bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design, Implementation, and Assessment of a Public Comprehensive Specialty Care Program for Early Psychosis
Authors: NORTH CAROL S. , SIMIC ZORICA , BURRUSS JOHN 
Published: November 2019

Introduction:
Promising outcomes from early psychosis intervention programs have prompted implementation of early psychosis initiatives nationwide through federal and state funding. The Enhanced Program for Early Psychosis (ePEP) model in north Texas is among the first, if not the first, of these state-funded initiatives to provide detailed reporting of its development and implementation.

Methods:
Restrictive inclusion/exclusion criteria with a 1% eligibility rate resulted in a highly disadvantaged, predominantly minority sample with low educational attainment, prevalent mood disorders and substance misuse, and criminal justice involvement. Program progress was assessed over 1 year through structured diagnostic assessments and measures of psychotic symptoms, depression and anxiety symptoms, psychosocial functioning, and service utilization and costs.

Results:
Implementation challenges included strict income/insurance inclusion and disqualification criteria for program participation, hiring and staff turnover problems, client transportation, and lack of available family to participate in family interventions. Despite these challenges, patients showed reduction in negative psychotic symptoms, hospitalization rates decreased from 29% to 5%, full-time employment improved from 6% to 24%, and probation/parole decreased from 24% to 5%. The mean 1-year per-patient cost was $10,639. Reduced negative symptoms and hospitalizations were associated with service use.

Discussion:
The development and implementation of this pioneering state-funded early psychosis program, based on the National Institute of Mental Health’s Recovery After an Initial Schizophrenia Episode (RAISE) initiative, provide experience and results to inform the implementation of future programs. Its demonstrated success, in spite of many implementation challenges, suggests the potential for future research, including randomized controlled trials to demonstrate substantial benefit and cost-effectiveness of early psychosis programs in real-world settings.
Effectiveness of a 6-Week Day Hospital Treatment for Personality Disorders: Data From a Naturalistic Study
Authors: SAVARD CLAUDIA , CHRÉTIEN MAXIME , GAMACHE DOMINICK , MARANDA JOHANNE , VILLENEUVE EVENS 
Published: November 2019

Objective:
To report on the effectiveness of a time-limited day-hospital crisis treatment for personality disorders (PDs) in a naturalistic setting.

Method:
Archival data from 260 patients diagnosed with PDs (202 female, 58 male) who completed a 6-week day-hospital treatment program between 2012 and 2015 were analyzed. Treatment was available upon referral by psychiatrists at local emergency rooms and short-term hospitalization units. Pre-post change was assessed using the Outcome Questionnaire (OQ-45.2).

Results:
Patients significantly improved during treatment on the total OQ-45.2 scale and its 3 subscales. Pre-post changes yielded large effect sizes for the total OQ-45.2 scale and the Symptom Distress subscale, and moderate effect sizes for the Interpersonal Relations and Social Role subscales. Reliable change was observed for 55% of patients for the total scale. Younger patients (18 to 24 y of age) showed larger improvements on social role satisfaction than patients over the age of 30. Overall improvement was larger for patients engaged in social participation at the beginning of treatment.

Conclusions:
This study conducted in a naturalistic setting suggests that a time-limited, 6-week day-hospital treatment program tailored to patients wiith PDs may be effective in reducing overall symptomatology in patients experiencing a crisis episode.
Clinical Experience in Emergency Management of Severe Facial Trauma
Authors: Gao Hai , Wang Wangshu , Geng Yujia , Shao Ying 
Published: November 2019

Background:
Published reports describing management of complex facial lacerations in the emergency department are limited, and there is little guidance on the treatment of massive soft tissue avulsions of the head and face or severely contaminated head and face lacerations. Here, the authors report on the wealth of clinical experience they have gained in treating major head and facial injuries through an emergency trauma repair platform that was established in the department of orthopedic surgery at their hospital.

Methods:
Six patients with massive soft tissue avulsions of the head and face caused by trauma were treated in our department between September 2017 and December 2018. Avulsion injuries occurred to the eyelids, ears, face, and part of the scalp. Defects extended from the skin to the surface of the bone. Emergency surgical repair involved reasonable debridement of the wound surface, accurate and meticulous suture, and use of local skin flaps.

Results:
No patients experienced postoperative complications, such as necrosis, infection, or scar hyperplasia. Our postoperative satisfaction survey showed that 3 patients were very satisfied and 1 patient was relatively satisfied with their outcomes. Several patients (2/6) still had some degree of deformity in the soft tissue around the eyes, which required further surgery

Conclusion:
Satisfactory functional and aesthetic outcomes can be achieved through reasonable debridement of the wound surface, accurate and meticulous suture, and use of local skin flaps in patients with massive soft tissue avulsions of the head and face caused by trauma.
Fatigue, effort perception and central activation failure in chronic stroke survivors: a TMS and fMRI investigation
Authors: Turner Isobel F , Ward Nick S , Kuppuswamy Annapoorna 
Published: November 2019

AbstractFatigue is commonly seen in stroke survivors and the most common manifestation of fatigue is the requirement of high effort for activities of daily life. In this study we set out to identify the neural correlates of perceived effort and central activation failure, a neurophysiological measure correlated with perceived effort. Methods: Twelve chronic stroke survivors participated in this study. Fatigue levels were quantified using the Fatigue Severity Scale -7, perceived effort was quantified using a 1-10 numerical rating scale while performing an isometric biceps hold task, Central Activation Failure was quantified using the modified twitch interpolation technique using Transcranial Magnetic Stimulation and functional Magnetic Resonance Imaging was used to measure blood-oxygen-level dependent signal (BOLD) from the brain while the participant performed a hand grip task. Analysis: Following standard pre-processing procedures for fMRI data using SPM software, co-variance of BOLD signal with perceived effort levels and central activation failure was evaluated. Correlation analysis was performed between measures of fatigue and effort. Results: The main findings of this study were 1) high fatigue was associated with high perceived effort 2) higher perceived effort was associated with greater increase in BOLD fMRI activity in pre-SMA and the ipsilateral inferior frontal gyrus with increasing force 3) greater Central Activation Failure was associated with higher increase in BOLD fMRI activity in bilateral caudate, contralateral superior frontal gyrus and pre-motor cortices with increasing force.
CDK13 Mutations Drive Melanoma via Accumulation of Prematurely Terminated Transcripts
Authors: Insco Megan L. , Abraham Brian J. , Dubbury Sara J. , Dust Sofia , Wu Constance , Chen Kevin Y. , Liu David , Ludwig Calvin G. , Bellaousov Stanislav , Fabo Tania , Henriques Telmo , Adelman Karen , Geyer Matthias , Sharp Phillip A. , Young Richard A. , Boutz Paul L. , Zon Leonard I. 
Published: November 2019

AbstractTranscriptional Cyclin Dependent Kinases modulate RNA Polymerase II function to impact gene expression. Here, we show that CDK13 is mutated in 4% of patient melanomas and mutation or downregulation is associated with poor overall survival. Mutant CDK13 lacks kinase activity and overexpression in zebrafish leads to accelerated melanoma. CDK13 mutant fish and human melanomas accumulate prematurely terminated RNAs that are translated into truncated proteins. CDK13 binds to and regulates the phosphorylation of ZC3H14, a member of the PolyA eXosome Targeting (PAXT) RNA degradation complex. ZC3H14 phosphorylation recruits the PAXT complex to degrade prematurely terminated polyadenylated transcripts in the nucleus. In the presence of mutant CDK13, ZC3H14 phosphorylation is compromised and consequently fails to recruit the PAXT complex, leading to truncated transcript stabilization. This work establishes a role for CDK13 and the PAXT nuclear RNA degradation complex in cancer and has prognostic significance for melanoma patients with mutated or downregulated CDK13.
iTRAQ-based proteomic and phosphoproteomic analyses of STRIPAK mutants from the fungusSordaria macrosporaidentifies a conserved serine phosphorylation site in PAK kinase CLA4 to be important for sexual development and polarized growth
Authors: Märker R , Blank-Landeshammer B , Beier-Rosberger A , Sickmann A , Kück U 
Published: November 2019

SummaryThe highly conserved striatin-interacting phosphatases and kinases (STRIPAK) complex regulates phosphorylation of developmental proteins in eukaryotic microorganisms, animals, and humans. To first identify potential targets of STRIPAK, we performed extensive isobaric tags for relative and absolute quantification (iTRAQ)-based proteomic and phosphoproteomic analyses in the filamentous fungusSordaria macrospora.In total, we identified 4,193 proteins and 2,489 phosphoproteins, which are represented by 10,635 phosphopeptides. By comparing phosphorylation data from wild-type and mutants, we identified 228 phosphoproteins to be regulated in all three STRIPAK mutants, thus representing potential targets of STRIPAK. To provide an exemplarily functional analysis of a STRIPAK-dependent phosphorylated protein, we selected CLA4, a member of the conserved p21-activated kinase (PAK) family. Functional characterization of the Δcla4 deletion strain showed that CLA4 controls sexual development and polarized growth. To determine the functional relevance of CLA4 phosphorylation and the impact of specific phosphorylation sites on development, we next generated phospho-mimetic and -deficient variants of CLA4. This analysis identified (de)phosphorylation of a highly conserved serine (S685) residue in the catalytic domain of CLA4 as being important for fungal cellular development. Collectively, these analyses significantly contribute to the understanding of the mechanistic function of STRIPAK as a phosphatase and kinase signaling complex.
Formal string instrument training in a class setting enhances cognitive and sensorimotor development of primary school children
Authors: James Clara E. , Zuber Sascha , Dupuis-Lozeron Elise , Abdili Laura , Gervaise Diane , Kliegel Matthias 
Published: November 2019

AbstractThis randomized controlled trial shows for the first time that focused musical instrumental practice as compared to traditional sensitization to music provokes robust cognitive and sensorimotor transfer effects. Over the last two years of primary school (10-12-year-old children), sixty-nine children received biweekly musical instruction by professional musicians within the regular school curriculum. The intervention group learned to play string instruments, whereas the control group, peers in parallel classes, was sensitized to music via listening, theory, and some practice. Broad benefits manifested in the intervention group as compared to the control group for working memory, attention, processing speed, cognitive flexibility, matrix reasoning, sensorimotor hand function and bimanual coordination Apparently, learning to play a complex instrument in a dynamic group setting impacts development much stronger than classical sensitization to music. Our results therefore highlight the added value of intensive musical instrumental training in a group setting, encouraging general implementation in public primary schools, better preparing children for secondary school and for daily living activities.Highlights-Music practice produces multiple cognitive transfer effects in school children-Making music causes stronger cognitive benefits than sensitization to music-Music practice in a class setting improves executive functions and abstract thinking-Playing string instruments enhances fine manual dexterity and bimanual coordination
The resolution revolution in cryoEM requires new sample preparation procedures: A rapid pipeline to high resolution maps of yeast FAS
Authors: Joppe Mirko , D’Imprima Edoardo , Salustros Nina , Paithankar Karthik S. , Vonck Janet , Grininger Martin , Kühlbrandt Werner 
Published: November 2019

AbstractSingle-particle electron cryo-microscopy (cryoEM) has undergone a “resolution revolution” that makes it possible to characterize megadalton (MDa) complexes at atomic resolution without crystals. To fully exploit the new opportunities in molecular microscopy, new procedures for the cloning, expression and purification of macromolecular complexes need to be explored. Macromolecular assemblies are often unstable, and invasive construct design or inadequate purification conditions or sample preparation methods can result in disassembly or denaturation. The structure of the 2.6 MDa yeast fatty acid synthase (FAS) has been studied by electron microscopy since the 1960s. We report a new, streamlined protocol for the rapid production of purified yeast FAS for structure determination by high-resolution cryoEM. Together with a companion protocol for preparing cryoEM specimens on a hydrophilized graphene layer, our new protocol has yielded a 3.1 Å map of yeast FAS from 15,000 automatically picked particles within a day. The high map quality enabled us to build a complete atomic model of an intact fungal FAS.
DeepDBP: Deep Neural Networks for Identification of DNA-binding Proteins
Authors: Shadab Shadman , Khan Md Tawab Alam , Neezi Nazia Afrin , Adilina Sheikh , Shatabda Swakkhar 
Published: November 2019

AbstractDNA-Binding proteins (DBP) are associated with many cellular level functions which includes but not limited to body’s defense mechanism and oxygen transportation. They bind DNAs and interact with them. In the past DBPs were identified using experimental lab based methods. However, in the recent years researchers are using supervised learning to identify DBPs solely from protein sequences. In this paper, we apply deep learning methods to identify DBPs. We have proposed two different deep learning based methods for identifying DBPs: DeepDBP-ANN and DeepDBP-CNN. DeepDBP-ANN uses a generated set of features trained on traditional neural network and DeepDBP-CNN uses a pre-learned embedding and Convolutional Neural Network. Both of our proposed methods were able to produce state-of-the-art results when tested on standard benchmark datasets.DeepDBP-ANN had a train accuracy of 99.02% and test accuracy of 82.80%.And DeepDBP-CNN though had train accuracy of 94.32%, it excelled at identifying test instances with 84.31% accuracy. All methods are available codes and methods are available for use at: https://github.com/antorkhan/DNABinding.
The olfactory bulb contributes to the adaptation of odor responses: the input-output transformation
Authors: Storace Douglas A. , Cohen Lawrence B. 
Published: November 2019

AbstractWhile humans and other animals exhibit adaptation to odorants, the neural mechanisms involved in this process are incompletely understood. One possibility is that it primarily occurs as a result of the interactions between odorants and odorant receptors expressed on the olfactory sensory neurons in the olfactory epithelium. In this scenario, adaptation would arise as a peripheral phenomenon transmitted into the brain. An alternative possibility is that adaptation occurs as a result of processing in the brain. Here we asked whether the olfactory bulb, the first stage of olfactory information processing in the brain, is involved in perceptual adaptation. Multicolor imaging was used to simultaneously measure the olfactory receptor nerve terminals (input) and mitral/tufted cell apical dendrites (output) that innervate the olfactory bulb glomerular layer. Repeated odor stimulation of the same concentration resulted in a decline in the output maps, while the input remained relatively stable. The results indicate that the mammalian olfactory bulb participates in olfactory adaptation.
Multiple chromosomal inversions contribute to adaptive divergence of a dune sunflower ecotype
Authors: Huang Kaichi , Andrew Rose L. , Owens Gregory L. , Ostevik Kate L. , Rieseberg Loren H. 
Published: November 2019

ABSTRACTBoth models and case studies suggest that chromosomal inversions can facilitate adaptation and speciation in the presence of gene flow by suppressing recombination between locally adapted alleles. Until recently, however, it has been laborious and time-consuming to identify and genotype inversions in natural populations. Here we apply RAD sequencing data and newly developed population genomic approaches to identify putative inversions that differentiate a sand dune ecotype of the prairie sunflower (Helianthus petiolaris) from populations found on the adjacent sand sheet. We detected seven large genomic regions that exhibit a different population structure than the rest of the genome and that vary in frequency between dune and non-dune populations. These regions also show high linkage disequilibrium and high heterozygosity between, but not within haplotypes, consistent with the behavior of large inversions, an inference subsequently validated in part by comparative genetic mapping. Genome-environment association analyses show that key environmental variables, including vegetation cover and soil nitrogen, are significantly associated with inversions. The inversions co-locate with previously described “islands of differentiation,” and appear to play an important role in adaptive divergence and incipient speciation withinH. petiolaris.
Patient stratification of clear cell renal cell carcinoma using the global transcription factor activity landscape derived from RNA-seq data
Authors: Zhu Yanyan , Cang Shundong , Chen Bowang , Gu Yue , Jiang Miaomiao , Yan Junya , Shao Fengmin , Huang Xiaoyun 
Published: November 2019

AbstractClear cell renal cell carcinoma represents the most common type of kidney cancer. Precision medicine approach to ccRCC requires an accurate stratification of patients that can predict prognosis and guide therapeutic decision. Transcription factors are implicated in the initiation and progression of human carcinogenesis. However, no comprehensive analysis of transcription factor activity has been proposed so far to realize patient stratification. Here we propose a novel approach to determine the subtypes of ccRCC patients based on global transcription factor activity landscape. Using the TCGA cohort dataset, we identified different subtypes that have distinct upregulated biomarkers and altered biological pathways. More important, this subtype information can be used to predict the overall survival of ccRCC patients. Our results suggest that transcription factor activity can be harnessed to perform patient stratification.
Biosynthetic engineering of the antifungal, anti-MRSA auroramycin
Authors: Yeo Wan Lin , Heng Elena , Tan Lee Ling , Lim Yi Wee , Ching Kuan Chieh , Tsai De-Juin , Jhang Yi Wun , Lauderdale Tsai-Ling , Shia Kak-Shan , Zhao Huimin , Ang Ee Lui , Zhang Mingzi M. , Lim Yee Hwee , Wong Fong T. 
Published: November 2019

AbstractUsing an established CRISPR-Cas mediated genome editing technique for streptomycetes, we explored the combinatorial biosynthesis potential of the auroramycin biosynthetic gene cluster in Streptomyces roseoporous. Auroramycin is a potent anti-MRSA polyene macrolactam. In addition, it also displays antifungal activities, which is unique among structurally similar polyene macrolactams, such as incednine and silvalactam. In this work, we employed different engineering strategies to target glycosylation and acylation biosynthetic machineries within its recently elucidated biosynthetic pathway. Six auroramycin analogs with variations in C-, N-methylation, hydroxylation and extender units incorporation were produced and characterized. By comparing the bioactivity profiles of these analogs, we determined that unique disaccharide motif of auroramycin is essential for its antimicrobial bioactivity. We further demonstrated that C-methylation of the 3, 5-epi-lemonose unit, which is unique among structurally similar polyene macrolactams, is key to its antifungal activity.
Redefining Interleukin 11 as a regeneration-limiting hepatotoxin
Authors: Widjaja Anissa A. , Dong Jinrui , Adami Eleonora , Viswanathan Sivakumar , Ng Benjamin , Singh Brijesh K. , Lim Wei Wen , Zhou Jin , Pakkiri Leroy S. , Shekeran Shamini G. , Tan Jessie , Lim Sze Yun , Wang Mao , Holgate Robert , Hearn Arron , Yen Paul M. , Chothani Sonia P. , Felkin Leanne E. , Dear James W. , Drum Chester L. , Schafer Sebastian , Cook Stuart A. 
Published: November 2019

AbstractAcetaminophen (APAP) overdose is a leading cause of untreatable liver failure. In the mouse model of APAP-induced liver injury (AILI), the administration of recombinant human interleukin 11 (rhIL11) is protective. Here we show that the beneficial effect of rhIL11 in the mouse is due to its unexpected and paradoxical inhibition of endogenous mouse IL11 activity. Contrary to the accepted paradigm IL11 is a potent hepatotoxin across species, which is secreted from damaged hepatocytes to drive an autocrine loop of NOX4 and JNK-dependent apoptosis. Mice with hepatocyte-specific Il11 expression spontaneously develop liver failure whereas those with Il11ra1 deletion are remarkably protected from AILI. Neutralizing anti-IL11R antibodies administered to moribund mice 10 hours following a lethal APAP overdose results in 90% survival that is associated with very large liver regeneration. Our data overturn a misconception, identify a new disease mechanism and suggest IL11 as a therapeutic target for liver regeneration.
The Mammalian Cytosolic Thioredoxin Reductase Pathway Acts via a Membrane Protein to Reduce ER-localised Proteins
Authors: Cao Xiaofei , Lilla Sergio , Cao Zhenbo , Pringle Marie Anne , Oka Ojore BV , Robinson Philip J , Szmaja Tomasz , van Lith Marcel , Zanivan Sara , Bulleid Neil J 
Published: November 2019

SummaryFolding of proteins entering the mammalian secretory pathway requires the insertion of the correct disulfide bonds. Disulfide formation involves both an oxidative pathway for their insertion and a reductive pathway to remove incorrectly formed disulfides. Reduction of these disulfides is critical for correct folding and degradation of misfolded proteins. Previously, we showed that the reductive pathway is driven by NADPH generated in the cytosol. Here, by reconstituting the pathway using purified proteins and ER microsomal membranes, we demonstrate that the thioredoxin reductase system provides the minimal cytosolic components required for reducing proteins within the ER lumen. In particular, saturation of the pathway and its protease sensitivity demonstrates the requirement for a membrane protein to shuttle electrons from the cytosol to the ER lumen. These results provide compelling evidence for the critical role of the cytosol in regulating ER redox homeostasis to ensure correct protein folding and to facilitate the degradation of misfolded ER proteins.