bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serologic assessment for exposure to spotted fever group rickettsiae in dogs in the Arizona–Sonora border region
Authors: Yaglom Hayley D. , Nicholson William L. , Casal Mariana , Nieto Nathan C. , Adams Laura 
Published: August 2018

AbstractRocky Mountain spotted fever (RMSF) is a severe tick‐borne rickettsial illness. In the south‐western United States and Mexico, RMSF displays unique epidemiologic and ecologic characteristics, including Rhipicephalus sanguineus sensu lato (brown dog tick) as the primary vector. Expansion and spread of the disease from hyperendemic regions of Arizona or Mexico to new areas is a key public health concern. Dogs are thought to play an important role in the emergence and circulation of R. rickettsii in these regions and are often one of earliest indicators of RMSF presence. A canine serosurvey was conducted in 2015 among owned and stray dogs at rabies clinic and animal shelters in three southern Arizona counties where RMSF had not previously been identified. Of the 217 dogs sampled, 11 (5.1%) tested positive for spotted fever group rickettsia (SFGR) IgG antibodies, with seropositivity ranging from 2.9% to 12.2% across the three counties. Large dogs were significantly more likely than small dogs to have positive titres reactive with R. rickettsii; no additional statistically significant relationships were observed between seropositivity of canine age, sex, neuter or ownership status. In addition, 17 (7.8%) dogs had ticks attached at the time of sampling, and stray dogs were significantly more likely to have ticks present than owned dogs (p < 0.001). All 57 ticks collected were identified as Rh. sanguineus s.l., and four (7%) had DNA evidence of genera‐wide Rickettsia species. The results of this project demonstrated canine seroprevalence levels lower than those previously reported from dogs in highly endemic areas, indicating a low risk of SFGR transmission to humans in the southern Arizona border region at this time. Continued surveillance is critical to identify SFGR emergence in new geographic regions and to inform prevention efforts for humans and dogs in those areas.
RETRACTED: Augmented venoarteriolar response with ageing is associated with morning blood pressure surge
Authors: Yoo Jeung‐Ki , Sun Dan‐Dan , Parker Rosemary S. , Urey Marcus A. , Romero Steven A. , Lawley Justin S. , Sarma Satyam , Vongpatanasin Wanpen , Crandall Craig G. , Fu Qi 
Published: August 2018

New Findings
What is the central question of this study?The venoarteriolar response (VAR) contributes substantially to the maintenance of orthostatic tolerance in humans. Despite its importance in haemodynamic homeostasis, the impact of ageing on the VAR remains understudied.
What is the main finding and its importance?Older adults exhibit an augmented VAR in response to leg dependency. The age‐related augmentation of the VAR might be linked with progressive increases of peripheral vascular resistance with ageing. We found a modest but significant correlation between the leg VAR and the morning blood pressure surge in older adults. Augmented leg VAR might contribute to the blood pressure elevation in the early morning.
AbstractThe venoarteriolar response (VAR) is a non‐adrenergic, non‐baroreflex‐mediated mechanism of vasoconstriction, which has been proposed to contribute ∼45% of the increase in total peripheral resistance during orthostasis. Despite its importance in human cardiovascular control during orthostatic stress, there is no information available regarding the impact of age and sex on the VAR or its role in diurnal blood pressure (BP) variation. We studied 33 (15 women) young (mean ± SD; 28 ± 4 years old) and 26 (12 women) older (71 ± 3 years old) healthy individuals. Brachial and femoral blood flow were measured using Doppler ultrasound. The percentage reduction in vascular conductance (blood flow/mean BP) during 4 min of limb dependency (35–40 cm below the heart level) was used to assess the VAR. The morning surge in BP was assessed using 24 h ambulatory BP monitoring. Peak VAR in the lower limb, but not in the upper limb, was significantly higher in the older than the younger adults (33 ± 4 versus 26 ± 6%, older versus young; P < 0.05). There was no sex difference in the VAR in either the young or the older group. A greater leg VAR was related to a greater morning surge in BP in older adults (r = −0.4, P = 0.02) but not in the young adults (r = −0.26, P = 0.1). Thus, advancing age enhances the VAR in the lower limb and is associated with the morning blood pressure surge in older adults. Sex does not affect this local axonal reflex in healthy humans.
Predictive value of electroencephalography in anti-NMDA receptor encephalitis
Authors: Sonderen Agnes van , Arends Samuel , Tavy Dénes L J , Bastiaansen Anna E M , Bruijn Marienke A A M de , Schreurs Marco W J , Sillevis Smitt Peter A E , Titulaer Maarten J 
Published: August 2018

ObjectivesAnti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARE) is a severe, but treatable disease. This study aims to give a detailed description of electroencephalogram (EEG) results in paediatric and adult patients to improve disease recognition, and analyses the predictive value of the first EEG for the final clinical outcome.MethodsThis nationwide cohort study includes patients with N-methyl-D-aspartate receptor antibodies confirmed with cell-based assay and immunohistochemistry in serum and cerebrospinal fluid. EEG recordings were re-evaluated by two experienced neurophysiologists, mixed with control EEGs for blinding. Initial EEG as well as follow-up registrations were analysed.Results35 adults and 18 children were included. Only two patients (4%) had a normal EEG. During the first recording, the majority of the patients had normal posterior rhythm (71%), which was associated with better modified Rankin Scale at final outcome (OR 4.74; 95% CI 1.56 to 14.47; p=0.006). In addition, EEGs showed focal (73%) or diffuse (67%) slowing. The first EEG was severely abnormal in 26%. However, 8 of 14 patients with a severely abnormal first EEG still had a favourable outcome. During the course of the disease, extreme delta brushes (EDBs) were present in 6 of 53(11%)patients.ConclusionsThe first EEG commonly shows normal posterior rhythm with focal or diffuse slowing. Although the sensitivity of an abnormal EEG is high (96%), normal EEG does not exclude anti-NMDARE. EDBs are only present in severely affected patients. The first EEG recording is predictive of the final clinical outcome.
Association of flavoured cigar regulations with wholesale tobacco volumes in Canada: an interrupted time series analysis
Authors: Chaiton Michael O , Schwartz Robert , Tremblay Gabrielle , Nugent Robert 
Published: August 2018

IntroductionThis study examines the association of Federal Canadian regulations passed in 2009 addressing flavours (excluding menthol) in small cigars with changes in cigar sales.MethodsQuarterly wholesale unit data as reported to Health Canada from 2001 through 2016 were analysed using interrupted time series analysis. Changes in sales of cigars with and without flavour descriptors were estimated. Analyses were seasonally adjusted. Changes in the flavour types were assessed over time.ResultsThe Federal flavour regulations were associated with a reduction in the sales of flavoured cigars by 59 million units (95% CI −86.0 to −32.4). Increases in sales of cigars with descriptors other than flavours (eg, colour or other ambiguous terms) were observed (9.6 million increase (95% CI −1.3 to 20.5), but the overall level (decline of 49.6 million units (95% CI −73.5 to −25.8) and trend of sales of cigars (6.9 million units per quarter (95% CI −8.1 to −5.7)) declined following the ban. Sensitivity analysis showed that there was no substantial difference in effect over time comparing Ontario and British Columbia, suggesting that other provincial tobacco control legislation was not associated with the changes in levels. Analyses suggested that the level change was sensitive to the specification of the date.ConclusionThis study demonstrates that flavour regulations have the potential to substantially impact tobacco sales. However, exemptions for certain flavours and product types may have reduced the effectiveness of the ban, indicating the need for comprehensive, well-designed regulations.
Evaluating the impact and equity of a tobacco-free pharmacy law on retailer density in New York City neighbourhoods
Authors: Giovenco Daniel P , Spillane Torra E , Mauro Christine M , Hernández Diana 
Published: August 2018

BackgroundIn 2018, New York City (NYC) implemented a tobacco-free pharmacy law as part of a comprehensive policy approach to curb tobacco use. This study models the reduction in tobacco retailer density following the ban to examine differences in the policy’s impact across neighbourhoods.MethodsTobacco retailer density per 1000 residents was calculated in July 2017 for each of NYC’s Neighborhood Tabulation Areas (NTAs, n=188) before and after removing pharmacies as licensed tobacco retailers. Pearson correlations and linear regression (with predictors scaled to 10 unit increments) measured associations between the projected change in retailer density after the ban and NTA demographic characteristics.ResultsOn average, retailer density decreased by 6.8% across neighbourhoods (SD: 6.3), with 17 NTAs experiencing reductions over 15%. Density reduction was greater in NTAs with higher median household income (r: 0.41, B: 1.00, p<0.0001) and a higher proportion of non-Hispanic white residents (r: 0.35, B: 0.79, p<0.0001). NTAs with a higher percentage of adults with less than a high school education (r: −0.44, B: −2.60, p<0.0001) and a higher proportion of Hispanic residents (r: −0.36, B: −1.07, p<0.0001) benefited less from the policy. These relationships held after assessing absolute changes in density (vs per cent change).ConclusionsNYC’s tobacco-free pharmacy law substantially reduces tobacco retailer density overall, but the impact is not equal across neighbourhoods. In order to minimise disparities in the tobacco retail environment, local governments considering a similar ban should supplement this strategy with other retailer restrictions to achieve equitable outcomes.
The motor repertoire of older adult fallers may constrain their response to balance perturbations
Authors: Allen Jessica L. , Franz Jason R. 
Published: August 2018

Older adults are at a high risk of falls, and most falls occur during locomotor activities like walking. This study aimed to improve our understanding of changes in neuromuscular control associated with increased risk of falls in older adults in the presence of dynamic balance challenges during walking. Motor module (also known as muscle synergy) analyses identified changes in the neuromuscular recruitment of leg muscles during walking with and without perturbations designed to elicit the visual perception of lateral instability. During normal walking we found that a history of falls (but not age) was associated with reduced motor module complexity and that age (but not a history of falls) was associated with increased step-to-step variability of module recruitment timing. Furthermore, motor module complexity was unaltered in the presence of optical flow perturbations. The specific effects of a history of falls on leg muscle recruitment included an absence and/or inability to independently recruit motor modules normally recruited to perform biomechanical functions important for walking balance control. These results suggest that fallers do not recruit the appropriate motor modules necessary for well-coordinated walking balance control even in the presence of perturbations. The identified changes in the modular control of walking balance in older fallers may either represent a neural deficit that leads to poor balance control or a prior history of falls that results in a compensatory motor adaptation. In either case, our study provides initial evidence that a reduced motor repertoire in older adult fallers may be a constraint on their ability to appropriately respond to balance challenges during walking. NEW & NOTEWORTHY This is the first study to demonstrate a reduced motor repertoire during walking in older adults with a history of falls but without any overt neurological deficits. Furthermore, using virtual reality during walking to elicit the visual perception of lateral instability, we provide initial evidence that a reduced motor repertoire in older adult fallers may be a constraint on their ability to appropriately respond to balance challenges during walking.
Situación socioeconómica familiar y neurodesarrollo de prematuros de muy bajo peso al nacer a los dos años de edad
Authors: Salinas Ulloa Viviana Monzerratt , D’Apremont Ivonne , Mena Patricia , Pittaluga Enrica 
Published: August 2018

Introducción: La relación entre neurodesarrollo y contexto social ha sido poco estudiada. Este artículo buscó caracterizar a las familias donde crecen los prematuros de muy bajo peso al nacer con nivel socioeconómico bajo y medio bajo y explorar la posible asociación entre las características socio-familiares y el neurodesarrollo a los dos años.Métodos: Prematuros en seguimiento de un hospital público de Santiago de Chile nacidos entre 2009 y 2012 con encuestas retrospectivas sobre aspectos familiares y sociales, y datos de la evolución clínica fueron analizados. Se evaluó la relación entre los datos biológicos y sociales con neurodesarrollo normal o en déficit.Resultados: 162 casos fueron analizados, 32% fueron considerados con déficit de neurodesarrollo. Las variables biológicas asociadas con el déficit de neurodesarrollo fueron peso al nacer menor a 1000 g. (p < 0,001), uso de ventilación mecánica (p < 0,001), oxígeno dependencia a las 36 semanas edad corregida (EC) (p < 0,001), sepsis tardía (p < 0,001), hemorragia intra-cerebral (p < 0,05), leucomalacia (p < 0,05), hidrocefalia (p < 0,05), convulsiones en período neonatal (p < 0,01) y enterocolitis necrotizante (p < 0,01). Los padres contaban con educación media y superior y se mantuvieron como parejas estables durante el período evaluado. El problema de consumo de alcohol a nivel familiar se asoció con déficit de neurodesarrollo (p<0,05).Conclusiones: Las familias en general tienen los recursos socioeconómicos y de estructura relacionados con desarrollo infantil. Los determinantes biológicos pesaron más que los sociales para el desarrollo infantil.
Enseñanza de la atención del parto vaginal utilizando simuladores
Authors: Rivera Muñoz Fernanda Paz , Valenzuela María , Carvajal Jorge 
Published: August 2018

Introducción: La simulación en docencia en ciencias de la salud, permite integrar conocimientos y desarrollar habilidades previo a la práctica clínica, logrando competencias complejas. Además, permite a los estudiantes implementar un cuidado personalizado, pensar críticamente y mejorar la confianza en sus capacidades. Objetivo: evaluar la contribución de la simulación de la atención del parto, en la adquisición de una habilidad esencial para alumnos que optan a desempeñarse en el área obstétrica. Materiales y métodos: se realizó una búsqueda bibliográfica basada en datos PubMed que incluyó las palabras claves simulation, labor y education y sus equivalentes en español. Se excluyeron los títulos relacionados con “anestesia en obstetricia” y “hemorragia postparto”. Se revisaron investigaciones observacionales, descriptivos, revisiones narrativas y sistemáticas, ensayos controlados, estudios cuasi experimentales y prospectivos. Resultados: Se seleccionaron 50 artículos que contenían al menos una de las palabras clave y estaban relacionados con “obstetricia” o “parto”, logrando acceder a 46 de ellos. La simulación de parto es una estrategia educativa exitosa, que permite a los alumnos sentirse más confiados, mejora el trabajo en equipo, incrementa el grado de conocimiento, mejora habilidades y permite cuidar a las usuarias sin riesgos. Conclusiones: la simulación es un método educativo que permite a los estudiantes practicar lo aprendido en clases antes de iniciar la experiencia clínica, disminuyendo el riesgo de la atención de pacientes por alumnos. Se recomienda el uso de la simulación en la docencia de atención del parto vaginal como una herramienta exitosa que contribuye en la adquisición de habilidades clínicas.
Gene Expression Integration into Pathway Modules Reveals a Pan-Cancer Metabolic Landscape
Authors: Cubuk Cankut , Hidalgo Marta R. , Amadoz Alicia , Pujana Miguel A. , Mateo Francesca , Herranz Carmen , Carbonell-Caballero Jose , Dopazo Joaquin 
Published: August 2018

AbstractMetabolic reprogramming plays an important role in cancer development and progression and is a well-established hallmark of cancer. Despite its inherent complexity, cellular metabolism can be decomposed into functional modules that represent fundamental metabolic processes. Here, we performed a pan-cancer study involving 9,428 samples from 25 cancer types to reveal metabolic modules whose individual or coordinated activity predict cancer type and outcome, in turn highlighting novel therapeutic opportunities. Integration of gene expression levels into metabolic modules suggests that the activity of specific modules differs between cancers and the corresponding tissues of origin. Some modules may cooperate, as indicated by the positive correlation of their activity across a range of tumors. The activity of many metabolic modules was significantly associated with prognosis at a stronger magnitude than any of their constituent genes. Thus, modules may be classified as tumor suppressors and oncomodules according to their potential impact on cancer progression. Using this modeling framework, we also propose novel potential therapeutic targets that constitute alternative ways of treating cancer by inhibiting their reprogrammed metabolism. Collectively, this study provides an extensive resource of predicted cancer metabolic profiles and dependencies.Significance: Combining gene expression with metabolic modules identifies molecular mechanisms of cancer undetected on an individual gene level and allows discovery of new potential therapeutic targets. Cancer Res; 78(21); 6059–72. ©2018 AACR.
Reduced Expression of PROX1 Transitions Glioblastoma Cells into a Mesenchymal Gene Expression Subtype
Authors: Goudarzi Kaveh M. , Espinoza Jaime A. , Guo Min , Bartek Jiri , Nistér Monica , Lindström Mikael S. , Hägerstrand Daniel 
Published: August 2018

Abstract
The homeodomain transcription factor PROX1 has been linked to several cancer types, including gliomas, but its functions remain to be further elucidated. Here we describe a functional role and the prognostic value of PROX1 in glioblastoma. Low expression of PROX1 correlated with poor overall survival and the mesenchymal glioblastoma subtype signature. The latter finding was recapitulated in vitro, where suppression or overexpression of PROX1 in glioma cell cultures transitioned cells to a mesenchymal or to a nonmesenchymal glioblastoma gene expression signature, respectively. PROX1 modulation affected proliferation rates that coincided with changes in protein levels of CCNA1 and CCNE1 as well as the cyclin inhibitors CDKN1A, CDKN1B, and CDKN1C. Overexpression of SOX2 increased PROX1 expression, but treatment with a CDK2 inhibitor subsequently decreased PROX1 expression, which was paralleled by decreased SOX2 levels. The THRAP3 protein was a novel binding partner for PROX1, and suppression of THRAP3 increased both transcript and protein levels of PROX1. Together, these findings highlight the prognostic value of PROX1 and its role as a regulator of glioblastoma gene expression subtypes, intratumoral heterogeneity, proliferation, and cell-cycle control.
Significance: These findings demonstrate the role and prognostic value of PROX1 in glioblastomas; low PROX1 levels correlate with a mesenchymal gene expression subtype and shorter survival in glioblastoma tumors. Cancer Res; 78(20); 5901–16. ©2018 AACR.
Dose and Schedule Determine Distinct Molecular Mechanisms Underlying the Efficacy of the p53–MDM2 Inhibitor HDM201
Authors: Jeay Sébastien , Ferretti Stéphane , Holzer Philipp , Fuchs Jeanette , Chapeau Emilie A. , Wartmann Markus , Sterker Dario , Romanet Vincent , Murakami Masato , Kerr Grainne , Durand Eric Y. , Gaulis Swann , Cortes-Cros Marta , Ruetz Stephan , Stachyra Therese-Marie , Kallen Joerg , Furet Pascal , Würthner Jens , Guerreiro Nelson , Halilovic Ensar , Jullion Astrid , Kauffmann Audrey , Kuriakose Emil , Wiesmann Marion , Jensen Michael R. , Hofmann Francesco , Sellers William R. 
Published: August 2018

Abstract
Activation of p53 by inhibitors of the p53–MDM2 interaction is being pursued as a therapeutic strategy in p53 wild-type cancers. Here, we report distinct mechanisms by which the novel, potent, and selective inhibitor of the p53–MDM2 interaction HDM201 elicits therapeutic efficacy when applied at various doses and schedules. Continuous exposure of HDM201 led to induction of p21 and delayed accumulation of apoptotic cells. By comparison, high-dose pulses of HDM201 were associated with marked induction of PUMA and a rapid onset of apoptosis. shRNA screens identified PUMA as a mediator of the p53 response specifically in the pulsed regimen. Consistent with this, the single high-dose HDM201 regimen resulted in rapid and marked induction of PUMA expression and apoptosis together with downregulation of Bcl-xL in vivo. Knockdown of Bcl-xL was identified as the top sensitizer to HDM201 in vitro, and Bcl-xL was enriched in relapsing tumors from mice treated with intermittent high doses of HDM201. These findings define a regimen-dependent mechanism by which disruption of MDM2–p53 elicits therapeutic efficacy when given with infrequent dosing. In an ongoing HDM201 trial, the observed exposure–response relationship indicates that the molecular mechanism elicited by pulse dosing is likely reproducible in patients. These data support the clinical comparison of daily and intermittent regimens of p53–MDM2 inhibitors.
Significance: Pulsed high doses versus sustained low doses of the p53-MDM2 inhibitor HDM201 elicit a proapoptotic response from wild-type p53 cancer cells, offering guidance to current clinical trials with this and other drugs that exploit the activity of p53. Cancer Res; 78(21); 6257–67. ©2018 AACR.