bluuebunny/crossref_metadata_2025_split huggingface dataset:
QseC Inhibitors as an Antivirulence Approach for Gram-Negative Pathogens
Authors: Curtis Meredith M. , Russell Regan , Moreira Cristiano G. , Adebesin Adeniyi M. , Wang Changguang , Williams Noelle S. , Taussig Ron , Stewart Don , Zimmern Philippe , Lu Biao , Prasad Ravi N. , Zhu Chen , Rasko David A. , Huntley Jason F. , Falck John R. , Sperandio Vanessa 
Published: November 2014

ABSTRACT

Invasive pathogens interface with the host and its resident microbiota through interkingdom signaling. The bacterial receptor QseC, which is a membrane-bound histidine sensor kinase, responds to the host stress hormones epinephrine and norepinephrine and the bacterial signal AI-3, integrating interkingdom signaling at the biochemical level. Importantly, the QseC signaling cascade is exploited by many bacterial pathogens to promote virulence. Here, we translated this basic science information into development of a potent small molecule inhibitor of QseC, LED209. Extensive structure activity relationship (SAR) studies revealed that LED209 is a potent prodrug that is highly selective for QseC. Its warhead allosterically modifies lysines in QseC, impairing its function and preventing the activation of the virulence program of several Gram-negative pathogens both
in vitro
and during murine infection. LED209 does not interfere with pathogen growth, possibly leading to a milder evolutionary pressure toward drug resistance. LED209 has desirable pharmacokinetics and does not present toxicity
in vitro
and in rodents. This is a unique antivirulence approach, with a proven broad-spectrum activity against multiple Gram-negative pathogens that cause mammalian infections.

IMPORTANCE
There is an imminent need for development of novel treatments for infectious diseases, given that one of the biggest challenges to medicine in the foreseeable future is the emergence of microbial antibiotic resistance. Here, we devised a broad-spectrum antivirulence approach targeting a conserved histidine kinase, QseC, in several Gram-negative pathogens that promotes their virulence expression. The LED209 QseC inhibitor has a unique mode of action by acting as a prodrug scaffold to deliver a warhead that allosterically modifies QseC, impeding virulence in several Gram-negative pathogens.
Oral health of elite athletes and association with performance: a systematic review
Authors: Ashley P , Di Iorio A , Cole E , Tanday A , Needleman I 
Published: November 2014

BackgroundWe aimed to systematically review the epidemiology of oral disease and trauma in the elite athlete population and to investigate the impact of oral health on sporting performance.MethodsAuthors searched Ovid MEDLINE (1950 to October 2013), Ovid EMBASE (1980 to October 2013), EBSCO SPORTDiscus (up to October 2013) and OpenGrey (http://www.opengrey.eu). No date or language restrictions were applied. Papers were included if they evaluated the oral health of professional athletes. The methodological quality of papers was evaluated using a modification of the Newcastle-Ottawa scale.ResultsThe literature search led to 9858 potentially relevant citations. Following a set of predefined exclusion criteria, 34 studies remained. Twenty-six studies reported on dental trauma, which ranged in prevalence from 14% to 47% varying by sport and country. Sixteen studies considered the oral health of athletes and reported high prevalence of oral diseases: dental caries 15–75%, dental erosion 36–85%, periodontal disease 15%. In four studies, a range between 5% and 18% of athletes reported negative impact of oral health or trauma on performance. The methodological quality of included studies was generally low.ConclusionsWithin the limits of the review, oral health of athletes is poor. We hypothesise that poor oral health associates with self-reported performance; however, this needs to be tested. Further studies on representative samples of athletes are needed to assess the size of the problem of poor oral health as well as to investigate the possible impact on performance using objective measures of performance.
Impact of maternal age on obstetric and neonatal outcome with emphasis on primiparous adolescents and older women: a Swedish Medical Birth Register Study
Authors: Blomberg Marie , Birch Tyrberg Rasmus , Kjølhede Preben 
Published: November 2014

ObjectivesTo evaluate the associations between maternal age and obstetric and neonatal outcomes in primiparous women with emphasis on teenagers and older women.DesignA population-based cohort study.SettingThe Swedish Medical Birth Register.ParticipantsPrimiparous women with singleton births from 1992 through 2010 (N=798 674) were divided into seven age groups: <17 years, 17–19 years and an additional five 5-year classes. The reference group consisted of the women aged 25–29 years.Primary outcomeObstetric and neonatal outcome.ResultsThe teenager groups had significantly more vaginal births (adjusted OR (aOR) 2.04 (1.79 to 2.32) and 1.95 (1.88 to 2.02) for age <17 years and 17–19 years, respectively); fewer caesarean sections (aOR 0.57 (0.48 to 0.67) and 0.55 (0.53 to 0.58)), and instrumental vaginal births (aOR 0.43 (0.36 to 0.52) and 0.50 (0.48 to 0.53)) compared with the reference group. The opposite was found among older women reaching a fourfold increased OR for caesarean section. The teenagers showed no increased risk of adverse neonatal outcome but presented an increased risk of prematurity <32 weeks (aOR 1.66 (1.10 to 2.51) and 1.20 (1.04 to 1.38)). Women with advancing age (≥30 years) revealed significantly increased risk of prematurity, perineal lacerations, preeclampsia, abruption, placenta previa, postpartum haemorrhage and unfavourable neonatal outcomes compared with the reference group.ConclusionsFor clinicians counselling young women it is of importance to highlight the obstetrically positive consequences that fewer maternal complications and favourable neonatal outcomes are expected. The results imply that there is a need for individualising antenatal surveillance programmes and obstetric care based on age grouping in order to attempt to improve the outcomes in the age groups with less favourable obstetric and neonatal outcomes. Such changes in surveillance programmes and obstetric interventions need to be evaluated in further studies.
Daytime napping, sleep duration and serum C reactive protein: a population-based cohort study
Authors: Leng Yue , Ahmadi-Abhari Sara , Wainwright Nick W J , Cappuccio Francesco P , Surtees Paul G , Luben Robert , Brayne Carol , Khaw Kay-Tee 
Published: November 2014

ObjectivesTo explore whether daytime napping and sleep duration are linked to serum C reactive protein (CRP), a pro-inflammatory marker, in an older aged British population.DesignCross-sectional study.SettingEuropean Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk study.ParticipantsA total of 5018 men and women aged 48–92 years reported their sleep habits and had serum CRP levels measured.Outcome and measuresCRP was measured (mg/L) during 2006–2011 in fresh blood samples using high-sensitivity methods. Participants reported napping habits during 2002–2004, and reported sleep quantity during 2006–2007. Multivariable linear regression models were used to examine the association between napping and log-transformed CRP, and geometric mean CRP levels were calculated.ResultsAfter adjustment for age and sex, those who reported napping had 10% higher CRP levels compared with those not napping. The association was attenuated but remained borderline significant (β=0.05 (95% CI 0.00 to 0.10)) after further adjustment for social class, education, marital status, body mass index, physical activity, smoking, alcohol intake, self-reported health, pre-existing diseases, systolic blood pressure, hypnotic drug use, depression and in women-only hormone replacement therapy use. The geometric means (95% CI) of CRP levels were 2.38 (2.29 to 2.47) mg/L and 2.26 (2.21 to 2.32) mg/L for those who reported napping and no napping, respectively. A U-shaped association was observed between time spent in bed at night and CRP levels, and nighttime sleep duration was not associated with serum CRP levels. The association between napping and CRP was stronger for older participants, and among extremes of time spent in bed at night.ConclusionsDaytime napping was associated with increased CRP levels in an older aged British population. Further studies are needed to determine whether daytime napping is a cause for systemic inflammation, or if it is a symptom or consequence of underlying health problems.
Combination of 4-1BB Agonist and PD-1 Antagonist Promotes Antitumor Effector/Memory CD8 T Cells in a Poorly Immunogenic Tumor Model
Authors: Chen Shihao , Lee Li-Fen , Fisher Timothy S. , Jessen Bart , Elliott Mark , Evering Winston , Logronio Kathryn , Tu Guang Huan , Tsaparikos Konstantinos , Li Xiaoai , Wang Hui , Ying Chi , Xiong Mengli , VanArsdale Todd , Lin John C. 
Published: November 2014

AbstractImmunotherapies targeting the programmed death 1 (PD-1) coinhibitory receptor have shown great promise for a subset of patients with cancer. However, robust and safe combination therapies are still needed to bring the benefit of cancer immunotherapy to broader patient populations. To search for an optimal strategy of combinatorial immunotherapy, we have compared the antitumor activity of the anti–4-1BB/anti–PD-1 combination with that of the anti–PD-1/anti–LAG-3 combination in the poorly immunogenic B16F10 melanoma model. Pronounced tumor inhibition occurred only in animals receiving anti–PD-1 and anti–4-1BB concomitantly, while combining anti–PD-1 with anti–LAG-3 led to a modest degree of tumor suppression. The activity of the anti–4-1BB/anti–PD-1 combination was dependent on IFNγ and CD8+ T cells. Both 4-1BB and PD-1 proteins were elevated on the surface of CD8+ T cells by anti–4-1BB/anti–PD-1 cotreatment. In the tumor microenvironment, an effective antitumor immune response was induced as indicated by the increased CD8+/Treg ratio and the enrichment of genes such as Cd3e, Cd8a, Ifng, and Eomes. In the spleen, the combination treatment shaped the immune system to an effector/memory phenotype and increased the overall activity of tumor-specific CD8+ CTLs, reflecting a long-lasting systemic antitumor response. Furthermore, combination treatment in C57BL/6 mice showed no additional safety signals, and only minimally increased severity of the known toxicity relative to 4-1BB agonist alone. Therefore, in the absence of any cancer vaccine, anti–4-1BB/anti–PD-1 combination therapy is sufficient to elicit a robust antitumor effector/memory T-cell response in an aggressive tumor model and is therefore a candidate for combination trials in patients. Cancer Immunol Res; 3(2); 149–60. ©2014 AACR.
Payments for Acute Myocardial Infarction Episodes-of-Care Initiated at Hospitals With and Without Interventional Capabilities
Authors: Ben-Josef Gal , Ott Lesli S. , Spivack Steven B. , Wang Changqin , Ross Joseph S. , Shah Sachin J. , Curtis Jeptha P. , Kim Nancy , Krumholz Harlan M. , Bernheim Susannah M. 
Published: November 2014

Background—
It is unknown whether hospitals with percutaneous coronary intervention (PCI) capability provide costlier care than hospitals without PCI capability for patients with acute myocardial infarction. The growing number of PCI hospitals and higher rate of PCI use may result in higher costs for episodes-of-care initiated at PCI hospitals. However, higher rates of transfers and postacute care procedures may result in higher costs for episodes-of-care initiated at non-PCI hospitals.

Methods and Results—

We identified all 2008 acute myocardial infarction admissions among Medicare fee-for-service beneficiaries by principal discharge diagnosis and classified hospitals as PCI- or non-PCI-capable on the basis of hospitals’ 2007 PCI performance. We added all payments from admission through 30 days postadmission, including payments to hospitals other than the admitting hospital. We calculated and compared risk-standardized payment for PCI and non-PCI hospitals using 2-level hierarchical generalized linear models, adjusting for patient demographics and clinical characteristics. PCI hospitals had a higher mean 30-day risk-standardized payment than non-PCI hospitals (PCI, $20 340; non-PCI, $19 713;
P
<0.001). Patients presenting to PCI hospitals had higher PCI rates (39.2% versus 13.2%;
P
<0.001) and higher coronary artery bypass graft rates (9.5% versus 4.4%;
P
<0.001) during index admissions, lower transfer rates (2.2% versus 25.4%;
P
<0.001), and lower revascularization rates within 30 days (0.15% versus 0.27%;
P
<0.0001) than those presenting to non-PCI hospitals.

Conclusions—
Despite higher PCI and coronary artery bypass graft rates for Medicare patients initially presenting to PCI hospitals, PCI hospitals were only $627 costlier than non-PCI hospitals for the treatment of patients with acute myocardial infarction in 2008.
Grading and Interpretation of White Matter Hyperintensities Using Statistical Maps
Authors: Ryu Wi-Sun , Woo Sung-Ho , Schellingerhout Dawid , Chung Moo K. , Kim Chi Kyung , Jang Min Uk , Park Kyoung-Jong , Hong Keun-Sik , Jeong Sang-Wuk , Na Jeong-Yong , Cho Ki-Hyun , Kim Joon-Tae , Kim Beom Joon , Han Moon-Ku , Lee Jun , Cha Jae-Kwan , Kim Dae-Hyun , Lee Soo Joo , Ko Youngchai , Cho Yong-Jin , Lee Byung-Chul , Yu Kyung-Ho , Oh Mi-Sun , Park Jong-Moo , Kang Kyusik , Lee Kyung Bok , Park Tai Hwan , Lee Juneyoung , Choi Heung-Kook , Lee Kiwon , Bae Hee-Joon , Kim Dong-Eog 
Published: November 2014

Background and Purpose—
We aimed to generate rigorous graphical and statistical reference data based on volumetric measurements for assessing the relative severity of white matter hyperintensities (WMHs) in patients with stroke.

Methods—
We prospectively mapped WMHs from 2699 patients with first-ever ischemic stroke (mean age=66.8±13.0 years) enrolled consecutively from 11 nationwide stroke centers, from patient (fluid-attenuated-inversion-recovery) MRIs onto a standard brain template set. Using multivariable analyses, we assessed the impact of major (age/hypertension) and minor risk factors on WMH variability.

Results—
We have produced a large reference data library showing the location and quantity of WMHs as topographical frequency-volume maps. This easy-to-use graphical reference data set allows the quantitative estimation of the severity of WMH as a percentile rank score. For all patients (median age=69 years), multivariable analysis showed that age, hypertension, atrial fibrillation, and left ventricular hypertrophy were independently associated with increasing WMH (0–9.4%, median=0.6%, of the measured brain volume). For younger (≤69) hypertensives (n=819), age and left ventricular hypertrophy were positively associated with WMH. For older (≥70) hypertensives (n=944), age and cholesterol had positive relationships with WMH, whereas diabetes mellitus, hyperlipidemia, and atrial fibrillation had negative relationships with WMH. For younger nonhypertensives (n=578), age and diabetes mellitus were positively related to WMH. For older nonhypertensives (n=328), only age was positively associated with WMH.

Conclusions—
We have generated a novel graphical WMH grading (Kim statistical WMH scoring) system, correlated to risk factors and adjusted for age/hypertension. Further studies are required to confirm whether the combined data set allows grading of WMH burden in individual patients and a tailored patient-specific interpretation in ischemic stroke-related clinical practice.
Isolated Gastrocnemius Recession for Treatment of Insertional Achilles Tendinopathy
Authors: Tallerico Valerie K. , Greenhagen Robert M. , Lowery Clinton 
Published: November 2014

Introduction. Many surgeries exist for treatment of insertional Achilles tendinopathy. Another surgical option to consider is an isolated gastrocnemius recession. Recent studies have demonstrated the success of a gastrocnemius recession for noninsertional Achilles tendinitis. We hypothesize that an isolated gastrocnemius recession can be a successful, effective, and less invasive surgery for patients with chronic insertional Achilles tendinopathy. Materials and Methods. This article presents a retrospective review of one surgeon’s results of 11 patients (2010-2012), with an average age of 59 years who presented with chronic insertional Achilles tendinopathy. Gastrocnemius recessions, either endoscopic or open, were performed after an average of 6.2 months of conservative treatment. All patients’ radiographs were reviewed preoperatively for any calcaneal spurs and divided into groups accordingly. Average follow-up time postoperatively was 13.8 months. Plantarflexion strength, equinus deformity, as well as the American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot instrument was assessed. Results. In all, 10/11 (91%) patients had high patient satisfaction, pain relief, no residual equinus deformity, loss in muscle strength and returned to regular activities successfully at 1-year follow up. All patients and groups had significant improvement in AOFAS scores. The median postoperative AOFAS score was 94.8. All patients and patient groups had significant improvement pre- to postoperatively. Patients without spurs appear to do better than patients with spurs. One patient developed recurrence of insertional heel pain and equinus deformity. Other complications included 2 sural nerve parasthesias, which resolved. Conclusion. An isolated gastrocnemius recession for chronic insertional Achilles tendinopathy can provide high satisfaction, pain relief, and a faster recovery period with few or no complications. Levels of Evidence: Therapeutic, Level IV: Case series
Four-month-old infant with intussusception presenting as altered mental status
Authors: Maldonado Luis , Takagishi Jennifer 
Published: November 2014

Objective: To remind pediatric care providers that an altered mental status can be the only presenting symptom for intussusception, a life-threatening diagnosis. Method: A case report that presents a unique presentation of intussusception: a 4-month old boy with neurological findings after a reported head injury. Conclusion: Diagnosis of intussusception in the pediatric population is highly dependent on its classical presenting signs and symptoms: sudden severe colicky abdominal pain, vomiting, and an abdominal mass in children between 3 months and 6 years of age. Consider that an altered mental status can be the only presenting symptom.
Bargaining-based jammer power allocation for dynamic eavesdropping scenario
Authors: Bowen Duan , Yueming Cai , Jianchao Zheng , Weiwei Yang , Wendong Yang 
Published: November 2014

Abstract
This paper proposes a bargaining-based jammer power allocation scheme for multi-source multi-destination wireless network in the presence of a friendly jammer and a malicious node which eavesdrops erratically. We formulate the erratic behavior of the eavesdropper as a novel model where the eavesdropper wiretaps the message of the legitimate sources with a certain probability in a time slot. Moreover, in order to obtain a fair and efficient solution, the jammer power allocation problem is modeled as a Nash bargaining game under the constraint of maximum transmit power of a friendly jammer, which is a convex optimization problem. Then, the closed form of the Nash bargaining solution (NBS) is derived, and a simple but effective centralized algorithm is proposed. Besides, we find that the even power allocation solution and the sum-secrecy-rate optimal solution are the special cases of the NBS, when the bargaining power is properly selected. Simulation results demonstrate that the NBS achieves a good performance in terms of both effectiveness and fairness.
Capacity analysis of LTE-Advanced HetNets with reduced power subframes and range expansion
Authors: Merwaday Arvind , Mukherjee Sayandev , Güvenç Ismail 
Published: November 2014

Abstract
The use of reduced power subframes in LTE Rel. 11 can improve the capacity of heterogeneous networks (HetNets) while also providing interference coordination to the picocell-edge users. However, in order to obtain maximum benefits from the reduced power subframes, setting the key system parameters, such as the amount of power reduction, carries critical importance. Using stochastic geometry, this paper lays down a theoretical foundation for the performance evaluation of HetNets with reduced power subframes and range expansion bias. The analytic expressions for average capacity and 5th percentile throughput are derived as a function of transmit powers, node densities, and interference coordination parameters in a two-tier HetNet scenario and are validated through Monte Carlo simulations. Joint optimization of range expansion bias, power reduction factor, scheduling thresholds, and duty cycle of reduced power subframes is performed to study the trade-offs between aggregate capacity of a cell and fairness among the users. To validate our analysis, we also compare the stochastic geometry-based theoretical results with the real macro base station (MBS) deployment (in the city of London) and the hexagonal grid model. Our analysis shows that with optimum parameter settings, the LTE Rel. 11 with reduced power subframes can provide substantially better performance than the LTE Rel. 10 with almost blank subframes, in terms of both aggregate capacity and fairness.
Gene expression profiling of immunomagnetically separated cells directly from stabilized whole blood for multicenter clinical trials
Authors: Letzkus Martin , Luesink Evert , Starck‐Schwertz Sandrine , Bigaud Marc , Mirza Fareed , Hartmann Nicole , Gerstmayer Bernhard , Janssen Uwe , Scherer Andreas , Schumacher Martin M , Verles Aurelie , Vitaliti Alessandra , Nirmala Nanguneri , Johnson Keith J , Staedtler Frank 
Published: November 2014

AbstractBackgroundClinically useful biomarkers for patient stratification and monitoring of disease progression and drug response are in big demand in drug development and for addressing potential safety concerns. Many diseases influence the frequency and phenotype of cells found in the peripheral blood and the transcriptome of blood cells. Changes in cell type composition influence whole blood gene expression analysis results and thus the discovery of true transcript level changes remains a challenge. We propose a robust and reproducible procedure, which includes whole transcriptome gene expression profiling of major subsets of immune cell cells directly sorted from whole blood.MethodsTarget cells were enriched using magnetic microbeads and an autoMACS® Pro Separator (Miltenyi Biotec). Flow cytometric analysis for purity was performed before and after magnetic cell sorting. Total RNA was hybridized on HGU133 Plus 2.0 expression microarrays (Affymetrix, USA). CEL files signal intensity values were condensed using RMA and a custom CDF file (EntrezGene‐based).ResultsPositive selection by use of MACS® Technology coupled to transcriptomics was assessed for eight different peripheral blood cell types, CD14+ monocytes, CD3+, CD4+, or CD8+ T cells, CD15+ granulocytes, CD19+ B cells, CD56+ NK cells, and CD45+ pan leukocytes. RNA quality from enriched cells was above a RIN of eight. GeneChip analysis confirmed cell type specific transcriptome profiles. Storing whole blood collected in an EDTA Vacutainer® tube at 4°C followed by MACS does not activate sorted cells. Gene expression analysis supports cell enrichment measurements by MACS.ConclusionsThe proposed workflow generates reproducible cell‐type specific transcriptome data which can be translated to clinical settings and used to identify clinically relevant gene expression biomarkers from whole blood samples. This procedure enables the integration of transcriptomics of relevant immune cell subsets sorted directly from whole blood in clinical trial protocols.
Stimmungen or "In the Mood for Differentiality"
Authors: Brito Matheus De 
Published: November 2014

Review of Hans Ulrich GUMBRECHT. Atmosphere, Mood, Stimmung: On a Hidden Potential of Literature, Trans. Erik Butler, Stanford, CA: Stanford University Press, 2012, pp. 148 [1st ed. Munich, Carl Hanser Verlag, 2011]. ISBN 978-0-8047-8121-0 DOI: http://dx.doi.org/10.14195/2182-8830_2-1_11