bluuebunny/crossref_metadata_2025 huggingface dataset:
Defining a Novel Role for the Coxsackievirus and Adenovirus Receptor in Human Adenovirus Serotype 5 Transduction
In Vitro
in the Presence of Mouse Serum
Authors: Lopez-Gordo Estrella , Doszpoly Andor , Duffy Margaret R. , Coughlan Lynda , Bradshaw Angela C. , White Katie M. , Denby Laura , Nicklin Stuart A. , Baker Andrew H.
Published: April 2017

Human adenoviral serotype 5 (HAdV-5) vectors have predominantly hepatic tropism when delivered intravascularly, resulting in immune activation and toxicity. Coagulation factor X (FX) binding to HAdV-5 mediates liver transduction and provides protection from virion neutralization in mice. FX is dispensable for liver transduction in mice lacking IgM antibodies or complement, suggesting that alternative transduction pathways exist. To identify novel factor(s) mediating HAdV-5 FX-independent entry, we investigated HAdV-5 transduction
in vitro
in the presence of serum from immunocompetent C57BL/6 or immunocompromised mice lacking IgM antibodies (Rag 2
−/−
and NOD-scid-gamma [NSG]). Sera from all three mouse strains enhanced HAdV-5 transduction of A549 cells. While inhibition of HAdV-5–FX interaction with FX-binding protein (X-bp) inhibited transduction in the presence of C57BL/6 serum, it had negligible effect on the enhanced transduction observed in the presence of Rag 2
−/−
or NSG serum. Rag 2
−/−
serum also enhanced transduction of the FX binding-deficient HAdV-5HVR5*HVR7*E451Q (AdT*). Interestingly, Rag 2
−/−
serum enhanced HAdV-5 transduction in a FX-independent manner in CHO-CAR and SKOV3-CAR cells (CHO or SKOV3 cells transfected to stably express human coxsackievirus and adenovirus receptor [CAR]). Additionally, blockade of CAR with soluble HAdV-5 fiber knob inhibited mouse serum-enhanced transduction in A549 cells, suggesting a potential role for CAR. Transduction of HAdV-5 KO1 and HAdV-5/F35 (CAR binding deficient) in the presence of Rag 2
−/−
serum was equivalent to that of HAdV-5, indicating that direct interaction between HAdV-5 and CAR is not required. These data suggest that FX may protect HAdV-5 from neutralization but has minimal contribution to HAdV-5 transduction in the presence of immunocompromised mouse serum. Alternatively, transduction occurs via an unidentified mouse serum protein capable of bridging HAdV-5 to CAR.

IMPORTANCE
The intravascular administration of HAdV-5 vectors can result in acute liver toxicity, transaminitis, thrombocytopenia, and injury to the vascular endothelium, illustrating challenges yet to overcome for HAdV-5-mediated systemic gene therapy. The finding that CAR and potentially an unidentified factor present in mouse serum might be important mediators of HAdV-5 transduction highlights that a better understanding of the complex biology defining the interplay between adenovirus immune recognition and cellular uptake mechanisms is still required. These findings are important to inform future optimization and development of HAdV-5-based adenoviral vectors for gene therapy.
Endovascular recanalisation of a chronic occlusion of the retrohepatic IVC associated to a filter in a patient with antiphospholipid syndrome
Authors: Hinojosa Carlos A , Lizola Rene , Laparra-Escareno Hugo , Anaya-Ayala Javier E
Published: April 2017

Inferior vena cava (IVC) filters are useful adjuncts to prevent venous thromboembolism to the pulmonary circulation in the setting of contraindication for anticoagulation. Despite their proven decreased rate of pulmonary embolism, IVC filters are not without complications. We herein present the case of a 22-year-old man with a history of antiphospholipid antibody syndrome who was sent to our institution for evaluation with Budd-Chiari and post-thrombotic syndromes associated to a chronic retrohepatic complete IVC occlusion secondary to an IVC filter placed 5 years earlier. Via common femoral, transjugular and transhepatic accesses, we performed a successful endovascular recanalisation and reconstruction of the IVC with a 16 mm×60 mm covered stent; the hepatic outflow was restored with an 8×20 mm Palmaz stent. At 12-month follow-up, his symptoms have resolved, and his liver tests are within normal limits. He remains on systemic anticoagulation.
A rare case of a non-traumatic neck of femur fracture in a 17-year-old boy associated with vitamin D deficiency
Authors: Moten Maliha , Mussa Mohamed , Naqvi Syeda , Kulkarni Shrikant
Published: April 2017

Hip fractures in the young, healthy population are rare and often the result of high-energy trauma. A previously healthy 17-year-old patient presented to our institution with a 5-week history of left hip and knee pain in the absence of any trauma. Pelvic radiograph revealed a subacute left femoral neck fracture. He subsequently underwent surgical fixation and made an uneventful recovery. Further endocrine evaluation revealed isolated vitamin D deficiency to be the likely underlying cause for this fracture. Multiple previous opportunities were missed to identify the cause for this patient's symptoms. An intracapsular fracture in a young adult requires early recognition and prompt anatomical reduction. This case emphasises the need to maintain a high index of suspicion for atraumatic fractures in healthy adolescents with unexplained joint pain. Further endocrine and metabolic investigations are warranted, and isolated vitamin D deficiency must be considered as a potential causative factor.
Non-invasive emergent cerclage using a plastic sling: case series
Authors: Azpurua Humberto , Paredes Otto , Navas Solanye , Moros Jose
Published: April 2017

Cervical incompetence represents a controversial problem for the modern obstetrician. Treatment modalities since its description have changed with time. Shirodkar and McDonald cerclage techniques have remained the mainstay in the treatment of women with incompetent cervices performed either electively or emergently. The most feared complication of an emergency cervical cerclage is the rupture of membranes during the procedure, especially when the cervix is wide open and the membranes are protruding. To decrease that complication, some methods to reduce the prolapsed membranes have been used: filling the bladder with 0.45% saline solution through a Foley catheter, performing an amniocentesis to decrease intra-amniotic pressure and subsequent reduction of the prolapsed membranes as well as the use of balloons to push the membranes back into the uterus before the placement of a suture. Nevertheless, the introduction of such a sharp instrument like a needle in order to place the suture is a very risky step. Lately, a silicone pessary has also been used to perform cerclages but with disparate results. We present the successful use of an innovative method in 3 patients with cervical incompetence who presented with pregnancies <24 weeks and cervical effacement with protruding membranes into the vagina.
The sensitivity argument against child euthanasia
Authors: Keeling Geoff
Published: April 2017

Is there a moral difference between euthanasia for terminally ill adults and euthanasia for terminally ill children? Luc Bovens considers five arguments to this effect, and argues that each is unsuccessful. In this paper, I argue that Bovens' dismissal of the sensitivity argument is unconvincing.
Multi-party quantum key agreement with teleportation
Authors: Cai Binbin , Guo Gongde , Lin Song
Published: April 2017

Based on the technique of quantum teleportation, a new multi-party quantum key agreement protocol is proposed. In this protocol, all users first share EPR pairs via public quantum channels. Afterwards, the states of signal particles can be transferred between two adjacent users by quantum teleportation. With the help of four unitary encoding operations, all users can encode their separate secret key into the traveling quantum states. In the end, all users can derive the final shared key synchronously. The security analysis shows that the presented protocol is secure against some common attacks and completely loss tolerant.
Prevision of vehicle headway effect on urban traffic with a new car-following model
Authors: Peng Guanghan , Lu Weizhen , He Hongdi , Gu Zhenghua
Published: April 2017

In this study, a new car-following model is established aiming to predict the variation of vehicle headways on urban road. The linear stability condition is derived corresponding to the prevision of headway in moving. The modified Korteweg–de Vries (mKdV) equation is deduced through the nonlinear analysis. The kink–antikink soliton solution of the mKdV equation can interpret the urban traffic jams near the critical point under the prevision of vehicle headway. Moreover, it is clear that the prevision of headway effect did improve the stability of urban traffic flow since the traffic jams are alleviated efficiently by taking into account the prevision of headway term in numerical simulations, which are consistent with the theoretical analysis.
Optimizing chaos time-delay signature in two mutually-coupled semiconductor lasers through controlling internal parameters
Authors: Mu Penghua , Pan Wei , Yan Lianshan , Luo Bin , Zou Xihua
Published: April 2017

In this contribution, the effects of two key internal parameters, i.e. the linewidth-enhancement factor [Formula: see text] and gain nonlinearity [Formula: see text], on time-delay signatures (TDS) concealment of two mutually-coupled semiconductor lasers (MCSLs) are numerically investigated. In particular, the influences of [Formula: see text] and [Formula: see text] on the TDS concealment are compared and discussed systematically by setting different values of frequency detuning [Formula: see text] and injection strength [Formula: see text]. The results show that the TDS can be better suppressed with high [Formula: see text] or lower [Formula: see text] in the MCSLs. Two sets of desired optical chaos with TDS being strongly suppressed can be generated simultaneously in a wide injection parameter plane provided that [Formula: see text] and [Formula: see text] are properly chosen, indicating that optimizing TDS suppression through controlling internal parameters can be generalized to any delayed-coupled laser systems.
Reionization effect enhancement due to primordial black holes
Authors: Belotsky K. M. , Kirillov A. A. , Nazarova N. O. , Rubin S. G.
Published: April 2017

Primordial black holes (PBHs) could account for variety of phenomena like dark matter, reionization of the universe, early quasars, coalescence of black holes registered through gravitational waves recently. Each phenomenon relates to PBH of a specific mass range. PBH mass spectra varies in a wide range depending on specific model. Earlier, we have shown that PBH with monochromatic mass distribution around [Formula: see text] g value allow to re-ionize the universe moderately. Here, we show that reionization effect and contribution to dark matter can be simultaneously enhanced with more natural extended mass distribution in the range around the same mass value.
Horizontal Resonance of a 13 Story Building Under External Machine Vibrations
Authors: Liu Pei , Lian Peng-Yu , Yang Wei-Guo
Published: April 2017

Excessive vibrations seriously affected the comfort of residents living on the upper floors of a high-rise shear walled building in Beijing. The ambient vibration tests were conducted to measure the floor acceleration responses, which were found to contain almost periodic signals likely to be excited by vibration sources with frequency of about 1.5[Formula: see text]Hz. The transverse vibration levels of the building above the 8th floor are not acceptable as revealed by the one-third octave spectra and weighted acceleration levels according to the ‘Standard for Allowable Vibration of Building Engineering’ of China. The modal properties of the building are identified by a Bayesian FFT method, indicating that the resonance between the building and the vibration sources caused the excessive vibrations. For comparison, the vibration test of an adjacent building with the same structural design was also conducted, together with modal analysis by the finite element method. It is found that as the story level increases, different trends of amplification in floor root mean square (RMS) acceleration and mode shape component of the two buildings cause different vibration levels. After tests outside the residence community, the main vibration sources were identified to be the working machines in two stone processing factories a few hundred meters away from the building. The vibration tests with measurements in the building and near the vibration sources with different number of machines in the two factories were also conducted. The results show that the vibration levels of the building can be controlled below the acceptance value by reducing the number of machines.
3D Finite Element Modeling of GFRP-Reinforced Concrete Deep Beams without Shear Reinforcement
Authors: Markou George , AlHamaydeh Mohammad
Published: April 2017

This paper presents the numerical investigation of nine Glass Fiber-Reinforced Polymer (GFRP) concrete deep beams through the use of numerically-efficient 20-noded hexahedral elements. Cracking is taken into account by means of the smeared crack approach and the bars are simulated as embedded rod elements. The developed numerical models are validated against published experimental results. The validation beams spanned a practical range of varying design parameters; namely, shear span-to-depth ratio, concrete specified compressive strength and flexural reinforcement ratio. The motivation for this research is to accurately yet efficiently capture the mechanical behavior of the GFRP-reinforced concrete deep beams. The presented numerical investigation demonstrated close correlations of the force–deformation relationships that are numerically predicted and their experimental counterparts. Moreover, the numerically predicted modes of failure are also found to be conformal to those observed experimentally. The proposed modeling approach that overcame previous computational limitations has further demonstrated its capability to accurately model larger and deeper beams in a computationally efficient manner. The validated modeling technique can then be efficiently used to perform extensive parametric investigations related to behavior of this type of structural members. The modeling method presented in this work paves the way for further parametric investigations of the mechanical behavior of GFRP-reinforced deep beams without shear reinforcement that will serve as the base for proposing new design guidelines. As a deeper understanding of the behavior and the effect of the design parameters is attained, more economical and safer designs will emerge.
Spectroscopic investigations on chiral J-aggregates induced by tartaric acid in alcoholic solution
Authors: Zagami Roberto , Castriciano Maria Angela , Romeo Andrea , Scolaro Luigi Monsù
Published: April 2017

Chiral J-aggregates of meso-tetrakis(4-sulfonatophenyl)porphyrin (TPPS[Formula: see text] have been obtained in ethanol solution triggered by addition of both enantiomeric forms of tartaric acid. A detailed spectroscopic investigation has been performed on aggregates obtained by a well-defined mixture protocol of reactants. Our findings show as both aggregation process and induced supramolecular chirality essentially depend on the concentration of the reactants. Contrary to what occurs in aqueous solution, TPPS4 in ethanol solution shows: (i) at low porphyrin concentration, an aggregation behavior characterized by a L-tartaric acid threshold whereas the D-tartaric does not work even at high concentrations, so revealing an enantiomeric discrimination; (ii) at high porphyrin concentration, a large kinetic discrimination of D- vs. L-enantiomer.
SYSTEMATIC INNOVATION CAPABILITY: EVIDENCE FROM CASE STUDIES AND A LARGE SURVEY
Authors: SAMSON DANNY , GLOET MARIANNE , SINGH PRAKASH
Published: April 2017

This study involved a series of case studies that were combined with an extensive literature review to frame and construct a large-scale survey, measuring systematic innovation capability, and innovation performance (IP). Previous literature is quite fragmented with little inherent cohesion. Relatively few truly holistic studies have been done, especially in a large-scale multi-industry context. The case studies and structural equation modelling (SEM) in the present study validated important predictor variables of IP, including leadership and innovation strategy, customer focus and innovation process management, culture and human resources management, knowledge and technology management. The SEM determined that systematic innovation capability is a valid concept and can be measured as such, relating strongly to IP and business performance. Based on deep case studies and our large sample, innovation capability was demonstrated to be a holistic concept comprising a number of core elements that act together to strongly determine performance outcomes.
Ages of Norwegian oils and bitumen based on age-specific biomarkers
Authors: Matapour Z. , Karlsen D. A.
Published: April 2017

Norwegian oils are generally considered sourced primarily from the Kimmeridge Clay equivalent shales such as the Draupne, Mandal, Spekk and Hekkingen formations, with secondary contributions from the mid–lower Jurassic, and also from the Triassic in the Barents Sea (Botneheia Formation). Still, as most of our age inferences concerning source-oil correlation are based on facies-specific biomarkers, a number of proposed correlations have been questioned.

Thus, source to oil correlations were frequently made on the basis of facies parameters, and rightfully so, but facies-specific signatures in oils will transgress age – and, in principle, not correlate with the phylogenetic evolution. This means that one could, in principle assign an oil to ‘the wrong’ age – when one is, in fact, linking it to a known source rock signature.

A series of 40 oil samples and core extracts, which cover a wide range both stratigraphically and geographically, have been analysed. In this paper, we present for the first time a Norwegian oil-age map based on age-specific biomarkers among the nordiacholestanes and triaromatic steroids parameters, and delineate also where we find Cretaceous- and Palaeozoic-derived oils. The reasons for this distribution pattern, compared to that of Mesozoic oils on the Norwegian Continental Shelf (NCS), are discussed.
Developmental profile of motor cortex transcallosal inhibition in children and adolescents
Authors: Ciechanski Patrick , Zewdie Ephrem , Kirton Adam
Published: April 2017

Transcallosal fibers facilitate interhemispheric networks involved in motor tasks. Despite their clinical relevance, interhemispheric motor control systems have not been completely defined in the developing brain. The objective of this study was to examine the developmental profile of transcallosal inhibition in healthy children and adolescents. Nineteen typically developing right-handed participants were recruited. Two transcranial magnetic stimulation (TMS) paradigms assessed transcallosal inhibition: ipsilateral silent periods (iSP) and paired-pulse interhemispheric inhibition (IHI). TMS was applied to the motor hotspot of the first dorsal interosseous muscle. Resting motor threshold (RMT), iSP latency, duration and suppression strength, and paired-pulse IHI were measured from both hemispheres. The Purdue Pegboard Test assessed unimanual motor function. Hemispheric differences were evident for RMT and iSP latency and suppression strength, where the left hemisphere had a lower RMT, prolonged latency, and greater suppression strength. iSP duration showed hemispheric symmetry. RMT and iSP latency decreased with age, whereas iSP suppression strength increased. Girls showed shorter iSP latency. Children typically displayed IHI, although hemispheric differences were observed. iSP suppression strength was uniquely associated with IHI within individuals. iSP duration correlated with motor performance. TMS can characterize transcallosal inhibition in normal children and adolescents with effects of age, directionality, sex, and motor performance. Establishing this developmental profile of interhemispheric interactions may advance understanding and therapeutic strategies for pediatric motor disorders such as cerebral palsy.

NEW & NOTEWORTHY Here we demonstrate that transcranial magnetic stimulation can characterize transcallosal inhibition in normal children and adolescents with effects of age, directionality, handedness, and motor performance. Interestingly, we also demonstrated sex effects, possibly related to the differing developmental profiles of boys and girls. Establishing this developmental profile of interhemispheric interactions may advance understanding and therapeutic strategies for pediatric motor disorders such as cerebral palsy.
Endophytic Actinobacteria Associated with Dracaena cochinchinensis Lour.: Isolation, Diversity, and Their Cytotoxic Activities
Authors: Salam Nimaichand , Khieu Thi-Nhan , Liu Min-Jiao , Vu Thu-Trang , Chu-Ky Son , Quach Ngoc-Tung , Phi Quyet-Tien , Narsing Rao Manik Prabhu , Fontana Angélique , Sarter Samira , Li Wen-Jun
Published: April 2017

Dracaena cochinchinensis Lour. is an ethnomedicinally important plant used in traditional Chinese medicine known as dragon’s blood. Excessive utilization of the plant for extraction of dragon’s blood had resulted in the destruction of the important niche. During a study to provide a sustainable way of utilizing the resources, the endophytic Actinobacteria associated with the plant were explored for potential utilization of their medicinal properties. Three hundred and four endophytic Actinobacteria belonging to the genera Streptomyces, Nocardiopsis, Brevibacterium, Microbacterium, Tsukamurella, Arthrobacter, Brachybacterium, Nocardia, Rhodococcus, Kocuria, Nocardioides, and Pseudonocardia were isolated from different tissues of D. cochinchinensis Lour. Of these, 17 strains having antimicrobial and anthracyclines-producing activities were further selected for screening of antifungal and cytotoxic activities against two human cancer cell lines, MCF-7 and Hep G2. Ten of these selected endophytic Actinobacteria showed antifungal activities against at least one of the fungal pathogens, of which three strains exhibited cytotoxic activities with IC50-values ranging between 3 and 33 μg·mL−1. Frequencies for the presence of biosynthetic genes, polyketide synthase- (PKS-) I, PKS-II, and nonribosomal peptide synthetase (NRPS) among these 17 selected bioactive Actinobacteria were 29.4%, 70.6%, and 23.5%, respectively. The results indicated that the medicinal plant D. cochinchinensis Lour. is a good niche of biologically important metabolites-producing Actinobacteria.
Abnormal Event Detection in Wireless Sensor Networks Based on Multiattribute Correlation
Authors: Wang Mengdi , Xue Anrong , Xia Huanhuan
Published: April 2017

Abnormal event detection is one of the vital tasks in wireless sensor networks. However, the faults of nodes and the poor deployment environment have brought great challenges to abnormal event detection. In a typical event detection technique, spatiotemporal correlations are collected to detect an event, which is susceptible to noises and errors. To improve the quality of detection results, we propose a novel approach for abnormal event detection in wireless sensor networks. This approach considers not only spatiotemporal correlations but also the correlations among observed attributes. A dependency model of observed attributes is constructed based on Bayesian network. In this model, the dependency structure of observed attributes is obtained by structure learning, and the conditional probability table of each node is calculated by parameter learning. We propose a new concept named attribute correlation confidence to evaluate the fitting degree between the sensor reading and the abnormal event pattern. On the basis of time correlation detection and space correlation detection, the abnormal events are identified. Experimental results show that the proposed algorithm can reduce the impact of interference factors and the rate of the false alarm effectively; it can also improve the accuracy of event detection.
Design of a Coupler with Three Reconfigurable Output Ports and a Beamwidth Reconfigurable Antenna
Authors: Kim Dong-Woo , Oh Soon-Soo
Published: April 2017

The design and fabrication of a coupler with three reconfigurable output ports have been proposed. The output ports of the proposed coupler can be adjusted by varying the number of shorting pins. An antenna with a reconfigurable beamwidth has been also involved in this paper. The proposed antenna has a coupler and a 1 × 3 array rectangular patch. The beamwidth is set by the number of output ports. The simulation and experiment show the verification of the proposed coupler and beamwidth variation of array antenna. The broadest measured beamwidth was 66.2° and the sharpest measured beamwidth was 24.1°.
Tumors Sharply Increased after Ceasing Pazopanib Therapy for a Patient with Advanced Uterine Leiomyosarcoma: Experience of Tumor Flare
Authors: Tanigawa Terumi , Morisaki Shintaro , Fukuda Hisanobu , Yoshimura Shuichiro , Nakajima Hisayoshi , Kotera Kohei
Published: April 2017

Pazopanib has activity in patients with soft-tissue sarcoma. We report an advanced uterine leiomyosarcoma case that suddenly worsened after cessation of pazopanib therapy. A 47-year-old woman had a primary uterine leiomyosarcoma tumor and multiple lung metastases, which progressed during her initial treatment. In subsequent treatment with pazopanib for 3 months, the sum of her tumor diameters after cessation sharply increased for two weeks. Symptoms such as dyspnea suddenly worsened also. She died of the disease one month after cessation of pazopanib therapy. Given the poor prognosis of recurrent uterine leiomyosarcoma and the rapid tumor enlargement after ending pazopanib therapy, control of this disease is especially important. Therefore, the decision to discontinue pazopanib therapy requires careful consideration.
The Relation of Diabetes Type 2 with Sexual Function among Reproductive Age Women in Iran, a Case-Control Study
Authors: Afshari Poorandokht , Yazdizadeh Shiva , Abedi Parvin , Rashidi Homayra
Published: April 2017

Background.Diabetic patients are at the greater risk of retinopathy, nephropathy, neuropathy, and sexual dysfunction compared to the general population.Objective.The aim of this study was to evaluate the sexual dysfunction in type 2 diabetes reproductive age women in Iran.Method.This was a case-control study carried out on 130 women with type 2 diabetes and 130 healthy women. The type 2 diabetes diagnosis was confirmed with abnormal fasting blood sugar, abnormal random blood sugar test, and abnormal level of HbA1C. Eligible women were requested to complete a demographic questionnaire and female sexual function index (FSFI). The chi-square test, independentt-test, and Multivariate Analysis of Covariance (MANCOVA) were used for analyzing data.Results.Results of this study showed that diabetic women had significantly lower sexual desire, arousal, lubrication, and orgasm and more pain compared to the healthy women (p<0.05). Also diabetic women had lower sexual satisfaction compared to the healthy women (p=0.002). The total score of sexual function was significantly lower in the diabetic women compared to the healthy women (21.25±7.04versus22.43±7.6,p=0.004).Conclusion.Results of this study showed that the score of all dimensions of sexual function in diabetic patients was lower than that in healthy women. Education and counseling about controlling diabetes and sexual function among diabetic women in reproductive age are recommended.
Anatomic Variation in Morphometry of Human Coracoid Process among Asian Population
Authors: Fathi Manal , Cheah Pike-See , Ahmad Umar , Nasir M. Nizlan , San Aye Aye , Abdul Rahim Ezamin , Hussin Paisal , Mahmud Rozi , Othman Fauziah
Published: April 2017

Ethnic origin plays an important role in bone morphometry. Studies examining the influence of coracoid process have focused primarily on adults and have not included people from diverse Asian ethnic backgrounds. Our goal was to explore ethnic differences in morphometry of coracoid among Asian population. We performed morphometric measurements of coracoid process on cadaveric shoulders and shoulder CT scans from 118 specimens. The cadaveric sample included Indian (46%), Chinese (27%), and Myanmarese (27%) subjects, while the CT scans sample included Chinese (67%) and Malay (33%) subjects. The morphometric measurements were performed using digital caliper and software developed at Golden Horses Health Sanctuary (GHHS). In the Indian cadaveric shoulders, the coracoid process is better developed than the other groups with the exception of the tip width of coracoid process. There are significant differences in almost all measurements (P<0.05) between the ethnic groups. On the other hand, the morphometry of coracoid process from CT scans data is bigger in Chinese than Malay subjects when stratified by sex (P<0.05). Moreover, in all morphometric measurements, the females had smaller measurements than males (P<0.05). Understanding such differences is important in anatomy, forensic and biological identity, and orthopaedic and shoulder surgeries.
Characterization of Chronic Mechanical Irritation in Oral Cancer
Authors: Lazos Jerónimo P. , Piemonte Eduardo D. , Lanfranchi Hector Eduardo , Brunotto Mabel N.
Published: April 2017

Objective. Oral mucosa could host many lesions originated by chronic mechanical irritation (CMI) from teeth or dentures, and it has been proposed as risk factor for oral cancer. Nevertheless, the features of CMI factors in oral cancer and other lesions are not assessed. The aim of this study is to describe CMI features regarding type (dental, prosthetic, and/or functional), localization, and time span.Materials and Methods. Three groups were studied in this cross-sectional study: Oral Cancer (OC); Chronic Traumatic Ulcer (CTU); and Benign Irritative Mechanical Lesions (BIML). All sources of mechanical irritation were included: dental, prosthetic, and functional.Results. 285 patients (176 females, 109 males) were studied: OC = 38, CTU = 44, and BIML = 203. The most frequent CMI factor was dental, followed by functional and prosthetic in all groups; 76.5% (n=218) presented functional factors. Buccal mucosa (45%) and tongue (42%) were the most affected sites. Time of action of CMI displayed statistically significant differences between BIML, CTU, and OC groups, with a mean of 21, 33, and 49 months, respectively.Conclusions. CMI should be properly recorded with as much detail as alcohol and tobacco consumption. CMI associated lesions are produced by dental or prosthetic factors, usually in relation to functional factors, involving mainly tongue and buccal mucosa.
Major Depressive Symptoms Increase 3-Year Mortality Rate in Patients with Mild Dementia
Authors: Petersen Jindong Ding , Waldorff Frans Boch , Siersma Volkert Dirk , Phung Thien Kieu Thi , Bebe Anna Carina Klara Magdalena , Waldemar Gunhild
Published: April 2017

Depression and dementia are commonly concurrent and are both associated with increased mortality among older people. However, little is known about whether home-dwelling patients newly diagnosed with mild dementia coexisting with depressive symptoms have excess mortality. We conducted a post hoc analysis based on data from the Danish Alzheimer’s Intervention Study of 330 individuals who were diagnosed with mild dementia within the past 12 months. Thirty-four patients were identified with major depressive symptoms (MD-S) at baseline. During the 3-year follow-up period, 56 patients died, and, among them, 12 were with MD-S at baseline. Multivariable analysis adjusting for the potential confounders (age, sex, smoking status, alcohol consumption, education, BMI, household status, MMSE, CCI, QoL-AD, NPIQ, ADSC-ADL, medication, and RCT allocation) showed that patients with MD-S had a 2.5-fold higher mortality as compared to the patients without or with only few depressive symptoms. Our result revealed that depression is possibly associated with increased mortality in patients with mild dementia. Given that depression is treatable, screening for depression and treatment of depression can be important already in the earliest stage of dementia to reduce mortality.
Adaptations in Evoked Pain Sensitivity and Conditioned Pain Modulation after Development of Chronic Neck Pain
Authors: Shahidi Bahar , Maluf Katrina S.
Published: April 2017

Numerous studies demonstrate elevated pain sensitivity and impaired conditioned pain modulation (CPM) in patients with chronic musculoskeletal pain compared to healthy individuals; however, the time course of changes in pain sensitivity and CPM after the development of a chronic pain condition is unclear. Secondary analysis of data from a prospective investigation examined changes in evoked pain sensitivity and CPM before and after development of chronic neck pain (CNP). 171 healthy office workers participated in a baseline assessment, followed by monthly online questionnaires to identify those who developed CNP over the subsequent year. These individuals (N=17) and a cohort of participants (N=10) who remained pain-free during the follow-up period returned for a 12-month follow-up assessment of mechanical and thermal pain sensitivity and CPM. Pain sensitivity measures did not differ between groups at baseline; however, cold pain threshold decreased in the CNP group at follow-up (p<0.05). CPM was lower at baseline in the CNP group compared to those who reported no neck pain (p<0.02) and remained unchanged one year later. These findings indicate that CPM is reduced in healthy individuals prior to the development of chronic neck pain and the subsequent reduction of thresholds for cold but not pressure pain.
Micromechanical Characterization of Complex Polypropylene Morphologies by HarmoniX AFM
Authors: Liparoti S. , Sorrentino A. , Speranza V.
Published: April 2017

This paper examines the capability of the HarmoniX Atomic Force Microscopy (AFM) technique to draw accurate and reliable micromechanical characterization of complex polymer morphologies generally found in conventional thermoplastic polymers. To that purpose, injection molded polypropylene samples, containing representative morphologies, have been characterized by HarmoniX AFM. Mapping and distributions of mechanical properties of the samples surface are determined and analyzed. Effects of sample preparation and test conditions are also analyzed. Finally, the AFM determination of surface elastic moduli has been compared with that obtained by indentation tests, finding good agreement among the results.
Construction Technology and Mechanical Properties of a Cement-Soil Mixing Pile Reinforced by Basalt Fibre
Authors: Hong Yingwei , Wu Xiaoping , Zhang Peng
Published: April 2017

A new type of cement-soil mixing pile reinforced by basalt fibre is proposed for increasing the bearing capacity of cement-soil mixing piles. This work primarily consists of three parts. First, the process of construction technology is proposed, which could allow uniform mixing of the basalt fibre in cement-soil. Second, the optimal proportions of the compound mixtures and the mechanical properties of the pile material are obtained from unconfined compression strength test, tensile splitting strength test, and triaxial shear test under different conditions. Third, the reliability of the construction technology, optimal proportions, and mechanical properties are verified by testing the mechanical properties of the drilling core sample on site.
A Phase 2/3 Multicenter, Randomized, Open-Label Study to Compare the Efficacy and Safety of Lenalidomide Versus Investigator's Choice in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Authors: Czuczman Myron S. , Trněný Marek , Davies Andrew , Rule Simon , Linton Kim M. , Wagner-Johnston Nina , Gascoyne Randy D. , Slack Graham W. , Brousset Pierre , Eberhard David A. , Hernandez-Ilizaliturri Francisco J. , Salles Gilles , Witzig Thomas E. , Zinzani Pier Luigi , Wright George W. , Staudt Louis M. , Yang Yandan , Williams P. Mickey , Lih Chih-Jian , Russo Jacqueline , Thakurta Anjan , Hagner Patrick , Fustier Pierre , Song Dale , Lewis Ian D.
Published: April 2017

Purpose: Randomized, multicenter, open-label, phase 2/3 trial investigating lenalidomide versus investigator's choice (IC) in relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

Experimental Design: Patients with DLBCL who received ≥2 prior therapies were stratified by DLBCL subtype [germinal center B-cell (GCB) vs. non-GCB; determined by immunohistochemistry (IHC)] and then randomized 1:1 to lenalidomide (25 mg/day, 21 days of 28-day cycle) or IC (gemcitabine, rituximab, etoposide, or oxaliplatin). Crossover to lenalidomide was permitted for IC-treated patients with radiologically confirmed progressive disease. The primary endpoint was overall response rate (ORR). Progression-free survival (PFS), overall survival, and subtype analysis [GCB vs. activated B-cell (ABC)] using gene expression profiling (GEP) were exploratory endpoints.

Results: Stage 1: 102 DLBCL patients (by IHC: non-GCB, n = 54; GCB, n = 48) received ≥1 dose of lenalidomide or IC. Hematologic treatment-emergent adverse events with lenalidomide versus IC included neutropenia (42.6%; 36.4%), anemia (33.3%; 47.3%), thrombocytopenia (24.1%; 43.6%), and leukopenia (5.6%; 12.7%), respectively. Overall, lenalidomide-treated patients had an ORR of 27.5% versus 11.8% in IC (ORRs were similar regardless of IHC-defined DLBCL subtype). Median PFS was increased in patients receiving lenalidomide (13.6 weeks) versus IC (7.9 weeks; P = 0.041), with greater improvements in non-GCB patients (15.1 vs. 7.1 weeks, respectively; P = 0.021) compared with GCB (10.1 vs. 9.0 weeks, respectively; P = 0.550).

Conclusions: The clinical benefit of lenalidomide monotherapy in DLBCL patients was more evident in the non-GCB subtype. Exploratory analyses suggest that this preferential benefit was more pronounced in the GEP-defined ABC population, demonstrating a need for additional studies of lenalidomide in DLBCL using GEP subtyping. Clin Cancer Res; 23(15); 4127–37. ©2017 AACR.
Antagonists of the system L neutral amino acid transporter (LAT) promote endothelial adhesivity of human red blood cells
Authors: Dosier Laura Beth Mann , Premkumar Vikram J. , Zhu Hongmei , Akosman Izzet , Wempe Michael F. , McMahon Timothy J.
Published: April 2017

The system L neutral amino acid transporter (LAT; LAT1, LAT2, LAT3, or LAT4) has multiple functions in human biology, including the cellular import of S-nitrosothiols (SNOs), biologically active derivatives of nitric oxide (NO). SNO formation by haemoglobin within red blood cells (RBC) has been studied, but the conduit whereby a SNO leaves the RBC remains unidentified. Here we hypothesised that SNO export by RBCs may also depend on LAT activity, and investigated the role of RBC LAT in modulating SNO-sensitive RBC-endothelial cell (EC) adhesion. We used multiple pharmacologic inhibitors of LAT in vitro and in vivo to test the role of LAT in SNO export from RBCs and in thereby modulating RBC-EC adhesion. Inhibition of human RBC LAT by type-1-specific or nonspecific LAT antagonists increased RBC-endothelial adhesivity in vitro, and LAT inhibitors tended to increase post-transfusion RBC sequestration in the lung and decreased oxygenation in vivo. A LAT1-specific inhibitor attenuated SNO export from RBCs, and we demonstrated LAT1 in RBC membranes and LAT1 mRNA in reticulocytes. The proadhesive effects of inhibiting LAT1 could be overcome by supplemental L-CSNO (S-nitroso-L-cysteine), but not D-CSNO or L-Cys, and suggest a basal anti-adhesive role for stereospecific intercellular SNO transport. This study reveals for the first time a novel role of LAT1 in the export of SNOs from RBCs to prevent their adhesion to ECs. The findings have implications for the mechanisms of intercellular SNO signalling, and for thrombosis, sickle cell disease, and post-storage RBC transfusion, when RBC adhesivity is increased.
Delayed-onset of procoagulant signalling revealed by kinetic analysis of COAT platelet formation
Authors: Alberio Lorenzo , Ravanat Catherine , Hechler Béatrice , Mangin Pierre H. , Lanza François , Gachet Christian
Published: April 2017

The combined action of collagen and thrombin induces the formation of COAT platelets, which are characterised by a coat of procoagulant and adhesive molecules on their surface. Although recent work has started to highlight their clinical relevance, the exact mechanisms regulating the formation of procoagulant COAT platelets remain unclear. Therefore, we employed flow cytometry in order to visualise in real time surface and intracellular events following simultaneous platelet activation with convulxin and thrombin. After a rapid initial response pattern characterised by the homogenous activation of the fibrinogen receptor glycoprotein IIb/IIIa in all platelets, starting with a delay of about 2 minutes an increasing fraction transforms to procoagulant COAT platelets. Their surface is characterised by progressive loss of PAC-1 binding, expression of negative phospholipids and retention of α-granule von Willebrand factor. Intracellular events in procoagulant COAT platelets are a marked increase of free calcium into the low micromolar range, concomitantly with early depolarisation of the mitochondrial membrane and activation of caspase-3, while non-COAT platelets keep the intracellular free calcium in the nanomolar range and maintain an intact mitochondrial membrane. We show for the first time that the flow-cytometrically distinct fractions of COAT and non-COAT platelets differentially phosphorylate two signalling proteins, PKCα and p38MAPK, which may be involved in the regulation of the different calcium fluxes observed in COAT versus non-COAT platelets. This study demonstrates the utility of concomitant cellular and signalling evaluation using flow cytometry in order to further dissect the mechanisms underlying the dichotomous platelet response observed after collagen/thrombin stimulation.

Supplementary Material to this article is available online at www.thrombosis-online.com.
Fibrin clot characteristics in acute ischaemic stroke patients treated with thrombolysis: the impact on clinical outcome
Authors: Bembenek Jan P. , Niewada Maciej , Siudut Jakub , Plens Krzysztof , Członkowska Anna , Undas Anetta
Published: April 2017

Fibrin clot properties in acute ischaemic stroke (AIS) are unfavourably altered, including faster formation of denser and poorly lysable fibre networks. We investigated clot properties in AIS patients treated with recombinant tissue plasminogen activator (rtPA) and their impact on clinical outcome. In 74 consecutive AIS patients eligible for rtPA treatment, we assessed ex vivo plasma fibrin clot formation, permeability (Ks), and rtPA-induced lysis, along with peak thrombin generation, fibrinolysis proteins and inhibitors at three time points – on admission, after 24 hours and 3 months since stroke. Clinical outcome was assessed using the NIHSS and mRS scores. Compared with the pretreatment values, fibrin networks assessed 24 hours since thrombolysis were formed more slowly (+20.5 % lag phase on turbidimetry), were less compact (+36.9 % Ks), composed of thinner fibres (-10.6 % lower maximum absorbancy [ΔAb]), which were lysed more rapidly (-20.8 % clot lysis time [CLT] and +7.1 % the rate of rtPA-induced D-dimer release from clots [D-Drate]). Thrombin generation and fibrinolysis proteins remained elevated. Lower ΔAb (<0.86 at 405 nm), shorter CLT (<105 min), and higher D-Drate (>0.072 mg/l/min) assessed at baseline predicted good outcome (mRS 0–2) at 3 months after adjustment for age and fibrinogen. Logistic regression adjusted for potential confounders showed that good outcome at 3 months was predicted by pretreatment D-Drate, while pretreatment CLT predicted excellent outcome (mRS of 0–1). In conclusion, formation of denser fibrin clots displaying impaired lysability and pattern of their changes induced by thrombolysis may affect clinical outcome in AIS patients.
SOX17 Regulates Conversion of Human Fibroblasts Into Endothelial Cells and Erythroblasts by Dedifferentiation Into CD34
+
Progenitor Cells
Authors: Zhang Lianghui , Jambusaria Ankit , Hong Zhigang , Marsboom Glenn , Toth Peter T. , Herbert Brittney-Shea , Malik Asrar B. , Rehman Jalees
Published: April 2017

Background:

The mechanisms underlying the dedifferentiation and lineage conversion of adult human fibroblasts into functional endothelial cells have not yet been fully defined. Furthermore, it is not known whether fibroblast dedifferentiation recapitulates the generation of multipotent progenitors during embryonic development, which give rise to endothelial and hematopoietic cell lineages. Here we established the role of the developmental transcription factor SOX17 in regulating the bilineage conversion of fibroblasts by the generation of intermediate progenitors.

Methods:

CD34
+
progenitors were generated after the dedifferentiation of human adult dermal fibroblasts by overexpression of pluripotency transcription factors. Sorted CD34
+
cells were transdifferentiated into induced endothelial cells and induced erythroblasts using lineage-specific growth factors. The therapeutic potential of the generated cells was assessed in an experimental model of myocardial infarction.

Results:

Induced endothelial cells expressed specific endothelial cell surface markers and also exhibited the capacity for cell proliferation and neovascularization. Induced erythroblasts expressed erythroid surface markers and formed erythroid colonies. Endothelial lineage conversion was dependent on the upregulation of the developmental transcription factor SOX17, whereas suppression of SOX17 instead directed the cells toward an erythroid fate. Implantation of these human bipotential CD34
+
progenitors into nonobese diabetic/severe combined immunodeficiency (NOD-SCID) mice resulted in the formation of microvessels derived from human fibroblasts perfused with mouse and human erythrocytes. Endothelial cells generated from human fibroblasts also showed upregulation of telomerase. Cell implantation markedly improved vascularity and cardiac function after myocardial infarction without any evidence of teratoma formation.

Conclusions:

Dedifferentiation of fibroblasts to intermediate CD34
+
progenitors gives rise to endothelial cells and erythroblasts in a SOX17-dependent manner. These findings identify the intermediate CD34
+
progenitor state as a critical bifurcation point, which can be tuned to generate functional blood vessels or erythrocytes and salvage ischemic tissue.