tbuckley/cabot-search huggingface dataset:
High Rate of Durable Remissions After Treatment of Newly Diagnosed Aggressive Mantle-Cell Lymphoma With Rituximab Plus Hyper-CVAD Alternating With Rituximab Plus High-Dose Methotrexate and Cytarabine
Authors: Jorge E. Romaguera, Luis Fayad, Maria A. Rodriguez, Kristine R. Broglio, Frederick B. Hagemeister, Barbara Pro, Peter McLaughlin, Anas Younes, Felipe Samaniego, Andre Goy, Andreas H. Sarris, Nam H. Dang, Michael Wang, Virginia Beasley, L. Jeffrey Medeiros, Ruth L. Katz, Harish Gagneja, Barry I. Samuels, Terry L. Smith, Fernando F. Cabanillas
Journal: Journal of Clinical Oncology (2005)

To determine the response, failure-free survival (FFS), and overall survival rates and toxicity of rituximab plus an intense chemotherapy regimen in patients with previously untreated aggressive mantle-cell lymphoma (MCL).This was a prospective phase II trial of rituximab plus fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD; considered one cycle) alternating every 21 days with rituximab plus high-dose methotrexate-cytarabine (considered one cycle) for a total of six to eight cycles.Of 97 assessable patients, 97% responded, and 87% achieved a complete response (CR) or unconfirmed CR. With a median follow-up time of 40 months, the 3-year FFS and overall survival rates were 64% and 82%, respectively, without a plateau in the curves. For the subgroup of patients < or = 65 years of age, the 3-year FFS rate was 73%. The principal toxicity was hematologic. Five patients died from acute toxicity. Four patients developed treatment-related myelodysplasia/acute myelogenous leukemia, and three patients died while in remission from MCL. A total of eight treatment-related deaths (8%) occurred.Rituximab plus hyper-CVAD alternating with rituximab plus high-dose methotrexate and cytarabine is effective in untreated aggressive MCL. Toxicity is significant but expected. Because of the shorter FFS concurrent with significant toxicity in patients more than 65 years of age, this regimen is not recommended as standard therapy for this age subgroup. Larger prospective randomized studies are needed to define the role of this regimen in the treatment of MCL patients compared with existing and new treatment modalities.
AMITRIPTYLINE PLASMA-CONCENTRATION AND CLINICAL EFFECT
Authors: A Coppen, S Montgomery, K Ghose, V.A.Rama Rao, J Bailey, J Christiansen, P.L Mikkleson, H.M.Van Praag, F VAN DE POEL, E.J Minsker, V.G Kozulja, N Matussek, G Kungkunz, A Jørgensen
Journal: The Lancet (1978)
FOLFIRI regimen in advanced colorectal cancer: the experience of the Gruppo Oncologico dell'Italia Meridionale (GOIM)
Authors: E. Maiello, V. Gebbia, F. Giuliani, G. Paoletti, N. Gebbia, N. Borsellino, G. Cartenì, G. Pezzella, L. Manzione, S. Romito, M. Lopez, G. Colucci
Journal: Annals of Oncology (2005)
Papillomaviruses, p53, and cervical cancer
Authors: R.M.Camille Busby-Earle, C.Michael Steel, AlistairR.W Williams, Brian Cohen, ColinC Bird, A.L Børresen, Å Helland, J Nesland, R Holm, C Trope, J Kaern, JaneM Mcgregor, DavidA Levison, DonaldM Macdonald, CarmenC Yu
Journal: The Lancet (1992)
What happened to <i>Homo habilis?</i> (Language and mirror neurons)
Authors: Giacomo Rizzolatti
Journal: Behavioral and Brain Sciences (1998)

The evolutionary continuity between the prespeech functions of premotor cortex and its new linguistic functions, the main thesis of MacNeilage's target article, is confirmed by the recent discovery of “mirror” neurons in monkeys and a corresponding action-observation/action-execution matching system in humans. Physiological data (and other considerations) appear to indicate, however, that brachiomanual gestures played a greater role in language evolution than MacNeilage would like to admit.
Risk Factors of Autonomic and Sensory Nerve Dysfunction in Patients With Newly Diagnosed Type 1 Diabetes
Authors: Katalin Keresztes, Ildiko Istenes, Zsolt Hermányi, Peter Vargha, Istvan Barna, Peter Kempler
Journal: Diabetes Care (2003)

Autonomic neuropathy (AN) in patients with newly diagnosed type 1 diabetes was first described by Fraser et al. (1). Of the six patients examined, two had evidence of AN. In this study, autonomic dysfunction detected during the initial metabolic derangement in newly diagnosed diabetic patients was not reversible after a prolonged period of improved control, indicating that established alterations may occur from the time of diagnosis onward. Other authors (2,3) have also shown that standard cardiovascular reflex tests are able to detect AN in newly diagnosed diabetic patients. A relationship between the severity of AN and prolongation of the corrected QT interval has also been noted (4).

According to the results of the EURODIAB IDDM Complications Study, the development of neuropathy is related to cardiovascular risk factors (5). The EURODIAB Prospective Complications Study (6) also confirms this finding.

However, there are no data regarding potential risk factors of nerve dysfunction in patients with newly diagnosed type 1 diabetes. We examined 40 patients with newly diagnosed type 1 …
Abolishing prescription charges for generic drugs should be considered, NHS Confederation says
Authors: Adrian O'Dowd
Journal: BMJ (2006)

NHS managers are considering the benefits of a system in which prescriptions for all generic drugs are free, MPs were told last week.

A system that made generic drugs free and that charged patients only if they wanted a branded drug could help improve equity in the NHS, while providing a choice of drugs, said the NHS Confederation, the representative body for NHS organisations.

The confederation's chief executive, Gill Morgan, was giving evidence to the parliamentary select committee on health as part of its inquiry into NHS charges, which are also known as co-payments.

Dame Gill said: “My personal …
Docetaxel and carboplatin is an active regimen in advancednon-small-cell lung cancer: a phase II study in Caucasian and Asian patients
Authors: M.J. Millward, M.J. Boyer, M. Lehnert, S. Clarke, D. Rischin, B.-C. Goh, J. Wong, E. McNeil, J.F. Bishop
Journal: Annals of Oncology (2003)
Effects of Photochemical Air Pollution and Allergen Exposure on Upper Respiratory Tract Inflammation in Asthmatics
Authors: T. J. N. HILTERMANN, C. R. de BRUIJNE, J. STOLK, A. H. ZWINDERMAN, F. Th. M. SPIEKSMA, W. ROEMER, P. A. STEERENBERG, P. H. FISCHER, L. van BREE, P. S. HIEMSTRA
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Asthma is an inflammatory disease of the airways, and exacerbations of this disease have been associated with high levels of air pollution. The objective of this study was to examine whether ambient air pollution and/or allergen exposure induces inflammatory changes in the upper airways of asthmatics. Sixty patients with intermittent to severe persistent asthma visited the Hospital's Out Patient Clinic every 2 wk for a period of 3 mo, and on each visit a nasal lavage was obtained. Associations between nasal inflammatory parameters and seasonal allergens and/or air pollution exposures were analyzed using linear regression analysis. The study ran from July 3 to October 6, 1995, during which period ozone (8-h mean: 80 μ g/m3) and PM10 (24-h mean: 40 μ g/m3) were the major air pollutants; the major aeroallergen was mugwort pollen (24-h mean: 27 pollen grains/m3). Effects on both cellular and soluble markers in nasal lavage were demonstrated for both ozone and mugwort pollen, but not for PM10. Ambient ozone exposure was associated with an increase in neutrophils (112% per 100 μ g/m3 increase in 8-h average ozone concentration), eosinophils (176%), epithelial cells (55%), IL-8 (22%), and eosinophil cationic protein (ECP) (19%). Increases in environmental mugwort pollen counts were associated with an increase in nasal eosinophils (107% per 100 pollen/m3) and ECP (23%), but not with neutrophils, epithelial cells, or IL-8. This study demonstrated that both ambient ozone and allergen exposure are associated with inflammatory responses in the upper airways of subjects with asthma, although the type of inflammation is qualitatively different.
Comment on: Harte et al. High Fat Intake Leads to Acute Postprandial Exposure to Circulating Endotoxin in Type 2 Diabetic Subjects. Diabetes Care 2012;35:375-382
Authors: Harald S. Hansen, Lise Moesby, Michael Timm, Erik W. Hansen
Journal: Diabetes Care (2013)

We read with great interest the article by Harte et al. (1), which reports that high intake of dietary fat results in increased levels of endotoxin in the blood of both type 2 diabetic patients and control subjects, thereby supporting an earlier article by Erridge et al. (2) who studied healthy subjects.

Low-grade inflammation is associated with obesity, and much evidence suggests that such chronic tissue inflammation is a key factor contributing to development of type 2 diabetes. Some of this inflammation may be caused by endotoxin from the gut microbiota, from where endotoxin may be absorbed together with dietary fat. In such a case, endotoxin should increase …
False-Positive Selection Identified by ML-Based Methods: Examples from the Sig1 Gene of the Diatom Thalassiosira weissflogii and the tax Gene of a Human T-cell Lymphotropic Virus
Authors: Yoshiyuki Suzuki, Masatoshi Nei
Journal: Molecular Biology and Evolution (2004)

Sexually induced gene 1 (Sig1) in the centric diatom Thalassiosira weissflogii is considered to encode a gamete recognition protein. Sorhannus (2003) analyzed nucleotide sequences of Sig1 using parsimony analysis and the maximum-likelihood (ML)-based Bayesian method for inferring positive selection at single amino acid sites and reported that positively selected sites were detected by the latter method but not by the former. He then concluded that for this type of study, the ML-based method is more reliable than parsimony analysis. Here we show that his results apparently represent false-positive cases of the ML-based method and that there is no solid evidence that this gene contains positively selected sites. We further demonstrate that in the tax gene of human T-cell lymphotropic virus type I (HTLV-I), all codon sites, including invariable sites, can be inferred as positively selected sites by the ML-based method. These observations indicate that the ML-based method may produce many false-positive sites. One of the main reasons for the occurrence of false positives is that in the ML-based method, codon sites are grouped into several categories, with different nonsynonymous/synonymous rate ratios (omegas), on a purely statistical basis, and positive selection is inferred indirectly by examining whether the average omega for each category is greater than 1. In parsimony analysis, however, the evolutionary change of nucleotides at each codon site is examined. For this reason, parsimony-based methods rarely produce false positives and are safer than ML-based methods for detecting positive selection at individual codon sites, although a large number of sequences are necessary.
Contrasting Maternal and Paternal Histories in the Linguistic Context of Burkina Faso
Authors: C. Barbieri, M. Whitten, K. Beyer, H. Schreiber, M. Li, B. Pakendorf
Journal: Molecular Biology and Evolution (2011)

Burkina Faso is located in the heart of West Africa and is a representative of the local structured patterns of human variability. Here, different cultures and languages are found in a geographic contiguity, as a result of several waves of migration and the succession of long- and short-term empires. However, historical documentation for this area is only partial, focusing predominantly on the recent empires, and linguistic surveys lack the power to fully elucidate the social context of the contact-induced changes. In this paper, we report Y-chromosomal data and complete mtDNA genome sequences for ten populations from Burkina Faso whose languages belong to two very distantly related branches of the Niger–Congo phylum, the Gur and Mande language families. In addition, two further populations, the Mande-speaking Mandenka from Senegal and the Yoruba from Nigeria, were included for regional comparison. We focus on the different historical trajectories undergone by the maternal and paternal lineages. Our results reveal a striking structure in the paternal line, which matches the linguistic affiliation of the ethnolinguistic groups, in contrast to the near-complete homogeneity of the populations in the maternal line. However, while the ancient structure along the linguistic lines is apparent in the Y-chromosomal haplogroup affiliation, this has clearly been overlain by more recent migrations, as shown by significant correlations between the genetic distances based on Y chromosome short tandem repeats and geographic distances between the populations, as well as by the patterns of shared haplotypes. Using the complete mtDNA sequences, we are able to reconstruct population size variation in the past, showing a strong sign of expansion in the concomitance with the Holocene Climate Optimum approximately 12,000–10,000 years ago, which has been suggested as the cause of the spread of the Niger–Congo phylum in the area. However, subsequent climatic fluctuations do not appear to have had an impact on the demography of the inhabitants of West Africa, probably reflecting the adaptive advantages of cultural innovations, such as pastoralism and agriculture.
Sensitive Detection of <i>BCR-ABL1</i> Mutations in Patients With Chronic Myeloid Leukemia After Imatinib Resistance Is Predictive of Outcome During Subsequent Therapy
Authors: Wendy T. Parker, Rebecca M. Lawrence, Musei Ho, Darryl L. Irwin, Hamish S. Scott, Timothy P. Hughes, Susan Branford
Journal: Journal of Clinical Oncology (2011)

Purpose BCR-ABL1 mutation analysis is recommended to facilitate selection of appropriate therapy for patients with chronic myeloid leukemia after treatment with imatinib has failed, since some frequently occurring mutations confer clinical resistance to nilotinib and/or dasatinib. However, mutations could be present below the detection limit of conventional direct sequencing. We developed a sensitive, multiplexed mass spectrometry assay (detection limit, 0.05% to 0.5%) to determine the impact of low-level mutations after imatinib treatment has failed. Patients and Methods Mutation status was assessed in 220 patients treated with nilotinib or dasatinib after they experienced resistance to imatinib. Results Mutations were detected by sequencing in 128 patients before commencing nilotinib or dasatinib therapy (switchover). In 64 patients, 132 additional low-level mutations were detected by mass spectrometry alone (50 of 132 mutations were resistant to nilotinib and/or dasatinib). When patients received the inhibitor for which the mutation confers resistance, 84% of the low-level resistant mutations rapidly became dominant clones detectable by sequencing, including 11 of 12 T315I mutations. Subsequent complete cytogenetic response rates were lower for patients with resistant mutations at switchover detected by sequencing (0%) or mass spectrometry alone (16%) compared with patients with other mutations or no mutations (41% and 49%, respectively; P &lt; .001). Failure-free survival among the 100 patients with chronic phase chronic myeloid leukemia when resistant mutations were detected at switchover by sequencing or mass spectrometry alone was 0% and 0% compared with 51% and 45% for patients with other mutations or no mutations (P = .003). Conclusion Detection of low-level mutations after imatinib resistance offers critical information to guide subsequent therapy selection. If an inappropriate kinase inhibitor is selected, there is a high risk of treatment failure with clonal expansion of the resistant mutant.
Fibrin Clot Retractile Activity in Normal, Established, and Tumorigenic Human Epithelial Cells in Culture<xref ref-type="fn" rid="FN2">2</xref>
Authors: B. Azzarone, A. Macieira-Coelho, L. Curatolo, D. Brouty-Boyé, O. Varnier, M. B. Donati, L. Morasca
Journal: JNCI Journal of the National Cancer Institute (1983)

Normal and established human epithelial cell lines obtained from the same organs were compared for their capacity to retract a fibrin clot. Fibrin clot retraction was maximal in normal epithelial cells, reduced in established nontumorigenic lines, and lost in tumorigenic cancer cell lines. Fibrin clot retraction efficiency seemed to be related to the degree of cellular spreading within the clot at the end of the test. Previous works and the present study suggest that fibrin clot retraction is correlated with some steps of cell transformation in vitro.
Treatment options for patients with triple-negative breast cancer
Authors: Rafael Santana-Davila, Edith A Perez
Journal: Journal of Hematology & Oncology (2010)

Breast cancer is a heterogeneous disease composed of different subtypes, characterized by their different clinicopathological characteristics, prognoses and responses to treatment. In the past decade, significant advances have been made in the treatment of breast cancer sensitive to hormonal treatments, as well as in patients whose malignant cells overexpress or amplify HER2. In contrast, mainly due to the lack of molecular targets, little progress has been made in the treatment of patients with triple-negative breast cancer. Recent improved understanding of the natural history, pathophysiology, and molecular features of triple-negative breast cancers have provided new insights into management and therapeutic strategies for women affected with this entity. Ongoing and planned translational clinical trials are likely to optimize and improve treatment of women with this disease.
Cure Violence: A Public Health Model to Reduce Gun Violence
Authors: Jeffrey A. Butts, Caterina Gouvis Roman, Lindsay Bostwick, Jeremy R. Porter
Journal: Annual Review of Public Health (2015)

Scholars and practitioners alike in recent years have suggested that real and lasting progress in the fight against gun violence requires changing the social norms and attitudes that perpetuate violence and the use of guns. The Cure Violence model is a public health approach to gun violence reduction that seeks to change individual and community attitudes and norms about gun violence. It considers gun violence to be analogous to a communicable disease that passes from person to person when left untreated. Cure Violence operates independently of, while hopefully not undermining, law enforcement. In this article, we describe the theoretical basis for the program, review existing program evaluations, identify several challenges facing evaluators, and offer directions for future research.
Spasmolytic polypeptide-expressing metaplasia (SPEM) in the gastric oxyntic mucosa does not arise from Lgr5-expressing cells
Authors: Ki Taek Nam, Ryan L O'Neal, Robert J Coffey, Paul E Finke, Nick Barker, James R Goldenring
Journal: Gut (2011)

Macdonald briefly discusses the geology of Mauna Kea. The rocks consist of the older Hamakua volcanic series, with a lower member composed largely of primitive basalts and an upper member containing more highly differentiated types, and the younger Laupahoehoe volcanic series composed largely of andesites, with which are interbedded glacial deposits. Besides the radial rift zones, Mauna Kea also shows concentric arcuate alignments of vents, indicating arcuate fractures occupied at depth by ring dikes or cone sheets. The arcuate alignment of vents appears to result from the intersection of shallow-seated radial fissures with the deeper arcuate intrusions.
Bezafibrate in men with lower extremity arterial disease: randomised controlled trial
Authors: T. Meade
Journal: BMJ (2002)

<b>Objective:</b> To assess the effect of bezafibrate on the risk of coronary heart disease and stroke in men with lower extremity arterial disease. <b>Design:</b> Double blind placebo controlled randomised trial. <b>Setting:</b> 85 general practices and nine hospital vascular clinics. <b>Participants:</b> 1568 men, mean age 68.2 years (range 35 to 92) at recruitment. <b>Interventions:</b> Bezafibrate 400 mg daily (783 men) or placebo (785 men). <b>Main outcome measures:</b> Combination of coronary heart disease and of stroke. All coronary events, fatal and non-fatal coronary events separately, and strokes alone (secondary end points). <b>Results:</b> Bezafibrate did not reduce the incidence of coronary heart disease and stroke. There were 150 and 160 events in the active and placebo groups respectively (relative risk 0.96, 95% confidence interval 0.76 to 1.21). There were 90 and 111 major coronary events in the active and placebo groups respectively (0.81, 0.60 to 1.08), of which 64 and 65 were fatal (0.95, 0.66 to 1.37) and 26 and 46 non-fatal (0.60, 0.36 to 0.99). Beneficial effects on non-fatal events were greatest in men aged &lt;65 years at entry, in whom benefit was also seen for all coronary events (0.38, 0.20 to 0.72). There were no significant effects in older men. There were 60 strokes in those on active treatment and 49 in those on placebo (1.34, 0.80 to 2.01). There were 204 and 195 deaths from all causes in the two groups respectively (1.03, 0.83 to 1.26). Bezafibrate reduced the severity of intermittent claudication for up to three years. <b>Conclusions:</b> Bezafibrate has no effect on the incidence of coronary heart disease and of stroke combined but may reduce the incidence of non-fatal coronary events, particularly in those aged &lt;65 years at entry, in whom all coronary events may also be reduced.
Asthma in Greenwich, UK: impact of the disease and current management practices
Authors: GB Marks, PG Burney, UN Premaratne, J Simpson, J Webb
Journal: European Respiratory Journal (1997)

A great deal of the care of patients with asthma takes place in general practices. The aim of the present study was to describe the impact of asthma in the community and to identify current asthma self-management practices. A two-part questionnaire survey was conducted in a random sample (23%; n=24,398) of persons aged 16-50 yrs, registered with one of the 41 general practices in Greenwich, London, UK. The two parts were: a screening questionnaire identifying persons with current asthma (defined as waking with shortness of breath in the last 12 months, attack of asthma in the last 12 months, or currently taking treatment for asthma); and an asthma questionnaire (completed by those with asthma) assessing quality of life, frequency of asthma symptoms, possession and use of self-management tools, and action in the event of an exacerbation of asthma. The crude response rate was 51%, but this may be an underestimate due to errors in the sampling frame. The prevalences of wheeze and asthma in the past 12 months were 26% and 14%, respectively. Among asthma patients: 43% reported symptoms occurring three or more times per week, and 20% were woken by asthma symptoms on three or more nights per week; most had asthma with a mild impact on quality of life; 26% used inhaled steroids on most days in the preceding month; 16% had a peak flow meter at home; and 7% had oral steroids available. Of the 44% of subjects with asthma, who could identify an exacerbation of asthma in the preceding 6 months: 19% had used a peak flow meter during the episode; 19% had changed their treatment without first being told to do so by a doctor; and 50% had sought urgent medical help. Smokers used less appropriate asthma management and subjects whose asthma had a severe impact on quality of life used more treatment and peak flow monitoring. In conclusion, the prevalence of asthma among adults in Greenwich, UK, has increased since a similar survey in 1986. Many people have fairly mild asthma and a smaller number have severe disease. Much remains to be done to promote appropriate strategies for self-management of asthma exacerbations.
915 SURVEILLANCE OF THIOPURINE INDUCED NODULAR REGENERATIVE HYPERPLASIA IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE BY TRANSIENT ELASTOGRAPHY (FIBROSCAN) OF THE LIVER
Authors: A. Ferlitsch, M. Homoncik, G. Ulbrich, T. Reiberger, A. Teml, W. Reinisch, A. Gangl, H. Vogelsang, M. Peck-Radosavljevic
Journal: Journal of Hepatology (2008)