studies linking the catechol O-methyltransferase (COMT) functional polymorphism to the specific phenotype in 22q11.2 deletion syndrome (22q11.2DS) have yielded inconsistent results. The goal of the present study was to replicate a recent finding that executive function is higher in individuals hemizygous for the Met allele. METHOD: Thirty-four children and young adults with a 22q11.2 microdeletion, hemizygous for the Val (N=14) or Met (N=20) polymorphism, were tested on measures of executive function, IQ, and memory. RESULTS: No significant differences were detected between Met- and Val-hemizygous participants on measures of executive function. The groups did not differ on full-scale, performance, and verbal IQ or on verbal and visual memory. CONCLUSIONS: These results suggest either a small effect of the COMT polymorphism on executive function in 22q11.2DS or no effect at all. Further research is needed to characterize the implications of hemizygosity of COMT in 22q11.2DS for cognitive function.