bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neural Noise and Movement-Related Codes in the Macaque Supplementary Motor Area
Authors: Averbeck Bruno B. , Lee Daeyeol 
Published: April 2018

We analyzed the variability of spike counts and the coding capacity of simultaneously recorded pairs of neurons in the macaque supplementary motor area (SMA). We analyzed the mean-variance functions for single neurons, as well as signal and noise correlations between pairs of neurons. All three statistics showed a strong dependence on the bin width chosen for analysis. Changes in the correlation structure of single neuron spike trains over different bin sizes affected the mean-variance function, and signal and noise correlations between pairs of neurons were much smaller at small bin widths, increasing monotonically with the width of the bin. Analyses in the frequency domain showed that the noise between pairs of neurons, on average, was most strongly correlated at low frequencies, which explained the increase in noise correlation with increasing bin width.The coding performance was analyzed to determine whether the temporal precision of spike arrival times and the interactions within and between neurons could improve the prediction of the upcoming movement. We found that in ∼62% of neuron pairs, the arrival times of spikes at a resolution between 66 and 40 msec carried more information than spike counts in a 200 msec bin. In addition, in 19% of neuron pairs, inclusion of within (11%)- or between-neuron (8%) correlations in spike trains improved decoding accuracy. These results suggest that in some SMA neurons elements of the spatiotemporal pattern of activity may be relevant for neural coding.
Palmitoylethanolamide Increases after Focal Cerebral Ischemia and Potentiates Microglial Cell Motility
Authors: Franklin Allyn , Parmentier-Batteur Sophie , Walter Lisa , Greenberg David A. , Stella Nephi 
Published: April 2018

Focal cerebral ischemia (FCI) induces rapid neuronal death in the ischemic core, which gradually expands toward the penumbra, partly as the result of a neuroinflammatory response. It is known that propagation of neuroinflammation involves microglial cells, the resident macrophages of the brain, which are highly motile when activated by specific signals. However, the signals that increase microglial cell motility in response to FCI remain mostly elusive.Here, we tested the hypothesis that endocannabinoids mediate neuroinflammation propagation by increasing microglial cell motility. We found that, in mouse cerebral cortex, FCI greatly increases palmitoylethanolamide (PEA), only moderately increases anandamide [arachidonylethanolamide (AEA)], and does not affect 2-arachidonoylglycerol levels. We also found that PEA potentiates AEA-induced microglial cell migration, without affecting other steps of microglial activation, such as proliferation, particle engulfment, and nitric oxide production. This potentiation of microglial cell migration by PEA involves reduction in cAMP levels. In line with this, we provide evidence that PEA acts through Gi/o-coupled receptors. Interestingly, these receptors engaged by PEA are pharmacologically distinct from CB1and CB2cannabinoid receptors, as well as from the WIN and abn-CBD (abnormal-cannabidiol) receptors, two recently identified cannabinoid receptors.Our results show that PEA and AEA increase after FCI and synergistically enhance microglial cell motility. Because such a response could participate in the propagation of the FCI-induced neuroinflammation within the CNS, and because PEA is likely to act through its own receptor, a better understanding of the receptor engaged by PEA may help guide the search for improved therapies against neuroinflammation.
Activity-Dependent Feedforward Inhibition Modulates Synaptic Transmission in a Spinal Locomotor Network
Authors: Parker David 
Published: April 2018

The analysis of synaptic properties in neural networks has focused on the properties of individual synapses. As a result, little is known of how neural assemblies arise from the connectivity and functional properties of different classes of network neurons.I examined synaptic properties in the lamprey locomotor network. Here I show that, in addition to their monosynaptic inputs to motor neurons, a proportion of the excitatory network interneurons (EINs) evoke an activity-dependent disynaptic feedforward inhibitory input. Connections from the excitatory interneurons to small ipsilateral inhibitory interneurons were found that could account for the feedforward inhibition. Both synapses in the disynaptic pathway exhibited activity-dependent facilitation during physiologically relevant spike trains, which could contribute to the delayed, activity-dependent development of the feedforward IPSP. Although it was not as common as the feedforward inhibition, the excitatory interneurons could also evoke feedforward excitatory inputs in motor neurons.EIN inputs to motor neurons usually depress during spike trains. In connections in which a delayed IPSP occurred, blocking the feedforward inhibition in motor neurons or preventing the activation of the disynaptic pathway abolished the depression of the direct EPSP during the spike train and could reveal an underlying facilitation. The feedforward inhibition thus heterosynaptically depressed the direct excitatory input to motor neurons. Activity-dependent heterosynaptic effects acting within network cellular assemblies can thus influence the integration of synaptic inputs in motor neurons. This could help to terminate ipsilateral motor neuron spiking during network activity.
NPY Induces Stress Resilience via Downregulation ofIhin Principal Neurons of Rat Basolateral Amygdala
Authors: Silveira Villarroel Heika , Bompolaki Maria , Mackay James P. , Miranda Tapia Ana Pamela , Michaelson Sheldon D. , Leitermann Randy J. , Marr Robert A. , Urban Janice H. , Colmers William F. 
Published: April 2018

Neuropeptide Y (NPY) expression is tightly linked with the development of stress resilience in rodents and humans. Local NPY injections targeting the basolateral amygdala (BLA) produce long-term behavioral stress resilience in male rats via an unknown mechanism. Previously, we showed that activation of NPY Y1receptors hyperpolarizes BLA principal neurons (PNs) through inhibition of the hyperpolarization-activated, depolarizing H-current,Ih. The present studies tested whether NPY treatment induces stress resilience by modulatingIh. NPY (10 pmol) was delivered daily for 5 d bilaterally into the BLA to induce resilience; thereafter, the electrophysiological properties of PNs and the expression ofIhin the BLA were characterized. As reported previously, increases in social interaction (SI) times persisted weeks after completion of NPY administration.In vitrointracellular recordings showed that repeated intra-BLA NPY injections resulted in hyperpolarization of BLA PNs at 2 weeks (2W) and 4 weeks (4W) after NPY treatment. At 2W, spontaneous IPSC frequencies were increased, whereas at 4W, restingIhwas markedly reduced and accompanied by decreased levels of HCN1 mRNA and protein expression in BLA. Knock-down of HCN1 channels in the BLA with targeted delivery of lentivirus containing HCN1-shRNA increased SI beginning 2W after injection and induced stress resilience. NPY treatment induced sequential, complementary changes in the inputs to BLA PNs and their postsynaptic properties that reduce excitability, a mechanism that contributes to less anxious behavior. Furthermore, HCN1 knock-down mimicked the increases in SI and stress resilience observed with NPY, indicating the importance ofIhin stress-related behavior.SIGNIFICANCE STATEMENTResilience improves mental health outcomes in response to adverse situations. Neuropeptide Y (NPY) is associated with decreased stress responses and the expression of resilience in rodents and humans. Single or repeated injections of NPY into the basolateral amygdala (BLA) buffer negative behavioral effects of stress and induce resilience in rats, respectively. Here, we demonstrate that repeated administration of NPY into the BLA unfolds several cellular mechanisms that decrease the activity of pyramidal output neurons. One key mechanism is a reduction in levels of the excitatory ion channel HCN1. Moreover, shRNA knock-down of HCN1 expression in BLA recapitulates some of the actions of NPY and causes potent resilience to stress, indicating that this channel may be a possible target for therapy.
Treatment of Addison’s disease during pregnancy
Authors: Oliveira Diana , Lages Adriana , Paiva Sandra , Carrilho Francisco 
Published: April 2018

Summary
Addison’s disease, or primary adrenocortical insufficiency, is a long-term, potentially severe, rare endocrine disorder. In pregnancy, it is even rarer. We report the case of a 30-year-old pregnant patient with Addison’s disease, referred to Obstetrics-Endocrinology specialty consult at 14 weeks gestation. She had been to the emergency department of her local hospital various times during the first trimester presenting with a clinical scenario suggestive of glucocorticoid under-replacement (nausea, persistent vomiting and hypotension), but this was interpreted as normal pregnancy symptoms. Hydrocortisone dose was adjusted, and the patient maintained regular follow-up. No complications were reported for the remainder of gestation and delivery. Pregnant patients with Addison’s disease should be monitored during gestation and in the peripartum period by multidisciplinary teams. Adjustments in glucocorticoid and mineralocorticoid replacement therapy are often necessary, and monitoring should be based mainly on clinical findings, which becomes increasingly difficult during pregnancy. Patient education and specialized monitoring are key to avoiding complications from under- or over-replacement therapy in this period.

Learning points:

An increase in glucocorticoid replacement dose is expected to be necessary during pregnancy in a woman with Addison’s disease.

Patient education regarding steroid cover and symptoms of acute adrenal crisis are fundamental.

Monitoring in this period is challenging and remains mainly clinical.

The increase in hydrocortisone dose often obviates the need to increase fludrocortisone dose.
Successful neoadjuvant peptide receptor radionuclide therapy for an inoperable pancreatic neuroendocrine tumour
Authors: da Silva Tiago Nunes , van Velthuysen M L F , van Eijck Casper H J , Teunissen Jaap J , Hofland J , de Herder Wouter W 
Published: April 2018

Summary
Non-functional pancreatic neuroendocrine tumours (NETs) can present with advanced local or distant (metastatic) disease limiting the possibility of surgical cure. Several treatment options have been used in experimental neoadjuvant settings to improve the outcomes in such cases. Peptide receptor radionuclide therapy (PPRT) using beta emitting radiolabelled somatostatin analogues has been used in progressive pancreatic NETs. We report a 55-year-old female patient with a 12.8 cm pancreatic NET with significant local stomach and superior mesenteric vein compression and liver metastases. The patient underwent treatment with [177Lutetium-DOTA0,Tyr3]octreotate (177Lu-octreotate) for the treatment of local and metastatic symptomatic disease. Six months after 4 cycles of 177lutetium-octreotate, resolution of the abdominal complaints was associated with a significant reduction in tumour size and the tumour was rendered operable. Histology of the tumour showed a 90% necrotic tumour with abundant hyalinized fibrosis and haemorrhage compatible with PPRT-induced radiation effects on tumour cells. This report supports that PPRT has a role in unresectable and metastatic pancreatic NET.

Learning points:

PRRT with 177Lu-octreotate can be considered a useful therapy for symptomatic somatostatin receptor-positive pancreatic NET.

The clinical benefits of PRRT with 177Lu-octreotate can be seen in the first months while tumour reduction can be seen up to a year after treatment.

PRRT with 177Lu-octreotate was clinically well tolerated and did not interfere with the subsequent surgical procedure.

PRRT with 177Lu-octreotate can result in significant tumour reduction and may improve surgical outcomes. As such, this therapy can be considered as a neoadjuvant therapy.
The genetic characteristics of congenital hypothyroidism in China by comprehensive screening of 21 candidate genes
Authors: Sun Feng , Zhang Jun-Xiu , Yang Chang-Yi , Gao Guan-Qi , Zhu Wen-Bin , Han Bing , Zhang Le-Le , Wan Yue-Yue , Ye Xiao-Ping , Ma Yu-Ru , Zhang Man-Man , Yang Liu , Zhang Qian-Yue , Liu Wei , Guo Cui-Cui , Chen Gang , Zhao Shuang-Xia , Song Ke-Yi , Song Huai-Dong 
Published: April 2018

Objective
Congenital hypothyroidism (CH), the most common neonatal metabolic disorder, is characterized by impaired neurodevelopment. Although several candidate genes have been associated with CH, comprehensive screening of causative genes has been limited.

Design and methods
One hundred ten patients with primary CH were recruited in this study. All exons and exon–intron boundaries of 21 candidate genes for CH were analyzed by next-generation sequencing. And the inheritance pattern of causative genes was analyzed by the study of family pedigrees.

Results
Our results showed that 57 patients (51.82%) carried biallelic mutations (containing compound heterozygous mutations and homozygous mutations) in six genes (DUOX2, DUOXA2, DUOXA1, TG, TPO and TSHR) involved in thyroid hormone synthesis. Autosomal recessive inheritance of CH caused by mutations in DUOX2, DUOXA2, TG and TPO was confirmed by analysis of 22 family pedigrees. Notably, eight mutations in four genes (FOXE1, NKX2-1, PAX8 and HHEX) that lead to thyroid dysgenesis were identified in eight probands. These mutations were heterozygous in all cases and hypothyroidism was not observed in parents of these probands.

Conclusions
Most cases of congenital hypothyroidism in China were caused by thyroid dyshormonogenesis rather than thyroid dysgenesis. This study identified previously reported causative genes for 57/110 Chinese patients and revealed DUOX2 was the most frequently mutated gene in these patients. Our study expanded the mutation spectrum of CH in Chinese patients, which was significantly different from Western countries.
Role of MRI T2-DRIVE in the assessment of pituitary stalk abnormalities without gadolinium in pituitary diseases
Authors: Godano Elisabetta , Morana Giovanni , Di Iorgi Natascia , Pistorio Angela , Allegri Anna Elsa Maria , Napoli Flavia , Gastaldi Roberto , Calcagno Annalisa , Patti Giuseppa , Gallizia Annalisa , Notarnicola Sara , Giaccardi Marta , Noli Serena , Severino Mariasavina , Tortora Domenico , Rossi Andrea , Maghnie Mohamad 
Published: April 2018

Objective
To investigate the role of T2-DRIVE MRI sequence in the accurate measurement of pituitary stalk (PS) size and the identification of PS abnormalities in patients with hypothalamic–pituitary disorders without the use of gadolinium.

Design
This was a retrospective study conducted on 242 patients who underwent MRI due to pituitary dysfunction between 2006 and 2015. Among 135 eligible patients, 102 showed eutopic posterior pituitary (PP) gland and 33 showed ‘ectopic’ PP (EPP).

Methods
Two readers independently measured the size of PS in patients with eutopic PP at the proximal, midpoint and distal levels on pre- and post-contrast T1-weighted as well as T2-DRIVE images; PS visibility was assessed on pre-contrast T1 and T2-DRIVE sequences in those with EPP. The length, height, width and volume of the anterior pituitary (AP), PP height and length and PP area were analyzed.

Results
Significant agreement between the two readers was obtained for T2-DRIVE PS measurements in patients with ‘eutopic’ PP; a significant difference was demonstrated between the intraclass correlation coefficient calculated on the T2-DRIVE and the T1-pre- and post-contrast sequences. The percentage of PS identified by T2-DRIVE in EPP patients was 72.7% compared to 30.3% of T1 pre-contrast sequences. A significant association was found between the visibility of PS on T2-DRIVE and the height of AP.

Conclusion
T2-DRIVE sequence is extremely precise and reliable for the evaluation of PS size and the recognition of PS abnormalities; the use of gadolinium-based contrast media does not add significant information and may thus be avoided.
Kartellordnungswidrigkeitenrecht nach der 9. GWB-Novelle
Authors: Haus Florian C. 
Published: April 2018

Zusammenfassung
Der Gesetzgeber der 9. GWB-Novelle hat das bestehende Bußgeldregime für Kartellverstöße tiefgreifend umgestaltet. Die Regelungen sind komplex und stellen die größte Zäsur seit der 7. GWB-Novelle dar. Mit der Einführung einer Konzernhaftung und enorm strengen Haftungsmechanismen für Fälle der Gesamt- und Einzelrechtsnachfolge sind zahlreiche rechtliche und rechtspraktische Fragen aufgeworfen, die von der (neuen) Normadressatenstellung über die Tatbestandsmerkmale insbesondere der Rechtsnachfolgeregelungen im Einzelnen bis hin zur drängenden Frage der Verfassungsmäßigkeit der sogenannten Ausfallhaftung für den Übergangszeitraum reichen.
Timing and Location of Emergency Department Revisits
Authors: Michelson Kenneth A. , Lyons Todd W. , Bachur Richard G. , Monuteaux Michael C. , Finkelstein Jonathan A. 
Published: April 2018

BACKGROUND:
Emergency department (ED) revisits are used as a measure of care quality. Many EDs measure only revisits to the same facility, underestimating true rates. We sought to determine the frequency, location, and predictors of ED revisits to the same or a different ED.

METHODS:
We studied ED discharges for children &lt;18 years old in Maryland and New York in the statewide ED and inpatient databases. Revisits were defined as ED visits within 7 days of an index visit. Our primary outcome was the proportion of revisits that were different-hospital revisits (DHRs). We measured the underestimation of total revisits when only same-hospital revisits were measured. We determined the risk of DHR by quartile of annual ED pediatric volume, adjusting for case mix, insurance, state, and urban location.

RESULTS:
Revisits across 261 EDs occurred after 5.9% of 4.3 million discharges. A per-ED median 21.9% of revisits were DHRs (interquartile range 14.2%–34.6%). Measuring only same-hospital revisits underestimated total revisits by 17.4%. The proportions of revisits that were DHRs by increasing volume quartile were 28.1%, 25.5%, 22.6%, and 14.5%. The adjusted risk of DHR was lower for increasing quartiles of pediatric volume (adjusted odds ratio for highest versus lowest quartile 0.27; 95% confidence interval, 0.19–0.36).

CONCLUSIONS:
Measuring ED revisits only at the index ED significantly underestimates total revisits. Lower pediatric volume is associated with higher DHRs as a proportion of revisits. When using revisits as a measure of emergency care quality, effort should be made to assess revisits to different EDs.
The personality, motivational, and need-based background of problematic Tinder use
Authors: Orosz Gábor , Benyó Mária , Berkes Bernadett , Nikoletti Edina , Gál Éva , Tóth-Király István , Bőthe Beáta 
Published: April 2018

Background and aims
Tinder is a geo-located online dating application, which is present in almost 200 countries and has 10 million daily users. The aim of the present research was to investigate the motivational, personality, and basic psychological need-related background of problematic Tinder use.

Methods
After qualitative pretest and item construction, in Study 1 (N = 414), confirmatory factor analysis was conducted to corroborate the different motivational factors behind Tinder use. In Study 2 (N = 346), the associations between Big Five traits, Tinder motivations, and problematic Tinder use were examined with structural equation modeling (SEM). In Study 3 (N = 298), the potential role of general self-esteem, relatedness need satisfaction, and frustration in relation to Tinder-use motivations and problematic Tinder use was examined with SEM.

Results
In Study 1, a 16-item first-order factor structure was identified with four motivational factors, such as sex, love, self-esteem enhancement, and boredom. In Study 2, problematic Tinder use was mainly related to using Tinder for self-esteem enhancement. The Big Five personality factors were only weakly related to the four motivations and to problematic Tinder use. Counterintuitively, Study 3 showed that instead of global self-esteem, relatedness need frustration was the strongest predictor of self-esteem enhancement Tinder-use motivation which, in turn, was the strongest predictor of problematic Tinder use.

Discussion
Four motivational factors were identified as predictors of problematic use with need frustration being a relevant background variable instead of general personality traits.
FDA Approval Summary: Mylotarg for Treatment of Patients with Relapsed or Refractory CD33-Positive Acute Myeloid Leukemia
Authors: Norsworthy Kelly J. , Ko Chia-Wen , Lee Jee Eun , Liu Jiang , John Christy S. , Przepiorka Donna , Farrell Ann T. , Pazdur Richard 
Published: April 2018

Abstract

On September 2, 2017, the U.S. Food and Drug Administration approved gemtuzumab ozogamicin (GO; Mylotarg; Pfizer, New York City, NY) for treatment of relapsed or refractory (R/R) CD33-positive acute myeloid leukemia (AML) in patients 2 years of age and older. GO is a CD33-directed antibody drug conjugate linked to the cytotoxic antibiotic calicheamicin. It originally received accelerated approval for treatment of older patients with relapsed CD33-positive AML in 2000, but it was withdrawn from the market in 2010 when the confirmatory trial failed to demonstrate clinical benefit among safety concerns, such as a higher rate of induction fatalities on the GO combination arm compared with chemotherapy alone. In addition, GO was associated with hepatic veno-occlusive disease (VOD), which has substantial morbidity and mortality. Pharmacokinetic analyses suggested a lower maximum concentration of GO would result in less VOD without affecting target saturation or efficacy. A meta-analysis across dose schedules of GO in patients with R/R AML showed that a lower-dose “fractionated” schedule of 3 mg/m2 days 1, 4, and 7 was associated with less early mortality, hemorrhage, and VOD, without an apparent decrease in complete remission (CR) rate. MyloFrance 1 was a single-arm study evaluating response rates in patients with relapsed CD33-positive AML treated with the lower-dose fractionated GO regimen. The CR rate was 26% (95% confidence interval 16%–40%). Common adverse reactions were fever, infections, nausea, vomiting, constipation, bleeding, increased liver enzymes, and mucositis. There were no cases of VOD. These results supported the approval of GO as monotherapy for R/R CD33-positive AML using the lower-dose fractionated regimen.

Implications for Practice
Gemtuzumab ozogamicin (GO) 3 mg/m2 days 1, 4, and 7 is an active regimen for induction of remission when used to treat patients with relapsed or refractory CD33-positive acute myeloid leukemia without curative intent. The risks of hepatic veno-occlusive disease and early mortality with this regimen appear to be lower than reported previously for GO 9 mg/m2 days 1 and 15. The data were not sufficient to enable conclusions about the safety of GO in children younger than 2 years of age.
The Eighth Edition of TNM Staging of Lung Cancer: Reference Chart and Diagrams
Authors: Lababede Omar , Meziane Moulay A. 
Published: April 2018

Abstract
Lung cancer is the leading cause of cancer-related mortality in the U.S. TNM staging of lung cancer is implemented to define the extent of disease and consequently assign prognosis and guide treatment. The newest edition of TNM staging of lung cancer has been released recently. In this article, we present the TNM staging of lung cancer in a concise, yet comprehensive, visual format.