tbuckley/cabot-search huggingface dataset:
BCG Vaccination and Leukemia Mortality
Authors: R. Rosenthal
Journal: JAMA (1972)

In Chicago from 1964 through 1969, one death from leukemia was recorded among 54,414 infants 0 through 6 years of age, who were vaccinated at birth with BCG vaccine, a rate of 0.31/100,000/yr. In contrast, among 172,986 infants of a similar age and race who were not vaccinated, 21 deaths were reported, a rate of 2.02/100,000/ yr. The difference is statistically significant (P =.04) and suggests the value of BCG vaccinations in preventing leukemia in children, but since this is a retrospective study, no firm conclusions can be drawn.
Ventilator-associated lung injury: a search for better therapeutic targets
Authors: R. A. Oeckler, R. D. Hubmayr
Journal: European Respiratory Journal (2007)

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) represent a continuum of injury that may arise from a number of primary insults. Localised injury may progress due to trauma from mechanical ventilation, a finding that has led to intense debate in the clinical and experimental literature over optimal ventilator management. The implementation of low tidal volume strategies has led to an improvement in outcomes; however, mortality remains unacceptably high. In the current review, ventilator-associated lung injury is examined, as it relates to the pathophysiological changes beyond direct airway trauma in ALI and ARDS, and an attempt is made to provide a historical perspective to outline potential current and future pitfalls in the use of surrogate end-points and the discovery of potential biomarkers. The systemic responses that lead to multi-organ dysfunction, the leading causes of morbidity and mortality in ALI and ARDS, are caused by pro-inflammatory signalling cascades and the activation of such diverse mediators as reactive oxygen species, immune response elements, apoptotic constituents and coagulation proteins. These areas are examined, including key mediators, and possible future areas of interest are discussed, including the potential of an “acute lung injury chip” to integrate measured surrogate biomarkers with real-time clinical information to improve patient outcomes.
OSU-03012, a Novel Celecoxib Derivative, Induces Reactive Oxygen Species–Related Autophagy in Hepatocellular Carcinoma
Authors: Ming Gao, Pei Yen Yeh, Yen-Shen Lu, Chih-Hung Hsu, Kuen-Feng Chen, Wei-Chung Lee, Wen-Chi Feng, Ching-Shih Chen, Min-Liang Kuo, Ann-Lii Cheng
Journal: Cancer Research (2008)

Abstract Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancer death worldwide. Systemic treatments for HCC have been largely unsuccessful. OSU-03012 is a derivative of celecoxib with anticancer activity. The mechanism of action is presumably 3-phosphoinositide–dependent kinase 1 (PDK1) inhibition. This study investigated the potential of OSU-03012 as a treatment for HCC. OSU-03012 inhibited cell growth of Huh7, Hep3B, and HepG2 cells with IC50 below 1 μmol/L. In Huh7 cells, OSU-03012 did not suppress PDK1 or AKT activity. Terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling assay and flow cytometry analysis indicated that OSU-03012 did not induce cellular apoptosis. Instead, morphologic studies by light and electron microscopy, as well as special biological staining with monodansylcadaverine, acridine orange, and microtubule-associated protein 1 light chain 3, revealed OSU-03012–induced autophagy of Huh7 cells. This OSU-03012–induced autophagy was inhibited by 3-methyladenine. Moreover, reactive oxygen species (ROS) accumulation was detected after OSU-03012 treatment. Blocking ROS accumulation with ROS scavengers inhibited autophagy formation, indicating that ROS accumulation and subsequent autophagy formation might be a major mechanism of action of OSU-03012. Daily oral treatment of BALB/c nude mice with OSU-03012 suppressed the growth of Huh7 tumor xenografts. Electron microscopic observation indicated that OSU-03012 induced autophagy in vivo. Together, our results show that OSU-03012 induces autophagic cell death but not apoptosis in HCC and that the autophagy-inducing activity is at least partially related to ROS accumulation. [Cancer Res 2008;68(22):9348–57]
A strategy for oligonucleotide microarray probe reduction
Authors: Alena A Antipova, Pablo Tamayo, Todd R Golub
Journal: Genome biology (2002)

One of the factors limiting the number of genes that can be analyzed on high-density oligonucleotide arrays is that each transcript is probed by multiple oligonucleotide probes. To reduce the number of probes required for each gene, a systematic approach to choosing the most representative probes is needed. A method is presented for reducing the number of probes per gene while maximizing the fidelity to the original array design. The methodology has been tested on a dataset comprising 317 Affymetrix HuGeneFL GeneChips. The performance of the original and reduced probe sets was compared in four cancer-classification problems. The results of these comparisons show that reduction of the probe set by 95% does not dramatically affect performance, and thus illustrate the feasibility of substantially reducing probe numbers without significantly compromising sensitivity and specificity of detection. The strategy described here is potentially useful for designing small, limited-probe genome-wide arrays for screening applications.
Consensus criteria for defining ‘successful outcome’ after ACL injury and reconstruction: a Delaware-Oslo ACL cohort investigation
Authors: Andrew D Lynch, David S Logerstedt, Hege Grindem, Ingrid Eitzen, Gregory E Hicks, Michael J Axe, Lars Engebretsen, May Arna Risberg, Lynn Snyder-Mackler
Journal: British Journal of Sports Medicine (2013)

Background No gold standard exists for identifying successful outcomes 1 and 2 years after operative and non-operative management of anterior cruciate ligament (ACL) injury. This limits the ability of a researcher and clinicians to compare and contrast the results of interventions. Purpose To establish a consensus based on expert consensus of measures that define successful outcomes 1 and 2 years after ACL injury or reconstruction. Methods Members of international sports medicine associations, including the American Orthopaedic Society for Sports Medicine, the European Society for Sports Traumatology, Surgery, and Knee Arthroscopy and the American Physical Therapy Association, were sent a survey via email. Blinded responses were analysed for trends with frequency counts. A summed importance percentage (SIP) was calculated and 80% SIP operationally indicated consensus. Results 1779 responses were obtained. Consensus was achieved for six measures in operative and non-operative management: the absence of giving way, patient return to sports, quadriceps and hamstrings’ strength greater than 90% of the uninvolved limb, the patient having not more than a mild knee joint effusion and using patient-reported outcomes (PRO). No single PRO achieved consensus, but threshold scores between 85 and 90 were established for PROs concerning patient performance. Conclusions The consensus identified six measures important for successful outcome after ACL injury or reconstruction. These represent all levels of the International Classification of Functioning: effusion, giving way, muscle strength (body structure and function), PRO (activity and participation) and return to sport (participation), and should be included to allow for comparison between interventions.
A defect in pyruvate decarboxylase in a child with an intermittent movement disorder
Authors: John P. Blass, Joel Avigan, B. William Uhlendorf
Journal: Journal of Clinical Investigation (1970)

A patient with an intermittent movement disorder has been found to have an inherited defect in pyruvate decarboxylase ((2-oxo-acid carboxy-lyase, E.C. 4.1.1.1.). The patient is a 9 yr old boy who since infancy has had repeated episodes of a combined cerebellar and choreoathetoid movement disorder. He has an elevated level of pyruvic acid in his blood, an elevated urinary alanine content, and less marked elevations in blood alanine and lactate.
A survey of the burden of allergic rhinitis in Europe
Authors: G. W. Canonica, J. Bousquet, J. Mullol, G. K. Scadding, J. C. Virchow
Journal: Allergy (2007)

The perceptions of patients and physicians regarding the symptoms and impact of allergic rhinitis (AR) were assessed in a prospective, cross-sectional, international survey. This paper presents the combined survey results from five European countries (Germany, France, Italy, Spain and the UK).Data were recorded by 1,482 patients and matched with records from 415 primary care physicians and specialists. Diagnostic tests to confirm AR had been performed on 1,279 (86.3%) patients. Both physicians and patients recorded the presence, severity and impact of symptoms at the time of consultation in addition to those symptoms frequently, but not currently, present. Health-related quality of life (HRQoL) was assessed using the Mini Rhinoconjunctivitis Quality of Life Questionnaire.A large proportion of patients had moderate-severe disease (67.2%; n = 996), persistent disease (42.5%; n = 630) and comorbidities such as asthma (31.5%; n = 467). Overall, patients rated their disease as more severe than did physicians (P < 0.001). At the time of the consultation, one-third of all patients reported that their current nasal and ocular symptoms were moderate or severe in nature. According to the physicians' assessment, good control of nasal and ocular symptoms was achieved in 45.4% (n = 673) and 51.3% (n = 760) of patients, respectively, and poor symptom control in 18.0% (n = 267) and 12.1% (n = 179). Overall, 43.3% (n = 641) of those surveyed were using two or more medicines for their AR. Health-related quality of life was correlated with disease severity and with the number of days without symptoms in the previous 4 weeks. Allergic rhinitis had a significantly greater impact in patients with more persistent disease than in those with intermittent disease (2.3 +/- 1.3 vs 1.9 +/- 1.2; P < 0.001). Nonetheless, 81.8% (n = 601) of patients with intermittent disease reported some impairment of their daily life as a result of their AR.Allergic rhinitis remains a significant health problem because of the high burden of symptoms and its impact on general well being and HRQoL among patients consulting for this condition. Overall, there was a poor correlation between patients and physicians in the reporting of disease severity.
Association between angiotensin II receptor gene polymorphism and serum angiotensin converting enzyme (SACE) activity in patients with sarcoidosis
Authors: B G MARSHALL, R J SHAW
Journal: Thorax (1998)

It is now 23 years since Lieberman first reported that serum angiotensin converting enzyme (SACE) levels were raised in patients with sarcoidosis.1 He concluded that raised SACE levels appeared to be associated with the active disease process and not a familial inherited enzyme abnormality. The paper by Takemoto and colleagues in this issue of Thorax 2 provides new evidence that the sarcoid granuloma load in patients is not the only factor to account for circulating SACE levels in sarcoidosis and that polymorphisms in both the ACE and angiotensin II receptor genes may also play a part.

Angiotensin converting enzyme (ACE), a zinc metalloproteinase, catalyses the hydrolysis of carboxyterminal dipeptides, particularly the largely inactive peptide angiotensin-1 to the active angiotensin-2. This enzyme has been hypothesised to be a marker of disease activity in sarcoidosis. It is thought that ACE is produced by epithelioid …
A high density SNP genotyping approach within the 19q13 chromosome region identifies an association of a CNOT3 polymorphism with ankylosing spondylitis
Authors: Roberto Díaz-Peña, Ana M Aransay, Beatriz Suárez-Álvarez, Jacome Bruges-Armas, Naiara Rodríguez-Ezpeleta, María Regueiro, Fernando M Pimentel-Santos, Juan Mulero, Alejandra Sánchez, Eduardo Collantes, Rubén Queiro, Javier Ballina, Helena Alves, Carlos López-Larrea
Journal: Annals of the Rheumatic Diseases (2012)

Objective To identify genomic variants in the 19q13 chromosome region associated with ankylosing spondylitis (AS) in human leucocyte antigen (HLA)-B27-positive populations. Methods High-throughput genotyping of 1536 haplotype-tag single nucleotide polymorphisms (SNPs) was performed in 249 patients with AS and 302 healthy controls. Some of the identified associations were validated by genotyping four SNPs in two additional cohorts consisting of 412 cases/301 controls and 144 cases/203 controls. All individuals selected (both cases and controls) were HLA-B27-positive. Results Two markers in two different genes ( CNOT3 and LAIR2 ) showed significant association (p&lt;10 −3 ) with AS. In addition, sliding windows analysis showed association of groups of adjacent SNPs in regions located around CNOT3 (Chr19: 59347459-59356564, p=2.43×10 −4 to 6.54×10 −4 ). The associations were validated by genotyping four SNPs from regions located near LAIR2 and CNOT3 genes (rs1055234, rs8111398, rs2287828 and rs4591276) in two additional cohorts. The CNOT3 polymorphism (rs1055234) remained associated with AS (combined p=9.73×10 −6 ). One SNP, located downstream of KIR3DL1 , was detected which, tested in combination with HLA-Bw4I80, was associated with AS. Conclusion A novel significant association was detected between SNP rs1055234 and AS susceptibility.
A High Proportion of DNA Variants of<i>BRCA1</i>and<i>BRCA2</i>Is Associated with Aberrant Splicing in Breast/Ovarian Cancer Patients
Authors: David J. Sanz, Alberto Acedo, Mar Infante, Mercedes Durán, Lucía Pérez-Cabornero, Eva Esteban-Cardeñosa, Enrique Lastra, Franco Pagani, Cristina Miner, Eladio A. Velasco
Journal: Clinical Cancer Research (2010)

Most BRCA1/2 mutations are of unknown clinical relevance. An increasing amount of evidence indicates that there can be deleterious effects through the disruption of the splicing process. We have investigated the effect of aberrant splicing of BRCA1/2 on hereditary breast/ovarian cancer (HBOC).DNA variants were analyzed with splicing prediction programs to select putative splicing mutations. Splicing assays of 57 genetic variants were done by lymphocyte reverse transcription-PCR and/or hybrid minigenes in HeLa and nontumor breast epithelial cells.Twenty-four BRCA1/2 variants of Spanish HBOC patients were bioinformatically preselected. Functional assays showed that 12 variants induced anomalous splicing patterns, 6 of which accounted for 58.5% of BRCA1 families. To further evaluate the defective splicing of BRCA1/2, we analyzed 31 Breast Cancer Information Core Database (BIC) and two artificial variants that were generated by mutagenesis. Sixteen variants induced different degrees of aberrant splicing. Altogether, anomalous splicing was caused by 28 BRCA1/2 variants of all types, indicating that any DNA change can disrupt pre-mRNA processing. We show that a wide range of regulatory elements can be involved, including the canonical and cryptic splice sites, the polypyrimidine tract, and splicing enhancers/silencers. Twenty mutations were predicted to truncate the BRCA proteins and/or to delete essential domains, thus supporting a role in HBOC.An important fraction of DNA variants of BRCA1/2 presents splicing aberrations that may represent a relevant disease-causing mechanism in HBOC. The identification of splicing disruptions by functional assays is a valuable tool to discriminate between benign polymorphisms and pathogenic mutations.
The alcohol hand rub: a good soap substitute?
Authors: G.A. Johnston, J.S.C. English
Journal: British Journal of Dermatology (2007)

Good hand hygiene prevents cross‐infection in healthcare environments but adherence is poor among healthcare workers.1 Short‐chain aliphatic alcohols, ‘alcohol‐based hand rubs’ (AHRs) are now in general use by healthcare professionals for hand disinfection in order to prevent transmission of pathogens. They are indicated in clinically clean hands and are designed to be used after washing hands with detergent/soap and water.2 AHRs are reported to be superior to traditional hand washing as they require less time to apply, are faster acting, are less irritating to the skin and have been shown to contribute significantly to decreased infection rates.1 There is a continued impression, however, that compliance rates are suboptimal3 possibly because of the subjective stinging and skin discomfort induced by AHRs.1 Occupational hand dermatitis may occur in up to 30% of healthcare workers.4 This figure is higher for nursing staff5, 6 but the problem is also reported to be common in healthcare workers without direct patient contact.7 In a U.S. hospital study 26% of nurses had damaged skin of the hands while 86% reported ever having skin problems.5 These changes correlate with the use of soap at work, the number of hand washes per shift and the frequency of glove changes. The figure is higher again for atopic individuals.5 The clinical picture is predominantly that of an irritant contact dermatitis and is mainly due to soaps and detergents used in routine hand cleaning. After using an AHR, healthcare workers may report burning, which may be explained by disruption of the skin barrier by frequent hand washing. This can trigger a vicious cycle whereby the healthcare worker increases the frequency of hand washing and reduces the frequency of hand disinfection.1,Staphylococcus aureus colonization is common in dermatitis and can further exacerbate the disease. Patients with atopic dermatitis also carry higher amounts of S. aureus on their hands.8 The importance of using an AHR is therefore arguably more important in those with damaged skin than it is in those with clinically normal skin.
Concomitant systemic lupus erythematosus and ankylosing spondylitis.
Authors: I Olivieri, G Gemignani, M Balagi, A Pasquariello, G Gremignai, G Pasero
Journal: Annals of the Rheumatic Diseases (1990)

The case is reported of a 42 year old white woman meeting currently used diagnostic criteria for both ankylosing spondylitis and systemic lupus erythematosus (SLE). As found in a previously described similar case of a black man, HLA typing showed antigens associated with both SLE and seronegative spondyloarthropathy. This case thus supports the hypothesis that the two diseases occur together only when this rare combination of HLA antigens is present.
A Novel Method to Precisely Assemble Loose Nanofiber Structures for Regenerative Medicine Applications
Authors: Vince Beachley, Eleni Katsanevakis, Ning Zhang, Xuejun Wen
Journal: Advanced Healthcare Materials (2012)

Abstract Polymer nanofibers are favorable for tissue engineering scaffolds because of their high surface‐to‐volume ratio and biomimicry of the extracellular matrix. Random and uniaxially oriented polymer nanofibers are easily fabricated by conventional electrospinning techniques; however, control over fiber organization within nanofiber structures is limited when they are collected directly from an electrospinning jet. The regenerative medicine applications of electrospun scaffolds could be expanded by developing assembly methods that allow better control of fiber organization. Here, a novel technique is presented that utilizes parallel automated tracks to orient and collect nanofibers from an electrospinning jet. The stabilized fibers are then subsequently assembled into desirable structures. It is difficult to assemble complex structures directly from an electrospinning jet because of high electrical charge and velocities, so this technology adds an intermediate step where nanofibers are immobilized on automated tracks. The result is a continuous steady‐state delivery of static stabilized nanofibers that provides a unique and promising platform for automated post processing into useful nanofiber structures. This technique also allows for an indefinite amount of time, as determined by design parameters, for fibers to dry or cool before they contact other nanofibers in the collection site, thus eliminating potential for fiber‐to‐fiber adhesions even with slow evaporating solvents or high‐temperature melts. To demonstrate potential in regenerative medicine applications, several nanofiber structures were fabricated, including: 2D structures with well‐controlled fiber density; 3D loosely assembled aligned nanofiber structures with good cell penetration properties; and, complex layer‐by‐layer 3D aligned fiber structures assembled by integration with post‐processing techniques.
Efficacy and safety of an oral live attenuated human rotavirus vaccine against rotavirus gastroenteritis during the first 2 years of life in Latin American infants: a randomised, double-blind, placebo-controlled phase III study
Authors: Alexandre C Linhares, F Raúl Velázquez, Irene Pérez-Schael, Xavier Sáez-Llorens, Hector Abate, Felix Espinoza, Pío López, Mercedes Macías-Parra, Eduardo Ortega-Barría, Doris Maribel Rivera-Medina, Luis Rivera, Noris Pavía-Ruz, Ernesto Nuñez, Silvia Damaso, Guillermo M Ruiz-Palacios, Béatrice De Vos, Miguel O'Ryan, Paul Gillard, Alain Bouckenooghe
Journal: The Lancet (2008)
Partial signaling by CD8+ T cells in response to antagonist ligands.
Authors: C Reis e Sousa, E H Levine, R N Germain
Journal: The Journal of Experimental Medicine (1996)

Structural variants of an agonist peptide-major histocompatibility complex (MHC) molecule ligand can show partial agonist and/or antagonist properties. A number of such altered ligands appear to act as pure antagonists. They lack any detectable ability to induce T cell effector function and have been described as unable to induce calcium transients and turnover of inositol phosphates. This has been interpreted as an inability of these ligands to initiate any T cell receptor (TCR)-dependent signal transduction, with their antagonist properties ascribed to competition with offered agonist for TCR occupancy. Yet antagonists for mature CD8+ T cells can induce positive selection of thymocytes, implying active induction of T cell differentiation events, and partial agonists or agonist/antagonist combinations elicit a distinctive pattern of early TCR-associated tyrosine phosphorylation events in CD4+ T cells. We have therefore directly examined proximal TCR signaling in a CD8+ T cell line in response to various related ligands. TCR engagement with natural peptide-MHC class I agonist resulted in the same pattern of early TCR-associated tyrosine phosphorylation events as seen with CD4+ cells, including accumulation of both the p21 and p23 forms of phosphorylated zeta, phosphorylation of CD3 epsilon, and association of phosphorylated ZAP-70 with the TCR. Two antagonists that lacked the ability to induce any detectable CTL effector response (cytolysis, esterase release, gamma interferon secretion, interleukin-2 receptor alpha upregulation) were nevertheless found to also induce TCR-dependent phosphorylation events. In these cases, there was preferential accumulation of the p21 form of phospho-zeta without net phosphorylation of CD3 epsilon, as well as the association of nonphosphorylated ZAP-70 kinase with the receptor. These data show that variant ligands induce similar TCR-dependent phosphorylation events in CD8+ T cells as first observed in CD4+ cells. More importantly, they demonstrate that some putatively pure antagonists are actually a subset of partial agonists able to induce intracellular biochemical changes through the TCR. This delivery of a partial signal by antagonists raises the possibility that antagonism in some cases may result from active interference with stimulation of effector activity by agonist in mature T cells, while the same variant signal could selectively trigger intracellular events that allow positive without negative selection in thymocytes.