bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of noise on the equivalence of word-lists in a phonemically balanced word test
Authors: Vaidyanath Ramya , Yathiraj Asha
Published: January 2019

Purpose:

The main purpose of the study was to determine the influence of noise on the equivalency of word-lists in a speech-in-noise test. Additionally, the performance of young and older adults was compared.

Method:

Thirty-four young adults with normal hearing, aged 18–36 years, were compared with 49 older adults, aged 55–75 years having hearing sensitivity ≤20 dB HL till 2000 Hz. The young adults were evaluated using a speech-in-noise test having four word-lists that were equivalent in quiet, with half being tested in the right ear and half in the left ear. The older adults were tested with two of the lists, one in each ear.

Results:

In the presence of speech-babble, the younger adults obtained no significant difference between the two ears as well as between gender. Their scores on all four lists of the test were equivalent. In contrast, in the older adults the females performed significantly better than the males on one of the two lists that they were evaluated on, but no ear difference was observed. There was a significant difference between the lists in the older adults. Additionally, the older adults performed significantly poorer when compared to the younger group.

Conclusions:

In the presence of noise, the lists were found to be equivalent in the young adults but was not in the older adults. A gender difference was absent in the younger adults but was present in the older listeners. The performance of the older listeners was consistently poorer compared to that of the younger listeners.
Emotional Intelligence and Self-Determined Behaviour Reduce Psychological Distress: Interactions with Resilience in Social Work Students in the UK
Authors: Bunce L , Lonsdale A J , King N , Childs J , Bennie R
Published: January 2019

Social workers in the UK experience higher levels of burnout compared with other healthcare professionals, making it important to understand how they can develop resilience to protect themselves from psychological distress. The current study aimed to deepen our understanding of the psychological predictors of resilience, which include emotional intelligence, reflective ability, social competence, and empathy, using self-determination theory. This theory suggests that fulfilment of the psychological needs for autonomy, competence, and relatedness will support resilience and protect against distress. We expected these needs to explain additional variance in resilience and distress beyond other emotional and social competencies. Analysis of questionnaire data from 211 social work students in the UK provided partial support for these hypotheses. Autonomy, competence, and relatedness were significantly positively correlated with resilience, and hierarchical regression analysis revealed that they explained somewhat more variance in resilience than previous factors alone (p = 0.06). Autonomy, competence, and relatedness explained significantly more variance than previous factors alone in psychological distress, although only autonomy and competence correlated with less psychological distress. Unexpectedly, relatedness correlated with more psychological distress. Furthermore, resilience played a mediating role between key variables and psychological distress. Implications for supporting the development of resilience in social work students are discussed.
The past and future of the social sciences. A Schumpeterian theory of scientific development?
Authors: Lucarelli Stefano , Giuliani Alfonso , Baron Hervé
Published: January 2019

The paper argues that Vergangenheit und Zukunft der Sozialwissenschaften (The Past and Future of the Social Sciences), a contribution not always well understood in the literature, is important to an understanding of Schumpeter’s concept of development as applied to the field of the social sciences. To this end, it addresses three key questions. First, can the book be taken as a starting point to reconstruct a Schumpeterian theory of scientific development? Second, is Vergangenheit und Zukunft merely ‘a brief outline of what first became the Epochen [der Dogmen- und Methodengeschichte] and finally the History of Economic Analysis’, as Elizabeth Boody Schumpeter wrote in her Editor’s Introduction (July 1952) to the latter work (p. XXXII), or should it be read as a complement to Epochen and perhaps the History? Third, is the eminent Japanese scholar Shionoya right to claim that Schumpeter’s work pursued the ambitious goal of developing a ‘comprehensive sociology’?
Locally different proteome in aortas from patients with stenotic tricuspid and bicuspid aortic valves†
Authors: Forte Amalia , Yin Xiaoke , Fava Marika , Bancone Ciro , Cipollaro Marilena , De Feo Marisa , Mayr Manuel , Jahangiri Marjan , Della Corte Alessandro
Published: January 2019

OBJECTIVES

We aimed to compare the intracellular proteome of ascending aortas from patients with stenotic bicuspid (BAV) and tricuspid aortic valves (TAV) to identify BAV-specific pathogenetic mechanisms of aortopathy and to verify the previously reported asymmetric expression of BAV aortopathy [concentrated at the convexity (CVX)] in its ‘ascending phenotype’ form.

METHODS

Samples were collected from the CVX and concavity sides of non-aneurysmal ascending aortas in 26 TAV and 26 BAV patients undergoing stenotic aortic valve replacement. Aortic lysates were subjected to cellular protein enrichment by subfractionation, and to proteome comparison by 2-dimensional fluorescence difference in-gel electrophoresis. Differentially regulated protein spots were identified by liquid chromatography–tandem mass spectrometry and analysed in silico. Selected results were verified by immunofluorescence and reverse transcription-polymerase chain reaction.

RESULTS

In BAV samples, 52 protein spots were differentially regulated versus TAV samples at the CVX and 10 spots at the concavity: liquid chromatography–tandem mass spectrometry identified 35 and 10 differentially regulated proteins, respectively. Charge trains of individual proteins (e.g. annexins) suggested the presence of post-translational modifications possibly modulating their activity. At the CVX, 37 of the 52 different protein spots showed decreased expression in BAV versus TAV. The affected biological pathways included those involved in smooth muscle cell contractile phenotype, metabolism and cell stress.

CONCLUSIONS

The observed differential proteomics profiles may have a significant impact on the pathogenesis of the aortopathy, pointing the way for further studies. At a preaneurysmal stage, an aorta with BAV shows more protein expression changes and potentially more post-translational modifications at the CVX of the ascending aorta than at the concavity, compared to that of TAV.
Safety and efficiency of a common and simplified protocol for pacemaker and defibrillator surveillance based on remote monitoring only: a long-term randomized trial (RM-ALONE)
Authors: García-Fernández Francisco Javier , Osca Asensi Joaquín , Romero Rafael , Fernández Lozano Ignacio , Larrazabal José María , Martínez Ferrer José , Ortiz Raquel , Pombo Marta , Tornés Francisco José , Moradi Kolbolandi Mehrard
Published: January 2019

Aims

This trial aimed to evaluate the safety and efficiency of a common and simplified protocol for the surveillance of cardiac implantable electronic devices based on remote monitoring (RM) in patients with pacemakers (PMs) and implantable cardiac defibrillators (ICDs) for at least 24 months.

Methods and results

The RM-ALONE is a multicentre prospective trial that randomly assigned 445 patients in two groups, both followed by RM: the home monitoring-only (HMo) based on RM + remote interrogations (RIs) every 6 months and the HM + IO that adds in-office evaluations every 6 months to RM. Four hundred and forty-five patients were enrolled in the study, 294 PMs and 151 ICDs recipients. In the HMo group, 20% of patients experienced ≥1 major adverse cardiac event (MACE) vs. 19.5% in HM + IO group (P = 0.006 for non-inferiority). The proportion of patients with a PM/ICD who experienced ≥1 MACE was 15.2/29.3% in HMo group and 16.1/26.3% in HM + IO group (hazard ratio 0.95/1.15, 95% confidence interval 0.53–1.70/0.62–2.10). There were 789 in-office evaluations (136 in the HMo and 653 in the HM + IO; P < 0.001). There was a 79.2% reduction of in-office evaluations with no significant differences in unscheduled visits between groups: 122 (54.5%) in HMo and 101 (45.3%) in HM + IO; P = 0.15. The time a physician/nurse spent per patient/follow-up was significantly reduced in the HMo group: 4/5 min (0–30)/(1–30) vs. 10/10 min (0–40)/(1–40) in HM + IO (P < 0.0001).

Conclusion

The RM-ALONE protocol common for ICD and PM surveillance, consisting of RM + RI every 6 months has proven safe and efficient in reducing hospital visits and staff workload.
A new analysis of a numerical method for the time-fractional Fokker–Planck equation with general forcing
Authors: Huang Can , Le Kim Ngan , Stynes Martin
Published: January 2019

First, a new convergence analysis is given for the semidiscrete (finite elements in space) numerical method that is used in Le et al. (2016, Numerical solution of the time-fractional Fokker–Planck equation with general forcing. SIAM J. Numer. Anal.,54 1763–1784) to solve the time-fractional Fokker–Planck equation on a domain $\varOmega \times [0,T]$ with general forcing, i.e., where the forcing term is a function of both space and time. Stability and convergence are proved in a fractional norm that is stronger than the $L^2(\varOmega )$ norm used in the above paper. Furthermore, unlike the bounds proved in Le et al., the constant multipliers in our analysis do not blow up as the order of the fractional derivative $\alpha $ approaches the classical value of $1$. Secondly, for the semidiscrete (L1 scheme in time) method for the same Fokker–Planck problem, we present a new $L^2(\varOmega )$ convergence proof that avoids a flaw in the analysis of Le et al.’s paper for the semidiscrete (backward Euler scheme in time) method.
Evaluating the Landscape of Clinical Research in Neurosurgery
Authors: Wilde Herschel W , Reese Jared C , Azab Mohammed A , Karsy Michael , Guan Jian , Rolston John D
Published: January 2019

BACKGROUND

Many clinical trials and observational research never reach publication in peer-reviewed journals. Unpublished research results, including neutral study findings, hinder generation of new research questions, utilize healthcare resources without benefit, and may place patients at risk without benefit.

OBJECTIVE

To examine the publication of neurosurgery trials listed in ClinicalTrials.gov.

METHODS

Clinical neurosurgery research was identified by searching the registry and categorized by study type. Associated publications were identified on Pubmed.gov.

RESULTS

Among the 709 studies identified, spine (292, 41.2%) studies were most common, followed by tumor and cranial (each 114, 16.1%). Funding was predominantly private (482, 68.0%), followed by industry (135, 19.0%) and National Institutes of Health (9, 1.3%). A lower proportion of published studies (vs unpublished) received private funding in functional (33.3 vs 65.3%) and tumor (80.0 vs 68.7%). Only 104/464 (22.4%) studies had an associated publication. The mean time from listed study completion to first publication was 31.0 ± 27.5 mo. Most published studies had significant study differences between treatment arms (n = 72, 69.2%); studies with neutral findings were less likely to be published (n = 13, 12.5%). Surgical discipline (P = .1), funding source (P = .8), patient age (P = .4), planned enrollment (P = .1), phase of trial (P = .3), and study type (P = .2) did not affect publication rates. However, the interaction between study category and funding source significantly affected publication rate (P = .04, generalized linear model, R2 = 0.05). Publication timing (1-way analysis of variance, P = .5) and frequency (chi-square, P = .2) did not differ among disciplines.

CONCLUSION

Clinical trials and observational research in neurosurgery are often not published promptly, especially if results were nonsignificant or the trial had private funding.
Reserved Bed Program Reduces Neurosciences Intensive Care Unit Capacity Strain: An Implementation Study
Authors: Shank Christopher D , Erickson Nicholas J , Miller David W , Lindsey Brittany F , Walters Beverly C
Published: January 2019

BACKGROUND

Neurosciences intensive care units (NICUs) provide institutional centers for specialized care. Despite a demonstrable reduction in morbidity and mortality, NICUs may experience significant capacity strain with resulting supraoptimal utilization and diseconomies of scale. We present an implementation study in the recognition and management of capacity strain within a large NICU in the United States. Excessive resource demand in an NICU creates significant operational issues.

OBJECTIVE

To evaluate the efficacy of a Reserved Bed Pilot Program (RBPP), implemented to maximize economies of scale, to reduce transfer declines due to lack of capacity, and to increase transfer volume for the neurosciences service-line.

METHODS

Key performance indicators (KPIs) were created to evaluate RBPP efficacy with respect to primary (strategic) objectives. Operational KPIs were established to evaluate changes in operational throughput for the neurosciences and other service-lines. For each KPI, pilot-period data were compared to the previous fiscal year.

RESULTS

RBPP implementation resulted in a significant increase in accepted transfer volume to the neurosciences service-line (P = .02). Transfer declines due to capacity decreased significantly (P = .01). Unit utilization significantly improved across service-line units relative to theoretical optima (P < .03). Care regionalization was achieved through a significant reduction in “off-service” patient placement (P = .01). Negative externalities were minimized, with no significant negative impact in the operational KPIs of other evaluated service-lines (P = .11).

CONCLUSION

Capacity strain is a significant issue for hospital units. Reducing capacity strain can increase unit efficiency, improve resource utilization, and augment service-line throughput. RBPP implementation resulted in a significant improvement in service-line operations, regional access to care, and resource efficiency, with minimal externalities at the institutional level.
Pipeline for Distal Cerebral Circulation Aneurysms
Authors: Atallah Elias , Saad Hassan , Mouchtouris Nikolaos , Bekelis Kimon , Walker Jackson , Chalouhi Nohra , Tjoumakaris Stavropoula , Smith Michelle , Rosenwasser Robert H , Zarzour Hekmat , Herial Nabeel , Feghali James , Gooch Michael Reid , Missios Symeon , Sweid Ahmad , Jabbour Pascal
Published: January 2019

BACKGROUND

Pipeline embolization device (PED; Medtronic, Dublin, Ireland) utilization is not limited to the treatment of giant wide-necked aneurysms. It has been expanded to handle small blisters, fusiforms, and dissecting intracranial aneurysms.

OBJECTIVE

To report the use of the PED in various off-label distal cerebral circulation (DCC) arteries with a follow-up to assess clinical outcomes.

METHODS

Between 2011 and 2016, of 437 consecutive patients, 23 patients with aneurysms located in DCCs were treated with PED. Data on patient presentation, aneurysm characteristics, procedural outcomes, postoperative course, and aneurysm occlusion were gathered. To control confounding, we used multivariable logistic regression and propensity score conditioning.

RESULTS

A total of 437 patients (mean age 52.12 years; 62 women [14.2%]) underwent treatment with PED in our institution. Twenty-three of 437 (5.2%) received a pipeline in a distal artery: 11/23 middle cerebral artery, 6/23 posterior cerebral artery, 3/23 anterior cerebral artery (A1/A2, pericallosal artery), and 3/23 posterior inferior cerebellar artery. Twenty percent of the aneurysms were treated in the past, 10% had previously ruptured, and 5.9% ruptured at presentation to our hospital. The mean aneurysm size was 9.0 ± 6 mm. The mean follow-up was 12 mo (SD = 12.5). In multivariable logistic regression, no associations were found between PED deployment in DCCs and aneurysm occlusion or thromboembolic complications. PED use in DCC was associated with a good clinical outcome. Twenty-two people of 23 (95%) had a good clinical outcome in the latest follow-up.

CONCLUSION

Treatment of DCC aneurysms with PED is technically challenging mainly because of the small caliber and tortuosity of the parent arteries. The results of this study further support the safety of flow diverters in the treatment of various distal aneurysms.
European consensus-based recommendations for diagnosis and treatment of immunoglobulin A vasculitis—the SHARE initiative
Authors: Ozen Seza , Marks Stephen D. , Brogan Paul , Groot Noortje , de Graeff Nienke , Avcin Tadej , Bader-Meunier Brigitte , Dolezalova Pavla , Feldman Brian M. , Kone-Paut Isabelle , Lahdenne Pekka , McCann Liza , Pilkington Clarissa , Ravelli Angelo , van Royen Annet , Uziel Yosef , Vastert Bas , Wulffraat Nico , Kamphuis Sylvia , Beresford Michael W.
Published: January 2019

Objectives

IgA vasculitis (IgAV, formerly known as Henoch–Schönlein purpura) is the most common cause of systemic vasculitis in childhood. To date, there are no internationally agreed, evidence-based guidelines concerning the appropriate diagnosis and treatment of IgAV in children. Accordingly, treatment regimens differ widely. The European initiative SHARE (Single Hub and Access point for paediatric Rheumatology in Europe) aims to optimize care for children with rheumatic diseases. The aim therefore was to provide internationally agreed consensus recommendations for diagnosis and treatment for children with IgAV.

Methods

Recommendations were developed by a consensus process in accordance with the EULAR standard operating procedures. An extensive systematic literature review was performed, and evidence-based recommendations were extrapolated from the included papers. These were evaluated by a panel of 16 international experts via online surveys and subsequent consensus meeting, using nominal group technique. Recommendations were accepted when ⩾80% of experts agreed.

Results

In total, 7 recommendations for diagnosis and 19 for treatment of paediatric IgAV were accepted. Diagnostic recommendations included: appropriate use of skin and renal biopsy, renal work-up and imaging. Treatment recommendations included: the importance of appropriate analgesia and angiotensin-converting enzyme inhibitor use and non-renal indications for CS use, as well as a structured approach to treating IgAV nephritis, including appropriate use of CS and second-line agents in mild, moderate and severe disease along with use of angiotensin-converting enzyme inhibitors and maintenance therapy.

Conclusion

The SHARE initiative provides international, evidence-based recommendations for the diagnosis and treatment of IgAV that will facilitate improvement and uniformity of care.
CO2conversion to methane and biomass in obligate methylotrophic methanogens in marine sediments
Authors: Yin Xiuran , Wu Weichao , Maeke Mara , Richter-Heitmann Tim , Kulkarni Ajinkya C. , Oni Oluwatobi E. , Wendt Jenny , Elvert Marcus , Friedrich Michael W.
Published: January 2019

Methyl substrates are important compounds for methanogenesis in marine sediments but diversity and carbon utilization by methylotrophic methanogenic archaea have not been clarified. Here, we demonstrate that RNA-stable isotope probing (SIP) requires13C-labeled bicarbonate as co-substrate for identification of methylotrophic methanogens in sediment samples of the Helgoland mud area, North Sea. Using lipid-SIP, we found that methylotrophic methanogens incorporate 60 to 86% of dissolved inorganic carbon (DIC) into lipids, and thus considerably more than what can be predicted from known metabolic pathways (∼40% contribution). In slurry experiments amended with the marine methylotrophMethanococcoides methylutens, up to 12% of methane was produced from CO2, indicating that CO2-dependent methanogenesis is an alternative methanogenic pathway and suggesting that obligate methylotrophic methanogens grow in fact mixotrophically on methyl compounds and DIC. Thus, the observed high DIC incorporation into lipds is likely linked to CO2-dependent methanogenesis, which was triggered when methane production rates were low. Since methylotrophic methanogenesis rates are much lower in marine sediments than under optimal conditions in pure culture, CO2conversion to methane is an important but previously overlooked methanogenic process in sediments for methylotrophic methanogens.
Planning Face, Hand, and Leg Movements: Anatomical Constraints on Preparatory Inhibition
Authors: Labruna Ludovica , Tischler Claudia , Cazares Cristian , Greenhouse Ian , Duque Julie , Lebon Florent , Ivry Richard B.
Published: January 2019

Motor-evoked potentials (MEPs), elicited by Transcranial Magnetic Stimulation (TMS) over the motor cortex, are reduced during the preparatory period in delayed response tasks. Here we examine how MEP suppression varies as a function of the anatomical organization of the motor cortex. MEPs were recorded from a left index muscle while participants prepared a hand or leg movement in Experiment 1, or prepared an eye or mouth movement in Experiment 2. In this manner, we assessed if the level of MEP suppression in a hand muscle varied as a function of the anatomical distance between the agonist for the forthcoming movement and the muscle targeted by TMS. MEPs suppression was attenuated when the cued effector was anatomically distant from the hand (e.g., leg or facial movement compared to finger movement). A similar effect was observed in Experiment 3 in which MEPs were recorded from a muscle in the leg and the forthcoming movement involved the upper limb or face. These results demonstrate an important constraint on preparatory inhibition: It is sufficiently broad to be manifest in a muscle that is not involved in the task, but is not global, showing a marked attenuation when the agonist muscle belongs to a different segment of the body.

New & Noteworthy

Using TMS, we examine changes in corticospinal excitability as people prepare to move. Consistent with previous work, we observe a reduction in excitability during the preparatory period, an effect observed in both task relevant and task irrelevant muscles. However, this preparatory inhibition is anatomically constrained, attenuated in muscles belonging to a different body segment than the agonist of the forthcoming movement.
Spatial sorting enables comprehensive characterization of liver zonation
Authors: Ben-Moshe Shani , Shapira Yonatan , Moor Andreas E. , Halpern Keren Bahar , Itzkovitz Shalev
Published: January 2019

The mammalian liver is composed of repeating hexagonal units termed lobules. Spatially-resolved single-cell transcriptomics revealed that about half of hepatocyte genes are differentially expressed across the lobule. Technical limitations impede reconstructing similar global spatial maps of other hepatocyte features. Here, we used zonated surface markers to sort hepatocytes from defined lobule zones with high spatial resolution. We applied transcriptomics, microRNA array measurements and Mass-spectrometry proteomics to reconstruct spatial atlases of multiple zonated hepatocyte features. We found that protein zonation largely overlapped mRNA zonation. We identified zonation of key microRNAs such as miR-122, and inverse zonation of microRNAs and their hepatocyte gene targets, implying potential regulation through zonated mRNA degradation. These targets included the pericentral Wnt receptors Fzd7 and Fzd8 and the periportal Wnt inhibitors Tcf7l1 and Ctnnbip1. Our approach facilitates reconstruction of spatial atlases of multiple cellular features in the liver and in other structured tissues.
Genomic analysis of the four ecologically distinct cactus host populations ofDrosophila mojavensis
Authors: Allan Carson W. , Matzkin Luciano M.
Published: January 2019

Background

Relationships between an organism and its environment can be fundamental in the understanding how populations change over time and species arise. Local ecological conditions can shape variation at multiple levels, among these are the evolutionary history and trajectories of coding genes. This study examines the rate of molecular evolution at protein-coding genes throughout the genome in response to host adaptation in the cactophilicDrosophila mojavensis. These insects are intimately associated with cactus necroses, developing as larvae and feeding as adults in these necrotic tissues.Drosophila mojavensisis composed of four isolated populations across the deserts of western North America and each population has adapted to utilize different cacti that are chemically, nutritionally, and structurally distinct.

Results

High coverage Illumina sequencing was performed on three previously unsequenced populations ofD. mojavensis. Genomes were assembled using the previously sequenced genome ofD. mojavensisfrom Santa Catalina Island (USA) as a template. Protein coding genes were aligned across all four populations and rates of protein evolution were determined for all loci using a several approaches.

Conclusions

Loci that exhibited elevated rates of molecular evolution tended to be shorter, have fewer exons, low expression, be transcriptionally responsive to cactus host use and have fixed expression differences across the four cactus host populations. Fast evolving genes were involved with metabolism, detoxification, chemosensory reception, reproduction and behavior. Results of this study gives insight into the process and the genomic consequences of local ecological adaptation.
A unified framework for inferring the multi-scale organization of chromatin domains from Hi-C
Authors: Bak Ji Hyun , Kim Min Hyeok , Liu Lei , Hyeon Changbong
Published: January 2019

Identifying chromatin domains (CDs) from high-throughput chromosome conformation capture (Hi-C) data is currently a central problem in genome research. Here we present a unified algorithm, Multi-CD, which infers CDs at various genomic scales by leveraging the information from Hi-C. By integrating a model of the chromosome from polymer physics, statistical physics-based clustering analysis, and Bayesian inference, Multi-CD identifies the CDs that best represent the global pattern of correlation manifested in Hi-C. The multi-scale intra-chromosomal structures compared across different cell types allow us to glean the principles of chromatin organization: (i) Sub-TADs, TADs, and meta-TADs constitute a robust hierarchical structure. (ii) The assemblies of compartments and TAD-based domains are governed by different organizational principles. (iii) Sub-TADs are the common building blocks of chromosome architecture. CDs obtained from Multi-CD applied to Hi-C data enable a quantitative and comparative analysis of chromosome organization in different cell types, providing glimpses into structure-function relationship in genome.
Short-range interactions govern cellular dynamics in microbial multi-genotype systems
Authors: Co A. Dal , van Vliet S. , Kiviet D. J. , Schlegel S. , Ackermann M.
Published: January 2019

Ecosystem processes result from interaction between organisms. When interactions are local, the spatial organization of organisms defines their network of interactions, and thus influences the system’s functioning. This can be especially relevant for microbial systems, which often consist of spatially structured communities of cells connected by a dense interaction network. Here we measured the spatial interaction network between cells in microbial systems and identify the factors that determine it. Combining quantitative single-cell analysis of synthetic bacterial communities with mathematical modeling, we find that cells only interact with other cells in their immediate neighbourhood. This short interaction range impacts the functioning of the whole system by reducing its ability to perform metabolic processes collectively. Our experiments and models demonstrate that the spatial scale of cell-to-cell interaction plays a fundamental role in understanding and controlling natural communities, and in engineering microbial systems for specific purposes.

Significance Statement

Communities of interacting microbes perform fundamental processes on earth. We do not understand well how these processes emerge from the interactions between individual microbial cells. Our work investigates how strongly individual cells interact and how the strength of the interaction depends on the distance between cells. The discovery that individual cells ‘live in a small world’, i.e. they only interact with a small number of cells around them, changes our understanding of how cells in natural microbial communities are metabolically coupled and how their spatial arrangement determines emergent properties at the community level. Our quantitative single-cell approach allows to address central questions on systems composed of interacting genotypes and to increase our understanding and ability to control microbial communities.
Using environmental DNA for the detection of Schistosoma mansoni: toward improved environmental surveillance of schistosomiasis
Authors: Sengupta Mita Eva , Hellström Micaela , Kariuki Henry Curtis , Olsen Annette , Thomsen Philip Francis , Mejer Helena , Willerslev Eske , Mwanje Mariam , Madsen Henry , Kristensen Thomas Krogsgaard , Stensgaard Anna-Sofie , Vennervald Birgitte Jyding
Published: January 2019

Schistosomiasis is a waterborne, infectious disease with high morbidity and significant economic burdens affecting more than 250 million people globally. Disease control has, with notable success, for decades focused on drug treatment of infected human populations, but a recent paradigm shift now entails moving from control to elimination. To achieve this ambitious goal more sensitive diagnostic tools are needed to monitor progress towards transmission interruption in the environment, especially in low-intensity infection areas. We report on the development of an environmental DNA (eDNA) based tool to efficiently detect DNA traces of the parasite Schistosoma mansoni directly in the aquatic environment, where the non-human part of the parasite life cycle occurs. To our knowledge, this is the first report of the successful detection of S. mansoni in freshwater samples using aquatic eDNA. True eDNA was detected in as few as 10 cercariae/L water in laboratory experiments. The field applicability of the method was tested at known transmission sites in Kenya, where comparison of schistosome detection by conventional snail surveys (snail collection and cercariae shedding) with eDNA (water samples) showed 71% agreement between the methods. The eDNA method furthermore detected schistosome presence at two additional sites where snail shedding failed, demonstrating a higher sensitivity of eDNA sampling. We conclude that eDNA provides a promising new tool to significantly improve the environmental surveillance of S. mansoni. Given the proper method and guideline development, eDNA could become an essential future component of the schistosomiasis control tool box needed to achieve the goal of elimination.

Significance

Accurate detection and delineation of schistosomiasis transmission sites will be vital in on-going efforts to control and ultimately eliminate one of the most neglected tropical parasitic diseases affecting more than 250 million people worldwide. Conventional methods to detect parasites in the environment are cumbersome and have low sensitivity. We therefore developed an environmental DNA (eDNA) based method for schistosome detection in aquatic environments. Aquatic eDNA showed higher sensitivity than conventional snail surveys. We conclude that eDNA is a promising non-invasive and sensitive tool for environmental surveillance of schistosomiasis transmission. As the efforts and aims to control the disease are transitioning towards complete transmission interruption, this could be the robust and cost-effective surveillance tool needed in the “end game” of schistosomiasis.
Modelling structural constraints on protein evolution via side-chain conformational states
Authors: Perron Umberto , Kozlov Alexey M. , Stamatakis Alexandros , Goldman Nick , Moal Iain H.
Published: January 2019

Few models of sequence evolution incorporate parameters describing protein structure, despite its high conservation, essential functional role and increasing availability. We present a structurally-aware empirical substitution model for amino acid sequence evolution in which proteins are expressed using an expanded alphabet that relays both amino acid identity and structural information. Each character specifies an amino acid as well a rotamer state: the discrete geometric pattern of permitted side-chain atomic positions. By assigning rotamer states in 251,194 protein structures and identifying 4,508,390 substitutions between closely related sequences, we generate a 55-state model that shows that the evolutionary properties of amino acids depend strongly upon side-chain geometry. The model performs as well as or better than traditional 20-state models for divergence time estimation, tree inference and ancestral state reconstruction. We conclude that the concomitant evolution of sequence and structure is a valuable source of phylogenetic information.
A nucleotide resolution map of Top2-linked DNA breaks in the yeast and human genome
Authors: Gittens William , Johnson Dominic J. , Allison Rachal M. , Cooper Tim J. , Thomas Holly , Neale Matthew J
Published: January 2019

DNA topoisomerases are required to resolve DNA topological stress. Despite this essential role, abortive topoisomerase activity generates aberrant protein-linked DNA breaks, jeopardising genome stability. Here, to understand the genomic distribution and mechanisms underpinning topoisomerase-induced DNA breaks, we map Top2 DNA cleavage with strand-specific nucleotide resolution across theS. cerevisiaeand human genomes—and use the meiotic Spo11 protein to validate the broad applicability of this method to explore the role of diverse topoisomerase family members. Our data characterises Mre11-dependent repair in yeast, and defines two strikingly different fractions of Top2 activity in humans: tightly localised CTCF-proximal, and broadly distributed transcription-proximal, the latter correlated with gene length and expression. Moreover, single nucleotide accuracy enables us to reveal the influence primary DNA sequence has upon Top2 cleavage—distinguishing canonical DNA double-strand breaks (DSBs) from a major population of DNA single-strand breaks (SSBs) induced by etoposide (VP16)in vivo.
Estimating virulence from relative survival
Authors: Agnew Philip
Published: January 2019

A pathogen’s virulence is a key parameter in the mathematical models on which most epidemiological theory is based. In these models virulence generally has a very specific definition where it is the increased per capita rate of mortality of infected hosts due to infection. Empirical studies involving the experimental infection of hosts often estimate virulence with the aim of comparing these estimates to values or patterns predicted in the theoretical literature. However most empirical studies do not estimate virulence as it is defined in the theoretical literature, thus potentially confounding comparisons between the two approaches. Here the analysis of relative survival is applied to the type of data routinely generated in empirical studies to estimate virulence as it is defined in the theoretical literature. The theoretical grounds for approach are outlined, followed by worked examples estimating the virulence of different pathogens with data from published studies. Code allowing virulence to be estimated by maximum likelihood withRis provided.
Antero-posterior versus lateral vestibular input processing in human visual cortex
Authors: Aedo-Jury Felipe , Cottereau Benoit R. , Celebrini Simona , Cauquil Alexandra Séverac
Published: January 2019

Visuo-vestibular integration is crucial for locomotion, yet cortical mechanisms involved remain poorly understood. We combined binaural monopolar galvanic vestibular stimulation (GVS) and functional magnetic resonance imaging (fMRI) to characterize the cortical networks activated during antero-posterior and lateral stimulations in humans. We focused on functional areas that selectively respond to egomotion-consistent optic flow patterns: the human middle temporal complex (hMT+), V6, the ventral intraparietal (VIP) area, the cingulate sulcus visual (CSv) area and the posterior insular cortex (PIC). Areas hMT+, CSv, and PIC were equivalently responsive during lateral and antero-posterior GVS while areas VIP and V6 were highly activated during antero-posterior GVS but remained silent during lateral GVS. Using psychophysiological interaction (PPI) analyses, we confirmed that a cortical network including areas V6 and VIP is engaged during antero-posterior GVS. Our results suggest that V6 and VIP play a specific role in processing multisensory signals specific to locomotion during navigation.
Earliest-known intentionally deformed human cranial fossil from Asia and the initiation of hereditary hierarchy in the early Holocene
Authors: Ni Xijun , Li Qiang , Stidham Thomas A. , Yang Yangheshan , Ji Qiang , Jin Changzhu , Samiullah Khizar
Published: January 2019

Hereditary hierarchy is one of the major features of complex societies. Without a written record, prehistoric evidence for hereditary hierarchy is rare. Intentional cranial deformation (ICD) is a cross-generational cultural practice that embodies social identity and culture beliefs in adults through the behavior of altering infant head shape. Therefore, ICD is usually regarded as an archeological clue for the occurrence of hereditary hierarchy. With a calibrated radiocarbon age of 11245-11200 years BP, a fossil skull of an adult male displaying ICD discovered in Northeastern China is among the oldest-known ICD practices in the world. Along with the other earliest global occurrences of ICD, this discovery points to the early initiation of complex societies among the non-agricultural local societies in Northeastern Asia in the early Holocene. A population increase among previously more isolated terminal Pleistocene/early Holocene hunter-gatherer groups likely increased their interactions, possibly fueling the formation of the first complex societies.
Tracing the evolution of the plastome and mitogenome in the Chloropicophyceae uncovered convergent tRNA gene losses and a variant plastid genetic code
Authors: Turmel Monique , Santos Adriana Lopes dos , Otis Christian , Sergerie Roxanne , Lemieux Claude
Published: January 2019

The tiny green algae belonging to the Chloropicophyceae play a key role in marine phytoplankton communities; this newly erected class of prasinophytes comprises two genera (ChloropiconandChloroparvula) containing each several species. We sequenced the plastomes and mitogenomes of eightChloropiconand fiveChloroparvulaspecies to better delineate the phylogenetic affinities of these taxa and to infer the suite of changes that their organelle genomes sustained during evolution. The relationships resolved in organelle-based phylogenomic trees were essentially congruent with previously reported rRNA trees, and similar evolutionary trends but distinct dynamics were identified for the plastome and mitogenome. Although the plastome sustained considerable changes in gene content and order at the time the two genera split, subsequently it remained stable and maintained a very small size. The mitogenome, however, was remodeled more gradually and showed more fluctuation in size, mainly as a result of expansions/contractions of intergenic regions. Remarkably, the plastome and mitogenome lost a common set of three tRNA genes, with thetrnI(cau) andtrnL(uaa) losses being accompanied with important variations in codon usage. Unexpectedly, despite the disappearance oftrnI(cau) from the plastome in theChloroparvulalineage, AUA codons (the codons recognized by this gene product) were detected in certain plastid genes. By comparing the sequences of plastid protein-coding genes from chloropicophycean and phylogenetically diverse chlorophyte algae with those of the corresponding predicted proteins, we discovered that the AUA codon was reassigned from isoleucine to methionine inChloroparvula. This noncanonical genetic code has not previously been uncovered in plastids.
Ecological niche differentiation in soil cyanobacterial communities across the globe
Authors: Cano-Díaz Concha , Maestre Fernando T. , Eldridge David J. , Singh Brajesh K. , Bardgett Richard D. , Fierer Noah , Delgado-Baquerizo Manuel
Published: January 2019

Cyanobacteria are key organisms in the evolution of life on Earth, but their distribution and environmental preferences in terrestrial ecosystems remain poorly understood. This lack of knowledge is particularly evident for two recently discovered non-photosynthetic cyanobacterial classes, Melainabacteria and Sericytochromatia, limiting our capacity to predict how these organisms and the important ecosystem functions they perform will respond to ongoing global change. Here, we conducted a global field survey covering a wide range of vegetation types and climatic conditions to identify the environmental factors associated with the distribution of soil cyanobacterial communities. Network analyses revealed three major clusters of cyanobacterial phylotypes, each one dominated by members of one of the extant classes of Cyanobacteria (Oxyphotobacteria, Melainabacteria and Sericytochromatia), suggesting that species within these taxonomic groups share similar environmental preferences. Melainabacteria appear mostly in acidic and humid ecosystems, especially forests, Oxyphotobacteria are prevalent in arid and semiarid areas, and Sericytochromatia are common in hyperarid oligotrophic environments. We used this information to construct a global atlas of soil cyanobacteria. Our results provide novel insights into the ecology and biogeography of soil cyanobacteria and highlight how their global distribution could change in response to increased aridity, a landmark feature of climate change in terrestrial ecosystems worldwide.

Significance statement

Cyanobacteria have shaped the history of life on Earth and can be important photosynthesizers and nitrogen fixers in terrestrial ecosystems worldwide. The recent discovery of two non-photosynthetic classes has advanced our understanding of their evolution, but their distribution and environmental preferences remain poorly described. Using a global survey conducted across 237 locations on six continents, we identified three main groups of soil cyanobacteria with contrasting environmental preferences: acidic and humid ecosystems, arid and semiarid areas, and hyperarid oligotrophic ecosystems. We then constructed the first global atlas of soil cyanobacteria, an important advance in our understanding of the ecology and biogeography of these functionally important organisms.
Identification of Anonymous DNA Using Genealogical Triangulation
Authors: Ellenbogen Paul , Narayanan Arvind
Published: January 2019

Abstract

Consumer genetics databases hold dense genotypes of millions of people, and the number is growing quickly [1] [2]. In 2018, law enforcement agencies began using such databases to identify anonymous DNA via long-range familial searches. We show that this technique is far more powerful if combined with a genealogical database of the type collected by online ancestry services. We present a “genealogical triangulation” algorithm and study its effectiveness on simulated datasets. We show that for over 50% of targets, their anonymous DNA can be identified (matched to the correct individual or same-sex sibling) when the genetic database includes just 1% of the population. We also show the effectiveness of “snowball identification” in which a successful identification adds to the genetic genealogical database, increasing the identification accuracy for future instances. We discuss our technique’s potential to enhance law enforcement capabilities as well as its privacy risks.
MOLI: Multi-Omics Late Integration with deep neural networks for drug response prediction
Authors: Sharifi-Noghabi Hossein , Zolotareva Olga , Collins Colin C. , Ester Martin
Published: January 2019

Motivation

Historically, gene expression has been shown to be the most informative data for drug response prediction. Recent evidence suggests that integrating additional omics can improve the prediction accuracy which raises the question of how to integrate the additional omics. Regardless of the integration strategy, clinical utility and translatability are crucial. Thus, we reasoned a multi-omics approach combined with clinical datasets would improve drug response prediction and clinical relevance.

Results

We propose MOLI, a Multi-Omics Late Integration method based on deep neural networks. MOLI takes somatic mutation, copy number aberration, and gene expression data as input, and integrates them for drug response prediction. MOLI uses type-specific encoding subnetworks to learn features for each omics type, concatenates them into one representation and optimizes this representation via a combined cost function consisting of a triplet loss and a binary cross-entropy loss. The former makes the representations of responder samples more similar to each and different from the non-responders, and the latter makes this representation predictive of the response values. We validate MOLI on in vitro and in vivo datasets for five chemotherapy agents and two targeted therapeutics. Compared to state-of-the-art single-omics and early integration multi-omics methods, MOLI achieves higher prediction accuracy in external validations. Moreover, a significant improvement in MOLI’s performance is observed for targeted drugs when training on a pan-drug input, i.e. using all the drugs with the same target compared to training only on drug-specific inputs. MOLI’s high predictive power suggests it may have utility in precision oncology.

Availability of the implemented codes

https://github.com/hosseinshn/MOLI

Contact

ccollins@prostatecentre.com and ester@cs.sfu.ca
Comparative Transcriptomic Signature of the Simulated Microgravity Response inCaenorhabditis elegans
Authors: Çelen İrem , Jayasinghe Aroshan , Doh Jung H. , Sabanayagam Chandran R.
Published: January 2019

Background

Given the growing interest in human exploration of space, it is crucial to identify the effect of space conditions on biological processes. The International Space Station (ISS) greatly helps researchers determine these effects. However, the impact of the ISS-introduced potential confounders (e.g., the combination of radiation and microgravity exposures) on the biological processes are often neglected, and separate investigations are needed to uncover the impact of individual conditions.

Results

Here, we analyze the transcriptomic response ofCaenorhabditis elegansto simulated microgravity and observe the maintained transcriptomic response after return to ground conditions for four, eight, and twelve days. Through the integration of our data with those in NASA GeneLab, we identify the gravitome, which we define as microgravity-responsive transcriptomic signatures. We show that 75% of the simulated microgravity-induced changes on gene expression persist after return to ground conditions for four days while most of these changes are reverted after twelve days return to ground conditions. Our results from integrative RNA-seq and mass spectrometry analyses suggest that simulated microgravity affects longevity regulating insulin/IGF-1 and sphingolipid signaling pathways.

Conclusions

Our results address the sole impact of simulated microgravity on transcriptome by controlling for the other space-introduced conditions and utilizing RNA-seq. Using an integrative approach, we identify a conserved transcriptomic signature to microgravity and its sustained impact after return to the ground. Moreover, we present the effect of simulated microgravity on distinct ceramide profiles. Overall, this work can provide insights into the sole effect of microgravity on biological systems.