tbuckley/cabot-search huggingface dataset:
Prognostic Scoring System for Primary CNS Lymphomas: The International Extranodal Lymphoma Study Group Experience
Authors: Andrés J.M. Ferreri, Jean-Yves Blay, Michele Reni, Felice Pasini, Michele Spina, Achille Ambrosetti, Antonello Calderoni, Andrea Rossi, Vittorio Vavassori, Annarita Conconi, Liliana Devizzi, Françoise Berger, Maurilio Ponzoni, Bettina Borisch, Marianne Tinguely, Michele Cerati, Mario Milani, Enrico Orvieto, Juvenal Sanchez, Christine Chevreau, Stefania Dell’Oro, Emanuele Zucca, Franco Cavalli
Journal: Journal of Clinical Oncology (2003)

To identify survival predictors and to design a prognostic score useful for distinguishing risk groups in immunocompetent patients with primary CNS lymphomas (PCNSL).The prognostic role of patient-, lymphoma-, and treatment-related variables was analyzed in a multicenter series of 378 PCNSL patients treated at 23 cancer centers from five different countries.Age more than 60 years, performance status (PS) more than 1, elevated lactate dehydrogenase (LDH) serum level, high CSF protein concentration, and involvement of deep regions of the brain (periventricular regions, basal ganglia, brainstem, and/or cerebellum) were significantly and independently associated with a worse survival. These five variables were used to design a prognostic score. Each variable was assigned a value of either 0, if favorable, or 1, if unfavorable. The values were then added together to arrive at a final score, which was tested in 105 assessable patients for which complete data of all five variables were available. The 2-year overall survival (OS) +/- SD was 80% +/- 8%, 48% +/- 7%, and 15% +/- 7% (P =.00001) for patients with zero to one, two to three, and four to five unfavorable features, respectively. The prognostic role of this score was confirmed by limiting analysis to assessable patients treated with high-dose methotrexate-based chemotherapy (2-year OS +/- SD: 85% +/- 8%, 57% +/- 8%, and 24% +/- 11%; P =.0004).Age, PS, LDH serum level, CSF protein concentration, and involvement of deep structures of the brain were independent predictors of survival. A prognostic score including these five parameters seems advisable in distinguishing different risk groups in PCNSL patients. The proposed score and its relevance in therapeutic decision deserve to be validated in further studies.
Sex differences in human mate preferences: Evolutionary hypotheses tested in 37 cultures
Authors: David M. Buss
Journal: Behavioral and Brain Sciences (1989)

Abstract Contemporary mate preferences can provide important clues to human reproductive history. Little is known about which characteristics people value in potential mates. Five predictions were made about sex differences in human mate preferences based on evolutionary conceptions of parental investment, sexual selection, human reproductive capacity, and sexual asymmetries regarding certainty of paternity versus maternity. The predictions centered on how each sex valued earning capacity, ambition— industriousness, youth, physical attractiveness, and chastity. Predictions were tested in data from 37 samples drawn from 33 countries located on six continents and five islands (total N = 10,047). For 27 countries, demographic data on actual age at marriage provided a validity check on questionnaire data. Females were found to value cues to resource acquisition in potential mates more highly than males. Characteristics signaling reproductive capacity were valued more by males than by females. These sex differences may reflect different evolutionary selection pressures on human males and females; they provide powerful cross-cultural evidence of current sex differences in reproductive strategies. Discussion focuses on proximate mechanisms underlying mate preferences, consequences for human intrasexual competition, and the limitations of this study.
A nosocomial outbreak of influenza during a period without influenza epidemic activity
Authors: J.P. Horcajada, T. Pumarola, J.A. Martínez, G. Tapias, J.M. Bayas, M. de la Prada, F. García, C. Codina, J.M. Gatell, M.T. Jiménez de Anta
Journal: European Respiratory Journal (2003)

The objective of this study was to describe a nosocomial outbreak of influenza during a period without influenza epidemic activity in the community. Outbreak investigation was carried out in an infectious diseases ward of a tertiary hospital. Presence of two or more of the following symptoms were used to define influenza: cough, sore throat, myalgia and fever. Epidemiological survey, direct immunofluorescence, viral culture, polymerase chain reaction, haemagglutination-inhibition test in throat swabs and serology for respiratory viruses were performed. Twenty-nine of 57 healthcare workers (HCW) (51%) and eight of 23 hospitalised patients (34%) fulfilled the case definition. Sixteen HCW (55%) and three inpatients (37%) had a definitive diagnosis of influenza A virus infection (subtype H1N1). Among the symptomatic HCW, 93% had not been vaccinated against influenza that season. Affected inpatients were isolated and admissions in the ward were cancelled for 2 weeks. Symptomatic HCW were sent home for 1 week. On the seventeenth day of the outbreak the last case was declared. The incidence of cases in this outbreak of influenza, which occurred during a period without influenza epidemic activity in the community, was notably high. Epidemiological data suggest transmission from healthcare workers to inpatients. Most healthcare workers were not vaccinated against influenza. Vaccination programmes should be reinforced among healthcare workers.
The Periodicity of Sun-spots, Influenza, and Cancer
Authors: J. H. D. Webster
Journal: BMJ (1940)

<b>Objective</b> To compare the efficacy of surgery with disc prosthesis versus non-surgical treatment for patients with chronic low back pain. <b>Design</b> A prospective randomised multicentre study. <b>Setting</b> Five university hospitals in Norway. <b>Participants</b> 173 patients with a history of low back pain for at least one year, Oswestry disability index of at least 30 points, and degenerative changes in one or two lower lumbar spine levels (86 patients randomised to surgery). Patients were treated from April 2004 to September 2007. <b>Interventions</b> Surgery with disc prosthesis or outpatient multidisciplinary rehabilitation for 12-15 days. <b>Main outcome measures</b> The primary outcome measure was the score on the Oswestry disability index after two years. Secondary outcome measures were low back pain, satisfaction with life (SF-36 and EuroQol EQ-5D), Hopkins symptom check list (HSCL-25), fear avoidance beliefs (FABQ), self efficacy beliefs for pain, work status, and patients’ satisfaction and drug use. A blinded independent observer evaluated scores on the back performance scale and Prolo scale at two year follow-up. <b>Results</b> The study was powered to detect a difference of 10 points on the Oswestry disability index between the groups at two years. At two years there was a mean difference of −8.4 points (95% confidence interval −13.2 to −3.6) in favour of surgery. In the analysis of prespecified secondary outcomes, there were significant differences in favour of surgery for low back pain (mean difference −12.2, −21.3 to −3.1), patients’ satisfaction (63% (n=46) <i>v</i> 39% (n=26)), SF-36 physical component score (mean difference 5.8, 2.5 to 9.1), self efficacy for pain (mean difference 1.0, 0.2 to 1.9), and the Prolo scale (mean difference 0.9, 0.1 to 1.6). There were no significant differences in return to work, SF-36 mental component score, EQ-5D, fear avoidance beliefs, Hopkins symptom check list, drug use, and the back performance scale. One serious complication of leg amputation occurred during surgical revision of a polyethylene dislodgement. The drop-out rate was 20% (34) and the crossover rate was 6% (5). <b>Conclusions</b> Surgical intervention with disc prosthesis for chronic low back pain resulted in a significantly greater improvement in the Oswestry score compared with rehabilitation, but this improvement did not clearly exceed the prespecified minimally important clinical difference between groups of 10 points, and the data are consistent with a wide range of differences between the groups, including values well below 10 points. The potential risks of surgery and the substantial amount of improvement experienced by a sizeable proportion of the rehabilitation group also have to be incorporated into overall decision making. <b>Trial registration</b> NCT 00394732.
Good news is no news
Authors: L. Farrell
Journal: BMJ (1999)

Long ago I used to read Time magazine every week; I liked to be kept informed about what was happening round the world, in an objective and concise fashion.

Then I began to realise how inaccurate its coverage of the Northern Ireland troubles was, and my doubts began to grow. If its Irish coverage is inaccurate, I surmised, the rest of its reports may be inaccurate as well. But flaws and lack of …
Intrinsic Defect in T Cell Production of Interleukin (IL)-13 in the Absence of Both IL-5 and Eotaxin Precludes the Development of Eosinophilia and Airways Hyperreactivity in Experimental Asthma
Authors: Joerg Mattes, Ming Yang, Surendran Mahalingam, Joachim Kuehr, Dianne C. Webb, Ljubov Simson, Simon P. Hogan, Aulikki Koskinen, Andrew N.J. McKenzie, Lindsay A. Dent, Marc E. Rothenberg, Klaus I. Matthaei, Ian G. Young, Paul S. Foster
Journal: The Journal of Experimental Medicine (2002)

Interleukin (IL)-5 and IL-13 are thought to play key roles in the pathogenesis of asthma. Although both cytokines use eotaxin to regulate eosinophilia, IL-13 is thought to operate a separate pathway to IL-5 to induce airways hyperreactivity (AHR) in the allergic lung. However, identification of the key pathway(s) used by IL-5 and IL-13 in the disease process is confounded by the failure of anti–IL-5 or anti–IL-13 treatments to completely inhibit the accumulation of eosinophils in lung tissue. By using mice deficient in both IL-5 and eotaxin (IL-5/eotaxin−/−) we have abolished tissue eosinophilia and the induction of AHR in the allergic lung. Notably, in mice deficient in IL-5/eotaxin the ability of CD4+ T helper cell (Th)2 lymphocytes to produce IL-13, a critical regulator of airways smooth muscle constriction and obstruction, was significantly impaired. Moreover, the transfer of eosinophils to IL-5/eotaxin−/− mice overcame the intrinsic defect in T cell IL-13 production. Thus, factors produced by eosinophils may either directly or indirectly modulate the production of IL-13 during Th2 cell development. Our data show that IL-5 and eotaxin intrinsically modulate IL-13 production from Th2 cells and that these signaling systems are not necessarily independent effector pathways and may also be integrated to regulate aspects of allergic disease.
Contribution of Homoplasy and of Ancestral Polymorphism to the Evolution of Genes in Anthropoid Primates
Authors: Colm O'hUigin, Yoko Satta, Naoyuki Takahata, Jan Klein
Journal: Molecular Biology and Evolution (2002)

Molecular phylogenies of lineages that split from one another in short succession are often difficult to resolve because different loci and different sites within the same locus yield incongruent relationships. The incongruity is commonly attributed to two causes: differential assortment of ancestral polymorphisms and homoplasy. To assess the relative contribution of these two causes, sequences of 57 segments from 51 loci in six primate lineages (human, chimpanzee, gorilla, orangutan, macaque, and tamarin, abbreviated as H, C, G, O, M, and T, respectively) were subjected to "partitioning" analysis, in which phylogenetically informative sites were identified in all 15 pairwise comparisons of each of the 57 segments and tallied for their support or lack thereof for each of the theoretically possible phylogenies. The six lineages include one of the best known cases of a difficult-to-resolve phylogeny: the trichotomy (H, C, G), in which the three lineages may have diverged from each other within a short period of time. In this period many of the ancestral polymorphisms apparently persisted and yielded phylogenetically incongruent signals. By contrast, no ancestral polymorphism is expected to have survived during the interval separating the divergences of the O, M, and T lineages from the ancestor of the (H, C, G) group. Any phylogenetic incompatibilities at sites in the O, M, and T lineages relative to the (H, C, G) group are therefore presumably the result of homoplasy. The frequency of homoplasy estimated in this manner is unexpectedly high: 12% for the (H, C, G) clade and 19% for the (H, C, G, O) clade. At least three-quarters of the 48% incompatibility observed in the (H, C) clade is attributable to the sorting out of ancestral polymorphisms coupled with intragenic recombination. Possible reasons for this high level of homoplasy in the O, M, and T lineages are discussed, and a computer simulation has been carried out to produce a model explaining the observed data.
ACID-BASE COMPOSITION OF PANCREATIC JUICE AND BILE
Authors: James L. Gamble, Monroe A. McIver
Journal: The Journal of Experimental Medicine (1928)

Pancreatic juice contains fixed base at approximately the concentration found in the blood plasma. Chloride ion is present in concentrations varying from one-fourth to one-half the fixed base value and the remainder of the acid equivalence is composed of bicarbonate ion. Fixed base being a nearly stationary factor, variation of bicarbonate and thereby of alkalinity is referable to change in the concentration of chloride ion. In bile, as delivered by the liver, both the fixed base and chloride ion values correspond closely with their respective concentrations in blood plasma. In gall bladder bile, however, the concentration of fixed base is, roughly, double that in hepatic duct bile, and chloride ion has been almost entirely removed. From these data it may be inferred that loss of digestive secretions entering the duodenum will, in the absence of replacement of the materials contained, cause dehydration of the blood plasma and reduction of the plasma bicarbonate.
A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease
Authors: W. J. Lukiw
Journal: Journal of Clinical Investigation (2005)

Deficiency in docosahexaenoic acid (DHA), a brain-essential omega-3 fatty acid, is associated with cognitive decline. Here we report that, in cytokine-stressed human neural cells, DHA attenuates amyloid-β (Aβ) secretion, an effect accompanied by the formation of NPD1, a novel, DHA-derived 10,17S-docosatriene. DHA and NPD1 were reduced in Alzheimer disease (AD) hippocampal cornu ammonis region 1, but not in the thalamus or occipital lobes from the same brains. The expression of key enzymes in NPD1 biosynthesis, cytosolic phospholipase A2 and 15-lipoxygenase, was altered in AD hippocampus. NPD1 repressed Aβ42-triggered activation of proinflammatory genes while upregulating the antiapoptotic genes encoding Bcl-2, Bcl-xl, and Bfl-1(A1). Soluble amyloid precursor protein-α stimulated NPD1 biosynthesis from DHA. These results indicate that NPD1 promotes brain cell survival via the induction of antiapoptotic and neuroprotective gene-expression programs that suppress Aβ42-induced neurotoxicity.
Potentiation of Vitamin K Antagonists by High-Dose Intravenous Methylprednisolone
Authors: Nathalie Costedoat-Chalumeau, Zahir Amoura, Guy Aymard, Odile Sevin, Bertrand Wechsler, Patrice Cacoub, Le Thi Huong Du, Bertrand Diquet, Annick Ankri, Jean-Charles Piette
Journal: Annals of Internal Medicine (2000)

Oral anticoagulants and pulse high-dose intravenous methylprednisolone are often administered concomitantly, but no data on potential interactions are available.To assess possible potentiation of oral anticoagulation by high-dose intravenous methylprednisolone.Prospective cohort study.University hospital in Paris, France.10 consecutive patients concomitantly receiving methylprednisolone and oral anticoagulants (fluindione and acenocoumarol) and 5 consecutive controls receiving methylprednisolone alone.Serial determinations of the international normalized ratio (INR) and clotting factors during administration of pulse methylprednisolone. The total plasma fluindione concentration was determined in 3 patients.The mean INR was 2.75 (range, 2.02 to 3.81) at baseline and increased to 8.04 (range, 5.32 to 20.0) after methylprednisolone administration. Plasma fluindione concentrations and the INR increased after methylprednisolone administration. Methylprednisolone alone did not increase prothrombin time.The action of oral anticoagulants is potentiated by intravenous high-dose methylprednisolone. The INR should be monitored daily during concomitant administration of these medications.
Transplantation of Human Embryonic Stem Cell–Derived Alveolar Epithelial Type II Cells Abrogates Acute Lung Injury in Mice
Authors: Dachun Wang, John E Morales, Daniel G Calame, Joseph L Alcorn, Rick A Wetsel
Journal: Molecular Therapy (2010)

Respiratory diseases are a major cause of mortality and morbidity worldwide. Current treatments offer no prospect of cure or disease reversal. Transplantation of pulmonary progenitor cells derived from human embryonic stem cells (hESCs) may provide a novel approach to regenerate endogenous lung cells destroyed by injury and disease. Here, we examine the therapeutic potential of alveolar type II epithelial cells derived from hESCs (hES-ATIICs) in a mouse model of acute lung injury. When transplanted into lungs of mice subjected to bleomycin (BLM)-induced acute lung injury, hES-ATIICs behaved as normal primary ATIICs, differentiating into cells expressing phenotypic markers of alveolar type I epithelial cells. Without experiencing tumorigenic side effects, lung injury was abrogated in mice transplanted with hES-ATIICs, demonstrated by recovery of body weight and arterial blood oxygen saturation, decreased collagen deposition, and increased survival. Therefore, transplantation of hES-ATIICs shows promise as an effective therapeutic to treat acute lung injury. Respiratory diseases are a major cause of mortality and morbidity worldwide. Current treatments offer no prospect of cure or disease reversal. Transplantation of pulmonary progenitor cells derived from human embryonic stem cells (hESCs) may provide a novel approach to regenerate endogenous lung cells destroyed by injury and disease. Here, we examine the therapeutic potential of alveolar type II epithelial cells derived from hESCs (hES-ATIICs) in a mouse model of acute lung injury. When transplanted into lungs of mice subjected to bleomycin (BLM)-induced acute lung injury, hES-ATIICs behaved as normal primary ATIICs, differentiating into cells expressing phenotypic markers of alveolar type I epithelial cells. Without experiencing tumorigenic side effects, lung injury was abrogated in mice transplanted with hES-ATIICs, demonstrated by recovery of body weight and arterial blood oxygen saturation, decreased collagen deposition, and increased survival. Therefore, transplantation of hES-ATIICs shows promise as an effective therapeutic to treat acute lung injury.
Identification of Subsets of Neuroblastomas by Combined Histopathologic and N-myc Analysis
Authors: H Shimada, D O Stram, J Chatten, V V Joshi, Y Hachitanda, G M Brodeur, J N Lukens, K K Matthay, R C Seeger
Journal: JNCI Journal of the National Cancer Institute (1995)

Neuroblastomas show different histopathologic phenotypes, and the tumor cells can carry normal or multiple copies of the N-myc proto-oncogene (MYCN). Studies of the N-myc gene and histopathology of untreated primary neuroblastomas have demonstrated that both these factors are important in risk assessment.Our purpose was to determine if there are any associations between N-myc gene copy number, histopathologic features, clinical stage, and progression-free survival (PFS) and if joint analyses of histopathology and N-myc gene copy number improve risk assessment.The histopathologic phenotype and N-myc gene copy number were determined for 232 biopsy/surgery specimens obtained from untreated primary neuroblastoma patients. Tumors were classified as having favorable or unfavorable histology on the basis of Schwannian stroma (rich versus poor), neuroblastic differentiation (differentiating versus undifferentiated), and mitosis-karyorrhexis (fragmenting nucleus) index (MKI; high, intermediate, or low) in the context of age at diagnosis (Shimada classification). N-myc gene amplification was considered significant when the gene copy number was at least 10-fold higher than normal as determined by Southern blot analysis. Otherwise, tumors were classified as nonamplified for N-myc.Among 19 stroma-rich tumors, 11 had grossly visible neuroblastic nodules, and two of these had N-myc amplification. Of 213 stroma-poor tumors, 51 had N-myc amplification, all of which were undifferentiated, and 45 (88% of 51) had high MKI. This histologic phenotype was present in less than 10% of tumors with nonamplified N-myc. Of 162 stroma-poor tumors that showed nonamplified N-myc, 45 (28%) were differentiating and 121 (75%) had low MKI. Neuroblastomas of clinical stages I, II, and IV-S nearly always had favorable histology and no amplification of N-myc. Stage III (regional) and particularly stage IV (metastatic) tumors, however, frequently had unfavorable histologic features with or without N-myc amplification. The estimated PFS at the end of 4 years after diagnosis was 83% for patients whose tumors had favorable histology and no N-myc amplification. The estimated PFS for the patients whose neuroblastomas had unfavorable histology, however, was 29% without and 13% with N-myc amplification, respectively. Subsets of patients with stage II, III, or IV disease were identified by both histologic evaluation and N-myc analysis. Multivariate Cox regression analysis indicated that both the histologic and N-myc-based stratifications provided prognostic information that was independent of staging.Neuroblastomas with N-myc amplification have a characteristic histopathologic phenotype and an aggressive clinical course. In contrast, neuroblastomas without N-myc amplification exhibit a wide range of histologic features that can define prognostic subsets.
Phase II trial of patupilone in patients with brain metastases from breast cancer
Authors: D. M. Peereboom, C. Murphy, M. S. Ahluwalia, A. Conlin, A. Eichler, C. Van Poznak, J. Baar, P. Elson, A. D. Seidman
Journal: Neuro-Oncology (2014)

For patients with progressive breast cancer brain metastasis (BCBM) after whole brain radiotherapy (WBRT), few options exist. Patupilone is an epothilone that crosses the blood–brain barrier. We hypothesized that patupilone would produce a 35% 3-month CNS progression-free survival in women with BCBM after WBRT. This multicenter phase II trial included 2 cohorts. Group A included women with progressive BCBM after WBRT. Group B was an exploratory cohort of patients with either leptomeningeal metastases or untreated brain metastases. The primary goal was to observe a 35% 3-month CNS progression-free survival in Group A. The sample size was 45 for Group A and 10 for Group B. Patients received patupilone 10 mg/m2 once every 3 weeks until progression. Responses were scored according to the Macdonald criteria. Fifty-five patients (45 in Group A, 10 in Group B) enrolled. In Group A, the 3-month CNS progression-free survival was 27%, the median overall survival was 12.7 months, and the overall response rate was 9%. In Group B, which enrolled 5 patients with leptomeningeal disease and 5 with no prior WBRT, no responses occurred and 8 patients had CNS progression before 3 months. Systemic responses occurred in 15% of patients, including a complete response in liver metastases. Diarrhea occurred in 87% of patients; 25% had grade 3 and 4 adverse events. Patupilone in patients with BCBM did not meet the efficacy criteria and had significant gastrointestinal toxicity. Further study of brain-penetrant agents is warranted for patients with CNS metastases from breast cancer.