bluuebunny/crossref_metadata_2025_split huggingface dataset:
Calcitonin and complementary biomarkers in the diagnosis of hereditary medullary thyroid carcinoma in children and adolescents
Authors: Eckelt Felix , Pfaeffle Roland , Kiess Wieland , Kratzsch Juergen 
Published: September 2021

Abstract

Objectives
Medullary thyroid carcinoma (MTC) is a rare malignancy that is effectively curable by surgery. Unlike in adults, hereditary MTC has a predominant role in children. A fast and safe diagnosis is important to assure the good prognosis for the patients. A major cornerstone is the assessment of biomarkers, but the interpretation must respect their pre-, post- and analytical features. Especially calcitonin (Ctn) is a challenging biomarker in daily laboratory diagnostics. However, Ctn is of particular relevance for the diagnostic in MTC. The American Thyroid Association recommends thyroidectomy if the upper reference range of Ctn is exceeded. Interestingly, age-dependent reference ranges for children and adolescents have become available only recently for Ctn assays. With this review, we aim to highlight the importance of a timely diagnosis of MTC in children and adolescents.

Content
Recent developments in pediatric biochemical diagnostics of MTC were summarized. This includes guidance on interpretation of RET, Ctn, procalcitonin, carcinoembryonic antigen, carbohydrate antigen 19-9, and chromogranin A.

Summary
Currently, Ctn is the most investigated biomarker in the diagnosis of MTC in children and adolescents. Other biomarkers as PCT suggest complementary evidence about pediatric MTC but their interpretation based largely on adult’s data. A successful treatment of MTC requires, besides results of biomarkers, information about medical history, RET gene analysis and recent guideline knowledge.

Outlook
More research is required to validate complementary biomarkers of Ctn in children. Additionally, the effect of different confounder on pediatric Ctn levels has to be further clarified.
Evaluation of mulberry branch waste as raw material for nanocellulose synthesis: effects of the synthesis method on product properties
Authors: Zhao Hui , Tao Wenjuan , Gu Haoming , Guo Lifang , Han Mai , Zhai Huamin , Ren Hao 
Published: September 2021

Abstract
The mechanical pulp of mulberry branches was evaluated as a raw material for the production of cellulose II and its subsequent conversion to nanocellulose via high-pressure homogenization, 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO)-oxidation, and sulfuric acid hydrolysis. The morphology, chemical structure, crystallinity, and thermal stability of the nanocellulose samples prepared by each method were characterized by Fourier transform infrared spectroscopy, X-ray diffraction, field-emission scanning electron microscopy, atomic force microscopy, and thermogravimetric analysis. The results showed that nanocellulose prepared by high-pressure homogenization exhibited higher aspect ratio (>100), and the weight loss peak in the DTG chart was 361 °C, with the best thermal stability, whereas that prepared by sulfuric acid hydrolysis featured shorter fiber length (96±31 nm) and a higher crystallinity (78.2 %).The TEMPO oxidized nanocellulose (TOCN) had smaller width (5.5±1.6 nm) and high carboxyl content (1.5 mmol/g). In addition, we have further studied the application of TOCN in the wet end of papermaking, replacing the colloidal SiO2 in CPAM/ colloidal SiO2/APAM retention system with the same amount (3600 ppm) of TOCN. The study found that the strength of the paper obtained by adding TOCN instead of the traditional wet end additives is similar, and the water drainage and retention properties of the pulp are improved.
Orthonormal Canonical Correlation Analysis
Authors: Lipovetsky Stan 
Published: September 2021

AbstractComplex managerial problems are usually described by datasets with multiple variables, and in lack of a theoretical model, the data structures can be found by special multivariate statistical techniques. For two datasets, the canonical correlation analysis and its robust version are known as good working research tools. This paper presents their further development via the orthonormal approximation of data matrices which corresponds to using singular value decomposition in the canonical correlations. The features of the new method are described and applications considered. This type of multivariate analysis is useful for solving various practical problems of applied statistics requiring operating with two data sets, and can be helpful in managerial estimations and decision making.
Intrauterine Growth Restriction Causes Abnormal Embryonic Dentate Gyrus Neurogenesis in Mouse Offspring That Leads to Adult Learning and Memory Deficits
Authors: Brown Ashley S. , Wieben Matthew , Murdock Shelby , Chang Jill , Dizon Maria L. V. , St. Pierre Mark , Chavez-Valdez Raul , Dorsky Richard I. , Fung Camille M. 
Published: September 2021

AbstractHuman infants who suffer from intrauterine growth restriction (IUGR), which is a failure to attain their genetically predetermined weight, are at increased risk for postnatal learning and memory deficits. Hippocampal dentate gyrus (DG) granule neurons play an important role in memory formation; however, it is unknown whether IUGR affects embryonic DG neurogenesis, which could provide a potential mechanism underlying abnormal postnatal learning and memory function. Using a mouse model of the most common cause of IUGR, induced by hypertensive disease of pregnancy, we first assessed adult learning and memory function. We quantified the percentages of embryonic hippocampal DG neural stem cells (NSCs) and progenitor cells and developing glutamatergic granule neurons, as well as hippocampal volumes and neuron cell count and morphology 18 and 40 d after delivery. We characterized the differential embryonic hippocampal transcriptomic pathways between appropriately grown and IUGR mouse offspring. We found that IUGR offspring of both sexes had short-term adult learning and memory deficits. Prenatally, we found that IUGR caused accelerated embryonic DG neurogenesis and Sox2+neural stem cell depletion. IUGR mice were marked by decreased hippocampal volumes and decreased doublecortin+neuronal progenitors with increased mean dendritic lengths at postnatal day 18. Consistent with its known molecular role in embryonic DG neurogenesis, we also found evidence for decreased Wnt pathway activity during IUGR. In conclusion, we have discovered that postnatal memory deficits are associated with accelerated NSC differentiation and maturation into glutamatergic granule neurons following IUGR, a phenotype that could be explained by decreased embryonic Wnt signaling.
Aperiodic and Periodic Components of Ongoing Oscillatory Brain Dynamics Link Distinct Functional Aspects of Cognition across Adult Lifespan
Authors: Thuwal Kusum , Banerjee Arpan , Roy Dipanjan 
Published: September 2021

AbstractSignal transmission in the brain propagates via distinct oscillatory frequency bands but the aperiodic component, 1/f activity, almost always co-exists which most of the previous studies have not sufficiently taken into consideration. We used a recently proposed parameterization model that delimits the oscillatory and aperiodic components of neural dynamics on lifespan aging data collected from human participants using magnetoencephalography (MEG). Since healthy aging underlines an enormous change in local tissue properties, any systematic relationship of 1/f activity would highlight their impact on the self-organized critical functional states. Furthermore, we have used patterns of correlation between aperiodic background and metrics of behavior to understand the domain general effects of 1/f activity. We suggest that age-associated global change in 1/f baseline alters the functional critical states of the brain affecting the global information processing impacting critically all aspects of cognition, e.g., metacognitive awareness, speed of retrieval of memory, cognitive load, and accuracy of recall through adult lifespan. This alteration in 1/f crucially impacts the oscillatory features peak frequency (PF) and band power ratio, which relates to more local processing and selective functional aspects of cognitive processing during the visual short-term memory (VSTM) task. In summary, this study leveraging on big lifespan data for the first time tracks the cross-sectional lifespan-associated periodic and aperiodic dynamical changes in the resting state to demonstrate how normative patterns of 1/f activity, PF, and band ratio (BR) measures provide distinct functional insights about the cognitive decline through adult lifespan.
Functional Characterization of Ovine Dorsal Root Ganglion Neurons Reveal Peripheral Sensitization after Osteochondral Defect
Authors: Chakrabarti Sampurna , Ai Minji , Wong Katherine , Newell Karin , Henson Frances M. D. , Smith Ewan St. John 
Published: September 2021

AbstractKnee joint trauma can cause an osteochondral defect (OD), a risk factor for osteoarthritis (OA) and cause of debilitating pain in patients. Rodent OD models are less translatable because of their smaller joint size and open growth plate. This study proposes sheep as a translationally relevant model to understand the neuronal basis of OD pain. A unilateral 6-mm deep OD was induced in adult female sheep. Two to six weeks after operation, lumbar dorsal root ganglia (DRG) neurons were collected from the contralateral (Ctrl) and OD side of operated sheep. Functional assessment of neuronal excitability and activity of the pain-related ion channels transient receptor potential vanilloid receptor 1 (TRPV1) and P2X3 was conducted using electrophysiology and Ca2+imaging. Immunohistochemistry was used to verify expression of pain-related proteins. We observed that an increased proportion of OD DRG neurons (sheep,N = 3; Ctrl neurons,n = 15, OD neurons,n = 16) showed spontaneous electrical excitability (Ctrl: 20.33 ± 4.5%; OD: 50 ± 10%;p = 0.009, unpairedttest) and an increased proportion fired a greater number of spikes above baseline in response to application of a TRPV1 agonist (capsaicin) application (Ctrl: 40%; OD: 75%;p = 0.04, χ2test). Capsaicin also produced Ca2+influx in an increased proportion of isolated OD DRG neurons (Ctrl: 25%; OD: 44%;p = 0.001, χ2test). Neither protein expression, nor functionality of the P2X3 ion channel were altered in OD neurons. Overall, we provide evidence of increased excitability of DRG neurons (an important neural correlate of pain) and TRPV1 function in an OD sheep model. Our data show that functional assessment of sheep DRG neurons can provide important insights into the neural basis of OD pain and thus potentially prevent its progression into arthritic pain.
Unsupervised Methods for Detection of Neural States: Case Study of Hippocampal-Amygdala Interactions
Authors: Cocina Francesco , Vitalis Andreas , Caflisch Amedeo 
Published: September 2021

AbstractThe hippocampus and amygdala are functionally coupled brain regions that play a crucial role in processes involving memory and learning. Because interareal communication has been reported both during specific sleep stages and in awake, behaving animals, these brain regions can serve as an archetype to establish that measuring functional interactions is important for comprehending neural systems. To this end, we analyze here a public dataset of local field potentials (LFPs) recorded in rats simultaneously from the hippocampus and amygdala during different behaviors. Employing a specific, time-lagged embedding technique, named topological causality (TC), we infer directed interactions between the LFP band powers of the two regions across six frequency bands in a time-resolved manner. The combined power and interaction signals are processed with our own unsupervised tools developed originally for the analysis of molecular dynamics simulations to effectively visualize and identify putative, neural states that are visited by the animals repeatedly. Our proposed methodology minimizes impositions onto the data, such as isolating specific epochs, or averaging across externally annotated behavioral stages, and succeeds in separating internal states by external labels such as sleep or stimulus events. We show that this works better for two of the three rats we analyzed, and highlight the need to acknowledge individuality in analyses of this type. Importantly, we demonstrate that the quantification of functional interactions is a significant factor in discriminating these external labels, and we suggest our methodology as a general tool for large, multisite recordings.
Somatostatin-Positive Interneurons Contribute to Seizures inSCN8AEpileptic Encephalopathy
Authors: Wengert Eric R. , Miralles Raquel M. , Wedgwood Kyle C.A. , Wagley Pravin K. , Strohm Samantha M. , Panchal Payal S. , Idrissi Abrar Majidi , Wenker Ian C. , Thompson Jeremy A. , Gaykema Ronald P. , Patel Manoj K. 
Published: September 2021

SCN8Aepileptic encephalopathy is a devastating epilepsy syndrome caused by mutantSCN8A, which encodes the voltage-gated sodium channel NaV1.6. To date, it is unclear if and how inhibitory interneurons, which express NaV1.6, influence disease pathology. Using both sexes of a transgenic mouse model ofSCN8Aepileptic encephalopathy, we found that selective expression of the R1872WSCN8Amutation in somatostatin (SST) interneurons was sufficient to convey susceptibility to audiogenic seizures. Patch-clamp electrophysiology experiments revealed that SST interneurons from mutant mice were hyperexcitable but hypersensitive to action potential failure via depolarization block under normal and seizure-like conditions. Remarkably, GqDREADD-mediated activation of WT SST interneurons resulted in prolonged electrographic seizures and was accompanied by SST hyperexcitability and depolarization block. Aberrantly large persistent sodium currents, a hallmark ofSCN8Amutations, were observed and were found to contribute directly to aberrant SST physiology in computational modeling and pharmacological experiments. These novel findings demonstrate a critical and previously unidentified contribution of SST interneurons to seizure generation not only inSCN8Aepileptic encephalopathy, but epilepsy in general.SIGNIFICANCE STATEMENTSCN8Aepileptic encephalopathy is a devastating neurological disorder that results fromde novomutations in the sodium channel isoform Nav1.6. Inhibitory neurons express NaV1.6, yet their contribution to seizure generation inSCN8Aepileptic encephalopathy has not been determined. We show that mice expressing a human-derivedSCN8Avariant (R1872W) selectively in somatostatin (SST) interneurons have audiogenic seizures. Physiological recordings from SST interneurons show thatSCN8Amutations lead to an elevated persistent sodium current which drives initial hyperexcitability, followed by premature action potential failure because of depolarization block. Furthermore, chemogenetic activation of WT SST interneurons leads to audiogenic seizure activity. These findings provide new insight into the importance of SST inhibitory interneurons in seizure initiation, not only inSCN8Aepileptic encephalopathy, but for epilepsy broadly.
CDKL5 Deficiency Augments Inhibitory Input into the Dentate Gyrus That Can Be Reversed by Deep Brain Stimulation
Authors: Hao Shuang , Wang Qi , Tang Bin , Wu Zhenyu , Yang Tingting , Tang Jianrong 
Published: September 2021

Cognitive impairment is a core feature of cyclin-dependent kinase-like 5 (CDKL5) deficiency, a neurodevelopmental disorder characterized by early epileptic seizures, intellectual disability, and autistic behaviors. Although loss of CDKL5 affects a number of molecular pathways, very little has been discovered about the physiological effects of these changes on the neural circuitry. We therefore studied synaptic plasticity and local circuit activity in the dentate gyrus of bothCdkl5−/yandCdkl5+/−mutant mice. We found that CDKL5 haploinsufficiency in both male and female mice impairs hippocampus-dependent learning and memory in multiple tasks.In vivo, loss of CDKL5 reduced LTP of the perforant path to the dentate gyrus and augmented feedforward inhibition in this pathway;ex vivoexperiments confirmed that excitatory/inhibitory input into the dentate gyrus is skewed toward inhibition. Injecting the GABAergic antagonist gabazine into the dentate improved contextual fear memory inCdkl5−/ymice. Finally, chronic forniceal deep brain stimulation rescued hippocampal memory deficits, restored synaptic plasticity, and relieved feedforward inhibition inCdkl5+/−mice. These results indicate that CDKL5 is important for maintaining proper dentate excitatory/inhibitory balance, with consequences for hippocampal memory.SIGNIFICANCE STATEMENTCognitive impairment is a core feature of cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder. Although CDKL5 deficiency has been found to affect a number of molecular pathways, little is known about its physiological effects on the neural circuitry. We find that CDKL5 loss reduces hippocampal synaptic plasticity and augments feedforward inhibition in the perforant path to the dentate gyrusin vivoinCdkl5mutant mice. Chronic forniceal deep brain stimulation rescued hippocampal memory deficits, restored synaptic plasticity, and relieved feedforward inhibition inCdkl5+/−mice, as it had previously done with Rett syndrome mice, suggesting that such stimulation may be useful for other neurodevelopmental disorders.
Selective Manipulation of G-Protein γ7Subunit in Mice Provides New Insights into Striatal Control of Motor Behavior
Authors: Brunori Gloria , Pelletier Oliver B. , Stauffer Anna M. , Robishaw Janet D. 
Published: September 2021

Stimulatory coupling of dopamine D1(D1R) and adenosine A2Areceptors (A2AR) to adenylyl cyclase within the striatum is mediated through a specific Gαolfβ2γ7heterotrimer to ultimately modulate motor behaviors. To dissect the individual roles of the Gαolfβ2γ7heterotrimer in different populations of medium spiny neurons (MSNs), we produced and characterized conditional mouse models, in which theGng7gene was deleted in either the D1R- or A2AR/D2R-expressing MSNs. We show that conditional loss of γ7disrupts the cell type-specific assembly of the Gαolfβ2γ7heterotrimer, thereby identifying its circumscribed roles acting downstream of either the D1Rs or A2ARs in coordinating motor behaviors, includingin vivoresponses to psychostimulants. We reveal that Gαolfβ2γ7/cAMP signal in D1R-MSNs does not impact spontaneous and amphetamine-induced locomotor behaviors in male and female mice, while its loss in A2AR/D2R-MSNs results in a hyperlocomotor phenotype and enhanced locomotor response to amphetamine. Additionally, Gαolfβ2γ7/cAMP signal in either D1R- or A2AR/D2R-expressing MSNs is not required for the activation of PKA signaling by amphetamine. Finally, we show that Gαolfβ2γ7signaling acting downstream of D1Rs is selectively implicated in the acute locomotor-enhancing effects of morphine. Collectively, these results support the general notion that receptors use specific Gαβγ proteins to direct the fidelity of downstream signaling pathways and to elicit a diverse repertoire of cellular functions. Specifically, these findings highlight the critical role for the γ7protein in determining the cellular level, and hence, the function of the Gαolfβ2γ7heterotrimer in several disease states associated with dysfunctional striatal signaling.SIGNIFICANCE STATEMENTDysfunction or imbalance of cAMP signaling in the striatum has been linked to several neurologic and neuropsychiatric disorders, including Parkinson's disease, dystonia, schizophrenia, and drug addiction. By genetically targeting the γ7subunit in distinct striatal neuronal subpopulations in mice, we demonstrate that the formation and function of the Gαolfβ2γ7heterotrimer, which represents the rate-limiting step for cAMP production in the striatum, is selectively disrupted. Furthermore, we reveal cell type-specific roles for Gαolfβ2γ7-mediated cAMP production in the control of spontaneous locomotion as well as behavioral and molecular responses to psychostimulants. Our findings identify the γ7protein as a novel therapeutic target for disease states associated with dysfunctional striatal cAMP signaling.
Emergency Department Pediatric Visits in Alberta for Cannabis After Legalization
Authors: Yeung Matthew E.M. , Weaver Colin G. , Hartmann Riley , Haines-Saah Rebecca , Lang Eddy 
Published: September 2021

BACKGROUND AND OBJECTIVES
Canada legalized nonmedical cannabis possession and sale in October 2018. In the United States, state legalization has been tied to an increase in cannabis-related emergency department (ED) visits; however, little research exists on provincial changes in pediatric visits after nationwide legislation. We compared pre- and postlegalization trends in pediatric cannabis-related ED visits and presentation patterns in urban Alberta EDs.

METHODS
Retrospective National Ambulatory Care Reporting System data were queried for urban Alberta cannabis-related ED visits among patients aged &lt;18 years from October 1, 2013, to February 29, 2020. Population subgroups included children (aged 0–11 years), younger adolescents (12 to 14 years), and older adolescents (15 to 17 years). We calculated interrupted time series, incident rate ratios (IRRs), and relative risk (RR) ratios to identify trend change. IRRs identified changes against growth-adjusted Alberta population, while RRs measured presentation pattern changes against prelegalization ED visits.

RESULTS
Pediatric visit volume did not change postlegalization when accounting for preexisting volume trends. Unintentional ingestions increased in children (IRR: 1.77, 95% confidence interval [CI]: 1.42 to 2.20 and RR: 1.24, 95% CI: 1.05 to 1.47, respectively) and older adolescents (IRR: 1.36, 95% CI: 1.07 to 1.71 and RR: 1.48, 95% CI: 1.21 to 1.81, respectively). Presentation patterns remained similar, although older adolescent co-ingestant use decreased (RR: 0.77, 95% CI: 0.67 to 0.88), whereas hyperemesis cases increased (RR: 1.64, 95% CI: 1.13 to 2.37).

CONCLUSIONS
Cannabis legalization has increased child and older adolescent unintentional cannabis ingestions, increasing child cannabis-related ED visits. Changes highlight need for public health interventions targeting pediatric exposures.
Kinship Loanwords in the Turkic Languages
Authors: Taşbaş Erhan 
Published: September 2021

Turkic kinship terminologies represent a mixture of words of native and foreign origin, and the proportion of loanwords reﬂects the degree of linguistic and cultural interference between the Turkic and other Eurasian languages. As the intensity of socio-cultural relations between languages and communities increases, the proportion of loanwords in kinship vocabulary also increases. This paper provides an overview of historical, linguistic, and cultural aspects of kinship loanwords in the Turkic languages.The paper covers the following eight kinds of kin types in the Turkic languages: (1) parents, (2) siblings, (3) cousins, (4) children, (5) grandparents, (6) uncles/aunts, (7) nephews/nieces, (8) grandchildren. Due to the fact that in the conventional Turkic system of kinship, which is especially well-represented in pre-modern Turkic languages, two or three of these kins may be merged in one single term on the basis of generation and lineage branch, kinship loanwords examined are ordered by this criterion.