tbuckley/cabot-search huggingface dataset:
Quadriceps Fatigability after Single Muscle Exercise in Patients with Chronic Obstructive Pulmonary Disease
Authors: M. Jeffery Mador, Omer Deniz, Ajay Aggarwal, Thomas J. Kufel
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

The purpose of this study was to compare quadriceps fatigability in patients with varying severity of chronic obstructive pulmonary disease with age-matched control subjects. Ten healthy control subjects, 8 patients with severe disease (FEV1 less than 35% predicted), and 11 patients with mild to moderate disease were studied. The FEV1 was 1.75 +/- 0.13 L (SE), 50.4 +/- 2.9% of predicted in the mild to moderate group, and 0.87 +/- 0.06 L, 25.9 +/- 1.9% of predicted in the severe group. Quadriceps fatigue was quantified by the reduction in potentiated twitch force after a potentially fatiguing task. All subjects performed three sets of 10 maximum voluntary contractions of the right quadriceps muscle. Quadriceps maximum voluntary contraction force was 58.3 +/- 3.3 kg for the healthy older group, 49.0 +/- 4.2 kg in the mild to moderate group, and 44.3 +/- 4.7 kg in the severe group. The fall in potentiated twitch force after exercise was significantly greater in the patients with severe disease than in the healthy control subjects. In conclusion, the quadriceps in patients with severe chronic obstructive pulmonary disease are more fatigable than those in age- and sex-matched healthy control subjects.
Urinary Melatonin Levels and Breast Cancer Risk
Authors: Eva S. Schernhammer, Susan E. Hankinson
Journal: JNCI Journal of the National Cancer Institute (2005)

Exposure to light at night suppresses melatonin production, and night-shift work (a surrogate for such exposure) has been associated with an increased risk of breast cancer. However, the association between circulating melatonin levels and breast cancer risk is unclear. In a prospective case-control study nested within the Nurses' Health Study II cohort, we measured the concentration of the major melatonin metabolite, 6-sulphatoxymelatonin (aMT6s), in the first morning urine of 147 women with invasive breast cancer and 291 matched control subjects. In logistic regression models, the relative risk (reported as the odds ratio [OR]) of invasive breast cancer for women in the highest quartile of urinary aMT6s compared with those in the lowest was 0.59 (95% confidence interval [CI] = 0.36 to 0.97). This association was essentially unchanged after adjustment for breast cancer risk factors or plasma sex hormone levels but was slightly weakened when the analysis included 43 case patients with in situ breast cancer and their 85 matched control subjects (OR = 0.70, 95% CI = 0.47 to 1.06). The exclusion of women who had a history of night-shift work left our findings largely unchanged. These prospective data support the hypothesis that higher melatonin levels, as measured in first morning urine, are associated with a lower risk of breast cancer.
Haemoglobin saturation during incremental arm and leg exercise.
Authors: S. K. Powers, S. Dodd, J. Woodyard, R. E. Beadle, G. Church
Journal: British Journal of Sports Medicine (1984)

There are few reports concerning the alterations in the percent of haemoglobin saturated with oxygen (%SO2) during non-steady state incremental exercise. Further, no data exist to describe the %SO2 changes during arm exercise. Therefore, the purpose of this study was made to assess the dynamic changes in %SO2 during incremental arm and leg work. Nine trained subjects (7 males and 2 females) performed incremental arm and leg exercise to exhaustion on an arm crank ergometer and a cycle ergometer, respectively. Ventilation and gas exchange measurements were obtained minute by minute via open circuit spirometry and changes in %SO2 were recorded via an ear oximeter. No significant difference (p greater than 0.05) existed between arm and leg work in end-tidal oxygen (PETO2), end-tidal carbon dioxide (PETCO2), or %SO2 when compared as a function of percent VO2 max. These results provide evidence that arterial O2 desaturation occurs in a similar fashion in both incremental arm and leg work with the greatest changes in %SO2 occurring at work rates greater than 70% VO2 max.
Analysis of Tumor Necrosis Factor- α , Lymphotoxin- α , Tumor Necrosis Factor Receptor II, and Interleukin-6 Polymorphisms in Patients with Idiopathic Pulmonary Fibrosis
Authors: PANAGIOTIS PANTELIDIS, GREGORY C. FANNING, ATHOL U. WELLS, KENNETH I. WELSH, ROLAND M. DU BOIS
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Idiopathic pulmonary fibrosis (IPF) is characterized by chronic inflammation that is associated with structural damage of the lung and fibrosis. Although the etiology of IPF is unknown, it is likely to involve an interaction between environmental and multiple genetic components. Animal models of pulmonary fibrosis have shown that proinflammatory mediators are critical at both the inflammatory and fibrotic stages of the disease. Genetic variants exist in genes encoding proinflammatory mediators, as well as in genes encoding their receptors, which makes these genes candidates for the pathogenesis of IPF. In the present study, we examined 12 biallelic polymorphisms in the genes for tumor necrosis factor (TNF)-alpha (+488[G/A], -238[G/A], -308[G/A]), lymphotoxin (LT)-alpha (+720[C/A], +365[C/G], and +249[A/G], determining haplotypes LT-alpha1 to LT-alpha4), tumor necrosis factor-receptor 2 (TNF-RII) (gb:M32315: 676[T/G], 1663[A/G], 1668[T/G], 1690[C/T]), and interleukin- (IL)-6 (promoter -174[G/C], intron 4[A/G]). We also examined the haplotypes determined by the three biallelic polymorphisms in each of the TNF-alpha and LT-alpha genes. As compared with a normal control population, the IPF group showed no significant deviations in genotype, allele, or haplotype frequencies. Surprisingly, in the IPF population, but not in the control population, an increased frequency of cocarriage of the IL-6 intron 4G and the TNF-RII 1690C alleles was observed, despite the location of the two genes on different chromosomes. Moreover, using impairment of carbon monoxide transfer (DL(CO)) adjusted for duration of dyspnea as a marker of rapidity of disease progression, we found that the IL-6 intron 4GG genotype was the only genotype independently associated with lower DL(CO) levels. These findings, if independently confirmed, will be the first to suggest that disease progression in IPF may be linked to a particular genetic marker or to functional polymorphisms in other genes near that marker.
An fMRI Study of Self-Regulatory Control and Conflict Resolution in Adolescents With Bulimia Nervosa
Authors: Rachel Marsh, Guillermo Horga, Zhishun Wang, Pengwei Wang, Kristin W. Klahr, Laura A. Berner, B. Timothy Walsh, Bradley S. Peterson
Journal: American Journal of Psychiatry (2011)

The authors examined functional activity in the frontostriatal systems that mediate self-regulatory capacities and conflict resolution in adolescents with bulimia nervosa.Functional magnetic resonance imaging was used to compare blood-oxygen-level-dependent response in 18 female adolescents with bulimia nervosa and 18 healthy female age-matched subjects during performance on a Simon spatial incompatibility task. Bayesian analyses were used to compare the two groups on patterns of brain activation during correct responses to conflict stimuli and to explore the effects of antecedent stimulus context on group differences in self-regulation and conflict resolution.Adolescents with and without bulimia nervosa performed similarly on the task. During correct responses in conflict trials, frontostriatal circuits-including the right inferolateral and dorsolateral prefrontal cortices and putamen-failed to activate to the same degree in adolescents with bulimia nervosa as in healthy comparison subjects. Instead, deactivation was seen in the left inferior frontal gyrus as well as a neural system encompassing the posterior cingulate cortex and superior frontal gyrus. Group differences in cortical and striatal regions were driven by the differential responses to stimuli preceded by conflict and nonconflict stimuli, respectively.When engaging the self-regulatory control processes necessary to resolve conflict, adolescents with bulimia nervosa displayed abnormal patterns of activation in frontostriatal and default-mode systems. Their abnormal processing of the antecedent stimulus context conditioned their brain response to conflict differently from that of healthy comparison subjects, specifically in frontal regions. It is suspected that functional disturbances in frontal portions of frontostriatal systems may release feeding behaviors from regulatory control, thereby perpetuating the conflicting desires to consume fattening foods and avoid weight gain that characterize bulimia nervosa.
Meta-Analysis: Acupuncture for Low Back Pain
Authors: Eric Manheimer, Adrian White, Brian Berman, Kelly Forys, Edzard Ernst
Journal: Annals of Internal Medicine (2005)

Background: Low back pain limits activity and is the second most frequent reason for physician visits. Previous research shows widespread use of acupuncture for low back pain. Purpose: To assess acupuncture's effectiveness for treating low back pain. Data Sources: Randomized, controlled trials were identified through searches of MEDLINE, Cochrane Central, EMBASE, AMED, CINAHL, CISCOM, and GERA databases through August 2004. Additional data sources included previous reviews and personal contacts with colleagues. Study Selection: Randomized, controlled trials comparing needle acupuncture with sham acupuncture, other sham treatments, no additional treatment, or another active treatment for patients with low back pain. Data Extraction: Data were dually extracted for the outcomes of pain, functional status, overall improvement, return to work, and analgesic consumption. In addition, study quality was assessed. Data Synthesis: The 33 randomized, controlled trials that met inclusion criteria were subgrouped according to acute or chronic pain, style of acupuncture, and type of control group used. The principal measure of effect size was the standardized mean difference, since the trials assessed the same outcome but measured it in various ways. For the primary outcome of short-term relief of chronic pain, the meta-analyses showed that acupuncture is significantly more effective than sham treatment (standardized mean difference, 0.54 [95% CI, 0.35 to 0.73]; 7 trials) and no additional treatment (standardized mean difference, 0.69 [CI, 0.40 to 0.98]; 8 trials). For patients with acute low back pain, data are sparse and inconclusive. Data are also insufficient for drawing conclusions about acupuncture's short-term effectiveness compared with most other therapies. Limitations: The quantity and quality of the included trials varied. Conclusions: Acupuncture effectively relieves chronic low back pain. No evidence suggests that acupuncture is more effective than other active therapies.
Precipitins in bird breeder's disease: how useful are they?
Authors: C Reynaud, DO Slosman, BS Polla
Journal: European Respiratory Journal (1990)

Precipitating antibodies to avian antigens play a controversial role in the diagnosis of bird breeder's disease (BBD). In order to establish the sensitivity, specificity and accuracy of precipitins in our laboratory, we conducted a prospective study including 128 sera received in 1988 for determination, by immunoelectrophoresis, of avian precipitins. Accurate information was obtained for 90 patients; definitive clinical diagnosis was given by the patient's own physician. We found a high sensitivity (86%), specificity (93%) and accuracy (92%) of avian precipitins in the diagnosis of BBD. Bayes' theorem was applied to determine the predictive value of the test with varying disease prevalence, and established that precipitins were particularly valuable for low or medium a priori probability. Using the receiver operating characteristic (ROC) curve we evaluated the effects of varying the positivity threshold of precipitins. The threshold used in this study appeared to offer the best compromise between sensitivity and specificity. These results suggest that the diagnostic value of avian precipitins in the work-up of BBD should be reconsidered, also because they represent a simple, cheap and non-invasive diagnostic test.
The window hypothesis: haemodynamic and non-haemodynamic effects of β-blockers improve survival of patients with cirrhosis during a window in the disease: Figure 1
Authors: Aleksander Krag, Reiner Wiest, Agustín Albillos, Lise Lotte Gluud
Journal: Gut (2012)

Cirrhosis is one of the most frequent and severe chronic diseases worldwide. In the initial stages it has few or no symptoms, but advanced stages of cirrhosis are characterised by reduced liver function, complications due to portal hypertension and neuroendocrine abnormalities with increased activity of the sympathetic nervous system (SNS) and renin-aldosterone axis. The prognosis is severe, with an increasing frequency of complications including variceal bleeding, ascites and spontaneous infections with subsequent development of hepatic encephalopathy and hepatorenal syndrome. More than one-third of patients diagnosed with cirrhosis develop oesophageal varices within 3 years after the diagnosis is made. Varices develop and later bleed when the portal pressure is increased and the hepatic vein pressure gradient (HVPG) is more than 10–12 mm Hg. Life-threatening spontaneous bacterial infections are another common complication of advanced cirrhosis. The infections are mainly triggered by gut bacterial translocation, which is the migration of microorganisms from the intestinal lumen to the mesenteric lymph nodes or other extraintestinal sites.1 Small intestinal bacterial overgrowth of Gram-negative rods, structural and functional alterations of the intestinal mucosa and deficiencies in defence mechanisms contribute to bacterial translocation.2 Increased serum levels of lipopolysaccharide binding protein and circulating bacterial DNA are markers of bacterial translocation and both predict a poor outcome in cirrhosis and ascites.3 4 Selective gut decontamination prevents spontaneous bacterial infections and improves survival in advanced cirrhosis.5

Non-selective β-blockers (BB) are the only drugs shown to improve survival in patients with cirrhosis and medium to large oesophageal varices.6 BB inhibit the binding of catecholamines (norepinephrine and epinephrine) to the β1 and β2 adrenoreceptors. β1 blockade reduces the cardiac output and β2 blockade leads to splanchnic …
Fevers, headache and abnormal liver function in a 68-year-old man
Authors: Jonathan MR Goulding, A Pitcher, J Piris, CP Conlon
Journal: Journal of the Royal Society of Medicine (2010)

A 68-year-old man was transferred to our unit from a local hospital for further investigation of pyrexia of unknown origin (PUO). He had consulted his GP intermittently over the previous two years with non-specific aches and pains, and mild fatigue. Two weeks prior to admission he noticed low back pain followed by high fevers, chills, nausea and diarrhoea. Past medical history included a nephrectomy for renal cell carcinoma and ischaemic heart disease. He was born in Kenya, but had been resident in the UK for 30 years, and was married with three children. He had never smoked and drank minimal alcohol. Two months prior to admission he had travelled to Kenya for a holiday, and had not taken anti-malarial prophylaxis. On presentation to our unit the patient was haemodynamically stable, with a temperature of 36.8°C. There was no lymphadenopathy or organomegaly, and there were no skin changes. Examination of the cardiovascular, respiratory, and neurological systems was unremarkable. Initial blood parameters demonstrated a mild normocytic anaemia (Hb 10.4 g/dL, MCV 85.8 fl), moderate renal impairment (urea 13.6 mmol/L, creatinine 234 mmol/L), significantly raised inflammatory markers (ESR 80 mm/hr, CRP 179 mg/L), and abnormal liver function (albumin 26 g/L, PT 14.5 s, ALT 47 U/L, ALP 715 U/L, GGT 300 U/L). Three thick and thin blood films were negative for malarial parasites as were multiple cultures of blood, stool and urine. A CT scan of the whole body was normal. Viral hepatitis, HIV and autoimmune serology were negative. Over subsequent days low-grade fevers were noted, and the patient complained of mild intermittent headaches. Renal function improved with increased oral fluid intake, but liver function continued to deteriorate (albumin 16 g/L, PT 15.3 s, ALT 338 U/L, ALP 1071 U/L, GGT 496 U/L). An ultrasound scan of the liver and biliary system was normal. A percutaneous liver biopsy revealed granulomatous arteritis with prominent giant cell involvement (Figure 1). No acid-fast bacilli were identified. Prompted by this unexpected finding, a temporal artery biopsy was undertaken which confirmed patchy granulomatous inflammation with giant cell involvement. A final diagnosis of giant cell arteritis (GCA) was, therefore, made and treatment with high-dose oral prednisolone was initiated. His symptoms improved rapidly, and he was discharged shortly afterwards on a tapering prednisolone regimen. Liver function has since normalized.
Intricate targeting of immunoglobulin somatic hypermutation maximizes the efficiency of affinity maturation
Authors: Nai-Ying Zheng, Kenneth Wilson, Matthew Jared, Patrick C. Wilson
Journal: The Journal of Experimental Medicine (2005)

It is believed that immunoglobulin-variable region gene (IgV) somatic hypermutation (SHM) is initiated by activation-induced cytidine deaminase (AID) upon deamination of cytidine to deoxyuracil. Patch-excision repair of these lesions involving error prone DNA polymerases such as polη causes mutations at all base positions. If not repaired, the deaminated nucleotides on the coding and noncoding strands result in C-to-T and G-to-A exchanges, respectively. Herein it is reported that IgV gene evolution has been considerably influenced by the need to accommodate extensive C deaminations and the resulting accumulation of C-to-T and G-to-A exchanges. Although seemingly counterintuitive, the precise placement of C and G nucleotides causes most C-to-T and G-to-A mutations to be silent or conservative. We hypothesize that without intricate positioning of C and G nucleotides the efficiency of affinity maturation would be significantly reduced due to a dominance of replacements caused by C and G transition mutations. The complexity of these evolved biases in codon use are compounded by the precise concomitant hotspot/coldspot targeting of AID activity and Polη errors to maximize SHM in the CDRs and minimize mutations in the FWRs.
Long-term suppression of ocular neovascularization by intraocular injection of biodegradable polymeric particles containing a serpin-derived peptide
Authors: Ron B. Shmueli, Masayuki Ohnaka, Akiko Miki, Niranjan B. Pandey, Raquel Lima e Silva, Jacob E. Koskimaki, Jayoung Kim, Aleksander S. Popel, Peter A. Campochiaro, Jordan J. Green
Journal: Biomaterials (2013)
On keeping word order straight
Authors: Alan Kennedy
Journal: Behavioral and Brain Sciences (2003)

E-Z Reader is a highly successful model of eye-movement control, employing the notion of a serial-sequential attentional spotlight switched from word to word. Evidence of parallel processing of words in text calls this notion into question. Modifications to the model to accommodate this evidence are possible but will not address the fundamental objection that reading should not be seen as “surrogate listening.”
Aberrant Expression of Neuropilin-1 and -2 in Human Pancreatic Cancer Cells
Authors: Kimi Fukahi, Mitsuharu Fukasawa, Gera Neufeld, Jun Itakura, Murray Korc
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Neuropilin (Np)-1 and -2 are coreceptors for vascular endothelial growth factor (VEGF). This study was designed to assess their role in pancreatic ductal adenocarcinoma (PDAC). Experimental Design: We assessed Np-1 and Np-2 expression by real-time quantitative PCR in relation to the expression of VEGF ligands and receptors in pancreatic cancer cell lines and tissues. Results: ASPC-1, CAPAN-1, and PANC-1 pancreatic cancer cells and tumor-derived, laser-captured pancreatic cancer cells exhibited higher Np-1 and Np-2 mRNA levels than VEGF receptor-1, -2, or -3 mRNA levels. Transfection of Np-1 and Np-2 cDNAs in COS-7 cells, and treatment with tunicamycin revealed that both proteins were glycosylated. Both proteins were expressed in pancreatic cancer cell lines, in the PDAC samples, and in acinar cells adjacent to the cancer cells. The normal pancreas was devoid of Np-1 immunoreactivity, whereas Np-2 immunoreactivity was present in the endocrine islets and in some acinar cells, but not in ductal cells. Conclusions: The aberrant localization of Np-1 and Np-2 in the cancer cells in PDAC suggests that in addition to exerting proangiogenic effects, these coreceptors may contribute to novel autocrine-paracrine interactions in this malignancy.
A Novel Tool for the Assessment of Pain: Validation in Low Back Pain
Authors: Joachim Scholz, Richard J. Mannion, Daniela E. Hord, Robert S. Griffin, Bhupendra Rawal, Hui Zheng, Daniel Scoffings, Amanda Phillips, Jianli Guo, Rodney J. C. Laing, Salahadin Abdi, Isabelle Decosterd, Clifford J. Woolf
Journal: PLoS Medicine (2009)

Background Adequate pain assessment is critical for evaluating the efficacy of analgesic treatment in clinical practice and during the development of new therapies. Yet the currently used scores of global pain intensity fail to reflect the diversity of pain manifestations and the complexity of underlying biological mechanisms. We have developed a tool for a standardized assessment of pain-related symptoms and signs that differentiates pain phenotypes independent of etiology. Methods and Findings Using a structured interview (16 questions) and a standardized bedside examination (23 tests), we prospectively assessed symptoms and signs in 130 patients with peripheral neuropathic pain caused by diabetic polyneuropathy, postherpetic neuralgia, or radicular low back pain (LBP), and in 57 patients with non-neuropathic (axial) LBP. A hierarchical cluster analysis revealed distinct association patterns of symptoms and signs (pain subtypes) that characterized six subgroups of patients with neuropathic pain and two subgroups of patients with non-neuropathic pain. Using a classification tree analysis, we identified the most discriminatory assessment items for the identification of pain subtypes. We combined these six interview questions and ten physical tests in a pain assessment tool that we named Standardized Evaluation of Pain (StEP). We validated StEP for the distinction between radicular and axial LBP in an independent group of 137 patients. StEP identified patients with radicular pain with high sensitivity (92%; 95% confidence interval [CI] 83%–97%) and specificity (97%; 95% CI 89%–100%). The diagnostic accuracy of StEP exceeded that of a dedicated screening tool for neuropathic pain and spinal magnetic resonance imaging. In addition, we were able to reproduce subtypes of radicular and axial LBP, underscoring the utility of StEP for discerning distinct constellations of symptoms and signs. Conclusions We present a novel method of identifying pain subtypes that we believe reflect underlying pain mechanisms. We demonstrate that this new approach to pain assessment helps separate radicular from axial back pain. Beyond diagnostic utility, a standardized differentiation of pain subtypes that is independent of disease etiology may offer a unique opportunity to improve targeted analgesic treatment.