tbuckley/cabot-search huggingface dataset:
Home mechanical ventilation in Hong Kong
Authors: C.M. Chu, W.C. Yu, C.M. Tam, C.W. Lam, D.S.C. Hui, C.K.W. Lai
Journal: European Respiratory Journal (2004)

Home mechanical ventilation (HMV) is increasingly used to treat chronic respiratory failure. This present study was aimed to examine the trend, the disease categories treated and the outcomes of HMV use in Hong Kong. In the year 2002, all adult respiratory units in Hong Kong were invited to report to a multicentre retrospective survey of HMV use. A total of 249 patients (156 males, mean age 62.7±13.8 yrs) were treated since 1980, with 197 (79%) continuing with HMV at the time of the survey. Cumulative number of HMV grew as a cubic function of time since 1980. Currently, there are 2.9 users per 100,000 population. The predominant mode of HMV was noninvasive ventilation by bilevel pressure support ventilators (n=236). Chronic obstructive pulmonary disease accounted for 48.6% of all cases. The overall 3‐yr HMV continuation rate was 66.2%. Death was the main reason for discontinuation. A rapidly rising trend of home mechanical ventilation use is observed in Hong Kong. In contrast to other series, chronic obstructive pulmonary disease was the major group treated and bilevel pressure support ventilation was the predominant mode chosen. Most patients tolerate home mechanical ventilation reasonably well, with approximately two-thirds continuing with its use at 36 months.
Measurement of skin texture through polarization imaging
Authors: P.R. Bargo, N. Kollias
Journal: British Journal of Dermatology (2010)

Determination of skin surface texture is of particular importance in the field of dermatology as such measurements can be used for skin diagnostics and evaluation of therapeutic or cosmetic treatments. Profilometry of skin replicas, three-dimensional imaging and computer vision have been successfully used to measure and document skin texture. Nevertheless, the development of a simpler and faster technique may prove to be advantageous in a clinical setting.We propose the use of polarization imaging with high angles of incidence as a simple alternative to measure/document skin texture/roughness.A system based on digital photography and polarization optics was developed to acquire and compute texture images. Optimization of the system configuration was conducted to enhance the contrast for measuring skin roughness. The method was validated against roughness standards and tested in clinical studies. Measurements were made in subjects aged from 9 to 70 years and image analysis was used to evaluate texture.The developed texture scale was shown to correlate closely to the results from clinical assessment and from roughness standards. Frequency domain analysis showed a significantly different power spectrum for the texture images of young subjects when compared with older subjects. The evaluation of texture as a function of age showed that facial skin roughness increased linearly from teenage to 40 years followed by a plateau thereafter.The system proved to be a useful clinical tool for assessing skin texture. The age-related results may indicate that some skin texture features are formed before the age of 40 years.
Current Treatment Options for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
Authors: Assuntina G. Sacco, Ezra E. Cohen
Journal: Journal of Clinical Oncology (2015)

This review highlights the evidence-based data to support current best management practices for patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Current limitations and areas of emerging therapeutics are also emphasized. The cornerstone of palliation for patients with R/M HNSCC is a platinum-based backbone. Platinum doublets induce higher response rates than single agents but do not demonstrate a survival advantage and are associated with increased toxicity. The only regimen to demonstrate survival superiority is platinum, fluorouracil, and cetuximab, a monoclonal antibody directed against the epidermal growth factor receptor (EGFR). EGFR inhibitors, including monoclonal antibodies and tyrosine kinase inhibitors, have achieved only modest success in R/M HNSCC, illustrating the importance of identifying predictive biomarkers and finding ways to overcome mechanisms of resistance. Although phosphoinositide 3-kinase pathway alterations are present at a high rate in HNSCC, the identification of efficacious agents in patients with activating alterations has yet to be discovered. Immunotherapy represents an attractive treatment strategy for R/M HNSCC, with promising preliminary data from studies involving immune checkpoint blockade and toll-like receptor agonists. Human papillomavirus has a prognostic role in R/M disease; therefore, stratification of patients by human papillomavirus status in clinical trials is indicated. Although under-represented in clinical trials, elderly patients experience similar survival outcomes compared with younger patients, albeit with increased toxicity. Despite therapeutic advances, prognosis nonetheless remains poor for patients with R/M HNSCC. Enrollment of patients onto clinical trials to investigate novel therapeutics and identify predictive biomarkers is necessary to further refine and improve outcomes.
Cancer Stem-like Cells Derived from Chemoresistant Tumors Have a Unique Capacity to Prime Tumorigenic Myeloid Cells
Authors: Tsunaki Yamashina, Muhammad Baghdadi, Akihiro Yoneda, Ichiro Kinoshita, Shinya Suzu, Hirotoshi Dosaka-Akita, Masahisa Jinushi
Journal: Cancer Research (2014)

Resistance to anticancer therapeutics greatly affects the phenotypic and functional properties of tumor cells, but how chemoresistance contributes to the tumorigenic activities of cancer stem-like cells remains unclear. In this study, we found that a characteristic of cancer stem-like cells from chemoresistant tumors (CSC-R) is the ability to produce a variety of proinflammatory cytokines and to generate M2-like immunoregulatory myeloid cells from CD14(+) monocytes. Furthermore, we identified the IFN-regulated transcription factor IRF5 as a CSC-R-specific factor critical for promoting M-CSF production and generating tumorigenic myeloid cells. Importantly, myeloid cells primed with IRF5(+) CSC-R facilitate the tumorigenic and stem cell activities of bulk tumors. Importantly, the activation of IRF5/M-CSF pathways in tumor cells were correlated with the number of tumor-associated CSF1 receptor(+) M2 macrophages in patients with non-small lung cancer. Collectively, our findings show how chemoresistance affects the properties of CSCs in their niche microenvironments.
Thyroid Dysfunction from Antineoplastic Agents
Authors: O.-P. R. Hamnvik, P. R. Larsen, E. Marqusee
Journal: JNCI Journal of the National Cancer Institute (2011)

Unlike cytotoxic agents that indiscriminately affect rapidly dividing cells, newer antineoplastic agents such as targeted therapies and immunotherapies are associated with thyroid dysfunction. These include tyrosine kinase inhibitors, bexarotene, radioiodine-based cancer therapies, denileukin diftitox, alemtuzumab, interferon-α, interleukin-2, ipilimumab, tremelimumab, thalidomide, and lenalidomide. Primary hypothyroidism is the most common side effect, although thyrotoxicosis and effects on thyroid-stimulating hormone secretion and thyroid hormone metabolism have also been described. Most agents cause thyroid dysfunction in 20%-50% of patients, although some have even higher rates. Despite this, physicians may overlook drug-induced thyroid dysfunction because of the complexity of the clinical picture in the cancer patient. Symptoms of hypothyroidism, such as fatigue, weakness, depression, memory loss, cold intolerance, and cardiovascular effects, may be incorrectly attributed to the primary disease or to the antineoplastic agent. Underdiagnosis of thyroid dysfunction can have important consequences for cancer patient management. At a minimum, the symptoms will adversely affect the patient's quality of life. Alternatively, such symptoms can lead to dose reductions of potentially life-saving therapies. Hypothyroidism can also alter the kinetics and clearance of medications, which may lead to undesirable side effects. Thyrotoxicosis can be mistaken for sepsis or a nonendocrinologic drug side effect. In some patients, thyroid disease may indicate a higher likelihood of tumor response to the agent. Both hypothyroidism and thyrotoxicosis are easily diagnosed with inexpensive and specific tests. In many patients, particularly those with hypothyroidism, the treatment is straightforward. We therefore recommend routine testing for thyroid abnormalities in patients receiving these antineoplastic agents.
Characterization of a probiotic-derived soluble protein which reveals a mechanism of preventive and treatment effects of probiotics on intestinal inflammatory diseases
Authors: Fang Yan, D. Brent Polk
Journal: Gut Microbes (2012)

The beneficial effects of probiotics have been demonstrated in many diseases, such as inflammatory bowel disease. The known mechanisms for probiotic action include blocking pathogenic bacterial effects, enhancing the innate immunity and decreasing pathogen-induced inflammation, and promoting intestinal epithelial cell survival, barrier function, and protective responses. We purified and cloned a Lactobacillus rhamnosus GG (LGG)-derived soluble protein, p40. This protein ameliorated cytokine-induced apoptosis in intestinal epithelial cells through activation of the EGF receptor and its down-stream target, Akt. By using special hydrogel beads to protect p40 from degradation, we showed that p40 reduced intestinal epithelial apoptosis and preserved barrier function in the colon epithelium in an EGF receptor-dependent manner, thereby preventing and treating intestinal inflammation in mouse models of colitis. Further works regarding structural analysis of p40, regulation of EGF receptor activation and immunoregulatory effects by p40 are discussed. These results may provide insights into the clinical application of probiotics for intestinal inflammatory disorders.
Decision aids for patients facing health treatment or screening decisions: systematic review
Authors: A. M O'Connor, A. Rostom, V. Fiset, J. Tetroe, V. Entwistle, H. Llewellyn-Thomas, M. Holmes-Rovner, M. Barry, J. Jones
Journal: BMJ (1999)

<h3>Abstract</h3> <b>Objective:</b> To conduct a systematic review of randomised trials of patient decision aids in improving decision making and outcomes. <b>Design:</b> We included randomised trials of interventions providing structured, detailed, and specific information on treatment or screening options and outcomes to aid decision making. Two reviewers independently screened and extracted data on several evaluation criteria. Results were pooled by using weighted mean differences and relative risks. <b>Results:</b> 17 studies met the inclusion criteria. Compared with the controls, decision aids produced higher knowledge scores (weighted mean difference=19/100, 95% confidence interval 14 to 25); lower decisional conflict scores (weighted mean difference=−0.3/5, −0.4 to −0.1); more active patient participation in decision making (relative risk = 2.27, 95% confidence interval 1.3 to 4); and no differences in anxiety, satisfaction with decisions (weighted mean difference=0.6/100, −3 to 4), or satisfaction with the decision making process (2/100,−3 to 7). Decision aids had a variable effect on decisions. When complex decision aids were compared with simpler versions, they were better at reducing decisional conflict, improved knowledge marginally, but did not affect satisfaction. <b>Conclusions:</b> Decision aids improve knowledge, reduce decisional conflict, and stimulate patients to be more active in decision making without increasing their anxiety. Decision aids have little effect on satisfaction and a variable effect on decisions. The effects on outcomes of decisions (persistence with choice, quality of life) remain uncertain.
Phase III Trial of Vandetanib Compared With Erlotinib in Patients With Previously Treated Advanced Non–Small-Cell Lung Cancer
Authors: Ronald B. Natale, Sumitra Thongprasert, F. Anthony Greco, Michael Thomas, Chun-Ming Tsai, Patrapim Sunpaweravong, David Ferry, Clive Mulatero, Robert Whorf, Joyce Thompson, Fabrice Barlesi, Peter Langmuir, Sven Gogov, Jacqui A. Rowbottom, Glenwood D. Goss
Journal: Journal of Clinical Oncology (2011)

Purpose Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling. This phase III study assessed the efficacy of vandetanib versus erlotinib in unselected patients with advanced non–small-cell lung cancer (NSCLC) after treatment failure with one to two prior cytotoxic chemotherapy regimens. Patients and Methods One thousand two hundred forty patients were randomly assigned to receive vandetanib 300 mg/d (n = 623) or erlotinib 150 mg/d (n = 617). The primary objective was to show superiority in progression-free survival (PFS) for vandetanib versus erlotinib. If the difference did not reach statistical significance for superiority, a noninferiority analysis was conducted. Results There was no significant improvement in PFS for patients treated with vandetanib versus erlotinib (hazard ratio [HR], 0.98; 95.22% CI, 0.87 to 1.10; P = .721); median PFS was 2.6 months for vandetanib and 2.0 months for erlotinib. There was also no significant difference for the secondary end points of overall survival (HR, 1.01; P = .830), objective response rate (both 12%), and time to deterioration of symptoms for pain (HR, 0.92; P = .289), dyspnea (HR, 1.07; P = .407), and cough (HR, 0.94; P = .455). Both agents showed equivalent PFS and overall survival in a preplanned noninferiority analysis. Adverse events (AEs; any grade) more frequent with vandetanib than erlotinib included diarrhea (50% v 38%, respectively) and hypertension (16% v 2%, respectively); rash was more frequent with erlotinib than vandetanib (38% v 28%, respectively). The overall incidence of grade ≥ 3 AEs was also higher with vandetanib than erlotinib (50% v 40%, respectively). Conclusion In patients with previously treated advanced NSCLC, vandetanib showed antitumor activity but did not demonstrate an efficacy advantage compared with erlotinib. There was a higher incidence of some AEs with vandetanib.
Scintigraphic Assessment of Left Ventricular Aneurysms
Authors: G.B. Hopkins, M.K. Kan, A.F. Salel
Journal: JAMA (1978)

Thirty-five patients with coronary artery disease and possible left ventricular aneurysm underwent routine clinical examination, gated cardiac blood pool scintigraphy, and radionuclide cineangiography. Thirty-three of the 35 patients had coronary angiography and contrast left ventriculography. Sixteen patients had segmental left ventricular akinesia or dyskinesia,and 17 demonstrated left ventricular hypokinesis on contrast ventriculograms. Two patients had aneurysm confirmed at autopsy. Routine clinical evaluation was not sufficient to separate patients with aneurysm from those with hypokinesis. Radionuclide cineangiography correctly identified all cases of aneurysm or hypokinesis. The cinescintigraphic technique was preferable to the gated cardiac blood pool technique for qualitatively assessing and classifying abnormal ventricular wall motion. There was good correlation of the left ventricular ejection fraction by contrast ventriculograms and gated scintigrams in patients with either aneurysm or hypokinesis. (<i>JAMA</i>240:2162-2165, 1978)
Temporal and topological clustering of diverged residues among enterobacterial dihydrofolate reductases.
Authors: Lorrie Daggett Garvin, Stephen C. Hardies
Journal: Molecular Biology and Evolution (1991)

The complete nucleotide and encoded amino acid sequences were determined for the dihydrofolate reductase (DHFR) from the bacteria Enterobacter aerogenes and Citrobacter freundii. These were compared with the closely related Escherichia coli DHFR sequence. The ancestral DHFR sequence common to these three species was reconstructed. Since that ancestor there have been seven, nine, and one amino acid replacements in E. coli, E. aerogenes, and C. freundii, respectively. In E. coli, five of its seven replacements were located in the beta-sheet portion of the protein, and all seven were located in a single restricted region of the protein. In E. aerogenes, all nine of its replacements were located within surface residues, with five clustered in a region topologically distinct from the E. coli cluster. The replaced side chains are sometimes in direct contact but more often are separated by an intervening side chain. It is argued that the temporal clustering of replacements is typical for the evolution of most proteins and that the associated topological clustering gives a picture of how evolutionary change is accommodated by protein structure.
The 30-Day LD-50 of Two Radiations of Different Ion Density
Authors: Joanne Weikel Hollcroft, Egon Lorenz
Journal: JNCI Journal of the National Cancer Institute (1951)

Journal Article The 30-Day LD-50 of Two Radiations of Different Ion Density Get access Joanne Weikel Hollcroft, Joanne Weikel Hollcroft National Cancer Institute2Bethesda, Md., and the Division of Biological and Medical Research, Argonne National Laboratory, Chicago, Ill. Search for other works by this author on: Oxford Academic PubMed Google Scholar Egon Lorenz Egon Lorenz National Cancer Institute2Bethesda, Md., and the Division of Biological and Medical Research, Argonne National Laboratory, Chicago, Ill. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 12, Issue 3, December 1951, Pages 533–544, https://doi.org/10.1093/jnci/12.3.533 Published: 01 December 1951 Article history Received: 20 September 1951 Published: 01 December 1951
Low concordance of multiple variant-calling pipelines: practical implications for exome and genome sequencing
Authors: Jason O'Rawe, Tao Jiang, Guangqing Sun, Yiyang Wu, Wei Wang, Jingchu Hu, Paul Bodily, Lifeng Tian, Hakon Hakonarson, W Evan Johnson, Zhi Wei, Kai Wang, Gholson J Lyon
Journal: Genome Medicine (2013)

To facilitate the clinical implementation of genomic medicine by next-generation sequencing, it will be critically important to obtain accurate and consistent variant calls on personal genomes. Multiple software tools for variant calling are available, but it is unclear how comparable these tools are or what their relative merits in real-world scenarios might be.We sequenced 15 exomes from four families using commercial kits (Illumina HiSeq 2000 platform and Agilent SureSelect version 2 capture kit), with approximately 120X mean coverage. We analyzed the raw data using near-default parameters with five different alignment and variant-calling pipelines (SOAP, BWA-GATK, BWA-SNVer, GNUMAP, and BWA-SAMtools). We additionally sequenced a single whole genome using the sequencing and analysis pipeline from Complete Genomics (CG), with 95% of the exome region being covered by 20 or more reads per base. Finally, we validated 919 single-nucleotide variations (SNVs) and 841 insertions and deletions (indels), including similar fractions of GATK-only, SOAP-only, and shared calls, on the MiSeq platform by amplicon sequencing with approximately 5000X mean coverage.SNV concordance between five Illumina pipelines across all 15 exomes was 57.4%, while 0.5 to 5.1% of variants were called as unique to each pipeline. Indel concordance was only 26.8% between three indel-calling pipelines, even after left-normalizing and intervalizing genomic coordinates by 20 base pairs. There were 11% of CG variants falling within targeted regions in exome sequencing that were not called by any of the Illumina-based exome analysis pipelines. Based on targeted amplicon sequencing on the MiSeq platform, 97.1%, 60.2%, and 99.1% of the GATK-only, SOAP-only and shared SNVs could be validated, but only 54.0%, 44.6%, and 78.1% of the GATK-only, SOAP-only and shared indels could be validated. Additionally, our analysis of two families (one with four individuals and the other with seven), demonstrated additional accuracy gained in variant discovery by having access to genetic data from a multi-generational family.Our results suggest that more caution should be exercised in genomic medicine settings when analyzing individual genomes, including interpreting positive and negative findings with scrutiny, especially for indels. We advocate for renewed collection and sequencing of multi-generational families to increase the overall accuracy of whole genomes.
Natural history of successive COPD exacerbations
Authors: Jadwiga A Wedzicha, Gavin C Donaldson
Journal: Thorax (2012)

Exacerbations of chronic obstructive pulmonary disease (COPD) are episodes of respiratory symptom worsening that are usually associated with infective triggers and variable amounts of airway and systemic inflammation.1 There has been much interest in COPD exacerbations as they lead to considerable morbidity, hospital admission and readmission and mortality. COPD exacerbations are the most important determinants of health status in COPD2 and are important targets for therapies both from the point of view of treating the event and prevention.

It is now known from a number of studies that COPD exacerbations affect disease progression3 ,4 and have an effect on accelerating forced expiratory volume in 1 s decline independent of cigarette smoking. Some patients with COPD across disease severities are particularly susceptible to exacerbations and are known as frequent exacerbators2 ,5 and these patients are at a greater risk of poor health status, faster disease progression and mortality. The best predictor of a subsequent exacerbation and hospital admission is a history of previous exacerbations.2 ,5 Thus, it is important to understand the natural history of exacerbations and especially how severe exacerbations evolve as these are associated with significant healthcare cost.

Most studies of the epidemiology of COPD exacerbations …
A requirement for Lim domain binding protein 1 in erythropoiesis
Authors: LiQi Li, Jan Y. Lee, Jennifer Gross, Sang-Hyun Song, Ann Dean, Paul E. Love
Journal: The Journal of Experimental Medicine (2010)

During erythrocyte development, the nuclear cofactor Lim domain binding protein 1 (Ldb1) functions as a core subunit of multiprotein DNA binding complexes that include the transcription factors Scl and Gata-1 and the Lim-only adapter Lmo2. Scl, Gata-1, and Lmo2 are each required for erythropoiesis, suggesting that Ldb1-nucleated transcription complexes regulate key steps during erythropoiesis. We documented a requirement for Ldb1 in erythropoiesis in mice. Analysis of ldb1(-/-) embryos revealed a critical requirement for Ldb1 during primitive erythropoiesis, and conditional inactivation of ldb1 at later stages of gestation and in adult mice demonstrated that Ldb1 is continuously required for both definitive erythropoiesis and megakaryopoiesis. Down-regulation of Ldb1 in erythroblasts inhibited the expression of multiple erythroid-specific and prosurvival genes. These results represent the first unequivocal demonstration of a role for Ldb1 in erythropoiesis in vivo and establish a critical function for Ldb1-nucleated complexes in regulating the erythroid/megakaryocyte transcriptional program.