bluuebunny/crossref_metadata_2025 huggingface dataset:
Patterns of Care and Age-Specific Impact of Extent of Resection and Adjuvant Radiotherapy in Pediatric Pineoblastoma
Authors: Jin Michael C , Prolo Laura M , Wu Adela , Azad Tej D , Shi Siyu , Rodrigues Adrian J , Soltys Scott G , Pollom Erqi L , Li Gordon , Hiniker Susan M , Grant Gerald A
Published: January 2020

BACKGROUND

Pediatric pineoblastomas are highly aggressive tumors that portend poor outcomes despite multimodal management. Controversy remains regarding optimal disease management.

OBJECTIVE

To evaluate patterns of care and optimal clinical management of pediatric pineoblastoma.

METHODS

A total of 211 pediatric (age 0-17 yr) histologically confirmed pineoblastoma patients diagnosed between 2004 and 2015 were queried from the National Cancer Database. Wilcoxon rank-sum statistics and chi-squared analyses were used to compare continuous and categorical variables, respectively. Univariable and multivariable Cox regressions were used to evaluate prognostic impact of covariates. Propensity-score matching was used to balance baseline characteristics.

RESULTS

Older patients (age ≥ 4 yr) experienced improved overall survival compared to younger patients (age < 4 yr) (hazard ratio [HR] = 0.41; 95% CI 0.25-0.66). Older patients (adjusted odds ratio [aOR] = 5.21; 95% CI 2.61-10.78) and those residing in high-income regions (aOR = 3.16; 95% CI 1.21-8.61) received radiotherapy more frequently. Radiotherapy was independently associated with improved survival in older (adjusted HR [aHR] = 0.31; 95% CI 0.12-0.87) but not younger (aHR = 0.64; 95% CI 0.20-1.90) patients. The benefits of radiotherapy were more pronounced in patients receiving surgery than in those not receiving surgery (aHR [surgical patients] = 0.23; 95% CI 0.08-0.65; aHR [nonsurgical patients] = 0.46; 95% CI 0.22-0.97). Older patients experienced improved outcomes associated with aggressive resection (P = .041); extent of resection was not associated with survival in younger patients (P = .880).

CONCLUSION

Aggressive tumor resection was associated with improved survival only in older pediatric patients. Radiotherapy was more effective in patients receiving surgery. Age-stratified approaches might allow for improved disease management of pediatric pineoblastoma.
Adult Social Environments and the Use of Combustible and Electronic Cigarettes: Opportunities for Reducing Smoking in the 30s
Authors: Kosterman Rick , Epstein Marina , Bailey Jennifer A , Oesterle Sabrina , Furlong Madeline , Hawkins J David
Published: January 2020

Introduction

Reducing cigarette use is a major public health goal in the United States. Questions remain, however, about the potential for the social environment in the adult years—particularly in the 30s and beyond—to influence cigarette use. This study tested pathways hypothesized by the social development model to understand the extent to which social environmental factors at age 33 (eg, involvement with smokers or with physically active people) contribute to changes in cigarette use from age 30 to age 39. Both combustible and electronic cigarette use were investigated.

Methods

Data were from the Seattle Social Development Project, a longitudinal study of 808 diverse participants with high retention. Self-reports assessed social developmental constructs, combustible and electronic cigarette use, and demographic measures across survey waves.

Results

At age 30, 32% of the sample reported past-month cigarette use. Using structural equation modeling, results showed high stability in cigarette use from age 30 to 39. After accounting for this stability, cigarette-using social environments at age 33 predicted personal beliefs or norms about smoking (eg, acceptability and social costs), which in turn predicted combustible cigarette use at age 39. Cigarette-using environments, however, directly predicted electronic cigarette use at age 39, with no significant role for beliefs about smoking.

Conclusions

Cigarette use was highly stable across the 30s, but social environmental factors provided significant partial mediation of this stability. Pathways were different for combustible and electronic cigarette use, however, with personal smoking norms playing an important role for the former but not the latter.

Implications

This study addresses the need for longitudinal investigation of social mechanisms and cigarette use in the 30s. Findings reinforce efforts to prevent the uptake of cigarettes prior to the 30s because, once started, smoking is highly stable. But social environmental factors remain viable intervention targets in the 30s to disrupt this stability. Addressing personal norms about smoking’s acceptability and social costs is likely a promising approach for combustible cigarette use. Electronic cigarettes, however, present a new challenge in that many perceived social costs of cigarette use do not readily translate to this relatively recent technology.
The Use of a Novel Perfusion-Based Human Cadaveric Model for Simulation of Dural Venous Sinus Injury and Repair
Authors: Strickland Ben A , Ravina Kristine , Kammen Alexandra , Chang Stephanie , Rutkowski Martin , Donoho Daniel A , Minneti Mike , Jackanich Anna , Bakhsheshian Joshua , Zada Gabriel
Published: January 2020

BACKGROUND

Dural sinus injuries are potentially serious complications associated with acute blood loss. It is imperative that neurosurgery trainees are able to recognize and manage this challenging scenario.

OBJECTIVE

To assess the feasibility of a novel perfusion-based cadaveric simulation model to provide the fundamentals of dural sinus repair to neurosurgical trainees.

METHODS

A total of 10 perfusion-based human cadaveric models underwent superior sagittal sinus (SSS) laceration. Neurosurgery residents were instructed to achieve hemostasis by any method in the first trial and then repeated the trial after watching the instructional dural flap technique video. Trials were timed until hemostasis and control of the region of injury was achieved. Pre- and post-trial questionnaires were administered to assess trainee confidence levels.

RESULTS

The high-flow extravasation of the perfusion-based cadaveric model mimicked similar conditions and challenges encountered during acute SSS injury. Mean ± standard deviation time to hemostasis was 341.3 ± 65 s in the first trial and 196.9 ± 41.8 s in the second trial (P < .0001). Mean trainee improvement time was 144.4 s (42.3%). Of the least-experienced trainees with longest repair times in the initial trial, a mean improvement time of 188.3 s (44.8%) was recorded. All participants reported increased confidence on post-trial questionnaires following the simulation (median pretrial confidence of 2 vs post-trial confidence of 4, P = .002).

CONCLUSION

A perfusion-based human cadaveric model accurately simulates acute dural venous sinus injury, affording neurosurgical trainees the opportunity to hone management skills in a simulated and realistic environment.
Prospective observational study to evaluate the use of musculoskeletal ultrasonography in rheumatoid arthritis management: the ECHO study
Authors: Stein Michael , Vaillancourt Julie , Rampakakis Emmanouil , Sampalis John S
Published: January 2020

Objectives

Since the creation of the Canadian Rheumatology Ultrasonography Society, an increasing number of rheumatologists has been trained in the use of musculoskeletal US (MSUS). We compared the effectiveness of MSUS to routine care (RC) as a disease management tool in patients with moderate-to-severe RA requiring a treatment change due to lack of efficacy. The predictive value of MSUS was also assessed.

Methods

This was a prospective, two-cohort, quasi-experimental study. Patients were managed either with MSUS (within the Canadian Rheumatology Ultrasonography Society) or as per RC for up to 1 year. Main outcomes included Clinical Disease Activity Index low disease activity/remission, DAS28 low disease activity/remission, MSUS scores, patient satisfaction and perception of participation in disease management.

Results

A total of 383 patients were enrolled (MSUS: n = 171; RC: n = 212). At baseline, a greater proportion of MSUS patients were treated with a biologic DMARD (50.3 vs 36.8%; P = 0.008) while more patients treated per RC received a non-biologic DMARD (84.2 vs 91.5%; P = 0.027). During follow-up, a greater number of RA treatment modifications was applied in the MSUS group compared with RC [adjusted incidence rate ratio (95% CI): 1.4 (1.1, 1.8)], including steroids, non-biologic DMARDs and biologic DMARDs. Regarding clinical and patient-reported outcomes, no remarkable differences were observed between groups. However, throughout the study, 50–80% of MSUS patients in clinical remission has a MSUS synovitis score of ≥1, and 37–73% an erosion score of ≥1. Significant associations were observed between baseline synovitis and joint erosion during follow-up.

Conclusion

MSUS assessments can be useful in detecting subclinical levels of inflammation and predicting future joint deterioration, thus allowing optimization of RA treatment and patient care.
Public health in genetic spaces: a statistical framework to optimize cluster-based outbreak detection
Authors: Chato Connor , Kalish Marcia L , Poon Art F Y
Published: January 2020

Genetic clustering is a popular method for characterizing variation in transmission rates for rapidly evolving viruses, and could potentially be used to detect outbreaks in ‘near real time’. However, the statistical properties of clustering are poorly understood in this context, and there are no objective guidelines for setting clustering criteria. Here, we develop a new statistical framework to optimize a genetic clustering method based on the ability to forecast new cases. We analysed the pairwise Tamura-Nei (TN93) genetic distances for anonymized HIV-1 subtype B pol sequences from Seattle (n = 1,653) and Middle Tennessee, USA (n = 2,779), and northern Alberta, Canada (n = 809). Under varying TN93 thresholds, we fit two models to the distributions of new cases relative to clusters of known cases: 1, a null model that assumes cluster growth is strictly proportional to cluster size, i.e. no variation in transmission rates among individuals; and 2, a weighted model that incorporates individual-level covariates, such as recency of diagnosis. The optimal threshold maximizes the difference in information loss between models, where covariates are used most effectively. Optimal TN93 thresholds varied substantially between data sets, e.g. 0.0104 in Alberta and 0.016 in Seattle and Tennessee, such that the optimum for one population would potentially misdirect prevention efforts in another. For a given population, the range of thresholds where the weighted model conferred greater predictive accuracy tended to be narrow (±0.005 units), and the optimal threshold tended to be stable over time. Our framework also indicated that variation in the recency of HIV diagnosis among clusters was significantly more predictive of new cases than sample collection dates (ΔAIC > 50). These results suggest that one cannot rely on historical precedence or convention to configure genetic clustering methods for public health applications, especially when translating methods between settings of low-level and generalized epidemics. Our framework not only enables investigators to calibrate a clustering method to a specific public health setting, but also provides a variable selection procedure to evaluate different predictive models of cluster growth.
Evolution of ecological structure of anole communities in tropical rain forests from north-western South America
Authors: Moreno-Arias Rafael A , Bloor Paul , Calderón-Espinosa Martha L
Published: January 2020

The coexistence of several anoles in the same place is attributed to differential partitioning of resources. Although several mainland and island communities show a similar structure, differences in life-history traits, absence of niche complementarity, higher food supply and higher numbers of predators in mainland environments support the idea that predation, rather than competition, is a more important structuring force in mainland than in island anole communities. To analyse the pattern of ecological structure in mainland anole communities, we studied communities in three tropical rain forests of north-western South America to obtain data about the use of resources on three niche axes [spatial, thermal and morphological (as a proxy of diet)] for 17 species of anoles. We analysed the patterns of niche overlap for each axis and found that overlap on the dietary axis was less than the overlap on the other axes, indicating that species using similar spatial or thermal resources diverge strongly in their diet. In addition, we identified a niche complementarity among niche axes, suggesting that intraspecific competition is also an important process in those communities. Finally, this study revealed a similar ecological structure in different communities of mainland rain-forest anoles, which share seven ecomorphs, suggesting ecological adaptation and convergence in mainland anoles.
Nighttime Application of UV-C to Control Cucumber Powdery Mildew
Authors: Patel Jaimin S. , Radetsky Leora C. , Nagare Rohan , Rea Mark S.
Published: January 2020

Nonionizing, ultraviolet (UV) radiation is effective for mitigating powdery mildew associated with a variety of crops including strawberry, grapes, rosemary, tomato, rose, and cucumber. The effectiveness of UV radiation depends upon the dose (irradiance × duration), the frequency of dosing, the time of application, and the sensitivity of the crop to UV radiation. Reported here are the results of two laboratory studies examining the impact of UV-C (254 nm) on cucumber and its obligate powdery-mildew-causing pathogen Podosphaera xanthii. In the first study, doses of UV-C (72 and 144 J m–2) applied every night were more effective at reducing disease severity than dosing every day. However, leaf area was reduced more following nighttime applications than daytime applications, suggesting that both day and night applications of UV-C could compromise yield without necessarily eliminating the disease. The second study showed that a dose of UV-C (7.2 J m–2) applied every night or a higher dose (70 J m–2) applied every fourth night were both effective for eliminating powdery mildew without significantly reducing leaf area. These findings, if confirmed in the field, could provide cucumber growers with additional options for controlling powdery mildew without compromising yield.
Hymenobacter sediminis sp. nov., isolated from lake sediment
Authors: Wang Chong , Liu Bang-Tao , Zhang Rui , Liu Chun-Li , Du Zong-Jun
Published: January 2020

A Gram-stain-negative, facultatively aerobic, rod-shaped, motile by gliding and pink-pigmented bacterial strain, designated ELS1360T, was isolated from a lake sediment sample collected in Inner Mongolia, PR China. Strain ELS1360T grew optimally at 33 °C, at pH 6.5–7.0 and without NaCl. Strain ELS1360T exhibited 97.3, 97.1 and 96.9 % 16S rRNA gene sequence similarities to

Hymenobacter aquatilis

HMF3095T,

Hymenobacter luteus

JCM 30328T and

Hymenobacter latericoloratus

JCM 30327T, respectively, and 90.4–96.9 % to other members of the genus

Hymenobacter

. Results of phylogenetic analysis based on 16S rRNA gene sequences showed that strain ELS1360T belonged to the genus

Hymenobacter

and clustered with

H. luteus

JCM 30328T and

H. latericoloratus

JCM 30327T. The predominant cellular fatty acids were iso-C15:0, summed feature 3 and C16:1ω5c. Strain ELS1360T contained MK-7 as the sole menaquinone. The major polar lipids contained phosphatidylethanolamine and two unidentified lipids. The genomic DNA G+C content of strain ELS1360T was 57.1 mol%. Based on the results of our phylogenetic, phenotypic, genotypic and chemotaxonomic analyses, it is concluded that strain ELS1360T represents a novel species within the genus

Hymenobacter

, for which the name Hymenobacter sediminis sp. nov. is proposed. The type strain is ELS1360T (=KCTC 62449T=MCCC 1H00319T).
ICTV Virus Taxonomy Profile: Spiraviridae
Authors: Prangishvili David , Mochizuki Tomohiro , Krupovic Mart ,   ICTV Report Consortium
Published: January 2020

The family Spiraviridae includes viruses that replicate in hyperthermophilic archaea from the genus

Aeropyrum

. The non-enveloped, hollow, cylindrical virions are formed from a coiling fibre that consists of two intertwining halves of a single circular nucleoprotein filament. A short appendage protrudes from each end of the cylindrical virion. The genome is circular, positive-sense, single-stranded DNA of 24 893 nucleotides. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) report on the family Spiraviridae, which is available at ictv.global/report/spiraviridae.
Motor cortex beta oscillations reflect motor skill learning ability after stroke
Authors: Espenhahn Svenja , Rossiter Holly E , van Wijk Bernadette CM , Redman Nell , Rondina Jane M , Diedrichsen Joern , Ward Nick S
Published: January 2020

Recovery of skilled movement after stroke is assumed to depend on motor learning. However, the capacity for motor learning and factors that influence motor learning after stroke have received little attention. In this study we firstly compared motor skill acquisition and retention between well-recovered stroke patients and age- and performance-matched healthy controls. We then tested whether beta oscillations (15–30Hz) from sensorimotor cortices contribute to predicting training-related motor performance.

Eighteen well-recovered chronic stroke survivors (mean age 64±8 years, range 50–74 years) and twenty age- and sex-matched healthy controls were trained on a continuous tracking task and subsequently retested after initial training (45–60 min and 24 hours later). Scalp EEG was recorded during the performance of a simple motor task before each training and retest session. Stroke patients demonstrated capacity for motor skill learning, but it was diminished compared to age- and performance-matched healthy controls. Further, although the properties of beta oscillations prior to training were comparable between stroke patients and healthy controls, stroke patients did show less change in beta measures with motor learning. Lastly, although beta oscillations did not help to predict motor performance immediately after training, contralateral (ipsilesional) sensorimotor cortex post-movement beta rebound (PMBR) measured after training helped predict future motor performance, 24 hours after training. This finding suggests that neurophysiological measures such as beta oscillations can help predict response to motor training in chronic stroke patients and may offer novel targets for therapeutic interventions.
Succinate can shuttle reducing power from the hypoxic retina to the O2-rich pigment epithelium
Authors: Bisbach Celia M. , Hass Daniel T. , Robbings Brian M. , Rountree Austin M. , Sadilek Martin , Sweet Ian R. , Hurley James B.
Published: January 2020

When O2is plentiful, the mitochondrial electron transport chain uses it as a terminal electron acceptor. However, the mammalian retina thrives within a hypoxic niche in the eye. We find that mitochondria in retinas adapt to their hypoxic environment by relying on the “reverse” succinate dehydrogenase reaction, where fumarate accepts electrons instead of O2. Reverse succinate dehydrogenase activity produces succinate and is enhanced by down-regulation of cytochrome oxidase subunits. Retinas can export the succinate to the neighboring retinal pigment epithelium/choroid complex. There, succinate stimulates O2consumption several fold and enhances synthesis and release of malate. Malate released from the pigment epithelium can be imported into the retina, where it is converted to fumarate and again used to accept electrons in the reverse succinate dehydrogenase reaction. Our findings show how a malate/succinate shuttle can sustain these two tissues by transferring reducing power from an O2-poor tissue (retina) to an O2-rich one (retinal pigment epithelium/choroid).
Graph biased feature selection of genes is better than random for many genes
Authors: Crawford Jake , Greene Casey S.
Published: January 2020

Recent work suggests that gene expression dependencies can be predicted almost as well by using random networks as by using experimentally derived interaction networks. We hypothesize that this effect is highly variable across genes, as useful and robust experimental evidence exists for some genes but not others. To explore this variation, we take thek-core decomposition of the STRING network, and compare it to a degree-matched random model. We show that when low-degree nodes are removed, expression dependencies in the remaining genes can be predicted better by the resulting network than by the random model.
Ancient BED-domain-containing immune receptor from wild barley confers widely effective resistance to leaf rust
Authors: Chen Chunhong , Clark Bethany , Martin Matthew , Matny Oadi , Steffenson Brian J , Franckowiak Jerome D , Mascher Martin , Singh Davinder , Perovic Dragan , Richardson Terese , Periyannan Sambasivam , Lagudah Evans S , Park Robert F , Dracatos Peter M
Published: January 2020

Leaf rust, caused byPuccinia hordeiis a devastating fungal disease affecting barley (Hordeum vulgaresubsp.vulgare) production globally. Race-specific resistance (R) genes have been deployed widely; however, their durability is often compromised due to the rapid emergence of virulentP. hordeiraces, prompting the search for new sources of broad-spectrum resistance. Here we report on the cloning ofRph15, a broadly effective resistance gene derived from the wild progenitorHordeum vulgaresubsp.spontaneum. We demonstrate using introgression mapping, mutation and complementation thatRph15encodes a coiled-coil nucleotide-binding leucine-rich repeat (NLR) protein with an integrated Zinc-finger BED (ZF-BED) domain. The allelic variation at theRph15locus was assessed using barley exome capture data that traced its origin to the western region of the Fertile Crescent bordering Jordan and Israel. To unravel the genetic relationship of two other leaf rust resistance genes (Rph14andRph16) mapped at similar locus on chromosome 2H, we re-sequenced theRph15gene from the near-isogenic line forRph15(Bowman+Rph15) and the two donor accessions ofRph14(PI 584760) andRph16, (PI 405292, Hs 680). Both whole genome and Sanger sequencing confirmed that Hs 680 carriedRph15, whileRph14in PI 584760 was an independent locus. A perfect diagnostic KASP marker was developed and validated to permit efficient introduction ofRph15into cultivated barley.
Heritable endogenization of an RNA virus in a mammalian species
Authors: Iida Atsuo , Tarigan Ronald , Shimoda Hiroshi , Endo Kanako , Furuta Masaya , Takemae Hitoshi , Hayasaka Daisuke , Ichiyanagi Kenji , Maeda Ken , Hondo Eiichi
Published: January 2020

Viruses are considered one of the driving forces for genome rearrangements via infection and endogenization into the host genome (Kazazian, 2004; Maksakova et al., 2006). In 2010, Horie and colleagues demonstrated that a non-retroviral RNA virus, Borna disease virus (BDV), could integrate into the genome in cultured somatic cells (Horie et al., 2010). However, germline transmission of viral-derived sequences using animal models is yet to be experimentally demonstrated. In this study, we reported a case of heritable endogenization using the encephalomyocarditis virus (EMCV) and laboratory mice. The EMCV is a small non-enveloped single-strand RNA virus without its own reverse transcriptase activity (Carocci et al., 2012). Here, we demonstrated that the EMCV genomic RNA was reverse transcribed into DNA fragments in the murine testes. The DNA sequence originated from the RNA genome of EMCV was also detected in the liver and earlobes of the offspring generated from the EMCV-infected father. This suggests that the exogenous sequence derived from the EMCV is transmitted into the host germline and inherited across subsequent generations. This first experimental demonstration of viral endogenization proposes reconsideration about the impact of viruses as a driving force for genome modification.
Reinforcement meta-learning optimizes visuomotor learning
Authors: Sugiyama Taisei , Schweighofer Nicolas , Izawa Jun
Published: January 2020

Reinforcement learning enables the brain to learn optimal action selection, such as go or not go, by forming state-action and action-outcome associations. Does this mechanism also optimize the brain’s willingness to learn, such as learn or not learn? Learning to learn by rewards, i.e., reinforcement meta-learning, is a crucial mechanism for machines to develop flexibility in learning, which is also considered in the brain without empirical examinations. Here, we show that humans learn to learn or not learn to maximize rewards in visuomotor learning tasks. We also show that this regulation of learning is not a motivational bias but is a result of an instrumental, active process, which takes into account the learning-outcome structure. Our results thus demonstrate the existence of reinforcement meta-learning in the human brain. Because motor learning is a process of minimizing sensory errors, our findings uncover an essential mechanism of interaction between reward and error.
Cocaine Triggers Glial-Mediated Synaptogenesis
Authors: Wang Junshi , Li King-Lun , Shukla Avani , Beroun Ania , Ishikawa Masago , Huang Xiaojie , Wang Yao , Wang Yao Q. , Bastola Noah D. , Huang Hugh H. , Kramer Lily E. , Chao Terry , Huang Yanhua H. , Sesack Susan R. , Nestler Eric J. , Schlüter Oliver M. , Dong Yan
Published: January 2020

Synaptogenesis is essential in forming new neurocircuits during development, and this is mediated in part by astrocyte-released thrombospondins (TSPs) and activation of their neuronal receptor, α2δ-1. Here, we show that this developmental synaptogenic mechanism is utilized during cocaine experience to induce spinogenesis and the generation of AMPA receptor-silent glutamatergic synapses in the adult nucleus accumbens (NAc). Specifically, cocaine administration activates NAc astrocytes, and preventing this activation blocks cocaine-induced generation of silent synapses. Furthermore, knockout of TSP2, or pharmacological inhibition or viral-mediated knockdown of α2δ-1, prevents cocaine-induced generation of silent synapses. Moreover, disrupting TSP2-α2δ-1-mediated spinogenesis and silent synapse generation in the NAc occludes cue-induced cocaine seeking after withdrawal from cocaine self-administration and cue-induced reinstatement of cocaine seeking after drug extinction. These results establish that silent synapses are generated by an astrocyte-mediated synaptogenic mechanism in response to cocaine experience and embed critical cue-associated memory traces that promote cocaine relapse.
Genetic diversity evaluation among fifty sugarcane accessions from the Zimbabwe Sugar Industry using DNA-SSR markers and qualitative traits
Authors: Mugehu E , Mpofu L.T. , Manjeru P
Published: January 2020

Due to the increasingly diverse needs of the Zimbabwe Sugar Industry, the need for developing improved varieties of sugarcane cannot be overemphasized. Since the establishment of experiment station in 1966, the Zimbabwe Sugar Industry (ZSI) has always been dependent on importation of crosses from other countries for development and release. However, the ZSI is now planning on developing its own crossing facilities. The ZSI’s gene bank has up to 746 imported varieties which can be used as potential parents in a breeding program. With the impending establishment of Zimbabwe’s own crossing facilities, morphological and molecular characterization of the available germplasm is essential to identify parental lines which can be used during crossing. The main objective of this study was to determine the genetic and phenotypic diversity of fifty ZSAES gene bank sugarcane varieties (accessions) and assess how the existing diversity can be utilized in a breeding program in parental selection and variety identification. Fifty sugarcane accessions were chosen based on country of origin and availability of seed and evaluated for qualitative morphological traits followed by molecular evaluation using DNA-SSR markers in a PCR based protocol. Fifty ‘one eyed’ setts were planted in the greenhouse and transplanted into labeled asbestos pots with ZSAES media. Fresh leaf samples were collected from the plants for DNA extraction using a modified CTAB method. Field trials for morphological assessment were laid out in a completely randomized design in a 1.5 × 4m plot. Agglomerative, hierarchical UPGMA clustering based on morphological traits with SAS®(9.3) categorized the fifty accessions into two main groups. The morphological traits managed to classify the accessions according to pedigree data, source of origin and similarities in traits like internode waxiness and adherence of leaf sheath. Contrastingly, molecular UPGMA cluster analysis by DarWin®(6.0) grouped the accessions into three main clusters. The three clusters were aligned according to time of release of varieties with the latter varieties in cluster III and the older ones in cluster I. The groups also showed clustering according to similarities in pedigree and source of origin. The molecular and morphological phylogenetic clusters suggest horizontal gene transfer through parallel and convergent evolution. Similarity trends observed also highlight similarities in breeding goals in different parts of the world. The information obtained from the study justifies the need for more importation of varieties from across the world to broaden the genetic base of the germplasm pool in the ZSI’s breeding program. Information from morphological data can be used for identification of released varieties in the ZSI using unique descriptors. More varieties should be analyzed and agronomic characterization should also be done to complement the results of this study and be incorporated into a database.
Deep learning for population size history inference: design, comparison and combination with approximate Bayesian computation
Authors: Sanchez Théophile , Cury Jean , Charpiat Guillaume , Jay Flora
Published: January 2020

Abstract

For the past decades, simulation-based likelihood-free inference methods have enabled researchers to address numerous population genetics problems. As the richness and amount of simulated and real genetic data keep increasing, the field has a strong opportunity to tackle tasks that current methods hardly solve. However, high data dimensionality forces most methods to summarize large genomic datasets into a relatively small number of handcrafted features (summary statistics). Here we propose an alternative to summary statistics, based on the automatic extraction of relevant information using deep learning techniques. Specifically, we design artificial neural networks (ANNs) that take as input single nucleotide polymorphic sites (SNPs) found in individuals sampled from a single population and infer the past effective population size history. First, we provide guidelines to construct artificial neural networks that comply with the intrinsic properties of SNP data such as invariance to permutation of haplotypes, long scale interactions between SNPs and variable genomic length. Thanks to a Bayesian hyperparameter optimization procedure, we evaluate the performance of multiple networks and compare them to well established methods like Approximate Bayesian Computation (ABC). Even without the expert knowledge of summary statistics, our approach compares fairly well to an ABC based on handcrafted features. Furthermore we show that combining deep learning and ABC can improve performance while taking advantage of both frameworks. Finally, we apply our approach to reconstruct the effective population size history of cattle breed populations.
Loss of Tet2 affects proliferation and drug sensitivity through altered dynamics of cell-state transitions
Authors: Morinishi Leanna , Kochanowski Karl , Levine Ross L. , Wu Lani F. , Altschuler Steven J.
Published: January 2020

A persistent puzzle in cancer biology is how mutations, which neither alter canonical growth signaling pathways nor directly interfere with drug mechanism, can still recur and persist in tumors. One notable example is the loss-of-function mutation of the DNA demethylase Tet2 in acute myeloid leukemias (AMLs) that frequently persists from diagnosis through remission and relapse (Rothenberg-Thurleyet al., 2018; Corces-Zimmermanet al., 2014; Nibourelet al., 2010), but whose fitness advantage in the setting of anti-leukemic chemotherapy is unclear. Here we use paired isogenic human AML cell lines to show that Tet2 loss-of-function alters the dynamics of transitions between differentiated and stem-like states. Mathematical modeling and experimental validation reveal that these altered cell-state dynamics can benefit the cell population by slowing population decay during drug treatment and lowering the number of survivor cells needed to re-establish the initial population. These studies shed light on the functional and phenotypic effects of a Tet2 loss-of-function in AML, illustrate how a single gene mutation can alter a cells’ phenotypic plasticity, and open up new avenues in the development of strategies to combat AML relapse.
Ethanol tolerance inEscherichia coliDH5-Alpha developed by serial exposure to sublethal doses is conferred to wild strains by horizontal gene transfer
Authors: Borana Ronak , Bari Shreya
Published: January 2020

Microorganisms evolve novel mechanisms and pathways to mitigate various stresses. These are developed by the accumulation of beneficial mutations over many generations. Such adaptations are often transferred from mutant microorganisms that develop it intrinsically to wild ones through horizontal gene transfer (HGT). It allows the latter to acquire favourable traits without having to employ resources to natively evolve. We ascertained this inEscherichia coliby first developing tolerance to ethanol, a potent disinfectant, by laboratory evolution and then transmitting it to the wild strain by HGT. Naturally, wild typeE. colicannot survive beyond 35% v/v ethanol in LB media. By serially increasing the concentration of ethanol by 5% v/v and selecting the surviving colonies, we were able to impose an artificial selection pressure. This in vitro microevolution increased the ethanol tolerance in our mutant to 75% v/v. To test if this tolerance could be transferred to the wild strain through HGT, we meticulously exposed the ancestral wildE. colito the newly tolerant mutants to facilitate the exchange of genetic material. After our exposure, the unadapted wild typeE. coliacquired tolerance up to 55% v/v through transformation and 45% v/v through transduction. The baseline tolerance of 35% v/v remained unchanged after conjugation. While our results are still preliminary, they provide interesting insights into the role horizontal gene transfer in developing resistance to bacteriocidal stressors.
High Content Phenotypic Profiling in Oesophageal Adenocarcinoma Identifies Selectively Active Pharmacological Classes of Drugs for Repurposing and Chemical Starting Points for Novel Drug Discovery
Authors: Hughes Rebecca E , Elliott Richard J R , Munro Alison F , Makda Ashraff , O’Neill J Robert , Hupp Ted , Carragher Neil O
Published: January 2020

Oesophageal adenocarcinoma (OAC) is a highly heterogeneous disease, dominated by large-scale genomic rearrangements and copy number alterations. Such characteristics have hampered conventional target-directed drug discovery and personalized medicine strategies contributing to poor outcomes for patients diagnosed with OAC. We describe the development and application of a phenotypic-led OAC drug discovery platform incorporating image-based, high-content cell profiling and associated image-informatics tools to classify drug mechanism-of-action (MoA). We applied a high-content Cell Painting assay to profile the phenotypic response of 19,555 compounds across a panel of six OAC cell lines representing the genetic heterogeneity of disease, a pre-neoplastic Barrett’s oesophagus line and a non-transformed squamous oesophageal line. We built an automated phenotypic screening and high-content image analysis pipeline to identify compounds that selectively modified the phenotype of OAC cell lines. We further trained a machine-learning model to predict the MoA of OAC selective compounds using phenotypic fingerprints from a library of reference compounds.

We identified a number of phenotypic clusters enriched with similar pharmacological classes e.g. Methotrexate and three other antimetabolites which are highly selective for OAC cell lines. We further identify a small number of hits from our diverse chemical library which show potent and selective activity for OAC cell lines and which do not cluster with the reference library of known MoA, indicating they may be selectively targeting novel oesophageal cancer biology. Our results demonstrate that our OAC phenotypic screening platform can identify existing pharmacological classes and novel compounds with selective activity for OAC cell phenotypes.
Innate immune gene expression inAcropora palmatais consistent despite variance in yearly disease events
Authors: Young Benjamin , Serrano Xaymara M. , Rosales Stephanie , Miller Margaret W. , Williams Dana , Traylor-Knowles Nikki
Published: January 2020

Coral disease outbreaks are expected to increase in prevalence, frequency and severity due to climate change and other anthropogenic stressors. This is especially worrying for the Caribbean branchingAcropora palmatawhich has already seen an 80% decrease in its coral cover, with this primarily due to disease. Despite the importance of this species, there has yet to be a characterization of its transcriptomic response to disease exposure. In this study we provide the first transcriptomic analysis of 12A. palmatagenotypes, and their symbiont Symbiodiniaceae, exposed to disease in 2016 and 2017. Year was the primary driver of sample variance forA. palmataand the Symbiodiniaceae. Lower expression of ribosomal genes in the coral, and higher expression of transmembrane ion transport genes in the Symbiodiniaceae indicate that the increased virulence in 2017 may have been due to a dysbiosis between the coral and Symbiodiniaceae. We also identified a conserved suite of innate immune genes responding to the disease challenge that was activated in both years. This included genes from the Toll-like receptor and lectin pathways, and antimicrobial peptides. Co-expression analysis identified a module positively correlated to disease exposure rich in innate immune genes, with D-amino acid oxidase, a gene implicated in phagocytosis and microbiome homeostasis, as the hub gene. The role of D-amino acid oxidase in coral immunity has not been characterized but holds potential as an important enzyme for responding to disease. Our results indicate thatA. palmatamounts a similar immune response to disease exposure as other coral species previously studied, but with unique features that may be critical to the survival of this keystone Caribbean species.
Optimal spectral templates for triggered feedback experiments
Authors: Kulkarni Anand S , Troyer Todd W
Published: January 2020

In the field of songbird neuroscience, researchers have used playback of aversive noise bursts to drive changes in song behavior for specific syllables within a bird’s song. Typically, a short (~5-10 msec) slice of the syllable is selected for targeting and the average spectrum of the slice is used as a template. Sounds that are sufficiently close to the template are considered a match. If other syllables have portions that are spectrally similar to the target, false positive errors will weaken the operant contingency. We present a gradient descent method for template optimization that increases the separation in distance between target and distractors slices, greatly improving targeting accuracy. Applied to songs from five adult Bengalese finches, the fractional reduction in errors for sub-syllabic slices was 51.54±22.92%. At the level of song syllables, we use an error metric that controls for the vastly greater number of distractors vs. target syllables. Setting 5% average error (misses + false positives) as a minimal performance criterion, the number of targetable syllables increased from 3 to 16 out of 61 syllables. At 10% error, targetable syllables increased from 11 to 26. By using simple and robust linear discriminant methods, the algorithm reaches near asymptotic performance when using 10 songs as training data, and the error increases by <2.3% on average when using only a single song for training. Targeting is temporally precise, with average jitter of 3.33 msec for the 16 accurately targeted syllables. Because the algorithm is concerned only with the problem of template selection, it can be used as a simple and robust front end for existing hardware and software implementations for triggered feedback.
Compressive Big Data Analytics: An Ensemble Meta-Algorithm for High-dimensional Multisource Datasets
Authors: Marino Simeone , Zhao Yi , Zhou Nina , Zhou Yiwang , Toga Arthur , Zhao Lu , Jian Yingsi , Yang Yichen , Chen Yehu , Wu Qiucheng , Wild Jessica , Cummings Brandon , Dinov Ivo D.
Published: January 2020

Health advances are contingent on continuous development of new methods and approaches to foster data driven discovery in the biomedical and clinical health sciences. Open-science offers hope for tackling some of the challenges associated with Big Data and team-based scientific discovery. Domain-independent reproducibility, area-specific replicability, curation, analysis, organization, management and sharing of health-related digital objects are critical components.

This study expands the functionality and utility of an ensemble semi-supervised machine learning technique called Compressive Big Data Analytics (CBDA). Applied to high-dimensional data, CBDA identifies salient features and key biomarkers for reliable and reproducible forecasting of binary or multinomial outcomes. The method relies on iterative subsampling, combines function optimization and statistical inference, and generates ensemble predictions of observed univariate outcomes. In this manuscript, we extend the CBDA technique by (1) efficiently handling extremely large datasets, (2) generalizing the internal and external validation steps, (3) expanding the set of base-learners for joint ensemble prediction, (4) introduce an automated selection of CBDA specifications, and (5) provide mechanisms to assess CBDA convergence, evaluate the prediction accuracy, and measure result consistency.

We validated the CBDA 2.0 technique using synthetic datasets as well as a population-wide census-like study, which grounds the mathematical models and the computational algorithm into translational health research settings. Specifically, we empirically validated the CBDA technique on a large-scale clinical study (UK Biobank), which includes imaging, cognitive, and clinical assessment data. The UK Biobank archive presents several difficult challenges related to the aggregation, harmonization, modeling, and interrogation of the information. These problems are related to the complex longitudinal structure, feature heterogeneity, multicollinearity, incongruency, and missingness, as well as violations of classical parametric assumptions that require novel health analytical approaches.

Our results showcase the scalability, efficiency and potential of CBDA tocompresscomplex data into structural information leading to derived knowledge and translational action. The results of the real case-study suggest new and exciting avenues of research in the context of identifying, tracking, and treating mental health and aging-related disorders. Following open-science principles, we share the entire end-to-end protocol, source-code, and results. This facilitates independent validation, result reproducibility, and team-based collaborative discovery.
CAM emerges in a leaf metabolic model under water-saving constraints in different environments
Authors: Töpfer Nadine , Braam Thomas , Shameer Sanu , Ratcliffe R. George , Sweetlove Lee J.
Published: January 2020

Crassulacean Acid Metabolism (CAM) evolved in arid environments as a water-saving alternative to C3photosynthesis. There is great interest in engineering more drought-resistant crop species by introducing CAM into C3plants. However, one of the open questions is whether full CAM or alternative water-saving flux modes would be more productive in the environments typically experienced by C3crops. To study the effect of temperature and relative humidity on plant metabolism we coupled a time-resolved diel model of leaf metabolism to an environment-dependent gas-exchange model. This model allowed us to study the emergence of CAM or CAM-like behaviour as a result of a trade-off between leaf productivity and water-saving. We show that vacuolar storage capacity in the leaf is a major determinant of the extent of CAM and shapes the occurrence of phase II and IV of the CAM cycle. Moreover, the model allows us to study alternative flux routes and we identify mitochondrial isocitrate dehydrogenase (ICDH) and an isocitrate-citrate-proline-2OG cycle as a potential contributor to initial carbon fixation at night. Simulations across a wide range of environmental parameters show that the water-saving potential of CAM strongly depends on the environment and that the additional water-saving effect of carbon fixation by ICDH can reach up to 4% for the conditions tested.
The Developing Human Connectome Project: typical and disrupted perinatal functional connectivity
Authors: Eyre Michael , Fitzgibbon Sean P , Ciarrusta Judit , Cordero-Grande Lucilio , Price Anthony N , Poppe Tanya , Schuh Andreas , Hughes Emer , O’Keeffe Camilla , Brandon Jakki , Cromb Daniel , Vecchiato Katy , Andersson Jesper , Duff Eugene P , Counsell Serena J , Smith Stephen M , Rueckert Daniel , Hajnal Joseph V , Arichi Tomoki , O’Muircheartaigh Jonathan , Batalle Dafnis , Edwards A David
Published: January 2020

The Developing Human Connectome Project (dHCP) is an Open Science project which provides the first large sample of neonatal functional MRI (fMRI) data with high temporal and spatial resolution. This data enables mapping of intrinsic functional connectivity between spatially distributed brain regions under normal and adverse perinatal circumstances, offering a framework to study the ontogeny of large-scale brain organisation in humans. Here, we characterise in unprecedented detail the maturation and integrity of resting-state networks (RSNs) at normal term age in 337 infants (including 65 born preterm).

First, we applied group independent component analysis (ICA) to define 11 RSNs in term-born infants scanned at 43.5-44.5 weeks postmenstrual age (PMA). Adult-like topography was observed in RSNs encompassing primary sensorimotor, visual and auditory cortices. Among six higher-order, association RSNs, analogues of the adult networks for language and ocular control were identified, but a complete default mode network precursor was not. Next, we regressed the subject-level datasets from an independent cohort of infants scanned at 37-43.5 weeks PMA against the group-level RSNs to test for the effects of age, sex and preterm birth. Brain mapping in term-born infants revealed areas of positive association with age across four of six association RSNs, indicating active maturation in functional connectivity from 37 to 43.5 weeks PMA. Female infants showed increased connectivity in inferotemporal regions of the visual association network. Preterm birth was associated with striking impairments of functional connectivity across all RSNs in a dose-dependent manner; conversely, connectivity of the superior parietal lobules within the lateral motor network was abnormally increased in preterm infants, suggesting a possible mechanism for specific difficulties such as developmental coordination disorder which occur frequently in preterm children.

Overall, we find a robust, modular, symmetrical functional brain organisation at normal term age. A complete set of adult-equivalent primary RSNs is already instated, alongside emerging connectivity in immature association RSNs, consistent with a primary-to-higher-order ontogenetic sequence of brain development. The early developmental disruption imposed by preterm birth is associated with extensive alterations in functional connectivity.