bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacological Therapy for Apathy in Alzheimer’s Disease: A Systematic Review and Meta-Analysis
Authors: Sepehry Amir A. , Sarai Michael , Hsiung Ging-Yuek R. 
Published: February 2017

AbstractIntroduction:Apathy is highly prevalent in Alzheimer’s disease (AD), but whether pharmacotherapy is effective in managing apathy is unclear.Methods:To assess the efficacy of pharmacotherapy for apathy in AD we searched for randomized controlled trials (RCT) and aggregate data reporting on apathy in several search engines, reference lists of articles, and reviews. Demographic characteristics and relevant data were extracted to assess apathy.Results:Fifteen RCTs’ were examined, and 11 were used in aggregate meta-analytic statistics. Drugs included were cholinesterase inhibitors, memantine, and psycho-stimulants. We found no significant treatment effect in favour of any of the drugs, and the effect-size estimates under a random effect model were heterogeneous. Most RCTs had a high attrition rate and used the NPI apathy subscale to measure apathy.Conclusion:The lack of an effect could be explained by methodological limitations, publication bias, and heterogeneity.
Special Considerations for Mass Violence Events in Senior Living Facilities: A Case Report on the Pinelake Health and Rehab Center Shooting
Authors: Martin Cody , Powell David 
Published: February 2017

AbstractThe 2009 Pinelake Health and Rehab Center shooting in Carthage, North Carolina, presents a unique case study for examining the specific considerations for mass violence events in senior living facilities. A variety of factors, including reduced sensory perception, reduced mobility, and cognitive decline, may increase the vulnerability of the populations of senior living facilities during mass violence events. Management of response aspects such as evacuation, relocation, and reunification also require special consideration in the context of mass violence at senior living facilities. Better awareness of these vulnerabilities and response considerations can assist facility administrators and emergency managers when preparing for potential mass violence events at senior living facilities. (Disaster Med Public Health Preparedness. 2017;11:150–152)
Cumulative semantic interference in young children's picture naming
Authors: CHAREST MONIQUE 
Published: February 2017

ABSTRACTIn children and adults, naming an item sometimes interferes with later attempts to name other items. Adult speakers experience cumulative semantic interference, interpreted as the result of incremental learning. Studies to date have not examined whether incremental learning can also account for interference in children. This study examined context effects on picture naming in 3-year-old children, and investigated whether children, like adults, show interference that is semantically based and cumulative. Children named pictures from semantically homogeneous and mixed sets. Response latency, accuracy, and repetition errors were recorded. The results demonstrated a progressive slowing of responses in the semantically homogeneous condition that was greater than that observed for the mixed condition. There were no significant effects for accuracy. Repetition errors, although infrequent, patterned similarly to previous reports for adults. The results indicate that preschool-aged children experience cumulative semantic interference in naming, and suggest that incremental learning may account for interference effects across development.
Design and initial results of a programme for routine standardised longitudinal follow-up after congenital heart surgery
Authors: Pasquali Sara K. , Ravishankar Chitra , Romano Jennifer C. , Kane Kristin , Viers Suzanne , Kennedy Andrea , Burnham Nancy , Lowery Ray , Uzark Karen , Retzloff Lauren , Rome Jonathon J. , Rossano Joseph W. , Charpie John R. , Spray Thomas L. , Gaies Michael G. , Ohye Richard G. , Gaynor J. William 
Published: February 2017

AbstractBackgroundWith improvements in early survival following congenital heart surgery, it has become increasingly important to understand longer-term outcomes; however, routine collection of these data is challenging and remains very limited. We describe the development and initial results of a collaborative programme incorporating standardised longitudinal follow-up into usual care at the Children’s Hospital of Philadelphia (CHOP) and University of Michigan (UM).MethodsWe included children undergoing benchmark operations of the Society of Thoracic Surgeons. Considerations regarding personnel, patient/parent engagement, funding, regulatory issues, and annual data collection are described, and initial follow-up rates are reported.ResultsThe present analysis included 1737 eligible patients undergoing surgery at CHOP from January 2007 to December 2014 and 887 UM patients from January 2010 to December 2014. Overall, follow-up data, of any type, were obtained from 90.8% of patients at CHOP (median follow-up 4.3 years, 92.2% survival) and 98.3% at UM (median follow-up 2.8 years, 92.7% survival), with similar rates across operations and institutions. Most patients lost to follow-up at CHOP had undergone surgery before 2010. Standardised questionnaires assessing burden of disease/quality of life were completed by 80.2% (CHOP) and 78.4% (UM) via phone follow-up. In subsequent pilot testing of an automated e-mail system, 53.4% of eligible patients completed the follow-up questionnaire through this system.ConclusionsStandardised follow-up data can be obtained on the majority of children undergoing benchmark operations. Ongoing efforts to support automated electronic systems and integration with registry data may reduce resource needs, facilitate expansion across centres, and support multi-centre efforts to understand and improve long-term outcomes in this population.
Training residents and fellows in paediatric cardiac anaesthesia
Authors: Andropoulos Dean B. 
Published: February 2017

AbstractThe significant increase in complex anaesthetic care for infants, children, adolescents, and adults with CHD has given rise to specialized fellowship training programs. Specialized paediatric cardiac anaesthesia training for residents and fellows has advanced significantly since the 1970’s, when there a handful of programs. With the advent of formal paediatric anaesthesia fellowship programs in the U.S., more specialized training became available in the 1990’s and early 2000’s. In the past decade, increasing numbers of second year advanced fellowships in paediatric cardiac anaesthesia have been organized; today in North America there are 18 programs with 25 positions. Standardized recommendations for case numbers and curriculum have been devised and are widely available via journal publications.
Training in paediatric cardiac surgery and the American Board of Thoracic Surgery
Authors: Bove Edward L. 
Published: February 2017

AbstractCongenital heart surgery has evolved into its own specialty requiring unique techniques and skills. Recognizing the need to establish a special certification in congenital heart surgery, the American Board of Thoracic Surgery began the process in 2005, eventually granting the first certifications to qualified applicants in 2009. The American Council for Graduate Medical Education and the Thoracic Surgery Residency Review Committee have now approved specific training programs throughout the United States that will help to ensure the proper training of congenital heart surgeons for the future.
The past, present, and future of paediatric cardiology training at the Johns Hopkins Hospital, in the tradition of Dr Helen Taussig
Authors: Beasley Gary S. , Murphy Anne M. , Brenner Joel I. , Ravekes William J. 
Published: February 2017

AbstractJohns Hopkins has been a leader in paediatric cardiology for over 85 years. In the 1940s, Dr Helen Taussig began training fellows in paediatric cardiology at Johns Hopkins at a time when the diagnosis and treatment of CHD were in the earliest stage. Under her leadership, the fellowship developed a strong foundation that has continued to evolve to meet the current needs of learners and educators. In the current era, the Johns Hopkins programme implements the current theories of adult education and actively engages our fellows in learning as well as teaching. The programme uses techniques such as flipped classroom, structured case-based small-group learning, observed and structured clinical examination, simulations, and innovative educational technology. These strategies combined with our faculty and rich history give our fellows a unique educational experience.
Training residents/fellows in paediatric cardiology: the Emory experience
Authors: Campbell Robert M. 
Published: February 2017

AbstractPediatric cardiology fellowship is a very busy time, with new responsibilities, new knowledge, new technology and fast pace. Above and beyond the science and art of pediatric cardiology, we emphasize that our cardiology fellows are in the middle of the “people business”, with additional roles and responsibilities as they serve their patients and communities. This manuscript provides insight into these opportunities for our pediatric cardiac professionals.
Paediatric cardiac surgical education: which are the important elements?
Authors: Karl Tom R. , Jacobs Jeffrey P. 
Published: February 2017

AbstractPediatric cardiac surgical education and the associated requirements for certification vary considerably from one country to another. Evolution and standardization for pediatric cardiac surgical education may not have kept pace with the evolution of other aspects of the specialty. Restriction of work hours and disqualification of foreign training experience constitute potential threats to our specialty. A global strategy for qualification and certification may help to address some of these difficult issues.
Reflections on the Projection of Ions in Atom Probe Tomography
Authors: De Geuser Frédéric , Gault Baptiste 
Published: February 2017

AbstractThere are two main projections used to transform, and reconstruct, field ion micrographs or atom probe tomography data into atomic coordinates at the specimen surface and, subsequently, in three dimensions. In this article, we present a perspective on the strength of the azimuthal equidistant projection in comparison with the more widely used and well-established point projection (or pseudo-stereographic projection), which underpins data reconstruction in most software packages currently in use across the community. After an overview of the reconstruction methodology, we demonstrate that the azimuthal equidistant is more robust with regards to errors on the parameters used to perform the reconstruction and is therefore more likely to yield more accurate tomographic reconstructions.
Star-PAP, a poly(A) polymerase, functions as a tumor suppressor in an orthotopic human breast cancer model
Authors: Yu C , Gong Y , Zhou H , Wang M , Kong L , Liu J , An T , Zhu H , Li Y 
Published: February 2017

AbstractStar-PAP is a noncanonical poly(A) polymerase and required for the expression of a select set of mRNAs. However, the pathological role of Star-PAP in cancer largely remains unknown. In this study, we observed decreased expression of Star-PAP in breast cancer cell lines and tissues. Ectopic Star-PAP expression inhibited proliferation as well as colony-forming ability of breast cancer cells. In breast cancer patients, high levels of Star-PAP correlated with an improved prognosis. Moreover, by regulating the expression of BIK (BCL2-interacting killer), Star-PAP induced apoptosis of breast cancer cells through the mitochondrial pathway. The growth of breast cancer xenografts in NOD/SCID mice was also inhibited by the doxycycline-induced Star-PAP overexpression. Furthermore, Star-PAP sensitized breast cancer cells to chemotherapy drugs both in vitro and in vivo. In mammary epithelial cells, Star-PAP knockdown partially transformed these cells and induced them to undergo epithelial–mesenchymal transition (EMT). These findings suggested that Star-PAP possesses tumor-suppressing activity and can be a valuable target for developing new cancer therapeutic strategies.
Regulation of glutamate transporter trafficking by Nedd4-2 in a Parkinson’s disease model
Authors: Zhang Yunlong , He Xiaoliang , Meng Xingjun , Wu Xiaojuan , Tong Huichun , Zhang Xiuping , Qu Shaogang 
Published: February 2017

AbstractGlutamate transporters play a key role in glutamate clearance and protect the central nervous system from glutamate excitotoxicity. Dysfunctional glutamate transporters contribute to the pathogenesis of Parkinson’s disease (PD); however, the mechanisms that underlie the regulation of glutamate transporters in PD are still not well characterized. Here we report that Nedd4-2 mediates the ubiquitination of glutamate transporters in 1-methyl-4- phenylpyridinium (MPP+)-treated astrocytes and in the midbrain of 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP)-constructed PD model mice. Nedd4-2-mediated ubiquitination induces abnormal glutamate transporter trafficking between the membrane and cytoplasm and consequently decreases the expression and function of glutamate transporters in the membrane. Conversely, Nedd4-2 knockdown decreases glutamate transporter ubiquitination, promotes glutamate uptake and increases glutamate transporter expression in vitro and in vivo. We report for the first time that Nedd4-2 knockdown ameliorates movement disorders in PD mice and increases tyrosine hydroxylase expression in the midbrain and striatum of PD mice; Nedd4-2 knockdown also attenuates astrogliosis and reactive microgliosis in the MPTP model that may be associated with glutamate excitotoxicity. Furthermore, the SGK/PKC pathway is regulated downstream of Nedd4-2 in MPTP-treated mice. These findings indicate that Nedd4-2 may serve as a potential therapeutic target for the treatment of PD.
NLRP3 inflammasome activation mediates radiation-induced pyroptosis in bone marrow-derived macrophages
Authors: Liu Yan-gang , Chen Ji-kuai , Zhang Zi-teng , Ma Xiu-juan , Chen Yong-chun , Du Xiu-ming , Liu Hong , Zong Ying , Lu Guo-cai 
Published: February 2017

AbstractA limit to the clinical benefit of radiotherapy is not an incapacity to eliminate tumor cells but rather a limit on its capacity to do so without destroying normal tissue and inducing inflammation. Recent evidence reveals that the inflammasome is essential for mediating radiation-induced cell and tissue damage. In this study, using primary cultured bone marrow-derived macrophages (BMDM) and a mouse radiation model, we explored the role of NLRP3 inflammasome activation and the secondary pyroptosis underlying radiation-induced immune cell death. We observed an increasing proportion of pyroptosis and elevating Caspase-1 activation in 10 and 20 Gy radiation groups. Nlrp3 knock out significantly diminished the quantity of cleaved-Caspase-1 (p10) and IL-1β as well as the proportion of pyroptosis. Additionally, in vivo research shows that 9.5 Gy of radiation promotes Caspase-1 activation in marginal zone cells and induces death in mice, both of which can be significantly inhibited by knocking out Nlrp3. Thus, based on these findings, we conclude that the NLRP3 inflammasome activation mediates radiation-induced pyroptosis in BMDMs. Targeting NLRP3 inflammasome and pyroptosis may serve as effective strategies to diminish injury caused by radiation.
Colon cancer cell treatment with rose bengal generates a protective immune response via immunogenic cell death
Authors: Qin Jianzhong , Kunda Nicholas , Qiao Guilin , Calata Jed F , Pardiwala Krunal , Prabhakar Bellur S , Maker Ajay V 
Published: February 2017

AbstractImmunotherapeutic approaches to manage patients with advanced gastrointestinal malignancies are desired; however, mechanisms to incite tumor-specific immune responses remain to be elucidated. Rose bengal (RB) is toxic at low concentrations to malignant cells and may induce damage-associated molecular patterns; therefore, we investigated its potential as an immunomodulator in colon cancer. Murine and human colon cancer lines were treated with RB (10% in saline/PV-10) for cell cycle, cell death, and apoptosis assays. Damage-associated molecular patterns were assessed with western blot, ELISA, and flow cytometry. In an immunocompetent murine model of colon cancer, we demonstrate that tumors regress upon RB treatment, and that RB induces cell death in colon cancer cells through G2/M growth arrest and predominantly necrosis. RB-treated colon cancer cells expressed distinct hallmarks of immunogenic cell death (ICD), including enhanced expression of calreticulin and heat-shock protein 90 on the cell surface, a decrease in intracellular ATP, and the release of HMGB1. To confirm the ICD phenotype, we vaccinated immunocompetent animals with syngeneic colon cancer cells treated with RB. RB-treated tumors served as a vaccine against subsequent challenge with the same CT26 colon cancer tumor cells, and vaccination with in vitro RB-treated cells resulted in slower tumor growth following inoculation with colon cancer cells, but not with syngeneic non-CT26 cancer cells, suggesting a specific antitumor immune response. In conclusion, RB serves as an inducer of ICD that contributes to enhanced specific antitumor immunity in colorectal cancer.
Critical role of reactive oxygen species (ROS) for synergistic enhancement of apoptosis by vemurafenib and the potassium channel inhibitor TRAM-34 in melanoma cells
Authors: Bauer Daniel , Werth Felix , Nguyen Ha An , Kiecker Felix , Eberle Jürgen 
Published: February 2017

AbstractInhibition of MAP kinase pathways by selective BRAF inhibitors, such as vemurafenib and dabrafenib, have evolved as key therapies of BRAF-mutated melanoma. However, tumor relapse and therapy resistance have remained as major problems, which may be addressed by combination with other pathway inhibitors. Here we identified the potassium channel inhibitor TRAM-34 as highly effective in combination with vemurafenib. Thus apoptosis was significantly enhanced and cell viability was decreased. The combination vemurafenib/TRAM-34 was also effective in vemurafenib-resistant cells, suggesting that acquired resistance may be overcome. Vemurafenib decreased ERK phosphorylation, suppressed antiapoptotic Mcl-1 and enhanced proapoptotic Puma and Bim. The combination resulted in enhancement of proapoptotic pathways as caspase-3 and loss of mitochondrial membrane potential. Indicating a special mechanism of vemurafenib-induced apoptosis, we found strong enhancement of intracellular ROS levels already at 1 h of treatment. The critical role of ROS was demonstrated by the antioxidant vitamin E (α-tocopherol), which decreased intracellular ROS as well as apoptosis. Also caspase activation and loss of mitochondrial membrane potential were suppressed, proving ROS as an upstream effect. Thus ROS represents an initial and independent apoptosis pathway in melanoma cells that is of particular importance for vemurafenib and its combination with TRAM-34.
Targeting the latent cytomegalovirus reservoir with an antiviral fusion toxin protein
Authors: Krishna B. A. , Spiess K. , Poole E. L. , Lau B. , Voigt S. , Kledal T. N. , Rosenkilde M. M. , Sinclair J. H. 
Published: February 2017

AbstractReactivation of human cytomegalovirus (HCMV) in transplant recipients can cause life-threatening disease. Consequently, for transplant recipients, killing latently infected cells could have far-reaching clinical benefits. In vivo, myeloid cells and their progenitors are an important site of HCMV latency, and one viral gene expressed by latently infected myeloid cells is US28. This viral gene encodes a cell surface G protein-coupled receptor (GPCR) that binds chemokines, triggering its endocytosis. We show that the expression of US28 on the surface of latently infected cells allows monocytes and their progenitor CD34+ cells to be targeted and killed by F49A-FTP, a highly specific fusion toxin protein that binds this viral GPCR. As expected, this specific targeting of latently infected cells by F49A-FTP also robustly reduces virus reactivation in vitro. Consequently, such specific fusion toxin proteins could form the basis of a therapeutic strategy for eliminating latently infected cells before haematopoietic stem cell transplantation.
Waveguide-coupled nanopillar metal-cavity light-emitting diodes on silicon
Authors: Dolores-Calzadilla V. , Romeira B. , Pagliano F. , Birindelli S. , Higuera-Rodriguez A. , van Veldhoven P. J. , Smit M. K. , Fiore A. , Heiss D. 
Published: February 2017

AbstractNanoscale light sources using metal cavities have been proposed to enable high integration density, efficient operation at low energy per bit and ultra-fast modulation, which would make them attractive for future low-power optical interconnects. For this application, such devices are required to be efficient, waveguide-coupled and integrated on a silicon substrate. We demonstrate a metal-cavity light-emitting diode coupled to a waveguide on silicon. The cavity consists of a metal-coated III–V semiconductor nanopillar which funnels a large fraction of spontaneous emission into the fundamental mode of an InP waveguide bonded to a silicon wafer showing full compatibility with membrane-on-Si photonic integration platforms. The device was characterized through a grating coupler and shows on-chip external quantum efficiency in the 10−4–10−2 range at tens of microamp current injection levels, which greatly exceeds the performance of any waveguide-coupled nanoscale light source integrated on silicon in this current range. Furthermore, direct modulation experiments reveal sub-nanosecond electro-optical response with the potential for multi gigabit per second modulation speeds.
Reduced GABAergic transmission in the ventrobasal thalamus contributes to thermal hyperalgesia in chronic inflammatory pain
Authors: Zhang Chan , Chen Rong-Xiang , Zhang Yu , Wang Jie , Liu Feng-Yu , Cai Jie , Liao Fei-Fei , Xu Fu-Qiang , Yi Ming , Wan You 
Published: February 2017

AbstractThe ventrobasal (VB) thalamus is innervated by GABAergic afferents from the thalamic reticular nucleus (TRN) and participates in nociception. But how the TRN-VB pathway regulates pain is not fully understood. In the present study, we reported decreased extracellular GABA levels in the VB of rats with CFA-induced chronic inflammatory pain, measured by microdialysis with HPLC analysis. In vitro whole-cell patch-clamp recording showed decreased amplitudes of tonic currents, increased frequencies of mIPSCs, and increased paired-pulse ratios in thalamic slices from chronic inflammatory rats (7 days). Microinjection of the GABAAR agonist muscimol and optogenetic activation of the TRN-VB pathway relieved thermal hyperalgesia in chronic inflammatory pain. By contrast, microinjecting the extrasynaptic GABAAR agonist THIP or selective knockout of synaptic GABAAR γ2 subunits aggravated thermal hyperalgesia in the chronic stage of inflammatory pain. Our findings indicate that reduced GABAergic transmission in the VB contributes to thermal hyperalgesia in chronic inflammatory pain, which could be a synaptic target for pharmacotherapy.