bluuebunny/crossref_metadata_2025 huggingface dataset:
The cognitive and behavioral effects of meningioma lesions involving the ventromedial prefrontal cortex
Authors: Abel Taylor J. , Manzel Kenneth , Bruss Joel , Belfi Amy M. , Howard Matthew A. , Tranel Daniel
Published: November 2015

OBJECT

Anterior skull base meningiomas are frequently associated with changes in personality and behavior. Although such meningiomas often damage the ventromedial prefrontal cortex (vmPFC), which is important for higher cognition, the cognitive and behavioral effects of these meningiomas remain poorly understood. Using detailed neuropsychological assessments in a large series of patients, this study examined the cognitive and behavioral effects of meningioma lesions involving the vmPFC.

METHODS

The authors reviewed neuropsychology and lesion mapping records of 70 patients who underwent resection of meningiomas. The patients were drawn from the Neurological Patient Registry at the University of Iowa. Patients were sorted into 2 groups: those with lesions involving the vmPFC and those with lesions that did not involve the vmPFC. Neuropsychological data pertaining to a comprehensive array of cognitive and behavioral domains were available preoperatively in 20 patients and postoperatively in all 70 patients.

RESULTS

No change occurred in basic cognitive functions (e.g., attention, perception, memory, construction and motor performance, language, or executive functions) from the preoperative to postoperative epochs for the vmPFC and non-vmPFC groups. There was a significant decline in the behavioral domain, specifically adaptive function, for both the vmPFC and non-vmPFC groups, and this decline was more pronounced for the vmPFC group. Additionally, postoperative data indicated that the vmPFC group had a specific deficit in value-based decision making, as evidenced by poor performance on the Iowa Gambling Task, compared with the non-vmPFC group. The vmPFC and non-vmPFC groups did not differ postoperatively on other cognitive measures, including intellect, memory, language, and perception.

CONCLUSIONS

Lesions of the vmPFC resulting from meningiomas are associated with specific deficits in adaptive function and value-based decision making. Meningioma patients showed a decline in adaptive function postoperatively, and this decline was especially notable in patients with vmPFC region meningiomas. Early detection and resection of meningiomas of the anterior skull base (involving the gyrus rectus) may prevent these deficits.
Predicting the limits of the endoscopic endonasal approach in children: a radiological anatomical study
Authors: Youssef Carl A. , Smotherman Carmen R. , Kraemer Dale F. , Aldana Philipp R.
Published: November 2015

OBJECT

The endoscopic endonasal approach (EEA) has been established as an alternative approach to craniovertebral junction (CVJ) pathology in adults. The authors have previously described the nasoaxial line (NAxL) as an accurate predictor of the lower limit of the EEA to the CVJ in adults. The surgical anatomy limiting the EEA to the pediatric CVJ has not been well studied. Furthermore, predicting the lower limit of the EEA in various pediatric age groups is important in surgical planning. To better understand the anatomy affecting the EEA to the CVJ, the authors examined the skull base anatomy relevant to the EEA in children of different age groups and used the NAxL to predict the EEA lower limit in children.

METHODS

Axial brain CT scans of 39 children with normal skull base anatomy were reconstructed sagittally. Children were divided into 4 groups according to age: 3–6, 7–10, 11–14, and 15–18 years old. The intersection of the NAxL with the odontoid process of C-2 was described for each group. Analyses of variance were used to estimate the effect of age, sex, interaction between age and sex on different anatomical parameters relevant to the endonasal corridor (including the length of the hard palate [HPLe]), dimensions of choana and piriform aperture, and the length of the NAxL to C-2. The effect of the HPLe on the working distance of NAxL to the odontoid was also estimated using analysis of covariance, controlling for age, sex, and their interaction.

RESULTS

The NAxL extended to the odontoid process in 38 of the 39 children. Among the 39 children, the NAxL intersected the upper third of the odontoid process in 25 while intersecting the middle third in the remaining 13 children. The measurements of the inferior limits did not differ with age, varying between 9 and 11 mm below the hard palate line at the ventral surface of C-2. Significant increases in the size of the piriform aperture and choana and the HPLe were observed after age 10. The HPLe predicted the length of the NAxL (p < 0.0001).

CONCLUSIONS

The caudal limit of the EEA extends as far as the middle third of the odontoid process in children, as predicted by the NAxL. The most prominent increase in the size of the choana and piriform aperture occurs after age 10. The HPLe is a significant predictor of the working distance to C-2. Utilizing the NAxL preoperatively may help in planning the EEA to the CVJ in children.
Ventriculo-bipleural shunt as last resort in a 4-year-old child in whom a VP and VA shunt failed
Authors: Ratliff Miriam , Unterberg Andreas , Bächli Heidi
Published: November 2015

The authors present the unusual case of a 4-year-old boy who had a complex history of posthemorrhagic hydrocephalus and who underwent more than 40 surgeries related to this condition. In the course of trying to treat his condition, ventriculoperitoneal, ventriculoatrial, and ventriculopleural shunts were inserted and failed.

The child presented with a dysfunction of his shunt system. A ventriculopleural shunt was inserted, but within days the patient developed dyspnea as a clinical symptom of pleural effusion that required repeated thoracentesis. A bipleural drainage system was inserted, and no relevant pleural effusions developed during the follow-up period.

Although the authors’ experience is based on a single case, they do suggest bipleural drainage in patients with clinically relevant pleural effusions when the more common alternatives are not a good choice. Bipleural drainage might particularly be an option in children, who are prone to pleural effusion because of the smaller absorbing pleural surface. The authors reviewed the English-language literature on PubMed dating back to 1952. To their knowledge, this is the only published case in which a patient was treated with a ventriculo-bipleural shunt.
Etiology of postoperative hyponatremia following pediatric intracranial tumor surgery
Authors: Williams Cydni N. , Riva-Cambrin Jay , Bratton Susan L.
Published: November 2015

OBJECT

Cerebral salt wasting (CSW) and the syndrome of inappropriate antidiuretic hormone secretion (SIADH) cause postoperative hyponatremia in neurosurgery patients, can be difficult to distinguish clinically, and are associated with increased morbidity. The authors aimed to determine risk factors associated with CSW and SIADH among children undergoing surgery for intracranial tumors.

METHODS

This retrospective cohort study included children 0–19 years of age who underwent a first intracranial tumor surgery with postoperative hyponatremia (sodium ≤ 130 mEq/L). CSW was differentiated from SIADH by urine output and fluid balance, exclusive of other causes of hyponatremia. The CSW and SIADH groups were compared with basic bivariate analysis and recursive partitioning.

RESULTS

Of 39 hyponatremic patients, 17 (44%) had CSW and 10 (26%) had SIADH. Patients with CSW had significantly greater natriuresis compared with those with SIADH (median urine sodium 211 vs 28 mEq/L, p = 0.01). Age ≤ 7 years and female sex were significant risk factors for CSW (p = 0.03 and 0.04, respectively). Both patient groups had hyponatremia onset within the first postoperative week. Children with CSW had trends toward increased sodium variability and symptomatic hyponatremia compared with those with SIADH. Most received treatment, but inappropriate treatment was noted to worsen hyponatremia.

CONCLUSIONS

The authors found that CSW was more common following intracranial tumor surgery and was associated with younger age and female sex. Careful assessment of fluid balance and urine output can separate patients with CSW from those who have SIADH, and high urine sodium concentrations (> 100 mEq/L) support a CSW diagnosis. Patients with CSW and SIADH had similar clinical courses, but responded to different interventions, making appropriate diagnosis and treatment imperative to prevent morbidity.
Effect of Tween-20 on Core Biomarkers Measured in Cerebrospinal Fluid from Patients with Alzheimer’s Disease, Mild Cognitive Impairment, or Healthy Control Individuals
Authors: Berge Guro , Lauridsen Camilla , Sando Sigrid Botne , Holder Daniel Joseph , Møller Ina , Aasly Jan Olav , Bråthen Geir , Savage Mary Josephine , White Linda Rosemary
Published: November 2015

Background: There is substantial variation caused by preanalytical procedures in the measurement of cerebrospinal fluid (CSF) biomarkers for Alzheimer’s disease (AD) reported in the literature. Objective: Determine whether the detergent Tween-20 improves diagnostic accuracy. Methods: CSF proteins (Aβ42, Aβ40, total tau, and phosphorylated tau) were measured by standard ELISA, in uncentrifuged CSF with or without 0.05% Tween-20 from patients with AD or amnestic mild cognitive impairment, and healthy elderly controls. In the main study, collection tubes containing Tween-20 (Sarstedt 15 mL) were filled with 5 mL CSF to ensure consistent detergent concentration across subsequent aliquots into Corning 2 mL tubes. These latter were also the primary collection vessel for samples without Tween-20. The effect of centrifugation, and extra tube transfer of samples with Tween-20 were also examined. Results: 0.05% Tween-20 significantly increased mean measured CSF concentration of Aβ42 (30% ), Aβ40 (23% ), and total tau (4% ), but not phosphorylated tau. Generally, these increases were similar in all groups, although for Aβ42, the mean percentage increase with Tween-20 was slightly larger for AD. Areas under receiver-operator characteristic curves were similar whether Tween-20 was present or not. Centrifuged CSF without Tween-20 significantly reduced the measured concentration of Aβ42 versus non-centrifuged samples, a difference not seen when detergent was added. Similar CSF Aβ42 levels were found whether Tween-20 was added at collection in an extra tube or directly to the main collection tube. Conclusion: Addition of Tween-20 to CSF did not improve differentiation of patients from controls.
Greater than the Sum of Its Parts: δ can be Constructed from Item Level Data
Authors: Royall Donald R. , Palmer Raymond F. , Matsuoka Teruyuki , Kato Yuka , Taniguchi Shogo , Ogawa Mayu , Fujimoto Hiroshi , Okamura Aiko , Shibata Keisuke , Nakamura Kaeko , Nakaaki Shutaro , Koumi Hiroyuki , Mimura Masaru , Fukui Kenji , Narumoto Jin
Published: November 2015

“δ”, a latent variable constructed from cognitive performance and functional status measures, can accurately diagnose dementia. The minimal assessment needed is unknown. We have constructed a δ homolog, “dTEXAS”, from Telephone Executive Assessment Scale (TEXAS) items, and validated it in a convenience sample of Japanese persons (n = 176). dTEXAS scores correlated strongly with both Instrumental Activities of Daily Living (IADL) (r = –0.86, p <  0.001) and Clinical Dementia Rating Scale (CDR) (r = 0.71, p <  0.001). Constructed independently of their diagnoses, dTEXAS scores accurately distinguished dementia versus controls [area under the receiver operating curve (AUC; ROC) = 0.92, dementia versus mild cognitive impairment (MCI) (AUC = 0.80) and controls versus MCI (AUC = 0.74)]. These AUCs are higher than those of multiple observed executive measures, as reported recently by Matsuoka et al., 2014. A dTEXAS score of –0.58 best discriminated between dementia versus controls with 90.1% sensitivity and 80.0% specificity.
Altered Affective Evaluations of Smells in Alzheimer’s Disease
Authors: Joussain Pauline , Bessy Marion , Fournel Arnaud , Ferdenzi Camille , Rouby Catherine , Delphin-Combe Floriane , Krolak-Salmon Pierre , Bensafi Moustafa
Published: November 2015

Background: Studies of olfaction in Alzheimer’s disease (AD) mainly focused on deficits in odor detection and identification, with very few investigations of olfactory emotional changes and their consequences for hedonics. Objective: The aim of the present study was to characterize affective evaluations of odors in AD patients. Methods: To this end, 20 AD patients and 20 matched controls were tested. Participants were screened for odor detection and identification ability and then asked to rate the intensity, pleasantness, and edibility of 20 odorants. Results: Results showed that, overall, AD patients had lower detection ability and perceived all odors as weaker than controls. As expected, they had lower identification ability on both cued and non-cued tasks. In addition, when smelling pleasant odors, patients had significantly lower hedonic ratings than controls (p <  0.02), whereas no group difference was found for neutral or unpleasant odors (p >  0.05 in both cases). Moreover, an analysis combining both intensity and pleasantness ratings showed that whereas intensity increased as a function of pleasantness and unpleasantness in controls, this quadratic relationship was not observed in AD patients. Conclusions: The study suggests that the simplest categorization criteria of odors (intensity and hedonic valence) are impaired in AD patients (especially for pleasant odors).
Targretin Improves Cognitive and Biological Markers in a Patient with Alzheimer’s Disease
Authors: Pierrot Nathalie , Lhommel Renaud , Quenon Lisa , Hanseeuw Bernard , Dricot Laurence , Sindic Christian , Maloteaux Jean-Marie , Octavea Jean-Noël , Ivanoiu Adrian
Published: November 2015

We present the effects of Targretin® (bexarotene) on cognition and biomarkers in a patient with mild Alzheimer’s disease (AD). Targretin® is a Retinoic X Receptor (RXR) agonist shown to improve synaptic and cognitive functions in animal models of AD by increasing neuronal cholesterol efflux. After 6 months of treatment with Targretin® 300 mg/day, memory improved by about 40% and the tau protein in the cerebrospinal fluid decreased by about 20% . No significant side effects were noticed. This observation in a single patient indicates that Targretin® may improve memory performance and biological markers at an early stage of AD.
Hippocampal Lipid Homeostasis in APP/PS1 Mice is Modulated by a Complex Interplay Between Dietary DHA and Estrogens: Relevance for Alzheimer’s Disease
Authors: Díaz Mario , Fabelo Noemí , Casañas-Sánchez Verónica , Marin Raquel , Gómez Tomás , Quinto-Alemany David , Pérez José A.
Published: November 2015

Current evidence suggests that lipid homeostasis in the hippocampus is affected by different genetic, dietary, and hormonal factors, and that its deregulation may be associated with the onset and progression of Alzheimer’s disease (AD). However, the precise levels of influence of each of these factors and their potential interactions remain largely unknown, particularly during neurodegenerative processes. In the present study, we have performed multifactorial analyses of the combined effects of diets containing different doses of docosahexaenoic acid (DHA), estrogen status (ovariectomized animals receiving vehicle or 17β-estradiol), and genotype (wild-type or transgenic APP/PS1 mice) in hippocampal lipid profiles. We have observed that the three factors affect lipid classes and fatty acid composition to different extents, and that strong interactions between these factors exist. The most aberrant lipid profiles were observed in APP/PS1 animals receiving DHA-poor diets and deprived of estrogens. Conversely, wild-type animals under a high-DHA diet and receiving estradiol exhibited a lipid profile that closely resembled that of the hippocampus of control animals. Interestingly, though the lipid signatures of APP/PS1 hippocampi markedly differed from wild-type, administration of a high-DHA diet in the presence of estrogens gave rise to a lipid profile that approached that of control animals. Paralleling changes in lipid composition, patterns of gene expression of enzymes involved in lipid biosynthesis were also altered and affected by combination of experimental factors. Overall, these results indicate that hippocampal lipid homeostasis is strongly affected by hormonal and dietary conditions, and that manipulation of these factors might be incorporated in AD therapeutics.
Linguistic Features Identify Alzheimer’s Disease in Narrative Speech
Authors: Fraser Kathleen C. , Meltzer Jed A. , Rudzicz Frank
Published: November 2015

Background: Although memory impairment is the main symptom of Alzheimer’s disease (AD), language impairment can be an important marker. Relatively few studies of language in AD quantify the impairments in connected speech using computational techniques. Objective: We aim to demonstrate state-of-the-art accuracy in automatically identifying Alzheimer’s disease from short narrative samples elicited with a picture description task, and to uncover the salient linguistic factors with a statistical factor analysis. Methods: Data are derived from the DementiaBank corpus, from which 167 patients diagnosed with “possible” or “probable” AD provide 240 narrative samples, and 97 controls provide an additional 233. We compute a number of linguistic variables from the transcripts, and acoustic variables from the associated audio files, and use these variables to train a machine learning classifier to distinguish between participants with AD and healthy controls. To examine the degree of heterogeneity of linguistic impairments in AD, we follow an exploratory factor analysis on these measures of speech and language with an oblique promax rotation, and provide interpretation for the resulting factors. Results: We obtain state-of-the-art classification accuracies of over 81% in distinguishing individuals with AD from those without based on short samples of their language on a picture description task. Four clear factors emerge: semantic impairment, acoustic abnormality, syntactic impairment, and information impairment. Conclusion: Modern machine learning and linguistic analysis will be increasingly useful in assessment and clustering of suspected AD.
MAPT H1 Haplotype is Associated with Late-Onset Alzheimer’s Disease Risk in APOE ɛ4 Noncarriers: Results from the Dementia Genetics Spanish Consortium
Authors: Pastor Pau ,   on behalf of The Dementia Genetic Spanish Consortium (DEGESCO), Moreno Fermín , Clarimón Jordi , Ruiz Agustín , Combarros Onofre , Calero Miguel , de Munain Adolfo López , Bullido Maria J. , de Pancorbo Marian M. , Carro Eva , Antonell Anna , Coto Eliecer , Ortega-Cubero Sara , Hernandez Isabel , Tárraga Lluís , Boada Mercè , Lleó Alberto , Dols-Icardo Oriol , Kulisevsky Jaime , Vázquez-Higuera José Luis , Infante Jon , Rábano Alberto , Fernández-Blázquez Miguel Ángel , Valentí Meritxell , Indakoetxea Begoña , Barandiarán Myriam , Gorostidi Ana , Frank-García Ana , Sastre Isabel , Lorenzo Elena , Pastor María A. , Elcoroaristizabal Xabier , Lennarz Martina , Maier Wolfang , Rámirez Alfredo , Serrano-Ríos Manuel , Lee Suzee E. , Sánchez-Juan Pascual
Published: November 2015

The MAPT H1 haplotype has been linked to several disorders, but its relationship with Alzheimer’s disease (AD) remains controversial. A rare variant in MAPT (p.A152T) has been linked with frontotemporal dementia (FTD) and AD. We genotyped H1/H2 and p.A152T MAPT in 11,572 subjects from Spain (4,327 AD, 563 FTD, 648 Parkinson’s disease (PD), 84 progressive supranuclear palsy (PSP), and 5,950 healthy controls). Additionally, we included 101 individuals from 21 families with genetic FTD. MAPT p.A152T was borderline significantly associated with FTD [odds ratio (OR) = 2.03; p = 0.063], but not with AD. MAPT H1 haplotype was associated with AD risk (OR = 1.12; p = 0.0005). Stratification analysis showed that this association was mainly driven by APOE ɛ4 noncarriers (OR = 1.14; p = 0.0025). MAPT H1 was also associated with risk for PD (OR = 1.30; p = 0.0003) and PSP (OR = 3.18; p = 8.59 × 10-8) but not FTD. Our results suggest that the MAPT H1 haplotype increases the risk of PD, PSP, and non-APOE ɛ4 AD.
Unstable Body Mass Index and Progression to Probable Alzheimer’s Disease Dementia in Patients with Amnestic Mild Cognitive Impairment
Authors: Ye Byoung Seok , Jang Eun Young , Kim Seong Yoon , Kim Eun-Joo , Park Sun Ah , Lee Yunhwan , Hong Chang Hyung , Choi Seong Hye , Yoon Bora , Yoon Soo Jin , Na Hae Ri , Lee Jae-Hong , Jeong Jee H. , Kim Hee Jin , Na Duk L. , Seo Sang Won
Published: November 2015

Background and Objective: We investigated the influence of body mass index (BMI) status at baseline and changes in BMI over a follow-up period on the development of dementia in amnestic mild cognitive impairment (aMCI) patients. Methods: The longitudinal data of 747 aMCI patients were used to investigate the relationships among baseline BMI status, subsequent changes in BMI (median follow-up duration: 1.6 years, interquartile range: 1.0–2.3 years), and risk of progression to probable Alzheimer’s disease dementia (pADD). The aMCI patients were classified into underweight, normal weight, overweight, and obese subgroups, and further categorized into increased BMI, stable BMI, and decreased BMI subgroups during follow-up using a 4% mean annual change in BMI cut-off value. Results: Compared to the normal weight group, the underweight group had a higher risk of pADD (hazard ratio [HR]: 1.89, 95% confidence interval [CI]: 1.07–3.37) while the obese group had a lower risk (HR: 0.70, 95% CI: 0.49–0.999). After controllingfor baseline BMI status, the decreased BMI (HR: 2.29, 95% CI: 1.41–3.72) and increased BMI (HR: 3.96, 95% CI: 2.62–6.00) groups were at increased risk of progression to pADD. Conclusions: Our findings suggested that underweight at baseline was associated with a higher risk of progression to pADD, while obesity at baseline predicted a lower risk. Furthermore, significant changes in BMI during the follow-up period reflected an increased risk of progression to pADD, regardless of BMI status at baseline.
Functional Characterization of a Central Core Disease RyR1 Mutation (p.Y4864H) Associated with Quantitative Defect in RyR1 Protein
Authors: Cacheux Marine , Blum Ariane , Sébastien Muriel , Wozny Anne Sophie , Brocard Julie , Mamchaoui Kamel , Mouly Vincent , Roux-Buisson Nathalie , Rendu John , Monnier Nicole , Krivosic Renée , Allen Paul , Lacour Arnaud , Lunardi Joël , Fauré Julien , Marty Isabelle
Published: November 2015

Background:

Central Core Disease (CCD) is a congenital myopathy often resulting from a mutation in RYR1 gene. Mutations in RyR1 can increase or decrease channel activity, or induce a reduction in the amount of protein. The consequences of a single mutation are sometimes multiple and the analysis of the functional effects is complex.

Objective:

The consequences of the p.Y4864H mutation identified in a CCD patient have been studied regarding both RyR1 function and amount.

Methods:

The amount of RyR1 in human and mouse muscles was evaluated using qRT-PCR and quantitative Western blot, and calcium release was studied using calcium imaging on primary cultures. The results were compared between human and mouse.

Results:

The p.Y4864H mutation induced an alteration of calcium release, and in addition was associated to a reduction in the amount of RyR1 in the patient’s muscle. This suggests two possible pathophysiological mechanisms: the alteration of calcium release could result from a modification of the channel properties of RyR1 or from a RyR1 reduction. In order to discriminate between the two hypotheses, we used the heterozygous RyR1 knockout (RyR1+/–) mouse model showing a comparable RyR1 protein reduction. No reduction in calcium release was observed in primary muscle culture from these mice, and no muscle weakness was measured.

Conclusions:

Because the reduction in the amount of RyR1 protein has no functional consequences in the murine model, the muscle weakness observed in the patient is most likely the result of a modification of the calcium channel function of RyR1 due to the p.Y4864H mutation.
An Antibody to Detect Alanine-Expanded PABPN1: A New Tool to Study Oculopharyngeal Muscular Dystrophy
Authors: Vest Katherine E. , Apponi Luciano H. , Banerjee Ayan , Pavlath Grace K. , Corbett Anita H.
Published: November 2015

Background:

Oculopharyngeal muscular dystrophy (OPMD), a late onset disorder affecting specific skeletal muscles, is caused by a (GCG) n expansion mutation in the gene encoding the mRNA processing protein, polyadenylate binding protein nuclear 1 (PABPN1). The expansion in PABPN1 leads to an increase in a stretch of N-terminal alanine residues in the PABPN1 protein from the normal 10 to 12-18. Given this modest change, detection of mutant protein has not been possible without the use of tagged constructs.

Objective:

We sought to generate a polyclonal antibody that recognizes alanine-expanded but not wild type PABPN1 with the goal of making possible analysis of expression and localization of alanine-expanded PABPN1.

Methods:

We immunized rabbits with a GST-tagged alanine peptide and tested the resulting serum against alanine-expanded PABPN1 expressed in cell culture as well as in animal models of OPMD.

Results:

The resulting α-alanine antibody detected PABPN1 proteins that contained 14 or more alanine residues. Importantly, the α-alanine antibody could be used to detect alanine-expanded PABPN1 in muscles from either a mouse or Drosophila model of OPMD.

Conclusions:

This α-alanine antibody provides a new tool that will allow for more in-depth study of how alanine expansion affects aggregation, localization, and steady-state levels of alanine-expanded PABPN1 levels in vivo, providing new insight into the molecular mechanisms underlying OPMD.
Genome Editing Gene Therapy for Duchenne Muscular Dystrophy
Authors: Hotta Akitsu
Published: November 2015

Duchenne muscular dystrophy (DMD) is a severe genetic disorder caused by loss of function of the dystrophin gene on the X chromosome. Gene augmentation of dystrophin is challenging due to the large size of the dystrophin cDNA. Emerging genome editing technologies, such as TALEN and CRISPR-Cas9 systems, open a new erain the restoration of functional dystrophin and are a hallmark of bona fide gene therapy. In this review, we summarize current genome editing approaches, properties of target cell types for ex vivo gene therapy, and perspectives of in vivo gene therapy including genome editing in human zygotes. Although technical challenges, such as efficacy, accuracy, and delivery of the genome editing components, remain to be further improved, yet genome editing technologies offer a new avenue for the gene therapy of DMD.
Aflatoxin Contamination of the Milk Supply: A Pakistan Perspective
Authors: Aslam Naveed , Wynn Peter
Published: November 2015

Improving both quality and quantity of food available is a pressing need especially when one eighth of the world’s population consumes less energy than is required for maintenance and is exposed to contaminated food, both of which lead to greater susceptibility to diseases. The Pakistani population depends heavily on milk for nutritional needs and 10% of household income is spent on milk. This commodity requires continuous monitoring and care from its site of production by smallholder dairy producers through to urban consumers along tradition milk marketing chains. Feed ingredients used as concentrate feed to enhance milk production are often contaminated with mycotoxins, which, after ingestion, are transferred into milk. Aflatoxins can contribute to the causation of liver cancers, immune system disorders, and growth-related issues in children. Moreover, deaths in both humans and animals have also been reported after ingestion of aflatoxin-contaminated food. Studies have shown contamination of food and feed ingredients with mycotoxins, especially aflatoxins. This review places the dairy industry into context, summarizes how milk and milk products are contaminated with aflatoxins, and discusses the present legislative regulation of milk quality implemented in Pakistan. There is a need to eliminate fungus-susceptible animal feed ingredients, which are the source of mycotoxins so prevalent in the milk marketed to the consumer in Pakistan.
NHL and RCGA Based Multi-Relational Fuzzy Cognitive Map Modeling for Complex Systems
Authors: Peng Zhen , Wu Lifeng , Chen Zhenguo
Published: November 2015

In order to model multi-dimensions and multi-granularities oriented complex systems, this paper firstly proposes a kind of multi-relational Fuzzy Cognitive Map (FCM) to simulate the multi-relational system and its auto construct algorithm integrating Nonlinear Hebbian Learning (NHL) and Real Code Genetic Algorithm (RCGA). The multi-relational FCM fits to model the complex system with multi-dimensions and multi-granularities. The auto construct algorithm can learn the multi-relational FCM from multi-relational data resources to eliminate human intervention. The Multi-Relational Data Mining (MRDM) algorithm integrates multi-instance oriented NHL and RCGA of FCM. NHL is extended to mine the causal relationships between coarse-granularity concept and its fined-granularity concepts driven by multi-instances in the multi-relational system. RCGA is used to establish high-quality high-level FCM driven by data. The multi-relational FCM and the integrating algorithm have been applied in complex system of Mutagenesis. The experiment demonstrates not only that they get better classification accuracy, but it also shows the causal relationships among the concepts of the system.
Theoretical Analysis of Dependence of Nonlinear Effects in Mode-Locked Yb:YAG Lasers with a Highly Nonlinear Intra-Cavity Medium
Authors: Yoshida Takeshi , Okunishi Hiroaki , Kyomoto Keisuke , Kato Kento , Shimabayashi Kyosuke , Inayoshi Shinichi , Morioka Motoki , Kawato Sakae
Published: November 2015

Nonlinear ultrashort pulse propagation in a mode-locked Yb:YAG laser with a highly nonlinear intra-cavity medium is analyzed using a nonlinear Schrodinger equation. The output spectra are extended by the increased laser intensity, and spectral bandwidths wider than those of the gain medium are achieved. Moreover, pulse widths are shortened by increased laser intensity to considerably less than those of the gain medium. The simulation results qualitatively agree with the experimental results.
Selective Oxidation of Glycerol with 3% H2O2 Catalyzed by LDH-Hosted Cr(III) Complex
Authors: Wu Gongde , Wang Xiaoli , Jiang Taineng , Lin Qibo
Published: November 2015

A series of layered double hydroxides (LDHs) –hosted sulphonato-salen Cr(III) complexes were prepared and characterized by various physico-chemical measurements, such as Fourier transform infrared spectroscopy (FTIR), ultraviolet-visible spectroscopy (UV-Vis), powder X-ray diffraction (XRD), transmission electron microscope (TEM), scanning electron microscope (SEM) and elemental analysis. Additionally, their catalytic performances were investigated in the selective oxidation of glycerol (GLY) using 3% H2O2 as an oxidant. It was found that all the LDH-hosted Cr(III) complexes exhibited significantly enhanced catalytic performance compared to the homogeneous Cr(III) complex. Additionally, it was worth mentioning that the metal composition of LDH plates played an important role in the catalytic performances of LDH-hosted Cr(III) complex catalysts. Under the optimal reaction conditions, the highest GLY conversion reached 85.5% with 59.3% of the selectivity to 1,3-dihydroxyacetone (DHA). In addition, the catalytic activity remained after being recycled five times.
Performance-Based Cognitive Screening Instruments: An Extended Analysis of the Time versus Accuracy Trade-off
Authors: Larner Andrew
Published: November 2015

Early and accurate diagnosis of dementia is key to appropriate treatment and management. Clinical assessment, including the use of cognitive screening instruments, remains integral to the diagnostic process. Many cognitive screening instruments have been described, varying in length and hence administration time, but it is not known whether longer tests offer greater diagnostic accuracy than shorter tests. Data from several pragmatic diagnostic test accuracy studies examining various cognitive screening instruments in a secondary care setting were analysed to correlate measures of test diagnostic accuracy and test duration, building on the findings of a preliminary study. High correlations which were statistically significant were found between one measure of diagnostic accuracy, area under the receiver operating characteristic curve, and surrogate measures of test duration, namely total test score and total number of test items/questions. Longer cognitive screening instruments may offer greater accuracy for the diagnosis of dementia, an observation which has possible implications for the optimal organisation of dedicated cognitive disorders clinics.
Imaging of HCC—Current State of the Art
Authors: Schraml Christina , Kaufmann Sascha , Rempp Hansjoerg , Syha Roland , Ketelsen Dominik , Notohamiprodjo Mike , Nikolaou Konstantin
Published: November 2015

Early diagnosis of hepatocellular carcinoma (HCC) is crucial for optimizing treatment outcome. Ongoing advances are being made in imaging of HCC regarding detection, grading, staging, and also treatment monitoring. This review gives an overview of the current international guidelines for diagnosing HCC and their discrepancies as well as critically summarizes the role of magnetic resonance imaging (MRI) and computed tomography (CT) techniques for imaging in HCC. The diagnostic performance of MRI with nonspecific and hepatobililiary contrast agents and the role of functional imaging with diffusion-weighted imaging will be discussed. On the other hand, CT as a fast, cheap and easily accessible imaging modality plays a major role in the clinical routine work-up of HCC. Technical advances in CT, such as dual energy CT and volume perfusion CT, are currently being explored for improving detection, characterization and staging of HCC with promising results. Cone beam CT can provide a three-dimensional analysis of the liver with tumor and vessel characterization comparable to cross-sectional imaging so that this technique is gaining an increasing role in the peri-procedural imaging of HCC treated with interventional techniques.
Dentinogenic Specificity in the Preclinical Evaluation of Vital Pulp Treatment Strategies: A Critical Review
Authors: Tziafas Dimitrios , Kodonas Konstantinos
Published: November 2015

Reviews on the clinical performance of vital pulp treatment strategies and capping materials repeatedly showed an insufficient grade of evidence concerning their therapeutic validity. The biological mechanisms underlying the regenerative potential of pulp-dentin complex have attracted much attention during the last two decades, since new pulp treatment modalities have been designed and tested at the preclinical level. It has been recognized that evaluation should be based on the specific ability of therapeutic interventions to signal recruitment and differentiation of odontoblast-like cells forming a matrix in a predentin-like pattern, rather than uncontrolled hard tissue deposition in a scar-like form. The aim of the present article was to critically review data from histological experimental studies on pulp capping, published during the last 7 decades. A comprehensive literature search covering the period from 1949 to 2015 was done using the Medline/Pubmed database. Inclusion of a study was dependent on having sufficient data regarding the type of capping material used and the unit of observation (human permanent tooth in vivo or animal permanent dentition; primary teeth were excluded). The post-operatively deposited matrix was categorized into three types: unspecified, osteotypic, or dentin-like matrix. One hundred fifty-two studies were included in the final evaluation. Data from the present systematic review have shown that only 30.2% of the 152 experimental histological pulp capping studies described the heterogenic nature of the hard tissue bridge formation, including osteotypic and tubular mineralized tissue. Structural characteristics of the new matrix and the associated formative cells were not provided by the remaining 106 studies. Analysis showed that more careful preclinical evaluation with emphasis on the evidence regarding the dentinogenic specificity of pulp therapies is required. It seems that selection of appropriate vital pulp treatment strategies and pulp capping materials would be further facilitated in terms of their therapeutic validity if international consensus could be reached on a select number of mandatory criteria for tissue-specific dentinogenic events.
Molecular and Cytogenetic Characterization of New Wheat—Dasypyrum breviaristatum Derivatives with Post-Harvest Re-Growth Habit
Authors: Zhang Hongjun , Li Guangrong , Li Donghai , Gao Dan , Zhang Jie , Yang Ennian , Yang Zujun
Published: November 2015

A novel Dasypyrum species, Dasypyrum breviaristatum, serves as a valuable source of useful genes for wheat improvement. The development and characterization of new wheat—D. breviaristatum introgression lines is important to determine the novel gene(s) on specific chromosome(s). We first used multi-color fluorescence in situ hybridization (FISH) to identify the individual D. breviaristatum Vb chromosomes in a common wheat—D. breviaristatum partial amphiploid, TDH-2. The FISH patterns of D. breviaristatum chromosomes were different from those of D. villosum chromosomes. Lines D2146 and D2150 were selected from a cross between wheat line MY11 and wheat—D. breviaristatum partial amphiploid TDH-2, and they were characterized by FISH and PCR-based molecular markers. We found that D2150 was a monosomic addition line for chromosome 5Vb of D. breviaristatum, while D2146 had the 5VbL chromosome arm translocated with wheat chromosome 5AS. Molecular marker analysis confirmed that the introduced D. breviaristatum chromosome 5VbL translocation possessed a duplicated region homoeologous to 5AS, revealing that the 5AS.5VbL translocation may not functionally compensate well. The dwarfing and the pre-harvest re-growth habits observed in the wheat—D. breviaristatum chromosome 5Vb derivatives may be useful for future development of perennial growth wheat lines.
The Ubiquity of Humanity and Textuality in Human Experience
Authors: Chung Daihyun
Published: November 2015

The so-called “crisis of the humanities” can be understood in terms of an asymmetry between the natural and social sciences on the one hand and the humanities on the other. While the sciences approach topics related to human experience in quantificational or experimental terms, the humanities turn to ancient, canonical, and other texts in the search for truths about human experience. As each approach has its own unique limitations, it is desirable to overcome or remove the asymmetry between them. The present article seeks to do just that by advancing and defending the following two claims: (a) that humanity is ubiquitous wherever language is used; and (b) that anything that can be experienced by humans is in need of an interpretation. Two arguments are presented in support of these claims. The first argument concerns the nature of questions, which are one of the fundamental marks or manifestations of human language. All questions are ultimately attempts to find meanings or interpretations of what is presented. As such, in questioning phenomena, one seeks to transcend the negative space or oppression of imposed structures; in doing so, one reveals one’s humanity. Second, all phenomena are textual in nature: that which astrophysicists find in distant galaxies or which cognitive neuroscientists find in the structures of the human brain are no less in need of interpretation than the dialogues of Plato or the poems of Homer. Texts are ubiquitous. The implications of these two arguments are identified and discussed in this article. In particular, it is argued that the ubiquity of humanity and textuality points to a view of human nature that is neither individualistic nor collectivist but rather integrational in suggesting that the realization of oneself is inseparable from the realization of others.
Relationships between Microstructural Parameters and Time-Dependent Mechanical Properties of a New Nickel-Based Superalloy AD730™
Authors: Thébaud Louis , Villechaise Patrick , Cormier Jonathan , Crozet Coraline , Devaux Alexandre , Béchet Denis , Franchet Jean-Michel , Organista Antoine , Hamon Florence
Published: November 2015

High temperature creep and dwell-fatigue properties of the new nickel-based superalloy AD730™ have been investigated. Three microstructures have been studied in creep (850 °C and 700 °C) and dwell-fatigue (700 °C stress control with trapezoidal signals, and dwell times ranging from 1 s to 3600 s): a coarse grains microstructure, a fine grains one, and single crystalline samples. The aim of this study is to assess the influence of the grain size on creep and creep-fatigue properties. It is demonstrated that fine and coarse grains microstructures perform similarly in creep at 700 °C, showing that the creep properties at this temperature are controlled by the intragranular precipitation. Moreover, both the coarse grains and the fine grains microstructures show changes in creep deformation mechanisms depending on the applied stress in creep at 700 °C. At higher creep temperatures, the coarse grains microstructure performs better and almost no effect is observed by suppressing grain boundaries. During dwell-fatigue tests at 700 °C, a clear effect of the mechanical cycling has been evidenced on the time to failure on both the coarse and the fine grains microstructures. At high applied stresses, a beneficial effect of the cyclic unloading to the lifetime has been observed whereas at lower applied stresses, mechanical cycling is detrimental compared to the pure creep lifetime due to the development of a fatigue damage. Complex creep-fatigue interactions are hence clearly evidenced and they depend on the pure creep behavior reference.
Stereo- and Regiocontrolled Syntheses of Exomethylenic Cyclohexane β-Amino Acid Derivatives
Authors: Kiss Loránd , Forró Enikő , Orsy György , Ábrahámi Renáta , Fülöp Ferenc
Published: November 2015

Cyclohexane analogues of the antifungal icofungipen [(1R,2S)-2-amino-4-methylenecyclopentanecarboxylic acid] were selectively synthesized from unsaturated bicyclic β-lactams by transformation of the ring olefinic bond through three different regio- and stereocontrolled hydroxylation techniques, followed by hydroxy group oxidation and oxo-methylene interconversion with a phosphorane. Starting from an enantiomerically pure bicyclic β-lactam obtained by enzymatic resolution of the racemic compound, an enantiodivergent procedure led to the preparation of both dextro- and levorotatory cyclohexane analogues of icofungipen.
A Copper-Based Metal-Organic Framework as an Efficient and Reusable Heterogeneous Catalyst for Ullmann and Goldberg Type C–N Coupling Reactions
Authors: Long Wei , Qiu Wenge , Guo Chongwei , Li Chuanqiang , Song Liyun , Bai Guangmei , Zhang Guizhen , He Hong
Published: November 2015

A highly porous metal-organic framework (Cu-TDPAT), constructed from a paddle-wheel type dinuclear copper cluster and 2,4,6-tris(3,5-dicarboxylphenylamino)-1,3,5-triazine (H6TDPAT), has been tested in Ullmann and Goldberg type C–N coupling reactions of a wide range of primary and secondary amines with halobenzenes, affording the corresponding N-arylation compounds in moderate to excellent yields. The Cu-TDPAT catalyst could be easily separated from the reaction mixtures by simple filtration, and could be reused at least five times without any significant degradation in catalytic activity.
Argentatin B Inhibits Proliferation of Prostate and Colon Cancer Cells by Inducing Cell Senescence
Authors: Alcántara-Flores Ela , Brechú-Franco Alicia , García-López Patricia , Rocha-Zavaleta Leticia , López-Marure Rebeca , Martínez-Vázquez Mariano
Published: November 2015

Argentatin B has been shown to inhibit the growth of colon HCT-15, and prostate PC-3 cancer cells. However, the mechanism by which argentatin B inhibits cell proliferation is still unknown. We aimed to investigate the mechanism by which argentatin B inhibits cell proliferation. The cell cycle was studied by flow cytometry. Apoptosis was evaluated by Annexin-V-Fluos, and Hoechst 33342 dye staining. Cell senescence was evaluated by proliferation tests, and staining for SA-β-galactosidase. Senescence-related proteins (PCNA, p21, and p27) were analyzed by Western blotting. Potential toxicity of argentatin B was evaluated in CD-1 mice. Its effect on tumor growth was tested in a HCT-15 and PC-3 xenograft model. Argentatin B induced an increment of cells in sub G1, but did not produce apoptosis. Proliferation of both cell lines was inhibited by argentatin B. Forty-three percent HCT-15, and 66% PC-3 cells showed positive SA-β-galactosidase staining. The expression of PCNA was decreased, p21 expression was increased in both cell lines, but p27 expression increased only in PC-3 cells after treatment. Administration of argentatin B to healthy mice did not produce treatment-associated pathologies. However, it restricted the growth of HCT-15 and PC-3 tumors. These results indicate that treatment with argentatin B induces cell senescence.
An Interdisciplinary Approach on the Mediating Character of Technologies for Recognizing Human Activity
Authors: Dietrich Manuel , Van Laerhoven Kristof
Published: November 2015

In this paper, we introduce a research project on investigating the relation of computers and humans in the field of wearable activity recognition. We use an interdisciplinary approach, combining general philosophical assumptions on the mediating character of technology with the current computer science design practice. Wearable activity recognition is about computer systems which automatically detect human actions. Of special relevance for our research project are applications using wearable activity recognition for self-tracking and self-reflection, for instance by tracking personal activity data like sports. We assume that activity recognition is providing a new perspective on human actions; this perspective is mediated by the recognition process, which includes the recognition models and algorithms chosen by the designer, and the visualization to the user. We analyze this mediating character with two concepts which are both based on phenomenological thoughts namely first Peter-Paul Verbeek’s theory on human-technology relations and second the ideas of embodied interaction. Embedded in the concepts is a direction which leads to the role of technical design in how technology mediates. Regarding this direction, we discuss two case studies, both in the possible using practice of self-tracking and the design practice. This paper ends with prospects towards a better design, how the technologies should be designed to support self-reflection in a valuable and responsible way.