bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnosis and Use of Psychotherapy Among Children and Adolescents Prescribed Antipsychotics
Authors: VANBRONKHORST SARA B. , ROBERTS DANIEL E. , EDWARDS EVONNE M. , BLANKENSHIP KELLY 
Published: January 2019

Objective:
To examine the diagnoses, demographics, and prevalence of psychotherapy use among children and adolescents prescribed antipsychotics by psychiatric providers in a community setting.

Methods:
Medical records from 1127 children aged 0 to 17 years who were prescribed antipsychotics in 2014-2015 at Pine Rest Christian Mental Health Services (PRCMHS) outpatient network were analyzed. Antipsychotics, diagnosis codes, demographics, and number of psychotherapy sessions during this time frame were analyzed using χ2 and logistic regression analyses.

Results:
During this year, 50.8% of the patients attended psychotherapy, and 35.6% attended 5 or more sessions of psychotherapy. The most prevalent primary diagnosis was bipolar disorder (37.1%), followed by attention-deficit/hyperactivity disorder (19.7%). Females being treated with antipsychotics were significantly more likely to attend psychotherapy than their male peers (55.7% vs. 47.9%, P=0.01). In the fully adjusted models, patients with diagnoses of bipolar disorder or disorders first diagnosed in infancy, childhood, or adolescence were less than half as likely to attend psychotherapy as patients with depressive disorders, with adjusted odds ratios of 0.41 and 0.42, respectively.

Conclusions:
Approximately half of the child and adolescent patients prescribed antipsychotics in this community sample did not attend psychotherapy, and 39% of the patients did not have a diagnosis of bipolar disorder, psychotic disorder, or autistic disorder.
Dual forms of aging-related NADPH diaphorase neurodegeneration in the sacral spinal cord of aged non-human primates
Authors: Li Yinhua , Wei Zichun , Jia Yunge , Hou Wei , Wang Yu , Yu Shun , Shi Geming , Du Guanghui , Tan Huibing 
Published: January 2019

AbstractWe discovered two different anomalous NADPH diaphorase (NADPH-d) positive alterations, which were expressed as aging-related NADPH-d positive spheroidal bodies and megaloneurites specially distributed in the superficial dorsal horn, dorsal gray commissure (DGC), lateral collateral pathway (LCP) and sacral parasympathetic nucleus (SPN) in the aged monkeys’ sacral spinal cord, compared with the cervical, thoracic and lumbar segments. In the gracile nucleus of aged monkeys, only aging-related spheroidal bodies were observed and no megaloneurites occurred. The dense, abnormal NADPH-d positive megaloneurites, extremely different from regular NADPH-d positive fibers, were prominent in the sacral segments and occurred in extending from Lissauer’s tract (LT) through lamina I along the lateral boundary of the dorsal horn to the region of the SPN. Meanwhile, large diameter punctate NADPH-d activity occurred and scattered in the lateral white matter of the LCP and dorsal root entry zone (DREZ) at the same level of NADPH-d abnormality in the gray matters. Those dot-like NADPH-d alterations were examined by horizontal sectioning and indicated ascending or descending oriental fibers. These NADPH-d megaloneurites had the same composition as the punctate NADPH-d alterations and were co-localized with the VIP immunoreaction, while the ANBs did not coexist with the VIP immunoreaction. Both ANBs and megaloneurites provide consistent evidence that the anomalous neuritic alterations in the aged sacral spinal cord are referred to as a specialized aging marker in the pelvic visceral organs in non-human primates.
Coarse-grain simulations on NMR conformational ensembles highlight functional residues in proteins
Authors: Sacquin-Mora Sophie 
Published: January 2019

AbstractDynamics are a key feature of protein function, and this is especially true of gating residues, which occupy cavity or tunnel lining positions in the protein structure, and will reversibly switch between open and closed conformations in order to control the diffusion of small molecules within a protein’s internal matrix. Earlier work on globins and hydrogenases have shown that these gating residues can be detected using a multiscale scheme combining all atom classic molecular dynamics simulations and coarse grain calculations of the resulting conformational ensemble mechanical properties. Here we show that the structural variations observed in the conformational ensembles produced by NMR spectroscopy experiments are sufficient to induce noticeable mechanical changes in a protein, which in turn can be used to identify residues important for function and forming a mechanical nucleus in the protein core. This new approach, which combines experimental data and rapid coarse-grain calculations and no longer needs to resort to time-consuming all-atom simulations, was successfully applied to five different protein families.
The Role of Orexin-1 Receptor Signaling in Demand for the Opioid Fentanyl
Authors: Fragale Jennifer E. , Pantazis Caroline B. , James Morgan H. , Aston-Jones Gary 
Published: January 2019

AbstractThe orexin system is a potential treatment target for drug addiction. Orexin-1 receptor (OxR1) antagonism reduces demand for cocaine and remifentanil indicating that orexin-based therapies may reduce demand for many classes of abused drugs. However, pharmacokinetics vary greatly among opioids and it is unclear if OxR1 antagonism would reduce demand for all opioids, particularly ones with particularly high abuse liability. Here, we establish a behavioral economics (BE) procedure to assess the effects of OxR1 antagonism on demand for the highly abused opioid fentanyl. We also investigate the utility of our novel procedure in predicting OxR1 antagonism efficacy and relapse propensity. The OxR1 antagonist SB-334867 (SB) increased demand elasticity (α; decreased motivation) for fentanyl without affecting preferred consumption of fentanyl at null cost (Qo). Baseline α values predicted SB efficacy, such that SB was most effective at increasing demand elasticity in highly motivated rats. SB also attenuated cue-induced fentanyl seeking and baseline α values predicted the amount of reinstatement behavior. These results highlight the promise of the orexin system as a treatment target for opioid addiction and emphasize the usefulness of BE procedures in the study of opioid abuse.
Highly efficient genome editing in primary bronchial epithelial cells establishes FOXJ1 as essential for ciliation in human airways
Authors: Rapiteanu Radu , Karagyozova Tina , Zimmermann Natalie , Wayne Gareth , Martufi Matteo , Belyaev Nikolai N , Singh Kuljit , Betts Joanna , Beinke Soren , Maratou Klio 
Published: January 2019

AbstractThe structure and composition of the bronchial epithelium is altered in respiratory diseases such as COPD and asthma, in which goblet cell hyperplasia and reduced numbers of ciliated cells impair mucociliary clearance. We describe a robust genome editing pipeline to interrogate modulators of primary human bronchial epithelial cell (HBEC) differentiation and function. By employing plasmid- and virus-free delivery of CRISPR/Cas9 to human airway basal cells we achieve highly efficient gene inactivation without the need for positive selection. Genome edited cells are differentiated at air liquid interface (ALI) into a pseudo-stratified epithelium. We focus on profiling ciliation using imaging cytometry coupled to confocal microscopy and immunohistochemistry. To our knowledge, this is the first study to describe highly efficient genome editing of ALI cultured primary HBECs. As proof of concept, we establish that inactivation of the gene encoding the transcription factor FOXJ1 in primary human airway basal cells precludes ciliation in ALI differentiated bronchial epithelia.
Genomics, evolutionary history and diagnostics of theAlternaria alternataspecies group including apple and Asian pear pathotypes
Authors: Armitage Andrew D. , Cockerton Helen M. , Sreenivasaprasad Surapareddy , Woodhall James , Lane Charles , Harrison Richard J. , Clarkson John P. 
Published: January 2019

AbstractTheAlternariasectionalternaria(A. alternataspecies group) represents a diverse group of saprophytes, human allergens and plant pathogens.Alternariataxonomy has benefited from recent phylogenetic revision but the basis of differentiation between major phylogenetic clades within the group is not yet understood. Furthermore, genomic resources have been limited for the study of host-specific pathotypes. We report near complete genomes of the apple and Asian pear pathotypes as well as draft assemblies for a further 10 isolates representingAlternaria tenuissimaandAlternaria arborescenslineages. These assemblies provide the first insights into differentiation of these taxa as well as allowing the description of effector and non-effector profiles of apple and pear conditionally dispensable chromosomes (CDCs). We define the phylogenetic relationship between the isolates sequenced in this study and a further 23Alternariaspp. based on available genomes. We determine which of these genomes represent MAT1-1-1 or MAT1-2-1 idiomorphs and designate host-specific pathotypes. We show for the first time that the apple pathotype is polyphyletic, present in both theA. arborescensandA. tenuissimalineages. Furthermore, we profile a wider set of 89 isolates for both mating type idiomorphs and toxin gene markers. Mating-type distribution indicated that gene flow has occurred since the formation ofA. tenuissimaandA. arborescenslineages. We also developed primers designed toAMT14,a gene from the apple pathotype toxin gene cluster with homologs in all tested pathotypes. These primers allow identification and differentiation of apple, pear and strawberry pathotypes, providing new tools for pathogen diagnostics.
Suppressed Osteocyte Perilacunar / Canalicular Remodeling Plays a Causal Role in Osteoarthritis
Authors: Mazur Courtney M. , Woo Jonathon J. , Yee Cristal S. , Fields Aaron J. , Acevedo Claire , Bailey Karsyn N. , Fowler Tristan W. , Lotz Jeffrey C. , Dang Alexis , Kuo Alfred C. , Vail Thomas P. , Alliston Tamara 
Published: January 2019

ABSTRACTOsteoarthritis (OA), long considered a primary disorder of articular cartilage, is commonly associated with subchondral bone sclerosis. However, the cellular mechanisms responsible for changes to subchondral bone in OA, and the extent to which these changes are drivers of or a secondary reaction to cartilage degeneration, remain unclear. In knee joints from human patients with end-stage OA, we found evidence of profound defects in osteocyte function. Suppression of osteocyte perilacunar/canalicular remodeling (PLR) was most severe in OA subchondral bone, with lower protease expression, diminished canalicular networks, and disorganized and hypermineralized extracellular matrix. To determine if PLR suppression plays a causal role in OA, we ablated the PLR enzyme MMP13 in osteocytes, while leaving chondrocytic MMP13 intact. Not only did osteocytic MMP13 deficiency suppress PLR in cortical and subchondral bone, but it also compromised cartilage. Even in the absence of injury, this osteocyte-intrinsic PLR defect was sufficient to reduce cartilage proteoglycan content and increase the incidence of cartilage lesions, consistent with early OA. Thus, in humans and mice, osteocyte PLR is a critical regulator of cartilage homeostasis. Together, these findings implicate osteocytes in bone-cartilage crosstalk in the joint and identify the causal role of suppressed perilacunar/canalicular remodeling in osteoarthritis.
Illuminating the dark depths inside coral
Authors: Liu Chichi , Cheng Shuk Han , Lin Senjie 
Published: January 2019

AbstractThe ability to observe in situ 3D distribution and dynamics of endosymbionts in corals is crucial for gaining a mechanistic understanding of coral bleaching and reef degradation. Here, we report the development of a tissue clearing (TC)-coupled light sheet fluorescence microscopy (LSFM) method for 3D imaging of the coral holobiont at single-cell resolution. The initial applications have demonstrated the ability of this technique to provide high space-resolution quantitative information of endosymbiont abundance and distribution within corals. With specific fluorescent probes or assays, TC-LSFM also revealed spatial distribution and dynamics of physiological conditions (such as cell proliferation, apoptosis, and hypoxia response) in both corals and their endosymbionts. This tool is highly promising for in situ and in-depth data acquisition to illuminate coral symbiosis and health conditions in the changing marine environment, providing fundamental information for coral reef conservation and restoration.
Protocol-dependent differences in IC50 values measured in hERG assays occur in a predictable way and can be used to quantify state preference of drug binding
Authors: Lee William , Windley Monique J. , Perry Matthew D. , Vandenberg Jamie I. , Hill Adam P. 
Published: January 2019

AbstractCurrent guidelines around preclinical screening for drug-induced arrhythmias require the measurement of the potency of block of Kv11.1 channels as a surrogate for risk. A shortcoming of this approach is that the measured IC50 of Kv11.1 block varies widely depending on the voltage protocol used in electrophysiological assays. In this study, we aimed to investigate the factors that that contribute to these differences and to identify whether it is possible to make predictions about protocol-dependent block that might facilitate comparison of potencies measured using different assaysOur data demonstrate that state preferential binding, together with drug binding kinetics and trapping, is an important determinant of the protocol-dependence of Kv11.1 block. We show for the first time that differences in IC50 measured between protocols occurs in a predictable way, such that machine learning algorithms trained using a selection of simple voltage protocols can indeed predict protocol-dependent potency. Furthermore, we also show that a drug’s preference for binding to the open versus the inactivated state of Kv11.1 can also be inferred from differences in IC50 measured between protocols.Our work therefore identifies how state preferential drug binding is a major determinant of the protocol dependence of IC50 measured in preclinical Kv11.1 assays. It also provides a novel method for quantifying the state dependence of Kv11.1 drug binding that will facilitate the development of more complete models of drug binding to Kv11.1 and improve our understanding of proarrhythmic risk associated with compounds that block Kv11.1.
The systemin signaling cascade as derived from phosphorylation time courses under stimulation by systemin and its inactive Thr17Ala (A17) analog
Authors: Ahmad Fatima Haj , Wu Xuna , Stintzi Annick , Schaller Andreas , Schulze Waltraud X 
Published: January 2019

AbstractSystemin is a small peptide with important functions in plant wound response signaling. Although transcriptional responses of systemin action are well described, the precise signaling cascades involved in its perception and signal transduction are poorly understood at the protein level. Here we use a phosphoproteomic profiling study involving stimulation time courses with systemin and its inactive analogon A17 to reconstruct a systemin-specific kinase/phosphatase signaling network. The time course analysis of systemin-induced phosphorylation patterns revealed early events at the plasma membrane, such dephosphorylation of H+-ATPase, rapid phosphorylation of NADPH-oxidase and Ca2+-ATPase. Later responses involved transient phosphorylation of small GTPases and vesicle trafficking proteins, as well as transcription factors. Based on a correlation analysis of systemin-specific phosphorylation profiles, we predict substrate candidates for 56 systemin specific kinases and 18 phosphatases. Among the kinases are several systemin-specific receptor kinases as well as kinases with downstream signaling functions, such as MAP-kinases. A regulatory circuit for plasma membrane H+-ATPase was predicted and confirmed by in-vitro activity assays. In this regulatory model we propose that upon systemin treatment, H+-ATPase LHA1 is rapidly de-phosphorylated at its C-terminal regulatory residue T955 by phosphatase PLL5, resulting in the alkalization of the growth medium within 2 minutes of systemin treatment. We further propose that the H+-ATPase LHA1 is re-activated by MAP-Kinase MPK2 later in the systemin response. MPK2 was identified with increased phosphorylation at its activating TEY-motif at 15 minutes of treatment and the predicted interaction with LHA1 was confirmed by in-vitro kinase assays. Our data set provides a valuable resource of proteomic events involved in the systemin signaling cascade with a focus on predictions of substrates to systemin-specific kinases and phosphatases.
PRINCIPAL COMPONENT ANALYSIS AND ITS GENERALIZATIONS FOR ANY TYPE SEQUENCE (PCA-SEQ)
Authors: Efimov V.M. , Efimov K.V. , Kovaleva V.Y. 
Published: January 2019

In the 40s of the last century, Karhunen and Loève proposed a method for processing of one-dimensional numeric time series by converting it into a multidimensional by shifts. In fact, a one-dimensional number series was decomposed into several orthogonal time series. This method has many times been independently developed and applied in practice under various names (EOF, SSA, Caterpillar, etc.). Nowadays, the name SSA (the Singular Spectral Analysis) is most often used. It turned out that it is universal, applicable to any time series without requiring stationary assumptions, automatically decomposes time series into a trend, cyclic components and noise. By the beginning of the 1980s Takens showed that for a dynamical system such a method makes it possible to obtain an attractor from observing only one of these variables, thereby bringing the method to a powerful theoretical basis. In the same years, the practical benefits of phase portraits became clear. In particular, it was used in the analysis and forecast of the animal abundance dynamics.In this paper we propose to extend SSA to one-dimensional sequence of any type elements, including numbers, symbols, figures, etc., and, as a special case, to molecular sequence. Technically, the problem is solved almost the same algorithm as the SSA. The sequence is cut by a sliding window into fragments of a given length. Between all fragments, the matrix of Euclidean distances is calculated. This is always possible. For example, the square root from the Hamming distance between fragments is the Euclidean distance. For the resulting matrix, the principal components are calculated by the principal-coordinate method (PCo). Instead of a distance matrix one can use a matrix of any similarity/dissimilarity indexes and apply methods of multidimensional scaling (MDS). The result will always be PCs in some Euclidean space.We called this method PCA-Seq. It is certainly an exploratory method, as its particular case SSA. For any sequence, including molecular, PCA-Seq without any additional assumptions allows to get its principal components in a numerical form and visualize them in the form of phase portraits. Long-term experience of SSA application for numerical data gives all reasons to believe that PCA-Seq will be not less useful in the analysis of non-numerical data, especially in hypothesizing.PCA-Seq is implemented in the freely distributed Jacobi 4 package (http://mrherrn.github.io/JACOBI4/).
Extremely Drug-ResistantPseudomonas aeruginosaST309 Harboring Tandem GES Enzymes: A Newly Emerging Threat in the United States
Authors: Khan Ayesha , Tran Truc T. , Rios Rafael , Hanson Blake , Shropshire William C. , Sun Zhizeng , Diaz Lorena , Dinh An Q. , Wanger Audrey , Ostrosky-Zeichner Luis , Palzkill Timothy , Arias Cesar A. , Miller William R. 
Published: January 2019

AbstractTwo ST309Pseudomonas aeruginosaclinical isolates resistant to carbapenems and newer β-lactam/β-lactamase inhibitor combinations were found to harbor the extended spectrum beta-lactamases GES 19 and 26 genetically clustered in tandem. The combination of ceftazidime/avibactam plus aztreonam achieved cure in one patient. Phylogenetic analysis suggests that ST309P. aeruginosacarrying tandem GES are an emerging lineage in the United States.
Thymosin β4 mediates vascular protection via regulation of Low Density Lipoprotein Related Protein 1 (LRP1)
Authors: Munshaw Sonali , Bruche Susann , Patel Jyoti , Redpath Andia , Dubé Karina N. , Davies Rachel , Neal Giles , Lee Regent , Handa Ashok , Channon Keith M. , Smart Nicola 
Published: January 2019

AbstractVascular stability and tone are maintained by contractile smooth muscle cells (VSMCs). However, injury-induced growth factors stimulate a contractile-synthetic phenotypic switch which promotes atherosclerosis and susceptibility to abdominal aortic aneurysm (AAA). As a regulator of embryonic VSMC differentiation, we hypothesised that Thymosin β4 (Tβ4) may additionally function to maintain healthy vasculature and protect against disease throughout postnatal life. This was supported by identification of an interaction with Low density lipoprotein receptor related protein 1 (LRP1), an endocytic regulator of PDGF-BB signalling and VSMC proliferation. LRP1 variants have been identified by GWAS as major risk loci for AAA and coronary artery disease. Tβ4-null mice display aortic VSMC and elastin defects, phenocopying LRP1 mutants and suggesting compromised vascular integrity. We confirmed predisposition to disease in models of atherosclerosis and AAA. Diseased vessels and plaques were characterised by accelerated contractile-synthetic VSMC switching and augmented PDGFRβ signalling. In vitro, enhanced sensitivity to PDGF-BB, upon loss of Tβ4, coincided with dysregulated endocytosis, leading to increased recycling of LRP1-PDGFRβ and reduced lysosomal targeting. Our study identifies Tβ4 as a key regulator of LRP1 for maintaining vascular health, providing insight which may reveal useful therapeutic targets for modulation of VSMC phenotypic switching and disease progression.
Temporal control of inhibitionviamuscarinic acetylcholine receptor signaling generates ON and OFF selectivity in a simple visual circuit
Authors: Qin Bo , Humberg Tim-Henning , Kim Anna , Kim Hyong , Short Jacob , Diao Fengqiu , White Benjamin H. , Sprecher Simon , Yuan Quan 
Published: January 2019

ABSTRACTON and OFF selectivity in visual processing is encoded by parallel pathways that respond to either increments or decrements of light. Despite lacking anatomical features to support split channels,Drosophilalarvae effectively perform visually-guided behaviors. To understand principles guiding visual computation in this simple circuit, we focus on the physiological properties and behavioral relevance of larval visual interneurons and elucidate their functions in visual processing. We find that the ON vs. OFF discrimination in the larval visual circuit emerges through light-elicited cholinergic signaling that depolarizes the cholinergic interneuron (cha-lOLP) and hyperpolarizes the glutamatergic interneuron (glu-lOLP). Genetic studies further indicate that muscarinic acetylcholine receptor (mAchR)/Gαo signaling in glu-lOLP separates the ON and OFF signals through temporal delays, the disruption of which strongly impacts both physiological responses of downstream projection neurons and dark-induced pausing behavior. Together, our studies identify cellular and molecular substrates for OFF detection in the larval visual circuit and suggests temporal control of inhibition functions as an effective strategy in generating ON and OFF selectivity without anatomical segregation.