tbuckley/cabot-search huggingface dataset:
Shifts in human skin and nares microbiota of healthy children and adults
Authors: Julia Oh, Sean Conlan, Eric C Polley, Julia A Segre, Heidi H Kong
Journal: Genome Medicine (2012)

Characterization of the topographical and temporal diversity of the microbial collective (microbiome) hosted by healthy human skin established a reference for studying disease-causing microbiomes. Physiologic changes occur in the skin as humans mature from infancy to adulthood. Thus, characterizations of adult microbiomes might have limitations when considering pediatric disorders such as atopic dermatitis (AD) or issues such as sites of microbial carriage. The objective of this study was to determine if microbial communities at several body sites in children differed significantly from adults.Using 16S-rRNA gene sequencing technology, we characterized and compared the bacterial communities of four body sites in relation to Tanner stage of human development. Body sites sampled included skin sites characteristically involved in AD (antecubital/popliteal fossae), a control skin site (volar forearm), and the nares. Twenty-eight healthy individuals aged from 2 to 40 years were evaluated at the outpatient dermatology clinic in the National Institutes of Health's Clinical Center. Exclusion criteria included the use of systemic antibiotics within 6 months, current/prior chronic skin disorders, asthma, allergic rhinitis, or other chronic medical conditions.Bacterial communities in the nares of children (Tanner developmental stage 1) differed strikingly from adults (Tanner developmental stage 5). Firmicutes (Streptococcaceae), Bacteroidetes, and Proteobacteria (β, γ) were overrepresented in Tanner 1 compared to Tanner 5 individuals, where Corynebacteriaceae and Propionibacteriaceae predominated. While bacterial communities were significantly different between the two groups in all sites, the most marked microbial shifts were observed in the nares, a site that can harbor pathogenic species, including Staphylococcus aureus and Streptococcus pneumonia.Significant shifts in the microbiota associated with progressive sexual maturation as measured by Tanner staging suggest that puberty-dependent shifts in the skin and nares microbiomes may have significant implications regarding prevention and treatment of pediatric disorders involving microbial pathogens and colonization.
The NAFLD fibrosis score: A noninvasive system that identifies liver fibrosis in patients with NAFLD
Authors: Paul Angulo, Jason M. Hui, Giulio Marchesini, Ellisabetta Bugianesi, Jacob George, Geoffrey C. Farrell, Felicity Enders, Sushma Saksena, Alastair D. Burt, John P. Bida, Keith Lindor, Schuyler O. Sanderson, Marco Lenzi, Leon A. Adams, James Kench, Terry M. Therneau, Christopher P. Day
Journal: Hepatology (2007)

Patients with nonalcoholic fatty liver disease (NAFLD) and advanced liver fibrosis are at the highest risk for progressing to end-stage liver disease. We constructed and validated a scoring system consisting of routinely measured and readily available clinical and laboratory data to separate NAFLD patients with and without advanced fibrosis. A total of 733 patients with NAFLD confirmed by liver biopsy were divided into 2 groups to construct (n = 480) and validate (n = 253) a scoring system. Routine demographic, clinical, and laboratory variables were analyzed by multivariate modeling to predict presence or absence of advanced fibrosis. Age, hyperglycemia, body mass index, platelet count, albumin, and AST/ALT ratio were independent indicators of advanced liver fibrosis. A scoring system with these 6 variables had an area under the receiver operating characteristic curve of 0.88 and 0.82 in the estimation and validation groups, respectively. By applying the low cutoff score (−1.455), advanced fibrosis could be excluded with high accuracy (negative predictive value of 93% and 88% in the estimation and validation groups, respectively). By applying the high cutoff score (0.676), the presence of advanced fibrosis could be diagnosed with high accuracy (positive predictive value of 90% and 82% in the estimation and validation groups, respectively). By applying this model, a liver biopsy would have been avoided in 549 (75%) of the 733 patients, with correct prediction in 496 (90%). Conclusion: a simple scoring system accurately separates patients with NAFLD with and without advanced fibrosis, rendering liver biopsy for identification of advanced fibrosis unnecessary in a substantial proportion of patients. (HEPATOLOGY 2007;45:846–854.)
Inner City Asthma Study: Relationships among sensitivity, allergen exposure, and asthma morbidity
Authors: Rebecca S. Gruchalla, Jacqueline Pongracic, Marshall Plaut, Richard Evans III, Cynthia M. Visness, Michelle Walter, Ellen F. Crain, Meyer Kattan, Wayne J. Morgan, Suzanne Steinbach
Journal: Journal of Allergy and Clinical Immunology (2005)
ADAMTS-1 Metalloproteinase Promotes Tumor Development through the Induction of a Stromal Reaction <i>In vivo</i>
Authors: Natacha Rocks, Geneviève Paulissen, Florence Quesada-Calvo, Carine Munaut, Maria-Luz Alvarez Gonzalez, Maud Gueders, Jonathan Hacha, Christine Gilles, Jean-Michel Foidart, Agnès Noel, Didier D. Cataldo
Journal: Cancer Research (2008)

Abstract ADAMTS-1 (a disintegrin and metalloproteinase with thrombospondin motifs), the first described member of the ADAMTS family, is differentially expressed in various tumors. However, its exact role in tumor development and progression is still unclear. The aim of this study was to investigate the effects of ADAMTS-1 transfection in a bronchial epithelial tumor cell line (BZR) and its potential to modulate tumor development. ADAMTS-1 overexpression did not affect in vitro cell properties such as (a) proliferation in two-dimensional culture, (b) proliferation in three-dimensional culture, (c) anchorage-independent growth in soft agar, (d) cell migration and invasion in modified Boyden chamber assay, (e) angiogenesis in the aortic ring assay, and (f) cell apoptosis. In contrast, ADAMTS-1 stable transfection in BZR cells accelerated the in vivo tumor growth after s.c. injection into severe combined immunodeficient mice. It also promoted a stromal reaction characterized by myofibroblast infiltration and excessive matrix deposition. These features are, however, not observed in tumors derived from cells overexpressing a catalytically inactive mutant of ADAMTS-1. Conditioned media from ADAMTS-1–overexpressing cells display a potent chemotactic activity toward fibroblasts. ADAMTS-1 overexpression in tumors was associated with increased production of matrix metalloproteinase-13, fibronectin, transforming growth factor β (TGF-β), and interleukin-1β (IL-1β). Neutralizing antibodies against TGF-β and IL-1β blocked the chemotactic effect of medium conditioned by ADAMTS-1–expressing cells on fibroblasts, showing the contribution of these factors in ADAMTS-1–induced stromal reaction. In conclusion, we propose a new paradigm for catalytically active ADAMTS-1 contribution to tumor development, which consists of the recruitment of fibroblasts involved in tumor growth and tumor-associated stroma remodeling. [Cancer Res 2008;68(22):9541–50]
Injuries on British climbing walls.
Authors: D Limb
Journal: British Journal of Sports Medicine (1995)

A postal survey was carried out of the 90 most accessible climbing walls in England, Scotland and Wales to determine the incidence and nature of injuries requiring emergency treatment associated with their use. Over a two year period, representing 1.021 million visits to the 56 walls used by more than 30 climbers per week, 55 significant injuries were recorded. The rate of injury was not related to any identified design or safety feature of the walls, although upper limb injuries were proportionally more common in walls which provided thinner fixed landing mats rather than thicker, moveable crash mats. The overall rate of injury was very low and climbers seem to modify risk taking behaviour and thus compensate for the level of safety equipment available. It may be possible to reduce the injury rate further by providing seamless ground cover with matting of adequate energy absorbency.
Evaluating joint destruction in rheumatoid arthritis: is it necessary to radiograph both hands and feet?
Authors: R Knevel, KY Kwok, DPC de Rooy, MD Posthumus, TWJ Huizinga, E Brouwer, AHM van der Helm-van Mil
Journal: Annals of the Rheumatic Diseases (2012)

Background Radiological damage is an important outcome measure in rheumatoid arthritis (RA), both for research and clinical purposes. Depending on the setting, both hands and feet are radiographed, or only a part of these. It is unknown whether radiographing part of the four extremities gives comparable information to radiographing both hands and feet. This study therefore aimed to compare the radiological information obtained both when evaluating single time point radiographs and progression over time, in early and advanced RA. Methods 6261 sets of hands and feet x-rays of 2193 RA patients from Leiden, Groningen (both from The Netherlands) and North America were studied. Correlations between joint damage at different regions were compared (unilateral vs bilateral and hands vs feet). Analyses were done at single time points (cross-sectional) and for progression over time (longitudinal), both for continuous severity measures (Sharp/van der Heijde score; SHS) and binomial measures of erosiveness. Results When studying single time points, the severity of joint damage (SHS) is highly correlated between left and right, but weakly correlated between hands and feet. Correlation coefficients were higher in advanced than early RA. These findings were comparable in the three datasets. When evaluating erosiveness using only unilateral x-rays or hands without feet, 19.3% and 24.0–40.4% are incorrectly classified as non-erosiveness. Similarly, when evaluating disease progression by imaging only unilateral x-rays or only hand x-rays, progression would have been missed in 11.6–16.2% and 21.2–31.0% of patients. Conclusion Performing x-rays of both hands and feet yields additive information compared with imaging only a part of these.
Expression patterns and predictive value of phosphorylated AKT in early-stage breast cancer
Authors: F. Andre, R. Nahta, R. Conforti, T. Boulet, M. Aziz, L.X.H. Yuan, F. Meslin, M. Spielmann, G. Tomasic, L. Pusztai, G.N. Hortobagyi, S. Michiels, S. Delaloge, F.J. Esteva
Journal: Annals of Oncology (2007)
Solving a 50 year mystery of a missing OPA1 mutation: more insights from the first family diagnosed with autosomal dominant optic atrophy
Authors: Nico Fuhrmann, Simone Schimpf, York Kamenisch, Beate Leo-Kottler, Christiane Alexander, Georg Auburger, Eberhart Zrenner, Bernd Wissinger, Marcel V Alavi
Journal: Molecular Neurodegeneration (2010)

Up to the 1950s, there was an ongoing debate about the diversity of hereditary optic neuropathies, in particular as to whether all inherited optic atrophies can be ascribed to Leber's hereditary optic neuropathy (LHON) or represent different disease entities. In 1954 W. Jaeger published a detailed clinical and genealogical investigation of a large family with explicit autosomal dominant segregation of optic atrophy thus proving the existence of a discrete disease different from LHON, which is nowadays known as autosomal dominant optic atrophy (ADOA). Since the year 2000 ADOA is associated with genomic mutations in the OPA1 gene, which codes for a protein that is imported into mitochondria where it is required for mitochondrial fusion. Interestingly enough, the underlying mutation in this family has not been identified since then.We have reinvestigated this family with the aim to identify the mutation and to further clarify the underlying pathomechanism. Patients showed a classical non-syndromic ADOA. The long term deterioration in vision in the two teenagers examined 50 years later is of particular note 5/20 to 6/120. Multiplex ligation probe amplification revealed a duplication of the OPA1 exons 7-9 which was confirmed by long distance PCR and cDNA analysis, resulting in an in-frame duplication of 102 amino acids. Segregation was verified in 53 available members of the updated pedigree and a penetrance of 88% was calculated. Fibroblast cultures from skin biopsies were established to assess the mitochondrial network integrity and to qualitatively and quantitatively study the consequences of the mutation on transcript and protein level. Fibroblast cultures demonstrated a fragmented mitochondrial network. Processing of the OPA1 protein was altered. There was no correlation of the OPA1 transcript levels and the OPA1 protein levels in the fibroblasts. Intriguingly an overall decrease of mitochondrial proteins was observed in patients' fibroblasts, while the OPA1 transcript levels were elevated.The thorough study of this family provides a detailed clinical picture accompanied by a molecular investigation of patients' fibroblasts. Our data show a classic OPA1-associated non-syndromic ADOA segregating in this family. Cell biological findings suggest that OPA1 is regulated by post-translational mechanisms and we would like to hypothesize that loss of OPA1 function might lead to impaired mitochondrial quality control. With the clinical, genetic and cell biological characterisation of a family described already more than 50 years ago, we span more than half a century of research in optic neuropathies.
Selective Hypoaldosteronism with Hyperkalemia
Authors: GUIDO PEREZ
Journal: Annals of Internal Medicine (1972)

A 59-year-old diabetic woman with moderate renal insufficiency had unexplained hyperkalemia, aggravated by sodium restriction and corrected with desoxycorticosterone acetate (Doca®) administration. Urinary aldosterone excretion was low and failed to increase despite several stimuli to its release; glucocorticoid excretion and response to adrenocorticotropic hormone stimulation were normal. Plasma renin activity in this patient was undetectable even after volume depletion and weight loss. We conclude that selective hypoaldosteronism in this case, unlike other reported cases, was caused by inadequate adrenal stimulation from the renin angiotensin system.
Clinical and laboratory parameters which affect soluble interleukin-2 receptor levels in the serum and synovial fluids of patients with rheumatoid arthritis.
Authors: T Matsumoto, K Iwasaki
Journal: Annals of the Rheumatic Diseases (1993)

To investigate whether soluble interleukin-2 receptor (sIL-2R) could be a useful marker of disease activity in rheumatoid arthritis (RA); sIL-2R levels in serum and in synovial fluid were determined by enzyme-linked immunosorbent assay. Sixty five serum and 27 synovial fluid samples were obtained from patients with RA. Twenty five serum and 28 synovial fluid samples from patients with osteoarthritis (OA) were used as controls. Furthermore, 10 synovial fluid samples from healthy volunteers were also examined. Variable laboratory and clinical data were compared with serum sIL-2R levels, in 26 patients with RA and serial samples from some patients were examined. Concentrations of sIL-2R in serum (median 81, range 40-350 pM) and synovial fluid (median 125, range 52-460 pM) from patients with RA were significantly higher than in serum (median 45, range 13-100 pM) and synovial fluid (median 37, range 15-140 pM) from patients with OA, and healthy control synovial fluid (median 2.5, range 0-10 pM). Serum sIL-2R levels correlated strongly with serum levels of C-reactive protein (p = 0.0001), and a significant correlation with erythrocyte sedimentation rate (ESR) (p = 0.048), IgG levels (p = 0.028), IgA levels (p = 0.044) and Lansbury Index (p = 0.037) was observed. However, serum sIL-2R levels showed no significant correlation with rheumatic factor, IgM or T cell subsets. These findings indicate that sIL-2R levels in patients with RA reflect disease activity.
<i>Tbata</i> modulates thymic stromal cell proliferation and thymus function
Authors: Francis A. Flomerfelt, Nahed El Kassar, Chandra Gurunathan, Kevin S. Chua, Stacy C. League, Sabrina Schmitz, Timothy R. Gershon, Veena Kapoor, Xiao-Yi Yan, Ronald H. Schwartz, Ronald E. Gress
Journal: The Journal of Experimental Medicine (2010)

Niche availability provided by stromal cells is critical to thymus function. Thymi with diminished function contain fewer stromal cells, whereas thymi with robust function contain proliferating stromal cell populations. Here, we show that the thymus, brain, and testes–associated gene (Tbata; also known as SPATIAL) regulates thymic epithelial cell (TEC) proliferation and thymus size. Tbata is expressed in thymic stromal cells and interacts with the enzyme Uba3, thereby inhibiting the Nedd8 pathway and cell proliferation. Thymi from aged Tbata-deficient mice are larger and contain more dividing TECs than wild-type littermate controls. In addition, thymic reconstitution after bone marrow transplantation occurred more rapidly in Rag2−/−Tbata−/− mice than in Rag2−/−Tbata+/+ littermate controls. These findings suggest that Tbata modulates thymus function by regulating stromal cell proliferation via the Nedd8 pathway.
Neuropilin-1 distinguishes natural and inducible regulatory T cells among regulatory T cell subsets in vivo
Authors: Mahesh Yadav, Cedric Louvet, Dan Davini, James M. Gardner, Marc Martinez-Llordella, Samantha Bailey-Bucktrout, Bryan A. Anthony, Francis M. Sverdrup, Richard Head, Daniel J. Kuster, Peter Ruminski, David Weiss, David Von Schack, Jeffrey A. Bluestone
Journal: The Journal of Experimental Medicine (2012)

Foxp3+ CD4+ T helper cells called regulatory T (T reg) cells play a key role in controlling reactivity to self-antigens and onset of autoimmunity. T reg cells either arise in thymus and are called natural T reg (nT reg) cells or are generated in the periphery through induction of Foxp3 and are called inducible T reg (iT reg) cells. The relative contributions of iT reg cells and nT reg cells in peripheral tolerance remain unclear as a result of an inability to separate these two subsets of T reg cells. Using a combination of novel TCR transgenic mice with a defined self-antigen specificity and conventional mouse models, we demonstrate that a cell surface molecule, neuropilin-1 (Nrp-1), is expressed at high levels on nT reg cells and can be used to separate nT reg versus iT reg cells in certain physiological settings. In addition, iT reg cells generated through antigen delivery or converted under homeostatic conditions lack Nrp-1 expression. Nrp-1lo iT reg cells show similar suppressive activity to nT reg cells in controlling ongoing autoimmune responses under homeostatic conditions. In contrast, their activity might be compromised in certain lymphopenic settings. Collectively, our data show that Nrp-1 provides an excellent marker to distinguish distinct T reg subsets and will be useful in studying the role of nT reg versus iT reg cells in different disease settings.
Tumours of the thymus: A review of 88 operation cases
Authors: T. H. Sellors, A. C. Thackray, A. D. Thomson
Journal: Thorax (1967)

Eighty-eight cases of thymoma are discussed with the object of trying to co-ordinate the histological and clinical features. The pathological specimens were in all cases obtained at operation. The pathology classification introduced by Thomson and Thackray in 1957 has been found to correspond adequately with the clinical pattern. The most common groups of tumours are basically epithelial and can be separated into five or six subdivisions, each of which has a separate pattern of behaviour. Lymphoid and teratomatous tumours also occur, but there were only two examples in this series. Clinically, separation of patients who suffered from myasthenia (38) and those who did not (50) affords the first main grouping. The majority of patients who had myasthenia gravis had tumours classified as epidermoid (19) and lymphoepithelial (14), the former with a more malignant appearance and behaviour than the latter. Removal of the tumour with or without radiation gave considerable and sometimes complete relief from myasthenic symptoms. Non-myasthenic thymoma (50) was usually discovered as a result of pressure signs or in the course of routine radiography. Spindle or oval celled tumours followed a benign pattern whereas undifferentiated thymoma was in every sense malignant, as also were teratomatous growths. Granulomatous or Hodgkin-like thymomas were of special interest and had an unpredictable course, some patients surviving many years after what was regarded as inadequate treatment. The place of radiotherapy as a pre- or post-operative agent complementary to surgery is discussed.
Human apoE Isoforms Differentially Regulate Brain Amyloid-β Peptide Clearance
Authors: Joseph M. Castellano, Jungsu Kim, Floy R. Stewart, Hong Jiang, Ronald B. DeMattos, Bruce W. Patterson, Anne M. Fagan, John C. Morris, Kwasi G. Mawuenyega, Carlos Cruchaga, Alison M. Goate, Kelly R. Bales, Steven M. Paul, Randall J. Bateman, David M. Holtzman
Journal: Science Translational Medicine (2011)

Human apoE4 increases the concentration of soluble Aβ in the brain by impairing its clearance.
Somatic Mutation Profiling and Associations With Prognosis and Trastuzumab Benefit in Early Breast Cancer
Authors: Sherene Loi, Stefan Michiels, Diether Lambrechts, Debora Fumagalli, Bart Claes, Pirkko-Liisa Kellokumpu-Lehtinen, Petri Bono, Vesa Kataja, Martine J. Piccart, Heikki Joensuu, Christos Sotiriou
Journal: JNCI Journal of the National Cancer Institute (2013)

Certain somatic alterations in breast cancer can define prognosis and response to therapy. This study investigated the frequencies, prognostic effects, and predictive effects of known cancer somatic mutations using a randomized, adjuvant, phase III clinical trial dataset. The FinHER trial was a phase III, randomized adjuvant breast cancer trial involving 1010 women. Patients with human epidermal growth factor receptor 2 (HER2)–positive breast cancer were further randomized to 9 weeks of trastuzumab or no trastuzumab. Seven hundred five of 1010 tumors had sufficient DNA for genotyping of 70 somatic hotspot mutations in 20 genes using mass spectrometry. Distant disease-free survival (DDFS), overall survival (OS), and interactions with trastuzumab were explored with Kaplan-Meier and Cox regression analyses. All statistical tests were two-sided. Median follow-up was 62 months. Of 705 tumors, 687 were successfully genotyped. PIK3CA mutations (exons 1, 2, 4, 9, 13, 18, and 20) were present in 25.3% (174 of 687) and TP53 mutations in 10.2% (70 of 687). Few other mutations were found: three ERBB2 and single cases of KRAS, ALK, STK11/LKB1, and AKT2. PIK3CA mutations were associated with estrogen receptor positivity (P < .001) and the luminal-A phenotype (P = .04) but were not statistically significantly associated with prognosis (DDFS: hazard ratio [HR] = 0.88, 95% confidence [CI] = 0.58 to 1.34, P = .56; OS: HR = 0.603, 95% CI = .32 to 1.13, P = .11), although a statistically significant nonproportional prognostic effect was observed for DDFS (P = .002). PIK3CA mutations were not statistically significantly associated with trastuzumab benefit (Pinteraction: DDFS P = .14; OS P = .24). In this dataset, targeted genotyping revealed only two alterations at a frequency greater than 10%, with other mutations observed infrequently. PIK3CA mutations were associated with a better outcome, however this effect disappeared after 3 years. There were no statistically significant associations with trastuzumab benefit.
A phase II study evaluating the tolerability and efficacy of CAELYX (liposomal doxorubicin, Doxil) in the treatment of unresectable pancreatic carcinoma
Authors: S. Halford, D. Yip, C.S. Karapetis, A.H. Strickland, A. Steger, H.T. Khawaja, P.G. Harper
Journal: Annals of Oncology (2001)