bluuebunny/crossref_metadata_2025 huggingface dataset:
Leveraging Interleaved Signal Edges for Concurrent Backscatter
Authors: Hu Pan , Zhang Pengyu , Ganesan Deepak
Published: January 2015

One of the central challenges in backscatter is how to enable concurrent transmissions. Most backscatter protocols operate in a sequential TDMA-like manner due to the fact that most nodes cannot overhear each other's transmissions, which is detrimental for throughout and energy consumption. Recent efforts to separate concurrent signals by inverting a system of linear equations is also problematic due to varying channel coefficients caused by system and environmental dynamics. In this paper, we introduce BST, a novel physical layer for backscatter communication that enables concurrent transmission by leveraging vintra-bit multiplexing of OOK signals from multiple tags. The key idea underlying BST is that the reader can sample at considerably higher rates than the tags, hence it can extract time-domain signal edges that result from interleaved transmissions of several tags. Our preliminary experiment results show that BST can achieve 5x the throughput of Buzz and 10x the throughput of TDMA-based solutions, such as EPC Gen 2.
ViFi
Authors: Guo Katherine , Sanadhya Shruti , Woo Thomas
Published: January 2015

We consider an architecture in which the same WiFi infrastructure can be dynamically shared among multiple operators. Our system, ViFi, virtualizes WLAN resources, allowing for controlled sharing of both the uplink and downlink bandwidth. ViFi operates with stock 802.11 clients, and can be implemented entirely as a software add-on for commodity 802.11 APs.

ViFi puts users (customers) of different operators in separate groups, each creating a virtual WLAN. ViFi guarantees proportional fair share of channel access time at group level, and isolates traffic between groups. The key technical contribution of ViFi is a useful form of virtualization without requiring changes to the underlying WiFi protocol.
Spartacus
Authors: Sun Zheng , Bose Raja , Zhang Pei
Published: January 2015

Recent developments in ubiquitous computing techniques enable applications that leverage personal mobile devices, such as smartphones, as a means to interact with other devices in their close proximity. Using these techniques, numerous applications can be supported in the near future, ranging from Person-to-Person interactions (for example, conference attendees exchanging contact information, or friends playing multi-player pass-the-parcel mobile games), to Person-to-Device interactions (for example, a student printing out a document by interacting with a nearby printer, remotely controlling projectors, accessing product information in stores, interacting with large displays, or changing thermostat settings).
A method for assessing heterogeneity of blood flow and metabolism in exercising normal human muscle by near-infrared spectroscopy
Authors: Vogiatzis Ioannis , Habazettl Helmut , Louvaris Zafeiris , Andrianopoulos Vasileios , Wagner Harrieth , Zakynthinos Spyros , Wagner Peter D.
Published: January 2015

Heterogeneity in the distribution of both blood flow (Q̇) and O2consumption (V̇o2) has not been assessed by near-infrared spectroscopy in exercising normal human muscle. We used near-infrared spectroscopy to measure the regional distribution of Q̇ and V̇o2in six trained cyclists at rest and during constant-load exercise (unloaded pedaling, 20%, 50%, and 80% of peak Watts) in both normoxia and hypoxia (inspired O2fraction = 0.12). Over six optodes over the upper, middle, and lower vastus lateralis, we recorded 1) indocyanine green dye inflow after intravenous injection to measure Q̇; and 2) fractional tissue O2saturation (StiO2) to estimate local V̇o2-to-Q̇ ratios (V̇o2/Q̇). Varying both exercise intensity and inspired O2fraction provided a (directly measured) femoral venous O2saturation range from about 10 to 70%, and a correspondingly wide range in StiO2. Mean Q̇-weighted StiO2over the six optodes related linearly to femoral venous O2saturation in each subject. We used this relationship to compute local muscle venous blood O2saturation from StiO2recorded at each optode, from which local V̇o2/Q̇ could be calculated by the Fick principle. Multiplying regional V̇o2/Q̇ by Q̇ yielded the corresponding local V̇o2. While six optodes along only in one muscle may not fully capture the extent of heterogeneity, relative dispersion of both Q̇ and V̇o2was ∼0.4 under all conditions, while that for V̇o2/Q̇ was minimal (only ∼0.1), indicating in fit young subjects 1) a strong capacity to regulate Q̇ according to regional metabolic need; and 2) a likely minimal impact of heterogeneity on muscle O2availability.
CD8+T-Cells Count in Acute Myocardial Infarction in HIV Disease in a Predominantly Male Cohort
Authors: Badejo Oluwatosin A. , Chang Chung-Chou , So-Armah Kaku A. , Tracy Russell P. , Baker Jason V. , Rimland David , Butt Adeel A. , Gordon Adam J. , Rinaldo Charles R. , Kraemer Kevin , Samet Jeffrey H. , Tindle Hilary A. , Goetz Matthew B. , Rodriguez-Barradas Maria C. , Bedimo Roger , Gibert Cynthia L. , Leaf David A. , Kuller Lewis H. , Deeks Steven G. , Justice Amy C. , Freiberg Matthew S.
Published: January 2015

Human Immunodeficiency Virus- (HIV-) infected persons have a higher risk for acute myocardial infarction (AMI) than HIV-uninfected persons. Earlier studies suggest that HIV viral load, CD4+T-cell count, and antiretroviral therapy are associated with cardiovascular disease (CVD) risk. Whether CD8+T-cell count is associated with CVD risk is not clear. We investigated the association between CD8+T-cell count and incident AMI in a cohort of 73,398 people (of which 97.3% were men) enrolled in the U.S. Veterans Aging Cohort Study-Virtual Cohort (VACS-VC). Compared to uninfected people, HIV-infected people with high baseline CD8+T-cell counts (>1065 cells/mm3) had increased AMI risk (adjustedHR=1.82, P<0.001, 95% CI: 1.46 to 2.28). There was evidence that the effect of CD8+T-cell tertiles on AMI risk differed by CD4+T-cell level: compared to uninfected people, HIV-infected people with CD4+T-cell counts ≥200 cells/mm3had increased AMI risk with high CD8+T-cell count, while those with CD4+T-cell counts <200 cells/mm3had increased AMI risk with low CD8+T-cell count. CD8+T-cell counts may add additional AMI risk stratification information beyond that provided by CD4+T-cell counts alone.
Complete Nucleotide Sequence Analysis of the Norovirus GII.4 Sydney Variant in South Korea
Authors: Park Ji-Sun , Lee Sung-Geun , Jin Ji-Young , Cho Han-Gil , Jheong Weon-Hwa , Paik Soon-Young
Published: January 2015

Norovirus is the primary cause of acute gastroenteritis in individuals of all ages. In Australia, a new strain of norovirus (GII.4) was identified in March 2012, and this strain has spread rapidly around the world. In August 2012, this new GII.4 strain was identified in patients in South Korea. Therefore, to examine the characteristics of the epidemic norovirus GII.4 2012 variant in South Korea, we conducted KM272334 full-length genomic analysis. The genome of the gg-12-08-04 strain consisted of 7,558 bp and contained three open reading frame (ORF) composites throughout the whole genome: ORF1 (5,100 bp), ORF2 (1,623 bp), and ORF3 (807 bp). Phylogenetic analyses showed that gg-12-08-04 belonged to the GII.4 Sydney 2012 variant, sharing 98.92% nucleotide similarity with this variant strain. According to SimPlot analysis, the gg-12-08-04 strain was a recombinant strain with breakpoint at the ORF1/2 junction between Osaka 2007 and Apeldoorn 2008 strains. This study is the first report of the complete sequence of the GII.4 Sydney 2012 strain in South Korea. Therefore, this may represent the standard sequence of the norovirus GII.4 2012 variant in South Korea and could therefore be useful for the development of norovirus vaccines.
A Rare Combination of Ovarian and Uterine Leiomyomas with Goblet Cell Carcinoid of the Appendix
Authors: Al-Shaikh Abdulrahman F. , Darwish Abdulla , Nagaraj Veena , Alsada Abeer
Published: January 2015

We present a case of the rare combination of unilateral ovarian leiomyoma, uterine leiomyoma, and goblet cell carcinoid tumor of the appendix in a premenopausal woman who presented with right iliac pain. Immunohistochemistry study for desmin (muscle marker) and chromogranin and synaptophysin (neuroendocrine markers) confirmed immunophenotyping origin. Interestingly, both tumors showed positive reaction for estrogen receptor. To our knowledge, such a combination has not been reported previously in the literature. In this paper, the pathogenesis and differential diagnosis of both types of tumors are discussed.
Geographic Tongue and Fissured Tongue in 348 Patients with Psoriasis: Correlation with Disease Severity
Authors: Picciani Bruna L. S. , Souza Thays T. , Santos Vanessa de Carla B. , Domingos Tábata A. , Carneiro Sueli , Avelleira João Carlos , Azulay David R. , Pinto Jane M. N. , Dias Eliane P.
Published: January 2015

Geographic tongue (GT) and fissured tongue (FT) are the more frequent oral lesions in patients with psoriasis. The aims of this study were to compare the prevalence of GT/FT between psoriasis group (PG) and healthy controls (HC) and investigate the correlation between GT/FT and psoriasis severity using the PASI and age of psoriasis onset. Three hundred and forty‐eight PG and 348 HC were selected. According to the age of psoriasis onset, the individuals were classified as having early psoriasis and late psoriasis. The severity of vulgaris psoriasis was determined according to PASI. A follow‐up was conducted in patients with psoriasis vulgaris (PV) with GT to evaluate the progression of oral and cutaneous lesions. The FT and GT were more frequent in PG than in HC. The incidence of GT was higher in patients with early psoriasis and that of FT in late‐psoriasis. There is association between psoriasis intensity and GT; and a higher monthly decrease of PASI score in patients without GT. The presence of GT and FT is higher in PG than in the HC. GT is associated with disease severity and may be a marker of the psoriasis severity.
Mammalian Cell Culture Process for Monoclonal Antibody Production: Nonlinear Modelling and Parameter Estimation
Authors: Selişteanu Dan , Șendrescu Dorin , Georgeanu Vlad , Roman Monica
Published: January 2015

Monoclonal antibodies (mAbs) are at present one of the fastest growing products of pharmaceutical industry, with widespread applications in biochemistry, biology, and medicine. The operation of mAbs production processes is predominantly based on empirical knowledge, the improvements being achieved by using trial-and-error experiments and precedent practices. The nonlinearity of these processes and the absence of suitable instrumentation require an enhanced modelling effort and modern kinetic parameter estimation strategies. The present work is dedicated to nonlinear dynamic modelling and parameter estimation for a mammalian cell culture process used for mAb production. By using a dynamical model of such kind of processes, an optimization-based technique for estimation of kinetic parameters in the model of mammalian cell culture process is developed. The estimation is achieved as a result of minimizing an error function by a particle swarm optimization (PSO) algorithm. The proposed estimation approach is analyzed in this work by using a particular model of mammalian cell culture, as a case study, but is generic for this class of bioprocesses. The presented case study shows that the proposed parameter estimation technique provides a more accurate simulation of the experimentally observed process behaviour than reported in previous studies.
A Novel Method of Early Diagnosis of Alzheimer’s Disease Based on EEG Signals
Authors: Al-Jumeily Dhiya , Iram Shamaila , Vialatte Francois-Benois , Fergus Paul , Hussain Abir
Published: January 2015

Studies have reported that electroencephalogram signals in Alzheimer’s disease patients usually have less synchronization than those of healthy subjects. Changes in electroencephalogram signals start at early stage but, clinically, these changes are not easily detected. To detect this perturbation, three neural synchrony measurement techniques: phase synchrony, magnitude squared coherence, and cross correlation are applied to three different databases of mild Alzheimer’s disease patients and healthy subjects. We have compared the right and left temporal lobes of the brain with the rest of the brain areas (frontal, central, and occipital) as temporal regions are relatively the first ones to be affected by Alzheimer’s disease. Moreover, electroencephalogram signals are further classified into five different frequency bands (delta, theta, alpha beta, and gamma) because each frequency band has its own physiological significance in terms of signal evaluation. A new approach using principal component analysis before applying neural synchrony measurement techniques has been presented and compared with Average technique. The simulation results indicated that applying principal component analysis before synchrony measurement techniques shows significantly better results as compared to the lateral one. At the end, all the aforementioned techniques are assessed by a statistical test (Mann‐Whitney U test) to compare the results.
Long Noncoding RNA HULC Modulates Abnormal Lipid Metabolism in Hepatoma Cells through an miR-9–Mediated RXRA Signaling Pathway
Authors: Cui Ming , Xiao Zelin , Wang Yue , Zheng Minying , Song Tianqiang , Cai Xiaoli , Sun Baodi , Ye Lihong , Zhang Xiaodong
Published: January 2015

HULC is a long noncoding RNA overexpressed in hepatocellular carcinoma (HCC), but its functional contributions in this setting have not been determined. In this study, we explored the hypothesis that HULC contributes to malignant development by supporting abnormal lipid metabolism in hepatoma cells. HULC modulated the deregulation of lipid metabolism in HCC by activating the acyl-CoA synthetase subunit ACSL1. Immunohistochemical analysis of tissue microarrays revealed that approximately 77% (180/233) of HCC tissues were positive for ACSL1. Moreover, HULC mRNA levels correlated positively with ACSL1 levels in 60 HCC cases according to real-time PCR analysis. Mechanistic investigations showed that HULC upregulated the transcriptional factor PPARA, which activated the ACSL1 promoter in hepatoma cells. HULC also suppressed miR-9 targeting of PPARA mRNA by eliciting methylation of CpG islands in the miR-9 promoter. We documented the ability of HULC to promote lipogenesis, thereby stimulating accumulation of intracellular triglycerides and cholesterol in vitro and in vivo. Strikingly, ACSL1 overexpression that generates cholesterol was sufficient to enhance the proliferation of hepatoma cells. Further, cholesterol addition was sufficient to upregulate HULC expression through a positive feedback loop involving the retinoid receptor RXRA, which activated the HULC promoter. Overall, we concluded that HULC functions as an oncogene in hepatoma cells, acting mechanistically by deregulating lipid metabolism through a signaling pathway involving miR-9, PPARA, and ACSL1 that is reinforced by a feed-forward pathway involving cholesterol and RXRA to drive HULC signaling. Cancer Res; 75(5); 846–57. ©2015 AACR.
Improvements in Radiographic Progression-Free Survival Stratified by ERG Gene Status in Metastatic Castration-Resistant Prostate Cancer Patients Treated with Abiraterone Acetate
Authors: Attard Gerhardt , de Bono Johann S. , Logothetis Christopher J. , Fizazi Karim , Mukherjee Som D. , Joshua Anthony M. , Schrijvers Dirk , van den Eertwegh Alfons J.M. , Li Weimin , Molina Arturo , Griffin Thomas W. , Kheoh Thian , Ricci Deborah S. , Zelinsky Kathy , Rathkopf Dana E. , Scher Howard I. , Ryan Charles J.
Published: January 2015

Purpose: Gene fusions leading to androgen receptor–modulated ERG overexpression occur in up to 70% of metastatic castration-resistant prostate cancers (mCRPC). We assessed the association between ERG rearrangement status and clinical benefit from abiraterone acetate.

Experimental Design: COU-AA-302 is a phase III trial comparing abiraterone acetate and prednisone versus prednisone in chemotherapy-naïve mCRPC. ERG status was evaluated by FISH on archival tumors. End points included radiographic progression-free survival (rPFS), time to PSA progression (TTPP), rate of ≥50% PSA decline from baseline, and overall survival (OS). Cox regression was used to evaluate association with time-to-event measures and Cochran–Mantel–Haenszel for PSA response.

Results: ERG status was defined for 348 of 1,088 intention-to-treat patients. ERG was rearranged in 121 of 348 patients with confirmed ERG status (35%). Cancers with an ERG fusion secondary to deletion of 21q22 and increased copy number of fusion sequences (class 2+ Edel) had a greater improvement in rPFS after abiraterone acetate and prednisone [22 vs. 5.4 months; HR (95% confidence interval, CI), 0.31 (0.15–0.68); P = 0.0033] than cancers with no ERG fusion [16.7 vs. 8.3 months; 0.53 (0.38–0.74); P = 0.0002] or other classes of ERG rearrangement. There was also greater benefit in this subgroup for TTPP.

Conclusions: Both ERG-rearranged and wild-type cancers had a significant improvement in rPFS with abiraterone acetate and prednisone in the COU-AA-302 trial. However, our data suggest that 2+ Edel cancers, accounting for 15% of all mCRPC patients and previously associated with a worse outcome, derived the greatest benefit. Clin Cancer Res; 21(7); 1621–7. ©2015 AACR.
Hedgehog Pathway Inhibitors Promote Adaptive Immune Responses in Basal Cell Carcinoma
Authors: Otsuka Atsushi , Dreier Jil , Cheng Phil F. , Nägeli Mirjam , Lehmann Holger , Felderer Lea , Frew Ian J. , Matsushita Shigeto , Levesque Mitchell P. , Dummer Reinhard
Published: January 2015

Purpose: Basal cell carcinomas (BCCs) are tumors ignored by immune surveillance. Activated Hedgehog (Hh) signaling within primary cilia is a key driver in the pathogenesis of BCCs. We examined immune alterations during treatment with systemic Hh inhibitors.

Experimental Design: We investigated biopsies from patients with BCC before (23 patients) and after 4 weeks of treatment (5 patients) with Hh signaling inhibitor. Ber-Ep4, BCL-2, Ki-67, CD4, CD8, MHC class I, HLA-DR-class II, and SOX9 were analyzed by immunohistochemistry. Primary cilia were analyzed by double immunofluorescence of acetylated tubulin and SOX9. Differential gene expression for 84 cytokines and chemokines was analyzed in 3 patients.

Results: After 4 weeks of treatment, we found reduction of Ki-67, SOX9, Ber-EP4, and BCL-2 expression in tumors associated with morphologic signs of squamous differentiation. In addition, the number of cilia-positive BCC cells was significantly decreased. An upregulation of MHC I expression on the cell membranes of residual tumor cells and an influx of CD4+, HLA-DR-class II+, and CD8+ cells with invasion into the tumor cell nests were found. Finally, qPCR arrays showed the differential expression of genes involved in modulating immune responses.

Conclusions: We show that Hh pathway inhibitor–induced tumor regression is accompanied by a dynamic change of the microenvironment with a disruption of immune privilege involving an influx of cytotoxic T cells, activation of the adaptive immune functions, and a profound alteration of the local chemokine/cytokine network. Clin Cancer Res; 21(6); 1289–97. ©2015 AACR.
State of Renal Replacement Therapy Services in Ghana
Authors: Antwi Sampson
Published: January 2015

Introduction: Renal replacement therapy (RRT) in the form of dialysis and kidney transplantation is a life-saving intervention for patients with kidney disease in failure for both acute and chronic cases. Ghana is an emerging economy in West Africa with close to 27 million people. The limited data that is available indicates a significant burden of kidney disease in Ghana. I analyzed the state of RRT in Ghana in this report. Method: A situational analysis report conducted to establish the availability and type of renal replacement therapy services across the country. Information was obtained from records at dialysis centers and also by interview of staff at these centers. Results: Haemodialysis services are available in 3 public and 3 private health institutions for adults in kidney failure both acute and chronic. These centers are located in the southern half of the country leaving the northern two-thirds uncovered. National Health Insurance Scheme pays for the cost of acute dialysis for up to GHC 850 (∼USD 265). However, there is no insurance cover for any aspect of chronic RRT putting huge financial constraints on families, which sometimes plunge entire extended families into serious financial crisis. Kidney transplantation is available on a limited scale at the national capital. Children only benefit from peritoneal dialysis for acute kidney injury, thanks to the partnership with Sustainable Kidney Care Foundation. There is no rescue intervention as of now for children with end stage renal failure. Conclusion: The current state of RRT services in Ghana is inadequate and calls for serious national consideration.
Wak Engineering Evolution
Authors: Armignacco Paolo , Garzotto Francesco , Neri Mauro , Lorenzin Anna , Ronco Claudio
Published: January 2015

The wearable artificial kidney (WAK) is a device that allows prolonged and frequent dialysis treatments for patients with end stage renal disease. It potentially provides a practical and feasible solution to satisfy the need for an optimal delivered dialysis. Until now, the WAK has already been presented in several models, proposing different therapeutic modalities and engineering approaches. The ideal solution of a WAK may come from a combination of all the prototypes developed and/or those currently in development. Consequently, it is important to have a complete overview and a deep knowledge of the possible engineering solutions in order to achieve the incremental steps necessary to solve the remaining issues of wearable extracorporeal blood purification devices. Since technical advances are continuously evolving and it is important to focus on clinical requirements and needs, a multidisciplinary collaboration has to be coordinated to achieve the final objective of the practical realization of a wearable artificial kidney. In such a context, the main aim of this article was to analyze more in detail the WAK Engineeristic Development.
The Salt Debate - Far More Salacious Than Salubrious
Authors: Satin Morton
Published: January 2015

The scientific evidence supporting dietary sodium reduction as a means of improving overall health outcomes is not yet confirmed and continues to generate considerable controversy. As previously with fat reduction, sodium reduction has become the dominant research subject in the global food industry. To comply with perceived public opinion, the largest multinational food companies have made public commitments to major reductions in sodium to meet current recommendations. This is the precise approach taken when fat came under criticism by public health agencies in the past and many believe that this precipitated our current obesity epidemic. The contradiction between the published scientific evidence on overall health outcomes and the aggressive promotion of sodium reduction policies by health authorities has inspired the characterization of this strategy as, ‘… the largest delusion in the history of preventative medicine' and others have concluded ‘… the concealment of scientific uncertainty in this case has been a mistake that has served neither the ends of science nor good policy'. While policy makers may occasionally be forced to act in the face of limited evidence to attempt to limit risks at the population level, this exception cannot be taken as a broad license to deny all new evidence that contradicts a planned agenda, if policies are to be the product of evidence rather than dogma. As was the case with fat, the strategy of sodium reduction may well qualify as a ‘Trojan Horse' of preventative medicine - a policy with an outward façade of great value but simultaneously concealing a significant risk to the population.
Ultrafiltration Failure in Peritoneal Dialysis: A Pathophysiologic Approach
Authors: Teitelbaum Isaac
Published: January 2015

Background: Ultrafiltration failure is a significant cause of technique failure for peritoneal dialysis and subsequent transfer to hemodialysis. Summary: Ultrafiltration failure is defined as failure to achieve at least 400 ml of net ultrafiltration during a 4 h dwell using 4.25% dextrose. Four major causes of ultrafiltration failure have been described. A highly effective peritoneal surface area is characterized by transition to a very rapid transport state with D/P creatinine >0.81. Low osmotic conductance to glucose is characterized by attenuation of sodium sieving and decreased peritoneal free water clearance to <26% of total ultrafiltration in the first hour of a dwell. Low effective peritoneal surface area manifests with decreases in the transport of both solute and water. A high total peritoneal fluid loss rate is the most difficult to diagnose clinically; failure to achieve ultrafiltration with an 8-10 h icodextrin dwell may provide a clue to diagnosis. Key Messages: Knowledge of the specific pathophysiology of the various causes of ultrafiltration failure will aid in the diagnosis thereof.
Single Incision versus Conventional Multiport Laparoscopic Appendectomy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Zhou Haiyang , Jin Kaizhou , Zhang Jian , Wang Weijun , Sun Yanping , Ruan Canping , Hu Zhiqian
Published: January 2015

Background: The efficacy of single incision laparoscopic appendectomy (SILA) in comparison with conventional multiport laparoscopic appendectomy (CMLA) has not been conclusively determined. Methods: A systematic literature review (Medline, EMBASE, Science Citation Index, and Cochrane Central Register of Controlled Trials) was performed. Meta-analyses of randomized controlled trials (RCTs) comparing SILA with CMLA were carried out by RevMan 5.0 software. Results: Eleven RCTs comparing SILA and CMLA were included. Overall, 1,216 patients were operated on: 611 cases by SILA versus 605 cases by CMLA. Compared with CMLA, SILA was associated with increased procedural difficulty, prolonged procedural duration, shorter length of hospital stay, earlier return to normal activity and better cosmesis. There were no significant differences in postoperative pain scores and complication rates between SILA and CMLA. Conclusion: The current best evidence shows SILA holds the promise of improving postoperative recovery and cosmetic result with equal efficacy and safety, whereas it is associated with higher surgical difficulty with longer surgical time when compared with CMLA.
Fast-Track Programs Versus Traditional Care in Hepatectomy: A Meta-Analysis of Randomized Controlled Trials
Authors: Lei Qiucheng , Wang Xinying , Tan Shanjun , Xia Xianfeng , Zheng Huazhen , Wu Chao
Published: January 2015

Background/Aims: The role of fast-track programs in hepatectomy is unclear. This meta-analysis aimed to evaluate the efficacy and safety of fast-track programs versus traditional care. Methods: We searched Pubmed, Embase, Cochrane Central Register of Controlled Trials, and Google Scholar for relevant randomized controlled trials (RCTs) comparing fast-track with traditional care in hepatectomy. Length of hospital stay, time to first flatus, postoperative complications, operating time, and intraoperative blood loss were assessed. Meta-analyses were performed using RevMan 5.2 software. Results: Four original RCTs with 372 patients were included: 187 in the fast-track and 185 in the traditional care group. Fast-track patients had shorter hospital stay (WMD -2.32; 95% CI, -3.54 to -1.11; p < 0.001) and time to first flatus (WMD -0.99; 95% CI, -1.15 to -0.84; p < 0.001), and less postoperative complications (RR 0.66; 95% CI, 0.47 to 0.93; p < 0.05). However, there was significant heterogeneity between the studies regarding hospital stay (I2 = 88%; p < 0.001). Operating time and intraoperative blood loss were not different. Conclusions: Patients in fast-track programs had less time to first flatus and postoperative complications compared to traditional care. Fast-track programs may reduce the length of hospital stay. Larger, higher quality prospective RCTs are necessary to draw more robust conclusions.
The Nuclear Receptor FXR Uncouples the Actions of miR-33 From SREBP-2
Authors: Tarling Elizabeth J. , Ahn Hannah , de Aguiar Vallim Thomas Q.
Published: January 2015

Objective—

To determine whether activation of farnesoid X receptor (FXR) alters cellular and plasma cholesterol homeostasis as a result of regulation of
Srebp-2
and miR-33.

Approach and Results—

Chromatin immunoprecipitation sequencing data identified an FXR response element within intron 10 of the
Srebp-2
gene. Consistent with this observation, treatment of mice with FXR-specific agonists (GSK2324 or GW4064) rapidly increased hepatic levels of
Srebp-2
mRNA, precursor sterol response element binding protein 2 (pSREBP-2) protein, and miR-33. Furthermore, miR-33 targets, that include ABCA1 (ATP binding cassette transporter A1), NSF (N-ethylmaleimide-sensitive factor), and CPT1 (carnitine palmitoyltransferase 1), were all reduced in GSK2324-treated mice. In contrast, neither nuclear SREBP-2 protein (nSREBP-2) nor SREBP-2 target genes were induced after FXR activation. The inability to process pSREBP-2 to nSREBP-2 is likely a consequence of the induction of insulin INSIG-2A (induced gene 2A) by FXR agonists. Finally, we show that FXR-dependent induction of both
Srebp-2
and miR-33 is ablated in
Scap
–/–
mice that lack nuclear SREBP-2.

Conclusions—

We demonstrate that the activation of FXR uncouples the expression of nuclear SREBP-2 and miR-33, and the regulation of their respective target genes. Further, we conclude that the FXR agonist-dependent increase in miR-33 requires transcription of the
Srebp-2
gene.
Vascular Smooth Muscle Cell Phenotypic Changes in Patients With Marfan Syndrome
Authors: Crosas-Molist Eva , Meirelles Thayna , López-Luque Judit , Serra-Peinado Carla , Selva Javier , Caja Laia , Gorbenko del Blanco Darya , Uriarte Juan José , Bertran Esther , Mendizábal Yolanda , Hernández Vanessa , García-Calero Carolina , Busnadiego Oscar , Condom Enric , Toral David , Castellà Manel , Forteza Alberto , Navajas Daniel , Sarri Elisabet , Rodríguez-Pascual Fernando , Dietz Harry C. , Fabregat Isabel , Egea Gustavo
Published: January 2015

Objective—

Marfan’s syndrome is characterized by the formation of ascending aortic aneurysms resulting from altered assembly of extracellular matrix microfibrils and chronic tissue growth factor (TGF)-β signaling. TGF-β is a potent regulator of the vascular smooth muscle cell (VSMC) phenotype. We hypothesized that as a result of the chronic TGF-β signaling, VSMC would alter their basal differentiation phenotype, which could facilitate the formation of aneurysms. This study explores whether Marfan’s syndrome entails phenotypic alterations of VSMC and possible mechanisms at the subcellular level.

Approach and Results—

Immunohistochemical and Western blotting analyses of dilated aortas from Marfan patients showed overexpression of contractile protein markers (α-smooth muscle actin, smoothelin, smooth muscle protein 22 alpha, and calponin-1) and collagen I in comparison with healthy aortas. VSMC explanted from Marfan aortic aneurysms showed increased in vitro expression of these phenotypic markers and also of myocardin, a transcription factor essential for VSMC-specific differentiation. These alterations were generally reduced after pharmacological inhibition of the TGF-β pathway. Marfan VSMC in culture showed more robust actin stress fibers and enhanced RhoA-GTP levels, which was accompanied by increased focal adhesion components and higher nuclear localization of myosin-related transcription factor A. Marfan VSMC and extracellular matrix measured by atomic force microscopy were both stiffer than their respective controls.

Conclusions—

In Marfan VSMC, both in tissue and in culture, there are variable TGF-β-dependent phenotypic changes affecting contractile proteins and collagen I, leading to greater cellular and extracellular matrix stiffness. Altogether, these alterations may contribute to the known aortic rigidity that precedes or accompanies Marfan’s syndrome aneurysm formation.
Maternal High-Fat Diet Exaggerates Atherosclerosis in Adult Offspring by Augmenting Periaortic Adipose Tissue-Specific Proinflammatory Response
Authors: Wakana Noriyuki , Irie Daisuke , Kikai Masakazu , Terada Kensuke , Yamamoto Keita , Kawahito Hiroyuki , Kato Taku , Ogata Takehiro , Ueyama Tomomi , Matoba Satoaki , Yamada Hiroyuki
Published: January 2015

Objective—

Maternal obesity elicits offspring’s metabolic disorders via developmental modifications of visceral adipose tissue; however, its effect on atherogenesis remains undefined. Perivascular adipose tissue has recently been implicated in vascular remodeling and vasoreactivity. We hypothesize that developmental modifications of perivascular adipose tissue by maternal high-fat diet (HFD) exposure promotes atherosclerosis in adult offspring.

Approach and Results—

Eight-week-old female apolipoprotein E-deficient mice were fed an HFD or normal diet (ND) during gestation and lactation. Offspring were fed a high-cholesterol diet from 8 weeks of age. Twenty-week-old male offspring of HFD-fed dams (O-HFD) showed a 2.1-fold increase in atherosclerotic lesion of the entire aorta compared with those of ND-fed dams (O-ND). Although mRNA expressions of interleukin-6, tumor necrosis factor, and monocyte chemotactic protein-1 and accumulation of macrophages in epididymal white adipose tissue were less in O-HFD than in O-ND, thoracic periaortic adipose tissue (tPAT) showed an exaggerated inflammatory response in O-HFD. Intra-abdominal transplantation of tPAT from 8-week-old O-HFD alongside the distal abdominal aorta exaggerated atherosclerosis development of the infrarenal aorta in recipient apolipoprotein E-deficient mice compared with tPAT from O-ND (210%,
P
<0.01). Although macrophage accumulation was rarely detected in tPAT of 8-week-old offspring, mRNA expression and protein levels of macrophage colony–stimulating factor were markedly elevated in O-HFD (2.3-fold, 3.3-fold, respectively,
P
<0.05), suggesting that increased macrophage colony–stimulating factor expression contributes to the augmented accumulation of macrophages, followed by the enhanced proinflammatory response.

Conclusions—

Our findings demonstrate that maternal HFD exaggerates atherosclerosis development in offspring by augmenting tPAT-specific inflammatory response proceeded by an increased expression of macrophage colony–stimulating factor.
Left Atrial Remodeling and Function in Advanced Heart Failure With Preserved or Reduced Ejection Fraction
Authors: Melenovsky Vojtech , Hwang Seok-Jae , Redfield Margaret M. , Zakeri Rosita , Lin Grace , Borlaug Barry A.
Published: January 2015

Background—

Left atrial (LA) structure and function are altered in most heart failure (HF) patients, but there may be fundamental differences in LA properties between HF with preserved (HFpEF) and reduced ejection fraction (HFrEF).

Methods and Results—

One hundred ninety-eight HF patients (51% HFpEF, New York Heart Association 3.1±0.7) and 40 HF-free controls underwent catheterization, echocardiography, and follow-up. Compared with controls, HF patients had larger and more dysfunctional left atria. At identical mean LA pressure (20 versus 20 mm Hg;
P
=0.9), HFrEF patients had larger LA volumes (LA volume index 50 versus 41 mL/m
2
;
P
<0.001), whereas HFpEF patients had higher LA peak pressures, lower LA minimal pressures, higher LA stiffness (0.79 versus 0.48 mm Hg/mL;
P
<0.001), greater LA pulsatility (19 versus 13 mm Hg;
P
<0.001), and higher wall stress variations. Despite smaller LA volumes, better function, and less mitral regurgitation, HFpEF patients had more atrial fibrillation (42 versus 26%;
P
=0.02). LA dysfunction was associated with increased pulmonary vascular resistance and right ventricular dysfunction in both HF phenotypes. After a median follow-up of 350 days, 31 HFpEF and 28 HFrEF patients died. LA function (total LA EF) was associated with lower mortality in HFpEF (hazard ratio 0.43; 95% confidence interval, 0.2–0.9;
P
<0.05), but not in HFrEF.

Conclusions—

HFrEF is characterized by greater eccentric LA remodeling, whereas HFpEF by increased LA stiffness, which might contribute to greater atrial fibrillation burden. LA function is associated with pulmonary vascular disease and right HF in both HF phenotypes, but is associated with outcome more closely in HFpEF, supporting efforts to improve LA function in this cohort.
Evaluation of Renal Function Before and After Percutaneous Mitral Valve Repair
Authors: Wang Andrew , Sangli Chithra , Lim Scott , Ailawadi Gorav , Kar Saibal , Herrmann Howard C. , Grayburn Paul , Foster Elyse , Weissman Neil J. , Glower Donald , Feldman Ted
Published: January 2015

Background—

Chronic kidney disease (CKD) is strongly related to outcome in cardiovascular diseases. The relationship between treatment of mitral regurgitation (MR) and renal function is not well described. We sought to evaluate renal function before and after mitral valve repair by the MitraClip device.

Methods and Results—

Patients with moderate-to-severe or severe (3+ or 4+, respectively) MR by core laboratory determination who underwent transcatheter mitral valve repair with the MitraClip device in multicenter, investigational trials were included in this study. Estimated glomerular filtration rate (eGFR) was evaluated before and at hospital discharge, 30 days, 6 months, and 1 year after mitral valve repair. Eight hundred fifty-four patients with baseline mean eGFR 61.5±23.1 mL/min/1.73 m
2
were studied, including 438 (51.3%) with eGFR ≥60 mL/min/1.73 m
2
(CKD stage 1 or 2), 371 (42.6%) with eGFR 30 to 59 mL/min/1.73 m
2
(CKD stage 3), and 52 (6.1%) with eGFR <30 mL/min/1.73 m
2
(CKD stage 4 or 5). Baseline renal dysfunction was more prevalent in older patients with a history of heart failure, coronary artery disease, cerebrovascular disease, diabetes mellitus, hypertension, and atrial fibrillation. Baseline eGFR was associated with 1-year survival (
P
<0.001) after MitraClip repair. At 1-year follow-up, the mean change in eGFR for the overall cohort was −1.0±15.1 mL/min/1.73 m
2
; for patients with CKD stage 1 or 2, stage 3, or stage 4 or 5, mean change was −4.1±16.6, +2.6±12.4, and +4.8±9.5 mL/min/1.73 m
2
, respectively. Linear mixed effect modeling demonstrated a strong association between MR and eGFR, and a statistically significant improvement in eGFR in patients with CKD stage 4 or 5 associated with MR reduction to ≤2+ (
P
=0.007).

Conclusions—

Renal dysfunction is associated with lower survival in patients with severe MR even after percutaneous mitral valve repair. Reduction in MR severity by the MitraClip device is associated with improvement in renal function at 1 year in patients with baseline renal dysfunction.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifiers: NCT00209274, NCT01931956, NCT01940120.
Macrophage Sortilin Promotes LDL Uptake, Foam Cell Formation, and Atherosclerosis
Authors: Patel Kevin M. , Strong Alanna , Tohyama Junichiro , Jin Xueting , Morales Carlos R. , Billheimer Jeffery , Millar John , Kruth Howard , Rader Daniel J.
Published: January 2015

Rationale:

Noncoding gene variants at the
SORT1
locus are strongly associated with low-density lipoprotein cholesterol (LDL-C) levels, as well as with coronary artery disease.
SORT1
encodes a protein called sortilin, and hepatic sortilin modulates LDL metabolism by targeting apolipoprotein B–containing lipoproteins to the lysosome. Sortilin is also expressed in macrophages, but its role in macrophage uptake of LDL and in atherosclerosis independent of plasma LDL-C levels is unknown.

Objective:

To determine the effect of macrophage sortilin expression on LDL uptake, foam cell formation, and atherosclerosis.

Methods and Results:

We crossed
Sort1
−/−
mice onto a humanized
Apobec1
−/−
;
hAPOB
transgenic background and determined that
Sort1
deficiency on this background had no effect on plasma LDL-C levels but dramatically reduced atherosclerosis in the aorta and aortic root. To test whether this effect was a result of macrophage sortilin deficiency, we transplanted
Sort1
−/−
;LDLR
−/−
or
Sort1
+/+
;LDLR
−/−
bone marrow into
Ldlr
−/−
mice and observed a similar reduction in atherosclerosis in mice lacking hematopoetic sortilin without an effect on plasma LDL-C levels. In an effort to determine the mechanism by which hematopoetic sortilin deficiency reduced atherosclerosis, we found no effect of sortilin deficiency on macrophage recruitment or lipopolysaccharide-induced cytokine release in vivo. In contrast, sortilin-deficient macrophages had significantly reduced uptake of native LDL ex vivo and reduced foam cell formation in vivo, whereas sortilin overexpression in macrophages resulted in increased LDL uptake and foam cell formation.

Conclusions:

Macrophage sortilin deficiency protects against atherosclerosis by reducing macrophage uptake of LDL. Sortilin-mediated uptake of native LDL into macrophages may be an important mechanism of foam cell formation and contributor to atherosclerosis development.
Deficiency of Brain ATP-Binding Cassette Transporter A-1 Exacerbates Blood–Brain Barrier and White Matter Damage After Stroke
Authors: Cui Xu , Chopp Michael , Zacharek Alex , Karasinska Joanna M. , Cui Yisheng , Ning Ruizhuo , Zhang Yi , Wang Yun , Chen Jieli
Published: January 2015

Background and Purpose—

The ATP-binding cassette transporter A-1 (ABCA1) gene is a key target of the transcription factors liver X receptors. Liver X receptor activation has anti-inflammatory and neuroprotective effects in animal ischemic stroke models. Here, we tested the hypothesis that brain ABCA1 reduces blood–brain barrier (BBB) and white matter (WM) impairment in the ischemic brain after stroke.

Methods—

Adult brain-specific ABCA1–deficient (ABCA1
−B/−B
) and floxed-control (ABCA1
fl/fl
) mice were subjected to permanent distal middle cerebral artery occlusion and were euthanized 7 days after distal middle cerebral artery occlusion. Functional outcome, infarct volume, BBB leakage, and WM damage were analyzed.

Results—

Compared with ABCA1
fl/fl
mice, ABCA1
−B/−B
mice showed marginally (
P
=0.052) increased lesion volume but significantly increased BBB leakage and WM damage in the ischemic brain and more severe neurological deficits. Brain ABCA1–deficient mice exhibited increased the level of matrix metalloproteinase-9 and reduced the level of insulin-like growth factor 1 in the ischemic brain. BBB leakage was inversely correlated (
r
=−0.073;
P
<0.05) with aquaporin-4 expression. Reduction of insulin-like growth factor 1 and aquaporin-4, but upregulation of matrix metalloproteinase-9 expression were also found in the primary astrocyte cultures derived from ABCA1
−B/−B
mice. Cultured primary cortical neurons derived from C57BL/6 wild-type mice with ABCA1
−B/−B
astrocyte–conditioned medium exhibited decreased neurite outgrowth compared with culture with ABCA1
fl/fl
astrocyte–conditioned medium. ABCA1
−B/−B
primary cortical neurons show significantly decreased neurite outgrowth, which was attenuated by insulin-like growth factor 1 treatment.

Conclusions—

We demonstrate that brain ABCA1 deficiency increases BBB leakage, WM/axonal damage, and functional deficits after stroke. Concomitant reduction of insulin-like growth factor 1 and upregulation of matrix metalloproteinase-9 may contribute to brain ABCA1 deficiency–induced BBB and WM/axonal damage in the ischemic brain.
Outcome in Patients Previously on Antithrombotic Therapy in the SAMMPRIS Trial
Authors: Lutsep Helmi L. , Barnwell Stanley L. , Larsen Darren T. , Lynn Michael J. , Hong Mindy , Turan Tanya N. , Derdeyn Colin P. , Fiorella David , Janis L. Scott , Chimowitz Marc I.
Published: January 2015

Background and Purpose—

Stenting has been used as a rescue therapy in patients with intracranial arterial stenosis and a transient ischemic attack or stroke when on antithrombotic therapy (AT). We determined whether the stenting versus aggressive medical therapy for intracranial arterial stenosis (SAMMPRIS) trial supported this approach by comparing the treatments within subgroups of patients whose qualifying event (QE) occurred on versus off of AT.

Methods—

The primary outcome, 30-day stroke and death and later strokes in the territory of the qualifying artery, was compared between (1) percutaneous transluminal angioplasty and stenting plus aggressive medical therapy (PTAS) versus aggressive medical management therapy alone (AMM) for patients whose QE occurred on versus off AT and between (2) patients whose QE occurred on versus off AT separately for the treatment groups.

Results—

Among the 284/451 (63%) patients who had their QE on AT, the 2-year primary end point rates were 15.6% for those randomized to AMM (n=140) and 21.6% for PTAS (n=144;
P
=0.043, log-rank test). In the 167 patients not on AT, the 2-year primary end point rates were 11.6% for AMM (n=87) and 18.8% for PTAS (n=80;
P
=0.31, log-rank test). Within both treatment groups, there was no difference in the time to the primary end point between patients who were on or off AT (AMM,
P
=0.96; PTAS,
P
=0.52; log-rank test).

Conclusions—

SAMMPRIS results indicate that the benefit of AMM over PTAS is similar in patients on versus off AT at the QE and that failure of AT is not a predictor of increased risk of a primary end point.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00576693.
Brain Mechanisms for Active Vision
Authors: Wurtz Robert H.
Published: January 2015

Active vision refers to the exploration of the visual world with rapid eye movements, or saccades, guided by shifts of visual attention. Saccades perform the critical function of directing the high-resolution fovea of our eyes to any point in the visual field two to three times per second. However, the disadvantage of saccades is that each one disrupts vision, causing significant visual disturbance for which the brain must compensate. Exploring the interaction of vision and eye movements provides the opportunity to study the organization of one of the most complex, yet best-understood, brain systems. Outlining this exploration also illustrates some of the ways in which neuroscientists study neuronal systems in the brain and how they relate this brain activity to behavior. It shows the advantages and limitations of current approaches in systems neuroscience, as well as a glimpse of its potential future.
Perceiving
Authors: Albright Thomas D.
Published: January 2015

Perceiving is the process by which evanescent sensations are linked to environmental cause and made enduring and coherent through the assignment of meaning, utility, and value. Fundamental to this process is the establishment of associations over space and time between sensory events and other sources of information. These associations provide the context needed to resolve the inherent ambiguity of sensations. Recent studies have explored the neuronal bases of contextual influences on perception. These studies have revealed systems in the brain through which context converts neuronal codes for sensory events into neuronal representations that underlie perceptual experience. This work sheds light on the cellular processes by which associations are learned and how memory retrieval impacts the processing of sensory information. Collectively, these findings suggest that perception is the consequence of a critical neuronal computation in which contextual information is used to transform incoming signals from a sensory-based to a scene-based representation.