bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-range temporal correlation in Auditory Brainstem Responses to Spoken Syllable/da/
Authors: Mozaffarilegha Marjan , Movahed S. M. S. 
Published: February 2019

AbstractThe speech auditory brainstem response (sABR) is an objective clinical tool to diagnose particular impairments along the auditory brainstem pathways. We explore the scaling behavior of the brainstem in response to synthetic /da/ stimuli using a proposed pipeline including Multifractal Detrended Moving Average Analysis (MFDMA) modified by Singular Value Decomposition. The scaling exponent confirms that all normal sABR are classified into the non-stationary process. The average Hurst exponent is H = 0:77 ± 0:12 at 68% confidence interval indicating long-range correlation which shows the first universality behavior of sABR. Our findings exhibit that fluctuations in the sABR series are dictated by a mechanism associated with long-term memory of the dynamic of the auditory system in the brainstem level. The q-dependency of h(q) demonstrates that underlying data sets have multifractal nature revealing the second universality behavior of the normal sABR samples. Comparing Hurst exponent of original sABR with the results of the corresponding shuffled and surrogate series, we conclude that its multifractality is almost due to the long-range temporal correlations which are devoted to the third universality. Finally, the presence of long-range correlation which is related to the slow timescales in the subcortical level and integration of information in the brainstem network is confirmed.
Molecular layer interneurons shape the spike activity of cerebellar Purkinje cells
Authors: Brown Amanda M. , Arancillo Marife , Lin Tao , Catt Daniel R. , Zhou Joy , Lackey Elizabeth P. , Stay Trace L. , Zuo Zhongyuan , White Joshua J. , Sillitoe Roy V. 
Published: February 2019

AbstractPurkinje cells receive synaptic input from several classes of interneurons. Here, we address the roles of inhibitory molecular layer interneurons in establishing Purkinje cell function in vivo. Using conditional genetics approaches in mice, we compare how the lack of stellate cell versus basket cell GABAergic neurotransmission sculpts the firing properties of Purkinje cells. We take advantage of an inducible Ascl1CreER allele to spatially and temporally target the deletion of the vesicular GABA transporter, Vgat, in developing neurons. Selective depletion of basket cell GABAergic neurotransmission increases the frequency of Purkinje cell simple spike firing and decreases the frequency of complex spike firing in adult behaving mice. In contrast, lack of stellate cell communication increases the regularity of Purkinje cell simple spike firing while increasing the frequency of complex spike firing. Our data uncover complementary roles for molecular layer interneurons in shaping the rate and pattern of Purkinje cell activity in vivo.
Empirical evaluation of variant calling accuracy using ultra-deep whole-genome sequencing data
Authors: Kishikawa Toshihiro , Momozawa Yukihide , Ozeki Takeshi , Mushiroda Taisei , Inohara Hidenori , Kamatani Yoichiro , Kubo Michiaki , Okada Yukinori 
Published: February 2019

AbstractIn the design of whole-genome sequencing (WGS) studies, sequencing depth is a crucial parameter to define variant calling accuracy and study cost, with no standard recommendations having been established. We empirically evaluated the variant calling accuracy of the WGS pipeline using ultra-deep WGS data (approximately 410×). We randomly sampled sequence reads and constructed a series of simulation WGS datasets with a variety of gradual depths (n = 54; from 0.05× to 410×). Next, we evaluated the genotype concordances of the WGS data with those in the SNP microarray data or the WGS data using all the sequence reads. In addition, we assessed the accuracy of HLA allele genotyping using the WGS data with multiple software tools (PHLAT, HLA-VBseq, HLA-HD, and SNP2HLA). The WGS data with higher depths showed higher concordance rates, and >13.7× depth achieved as high as >99% of concordance. Comparisons with the WGS data using all the sequence reads showed that SNVs achieved >95% of concordance at 17.6× depth, whereas indels showed only 60% concordance. For the accuracy of HLA allele genotyping using the WGS data, 13.7× depth showed sufficient accuracy while performance heterogeneity among the software tools was observed (the highest concordance of 96.9% was observed with HLA-HD). Improvement in HLA genotyping accuracy by further increasing the depths was limited. These results suggest a medium degree of the WGS depth setting (approximately 15×) to achieve both accurate SNV calling and cost-effectiveness, whereas relatively higher depths are required for accurate indel calling.
Diabetes-induced hypomagnesemia is not modulated by metformin treatment in mice
Authors: Kurstjens Steef , Bouras Hacene , Overmars-Bos Caro , Kebieche Mohamed , Bindels René J. M. , Hoenderop Joost G. J. , de Baaij Jeroen H. F. 
Published: February 2019

AbstractApproximately 30% of patients with type 2 diabetes mellitus (T2D) have hypomagnesemia (blood magnesium (Mg2+) concentration <0.7 mmol/L). In T2D patients, treatment with metformin is associated with reduced blood Mg2+ levels. To investigate how T2D and metformin affect Mg2+ homeostasis db/m and db/db mice were treated with metformin or placebo. Mice were housed in metabolic cages to measure food and water intake, and to collect urine and feces. Serum and urinary Mg2+ concentrations were determined and mRNA expression of magnesiotropic genes was determined in kidney and distal colon using RT-qPCR. Db/db mice had significantly lower serum Mg2+ levels than db/m mice. Mild hypermagnesuria was observed in the db/db mice at two weeks, but not at four weeks. Metformin-treatment had no effect on the serum Mg2+ concentration and on the urinary Mg2+ excretion. Both in kidney and distal colon of db/db mice, there was a compensatory upregulation in the mRNA expression of magnesiotropic genes, such as transient receptor potential melastatin 6 (Trpm6), whereas metformin treatment did not affect gene expression levels. In conclusion, we show that T2D causes hypomagnesemia and that metformin treatment has no effect on Mg2+ homeostasis in mice.
Traceability and dynamical resistance of precursor of extreme events
Authors: Rings Thorsten , Mazarei Mahmood , Akhshi Amin , Geier Christian , Tabar M. Reza Rahimi , Lehnertz Klaus 
Published: February 2019

AbstractExtreme events occur in a variety of natural, technical, and societal systems and often have catastrophic consequences. Their low-probability, high-impact nature has recently triggered research into improving our understanding of generating mechanisms, providing early warnings as well as developing control strategies. For the latter to be effective, knowledge about dynamical resistance of a system prior to an extreme event is of utmost importance. Here we introduce a novel time-series-based and non-perturbative approach to efficiently monitor dynamical resistance and apply it to high-resolution observations of brain activities from 43 subjects with uncontrollable epileptic seizures. We gain surprising insights into pre-seizure dynamical resistance of brains that also provide important clues for success or failure of measures for seizure prevention. The novel resistance monitoring perspective advances our understanding of precursor dynamics in complex spatio-temporal systems with potential applications in refining control strategies.
Enhancement of immune maturation in suckling rats by leptin and adiponectin supplementation
Authors: Grases-Pintó Blanca , Abril-Gil Mar , Castell Margarida , Pérez-Cano Francisco J. , Franch Àngels 
Published: February 2019

AbstractLeptin and adiponectin, adipokines present in breast milk, have shown immunomodulatory properties. The current study aimed to ascertain whether a nutritional supplementation with leptin or adiponectin in neonatal rats was able to influence the maturation of the systemic immune response in early life. To achieve this, suckling Wistar rats were supplemented with either leptin (0.7 μg/kg/day) or adiponectin (35 μg/kg/day) during the whole suckling period. Plasmatic immunoglobulins were quantified, and spleen lymphocyte composition and their ability to proliferate and release cytokines were evaluated during (day 14) and at the end (day 21) of the suckling period. Rats fed with either adipokine showed higher plasma IgM and IgG1 concentrations and adiponectin supplementation also increased IgG2a at both studied days (P < 0.05). With regard to the lymphocyte composition, both adipokine supplementations increased T cell proportion and both CD4+and CD8+T cell subsets after two weeks of supplementation (P < 0.05). Moreover, only leptin administration increased NK and NKT cell proportions at the end of the suckling period. Finally, both adipokines influenced the cytokine secretion pattern by splenocytes. In conclusion, these results suggest that leptin and adiponectin play a role in the maturation of the systemic immune response during the suckling period.
Food decisions of an omnivorous thrips are independent from the indirect effects of jasmonate-inducible plant defences on prey quality
Authors: Ataide Livia M. S. , Dias Cleide R. , Schimmel Bernardus C. J. , van Erp Thijs , Pallini Angelo , Kant Merijn R. 
Published: February 2019

AbstractPlant defensive substances can affect the quality of herbivores as prey for predators either directly or indirectly. Directly when the prey has become toxic since it ingested toxic plant material and indirectly when these defences have affected the size and/or nutritional value (both quality parameters) of prey or their abundance. To disentangle direct and indirect effects of JA-defences on prey quality for predators, we used larvae of the omnivorous thrips Frankliniella occidentalis because these are not directly affected by the jasmonate-(JA)-regulated defences of tomato. We offered these thrips larvae the eggs of spider mites (Tetranychus urticae or T. evansi) that had been feeding from either normal tomato plants, JA-impaired plants, or plants treated with JA to artificially boost defences and assessed their performance. Thrips development and survival was reduced on the diet of T. evansi eggs relative to the diet of T. urticae eggs yet these effects were independent from the absence/presence of JA-defences. This indicates that the detrimental effects of tomato JA-defences on herbivores not necessarily also affects their quality as prey.
Wavelength-scale ptychographic coherent diffractive imaging using a high-order harmonic source
Authors: Tadesse Getnet K. , Eschen Wilhelm , Klas Robert , Tschernajew Maxim , Tuitje Frederik , Steinert Michael , Zilk Matthias , Schuster Vittoria , Zürch Michael , Pertsch Thomas , Spielmann Christian , Limpert Jens , Rothhardt Jan 
Published: February 2019

AbstractPtychography enables coherent diffractive imaging (CDI) of extended samples by raster scanning across the illuminating XUV/X-ray beam, thereby generalizing the unique advantages of CDI techniques. Table-top realizations of this method are urgently needed for many applications in sciences and industry. Previously, it was only possible to image features much larger than the illuminating wavelength with table-top ptychography although knife-edge tests suggested sub-wavelength resolution. However, most real-world imaging applications require resolving of the smallest and closely-spaced features of a sample in an extended field of view. In this work, resolving features as small as 2.5 λ (45 nm) using a table-top ptychography setup is demonstrated by employing a high-order harmonic XUV source with record-high photon flux. For the first time, a Rayleigh-type criterion is used as a direct and unambiguous resolution metric for high-resolution table-top setup. This reliably qualifies this imaging system for real-world applications e.g. in biological sciences, material sciences, imaging integrated circuits and semiconductor mask inspection.
Acute restraint stress modifies the heart rate biorhythm in the poststress period
Authors: Varejkova Eva , Janisova Katerina , Myslivecek Jaromir 
Published: February 2019

AbstractWe studied the changes in the heart and the activity biorhythms in mice exposed to acute (one 120-minute session) and repeated (7 two-hour sessions) restraint stress in 129J1/CF1 mice (WT) and in mice without M2 muscarinic receptors (M2KO) during the prestress period, during stress (STR) and for five days after the last stress session (POST). There were changes in the mesor (a midline based on the distribution of values across the circadian cycles; decreased in M2KO by 6% over all POST), day means (inactive period of diurnal rhythm in mice; higher in M2KO and further increased on STR and on the second to the fifth POST) and night means (active period; lower by 13% in M2KO and remained decreased in STR and in POST). The total area under the curve was decreased both in the WT and M2KO on STR and in all POST. Repeated stress caused changes over all days of STR, but the initial values were restored in POST. The average night values were decreased, and the day means were increased by 16% over all STR in M2KO. The day means decreased by 14% in the 4 POST in WT. The activity biorhythm parameters were almost unchanged. We show here that stress can specifically affect heart biorhythm in M2KO mice, especially when the stress is acute. This implies the role of M2 muscarinic receptor in stress response.
Nkx2–5 Second Heart Field Target Gene Ccdc117 Regulates DNA Metabolism and Proliferation
Authors: Horton Anthony J. , Brooker John , Streitfeld William S. , Flessa Meaghan E. , Pillai Balakrishnan , Simpson Raychel , Clark Christopher D. , Gooz Monika B. , Sutton Kimberly K. , Foley Ann C. , Lee Kyu-Ho 
Published: February 2019

AbstractThe cardiac transcription factor Nkx2-5 is essential for normal outflow tract (OFT) and right ventricle (RV) development. Nkx2-5−/− null mouse embryos display severe OFT and RV hypoplasia and a single ventricle phenotype due to decreased proliferation of Second Heart Field (SHF) cells, a pool of cardiac progenitors present in anterior pharyngeal arch mesoderm at mid-gestation. However, definition of the precise role of Nkx2-5 in facilitating SHF expansion is incomplete. We have found that Nkx2-5 positively and directly regulates a novel target gene, Ccdc117, in cells of the SHF at these stages. The nuclear/mitotic spindle associated protein Ccdc117 interacts with the MIP18/MMS19 cytoplasmic iron-sulfur (FeS) cluster assembly (CIA) complex, which transfers critical FeS clusters to several key enzymes with functions in DNA repair and replication. Loss of cellular Ccdc117 expression results in reduced proliferation rates associated with a delay at the G1-S transition, decreased rates of DNA synthesis, and unresolved DNA damage. These results implicate a novel role for Nkx2-5 in the regulation of cell cycle events in the developing heart, through Ccdc117′s interaction with elements of the CIA pathway and the facilitation of DNA replication during SHF expansion.
Preference for in-person psychotherapy versus digital psychotherapy options for depression: survey of adults in the U.S
Authors: Renn Brenna N. , Hoeft Theresa J. , Lee Heather Sophia , Bauer Amy M. , Areán Patricia A. 
Published: February 2019

AbstractSeveral barriers complicate access to psychotherapy for depression, including time commitment, location of services, and stigma. Digital treatment has the potential to address these barriers, yet long term use of digital psychotherapy is poor. This paper presents data from a mixed-methods, online survey to document concerns patients with depression face when given the choice of in-person psychotherapy and digital psychotherapy. Participants were 164 adults living in the United States who had previously used or considered psychotherapy for depression. Rural-dwelling and racial/ethnic minority (Native American, African American, and Spanish-speaking) respondents were purposively sampled. Participants were asked their preferences for and opinions about four treatment modalities: self-guided digital, peer-supported digital, expert-guided digital, or in-person psychotherapy. Less than half (44.5%) of participants preferred in-person psychotherapy, 25.6% preferred self-guided digital treatment, 19.7% preferred expert-guided digital treatment, and 8.5% peer-supported digital treatment. Principal themes extracted from qualitative analysis centered on the efficacy of digital treatment, access to digital treatment, concerns about peer-supported care, confidentiality and privacy concerns, preference for in-person treatment, skepticism about self-guided therapy, and the impact of social anxiety on the use of video-chat based care. Future development of digital psychotherapy will need to address concerns regarding efficacy, privacy, data security, and methods to enhance motivation to use these treatments.
Loss of stretch-activated channels, PIEZOs, accelerates non-small cell lung cancer progression and cell migration
Authors: Huang Zhicheng , Sun Zhiqiang , Zhang Xueying , Niu Kai , Wang Ying , Zheng Jun , Li Hang , Liu Ying 
Published: February 2019

Abstract
PIEZO channels are stretch-activated channels involved in wound sealing and cell proliferation in many cell types. A recent study focussing on lung cancer (LC), using next-generation sequencing analysis, has indicated that PIEZO functions were implicated in LC development. However, the expression and role of PIEZO channels in non-small cell LC (NSCLC) progression require elucidation. In the current study, we investigated the gene expression and alteration frequency in human NSCLC tissue, accessed the prognostic roles of PIEZO channels in NSCLC patients, and further studied the effect of PIEZOs in NSCLC cell proliferation and tumor growth in vivo. The mRNA expression of PIEZO1 and 2 was clearly decreased in NSCLC tumor tissue compared with that in matched adjacent non-tumor tissue. In human NSCLC tissues, PIEZO1 gene expression exhibits a highly deep deletion rate, and PIEZO2 mainly exhibits mutation in gene expression. High mRNA expression of PIEZO channels was found to correlate with better overall survival (OS) for NSCLC patients, especially for patients with lung adenocarcinoma (LUAD), but not for patients with lung squamous cell carcinoma (LUSC). The prognostic role of PIEZO channels was more sensitive in female patients than male patients, and more sensitive in patients at earlier stages than patients at latter stages. Knockdown of PIEZO1 or PIEZO2 in NSCLC cells significantly promoted cell migration in vitro and tumor growth in vivo. These results indicate the critical prognostic values of the PIEZO channels in NSCLC. This information will be beneficial to understand the pathological mechanism of NSCLC and to generate effective therapeutic approaches for NSCLC patients.
MiR-144inhibits growth and metastasis in colon cancer by down-regulating SMAD4
Authors: Sheng Shihou , Xie Lin , Wu Yuanyu , Ding Meng , Zhang Tao , Wang Xu 
Published: February 2019

AbstractMicroRNAs (MiRs) are thought to display regulator action in tumor suppression and oncogenesis. miR-144 plays an important role in the development of various cancers, such as colorectal cancer, breast cancer, and lung cancer, by targetting different molecules potentially involved in many signaling pathways. SMAD4 is a common signaling during tumor progression, and it can inhibit cell proliferation and promote cell motility in most epithelial cells. The present study focused on the effect of miR-144 and SMAD4 on colon cancer in order to find the novel gene therapy target for the treatment of colon cancer. Quantitative real-time polymerase chain reaction was used to assess the expression level of miR-144 in colon cancer tissues and SW620 cells. MTT assay, scratch test, and transwell assay were used to evaluate cell proliferation, migration, and invasion, respectively. Moreover, luciferase assays were utilized to identify the predictive effect of miR-144 on SMAD4. Western blotting was performed to determine the relative expression of protein related to SMAD4. We found miR-144 level was significantly lower in colon cancer tissues and SW620 cells. Moreover, SMAD4 level, both in mRNA and protein, was obviously elevated in colon cancer tissues. Further, miR-144 mimics treatment inhibited cells proliferation, invasion, and migration. Fluorescence intensity of miR-144 mimics group in wild type cells was decreased. MiR-144 mimics repressed the SMAD4 expression both in mRNA and protein. These findings about miR-144/SMAD4 pair provide a novel therapeutic method for colon cancer patients.
Ablation of both Cx40 and Panx1 results in similar cardiovascular phenotypes exhibited in Cx40 knockout mice
Authors: Novielli-Kuntz Nicole M. , Jelen Meghan , Barr Kevin , DeLalio Leon J. , Feng Qingping , Isakson Brant E. , Gros Robert , Laird Dale W. 
Published: February 2019

Abstract
Connexins (Cxs) and pannexins (Panxs) are highly regulated large-pore channel-forming proteins that participate in cellular communication via small molecular exchange with the extracellular microenvironment, or in the case of connexins, directly between cells. Given the putative functional overlap between single membrane-spanning connexin hemichannels and Panx channels, and cardiovascular system prevalence, we generated the first Cx40−/−Panx1−/− mouse with the anticipation that this genetic modification would lead to a severe cardiovascular phenotype. Mice null for both Cx40 and Panx1 produced litter sizes and adult growth progression similar to wild-type (WT), Cx40−/− and Panx1−/− mice. Akin to Cx40−/− mice, Cx40−/−Panx1−/− mice exhibited cardiac hypertrophy and elevated systolic, diastolic, and mean arterial blood pressure compared with WT and Panx1−/− mice; however assessment of left ventricular ejection fraction and fractional shortening revealed no evidence of cardiac dysfunction between groups. Furthermore, Cx40−/−, Panx1−/−, and Cx40−/−Panx1−/− mice demonstrated impaired endothelial-mediated vasodilation of aortic segments to increasing concentrations of methacholine (MCh) compared with WT, highlighting roles for both Cx40 and Panx1 in vascular endothelial cell (EC) function. Surprisingly, elevated kidney renin mRNA expression, plasma renin activity, and extraglomerular renin-producing cell populations found in Cx40−/− mice was further exaggerated in double knockout mice. Thus, while gestation and gross development were conserved in Cx40−/−Panx1−/− mice, they exhibit cardiac hypertrophy, hypertension, and impaired endothelial-mediated vasodilation that phenocopies Cx40−/− mice. Nevertheless, the augmented renin homeostasis observed in the double knockout mice suggests that both Cx40 and Panx1 may play an integrative role.
Auf Fixierungen kann in der klinischen Praxis verzichtet werden – ohne dass auf Zwangsmedikation oder Isolierungen zurückgegriffen wird
Authors: Zinkler Martin , Waibel Michael 
Published: February 2019

ZusammenfassungAusgehend von der Situation der Heidenheimer Klinik beschreiben wir die notwendigen Veränderungen, um völlig auf Fixierungen in der Allgemeinpsychiatrie einschließlich Gerontopsychiatrie und Suchtbehandlung zu verzichten, ohne auf andere Zwangsmaßnahmen wie Isolierung oder Zwangsmedikation zurückzugreifen. Dabei werden die bisherigen Fixierungen durch 2:1- oder 3:1-Betreuungen ersetzt. Die Klinik erfasst die Fixierungshäufigkeit und -dauer minutengenau. Dies erlaubt die Bestimmung der Zeiten für intensive Einzelbetreuungen. Die Anlässe für die bislang durchgeführten Fixierungen und individuelle Besonderheiten bei der Begleitung erlauben eine Einschätzung der Betreuungsintensität und damit des erforderlichen Personalaufwands. Die Personalressourcen und dafür erforderlichen Kosten werden mit den üblichen Ausfallzeiten und Personalkosten für qualifiziertes Pflegepersonal errechnet und ergeben einen zusätzlichen Bedarf von 4 % des jährlichen Klinikbudgets. Problematisch für die Umsetzung erscheint der Fachkräftemangel in der Krankenpflege in Deutschland.