tbuckley/cabot-search huggingface dataset:
Bridging to transplant by bronchoscopic lung volume reduction: Case reports of two COPD patients undergoing coil implantation
Authors: Manuel Jonas Richter, Hossein A. Ghofrani, Robert Voswinckel, Henning Tiede, Friedrich Grimminger, Eckhard Mayer, Thorsten Kramm
Journal: European Respiratory Journal (2014)

Background:  Endoscopic lung volume reduction by coil implantation (ELVR-coil) improves pulmonary function and exercise capacity. Since the introduction of the lung allocation score (LAS) for patients awaiting lung transplantation, the total waiting time for COPD patients has increased. We investigated ELVR-coil therapy as bridging therapy to lung transplantation in end-stage COPD.   Methods:  Two COPD patients (baseline FEV1, 18% and 23%, residual volume (RV) 294% and 446% (all as % of predicted)) on the waiting list for lung transplantation were offered therapy by ELVR-coil in two sequential procedures. Follow-up after 3 months included the COPD Assessment Test (CAT), pulmonary function testing and a 6-min walking test (6MWT).   Results:  At the time of intervention, patients time on the waiting list for lung transplantation was 3 and 29 months. Each patient received 20 coils (10 on each side into both upper lobes). No treatment emerging adverse event was observed during the first 30 days after the procedure. During the 3 months follow-up, 1 exacerbation occurred and was treated in-hospital. Three months after ELVR-coil, mixed results were observed for the change in CAT (- 3 and +2) and FEV1 %pred. (+3.1% and -1.6%) while RV %pred. (-78% and - 39%) and 6MWT (+26m and +107m) improved substantially in both patients.   Conclusions:  ELVR-coil may offer a promising bridging option for selected COPD patients waiting for lung transplantation. After three months, partial improvements in pulmonary function and exercise capacity were noted in the presented cases. Future studies are warranted to assess the safety and efficacy in this selected patient cohort.
The History and Future of Treatment of Hypothyroidism
Authors: Elizabeth A. McAninch, Antonio C. Bianco
Journal: Annals of Internal Medicine (2016)

This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Thyroid hormone replacement has been used for more than a century to treat hypothyroidism. Natural thyroid preparations (thyroid extract, desiccated thyroid, or thyroglobulin), which contain both thyroxine (T4) and triiodothyronine (T3), were the first pharmacologic treatments available and dominated the market for the better part of the 20th century. Dosages were adjusted to resolve symptoms and to normalize the basal metabolic rate and/or serum protein-bound iodine level, but thyrotoxic adverse effects were not uncommon. Two major developments in the 1970s led to a transition in clinical practice: 1) The development of the serum thyroid-stimulating hormone (TSH) radioimmunoassay led to the discovery that many patients were overtreated, resulting in a dramatic reduction in thyroid hormone replacement dosage, and 2) the identification of peripheral deiodinase-mediated T4-to-T3 conversion provided a physiologic means to justify l-thyroxine monotherapy, obviating concerns about inconsistencies with desiccated thyroid. Thereafter, l-thyroxine monotherapy at doses to normalize the serum TSH became the standard of care. Since then, a subgroup of thyroid hormone–treated patients with residual symptoms of hypothyroidism despite normalization of the serum TSH has been identified. This has brought into question the inability of l-thyroxine monotherapy to universally normalize serum T3 levels. New research suggests mechanisms for the inadequacies of l-thyroxine monotherapy and highlights the possible role for personalized medicine based on deiodinase polymorphisms. Understanding the historical events that affected clinical practice trends provides invaluable insight into formulation of an approach to help all patients achieve clinical and biochemical euthyroidism.
Skin-resident T cells keep parasites on a Leish
Authors: Laura K. Mackay, Francis R. Carbone
Journal: The Journal of Experimental Medicine (2015)

The Journal of Experimental MedicineAfter their inoculation by mosquitos and entry into the bloodstream, malaria sporozoites must cross the liver sinusoidal barrier to gain access to hepatocytes, where they can multiply as erythrocyte-infecting forms.In this issue, Cha et al. provide further evidence that Kupffer cells (KCs) offer a gateway for entry of sporozoites into the liver parenchyma and identify the receptor on the KCs that directs the passage of the parasite through this portal.A remarkably fruitful phage display strategy led to the identification of a peptide, P39, that bound to KCs.P39 strongly inhibited sporozoite entry into KCs in vitro and reduced liver infection in vivo.It was also shown to bind specifically to CD68, a heavily glycosylated transmembrane protein similar to LAMPs in its cellular distribution, sequence, and structure.Furthermore, the expression of CD68, at least in the liver, is confined to KCs.The function of CD68 as a receptor for sporozoite entry into KCs in vitro was supported by silencing, overexpression, and ectopic expression of the CD68 gene and by antibody inhibition.More critically, parasite liver burden in CD68 knockout mice was reduced by 71%, substantiating CD68 as a key receptor for sporozoite interaction with KCs in vivo, and KCs as the paramount gateway cells.Finally, CD68 knockout mice treated with clodronate to deplete KCs showed liver parasite burdens that were comparable to clodronate-treated, wild-type mice, which in turn had comparable infections to untreated wildtype mice.The authors conclude that CD68 serves as such an efficient gateway that sporozoite transit to the liver parenchyma proceeds as if the sinusoidal barrier did not exist.These findings still need to be reconciled with prior quantitative imaging studies that attribute a greater role for endothelial cells in sinusoid traversal and that reveal a negative impact of KCs on sporozoite survival.Beyond its function as a receptor for sporozoite entry, the nature and consequences of CD68 engagement need to be further explored.Does CD68-mediated sporozoite entry into KCs involve active penetration or phagocytosis?Is there damage to the host cell?Does CD68 engagement inhibit antigen presentation function and/or trigger release of antiinflammatory cytokines that contribute to the state of relative immune tolerance in the liver?And, crucially, what is the parasite ligand for CD68?Assuming its accessibility for antibody targeting in its native state, it would seem an ideal component of a pre-erythrocytic vaccine.
Reactionary approach inhibits progress
Authors: M Baum
Journal: BMJ (1994)

weeky consumption than 21 units.Common sense and scientific evidence suggest that some of these problems are more strongly associated with extreme consumption on single occasions than total consumption over a particular period (N Kreitman and J C Duffy, eighth annual alcohol epidemiology symposium, Helsinki, 1982).It might be argued that as there is no scientific basis for the limits of 21 and 14 units a week new scientific information can be regarded as irrelevant.Such an attitude is short sighted and ultimately counterproductive, allowing legitimate public health interests and health advocacy to be portrayed as either ill informed or incompetent.Greater public health gain might result from giving advice that is both coherent and credible.
Giving guidance on child discipline
Authors: T. Waterston
Journal: BMJ (2000)

The consultation document issued this month by the Department of Health on the physical punishment of children states clearly that “many parents would welcome support in learning effective measures of disciplining their child which do not involve physical punishment” while adding that “there may still be occasions when parents … may consider it appropriate to discipline a child through physical punishment.”1 Most British parents do use physical punishment2 and this fact is used by the government to justify continuing to allow some form of smacking in their proposals for new legislation. At a time when parenting has become a political issue and when child behaviour is causing difficulties both at home and in school, is there a consistent line which health professionals can follow in giving advice on discipline?

Most research on child discipline has been done in the United States. The American Academy of Pediatrics consensus conference on corporal punishment3 and guidelines on effective discipline4 identified three essential elements: a learning environment characterised by positive supportive parent—child relationships; a strategy for systematic teaching and strengthening of desired behaviours; and a strategy of decreasing or eliminating undesired or ineffective behaviours. Each component needs to function adequately for discipline to result in improved child behaviour. Most of these principles have been developed over many years …
Mobile Microplates for Morphological Control and Assembly of Individual Neural Cells
Authors: Shotaro Yoshida, Tetsuhiko Teshima, Kaori Kuribayashi‐Shigetomi, Shoji Takeuchi
Journal: Advanced Healthcare Materials (2015)

A microfabricated device that enables morphological control and assembly of cultured single neural cells is described. Assembly of morphologically controlled single neural cells allows neuroengineers to design in vitro neural circuits with a single-cell resolution. Compared to conventional cell-patterning techniques, the device allows for the highly precise positioning of neural somas and neurites in a reproducible fashion. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Phase II trial of piritrexim in metastatic melanoma using intermittent, low-dose administration.
Authors: L G Feun, R Gonzalez, N Savaraj, J Hanlon, M Collier, W A Robinson, N J Clendeninn
Journal: Journal of Clinical Oncology (1991)

A phase II trial of piritrexim (2,4-diamino-6[2,5-dimethoxybenzyl]-5-methyl pyrido-[2,3d] pyrimidine, 301U74; PTX) was conducted for patients with metastatic malignant melanoma using an intermittent, low-dose oral administration schedule. PTX was administered at a starting dose of 25 mg orally three times per day for 5 days weekly for 3 weeks followed by 1 week of rest. Thirty-one patients were entered onto the study. Among 31 patients assessable for response, there were two complete responses (CRs) and five partial responses (PRs) for a response rate (CR plus PR) of 23% (95% confidence limit, 10% to 42%). Five responses occurred in soft tissue lesions, and two responses occurred in lung lesions. The initial dose schedule was well tolerated. The dose-limiting toxicity was myelosuppression. PTX administered in this schedule appears to be active against malignant melanoma. Further clinical trials to confirm these results are underway.
Abstract P150: Weight-Loss Diets and 2-Year Change of Circulating Amino Acids in Two Randomized Intervention Trials
Authors: Yan Zheng, Uta Ceglarek, Tao Huang, Lerong Li, Jennifer Rood, Donna H Ryan, George A Bray, Frank M Sacks, Dan Schwarzfuchs, Joachim Thiery, Iris Shai, Lu Qi
Journal: Circulation (2015)

Background: Emerging evidence has related circulating amino acids to diabetes and cardiovascular risk. Little is known about how diet modifications affect circulating amino acids. The present study aimed to examine the effects of weight-loss diets on long-term changes in plasma amino acids, and their relations with weight loss and metabolic outcomes. Methods and Results: We repeatedly measured plasma amino acid profiles over 2 years among overweight or obese participants from two randomized dietary interventional weight-loss trials: 774 from the Preventing Overweight Using Novel Dietary Strategies trial (POUNDS LOST) and 318 from Dietary Intervention Randomized Controlled Trial (DIRECT). The plasma levels of most amino acids decreased from baseline during follow-up in both trials. In the POUNDS LOST trial, compared to the high-protein diets, the average-protein weight-loss diets showed a greater effect on decreasing plasma levels of a diabetes-associated branched-chain amino acid (BCAA) valine and another amino acid methyl-histidine at 6 months, independent of weight change (p&lt;0.002). Furthermore, the changes of plasma BCAA leucine/isoleucine, aromatic amino acid tyrosine and phenylalanine, and four other amino acids (alanine, sarcosine, hydroxyproline, and methionine) were positively related to concurrent weight loss, consistently in both trials (5-13g weight loss per 1 unit decease in log[amino acid in μmol/L], p&lt;0.002). Moreover, the changes in tyrosine and alanine were positively related to changes in insulin resistance, independent of weight change, in both trials (p&lt;0.05). Conclusion: Our findings underscore the potential importance of weight-loss dietary interventions in improvement of amino acid profiles and related cardiometabolic risk.
Abstract P119: Tailored Lifestyle Intervention for Obese, Sedentary Patients in Primary Care: Choose to Lose Study
Authors: Charles B Eaton, Sheri Hartman, Patricia M Risica, Kim M Gans, Bess H Marcus
Journal: Circulation (2015)

Background: Poor diet and lack of physical activity are linked conditions, both are risk factors for obesity and cardiovascular disease and prevalent in primary care. Studies of how to accomplish effective changes in physical activity and weight loss simultaneously in obese, sedentary patients in primary care are limited. In this report we present the findings of the physical activity intervention.

Methods: We conducted a randomized, controlled translational research trial of behavioral Interventions in 207 obese, sedentary patients recruited from 24 primary care practices. Participants were 79% women, 17% minority, with a mean age of 48.8 years, and 66% had at least one CVD risk factor. The primary care physicians identified obese , sedentary patients motivated to lose weight and increase physical activity , who were then randomized to one of two experimental groups ( enhanced or standard). Both groups received 3 face-to-face visits with a lifestyle counselor(baseline, 6 months and 12 months) that included physical activity goal setting and exercise log tracking. The enhanced intervention also received frequent mailings related to diet and exercise, monthly tailored mailings using an expert system related to the transtheoretical model of change for physical activity, 2 DVDs related to exercise and monthly phone calls by lifestyle counselors for the first 12 months related to diet and exercise . A maintenance phase with twice monthly mailings for 6 months and then monthly occurred for the last 6 months. The trial was 24 months in duration with follow-up research visits at 6, 12, 18 and 24 months. Statistical analysis used a mixed model adjusted for age, gender, and race accounting for clustering within primary care practice site.

Results: The minutes of moderate and vigorous physical activity(MVPA) per week for the enhanced intervention group were 20.7, 95.7, 126.1, 103.7, 101.3 at baseline, 6,12, 18 and 24 months compared to 22.9, 68.3, 73.7, 63.7, 75.4 for the standard intervention group ( p=0.037 group*visit). Compared to baseline both groups increased physical activity at each time point ( p<.001). Comparing enhanced to standard interventions at each time point showed increased physical activity for the enhanced group at 12 months and 18 months, but by 24 months the differences were no longer statistically significant ( p=.10)

Conclusion: A lifestyle intervention increased physical activity over 24 months in primary care practice in motivated obese, sedentary adults . The added benefits of a tailored approach using an expert system, appear to limited to 12 and 18 months of intervention. Much less contact was provided between 18-24 months. Future research should focus on the optimal dose of the intervention to maintain increased physical activity.
Haptoglobin Preserves Vascular Nitric Oxide Signaling during Hemolysis
Authors: Christian A. Schaer, Jeremy W. Deuel, Daniela Schildknecht, Leila Mahmoudi, Ines Garcia-Rubio, Catherine Owczarek, Stefan Schauer, Reinhard Kissner, Uddyalok Banerjee, Andre F. Palmer, Donat R. Spahn, David C. Irwin, Florence Vallelian, Paul W. Buehler, Dominik J. Schaer
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Rationale: Hemolysis occurs not only in conditions such as sickle cell disease and malaria but also during transfusion of stored blood, extracorporeal circulation, and sepsis. Cell-free Hb depletes nitric oxide (NO) in the vasculature, causing vasoconstriction and eventually cardiovascular complications. We hypothesize that Hb-binding proteins may preserve vascular NO signaling during hemolysis.Objectives: Characterization of an archetypical function by which Hb scavenger proteins could preserve NO signaling during hemolysis.Methods: We investigated NO reaction kinetics, effects on arterial NO signaling, and tissue distribution of cell-free Hb and its scavenger protein complexes.Measurements and Main Results: Extravascular translocation of cell-free Hb into interstitial spaces, including the vascular smooth muscle cell layer of rat and pig coronary arteries, promotes vascular NO resistance. This critical disease process is blocked by haptoglobin. Haptoglobin does not change NO dioxygenation rates of Hb; rather, the large size of the Hb:haptoglobin complex prevents Hb extravasation, which uncouples NO/Hb interaction and vasoconstriction. Size-selective compartmentalization of Hb functions as a substitute for red blood cells after hemolysis and preserves NO signaling in the vasculature. We found that evolutionarily and structurally unrelated Hb-binding proteins, such as PIT54 found in avian species, functionally converged with haptoglobin to protect NO signaling by sequestering cell-free Hb in large protein complexes.Conclusions: Sequential compartmentalization of Hb by erythrocytes and scavenger protein complexes is an archetypical mechanism, which may have supported coevolution of hemolysis and normal vascular function. Therapeutic supplementation of Hb scavengers may restore vascular NO signaling and attenuate disease complications in patients with hemolysis.
P1212 : Impact of sebelipase alfa on survival and liver function in infants with raidly progressive lysosomal acid lipase deficiency
Authors: S. Jones, D. Plantaz, R. Vara, J.J. Gargus, J. Hughes, S. Rojas-Caro, A.G. Quinn, V. Valayannopoulos
Journal: Journal of Hepatology (2015)
Should antireflux surgery be considered after successful endoscopic treatment of Barrett’s esophagus with dysplasia and early cancer?
Authors: Ivan Kristo, Martin Riegler, Sebastian Schoppmann
Journal: Endoscopy (2015)

We read with interest the article by Haidry et al. [1] entitled “Comparing outcome of radiofrequency ablation in Barrett’s with high grade dysplasia and intramucosal carcinoma: a prospective multicenter UK registry,” which was published recently in Endoscopy. The UK registry data support the effectiveness and superiority of radiofrequency ablation (RFA) with or without endoscopic mucosal resection (EMR) for the management of Barrett’s esophagus containing high grade dysplasia and early cancer. The study therefore confirms other recent observations that have shown the benefits of RFA for the treatment of Barrett’s esophagus [2] [3], the morphologic complication of gastroesophageal reflux disease (GERD) [2] [4].
When should we intervene to control the 2009 influenza A(H1N1) pandemic?
Authors: H Sato, H Nakada, R Yamaguchi, S Imoto, S Miyano, M Kami
Journal: Eurosurveillance (2010)

We simulated the early phase of the 2009 influenza A(H1N1) pandemic and assessed the effectiveness of public health interventions in Japan. We show that the detection rate of border quarantine was low and the timing of the intervention was the most important factor involved in the control of the pandemic, with the maximum reduction in daily cases obtained after interventions started on day 6 or 11. Early interventions were not always effective.
Global survey on nebulization of antimicrobial agents in mechanically ventilated patients: a call for international guidelines
Authors: C. Solé-Lleonart, J.A. Roberts, J. Chastre, G. Poulakou, L.B. Palmer, S. Blot, T. Felton, M. Bassetti, C.-E. Luyt, J.M. Pereira, J. Riera, T. Welte, H. Qiu, J.-J. Rouby, J. Rello
Journal: Clinical Microbiology and Infection (2015)
Abstract 515: Cell fate determination factor DACH1 inhibits lung adenocarcinoma invasion and tumor growth through repression of CXCL5 signaling
Authors: Na Han, Xun Yuan, Hua Wu, Hanxiao Xu, Qian Chu, Mingzhou Guo, Shiying Yu, Yuan Chen, Kongming Wu
Journal: Cancer Research (2015)

Abstract The onset of human lung cancer involves the loss of tumor suppressor genes and activation of tumor inducing genes. Current studies have proved EGFR, RAS, ALK as as key driver genes, however, in about 50% lung cancer samples there are no known genes to explain tumorigenesis, suggesting many novel pathways remain to be elucidated. Recent study on whole-genome and transcriptome sequencing NSCLC identified cell fate determinatiton gene DACH1 as novel alteration in genes involved in NSCLC. However, the role of DACH1 in NSCLC and its downstrem targets are largely unknown. We showed that expression of DACH1 was significantly decreased in human NSCLC tissues andits protein abundance was inversely correlated with the tumor stage and grade. Restoration of DACH1 function in NSCLC cells significantly reduced cellular proliferation, clone formation, migrasion and invasion in vitro, as well as tumor growth in vivo. By unbiased screen of secreting factors, we found out that CXCL5 was dramaticcaly repressed by DACH1. Furthermore, functional study suggested that CXCL5 was contribute to the DACH1-mediated repression of migrative in vitro and tumorigenesis in vivo. Consistingly, there was a inverse relationship between the mRNA level of DACH1 and CXCL5 in both lung cancer cell lines and huamn NSCLC tissues. Moreover, Kaplan-Meier analysis of human NSCLC samples demonstrated that high mRNA abundance of DACH1 was predicted favorate prognosis for both relaspse-free survivl and overall survival; in contrast, high CXCL5 expression predict worse prognosis for survival. To our understanding, this is the first study to demonstrate DACH1 regulated paracrine signaling in lung cancer and DACH1 could predict prognosis. In conclusion, DACH1 acts as a tumor suppressor gene through repression of paracrine signaling and is a potential biomarker for prognosis. Citation Format: Na Han, Xun Yuan, Hua Wu, Hanxiao Xu, Qian Chu, Mingzhou Guo, Shiying Yu, Yuan Chen, Kongming Wu. Cell fate determination factor DACH1 inhibits lung adenocarcinoma invasion and tumor growth through repression of CXCL5 signaling. [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 515. doi:10.1158/1538-7445.AM2015-515
GATA-3 Expression Promotes IL-10 Production, Alternative Macrophage Polarization, and Identifies a Subset Of High-Risk PTCL, NOS
Authors: Tianjiao Wang, Andrew L. Feldman, David A Wada, Ye Lu, Avery Polk, Robert Briski, Kay M. Ristow, Thomas M Habermann, Dafydd G Thomas, Steven C. Ziesmer, Linda E Wellik, Thomas Lanigan, Thomas E Witzig, Mark Pittelkow, Nathanael G. Bailey, Megan Lim, Stephen M Ansell, Ryan A. Wilcox
Journal: Blood (2013)