tbuckley/cabot-search huggingface dataset:
No Genome-Wide Protein Sequence Convergence for Echolocation
Authors: Z. Zou, J. Zhang
Journal: Molecular Biology and Evolution (2015)

Toothed whales and two groups of bats independently acquired echolocation, the ability to locate and identify objects by reflected sound. Echolocation requires physiologically complex and coordinated vocal, auditory, and neural functions, but the molecular basis of the capacity for echolocation is not well understood. A recent study suggested that convergent amino acid substitutions widespread in the proteins of echolocators underlay the convergent origins of mammalian echolocation. Here, we show that genomic signatures of molecular convergence between echolocating lineages are generally no stronger than those between echolocating and comparable nonecholocating lineages. The same is true for the group of 29 hearing-related proteins claimed to be enriched with molecular convergence. Reexamining the previous selection test reveals several flaws and invalidates the asserted evidence for adaptive convergence. Together, these findings indicate that the reported genomic signatures of convergence largely reflect the background level of sequence convergence unrelated to the origins of echolocation.
Structure of a human pulmonary acinus.
Authors: N Berend, A C Rynell, H E Ward
Journal: Thorax (1991)

The structure of the human pulmonary acinus has been described infrequently. The aim of the study was to determine the branching pattern of respiratory bronchioles and alveolar ducts in a human acinus from the peripheral part of the lung, where space constraints may have affected airway branching patterns. The lungs were obtained from an 18 year old victim of a motor vehicle accident and fixed in inflation under a pressure of 25 cm H2O. A block was cut from the lower edge of the right lower lobe and embedded in plastic. Serial sections were cut and the branching pattern of airways subtended by a terminal bronchiole were followed. The acinus was bounded on two sides by pleura and on the remaining sides by connective tissue septa. The terminal bronchiole divided into two respiratory bronchioles, each of which gave rise to four systems of alveolar ducts. Between successive systems of alveolar ducts the respiratory bronchioles continued as single airways, becoming progressively more alveolated towards the periphery but not subtending further branches of respiratory bronchioles. The duct systems became less complex towards the periphery, near to the edge of the lung. The total volume of the acinus was similar to that found in previous studies. This branching pattern has not been described previously in a human acinus.
Minimal access surgery compared with medical management for chronic gastro-oesophageal reflux disease: UK collaborative randomised trial
Authors: A. M Grant, S. M Wileman, C. R Ramsay, N A. Mowat, Z. H Krukowski, R. C Heading, M. R Thursz, M. K Campbell
Journal: BMJ (2008)

<b>Objective</b> To determine the relative benefits and risks of laparoscopic fundoplication surgery as an alternative to long term drug treatment for chronic gastro-oesophageal reflux disease (GORD). <b>Design</b> Multicentre, pragmatic randomised trial (with parallel preference groups). <b>Setting</b> 21 hospitals in the United Kingdom. <b>Participants</b> 357 randomised participants (178 surgical, 179 medical) and 453 preference participants (261, 192); mean age 46; 66% men. All participants had documented evidence of GORD and symptoms for &gt;12 months. <b>Intervention</b> The type of laparoscopic fundoplication used was left to the discretion of the surgeon. Those allocated to medical treatment had their treatment reviewed and adjusted as necessary by a local gastroenterologist, and subsequent clinical management was at the discretion of the clinician responsible for care. <b>Main outcome measures</b> The disease specific REFLUX quality of life score (primary outcome), SF-36, EQ-5D, and medication use, measured at time points equivalent to three and 12 months after surgery, and surgical complications. <b>Main results</b> Randomised participants had received drugs for GORD for median of 32 months before trial entry. Baseline REFLUX scores were 63.6 (SD 24.1) and 66.8 (SD 24.5) in the surgical and medical randomised groups, respectively. Of those randomised to surgery, 111 (62%) actually had total or partial fundoplication. Surgical complications were uncommon with a conversion rate of 0.6% and no mortality. By 12 months, 38% (59/154) randomised to surgery (14% (14/104) among those who had fundoplication) were taking reflux medication versus 90% (147/164) randomised medical management. The REFLUX score favoured the randomised surgical group (14.0, 95% confidence interval 9.6 to 18.4; P&lt;0.001). Differences of a third to half of 1 SD in other health status measures also favoured the randomised surgical group. Baseline scores in the preference for surgery group were the worst; by 12 months these were better than in the preference for medical treatment group. <b>Conclusion</b> At least up to 12 months after surgery, laparoscopic fundoplication significantly increased measures of health status in patients with GORD. <b>Trial registration</b>ISRCTN15517081.
Investigation of the effect of short-term change in dietary magnesium intake in asthma
Authors: J Hill, A Micklewright, S Lewis, J Britton
Journal: European Respiratory Journal (1997)

Epidemiological evidence suggests that a low dietary intake of magnesium is associated with impaired lung function, bronchial hyperreactivity and wheezing. This study was designed to investigate whether short-term alterations of dietary magnesium intake have an effect on the clinical control of asthma. In a randomized, double-blind, placebo-controlled, cross-over study, 17 asthmatic subjects adhered to a low magnesium diet for two periods of 3 weeks, preceded and separated by a 1 week run-in/wash-out, in which they took either placebo or magnesium (400 mg x day(-1)) tablet supplementation. Forced expiratory volume in one second (FEV1) and the provocative dose of methacholine required to cause a 20% fall in FEV1 from baseline (PD20,FEV1) were measured at the beginning and end of each treatment period, and variation in peak expiratory flow (PEF) rate, bronchodilator use and symptom scores recorded throughout. Asthma symptom scores were significantly lower during the magnesium treatment period, the median (95% confidence interval) difference from placebo being 3.8 (0.5-7.0) symptom points per 7 days (p=0.02). However, there was no significant improvement in FEV1, PD20,FEV1, log amplitude percentage mean PEF variation or bronchodilator use during magnesium supplementation. A high magnesium intake was associated with improvement in symptom scores, though not in objective measures of airflow or airway reactivity, in these stable asthmatic subjects.
Visualization of <i>Plasmodium falciparum–</i>Endothelium Interactions in Human Microvasculature
Authors: May Ho, Michael J. Hickey, Allan G. Murray, Graciela Andonegui, Paul Kubes
Journal: The Journal of Experimental Medicine (2000)

Plasmodium falciparum–infected erythrocytes roll on and/or adhere to CD36, intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and P-selectin under shear conditions in vitro. However, the lack of an adequate animal model has made it difficult to determine whether infected erythrocytes do indeed interact in vivo in microvessels. Therefore, we made use of an established model of human skin grafted onto severe combined immunodeficient (SCID) mice to directly visualize the human microvasculature by epifluorescence intravital microscopy. In all grafts examined, infected erythrocytes were observed to roll and/or adhere in not just postcapillary venules but also in arterioles. In contrast, occlusion of capillaries by infected erythrocytes was noted only in approximately half of the experiments. Administration of an anti-CD36 antibody resulted in a rapid reduction of rolling and adhesion. More importantly, already adherent cells quickly detached. The residual rolling after anti-CD36 treatment was largely inhibited by an anti–ICAM-1 antibody. Anti–ICAM-1 alone reduced the ability of infected erythrocytes to sustain rolling and subsequent adhesion. These findings provide conclusive evidence that infected erythrocytes interact within the human microvasculature in vivo by a multistep adhesive cascade that mimics the process of leukocyte recruitment.
Synergistic Effect between Erlotinib and MEK Inhibitors in KRAS Wild-Type Human Pancreatic Cancer Cells
Authors: Caroline H. Diep, Ruben M. Munoz, Ashish Choudhary, Daniel D. Von Hoff, Haiyong Han
Journal: Clinical Cancer Research (2011)

Abstract Purpose: The combination of erlotinib and gemcitabine has shown a small but statistically significant survival advantage when compared with gemcitabine alone in patients with advanced pancreatic cancer. However, the overall survival rate with the erlotinib and gemcitabine combination is still low. In this study, we sought to identify gene targets that, when inhibited, would enhance the activity of epidermal growth factor receptor (EGFR)-targeted therapies in pancreatic cancer cells. Experimental Design: A high-throughput RNA interference (RNAi) screen was carried out to identify candidate genes. Selected gene hits were further confirmed and mechanisms of action were further investigated using various assays. Results: Six gene hits from siRNA screening were confirmed to significantly sensitize BxPC-3 pancreatic cancer cells to erlotinib. One of the hits, mitogen-activated protein kinase (MAPK) 1, was selected for further mechanistic studies. Combination treatments of erlotinib and two MAP kinase kinase (MEK) inhibitors, RDEA119 and AZD6244, showed significant synergistic effect for both combinations (RDEA119–erlotinib and AZD6244–erlotinib) compared with the corresponding single drug treatments in pancreatic cancer cell lines with wild-type KRAS (BxPC-3 and Hs 700T) but not in cell lines with mutant KRAS (MIA PaCa-2 and PANC-1). The enhanced antitumor activity of the combination treatment was further verified in the BxPC-3 and MIA PaCa-2 mouse xenograft model. Examination of the MAPK signaling pathway by Western blotting indicated effective inhibition of the EGFR signaling by the drug combination in KRAS wild-type cells but not in KRAS mutant cells. Conclusions: Overall, our results suggest that combination therapy of an EGFR and MEK inhibitors may have enhanced efficacy in patients with pancreatic cancer. Clin Cancer Res; 17(9); 2744–56. ©2011 AACR.
Regional Distribution of Glycogen and Phosphorylase in the Ventricles of the Heart
Authors: LILLIAN A. JEDEIKIN
Journal: Circulation Research (1964)

In rat, rabbit, dog, and ox hearts, the glycogen concentration varied throughout the walls. The concentration gradient decreased from endocardium to epicardium in the right and left ventricles. In the septum, the interior part of the wall had a lower concentration of glycogen than tissue sections closer to the endocardial surfaces. The maximum values for glycogen concentration in endocardial sections were from two to six times higher than the minimum values. This gradient was much greater than the 30% differences observed between apex and base of the ventricles. Since our studies have demonstrated a very large variation for glycogen content in layers of myocardium parallel to sides of the ventricular wall, there is an obvious need for caution in sampling hearts for glycogen analysis. In the ox heart, the right bundle branch and A-V node were dissected out, and the glycogen values were compared with those for the rest of the myocardium. Glycogen values of the conduction system, especially of the bundle of His, were considerably higher than for any part of the myocardium studied, indicating that the myocardial gradients observed may be related to distribution of the Purkinje fibers. Phosphorylase values decreased from endocardium to epicardium in a pattern similar to that observed for glycogen, indicating a possible function in association with glycogen concentration. In the hearts perfused with a glucose-free medium by the Langendorff technique, glycogen diminished throughout the heart, but the general pattern of gradients was preserved. This suggested that glycogen is utilized as an energy source for contraction.
Limitations of ultracentrifugation and in vivo dialysis as methods of stool analysis.
Authors: C W Owens, W Padovan
Journal: Gut (1976)

Extracellular stool fluid has been sampled by in vivo dialysis, in vitro dialysis, and high speed centrifugation. Detailed comparisons of amino acids and electrolytes have been made between each fluid; normal values and significant differences are summarized. Evidence is provided which suggests that there is release of intracellular contents during normal handling of stool in the laboratory. The amino acids which display the greatest differences between centrifugate and dialysate from given stool specimens are those which are liberated by ultrasonication or aerobic incubation of stool. Factors affecting the chemical stability of stool are discussed. In most circumstances in vivo dialysis would seem to provide the closest approximation to extracellular fluid, providing the faeces remain in the descending colon or rectum for at least two hours.
Effect of l-Arterenol Infusion on "Central Blood Volume" in the Dog
Authors: OSCAR W. SHADLE, JAMES C. MOORE, DONAL M. BILLIG
Journal: Circulation Research (1955)

Infusion of l-arterenol into anesthetized dogs increased the volume of blood in the heart and lungs, as indicated by an increase in "central blood volume," estimated lung volume and pressure changes in the heart and lungs. An analysis of pressure and flow data in the systemic venous bed during infusion of the drug suggests that important sources of the shifted blood are the peripheral veins and venules.
Involvement of H-2L gene products in virus-immune T-cell recognition. Evidence for an H-2L-restricted T-cell response.
Authors: W E Biddison, T H Hansen, R B Levy, P C Doherty
Journal: The Journal of Experimental Medicine (1978)

The H-2L locus is closely linked to H-2D and codes for antigenic specificities present on a 45,000 mol wt glycoprotein that is distinct from the molecule which bears the D region private specificity. It was found that BALB/c-H-2db mice, which lack detectable cell-surface H-2L gene products, were able to generate influenza- and vaccinia-immune cytotoxic T cells which lyse D region-compatible target cells, although they have been reported to be incapable of making a similar response to ectromelia virus (7). Thus, the lack of H-2L antigenic specificities does not produce a general loss of responsiveness for other viruses even when a highly cross-reactive pox virus (vaccinia) was studied. Antisera-blocking experiments utilizing sera specific for either L or D molecules indicated that BALB/c mice generate influenza virus-immune cytotoxic T-cell subsets which independently recognize H-2L and H-2D gene products in association with viral antigens. These results are the first indication that products of the H-2L locus can operate analogously to H-2K/D gene products in virus-immune T-cell recognition.
Cervical muscle strength measurement in two groups of elite Greco-Roman and free style wrestlers and a group of non-athletic subjects
Authors: A Rezasoltani, A Ahmadi, M Nehzate-Khoshroh, F Forohideh, J Ylinen
Journal: British Journal of Sports Medicine (2005)

Free style and Greco-Roman are two types of wrestling. [figure: see text]The aim of this study was to examine the maximal isometric strength of cervical extension (ISCE) and the maximal isometric strength of cervical flexion (ISCF) in two groups of elite wrestlers and a group of non-athletic subjects.Fourteen elite Greco-Roman wrestlers (aged 19-25 years), 16 elite free style wrestlers (aged 18-25 years), and 16 non-athletic subjects (aged 18-25 years) participated in this study. All wrestlers competed at international level with the Iranian national team. Maximum voluntary contractions (MVC) of cervical extensor and flexor muscles were measured using a custom made device. The ratios of ISCE to weight (ISCE/weight), ISCF to weight (ISCF/weight), and ISCF to ISCE (ISCF/ISCE) were calculated for group comparisons. Pearson product moment test was used to estimate correlation between maximal isometric strength measurements and anthropometric variables. A one way analysis of variance was computed to compare ISCE/weight, ISCF/weight, and ISCF/ISCE among groups.There was significant correlation between maximum cervical extension and flexion strengths and weight in all groups (p<0.05, n = 46). The ratios of cervical muscle strengths to weight were significantly higher in wrestlers than in non-athletic subjects (p<0.00). Greco-Roman wrestlers appeared to be stronger than free style wrestlers following comparison of all ratios.Neck muscle force measurements may be a useful test for athletes in combat sports like wrestling. They can be applied to identify the weakness of a group of muscles in the neck area and to devise a proper training program.
Long-Term Inhaled Dry Powder Mannitol in Cystic Fibrosis
Authors: Moira L. Aitken, Gabriel Bellon, Kris De Boeck, Patrick A. Flume, Howard G. Fox, David E. Geller, Eric G. Haarman, Helge U. Hebestreit, Allen Lapey, I. Manjula Schou, Jonathan B. Zuckerman, Brett Charlton
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

New treatment strategies are needed to improve airway clearance and reduce the morbidity and the time burden associated with cystic fibrosis (CF).To determine whether long-term treatment with inhaled mannitol, an osmotic agent, improves lung function and morbidity.Double-blind, randomized, controlled trial of inhaled mannitol, 400 mg twice a day (n = 192, "treated" group) or 50 mg twice a day (n = 126, "control" group) for 26 weeks, followed by 26 weeks of open-label treatment.The primary endpoint was absolute change in FEV(1) from baseline in treated versus control groups, averaged over the study period. Secondary endpoints included other spirometric measurements, pulmonary exacerbations, and hospitalization. Clinical, microbiologic, and laboratory safety were assessed. The treated group had a mean improvement in FEV(1) of 105 ml (8.2% above baseline). The treated group had a relative improvement in FEV(1) of 3.75% (P = 0.029) versus the control group. Adverse events and sputum microbiology were similar in both treatment groups. Exacerbation rates were low, but there were fewer in the treated group (hazard ratio, 0.74; 95% confidence interval, 0.42-1.32; P = 0.31), although this was not statistically significant. In the 26-week open-label extension study, FEV(1) was maintained in the original treated group, and improved in the original control group to the same degree.Inhaled mannitol, 400 mg twice a day, resulted in improved lung function over 26 weeks, which was sustained after an additional 26 weeks of treatment. The safety profile was also acceptable, demonstrating the potential role for this chronic therapy for CF. Clinical trial registered with www.clinicaltrials.gov (NCT 00630812).
Colorectal cancer: dichotomous or continuum model? Perhaps, a combination of both: Table 1
Authors: Petros Papagiorgis
Journal: Gut (2013)

I read with interest the paper by Yamauchi et al ,1 which disputes the prevailing (to date) ‘two-colon’ concept suggesting that proximal and distal colorectal cancer (CRC) may represent two distinct disease entities (with the splenic flexure as a discrete point).2 The emerging new approach supports a gradual rather than an abrupt change of tumour molecular features throughout the colorectum and also the existence of certain disparities among particular colonic subsites (‘continuum/multisegmental’ concept).1

However, the two concepts are not necessarily conflicting. First, the existing differences between proximal and distal normal colon in embryologic origin, blood supply, innervation, bile acids metabolism, fermentation reactions and function are indisputable. Similarly acceptable are the long-ago known disparities between proximal and distal tumours in macroscopic appearance and clinical manifestation.1 , …
The at-risk registers in severe asthma (ARRISA) study: a cluster-randomised controlled trial examining effectiveness and costs in primary care
Authors: Jane Rebecca Smith, Michael J Noble, Stanley Musgrave, Jamie Murdoch, Gill M Price, Garry R Barton, Jennifer Windley, Richard Holland, Brian DW Harrison, Amanda Howe, David B Price, Ian Harvey, Andrew M Wilson
Journal: Thorax (2012)

<h3>Background</h3> Patients at risk of severe exacerbations contribute disproportionally to asthma mortality, morbidity and costs. We evaluated the effectiveness and costs of using 'asthma risk registers' for these patients in primary care. <h3>Methods</h3> In a cluster-randomised trial, 29 primary care practices identified 911 at-risk asthma patients using British asthma guideline criteria (severe asthma plus adverse psychosocial characteristics). Intervention practices added electronic alerts to identified patients9 records to flag their at-risk status and received practice-based training about using the alerts to improve patient access and opportunistic management. Control practices continued routine care. Numbers of patients experiencing the primary outcome of a moderate-severe exacerbation (resulting in death, hospitalisation, accident and emergency attendance, out-of-hours contact, or a course/boost in oral prednisolone for asthma), other healthcare and medication usage, and costs over 1 year were derived from practice-based records. <h3>Results</h3> There was no significant effect on exacerbations (control: 46.5%; intervention: 53.6%, OR, 95% CI 1.30, 0.93 to 1.80). However, this composite outcome masked relative reductions in intervention patients experiencing hospitalisations (OR 0.50, 95% CI 0.26 to 0.94), accident and emergency (OR 0.74, 95% CI 0.42 to 1.31) and out-of-hours contacts (OR 0.79, 95% CI 0.45 to 1.37); and a relative increase in prednisolone prescription for exacerbations (OR 1.31, 95% CI 0.92 to 1.85). Furthermore, prescription of nebulised short-acting β-agonists reduced and long-acting β-agonists increased for intervention relative to control patients. The adjusted mean per patient healthcare cost was £138.21 lower (p=0.837) among intervention practices. <h3>Conclusion</h3> Using asthma risk registers in primary care did not reduce treated exacerbations, but reduced hospitalisations and increased prescriptions of recommended preventative therapies without increasing costs.