tbuckley/cabot-search huggingface dataset:
Food-Grade Bacteria Expressing Elafin Protect Against Inflammation and Restore Colon Homeostasis
Authors: Jean-Paul Motta, Luis G. Bermúdez-Humarán, Céline Deraison, Laurence Martin, Corinne Rolland, Perrine Rousset, Jérôme Boue, Gilles Dietrich, Kevin Chapman, Pascale Kharrat, Jean-Pierre Vinel, Laurent Alric, Emmanuel Mas, Jean-Michel Sallenave, Philippe Langella, Nathalie Vergnolle
Journal: Science Translational Medicine (2012)

Lactic acid–producing bacteria engineered to produce the antiprotease Elafin restore colon homeostasis in mice with colitis and protect human tissue from inflammation.
Nanogels from Metal-Chelating Crosslinkers as Versatile Platforms Applied to Copper-64 PET Imaging of Tumors and Metastases
Authors: Jacques Lux, Alexander G. White, Minnie Chan, Carolyn J. Anderson, Adah Almutairi
Journal: Theranostics (2015)

Metals are essential in medicine for both therapy and diagnosis.We recently created the first metal-chelating nanogel imaging agent, which employed versatile, reproducible chemistry that maximizes chelation stability.Here we demonstrate that our metal chelating crosslinked nanogel technology is a powerful platform by incorporating 64 Cu to obtain PET radiotracers.Polyacrylamide-based nanogels were crosslinked with three different polydentate ligands (DTPA, DOTA, NOTA).NOTA-based nanogels stably retained 64 Cu in mouse serum and accumulated in tumors in vivo as detected by PET/CT imaging.Measurement of radioactivity in major organs ex vivo confirmed this pattern, revealing a high accumulation (12.3% ID/g and 16.6% ID/g) in tumors at 24 and 48 h following administration, with lower accumulation in the liver (8.5% ID/g at 24 h) and spleen (5.5% ID/g).Nanogels accumulated even more efficiently in metastases (29.9% and 30.4% ID/g at 24 and 48 h).These metal-chelating nanogels hold great promise for future application as bimodal PET/MRI agents; chelation of β-emitting radionuclides could enable radiation therapy.
NT-proBNP reflects right ventricular structure and function in pulmonary hypertension
Authors: C. T. Gan, G. P. McCann, J. T. Marcus, S. A. van Wolferen, J. W. Twisk, A. Boonstra, P. E. Postmus, A. Vonk-Noordegraaf
Journal: European Respiratory Journal (2006)

The aim of the current study was to investigate whether alterations in N-terminal pro brain natriuretic peptide (NT-proBNP) reflect changes in right ventricular structure and function in pulmonary hypertension patients during treatment. The study consisted of 30 pulmonary hypertension patients; 15 newly diagnosed and 15 on long-term treatment. NT-proBNP, right heart catheterisation and cardiac magnetic resonance imaging measurements were performed, at baseline and follow-up. There were no significant differences between newly diagnosed patients and those on treatment at baseline or follow-up with respect to NT-proBNP, haemodynamics and right ventricular parameters. Relative changes in NT-proBNP during treatment were correlated to the relative changes in right ventricular end-diastolic volume index (r = 0.59), right ventricular mass index (r = 0.62) and right ventricular ejection fraction (r = -0.81). N-terminal pro brain natriuretic peptide measurements reflect changes in magnetic resonance imaging-measured right ventricular structure and function in pulmonary hypertension patients. An increase in N-terminal pro brain natriuretic peptide over time reflects right ventricular dilatation concomitant to hypertrophy and deterioration of systolic function.
Psoriasis assessment tools in clinical trials
Authors: S R Feldman, G G Krueger
Journal: Annals of the Rheumatic Diseases (2005)

<b>Aim:</b> To examine whether high spatial resolution perimetry (HSRP) could identify fine scale scotomata which may not be apparent with conventional perimetry. The HSRP was performed in the nasal field, as this location is a recognised site for the early occurrence of glaucomatous defects. <b>Method:</b> 16 early glaucoma eyes, 17 glaucoma suspect eyes, and 20 age matched healthy control eyes underwent conventional automated perimetry using the 24-2 program of the Humphrey field analyser (HFA) and HSRP. The HSRP was performed in the nasal field by testing 9 × 9 degrees of 100 tested points separated by 1 degree and the results compared with the HFA 24-2 program. <b>Results:</b> Mean HSRP thresholds were significantly abnormal in the suspect and glaucoma eyes, with elevated levels of asymmetry between the superior and inferior nasal field. Overall, 7/17 (41%) suspect eyes (95% confidence interval 5/17 (29%) to 7/17 (41%)) had nasal scotomata on HSRP, although their HFA 24-2 fields failed to identify any defects. In glaucomatous eyes, 15/16 (94%) eyes had HSRP scotomata (95% CI 14/16 (88%) to 15/16 (94%)). In 12 these coexisted with HFA 24-2 defects at the same location, while in three eyes only HSRP identified scotomata in the nasal field. <b>Conclusion:</b> HSRP can identify scotoma in glaucomatous eyes in the nasal field which may be missed with the lower spatial resolution of conventional perimetry.
The diagnostic and economic impact of contrast imaging techniques in the diagnosis of small hepatocellular carcinoma in cirrhosis
Authors: A. Sangiovanni, M. A. Manini, M. Iavarone, R. Romeo, L. V. Forzenigo, M. Fraquelli, S. Massironi, C. Della Corte, G. Ronchi, M. G. Rumi, P. Biondetti, M. Colombo
Journal: Gut (2009)

Contrast-enhanced ultrasound (CE-US), contrast CT scan and gadolinium dynamic MRI are recommended for the characterisation of liver nodules detected during surveillance of patients with cirrhosis with US.To assess the sensitivity, specificity, diagnostic accuracy and economic impact of all possible sequential combinations of contrast imaging techniques in patients with cirrhosis with 1-2 cm liver nodules undergoing US surveillance.64 patients with 67 de novo liver nodules (55 with a size of 1-2 cm) were consecutively examined by CE-US, CT, MRI, and a fine-needle biopsy (FNB) as diagnostic standard. Undiagnosed nodules were re-biopsied; non-malignant nodules underwent enhanced imaging follow-up. The typical radiological feature of hepatocellular carcinoma (HCC) was arterial phase hypervascularisation followed by portal/venous phase washout.HCC was diagnosed in 44 (66%) nodules (2, <1 cm; 34, 1-2 cm; 8, >2 cm). The sensitivity of CE-US, CT and MRI for 1-2 cm HCC was 26, 44 and 44%, with 100% specificity, the typical vascular pattern of HCC being identified in 22 (65%) by a single technique versus 12 (35%) by at least two techniques carried out at the same time point (p=0.028). Compared with the cheapest dual examination (CE-US+CT), the cheapest single technique of stepwise imaging diagnosis of HCC was equally expensive (euro 26 440 vs euro 28 667), but led to a 23% reduction of FNB procedures (p=0.031).In patients with cirrhosis with a 1-2 cm nodule detected during surveillance, a single imaging technique showing a typical contrast pattern confidently permits the diagnosis of HCC, thereby reducing the need for FNB examinations.
Parathyroid hormone decreases HCO3 reabsorption in the rat proximal tubule by stimulating phosphatidylinositol metabolism and inhibiting base exit.
Authors: E Pastoriza-Munoz, R M Harrington, M L Graber
Journal: Journal of Clinical Investigation (1992)

The mechanism of inhibition of HCO3 transport by parathyroid hormone (PTH) in the proximal tubule is not clearly defined. Previous studies in vitro have suggested that this effect is mediated via cAMP generation, which acts to inhibit Na/H exchange, resulting in cell acidification. To examine this question in vivo, intracellular pH (pHi) was measured in the superficial proximal tubule of the rat using the pH-sensitive fluoroprobes 4-methylumbelliferone (4MU) and 2',7'-bis(carboxyethyl)-(5, and 6)-carboxyfluorescein (BCECF). PTH was found to alkalinize the cell. This alkalinization suggested inhibition of basolateral base exit, which was confirmed by in situ microperfusion studies: lowering HCO3 in peritubular capillaries acidified the cell, an effect blunted by PTH. Removal of luminal Na promoted basolateral base entry, alkalinizing the cell. This response was also blunted by PTH. Readdition of luminal Na stimulated the luminal Na/H exchanger, causing an alkalinization overshoot that was partially inhibited by PTH. cAMP inhibited luminal H secretion but did not alkalinize the cell. Stimulation of phosphatidylinositol-bis-phosphate turnover by PTH was suggested by the effect to the hormone to increase cell Ca. Blocking the PTH-induced rise in cell Ca blunted the effect of the hormone to alkalinize the cell, as did inhibition of phosphatidylinositol breakdown. Furthermore, stimulation of protein kinase C by a phorbol ester and a diacylglycerol applied basolaterally alkalinized the cell and inhibited luminal H secretion. The findings indicate that both arms of the phosphatidylinositol-bis-phosphate cascade play a role in mediating the effect of PTH on the cell pH. The results are consistent with the view that PTH inhibits base exit in the proximal tubule by activation of the phosphatidylinositol cascade. The resulting alkalinization may contribute, with cAMP, to inhibit apical Na/H exchange and the PTH-induced depression of proximal HCO3 reabsorption.
Relationship between splenic size and splenic function.
Authors: R C Smart, F P Ryan, C D Holdworth, F E Preston
Journal: Gut (1978)

The rate of clearance of 51Cr labelled heat-damaged red cells from the circulation has been compared with the dimensions of the posterior scan of the spleen in 79 cases including nine controls. A strong negative correlation was found between the clearance half-time and the parameters of the scan but, as there was a large variation about the regression line, in the assessment of hyposplenism determination of the rate of clearance of heat-damaged red cells cannot be replaced by the easier determination of spleen size by scanning.
Focal segmental glomerulosclerosis plays a major role in the progression of IgA nephropathy. II. Light microscopic and clinical studies
Authors: Khalil El Karoui, Gary S. Hill, Alexandre Karras, Luc Moulonguet, Valérie Caudwell, Alexandre Loupy, Patrick Bruneval, Christian Jacquot, Dominique Nochy
Journal: Kidney International (2010)
Trends and Variation in Use of Breast Reconstruction in Patients With Breast Cancer Undergoing Mastectomy in the United States
Authors: Reshma Jagsi, Jing Jiang, Adeyiza O. Momoh, Amy Alderman, Sharon H. Giordano, Thomas A. Buchholz, Steven J. Kronowitz, Benjamin D. Smith
Journal: Journal of Clinical Oncology (2014)

Concerns exist regarding breast cancer patients' access to breast reconstruction, which provides important psychosocial benefits.Using the MarketScan database, a claims-based data set of US patients with employment-based insurance, we identified 20,560 women undergoing mastectomy for breast cancer from 1998 to 2007. We evaluated time trends using the Cochran-Armitage test and correlated reconstruction use with plastic-surgery workforce density and other treatments using multivariable regression.Median age of our sample was 51 years. Reconstruction use increased from 46% in 1998 to 63% in 2007 (P < .001), with increased use of implants and decreased use of autologous techniques over time (P < .001). Receipt of bilateral mastectomy also increased: from 3% in 1998 to 18% in 2007 (P < .001). Patients receiving bilateral mastectomy were more likely to receive reconstruction (odds ratio [OR], 2.3; P < .001) and patients receiving radiation were less likely to receive reconstruction (OR, 0.44; P < .001). Rates of reconstruction receipt varied dramatically by geographic region, with associations with plastic surgeon density in each state and county-level income. Autologous techniques were more often used in patients who received both reconstruction and radiation (OR, 1.8; P < .001) and less frequently used in patients with capitated insurance (OR, 0.7; P < .001), patients undergoing bilateral mastectomy (OR, 0.5; P < .001), or patients in the highest income quartile (OR, 0.7; P = .006). Delayed reconstruction was performed in 21% of patients who underwent reconstruction.Breast reconstruction has increased over time, but it has wide geographic variability. Receipt of other treatments correlates with the use of and approaches toward reconstruction. Further research and interventions are needed to ensure equitable access to this important component of multidisciplinary treatment of breast cancer.
Hyperglycemia and Diabetes in Patients With Schizophrenia or Schizoaffective Disorders
Authors: Ripu D. Jindal, Matcheri S. Keshavan
Journal: Diabetes Care (2007)

We commend Cohen et al. (1) on their report on hyperglycemia and diabetes in patients with schizophrenia and schizoaffective disorders. To our knowledge, this is the first large study of oral glucose tolerance tests in this population.

Cohen et al. found that the prevalence rate of diabetes was significantly higher in patients with schizophrenia and schizoaffective disorders than in the general population. They did not detect a differential effect of antipsychotic monotherapy in diabetogenic effects, and they consequently proposed a modification of the consensus statement on antipsychotic drugs, obesity, and diabetes, i.e., measurement of fasting glucose in all patients with schizophrenia irrespective of the prescribed antipsychotic drug. We …
Developing Interventions for Cancer-Related Cognitive Dysfunction in Childhood Cancer Survivors
Authors: S. M. Castellino, N. J. Ullrich, M. J. Whelen, B. J. Lange
Journal: JNCI Journal of the National Cancer Institute (2014)

Survivors of childhood cancer frequently experience cancer-related cognitive dysfunction, commonly months to years after treatment for pediatric brain tumors, acute lymphoblastic leukemia (ALL), or tumors involving the head and neck. Risk factors for cancer-related cognitive dysfunction include young age at diagnosis, treatment with cranial irradiation, use of parenteral or intrathecal methotrexate, female sex, and pre-existing comorbidities. Limiting use and reducing doses and volume of cranial irradiation while intensifying chemotherapy have improved survival and reduced the severity of cognitive dysfunction, especially in leukemia. Nonetheless, problems in core functional domains of attention, processing speed, working memory and visual-motor integration continue to compromise quality of life and performance. We review the epidemiology, pathophysiology and assessment of cancer-related cognitive dysfunction, the impact of treatment changes for prevention, and the broad strategies for educational and pharmacological interventions to remediate established cognitive dysfunction following childhood cancer. The increased years of life saved after childhood cancer warrants continued study toward the prevention and remediation of cancer-related cognitive dysfunction, using uniform assessments anchored in functional outcomes.
Müller glia cells regulate Notch signaling and retinal angiogenesis via the generation of 19,20-dihydroxydocosapentaenoic acid
Authors: Jiong Hu, Rüdiger Popp, Timo Frömel, Manuel Ehling, Khader Awwad, Ralf H. Adams, Hans-Peter Hammes, Ingrid Fleming
Journal: The Journal of Experimental Medicine (2014)

Cytochrome P450 (CYP) epoxygenases generate bioactive lipid epoxides which can be further metabolized to supposedly less active diols by the soluble epoxide hydrolase (sEH). As the role of epoxides and diols in angiogenesis is unclear, we compared retinal vasculature development in wild-type and sEH−/− mice. Deletion of the sEH significantly delayed angiogenesis, tip cell, and filopodia formation, a phenomenon associated with activation of the Notch signaling pathway. In the retina, sEH was localized in Müller glia cells, and Müller cell–specific sEH deletion reproduced the sEH−/− retinal phenotype. Lipid profiling revealed that sEH deletion decreased retinal and Müller cell levels of 19,20–dihydroxydocosapentaenoic acid (DHDP), a diol of docosahexenoic acid (DHA). 19,20-DHDP suppressed endothelial Notch signaling in vitro via inhibition of the γ-secretase and the redistribution of presenilin 1 from lipid rafts. Moreover, 19,20-DHDP, but not the parent epoxide, was able to rescue the defective angiogenesis in sEH−/− mice as well as in animals lacking the Fbxw7 ubiquitin ligase, which demonstrate strong basal activity of the Notch signaling cascade. These studies demonstrate that retinal angiogenesis is regulated by a novel form of neuroretina–vascular interaction involving the sEH-dependent generation of a diol of DHA in Müller cells.
Increased Frequency of Myeloid-derived Suppressor Cells during Active Tuberculosis and after Recent<i>Mycobacterium tuberculosis</i>Infection Suppresses T-Cell Function
Authors: Nelita du Plessis, Laurianne Loebenberg, Magdalena Kriel, Florian von Groote-Bidlingmaier, Eliana Ribechini, Andre G. Loxton, Paul D. van Helden, Manfred B. Lutz, Gerhard Walzl
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Inadequacy of T-cell responses may result in the development of tuberculosis (TB). Myeloid-derived suppressor cells (MDSCs) have been described as suppressors of T-cell function in cancer biology and recently in several infectious diseases.To explore the presence and role of MDSCs in TB.We analyzed surface markers of MDSCs in peripheral blood and at the site of disease in TB cases and in patients with lung cancer, and in peripheral blood of asymptomatic tuberculin skin test-positive individuals with recent (household) or remote exposure to Mycobacterium tuberculosis (M.tb) and in uninfected healthy control subjects. To evaluate the suppressive capacity of MDSCs, cells of household contacts infected with M.tb and TB cases were isolated and cocultured with CD3(+) T cells.Our results demonstrate an increased presence of MDSCs after recent M.tb infection and disease. We confirm their suppression of CD4(+) T-cell function, including reduced cytokine responses and inhibition of CD4(+) T-cell proliferation. Only MDSCs from TB cases reduced T-cell activation, altered T-cell trafficking, and suppressed CD8(+) T-cell functions. M.tb-expanded MDSCs were associated with significantly higher IL-1β, IL-6, IL-8, granulocyte colony-stimulating factor, and monocyte chemotactic protein-1, and reduced granulocyte-macrophage colony-stimulating factor and macrophage inflammatory protein-1 beta levels in coculture.These data reveal that innate MDSCs are induced not only during active TB at similar levels as found in cancer, but also in healthy individuals after recent exposure to M.tb. These cells diminish protective T-cell responses and may contribute to the inability of hosts to eradicate the infection and add to the subsequent development of TB disease.
Spiritual Care in Patients With Advanced Cancer: What Does It Imply?
Authors: Hanneke W.M. van Laarhoven, Johannes Schilderman, Constans A. Verhagen, Judith Prins
Journal: Journal of Clinical Oncology (2010)

TO THE EDITOR: Balboni et al report that patients with advanced cancer whose spiritual needs are met by the medical team have greater odds of receiving hospice care at the end of life. Receiving spiritual care was associated with better quality of life at the end of life. However, it remains unclear what kind of spiritual care was provided to achieve this result. The observations that patients with high religious coping have a higher likelihood of receiving aggressive care at the end of life, which may be reduced when spiritual needs were supported by the medical team, may suggest that the care provided by the medical team to patients with high religious coping either changed their belief system or changed their coping strategies. To allow for the first—a change in belief system—in-depth knowledge of and familiarity with the patient’s religious beliefs and values is required, as well as excellent pastoral skills to counsel a patient toward a different frame of (religious) reference. In fact, going through such a transformation of significance is a difficult and intensive process, requiring professional spiritual care. It is unlikely that support of doctors and nurses would have been sufficient to guide this process. The second option—a change of a patient’s coping strategy—is also unlikely to have occurred. It has been shown previously that cognitive behavioral interventions in patients with advanced cancer may have a positive influence on patients’ well-being, but this required an elaborate support program. It is doubtful that medical professionals could have provided the kind of cognitive behavioral interventions that lead to a change in coping strategies. It is more likely that in this study, discussions of preparation and life completion were crucial in supporting the patients. As has been shown previously, end-of-life discussions are essential and valuable in optimal medical care for patients with advanced cancer. Although it may well be true that patients have labeled this kind of care as spiritual care, in fact, this is not spiritual in terms of the definition of spirituality, viz. “an individual’s relationship to and experience of the transcendent.” Although we agree with the authors that medical caregivers should be educated in providing patient-centered spiritual care, it is unlikely that the current study demonstrated “associations of spiritual care with medical care and quality of life near death,” given that the conceptual and professional validity of the interventions labeled as spiritual care have not been established in the study.
Computational identification of obligatorily autocatalytic replicators embedded in metabolic networks
Authors: Ádám Kun, Balázs Papp, Eörs Szathmáry
Journal: Genome biology (2008)

If chemical A is necessary for the synthesis of more chemical A, then A has the power of replication (such systems are known as autocatalytic systems). We provide the first systems-level analysis searching for small-molecular autocatalytic components in the metabolisms of diverse organisms, including an inferred minimal metabolism. We find that intermediary metabolism is invariably autocatalytic for ATP. Furthermore, we provide evidence for the existence of additional, organism-specific autocatalytic metabolites in the forms of coenzymes (NAD+, coenzyme A, tetrahydrofolate, quinones) and sugars. Although the enzymatic reactions of a number of autocatalytic cycles are present in most of the studied organisms, they display obligatorily autocatalytic behavior in a few networks only, hence demonstrating the need for a systems-level approach to identify metabolic replicators embedded in large networks. Metabolic replicators are apparently common and potentially both universal and ancestral: without their presence, kick-starting metabolic networks is impossible, even if all enzymes and genes are present in the same cell. Identification of metabolic replicators is also important for attempts to create synthetic cells, as some of these autocatalytic molecules will presumably be needed to be added to the system as, by definition, the system cannot synthesize them without their initial presence.