bluuebunny/crossref_metadata_2025_split huggingface dataset:
Roles of Family Caregivers and Perceived Burden When Caring for Hospitalized Adult Cancer Patients
Authors: Muliira Joshua K. , Kizza Irene B. , Nakitende Gloria 
Published: March 2018

Background
Family caregivers (FCGs) of adult cancer patients (ACPs) are typically involved in the entire trajectory of cancer disease, from diagnosis to survivorship or end of life. In developing countries, FCGs are more intensely involved in the process of providing care to the hospitalized ACPs because of lack of adequate cancer care resources. Active performance of tasks to meet the needs of ACPs in the hospital setting is likely to elicit significant caregiver burden.

Objective
The aim of this study was to explore the tasks performed and the caregiver burden experienced by FCGs of hospitalized ACPs in a sub-Saharan country.

Methods
A cross-sectional descriptive design was used to collect data from 168 FCGs of ACPs. The Caregiver Burden Scale was used to measure burden.

Results
The most common cancer diagnosis in male and female ACPs was Kaposi's sarcoma (32.1%) and breast cancer (37.9%), respectively. The tasks regularly performed by most FCGs for the ACPs were providing emotional support (79.8%), feeding (68.5%), transporting to other appointments (62.5%), preparing meals (55%), and giving medications (46.4%). Most FCGs (75%) were experiencing severe or very severe general caregiver burden. The dimensions of caregiver burden that were most severely impacted were general strain (70.6%), disappointment (85.8%), and isolation (72%). Predictors of caregiver burden are reported.

Conclusion
Family caregivers of hospitalized ACPs experience severe caregiver burden. The main forms of burden experienced were general strain, disappointment, and isolation.

Implications for Practice
Cancer care services in developing countries should be strengthened with services that address FCGs' emotional needs and human resources to curtail the strain imposed on FCGs.
Longitudinal Clival Fracture in a Child
Authors: Gulen Bedia , Serinken Mustafa , Karcioglu Ozgur , Kucukdagli Okkes Taha 
Published: March 2018

Abstract
Clival fracture is a rare and serious injury, which mostly results in the death of the victim before reaching the hospital. The entity is hardly diagnosed in the early phase because of high mortality rates and deficiencies in completion of radiological imaging. The incidence of diagnoses increased year by year after the usage of computed tomography gained widespread availability. In this article, we aimed to present radiological and clinical characteristics of a 5-year-old patient brought to the emergency department after a motor vehicle accident. The most current recommendations with regard to the management of clival fracture of a pediatric patient are also discussed.
Pathways to Academic Leadership in Plastic Surgery: A Nationwide Survey of Program Directors, Division Chiefs, and Department Chairs of Plastic Surgery
Authors: Fishman Jordan E. , Pang John Henry Y. , Losee Joseph E. , Rubin J. Peter , Nguyen Vu T. 
Published: March 2018

Background:
Many aspire to leadership in academic plastic surgery yet there is no well-documented pathway.

Methods:
Information regarding plastic surgery residencies and program directors was obtained from the American Medical Association’s FREIDA database. The division chief or department chair (academic head) of every academic plastic surgery program was identified. One Internet-based survey was distributed to academic heads; another, to program directors.

Results:
Ninety academic heads were identified, 35 of whom also serve as program director. Sixty-seven unique program directors were identified. There was a 51 percent academic head response rate and a 65 percent program director response rate. Academic plastic surgery is overwhelmingly administered by midcareer men. The average program director was appointed at age 45 and has served for 7 years. She or he was trained through the independent track, completed additional training in hand surgery, and is a full professor. She or he publishes two or three peer-reviewed manuscripts per year and spends 9 hours per week in administration. The average academic head was appointed at age 45 and has held the position for 12 years. She or he was trained in the independent model, completed fellowship training, and is a full professor. She or he publishes five peer-reviewed manuscripts per year and spends 12 hours per week involved in administration.

Conclusions:
Program directors and academic heads serve nonoverlapping roles. Few program directors will advance to the role of academic head. Successful applicants to the program director position often serve as an associate program director and are seen as motivated resident educators. In contrast, those faculty members selected for the academic head role are academically accomplished administrators with business acumen.
Comparison of Genotypic and Phenotypic Correlations: Cheverud’s Conjecture in Humans
Authors: Sodini Sebastian M. , Kemper Kathryn E. , Wray Naomi R. , Trzaskowski Maciej 
Published: March 2018

AbstractAccurate estimation of genetic correlation requires large sample sizes and access to genetically informative data, which are not always available. Accordingly, phenotypic correlations are often assumed to reflect genotypic correlations in evolutionary biology. Cheverud’s conjecture asserts that the use of phenotypic correlations as proxies for genetic correlations is appropriate. Empirical evidence of the conjecture has been found across plant and animal species, with results suggesting that there is indeed a robust relationship between the two. Here, we investigate the conjecture in human populations, an analysis made possible by recent developments in availability of human genomic data and computing resources. A sample of 108,035 British European individuals from the UK Biobank was split equally into discovery and replication datasets. 17 traits were selected based on sample size, distribution and heritability. Genetic correlations were calculated using linkage disequilibrium score regression applied to the genome-wide association summary statistics of pairs of traits, and compared within and across datasets. Strong and significant correlations were found for the between-dataset comparison, suggesting that the genetic correlations from one independent sample were able to predict the phenotypic correlations from another independent sample within the same population. Designating the selected traits as morphological or non-morphological indicated little difference in correlation. The results of this study support the existence of a relationship between genetic and phenotypic correlations in humans. This finding is of specific interest in anthropological studies, which use measured phenotypic correlations to make inferences about the genetics of ancient human populations.
Emergent sub-population behavior uncovered with a community dynamic metabolic model ofEscherichia colidiauxic growth
Authors: Succurro Antonella , Segrè Daniel , Ebenhöh Oliver 
Published: March 2018

AbstractMicrobes have adapted to greatly variable environments in order to survive both short-term perturbations and permanent changes. A classical, yet still actively studied example of adaptation to dynamic environments is the diauxic shift ofEscherichia coli, in which cells grow on glucose until its exhaustion, and then transition to using previously secreted acetate. Here we tested different hypotheses concerning the nature of this transition by using dynamic metabolic modeling. Towards this goal, we developed an open source modeling framework integrating dynamic models (ordinary differential equation systems) with structural models (metabolic networks), which can take into account the behavior of multiple sub-populations, and smooth ux transitions between different time points. We used this framework to model the diauxic shift, first with a singleE. colimodel whose metabolic state represents the overall population average, and then with a community of two sub-populations each growing exclusively on one carbon source (glucose or acetate). After introducing an environment-dependent transition function that determines the balance between different sub-populations, our model generates predictions that are in strong agreement with published data. We thus support recent experimental evidence that, rather than a coordinated metabolic shift, diauxie would be the emergent pattern of individual cells differentiating for optimal growth on different sub-strates. This work offers a new perspective on the use of dynamic metabolic modeling to investigate population heterogeneity dynamics. The proposed approach can easily be applied to other biological systems composed of metabolically distinct, interconverting sub-populations, and could be extended to include single-cell level stochasticity.ImportanceEscherichia colidiauxie is a fundamental example of metabolic adaptation that is not yet completely understood. Further insight into this process can be achieved by integrating experimental and computational modeling methods. We present a dynamic metabolic modeling approach that captures diauxie as an emergent property of sub-population dynamics inE. colimonocultures. Without fine tuning the parameters of theE. colicore metabolic model, we achieve good agreement with published data. Our results suggest that single-organism metabolic models can only approximate the average metabolic state of a population, therefore offering a new perspective on the use of such modeling approaches. The open source modeling framework we provide can be applied to model general sub-population systems in more complex environments, and can be extended to include single-cell level stochasticity.
FIT2 is a lipid phosphate phosphatase crucial for endoplasmic reticulum homeostasis
Authors: Becuwe Michel , Bond Laura M. , Mejhert Niklas , Boland Sebastian , Elliott Shane D. , Cicconet Marcelo , Liu Xinran N. , Graham Morven M. , Walther Tobias C. , Farese Robert V. 
Published: March 2018

SUMMARYThe endoplasmic reticulum (ER) protein Fat-Induced Transcript 2 (FIT2) has emerged as a key factor in lipid droplet (LD) formation, although its molecular function is unknown. Highlighting its importance, FIT2 orthologs are essential in worms and mice, and FIT2 deficiency causes a deafness/dystonia syndrome in humans. Here we show that FIT2 is a lipid phosphate phosphatase (LPP) enzyme that is required for maintaining the normal structure of the ER. Recombinant FIT2 exhibits LPP activityin vitroand loss of this activity in cells leads to ER membrane morphological changes and ER stress. Defects in LD formation in FIT2 depletion appear to be secondary to membrane lipid abnormalities, possibly due to alterations in phospholipids required for coating forming LDs. Our findings uncover an enzymatic role for FIT2 in ER lipid metabolism that is crucial for ER membrane homeostasis.
Locality Sensitive Imputation for Single-Cell RNA-Seq Data
Authors: Moussa Marmar , Măndoiu Ion I. 
Published: March 2018

AbstractOne of the most notable challenges in single cell RNA-Seq data analysis is the so called drop-out effect, where only a fraction of the transcriptome of each cell is captured. The random nature of drop-outs, however, makes it possible to consider imputation methods as means of correcting for drop-outs. In this paper we study some existing scRNA-Seq imputation methods and propose a novel iterative imputation approach based on efficiently computing highly similar cells. We then present the results of a comprehensive assessment of existing and proposed methods on real scRNA-Seq datasets with varying per cell sequencing depth.
Maturing Mycobacterial Peptidoglycan Requires Non-canonical Crosslinks to Maintain Shape
Authors: Baranowski Catherine , Welsh Michael A. , Sham Lok-To , Eskandarian Haig A. , Lim Hoong C. , Kieser Karen J. , Wagner Jeffrey C. , McKinney John D. , Fantner Georg E. , Ioerger Thomas R. , Walker Suzanne , Bernhardt Thomas G. , Rubin Eric J. , Rego E. Hesper 
Published: March 2018

AbstractIn most well studied rod-shaped bacteria, peptidoglycan is primarily crosslinked by penicillin binding proteins (PBPs). However, in mycobacteria, L,D-transpeptidase (LDT)-mediated crosslinks are highly abundant. To elucidate the role of these unusual crosslinks, we characterized mycobacterial cells lacking all LDTs. We find that LDT-mediated crosslinks are required for rod shape maintenance specifically at sites of aging cell wall, a byproduct of polar elongation. Asymmetric polar growth leads to a non-uniform distribution of these two types of crosslinks in a single cell. Consequently, in the absence of LDT-mediated crosslinks, PBP-catalyzed crosslinks become more important. Because of this,Mycobacterium tuberculosis(Mtb) is more rapidly killed using a combination of drugs capable of PBP- and LDT-inhibition. Thus, knowledge about the single-cell distribution of drug targets can be exploited to more effectively treat this pathogen.
Isw2 and Ino80 chromatin remodeling factors regulate chromatin, replication, and copy number at the yeast ribosomal DNA locus
Authors: Cutler Sam , Lee Laura J , Tsukiyama Toshio 
Published: March 2018

AbstractIn the budding yeastSaccharomyces cerevisiae, ribosomal RNA genes are encoded in a highly repetitive tandem array referred to as the ribosomal DNA (rDNA) locus. The yeast rDNA is the site of a diverse set of DNA-dependent processes, including transcription of ribosomal RNAs by RNA Polymerases I and III, transcription of non-coding RNAs by RNA Polymerase II, DNA replication initiation, replication fork blocking, and recombination-mediated regulation of rDNA repeat copy number. All of this takes place in the context of chromatin, but relatively little is known about the roles played by ATP-dependent chromatin remodeling factors at the yeast rDNA. In this work, we report that the Isw2 and Ino80 chromatin remodeling factors are targeted to this highly repetitive locus. We characterize for the first time their function in modifying local chromatin structure, finding that loss of these factors affects the occupancy of nucleosomes in the 35S ribosomal RNA gene and the positioning of nucleosomes flanking the ribosomal origin of replication. In addition, we report that Isw2 and Ino80 promote efficient firing of the ribosomal origin of replication and facilitate the regulated increase of rDNA repeat copy number. This work significantly expands our understanding of the importance of ATP-dependent chromatin remodeling for rDNA biology.Author SummaryTo satisfy high cellular demand for ribosomes, genomes contain many copies of the genes encoding the RNA components of ribosomes. In the budding yeastSaccharomyces cerevisiae, these ribosomal RNA genes are located in the “ribosomal DNA locus”, a highly repetitive array that contains approximately 150 copies of the same unit, in contrast to the single copies that suffice for most genes. This repetitive quality creates unique regulatory needs. Chromatin structure, the packaging and organization of DNA, is a critical determinant of DNA-dependent processes throughout the genome. ATP-dependent chromatin remodeling factors are important regulators of chromatin structure, and yet relatively little is known about how members of this class of protein affect DNA organization or behavior at the rDNA. In this work, we show that the Isw2 and Ino80 chromatin remodeling factors regulate two features of chromatin structure at the rDNA, the occupancy and the positioning of nucleosomes. In addition, we find that these factors regulate two critical processes that function uniquely at this locus: DNA replication originating from within the rDNA array, and the regulated increase of rDNA repeat copy number.
HDAC11 Suppresses the Thermogenic Program of Adipose Tissue via BRD2
Authors: Bagchi Rushita A. , Ferguson Bradley S. , Stratton Matthew S. , Hu Tianjing , Cavasin Maria A. , Sun Lei , Lin Ying-Hsi , Liu Dianxin , Londono Pilar , Song Kunhua , Pino Maria F. , Sparks Lauren M. , Smith Steven R. , Scherer Philipp E. , Collins Sheila , Seto Edward , McKinsey Timothy A. 
Published: March 2018

AbstractLittle is known about the biological function of histone deacetylase 11 (HDAC11), which is the lone class IV HDAC. Here, we demonstrate that deletion of HDAC11 in mice stimulates brown adipose tissue (BAT) formation and beiging of white adipose tissue (WAT). Consequently, HDAC11-deficient mice exhibit dramatically enhanced thermogenic potential and, in response to high fat feeding, attenuated obesity, insulin resistance, and hepatic steatosis. Ex vivo and cell-based assays revealed that HDAC11 catalytic activity suppresses the BAT transcriptional program, in both the basal state and in response to β-adrenergic receptor signaling, through a mechanism that is dependent on physical association with BRD2, a bromodomain and extraterminal (BET) acetyl-histone binding protein. These findings define a novel epigenetic pathway for the regulation of energy homeostasis, and suggest potential for HDAC11-selective inhibitors for the treatment of obesity and diabetes.
Task activations produce spurious but systematic inflation of task functional connectivity estimates
Authors: Cole Michael W. , Ito Takuya , Schultz Douglas , Mill Ravi , Chen Richard , Cocuzza Carrisa 
Published: March 2018

AbstractMost neuroscientific studies have focused on task-evoked activations (activity amplitudes at specific brain locations), providing limited insight into the functional relationships between separate brain locations. Task-state functional connectivity (FC) - statistical association between brain activity time series during task performance moves beyond task-evoked activations by quantifying functional interactions during tasks. However, many task-state FC studies do not remove the first-order effect of taskevoked activations prior to estimating task-state FC. It has been argued that this results in the ambiguous inference “likely active or interacting during the task”, rather than the intended inference “likely interacting during the task”. Utilizing a neural mass computational model, we verified that task-evoked activations substantially and inappropriately inflate task-state FC estimates, especially in functional MRI (fMRI) data. Various methods attempting to address this problem have been developed, yet the efficacies of these approaches have not been systematically assessed. We found that most standard approaches for fitting and removing mean task-evoked activations were unable to correct these inflated correlations. In contrast, methods that flexibly fit mean task-evoked response shapes effectively corrected the inflated correlations without reducing effects of interest. Results with empirical fMRI data confirmed the model’s predictions, revealing activation-induced task-state FC inflation for both Pearson correlation and psychophysiological interaction (PPI) approaches. These results demonstrate that removal of mean task-evoked activations using an approach that flexibly models task-evoked response shape is an important preprocessing step for valid estimation of task-state FC.HighlightsComputational model shows task inflation of functional connectivity estimatesHemodynamic responses cause task activations to further inflate estimatesStandard approaches to remove task activations leave many false positivesMethods that flexibly fit hemodynamic response shape effectively correct inflationCorrection of functional connectivity inflation verified with empirical fMRI data
Oxford Nanopore MinION sequencing enables rapid whole-genome assembly ofRickettsia typhiin a resource-limited setting
Authors: Elliott Ivo , Batty Elizabeth M. , Ming Damien , Robinson Matthew T. , Nawtaisong Pruksa , de Cesare Mariateresa , Newton Paul N. , Bowden Rory 
Published: March 2018

AbstractThe infrastructure challenges and costs of next-generation sequencing have been largely overcome, for many sequencing applications, by Oxford Nanopore Technologies’ portable MinION sequencer. However the question remains open whether MinION-based bacterial whole-genome sequencing (WGS) is by itself sufficient for the accurate assessment of phylogenetic and epidemiological relationships between isolates and whether such tasks can be undertaken in resource-limited settings. To investigate this question, we sequenced the genome of an isolate ofRickettsia typhi, an important and neglected cause of fever across much of the tropics and subtropics, for which only three genomic sequences previously existed. We prepared and sequenced libraries on a MinION in Vientiane, Lao PDR using v9.5 chemistry and in parallel we sequenced the same isolate on the Illumina platform in a genomics laboratory in the UK. The MinION sequence reads yielded a single contiguous assembly, in which the addition of Illumina data revealed 226 base-substitution and 5,856 in/del errors. The combined assembly represents the first complete genome sequence of a humanR. typhiisolate collected in the last 50 years and differed from the genomes of existing strains collected over a 90-year time period at very few sites, and with no re-arrangements. Filtering based on the known error profile of MinION data improved the accuracy of the Nanopore-only assembly. However, the frequency of false-positive errors remained greater than true sequence divergence from recorded sequences. While Nanopore-only sequencing cannot yet recover phylogenetic signal inR. typhi, such an approach may be applicable for more diverse organisms.
System level analyses of motor-related neural activities in larval Drosophila
Authors: Yoon Youngteak , Park Jeonghyuk , Taniguchi Atsushi , Kohsaka Hiroshi , Nakae Ken , Nonaka Shigenori , Ishii Shin , Nose Akinao 
Published: March 2018

ABSTRACTThe way in which the central nervous system (CNS) governs animal movement is complex and difficult to solve solely by the analyses of muscle movement patterns. We tackle this problem by observing the activity of a large population of neurons in the CNS of larval Drosophila. We focused on two major behaviors of the larvae, forward and backward locomotion, and analyzed the neuronal activity related to these behaviors during fictive locomotion that spontaneously occurs in the isolated CNS. We expressed genetically-encoded calcium indicator, GCaMP, and a nuclear marker in all neurons and used digital scanned light-sheet microscopy to record neural activities in the entire ventral nerve cord at a fast frame rate. We developed image processing tools that automatically detect the cell position based on the nuclear staining and allocate the activity signals to each detected cell. We also applied a machine learning-based method that we developed recently to assign motor status in each time frame. Based on these methods, we find cells whose activity is biased to forward versus backward locomotion and vice versa. In particular, we identified a group of neurons near the boundary of subesophageal zone (SEZ) and thoracic neuromeres, which are strongly active during an early phase of backward but not forward fictive locomotion. Our experimental procedure and computational pipeline enable systematic identification of neurons to show characteristic motor activities in larval Drosophila.
Can AI reproduce observed chemical diversity?
Authors: Benhenda Mostapha 
Published: March 2018

AbstractGenerating diverse molecules with desired chemical properties is important for drug discovery. The use of generative neural networks is promising for this task. To facilitate evaluation of generative models, this paper introduces a metric of internal chemical diversity, and raises the following challenge: can a nontrivial AI model reproduce observed internal diversity for desired molecules? To illustrate this metric, a mini-benchmark is performed with two generative models: a Reinforcement Learning model and the recently introduced ORGAN. The aim of this paper is to encourage research about internal diversity metrics.