tbuckley/cabot-search huggingface dataset:
The Modified Pre-Transplant EBMT Risk Score Is Superior To The HCT-CI Score In Predicting Overall Survival and Non-Relapse Mortality After Allogeneic Hematopoietic Cell Transplantation In Patients With Acute Myeloid Leukemia
Authors: Fotios V. Michelis, Hans A. Messner, Jieun Uhm, Anna Lambie, Laura McGillis, Vikas Gupta, John Kuruvilla, Jeffrey H. Lipton, Dennis Dong Hwan Kim
Journal: Blood (2013)
Detection of livestock-associated meticillin-resistant Staphylococcus aureus CC398 in retail pork, United Kingdom, February 2015
Authors: N F Hadjirin, E M Lay, G K Paterson, E M Harrison, S J Peacock, J Parkhill, R N Zadoks, M A Holmes
Journal: Eurosurveillance (2015)

Livestock-associated meticillin-resistant Staphylococcus aureus belonging to clonal complex 398 (LA-MRSA CC398) is an important cause of zoonotic infections in many countries. Here, we describe the isolation of LA-MRSA CC398 from retail meat samples of United Kingdom (UK) farm origin. Our findings indicate that this lineage is probably established in UK pig farms and demonstrate a potential pathway for the transmission of LA-MRSA CC398 from livestock to humans in the UK.
Challenging the assumptions
Authors: CW Schmidt
Journal: Environmental Health Perspectives (2000)

chemicals and ionizing radiation.While an earlier study by other researchers did not find any correlation between increased placental UGT activity and maternal cigarette smoking, this study found a strong correlation for moth- ers who were both drug abusers and smokers.This suggests that illicit drugs compound the problems associated with smoking.The study also reports the discovery of a previously unknown placental biochemical marker activity.Among maternal drug abusers, P1OH correlated consistently with ECOD activity but not with EROD activity.However, P1OH correlated with EROD or testosterone hydroxylase activity only among the-cigarette smoking controls.The authors suggest that because ECOD and EROD activity always exhibit a positive correlation in normal cigarette smoking conditions., this may be evidence that in normal conditions a "silent" cytochrome P450 gene form may be responsible for P1OH activity.This change in the steroid metabolism profile in vitro suggests that maternal drug abuse may alter normal hormonal balance during pregnancy.The use of illicit drugs by pregnant women may disrupt placental metabolism and exacerbate the effects of smoking.
Abstract P050: Serum Fibroblast Growth Factor 23 and Incident Hypertension: The Atherosclerosis Risk in Communities Study
Authors: Amber L Fyfe-Johnson, Alvaro Alonso, Elizabeth Selvin, Sunil K Agarwal, James S Pankow, Julie K Bower, Pamela L Lutsey
Journal: Circulation (2014)

Background: Elevated serum fibroblast growth factor-23 (FGF23), an endogenous hormone, is associated with endothelial dysfunction, chronic kidney disease, arterial wall stiffness, and inflammation. These factors may contribute to an increased risk of hypertension. To date, the association of FGF23 with incident hypertension has not been examined. Hypothesis: Elevated serum FGF23 will be positively associated with risk of incident hypertension. Methods: The ARIC study measured intact FGF23 in stored serum from 7,948 middle-aged men and women without hypertension at baseline (1990-92). Participants were examined during two follow-up visits, in 1993-95 and 1996-98. Incident hypertension was determined by measured blood pressure (DBP 90 mm Hg, or SBP140 mm Hg) and/or hypertension medication use during the follow-up exams. Multivariate Cox proportional hazards regression models and complementary log-log models were used to adjust for potential confounding variables. Results: During a median follow-up of 5.9 years, 27% (2,152/7,948) participants developed hypertension. A nonlinear association between serum FGF23 and incident hypertension was observed; only the highest decile of serum FGF23 was positively associated with incident hypertension (Table). After adjustment for demographics, the hazard ratio for incident hypertension was 1.37 (95% CI: 1.17, 1.60) for the highest decile of FGF23 compared to the lowest quintile. After adjustment for behaviors and adiposity the HR was 1.25 (95% CI: 1.07, 1.46). The association was further attenuated in the final model after adjusting for renal function (HR: 1.20, 95% CI: 1.03, 1.41). Complementary log-log models that accounted for interval censoring did not alter results. Conclusions: High levels ( 60.6 pg/mL) of FGF23 are associated with a modestly increased risk of incident hypertension in the general population. Next steps include replication of these findings in other cohorts, and examining the association with a longer follow-up period.
A feasibility and safety study, of bronchoscopic hot saline ablation (BHSA) of emphysematous lung. A different emphysema therapy
Authors: David Stav, Noam Natiff, Isaac Shpirer
Journal: European Respiratory Journal (2013)

Aim:  We evaluated feasibility and safety of relatively simple approach of bronchoscopic lung volume reduction (LVR) technology, independent of collateral ventilation.   Description:  Six patients with severe upper lobes heterogeneous emphysema, underwent unilateral bronchoscopic instillation of saline thermal energy (temperature 50°C, average volume 130 ml) intending to induce an inflammatory airway and parenchymal and consequently fibrotic response resulting in LVR.   Evaluation:  Six men and women, with a mean age of 61 years, forced expiratory volume in 1 second (FEV 1 )) of 0.77 +/- 0.17 L (32% of predicted), residual volume (RV) of 4.1 +/- 0.9 L (219% predicted), and gas transfer of 7.8 +/- 2.2 (34% of predicted), underwent unilateral upper lobe treatments. Serious adverse events in 5 included probable bacterial pneumonia and exacerbations of airways disease in 2. Although no important FEV 1 ) or RV changes occurred during 6 months of follow-up, gas transfer improved, 16% to 9.0% +/- 2.1% (38% of predicted), the COPD assessment test (CAT) improved from 22 to 12,   Conclusion:  These preliminary data on unilateral BHSA therapy confirm feasibility, an acceptable safety profile, and the potential for efficacy of LVR in severe upper lobes emphysematous changes.
19-nor Vitamin-D Analogs: A New Class of Potent Inhibitors of Proliferation and Inducers of Differentiation of Human Myeloid Leukemia Cell Lines
Authors: Hiroya Asou, Michiaki Koike, Elena Elstner, Moray Cambell, Jennifer Le, Milan R. Uskokovic, Nanao Kamada, H. Phillip Koeffler
Journal: Blood (1998)
Progress toward prevention of cardiovascular disease. A 30-year retrospective.
Authors: R I Levy
Journal: Circulation (1979)

Since its creation as the National Heart Institute in 1948, the National Heart, Lung, and Blood Institute (NHLBI) has led a national biomedical research program in heart, lung, blood, and blood vessel diseases, and has become increasingly involved in complex clinical trials to validate its research findings. In addition, NHLBI sponsors demonstrations and educational activities to apply proved research findings in the health care community. NHLBI's approach to these responsibilities involves acquiring new and basic information, testing and evaluating the information, and applying it to improve prevention, detection, and treatment of disease. New equipment such as the heart-lung machine and the pacemaker, better diagnostic procedures, new operative and treatment devices, new drugs, and increased use of preventive medicine have dramatically reduced mortality from heart attack, hypertension and stroke.
Highly divergent neurovirulent vaccine-derived polioviruses of all three serotypes are recurrently detected in Finnish sewage
Authors: M Roivainen, S Blomqvist, H al-Hello, A Paananen, F Delpeyroux, M Kuusi, T Hovi
Journal: Eurosurveillance (2010)

In Finland, surveillance of potential re-emergence of poliovirus transmission is mainly based on environmental surveillance, i.e. search for infectious poliovirus in sewage samples. Since December 2008, 21 genetically highly divergent, neurovirulent vaccine-derived polioviruses (VDPV) have been isolated from sewage in Tampere, Finland. While the source of the VDPV is unknown, characteristics of the viruses resemble those of strains isolated from immunodeficient, persistently infected persons. No cases of suspected poliomyelitis have been reported in Finland since 1985.
Metabolism of steroid and amino acid moieties of conjugated bile acids in man
Authors: Gershon W. Hepner, Alan F. Hofmann, Paul J. Thomas
Journal: Journal of Clinical Investigation (1972)

Chenodeoxycholyl-2,4-(3)H-glycine-1-(14)C and deoxycholyl-2,4-(3)H-glycine-1-(14)C were synthesized and administered orally to 10 healthy subjects. Distribution of radioactivity among bile acids and specific activity of steroid and amino acid moieties were determined in bile samples. (3)H and (14)C were measured in feces. (14)C in breath was calculated from interval (14)CO(2) specific activity determinations. The daily fractional turnover of the glycine moiety of chenodeoxycholyl and deoxycholylglycines was more than three times that of the steroid moiety. Pool size of chenodeoxycholylglycine was about twice that of deoxycholylglycine, but similar fractional turnover rates of steroid and amino acid moieties suggested that intestinal absorption of the two conjugated bile acids was equally efficient (about 95%). The amount of unlabeled deoxycholic acid (newly formed by bacterial 7alpha-dehydroxylation) absorbed from the intestine approximated 30% of the cholic acid that was lost. (3)H radioactivity remained predominantly in administered bile acid implying that, normally, secondary bile acids derived from chenodeoxycholic acid are not appreciably absorbed from the intestine and that deoxycholic acid is not hydroxylated by the liver. Approximately 25% of administered (14)C was recovered in the breath in the first 24 hr and less than 8% in the feces in 8 days; (14)CO(2) excretion correlated highly with fractional turnover of the glycine moiety. (3)H appeared predominantly in feces, and the rate of excretion correlated highly with the fractional turnover of the steroid moiety of bile acids. From the results in this paper plus previous measurements on the metabolism of cholylglycine, we calculated that about 6 mmoles/day of glycine is used for bile acid conjugation in health.
Abstract 11865: Electrical Reverse Remodeling Associated with Improvements in Mechanical Dyssynchrony and Ventricular Function After Cardiac Resynchronization Therapy
Authors: Hideyuki Hara, Olusegun A Oyenuga, Evan C Adelstein, David Schwartzman, Samir Saba, John Gorcsan
Journal: Circulation (2011)

Background: Although cardiac resynchronization therapy (CRT) has been shown to benefit heart failure (HF) patients with widened QRS and mechanical dyssynchrony by left ventricular (LV) reverse remo...
Placenta growth factor promotes autophagy in lung epithelial cell through JNK and p38 MAPK pathway
Authors: Shih-Lung Cheng
Journal: European Respiratory Journal (2013)

Purpose: Increased placenta growth factor (PlGF) level was discovered in patients with chronic obstructive pulmonary disease (COPD). Autophagy was emerging importance in pulmonary disease, exp COPD. However, underlying mechanism between PlGF and autophagy was still unknown.  Materials and Methods: In this study, the stimulated concentrations of PlGF were 25, 50, 100 pg/ml respectively for apoptosis detection in human lung epithelial cells (S-cells). Quantification with autophagy was measured by the Fluorescein microscope for GFP detection and LC3B II expression. Besides, signaling pathways with different kinases were also assayed with ELISA and Western Blotting. Besides, in vivo with animal study with instillation procine pancreatic elastase (PPE) from trachea was also performed for evaluation.  Results: In cultured human bronchial epithelial cells, PlGF (dose: 100ng/ml) induced LC3B II expression by over 3-fold (p  Conclusion: Our findings revealed that PlGF induced autophagy with LC3B II over-expression in vitro and vivo study and underlying mechanism was via JNK and p38 MAPK signaling cascades. Further studies should be performed in human lung tissue for confirmation.
Is Undergraduate Otoscopy Teaching Adequate?-An Audit of Clinical Teaching
Authors: E W Fisher, A G Pfleiderer
Journal: Journal of the Royal Society of Medicine (1992)

Otoscopy is an important skill for the general practitioner, yet skill in the technique is rarely assessed formally at undergraduate level. This study aimed to assess the effect of teaching on the acquisition of otoscopic skill. Thirty-five medical students were assessed prospectively during their ENT attachments. Seventeen students were randomized to the standard course and 18 attended an additional seminar on otoscopy. Students' confidence was assessed for various aspects of otoscopy using a visual analogue scale, and clinical skill was assessed in examining four patients. Assessments took place at the beginning and end of the course. Students gained in their confidence and skill for all parameters, although the clinical ability to distinguish normal from abnormal tympanic membranes changed little from baseline levels. Extra teaching produced better gains in confidence (P&lt;0.05) and skill (P&lt;0.01) in identifying specific features of the tympanic membrane and eliminated errors of the ‘false negative’ variety. A minimal investment in teaching effort produces appreciable gains in students' otoscopic skills. This has implication for the planning of undergraduate ENT courses and vocational training for general practice.
Abstract P3-06-27: BRCAness is important to identify TNBC subtype resistant to taxanes
Authors: Takashi Ishikawa, Kazutaka Narui, Kazuhiro Shimada, Kumiko Kida, Mari S Oba, Mikiko Tanabe, Yasushi Ichikawa, Sadatoshi Sugae, Itaru Endo
Journal: Cancer Research (2015)

Abstract BACKGROUND: Triple negative breast cancer (TNBC) is heterogeneous and consists of tumors associated with basal like, BRCA related and cancer stem cell (CSC) phenotypes. Although anti-cancer agents are substantial for treating TNBC, existing ones do not work in some subpopulation in TNBC at all. However, it has not been reported that subdivision of TNBC is useful for choosing ant-cancer agents. AIM: To examine whether subdividing TNBC is beneficial for tailored chemotherapy and to identify predictive factors for existing anti-cancer agents in TNBC. METHODS: Sixty-six TNBC cases from a randomized phase II trial comparing TCx6 (TC6) with FEC followed by docetaxel (FEC-D) as neoadjuvant chemotherapy for hormone receptor-negative breast cancer (Kanagawa Breast Oncology Group 1101 Study). TNBC was subdivided by 1) IHC of CK 5/6 and EGFR into basal- and non-basal subtypes, and 2) MLPA of BRCA1 into BRCA1 and non-BRCA1 subtypes. The pCR rates were examined according to each regimen and subtype. 3) The association of grade 3 pCR was examined with Ki-67, p53, aldehyde dehydrogenase (ALDH) 1 and topoisomerase 2A (topoIIα) by IHC and TOP2A by FISH for each regimen. RESULTS: 1) In basal subtype, the pCR rate was significantly higher for FEC-D (42.9%) compared with TC6 (13.6%) (p=0.033), but it was equivalent in non-basal subtype (FEC-D vs TC: 25.0% vs 36.4%, p=0.554). 2) In BRCA1 subtype, it was more significant (FEC-D vs TC: 53.8 % vs 13.3%, p=0.022). 3) An association between pCR and low ALDH1 expression was found in both FEC-D and TC6 (OR: 3.75 and 2.73). High topo IIα protein expression was associated with pCR in FEC-D (OR: 3.5). DISCUSSION: TC6 was less effective than FEC-D in basal subtype and BRCA1 subtype, showing that taxanes cannot exert their anticancer role in tumors with BRCA1 dysfunction. Although basal subtype may contain more BRCA1-defective tumors than non-basal subtype, MLPA of BRCA1 was better to identify subtype resistant to taxanes than CK5/6 and EGFR. ALDH1 predicted treatment efficacy, and could therefore represent a marker of resistance to conventional chemotherapy. Citation Format: Takashi Ishikawa, Kazutaka Narui, Kazuhiro Shimada, Kumiko Kida, Mari S Oba, Mikiko Tanabe, Yasushi Ichikawa, Sadatoshi Sugae, Itaru Endo. BRCAness is important to identify TNBC subtype resistant to taxanes [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-06-27.
Exploring drug delivery for the DOT1L inhibitor pinometostat (EPZ-5676): Subcutaneous administration as an alternative to continuous IV infusion, in the pursuit of an epigenetic target
Authors: Nigel J Waters, Scott R Daigle, Bruce N Rehlaender, Aravind Basavapathruni, Carly T Campbell, Tyler B Jensen, Brett F Truitt, Edward J Olhava, Roy M Pollock, Kim A Stickland, Angelos Dovletoglou
Journal: Journal of Controlled Release (2015)
Evaluation and management of anemia in the elderly
Authors: Lawrence Tim Goodnough, Stanley L. Schrier
Journal: American Journal of Hematology (2013)

Anemia is now recognized as a risk factor for a number of adverse outcomes in the elderly, including hospitalization, morbidity, and mortality. What constitutes appropriate evaluation and management for an elderly patient with anemia, and when to initiate a referral to a hematologist, are significant issues. Attempts to identify suggested hemoglobin levels for blood transfusion therapy have been confounded for elderly patients with their co-morbidities. Since no specific recommended hemoglobin threshold has stood the test of time, prudent transfusion practices to maintain hemoglobin thresholds of 9-10 g/dL in the elderly are indicated, unless or until evidence emerges to indicate otherwise.
Relationship of intracellular glutathione concentrations with the cytotoxicity of cisplatin, acetaminophen and arsenic in tumor cell lines
Authors: Farshad H. Shirazi, Mohamad Shokrzadeh, Laila Hosseinzadeh, Matsheal Molepo, Samya El-Harran, Rakesh Goel
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

1485 

Intracellular glutathione (GSHi) is one of the molecules considered to be a leading candidate involved in the detoxification of many chemicals including cisplatin (DDP), acetaminophen (ACT) and arsenic compounds (Olson, Poisoning & Drug Overdose , McGraw-Hill, 2004). Higher GSHi levels have been shown in cell lines that exhibit resistance to cisplatin (DDP) as well as the other platinum compounds (Fokkema E, et al. , Biochem Pharmacol ., 2002). However, we have previously shown that tumor cells’ GSHi levels during the exposure to cytotoxic agents are not as important as kinetics of GSHi during and after the end of exposure. To investigate the importance of GSHi in the prediction of resistance to cytotoxic agents, we have selected four different tumor cell lines: hepatic HepG2, lung A549, ovary SKOV3 and kidney LLC-PK1. IC50 was calculated using clonogenic assay after 1 hour exposure of these cell lines to different agents. GSHi was measured before, during and after exposure of each cell line to different agents of DDP, ACT and As2O3 (As) up to 48 hours post-exposure. As is ranked in [table][1] below, different cell lines have shown different cytotoxicity patterns (average of IC50s in brackets, SDs are deleted to save space) in respect to GSHi level (average of the percentage of change compare to baseline in brackets, SDs are deleted to save space) after 1 hour exposure to these agents. As indicated in the table, the GSHi levels in two cell lines (ie, HepG2 and LLC-PK1) were decreasing during the exposure to the three agents. However, the GSHi levels at the end of exposure to the three agents with the other two cell lines (ie A549 & SKOV3) were significantly higher than the baseline. Only two cell lines of LLC-PK1 (r2=1 and p=0.028) and HepG2 (r2=0.98 and p=0.085) have shown a good correlation of GSHi with IC50s for different agents. Experiments using GSH depleted cells and intracellular pharmacokinetics of GSHi are on going and these results will be presented at the congress. In conclusion, there is no consistent pattern of GSHi changes between different cell lines upon exposure to cisplatin, acetaminophen or As2O3 between these four cell lines.



![Figure][2]  [1]: #F1
 [2]: pending:yes
Medicine and multimedia: Cannabis and Cognitive Functioning
Authors: Philip Wilson
Journal: BMJ (1998)

Nadia Solowij







Cambridge University Press, £50, pp 290

ISBN 0 521 59114 7

———————

Rating: ★★★

People who have enjoyed using cannabis describe feelings of mild euphoria, pleasant alterations of perception, relaxation, and increased sociability. Others may experience anxiety, panic, or even psychotic reactions. Cannabis intoxication can produce measurable impairments in concentration and short term memory, difficulties in goal directed activity, slowed reaction times, and altered perceptions of the passage of time.

Despite public interest, and consequent generous research funding, evidence for persistent cognitive dysfunction has so far proved elusive. It is difficult to assess the level of intake of cannabinoids over a long period in humans, and other drug use may be a major confounder. Cannabinoids such as δ-9-tetrahydrocannabinol (THC) may lie in body fat stores for months, so the identification of irreversible cognitive effects requires the testing of subjects who have been drug free for a long period.

In the first part of her monograph Solowij presents a historical perspective on the neuroscience of cannabis. Early research on brain morphology in animals exposed to cannabis produced no obvious evidence for long term changes. The identification of a brain receptor with high affinity for THC in 1988 gave some direction to further work. Receptors are richly distributed in brain areas involved in memory and attention such as the hippocampus, and hippocampal lesions mimic many of the acute effects of cannabis. In animal models THC receptor function has been shown to change with chronic exposure, and the changes may explain tolerance to some of the acute cognitive effects of cannabis. A natural ligand, anandamide (from the Sanskrit word for bliss), was identified in 1992. Intriguingly, compounds extracted from chocolate have recently been shown to interact with cannabinoid receptors.

Since memory and attention are affected strongly by cannabis intoxication, and since long term users often complain of being easily distracted, the author developed an elegant experimental model for studying selective attention. Subjects were presented with auditory stimuli of varied tone and position, and asked to respond only to one type of stimulus by pushing a button. The more difficult the discrimination task, the poorer the performance of intoxicated subjects compared with controls.

Electroencephalograms entrained to the auditory signals (event related potentials) provide evidence that irrelevant stimuli are processed more fully in the brains of non-intoxicated long term users than in non-users. Long term cannabis users therefore seem to fail to ignore irrelevant stimuli. The longer the duration of cannabis use, the greater the effect.

Solowij argues that there are subtle effects of long term cannabis use which may, in some individuals, be irreversible. Whether the cognitive deficits she describes represent real handicap remains to be seen.