bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenetic Profile of Human Adventitial Progenitor Cells Correlates With Therapeutic Outcomes in a Mouse Model of Limb Ischemia
Authors: Gubernator Miriam , Slater Sadie C. , Spencer Helen L. , Spiteri Inmaculada , Sottoriva Andrea , Riu Federica , Rowlinson Jonathan , Avolio Elisa , Katare Rajesh , Mangialardi Giuseppe , Oikawa Atsuhiko , Reni Carlotta , Campagnolo Paola , Spinetti Gaia , Touloumis Anestis , Tavaré Simon , Prandi Francesca , Pesce Maurizio , Hofner Manuela , Klemens Vierlinger , Emanueli Costanza , Angelini Gianni , Madeddu Paolo 
Published: January 2015

Objective—
We investigated the association between the functional, epigenetic, and expressional profile of human adventitial progenitor cells (APCs) and therapeutic activity in a model of limb ischemia.

Approach and Results—

Antigenic and functional features were analyzed throughout passaging in 15 saphenous vein (SV)–derived APC lines, of which 10 from SV leftovers of coronary artery bypass graft surgery and 5 from varicose SV removal. Moreover, 5 SV-APC lines were transplanted (8×10
5
cells, IM) in mice with limb ischemia. Blood flow and capillary and arteriole density were correlated with functional characteristics and DNA methylation/expressional markers of transplanted cells. We report successful expansion of tested lines, which reached the therapeutic target of 30 to 50 million cells in ≈10 weeks. Typical antigenic profile, viability, and migratory and proangiogenic activities were conserved through passaging, with low levels of replicative senescence. In vivo, SV-APC transplantation improved blood flow recovery and revascularization of ischemic limbs. Whole genome screening showed an association between DNA methylation at the promoter or gene body level and microvascular density and to a lesser extent with blood flow recovery. Expressional studies highlighted the implication of an angiogenic network centered on the vascular endothelial growth factor receptor as a predictor of microvascular outcomes.
FLT-1
gene silencing in SV-APCs remarkably reduced their ability to form tubes in vitro and support tube formation by human umbilical vein endothelial cells, thus confirming the importance of this signaling in SV-APC angiogenic function.

Conclusions—
DNA methylation landscape illustrates different therapeutic activities of human APCs. Epigenetic screening may help identify determinants of therapeutic vasculogenesis in ischemic disease.
Relationship Between White Matter Hyperintensities, Cortical Thickness, and Cognition
Authors: Tuladhar Anil M. , Reid Andrew T. , Shumskaya Elena , de Laat Karlijn F. , van Norden Anouk G.W. , van Dijk Ewoud J. , Norris David G. , de Leeuw Frank-Erik 
Published: January 2015

Background and Purpose—
White matter hyperintensities (WMH) are associated with clinically heterogeneous symptoms that cannot be explained by these lesions alone. It is hypothesized that these lesions are associated with distant cortical atrophy and cortical thickness network measures, which can result in an additional cognitive impairment. Here, we investigated the relationships between WMH, cortical thickness, and cognition in subjects with cerebral small vessel disease.

Methods—
A total of 426 subjects with cerebral small vessel disease were included, aged between 50 and 85 years, without dementia, and underwent MRI scanning. Cortical thickness analysis was performed, and WMH were manually segmented. Graph theory was applied to examine the relationship between network measures and WMH, and structural covariance matrices were constructed using inter-regional cortical thickness correlations.

Results—
Higher WMH load was related to lower cortical thickness in frontotemporal regions, whereas in paracentral regions, this was related to higher cortical thickness. Network analyses revealed that measures of network disruption were associated with WMH and cognitive performance. Furthermore, WMH in specific white matter tracts were related to regional-specific cortical thickness and network measures. Cognitive performances were related to cortical thickness in frontotemporal regions and network measures, and not to WMH, while controlling for cortical thickness.

Conclusions—
These cross-sectional results suggest that cortical changes (regional-specific damage and network breakdown), mediated (in)directly by WMH (tract-specific damage) and other factors (eg, vascular risk factors), might lead to cognitive decline. These findings have implications in understanding the relationship between WMH, cortical morphology, and the possible attendant cognitive decline and eventually dementia.
MJO Initiation Processes over the Tropical Indian Ocean during DYNAMO/CINDY2011*
Authors: Li Tim , Zhao Chongbo , Hsu Pang-chi , Nasuno Tomoe 
Published: January 2015

Abstract
A multination joint field campaign called the Dynamics of MJO/Cooperative Indian Ocean Experiment on Intraseasonal Variability in Year 2011 (DYNAMO/CINDY2011) took place in the equatorial Indian Ocean (IO) in late 2011. During the campaign period, two strong MJO events occurred from the middle of October to the middle of December (referred to as MJO I and MJO II, respectively). Both the events were initiated over the western equatorial Indian Ocean (WIO) around 50°–60°E. Using multiple observational data products (ERA-Interim, the ECMWF final analysis, and NASA MERRA), the authors unveil specific processes that triggered the MJO convection in the WIO. It is found that, 10 days prior to MJO I initiation, a marked large-scale ascending motion anomaly appeared in the lower troposphere over the WIO. The cause of this intraseasonal vertical motion anomaly was attributed to anomalous warm advection by a cyclonic gyre anomaly over the northern IO. The MJO II initiation was preceded by a low-level specific humidity anomaly. This lower-tropospheric moistening was attributed to the advection of mean moisture by anomalous easterlies over the equatorial IO. The contrast of anomalous precursor winds at the equator (westerly versus easterly) implies different triggering mechanisms for the MJO I and II events. It was found that upper-tropospheric circumnavigating signals did not contribute the initiation of both the MJO events. The EOF-based real-time multivariate MJO (RMM) indices should not be used to determine MJO initiation time and location because they are primarily used to capture large zonal scale and eastward-propagating signals, not localized features.
Examining the Roles of the Easterly Wave Critical Layer and Vorticity Accretion during the Tropical Cyclogenesis of Hurricane Sandy*
Authors: Lussier Louis L. , Rutherford Blake , Montgomery Michael T. , Boothe Mark A. , Dunkerton Timothy J. 
Published: January 2015

Abstract
The tropical cyclogenesis sequence of Hurricane Sandy is examined. It is shown that genesis occurs within a recirculating Kelvin cat’s-eye flow of a westward-propagating tropical wave. The cat’s-eye flow is able to provide a protective environment for the mesoscale vortex to grow and is characterized by gradual column moistening and increased areal coverage of deep cumulus convection. These findings are generally consistent with a recently proposed tropical cyclogenesis sequence referred to as the “marsupial paradigm.” Sandy’s cyclogenesis provides a useful illustration of the marsupial paradigm within a partially open recirculating region, with the opening located south of the pouch center. It is suggested that the opening acts to enhance the genesis process because it is adjacent to an environment characterized by warm, moist air, conditions favorable for tropical cyclogenesis. From a dynamical perspective, accretion of low-level cyclonic vorticity filaments into the developing vortex from several sources (the South American convergence zone, an easterly wave located west of the pre-Sandy wave, and cyclonic vorticity generated along Hispaniola) is documented. Organization and growth of the nascent storm is enhanced by this accretion of cyclonic vorticity. A Lagrangian trajectory analysis is used to assess potential contributions to Sandy’s spinup from a Caribbean gyre and the easterly wave that formed Hurricane Tony. This analysis indicates that these features are outside of the Lagrangian flow boundaries that define the pre-Sandy wave and do not directly contribute to spinup of the vortex. Finally, the effectiveness of forecasts from the U.S. and European operational numerical weather prediction models is discussed for this case.
Psychosocial Distress in Patients with Thyroid Cancer
Authors: Buchmann Luke , Ashby Shaelene , Cannon Richard B. , Hunt Jason P. 
Published: January 2015

ObjectiveThe purpose of this study is to evaluate levels of psychosocial distress in thyroid cancer patients. An analysis of factors contributing to levels of distress is included.Study DesignIndividual retrospective cohort study.SettingHead and neck cancer clinic at the Huntsman Cancer Institute.Subjects and MethodsA total of 118 newly diagnosed thyroid cancer patients were included in the study. Univariate and multivariate analyses evaluated levels of and factors contributing to distress.ResultsAlmost half (43.3%) of patients had significant distress. Those with self‐reported psychiatric history, use of antidepressant medication, and history of radiation treatment had higher levels of distress. On multivariate analysis, patient endorsement of emotional issues predicted a higher distress level.ConclusionsThyroid cancer patients have high distress levels. Identification of thyroid cancer patients with high distress levels is important to offer additional support during cancer therapy.
Trifurcation of MCD: First Budget as Essential Tool of Governance
Authors: Singhania Monica , Sharma Mayank 
Published: January 2015

Trifurcation of Municipal Corporation of Delhi (MCD) in May 2012 posed a big challenge in terms of distribution of assets and liabilities in limited time considering the notification was issued only in December 2011. One of the biggest tasks was to prepare the budget of three newly formed corporations, namely, North, South and East Delhi Municipal Corporation, and its presentation and adoption on the very first day of their formation. This was essential to authorize the three newly formed corporations to start functioning, from day one, as distinct legal entities and to incur expenditure for development, socio-economic welfare and day to day administration. While trifurcating the budget, the importance of each head of revenue and expenditure and its significance in monitoring and control of associated physical activities was especially considered. We showcase in a step-by-step approach the installation and innovative development of budgetary system in the trifurcated MCD so as to highlight the use of this management tool as a prerequisite to good governance. From social perspective, budget plays a significant role in urban local bodies to enable them to meet their socio-political obligations. Good estimations are extremely important in order to be able to strike appropriate balance among multiple obligations. Trifurcation of budget was undertaken not only by adopting objective criteria based on availability of data but also keeping in mind the social and developmental obligations of the newly formed Corporations.
HSPH1 inhibition downregulates Bcl-6 and c-Myc and hampers the growth of human aggressive B-cell non-Hodgkin lymphoma
Authors: Zappasodi Roberta , Ruggiero Giusi , Guarnotta Carla , Tortoreto Monica , Tringali Cristina , Cavanè Alessandra , Cabras Antonello D. , Castagnoli Lorenzo , Venerando Bruno , Zaffaroni Nadia , Gianni Alessandro M. , De Braud Filippo , Tripodo Claudio , Pupa Serenella M. , Di Nicola Massimo 
Published: January 2015

Key Points
In human aggressive B-NHLs, HSPH1 favors c-Myc and Bcl-6 expression, and its inhibition provides significant antilymphoma activity. HSPH1 is expressed in function of Bcl-6 and c-Myc and constitutes a valuable alternative lymphoma therapeutic target of aggressive B-NHLs.
R-MPV followed by high-dose chemotherapy with TBC and autologous stem-cell transplant for newly diagnosed primary CNS lymphoma
Authors: Omuro Antonio , Correa Denise D. , DeAngelis Lisa M. , Moskowitz Craig H. , Matasar Matthew J. , Kaley Thomas J. , Gavrilovic Igor T. , Nolan Craig , Pentsova Elena , Grommes Christian C. , Panageas Katherine S. , Baser Raymond E. , Faivre Geraldine , Abrey Lauren E. , Sauter Craig S. 
Published: January 2015

Key Points
We conducted a phase-2 study in newly diagnosed PCNSL utilizing R-MPV and HDC with ASCT. Excellent disease control and OS (2-year PFS: 79%) were observed, with an acceptable toxicity profile and minimal neurotoxicity.
Polycomb genes, miRNA, and their deregulation in B-cell malignancies
Authors: Wang Gang Greg , Konze Kyle D. , Tao Jianguo 
Published: January 2015

Abstract
Posttranslational modifications of histone proteins represent a fundamental means to define distinctive epigenetic states and regulate gene expression during development and differentiation. Aberrations in various chromatin-modulation pathways are commonly used by tumors to initiate and maintain oncogenesis, including lymphomagenesis. Recently, increasing evidence has demonstrated that polycomb group (PcG) proteins, a subset of histone-modifying enzymes known to be crucial for B-cell maturation and differentiation, play a central role in malignant transformation of B cells. PcG hyperactivity in B-cell lymphomas is caused by overexpression or recurrent mutations of PcG genes and deregulation of microRNAs (miRNAs) or transcription factors such as c-MYC, which regulate PcG expression. Interplays of PcG and miRNA deregulations often establish a vicious signal-amplification loop in lymphoma associated with adverse clinical outcomes. Importantly, aberrant enzymatic activities associated with polycomb deregulation, notably those caused by EZH2 gain-of-function mutations, have provided a rationale for developing small-molecule inhibitors as novel therapies. In this review, we summarize our current understanding of PcG-mediated gene silencing, interplays of PcG with other epigenetic regulators such as miRNAs during B-cell differentiation and lymphomagenesis, and recent advancements in targeted strategies against PcG as promising therapeutics for B-cell malignancies.
Obesity as a susceptibility factor to indoor particulate matter health effects in COPD
Authors: McCormack Meredith C. , Belli Andrew J. , Kaji Deepak A. , Matsui Elizabeth C. , Brigham Emily P. , Peng Roger D. , Sellers Cortlandt , Williams D'Ann L. , Diette Gregory B. , Breysse Patrick N. , Hansel Nadia N. 
Published: January 2015

Our goal was to investigate whether obesity increases susceptibility to the adverse effects of indoor particulate matter on respiratory morbidity among individuals with chronic obstructive pulmonary disease (COPD).Participants with COPD were studied at baseline, 3 and 6 months. Obesity was defined as a body mass index ≥30 kg·m−2. At each time point, indoor air was sampled for 5–7 days and particulate matter (PM) with an aerodynamic size ≤2.5 μm (PM2.5) and 2.5–10 μm (PM2.5–10) was measured. Respiratory symptoms, health status, rescue medication use, exacerbations, blood biomarkers and exhaled nitric oxide were assessed simultaneously.Of the 84 participants enrolled, 56% were obese and all were former smokers with moderate-to-severe COPD. Obese participants tended to have less severe disease as assessed by Global Initiative for Chronic Obstructive Pulmonary Disease stage and fewer pack-years of smoking. There was evidence that obesity modified the effects of indoor PM on COPD respiratory outcomes. Increases in PM2.5 and PM2.5–10 were associated with greater increases in nocturnal symptoms, dyspnoea and rescue medication use among obeseversusnon-obese participants. The impact of indoor PM on exacerbations, respiratory status and wheeze also tended to be greater among obeseversusnon-obese participants, as were differences in airway and systemic inflammatory responses to indoor PM.We found evidence that obesity was associated with exaggerated responses to indoor fine and coarse PM exposure among individuals with COPD.
Neuraminidase inhibitors, superinfection and corticosteroids affect survival of influenza patients
Authors: Lee Nelson , Leo Yee-Sin , Cao Bin , Chan Paul K.S. , Kyaw W.M. , Uyeki Timothy M. , Tam Wilson W.S. , Cheung Catherine S.K. , Yung Irene M.H. , Li Hui , Gu Li , Liu Yingmei , Liu Zhenjia , Qu Jiuxin , Hui David S.C. 
Published: January 2015

We aimed to study factors influencing outcomes of adults hospitalised for seasonal and pandemic influenza. Individual-patient data from three Asian cohorts (Hong Kong, Singapore and Beijing; N=2649) were analysed. Adults hospitalised for laboratory-confirmed influenza (prospectively diagnosed) during 2008–2011 were studied. The primary outcome measure was 30-day survival. Multivariate Cox regression models (time-fixed and time-dependent) were used.Patients had high morbidity (respiratory/nonrespiratory complications in 68.4%, respiratory failure in 48.6%, pneumonia in 40.8% and bacterial superinfections in 10.8%) and mortality (5.9% at 30 days and 6.9% at 60 days). 75.2% received neuraminidase inhibitors (NAI) (73.8% received oseltamivir and 1.4% received peramivir/zanamivir; 44.5% of patients received NAI ≤2 days and 65.5% ≤5 days after onset of illness); 23.1% received systemic corticosteroids. There were fewer deaths among NAI-treated patients (5.3%versus7.6%; p=0.032). NAI treatment was independently associated with survival (adjusted hazard ratio (HR) 0.28, 95% CI 0.19–0.43), adjusted for treatment-propensity score and patient characteristics. Superinfections increased (adjusted HR 2.18, 95% CI 1.52–3.11) and chronic statin use decreased (adjusted HR 0.44, 95% CI 0.23–0.84) death risks. Best survival was shown when treatment started within ≤2 days (adjusted HR 0.20, 95% CI 0.12–0.32), but there was benefit with treatment within 3–5 days (adjusted HR 0.35, 95% CI 0.21–0.58). Time-dependent analysis showed consistent results of NAI treatment (adjusted HR 0.39, 95% CI 0.27–0.57). Corticosteroids increased superinfection (9.7%versus2.7%) and deaths when controlled for indications (adjusted HR 1.73, 95% CI 1.14–2.62). Early NAI treatment was associated with shorter length of stay in a subanalysis.NAI treatment may improve survival of hospitalised influenza patients; benefit is greatest from, but not limited to, treatment started within 2 days of illness. Superinfections and corticosteroids increase mortality. Antiviral and non-antiviral management strategies should be considered.
Evaluation of lung recruitment maneuvers in acute respiratory distress syndrome using computer simulation
Authors: Das Anup , Cole Oana , Chikhani Marc , Wang Wenfei , Ali Tayyba , Haque Mainul , Bates Declan G , Hardman Jonathan G 
Published: January 2015

Abstract
Introduction
Direct comparison of the relative efficacy of different recruitment maneuvers (RMs) for patients with acute respiratory distress syndrome (ARDS) via clinical trials is difficult, due to the heterogeneity of patient populations and disease states, as well as a variety of practical issues. There is also significant uncertainty regarding the minimum values of positive end-expiratory pressure (PEEP) required to ensure maintenance of effective lung recruitment using RMs. We used patient-specific computational simulation to analyze how three different RMs act to improve physiological responses, and investigate how different levels of PEEP contribute to maintaining effective lung recruitment.

Methods
We conducted experiments on five ‘virtual’ ARDS patients using a computational simulator that reproduces static and dynamic features of a multivariable clinical dataset on the responses of individual ARDS patients to a range of ventilator inputs. Three recruitment maneuvers (sustained inflation (SI), maximal recruitment strategy (MRS) followed by a titrated PEEP, and prolonged recruitment maneuver (PRM)) were implemented and evaluated for a range of different pressure settings.

Results
All maneuvers demonstrated improvements in gas exchange, but the extent and duration of improvement varied significantly, as did the observed mechanism of operation. Maintaining adequate post-RM levels of PEEP was seen to be crucial in avoiding cliff-edge type re-collapse of alveolar units for all maneuvers. For all five patients, the MRS exhibited the most prolonged improvement in oxygenation, and we found that a PEEP setting of 35 cm H2O with a fixed driving pressure of 15 cm H2O (above PEEP) was sufficient to achieve 95% recruitment. Subsequently, we found that PEEP titrated to a value of 16 cm H2O was able to maintain 95% recruitment in all five patients.

Conclusions
There appears to be significant scope for reducing the peak levels of PEEP originally specified in the MRS and hence to avoid exposing the lung to unnecessarily high pressures. More generally, our study highlights the huge potential of computer simulation to assist in evaluating the efficacy of different recruitment maneuvers, in understanding their modes of operation, in optimizing RMs for individual patients, and in supporting clinicians in the rational design of improved treatment strategies.
Integration of metabolic and inflammatory mediator profiles as a potential prognostic approach for septic shock in the intensive care unit
Authors: Mickiewicz Beata , Tam Patrick , Jenne Craig N , Leger Caroline , Wong Josee , Winston Brent W , Doig Christopher , Kubes Paul , Vogel Hans J ,   for the Alberta Sepsis Network
Published: January 2015

Abstract
Introduction
Septic shock is a major life-threatening condition in critically ill patients and it is well known that early recognition of septic shock and expedient initiation of appropriate treatment improves patient outcome. Unfortunately, to date no single compound has shown sufficient sensitivity and specificity to be used as a routine biomarker for early diagnosis and prognosis of septic shock in the intensive care unit (ICU). Therefore, the identification of new diagnostic tools remains a priority for increasing the survival rate of ICU patients. In this study, we have evaluated whether a combined nuclear magnetic resonance spectroscopy-based metabolomics and a multiplex cytokine/chemokine profiling approach could be used for diagnosis and prognostic evaluation of septic shock patients in the ICU.

Methods
Serum and plasma samples were collected from septic shock patients and ICU controls (ICU patients with the systemic inflammatory response syndrome but not suspected of having an infection). 1H Nuclear magnetic resonance spectra were analyzed and quantified using the targeted profiling methodology. The analysis of the inflammatory mediators was performed using human cytokine and chemokine assay kits.

Results
By using multivariate statistical analysis we were able to distinguish patient groups and detect specific metabolic and cytokine/chemokine patterns associated with septic shock and its mortality. These metabolites and cytokines/chemokines represent candidate biomarkers of the human response to septic shock and have the potential to improve early diagnosis and prognosis of septic shock.

Conclusions
Our findings show that integration of quantitative metabolic and inflammatory mediator data can be utilized for the diagnosis and prognosis of septic shock in the ICU.