tbuckley/cabot-search huggingface dataset:
STUDIES ON BACTERIAL ENZYMES
Authors: Louis Lowenstein, William L. Fleming, James M. Neill
Journal: The Journal of Experimental Medicine (1929)

Colon bacilli possess endocellular heat-labile lactase and lipase enzymes which remain operative in sterile filtered solutions of the intracellular substances obtained through physical disintegration the bacillary bodies. The demonstration of the lactase and detection of the hexose products of its action constitute experimental evidence that hydrolysis of the disaccharide is the first step in the fermentation of lactose by colon bacilli.
Network Analysis of Human In-Stent Restenosis
Authors: Euan A. Ashley, Rossella Ferrara, Jennifer Y. King, Aditya Vailaya, Allan Kuchinsky, Xuanmin He, Blake Byers, Ulrich Gerckens, Stefan Oblin, Anya Tsalenko, Angela Soito, Joshua M. Spin, Raymond Tabibiazar, Andrew J. Connolly, John B. Simpson, Eberhard Grube, Thomas Quertermous
Journal: Circulation (2006)

Recent successes in the treatment of in-stent restenosis (ISR) by drug-eluting stents belie the challenges still faced in certain lesions and patient groups. We analyzed human coronary atheroma in de novo and restenotic disease to identify targets of therapy that might avoid these limitations.We recruited 89 patients who underwent coronary atherectomy for de novo atherosclerosis (n=55) or in-stent restenosis (ISR) of a bare metal stent (n=34). Samples were fixed for histology, and gene expression was assessed with a dual-dye 22,000 oligonucleotide microarray. Histological analysis revealed significantly greater cellularity and significantly fewer inflammatory infiltrates and lipid pools in the ISR group. Gene ontology analysis demonstrated the prominence of cell proliferation programs in ISR and inflammation/immune programs in de novo restenosis. Network analysis, which combines semantic mining of the published literature with the expression signature of ISR, revealed gene expression modules suggested as candidates for selective inhibition of restenotic disease. Two modules are presented in more detail, the procollagen type 1 alpha2 gene and the ADAM17/tumor necrosis factor-alpha converting enzyme gene. We tested our contention that this method is capable of identifying successful targets of therapy by comparing mean significance scores for networks generated from subsets of the published literature containing the terms "sirolimus" or "paclitaxel." In addition, we generated 2 large networks with sirolimus and paclitaxel at their centers. Both analyses revealed higher mean values for sirolimus, suggesting that this agent has a broader suppressive action against ISR than paclitaxel.Comprehensive histological and gene network analysis of human ISR reveals potential targets for directed abrogation of restenotic disease and recapitulates the results of clinical trials of existing agents.
Radiological and functional changes over 3 years in young children with cystic fibrosis
Authors: S. W. J. Terheggen-Lagro, H. G. M. Arets, J. van der Laag, C. K. van der Ent
Journal: European Respiratory Journal (2007)

The aim of the present study was to evaluate airway disease progression assessed by chest radiology, expiratory interrupter resistance ( R int,exp ) and spirometry in young children with cystic fibrosis (CF) over a 3-yr period. Two chest radiographs combined with two R int,exp measurements were performed with a 3-yr interval in 21 preschool children (age (mean± sd) 3.2±0.9 yrs) and 30 schoolchildren with CF (age 7.2±1.9 yrs). Chest radiographs were scored using five different CF scoring systems and R int,exp measurements were expressed as height-adjusted Z-scores. Spirometry was assessed in schoolchildren and the results were expressed as a percentage of predicted values. Chest radiograph scores worsened significantly over the 3-yr period and a tendency towards more pronounced changes was observed, especially for the Wisconsin score, in preschool children. Most preschool and schoolchildren had R int,exp Z-scores within the normal range at start and follow-up, and the annual change in R int,exp Z-score was not significant. In schoolchildren, only the forced expiratory volume in one second as a percentage of forced vital capacity declined significantly during the study period. In summary, in young children with cystic fibrosis, chest radiograph scores worsen significantly over time even while lung function remains stable.
Abstract 486A: Biological characterization of recombinant maspin in breast cancer cells
Authors: Thomas M. Bodenstine, Richard E. B. Seftor, Elisabeth A. Seftor, Zhila Khalkhali-Ellis, Philip A. Pemberton, Mary J. C. Hendrix
Journal: Cancer Research (2012)

Abstract Mammary serine protease inhibitor (maspin) is a non-inhibitory member of the serine protease inhibitor (serpin) superfamily and is involved in mammary gland development. Loss of maspin expression is commonly observed during breast cancer progression while re-expression of maspin confers tumor suppressive capabilities. Cellular localization of maspin within the cytosol, nucleus, and association in complexes at the plasma membrane confer different properties in cancer cells adding to the complexity of maspin function. The recombinant form of maspin (rMas) when added to growth media of maspin-null cancer cells recapitulates many of the effects of exogenous maspin re-expression including inhibition of invasion through 3D matrices. These effects highlight the potential of rMas for therapeutic development as a novel adjuvant therapy. The aim of this study was to characterize the uptake, processing and distribution of wild-type and mutated forms of rMas in cancer cells. Using the MDA-MB-231, BT549 and Hs578T breast cancer cell lines we demonstrate that rMas is directly internalized by cancer cells and degraded rapidly. Time-lapse confocal microscopy using Alexa Fluor 594 labeled rMas and nuclear/cytoplasmic extraction of rMas following cellular uptake demonstrate that rMas is predominantly localized and processed in the cytosol. Wild-type rMas inhibited cancer cell invasion through collagen based matrices and this effect was independent of nuclear localization. Interestingly, site-directed mutagenesis of rMas to induce reported polymorphisms (Ile to Val 66, Pro to Ser 176, Leu to Val 187, Ile to Val 319) abrogated the ability of rMas to inhibit invasion. These preliminary experiments contribute to the characterization of rMas following internalization by cancer cells and aid in the therapeutic development of rMas as a potential therapy. Additionally, mutational data from this study support growing evidence that mutations in the maspin gene alter functionality in vitro, and may correlate to clinical outcomes in patients in which maspin is expressed in tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 486A. doi:1538-7445.AM2012-486A
Epidermolysis bullosa simplex with mottled pigmentation
Authors: R. COLEMAN, J.I. HARPER, B.D. LAKE
Journal: British Journal of Dermatology (1993)

A family in which epidermolysis bullosa simplex and mottled pigmentation are inherited as an autosomal dominant disorder is described. Clinical features include: non‐scarring blistering, mainly affecting the limbs, mottled pigmentation, predominantly affecting the trunk and neck, warty hyperkeratotic papules of the palms and soles, small red scaly plaques, and skin atrophy. Histology showed an atrophic epidermis, basal cell lysis and significant colloid body formation in an infant from the family.
Respiratory illness and healthcare utilization in children: the primary and secondary care interface
Authors: J.A. Cropper, T.L. Frank, P.I. Frank, M.L. Laybourn, P.C. Hannaford
Journal: European Respiratory Journal (2001)

The aim of the present study was to quantify the healthcare utilization of a child population according to level of respiratory illness. A stratified random sample of 713 children was selected from respondents to a postal respiratory questionnaire, carried out in two general practice populations in 1993. Children were stratified into four groups according to the number of positive responses to five key questions. These groups were used as indicators of likelihood of asthma diagnosis. A search was made of these childrens' practice records covering a 2-yr period, to include both primary and secondary healthcare. There was a significant increase across positive response groups in the proportion of children having primary and secondary care based consultations, particularly for respiratory conditions (p=0.001). There was also a significant increase in prescribing. Of those children considered to be “likely asthmatics” from their questionnaire responses, 8.1% (n=31) did not receive any primary or secondary care for a respiratory problem over the 2-yr period. As the likelihood of respiratory illness increased in this population, more demand was made upon resources for the treatment of respiratory illness. Quantification of this demand enables evidence based resource allocation decisions to be made. This method of quantification could be applied in other populations.
Injuries in men's international ice hockey: a 7-year study of the International Ice Hockey Federation Adult World Championship Tournaments and Olympic Winter Games
Authors: Markku Tuominen, Michael J Stuart, Mark Aubry, Pekka Kannus, Jari Parkkari
Journal: British Journal of Sports Medicine (2014)

Information on ice hockey injuries at the international level is very limited. The aim of the study was to analyse the incidence, type, mechanism and severity of ice hockey injuries in men's international ice hockey tournaments.
A treatment protocol for infants younger than 1 year with acute lymphoblastic leukaemia (Interfant-99): an observational study and a multicentre randomised trial
Authors: Rob Pieters, Martin Schrappe, Paola De Lorenzo, Ian Hann, Giulio De Rossi, Maria Felice, Liisa Hovi, Thierry LeBlanc, Tomasz Szczepanski, Alice Ferster, Gritta Janka, Jeffrey Rubnitz, Lewis Silverman, Jan Stary, Myriam Campbell, Chi-Kong Li, Georg Mann, Ram Suppiah, Andrea Biondi, Ajay Vora, Maria Grazia Valsecchi
Journal: The Lancet (2007)
Danger signals and skin sensitization
Authors: I. Kimber, M. Cumberbatch, R.J. Dearman, C.E.M. Griffiths
Journal: British Journal of Dermatology (2002)

Sir, We read with great interest the recent topical review by Dr English1 in which he considered the influence of exposure (dose per unit area) and the availability of 'danger signals' on the development and clinical investigation of allergic contact dermatitis. In the spirit of scientific dialogue we thought it would be interesting to explore further what Dr English had to say about danger signals and the relevance of these for the induction of skin sensitization. The danger hypothesis as articulated by Matzinger2 has had a major, but controversial, impact on how the operational basis for adaptive immunity is viewed. A central premise has been that a cardinal characteristic of immune function is the ability to discriminate between 'self' and 'non‐self'. However, it is apparent that this paradigm cannot necessarily accommodate all features of adaptive immunity; many 'foreign' antigens to which there is considerable and sustained exposure are tolerated (food and commensal bacteria), while 'self‐antigens' may be the target of responses in autoimmune disease. In attempting to resolve these and other apparent anomalies the danger hypothesis argues that it is not foreignness per se that is the key element in provoking an immune response, but rather the changes associated with cell or tissue damage. In effect, the model is based on the view that control of immune activation is essentially effected by endogenous, rather than exogenous, signals.3 In the context of contact sensitization it is relevant that antigen‐presenting cells, and in particular dendritic cells (DCs), may play a central role in sensing danger signals within the local microenvironment.4, 5
Association Between Smoking and Risk of Bladder Cancer Among Men and Women
Authors: Neal D Freedman, Debra T Silverman, Albert R Hollenbeck, Arthur Schatzkin, Christian C Abnet
Journal: JAMA (2011)

Previous studies indicate that the population attributable risk (PAR) of bladder cancer for tobacco smoking is 50% to 65% in men and 20% to 30% in women and that current cigarette smoking triples bladder cancer risk relative to never smoking. During the last 30 years, incidence rates have remained stable in the United States in men (123.8 per 100,000 person-years to 142.2 per 100,000 person-years) and women (32.5 per 100,000 person-years to 33.2 per 100,000 person-years); however, changing smoking prevalence and cigarette composition warrant revisiting risk estimates for smoking and bladder cancer.
Early life adversity and/or posttraumatic stress disorder severity are associated with poor diet quality, including consumption of trans fatty acids, and fewer hours of resting or sleeping in a US middle-aged population: A cross-sectional and prospective study
Authors: Anna Gavrieli, Olivia M. Farr, Cynthia R. Davis, Judith A. Crowell, Christos S. Mantzoros
Journal: Metabolism (2015)
Liver-enriched transcription factors regulate MicroRNA-122 that targets CUTL1 during liver development
Authors: Hui Xu, Jie-Hua He, Zhen-Dong Xiao, Qian-Qian Zhang, Yue-Qin Chen, Hui Zhou, Liang-Hu Qu
Journal: Hepatology (2010)

MicroRNA-122 (miR-122) is a liver-specific microRNA whose expression is specifically turned on in the mouse liver during embryogenesis, thus it is expected to be involved in liver development. However, the role of miR-122 in liver development and its potential underlying mechanism remain unclear. Here, we show that the expression of miR-122 is closely correlated with four liver-enriched transcription factors (LETFs)—hepatocyte nuclear factor (HNF) 1α, HNF3β, HNF4α, and CCAAT/enhancer-binding protein (C/EBP) α—in the livers of developing mouse embryos and in human hepatocellular carcinoma (HCC) cell lines. Correspondingly, promoter analysis revealed that these LETFs are coordinately involved in the transcriptional regulation of miR-122, and three HNFs directly bind to the miR-122 promoter as transcriptional activators. Using a luciferase reporter system, we identified a group of miR-122 targets involved in proliferation and differentiation regulation. Among these targets, the most prominently repressed target was CUTL1, a transcriptional repressor of genes specifying terminal differentiation in multiple cell lineages, including hepatocytes. We show that CUTL1 expression is gradually silenced at the posttranscriptional level during mouse liver development. Overexpression and knockdown studies both showed that miR-122 repressed CUTL1 protein expression in HCC cell lines. Finally, we show that the stable restoration of miR-122 in HepG2 cells suppresses cellular proliferation and activates the expression of three hepatocyte functional genes, including the cholesterol-7α hydroxylase gene (CYP7A1), a known target of CUTL1 in hepatocytes. Conclusion: Our study provides a model in which miR-122 functions as an effector of LETFs and contributes to liver development by regulating the balance between proliferation and differentiation of hepatocytes, at least by targeting CUTL1. Hepatology 2010
Intrabullous blood injection for lung volume reduction
Authors: S Kanoh, H Kobayashi, K Motoyoshi
Journal: Thorax (2008)

Bronchoscopic treatment for emphysematous lung diseases has attracted clinical attention, and several different approaches are being investigated. We present a case of emphysematous bullae that was effectively treated with a newly developed bronchoscopic intervention, autologous blood injection. A 59-year-old man was referred to our institution with exertional dyspnoea. Chest CT showed emphysema and bullae with a diameter of 12 cm in the right upper lobe. Bronchoscopic treatment was introduced as an alternative to surgery. Autologous blood and fibrinogen solution were infused into bullae via the transbronchial catheter, under fluoroscopic guidance. Post-treatment CT showed marked contraction of bullae to a diameter of 3 cm, corresponding to a volume reduction of 800 ml on body plethysmography. A significant reduction in dyspnoea was also noted. This therapeutic approach is less invasive and may represent a good option for reducing lung volume.
Ethnicity and Breast Cancer: Factors Influencing Differences in Incidence and Outcome
Authors: R. T. Chlebowski, Z. Chen, G. L. Anderson, T. Rohan, A. Aragaki, D. Lane, N. C. Dolan, E. D. Paskett, A. McTiernan, F. A. Hubbell, L. L. Adams-Campbell, R. Prentice
Journal: JNCI Journal of the National Cancer Institute (2005)

The lower breast cancer incidence in minority women and the higher breast cancer mortality in African American women than in white women are largely unexplained. The influence of breast cancer risk factors on these differences has received little attention.Racial/ethnic differences in breast cancer incidence and outcome were examined in 156,570 postmenopausal women participating in the Women's Health Initiative. Detailed information on breast cancer risk factors including mammography was collected, and participants were followed prospectively for breast cancer incidence, pathological breast cancer characteristics, and breast cancer mortality. Comparisons of breast cancer incidence and mortality across racial/ethnic groups were estimated as hazard ratios (HRs) and 95% confidence intervals (CIs) from Cox proportional hazard models. Tumor characteristics were compared as odds ratios (ORs) and 95% confidence intervals in logistic regression models.After median follow-up of 6.3 years, 3938 breast cancers were diagnosed. Age-adjusted incidences for all minority groups (i.e., African American, Hispanic, American Indian/Alaskan Native, and Asian/Pacific Islander) were lower than for white women, but adjustment for breast cancer risk factors accounted for the differences for all but African Americans (HR = 0.75, 95% CI = 0.61 to 0.92) corresponding to 29 cases and 44 cases per 10,000 person years for African American and white women, respectively. Breast cancers in African American women had unfavorable characteristics; 32% of those in African Americans but only 10% in whites were both high grade and estrogen receptor negative (adjusted OR = 4.70, 95% CI = 3.12 to 7.09). Moreover, after adjustment for prognostic factors, African American women had higher mortality after breast cancer than white women (HR = 1.79, 95% CI = 1.05 to 3.05) corresponding to nine and six deaths per 10 000 person-years from diagnosis in African American and white women, respectively.Differences in breast cancer incidence rates between most racial/ethnic groups were largely explained by risk factor distribution except in African Americans. However, breast cancers in African American women more commonly had characteristics of poor prognosis, which may contribute to their increased mortality after diagnosis.
Evidence for Increased Levels of Positive and Negative Selection on the X Chromosome versus Autosomes in Humans
Authors: Krishna R. Veeramah, Ryan N. Gutenkunst, August E. Woerner, Joseph C. Watkins, Michael F. Hammer
Journal: Molecular Biology and Evolution (2014)

Partially recessive variants under positive selection are expected to go to fixation more quickly on the X chromosome as a result of hemizygosity, an effect known as faster-X.Conversely, purifying selection is expected to reduce substitution rates more effectively on the X chromosome.Previous work in humans contrasted divergence on the autosomes and X chromosome, with results tending to support the faster-X effect.However, no study has yet incorporated both divergence and polymorphism to quantify the effects of both purifying and positive selection, which are opposing forces with respect to divergence.In this study, we develop a framework that integrates previously developed theory addressing differential rates of X and autosomal evolution with methods that jointly estimate the level of purifying and positive selection via modeling of the distribution of fitness effects (DFE).We then utilize this framework to estimate the proportion of nonsynonymous substitutions fixed by positive selection (a) using exome sequence data from a West African population.We find that varying the female to male breeding ratio (b) has minimal impact on the DFE for the X chromosome, especially when compared with the effect of varying the dominance coefficient of deleterious alleles (h).Estimates of a range from 46% to 51% and from 4% to 24% for the X chromosome and autosomes, respectively.While dependent on h, the magnitude of the difference between a values estimated for these two systems is highly statistically significant over a range of biologically realistic parameter values, suggesting faster-X has been operating in humans.
From Modic 1 vertebral-endplate subchondral bone signal changes detected by MRI to the concept of ‘active discopathy’
Authors: Christelle Nguyen, Serge Poiraudeau, François Rannou
Journal: Annals of the Rheumatic Diseases (2015)

Late-1980s MRI-detected vertebral-endplate subchondral bone signal changes associated with degenerative disc disease as well as recent studies suggest that in some patients, non-specific chronic low back pain (NS cLBP) can be defined by specific clinical, radiological and biological features, for a concept of active discopathy. This concept allows for associating a particular NS cLBP phenotype to a specific anatomical lesion, namely those with Modic 1 signal changes seen on MRI. Local inflammation is thought to play a pivotal role in these changes. Other etiopathogenic processes may include local infection and mechanical or biochemical stress combined with predisposing genetic factors; treatment strategies remain debated. Modic 1 changes detected by MRI can be considered a first biomarker in NS cLBP. Such changes are of high clinical relevance because they are associated with a specific clinical phenotype and can be targeted by specific treatments.
The Influence of Shoe Design on Plantar Pressures in Neuropathic Feet
Authors: Stephan F.E. Praet, Jan-Willem K. Louwerens
Journal: Diabetes Care (2003)

OBJECTIVE—The aim of this study was to investigate the effect of shoe design on the plantar pressure dynamics of patients with diabetic neuropathy during walking. RESEARCH DESIGN AND METHODS—Three shoe design categories were tested. Total contact area and biomechanical variables in multiple areas under the foot were measured. RESULTS—Shoes with a rocker bottom principle reduced pressure 35–65% underneath the heel and the central metatarsal heads. Increased contact area did not result in significant pressure reductions underneath the forefoot. Pressure dynamics underneath the heel and medial forefoot (first metatarsal head and hallux) on average showed no significant differences among the different shoes with a cushioning insole. CONCLUSIONS—The most effective way to offload the forefoot of patients with neuropathic feet is through the use of the rocker sole principle. In general, the effect of an insole depends on the design characteristics of a shoe. Predicting the effect of therapeutic footwear on an individual scale, however, remains difficult. Therefore, in-shoe pressure measurements seem to be necessary to evaluate a therapeutic shoe prescription in certain individual cases.