bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of BMI, airflow obstruction, St George's Respiratory Questionnaire and age index in prognostication of Asian COPD
Authors: Chan Hiang Ping , Mukhopadhyay Amartya , Chong Pauline Lee Poh , Chin Sally , Wong Xue Yun , Ong Venetia , Chan Yiong Huak , Lim Tow Keang , Phua Jason 
Published: September 2016

ABSTRACT
Background and objective
COPD is a complex condition with a heavy burden of disease. Many multidimensional tools have been studied for their prognostic utility but none has been universally adopted as each has its own limitations. We hypothesize that a multidimensional tool examining four domains, health‐related quality of life, disease severity, systemic effects of disease and patient factors, would better categorize and prognosticate these patients.MethodsWe first evaluated 300 patients and found four factors that predicted mortality: BMI, airflow obstruction, St George's Respiratory Questionnaire and age (BOSA). A 10‐point index (BOSA index) was constructed and prospectively validated in a cohort of 772 patients with all‐cause mortality as the primary outcome. Patients were categorized into their respective BOSA quartile group based on their BOSA score. Multivariate survival analyses and receiver operator characteristic (ROC) curves were used to assess the BOSA index.ResultsPatients in BOSA Group 4 were at higher risk of death compared with their counterparts in Group 1 (hazard ratio (HR): 0.29, 95% CI: 0.16–0.51, P < 0.001) and Group 2 (HR: 0.53, 95% CI: 0.34‐0.82, P = 0.005). Race and gender did not affect mortality. The area under the ROC curve for BOSA index was 0.690 ± 0.025 while that for Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 was 0.641 ± 0.025 (P = 0.17).ConclusionThe BOSA index predicts mortality well and it has at least similar prognostic utility as GOLD 2011 in Asian patients. The BOSA index is a simple tool that does not require complex equipment or testing. It has the potential to be used widely.
Subgroup Selection in Adaptive Signature Designs of Confirmatory Clinical Trials
Authors: Zhang Zhiwei , Li Meijuan , Lin Min , Soon Guoxing , Greene Tom , Shen Changyu 
Published: September 2016

SummaryThe increasing awareness of treatment effect heterogeneity has motivated flexible designs of confirmatory clinical trials that prospectively allow investigators to test for treatment efficacy for a subpopulation of patients in addition to the entire population. If a target subpopulation is not well characterized in the design stage, it can be developed at the end of a broad eligibility trial under an adaptive signature design. The paper proposes new procedures for subgroup selection and treatment effect estimation (for the selected subgroup) under an adaptive signature design. We first provide a simple and general characterization of the optimal subgroup that maximizes the power for demonstrating treatment efficacy or the expected gain based on a specified utility function. This characterization motivates a procedure for subgroup selection that involves prediction modelling, augmented inverse probability weighting and low dimensional maximization. A cross-validation procedure can be used to remove or reduce any resubstitution bias that may result from subgroup selection, and a bootstrap procedure can be used to make inference about the treatment effect in the subgroup selected. The approach proposed is evaluated in simulation studies and illustrated with real examples.
Bacterial resistance to antimicrobial agents and its impact on veterinary and human medicine
Authors: Schwarz Stefan , Loeffler Anette , Kadlec Kristina 
Published: September 2016

BackgroundAntimicrobial resistance has become a major challenge in veterinary medicine, particularly in the context of bacterial pathogens that play a role in both humans and animals.ObjectivesThis review serves as an update on acquired resistance mechanisms in bacterial pathogens of human and animal origin, including examples of transfer of resistant pathogens between hosts and of resistance genes between bacteria.ResultsAcquired resistance is based on resistance‐mediating mutations or on mobile resistance genes. Although mutations are transferred vertically, mobile resistance genes are also transferred horizontally (by transformation, transduction or conjugation/mobilization), contributing to the dissemination of resistance. Mobile genes specifying any of the three major resistance mechanisms – enzymatic inactivation, reduced intracellular accumulation or modification of the cellular target sites – have been found in a variety of bacteria that may be isolated from animals. Such resistance genes are associated with plasmids, transposons, gene cassettes, integrative and conjugative elements or other mobile elements. Bacteria, including zoonotic pathogens, can be exchanged between animals and humans mainly via direct contact, but also via dust, aerosols or foods. Proof of the direction of transfer of resistant bacteria can be difficult and depends on the location of resistance genes or mutations in the chromosomal DNA or on a mobile element.ConclusionThe wide variety in resistance and resistance transfer mechanisms will continue to ensure the success of bacterial pathogens in the future. Our strategies to counteract resistance and preserve the efficacy of antimicrobial agents need to be equally diverse and resourceful.
Arquitectura y patrimonio “indígena”: museos nacionales de Canadá, Estados Unidos y México
Authors: López Ruiz Francisco 
Published: September 2016

<p>Este artículo analiza los edificios que albergan tres instituciones arqueológicas y etnográficas de primer orden en tres países: el Museo Nacional de Antropología en la ciudad de México, concebido por Pedro Ramírez Vázquez (1964); el Canadian Museum of Civilization, en Ottawa/Gatineau, obra de Douglas Cardinal (1989); y el National Museum of the American Indian de Washington, D.C., proyectado también por el despacho de Cardinal (2004). La primera parte del texto describe aspectos arquitectónicos, curatoriales y museográficos de los tres museos. Posteriormente se presenta una interpretación patrimonial comparada de los tres recintos y sus respectivos acervos arqueológicos y etnográficos. Finalmente se comparan los riesgos conceptuales de la construcción de “patrimonios culturales indígenas”.</p><p> </p>
La valorizarción del espacio para la transformación de la Costa de Aquiraz, Ceará, Brasil: el cambio del paisaje
Authors: Ribeiro Moura de Abreu Marisa 
Published: September 2016

<p>Durante el período colonial, la zona costera de Ceará tuvo un papel económico secundario. El cambio del enfoque a principios del siglo XX fue la atracción de las zonas de playa, que generado un estrés ambiental en esos lugares. En Aquiraz, costa este del Estado de Ceará, Brasil, hubo un aumento de edificios de verano, resorts, condominios, parques acuáticos, entre otros, debido a la promoción turística que aumentó la ocupación de la frágil costa. El objetivo de esta investigación fue identificar los cambios en el paisaje y los impactos debidos a la ocupación y la valorización<ins cite="mailto:Claudia%20Burgos" datetime="2015-11-20T11:43"> </ins>de la costa. Esta se realizó en dos etapas: la primera, a partir de la obtención de material bibliográfico teórico metodológico, documental y cartográfico y la segunda fue el<ins cite="mailto:Claudia%20Burgos" datetime="2015-11-20T11:53"> </ins>trabajo de campo, centrado en cuestionarios. Se encontró que las nuevas formas de ocupación generaron cambios en el paisaje, que se evidencian en la disminución de los nativos<ins cite="mailto:Claudia%20Burgos" datetime="2015-11-20T12:18"> </ins>las instalaciones turísticas. Se identificó que a falta de ordenamiento para el uso y la ocupación más la especulación inmobiliaria, produjeron varios impactos socio-ambientales , entre ellos, el aumento de las zonas urbanizadas sin saneamiento básico que producen contaminación y degradación del medio ambiente, poniendo en peligro la calidad de vida de la población costera y la continuidad del propio turismo.</p><p> </p>
El ciudadano expuesto: Modernización energética, quemados y sociedad del riesgo en Colombia
Authors: Clavijo Poveda Jairo , Venegas Carrillo Juan Camilo 
Published: September 2016

<p>Entre las décadas de 1950 y 1980 el Estado Colombiano experimentó un acelerado proceso de modernización que se plasmó en la reorganización burocrática y en políticas públicas que tocaron el fondo de la sociedad y que marcaron el futuro de la relación del Estado con los ciudadanos. En este artículo centraremos la atención en una política energética que impactó dolorosamente a la sociedad colombiana, pues generó más de cuatro décadas de personas quemadas. El texto recoge un estudio cuya temática y abordaje articulan perspectivas socio-antropológicas que ponen en evidencia los costos físicos y morales de la modernización del país. Buscamos desarrollar un enfoque crítico a partir de la noción de <em>dispositivo </em>sobre un fenómeno hasta hora poco estudiado en Colombia. Para este fin se hizo un análisis cualitativo que tuvo como fuentes principales, la prensa de la época, entrevistas a actores sobrevivientes y datos estadísticos. </p>
Cárceles de la muerte: necropolítica y sistema carcelario en Colombia
Authors: Parra Gallego Germán , Bello Ramírez Jei Alanis 
Published: September 2016

<p>Este artículo propone una reflexión en torno al ejercicio punitivo estatal, con el propósito de evidenciar que el proyecto neoliberal en Colombia, en marcha desde finales del siglo XX, se ha sostenido sobre la expansión del sistema carcelario como una estrategia para controlar a aquellos grupos sociales marginados por el mercado y las matrices interseccionales de género, raza, clase y sexualidad. Nuestro argumento central es que en las cárceles de Colombia la muerte biológica y social se ha convertido en la principal herramienta de gobierno. Desarrollamos esta idea por medio de un análisis crítico de los informes sobre derechos humanos en las cárceles del país, empleando categorías interpretativas del <em>black feminism</em> como la necropolítica, el complejo industrial carcelario y la interseccionalidad, para señalar que en las cárceles opera una racionalidad que excede la biopolítica y que instala la muerte, la destrucción y la deshumanización como elementos cotidianos de su funcionamiento.</p><h1> </h1>
Forma y fondo: una etnografía de la materialidad de la justicia en Cali
Authors: Abello Claudia Jimena 
Published: September 2016

<p>El artículo busca hacer una reflexión acerca de la burocracia judicial pero desde una mirada centrada en la interacción entre las personas y las cosas. En otras palabras, se desea aportar en la comprensión de la configuración del Estado desde los múltiples vínculos entre objetos (los expedientes) y la gente (funcionarios y ciudadanos). Para ello el artículo está dividido en tres partes. En la primera, se hace un balance bibliográfico de la forma como se han investigado los juzgados y los expedientes dentro y fuera del país. Seguidamente, se iniciará con la descripción etnográfica del despacho, explicando los cargos y funciones de los empleados, el ciclo que cumplen los expedientes, las etapas por las que atraviesan los documentos y la experiencia personal de la etnógrafa como auxiliar del juzgado y encargada de hacer circular los papeles dentro y fuera del juzgado. Finalmente se hace una reflexión teórica acerca de la materialidad de la justicia a partir de los datos etnográficos.</p>
Small-Volume Adenosine, Lidocaine, and Mg
2+
4-Hour Infusion Leads to 88% Survival after 6 Days of Experimental Sepsis in the Rat without Antibiotics
Authors: Griffin Maddison Jade , Letson Hayley Louise , Dobson Geoffrey Phillip 
Published: September 2016

ABSTRACT

Innovative host-directed drug therapies are urgently required to treat sepsis. We tested the effect of a small-volume 0.9% NaCl adenosine, lidocaine, and Mg
2+
(ALM) bolus and a 4-h intravenous infusion on survivability in the rat model of polymicrobial sepsis over 6 days. ALM treatment led to a significant increase in survivability (88%) compared to that of controls (25%). Four controls died on day 2 to 3, and two died on day 5. Early death was associated with elevated plasma and lung inflammatory markers (interleukin-6 [IL-6], IL-1β, C-reactive protein), reduced white blood cell (WBC) count, hypoxemia, hypercapnia, acidosis, hyperkalemia, and elevated lactate, whereas late death was associated with a massive cytokine storm, a neutrophil-dominated WBC rebound/overshoot, increased lung oxidant injury, edema, and persistent ischemia. On day 6, seven of eight ALM survivors had inflammatory and immunological profiles not significantly different from those of sham-treated animals. We conclude in the rat model of experimental sepsis that small-volume ALM treatment led to higher survivability at 6 days (88%) than that of controls (25%). Early death in controls (day 2 to 3) was associated with significantly elevated plasma levels of IL-1β, IL-6, and C-reactive protein, severe plasma lymphocyte deficiency, reduced neutrophils, and acute lung injury. Late death (day 5) was associated with a massive neutrophil inflammatory storm, increased lung injury, and persistent ischemia. Possible mechanisms of ALM protection are discussed.
Antibody Responses to Immunizations in Children with Type I Diabetes Mellitus: a Case-Control Study
Authors: Eisenhut Michael , Chesover Alexander , Misquith Ronald , Nathwani Nisha , Walters Andrew 
Published: September 2016

ABSTRACT

Type I diabetes mellitus (DM) has been associated with abnormalities of T cells. Our objective was to assess whether antibody responses to T-cell-dependent and -independent antigens in children with DM are lower than those of children without DM. We performed a case-control study matching children with DM to children without DM by age and by assessing antibody levels to pneumococcal serotypes,
Haemophilus influenzae
, and tetanus and diphtheria toxoids and reassessing antibody levels in patients with antibody levels below protective thresholds after booster immunization. We recruited 36 children with DM and 36 age-matched controls. The mean age was 10 years. There was no difference between groups in antibody levels against the antigens tested. Pneumococcal antibody levels below the protective threshold were found in 35.9% of DM patients after conjugate pneumococcal vaccination with no difference between groups. Booster immunization with unconjugated pneumococcal vaccine resulted in a median level against pneumococcal serotypes of 2.3 μg/ml (range, 0.05 to 664.7 μg/ml) in children with DM and 6.1 μg/ml (0.12 to 203.36 μg/ml) in children without DM (
P
= 0.013). Over 85% of children had levels above the protective threshold after booster immunization with no difference between groups. There was no evidence for a reduced antibody response to T-cell-dependent antigens given during childhood immunizations in children with DM. There was a reduced antibody response to antigens of pneumococcal strains in children with DM given unconjugated pneumococcal polysaccharide vaccine compared to that of children without DM without being associated with a difference in percentage of antibody levels below the protective threshold between groups.
Identification and Analysis of Informative Single Nucleotide Polymorphisms in 16S rRNA Gene Sequences of the Bacillus cereus Group
Authors: Hakovirta Janetta R. , Prezioso Samantha , Hodge David , Pillai Segaran P. , Weigel Linda M. 
Published: September 2016

ABSTRACT

Analysis of 16S rRNA genes is important for phylogenetic classification of known and novel bacterial genera and species and for detection of uncultivable bacteria. PCR amplification of 16S rRNA genes with universal primers produces a mixture of amplicons from all rRNA operons in the genome, and the sequence data generally yield a consensus sequence. Here we describe valuable data that are missing from consensus sequences, variable effects on sequence data generated from nonidentical 16S rRNA amplicons, and the appearance of data displayed by different software programs. These effects are illustrated by analysis of 16S rRNA genes from 50 strains of the
Bacillus cereus
group, i.e.,
Bacillus anthracis
,
Bacillus cereus
,
Bacillus mycoides
, and
Bacillus thuringiensis
. These species have 11 to 14 rRNA operons, and sequence variability occurs among the multiple 16S rRNA genes. A single nucleotide polymorphism (SNP) previously reported to be specific to
B. anthracis
was detected in some
B. cereus
strains. However, a different SNP, at position 1139, was identified as being specific to
B. anthracis
, which is a biothreat agent with high mortality rates. Compared with visual analysis of the electropherograms, basecaller software frequently missed gene sequence variations or could not identify variant bases due to overlapping basecalls. Accurate detection of 16S rRNA gene sequences that include intragenomic variations can improve discrimination among closely related species, improve the utility of 16S rRNA databases, and facilitate rapid bacterial identification by targeted DNA sequence analysis or by whole-genome sequencing performed by clinical or reference laboratories.
Production of Cytomegalovirus Dense Bodies by Scalable Bioprocess Methods Maintains Immunogenicity and Improves Neutralizing Antibody Titers
Authors: Schneider-Ohrum Kirsten , Cayatte Corinne , Liu Yi , Wang Zhaoti , Irrinki Alivelu , Cataniag Floro , Nguyen Nga , Lambert Stacie , Liu Hui , Aslam Shahin , Duke Greg , McCarthy Michael P. , McCormick Louise 
Published: September 2016

ABSTRACT

With the goal of developing a virus-like particle-based vaccine based on dense bodies (DB) produced by human cytomegalovirus (HCMV) infections, we evaluated scalable culture, isolation, and inactivation methods and applied technically advanced assays to determine the relative purity, composition, and immunogenicity of DB particles. Our results increase our understanding of the benefits and disadvantages of methods to recover immunogenic DB and inactivate contaminating viral particles. Our results indicate that (i) HCMV strain Towne replicates in MRC-5 fibroblasts grown on microcarriers, (ii) DB particles recovered from 2-bromo-5,6-dichloro-1-beta-
d
-ribofuranosyl benzimidazole riboside (BDCRB)-treated cultures and purified by tangential flow filtration (TFF-DB) or glycerol tartrate gradient sedimentation (GT-DB) constitute 92% or 98%, respectively, of all particles in the final product, (iii) epithelial cell-tropic DB particles are recovered from a single round of coinfection by AD169 and Towne strain viruses, consistent with complementation between the UL130 and UL131A expressed by these strains and restoration of gH/gL/UL128-UL131A (gH pentamer), (iv) equivalent neutralizing antibody titers are induced in mice following immunization with epithelial cell-tropic DB or gH pentamer-deficient DB preparations, (v) UV-inactivated residual virus in GT-DB or TFF-DB preparations retained immunogenicity and induced neutralizing antibody, preventing viral entry into epithelial cells, and (vi) GT-DB and TFF-DB induced cellular immune responses to multiple HCMV peptides. Collectively, this work provides a foundation for future development of DB as an HCMV-based particle vaccine.

IMPORTANCE
Development of a vaccine to prevent congenital HCMV infection remains a high priority. Vaccination with human cytomegalovirus-derived noninfectious particles, or dense bodies, may constitute a safe vaccination strategy that mimics natural infection. The standard approach for purification of virus particles has been to use a multiple-step, complex gradient that presents a potential barrier to production scale-up and commercialization. In the study described here, we employed an approach that combines treatment with an antiviral terminase inhibitor and purification by a simplified process to produce a vaccine candidate providing broad antiviral humoral and cellular immunity as a foundation for future development.
Imperfect Symmetry of Sp1 and Core Promoter Sequences Regulates Early and Late Virus Gene Expression of the Bidirectional BK Polyomavirus Noncoding Control Region
Authors: Bethge Tobias , Ajuh Elvis , Hirsch Hans H. 
Published: September 2016

ABSTRACT

Rearrangements or point mutations in the noncoding control region (NCCR) of BK polyomavirus (BKPyV) have been associated with higher viral loads and more pronounced organ pathology in immunocompromised patients. The respective alterations affect a multitude of transcription factor binding sites (TFBS) but consistently cause increased expression of the early viral gene region (EVGR) at the expense of late viral gene region (LVGR) expression. By mutating TFBS, we identified three phenotypic groups leading to strong, intermediate, or impaired EVGR expression and corresponding BKPyV replication. Unexpectedly, Sp1 TFBS mutants either activated or inhibited EVGR expression when located proximal to the LVGR (
sp1-4
) or the EVGR (
sp1-2
), respectively. We now demonstrate that the bidirectional balance of EVGR and LVGR expression is dependent on affinity, strand orientation, and the number of Sp1 sites. Swapping the LVGR-proximal high-affinity
SP1-4
with the EVGR-proximal low-affinity
SP1-2
in site strand flipping or inserting an additional
SP1-2
site caused a rearranged NCCR phenotype of increased EVGR expression and faster BKPyV replication. The 5′ rapid amplification of cDNA ends revealed an imperfect symmetry between the EVGR- and LVGR-proximal parts of the NCCR, consisting of
TATA
and
TATA
-like elements, initiator elements, and downstream promoter elements. Mutation or deletion of the archetypal LVGR promoter, which is found in activated NCCR variants, abrogated LVGR expression, which could be restored by providing large T antigen (LTag) in
trans
. Thus, whereas Sp1 sites control the initial EVGR-LVGR expression balance, LTag expression can override inactivation of the LVGR promoter and acts as a key driver of LVGR expression independently of the Sp1 sites and core promoter elements.

IMPORTANCE
Polyomaviridae
currently comprise more than 70 members, including 13 human polyomaviruses (PyVs), all of which share a bidirectional genome organization mediated by the NCCR, which determines species and host cell specificity, persistence, replication, and virulence. Here, we demonstrate that the BKPyV NCCR is fine-tuned by an imperfect symmetry of core promoter elements centered around
TATA
and
TATA
-like sequences close to the EVGR and LVGR, respectively, which are governed by the directionality and affinity of two Sp1 sites. The data indicated that the BKPyV NCCR is poised toward EVGR expression, which can be readily unlatched by a simple switch affecting Sp1 binding. The resulting LTag, which is the major EVGR protein, drives viral genome replication, renders subsequent LVGR expression independently of archetypal promoter elements, and can overcome enhancer/promoter mutations and deletions. The data are pivotal for understanding how human PyV NCCRs mediate secondary host cell specificity, reactivation, and virulence in their natural hosts.