tbuckley/cabot-search huggingface dataset:
Reflections in the Rubble: Some Thoughts in the Aftermath of Civil Disorder
Authors: GARRETT O'CONNOR
Journal: American Journal of Psychiatry (1969)

Current approaches to the problem of ensuring civil rights for all have failed to reach the root of the matter, this author suggests, because they do not take into consideration the real and imagined social and economic threats that are important factors in the maintenance of racial prejudice. An impasse is created in which stereotypes thrive and violence brews. Programs that will make desegregation profitable and attractive for the black and white communities alike are desperately needed.
Inadequate peak expiratory flow meter characteristics detected by a computerised explosive decompression device
Authors: M R Miller
Journal: Thorax (2003)

<b>Background:</b> Recent evidence suggests that the frequency response requirements for peak expiratory flow (PEF) meters are higher than was first thought and that the American Thoracic Society (ATS) waveforms to test PEF meters may not be adequate for the purpose. <b>Methods:</b> The dynamic response of mini-Wright (MW), Vitalograph (V), TruZone (TZ), MultiSpiro (MS) and pneumotachograph (PT) flow meters was tested by delivering two differently shaped flow-time profiles from a computer controlled explosive decompression device fitted with a fast response solenoid valve. These profiles matched population 5th and 95th centiles for rise time from 10% to 90% of PEF and dwell time of flow above 90% PEF. Profiles were delivered five times with identical chamber pressure and solenoid aperture at PEF. Any difference in recorded PEF for the two profiles indicates a poor dynamic response. <b>Results:</b> The absolute (% of mean) flow differences in l/min for the V, MW, and PT PEF meters were 25 (4.7), 20 (3.9), and 2 (0.3), respectively, at PEF ≈500 l/min, and 25 (10.5), 20 (8.7) and 6 (3.0) at ≈200 l/min. For TZ and MS meters at ≈500 l/min the differences were 228 (36.1) and 257 (39.2), respectively, and at ≈200 l/min they were 51 (23.9) and 1 (0.5). All the meters met ATS accuracy requirements when tested with their waveforms. <b>Conclusions:</b> An improved method for testing the dynamic response of flow meters detects marked overshoot (underdamping) of TZ and MS responses not identified by the 26 ATS waveforms. This error could cause patient misclassification when using such meters with asthma guidelines.
Primate-specific evolution of an LDLR enhancer.
Authors: Qian-fei Wang, Shyam Prabhakar, Qianben Wang, Alan M Moses, Sumita Chanan, Myles Brown, Michael B Eisen, Jan-Fang Cheng, Edward M Rubin, Dario Boffelli
Journal: Genome biology (2006)

Background Sequence changes in regulatory regions have often been invoked to explain phenotypic divergence among species, but molecular examples of this have been difficult to obtain. Results In this study we identified an anthropoid primate-specific sequence element that contributed to the regulatory evolution of the low-density lipoprotein receptor. Using a combination of close and distant species genomic sequence comparisons coupled with in vivo and in vitro studies, we found that a functional cholesterol-sensing sequence motif arose and was fixed within a pre-existing enhancer in the common ancestor of anthropoid primates. Conclusion Our study demonstrates one molecular mechanism by which ancestral mammalian regulatory elements can evolve to perform new functions in the primate lineage leading to human.
Influence of preseason training, fitness, and existing injury on subsequent rugby injury
Authors: A J Lee, W M Garraway, D W Arneil
Journal: British Journal of Sports Medicine (2001)

Objectives —To examine the influence of preseason fitness, existing injury, and preseason rugby training on subsequent injury. Methods —Players were eligible for the survey if they were a member of a Scottish Rugby Union (SRU) affiliated rugby club in the Border Reivers District of the SRU during the 1997–1998 season. A total of 803 (84%) players from 22 (88%) participating clubs provided details of rugby training, injuries sustained, and physical activity undertaken during the 16 week summer period (26 April to 16 August 1997) and their perceived fitness before the start of the season. Observers at participating clubs reported all injury episodes occurring to club players throughout the 1997–1998 season. Results —One fifth of players did not attend any rugby training during the 16 week summer period; the remainder attended a median of 14 sessions. Throughout the 1997–1998 season, 675 injury episodes occurred to 423 (53%) players during training or in matches. After adjustment for whether players held a professional contract or were amateurs, Cox regression showed a 3.9% relative increase (95% confidence interval (CI) 1.9 to 5.9%) in the risk of injury over the season for each additional preseason training week attended, and a 61% relative increase (95% CI 32 to 97%) for those players who had been injured or were carrying an injury at the end of the previous season. Conclusions —Injury risk is more likely to be related to rugby training (type of activities undertaken in rugby training, or personalities and characteristics of players undertaking training more frequently) than to overall player fitness. Players who were injured at the end of the previous season were more likely to be injured in the following season. This may be because they do not allow previous injuries to heal sufficiently before returning to the game, or the intensity of their participation may increase their risk of injury.
IL-10 production differentially influences the magnitude, quality, and protective capacity of Th1 responses depending on the vaccine platform
Authors: Patricia A. Darrah, Sonia T. Hegde, Dipti T. Patel, Ross W. B. Lindsay, Linda Chen, Mario Roederer, Robert A. Seder
Journal: The Journal of Experimental Medicine (2010)

The quality of a Th1 response can be a prospective correlate of vaccine-mediated protection against certain intracellular pathogens. Using two distinct vaccine platforms, we evaluate the influence of interleukin (IL) 10 production on the magnitude, quality, and protective capacity of CD4+ T cell responses in the mouse model of Leishmania major infection. Multiparameter flow cytometry was used to delineate the CD4+ T cell production of interferon (IFN) γ, IL-2, tumor necrosis factor (TNF), and IL-10 (or combinations thereof) after vaccination. Immunization with a high dose of adenovirus (ADV) expressing leishmanial proteins (MML-ADV) elicited a limited proportion of multifunctional IFN-γ+IL-2+TNF+ Th1 cells, a high frequency of IL-10–producing CD4+ T cells, and did not protect against subsequent challenge. Surprisingly, in the absence of IL-10, there was no change in the magnitude, quality, or protective capacity of the Th1 response elicited by high-dose MML-ADV. In contrast, after immunization with MML protein and CpG (MML + CpG), IL-10 limited the production of IL-12 by DCs in vivo, thereby decreasing the generation of multifunctional Th1 cells. Consequently, three immunizations with MML + CpG were required for full protection. However, inhibiting IL-10 at the time of immunization enhanced the magnitude and quality of the Th1 response sufficiently to mediate protection after only a single immunization. Overall, we delineate distinct mechanisms by which vaccines elicit protective Th1 responses and underscore the importance of multifunctional CD4+ T cells.
Allogeneic hematopoietic transplantation for mantle-cell lymphoma: Molecular remissions and evidence of graft-versus-malignancy
Authors: I.F. Khouri, M.-S. Lee, J. Romaguera, N. Mirza, H. Kantarjian, M. Korbling, M. Albitar, S. Giralt, B. Samuels, P. Anderlini, J. Rodriguez, B. von Wolff, J. Gajewski, F. Cabanillas, R. Champlin
Journal: Annals of Oncology (1999)
Effectiveness of haemodialysis access with an autologous tissue-engineered vascular graft: a multicentre cohort study
Authors: Todd N McAllister, Marcin Maruszewski, Sergio A Garrido, Wojciech Wystrychowski, Nathalie Dusserre, Alicia Marini, Krzysztof Zagalski, Alejandro Fiorillo, Hernan Avila, Ximena Manglano, Jorge Antonelli, Alfred Kocher, Marian Zembala, Lech Cierpka, Luis M de la Fuente, Nicolas L'Heureux
Journal: The Lancet (2009)
Comment on impact on colorectal cancer mortality of screening programmes based on the faecal immunochemical test
Authors: Richard F Logan, Stephen P Halloran
Journal: Gut (2014)

Sir,

Zorzi et al 1 are to be commended for their timely analysis of the impact of using a faecal immunochemical test (FIT) on colorectal cancer mortality in their screening programme. The 24% colorectal cancer mortality reduction they report will surely give impetus to efforts to introduce FIT into other screening programmes. As they rightly observe, the impact of these newer screening tests is likely only to be determined from observational studies such as their study rather than further randomised trials.

Nevertheless, some …
Association of Posttraumatic Stress Disorder With Reduced In Vivo Norepinephrine Transporter Availability in the Locus Coeruleus
Authors: Robert H. Pietrzak, Jean-Dominique Gallezot, Yu-Shin Ding, Shannan Henry, Marc N. Potenza, Steven M. Southwick, John H. Krystal, Richard E. Carson, Alexander Neumeister
Journal: JAMA Psychiatry (2013)

Animal data suggest that chronic stress is associated with a reduction in norepinephrine transporter (NET) availability in the locus coeruleus. However, it is unclear whether such models are relevant to posttraumatic stress disorder (PTSD), which has been linked to noradrenergic dysfunction in humans.
Influence of Study Features and Methods on Overdiagnosis Estimates in Breast and Prostate Cancer Screening
Authors: Ruth Etzioni, Roman Gulati, Leslie Mallinger, Jeanne Mandelblatt
Journal: Annals of Internal Medicine (2013)

Knowledge of the likelihood that a screening-detected case of cancer has been overdiagnosed is vitally important to make treatment decisions and develop screening policy. An overdiagnosed case is an excess case detected by screening. Estimates of the frequency of overdiagnosis in breast and prostate cancer screening vary greatly across studies. This article identifies features of overdiagnosis studies that influence results and shows their effect by using published research. First, different ways to define and measure overdiagnosis are considered. Second, contextual features and how they affect overdiagnosis estimates are examined. Third, the effect of estimation approach is discussed. Many studies use excess incidence under screening as a proxy for overdiagnosis. Others use statistical models to make inferences about lead time or natural history and then derive the corresponding fraction of cases that are overdiagnosed. This article concludes with questions that readers of overdiagnosis studies can use to evaluate the validity and relevance of published estimates and recommends that authors of studies quantifying overdiagnosis provide information about these features.
1157 NUCLEOSIDE TRANSPORTER SLC28A2/3 AND SLC29A1/2 GENETICS: PROTECTION AGAINST ANAEMIA IN CHRONIC HEPATITIS C PATIENTS RECEIVING RIBAVIRIN
Authors: W.P. Hofmann, A. Doehring, C. Schlecker, S. Zeuzem, C. Sarrazin, T. Berg, T. Müller, E. Herrmann, G. Geisslinger, J. Lötsch
Journal: Journal of Hepatology (2011)
Time-dependent Cox regression model is superior in prediction of prognosis in primary sclerosing cholangitis
Authors: Kirsten Muri Boberg, Giuseppe Rocca, Thore Egeland, Annika Bergquist, Ulrika Broomé, Llorenc Caballeria, Roger Chapman, Rolf Hultcrantz, Stephen Mitchell, Albert Pares, Floriano Rosina, Erik Schrumpf
Journal: Hepatology (2002)

More precise prognostic models are needed for prediction of survival in patients with primary sclerosing cholangitis (PSC), particularly for the selection of candidates for liver transplantation. The aim of this study was to develop a time-dependent prognostic model for the calculation of updated short-term survival probability in PSC. Consecutive clinical and laboratory follow-up data from the time of diagnosis were collected from the files of 330 PSC patients from 5 European centers, followed for a median of 8.4 years since diagnosis. Time-fixed and time-dependent Cox regression analyses, as well as the additive regression model, were applied. The reliability of the models was tested by a cross-validation procedure. Bilirubin (on a logarithmic scale), albumin, and age at diagnosis of PSC were identified as independent prognostic factors in multivariate analysis of both the time-fixed and the time-dependent Cox regression models. The importance of bilirubin was more pronounced in the time-dependent model (hazard ratio [HR], 2.84) than in the time-fixed analysis (hazard ratio, 1.51). The additive regression model indicated that once the patients survive beyond the first 5 years, the impact on prognosis of albumin at diagnosis ceases. The time-dependent prognostic model was superior to the time-fixed variant in assigning low 1-year survival probabilities to patients that actually survived less than 1 year. In conclusion, a time-dependent Cox regression model has the potential to estimate a more precise short-term prognosis in PSC compared with the traditional time-fixed models.
John Montague Graham
Authors: L. Adams
Journal: BMJ (2002)

Former bacteriologist Southampton and Winchester (b India 1925; q King's College Hospital 1949), died from prostate cancer on 9 March.

To those of us who knew him since the early 1940s he was nicknamed “Jive” because of his addiction to the “big band” sound of the time. After posts in Manchester and at the School of Hygiene and Tropical Medicine, he moved to Southampton, where he spent time at the Royal South Hants and Southampton General Hospitals. His last and most enjoyable appointment was to the Royal Hants County Hospital in Winchester. A keen and natural sportsman, he played tennis to a high standard. He leaves a wife, Shirley; three children; and his grandchildren.
Membrane raft–lysosome redox signalling platforms in coronary endothelial dysfunction induced by adipokine visfatin
Authors: Min Xia, Chun Zhang, Krishna M Boini, Audrey M Thacker, Pin-Lan Li
Journal: Cardiovascular Research (2010)

AimsThe adipokine visfatin, produced during obesity, has been reported to participate in the development of cardiovascular disease associated with metabolic syndrome. The present study was designed to test a hypothesis that visfatin causes coronary endothelial dysfunction through lysosome trafficking and fusion to cell membranes, membrane raft (MR) clustering, and formation of redox signalosomes.
Disruption of Sphingosine 1-Phosphate Lyase Confers Resistance to Chemotherapy and Promotes Oncogenesis through Bcl-2/Bcl-xL Upregulation
Authors: Sandra Colié, Paul P. Van Veldhoven, Blandine Kedjouar, Carmen Bedia, Virginie Albinet, Sonia-Caroline Sorli, Virginie Garcia, Mojgan Djavaheri-Mergny, Chantal Bauvy, Patrice Codogno, Thierry Levade, Nathalie Andrieu-Abadie
Journal: Cancer Research (2009)

Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid metabolite involved in cancer development through stimulation of cell survival, proliferation, migration, and angiogenesis. Irreversible degradation of S1P is catalyzed by S1P lyase (SPL). The human SGPL1 gene that encodes SPL maps to a region often mutated in cancers. To investigate the effect of SPL deficiency on cell survival and transformation, the susceptibility to anticancer drugs of fibroblasts generated from SPL-deficient mouse embryos (Sgpl1(-/-)) was compared with that of cells from heterozygous (Sgpl1(+/-)) or wild-type (Sgpl1(+/+)) embryos. First, loss of SPL caused resistance to the toxic effects of etoposide and doxorubicin. Interestingly, heterozygosity for the Sgpl1 gene resulted in partial resistance to apoptosis. Secondly, doxorubicin-induced apoptotic signaling was strongly inhibited in Sgpl1(-/-) cells (phosphatidylserine externalization, caspase activation, and cytochrome c release). This was accompanied by a strong increase in Bcl-2 and Bcl-xL protein content. Whereas correction of SPL deficiency in Sgpl1(-/-) cells led to downregulation of antiapoptotic proteins, Bcl-2 and Bcl-xL small interfering RNA-mediated knockdown in SPL-deficient cells resulted in increased sensitivity to doxorubicin, suggesting that Bcl-2 upregulation mediates SPL protective effects. Moreover, SPL deficiency led to increased cell proliferation, anchorage-independent cell growth, and formation of tumors in nude mice. Finally, transcriptomic studies showed that SPL expression is downregulated in human melanoma cell lines. Thus, by affecting S1P metabolism and the expression of Bcl-2 members, the loss of SPL enhances cell resistance to anticancer regimens and results in an increased ability of cells to acquire a transformed phenotype and become malignant.
Whole-Genome Expression Plasticity across Tropical and Temperate Drosophila melanogaster Populations from Eastern Australia
Authors: M. T. Levine, M. L. Eckert, D. J. Begun
Journal: Molecular Biology and Evolution (2010)

The genotypic signature of spatially varying selection is ubiquitous across the Drosophila melanogaster genome. Spatially structured adaptive phenotypic differences are also commonly found, particularly along New World and Australian latitudinal gradients. However, investigation of gene expression variation in one or multiple environments across these well-studied populations is surprisingly limited. Here, we report genome-wide transcript levels of tropical and temperate eastern Australian populations reared at two temperatures. As expected, a large number of genes exhibit geographic origin-dependent expression plasticity. Less expected was evidence for an enrichment of down-regulated genes in both temperate and tropical populations when lines were reared at the temperature less commonly encountered in the native range; that is, evidence for significant differences in a "directionality" of plasticity across these two climatic regions. We also report evidence of small scale "neighborhood effects" around those genes significant for geographic origin-dependent plasticity, a result consistent with the evolution of high level, likely chromatin based gene regulation during range expansion in D. melanogaster populations.
Topical hyaluronidase decreases hyaluronic acid and CD44 in human skin and in reconstituted human epidermis: evidence that hyaluronidase can permeate the stratum corneum
Authors: J-P. Laugier, S. Shuster, M. Rosdy, A.B. Csóka, R. Stern, H.I. Maibach
Journal: British Journal of Dermatology (2000)

Hyaluronic acid (HA), a high molecular weight glycosaminoglycan of the extracellular matrix involved in growth, inflammation and wound healing, also contributes to the hydration and plastic properties of skin. Several drug and cosmetic formulations contain HA. We have initiated investigations that explore whether it is possible, by topical application, to modulate endogenous HA levels in skin. We developed a model epidermal culture system that exhibited a differentiated stratum corneum, and expressed HA and the HA receptor CD44, in a pattern similar to that observed in intact skin. Such in vitro skin equivalents are useful models for investigating the effect of topical drugs. HA and bacterial hyaluronidase were applied to the in vitro skin equivalent and to human skin. Their effects on endogenous HA and CD44 expression were examined using histochemical analysis. Topical HA treatment had no significant effect on HA or CD44 expression in either system. However, hyaluronidase decreased HA and CD44 expression in a dose-dependent manner in both the epidermal culture system and in skin. Apparently, HA is not able to permeate the epidermal culture system or human skin to a significant degree, but bacterial hyaluronidase does permeate both human skin and the culture system, depleting HA and decreasing CD44 expression. These effects were more prominent in the dermal than in the epidermal layers, suggesting that marked differences in HA metabolism exist in these two skin compartments. The ability of hyaluronidase to permeate the stratum corneum suggests that topical application may, additionally, be useful as a clinical modality.
L1 Cell Adhesion Molecule Promotes Tumorigenicity and Metastatic Potential in Non–Small Cell Lung Cancer
Authors: Josephine Hai, Chang-Qi Zhu, Bizhan Bandarchi, Yu-Hui Wang, Roya Navab, Frances A. Shepherd, Igor Jurisica, Ming-Sound Tsao
Journal: Clinical Cancer Research (2012)

Non-small cell lung cancer (NSCLC) is a highly metastatic cancer with limited treatment options, thus requiring development of novel targeted therapies. Our group previously identified L1 cell adhesion molecule (L1CAM) expression as a member of a prognostic multigene expression signature for NSCLC patients. However, there is little information on the biologic function of L1CAM in lung cancer cells. This study investigates the functional and prognostic role of L1CAM in NSCLC.Cox proportional hazards regression analysis was done on four independent published mRNA expression datasets of primary NSCLCs. L1CAM expression was suppressed by short-hairpin RNA (shRNA)-mediated silencing in human NSCLC cell lines. Effects were assessed by examining in vitro migration and invasion, in vivo tumorigenicity in mice, and metastatic potential using an orthotopic xenograft rat model of lung cancer.L1CAM is an independent prognostic marker in resected NSCLC patients, with overexpression strongly associated with worse prognosis. L1CAM downregulation significantly decreased cell motility and invasiveness in lung cancer cells and reduced tumor formation and growth in mice. Cells with L1CAM downregulation were deficient in constitutive extracellular signal-regulated kinase (Erk) activation. Orthotopic studies showed that L1CAM suppression in highly metastatic lung cancer cells significantly decreases spread to distant organs, including bone and kidney.L1CAM is a novel prometastatic gene in NSCLC, and its downregulation may effectively suppress NSCLC tumor growth and metastasis. Targeted inhibition of L1CAM may be a novel therapy for NSCLC.
Phase II Randomized Study of Vaccine Treatment of Advanced Prostate Cancer (E7897): A Trial of the Eastern Cooperative Oncology Group
Authors: Howard L. Kaufman, Wei Wang, Judith Manola, Robert S. DiPaola, Yoo-Joung Ko, Christopher Sweeney, Theresa L. Whiteside, Jeffrey Schlom, George Wilding, Louis M. Weiner
Journal: Journal of Clinical Oncology (2004)

Purpose A phase II clinical trial was conducted to evaluate the feasibility and tolerability of a prime/boost vaccine strategy using vaccinia virus and fowlpox virus expressing human prostate-specific antigen (PSA) in patients with biochemical progression after local therapy for prostate cancer. The induction of PSA-specific immunity was also evaluated. Patients and Methods A randomized clinical trial was conducted by the Eastern Cooperative Oncology group and 64 eligible patients were randomly assigned to receive four vaccinations with fowlpox-PSA (rF-PSA), three rF-PSA vaccines followed by one vaccinia-PSA (rV-PSA) vaccine, or one rV-PSA vaccine followed by three rF-PSA vaccines. The major end point was PSA response at 6 months, and immune monitoring included measurements of anti-PSA and anti-vaccinia antibody titers and PSA-specific T-cell responses. Results The prime/boost schedule was well tolerated with few adverse events. Of the eligible patients, 45.3% of men remained free of PSA progression at 19.1 months and 78.1% demonstrated clinical progression-free survival. There was a trend favoring the treatment group that received a priming dose of rV-PSA. Although no significant increases in anti-PSA antibody titers were detected, 46% of patients demonstrated an increase in PSA-reactive T-cells. Conclusion Therapy with poxviruses expressing PSA and delivered in a prime/boost regimen was feasible and associated with minimal toxicity in the cooperative group setting. A significant proportion of men remained free of PSA and clinical progression after 19 months follow-up, and nearly half demonstrated an increase in PSA-specific T-cell responses. Phase III studies are needed to define the role of vaccination in men with prostate cancer or those who are at risk for the disease.