tbuckley/cabot-search huggingface dataset:
Ageing and changes in lung mechanics
Authors: N. B. Pride
Journal: European Respiratory Journal (2005)

<h3>Abstract</h3> <h3>Background</h3> One of the primary reasons for hesitancy in taking COVID-19 vaccines is the fear of side effects. This study primarily aims to inspect the potential side effects of the COVID-19 vaccines circulated in Bangladesh. <h3>Methods</h3> The study was a cross-sectional anonymous online survey conducted across Bangladesh. Data were collected from December 2 to December 26, 2021. The study included consenting (informed) Bangladeshi individuals aged 12 and above who had received at least one dose of the COVID-19 vaccines. Analyses were carried out through exploratory analysis, Chi-square test, and logistic regression. <h3>Results</h3> A total of 1,180 (males-63.89%, age 50 years or over-65.4%, rural-52.86%) vaccinated people participated in the study. Less than half of the participants (39.48%) reported at least one side effect after receiving their COVID-19 vaccine. Injection-site pain, fever, headache, redness/swelling at the injection site, and lethargy were the most commonly reported adverse effects, all of which were mild and lasted 1-3 days. Side effects were most prevalent (about 80%) among individuals who received Pfizer-BioNTech and Moderna vaccines and were least common among those who received Sinopharm and Sinovac vaccines (21%-28%). When compared to the Sinopharm vaccines, the OxfordAstraZeneca, Pfizer-BioNTech, and Moderna vaccines were 4.51 (95% CI: 2.53-8.04) times, 5.37 (95% CI: 2.57-11.22) times, and 4.28 (95% CI: 2.28-8.05) times likelier to produce side effects. Furthermore, males, those over 50 years old, urban dwellers, smokers, and those with underlying health issues had a considerably increased risk of developing side effects. A lack of confidence in vaccines' efficacy and a substantial level of hesitancy in allowing children (age five years or over) and older people (70 years or over) to receive COVID-19 vaccines were also observed. <h3>Conclusion</h3> Side effects of COVID-19 vaccines are minimal, demonstrating their safety. Further studies are required to establish the efficacy of the vaccines.
Attitude Toward Drug and Clinical Outcome
Authors: BURTON S. GLICK
Journal: American Journal of Psychiatry (1968)

To test the validity of current assumptions about the relationship between the patient's attitude toward drug therapy and his clinical response to it, a double-blind study was conducted with 20 outpatients. The author found that treatment outcome, as measured by degree of clinical change, was related to severity of illness but was not related to patients' attitudes toward drug therapy.
Studies on mechanisms of augmentation of liver regeneration by cyclosporine and FK 506
Authors: Antonio Francavilla, Thomas E. Starzl, Michele Barone, Qi-Hua Zeng, Kendrick A. Porter, Adrianni Zeevi, Peter M. Markus, Marcell R. M. van den Brink, Satoru Todo
Journal: Hepatology (1991)

Evidence could not be found of immune modulation of liver regeneration. The powerful immunosuppressive drug FK 506, which augments the response after partial hepatectomy in normal rats, had the same effect in T cell—deficient nude rats. The cytotoxicity of natural killer cells in treated nude rats was not significantly changed by FK 506 therapy. However, the serum of FK 506—treated nude rats increased hepatocyte proliferation when added to third-party hepatocyte cultures, suggesting that FK 506 had induced a serum growth factor in the nude rats or had suppressed an inhibitory factor. A hypothesis was advanced that FK 506 (and cyclosporine) affects hepatic growth by nonimmunological pathways. (HEPATOLOGY 1991;14:140-143.)
Selectively Advantageous Mutations and Hitchhikers in Neoplasms
Authors: Carlo C. Maley, Patricia C. Galipeau, Xiaohong Li, Carissa A. Sanchez, Thomas G. Paulson, Brian J. Reid
Journal: Cancer Research (2004)

Abstract Neoplastic progression is an evolutionary process characterized by genomic instability and waves of clonal expansions carrying genetic and epigenetic lesions to fixation (100% of the cell population). However, an evolutionarily neutral lesion may also reach fixation if it spreads as a hitchhiker on a selective sweep. We sought to distinguish advantageous lesions from hitchhikers in the premalignant condition Barrett’s esophagus. Patients (211) had biopsies taken at 2-cm intervals in their Barrett’s segments. Purified epithelial cells were assayed for loss of heterozygosity and microsatellite shifts on chromosomes 9 and 17, sequence mutations in CDKN2A/MTS1/INK4a (p16) and TP53 (p53), and methylation of the p16 promoter. We measured the expanse of a lesion in a Barrett’s segment as the proportion of proliferating cells that carried a lesion in that locus. We then selected the lesion having expanses &amp;gt;90% in the greatest number of patients as our first putative advantageous lesion. We filtered out hitchhikers by removing all expanses of other lesions that did not occur independent of the advantageous lesion. The entire process was repeated on the remaining expanses to identify additional advantageous lesions. p16 loss of heterozygosity, promoter methylation, and sequence mutations have strong, independent, advantageous effects on Barrett’s cells early in progression. Second lesions in p16 and p53 are associated with later selective sweeps. Virtually all of the other lesion expansions, including microsatellite shifts, could be explained as hitchhikers on p16 lesion clonal expansions. These techniques can be applied to any neoplasm.
Pharmacogenetics of Endocrine Therapy for Breast Cancer
Authors: Michaela J. Higgins, Vered Stearns
Journal: Annual Review of Medicine (2010)

The selective estrogen receptor modulator tamoxifen has been used for more than three decades for the treatment, and more recently prevention, of breast cancer in women of all ages. The conversion of tamoxifen to active metabolites involves several cytochrome P450 (CYP) enzymes. CYP2D6 is the key enzyme responsible for the conversion of N-desmethyl tamoxifen to endoxifen. Single nucleotide polymorphisms in the CYP2D6 gene are not uncommon, and some alleles code for enzymes with reduced, null, or increased activity. Multiple studies suggest that women who carry one or two variant CYP2D6 alleles that encode enzymes with null or reduced activity may have an inferior breast cancer outcome when treated with tamoxifen in the adjuvant setting compared to women carrying two alleles encoding an enzyme with normal activity. Unfortunately, the data are not uniformly concordant, and definitive evidence that would change routine clinical practice is not yet available. CYP2D6 activity can also be reduced by concomitant use of drugs that inhibit the enzyme, including antidepressants used for psychiatric conditions or to relieve hot flashes, and these should be avoided in tamoxifen users whenever possible. Emerging data suggest that host factors may also predict interpatient variability in response to aromatase inhibitors.
Complement activation following first exposure to pegylated liposomal doxorubicin (Doxil®): possible role in hypersensitivity reactions
Authors: A. Chanan-Khan, J. Szebeni, S. Savay, L. Liebes, N.M. Rafique, C.R. Alving, F.M. Muggia
Journal: Annals of Oncology (2003)
Bone marrow transplantation and the lung.
Authors: P J Hamilton, A D Pearson
Journal: Thorax (1986)

Bone marrow transplantation and the lungBone marrow transplantation is a remarkably easy technical procedure with enormous therapeutic potential, which is as yet only partially tapped because of a paucity of suitable donors and a high complication rate.Nevertheless the procedure offers the hope of curing the many and diverse clinical disor- ders that result from malfunction of the progeny of haemopoietic pleuripotential stem cells.The technique is capable of restoring normal haematological function in primary red cell, white cell, or platelet dis- orders after ablation of aberrant cells and can be used to rescue patients with marrow failure secondary to chemical or radiation insult.Immunological com- petence can be restored as grafted haematological stem cells are able to differentiate into T and B lymphocytes.Possibly many immunological disorders will be treated with bone marrow transplantation in the forseeable future.Bone marrow transplantation is also being studied as a form of treatment for meta- bolic disorders, including mucopolysaccharidoses, Gaucher's disease, and adenosine deaminase deficiency.'By means of a graft of normal stem cells into an affected patient erythrocytes, granulocytes, and macrophages are produced and normal enzymes are manufactured, which then diffuse into enzyme deficient tissues.In 1986 two major difficulties, graft versus host disease and pulmonary damage, limit the widespread exploitation of bone marrow trans- plantation.24Graft versus host disease is thought to result because donor T lymphocytes recognise the recipient's tissues as foreign and, by mounting an immune response, damage them.In the first 100 days acute graft versus host disease presents as a rash, often accompanied by evidence of damage to the gut and liver, in 25-75% of patients.5 6 Later, chronic graft versus host disease may present by mimicking multi- organ autoimmune disease with rash, oral and oph- thalmic sicca syndrome, hepatic damage, immune deficiency, and opportunistic infections.7 8 This may follow acute graft versus host disease or may occur de novo.For the accurate diagnosis of graft versus host disease biopsy and histological examination of the affected organ is required.Despite increasing under- standing of histocompatibility determinants and recent advances in manipulating T cell function, in most centres bone marrow transplantation is confined
Inhibition of Nuclear Import of Calcineurin Prevents Myocardial Hypertrophy
Authors: Matthias Hallhuber, Natalie Burkard, Rongxue Wu, Mamta H. Buch, Stefan Engelhardt, Lutz Hein, Ludwig Neyses, Kai Schuh, Oliver Ritter
Journal: Circulation Research (2006)

The time that transcription factors remain nuclear is a major determinant for transcriptional activity. It has recently been demonstrated that the phosphatase calcineurin is translocated to the nucleus with the transcription factor nuclear factor of activated T cells (NF-AT). This study identifies a nuclear localization sequence (NLS) and a nuclear export signal (NES) in the sequence of calcineurin. Furthermore we identified the nuclear cargo protein importinbeta(1) to be responsible for nuclear translocation of calcineurin. Inhibition of the calcineurin/importin interaction by a competitive peptide (KQECKIKYSERV), which mimicked the calcineurin NLS, prevented nuclear entry of calcineurin. A noninhibitory control peptide did not interfere with the calcineurin/importin binding. Using this approach, we were able to prevent the development of myocardial hypertrophy. In angiotensin II-stimulated cardiomyocytes, [(3)H]-leucine incorporation (159%+/-9 versus 111%+/-11; P<0.01) and cell size were suppressed significantly by the NLS peptide compared with a control peptide. The NLS peptide inhibited calcineurin/NF-AT transcriptional activity (227%+/-11 versus 133%+/-8; P<0.01), whereas calcineurin phosphatase activity was unaffected (298%+/-9 versus 270%+/-11; P=NS). We conclude that calcineurin is not only capable of dephosphorylating NF-AT, thus enabling its nuclear import, but the presence of calcineurin in the nucleus is also important for full NF-AT transcriptional activity.
Courage Beyond Science
Authors: E. Grey Dimond
Journal: JAMA (1976)

THE NEW University of Missouri-Kansas City School of Medicine graduated its "charter" class in the Spring of 1976. This class represented the original group of high school graduates who entered six years earlier. From the considerable experience of these past six years, augmented by my own 32 years as a physician, surely I have learned something regarding either health, illness, education, or, remotely, wisdom. However, the more experience I have, the less I am certain that I know the message. <h3>TODAY'S MEDICINE</h3> At this point in my career, I should be accumulating a supply of useful homilies. However, the truth is that the farther I go along the path of experience, the less I seem to know for sure. It was a bit discouraging to offer this information to these new, enthusiastic medical school graduates and their proud families. In fact, it is probably anti-intellectual to admit the basic truth:
TYPHUS FEVER
Authors: Henry Pinkerton
Journal: The Journal of Experimental Medicine (1931)

1. A satisfactory method is described for the topographical study of Rickettsia prowazeki in sections of the scrotal sac of typhus-infected guinea pigs. 2. In such sections Rickettsiae are always intracellular. 3. Typhus Rickettsiae multiply luxuriantly in the serosal cells and produce great distention of these cells. 4. Rickettsiae may be found in small numbers in the endothelial cells lining the underlying capillaries in the testes and scrotum, but are not seen in perivascular macrophages, connective tissue cells, fat cells, smooth or striated muscle fibres or epithelial cells. 5. Rickettsiae are rarely phagocytosed in small numbers by polymorphonuclears but are never seen in lymphocytes, plasma cells or eosinophiles. 6. When infected mesothelial cells proliferate and desquamate, they rapidly lose their content of Rickettsiae. 7. The large mononuclear cells seen in smears of the scrotal sac exudate may be separated into two groups: (1) the serosal (mesothelial) cells which become heavily infected with Rickettsiae but which are not phagocytic for graphite ink and (2) the macrophages (phagocytic cells) which do not contain Rickettsiae.
Chikungunya virus–induced autophagy delays caspase-dependent cell death
Authors: Pierre-Emmanuel Joubert, Scott W. Werneke, Claire de la Calle, Florence Guivel-Benhassine, Alessandra Giodini, Lucie Peduto, Beth Levine, Olivier Schwartz, Deborah J. Lenschow, Matthew L. Albert
Journal: The Journal of Experimental Medicine (2012)

Autophagy is an important survival pathway and can participate in the host response to infection. Studying Chikungunya virus (CHIKV), the causative agent of a major epidemic in India, Southeast Asia, and southern Europe, we reveal a novel mechanism by which autophagy limits cell death and mortality after infection. We use biochemical studies and single cell multispectral assays to demonstrate that direct infection triggers both apoptosis and autophagy. CHIKV-induced autophagy is mediated by the independent induction of endoplasmic reticulum and oxidative stress pathways. These cellular responses delay apoptotic cell death by inducing the IRE1α–XBP-1 pathway in conjunction with ROS-mediated mTOR inhibition. Silencing of autophagy genes resulted in enhanced intrinsic and extrinsic apoptosis, favoring viral propagation in cultured cells. Providing in vivo evidence for the relevance of our findings, Atg16LHM mice, which display reduced levels of autophagy, exhibited increased lethality and showed a higher sensitivity to CHIKV-induced apoptosis. Based on kinetic studies and the observation that features of apoptosis and autophagy were mutually exclusive, we conclude that autophagy inhibits caspase-dependent cell death but is ultimately overwhelmed by viral replication. Our study suggests that inducers of autophagy may limit the pathogenesis of acute Chikungunya disease.
Continuation or reintroduction of bevacizumab beyond progression to first-line therapy in metastatic colorectal cancer: final results of the randomized BEBYP trial
Authors: G Masi, L Salvatore, L Boni, F Loupakis, C Cremolini, L Fornaro, M Schirripa, S Cupini, C Barbara, V Safina, C Granetto, E Fea, L Antonuzzo, C Boni, G Allegrini, S Chiara, D Amoroso, A Bonetti, A Falcone
Journal: Annals of Oncology (2015)
Mortality in patients with rheumatoid arthritis treated actively from the time of diagnosis
Authors: R Peltomaa
Journal: Annals of the Rheumatic Diseases (2002)

<b>Objectives:</b> To evaluate the mortality rates among patients with early rheumatoid arthritis (RA) treated actively according to the "sawtooth" strategy. <b>Methods:</b> The study included 150 early, disease modifying antirheumatic drug (DMARD) naive patients with RA from two patient cohorts. The first cohort was assembled between 1986 and 1989 (87 patients, aged 19–65 years at onset) and the second between 1991 and 1993 (63 patients, aged 27–83 years at onset). The mean duration of symptoms at the time of diagnosis was 7.1 months (range 2–24). The clinical data and the use of DMARDs were systematically recorded. The causes of death were obtained from death certificates and medical records, if available. The data were collected up to 1 November 2000. <b>Results:</b> During a follow up time of 7–14 years, 24 patients died. The standardised mortality ratio was not increased (0.93 in the first cohort and 1.62 in the second cohort). Age adjusted mortality rates did not differ statistically significantly between the two patient cohorts. The causes of death included malignancy (8 patients); cardiovascular diseases (10); respiratory disease (4), including two patients with pneumonia; sepsis (one); and RA (one). High inflammatory activity, disease activity, and poor functional ability at study entry, and the presence of extra-articular features during the follow up were more common among the patients who had died. <b>Conclusions:</b> No statistically significant increase in mortality rates was seen in these actively treated early RA cohorts during the follow up. High disease activity at the onset and the development of extra-articular features seem to be associated with mortality.
Structure of the Human Type IV Collagen Gene COL4A3 and Mutations in Autosomal Alport Syndrome
Authors: LAURENCE HEIDET, CHRISTELLE ARRONDEL, LIONEL FORESTIER, LOLA COHEN-SOLAL, GERALDINE MOLLET, BRUNO GUTIERREZ, CHRISTOPHOROS STAVROU, MARIE CLAIRE GUBLER, CORINNE ANTIGNAC
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Mutations in either the COL4A3 or the COL4A4 genes, encoding the α3 and α4 chains of type IV collagen, are responsible for the autosomal-recessive form of Alport syndrome, a progressive hematuric nephropathy characterized by glomerular basement membrane abnormalities. Reported here are the complete COL4A3 exon-intron structure and a comprehensive screen for mutations of the 52 COL4A3 exons in 41 unrelated patients diagnosed as having autosomal Alport syndrome. This resulted in the identification of 21 mutations that are expected to be causative. Furthermore, it is shown that heterozygous COL4A3 missense mutations, when symptomatic, can be associated with a broad range of phenotypes, from familial benign hematuria to the complete features of Alport syndrome nephropathy.
Comparison of Two Methods of Processing Induced Sputum: Selected versus Entire Sputum
Authors: ANTONIO SPANEVELLO, BIANCA BEGHÉ, ACHILLE BIANCHI, GIOVANNI BATTISTA MIGLIORI, MARCO AMBROSETTI, MARGHERITA NERI, PHILIP W. IND
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Sputum analysis is increasingly used to assess airway inflammation in asthma. The analysis of sputum is currently performed with two techniques, i.e., analysis of selected sputum (plugs) and analysis of entire sputum. To investigate the diagnostic value of these two methods, we compared total and differential cell counts and supernatant eosinophil cationic protein (ECP) in selected and entire sputum collected on two occasions in a group of healthy and asthmatic subjects. We induced sputum with hypertonic saline in 18 asthmatics and in eight healthy subjects. On one occasion we analyzed selected sputum, and on another occasion we analyzed entire sputum. In each sample we measured total and differential cell counts and ECP concentration in supernatant. We found a higher percentage of eosinophils (15.3 versus 8.3%; p < 0.01), more viable nonsquamous cells (80.6 versus 71.8%; p < 0.01), and higher levels of ECP (548 versus 105 μ g/L; p < 0.001) in selected sputum as compared with entire sputum, whereas the percentage of neutrophils was higher in the entire sputum (42.7 versus 33.3%; p < 0.05). The percentage of eosinophils and ECP concentration were significantly and similarly increased in both selected and entire sputum of asthmatic subjects, i.e., independent of the method of sputum analysis. In conclusion, the selected sputum method may indeed provide more viable cells, more eosinophils, and a higher concentration of ECP. However, both the selected sputum and the entire sputum method have the same diagnostic value in distinguishing asthmatics from healthy subjects.
Tobacco Industry Manipulation of Tobacco Excise and Tobacco Advertising Policies in the Czech Republic: An Analysis of Tobacco Industry Documents
Authors: Risako Shirane, Katherine Smith, Hana Ross, Karin E. Silver, Simon Williams, Anna Gilmore
Journal: PLoS Medicine (2012)

Risako Shirane and colleagues examined the the Legacy Tobacco Documents Library and found evidence of transnational tobacco company influence over tobacco advertising and excise policy in the Czech Republic, a country with one of the poorest tobacco control records in Europe.
Signal Transducer and Activator of Transcription 1 Regulates Both Cytotoxic and Prosurvival Functions in Tumor Cells
Authors: Nikolai N. Khodarev, Andy J. Minn, Elena V. Efimova, Thomas E. Darga, Edwardine Labay, Michael Beckett, Helena J. Mauceri, Bernard Roizman, Ralph R. Weichselbaum
Journal: Cancer Research (2007)

Abstract Elsewhere, we reported that multiple serial in vivo passage of a squamous cell carcinoma cells (SCC61) concurrent with ionizing radiation (IR) treatment resulted in the selection of radioresistant tumor (nu61) that overexpresses the signal transducer and activator of transcription 1 (Stat1)/IFN-dependent pathway. Here, we report that (a) the Stat1 pathway is induced by IR, (b) constitutive overexpression of Stat1 is linked with failure to transmit a cytotoxic signal by radiation or IFNs, (c) selection of parental cell line SCC61 against IFN-α and IFN-γ leads to the same IR- and IFN-resistant phenotype as was obtained by IR selection, and (d) suppression of Stat1 by short hairpin RNA renders the IR-resistant nu61 cells radiosensitive to IR. We propose a model that transient induction of Stat1 by IFN, IR, or other stress signals activates cytotoxic genes and cytotoxic response. Constitutive overexpression of Stat1 on the other hand leads to the suppression of the cytotoxic response and induces prosurvival genes that, at high levels of Stat1, render the cells resistant to IR or other inducers of cell death. [Cancer Res 2007;67(19):9214–20]
Structural insight into MR1-mediated recognition of the mucosal associated invariant T cell receptor
Authors: Rangsima Reantragoon, Lars Kjer-Nielsen, Onisha Patel, Zhenjun Chen, Patricia T. Illing, Mugdha Bhati, Lyudmila Kostenko, Mandvi Bharadwaj, Bronwyn Meehan, Ted H. Hansen, Dale I. Godfrey, Jamie Rossjohn, James McCluskey
Journal: The Journal of Experimental Medicine (2012)

Mucosal-associated invariant T (MAIT) cells express a semiinvariant αβ T cell receptor (TCR) that binds MHC class I-like molecule (MR1). However, the molecular basis for MAIT TCR recognition by MR1 is unknown. In this study, we present the crystal structure of a human Vα7.2Jα33-Vβ2 MAIT TCR. Mutagenesis revealed highly conserved requirements for the MAIT TCR-MR1 interaction across different human MAIT TCRs stimulated by distinct microbial sources. Individual residues within the MAIT TCR β chain were dispensable for the interaction with MR1, whereas the invariant MAIT TCR α chain controlled specificity through a small number of residues, which are conserved across species and located within the Vα-Jα regions. Mutagenesis of MR1 showed that only two residues, which were centrally positioned and on opposing sides of the antigen-binding cleft of MR1, were essential for MAIT cell activation. The mutagenesis data are consistent with a centrally located MAIT TCR-MR1 docking that was dominated by the α chain of the MAIT TCR. This candidate docking mode contrasts with that of the NKT TCR-CD1d-antigen interaction, in which both the α and β chain of the NKT TCR is required for ligation above the F'-pocket of CD1d.