tbuckley/cabot-search huggingface dataset:
Improved analyses of human mtDNA sequences support a recent African origin for Homo sapiens.
Authors: D Penny, M Steel, P J Waddell, M D Hendy
Journal: Molecular Biology and Evolution (1995)

New quantitative methods are applied to the 135 human mitochondrial sequences from the Vigilant et al. data set. General problems in analyzing large numbers of short sequences are discussed, and an improved strategy is suggested. A key feature is to focus not on individual trees but on the general "landscape" of trees. Over 1,000 searches were made from random starting trees with only one tree (a local optimum) being retained each time, thereby ensuring optima were found independently. A new tree comparison metric was developed that is unaffected by rearrangements of trees around many very short internal edges. Use of this metric showed that downweighting hypervariable sites revealed more evolutionary structure than studies that weighted all sites equally. Our results are consistent with convergence toward a global optimum. Crucial features are that the best optima show very strong regional differentiation, a common group of 49 African sequences is found in all the best optima, and the best optima contain the 16 !Kung sequences in a separate group of San people. The other 86 sequences form a heterogeneous mixture of Africans, Europeans, Australopapuans, and Asians. Thus all major human lineages occur in Africa, but only a subset occurs in the rest of the world. The existence of these African-only groups strongly contradicts multiregional theories for the origin of Homo sapiens that require widespread migration and interbreeding over the entire range of H. erectus. Only when the multiregional model is rejected is it appropriate to consider the root, based on a single locus, to be the center of origin of a population (otherwise different loci could give alternative geographic positions for the root). For this data, several methods locate the root within the group of 49 African sequences and are thus consistent with the recent African origin of H. sapiens. We demonstrate that the time of the last common ancestor cannot be the time of major expansion in human numbers, and our results are thus also consistent with recent models that differentiate between the last common ancestor, expansion out of Africa, and the major expansion in human populations. Such a two-phase model is consistent with a wide range of molecular and archeological evidence.
Incidence and risk factors of central nervous system relapse in histologically aggressive non-Hodgkin's lymphoma uniformly treated and receiving intrathecal central nervous system prophylaxis: A GELA study on 974 patients
Authors: C. Haioun, C. Besson, E. Lepage, C. Thieblemont, D. Simon, C. Rose, H. Tilly, A. Sonet, P. Lederlin, M. Attal, J. Brière, F. Reyes
Journal: Annals of Oncology (2000)
Severe hepatic toxicity after treatment with vincristine and dactinomycin using single-dose or divided-dose schedules: a report from the National Wilms' Tumor Study.
Authors: D M Green, P Norkool, N E Breslow, J Z Finklestein, G J D'Angio
Journal: Journal of Clinical Oncology (1990)

To evaluate the effect of dactinomycin (AMD) dose and schedule on the frequency of severe hepatic toxicity in unirradiated National Wilms' Tumor Study-4 (NWTS-4) patients, we reviewed the records of 154 children randomized to single-dose AMD and 176 children randomized to divided-dose AMD administration. All the children also received vincristine in identical dose schedules for the first 10 weeks. The frequency of severe hepatic toxicity encountered in the early weeks of therapy was 14.3% (five of 35) among patients treated with 60 micrograms/kg of AMD, 3.7% (four of 108) among patients given 45 micrograms/kg, and 2.8% (five of 176) among patients treated with 15 micrograms/kg per dose times five doses (P = .025). The data suggest an increased frequency of severe hepatic toxicity with the higher, single-dose schedule of administration. However, the frequency of severe hepatic toxicity among the patients in the two remaining groups is markedly higher than the 0.4% observed among similar unirradiated patients in NWTS-3. The relationship of this toxicity to factors such as anesthetic agents, blood transfusions, intercurrent viral infection, or other presently unrecognized causes can be further evaluated only with a detailed investigation such as a case-control study.
Increased incidence of acute parvovirus B19 infections in Marseille, France, in 2012 compared with the 2002–2011 period
Authors: S. Aherfi, L. Ninove, C. Zandotti, P. Crepey, H. Richet, A. Nougairede, X. de Lamballerie, R.N. Charrel
Journal: Clinical Microbiology and Infection (2013)
The Relationship between Epidermal Growth Factor Receptor Mutations and Clinicopathologic Features in Non–Small Cell Lung Cancers
Authors: Masaki Tokumo, Shinichi Toyooka, Katsuyuki Kiura, Hisayuki Shigematsu, Kunitoshi Tomii, Motoi Aoe, Kouichi Ichimura, Toshihide Tsuda, Masaaki Yano, Kazunori Tsukuda, Masahiro Tabata, Hiroshi Ueoka, Mitsune Tanimoto, Hiroshi Date, Adi F. Gazdar, Nobuyoshi Shimizu
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Recent studies reported that clinical responsiveness to gefitinib was associated with somatic mutation of epidermal growth factor receptor (EGFR) gene in non–small cell lung cancers (NSCLC). Here, we investigated the relationship between EGFR mutation and clinicopathologic features. Experimental Design: EGFR mutational status of 120 NSCLCs was determined mainly in EGFR exons 18 to 21 by direct sequence and correlated with clinicopathologic parameters. Results: EGFR mutations were present in 38 cases (32%) and the majority of mutations were in-frame deletions of exon 19 (19 cases) and a missense mutation in exon 21 (18cases). EGFR mutations were frequently associated with adenocarcinoma (P &amp;lt; 0.0001), never smoker (P &amp;lt; 0.0001), and female gender (P = 0.0001). Of interest, increasing smoke exposure was inversely related to the rate of EGFR mutation (P &amp;lt; 0.0001). Multivariate analysis showed that smoking and histology were independent variables. Furthermore, gender difference was observed for the mutational location (P = 0.01) dominance of exon 19 for males and exon 21 for females. Twenty-one cases were treated with gefitinib and found that EGFR mutation was significantly related to gefitinib responsiveness (P = 0.002). In addition, median survival times of patients with and without EGFR mutations treated with gefitinib were 25.1 and 14.0 months, respectively. Patients with EGFR mutations had approximately 2-fold survival advantage; however, the difference was not significant. Conclusions: We show that EGFR mutations were significantly related to histology and smoke exposure and were a strong predictive factor for gefitinib responsiveness in NSCLC.
Breast cancer patients' quality of care: Does racial concordance matter or is it just a matter of trust?
Authors: K. P. Joseph, R. Franco, K. Fei, N. Bickell
Journal: Journal of Clinical Oncology (2009)

6537 Background: As insurers consider paying for performance and quality measures grow in importance, factors that affect patients' perceived quality of cancer care matter. Concordance by race in physician-patient relationships has been associated with patient satisfaction and use of health care, however how that is mediated is unclear. Methods: 210 of 300 eligible women stage I or II breast cancer at 1 of 8 participating NYC hospitals responded to our survey (70% response rate): 20% were African-American (AA), 40% were white, and 30% were Hispanic and 9% were other races. Trust is based on a validated scale and calibrated to a 100 point scale (Cronbach α = 0.76). Bivariate analyses and logistic models were used to identify factors associated with patient ratings of quality of care. Results: Only 55% of women rated the quality of their cancer care as excellent. AA women breast cancer patients were less likely to rate their care as excellent (p=0.004). Compared to women who didn't rate their care as excellent, those who rated it excellent had greater trust in their physician (p &lt; 0.0001) and indicated that were treated well by their physicians' office staff (p = 0.01). Of note, AA patients had lower levels of trust (p = 0.004). Women who were of the same race as their physician did not perceive better quality of care as compared to those who were not racially concordant (p = 0.18); nor did they have higher trust in their physician (p = 0.59). Multivariate models evaluating the role of patient race, education, income, knowing which physician to talk to, how well the staff treated the patient, and racial concordance with physician, found that trust in physician was significantly associated with patient perception of excellent quality care (aRR = 1.38; 95%CI: 1.03–1.65) and being AA was associated with worse perceived quality (aRR = 0.47; 95%CI: 0.21–0.88) (model c = 0.79; p &lt; 0.0001). Conclusions: Racial concordance between physicians and patients does not directly affect patients' perceived quality of care. However, women's trust in their physician and their perceived treatment by office staff are associated with excellent cancer care quality ratings. Efforts should be made to increase effective intercultural communication particularly among AA women in order to improve ratings of cancer care quality. No significant financial relationships to disclose.
Primary and secondary ciliary dyskinesia: Clinical phenotypes and their correlation with ciliary ultrastructural analysis
Authors: Deborah Snijders, Serena Calgaro, Ilaria Bertozzi, Silvia Quartesan, Ivana Kozuh, Francesca Lunardi, Maria Angela Cangiotti, Angelo Barbato
Journal: European Respiratory Journal (2013)

Ciliary dyskinesia (CD) is a disorder in ciliary beating that can either be primary (PCD) or secondary (SCD).  The aim of this study is to identify CD phenotypes by the correlation between clinical picture and ciliary ultrastructural analysis.  METHODS  We have retrospectively recruited 86 patients that have undergone ultrastructural analysis for a suspicion of PCD.  RESULTS  A total of 108 brushing have been analysed, of which 37 with PCD, 56 with SCD, 5 with normal ultrastructure (nEM). No differences were found in age at the diagnosis.  Children with nEM had a mean % of pathologic cilia of 8%, in respect to 41% in the SCD and 77% in the PCD group (p  The ultrastructural abnormalities between the children with PCD, SCD and nEM showed a significant difference not only in the % of pathologic cilia, but also in dynein arm, peripheral pair and microtubuli defects.  Situs inversus, respiratory distress, rhinitis, “wet” cough and bronchiectasis were significantly more seen in PCD (p  CONCLUSIONS  Classical PCD, easy to diagnose by TEM, should be able to be identified in an early, in order to preserve lung function.  The overlap of PCD and SCD in the symptoms caused by altered mucociliary clearance, and in the ultrastructural analysis makes diagnosis difficult.  PCD is likely to include milder phenotypes that may be manifested by subtle or no apparent structural defects and ciliary dysfunction.  Obviously the diagnosis of PCD is not only based on TEM results but includes also beating pattern and frequency analysis.  If the suspicion of PCD is high, further testing should be done in order to verify the diagnosis, such as nNO, IF of ciliated cells and genetic analysis.
Host Response to the Lung Microbiome in Chronic Obstructive Pulmonary Disease
Authors: Marc A. Sze, Pedro A. Dimitriu, Masaru Suzuki, John E. McDonough, Josh D. Campbell, John F. Brothers, John R. Erb-Downward, Gary B. Huffnagle, Shizu Hayashi, W. Mark Elliott, Joel Cooper, Don D. Sin, Marc E. Lenburg, Avrum Spira, William W. Mohn, James C. Hogg
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

The relatively sparse but diverse microbiome in human lungs may become less diverse in chronic obstructive pulmonary disease (COPD). This article examines the relationship of this microbiome to emphysematous tissue destruction, number of terminal bronchioles, infiltrating inflammatory cells, and host gene expression.Culture-independent pyrosequencing microbiome analysis was used to examine the V3-V5 regions of bacterial 16S ribosomal DNA in 40 samples of lung from 5 patients with COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 4) and 28 samples from 4 donors (controls). A second protocol based on the V1-V3 regions was used to verify the bacterial microbiome results. Within lung tissue samples the microbiome was compared with results of micro-computed tomography, infiltrating inflammatory cells measured by quantitative histology, and host gene expression.Ten operational taxonomic units (OTUs) was found sufficient to discriminate between control and GOLD stage 4 lung tissue, which included known pathogens such as Haemophilus influenzae. We also observed a decline in microbial diversity that was associated with emphysematous destruction, remodeling of the bronchiolar and alveolar tissue, and the infiltration of the tissue by CD4(+) T cells. Specific OTUs were also associated with neutrophils, eosinophils, and B-cell infiltration (P < 0.05). The expression profiles of 859 genes and 235 genes were associated with either enrichment or reductions of Firmicutes and Proteobacteria, respectively, at a false discovery rate cutoff of less than 0.1.These results support the hypothesis that there is a host immune response to microorganisms within the lung microbiome that appears to contribute to the pathogenesis of COPD.
Association of MBL2 polymorphism with Leg Ulcers Development in Sickle Cell Anemia Patients
Authors: Marcos André Cavalcanti Bezerra, Isabela Cristina Farias, Diego Arruda Falcão, Igor de Farias Domingos, Luana Laranjeira Prado, Mariana Rezende Bandeira Mello, Taciana Mendonça, Luydson Vasconcelos, Maria do Socorro Cavalcanti, Kleber Yotsumoto Fertrin, Antonio Lucena Araujo, Aderson da Silva Araujo, PatrÃ­cia Moura, Fernando Ferreira Costa
Journal: Blood (2014)
Proliferative capacity of mouse peritoneal macrophages in vitro.
Authors: B A van der Zeijst, C C Stewart, S Schlesinger
Journal: The Journal of Experimental Medicine (1978)

Thioglycolate-stimulated mouse peritoneal macrophages cultured in the presence of macrophage growth factor (MGF) will continue to proliferate when they are removed from culture dishes with the local anesthetic lidocaine and subcultured. The number of times the cells can be subcultured and remain in a proliferative state is dependent on the number of previous cell divisions. One precursor cell (colony-forming cell) yields about 2.6 X 10(4) daughter cells. When MGF is removed from actively proliferating macrophages, they leave the cell cycle and enter a "resting" condition. When MGF is readded, cells reenter the cell cycle and proliferate with the same doubling time as if MGF had not been removed. Membrane 5'-nucleotidase activity was used as a probe to identify the state of macrophage activation. Proliferating macrophage populations had significantly higher enzyme levels than stimulated macrophages cultured without MGF. These enzymes levels were, however, lower than those found for resident (unstimulated) macrophages.
Ifosfamide (IFO) is a valuable alternative to cisplatin (CDDP) for first-line chemotherapy (CT) in advanced non-small cell lung cancer (NSCLC): A meta-analysis
Authors: Thierry Berghmans, Marianne Paesmans, Anne-Pascale Meert, Marcello Tiseo, Jean-Paul Sculier
Journal: European Respiratory Journal (2013)

Background: CDDP is the cornerstone of CT in advanced NSCLC while presenting with substantial acute and chronic toxicity. IFO-based regimens were tested in 3 phase III trials with conflicting results. We aimed to compare IFO to CDDP regimens by meta-analysing those studies.  Methods: From each trial, we extracted an estimate of the hazard ratio (HR) for group comparisons and aggregated them into a combined HR. Individual patients’ data were used when available; otherwise HR and 95% CI were provided by the authors.  Results: Three trials are available for the meta-analysis. Sculier et al (2002) compared CDDP (plus carboplatin) with either gemcitabine (GEM)(CCG) or IFO (CCI) to IFO-GEM (IG). Berghmans et al (yet unpublished) randomised patients to CDDP-IFO-GEM (GIP), IG or CDDP-Docetaxel (DP). In the FAST trial (Boni et al, 2012), cisplatin-based regimens (GIP, CDDG-GEM) were compared to GEM-vinorelbine (VNR) and IFO-GEM-VNR.  Q HET: heterogeneity test; CI = confidence interval  Conclusion: Regimens with cisplatin and with ifosfamide are associated with similar survival (at least no detectable difference), suggesting that ifosfamide-based doublets are an alternative to cisplatin-based ones.
The psychological factors associated with poor compliance with treatment in asthma
Authors: CM Bosley, JA Fosbury, GM Cochrane
Journal: European Respiratory Journal (1995)

Poor patient compliance with inhaled medication is known to cause morbidity and mortality in asthma. The reasons for nonadherence are not fully understood. We wondered whether psychological factors, such as patient attitudes to asthma and its treatment, anxiety, depression, and interpersonal problems, may be related to asthma self-care and compliance. In a prospective study, 102 patients with asthma, aged 18-70 yrs, requiring treatment with regular inhaled corticosteroids and beta-agonists were recruited from a hospital out-patient clinic and four general practices in South East London. They underwent psychological assessment using the Hospital Anxiety and Depression Scale (HADS), the Inventory of Interpersonal Problems (IIP), and a semi-structured interview focusing on patient attitudes, self-care, compliance, social support and treatment beliefs. Patients were given terbutaline and budesonide turbohalers to use twice daily over 12 weeks. Turbohaler Inhalation Computers (TICs) recorded each inhalation, providing a measurement of compliance. Seventy two patients completed the study. Thirty seven took less than 70% of the prescribed dose over the study period or omitted doses for 1 week and were defined as noncompliant. The noncompliant group had a higher mean (SD) score for depression (4.7 (3.3)) than the compliant group (3.2 (2.5)). The sample had a high mean (SD) score for anxiety (8.3 (4.4)), but there was no significant difference between the compliant and noncompliant groups. Patients' self-report and clinicians' impressions of compliance were not good predictors of actual compliance. Using discriminant analysis, a model was obtained from the questionnaires and interview items, which correctly classified 74% of the patients as compliant or non-compliant.(ABSTRACT TRUNCATED AT 250 WORDS)
Enhanced responsiveness of endothelium in the growing/motile state to tumor necrosis factor/cachectin.
Authors: H Gerlach, H Lieberman, R Bach, G Godman, J Brett, D Stern
Journal: The Journal of Experimental Medicine (1989)

Some in vivo observations have suggested that growing or perturbed endothelium, such as that which occurs during angiogenesis, is more sensitive to the action of cytokines (TNF/cachectin, TNF, or IL-1) than normal quiescent endothelial cells. This led us to examine the responsiveness of endothelium to TNF as a function of the growth/motile state of the cell. TNF-induced modulation of endothelial cell surface coagulant function was half-maximal at a concentration of approximately 0.1 nM in subconfluent cultures, whereas 1-2 nM was required for the same effect in postconfluent cultures. Perturbation of endothelial cell shape/cytoskeleton was similarly more sensitive to TNF in subconfluent cultures. Consistent with these results, radioligand binding studies demonstrated high affinity TNF binding sites, Kd approximately 0.1 nM on subconfluent cultures, whereas only lower affinity sites (Kd approximately 1.8 nM) were detected on postconfluent cultures. The mechanisms underlying this change in the affinity of endothelium for TNF were studied in four settings. Crosslinking experiments with 125I-TNF and endothelium showed additional bands corresponding to Mr approximately 66,000 and approximately 84,000 with subconfluent cultures that were not observed with postconfluent cultures. Experiments with X-irradiated endothelium, whose growth but not motility was blocked, indicated that proliferation was not required for induction of high affinity TNF sites. Postconfluent endothelium, triggered to enter the proliferative cycle by microbutuble poisons, expressed high affinity TNF binding sites together with changes in cell shape/cytoskeleton well before their entry into S phase. Using wounded postconfluent monolayers, cells that migrated into the wound and those close to the wound edge displayed enhanced TNF binding and modulation of coagulant properties. These results suggest a model for targetting TNF action within the vasculature; regulation of high affinity endothelial cell binding sites can direct TNF to activated cells in particular parts of the vascular tree.
CMS Proposes Payment for Advance Care Planning Discussions
Authors: Julie A. Jacob
Journal: JAMA (2015)

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