bluuebunny/crossref_metadata_2025_split huggingface dataset:
Online couple interventions in cancer
Authors: Vanstone Ruth , Fergus Karen D. 
Published: December 2019

Purpose of review
Cancer diagnosis and treatment can have long-lasting psychological and physical consequences that affect both patients and their intimate partners. Improved understanding of extant dyadic interventions in the context of cancer, and how access to these may be enhanced through web-based technologies, introduce new directions for how cancer-related psychological distress for couples may be ameliorated.

Recent findings
Couples are negatively impacted by cancer, both individually, and as a dyad. Bolstering techniques to support effective communication about common cancer-related concerns and support for adjusting to new roles and responsibilities may help to strengthen the couple's relationship so partners are better able to cope with cancer. Although there are various intervention options available for couples dealing with cancer, many pose barriers to participation because of constraints on time and/or distance. However, online interventions have been shown to be effective, both in easing psychological distress and reducing participant burden.

Summary
Couples dealing with cancer experience psychological distress and must learn to navigate changing roles and responsibilities in the face of the disease. Online interventions offer flexible and innovative platforms and programs that help to address couples’ educational needs while strengthening dyadic coping.
Using Saccharomyces cerevisiae as a tool for mapping genetic variants underlying differences in response to anti-cancer agents
Authors: Almayouf Salwa , Barton David B.H. , Hu Yue , Foster Steven , Louis Ed J. 
Published: December 2019

Background
There are variations in response to anti-cancer agents amongst individuals because they are complex traits controlled by multiple genes and environmental factors. Here, we aimed to decipher the genes controlling the variations in response to aspirin, metformin, disulfiram and 5-fluorouracil using quantitative trait loci (QTL) mapping in yeast before translating findings to humans. This approach was feasible due to the conservation of genes between these two organisms.

Method
A panel of 111 F12 meiotic segregants generated from a four-parent S. cerevisiae cross were genotyped by whole genome sequencing. Segregants growth in different treatments were phenotyped using PHENOS. Subsequently, linkage-based fine QTL mapping was performed to locate regions of the genome and the identification of causative genes.

Results
Linkage analysis has mapped hundreds of genetic loci in the yeast genome responsible for the variations in response to the agents tested. Conserved homologs to human genes were identified. Some hits have been previously supported in the literature such as the effect of aspirin and metformin on MTOR thus validating this screening approach. Novel genes identified and pathway enrichment revealed mechanisms by which these agents may exhibit their anti-cancer properties.

Conclusion
Detection of genetic variants influencing the differences in drug response could help identify individuals at risk or benefit of using anti-cancer agents. Current work includes validating the alleles of causative genes (Rad57 and VMA22) in yeast by reciprocal hemizygosity and allele swapping. This study could aid the development of biomarkers for drug response and validate the repurposing of drugs for cancer prevention.
Drug resistant Candida colonization among ICU patients in a Nigerian teaching hospital
Authors: Abiri Oyekola 
Published: December 2019

Introduction:
Colonisation of body surfaces with resistant strains is an initial step in the pathogenesis of drug resistant invasive Candida infections. Nigeria has little data on the species distribution and resistance pattern of colonising Candida species in intensive care unit(ICU) patients. This study set out to investigate the burden of Candida colonisation in the ICU of a tertiary health institution in Ile-Ife, Nigeria.

Methodology:
At admission, 72 hours and 7 days, swabs of skin, oropharynx, perianal region, surgical wounds, tracheal aspirates and urine samples taken from adult ICU patients were cultured on media selective for fungi. Candida species were identified by standard microbiological methods. Sensitivity to fluconazole, voriconazole and caspofungin was determined by disc diffusion according to CLSI guidelines. Strain interrelatedness was investigated by Randomly Amplified Polymorphic DNA (RAPD).

Results:
Of 744 samples from 110 patients, 142 samples (18.3%) yielded Candida. The average colonisation index increased with duration of admission (p=0.001). Most frequently colonized were the oropharynx (39.5%) and the perianal region (22.4%). Species isolated were C. albicans 97 (68.3%), C. tropicalis 20 (14.1%), C. glabrata 12 (8.5%), C. parapsilosis 7 (4.9%) and C. krusei 6 (4.2%). About 1 in every 3 isolates was resistant to fluconazole (42/142; 29.6%). In addition, resistance to voriconazole was 12/142 (8.5%) while 10/142 (7%) were resistant to caspofungin. RAPD showed identical strains across several body sites of many patients.

Conclusion:

Candida species with high rates of resistance to the first line antifungal agent colonise and are transmitted among ICU patients. These can potentially cause difficult to treat invasive infections, underscoring a need for better infection control practices.
Rough and smooth variant Mycobacterium abscessus infections are differentially controlled by host immunity during chronic infection
Authors: Hortle Elinor , Kam Julia Y , Krogman Elizabeth , Warner Sherridan E , Luo Kaiming , Cheng Tina , Cholan Pradeep Manuneedhi , Kikuchi Kazu , Triccas James A , Britton Warwick J , Johansen Matt D , Kremer Laurent , Oehlers Stefan H 
Published: December 2019

AbstractInfections caused by Mycobacterium abscessus are increasing in prevalence within patient groups with respiratory comorbidities. Initial colonisation by the smooth colony M. abscessus (S) can be followed by an irreversible genetic switch into a highly inflammatory rough colony M. abscessus (R), often associated with a decline in pulmonary function. Our understanding of the role of adaptive immunity in M. abscessus pathogenesis is largely unknown. Here, we have used intraperitoneal infection of adult zebrafish to model M. abscessus pathogenesis in the context of fully functioning host immunity. We find infection with the R variant penetrates host organs causing an inflammatory immune response leading to necrotic granuloma formation within 2 weeks. The R bacilli are targeted by T cell-mediated immunity and burden is constrained. Strikingly, the S variant colonises host internal surfaces at high loads and is met with a robust innate immune response but little T cell-mediated immunity. Invasive granuloma formation is delayed in S variant infection compared to R variant infection upon which T cell-mediated immunity is required to control infection. In mixed infections, the S variant outcompetes the R variant. We also find the R variant activates host immunity to the detriment of S variant M. abscessus in mixed infections. These findings demonstrate the applicability of the adult zebrafish to model persistent M. abscessus infection and provide insight into the immunopathogenesis of chronic M. abscessus infection.
Theoretical properties of nearest-neighbor distance distributions and novel metrics for high dimensional bioinformatics data
Authors: Dawkins Bryan A. , Le Trang T. , McKinney Brett A. 
Published: December 2019

AbstractThe performance of nearest-neighbor feature selection and prediction methods depends on the metric for computing neighborhoods and the distribution properties of the underlying data. The effects of the distribution and metric, as well as the presence of correlation and interactions, are reflected in the expected moments of the distribution of pairwise distances. We derive general analytical expressions for the mean and variance of pairwise distances for Lq metrics for normal and uniform random data with p attributes and m instances. We use extreme value theory to derive results for metrics that are normalized by the range of each attribute (max – min). In addition to these expressions for continuous data, we derive similar analytical formulas for a new metric for genetic variants (categorical data) in genome-wide association studies (GWAS). The genetic distance distributions account for minor allele frequency and transition/transversion ratio. We introduce a new metric for resting-state functional MRI data (rs-fMRI) and derive its distance properties. This metric is applicable to correlation-based predictors derived from time series data. Derivations assume independent data, but empirically we also consider the effect of correlation. These analytical results and new metrics can be used to inform the optimization of nearest neighbor methods for a broad range of studies including gene expression, GWAS, and fMRI data. The summary of distribution moments and detailed derivations provide a resource for understanding the distance properties for various metrics and data types.
rgenesconverged : An R Package for the Exploration of Molecular Convergent Evolution
Authors: Issakova Dina 
Published: December 2019

AbstractSequence convergence is a type of convergent evolution that results in similarity between orthologous genetic sequences. However, this can be difficult to evaluate statistically given classical paradigms for convergent evolution, which rest on the assumption that convergent phenotypes are achieved by unrelated genetic mechanisms. While sophisticated models exist to model this process and to evaluate the probability of this explanation of genetic similarity across two different species, no tool has currently been implemented in R to carry out these analyses. Here we present rgenesconverged, an R package allowing the exploration of sequence convergence hypotheses in a given phylogeny.
High-throughput reclassification ofSCN5Avariants
Authors: Glazer Andrew M. , Wada Yuko , Li Bian , Muhammad Ayesha , Kalash Olivia R. , O’Neill Matthew J. , Shields Tiffany , Hall Lynn , Short Laura , Blair Marcia A. , Kroncke Brett M. , Capra John A. , Roden Dan M. 
Published: December 2019

AbstractRationalePartial or complete loss of function variants inSCN5Aare the most common genetic cause of the arrhythmia disorder Brugada Syndrome (BrS1). However, the pathogenicity ofSCN5Avariants is often unknown or disputed; 80% of the 1,390SCN5Amissense variants observed in at least one individual to date are variants of uncertain significance (VUS). The designation of VUS is a barrier to the use of sequence data in clinical care.ObjectiveWe selected 83 variants for study: 10 previously studied control variants, 10 suspected benign variants, and 63 suspected Brugada Syndrome-associated variants, selected on the basis of their frequency in the general population and in patients with Brugada Syndrome. We used high-throughput automated patch clamping to study the function of the 83 variants, with the goal of reclassifying variants with functional data.Methods and ResultsTen previously studied variants had functional properties concordant with published manual patch clamp data. All 10 suspected benign variants had wildtype-like function. 22 suspected BrS variants had loss of channel function (<10% normalized peak current) and 23 variants had partial loss of function (10-50% normalized peak current). The 73 previously unstudied variants were initially classified as likely benign (n=2), likely pathogenic (n=11), or VUS (n=60). After the patch clamp studies, 16 variants were benign/likely benign, 47 were pathogenic/likely pathogenic, and only 10 were still VUS. 8/22 loss of function variants were partially rescuable by incubation at lower temperature or pretreatment with a sodium channel blocker. Structural modeling identified likely mechanisms for loss of function including altered thermostability, and disruptions to alpha helices, disulfide bonds, or the permeation pore.ConclusionsHigh-throughput automated patch clamping enabled the reclassification of the majority of tested VUS’s inSCN5A.
Diverse and complex muscle spindle afferent firing properties emerge from multiscale muscle mechanics
Authors: Blum Kyle P. , Campbell Kenneth S. , Horslen Brian C. , Nardelli Paul , Housley Stephen N. , Cope Timothy C. , Ting Lena H. 
Published: December 2019

AbstractDespite decades of research, we lack a mechanistic framework capable of predicting how movement-related signals are transformed into the diversity of muscle spindle afferent firing patterns observed experimentally, particularly in naturalistic behaviors. Here, a biophysical model demonstrates that well-known firing characteristics of muscle spindle Ia afferents – including dependence on movement history, and nonlinear scaling with muscle stretch velocity – emerge from first principles of muscle contractile mechanics. Further, mechanical interactions of the muscle spindle with muscle-tendon dynamics reveal how motor commands to the muscle (alpha drive) versus muscle spindle (gamma drive) can cause highly variable and complex activity during active muscle contraction and muscle stretch that defy simple explanation. Depending on the neuromechanical conditions, the muscle spindle model output appears to “encode” aspects of muscle force, yank, length, stiffness, velocity, and/or acceleration, providing an extendable, multiscale, biophysical framework for understanding and predicting proprioceptive sensory signals in health and disease.
The effect of single-task training on learning transfer to a novel bimanual task
Authors: Hadi Zaeem , Shakeel Aqsa , Ahmad Hafsa , Anwar Muhammad Nabeel , Navid Muhammad Samran 
Published: December 2019

AbstractBackgroundThe contextual interference effect suggests that the random practice of multiple-tasks is more beneficial for the retention and transfer of the learning as compared to blocked practice. Therefore, the transfer of learning is usually attributed to the contextual interference effect and is studied in a multi-task setting.ObjectiveThe goals of this study were to evaluate whether the transfer of learning (i) can occur when a single bimanual task is practiced, (ii) is affected by the knowledge of results (feedback), and (iii) sustains over an extended number of trials.MethodsFifty-two healthy subjects were equally divided into four groups. Before the transfer test, two groups practiced a bimanual finger-tapping task with feedback (EF) and without feedback (ENF). The third group (IM) practiced the same task using the kinesthetic motor imagery, whereas the last group acted as a control (CTRL) and performed only a bimanual button-pressing task used for the transfer test.ResultsLinear mixed-model showed that in the transfer test, groups EF, ENF and IM had similar performance but significantly higher scores compared to the CTRL group. Compared to the CTRL, the EF and IM groups showed significantly improved performance in most of the sessions but group ENF had similar results.ConclusionThis study suggests that the single-task practice of a discrete bimanual task can facilitate the learning transfer to a novel task and knowledge of results (feedback) have no significant impact on the transfer of learning. Moreover, the transfer of learning effect does not disappear in extended trials.HighlightsSingle-task practice of a discrete bimanual task can facilitate the learning of a novel bimanual taskKnowledge of results (feedback) does not improve learning transfer in single-task settingTransfer of learning effect does not disappear in extended trials
A common pattern of influenza A virus single cell gene expression heterogeneity governs the innate antiviral response to infection
Authors: Vera J. Cristobal , Sun Jiayi , Lin Yen Ting , Drnevich Jenny , Ke Ruian , Brooke Christopher B. 
Published: December 2019

ABSTRACTViral infection outcomes are governed by the complex and dynamic interplay between the infecting virus population and the host response. It is increasingly clear that both viral and host cell populations are highly heterogeneous, but little is known about how this heterogeneity influences infection dynamics or viral pathogenicity. To dissect the interactions between influenza A virus (IAV) and host cell heterogeneity, we examined the combined host and viral transcriptomes of thousands of individual, single virion-infected cells. We observed complex patterns of viral gene expression and the existence of multiple distinct host transcriptional responses to infection at the single cell level. Our analyses reveal that viral NS segment gene expression diverges from that of the rest of the viral genome within a subset of infected cells, and that this unique pattern of NS segment expression can play a dominant role in shaping the host cell response to infection. Finally, we show that seasonal human H1N1 and H3N2 strains differ significantly in patterns of host anti-viral gene transcriptional heterogeneity at the single cell level. Altogether, these data reveal a common pattern of viral gene expression heterogeneity across human IAV subtypes that can serve as a major determinant of antiviral gene activation.
An Epigenetic LTR-retrotransposon insertion in the upstream region ofBnSHP1.A9controls quantitative pod shattering resistance inBrassica napus
Authors: Liu Jia , Zhou Rijin , Wang Wenxiang , Wang Hui , Qiu Yu , Rosy Raman , Mei Desheng , Harsh Raman , Hu Qiong 
Published: December 2019

AbstractSeed loss resulting from pod shattering is a major problem in oilseed rape (Brassica napusL.) production worldwide. However, the molecular mechanisms underlying pod shatter resistance are not well understood. Here we show that the pod shatter resistance at quantitative trait locus, qSRI.A9.1 is controlled by aSHATTERPROOF1(SHP1) paralog inB. napus(BnSHP1.A9). Expression analysis by quantitative RT-PCR showed that BnSHP1.A9was specifically expressed in flower buds, flowers and developing siliques in the oilseed rape line (R1) carrying the qSRI.A9.1 allele with negative effect, but not expressed in any tissue of the line (R2) carrying the positive effect qSRI.A9.1 allele. Transgenic plants constitutively expressing BnSHP1.A9alleles from pod resistant and pod shattering parental lines showed that both alleles are responsible for pod shattering via promoting lignification of enblayer, which indicated allelic difference of BnSHP1.A9geneper seis not the causal factor of the QTL. The upstream sequence of BnSHP1.A9in the promotor region harboring highly methylated long terminal repeat retrotransposon insertion (LTR, 4803bp) in R2 repressed the expression of BnSHP.A9,and thus contributed to the positive effect on pod shatter resistance. Genetic and association analysis revealed that thecopiaLTR retrotransposon based markerBnSHP1.A9-R2can be used for breeding for pod shatter resistant varieties and reducing the loss of seed yield in oilseed rape.
Localizing components of shared transethnic genetic architecture of complex traits from GWAS summary data
Authors: Shi Huwenbo , Burch Kathryn S. , Johnson Ruth , Freund Malika K. , Kichaev Gleb , Mancuso Nicholas , Manuel Astrid M. , Dong Natalie , Pasaniuc Bogdan 
Published: December 2019

AbstractDespite strong transethnic genetic correlations reported in the literature for many complex traits, the non-transferability of polygenic risk scores across populations suggests the presence of population-specific components of genetic architecture. We propose an approach that models GWAS summary data for one trait in two populations to estimate genome-wide proportions of population-specific/shared causal SNPs. In simulations across various genetic architectures, we show that our approach yields approximately unbiased estimates with in-sample LD and slight upward-bias with out-of-sample LD. We analyze 9 complex traits in individuals of East Asian and European ancestry, restricting to common SNPs (MAF > 5%), and find that most common causal SNPs are shared by both populations. Using the genome-wide estimates as priors in an empirical Bayes framework, we perform fine-mapping and observe that high-posterior SNPs (for both the population-specific and shared causal configurations) have highly correlated effects in East Asians and Europeans. In population-specific GWAS risk regions, we observe a 2.8x enrichment of shared high-posterior SNPs, suggesting that population-specific GWAS risk regions harbor shared causal SNPs that are undetected in the other GWAS due to differences in LD, allele frequencies, and/or sample size. Finally, we report enrichments of shared high-posterior SNPs in 53 tissue-specific functional categories and find evidence that SNP-heritability enrichments are driven largely by many low-effect common SNPs.
Comparative evaluation ofAspergillus nigerstrains for endogenous pectin depolymerization capacity and suitability for D-galacturonic acid production
Authors: Schäfer Dominik , Schmitz Kevin , Weuster-Botz Dirk , Benz J. Philipp 
Published: December 2019

AbstractPectinaceous agricultural residues rich ind-galacturonic acid (d-GalA), such as sugar beet pulp, are considered as promising feedstocks for waste-to-value conversions.Aspergillus nigeris known for its strong pectinolytic activity. However, while specialized strains for production of citric acid or proteins are openly available, this is not the case for the production of pectinases. We therefore systematically compared the pectinolytic capabilities of sixA. nigerstrains (ATCC 1015, ATCC 11414, NRRL 3122, CBS 513.88, NRRL 3, N402) using controlled batch cultivations in stirred-tank bioreactors.A. nigerATCC 11414 showed the highest polygalacturonase activity, specific protein secretion and a suitable morphology. Furthermore,d-GalA release from sugar beet pulp was 75% higher compared to the standard lab strainA. nigerN402. Our study therefore presents a robust initial strain selection to guide future process improvement ofd-GalA production from agricultural residues and identifies the most suitable base strain for further genetic optimizations.
Checkpoint defects require WRNIP1 to counteract R-loop-associated genomic instability
Authors: Marabitti Veronica , Lillo Giorgia , Malacaria Eva , Palermo Valentina , Pichierri Pietro , Franchitto Annapaola 
Published: December 2019

ABSTRACTConflicts between replication and transcription are common source of genome instability and many factors participate in prevention or removal of harmful R-loops. Here, we demonstrate that a WRNIP1-mediated response plays an important role in counteracting accumulation of aberrant R-loops. Using human cellular models with compromised ATR-dependent checkpoint activation, we show that WRNIP1 is stabilised in chromatin and is needed for maintaining genome integrity by mediating the ATM-dependent phosphorylation of CHK1. Furthermore, we show that loss of WRN or ATR signalling leads to accumulation of R-loop-dependent parental ssDNA, which is covered by RAD51. We demonstrate that WRNIP1 chromatin retention is also required to stabilise the association of RAD51 with ssDNA in proximity of R-loops. Therefore, in these pathological contexts, ATM inhibition or WRNIP1 abrogation is accompanied by increased levels of genomic instability. Overall our findings reveal a novel function of WRNIP1 in preventing R-loop-driven genome instability, providing new clues to understand the way replication-transcription conflicts are resolved.