bluuebunny/crossref_metadata_2025_split huggingface dataset:
A cross-modal feedback scheme for control of prosthetic grasp strength
Authors: Kaneris Ioannis , Gibson Alison , Artemiadis Panagiotis 
Published: August 2016

Introduction Given the lack of haptic feedback inherent in prosthetic devices, a natural and adaptable feedback scheme must be implemented. While multimodal feedback has proven successful in aiding dexterous performance, it can be mentally tasking on the individual. Conversely, cross-modal schemes relying on sensory substitution have proven to be equally effective in aiding task performance without cognitively burdening the user to the same degree. Objectives This experiment investigated the effectiveness of the cross-modal feedback scheme through using audio feedback to represent prosthetic grasping strength during dynamic control of a prosthetic hand. Methods A total of five individuals participated in two sets of experiments (four subjects in the first, one subject in the second). Participants were asked to control the grasping strength exerted by a prosthetic hand while using real-time audio feedback in order to reach up to three different levels of force within a trial set. Results The cross-modal feedback scheme successfully provided users with the robust ability to modulate grasping strength in real-time using only audio feedback. Conclusion Audio feedback effectively conveys haptic information to the user of a prosthetic hand. Retention of the training knowledge is evident and can be generalized to perform new (i.e. untrained) tasks.
Yield of angiographic examinations in isolated intraventricular hemorrhage: A case series and systematic review of the literature
Authors: Hilkens Nina A , van Asch Charlotte JJ , Rinkel Gabriel JE , Klijn Catharina JM 
Published: August 2016

Background It is unknown which patients with non-traumatic isolated intraventricular hemorrhage should undergo angiographic imaging to detect an underlying macrovascular cause and which modality has the highest yield. We studied yield of angiographic examinations in patients with isolated intraventricular hemorrhage. Methods We reviewed medical records of patients with intraventricular hemorrhage admitted to the University Medical Center Utrecht between 2002 and 2012. We searched PubMed and Embase for studies on angiographic examinations in intraventricular hemorrhage until January 2014. We calculated yield of angiographic imaging and investigated influence of age, hypertension and anticoagulant use with meta-regression analysis. Results We identified 39 patients of whom 30 underwent an angiographic study. CTA suggested a macrovascular abnormality in nine patients, which was confirmed by DSA in seven. In the literature, we found 16 studies describing 209 patients. Pooled analysis showed a yield of 58% for DSA (95% CI 48–68%; 147 patients). One small study described the yield of CTA or MRA (0%; 4 patients). Yield of angiographic imaging decreased with increasing age (−2.6%; −5.0 to −0.2 per year increase) but was not affected by history of hypertension (−8.3%; −80.8 to 64.2) or anticoagulant use (−47.1%; −110.3 to 16.1). Conclusion The reported yield of DSA in isolated intraventricular hemorrhage is around 50% but varies considerably, probably due to differences in clinical judgment on the need for angiography performance. The yield is higher in younger patients but based on the available data, it is not possible to set age or other criteria for patients in whom DSA can be safely omitted.
Impact of pre-stroke sulphonylurea and metformin use on mortality of intracerebral haemorrhage
Authors: Wu Teddy Y , Campbell Bruce CV , Strbian Daniel , Yassi Nawaf , Putaala Jukka , Tatlisumak Turgut , Davis Stephen M , Meretoja Atte ,   on behalf of the VISTA-ICH Collaboration
Published: August 2016

Introduction Few proven therapies for intracerebral haemorrhage exist. Preliminary observational evidence suggests that sulphonylurea and metformin may be protective in ischaemic stroke. We assessed the association of pre-intracerebral haemorrhage sulphonylurea and metformin use on outcome in diabetic patients. Methods We merged datasets from the consecutive single-centre Helsinki ICH Study, the intracerebral haemorrhage arm of the Virtual International Stroke Trials Archive (VISTA-ICH) and the Royal Melbourne Hospital ICH Study. Logistic regression adjusting for known predictors of intracerebral haemorrhage outcome (age, sex, baseline Glasgow Coma Scale, National Institutes of Health Stroke Scale, intracerebral haemorrhage volume, infratentorial location, intraventricular extension, and pre-intracerebral haemorrhage warfarin use) estimated the association of metformin and sulphonylurea with all-cause 90-day mortality. Results From a dataset of 2404 consecutive intracerebral haemorrhage patients, we included 374 (16%) patients with diabetes. Of these, 113 (30%) died by 90 days. Metformin was used in 148 (40%) patients and sulphonylurea in 115 (31%) patients at intracerebral haemorrhage onset. After adjusting for baseline characteristics, metformin use was associated with lower 90-day mortality (OR 0.51; 95% CI 0.26–0.97; p = 0.041) irrespective of whether the drug was continued or not during the admission, while sulphonylurea use was not associated with mortality (OR 0.96; 95% CI 0.49–1.88; p = 0.906). Haematoma location or evacuation did not modify the association between metformin and mortality; neither did adding insulin use, baseline glucose and serum creatinine into the model (OR 0.50; 95% CI 0.25–0.99; p = 0.047). Conclusion Pre-intracerebral haemorrhage metformin use was associated with improved outcome in diabetic intracerebral haemorrhage patients. Our results generate hypotheses which after further validation could be tested in clinical trials.
Chemotaxis-driven disease-site targeting of therapeutic adult stem cells in dystrophic epidermolysis bullosa
Authors: Alexeev Vitali , Donahue Adele , Uitto Jouni , Igoucheva Olga 
Published: August 2016

Abstract
Background
Dystrophic epidermolysis bullosa (DEB), a rare genodermatosis, is characterized by the formation of intra-epidermal blistering and the development of chronic nonhealing skin wounds. Recently, attempts have been made to develop cell-based therapies for this currently intractable disorder. The molecular mechanisms that govern directional migration of the adult stem cells, allowing their efficient and controlled homing to the skin affected with DEB, are poorly understood. The key mechanism that regulates recruitment of leukocytes and progenitor stem cells to distal anatomical tissues affected with disease is chemotaxis, which depends on the signaling molecules, chemokines, and acts primarily as part of the host defense and repair mechanism.

Methods
Comprehensive proteomic screening of chemokines in the blister fluids of DEB-affected mice was conducted to define the inflammatory and immune activities, thus providing potential to examine local biological mechanisms and define the protein signature within lesional skin as a potential marker of disease activity. Also, the therapeutic relevance of identified chemotactic pathways was investigated in vivo, providing a basis for future clinical investigations.

Results
Assessment of blister fluid-derived chemokines showed a persistent presence of several chemotactic molecules, including CXCL1 + 2 and CXCL5. The majority of blister-originated chemotactic signals were associated with preferential recruitment of CD45+CXCR2+ and CD11b+CXCR2+ leukocytes. Systemic transplantation of an enriched CXCR2 population of mouse adipose-derived stem cells (mADSC) into DEB-affected mice demonstrated effective recruitment of cells to the blistering skin under the influence of blister-derived ligands and deposition of therapeutic type VII collagen.

Conclusions
Collectively, these studies demonstrate that recruitment of mADSC into DEB skin is tightly controlled by disease-site chemotactic activities and suggest a potential mechanism for effective application of therapeutic stem cells for DEB.
Leukocyte-borne α(1,3)-fucose is a negative regulator of β2-integrin-dependent recruitment in lung inflammation
Authors: Buffone Alexander , Nasirikenari Mehrab , Manhardt Charles T , Lugade Amit , Bogner Paul N , Sackstein Robert , Thanavala Yasmin , Neelamegham Sriram , Lau Joseph T Y 
Published: August 2016

Abstract
Leukocyte recruitment in inflammation is a multistep, sequential cascade where the initial step is the selectin-dependent tethering, followed by the formation of firmer integrin-mediated adhesive forces leading to extravasation. The α(1,3)-fucose-containing sialyl-Lewis X (sLeX) is the archetypical ligand on leukocyte surfaces mediating selectin interactions. Canonically, disruption of α(1,3)-fucose formation ablates selectin-mediated adhesion, dramatically reducing trafficking. We report a paradoxical response to α(1,3)-fucose deficiency in which the loss exacerbated rather than attenuated leukocyte recruitment in a murine model of acute airway inflammation. The architecture of the capillary-dominated vasculature in the lung minimized the importance of the selectin dependent step, and we observed that α(1,3)-fucose deficiency augmented CXCR2-mediated Rap1-GTP signaling to enhance the β2-integrin-ICAM-1-binding axis. The data disclose a previously unknown function for α(1,3)-fucose, in which this structure negatively regulates the integrin activation step in leukocyte recruitment.
STAT6 inhibitory peptide given during RSV infection of neonatal mice reduces exacerbated airway responses upon adult reinfection
Authors: Srinivasa Bharat T , Restori Katherine H , Shan Jichuan , Cyr Louis , Xing Li , Lee Soojin , Ward Brian J , Fixman Elizabeth D 
Published: August 2016

Abstract
Respiratory syncytial virus (RSV)-related hospitalization during infancy is strongly associated with the subsequent development of asthma. Early life RSV infection results in a Th2-biased immune response, which is also typical of asthma. Murine models of neonatal RSV infection have been developed to examine the possible contribution of RSV-driven Th2 responses to the development of airway hyper-responsiveness later in childhood. We have investigated the ability of a cell-penetrating STAT6 inhibitory peptide (STAT6-IP), when delivered selectively during neonatal RSV infection, to modify pathogenesis induced upon secondary RSV reinfection of adults 6 wk later. Neonatal STAT6-IP treatment inhibited the development of airway hyper-responsiveness (AHR) and significantly reduced lung eosinophilia and collagen deposition in adult mice following RSV reinfection. STAT6-IP-treated, RSV-infected neonates had reduced levels of both IL-4 and alternatively activated macrophages (AAMs) in the lungs. Our findings suggest that targeting STAT6 activity at the time of early-life RSV infection may effectively reduce the risk of subsequent asthma development.
CMV induces expansion of highly polyfunctional CD4+ T cell subset coexpressing CD57 and CD154
Authors: Pera Alejandra , Vasudev Anusha , Tan Crystal , Kared Hassen , Solana Rafael , Larbi Anis 
Published: August 2016

Abstract
CD4+ T cells are essential for human CMV infection control. CMV-specific CD4+ T cells possess antiviral functions and participate in anti-CMV humoral/cellular responses. In the elderly, CMV infection impairs immunity to other viruses and has been traditionally associated with T cell senescence; however, recent results suggest that, in younger people, CMV confers immune protection against other pathogens (heterologous immunity). To shed light on this controversy, we analyzed latent CMV infection effects on the quality of young individuals’ immune response, specifically, the presence of polyfunctional T cells through an extensive phenotypic and functional characterization of the CD4+ T cell subset. CD154 expression, degranulation (CD107a), and cytokine production (IFN-γ, TNF-α, and IL-2) as well as T cell phenotype markers (CD57, CD28, and CD27) were analyzed. We demonstrate that CD4+ T cells that coexpress CD57 and CD154, which are exclusively present in CMV-positive individuals, are the most polyfunctional CD4+ subset, whereas CD4+CD27+CD28− T cells associate with lower polyfunctionality. Conversely, the frequency of CD4+CD28+ T cells correlates with higher polyfunctionality of CD4+CD57− T cells from CMV-seronegative individuals and CD4+CD57+CD154+ T cells from CMV-seropositive individuals. Thus, polyfunctionality is a property of central memory CD4+ T cells in CMV-seronegative individuals, whereas after CMV infection, polyfunctional T cells become highly differentiated, which allows efficient eradication of infections. We extend previous observations of the impact of CMV on CD8+ T cell functionality to the CD4+ T cell compartment, revealing CD57 as a polyfunctionality marker of T cells which expands after CMV infection. CD57+ T cells have been associated with inflammatory conditions, but their potential role in the response against infectious disease and vaccination should now be investigated.
Use of Aspirin and P2Y12 Response Assays in Detecting Reversal of Platelet Inhibition With Platelet Transfusion in Patients With Traumatic Brain Injury on Antiplatelet Therapy
Authors: Choi Phillip A. , Parry Phillip V. , Bauer Joshua S. , Zusman Benjamin E. , Panczykowski David M. , Puccio Ava M. , Okonkwo David O. 
Published: August 2016

Abstract

BACKGROUND: At present, guidelines are lacking on platelet transfusion in patients with a traumatic intracranial bleed and history of antiplatelet therapy. The aspirin and P2Y12 response unit (ARU and PRU, respectively) assays detect the effect of aspirin and P2Y12 inhibitors in the cardiac population.

OBJECTIVE: To describe the reversal of platelet inhibition after platelet transfusion using the ARU and PRU assays in patients with traumatic brain injury.

METHODS: Between 2010 and 2015, we conducted a prospective comparative cohort study of patients presenting with a positive head computed tomography and a history of antiplatelet therapy. ARU and PRU assays were performed on admission and 6 hours after transfusion, with a primary end point of detection of disinhibition after platelet transfusion.

RESULTS: One hundred seven patients were available for analysis. Seven percent of patients taking aspirin and 27% of patients taking clopidogrel were not therapeutic on admission per the ARU and PRU, respectively. After platelet transfusion, 51% of patients on any aspirin and 67% of patients on any clopidogrel failed to be reversed. ARU increased by 71 ± 76 per unit of apheresis platelets for patients taking any aspirin, and PRU increased by 48 ± 46 per unit of apheresis platelets for patients taking any clopidogrel.

CONCLUSION: A significant percentage of patients taking aspirin or clopidogrel were not therapeutic and thus would be unlikely to benefit from a platelet transfusion. In patients with measured platelet inhibition, a single platelet transfusion was not sufficient to reverse platelet inhibition in almost half.
Utility of the Aspirin and P2Y12 Response Assays to Determine the Effect of Antiplatelet Agents on Platelet Reactivity in Traumatic Brain Injury
Authors: Parry Phillip V. , Choi Phillip A. , Bauer Joshua S. , Panczykowski David M. , Puccio Ava M. , Okonkwo David O. 
Published: August 2016

Abstract

BACKGROUND: Premorbid antithrombotic medication may worsen intracranial injury and outcome after traumatic brain injury (TBI). Routine laboratory tests are insufficient to evaluate platelet activity.

OBJECTIVE: To profile the spectrum of platelet inhibition, as measured by aspirin and P2Y12 response unit assays, in a TBI population on antiplatelet therapy.

METHODS: This single-center, prospective cohort study included patients presenting to our institution between November 2010 and January 2015 with a clinical history of TBI. Serum platelet reactivity levels were determined immediately on admission and analyzed using the aspirin and P2Y12 response unit assays; test results were reported as aspirin response units and P2Y12 response units. We report congruence between assay results and clinical history as well as differences in assay results between types of antiplatelet therapy.

RESULTS: A sample of 317 patients was available for analysis, of which 87% had experienced mild TBI, 7% moderate, and 6% severe; the mean age was 71.5 years. The mean aspirin response units in patients with a history of any aspirin use was 456 ± 67 (range, 350-659), with 88% demonstrating therapeutic platelet inhibition. For clopidogrel, the mean P2Y12 response unit was 191 ± 70 (range, 51-351); 77% showed therapeutic response.

CONCLUSION: Rapid measurement of antiplatelet function using the aspirin and P2Y12 response assays indicated as many as one fourth of patients on antiplatelet therapy do not have platelet dysfunction. Further research is required to develop guidelines for the use of these assays to guide platelet transfusion in the setting of TBI.
Ten-Year Follow-up on Tumor Growth and Hearing in Patients Observed With an Intracanalicular Vestibular Schwannoma
Authors: Kirchmann Malene , Karnov Kirstine , Hansen Søren , Dethloff Thomas , Stangerup Sven-Eric , Caye-Thomasen Per 
Published: August 2016

Abstract

BACKGROUND: Reports on the natural history of tumor growth and hearing in patients with a vestibular schwannoma (VS) are almost exclusively short-term data. Long-term data are needed for comparison with results of surgery and radiotherapy.

OBJECTIVE: To report the long-term occurrence of tumor growth and hearing loss in 156 patients diagnosed with an intracanalicular VS and managed conservatively.

METHODS: In this longitudinal cohort study, diagnostic and follow-up magnetic resonance imaging and audiometry were compared.

RESULTS: After a follow-up of 9.5 years, tumor growth had occurred in 37% and growth into the cerebellopontine angle had occurred in 23% of patients. Conservative treatment failed in 15%. The pure tone average had increased from 51- to 72-dB hearing level, and the speech discrimination score (SDS) had decreased from 60% to 34%. The number of patients with good hearing (SDS > 70%) was reduced from 52% to 22%, and the number of patients with American Academy of Otolaryngology–Head and Neck Surgery (AAO-HNS) class A hearing was reduced from 19% to 3%. Hearing was preserved better in patients with 100% SDS at diagnosis than in patients with even a small loss of SDS. Serviceable hearing was preserved in 34% according to AAO-HNS (class A-B) and in 58% according to the word recognition score (class I-II). Rate of hearing loss was higher in patients with growing tumors.

CONCLUSION: Tumor growth occurred in only a minority of patients diagnosed with an intracanalicular VS during 10 years of observation. The risk of hearing loss is small in patients with normal discrimination at diagnosis. Serviceable hearing is preserved spontaneously in 34% according to AAO-HNS and in 58% according to the word recognition score.
Lumbar Cerebrospinal Fluid Biomarkers of Posthemorrhagic Hydrocephalus of Prematurity: Amyloid Precursor Protein, Soluble Amyloid Precursor Protein α, and L1 Cell Adhesion Molecule
Authors: Morales Diego M. , Silver Shawgi A. , Morgan Clinton D. , Mercer Deanna , Inder Terri E. , Holtzman David M. , Wallendorf Michael J. , Rao Rakesh , McAllister James P. , Limbrick David D. 
Published: August 2016

Abstract

BACKGROUND: Intraventricular hemorrhage (IVH) is the most frequent, severe neurological complication of prematurity and is associated with posthemorrhagic hydrocephalus (PHH) in up to half of cases. PHH requires lifelong neurosurgical care and is associated with significant cognitive and psychomotor disability. Cerebrospinal fluid (CSF) biomarkers may provide both diagnostic information for PHH and novel insights into its pathophysiology.

OBJECTIVE: To explore the diagnostic ability of candidate CSF biomarkers for PHH.

METHODS: Concentrations of amyloid precursor protein (APP), soluble APPα (sAPPα), soluble APPβ, neural cell adhesion molecule-1 (NCAM-1), L1 cell adhesion molecule (L1CAM), tau, phosphorylated tau, and total protein (TP) were measured in lumbar CSF from neonates in 6 groups: (1) no known neurological disease (n = 33); (2) IVH grades I to II (n = 13); (3) IVH grades III to IV (n = 12); (4) PHH (n = 12); (5) ventricular enlargement without hydrocephalus (n = 10); and (6) hypoxic ischemic encephalopathy (n = 13). CSF protein levels were compared using analysis of variance, and logistic regression was performed to examine the predictive ability of each marker for PHH.

RESULTS: Lumbar CSF levels of APP, sAPPα, L1CAM, and TP were selectively increased in PHH compared with all other conditions (all P < .001). The sensitivity, specificity, and odds ratios of candidate CSF biomarkers for PHH were determined for APP, sAPPα, and L1CAM; cut points of 699, 514, and 113 ng/mL yielded odds ratios for PHH of 80.0, 200.0, and 68.75, respectively.

CONCLUSION: Lumbar CSF APP, sAPPα, L1CAM, and TP were selectively increased in PHH. These proteins, and sAPPα, in particular, hold promise as biomarkers of PHH and provide novel insight into PHH-associated neural injury and repair.
Vertically- and horizontally-transmitted memories – the fading boundaries between regeneration and inheritance in planaria
Authors: Neuhof Moran , Levin Michael , Rechavi Oded 
Published: August 2016

ABSTRACT
The Weismann barrier postulates that genetic information passes only from the germline to the soma and not in reverse, thus providing an obstacle to the inheritance of acquired traits. Certain organisms such as planaria – flatworms that can reproduce through asymmetric fission – avoid the limitations of this barrier, thus blurring the distinction between the processes of inheritance and development. In this paper, we re-evaluate canonical ideas about the interaction between developmental, genetic and evolutionary processes through the lens of planaria. Biased distribution of epigenetic effects in asymmetrically produced parts of a regenerating organism could increase variation and therefore affect the species' evolution. The maintenance and fixing of somatic experiences, encoded via stable biochemical or physiological states, may contribute to evolutionary processes in the absence of classically defined generations. We discuss different mechanisms that could induce asymmetry between the two organisms that eventually develop from the regenerating parts, including one particularly fascinating source – the potential capacity of the brain to produce long-lasting epigenetic changes.
Prolyl endopeptidase is involved in the degradation of neural cell adhesion molecules in vitro
Authors: Jaako Külli , Waniek Alexander , Parik Keiti , Klimaviciusa Linda , Aonurm-Helm Anu , Noortoots Aveli , Anier Kaili , Van Elzen Roos , Gérard Melanie , Lambeir Anne-Marie , Roßner Steffen , Morawski Markus , Zharkovsky Alexander 
Published: August 2016

ABSTRACT
Membrane-associated glycoprotein neural cell adhesion molecule (NCAM) and its polysialylated form (PSA-NCAM) play an important role in brain plasticity by regulating cell–cell interactions. Here, we demonstrate that the cytosolic serine protease prolyl endopeptidase (PREP) is able to regulate NCAM and PSA-NCAM. Using a SH-SY5Y neuroblastoma cell line with stable overexpression of PREP, we found a remarkable loss of PSA-NCAM, reduced levels of NCAM180 and NCAM140 protein species, and a significant increase in the NCAM immunoreactive band migrating at an apparent molecular weight of 120 kDa in PREP-overexpressing cells. Moreover, increased levels of NCAM fragments were found in the concentrated medium derived from PREP-overexpressing cells. PREP overexpression selectively induced an activation of matrix metalloproteinase-9 (MMP-9), which could be involved in the observed degradation of NCAM, as MMP-9 neutralization reduced the levels of NCAM fragments in cell culture medium. We propose that increased PREP levels promote epidermal growth factor receptor (EGFR) signaling, which in turn activates MMP-9. In conclusion, our findings provide evidence for newly-discovered roles for PREP in mechanisms regulating cellular plasticity through NCAM and PSA-NCAM.