bluuebunny/crossref_metadata_2025_split huggingface dataset:
Olfactory dysfunction in fragile X tremor ataxia syndrome
Authors: Juncos Jorge L. , Lazarus Joash T. , Rohr Julia , Allen Emily G. , Shubeck Lisa , Hamilton Debra , Novak Gloria , Sherman Stephanie L. 
Published: September 2012

AbstractIntroduction:We investigated olfactory defects in fragile X‐associated tremor/ataxia syndrome (FXTAS), a finding reported on in other neurodegenerative disorders with clinical features that overlap those of FXTAS.Methods:We measured olfactory identification capacity in 41 FMR1 premutation carriers and 42 controls using the University of Pennsylvania Smell Identification Test (UPSIT). Carriers received neurologic evaluations using motor rating scales for tremor, ataxia, and parkinsonism. Cognitive function was measured using the Montreal Cognitive Assessment test.Results:Frequency of olfactory defects was higher in carriers, compared to controls (61% versus 29%; P = 0.003). There was no statistically significant group difference in severity of olfaction defects, after accounting for differences in age, and in rates of head injury and smoking. However, both the frequency (odds ratio = 3.9; 95% confidence interval: 0.81–19.1) and severity (28.6 versus 33.4; P = 0.01) of these defects were greater in cognitively impaired, compared to cognitively intact, carriers. There was no correlation between UPSIT scores and the above‐mentioned motor rating scales.Conclusions:FMR1 premutation carriers are susceptible to olfactory identification defects. The severity of these defects is comparable to that reported in hereditary ataxias, but less than that in PD and Alzheimer's disease. This concurrence across neurodegenerative disorders suggests a shared system vulnerability that correlates with, but is not limited to, cognitive impairment, because it is also found in cognitively intact carriers. These results need to be corroborated in a larger prospective study of FMR1 premutation carriers that extends beyond olfactory identification to include measures of smell thresholds. © 2012 Movement Disorder Society
Living on the edge with too many mouths to feed: Why dopamine neurons die
Authors: Bolam J. Paul , Pissadaki Eleftheria K. 
Published: September 2012

AbstractAlthough genes, protein aggregates, environmental toxins, and other factors associated with Parkinson's disease (PD) are widely distributed in the nervous system and affect many classes of neurons, a consistent feature of PD is the exceptional and selective vulnerability of dopamine (DA) neurons of the SNc. What is it about these neurons, among all other neurons in the brain, that makes them so susceptible in PD? We hypothesize that a major contributory factor is the unique cellular architecture of SNc DA neuron axons. Their large, complex axonal arbour puts them under such a tight energy budget that it makes them particularly susceptible to factors that contribute to cell death, including unique molecular characteristics associated with SNc DA neurons and nonspecific, nervous‐system–wide factors. © 2012 Movement Disorder Society
Brain activation pattern related to gait disturbances in Parkinson's disease
Authors: Crémers Julien , D'Ostilio Kevin , Stamatakis Julien , Delvaux Valérie , Garraux Gaëtan 
Published: September 2012

AbstractGait disturbances represent a therapeutic challenge in Parkinson's disease (PD). To further investigate their underlying pathophysiological mechanisms, we compared brain activation related to mental imagery of gait between 15 PD patients and 15 age‐matched controls using a block‐design functional MRI experiment. On average, patients showed altered locomotion relatively to controls, as assessed with a standardized gait test that evaluated the severity of PD‐related gait disturbances on a 25‐m path. The experiment was conducted in the subjects as they rehearsed themselves walking on the same path with a gait pattern similar as that during locomotor evaluation. Imagined walking times were measured on a trial‐by‐trial basis as a control of behavioral performance. In both groups, mean imagined walking time was not significantly different from that measured during real gait on the path used for evaluation. The between‐group comparison of the mental gait activation pattern with reference to mental imagery of standing showed hypoactivations within parieto‐occipital regions, along with the left hippocampus, midline/lateral cerebellum, and presumed pedunculopontine nucleus/mesencephalic locomotor area, in patients. More specifically, the activation level of the right posterior parietal cortex located within the impaired gait‐related cognitive network decreased proportionally with the severity of gait disturbances scored on the path used for gait evaluation and mental imagery. These novel findings suggest that the right posterior parietal cortex dysfunction is strongly related to the severity of gait disturbances in PD. This region may represent a target for the development of therapeutic interventions for PD‐related gait disturbances. © 2012 Movement Disorder Society
Maternal B vitamin status in pregnancy week 18 according to reported use of folic acid supplements
Authors: Bjørke‐Monsen Anne Lise , Roth Christine , Magnus Per , Midttun Øivind , Nilsen Roy M. , Reichborn‐Kjennerud Ted , Stoltenberg Camilla , Susser Ezra , Vollset Stein Emil , Ueland Per Magne 
Published: September 2012

ScopeEpidemiological studies on the association between pregnancy outcomes and use of periconceptional folic acid are often based on maternal reported intake. Use of folic acid during pregnancy is associated with a higher socioeconomic status known to have an impact on diet quality. We have studied plasma B vitamin status according to reported use of folic acid supplements during the periconceptional period in Norwegian women.Methods and resultsPlasma levels of folate, cobalamin, pyridoxal 5′‐phosphate (vitamin B6), riboflavin, and the metabolic markers total homocysteine, methylmalonic acid and 3‐hydro‐xykynurenine were measured in pregnancy week 18 and related to reported intake of folic acid from 4 weeks prior to conception throughout week 18 in 2911 women from the Norwegian Mother and Child Cohort Study (MoBa) conducted by the Norwegian Institute of Public Health.Being a folic acid user during the periconceptional period was associated with a better socioeconomic status, and a higher intake of several micronutrients, including vitamins, trace‐metals, and omega 3 fatty acids. Folic acid users had a significantly better plasma B vitamin status.ConclusionEpidemiological data based on maternal reported intake of folic acid supplements during pregnancy, should take into account the numerous nutritional implications, in addition to higher blood folate levels, of being a folic acid user.
Differential gene expression and methylation in the retinoid/PPARA pathway and of tumor suppressors may modify intestinal tumorigenesis induced by low folate in mice
Authors: Leclerc Daniel , Cao Yuanhang , Deng Liyuan , Mikael Leonie G. , Wu Qing , Rozen Rima 
Published: September 2012

ScopeInadequate folate intake increases risk for colorectal cancer. We previously showed that low‐folate diets induced intestinal tumors in BALB/c mice, but not in C57BL/6 mice. We suggested that DNA damage, altered methylation, and reduced apoptosis could contribute to tumorigenesis in this model.Methods and resultsTo identify genes involved in tumorigenesis, we compared gene expression profiles in preneoplastic intestine of BALB/c and C57BL/6 mice‐fed low folate. We identified 74 upregulated and 90 downregulated genes in BALB/c compared to C57BL/6 mice. We validated decreased expression of Bcmo1 and increased expression of Aldh1a, which would be expected to upregulate the peroxisome proliferator‐activated receptor alpha (PPARA) pathway, and confirmed the expected upregulation of several Ppara downstream genes. We verified, in BALB/c mice, reduced expression of Sprr2a, a gene that increases resistance to oxidative damage, and of two oncosuppressors (Bmp5 and Arntl). Low folate increased Ppara and Aldh1a1 expression, and decreased Bcmo1, Sprr2a, and Bmp5 expression in BALB/c, compared to BALB/c on control diets. Bcmo1, Ppara, and Bmp5 showed differential DNA methylation related to strain, diet, and/or Mthfr genotype.ConclusionDisturbed regulation of the retinoid/PPARA pathway, which influences oxidative damage, and altered expression of tumor suppressors may contribute to intestinal tumorigenesis induced by low‐folate intake.
Experimental and theoretical investigation of the high‐pressure, undrained response of a cohesionless sand
Authors: Martin B.E. , Cazacu O. 
Published: September 2012

SUMMARYKey in predicting stability in sands during dynamic events is gaining a fundamental understanding of the physics of its deformation and failure at high pressures. In this paper are reported results of an experimental investigation into the high‐pressure (up to 700 MPa) mechanical response of Quikrete sand. During all triaxial compression tests, the material exhibited hardening up to failure while both compressibility and dilatancy regimes of the volumetric response were observed. Furthermore, the transition from compressibility to dilatancy was found to be highly dependent on confining pressure. By performing triaxial compression tests with several creep stages followed by unloading–reloading cycles, the time influence of the overall response was detected. Using the experimental data, a new model that captures both compressibility and dilatancy has been developed. Comparison between model predictions and data showed that the proposed model describes well the main characteristics of the high‐pressure response of sand. Copyright © 2012 John Wiley & Sons, Ltd.
Emerging philanthropy markets
Authors: Michon Richard , Tandon Atul 
Published: September 2012

Entrepreneurs are not the only ones to salivate at the call of emerging markets. Major nonprofit organizations that raise money in high‐income Organisation for Economic Co‐operation and Development countries for redistribution in developing countries are also looking for new sources of funds. Some of the countries that benefited from private philanthropy not too long ago are now in a position to help. The contribution of this paper is two‐prong. First, it introduces a robust market screening methodology to determine countries' capacities to give on the basis of macroeconomic and infrastructure indicators. Second, it identifies cross‐cultural predictors for charitable donations taken from the World Value Survey. A logistic regression calibrated on already successful fundraising operation scores countries on their propensity for private philanthropy. Research findings receive theoretical support from Max Weber's Protestant Ethic and the Spirit of Capitalism. Top countries for private philanthropy are of Protestant tradition and are at the origin of capitalism, as we know it today. Confucian countries that share a similar ethic and have opted for capitalist economies are first class candidates for private philanthropy.Copyright © 2012 John Wiley & Sons, Ltd.
Survey of patients on an alcohol in‐patient unit in relation to group therapeutic factors
Authors: Ogilvie Sheena S , Blair Sheena EE , Paul Anna Louise 
Published: September 2012

AbstractThis study was prompted by the clinical research of Lovett and Lovett (1991) and Yalom's theory of group therapy (Yalom, 1985). The investigators examined perceptions of therapeutic factors in groups, in relation to outcome measures. Twenty‐one patients admitted consecutively to an Alcohol Problems clinic engaged in a three‐week programme, led by an interdisciplinary treatment team, including occupational therapy‐led groups, were interviewed using an ‘important events’ questionnaire in the second and third week. A modified version of Yalom's therapeutic factor questionnaire was used at the end of the programme and patients were also asked if they had additional comments. Outcome factors were assessed at three months after discharge from reports by key workers and self‐report. Results indicated that patients most valued existential factors, self‐understanding, cohesiveness and catharsis. Existential factors were not identified as helpful by the group who were unchanged and continued to drink. The implications for occupational therapy in the treatment of alcohol problems were discussed.
Harnessing monocyte‐derived macrophages to control central nervous system pathologies: no longer ‘if’ but ‘how’
Authors: Shechter Ravid , Schwartz Michal 
Published: September 2012

AbstractThe central nervous system (CNS) tissues, including the brain, the eye, and the spinal cord, are immune‐privileged, secluded from the circulation by a complex of barriers, and equipped with their own myeloid cell population, the resident microglia. Based on the classical perspective of immune–brain interactions and on the contribution of such interactions to the progression of multiple sclerosis, an autoimmune inflammatory disease of the CNS, infiltrating macrophages were traditionally viewed as an enemy of the nervous system. However, over the past two decades, research has revealed the pivotal role of monocyte‐derived macrophages in CNS repair, and opened up a new era in understanding and treating CNS pathologies. Here, we gather current knowledge regarding macrophage broad spectrum of activities in the CNS, whose two poles correspond to the classical pro‐inflammatory M1 and the ‘alternatively‐activated’ M2 cells previously described in various non‐CNS pathologies, and their diverse, multi‐functional contribution in various neurological conditions, ranging from acute traumas to neurodegenerative disorders, and autoimmune diseases. The diverse functions are manifested by induction and resolution of inflammation as well as their involvement in neural tissue regeneration and renewal, matrix remodelling, debris clearance, and angiogenesis. A special focus is devoted to current evidence suggesting that resident microglia and infiltrating monocyte‐derived macrophages are functionally non‐redundant cell types. Taken together, these recent advances reveal a dramatic therapeutic opportunity for controlled harnessing of macrophages for repair of the damaged CNS following acute insults, in neurodegenerative conditions, and in psychiatric disorders.
Hanging in the balance: endogenous anti‐inflammatory mechanisms in tissue repair and fibrosis
Authors: Ariel Amiram , Timor Orly 
Published: September 2012

AbstractInflammation is the physiological response to tissue injury caused by pathogens or trauma. Nevertheless, inflammation should be resolved in a timely manner, resulting in elimination of the inflammatory cells and mediators from the injured tissue, to avoid its deleterious consequences. Uncontrolled inflammation can lead to inflammatory, autoimmune, and cancerous disorders that are the result of improper resolution. The healing of the injured tissue during the termination of inflammation must also be tightly controlled since excessive tissue repair can lead to fibrosis and scarring of the affected organ. In the last three decades, it has been revealed that the resolution of inflammation is tightly orchestrated by specific cells, protein, and lipid mediators that are produced at proper timing and distinct locations. The bioactivity of these anti‐inflammatory, pro‐resolving, and immunoregulatory agents results in clearance of the tissue from inflammatory leukocytes and their products, and the return of homeostatic tissue architecture and function. Here, we will survey the current endogenous mechanisms governing the resolution of inflammation and directing it towards injury healing and halting of acquired immune responses while preventing excessive tissue repair and fibrosis. We focus on the role played by apoptotic polymorphonuclear cells (PMNs), 15‐lipoxygenase (LO)‐derived lipid mediators, and TGFβ in this macrophage‐governed decision‐making process and suggest new modes of action for fibrosis prevention and return to homeostasis.
Transcriptome and small RNA deep sequencing reveals deregulation of miRNA biogenesis in human glioma
Authors: Moore Lynette M , Kivinen Virpi , Liu Yuexin , Annala Matti , Cogdell David , Liu Xiuping , Liu Chang‐Gong , Sawaya Raymond , Yli‐Harja Olli , Shmulevich Ilya , Fuller Gregory N , Zhang Wei , Nykter Matti 
Published: September 2012

AbstractAltered expression of oncogenic and tumour‐suppressing microRNAs (miRNAs) is widely associated with tumourigenesis. However, the regulatory mechanisms underlying these alterations are poorly understood. We sought to shed light on the deregulation of miRNA biogenesis promoting the aberrant miRNA expression profiles identified in these tumours. Using sequencing technology to perform both whole‐transcriptome and small RNA sequencing of glioma patient samples, we examined precursor and mature miRNAs to directly evaluate the miRNA maturation process, and examined expression profiles for genes involved in the major steps of miRNA biogenesis. We found that ratios of mature to precursor forms of a large number of miRNAs increased with the progression from normal brain to low‐grade and then to high‐grade gliomas. The expression levels of genes involved in each of the three major steps of miRNA biogenesis (nuclear processing, nucleo‐cytoplasmic transport, and cytoplasmic processing) were systematically altered in glioma tissues. Survival analysis of an independent data set demonstrated that the alteration of genes involved in miRNA maturation correlates with survival in glioma patients. Direct quantification of miRNA maturation with deep sequencing demonstrated that deregulation of the miRNA biogenesis pathway is a hallmark for glioma genesis and progression. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
A novel blueprint for ‘top down’ differentiation defines the cervical squamocolumnar junction during development, reproductive life, and neoplasia
Authors: Herfs Michael , Vargas Sara O , Yamamoto Yusuke , Howitt Brooke E , Nucci Marisa R , Hornick Jason L , Mckeon Frank D , Xian Wa , Crum Christopher P 
Published: September 2012

AbstractThe cervical squamocolumnar (SC) junction is the site of a recently discovered ‘embryonic’ cell population that was proposed as the cell of origin for cervical cancer and its precursors. How this population participates in cervical remodelling and neoplasia is unclear. In the present study, we analysed the SC junction immunophenotype during pre‐ and post‐natal human and mouse development and in the adult, processes of metaplastic evolution of the SC junction, microglandular change, and early cervical neoplasia. Early in life, embryonic cervical epithelial cells were seen throughout the cervix and subsequently diminished in number to become concentrated at the SC junction in the adult. In all settings, there was a repetitive scenario in which cuboidal embryonic/SC junction cells gave rise to subjacent metaplastic basal/reserve cells with a switch from the SC junction positive to negative immunophenotype. This downward or basal (rather than upward or apical) evolution from progenitor cell to metaplastic progeny was termed reverse or ‘top down’ differentiation. A similar pattern was noted in high‐grade squamous intraepithelial lesions (HSILs), suggesting that HPV infection of the cuboidal SC junction cells initiated outgrowth of basally‐oriented neoplastic progeny. The progressive loss of the embryonic/SC junction markers occurred with ‘top down’ differentiation during development, remodelling, and early neoplasia. Interestingly, most low‐grade SILs were SC junction‐negative, implying infection of metaplastic progeny rather than the original SC junction cells. This proposed model of ‘top down’ differentiation resolves the mystery of how SC junction cells both remodel the cervix and participate in neoplasia and provides for a second population of metaplastic progeny (including basal and reserve cells), the infection of which is paradoxically less likely to produce a biologically aggressive precursor. It also provides new targets in animal models to determine why the SC junction is uniquely susceptible to carcinogenic HPV infection. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Prevalence and correlates of exceeding the labeled maximum dose of acetaminophen among adults in a U.S.‐based internet survey
Authors: Kaufman David W , Kelly Judith P , Rohay Jeffrey M , Malone Mary Kathryn , Weinstein Rachel B , Shiffman Saul 
Published: September 2012

ABSTRACTPurposeAcetaminophen is a commonly used analgesic; excessive doses can lead to liver damage. We sought to determine the proportion of acetaminophen users exceeding the recommended maximum daily dose of 4 g and identify correlates of such behavior.MethodsU.S. adults were recruited from an internet panel in summer 2010, oversampling past 30‐day acetaminophen users. Among 47 738 starting the study, 5649 completed all phases; individuals with low education were underrepresented. Subjects completed a 7‐day daily diary online, reporting intake of acetaminophen products selected from a comprehensive list; total daily dose was computed from product names. An exit survey elicited: attitudes/knowledge related to product ingredients, label reading, dosing behavior; demographics, medical history, general physical, and mental health status. Unconditional logistic regression identified variables independently associated with use exceeding 4 g.ResultsAmong 3618 acetaminophen users, 163 took >4 g on ≥1 day (4.5%); the median dose was 5.5 g; 26 took >8 g (0.7%). >4‐g users were characterized by chronic pain, poor physical status, and heavy use of medical care. Knowledge of ingredients and recommended OTC doses for all products taken was inversely associated with >4‐g use (multivariable odds ratios [ORs] = 0.5–0.6), as was the attitude to start with the lowest dose (OR = 0.6). The attitude that users could choose their own dose was positively associated (OR = 1.3).ConclusionsThe results estimate the proportion of acetaminophen users exceeding 4 g in a group of U.S. adults, identify potentially modifiable attitudes and knowledge associated with such use, and characterize subpopulations at higher risk. Copyright © 2012 John Wiley & Sons, Ltd.
The effect of Young's modulus of contact‐etch‐stop layer (CESL) stressor on the strained‐Si MOSFET
Authors: Chiou Yung‐Chuan , Chen Hou‐Yu , Huang Chien‐Chao 
Published: September 2012

AbstractIn the analytic solution of residual stresses and bending in multi‐layer/substrate systems, Young's modulus of contact‐etch‐stop layer (CESL) stressor is a potential factor affecting the channel stress of complementary metal–oxide–semiconductor (CMOS) devices. To increase the level of Young's modulus of CESL stressor, the stress level of silicon channels could be boosted at a constant stress level and thickness of CESL as the result of stress simulation. Young's moduli of two widely adopted CESL stressors measured by a nanoindenter instrument, low‐pressure chemical vapor deposition silicon nitride (LP‐SiN) and plasma‐enhanced chemical vapor deposition silicon nitride (PE‐SiN), were 375.7 and 224.7 GPa, respectively. As a result of stress stimulation, the channel stress induced by LPSiN CESL could increase 30% higher than that of PE‐SiN CESL. Through the use of a tensile 1 GPa CESL stressor for the 90 nm n‐FETs, an extra 4% enhancement in drive current ID,sat was obtained in the device with an LP‐SiN CESL as compared to that with PE‐SiN. The electrical data is in good agreement with the prediction of the stress simulation.