tbuckley/cabot-search huggingface dataset:
The value of complaints
Authors: Fiona Godlee
Journal: BMJ (2008)

<h3>Abstract</h3> Transposable elements (TEs) are key drivers of adaptive evolution within species. Yet, the propagation of TEs across the genome can be highly deleterious and ultimately lead to genome expansions. Hence, TE activity is likely under complex selection regimes within species. To address this, we analyzed a large whole-genome sequencing dataset of the fungal wheat pathogen <i>Zymoseptoria tritici</i> harboring TE-mediated adaptations to overcome host defenses and fungicides. We built a robust map of genome-wide TE insertion and deletion loci for six populations and 284 fungal individuals across the world. We identified a total of 2’456 unfixed TE loci within the species and a significant excess of rare insertions indicating strong purifying selection. A subset of TEs recently swept to near complete fixation with at least one locus likely contributing to higher levels of fungicide resistance. TE-driven adaptation was also supported by evidence for selective sweeps. In parallel, we identified a substantial genome-wide expansion of TE families from the pathogen’s center of origin to more recently founded populations, suggesting that population bottlenecks played a major role in shaping TE content of the genome. The most dramatic expansion occurred among a pair of North American populations collected in the same field at an interval of 25 years. We show that both the activation of specific TEs and relaxed purifying selection likely underpin the expansion. Our study disentangles the effects of selection and TE bursts leading to intra-specific genome expansions, providing a model to recapitulate TE-driven genome evolution over deeper evolutionary timescales.
Management of the Obstructed Airway
Authors: Henry J. Heimlich
Journal: JAMA (1980)

To the Editor.—  In his COMMENTARY (243:1141, 1980), Donald S. Gann, MD, explains that the National Academy of Sciences' recommendation that backslaps be the first method used to save a choking victim is based on the results of an American Heart Association (AHA) survey of 343 choking victims.  The survey's conclusions were reached by the following interpretation: If more than one method was used on a choking victim, and the victim was saved by one of the methods, then both methods were counted as having saved the victim. In other words, if a backslap failed to help and the Heimlich maneuver then saved the victim's life, this was recorded as a success for the backslap as well as, for the Heimlich maneuver. This explains why 587 successes were recorded although there were only 343 choking victims.'1-3  The AHA Data Processing Department in a memo concerning the survey stated:  These data
Studies of the human liver insulin receptor in noninsulin-dependent diabetes mellitus.
Authors: P Arner, K Einarsson, S Ewerth, J Livingston
Journal: Journal of Clinical Investigation (1986)

The insulin binding characteristics and the structural components of the insulin receptor were studied in the purified liver plasma membranes from seven patients with noninsulin-dependent diabetes (NIDDM) and seven control subjects. In comparison to the controls, diabetic subjects had a 65% reduction in plasma insulin levels in response to an oral glucose load. Specific insulin binding by liver membranes from diabetic patients was, however, twofold greater than the binding activity by membranes from control subjects. This alteration resulted largely from an increase in the number of insulin receptors and a modest increase in receptor binding affinity. Holo (nonreduced) receptor species of similar molecular weights were detected by an affinity labeling technique in the two membrane preparations and sulfhydryl reduction demonstrated an insulin binding subunit of 125,000 mol wt. Overall, these results show that the hepatic insulin resistance of NIDDM cannot be explained by a deficiency in insulin binding.
Survival (time to event) data: censored observations
Authors: P. Sedgwick
Journal: BMJ (2011)

Researchers assessed the effectiveness of low dose high frequency ultrasound when combined with standard care in healing venous leg ulcers that had previously been hard to heal. Ultrasound was given for 12 weeks, after which participants returned to standard care alone. A multicentre randomised controlled trial was performed. Control treatment was standard care.1

Trial participants were recruited if they had at least one venous leg ulcer of greater than six months’ duration or greater than 5 cm2 in area, and an ankle brachial pressure index greater than 0.8. In total, 168 people were randomised to ultrasound and standard care, with 169 allocated to standard care alone. Each trial participant was treated for a total of 12 …
The Spanish Language and the P.-A.M. Congress.
Authors: A. M. Fernandez-Ybarra.
Journal: JAMA (1896)

New York, Sept. 23, 1896. <h3>To the Editor:</h3> —Several physicians who think of attending the Second Pan-American Medical Congress, to be held in the city of Mexico, if they could secure the services of a well known Spanish speaking physician to act as their guide and general translator, have asked me whether I am willing to go with them in that capacity. I replied that I have no objections, but in order that the number of physicians composing the party be still larger will you be so kind as to say a few words about this matter in theJournal? There are, no doubt a large number of professional gentlemen who would willingly go to Mexico, taking advantage of the reduction of the price of the trip for that occasion, if they could find some confrère thoroughly qualified to act as their<i>cicerone</i>. I remain sincerely yours, 235 Thompson Street.
Extracellular matrix in airway smooth muscle is associated with dynamics of airway function in asthma
Authors: C. Y. Yick, D. S. Ferreira, R. Annoni, J. H. von der Thüsen, P. W. Kunst, E. H. Bel, R. Lutter, T. Mauad, P. J. Sterk
Journal: Allergy (2012)

Altered deposition of extracellular matrix (ECM) in the airway smooth muscle (ASM) layer as observed in asthma may influence ASM mechanical properties. We hypothesized that ECM in ASM is associated with airway function in asthma. First, we investigated the difference in ECM expression in ASM between asthma and controls. Second, we examined whether ECM expression is associated with bronchoconstriction and bronchodilation in vivo.Our cross-sectional study comprised 19 atopic mild asthma patients, 15 atopic and 12 nonatopic healthy subjects. Spirometry, methacholine responsiveness, deep-breath-induced bronchodilation (ΔR(rs) ) and bronchoscopy with endobronchial biopsies were performed. Positive staining of elastin, collagen I, III and IV, decorin, versican, fibronectin, laminin and tenascin in ASM was quantified as fractional area and mean density. Data were analysed using Pearson's or Spearman's correlation coefficient.Extracellular matrix expression in ASM was not different between asthma and controls. In asthmatics, fractional area and mean density of collagen I and III were correlated with methacholine dose-response slope and ΔR(rs) , respectively (r = 0.71, P < 0.01; r = 0.60, P = 0.02). Furthermore, ASM collagen III and laminin in asthma were correlated with FEV(1) reversibility (r = -0.65, P = 0.01; r = -0.54, P = 0.04).In asthma, ECM in ASM is related to the dynamics of airway function in the absence of differences in ECM expression between asthma and controls. This indicates that the ASM layer in its full composition is a major structural component in determining variable airways obstruction in asthma.
Conditional Voluntary Mental-Hospital Admission
Authors: A. Louis McGarry, Milton Greenblatt
Journal: New England Journal of Medicine (1972)

Abstract The continuation of the practice of voluntary mental-hospital admission under certain contractual conditions is a desirable alternative to court-mediated involuntary commitment. Total abolition of involuntary civil commitment of the mentally ill, however, is likely to be regressive, leading to an increased use of the criminal-justice system in the management of the mentally ill, with destructive consequences. There will probably always be some citizens who require conditional voluntary or involuntary commitment status in mental-health facilities.
Chronic heart failure in the elderly: NYHA vs 6‐minute Walk Test as valid instruments to evaluate cardiac functional capacity
Authors: S. Baldasseroni, M. Cappugi, B. Dilaghi, S. Fumagalli, F. Fattirolli, B. Cappelli, G.F. Gensini, G. Masotti, N. Marchionni
Journal: European Journal of Heart Failure (2000)
Additional Follow-up of Congenital Limb Disorders in Relation to Bendectin Use
Authors: Pamela J. Aselton
Journal: JAMA (1983)

<h3>To the Editor.—</h3> The relation of Bendectin (combination product of doxylamine succinate and pyridoxine hydrochloride) exposure during the first trimester of pregnancy to congenital limb disorders is a matter of great interest. As part of a long-term follow-up study of pregnant women at Group Health Cooperative of Puget Sound in Seattle, we examined the most recent drug experience (January 1980 through December 1981) of mothers in relation to the presence of serious limb disorders in their offspring. In the cohort of 5,255 women included in this study, 1,364 (26%) filled one or more prescriptions for Bendectin during the first trimester of their pregnancy and were considered to be users; 3,891 did not. Among the 1,364 Bendectin users, 556 (41%) filled two to four prescriptions for the drug and 167 (12%) filled five or more. We excluded from consideration infants with minor familial and positional limb disorders, eg, clubfoot, syndactyly of
IgA antiendomysium antibodies in human umbilical cord sections as a screening test in relatives of patients with celiac disease
Authors: M. Bagnasco, P. Montagna, A. De Alessandri, E. Castellano, G. P. Pesce, R. Gatti
Journal: Allergy (1997)

We performed the serum IgA antiendomysium antibody (EmA) assay by indirect immunofluorescence on human umbilical cord sections in 86 subjects with celiac disease, in 187 first‐degree relatives of such patients, and in a control group of 68 unrelated subjects, to investigate the suitability of the method in the screening of populations at risk of gluten sensitivity. Conventional EmA assay using monkey esophagus sections was performed in parallel experiments. The results obtained showed a perfpect correlation between the two methods. All the celiac patients and none of the controls were positive for EmA. EmA positivity was also observed in 11 apparently healthy relatives: intestinal biopsy performed in five of them invariably showed villous atrophy and increase of mucosal lymphocytes. Taking into account the low cost of EmA assay on human umbilical cord, especially when compared to monkey esophagus sections, the method is probably suitable and effective in identifying latent, asymptomatic gluten sensitivity in at‐risk populations.
Gynaecological Problems in the Young
Authors: J. Barnes
Journal: BMJ (1967)

Reviewsof the chemistry, pharmacology, and chemical uses -of the Vinca alkaloids was discussed in very great detail.It is striking that more than half of the papers are from French and Swiss workers and this volume is almost equally in the French and English languages.The papers dealing with the chemistry and pharmacology of the Vinca Alkaloids are extremely detailed and in fact not particularly valuable to any of the clinicians who use these drugs.Their attention will more naturally turn to the later part, where experi- ence from the Continental schools of the use of these drugs in the management of reticu- loses is described.
α<sub>1</sub>-Antitrypsin Activates Protein Phosphatase 2A to Counter Lung Inflammatory Responses
Authors: Patrick Geraghty, Edward Eden, Manju Pillai, Michael Campos, Noel G. McElvaney, Robert F. Foronjy
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Rationale: α1-Antitrypsin (A1AT) was identified as a plasma protease inhibitor; however, it is now recognized as a multifunctional protein that modulates immunity, inflammation, proteostasis, apoptosis, and cellular senescence. Like A1AT, protein phosphatase 2A (PP2A), a major serine-threonine phosphatase, regulates similar biologic processes and plays a key role in chronic obstructive pulmonary disease.Objectives: Given their common effects, this study investigated whether A1AT acts via PP2A to alter tumor necrosis factor (TNF) signaling, inflammation, and proteolytic responses in this disease.Methods: PP2A activity was measured in peripheral blood neutrophils from A1AT-deficient (PiZZ) and healthy (PiMM) individuals and in alveolar macrophages from normal (60 mg/kg) and high-dose (120 mg/kg) A1AT-treated PiZZ subjects. PP2A activation was assessed in human neutrophils, airway epithelial cells, and peripheral blood monocytes treated with plasma purified A1AT protein. Similarly, lung PP2A activity was measured in mice administered intranasal A1AT. PP2A was silenced in lung epithelial cells treated with A1AT and matrix metalloproteinase and cytokine production was then measured following TNF-α stimulation.Measurements and Main Results: PP2A was significantly lower in neutrophils isolated from PiZZ compared with PiMM subjects. A1AT protein activated PP2A in human alveolar macrophages, monocytes, neutrophils, airway epithelial cells, and in mouse lungs. This activation required functionally active A1AT protein and protein tyrosine phosphatase 1B expression. A1AT treatment acted via PP2A to prevent p38 and IκBα phosphorylation and matrix metalloproteinase and cytokine induction in TNF-α–stimulated epithelial cells.Conclusions: Together, these data indicate that A1AT modulates PP2A to counter inflammatory and proteolytic responses induced by TNF signaling in the lung.
Effect of bucindolol on heart failure outcomes and heart rate response in patients with reduced ejection fraction heart failure and atrial fibrillation
Authors: David P. Kao, Gordon Davis, Ryan Aleong, Christopher M. O'Connor, Mona Fiuzat, Peter E. Carson, Inder S. Anand, Jonathan F. Plehn, Stephen S. Gottlieb, Marc A. Silver, JoAnn Lindenfeld, Alan B. Miller, Michel White, Guinevere A. Murphy, Will Sauer, Michael R. Bristow
Journal: European Journal of Heart Failure (2012)
The Late William Warren Greene.
Authors: Charles Lyman Greene
Journal: JAMA (1897)

St. Paul, Minn., Nov. 26, 1897. <h3>To the Editor:</h3> —I am making an effort to obtain a complete list of the articles published by my father, the late William Warren Greene of Portland. The references are scattered and difficult to obtain, and I would ask that any of his old students or professional friends who have reprints or references to articles, will kindly advise me concerning them, thereby conferring a favor which will be greatly appreciated.
Quantification of the Glycemic Response to Microdoses of Subcutaneous Glucagon at Varying Insulin Levels
Authors: Joseph El Youssef, Jessica R. Castle, Parkash A. Bakhtiani, Ahmad Haidar, Deborah L. Branigan, Matthew Breen, W. Kenneth Ward
Journal: Diabetes Care (2014)

Glucagon delivery in closed-loop control of type 1 diabetes is effective in minimizing hypoglycemia. However, high insulin concentration lowers the hyperglycemic effect of glucagon, and small doses of glucagon in this setting are ineffective. There are no studies clearly defining the relationship between insulin levels, subcutaneous glucagon, and blood glucose.Using a euglycemic clamp technique in 11 subjects with type 1 diabetes, we examined endogenous glucose production (EGP) of glucagon (25, 75, 125, and 175 μg) at three insulin infusion rates (0.016, 0.032, and 0.05 units/kg/h) in a randomized, crossover study. Infused 6,6-dideuterated glucose was measured every 10 min, and EGP was determined using a validated glucoregulatory model. Area under the curve (AUC) for glucose production was the primary outcome, estimated over 60 min.At low insulin levels, EGP rose proportionately with glucagon dose, from 5 ± 68 to 112 ± 152 mg/kg (P = 0.038 linear trend), whereas at high levels, there was no increase in glucose output (19 ± 53 to 26 ± 38 mg/kg, P = NS). Peak glucagon serum levels and AUC correlated well with dose (r2 = 0.63, P < 0.001), as did insulin levels with insulin infusion rates (r2 = 0.59, P < 0.001).EGP increases steeply with glucagon doses between 25 and 175 μg at lower insulin infusion rates. However, high insulin infusion rates prevent these doses of glucagon from significantly increasing glucose output and may reduce glucagon effectiveness in preventing hypoglycemia when used in the artificial pancreas.
Role of enhanced glomerular synthesis of thromboxane A2 in progressive kidney disease
Authors: Patricia Salvati, Corrado Ferti, Romana G. Ferrario, Ernesto Lamberti, Liliana Duzzi, Giuseppe Bianchi, Giuseppe Remuzzi, Norberto Perico, Ariela Benigni, Paola Braidotti, Guido Coggi, Francesco Pugliese, Carlo Patrono
Journal: Kidney International (1990)
Doxorubicin Plus Sorafenib vs Doxorubicin Alone in Patients With Advanced Hepatocellular Carcinoma
Authors: Ghassan K. Abou-Alfa, Philip Johnson, Jennifer J. Knox, Marinela Capanu, Irina Davidenko, Juan Lacava, Thomas Leung, Bolorsukh Gansukh, Leonard B. Saltz
Journal: JAMA (2010)

In a randomized phase 3 trial, 400 mg of sorafenib twice daily prolonged overall survival of patients with advanced hepatocellular carcinoma (HCC) and Child-Pugh A disease. In a phase 1 study, sorafenib combined with doxorubicin, 60 mg/m(2), was well tolerated by patients with refractory solid tumors. The combination of sorafenib and doxorubicin in patients with advanced HCC has not been evaluated in a phase 2 or 3 trial.To evaluate the efficacy and safety of doxorubicin plus sorafenib compared with doxorubicin alone in patients with advanced HCC and Child-Pugh A disease.In a double-blind phase 2 multinational study, conducted from April 2005 to October 2006, 96 patients (76% male; median age, 65 years [range, 38-82 years]) with advanced HCC, Eastern Cooperative Oncology Group performance status 0 to 2, Child-Pugh A status, and no prior systemic therapy were randomly assigned to receive 60 mg/m(2) of doxorubicin intravenously every 21 days plus either 400 mg of sorafenib or placebo orally twice a day. The date of the last patient's follow-up was April 2008.Time to progression as determined by independent review.Following complete accrual, an unplanned early analysis for efficacy was performed by the independent data monitoring committee, so the trial was halted. The 2 patients remaining in the placebo group at that time were offered sorafenib. Based on 51 progressions, 63 deaths, and 70 events for progression-free survival, median time to progression was 6.4 months in the sorafenib-doxorubicin group (95% confidence interval [CI], 4.8-9.2), and 2.8 months (95% CI, 1.6-5) in the doxorubicin-placebo monotherapy group (P = .02). Median overall survival was 13.7 months (95% CI, 8.9--not reached) and 6.5 months (95% CI, 4.5-9.9; P = .006), and progression-free survival was 6.0 months (95% CI, 4.6-8.6) and 2.7 months (95% CI, 1.4-2.8) in these groups, respectively (P = .006). Toxicity profiles were similar to those for the single agents.Among patients with advanced HCC, treatment with sorafenib plus doxorubicin compared with doxorubicin monotherapy resulted in greater median time to progression, overall survival, and progression-free survival. The degree to which this improvement may represent synergism between sorafenib and doxorubicin remains to be defined. The combination of sorafenib and doxorubicin is not yet indicated for routine clinical use.clinicaltrials.gov Identifier: NCT00108953.
S109 Mesenchymal Stem Cells Expressing Full Length Trail - A Promising Therapy For Cancer
Authors: Z. Yuan, K. Kolluri, S. Janes
Journal: Thorax (2014)

<h3></h3> Bone marrow derived mesenchymal stem cells (MSC) are promising tools for lung cancer therapy considering their tendencies for tumour homing and low immunogenicity. Tumour necrosis factor related apoptosis inducing ligand (TRAIL) is a pro-apoptotic protein that induces selective apoptosis of tumour cells, while sparing normal cells. Therefore, it is expected that MSCs engineered to produce TRAIL will home to and kill cancer cells. In this study, two lentiviral vectors were constructed to express the full-length (flT) or a truncated soluble form of TRAIL (sT) driven by a CMV promoter/enhancer. A secretion targeting sequence and an isoleucine zipper (ILZ) peptide were sequentially added to the N-terminal of the soluble TRAIL to produce secreted and trimerised TRAIL. TRAIL lentiviruses were prepared and human BM-MSCs were transduced with a multiplicity of infection (MOI) of 2. FACS analysis by anti-TRAIL antibody staining demonstrated that over 99% of flT or sT viruses transduced cells are positive for TRAIL expression. TRAIL expression was further confirmed by Western blotting and ELISA assays. The flT or sT expressing MSCs both showed similar level of cellular TRAIL expression (~350 ng TRAIL per 1 mg of total cellular protein). Co-culture of cancer cells with transduced MSCs determined the cancer killing efficacy of MSCs expressing flT or sT. Twenty cancer cell lines were tested and classified into four TRAIL response groups; high, medium, low, and no sensitivity to recombinant TRAIL (rTRAIL) at the concentration of 50 ng/ml. At the co-culture ratio of 4:1 cancer to MSC cells, MSC-sT treatment showed no or only marginal cancer cell killing effect, in contrast, MSC-flT showed promising effects on all tested cell lines, with an apoptosis induction rate ranging between 35–75%. In groups designated as high, moderate and low, MSC-flT are as effective as rTRAIL and induced marked cell death (p &lt; 0.001) in cell lines which showed no sensitivity to rTRAIL (Figure). In conclusion, these results demonstrate MSC-flT is a promising cell therapy and have great potential for clinical treatment of lung cancers and pleural metastases.
THE NORMAL FATE OF ERYTHROCYTES
Authors: Oswald H. Robertson, Peyton Rous
Journal: The Journal of Experimental Medicine (1917)

1. The increased destruction of red cells in animals rendered plethoric by transfusion takes place predominantly by a fragmentation of the corpuscles without loss of hemoglobin. 2. The microcytes and poikilocytes observed in animals with a severe anemia due to hemorrhage are not put forth as such by the bone marrow, but are portions of cells fragmented while circulating. 3. The cells thus fragmented are for the most part those newformed to meet the exigencies of the situation. Such cells are in large part unable to withstand the wear and tear of function. There results a vicious circle. The anemia renders the bone marrow unable to put forth proper cells, and those it does produce are soon destroyed, thus prolonging the condition. A similar state of affairs probably exists in many human anemias. 4. The occurrence of large accumulations of microcytes and poikilocytes in the spleen of anemic and plethoric animals indicates that the organ exercises some important function in connection with these forms. The same is true of normal animals, for the findings in them are similar, though less striking. 5. The normal fate of the red corpuscles, in those species in which phagocytosis is negligible, is to be fragmented one by one, while still circulating, to a fine, hemoglobin-containing dust. The cell fragments are rapidly removed from the blood, but their ultimate fate remains to be determined. The facts indicate that they are removed from the blood by the spleen, and under exceptional conditions, by the bone marrow.