tbuckley/cabot-search huggingface dataset:
Litigation-Generated Science: Why Should We Care?
Authors: Leslie I. Boden, David Ozonoff
Journal: Environmental Health Perspectives (2007)

BackgroundIn a 1994 Ninth Circuit decision on the remand of Daubert v. Merrell Dow Pharmaceuticals, Inc., Judge Alex Kosinski wrote that science done for the purpose of litigation should be subject to more stringent standards of admissibility than other science.ObjectivesWe analyze this proposition by considering litigation-generated science as a subset of science involving conflict of interest.DiscussionJudge Kosinski's formulation suggests there may be reasons to treat science involving conflict of interest differently but raises questions about whether litigation-generated science should be singled out. In particular we discuss the similar problems raised by strategically motivated science done in anticipation of possible future litigation or otherwise designed to benefit the sponsor and ask what special treatment, if any, should be given to science undertaken to support existing or potential future litigation.ConclusionThe problems with litigation-generated science are not special. On the contrary, they are very general and apply to much or most science that is relevant and reliable in the courtroom setting.
Invasive Pulmonary Aspergillosis Associated With Influenza
Authors: Janet J. Fischer, David H. Walker
Journal: JAMA (1979)

Fatal invasive pulmonary aspergillosis may follow viral influenza infections. Two cases with verified influenza A infection were followed by fatal necrotizing pneumonia due to<i>Aspergillus fumigatus</i>. Both patients demonstrated cutaneous anergy and lymphocytopenia. Influenza and perhaps other viruses that depress T-cell function may result in increased susceptibility to infections in which T cells are important in host defenses. (<i>JAMA</i>241:1493-1494, 1979)
Impact of Rapid Response System Implementation on Critical Deterioration Events in Children
Authors: Christopher P. Bonafide, A. Russell Localio, Kathryn E. Roberts, Vinay M. Nadkarni, Christine M. Weirich, Ron Keren
Journal: JAMA Pediatrics (2013)

Rapid response systems aim to identify and rescue deteriorating hospitalized patients. Previous pediatric rapid response system implementation studies have shown variable effectiveness in preventing rare, catastrophic outcomes such as cardiac arrest and death.To evaluate the impact of pediatric rapid response system implementation inclusive of a medical emergency team and an early warning score on critical deterioration, a proximate outcome defined as unplanned transfer to the intensive care unit with noninvasive or invasive mechanical ventilation or vasopressor infusion in the 12 hours after transfer.Quasi-experimental study with interrupted time series analysis using piecewise regression. At an urban, tertiary care children's hospital in the United States, we evaluated 1810 unplanned transfers from the general medical and surgical wards to the pediatric and neonatal intensive care units that occurred during 370,504 non-intensive care patient-days between July 1, 2007, and May 31, 2012.Implementation of a hospital-wide rapid response system inclusive of a medical emergency team and an early warning score in February 2010.Rate of critical deterioration events, adjusted for season, ward, and case mix.Rapid response system implementation was associated with a significant downward change in the preintervention trajectory of critical deterioration and a 62% net decrease relative to the preintervention trend (adjusted incidence rate ratio = 0.38; 95% CI, 0.20-0.75). We observed absolute reductions in ward cardiac arrests (from 0.03 to 0.01 per 1000 non-intensive care patient-days) and deaths during ward emergencies (from 0.01 to 0.00 per 1000 non-intensive care patient-days), but these were not statistically significant (P = .21 and P = .99, respectively). Among all unplanned transfers, critical deterioration was associated with a 4.97-fold increased risk of death (95% CI, 3.33-7.40; P < .001).Rapid response system implementation reversed an increasing trend of critical deterioration. Cardiac arrest and death were extremely rare at baseline, and their reductions were not statistically significant despite using nearly 5 years of data. Hospitals seeking to measure rapid response system performance may consider using valid proximate outcomes like critical deterioration in addition to rare, catastrophic outcomes.
Virological and immunological determinants of intrahepatic virus-specific CD8+ T-cell failure in chronic hepatitis C virus infection
Authors: Christoph Neumann-Haefelin, Jörg Timm, Hans Christian Spangenberg, Natalie Wischniowski, Natalja Nazarova, Nadine Kersting, Michael Roggendorf, Todd M. Allen, Hubert E. Blum, Robert Thimme
Journal: Hepatology (2008)

Virus-specific CD8+ T-cells play an important role in the outcome of acute hepatitis C virus (HCV) infection. In the chronic phase, however, HCV can persist despite the presence of virus-specific T-cell responses. Therefore, we set out to perform a full-breadth analysis of the intrahepatic virus-specific CD8+ T-cell response, its relation to the peripheral T-cell response, and the overall influence of viral escape and the genetic restriction on intrahepatic CD8+ T-cell failure. Intrahepatic and peripheral CD8+ T-cells from 20 chronically HCV infected patients (genotype 1) were comprehensively analyzed using overlapping peptides spanning the entire HCV polyprotein in concert with autologous viral sequences that were obtained for all targeted regions. HCV-specific CD8+ T-cell responses were detectable in most (90%) chronically HCV-infected patients, and two thirds of these responses targeted novel previously undescribed epitopes. Most of the responses were detectable only in the liver but not in the peripheral blood, indicating accumulation and enrichment at the site of disease. Of note, only approximately half of the responses were associated with viral sequence variations supported by functional analysis as viral escape mutations. Escape mutations were more often associated with HLA-B alleles.Our results show an unexpected high frequency of intrahepatic virus-specific CD8+ T-cells, a large part of which continue to target the present viral antigens. Thus, our results suggest that factors other than mutational escape contribute to the failure of intrahepatic virus-specific CD8+ T-cells.
Abstract 2445: Cucurbitacin B suppresses breast cancer growth by inhibiting TGFβ-mediated integrin-HER2 signaling.
Authors: Parul Gupta, Sanjay K. Srivastava
Journal: Cancer Research (2013)

Abstract Integrins have recently been shown to play an important role in promotion of cell motility and survival in various cancers through cooperative signaling with EGFRs. Integrins transmit cell survival signals through ILK-Paxillin complex and further play role in activating AKT signaling. Curcubitacin B (CuB) is a steroidal class of chemical present in the plants belonging to cucurbitaceae family. CuB has shown cytotoxic potential in several cancers by causing G2/M cell cycle arrest and inhibition of JAK/STAT3 pathway. However, the exact mechanism of CuB and its role in metastasis and cell survival is not known. Our results show that CuB significantly suppressed the growth of MDA-MB-231, SKBR3, MCF-7, MDA-MB-231 (HER2) and MCF-7 (HER2), five different breast cancer cells in a concentration and time-dependent manner. CuB also induced apoptosis and down-regulated Integrin linked kinase 1(ILK1) expression. In addition, CuB down-regulated Integrin β4 (ITGB4) and Integrin α 6 (ITGA6) protein expression and suppressed the phosphorylation of AKT at Ser473, paxillin at Tyr118. Previous studies have shown that Transforming growth factor β (TGFβ) mediates crosstalk between ITGB4 and HER2, through Src kinase to enhance cell survival and motility. Interestingly we observed significant downregulation of Src, EGFR and HER2 in various breast cancer cells, suggesting that CuB suppresses cooperative signaling of Integrins and HER2. We also observed that TGFβ pretreatment imparted protection against CuB induced cytotoxic effects, indicating that CuB modulates TGFβ mediated Integrin signaling. Taken together our results indicate the anti-cancer effects of CuB in breast cancer cells by targeting ITGB4/ITGA6, Src, ILK and TGFβ. Further detailed mechanistic work is in progress. [Supported in part by R01 grants CA129038 (to S.K.S) awarded by the National Cancer Institute]. Citation Format: Parul Gupta, Sanjay K. Srivastava. Cucurbitacin B suppresses breast cancer growth by inhibiting TGFβ-mediated integrin-HER2 signaling. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2445. doi:10.1158/1538-7445.AM2013-2445
Altered Structure, Regulation, and Function of the Gene Encoding the Atrial Natriuretic Peptide in the Stroke-Prone Spontaneously Hypertensive Rat
Authors: Speranza Rubattu, Min Ae Lee-Kirsch, Paola DePaolis, Rosangela Giliberti, Bruna Gigante, Alessia Lombardi, Massimo Volpe, Klaus Lindpaintner
Journal: Circulation Research (1999)

Abstract —Through the genotype/phenotype cosegregation analysis of an F 2 intercross, from the crossbreeding of stroke-prone spontaneously hypertensive rats (SHRSP) and stroke-resistant spontaneously hypertensive rats (SHR), we previously identified a quantitative trait locus for stroke on rat chromosome 5 ( STR2 ) that colocalized with the genes encoding atrial and brain natriuretic peptides ( ANP and BNP ) and conferred a stroke-delaying effect. To further characterize ANP and BNP as candidates for stroke, we performed additional studies. Comparative sequence analysis revealed point mutations in both the coding and regulatory regions of ANP , whereas no interstrain differences were found for BNP . In in vitro studies in COS-7 and AtT-20 cells that were performed to test the relevance of a G→A substitution at position 1125, a Gly→Ser transposition in the SHRSP pro-ANP peptide resulted in different posttranslational processing of the SHRSP ANP gene product that was also associated with higher cGMP production ( P &lt;0.05). Furthermore, an analysis of a 5′ end mutation affecting a PEA2 regulatory binding site in the 5′ untranslated regulatory sequence of SHRSP ANP demonstrated a significantly lower ANP promoter activation in endothelial cells (P&lt;0.05 versus the SHR ANP ). In addition, the expression of ANP was significantly reduced in the brain, but not in the atria, of SHRSP compared with SHR ( P &lt;0.0001). No differences were detected with regard to BNP expression. The present results reveal substantial differences in ANP , but not BNP , structure and product among SHR and SHRSP, which supports a role of ANP in the pathogenesis of stroke in the SHRSP animal model.
Activated charcoal for chloroquine poisoning.
Authors: K T Kivisto, P J Neuvonen
Journal: BMJ (1993)

normal.Haemoglobin concentration was 85 g/l and the erythrocyte sedimentation rate was 30 mm in the first hour.Serum concentrations of electro- lytes, including calcium, were within normal limits, and angiotensin converting enzyme activity was normal.Results of tests for complement component (C3, C4), antinuclear antibodies, rheumatoid factor, antineutrophil cytoplasm anti- bodies, and paraprotein were negative.A tuber- culin test also yielded negative results.Other investigations showed the presence of a malabsorption syndrome with steatorrhea.A jejunal biopsy specimen showed a pattern typical of Whipple's disease with the presence in the mucosa of numerous macrophages that were positive on periodic acid Schiff and Gram staining.Renal biopsy showed tubulointerstitial nephritis with many granulomatous formations; there was diffuse infiltration of interstitial cells and fibrosis with tubular degeneration.There was no central caseation, and no acid fast bacilli were seen on Ziehl-Neelsen staining.Immunofluorescence yielded unremarkable findings.Treatment with doxycycline was started.His diarrhoea resolved and his weight increased concurrently.His renal impairment, however, remained stable.Although Whipple's disease is a systemic con- dition that can cause granulomas in other organs, only one previous case of well documented granu- lomatous interstitial nephritis has been reported.2We believe that we ruled out other causes of granulomatous interstitial nephritis in our patient and that a link between the nephropathy and Whipple's disease is probable.Crohn's disease and Whipple's disease should probably be added to the list of aetiologic factors in granulomatous inter- stitial nephritis already cited.
A nanocarrier system for the delivery of nucleic acids targeted to a pancreatic beta cell line
Authors: Yuma Yamada, Mai Tabata, Yukari Yasuzaki, Masatoshi Nomura, Atsushi Shibata, Yuta Ibayashi, Yosuke Taniguchi, Shigeki Sasaki, Hideyoshi Harashima
Journal: Biomaterials (2014)
Prophylaxis against Opportunistic Infections in Patients with Human Immunodeficiency Virus Infection
Authors: Joseph A. Kovacs, Henry Masur
Journal: New England Journal of Medicine (2000)

Soon after the acquired immunodeficiency syndrome (AIDS) was first described in 1981,14 it became clear that opportunistic infections occurred with remarkable frequency and caused substantial morbidity and mortality among patients with AIDS. On the basis of a series of clinical trials, chemoprophylaxis to prevent initial episodes of certain opportunistic infections (primary prophylaxis) and subsequent episodes (secondary prophylaxis) became the standard of care. The success of highly active antiretroviral therapy (defined as combination antiretroviral regimens that include either a potent viral-protease inhibitor or a nonnucleoside reverse-transcriptase inhibitor) in reducing the incidence of AIDS-related opportunistic infections and consequent morbidity and mortality . . .
Lymph node IL-18 expression in adult-onset Still’s disease
Authors: P Conigliaro, R Priori, M Bombardieri, C Alessandri, F Barone, C Pitzalis, I B McInnes, G Valesini
Journal: Annals of the Rheumatic Diseases (2009)

IL-18 is a pleiotropic immunoregulatory cytokine that has been described and implicated in the pathogenesis of a variety of inflammatory diseases.1–4

Studies in murine models of arthritis and clinical studies suggest that dendritic cells, macrophages and synoviocites within the synovial membrane can produce IL-18.1 5–7 IL-18 expression has in turn been implicated in the reciprocal regulation of other pro-inflammatory cytokines, such as tumour necrosis factor alpha.8

Recent data clearly demonstrated that IL-18 serum levels were significantly elevated in adult-onset Still’s disease (AOSD) and correlated with disease activity and serum ferritin levels.2–4 AOSD is characterised by substantial and dysregulated …
Scintiangiographic Diagnosis of Acute Mesenteric Vascular Occlusion
Authors: JOHN R. STY, PANAYIOTIS J. ASIMACOPOULOS
Journal: Clinical Nuclear Medicine (1980)

The scintiangiographic abnormalities associated with acute mesenteric vascular occlusion in a child are described. The examination demonstrated absence of mesenteric vascular perfusion and arterialization of the liver. The scintiangiographic examination was instrumental in the patient's management.
Hepatitis B virus as a gene delivery vector activating foreign antigenic T cell response that abrogates viral expression in mouse models
Authors: Qiang Deng, Maryline Mancini-Bourgine, Xiaoming Zhang, Marie-Christine Cumont, Ren Zhu, Yu-Chun Lone, Marie-Louise Michel
Journal: Hepatology (2009)

Chronic hepatitis B virus (HBV) infection is characterized by functionally impaired T cell responses. To ensure active immunotherapy, the immune response must be switched from exhausted T cells to functional effectors that can attain the liver and cure the viral infection. We thus designed a recombinant HBV (rHBV) containing a modified viral core gene that specifically delivers a foreign antigenic polyepitope to the liver. This recombinant virus could only be self-maintained in hepatocytes already infected by HBV through capsid complementation. A strong foreign epitope-specific T cell response was first primed in the periphery by way of DNA immunization in human leukocyte antigen (HLA)-A2/DR1 transgenic mice. After the hydrodynamic (hyd.) injection of rHBV, expression of the foreign antigenic polyepitope in hepatocytes attracted/reactivated a vigorous T cell response in situ. Most liver-infiltrating CD8(+) T cells proved to be functional effectors. Following DNA priming and hyd. injection, the rHBV-based expression of hepatitis B surface antigen (HBsAg) in mouse liver was almost completely inhibited without causing major liver injury. Studies in HBsAg/HLA-A2/DR1 transgenic mice further validated our approach.For the first time, HBV was used as a gene delivery vector, which strongly triggered functional T cell response and subsequently controlled the viral expression in the liver of surrogate mouse models for HBV infection. It might represent an innovative and promising strategy of active immunotherapy during HBV persistent infection. This concept could even be more generally extended to other chronic viral diseases.
Rates of lobular carcinoma increased markedly in the 1990s
Authors: S. Gottlieb
Journal: BMJ (2003)

A type of breast cancer known as invasive lobular carcinoma, which was once considered a fairly uncommon form of breast cancer, increased markedly in incidence during the 1990s in the United States.

Researchers looked at data on women aged 30 years or older drawn from nine cancer registries that participate in the surveillance, epidemiology, and end results (SEER) programme of the National Cancer Institute. The registries cover …
Increasing Prevalence of Gestational Diabetes Mellitus
Authors: Assiamira Ferrara
Journal: Diabetes Care (2007)

Recent data show that gestational diabetes mellitus (GDM) prevalence has increased by ∼10–100% in several race/ethnicity groups during the past 20 years. A true increase in the prevalence of GDM, aside from its adverse consequences for infants in the newborn period, might also reflect or contribute to the current patterns of increasing diabetes and obesity, especially in the offspring. Therefore, the public health aspects of increasing GDM need more attention.

The frequency of GDM usually reflects the frequency of type 2 diabetes in the underlying population (1,2). Established risk factors for GDM are advanced maternal age, obesity, and family history of diabetes (3). Unquestionably, there are ethnic differences in the prevalence of GDM (4–15). In the U.S., Native Americans, Asians, Hispanics, and African-American women are at higher risk for GDM than non-Hispanic white women (4–6,8–11,13–15). In Australia, GDM prevalence was found to be higher in women whose country of birth was China or India than in women whose country of birth was in Europe or Northern Africa (7). GDM prevalence was also higher in Aboriginal women than in non-Aboriginal women (12). In Europe, GDM has been found to be more common among Asian women than among European women (16). The proportion of pregnancies complicated by GDM in Asian countries has been reported to be lower than the proportion observed in Asian women living in other continents (17). In India, GDM has been found to be more common in women living in urban areas than in women living in rural areas (18).

The trend toward older maternal age (19), the epidemic of obesity (20) and diabetes (21), and the decrease in physical activity (22) and the adoption of modern lifestyles in developing countries (23) may all …
Computational purification of individual tumor gene expression profiles leads to significant improvements in prognostic prediction
Authors: Gerald Quon, Syed Haider, Amit G Deshwar, Ang Cui, Paul C Boutros, Quaid Morris
Journal: Genome Medicine (2013)

Tumor heterogeneity is a limiting factor in cancer treatment and in the discovery of biomarkers to personalize it. We describe a computational purification tool, ISOpure, to directly address the effects of variable normal tissue contamination in clinical tumor specimens. ISOpure uses a set of tumor expression profiles and a panel of healthy tissue expression profiles to generate a purified cancer profile for each tumor sample and an estimate of the proportion of RNA originating from cancerous cells. Applying ISOpure before identifying gene signatures leads to significant improvements in the prediction of prognosis and other clinical variables in lung and prostate cancer.
A new oligomeric parvalbumin allergen of Atlantic cod (Gad mI) encoded by a gene distinct from that of Gad cI
Authors: S. Das Dores, C. Chopin, C. Villaume, J. Fleurence, J.‐L. Guéant
Journal: Allergy (2002)

The major allergen of Baltic cod (Gadus callarias) is a 12.3-kDa parvalbumin with two calcium-binding sites corresponding to EF-hand motifs. Our group found a 24-kDa IgE-reactive band that was also recognized by a monoclonal antiparvalbumin antibody in Atlantic cod (Gadus morhua). Our purpose was to purify and to determine the cDNA deduced sequence of this new cod allergen.Proteins from pre rigor mortis Atlantic cod were separated by gel filtration and the eluted peaks were analysed by SDS-PAGE and Western blotting with sera of sensitized patients and with antiparvalbumin. Protein bands were microsequenced, RNA transcripts were amplified by reverse transcription and polymerase chain reaction (RT-PCR) using primer combinations overlapping the open reading frame.Four IgE and antiparvalbumin reactive proteins(12.5, 24, 38 and 51 kDa) were detected in gel filtration eluate. The cDNA deduced sequence of the 24 kDa protein had 109 amino acid residues with a molecular weight of 11.5 kDa and a theoretical pI of 4.34. The 24 kDa band corresponded therefore to a dimer of a beta-parvalbumin. Its homology was higher with Sal sI than with Gad cI. This new allergen was named Gad mI.We have characterized a new parvalbumin allergen in Gadus morhua. This protein formed oligomers in native and in reducing conditions. Gad mI and Gad cI may correspond to two distinct genes of Gadus species.
Balloon Embolization for Treatment of Pulmonary Arteriovenous Fistulas
Authors: Peter B. Terry, Klemens H. Barth, Stephen L. Kaufman, Robert I. White
Journal: New England Journal of Medicine (1980)

Pulmonary arteriovenous malformations associated with hereditary hemorrhagic telangiectasia are often multiple and may enlarge with time.1 Shunt-induced hypoxemia is surgically correctable when the lesions are solitary or localized to one or two lobes.2 When surgery is contraindicated the therapeutic options are limited. We wish to describe a patient with hereditary hemorrhagic telangiectasia in whom multiple balloons were embolized into eight pulmonary arteriovenous malformations to correct severe shunt-induced hypoxemia.Case ReportA 55-year-old man with hereditary hemorrhagic telangiectasia noted the onset of dyspnea in January 1979 and was hospitalized for evaluation of its progression in March 1979. The chest film showed . . .