bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clozapine Use in a Cohort of First-Episode Psychosis
Authors: Doyle Roisin , Behan Caragh , O'Keeffe Donal , Masterson Sarah , Kinsella Anthony , Kelly Aine , Sheridan Ann , Keating Dolores , Hynes Caroline , Madigan Kevin , Lawlor Elizabeth , Clarke Mary 
Published: June 2017

Abstract

Purpose/Background
For approximately one third of individuals treated for psychosis or schizophrenia, antipsychotic medications will have little or no therapeutic benefit. Clozapine remains the sole medication approved for treatment-resistant schizophrenia, and studies have demonstrated its superior efficacy in reducing psychotic symptoms.

Methods/Procedures
Data were collected from the medical records of people who originally presented with a first-episode psychosis between 1995 and 1999 (N = 171). Data were obtained from first presentation up to December 31, 2013 or until the patient was discharged or transferred. Information on service use and physical health was gathered using a data collection template designed specifically for this audit.

Findings/Results
Twenty-eight (16.3%) of the cohort were prescribed clozapine. Data were available for 24 individuals. Of this clozapine subsample, the mean age at baseline was 23.11 (SD = 4.58); 82.14% (n = 23) were male; and 82.14% (n = 23) had a baseline diagnosis of schizophrenia. The mean time to first trial of clozapine was 6.7 years. The mean number of antipsychotics prescribed before clozapine trial was 4.85. After the initiation of clozapine, the mean number of hospital admissions reduced from 6.04 per year to 0.88 per year.

Implications/Conclusions
Nearly 1 in 5 of the original cohort was considered to have a suboptimal response to trials of antipsychotic medication. The use of clozapine for treatment-resistant schizophrenia is underutilized, and better understanding of the barriers to prescribing clozapine is necessary given the implications for patient's quality of life and hospital admission rates. Physical health data further emphasizes the importance of physical health monitoring in this vulnerable population.
Early Cutaneous Signs of Neurofibromatosis Type 1
Authors: Sirvaitis Skirmante , Sirvaitis Ringaile , Perusek Thomas , Garcia-Zuazaga Jorge 
Published: June 2017

ABSTRACT

Purpose
Neurofibromatosis type 1 (NF1), also known as von Recklinghausen disease, is a multisystem disease with cutaneous symptoms occurring from birth to adulthood. It is a disorder with multiple malformations and tumors involving the skin, nervous system, and skeleton. The purpose of this report is to provide dermatology nurse practitioners with an unusual case involving axillary freckling as well as evidence-based guidance for the diagnosis and management of cutaneous NF1 symptoms.

Relevance
NF1 affects approximately 1 in 3,500 people. There is an equal incidence in men and women as well as in all races and ethnic groups. Most of the time, patients initially present to a primary care provider; however, patients may also present to a dermatology practice. It is indispensable for dermatology nurse practitioners to recognize early manifestations of this disorder so that the patient may be referred to seek specialized care and decrease the chance of disease complications.

Essential Points
This report provides a case of NF1 as well as background, pathophysiology, diagnostic criteria, differential diagnoses, prognosis, and treatment of cutaneous manifestations of this disease.
Oxygen–Flow–Pressure Targets for Resuscitation in Critical Hemodynamic Therapy
Authors: He Huaiwu , Long Yun , Zhou Xiang , Wang Xiaoting , Zhang Hongmin , Chai Wenzhao , Cui Na , Wang Hao , Liu Dawei 
Published: June 2017

ABSTRACT
Far from traditional “vital signs,” the field of hemodynamic monitoring (HM) is rapidly developing. However, it is also easy to misunderstand hemodynamic therapy as merely HM and some concrete bundles or guidelines for circulation support. Here, we describe the concept of “critical hemodynamic therapy” and clarify the concepts of the “therapeutic target” and “therapeutic endpoint” in clinical practice. Three main targets (oxygen delivery, blood flow, perfusion pressure) for resuscitation are reviewed in critically ill patients according to the sepsis guidelines and hemodynamic consensus. ScvO2 at least 70% has not been recommended as a directed target for initial resuscitation, and the directed target of mean arterial pressure (MAP) still is 65 mmHg. Moreover, the individual MAP target is underlined, and using flow-dependent monitoring to guide fluid infusion is recommended. The flow-directed target for fluid infusion might be a priority, but it remains controversial in resuscitation. The interpretation of these targets is necessary for adequate resuscitation and the correction of tissue hypoxia. The incoherence phenomenon of resuscitation (macrocirculation and microcirculation, tissue perfusion, and cellular oxygen utilization) is gaining increased attention, and early identification of these incoherences might be helpful to reduce the risk of over-resuscitation.
Ultrasonographic Evaluation of the Urethral Rhabdosphincter Morphology in Female Patients With Urodynamic Stress Incontinence
Authors: Zacharakis Dimitrios , Grigoriadis Themos , Pitsouni Eleni , Domali Ekaterini , Protopapas Athanasios , Athanasiou Stavros 
Published: June 2017

Objectives
During the last 2 decades, ultrasonography has been proposed for the morphologic evaluation of the urethral rhabdosphincter. The aims of this study were to evaluate the feasibility of a simple sonographic technique for the assessment of the urethral rhabdosphincter morphology by using a 2-dimensional (2D) transvaginal transducer and to evaluate any associations between the sonographic parameters of rhabdosphincter morphology with the presence of urodynamic stress incontinence (USI).

Methods
This was a prospective study of women who underwent urodynamic studies and an introital 2D ultrasonography and divided in 2 groups based on the presence or absence of USI. Measurements included rhabdosphincter thickness at the 3-o’clock (right) and 9-o’clock (left) positions and the rhabdosphincter outer (Π) and inner circumference (π). Based on these values, the mean thickness of the rhabdosphincter (R + L / 2), the rhabdosphincter differential perimeter (Π − π), and area (A − α) were also calculated.

Results
Statistical analysis showed that women with a rhabdosphincter area of less than 0.65 cm2, mean thickness of less than 0.24 cm, and differential perimeter of less than 1.08 cm had 3.98, 5.67, and 5.41 times greater odds for USI, respectively. Receiver operating characteristic curve analysis results showed that the optimal cutoff values for the prediction of USI from rhabdosphincter thickness, differential perimeter. and surface area were 0.24 cm (79.6% sensitivity, 63.4% specificity), 1.08 cm (70.8% sensitivity and 69.1% specificity), and 0.65 cm2 (71.9% sensitivity, 57.1% specificity), respectively.

Conclusions
Introital ultrasonography with a 2D transvaginal probe allowed the visualization of the urethral rhabdosphincter morphology in greater than 90% of the cases. Sonographic measurements showed that patients with USI had a thinner urethral rhabdosphincter than did women with a normal sphincteric mechanism.
Correction of copy number induced false positives in CRISPR screens
Authors: de Weck Antoine , Golji Javad , Jones Mike , Korn Joshua , Billy Eric , McDonald E. Robert , Schmelzle Tobias , Bitter Hans , Kauffmann Audrey 
Published: June 2017

AbstractCell autonomous cancer dependencies are now routinely identified using CRISPR loss-of-function screens. However, a bias exists that makes it difficult to assess the true essentiality of genes located in amplicons, since the entire amplified region can exhibit lethal scores. These false-positive hits can either be discarded from further analysis, which in cancer models can represent a significant number of hits, or methods can be developed to rescue the true-positives within amplified regions. We propose two methods to rescue true positive hits in amplified regions by correcting for this copy number artefact. The Local Drop Out (LDO) method uses the relative lethality scores within genomic regions to assess true essentiality and does not require additional orthogonal data (e.g. copy number value). LDO is meant to be used in screens covering a dense region of the genome (e.g. a whole chromosome or the whole genome). The General Additive Model (GAM) method models the screening data as a function of the known copy number values and removes the systematic effect from the measured lethality. GAM does not require the same density as LDO, but does require prior knowledge of the copy number values. Both methods have been developed with single sample experiments in mind so that the correction can be applied even in smaller screens. Here we demonstrate the efficacy of both methods at removing the copy number effect and rescuing hits from some of the amplified regions. We estimate a 70-80% decrease of false positive hits in regions of high copy number with either method.
Online, Interactive Tutorials Provide Effective Instruction in Science Process Skills
Authors: Kramer Maxwell , Olson Dalay , Walker J.D. 
Published: June 2017

AbstractExplicit emphasis on teaching science process skills leads to both gains in the skills themselves and, strikingly, deeper understanding of content. Here, we created and tested a series of online, interactive tutorials with the goal of helping undergraduate students develop science process skills. We designed the tutorials in accordance with evidence-based multimedia design principles and student feedback from usability testing. We then tested the efficacy of the tutorials in an introductory undergraduate biology class. Based on a multivariate ordinary least squares regression model, students that received the tutorials are predicted to score 0.824 points higher on a 15 point science process skill assessment than their peers that received traditional textbook instruction on the same topic. This moderate but significant impact indicates that well designed online tutorials can be more effective than traditional ways of teaching science process skills to undergraduate students. We also found trends that suggest the tutorials are especially effective for non-native English speaking students. However, due to a limited sample size, we were unable to confirm that these trends occurred due to more than just variation in the sampled student group.
The grayling genome reveals selection on gene expression regulation after whole genome duplication
Authors: Varadharajan Srinidhi , Sandve Simen R. , Gillard Gareth B. , Tørresen Ole K. , Mulugeta Teshome D. , Hvidsten Torgeir R. , Lien Sigbjørn , Vøllestad Leif Asbjørn , Jentoft Sissel , Nederbragt Alexander J. , Jakobsen Kjetill S. 
Published: June 2017

AbstractWhole genome duplication (WGD) has been a major evolutionary driver of increased genomic complexity in vertebrates. One such event occurred in the salmonid family ~80 million years ago (Ss4R) giving rise to a plethora of structural and regulatory duplicate-driven divergence, making salmonids an exemplary system to investigate the evolutionary consequences of WGD. Here, we present a draft genome assembly of European grayling(Thymallus thymallus)and use this in a comparative framework to study evolution of gene regulation following WGD. Among the Ss4R duplicates identified in European grayling and Atlantic salmon(Salmo salar), one third reflect non-neutral tissue expression evolution, with strong purifying selection, maintained over ~50 million years. Of these, the majority reflect conserved tissue regulation under strong selective constraints related to brain and neural-related functions, as well as higher-order protein-protein interactions. A small subset of the duplicates has evolved tissue regulatory expression divergence in a common ancestor, which have been subsequently conserved in both lineages, suggestive of adaptive divergence following WGD. These candidates for adaptive tissue expression divergence have elevated rates of protein coding- and promoter-sequence evolution and are enriched for immune- and lipid metabolism ontology terms. Lastly, lineage-specific duplicate divergence points towards underlying differences in adaptive pressures on expression regulation in the non-anadromous grayling versus the anadromous Atlantic salmon.Our findings enhance our understanding of the role of WGD in genome evolution and highlights cases of regulatory divergence of Ss4R duplicates, possibly related to a niche shift in early salmonid evolution.
Mapping-free variant calling using haplotype reconstruction from k-mer frequencies
Authors: Audano Peter , Ravishankar Shashidhar , Vannberg Fredrik 
Published: June 2017

1AbstractMotivationThe standard protocol for detecting variation in DNA is to map millions of short sequence reads to a known reference and find loci that differ. While this approach works well, it cannot be applied where the sample contains dense variants or is too distant from known references.De novoassembly or hybrid methods can recover genomic variation, but the cost of computation is often much higher. We developed a novel k-mer algorithm and software implementation, Kestrel, capable of characterizing densely-packed SNPs and large indels without mapping, assembly, or de Bruijn graphs.ResultsWhen applied to mosaic penicillin binding protein (PBP) genes inStreptococcus pneumoniae,we found near perfect concordance with assembled contigs at a fraction of the CPU time. Multilocus sequence typing (MLST) with this approach was able to bypassde novoassemblies. Kestrel has a very low false-positive rate when calling variants over the whole genome, but limitations of a purely k-mer based approach affect sensitivity.AvailabilitySource code and documentation for a Java implementation of Kestrel can be found athttps://github.com/paudano/kestrel. All test code for this publication is located athttps://github.com/paudano/kescases.Contactpaudano@gatech.edu,fredrik.vannberg@biology.gatech.edu
Low-complexity domains adhere by reversible amyloid-like interactions between kinked β-sheets
Authors: Hughes Michael P. , Sawaya Michael R. , Goldschmidt Lukasz , Rodriguez Jose A. , Cascio Duilio , Gonen Tamir , Eisenberg David S. 
Published: June 2017

AbstractControl of metabolism by compartmentation is a widespread feature of higher cells. Recent studies have focused on dynamic intracellular bodies such as stress granules, P-bodies, nucleoli, and metabolic puncta. These bodies appear as separate phases, some containing reversible, amyloid-like fibrils formed by interactions of low-complexity protein domains. Here we report five atomic structures of segments of low-complexity domains from granule-forming proteins, one determined to 1.1 Å resolution by micro-electron diffraction. Four of these interacting protein segments show common characteristics, all in contrast to pathogenic amyloid: kinked peptide backbones, small surface areas of interaction, and predominate attractions between aromatic side-chains. By computationally threading the human proteome on three of our kinked structures, we identified hundreds of low-complexity segments potentially capable of forming such reversible interactions. These segments are found in proteins as diverse as RNA binders, nuclear pore proteins, keratins, and cornified envelope proteins, consistent with the capacity of cells to form a wide variety of dynamic intracellular bodies.One Sentence SummaryAtomic structures show transient membraneless organelles of cells formed by a new type of protein interaction akin to pathogenic amyloid fibrils.
Genomic variations in paired normal controls for lung adenocarcinomas
Authors: Qu Li-Wei , Zhou Bo , Wang Gui-Zhen , Chen Ying , Zhou Guang-Biao 
Published: June 2017

AbstractSomatic genomic mutations in lung adenocarcinomas (LUADs) have been extensively dissected, but whether the counterpart normal lung tissues that are exposed to ambient air or tobacco smoke as the tumor tissues do, harbor genomic variations, remains unclear. Here, the genome of normal lung tissues and paired tumors of 11 patients with LUAD were sequenced, the genome sequences of counterpart normal controls (CNCs) and tumor tissues of 513 patients were downloaded from TCGA database and analyzed. In the initial screening, genomic alterations were identified in the “normal” lung tissues and verified by Sanger capillary sequencing. In CNCs of TCGA datasets, a mean of 0.2721 exonic variations/Mb and 5.2885 altered genes per sample were uncovered. The C:G→T:A transitions, a signature of tobacco carcinogen N-methyl-N-nitro-N-nitrosoguanidine, were the predominant nucleotide changes in CNCs. 16 genes had a variant rate of more than 2%, and CNC variations inMUC5B,ZXDB,PLIN4,CCDC144NL,CNTNAP3B, andCCDC180were associated with poor prognosis whereas alterations inCHD3andKRTAP5-5were associated with favorable clinical outcome of the patients. This study identified the genomic alterations in CNC samples of LUADs, and further highlighted the DNA damage effect of tobacco on lung epithelial cells.
Genome reconstruction and characterisation of extensively drug-resistant bacterial pathogens through direct metagenomic sequencing of human faeces
Authors: Mu Andre , Kwong Jason C. , Isles Nicole S. , Gonçalves da Silva Anders , Schultz Mark B. , Ballard Susan A. , Carter Glen P. , Williamson Deborah A. , Seemann Torsten , Stinear Timothy P. , Howden Benjamin P. 
Published: June 2017

AbstractWhole-genome sequencing of microbial pathogens is revolutionising modern approaches to outbreaks of infectious diseases and is reliant upon organism culture. Culture-independent methods have shown promise in identifying pathogens, but high level reconstruction of microbial genomes from microbiologically complex samples for more in-depth analyses remains a challenge. Here, using metagenomic sequencing of a human faecal sample and analysis by tetranucleotide frequency profiling projected onto emergent self-organising maps, we were able to reconstruct the underlying populations of two extensively-drug resistant pathogens,Klebsiella pneumoniaecarbapenemase (KPC)-producingKlebsiella pneumoniaeand vancomycin-resistantEnterococcus faecium.From these genomes, we were able to ascertain molecular typing results, such as MLST, and identify highly discriminatory mutations in the metagenome to distinguish closely related strains. These proof-of-principle results demonstrate the utility of clinical sample metagenomics to recover sequences of important drug-resistant bacteria and application of the approach in outbreak investigations, independent of the need to culture the organisms.
UFBoot2: Improving the Ultrafast Bootstrap Approximation
Authors: Hoang Diep Thi , Chernomor Olga , Haeseler Arndt von , Minh Bui Quang , Vinh Le Sy 
Published: June 2017

AbstractThe standard bootstrap (SBS), despite being computationally intensive, is widely used in maximum likelihood phylogenetic analyses. We recently proposed the ultrafast bootstrap approximation (UFBoot) to reduce computing time while achieving more unbiased branch supports than SBS under mild model violations. UFBoot has been steadily adopted as an efficient alternative to SBS and other bootstrap approaches.Here, we present UFBoot2, which substantially accelerates UFBoot and reduces the risk of overestimating branch supports due to polytomies or severe model violations. Additionally, UFBoot2 provides suitable bootstrap resampling strategies for phylogenomic data. UFBoot2 is 778 and 8.4 times (median) faster than SBS and RAxML rapid bootstrap on tested datasets, respectively. UFBoot2 is implemented in the IQ-TREE software package version 1.6 and freely available athttp://www.iqtree.org.
Brazilian Air Force operations in disaster response – a process analysis
Authors: da Costa Natália de Brito Oliveira Luiz , Fontainha Tharcisio Cotta , Leiras Adriana 
Published: June 2017

Purpose
The purpose of this paper is to analyze the status of the current Brazilian regulations regarding the Brazilian Air Force (BAF) operations during disaster response compared with the real BAF operations in the landslides that affected the state of Rio de Janeiro, Brazil, in 2011. This analysis reveals the evolutions and challenges that warrant further discussion, even six years after the deadliest disaster in recent Brazilian history.

Design/methodology/approach
The research is structured using a case study method and a process approach. The data gathered from official BAF reports and professionals and BAF regulations are compared using a theoretical reference process model as a guide.

Findings
The spread of documentations and laws that prescribe the BAF operations during disaster response limit the replication of BAF standards in future disasters. Among the 96 processes described in the theoretical reference process model, 12 processes that are identified in the BAF reports and interviews that address the response to the Rio landslides of 2011 remain unaddressed in the BAF regulations. Considering the BAF expertise, three additional processes are suggested for future consideration in the reference process model that guided this research.

Research limitations/implications
This paper does not discuss the collaborative perspective of BAF operations with other military forces and stakeholders in disaster response.

Practical implications
The findings are indications of improvement in BAF regulations.

Originality/value
In addition to providing an analysis of the military force operations in response to a massive disaster, this paper can also serve as a reference for a benchmark discussion of military operations in disaster response.
The impact research of online reviews’ sentiment polarity presentation on consumer purchase decision
Authors: Wang Qi , Wang Lin , Zhang Xiaohang , Mao Yunxia , Wang Peng 
Published: June 2017

Purpose
Because online shopping is risky, there is a strong need to develop better presentation of online reviews, which may reduce the perceived risk and create more pleasurable shopping experiences. To test the impact of online reviews’ sentiment polarity presentation, the purpose of this paper is to adopt a scenario experiment to study consumers’ decision-making process under the two scenarios of mixed presentation and classified presentation of online reviews collected from Jingdong.com in China: focusing on the comparative analysis on the differences of the consumers’ perceived risk, purchase intention and purchase delay, and further studying the interaction effect of involvement and online reviews’ sentiment polarity presentation.

Design/methodology/approach
This paper employed a 2×2 factorial experiment to test the hypothesis. The experimental design is divided into four groups: 2 (online reviews’ sentiment polarity presentation: mixed presentation vs classified presentation) × 2 (involvement: low vs high), each of which contains 90 samples. Through the data analysis, the main effect, mediation effect and moderating effect were examined.

Findings
The results show that compared with mixed presentation, classified presentation can reduce purchase intention and increase purchase delay due to the existence of loss aversion and availability heuristic. Furthermore, the paper also confirms that there is a significant interaction effect between involvement and online reviews’ sentiment polarity presentation.

Originality/value
The existing research pays less attention to the impact of online reviews presentation on consumers’ decision making, especially the lack of discussion on the interaction effect between involvement and online reviews presentation. For this reason, this paper proposes a problem, which concerns whether mixed presentation and classified presentation of online reviews will affect consumers’ decision making differently.