bluuebunny/crossref_metadata_2025_split huggingface dataset:
Securing the Appendiceal Stump During Emergency Appendicectomy: Options and Influencing Factors in Current UK Surgical Practice
Authors: Wilson Michael S.J. , Knight Stephen R. , Vaughan-Shaw Peter 
Published: July 2018

Introduction:
The aim of our study was to identify the most commonly employed methods and influencing factors for securing the appendiceal stump in current NHS practice.

Methods:
An electronic survey of the Scottish Surgical Research Group network, invitation extended to the UK National Research Collaborative.

Results:
A total of 111 responses were received from 32 surgical centers; 28 (25.2%) consultants, 66 (59.5%) specialty trainees and 12 (10.8%) core trainees. Endoscopic ligatures were the preferred method in 96 (86.5%) with no difference in those with the greatest operative experience (P=0.79), 12 (10.8%) preferred polymeric clips. Ease of application (70.3%) and severity of stump inflammation (65.8%) had the greatest influence on the method chosen. Cost was a factor in 36.0%.

Conclusions:
The preferred method for securing the appendiceal stump in UK practice is endoscopic ligatures regardless of operative experience. Factors with the greatest influence on the method employed include the ease of application and severity of stump inflammation. Our findings are likely to be representative of current NHS practice in Scotland.
Introduction to redundancy rules: the continuous wavelet transform comes of age
Authors: Addison Paul S. 
Published: July 2018

Redundancy: it is a word heavy with connotations of lacking usefulness. I often hear that the rationale for not using the continuous wavelet transform (CWT)—even when it appears most appropriate for the problem at hand—is that it is ‘redundant’. Sometimes the conversation ends there, as if self-explanatory. However, in the context of the CWT, ‘redundant’ is not a pejorative term, it simply refers to a less compact form used to represent the information within the signal. The benefit of this new form—the CWT—is that it allows for intricate structural characteristics of the signal information to be made manifest within the transform space, where it can be more amenable to study: resolution over redundancy. Once the signal information is in CWT form, a range of powerful analysis methods can then be employed for its extraction, interpretation and/or manipulation. This theme issue is intended to provide the reader with an overview of the current state of the art of CWT analysis methods from across a wide range of numerate disciplines, including fluid dynamics, structural mechanics, geophysics, medicine, astronomy and finance.
This article is part of the theme issue ‘Redundancy rules: the continuous wavelet transform comes of age’.
A non-coding genetic variant maximally associated with serum urate levels is functionally linked to HNF4A-dependent PDZK1 expression
Authors: Ketharnathan Sarada , Leask Megan , Boocock James , Phipps-Green Amanda J. , Antony Jisha , O’Sullivan Justin M. , Merriman Tony R. , Horsfield Julia A. 
Published: July 2018

ABSTRACTSeveral dozen genetic variants associate with serum urate levels, but the precise molecular mechanisms by which they affect serum urate are unknown. Here we tested for functional linkage of the maximally-associated genetic variant rs1967017 at the PDZK1 locus to elevated PDZK1 expression.We performed expression quantitative trait locus (eQTL) and likelihood analyses followed by gene expression assays. Zebrafish were used to determine the ability of rs1967017 to direct tissue-specific gene expression. Luciferase assays in HEK293 and HepG2 cells measured the effect of rs1967017 on transcription amplitude.PAINTOR analysis revealed rs1967017 as most likely to be causal and rs1967017 was an eQTL for PDZK1 in the intestine. The region harboring rs1967017 was capable of directly driving green fluorescent protein expression in the kidney, liver and intestine of zebrafish embryos, consistent with a conserved ability to confer tissue-specific expression. The urate-increasing T-allele of rs1967017 strengthens a binding site for the transcription factor HNF4A. siRNA depletion of HNF4A reduced endogenous PDZK1 expression in HepG2 cells. Luciferase assays showed that the T-allele of rs1967017 gains enhancer activity relative to the urate-decreasing C-allele, with T-allele enhancer activity abrogated by HNF4A depletion. HNF4A physically binds the rs1967017 region, suggesting direct transcriptional regulation of PDZK1 by HNF4A.With other reports our data predict that the urate-raising T-allele of rs1967017 enhances HNF4A binding to the PDZK1 promoter, thereby increasing PDZK1 expression. As PDZK1 is a scaffold protein for many ion channel transporters, increased expression can be predicted to increase activity of urate transporters and alter excretion of urate.
Representation Learning of Genomic Sequence Motifs with Convolutional Neural Networks
Authors: Koo Peter K. , Eddy Sean R. 
Published: July 2018

AbstractAlthough convolutional neural networks (CNNs) have been applied to a variety of computational genomics problems, there remains a large gap in our understanding of how they build representations of regulatory genomic sequences. Here we perform systematic experiments on synthetic sequences to reveal how CNN architecture, specifically convolutional filter size and max-pooling, influences the extent that sequence motif representations are learned by first layer filters. We find that CNNs designed to foster hierarchical representation learning of sequence motifs - assembling partial features into whole features in deeper layers - tend to learn distributed representations, i.e. partial motifs. On the other hand, CNNs that are designed to limit the ability to hierarchically build sequence motif representations in deeper layers tend to learn more interpretable localist representations, i.e. whole motifs. We then validate that this representation learning principle established from synthetic sequences generalizes to in vivo sequences.
Predictors of Malaria Rapid Diagnostic Tests’ Utilisation Among Healthcare Workers in Zamfara State
Authors: Rabi Usman , Umar Ahmad A. , Gidado Saheed , Gobir A.A , Obi Izuchukwu F. , Ajayi IkeOluwapo , Ajumobi Olufemi 
Published: July 2018

AbstractIntroductionEarly diagnosis and prompt and effective treatment is one of the pillars of malaria control Malaria case management guidelines recommend diagnostic testing before treatment using malaria Rapid Diagnostic Test (mRDT) or microscopy and this was adopted in Nigeria in 2010. However, despite the deployment of mRDT, the use of mRDTs by health workers varies by settings. This study set out to assess factors influencing utilisation of mRDT among healthcare workers in Zamfara State, Nigeria.MethodsA cross-sectional study was carried out among 306 healthcare workers selected using multistage sampling from six Local Government Areas between January and February 2017. Mixed method was used for data collection. A pre-tested self-administered questionnaire was used to collect information on knowledge, use of mRDT and factors influencing utilization. An observational checklist was used to assess the availability of mRDT in the six months prior to this study. Data were analyzed using descriptive statistics such as means and proportions. Association between mRDT use and independent variables was tested using Chi square while multiple regression was used to determine predictors of use at 5% level of significance.ResultsMean age of respondents was 36.0 ± 9.4years. Overall, 198 (64.7%) of health workers had good knowledge of mRDT; malaria RDT was available in 33 (61.1%) facilities. Routine use of mRDT was reported by 253 (82.7%) healthcare workers. This comprised 89 (35.2%) laboratory scientists/technicians, 89 (35.2%) community health extension workers/community health officers; 59 (23.3%) nurses and 16 (6.3%) doctors. Predictors of mRDT utilisation were good knowledge of mRDT (adjusted OR (aOR):3.3, CI: 1.6-6.7), trust in mRDT results (aOR: 4.0, CI: 1.9 - 8.2), having being trained on mRDT (aOR: 2.7, CI: 1.2 - 6.6), and provision of free mRDT (aOR: 2.3, CI: 1.0 - 5.0).ConclusionThis study demonstrated that healthcare worker utilisation of mRDT was associated with health worker and health system-related factors that are potentially modifiable. There is need to sustain training of healthcare workers on benefits of using mRDT and provision of free mRDT in health facilities.
Help-seeking behavior for problematic substance uses in Bahir Dar town, North-West Ethiopia
Authors: Belete Habte , Mekonen Tesfa , Fekadu Wubalem , Legas Getasew , Getnet Asmamaw 
Published: July 2018

AbstractBackgroundMental, neurological and substance use disorders are common, but 76% to 85% of people with those disorders in low and middle-income countries did not receive treatment.ObjectiveOur objective was to assess the level of help seeking behavior and associated factors among residents with problematic substance uses (alcohol, khat, tobacco and hashish).MethodsCommunity based cross sectional study was conducted in Bahir Dar town among total of 548 participants with problematic substance users. We had interviewed for help seeking behavior by pre-tested modified General Help Seeking Questionnaire. Logistic regression was done and p-value < 0.05 was used for declaration of significant level. Adjusted odds ratios (AOR) and 95% confidence intervals (CI) have been used.ResultsAmong five hundred and forty-eight participants with problematic substance users, only one hundred and sixty-eight (30.7%) sought help for their substance related problems. Participants’ age above 35 years [AOR = .47 95% CI (.25, .90)], positively screened for common mental disorders [AOR = 4.12, 95% CI (2.7, 6.3)], comorbid medical [AOR = 3.0, 95% CI (1.7, 5.3)], and grand-families’ history of substance user [AOR = 2.18, 95% CI (1.4, 3.4)] found significantly associated with help seeking.ConclusionThere was low proportion of help seeking behavior among participants with problematic substance users. Advanced age was a barrier to seek help while medical illnesses, common mental disorders and history of substance use in grand families were found to enforce to seek help.
Identification of substrates for the conserved prolyl hydroxylase Ofd1 using quantitative proteomics in fission yeast
Authors: Gu He , Hughes Bridget T. , Espenshade Peter J. 
Published: July 2018

AbstractProlyl hydroxylation functions in diverse cellular pathways, such as collagen biogenesis, oxygen sensing, and translation termination. Prolyl hydroxylation is catalyzed by 2-oxoglutarate (2-OG) oxygenases. The fission yeast 2-OG oxygenase Ofd1 dihydroxylates the 40S ribosomal protein Rps23 and regulates the hypoxic response by controlling activity and stability of the sterol regulatory element-binding protein Sre1. Multiple substrates have been found for 2-OG oxygenases, yet the only known substrate of Ofd1 and its homologs is Rps23. Here, we report the first fission yeast prolyl hydroxylome and demonstrate that hydroxylation is more prevalent than previously known. Using quantitative mass spectrometry, we identify Rpb10, a shared subunit in RNA polymerase I, II, and III, as a novel Ofd1 substrate. In addition, we discovered six Ofd1 binding partners and 16 additional Ofd1 candidate substrates. Although Ofd1 promotes Sre1 degradation, proteomic analysis revealed that Ofd1 does not broadly regulate protein degradation. Instead, the effect of Ofd1 on the proteome is through negative regulation of Sre1N. Finally, we show that the interaction between Ofd1 and the Sre1 bHLH region is conserved across Sre1 homologs suggesting that Ofd1-dependent regulation of SREBPs may be conserved in other fungi. Collectively, these studies provide a new dataset of post-translational modifications and expand the biological functions for a conserved prolyl hydroxylase.
Filamentous calcareous alga provides a substrate for coral-competitive macroalgae in the degraded lagoon of Dongsha Atoll, Taiwan
Authors: Nieder Carolin , Chen Chaolun Allen , Liu Shao-Lun 
Published: July 2018

AbstractBackgroundThe chemically-rich seaweed Galaxaura is not only highly competitive with corals, but also provides substrate for other macroalgae. Its ecology and associated epiphytes remain largely unexplored. To fill this knowledge gap, we herein undertook an ecological assessment to explore the spatial variation, temporal dynamics, and epiphytic macroalgae of G. divaricata on patch reefs in the lagoon of Dongsha Atoll, a shallow coral reef ecosystem in the northern South China Sea, repeatedly impacted by mass coral bleaching events.MethodsTwelve spatially independent patch reefs in the Dongsha lagoon were first surveyed to assess the benthic composition in April 2016, and then revisited to determine G. divaricata percent cover in September 2017, with one additional Galaxaura-dominated reef (site 9). Four surveys over a period of 17 months were carried out on a degraded patch reef (site 7) to assess the temporal variation in G. divaricata cover. Epiphytic macroalgae associated with G. divaricata were quantified and identified through the aid of DNA barcoding.ResultsPatch reefs in the Dongsha lagoon were degraded, exhibiting relatively low live coral cover (5-43%), but high proportions of macroalgae (13-58%) and other substrates (rubble and dead corals; 23-69%). The distribution of G. divaricata was heterogeneous across the lagoon, with highest abundance (16-41%) in the southeast area. Temporal surveys from site 7 and photo-evidence from site 9 suggested that an overgrowth by G. divaricata was still present to a similar extend after 17 months and 3.5 years. Yet, G. divaricata provides a suitable substrate some allelopathic macroalgae (e.g., Lobophora sp.).ConclusionsOur study demonstrates that an allelopathic seaweed, such as G. divaricata, can overgrow degraded coral reefs for extended periods of time. By providing habitat for harmful macroalgae, a prolonged Galaxaura overgrowth could strengthen negative feedback loops on degraded coral reefs, further decreasing their recovery potential.
Disparate expression specificities coded by a shared Hox-C enhancer
Authors: Miller Steven W. , Posakony James W. 
Published: July 2018

AbstractCan a single regulatory sequence be shared by two genes undergoing functional divergence? Here we describe a single promiscuous enhancer within theDrosophilaAntennapedia Complex, EO053, that directs aspects of the expression of two adjacent genes,pb(aHox2ortholog) andzen2(a divergentHox3paralog), with disparate spatial and temporal expression patterns. We were unable to separate thepb-like andzen2-like specificities within EO053, and we identify sequences affecting both expression patterns. Importantly, deletion of EO053 affects expression of both genes as well, despite each gene having additional enhancers. We examine sequence conservation of EO053 within the Schizophora, and show that patterns of synteny between theHox2andHox3orthologs in Arthropods are consistent with a shared regulatory relationship extending prior to theHox3/zendivergence. Thus, EO053 represents an example of two genes having evolved disparate outputs while utilizing this shared regulatory region.
A smartphone-based tool for rapid, portable, and automated wide-field retinal imaging
Authors: Kim Tyson N. , Myers Frank , Reber Clay , Loury PJ , Loumou Panagiota , Webster Doug , Echanique Chris , Li Patrick , Davila Jose R. , Maamari Robi N. , Switz Neil A. , Keenan Jeremy , Woodward Maria A. , Paulus Yannis M. , Margolis Todd , Fletcher Daniel A. 
Published: July 2018

AbstractPurposeHigh-quality, wide-field retinal imaging is a valuable method to screen preventable, vision-threatening diseases of the retina. Smartphone-based retinal cameras hold promise for increasing access to retinal imaging, but variable image quality and restricted field of view can limit their utility. We developed and clinically tested a smartphone-based system that addresses these challenges with automation-assisted imaging.MethodsThe system was designed to improve smartphone retinal imaging by combining automated fixation guidance, photomontage, and multi-colored illumination with optimized optics, user-tested ergonomics, and touch-screen interface. System performance was evaluated from images of ophthalmic patients taken by non-ophthalmic personnel. Two masked ophthalmologists evaluated images for abnormalities and disease severity.ResultsThe system automatically generated 100-degree retinal photomontages from five overlapping images in under 1 minute at full resolution (52.3 pixels per retinal degree) fully on-phone, revealing numerous retinal abnormalities. Feasibility of the system for DR screening using the retinal photomontages was performed in 71 diabetics by masked graders. DR grade matched perfectly with dilated clinical examination in 55.1% of eyes and within 1 severity level for 85.2% of eyes. For referral-warranted DR, average sensitivity was 93.3% and specificity 56.8%.ConclusionsAutomation-assisted imaging produced high-quality, wide-field retinal images that demonstrate the potential of smartphone-based retinal cameras to be used for retinal disease screening.Translational RelevanceEnhancement of smartphone-based retinal imaging through automation and software intelligence holds great promise for increasing the accessibility of retinal screening.
The Human Kinesin Kif18A’s Neck Linker Permits Navigation of Microtubule Bound Obstacles within the Mitotic Spindle
Authors: Malaby Heidi L. H. , Lessard Dominique V. , Berger Christopher L. , Stumpff Jason 
Published: July 2018

AbstractMitotic chromosome alignment is essential for the robust separation of genetic material into daughter cells. In mammalian cells, this process requires the function of Kif18A, a kinesin-8 motor protein. Kif18A confines chromosome movement to the mitotic spindle equator by accumulating at the plus-ends of kinetochore microtubule bundles (K-fibers), where it functions to suppress K-fiber dynamics. It is not understood how the motor accumulates at K-fiber plus-ends, a difficult feat requiring the motor to navigate protein dense microtubule tracks. Our data indicate that Kif18A’s relatively long (17 amino acid) neck linker is required for the motor’s accumulation at K-fiber plus-ends. Shorter neck linker (sNL) variants of Kif18A display a deficiency in K-fiber accumulation, especially on K-fibers near the center of the spindle. This pattern correlates with the more uniform concentration of the microtubule bundling protein HURP on central K-fibers compared to peripheral K-fibers. Depletion of HURP permits Kif18A sNL to accumulate on central K-fibers, while HURP overexpression reduces wild-type Kif18A’s ability to accumulate on this same K-fiber subset. Furthermore, single molecule assays indicate that Kif18A sNL motors are less proficient at navigating microtubules coated with the microtubule associated protein tau. Taken together, these results support a model in which Kif18A’s neck linker length permits efficient navigation of obstacles such as HURP to reach K-fiber ends during mitosis.Signficiance StatementKinesin motor proteins play key roles in controlling chromosome alignment and segregation during cell division. The kinesin Kif18A confines chromosomes to the middle of the spindle by accumulating at the ends of microtubules attached to chromosomes. We show here that Kif18A’s ability to accumulate at the end of these microtubules requires navigation of microtubule-associated protein obstacles, and that this activity is imparted by a relatively long neck linker region. These findings demonstrate a molecular mechanism for navigation of densely populated microtubules inside a cell.
Cascading regime shifts within and across scales
Authors: Rocha Juan C. , Peterson Garry , Bodin Örjan , Levin Simon A. 
Published: July 2018

AbstractRegime shifts are large, abrupt and persistent critical transitions in the function and structure of systems (1,2). Yet it is largely unknown how these transitions will interact, whether the occurrence of one will increase the likelihood of another, or simply correlate at distant places. Here we explore two types of cascading effects: domino effects create one-way dependencies, while hidden feedbacks produce two-way interactions; and compare them with the control case of driver sharing which can induce correlations. Using 30 regime shifts described as networks, we show that 45% of the pair-wise combinations of regime shifts present at least one plausible structural interdependence. Driver sharing is more common in aquatic systems, while hidden feedbacks are more commonly found in terrestrial and Earth systems tipping points. The likelihood of cascading effects depends on cross-scale interactions, but differs for each cascading effect type. Regime shifts should not be studied in isolation: instead, methods and data collection should account for potential teleconnections.
Elucidation of ion effects on the Thermodynamics of RNA Folding
Authors: Denesyuk Natalia A. , Thirumalai D. 
Published: July 2018

AbstractHow ions affect RNA folding thermodynamics and kinetics is an important but a vexing problem that remains unsolved. Experiments have shown that the free energy change, ΔG(c), of RNA upon folding varies with the salt concentration (c) as, ΔG(c) = kc ln c + const, where the coefficient kc is proportional to the difference in the uptake of ions (ion preferential coefficient), ΔΓ, between the folded and unfolded states. We performed simulations of a coarse-grained model, by modeling electrostatic interactions implicitly and with explicit representation of ions, to elucidate the molecular underpinnings of the relationship between folding free energy and ion preferential coefficient. Without any input from experiments, the simulations quantitatively reproduce the heat capacity for the −1 frame shifting pseudoknot (PK) from Beet Western Yellow Virus, thus validating the model. We show that ΔG(c) calculated directly from ΔΓ varies linearly with ln c (c < 0.2M), for a hairpin and the PK, thus demonstrating a molecular link between the two quantities for RNA molecules that undergo substantial conformational changes during folding. Explicit ion simulations also show the linear dependence of ΔG(c) on ln c at all c with kc = 2kBT, except that ΔG(c) values are shifted by about 2 kcal/mol higher than experiments at all salt concentrations. The discrepancy is due to an underestimate the Γ values for both the folded and unfolded states, while giving accurate values for ΔΓ. The predictions for the salt dependence of ΔΓ are amenable to test using single molecule pulling experiments. Our simulations, representing a significant advance in quantitatively describing ion effects in RNA, show that the framework provided here can be used to obtain accurate thermodynamics of RNA folding.