tbuckley/cabot-search huggingface dataset:
Nasopharyngeal Brush Biopsies and Detection of Nasopharyngeal Cancer in a High-Risk Population
Authors: C. E. Tune, P.-G. Liavaag, J. L. Freeman, M. W. M. van den Brekel, T. Shpitzer, J. D. F. Kerrebijn, D. Payne, J. C. Irish, R. Ng, R. K. Cheung, H.-M. Dosch
Journal: JNCI Journal of the National Cancer Institute (1999)

BACKGROUND: Nasopharyngeal carcinoma (NPC) is an important tumor in many countries. Ethnic and regional factors strongly influence disease risk. NPC is usually diagnosed late in disease development, and 10-year survival rates are as low as 10%. Epstein-Barr virus (EBV), a possibly causative agent, is present in all cells of essentially all undifferentiated NPCs. We wished to determine the following: 1) whether an ambulatory nasopharyngeal brush biopsy could provide sufficient tumor cell DNA for the detection of EBV and 2) whether the detection of EBV in this locale reflects the presence of tumor cells or simply EBV carrier status. METHODS: We collected nasopharyngeal tissue via ambulatory brush biopsies from 21 patients with newly diagnosed NPC and from 157 subjects with other otolaryngologic complaints. The majority of study subjects were from high-risk populations. Sample DNA was analyzed for the presence of EBV genomic sequences by use of the polymerase chain reaction (PCR). RESULTS: Ninety-six percent of samples yielded sufficient DNA for PCR amplification. Nineteen of 21 patients with NPC brushed positive for EBV DNA, while all but two (1.3%) of 149 informative control subjects were negative for EBV (two-sided P <.0001). One of the EBV-positive control subjects had an EBV-positive inverted sinonasal papilloma; the other EBV-positive control subject exhibited no overt clinical disease. CONCLUSION: Demonstration of EBV DNA in nasopharyngeal brush biopsy specimens detects NPC with a sensitivity of at least 90% (95% confidence interval = 89.63%-91.32%) and a specificity of approximately 99% (95% confidence interval = 98.64%-98.68%). This technique merits further testing as a possible ambulatory screening strategy in high-risk populations.
EPIDEMIC YELLOW FEVER IN UPPER VOLTA
Authors: D. Baudon, J. Roux, P. Gazin, M.L. Huillier, J.F. Saluzzo, L. Bibane, T.R. Guiguemde, V. Robert, A. Stanghellini, J.F. Molez, J.L. Sartholi, M. Cornet, L. Some, B.R. Soudre
Journal: The Lancet (1984)
β2-Integrin and Notch-1 differentially regulate CD34+CD31+ cell plasticity in vascular niches
Authors: Yu-Tsung Shih, Mei-Cun Wang, Tung-Lin Yang, Jing Zhou, Ding-Yu Lee, Pei-Ling Lee, Shaw-Fang Yet, Jeng-Jiann Chiu
Journal: Cardiovascular Research (2012)

AimsThe implication of circulating haematopoietic CD34+ progenitors in the vasculature is unclear due to the lack of understanding of their characteristics and plasticity mediated by their cellular microenvironment. We investigated how vascular smooth muscle cells (SMCs) and their interactions with endothelial cells (ECs) affect the behaviour and plasticity of CD34+CD31+ progenitors and the underlying mechanisms.
Computational modeling of analogy: Destined ever to only be metaphor?
Authors: Ann Speed
Journal: Behavioral and Brain Sciences (2008)

Abstract The target article by Leech et al. presents a compelling computational theory of analogy-making. However, there is a key difficulty that persists in theoretical treatments of analogy-making, computational and otherwise: namely, the lack of a detailed account of the neurophysiological mechanisms that give rise to analogy behavior. My commentary explores this issue.
A Phase I Clinical Trial of Ad5.SSTR/TK.RGD, a Novel Infectivity-Enhanced Bicistronic Adenovirus, in Patients with Recurrent Gynecologic Cancer
Authors: Kenneth H. Kim, Igor Dmitriev, Janis P. O'Malley, Minghui Wang, Souheil Saddekni, Zhiying You, Meredith A. Preuss, Raymond D. Harris, Rosemarie Aurigemma, Gene P. Siegal, Kurt R. Zinn, David T. Curiel, Ronald D. Alvarez
Journal: Clinical Cancer Research (2012)

Ad5.SSTR/TK.RGD is an infectivity-enhanced adenovirus expressing a therapeutic thymidine kinase suicide gene and a somatostatin receptor (SSTR) that allows for noninvasive gene transfer imaging. The purpose of this study was to identify the maximum tolerated dose (MTD), toxicities, clinical efficacy, and biologic effects of Ad5.SSTR/TK.RGD in patients with recurrent gynecologic cancer.Eligible patients were treated intraperitoneally for 3 days with 1 × 10(9) to 1 × 10(12) vp/dose of Ad5.SSTR/TK.RGD followed by intravenous ganciclovir for 14 days. Toxicity and clinical efficacy were assessed using Common Toxicity Criteria (CTC) Adverse Events grading and Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Imaging using In-111 pentetreotide was obtained before and after treatment. Tissue samples were obtained to evaluate for gene transfer, generation of wild-type virus, viral shedding, and antibody response.Twelve patients were treated in three cohorts. The most common vector-related clinical toxicities were grade I/II constitutional or pain symptoms, experienced most often in patients treated at the highest dose. MTD was not identified. Five patients showed stable disease; all others experienced progressive disease. One patient with stable disease experienced complete resolution of disease and normalization of CA125 on further follow-up. Imaging detected increased In-111 pentetreotide retention in patients treated at the highest dose. Ancillary studies showed presence of Ad5.SSTR/TK.RGD virus and HSV1-tk expression in ascites samples collected at various time points in most patients treated within the higher dose cohorts.This study shows the safety, potential efficacy, and possible gene transfer imaging capacity of Ad5.SSTR/TK.RGD in patients with recurrent gynecologic cancer. Further development of this novel gene therapeutic appears to be warranted.
Worldwide patterns of haplotype diversity at 9p21.3, a locus associated with type 2 diabetes and coronary heart disease
Authors: Kaisa Silander, Hua Tang, Sean Myles, Eveliina Jakkula, Nicholas J Timpson, Luigi Cavalli-Sforza, Leena Peltonen
Journal: Genome Medicine (2009)

A 100 kb region on 9p21.3 harbors two major disease susceptibility loci: one for type 2 diabetes (T2D) and one for coronary heart disease (CHD). The single nucleotide polymorphisms (SNPs) associated with these two diseases in Europeans reside on two adjacent haplotype blocks with independent effects on disease. To help delimit the regions that likely harbor the disease-causing variants in populations of non-European origin, we studied the haplotype diversity and allelic history of the 9p21.3 region using 938 unrelated individuals from 51 populations (Human Genome Diversity Panel). We used SNP data from Illumina's 650Y SNP arrays supplemented with five additional SNPs within the region of interest. Haplotype frequencies were analyzed with the EM algorithm implemented in PLINK. For the T2D locus, the TT risk haplotype of SNPs rs10811661 and rs10757283 was present at similar frequencies in all global populations, while a shared 6-SNP haplotype that carries the protective C allele of rs10811661 was found at a frequency of 2.9% in Africans and 41.3% in East Asians and was associated with low haplotype diversity. For the CHD locus, all populations shared a core risk haplotype spanning >17.5 kb, which shows dramatic increase in frequency between African (11.5%) and Middle Eastern (63.7%) populations. Interestingly, two SNPs (rs2891168 and rs10757278) tagging this CHD risk haplotype are most strongly associated with CHD disease status according to independent clinical fine-mapping studies. The large variation in linkage disequilibrium patterns identified between the populations demonstrates the importance of allelic background data when selecting SNPs for replication in global populations. Intriguingly, the protective allele for T2D and the risk allele for CHD show an increase in frequency in non-Africans compared to Africans, implying different population histories for these two adjacent disease loci.
Exercise during pregnancy and gestational diabetes-related adverse effects: a randomised controlled trial
Authors: Ruben Barakat, Mireia Pelaez, Carmina Lopez, Alejandro Lucia, Jonatan R Ruiz
Journal: British Journal of Sports Medicine (2013)

Objective To examine the effect of regular moderate-intensity exercise (three training sessions/week) on the incidence of gestational diabetes mellitus (GDM, primary outcome). We also examined if the exercise intervention modifies the association between GDM and birth weight and risk of macrosomia, gestational age, risk of caesarean delivery and maternal weight gain (secondary outcomes). Methods We randomly assigned 510 healthy gravida to either an exercise intervention or a usual care (control) group (n=255 each). The exercise programme focused on moderate-intensity resistance and aerobic exercises (three times/week, 50–55 min/session). GDM diabetes was diagnosed according to the WHO criteria and the International Association for Diabetes in Pregnancy Study Group (IADPSG). Results The intervention did not reduce the risk of developing GDM (OR 0.84, 95% CI 0.50 to 1.40) when using the WHO criteria. We observed that the intervention reduced by 58% the GDM-related risk (WHO criteria) of having a newborn with macrosomia (OR 1.76, 95% CI 0.04 to 78.90 vs 4.22, 95% CI 1.35 to 13.19) in exercise and control groups, respectively), and by 34% the GDM-related risk of having acute and elective caesarean delivery (OR 1.30, 95% CI 0.44 to 3.84 vs 1.99, 95% CI 0.98 to 4.06 in exercise and control groups, respectively). Gestational age was similar across the treatment groups (control, exercise) and GDM category (GDM or non-GDM), and maternal weight gain was ∼12% lower in the exercise group independent of whether women developed GDM. The results were similar when the IADPSG criteria were used instead. Conclusions Regular moderate-intensity exercise performed over the second-third trimesters of pregnancy can be used to attenuate important GDM-related adverse outcomes.
Fatal asthma in a young patient with severe bronchial hyperresponsiveness but stable peak flow records
Authors: M Saetta, G Thiene, S Crescioli, LM Fabbri
Journal: European Respiratory Journal (1989)

We report the sudden death of a 16 yr old boy with asthma. At presentation, the patient had symptoms of active asthma, mild bronchoconstriction, severe airway hyperresponsiveness to methacholine, and increased variability of peak expiratory flow records. After the patient was placed on inhaled beclomethasone (1 mg b.i.d preceded by inhaled fenoterol 0.4 mg b.i.d) he rapidly felt better, lung function improved, but airway responsiveness remained severe. Four months later, on the day he died, he was well until a fatal attack of asthma occurred around midnight without identifiable precipitating factors. Taken to hospital, he was dead on arrival. Necroscopy and microscopy showed the characteristic features of asthma death. This case report suggests that; a) asthma death may occur suddenly and unexpectedly; b) asthma death may not be prevented by long-term treatment with high-dose inhaled beclomethasone; c) severe bronchial hyperresponsiveness, even in the presence of stable peak flow records, may identify asthmatic patients at risk of sudden death.
Extreme Reconfiguration of Plastid Genomes in the Angiosperm Family Geraniaceae: Rearrangements, Repeats, and Codon Usage
Authors: M. M. Guisinger, J. V. Kuehl, J. L. Boore, R. K. Jansen
Journal: Molecular Biology and Evolution (2010)

Geraniaceae plastid genomes (plastomes) have experienced a remarkable number of genomic changes. The plastomes of Erodium texanum, Geranium palmatum, and Monsonia speciosa were sequenced and compared with other rosids and the previously published Pelargonium hortorum plastome. Geraniaceae plastomes were found to be highly variable in size, gene content and order, repetitive DNA, and codon usage. Several unique plastome rearrangements include the disruption of two highly conserved operons (S10 and rps2-atpA), and the inverted repeat (IR) region in M. speciosa does not contain all genes in the ribosomal RNA operon. The sequence of M. speciosa is unusually small (128,787 bp); among angiosperm plastomes sequenced to date, only those of nonphotosynthetic species and those that have lost one IR copy are smaller. In contrast, the plastome of P. hortorum is the largest, at 217,942 bp. These genomes have experienced numerous gene and intron losses and partial and complete gene duplications. Some of the losses are shared throughout the family (e.g., trnT-GGU and the introns of rps16 and rpl16); however, other losses are homoplasious (e.g., trnG-UCC intron in G. palmatum and M. speciosa). IR length is also highly variable. The IR in P. hortorum was previously shown to be greatly expanded to 76 kb, and the IR is lost in E. texanum and reduced in G. palmatum (11 kb) and M. speciosa (7 kb). Geraniaceae plastomes contain a high frequency of large repeats (>100 bp) relative to other rosids. Within each plastome, repeats are often located at rearrangement end points and many repeats shared among the four Geraniaceae flank rearrangement end points. GC content is elevated in the genomes and also in coding regions relative to other rosids. Codon usage per amino acid and GC content at third position sites are significantly different for Geraniaceae protein-coding sequences relative to other rosids. Our findings suggest that relaxed selection and/or mutational biases lead to increased GC content, and this in turn altered codon usage. We propose that increases in genomic rearrangements, repetitive DNA, nucleotide substitutions, and GC content may be caused by relaxed selection resulting from improper DNA repair.
Inhibition of GSK3β-mediated BACE1 expression reduces Alzheimer-associated phenotypes
Authors: Philip T.T. Ly, Yili Wu, Haiyan Zou, Ruitao Wang, Weihui Zhou, Ayae Kinoshita, Mingming Zhang, Yi Yang, Fang Cai, James Woodgett, Weihong Song
Journal: Journal of Clinical Investigation (2012)

Deposition of amyloid β protein (Aβ) to form neuritic plaques in the brain is the pathological hallmark of Alzheimer’s disease (AD). Aβ is generated from sequential cleavages of the β-amyloid precursor protein (APP) by the β- and γ-secretases, and β-site APP-cleaving enzyme 1 (BACE1) is the β-secretase essential for Aβ generation. Previous studies have indicated that glycogen synthase kinase 3 (GSK3) may play a role in APP processing by modulating γ-secretase activity, thereby facilitating Aβ production. There are two highly conserved isoforms of GSK3: GSK3α and GSK3β. We now report that specific inhibition of GSK3β, but not GSK3α, reduced BACE1-mediated cleavage of APP and Aβ production by decreasing BACE1 gene transcription and expression. The regulation of BACE1 gene expression by GSK3β was dependent on NF-κB signaling. Inhibition of GSK3 signaling markedly reduced Aβ deposition and neuritic plaque formation, and rescued memory deficits in the double transgenic AD model mice. These data provide evidence for regulation of BACE1 expression and AD pathogenesis by GSK3β and that inhibition of GSK3 signaling can reduce Aβ neuropathology and alleviate memory deficits in AD model mice. Our study suggests that interventions that specifically target the β-isoform of GSK3 may be a safe and effective approach for treating AD.
Peritoneal equilibration test results are different in infants, children, and adults.
Authors: S R Mendley, N L Majkowski
Journal: Journal of the American Society of Nephrology (1995)

Peritoneal equilibration test (PET) curves have been standardized in adult peritoneal dialysis (PD) patients. However, it appears that norms for pediatric PD patients may be different. A series of PET in 29 stable, chronic PD patients < or = 14 yr old performed at dwell volumes of 33 +/- 6 mL/kg with 2.5% Dianeal is reported. PET results for glucose and creatinine transport were compared between patients age < or = 2 and those 3 to 14 and published adult values by analysis of variance. Children < or = 2 transport glucose and creatinine more rapidly than do children 3 to 14 and adults. Children 3 to 14 transport glucose more rapidly than do adults; creatinine transport is not significantly different. These data demonstrate that transport characteristics differ between very young children, older children, and adults. Because PET are usually performed to plan mode of therapy, to address inadequate ultrafiltration, or to increase clearance, awareness of these results should assist in the clinical care of children on PD.
Divergent, Coexisting <i>Pseudomonas aeruginosa</i> Lineages in Chronic Cystic Fibrosis Lung Infections
Authors: David Williams, Benjamin Evans, Sam Haldenby, Martin J. Walshaw, Michael A. Brockhurst, Craig Winstanley, Steve Paterson
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Rationale: Pseudomonas aeruginosa, the predominant cause of chronic airway infections of patients with cystic fibrosis, exhibits extensive phenotypic diversity among isolates within and between sputum samples, but little is known about the underlying genetic diversity.Objectives: To characterize the population genetic structure of transmissible P. aeruginosa Liverpool Epidemic Strain in chronic infections of nine patients with cystic fibrosis, and infer evolutionary processes associated with adaptation to the cystic fibrosis lung.Methods: We performed whole-genome sequencing of P. aeruginosa isolates and pooled populations and used comparative analyses of genome sequences including phylogenetic reconstructions and resolution of population structure from genome-wide allele frequencies.Measurements and Main Results: Genome sequences were obtained for 360 isolates from nine patients. Phylogenetic reconstruction of the ancestry of 40 individually sequenced isolates from one patient sputum sample revealed the coexistence of two genetically diverged, recombining lineages exchanging potentially adaptive mutations. Analysis of population samples for eight additional patients indicated coexisting lineages in six cases. Reconstruction of the ancestry of individually sequenced isolates from all patients indicated smaller genetic distances between than within patients in most cases.Conclusions: Our population-level analysis demonstrates that coexistence of distinct lineages of P. aeruginosa Liverpool Epidemic Strain within individuals is common. In several cases, coexisting lineages may have been present in the infecting inoculum or assembled through multiple transmissions. Divergent lineages can share mutations via homologous recombination, potentially aiding adaptation to the airway during chronic infection. The genetic diversity of this transmissible strain within infections, revealed by high-resolution genomics, has implications for patient segregation and therapeutic strategies.
Quality of Abstracts Describing Randomized Trials in the Proceedings of American Society of Clinical Oncology Meetings: Guidelines for Improved Reporting
Authors: Monika K. Krzyzanowska, Melania Pintilie, Christine Brezden-Masley, Rebecca Dent, Ian F. Tannock
Journal: Journal of Clinical Oncology (2004)

To evaluate the quality of reporting in abstracts describing randomized controlled trials (RCTs) included in the Proceedings of American Society of Clinical Oncology (ASCO) meetings and to propose reporting guidelines for abstracts that are submitted to future meetings.Guidelines for reporting of RCTs in abstracts were developed by extracting key elements from published guidelines for full reports of RCTs, and modified based on an expert survey. Abstracts presenting results of RCTs with sample size > or = 200 were identified from the ASCO Proceedings for the years 1989 to 1998. Information regarding the quality of each abstract was extracted, and a quality score (possible range, 0 to 10) was assigned based on adherence to the guidelines.Brief description of the intervention, explicit identification of the primary end point, and presentation of results accompanied by statistical tests were regarded by experts as the most important items to include in an abstract, whereas presentation of secondary and subgroup analyses was the least important. Deficiencies in reporting were present in almost all of the 510 abstracts; for example, only 22% of the abstracts provided explicit identification of the primary end point. The median quality score was 5.5 (range, 2.0 to 8.5); the quality score improved with time (P <.0001) and was better for oral or plenary presentations (P =.0003).The quality of reporting of RCTs in abstracts submitted to Annual Meetings of ASCO is suboptimal. Although space precludes the inclusion of details required in the final report, abstracts could be improved through the use of explicit minimal guidelines, which are suggested in this article.
Efficacy and Safety of Trabectedin in Patients With Advanced or Metastatic Liposarcoma or Leiomyosarcoma After Failure of Prior Anthracyclines and Ifosfamide: Results of a Randomized Phase II Study of Two Different Schedules
Authors: George D. Demetri, Sant P. Chawla, Margaret von Mehren, Paul Ritch, Laurence H. Baker, Jean Y. Blay, Kenneth R. Hande, Mary L. Keohan, Brian L. Samuels, Scott Schuetze, Claudia Lebedinsky, Yusri A. Elsayed, Miguel A. Izquierdo, Javier Gómez, Youn C. Park, Axel Le Cesne
Journal: Journal of Clinical Oncology (2009)

To evaluate the safety and efficacy of trabectedin in a phase II, open-label, multicenter, randomized study in adult patients with unresectable/metastatic liposarcoma or leiomyosarcoma after failure of prior conventional chemotherapy including anthracyclines and ifosfamide.Patients were randomly assigned to one of two trabectedin regimens (via central venous access): 1.5 mg/m(2) 24-hour intravenous infusion once every 3 weeks (q3 weeks 24-hour) versus 0.58 mg/m(2) 3-hour IV infusion every week for 3 weeks of a 4-week cycle (qwk 3-hour). Time to progression (TTP) was the primary efficacy end point, based on confirmed independent review of images.Two hundred seventy patients were randomly assigned; 136 (q3 weeks 24-hour) versus 134 (qwk 3-hour). Median TTP was 3.7 months versus 2.3 months (hazard ratio [HR], 0.734; 95% CI, 0.554 to 0.974; P = .0302), favoring the q3 weeks 24-hour arm. Median progression-free survival was 3.3 months versus 2.3 months (HR, 0.755; 95% CI, 0.574 to 0.992; P = .0418). Median overall survival (n = 235 events) was 13.9 months versus 11.8 months (HR, 0.843; 95% CI, 0.653 to 1.090; P = .1920). Although somewhat more neutropenia, elevations in AST/ALT, emesis, and fatigue occurred in the q3 weeks 24-hour, this regimen was reasonably well tolerated. Febrile neutropenia was rare (0.8%). No cumulative toxicities were noted.Prior studies showed clinical benefit with trabectedin in patients with sarcomas after failure of standard chemotherapy. This trial documents superior disease control with the q3 weeks 24-hour trabectedin regimen in liposarcomas and leiomyosarcomas, although the qwk 3-hour regimen also demonstrated activity relative to historical comparisons. Trabectedin may now be considered an important new option to control advanced sarcomas in patients after failure of available standard-of-care therapies.