bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incorporating Midbrain Adaptation to Mean Sound Level Improves Models of Auditory Cortical Processing
Authors: Willmore Ben D.B. , Schoppe Oliver , King Andrew J. , Schnupp Jan W.H. , Harper Nicol S. 
Published: January 2016

Adaptation to stimulus statistics, such as the mean level and contrast of recently heard sounds, has been demonstrated at various levels of the auditory pathway. It allows the nervous system to operate over the wide range of intensities and contrasts found in the natural world. Yet current standard models of the response properties of auditory neurons do not incorporate such adaptation. Here we present a model of neural responses in the ferret auditory cortex (the IC Adaptation model), which takes into account adaptation to mean sound level at a lower level of processing: the inferior colliculus (IC). The model performs high-pass filtering with frequency-dependent time constants on the sound spectrogram, followed by half-wave rectification, and passes the output to a standard linear–nonlinear (LN) model. We find that the IC Adaptation model consistently predicts cortical responses better than the standard LN model for a range of synthetic and natural stimuli. The IC Adaptation model introduces no extra free parameters, so it improves predictions without sacrificing parsimony. Furthermore, the time constants of adaptation in the IC appear to be matched to the statistics of natural sounds, suggesting that neurons in the auditory midbrain predict the mean level of future sounds and adapt their responses appropriately.SIGNIFICANCE STATEMENTAn ability to accurately predict how sensory neurons respond to novel stimuli is critical if we are to fully characterize their response properties. Attempts to model these responses have had a distinguished history, but it has proven difficult to improve their predictive power significantly beyond that of simple, mostly linear receptive field models. Here we show that auditory cortex receptive field models benefit from a nonlinear preprocessing stage that replicates known adaptation properties of the auditory midbrain. This improves their predictive power across a wide range of stimuli but keeps model complexity low as it introduces no new free parameters. Incorporating the adaptive coding properties of neurons will likely improve receptive field models in other sensory modalities too.
Attenuation of β-Amyloid Deposition and Neurotoxicity by Chemogenetic Modulation of Neural Activity
Authors: Yuan Peng , Grutzendler Jaime 
Published: January 2016

Aberrant neural hyperactivity has been observed in early stages of Alzheimer's disease (AD) and may be a driving force in the progression of amyloid pathology. Evidence for this includes the findings that neural activity may modulate β-amyloid (Aβ) peptide secretion and experimental stimulation of neural activity can increase amyloid deposition. However, whether long-term attenuation of neural activity prevents the buildup of amyloid plaques and associated neural pathologies remains unknown. Using viral-mediated delivery of designer receptors exclusively activated by designer drugs (DREADDs), we show in two AD-like mouse models that chronic intermittent increases or reductions of activity have opposite effects on Aβ deposition. Neural activity reduction markedly decreases Aβ aggregation in regions containing axons or dendrites of DREADD-expressing neurons, suggesting the involvement of synaptic and nonsynaptic Aβ release mechanisms. Importantly, activity attenuation is associated with a reduction in axonal dystrophy and synaptic loss around amyloid plaques. Thus, modulation of neural activity could constitute a potential therapeutic strategy for ameliorating amyloid-induced pathology in AD.SIGNIFICANCE STATEMENTA novel chemogenetic approach to upregulate and downregulate neuronal activity in Alzheimer's disease (AD) mice was implemented. This led to the first demonstration that chronic intermittent attenuation of neuronal activityin vivosignificantly reduces amyloid deposition. The study also demonstrates that modulation of β-amyloid (Aβ) release can occur at both axonal and dendritic fields, suggesting the involvement of synaptic and nonsynaptic Aβ release mechanisms. Activity reductions also led to attenuation of the synaptic pathology associated with amyloid plaques. Therefore, chronic attenuation of neuronal activity could constitute a novel therapeutic approach for AD.
Disrupted Prediction Error Links Excessive Amygdala Activation to Excessive Fear
Authors: Sengupta Auntora , Winters Bryony , Bagley Elena E. , McNally Gavan P. 
Published: January 2016

Basolateral amygdala (BLA) is critical for fear learning, and its heightened activation is widely thought to underpin a variety of anxiety disorders. Here we used chemogenetic techniques in rats to study the consequences of heightened BLA activation for fear learning and memory, and to specifically identify a mechanism linking increased activity of BLA glutamatergic neurons to aberrant fear. We expressed the excitatory hM3Dq DREADD in rat BLA glutamatergic neurons and showed that CNO acted selectively to increase their activity, depolarizing these neurons and increasing their firing rates. This chemogenetic excitation of BLA glutamatergic neurons had no effect on the acquisition of simple fear learning, regardless of whether this learning led to a weak or strong fear memory. However, in an associative blocking task, chemogenetic excitation of BLA glutamatergic neurons yielded significant learning to a blocked conditioned stimulus, which otherwise should not have been learned about. Moreover, in an overexpectation task, chemogenetic manipulation of BLA glutamatergic neurons prevented use of negative prediction error to reduce fear learning, leading to significant impairments in fear inhibition. These effects were not attributable to the chemogenetic manipulation enhancing arousal, increasing asymptotic levels of fear learning or fear memory consolidation. Instead, chemogenetic excitation of BLA glutamatergic neurons disrupted use of prediction error to regulate fear learning.SIGNIFICANCE STATEMENTSeveral neuropsychiatric disorders are characterized by heightened activation of the amygdala. This heightened activation has been hypothesized to underlie increased emotional reactivity, fear over generalization, and deficits in fear inhibition. Yet the mechanisms linking heightened amygdala activation to heightened emotional learning are elusive. Here we combined chemogenetic excitation of rat basolateral amygdala glutamatergic neurons with a variety of behavioral approaches to show that, although simple fear learning is unaffected, the use of prediction error to regulate this learning is profoundly disrupted, leading to formation of inappropriate fear associations and impaired fear inhibition.
Testosterone replacement in 49,XXXXY syndrome: andrological, metabolic and neurological aspects
Authors: Mazzilli Rossella , Delfino Michele , Elia Jlenia , Benedetti Francesco , Alesi Laura , Chessa Luciana , Mazzilli Fernando 
Published: January 2016

Summary
We report the case of a 19-year-old boy, presenting several congenital malformations (facial dysmorphisms, cardiac and musculoskeletal abnormalities), mental retardation, recurrent respiratory infections during growth and delayed puberty. Although previously hospitalised in other medical centres, only psychological support had been recommended for this patient. In our department, genetic, biochemical/hormonal and ultrasound examinations were undertaken. The karyotype was 49,XXXXY, a rare aneuploidy with an incidence of 1/85 000–100 000, characterised by the presence of three extra X chromosomes in phenotypically male subjects. The hormonal/biochemical profile showed hypergonadotropic hypogonadism, insulin resistance and vitamin D deficiency. The patient was then treated with testosterone replacement therapy. After 12 months of treatment, we observed the normalisation of testosterone levels. There was also an increase in pubic hair growth, testicular volume and penis size, weight loss, homeostatic model assessment index reduction and the normalisation of vitamin D values. Moreover, the patient showed greater interaction with the social environment and context.

Learning points

In cases of plurimalformative syndrome, cognitive impairment, recurrent infections during growth and, primarily, delayed puberty, it is necessary to ascertain as soon as possible whether the patient is suffering from hypogonadism or metabolic disorders due to genetic causes. In our case, the diagnosis of hypogonadism, and then of 49,XXXXY syndrome, was unfortunately made only at the age of 19 years.

The testosterone replacement treatment, even though delayed, induced positive effects on: i) development of the reproductive system, ii) regulation of the metabolic profile and iii) interaction with the social environment and context.

However, earlier and timely hormonal replacement treatment could probably have improved the quality of life of this subject and his family.
Adiponectin, markers of subclinical inflammation and nerve conduction in individuals with recently diagnosed type 1 and type 2 diabetes
Authors: Schamarek Imke , Herder Christian , Nowotny Bettina , Carstensen-Kirberg Maren , Straßburger Klaus , Nowotny Peter , Strom Alexander , Püttgen Sonja , Müssig Karsten , Szendroedi Julia , Roden Michael , Ziegler Dan , _ _ 
Published: January 2016

ObjectiveSubclinical inflammation has been implicated in the development of diabetic sensorimotor polyneuropathy (DSPN), but studies using electrophysiological assessment as outcomes are scarce. Therefore, we aimed to investigate associations of biomarkers reflecting different aspects of subclinical inflammation with motor and sensory nerve conduction velocity (NCV) in individuals with diabetes.Design and methodsMotor and sensory NCV was assessed in individuals with recently diagnosed type 2 (n=352) or type 1 diabetes (n=161) from the baseline cohort of the observational German Diabetes Study. NCV sum scores were calculated for median, ulnar and peroneal motor as well as median, ulnar and sural sensory nerves. Associations between inflammation-related biomarkers, DSPN and NCV sum scores were estimated using multiple regression models.ResultsIn type 2 diabetes, high serum interleukin (IL)-6 was associated with the presence of DSPN and reduced motor NCV. Moreover, higher levels of high-molecular weight (HMW) adiponectin, total adiponectin and their ratio were associated with prevalent DSPN and both diminished motor and sensory NCV, whereas no consistent associations were observed for C-reactive protein, IL18, soluble intercellular adhesion molecule-1 and E-selectin. In type 1 diabetes, only HMW and total adiponectin showed positive associations with motor NCV.ConclusionsOur results point to a link between IL6 and both DSPN and slowed motor NCV in recently diagnosed type 2 diabetes. The reverse associations between adiponectin and NCV in type 1 and type 2 diabetes are intriguing, and further studies should explore whether they may reflect differences in the pathogenesis of DSPN in both diabetes types.
Effects of vitamin D binding protein phenotypes and vitamin D supplementation on serum total 25(OH)D and directly measured free 25(OH)D
Authors: Sollid Stina T , Hutchinson Moira Y S , Berg Vivian , Fuskevåg Ole M , Figenschau Yngve , Thorsby Per M , Jorde Rolf 
Published: January 2016

ObjectiveTo determine the relationship between serum total 25-hydroxyvitamin D (25(OH)D), directly measured free 25(OH)D and calculated free 25(OH)D with regard to vitamin D-binding protein (DBP) phenotypes, sex, BMI, age and season, and their interrelationship to vitamin D supplementation.Design, patients and interventionsA randomized controlled trial with 20 000 IU of vitamin D3per week or placebo for 12 months was designed. A total of 472 subjects, 236 in each of the intervention groups, were included in the analyses.Main outcome measuresBaseline serum concentrations and increases in serum total 25(OH)D, directly measured free 25(OH)D, calculated free 25(OH)D and DBP.ResultsSerum total 25(OH)D and DBP concentrations were significantly lower in subjects with the phenotype Gc2/Gc2 compared to phenotypes with the Gc1S allele, and lower in males compared to females. When using directly measured free 25(OH)D, the differences related to DBP phenotypes and sexes were clearly diminished. All calculated free 25(OH)D concentrations were overestimated compared to the directly measured free 25(OH)D. Serum parathyroid hormone showed an inverse correlation with all vitamin D parameters analyzed. The increases after 12 months of vitamin D supplementation were not significantly different for any of the vitamin D parameters regardless of DBP phenotype, sex or age. Supplementation with vitamin D did not affect serum DBP.ConclusionDirect measurements of free 25(OH)D reduce the differences seen in total 25(OH)D between DBP phenotype groups and sexes, probably caused by differences in DBP concentrations. With conditions affecting serum DBP concentrations, direct measurements of free 25(OH)D should be considered.
Outcomes From Polyhydramnios With Normal Ultrasound
Authors: Yefet Enav , Daniel-Spiegel Etty 
Published: January 2016

OBJECTIVE:
To investigate the short- and long-term outcomes of children from pregnancies complicated with polyhydramnios, defined as amniotic fluid index (AFI) &gt;24 cm, and with a normal detailed ultrasound examination.

METHODS:
This retrospective cohort study examined 134 children aged 4 to 9 years with polyhydramnios and normal detailed ultrasound examination during pregnancy compared with 268 controls with normal AFI and normal detailed ultrasound examination matched for maternal age, year of delivery, gestational week at delivery, and presence or absence of diabetes. The primary outcome was the rate of malformations diagnosed postnatally. Additional outcomes were obstetrics outcomes, genetic syndromes, and neurodevelopment.

RESULTS:
Polyhydramnios was associated with increased risk for cesarean delivery (CD) and birth weight &gt;90th percentile. This elevation in CD was attributed to increased rate of elective CD due to suspected macrosomia. Polyhydramnios was associated with increased risk for congenital malformations (n = 25 [19%] compared with 27 [10%], respectively; P = .016) without a statistically significant increase in the rate of major malformations (11 [8%] vs. 10 [4%]; P = .057). Genetic syndromes were more prevalent in the polyhydramnios group (5 [3.7%] vs. 2 [0.75%]; P = .043), as were neurologic disorders and developmental delay (9.7% vs. 3%; P = .004).

CONCLUSIONS:
Despite a normal detailed ultrasound examination, polyhydramnios is associated with increased rate of fetal malformations, genetic syndromes, neurologic disorders, and developmental delay, which may be diagnosed only after birth.
Prevalence and Determinants of Secondhand Smoke Exposure Among Middle and High School Students
Authors: Agaku Israel T. , Singh Tushar , Rolle Italia , Olalekan Ayo-Yusuf , King Brian A. 
Published: January 2016

BACKGROUND:
Secondhand smoke (SHS) causes disease and death among nonsmokers. Private settings are major sources of exposure for children. We assessed prevalence and determinants of self-reported SHS exposure in homes and vehicles, as well as school, work, and indoor/outdoor public areas, among US students in grades 6 through 12.

METHODS:
Data were from the 2013 National Youth Tobacco Survey (n = 18 406). Self-reported SHS exposure within the past 7 days was assessed overall and by extent of smoke-free home and vehicle rules among never users of 10 tobacco product types. Descriptive statistics were used to compare estimates, and adjusted prevalence ratios were calculated to assess determinants of SHS exposure.

RESULTS:
Among never tobacco users, 48.0% reported SHS exposure in 1 or more locations, including 15.5% in the home, 14.7% in a vehicle, 16.8% at school, 27.1% at work, and 35.2% in an indoor/outdoor public area. Home exposure was 8.5%, 55.3%, and 79.4% among never tobacco users with complete, partial, or no smoke-free home rules, respectively (P &lt; .05). Vehicle exposure was 7.1%, 44.8%, and 70.2% among never tobacco users with complete, partial, or no smoke-free vehicle rules, respectively (P &lt; .05). Factors associated with higher prevalence ratio of SHS exposure included current tobacco use, truant behavior, and having tobacco using household members/friends

CONCLUSIONS:
Approximately half of US students in grades 6 through 12 reported exposure to SHS in 2013. Smoke-free home and vehicle rules, coupled with intensified implementation and enforcement of comprehensive smoke-free laws, could help protect youth from this preventable health hazard.
Effects of Market Orientation and Breakthrough Innovation on Organizational Performance of International Enterprises
Authors: Zhang Zaixu , Jin Chunqing 
Published: January 2016

In the economic growth process when China joined in WTO, internationalized operation has become an inevitable issue. Under the new normal economic condition, including the cut offtariffs on imported goods, businesses in China have realized the importance of enhancing the overall brand image, quality of products and services, and the international compatibility. Businesses of China need to develop creative and high-value-added products, and shall be able to rapidly change to satisfy market requirements to distinguish themselves from other products. It is the way of creating a new pattern of upgrading. It is the market-orientated development that is a primary condition for enterprises to adapt to the rapidly changing environment, keeping growth and attracting customers, acquiring competitive advantages, and creating excellent value for customers. It reveals the fact that in the future, businesses must change the focus from product to market needs. It is the marketorientation which could generate the competitive strength to resist competitors.
The research involves in total 45 international enterprises, which are distributed with the questionnaires. There are totally 124 and 107 copies of questionnaires retrieved from manufacturing industry and service industry, with valid retrieval rates of 54% and 46%, respectively. The research results show that: 1. there is positive effect of market orientation on breakthrough innovation, 2. there is positive effect of breakthrough innovation on organizational performance, and 3. there is positive effect of market orientation on organizational performance. Based upon the results, some suggestions are proposed in this study, expecting to help international enterprises develop market orientation, enhance breakthrough innovation, and improve organizational performance.
A Relationship Study on Marketing Strategy Management towards Customer Relationship Management and Perceived Value
Authors: Yang Qiong , Hu Zen-hua 
Published: January 2016

With the promotion of economic liberalization and internationalization, consumer demands have become complex and diversified. Businesses have to actively promote themselves and bring forth new marketing tactics to attract buying and cope with fierce competition so as to enhance the global competitiveness and implement the idea of sustainable operation. This study aims to investigate the relationship between marketing strategy management, customer relationship management, and perceived value.
Aiming at Suzhou Industrial Park, the executives and employees of the manufacturers are distributed 500 copies of questionnaire for this study, and 367 valid copies are retrieved, with the retrieval rate 73%. The research results show the significant correlations between 1. marketing strategy management and customer relationship management, 2. customer relationship management and perceived value, and 3. marketing strategy management and perceived value. Aiming at above results, suggestions are proposed to create better organizational performance for a business.
Négligence infantile et pauvreté : les enjeux de la prévention au Bas-Saint-Laurent (Québec, Canada)
Authors: Pelletier Celine , Malanda Rahn Rendaud 
Published: January 2016

Résumé Mots clé: Négligence ; région ; santé ; Québec ; développement économique ; développement social Abstract: Can and does poverty lead to childhood maltreatment? This is the nature of the question raised by the authors who attempts at grasping the complexity of the relationship between poverty and childhood maltreatment in the region of Bas-Saint-Laurent (Québec). Family is where children develop; it has tremendous impact on children health and well-being. On the other hand, poverty is the most important source of stress as it renders meeting the most basic needs much more challenging for families. Such conditions have often been seen as the most important cause of childhood maltreatment, and most children who suffer from neglect come from familial environment where economic and social distress have been previously experienced. Keywords: Maltreatment; region; health; Québec; economic development; social development : La pauvreté caractérisée par des lacunes au niveau du revenu familial peut-elle conduire à la négligence infantile? Tel est le propos de cet article où les auteurs tenteront de saisir la complexité des liens entre la pauvreté et les situations de négligence infantile au Bas-Saint-Laurent (Québec). La famille est le creuset dans lequel se développent les enfants, elle a de multiples impacts sur leur santé et leur bien-être. La pauvreté amène une situation économique précaire où les besoins humains à la base ne sont pas comblés. Il en résulte des retombées très graves sur les individus et les familles et parfois ces problématiques sociales engendrent des situations de négligence infantile. De fait, les enfants négligés proviennent régulièrement de milieux où la misère sociale est présente. Ces enfants exposés à la négligence sont surreprésentés dans les familles à faible revenu, c'est-à-dire celles qui occupent les emplois les moins rémunérés et les plus précaires de la société. Les parents « économiquement défavorisés » sont alors incapables de combler les besoins de leurs enfants notamment l’alimentation, l’éducation, le logement, l’habillement, les soins de santé, la protection et l’affection, parce qu’ils n’ont pas assez d’argent pour subvenir à ces besoins essentiels. Il peut donc survenir chez ces enfants, des carences physiques, sociales, affectives, intellectuelles et comportementales, ce qui peut entraver leur développement normal et leur sécurité.