tbuckley/cabot-search huggingface dataset:
Systematic prediction of health-relevant human-microbial co-metabolism through a computational framework
Authors: Almut Heinken, Ines Thiele
Journal: Gut Microbes (2015)

The gut microbiota is well known to affect host metabolic phenotypes. The systemic effects of the gut microbiota on host metabolism are generally evaluated via the comparison of germfree and conventional mice, which is impossible to perform for humans. Hence, it remains difficult to determine the impact of the gut microbiota on human metabolic phenotypes. We demonstrate that a constraint-based modeling framework that simulates “germfree” and “ex-germfree” human individuals can partially fill this gap and allow for in silico predictions of systemic human-microbial co-metabolism. To this end, we constructed the first constraint-based host-microbial community model, comprising the most comprehensive model of human metabolism and 11 manually curated, validated metabolic models of commensals, probiotics, pathogens, and opportunistic pathogens. We used this host-microbiota model to predict potential metabolic host-microbe interactions under 4 in silico dietary regimes. Our model predicts that gut microbes secrete numerous health-relevant metabolites into the lumen, thereby modulating the molecular composition of the body fluid metabolome. Our key results include the following: 1. Replacing a commensal community with pathogens caused a loss of important host metabolic functions. 2. The gut microbiota can produce important precursors of host hormone synthesis and thus serves as an endocrine organ. 3. The synthesis of important neurotransmitters is elevated in the presence of the gut microbiota. 4. Gut microbes contribute essential precursors for glutathione, taurine, and leukotrienes. This computational modeling framework provides novel insight into complex metabolic host-microbiota interactions and can serve as a powerful tool with which to generate novel, non-obvious hypotheses regarding host-microbe co-metabolism.
Pneumothorax as a predictor of beneficial outcome following endoscopic lung volume reduction
Authors: Daniela Gompelmann, Ralf Eberhardt, Dirk-Jan Slebos, Joachim Ficker, Manfred Wagner, Bernd Schmidt, Lars Ek, Felix J.F. Herth
Journal: European Respiratory Journal (2012)

Introduction:  Patients developing significant target lobe volume reduction (TLVR) following endobronchial valve (EBV) treatment experience great improvement in clinical outcome measures. A prospective multicenter study confirmed an improvement in FEV1, SGRQ and 6MWD in patients with a TLVR > 350 ml. However, the risk of pneumothorax increases in case of rapid TLVR by parenchymal rupture. Therefore it is thought, that a pneumothorax is a predictor of beneficial outcome following EBV therapy.  Objective:  To evaluate the impact of the pneumothorax on outcome following EBV treatment.  Methods:  Retrospective analysis of a multicenter trial evaluating the impact of the pneumothorax on outcome following EBV treatment. All patients underwent chest x-ray the same day of EBV implantation for exploration of pneumothorax. 30 days following valve implantation, TLVR assessed by high resolution computed tomography (HRCT) and clinical outcome measures (FEV1, SGRQ, 6MWT) were evaluated.  Results:  96 emphysema patients received EBV therapy, of which 41 patients experienced a TLVR > 350 ml. In totally, 8 patients (8.3%) experienced a pneumothorax following EBV placement. TLVR values were available for 6 out of the 8 patients. All 6 achieved TLVR > 350ml cut off for the study. The mean TLVR as well as the improvement in FEV1 was greater in the group of patients who experienced a pneumothorax (n=6; mean TLVR -2273.2 ml, mean % FEV1 23.8 ± 10.6) compared to those who did not (n=35; mean TLVR -1222.1 ml, mean % FEV1 22.3 ± 24.01). All patients required chest drainage and recovered within 3-14 days.  Conclusion:  The event of pneumothorax seems to be a predictor of a great outcome following EBV therapy.
Carboplatin pharmacokinetics in children: the development of a pediatric dosing formula. The United Kingdom Children's Cancer Study Group.
Authors: D R Newell, A D Pearson, K Balmanno, L Price, R A Wyllie, M Keir, A H Calvert, I J Lewis, C R Pinkerton, M C Stevens
Journal: Journal of Clinical Oncology (1993)

PURPOSE The aim of this study was to define the pharmacokinetics of carboplatin in children and use the data to develop a pediatric dose formula. It was anticipated that renal function would be a major determinant of carboplatin disposition and the relationship between carboplatin clearance and glomerular filtration rate (GFR) was examined in detail. PATIENTS AND METHODS Plasma carboplatin pharmacokinetics were measured as ultrafiltrable platinum in 22 patients (5 to 63 kg) following 200 to 1,000 mg/m2 of carboplatin. GFR was measured by the plasma clearance of chromium 51-edathamil (51Cr-EDTA). RESULTS Carboplatin pharmacokinetics in children were best described in most patients (16 of 22) by a two-compartment model. The dose-normalized area under the plasma carboplatin concentration versus time curve (AUC) ranged from 3.1 to 9.6 mg/mL.min/400 mg/m2 and there was only a weak linear relationship between carboplatin dose and AUC (R2 = .31). There was a significant relationship between absolute carboplatin and 51Cr-EDTA clearances (R2 = .56), but the relationship was weaker (R2 = .28) when both clearances were normalized for body surface area. Carboplatin plasma clearance was predicted by the equation: clearance = GFR (mL/min) + 0.36 x body weight (BW; kg), and a modified form of the adult carboplatin dose formula is proposed: dose (mg) = target AUC x (GFR [mL/min] + [0.36 x BW(kg)]). Two further equations were developed that use the 51Cr-EDTA half-life (t1/2) to calculate the GFR and these may reduce errors resulting from inaccurate measurement of the volume of distribution for 51Cr-EDTA. In patients treated with single-agent carboplatin or carboplatin plus vincristine, there was a significant sigmoidal relationship between AUC and thrombocytopenia (R2 = .56). CONCLUSION GFR-based carboplatin dosing in children should be feasible and will be evaluated prospectively.
P1285 : Forecasting the disease burden of chronic hepatitis C in Russia
Authors: V. Chulanov, O. Sagalova, N. Blokhina, N. Mamonova, E. Nurmukhametova, N. Pimenov, A. Rakhmanova, H. Razavi, K. Razavi-Shearer, A. Shevaldin, E. Chesnokov, S. Sokolov, E. Strebkova, O. Znoiko, I. Shestakova
Journal: Journal of Hepatology (2015)
Respiratory Electrodialysis. A Novel, Highly Efficient Extracorporeal CO<sub>2</sub> Removal Technique
Authors: Alberto Zanella, Luigi Castagna, Domenico Salerno, Vittorio Scaravilli, Salua Abd El Aziz El Sayed Deab, Federico Magni, Marco Giani, Silvia Mazzola, Mariangela Albertini, Nicolò Patroniti, Francesco Mantegazza, Antonio Pesenti
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

We developed an innovative, minimally invasive, highly efficient extracorporeal CO2 removal (ECCO2R) technique called respiratory electrodialysis (R-ED).To evaluate the efficacy of R-ED in controlling ventilation compared with conventional ECCO2R technology.Five mechanically ventilated swine were connected to a custom-made circuit optimized for R-ED, consisting of a hemofilter, a membrane lung, and an electrodialysis cell. Electrodialysis regionally modulates blood electrolyte concentration to convert bicarbonate to CO2 before entering the membrane lung, enhancing membrane lung CO2 extraction. All animals underwent three repeated experimental sequences, consisting of four steps: baseline (1 h), conventional ECCO2R (2 h), R-ED (2 h), and final NO-ECCO2R (1 h). Blood and gas flow were 250 ml/min and 10 L/min, respectively. Tidal volume was set at 8 ml/kg, and respiratory rate was adjusted to maintain arterial Pco2 at 50 mm Hg.During R-ED, chloride and H(+) concentration increased in blood entering the membrane lung, almost doubling CO2 extraction compared with ECCO2R (112 ± 6 vs. 64 ± 5 ml/min, P < 0.001). Compared with baseline, R-ED and ECCO2R reduced minute ventilation by 50% and 27%, respectively. Systemic arterial gas analyses remained stable during the experimental phases. No major complication occurred, but there was an increase in creatinine level.In this first in vivo application, we proved electrodialysis feasible and effective in increasing membrane lung CO2 extraction. R-ED was more effective than conventional ECCO2R technology in controlling ventilation. Further studies are warranted to assess the safety profile of R-ED, especially regarding kidney function.
Splenectomy attenuates obesity and decreases insulin hypersecretion in hypothalamic obese rats
Authors: Nayara de Carvalho Leite, Elisangela Gueiber Montes, Stefani Valéria Fisher, Cláudia Regina Capriglioni Cancian, Júlio Cezar de Oliveira, Marli Cardoso Martins-Pinge, Carla Cristine Kanunfre, Kleber Luiz Araujo Souza, Sabrina Grassiolli
Journal: Metabolism (2015)
Cisplatin neurotoxicity: the relationship between dosage, time, and platinum concentration in neurologic tissues, and morphologic evidence of toxicity.
Authors: R W Gregg, J M Molepo, V J Monpetit, N Z Mikael, D Redmond, M Gadia, D J Stewart
Journal: Journal of Clinical Oncology (1992)

PURPOSE To identify the major sites of platinum accumulation within neural tissues after treatment with cisplatin and to determine the relationship between cumulative dosage, time, and the development of histopathological and clinical neurotoxicity. PATIENTS AND METHODS Twenty-one patients treated antemortem with cisplatin had neural tissue harvested at autopsy. Neural tissues were assayed for platinum and examined for histopathologic evidence of neurotoxicity. The relationship between histopathologic neurotoxicity and various pharmacologic parameters was analyzed. RESULTS Tissue platinum levels were found to be highest in the dorsal root ganglia and lowest in tissue protected by the blood-brain barrier. For peripheral nerve, dorsal root, and dorsal root ganglia, a linear relationship was observed between platinum levels and cumulative dose. Platinum levels in neural tissue were not observed to decrease with time. Histopathologic toxicity closely matched an index of exposure to platinum (cumulative dose and log of time). Clinical and histopathologic neurotoxicity was found to occur with higher accumulations of platinum, with the highest levels found in patients with clinical evidence of neurotoxicity. CONCLUSIONS The dorsal root ganglia was the most vulnerable neural structure. This is consistent with the clinical presentation of sensory neuropathy in cisplatin neurotoxicity. Central structures of the spinal cord and brain were protected from platinum accumulation. The increasing histopathologic toxicity, with an index of exposure to platinum, suggests that it is retained indefinitely in an actively neurotoxic form. The pharmacologic parameters examined correlate with the development of and are consistent with the clinical and laboratory features of cisplatin neurotoxicity.
Lipoxin A4 Attenuates Obesity-Induced Adipose Inflammation and Associated Liver and Kidney Disease
Authors: Emma Börgeson, Andrew M.F. Johnson, Yun Sok Lee, Andreas Till, Gulam Hussain Syed, Syed Tasadaque Ali-Shah, Patrick J. Guiry, Jesmond Dalli, Romain A. Colas, Charles N. Serhan, Kumar Sharma, Catherine Godson
Journal: Cell Metabolism (2015)
Nurse practitioner insertion of Seldinger chest drains. A pilot study
Authors: Heather Lloyd, Steve O'Hickey, Joanne Ingram
Journal: European Respiratory Journal (2012)

Background: In 2008 the National Patient Safety Agency encouraged UK hospitals to develop local policies that reduced the risks associated with chest drain insertion. A key theme that emerged from the 2008 Rapid Response Report was that the inexperience of junior doctors and inadequate supervision increased the risk of complications associated with the procedure.  Aims: We proposed that a ward based nurse practitioner, trained in thoracic ultrasound and chest drain insertion could: 1. Safely perform this procedure in the absence of a competently trained doctor. 2. Optimise training opportunities for junior doctors to undertake this procedure under appropriate supervision.  Method: Following a tailored education programme including ultrasound interpretation and chest drain insertion we reviewed 10 chest drain insertions performed by the nurse practitioner. Various aspects relating to chest drain insertion including consent practice, use of thoracic ultrasound and incidence of any adverse events were audited. Data was collected over a four month period (June to September 2011).  Results: All 10 chest drain insertions performed by the nurse practitioner were correctly sited, written consent was obtained in 100% of procedures undertaken, thoracic ultrasound was used to guide drain placement in 100% of cases and there were no adverse incidents or complications related to chest drain insertion.  Conclusion: Training of specialist nurses in the procedure of chest drain insertion for elective patients with uncomplicated pleural effusion is an acceptable model within the district hospital setting and has the additional benefit of providing appropriate support and supervision for junior doctors undertaking this procedure.
Enhanced training on how to use a dry powder inhaler (DPI) improves the inhalation manoeuvre (IM) of patients with asthma (child 6-17 yrs and adult >17 yrs) or COPD and in healthy adults (HA) when they use a Spiromax® (S) and Turbuhaler® (T) DPI
Authors: Wahida Azouz, Philip Chetcuti, Harold Hosker, Dinesh Saralaya, Henry Chrystyn
Journal: European Respiratory Journal (2013)

Objective: A DPI should be used with an IM that is as deep and as fast as possible from the start of inhalation (Laube BL et al Eur Respir J 2011;37:1308–1331). We have determined the effect of enhanced training using the In-Check Dial (IC) while subjects inhaled through a S and a T DPI.  Method: Child (CA: 6–17y) and adult (AA:18–45y) patients with asthma (mean FEV 1  57 and 69% pred), COPD (52 % pred) and HA were randomised in an open-label design to receive IC with a S and a T. Two separate inhalations were measured using an inhalation profile recorder. The profile with the highest peak inhalation flow (PIF, L/min) was used for data analysis.  Results: Figures 1 and 2 show the % improvement in the maximum pressure change (MPC, kPa) and the acceleration of the flow (ACC, kPa/sec) inside each DPI during an inhalation after IC.  Conclusion: Enhanced training on DPI use may be an important factor in achieving greater drug delivery to the airways.  Funding: Teva Pharmaceuticals.
Abstract 2509: Spouses Enhance Medication Adherence in Patients with Heart Failure
Authors: Misook L Chung, Debra K Moser, Terry A Lennie, Barbara Riegel
Journal: Circulation (2006)

Background: Nonadherence to prescribed medications is a primary cause of rehospitalization in patients with heart failure (HF). Although positive spousal support is related to long-term outcomes in...
Abstract 2662: Hypoxic, Normoxic and Hyperoxic Resuscitation of Hypoxic Newborn Pigs: The Hemodynamic and Histopathologic Comparisons
Authors: Po-Yin Cheung, Laila Obaid, Yann A Brierley, Marwan Emara, Scott Johnson, Grace S Chan, Gregory Korbutt, Laurence Jewell, David L Bigam
Journal: Circulation (2006)

Background: The optimal oxygen concentration used in the neonatal resuscitation is uncertain. Hypothesis: In a survival model of neonatal hypoxia-reoxygenation (HR), the resuscitation with 18% or 2...
Consecutive actions of different gene-altering mechanisms in the evolution of involucrin.
Authors: H Green, P Djian
Journal: Molecular Biology and Evolution (1992)

During the evolution of primates from nonprimates, the gene for involucrin was greatly altered by changes in the short tandem repeats that are present in some form in the gene of each of 17 species examined. The evolution of involucrin was not the result of a single continuum of more or less random changes, and it was not confined to the process of nucleotide substitution, the most commonly studied evolutionary change in DNA. Instead, the evolution of this gene took place through different mechanisms that shortened the length of the repeats, increased their number, and changed their codon sequence. As part of this trend, one entire segment of repeats was replaced by another located elsewhere in the coding region. To bring about these changes, specific mechanisms have been activated, deactivated, and replaced by other mechanisms. The resulting serial revisions in the involucrin gene must depend on gene-altering machinery whose synthesis or activity can be controlled.
Use of tissue adhesives in sport? A new application in international ice hockey * Commentary
Authors: A S Branfield
Journal: British Journal of Sports Medicine (2004)

In the tough, competitive environment of international ice hockey, it is vital that a player who sustains a minor facial laceration is returned to play as soon as possible. A method of wound closure that is fast to apply, water resistant, and effective was sought. Dermabond, a cyanoacrylate tissue adhesive, was selected for use during the 2002 International Ice Hockey Federation World Championships for the closure of selected facial wounds. The wounds were all closed using prescribed aseptic techniques. The results are presented and discussed. The tissue adhesive met the criteria set out.
Abstract 10361: Electrogram Surrogates of the Transmural Extent of Late Gadolinium Enhancement on Cardiac Magnetic Resonance in Patients with Post-Infarct Ventricular Tachycardia
Authors: Takeshi Sasaki, Rozann Hansford, Christopher F Miller, Menekhem M Zviman, Charles Henrikson, Joseph E Marine, David Spragg, Alan Cheng, Harikrishna Tandri, Sunil Sinha, Gordon Tomaselli, Ronald D Berger, Hugh Calkins, David Bluemke, Henry R Halperin, Saman Nazarian
Journal: Circulation (2010)

Introduction: Late gadolinium enhancement on cardiac magnetic resonance (LGE-CMR) can accurately characterize scar transmurality and location. However, the correlation of scar transmurality and ele...
Blood Pressure Response to Losartan and Continuous Positive Airway Pressure in Hypertension and Obstructive Sleep Apnea
Authors: Erik Thunström, Karin Manhem, Annika Rosengren, Yüksel Peker
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Obstructive sleep apnea (OSA) is common in people with hypertension, particularly resistant hypertension. Treatment with an antihypertensive agent alone is often insufficient to control hypertension in patients with OSA.To determine whether continuous positive airway pressure (CPAP) added to treatment with an antihypertensive agent has an impact on blood pressure (BP) levels.During the initial 6-week, two-center, open, prospective, case-control, parallel-design study (2:1; OSA/no-OSA), all patients began treatment with an angiotensin II receptor antagonist, losartan, 50 mg daily. In the second 6-week, sex-stratified, open, randomized, parallel-design study of the OSA group, all subjects continued to receive losartan and were randomly assigned to either nightly CPAP as add-on therapy or no CPAP.Twenty-four-hour BP monitoring included assessment every 15 minutes during daytime hours and every 20 minutes during the night. Ninety-one patients with untreated hypertension underwent a home sleep study (55 were found to have OSA; 36 were not). Losartan significantly reduced systolic, diastolic, and mean arterial BP in both groups (without OSA: 12.6, 7.2, and 9.0 mm Hg; with OSA: 9.8, 5.7, and 6.1 mm Hg). Add-on CPAP treatment had no significant changes in 24-hour BP values but did reduce nighttime systolic BP by 4.7 mm Hg. All 24-hour BP values were reduced significantly in the 13 patients with OSA who used CPAP at least 4 hours per night.Losartan reduced BP in OSA, but the reductions were less than in no-OSA. Add-on CPAP therapy resulted in no significant changes in 24-hour BP measures except in patients using CPAP efficiently. Clinical trial registered with www.clinicaltrials.gov (NCT00701428).​
Clinical outcomes of patients with acute myeloid leukemia: evaluation of genetic and molecular findings in a real-life setting
Authors: Aleide S. Lima, Mariana R. de Mello, Eliana Fernandes, Matheus F. Bezerra, Mayara M. Oliveira, Bruno K. Duarte, Reijane A. de Assis, Fernanda R. Souto, Clarisa F. Ramos, Cintia G. Machado, Katia Pagnano, Antonio R. Lucena-Araujo, Irene Lorand-Metze, Marcos A. Bezerra
Journal: Blood (2015)
A double-blind comparison of valproate and lithium in the treatment of acute mania
Authors: T W Freeman, J L Clothier, P Pazzaglia, M D Lesem, A C Swann
Journal: American Journal of Psychiatry (1992)

This study was carried out to compare the efficacy of lithium carbonate with that of valproate in acute mania and to determine whether pretreatment clinical characteristics, such as the presence of a mixed affective state, might predict a differential response to the two drugs.Twenty-seven patients meeting DSM-III-R criteria for acute manic episodes underwent a 3-week, randomized, double-blind, parallel-groups trial of treatment with lithium carbonate or valproate. Symptom severity was measured by using the Schedule for Affective Disorders and Schizophrenia, change version (SADS-C), the Global Assessment Scale (GAS), and the Brief Psychiatric Rating Scale (BPRS). Drug effects were compared by using repeated measures analysis of variance (ANOVA).At the end of the study, nine of 14 patients treated with valproate and 12 of 13 patients treated with lithium had responded favorably, as measured by changes in the SADS-C mania, BPRS, and GAS scores. Elevated pretreatment SADS-C depression scores were associated with good response to valproate. ANOVA revealed a significant interaction between drug and mixed affective state with respect to treatment response.Lithium and valproate were both effective in improving manic symptoms, and lithium was slightly more efficacious overall. Unlike the case with lithium, favorable response to valproate was associated with high pretreatment depression scores. Therefore, treatment with valproate alone may be particularly effective in manic patients with mixed affective states.
Hepatitis C virus (HCV) genotypes infection: A curable disease
Authors: M.L. Shiffman, F.L. Goncales, J.-P. Bronowicki, M.W. Fried, T. Wright, S. Hadziyannis, J. Brouwer, S. Zeuzem, F. Sederati, J. Hoffman
Journal: Journal of Hepatology (2003)
Phenethyl Isothiocyanate (PEITC) Regulates Autophagy in Chronic Lymphocytic Leukemia.
Authors: Jemimah Adams, R Gitendra Wickremasinghe, Archibald G Prentice, Jonathan C. Strefford, Andrew Duncombe, Francesco Forconi, Freda K. Stevenson, Graham Packham, Andrew Steele
Journal: Blood (2012)