tbuckley/cabot-search huggingface dataset:
Comparison of carbon monoxide diffusion using breath hold and rebreathing techniques in children with interstitial disease
Authors: Nicole Beydon, Lucia Maingot, Houda Guillo, Marie-Claude La Rocca, Noria Medjahdi, Marc Koskas, Michèle Boulé
Journal: European Respiratory Journal (2013)

Background Carbon monoxide diffusion (DLCO) measured with reabreathing (RB) technique and hyperventilation has been found to equal breath holding (BH) measure in healthy adults using homemade device. No assessment of the commercially available RB machine has been performed in sick children in whom BH technique might be difficult to achieve.  Objectives 1) to assess feasibility and repeatability of DLCORB 2) to compare DLCOBH and DLCORB in sick children.  Methods Prospective monocentre study in 46 children with suspicion or actual interstitial disease, able to perform DLCOBH. DLCOBH and RB were measured in duplicate (Masterscreen, Jaeger, Hoechberg, Germany).  Results Correct DLCORB measurements during tidal breathing was obtained in 41 (89%) children (age median 11.8 [8.2 to 18.2]y). Median (IQR) z-score of DCLOAP was -1.94 (-3.30;-1.84)[-9.9 to 1.37].  Functional residual capacity of the two DCLORB measurements was reproducible (within 15%). Alveolar volume (VA) of DLCORB was lower to that of DCLOBH (VARB median 52.6 [41.9 to 75.1]% of VABH). The duplicated measurements of DLCORB and DLCOBH were within 15% in 76% and 95% of the children, respectively.  DLCORB and DLCOBH were highly correlated (r2 = 0.72, p  Conclusion DLCORB technique is feasible (89%) and reproducible (76%) in children able to perform BH technique despite various level of interstitial impairment. DLCORB is highly correlated to DCLOAP. Further studies to determine reference values and measurement in younger children are warranted before using RB technique in routine.
Trichophyton Sulphureum Ringworm
Authors: D. Sharvill
Journal: BMJ (1955)

MrEDIC AL JOURNAL 4 1 should, in general, be admitted to hospital for stabilization on the-new insulins.In the two out-patients frequent attendances over a long period were necessary before good control was achieved.Like FitzGerald et al. (1954) we found that transfer from a mixture of P.Z.I. and S.I. or G.I. to I.Z.S. necessitated an increase in dose.This increase reflects, at least in part, a better 24-hour control, but Venning has shown that even a well-controlled patient may need an increased dose after transfer to the new insulin to maintain a comparable degree of control.Similarly, in Ferguson's series 6 out of 10 well- controlled children required more insulin when changed to l.Z.S., and only one a smaller dose.We agree with Venning that estimation of the 24-hour urinary sugar excretion is a most useful method of assessing control after discharge from hospital.In several children routine twice-daily urine tests before breakfast and the evening meal showed no sugar or only a trace, but the amount of sugar excreted in 24 hours exceeded 10 g. and indicated the need to increase the dose of insulin.We adopted this method for the first time in the present study, and it has taught us that, though in the majority of diabetic children it is relatively easy to establish good con- trol in hospital, it is much more difficult to maintain such control over prolonged periods at home. SummaryA single daily injection of insulin zinc suspension (a 3/7 mixture of amorphous/crystalline I.Z.S.) achieved good diabetic control in 18 out of 20 children.We are grateful to Professor J. M.
Abstract 4551: Impairment of c-kit expression in human cancer cell lines by a novel pharmacophoric unit selected for the recognition of the proto-oncogene KIT promotorial region
Authors: Claudia Sissi, Silvia Da Ros, Eleonora Zorzan, Caterina Musetti, Lara Zorro Shahidian, Manlio Palumbo, Mery Giantin, Mauro Dacasto
Journal: Cancer Research (2015)

Abstract G-quadruplex structures at telomeric region and in oncogene promotorial sequences represent promising chemotherapeutic targets. Among these latter ones, an interesting site of intervention is represented by the promotorial sequence of KIT, a proto-oncogene whose overexpression or mutations characterize several human cancers. This region contains two G-rich sequences, kit1 and kit2, whose G-quadruplex structures have been extensively studied by using X-ray crystallography and NMR. The stabilization of these secondary structures by small molecules has been shown to result in a suppression of gene transcription. The peculiarity of these G-quadruplex structures rest in the presence of unprecedented structural domains which foresees the possibility to design small molecules able to recognize them, with a higher selectivity in comparison to other nucleic acid tetra-helixes. In order to identify novel ligands for these sequences, we started a screening program by using an available “in house” library of compounds. Each member was previously confirmed to provide a basal level of nucleic acid recognition. Ligand selection was performed by applying two validated different screening assays (FRET and FID); they were properly designed to identify the best binders and to preliminary exclude compounds with low selectivity among different G-quadruplexes. For selected compounds, the DNA binding properties were fully characterized in terms of binding affinity, binding mode and ability to convert unfolded sequences into a G-quadruplex structure. On parallel, the ligands cellular effects were explored in two human cancer cell lines (MCF7 and HCG27). At first, we evaluated their cytotoxic potential; then, we examined the extent of potential c-kit down-regulation following the exposure to candidates at both mRNA and protein level. By merging these results we were able to highlight the relevance of one pharmacophore as potential selective KIT targeting agent. Citation Format: Claudia Sissi, Silvia Da Ros, Eleonora Zorzan, Caterina Musetti, Lara Zorro Shahidian, Manlio Palumbo, Mery Giantin, Mauro Dacasto. Impairment of c-kit expression in human cancer cell lines by a novel pharmacophoric unit selected for the recognition of the proto-oncogene KIT promotorial region. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4551. doi:10.1158/1538-7445.AM2015-4551
Dendritic cell (DC) reconstitution is associated with less opportunistic infections (OI) after allogeneic hematopoetic stem-cell transplantation (HSCT)
Authors: E. M. Dunbar, J. B. Levine, J. D. Schold, G. S. Samantha, H. Meier-Kriesche, E. Marchand, S. S. Mahmood, V. S. Reddy
Journal: Journal of Clinical Oncology (2006)

6539 Background: Dendritic cells are key antigen presenting cells which coordinate immune responses against infections. We investigated the correlation between DC reconstitution after HSCT and the onset of OI. Methods: We prospectively studied immune reconstitution of DC in 124 patients with predominantly high-risk hematopoetic malignancies. Peripheral blood underwent flow cytometry analysis for DC, defined as lineage negative, HLA-DR+, CD11c+ and CD123+. Cluster analysis demonstrated patients at engraftment with high DC (&gt;6.92/mm 3 ) (n =68), low DC (n=56), and at 60 days with high DC (&gt;3.95/mm 3 ) (n=48), and low DC (n=43). Primary study endpoint was onset of OI, defined as viral and invasive fungal (proven and probable) OI within 6 months of HSCT. A cox proportional hazard multivariate model was adjusted for important covariates, including age, transplant conditioning (myeloablative vs. non-myeloablative), graft source (peripheral blood vs. bone marrow), donor-type (HLA-matched related vs. unrelated), and ANC. Results: Patients with low DC at engraftment had significantly increased onset of acute grade II-IV GVHD by Kaplan-Meier analysis (p=0.004). Patients with onset of GVHD prior to day 60 were less likely to have high DC (32% with GVHD, 72% without GVHD) (p=0.001). Furthermore, low DC at 60 days was adversely associated with: time to viral OI (p=0.04), time to composite of viral OI and death (p=0.02), time to viral or fungal OI (p=0.009), and time to composite of viral or fungal OI and death (p=0.02). In the Cox model, low DC at 60 days, was associated with a 3.7 relative risk (RR) (1.2, 11.8) for onset of OI. Patients with onset of OI prior to day 60 were significantly less likely to have high DC (41% with OI, 61% without OI) (p=0.05). Conclusions: This study emphasizes the clinical importance of measuring DC after transplant. Patients with low DC reconstitution are at an increased risk of OI and death. Measuring DC, and further understanding of the likely complex factors involved in DC reconstitution, may provide rationale towards future therapeutic immune interventions. No significant financial relationships to disclose.
Smoking rates in UK continue to fall
Authors: Zosia Kmietowicz
Journal: BMJ (2015)

The proportion of adult smokers in the United Kingdom was 18.3% in 2014, down from 18.7% in 2013 and 21.0% in 2010, figures show.1

Smoking prevalence in 2014 was highest in Scotland, where 20.3% of adults smoked, and lowest in England, at 18%. Men (20.7%) were more likely to smoke than women (15.9%), show data from the Office for National Statistics’ Integrated Household Survey covering January to …
Advances in Time Estimation Methods for Molecular Data
Authors: Sudhir Kumar, S. Blair Hedges
Journal: Molecular Biology and Evolution (2016)

Molecular dating has become central to placing a temporal dimension on the tree of life. Methods for estimating divergence times have been developed for over 50 years, beginning with the proposal of molecular clock in 1962. We categorize the chronological development of these methods into four generations based on the timing of their origin. In the first generation approaches (1960s-1980s), a strict molecular clock was assumed to date divergences. In the second generation approaches (1990s), the equality of evolutionary rates between species was first tested and then a strict molecular clock applied to estimate divergence times. The third generation approaches (since ∼2000) account for differences in evolutionary rates across the tree by using a statistical model, obviating the need to assume a clock or to test the equality of evolutionary rates among species. Bayesian methods in the third generation require a specific or uniform prior on the speciation-process and enable the inclusion of uncertainty in clock calibrations. The fourth generation approaches (since 2012) allow rates to vary from branch to branch, but do not need prior selection of a statistical model to describe the rate variation or the specification of speciation model. With high accuracy, comparable to Bayesian approaches, and speeds that are orders of magnitude faster, fourth generation methods are able to produce reliable timetrees of thousands of species using genome scale data. We found that early time estimates from second generation studies are similar to those of third and fourth generation studies, indicating that methodological advances have not fundamentally altered the timetree of life, but rather have facilitated time estimation by enabling the inclusion of more species. Nonetheless, we feel an urgent need for testing the accuracy and precision of third and fourth generation methods, including their robustness to misspecification of priors in the analysis of large phylogenies and data sets.
Preliminary Results of the Experience of Dar El Amal and Analysis of Feasibility of Mammographiy in Screening for Breast Cancer in Women Younger Than 50 Years
Authors: J. Daoud, W. Ben Kridis, F. Elloumi, I. Ayedi, W. Mnejja, O. Yaich, M. Frikha
Journal: Annals of Oncology (2014)
Results of randomized study on dexrazoxane administration in children with de novo acute leukemia
Authors: E. De Berranger, G. Vaksmann, E. Thebaud-Leculee, I. Wyckaert, F. Mazingue, C. Francart, J. Dalle, B. Nelken
Journal: Journal of Clinical Oncology (2006)

9037 Background: Anthracyclins and anthracenediones represent major drugs for both AML and ALL. Among other mechanisms, these drugs induce free radical production responsible of cardiac toxicity. It appeared very important to protect cardiomyocytes. Dexrazoxane (DZ) was developed in this goal. In adult patients, its efficiency was demonstrated both to protect heart and to respect anticancer therapy. We conducted a prospective single bind randomized study using DZ in pediatric acute leukemia. Methods: From Dec 00 to Sept 03, 16 patients (pts) were enrolled for receiving or not DZ (1g for 50mg of doxorubicin equivalent dose) with chemotherapy. Cardiac function was evaluated by echocardiogram before induction and after each chemotherapy course of either EORTC 58951 (arm VHR) or LAME01 trials and each year after treatment completion. The cardiologist operator did not know if child received DZ or not. The cumulative equivalent doxorubicin doses were 310 and 450mg/m 2 for EORTC 58951 and LAME01, respectively. The primary end-point was cardiac function evolution. The secondary end points were OS, EFS and the respect of therapy schedule. Results: 16 pts (9M/7F, 11AML/5ALL), median age 8.5y (2.4 - 16.1) were enrolled. 5 AML and 3 ALL pts received DZ. Median f-up was 28.5 months (10–47). Mean left ventricular shortening fractions were 39 and 35% in pts without DZ and 40 and 39% in pts with DZ before chemotherapy and 1 year after diagnosis, respectively. Mean wall stress values were 50 and 50g/cm 2 for patients without DZ and 39 and 38g/cm 2 for pts with DZ. All these values were comparable. 12 pts were alive, 6 in each arm. 1 pt relapsed in DZ arm and 3 in the other arm. 2 pts died of disease and 2 from infection equally dispatched in the 2 arms. Mean time between successive chemotherapy courses was identical in different groups. 2 patients given DZ presented severe hepatic toxicity (≥grade 3 of WHO classification) followed by quick and spontaneous regression. None other toxicity &gt; grade 1 were observed. Conclusions: DZ may be used safely in children receiving anthracycline. No difference in OS and DFS appear in our study. Median follow-up was probably too short for distinguishing any cardiac alteration, and patient number was low. No significant financial relationships to disclose.
A Critical Role for Airway Microvessels in Lung Transplantation
Authors: Mark R. Nicolls, Gundeep S. Dhillon, Niccolò Daddi
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

With the recent decision by the Centers for Medicare & Medicaid Services and other payers to cover the costs of lung cancer screening, the implementation in the United States is marching forward.European authorities, in contrast, have largely chosen to await the results of the NELSON trial.In centers where screening is performed, the results of the DLCST should be used as an opportunity to recognize the importance of strategies that result in careful patient selection to minimize any potential harms.The DLCST investigators are to be congratulated for including pulmonary function in their trial, which confirms the importance of COPD in identifying those at greatest risk for lung cancer.Although more work is needed to identify the best methods for identifying populations that will benefit from screening, one recent advance is the development of PLCO m2012 , a logistic model incorporating four smoking variables and seven other variables, including COPD, to estimate lung cancer risk (16).A 6-year risk greater than 0.015% using this model identifies patients most likely to benefit from screening and, importantly, was more efficient than the currently recommended NLST criteria using only age and smoking history.Better selection of patients for screening, using model based tools such as PLCO m2012 , will likely result in greater benefits and fewer harms from screening and warrants further evaluation.
Reprogramming Approaches for Cardiovascular Disease
Authors: Deepak Srivastava
Journal: Circulation (2012)

Heart disease is a leading cause of death in adults and children. We, and others, have described complex signaling, transcriptional and translational networks that guide early differentiation of cardiac progenitors and later morphogenetic events during cardiogenesis. We found that networks of transcription factors and miRNAs function through intersecting positive and negative feedback loops to reinforce differentiation and proliferation decisions. For example, we found the human mutations in the transcription factor GATA4 disrupt cardiogenesis, in part by affecting GATA4's interaction with TBX5. Many of the developmental cues have been leveraged to control differentiation of pluripotent stem cells into cardiac, endothelial and smooth muscle cells that may be useful for regenerative purposes. We have used similar approaches to direct differentiation of disease-specific human induced pluripotent stem cells in order to model human heart disease. Recently, we utilized a combination of major cardiac regulatory factors, Gata4/Mef2c/Tbx5, to induce direct reprogramming of cardiac fibroblasts into cardiomyocyte-like cells with global gene expression and electrical activity similar to cardiomyocytes. The reprogramming was a stable event at the epigenetic level. We have now used genetic lineage-tracing techniques to demonstrate that resident cardiac fibroblasts can be reprogrammed into induced cardiomyocytes in vivo using a gene therapy approach. The in vivo efficiency of reprogramming into cells that are more fully reprogrammed into beating cardiomyocytes was greater than in vitro and resulted in improved cardiac function after injury. Knowledge regarding the early steps of cardiac differentiation in vivo has led to effective strategies to generate necessary cardiac cell types for disease-modeling and regenerative approaches, and promise to lead to new strategies for human heart disease.
Cetuximab and irinotecan in patients with colorectal cancer refractory to oxaliplatin and irinotecan
Authors: M. Gonzalez-Baron, M. Blanco, J. Feliu, C. Gómez, E. Casado, J. Castro, C. Belda-Iniesta, M. Garrido, C. Aguayo, M. A. Campos
Journal: Journal of Clinical Oncology (2007)

14600 Background: Patients with chemotherapy-resistant metastasic colorectal cancer have a poor prognosis with few therapeutic options. The purpose of this work is to evaluate the results of treatment with cetuximab and irinotecan in this group of patients. Methods: Between January 01 and July 06, 24 patients were treated in our centre with cetuximab. 19 patients received irinotecan 180 mg/m2 every two weeks with cetuximab at standard doses: 400 mg/m2 loading dose over 2 hours, then 250 mg/m2 over 1 hour weekly, and 5 patients received FOLFIRI schedule and cetuximab at the same doses as previously. Results: Characteristics of the 24 patients were: male/female 15/9; median age 63 years old (range 48–75); performance status 0–1 (10 patients), and 2–3 (14 patients). The median number of chemotherapy regimens preceding first cetuximab administration was 2 (range 1 to 4).12% had received one chemotherapy line, 64% two chemotherapy lines, 16% three chemotherapy lines and 8% received four chemotherapy lines. EGFR status was positive in all patients. The median of administrated cycles was 7.5 (range 2–26). There were 4 objective responses (16%; 95% CI: 5–38.5%) and 7 patients with stable disease (29%). The median progression free survival was 3.2 months and median overall survival was 7.8 months (95% CI: 3–14). The treatment was well tolerated. 6% of the patients had not cutaneous toxicity with the cetuximab treatment, 14 (25%) had a cutaneous toxicity grade 1 or 2 while 25% had a grade 3 or 4 toxicity, that lead to dose reduction in three cases and treatment drop out in one case. Other adverse effects with the treatment included four cases (17%) with diarrhoea grade 3, all of them in treatments with irinotecan, two patients (8%) suffered vomits grade 3, and one patient with grade 3 trombopenia. Conclusions: This therapeutic survey in an unselected population is in accordance with the results of the BOND survey for OS, tumour responses and toxicity. No significant financial relationships to disclose.
Abstract P056: Fructose Intake May Decrease Diastolic and Mean Arterial Blood Pressure: A Systematic Review and Meta-analysis of Controlled Feeding Trials
Authors: Vanessa Ha, John L Sievenpiper, Russell J de Souza, Laura Chiavaroli, Dawei D Wang, Adrian I Cozma, Arash Mir-rahimi, Matthew Yu, Amanda J Carleton, Marco di Buono, Alexandra L Jenkins, Lawrence A Leiter, Thomas M Wolever, Joseph Beyene, Cyril W Kendall, David J Jenkins
Journal: Circulation (2012)

Background: Concerns have been raised about the adverse effect of fructose on blood pressure. International dietary guidelines for the prevention of hypertension, however, have not addressed fructose intake directly. Purpose: A systematic review and meta-analysis was conducted to assess the effect of fructose in isocaloric exchange for other carbohydrate on systolic (SBP), diastolic (DBP), and mean arterial blood pressure (MAP). Hypothesis: We hypothesized fructose intake in isocaloric and hypercaloric exchange for other carbohydrate sources would not have a significant effect on SBP, DBP, and MAP. Methods: Studies were identified using MEDLINE, EMBASE, and Cochrane databases (through September 29 2011). Human clinical trials that investigated isocaloric oral fructose exchange for other carbohydrate sources for at least 7 days were included in the analysis. A generic inverse variance method using random effects weighting was used to pool data. Pooled data were expressed as mean differences (MD) with 95% confidence intervals. Heterogeneity was assessed by the Q statistic and quantified by I2. Study quality was assessed using the Heyland Methodological Quality Score (MQS). Results: Thirteen isocaloric (n= 325 participants) and two hypercaloric (n= 24) trials met the eligibility criteria. Overall, fructose intake in isocaloric exchange for other carbohydrate decreased DBP (MD=−1.40 [95% CI: −2.69, −0.10]) and MAP (MD= −1.16 [95% CI: −2.11, −0.20]). There was no significant effect of fructose on SBP (MD= −1.05 [95% CI: −2.46, 0.36]). However, subgroup analyses revealed potentially important heterogeneous findings. In a priori subgroups, fructose format (fluid) was a significant modifier of the SBP effect. The effects of both DBP and MAP were modified by aspects of study design (non-randomization, parallel design) and study quality (MQS &lt;8). Furthermore, the DBP effect was modified under conditions of follow-up &gt;4weeks and MAP by carbohydrate comparator (high fructose corn syrup). The two hypercaloric fructose feeding trials found no significant MAP effect of fructose in comparison to other carbohydrate. Limitations: A small number of isocaloric trials and two hypercaloric trials were included, limiting the strength of the conclusion. Conclusion: Contrary to previous concerns, we found isocaloric substitution of fructose for other carbohydrate did not adversely affect SBP, DBP, or MAP in humans. Further larger and longer trials are needed to confirm results.