tbuckley/cabot-search huggingface dataset:
No Advantage of Dexamethasone Over Prednisolone for the Outcome of Standard- and Intermediate-Risk Childhood Acute Lymphoblastic Leukemia in the Tokyo Children's Cancer Study Group L95-14 Protocol
Authors: Shunji Igarashi, Atsushi Manabe, Akira Ohara, Masaaki Kumagai, Tomohiro Saito, Yuri Okimoto, Takehiko Kamijo, Keiichi Isoyama, Michiko Kajiwara, Manabu Sotomatsu, Ken-ichi Sugita, Kanji Sugita, Miho Maeda, Hiromasa Yabe, Akitoshi Kinoshita, Takashi Kaneko, Yasuhide Hayashi, Kouichiro Ikuta, Ryohji Hanada, Masahiro Tsuchida
Journal: Journal of Clinical Oncology (2005)

Purpose To evaluate whether dexamethasone (DEXA) yields a better outcome than prednisolone (PRED) in a prospective, randomized, controlled trial for the treatment of childhood acute lymphoblastic leukemia (ALL). Patients and Methods Two hundred thirty-one standard-risk (SR) patients and 128 intermediate-risk (IR) non–B-cell ALL patients were registered from March 1995 to March 1999. After random assignment in each group, the PRED arm patients received PRED 60 mg/m 2 during induction followed by PRED 40 mg/m 2 over four intensifications in the SR group and three intensifications in the IR group. DEXA arm patients received DEXA 8 mg/m 2 during induction and DEXA 6 mg/m 2 during the intensifications. The maintenance phase was continued until week 104. Results Event-free survival rates at 8 years in the DEXA and PRED arms were 81.1% ± 3.9% (n = 117) and 84.4% ± 5.2% (n = 114), respectively, in the SR group (P = .217) and 84.9% ± 4.6% (n = 62) and 80.4% ± 5.1% (n = 66), respectively, in the IR group (P = .625). The primary reason for treatment failure was marrow relapse. Only two extramedullary relapses occurred in the DEXA arm compared with seven relapses in the PRED arm. Although complications were more prevalent in the DEXA arm than in the PRED arm, fatal toxicity was rare both groups. Conclusion DEXA administered at 8 mg/m 2 during induction and 6 mg/m 2 during intensification showed no advantage over PRED administered at 60 mg/m 2 during induction and 40 mg/m 2 during intensification in both the SR and IR groups.
Molecular alterations of the IDH1 gene in AML: a Children's Oncology Group and Southwest Oncology Group study
Authors: P A Ho, T A Alonzo, K J Kopecky, K L Miller, J Kuhn, R Zeng, R B Gerbing, S C Raimondi, B A Hirsch, V Oehler, C A Hurwitz, J L Franklin, A S Gamis, S H Petersdorf, J E Anderson, G H Reaman, L H Baker, C L Willman, I D Bernstein, J P Radich, F R Appelbaum, D L Stirewalt, S Meshinchi
Journal: Leukemia (2010)
TYPHUS FEVER
Authors: Henry Pinkerton, G. M. Hass
Journal: The Journal of Experimental Medicine (1932)

In tissue cultures grown at 32 degrees C., typhus Rickettsiae increase rapidly within the cytoplasm of infected cells up to about the 14th day. At this time practically every cell is infected and the majority of cells are distended with organisms. This condition remains constant as long as successful cultures of the cells can be maintained (up to 52 days). Loss in virulence does not take place during this period in vitro. The number of Rickettsia-filled cells found in sections and the incubation period of the infection resulting from inoculation of cultures from each age group are definitely correlated. The behavior of typhus Rickettsiae in dividing cells is described and methods of spread of the infection other than by mitosis of cells are discussed. Normal tissues do not become infected in vitroto any considerable extent in spite of prolonged proximity to heavily infected cultures of scrotal sac exudate. Complete anaerobiosis and alterations in pH do not alter the intracellular location of the organism in tissue cultures. The organisms are not seen within nuclei of infected cells. They remain intact and infective for several weeks in cells which are kept alive but not multiplying. They disappear in less than 1 week, however, when the cells undergo degeneration.
Acute osteomyelitis in Nigerians with sickle cell disease.
Authors: W W Ebong
Journal: Annals of the Rheumatic Diseases (1986)

Acute osteomyelitis comprised 78 (29.3%) of the 266 major skeletal complications seen in 207 patients with sickle cell disease in a five and a half year period. Forty eight (61.5%) of the 78 patients were under the age of 15 years, and the mean age at onset was 12 years (range 9 months to 50 years). Osteomyelitis was often multifocal (in 42% of the cases) and associated with some life threatening disorders. Salmonella accounted for 50% of the 36 organisms isolated from 32 patients with bacteriologically confirmed diagnosis. The 9best guess9 antibiotic was a combination of chloramphenicol and cloxacillin. Medical treatment alone proved adequate in most cases. No deaths resulted, but 55% of the patients developed serious complications due partly to the severity of the disease and also to infection involving the epiphyses and joints.
Randomized phase II trial of gemcitabine–cisplatin with or without trastuzumab in HER2-positive non-small-cell lung cancer
Authors: U. Gatzemeier, G. Groth, C. Butts, N. Van Zandwijk, F. Shepherd, A. Ardizzoni, C. Barton, P. Ghahramani, V. Hirsh
Journal: Annals of Oncology (2003)
Statistical tests for differential expression in cDNA microarray experiments
Authors: Xiangqin Cui, Gary A Churchill
Journal: Genome biology (2003)

Extracting biological information from microarray data requires appropriate statistical methods. The simplest statistical method for detecting differential expression is the t test, which can be used to compare two conditions when there is replication of samples. With more than two conditions, analysis of variance (ANOVA) can be used, and the mixed ANOVA model is a general and powerful approach for microarray experiments with multiple factors and/or several sources of variation.
A–Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance—Part 30
Authors: N M DiMarco, N P West, L M Burke, S J Stear, L M Castell
Journal: British Journal of Sports Medicine (2012)

Part 30 includes just two supplements: potassium and prebiotics. The role of potassium in exercise metabolism has been well documented in the literature but it seems that its appearance as a component of electrolyte-replacement products is a custom, rather than a necessity, since it is widely found in the diet. By contrast, prebiotics are at the beginning of an investigative story which may conclude by finding some beneficial uses for athletes to promote immune or gastrointestinal (GI) health during times of increased stress.

### Potassium

#### Nancy DiMarco

Potassium (K+) is the major intracellular cation in the body, with ∼98% of the body potassium stores located inside the cells with a concentration maintained at about 145 mM. Its major functions are to promote contractility of ciac, smooth and skeletal muscle and to influence the regulation of nerve conduction through the influx of sodium (Na+) and efflux of K+ on either side of the nerve terminal, occurring at the rate of 107 ions per second. On the surface of a nerve terminal, there are voltage-dependent channels for K+. In humans, at least 15 different K+-specific voltage-dependent channels have been identified. The Na+/K+ ATPase, also known as the Na pump, is the primary active transporter system that maintains the high K+ and low Na+ intracellular concentrations. The plasma membrane ATPase of all mammalian cells catalyses the reaction: ATP→ADP+Pi with obligatory requirements for Na+ and K+ and Mg2+ required for the dephosphorylation of ATP. Muscle has an especially high activity of this P-type Na+ pump which has been estimated to use 60% to 70% of the ATP synthesised in nerve and muscle cells.1 2

For active individuals/athletes, sweat is the …
Gut microbiota disturbance during antibiotic therapy: a multi-omic approach
Authors: Ana Elena Pérez-Cobas, María José Gosalbes, Anette Friedrichs, Henrik Knecht, Alejandro Artacho, Kathleen Eismann, Wolfgang Otto, David Rojo, Rafael Bargiela, Martin von Bergen, Sven C Neulinger, Carolin Däumer, Femke-Anouska Heinsen, Amparo Latorre, Coral Barbas, Jana Seifert, Vitor Martins dos Santos, Stephan J Ott, Manuel Ferrer, Andrés Moya
Journal: Gut (2012)

<h3>Objective</h3> Antibiotic (AB) usage strongly affects microbial intestinal metabolism and thereby impacts human health. Understanding this process and the underlying mechanisms remains a major research goal. Accordingly, we conducted the first comparative omic investigation of gut microbial communities in faecal samples taken at multiple time points from an individual subjected to β-lactam therapy. <h3>Methods</h3> The total (16S rDNA) and active (16S rRNA) microbiota, metagenome, metatranscriptome (mRNAs), metametabolome (high-performance liquid chromatography coupled to electrospray ionisation and quadrupole time-of-flight mass spectrometry) and metaproteome (ultra high performing liquid chromatography coupled to an Orbitrap MS<sup>2</sup> instrument [UPLC-LTQ Orbitrap-MS/MS]) of a patient undergoing AB therapy for 14 days were evaluated. <h3>Results</h3> Apparently oscillatory population dynamics were observed, with an early reduction in Gram-negative organisms (day 6) and an overall collapse in diversity and possible further colonisation by ‘presumptive’ naturally resistant bacteria (day 11), followed by the re-growth of Gram-positive species (day 14). During this process, the maximum imbalance in the active microbial fraction occurred later (day 14) than the greatest change in the total microbial fraction, which reached a minimum biodiversity and richness on day 11; additionally, major metabolic changes occurred at day 6. Gut bacteria respond to ABs early by activating systems to avoid the antimicrobial effects of the drugs, while ‘presumptively’ attenuating their overall energetic metabolic status and the capacity to transport and metabolise bile acid, cholesterol, hormones and vitamins; host–microbial interactions significantly improved after treatment cessation. <h3>Conclusions</h3> This proof-of-concept study provides an extensive description of gut microbiota responses to follow-up β-lactam therapy. The results demonstrate that ABs targeting specific pathogenic infections and diseases may alter gut microbial ecology and interactions with host metabolism at a much higher level than previously assumed.
2010 ACCF/AHA Guideline for Assessment of Cardiovascular Risk in Asymptomatic Adults
Authors: Philip Greenland, Joseph S. Alpert, George A. Beller, Emelia J. Benjamin, Matthew J. Budoff, Zahi A. Fayad, Elyse Foster, Mark A. Hlatky, John McB. Hodgson, Frederick G. Kushner, Michael S. Lauer, Leslee J. Shaw, Sidney C. Smith, Allen J. Taylor, William S. Weintraub, Nanette K. Wenger
Journal: Journal of the American College of Cardiology (2010)
Isolation and partial characterization of the reduction-modifiable protein of Neisseria gonorrhoeae.
Authors: E J Lytton, M S Blake
Journal: The Journal of Experimental Medicine (1986)

We have isolated and purified the reduction-modifiable protein (protein III) from several strains of Neisseria gonorrhoeae. We have found them to be basic proteins (pI 8.6) and virtually identical. A similar but not identical protein was isolated from a meningococcal strain. Antibodies raised against this purified protein would absorb to whole bacteria, confirming that the protein is exposed on the surface of the organism.
Psychotherapy and Pharmacotherapy in Chronic Schizophrenia
Authors: LESTER GRINSPOON, JACK R. EWALT, RICHARD SHADER
Journal: American Journal of Psychiatry (1968)

The relative merits of psychotherapy alone and psychotherapy in conjunction with phenothiazine therapy were investigated in the treatment of 20 chronic schizophrenic patients. Psychotherapy alone produced no demonstrable change over a two-year period in the nondrug group. The combination of drug and psychotherapy reduced florid symptomatology and seemed, for some patients, to promote sensitivity in responding to loss and to make the patients more receptive to communication with therapists and others. The authors conclude that phenothiazine therapy is one of the most useful tools now available in the treatment of chronic schizophrenia.
Intracellular distribution of amyloid beta peptide and its relationship to the lysosomal system
Authors: Lin Zheng, Angel Cedazo-Minguez, Martin Hallbeck, Fredrik Jerhammar, Jan Marcusson, Alexei Terman
Journal: Translational Neurodegeneration (2012)

Amyloid beta peptide (Aβ) is the main component of extraneuronal senile plaques typical of Alzheimer's disease (AD) brains. Although Aβ is produced by normal neurons, it is shown to accumulate in large amounts within neuronal lysosomes in AD. We have recently shown that under normal conditions the majority of Aβ is localized extralysosomally, while oxidative stress significantly increases intralysosomal Aβ content through activation of macroautophagy. It is also suggested that impaired Aβ secretion and resulting intraneuronal increase of Aβ can contribute to AD pathology. However, it is not clear how Aβ is distributed inside normal neurons, and how this distribution is effected when Aβ secretion is inhibited.Using retinoic acid differentiated neuroblastoma cells and neonatal rat cortical neurons, we studied intracellular distribution of Aβ by double immunofluorescence microscopy for Aβ40 or Aβ42 and different organelle markers. In addition, we analysed the effect of tetanus toxin-induced exocytosis inhibition on the intracellular distribution of Aβ.Under normal conditions, Aβ was found in the small cytoplasmic granules in both neurites and perikarya. Only minor portion of Aβ was colocalized with trans-Golgi network, Golgi-derived vesicles, early and late endosomes, lysosomes, and synaptic vesicles, while the majority of Aβ granules were not colocalized with any of these structures. Furthermore, treatment of cells with tetanus toxin significantly increased the amount of intracellular Aβ in both perikarya and neurites. Finally, we found that tetanus toxin increased the levels of intralysosomal Aβ although the majority of Aβ still remained extralysosomally.Our results indicate that most Aβ is not localized to Golgi-related structures, endosomes, lysosomes secretory vesicles or other organelles, while the suppression of Aβ secretion increases intracellular intra- and extralysosomal Aβ.
Pulmonary arterial pressure during rest and exercise in healthy subjects: a systematic review
Authors: G. Kovacs, A. Berghold, S. Scheidl, H. Olschewski
Journal: European Respiratory Journal (2009)

According to current guidelines, pulmonary arterial hypertension (PAH) is diagnosed when mean pulmonary arterial pressure ( P̄ pa ) exceeds 25 mmHg at rest or 30 mmHg during exercise. Issues that remain unclear are the classification of P̄ pa values &lt;25mmHg and whether P̄ pa &gt;30 mmHg during exercise is always pathological. We performed a comprehensive literature review and analysed all accessible data obtained by right heart catheter studies from healthy individuals to determine normal P̄ pa at rest and during exercise. Data on 1,187 individuals from 47 studies in 13 countries were included. Data were stratified for sex, age, geographical origin, body position and exercise level. P̄ pa at rest was 14.0±3.3 mmHg and this value was independent of sex and ethnicity. Resting P̄ pa was slightly influenced by posture (supine 14.0±3.3 mmHg, upright 13.6±3.1 mmHg) and age (&lt;30 yrs: 12.8± 3.1mmHg; 30–50 yrs: 12.9±3.0 mmHg; ≥50 yrs: 14.7±4.0 mmHg). P̄ pa during exercise was dependent on exercise level and age. During mild exercise, P̄ pa was 19.4±4.8 mmHg in subjects aged &lt;50 yrs compared with 29.4±8.4 mmHg in subjects ≥50 yrs (p&lt;0.001). In conclusion, while P̄ pa at rest is virtually independent of age and rarely exceeds 20 mmHg, exercise P̄ pa is age-related and frequently exceeds 30 mmHg, especially in elderly individuals, which makes it difficult to define normal P̄ pa values during exercise.
Long-term follow-up of 61 coeliac patients diagnosed in childhood: evolution toward latency is possible on a normal diet
Authors: T. Matysiak-Budnik, G. Malamut, N. P.-M. de Serre, E. Grosdidier, S. Seguier, N. Brousse, S. Caillat-Zucman, N. Cerf-Bensussan, J. Schmitz, C. Cellier
Journal: Gut (2007)

Whether a life-long gluten-free diet (GFD) is necessary in all children with diagnosed coeliac disease (CD) remains debated. To address this question, a retrospective analysis of the clinical and biological status of adult coeliac patients diagnosed in childhood, who remained on a normal diet after gluten challenge and were clinically silent, was carried out.Patients aged 18-65 years with CD diagnosed in childhood were included. Clinical status, gluten intake, biological parameters of malabsorption, bone mineral density, human leucocyte antigen (HLA) genotype, serological markers of CD, and histological and immunohistochemical parameters in duodenal biopsies were recorded.Sixty-one patients had resumed a normal diet and were asymptomatic. Forty-eight showed different degrees of villous atrophy (silent CD), while 13 had no detectable atrophy (latent CD) on duodenal biopsies. Latent CD patients had significantly less osteopenia/osteoporosis (1/9 (11%) vs 23/33 (70%), p<0.001)), and lower T cell receptor (TCR) alphabeta+ intraepithelial T cell counts (38+/-20 vs 55+/-15, p<0.01) than silent CD patients. The mean age at diagnosis and first GFD was lower in latent than in silent patients (14.4+/-5 vs 40.1+/-47 months, p<0.05). Latent patients did not differ significantly from the seven control patients on a long-term GFD, except for a higher frequency of CD-specific serum antibodies. However, two latent patients relapsed clinically and histologically during subsequent follow-up.Long-term latency developed in about 20% of CD patients who remained symptom free after gluten reintroduction. This latency can be transient and thus a regular follow-up is mandatory. In silent patients, the increased risk of osteoporosis substantiates the need for a GFD.
Immunotherapy Targeting Folate Receptor Induces Cell Death Associated with Autophagy in Ovarian Cancer
Authors: Yunfei Wen, Whitney S. Graybill, Rebecca A. Previs, Wei Hu, Cristina Ivan, Lingegowda S. Mangala, Behrouz Zand, Alpa M. Nick, Nicholas B. Jennings, Heather J. Dalton, Vasudha Sehgal, Prahlad Ram, Ju-Seog Lee, Pablo E. Vivas-Mejia, Robert L. Coleman, Anil K. Sood
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Cancer cells are highly dependent on folate metabolism, making them susceptible to drugs that inhibit folate receptor activities. Targeting overexpressed folate receptor alpha (FRα) in cancer cells offers a therapeutic opportunity. We investigated the functional mechanisms of MORAB-003 (farletuzumab), a humanized mAb against FRα, in ovarian cancer models. Experimental Design: We first examined FRα expression in an array of human ovarian cancer cell lines and then assessed the in vivo effect of MORAB-003 on tumor growth and progression in several orthotopic mouse models of ovarian cancer derived from these cell lines. Molecular mechanisms of tumor cell death induced by MORAB-003 were investigated by cDNA and protein expression profiling analysis. Mechanistic studies were performed to determine the role of autophagy in MORAB-003–induced cell death. Results: MORAB-003 significantly decreased tumor growth in the high-FRα IGROV1 and SKOV3ip1 models but not in the low-FRα A2780 model. MORAB-003 reduced proliferation, but had no significant effect on apoptosis. Protein expression and cDNA microarray analyses showed that MORAB-003 regulated an array of autophagy-related genes. It also significantly increased expression of LC3 isoform II and enriched autophagic vacuolization. Blocking autophagy with hydroxychloroquine or bafilomycin A1 reversed the growth inhibition induced by MORAB-003. In addition, alteration of FOLR1 gene copy number significantly correlated with shorter disease-free survival in patients with ovarian serous cancer. Conclusions: MORAB-003 displays prominent antitumor activity in ovarian cancer models expressing FRα at high levels. Blockade of folate receptor by MORAB-003 induced sustained autophagy and suppressed cell proliferation. Clin Cancer Res; 21(2); 448–59. ©2014 AACR.
Raw feeling: A model for affective consciousness
Authors: Jack van Honk, Barak E. Morgan, Dennis J. L. G. Schutter
Journal: Behavioral and Brain Sciences (2007)

Seeking to unlock the secrets of consciousness, neuroscientists have been studying neural correlates of sensory awareness, such as meaningless randomly moving dots. But in the natural world of species' survival, “raw feelings” mediate conscious adaptive responses. Merker connects the brainstem with vigilance, orientating, and emotional consciousness. However, depending on the brain's phylogenetic level, raw feeling takes particular forms.
Right Ventricular Myocardium Derives From the Anterior Heart Field
Authors: Stéphane Zaffran, Robert G. Kelly, Sigolène M. Meilhac, Margaret E. Buckingham, Nigel A. Brown
Journal: Circulation Research (2004)

The mammalian heart develops from a primary heart tube, which is formed by fusion of bilateral cardiac territories in which myocardial and endothelial cells have already begun to differentiate from splanchnic mesoderm. A population of myocardial precursors has been identified in pharyngeal mesoderm, anterior to the early heart tube. Cell labeling studies have indicated that this novel territory, called the anterior heart field (AHF), gives rise to the myocardial wall of the outflow tract. We now report that not only the myocardium of the outflow tract but also myocardial cells of the embryonic right ventricle are derived from this source. Explants of pharyngeal mesoderm or of the early heart tube were cultured from transgenic mice in which transgene expression marks different regions of the heart. Pharyngeal mesoderm from 5 to 7 somite embryos gives rise to cardiomyocytes with right ventricular and outflow tract identities, whereas the heart tube as this stage has an essentially left ventricular identity. DiI labeling confirms that the early heart tube is destined to contribute to the embryonic left ventricle and indicates that right ventricular myocardium is added from extracardiac mesoderm. Retrospective clonal analysis of the heart at embryonic day (E) 10.5 reveals the existence of a clonal boundary in the interventricular region, which appears during ventricular septation, underlining different origins of the two ventricular compartments. This study demonstrates the differences in the embryological origin of right and left ventricular myocardium, which has important implications for congenital heart disease.