bluuebunny/crossref_metadata_2025_split huggingface dataset:
Semi-supervised Calibration of Risk with Noisy Event Times (SCORNET) Using Electronic Health Record Data
Authors: Ahuja Yuri , Liang Liang , Huang Selena , Cai Tianxi 
Published: January 2021

AbstractLeveraging large-scale electronic health record (EHR) data to estimate survival curves for clinical events can enable more powerful risk estimation and comparative effectiveness research. However, use of EHR data is hindered by a lack of direct event times observations. Occurrence times of relevant diagnostic codes or target disease mentions in clinical notes are at best a good approximation of the true disease onset time. On the other hand, extracting precise information on the exact event time requires laborious manual chart review and is sometimes altogether infeasible due to a lack of detailed documentation. Current status labels – binary indicators of phenotype status during follow up – are significantly more efficient and feasible to compile, enabling more precise survival curve estimation given limited resources. Existing survival analysis methods using current status labels focus almost entirely on supervised estimation, and naive incorporation of unlabeled data into these methods may lead to biased results. In this paper we propose Semi-supervised Calibration of Risk with Noisy Event Times (SCORNET), which yields a consistent and efficient survival curve estimator by leveraging a small size of current status labels and a large size of imperfect surrogate features. In addition to providing theoretical justification of SCORNET, we demonstrate in both simulation and real-world EHR settings that SCORNET achieves efficiency akin to the parametric Weibull regression model, while also exhibiting non-parametric flexibility and relatively low empirical bias in a variety of generative settings.
Evolvability and constraint in the primate basicranium, shoulder, and hip and the importance of multi-trait evolution
Authors: Agosto Elizabeth R. , Auerbach Benjamin M. 
Published: January 2021

AbstractThe scapula shares developmental and functional relationships with traits of the basicranium, vertebral column, humerus, and clavicle. As a limb girdle, it also shares analogous characteristics with the pelvis. Despite these relationships, studies of primate shoulder evolution often focus on traits of the scapula in isolation. Such analyses may lead to spurious conclusions, as they implicitly model the scapula as evolving independent of other anatomical regions. Traits of the shoulder girdle share genetic covariances with each other, as well as potential covariances with dimensions of other skeletal elements. To create accurate models of shoulder evolution, it is imperative to account for the constraints imposed by these sources of covariance. Here, we use evolutionary quantitative methods to test a model in which shoulder morphological evolution is influenced by its developmental and functional covariances with the basicranium in theColobusgenus. This evolutionary relationship is also assessed with morphology of the pelvis to provide context to the evolutionary covariance among traits of the basicranium and shoulder girdle. Our results indicate potential evolutionary implications arising from covariances among the basicranium, shoulder, and pelvis. We further propose that the shoulder and basicranium may be examples of developmental, functional, and genetic covariances among traits that manifest an evolutionary suite of mutually constrained morphologies. We demonstrate novel evolutionary relationships among the shoulder girdle and basicranium that affect not only models of primate shoulder evolution but have broader implications for modeling trait evolution across the skeleton.
Developmental exposure to domoic acid disrupts startle response behavior and circuitry
Authors: Panlilio Jennifer M. , Jones Ian T. , Salanga Matthew C. , Aluru Neelakanteswar , Hahn Mark E. 
Published: January 2021

ABSTRACTHarmful algal blooms produce potent neurotoxins that accumulate in seafood and are hazardous to human health. Developmental exposure to the harmful algal bloom toxin, domoic acid (DomA), has behavioral consequences well into adulthood, but the cellular and molecular mechanisms are largely unknown. To assess these, we exposed zebrafish embryos to DomA during the previously identified window of susceptibility (2 days post-fertilization) and used the well-known startle response circuit as a tool to identify specific neuronal components that are targeted by exposure to DomA. Exposure to DomA reduced the probability of eliciting a startle after auditory/vibrational or electrical stimuli and led to the dramatic reduction of one type of startle, short latency c-start (SLC) responses. Furthermore, DomA-exposed larvae had altered kinematics of both SLC and long latency c-start (LLC) startle responses, exhibiting shallower bend angles and slower maximal angular velocities. Using vital dye staining, immunolabelling, and live imaging of transgenic lines, we determined that while the sensory inputs were intact, the reticulospinal neurons required for SLC responses were absent in most DomA-exposed larvae. Furthermore, axon tracing revealed that DomA-treated larvae also showed significantly reduced primary motor neuron axon collaterals. Overall, these results show that developmental exposure to DomA leads to startle deficits by targeting specific subsets of neurons. These findings provide mechanistic insights into the neurodevelopmental effects of excess glutamatergic signaling caused by exposure to DomA. It further provides a model for using the startle response circuit to identify neuronal populations targeted by toxin or toxicant exposures.Summary statementWe used the zebrafish startle response as a tool to identify sensory-motor deficits and the loss of specific neural populations after developmental exposure to the harmful algal bloom toxin domoic acid.GRAPHICAL ABSTRACT
The effect of root exudates on the transcriptome of rhizospherePseudomonasspp
Authors: Mavrodi Olga V. , McWilliams Janiece R. , Peter Jacob O. , Berim Anna , Hassan Karl A. , Elbourne Liam D. H. , LeTourneau Melissa K. , Gang David R. , Paulsen Ian T. , Weller David M. , Thomashow Linda S. , Flynt Alex S. , Mavrodi Dmitri V. 
Published: January 2021

AbstractPlants live in association with microorganisms that positively influence plant development, vigor, and fitness in response to pathogens and abiotic stressors. The bulk of the plant microbiome is concentrated belowground at the plant root-soil interface. Plant roots secrete carbon-rich rhizodeposits containing primary and secondary low molecular-weight metabolites, lysates, and mucilages. These exudates provide nutrients for soil microorganisms and modulate their affinity to host plants, but molecular details of this process are largely unresolved. We addressed this gap by focusing on the molecular dialogue between eight well-characterized beneficial strains of thePseudomonas fluorescensgroup andBrachypodium distachyon, a model for economically important food, feed, forage, and biomass crops of the grass family. We collected and analyzed root exudates ofB. distachyonand demonstrated the presence of multiple carbohydrates, amino acids, organic acids and phenolic compounds. The subsequent screening of bacteria by Biolog Phenotype MicroArrays revealed that many of these metabolites provide carbon and energy for thePseudomonasstrains. RNA-seq profiling of bacterial cultures amended with root exudates revealed changes in the expression of genes encoding numerous catabolic and anabolic enzymes, transporters, transcriptional regulators, stress response, and conserved hypothetical proteins. Almost half of the differentially expressed genes mapped to the variable part of the strains’ pangenome, reflecting the importance of the variable gene content in the adaptation ofP. fluorescensto the rhizosphere lifestyle. Our results collectively reveal the diversity of cellular pathways and physiological responses underlying the establishment of mutualistic interactions between these beneficial rhizobacteria and their plant hosts.
Description, taxonomy, and comparative genomics of a novelThermoleptolyngbyastrain isolated from hot springs of Ganzi, Sichuan China
Authors: Tang Jie , Li Liheng , Li Meijin , Du Lianming , Waleron Michał , Waleron Małgorzata , Waleron Krzysztof , Daroch Maurycy 
Published: January 2021

AbstractThermoleptolyngbyais a newly proposed genus of thermophilic cyanobacteria that are often abundant in thermal environments. However, a vast majority ofThermoleptolyngbyastrains were not systematically identified, and genomic features of this genus are also sparse. Here, polyphasic approaches were employed to identify a thermophilicThermoleptolyngbyaA183 (FACHB-2491) isolated from hot spring Erdaoqiao, Ganzi prefecture, China. Morphological characterization was investigated by microscopy. Whilst the results of 16S rRNA were inconclusive, the phylogenetic reconstruction and secondary structures of 16S-23S ITS strongly suggested that A183 strain is a novel species withinThermoleptolyngbya. Moreover, genome-scale average nucleotide identity (ANI) confirmed the genetic divergence of A183 fromThermoleptolyngbyaO-77. Comparative genome analysis revealed inconsistent genome structures ofThermoleptolyngbyastrains. Further GO analysis showed that the specific genes were distributed in a wide range of functional categories. In addition, analysis of genes related to thermotolerance, signal transduction, and carbon/nitrogen/sulfur assimilation revealed the ability of this strain to adapt to inhospitable niches in hot springs.
Targeting the artemisinin resistant malaria by repositioning of the anti-Hepatitis C Virus drug Alisporivir
Authors: Chaurasiya Ayushi , Garg Swati , Anam Zill e , Kumari Geeta , Joshi Nishant , Kumari Jyoti , Singhal Jhalak , Singh Niharika , Kaushik Shikha , Kaur Amandeep , Dubey Neha , Srivastava Pallavi , Marothia Manisha , Kumar Mukesh , Das Gobardhan , Bhattacharjee Souvik , Singh Shailja , Ranganathan Anand 
Published: January 2021

ABSTRACTThe rapid emergence ofP. falciparum-resistantstrains raises an urgent need to find new antimalarial drug candidates. This study reports the rational repositioning of the anti-Hepatitis C Virus drug, Alisporivir, a non-immunosuppressive analog of cyclosporin A (CsA) against multiple, drug-resistant strains ofP. falciparum. Alisporivir being non-hemolytic has been proven to be a better drug than CsA. Indeed, our study also demonstrated the same. Alisporivir inhibited chloroquine-sensitive parasite growth with an IC50of 196.6nM. Alisporivir also inhibited the growth of chloroquine-resistant parasites with an IC50of 422.1nM. Alisporivir exhibited, anti-malarial activity inin vivo. Further, we exploited the Cyclophilins targeting potential of Alisporivir against artemisinin-resistant malaria parasite owing to the fact that PfCyP-19B is one of the genes that is overexpressed in artemisinin-resistant parasite revealed by a population transcriptomic study. Our semiquantitative real-time transcript and immunofluorescence analysis confirmed the overexpression of PfCyP-19B in Artemisinin-resistantP. falciparum(PfKelch13R539T). Artemisinin resistance is attributed to slow clearance of ring stage parasites. Ring survival assay (RSA) is designed to access the potency of compounds on these dormant slow clearing parasites leading to drug resistance. Thus, the potency of Alisporivir against PfKelch13R539Twas evaluated by RSA. A 2.5-fold decrease in parasite survival was detected with Alisporivir. Further, combination of Alisporivir with DHA found to potentiate the efficacy of DHA by 4.55-fold. These results support the hypothesis that targeting of resistance mechanism is a potential approach to deal with resistant parasite. Overall, this study demonstrates the rational reposition of Alisporivir against resistant malaria resistance.
The importance of non-pharmaceutical interventions during the COVID-19 vaccine rollout
Authors: Gozzi Nicolò , Bajardi Paolo , Perra Nicola 
Published: January 2021

AbstractThe promise of efficacious vaccines against SARS-CoV-2 is fulfilled and vaccination campaigns have started worldwide. However, the fight against the pandemic is far from over. Here, we propose an age-structured compartmental model to study the interplay of disease transmission, vaccines rollout, and behavioural dynamics. We investigate, via in-silico simulations, individual and societal behavioural changes, possibly induced by the start of the vaccination campaigns, and manifested as a relaxation in the adoption of non-pharmaceutical interventions. We explore different vaccine efficacy, vaccination rollout speeds, prioritization strategies, as well as multiple behavioural responses. We apply our model to six countries worldwide (Egypt, Peru, Serbia, Ukraine, Canada, and Italy) selected to sample diverse socio-demographic and socio-economic contexts. To isolate the effects of age-structures and contacts patterns from the particular pandemic history of each location, we first study the model considering the same hypothetical initial epidemic scenario in all countries. We then calibrate the model using real epidemiological and mobility data for the different countries. Our findings suggest that early relaxation of safe behaviours can jeopardize the benefits brought by the vaccine in the short term: a fast vaccine distribution and policies aimed at keeping high compliance of individual safe behaviours are key to mitigate disease resurgence.
Engineering neurovascular organoids with 3D printed microfluidic chips
Authors: Salmon Idris , Grebenyuk Sergei , Fattah Abdel Rahman Abdel , Rustandi Gregorius , Pilkington Thomas , Verfaillie Catherine , Ranga Adrian 
Published: January 2021

AbstractThe generation of tissues and organs requires close interaction with vasculature from the earliest moments of embryonic development. Tissue-specific organoids derived from pluripotent stem cells allow for the in vitro recapitulation of elements of embryonic development, however they are not intrinsically vascularized, which poses a major challenge for their sustained growth and for understanding the role of vasculature in fate specification and morphogenesis. Current organoid vascularization strategies do not recapitulate the temporal synchronization and spatial orientation needed to ensure in-vivo-like early co-development. Here, we developed a human pluripotent stem cell (hPSC)-based approach to generate organoids which interact with vascular cells in a spatially determined manner. The spatial interaction between organoid and vasculature is enabled by the use of a custom designed 3D printed microfluidic chip which allows for a sequential and developmentally matched co-culture system. We show that on-chip hPSC-derived pericytes and endothelial cells sprout and self-assemble into organized vascular networks, and use cerebral organoids as a model system to explore interactions with this de novo generated vasculature. Upon co-development, vascular cells interact with the cerebral organoid and form an integrated neurovascular organoid on chip. This 3D printing-based platform is designed to be compatible with any organoid system and is an easy and highly cost-effective way to vascularize organoids. The use of this platform, readily performed in any lab, could open new avenues for understanding and manipulating the co-development of tissue-specific organoids with vasculature.
Dependency of LKB1-inactivated lung cancer on aberrant CRTC-CREB activation
Authors: Zhou Xin , Li Jennifer W. , Chen Zirong , Ni Wei , Li Xuehui , Yang Rongqiang , Shen Huangxuan , Liu Jian , DeMayo Francesco J. , Lu Jianrong , Kaye Frederic J. , Wu Lizi 
Published: January 2021

AbstractLung cancer with loss-of-function of theLKB1tumor suppressor is a common aggressive subgroup with no effective therapies.LKB1-deficiency induces constitutive activation of cAMP/CREB-mediated transcription by a family of three CREB-regulated transcription coactivators (CRTC1-3). However, the significance and mechanism of CRTC activation in promoting the aggressive phenotype of LKB1-null cancer remain poorly characterized. Here we observed overlapping CRTC expression patterns and mild growth phenotypes of individual CRTC-knockouts in lung cancer, suggesting functional redundancy of CRTC1-3. We consequently designed a dominant-negative mutant (dnCRTC) to block all three CRTCs to bind and co-activate CREB. Expression of dnCRTC efficiently inhibited the aberrantly activated cAMP/CREB-mediated oncogenic transcriptional program induced by LKB1-deficiency, and specifically blocked the growth of LKB1-inactivated lung cancer. Collectively, this study provides direct proof for an essential role of the CRTC-CREB activation in promoting the malignant phenotypes of LKB1-null lung cancer and proposes the CRTC-CREB interaction interface as a novel therapeutic target.
Multiple Shoot Regeneration from Excised Embryonic Axis Explants of Jute,Corchorus capsulariscv. JRC321
Authors: Joshi Alpana , Das Subrata K. , Das Dipak 
Published: January 2021

AbstractInterspecific hybrids development by traditional breeding is challenging because of the incompatibility between two cultivated species of genusCorchorus. Under this condition, plant genetic transformation is an alternative tool for the improvement of jute cultivar. In the present study,in vitromultiple shoot regeneration protocol has been developed in jute (Corchorus capsulariscv. JRC 321) from excised embryonic axis as an explant by removing cotyledons, radicle, and tip of epicotyl. The explant is cultured in medium SMM1 supplemented with BAP (1.0 mg/L) for one week and sub-cultured in SMM6 containing IBA (0.5 mg/L) and BAP (0.2 mg/L). Direct adventitious shoot bud formation was observed from cotyledonary nodes and the adjacent region of excised embryonic axis. Interestingly, shoot bud formation was reduced when excised explants with intact epicotyl were cultured in the media combination (SMM1+SMM6) indicating the presence of apical dominance might be the cause of fewer shoot bud formation. While, hypocotyl explants did not produce any shoot in this media combination because nodal meristem was removed. However, the shoot buds developed from the excised embryonic axis were differentiated successfully into multiple shoots and showed further elongation in SMM6 which ultimately rooted in MS-B5 medium (+0.5 mg/L IBA). The plants were transferred successfully in the glasshouse conditions and appeared phenotypically normal.
itsfm, an open-source package to reliably segment and measure sounds by frequency modulation
Authors: Beleyur Thejasvi 
Published: January 2021

AbstractAnalysing animal vocalisations in detail provides insights into the biomechanics, decision making and sensory processes behind their behaviours. Echolocating bats, and in particular, the CF-FM calls of high-duty cycle bats serve as a convenient model system to illustrate this point. The CF component in the CF-FM call is used for prey detection and the FM component is used in target ranging. According to the behavioural context at hand such as flight with conspecifics or prey capture, bats choose to increase the duration, intensity or spectral range of the components differently. Studying the call component alterations requires an objective methodology that first segments the components and then allows measurements on them. Studies till now have segmented the call components manually, or automatically using what I term the ‘peak-frequency’ method. Manual segmentation is error prone, while the ‘peak-frequency’ method requires on-axis recordings for good results. Despite multiple papers using a peak-frequency based segmentation, there remain no publicly available software implementations. itsfm is an open-source package that fills this gap with two implemntations that can segment CF-FM calls, one of them being an implementation of the peak-percentage method. itsfm additionally introduces the ‘pseudo-Wigner-Ville distribution’ (PWVD) method for call segmentation, thus allowing the segmentation of calls captured under a wider variety of recording conditions. I create a synthetic dataset and assess the performance of the PWVD method and the ‘peak-frequency’ method. The PWVD performs consistently well in call component segmentation in comparison to the peak-percentage method. I also discuss the supporting methods in the itsfm package that can help the further automatic segmentation, measurement and analysis of sounds. Though originally developed for the segmentation and measurement of CF-FM bat calls, the methods in itsfm are speciesagnostic, and may be used for vocalisations of any type.
Evolution of Crassulacean Acid Metabolism (CAM) as an escape from ecological niche conservatism in MalagasyBulbophyllum(Orchidaceae)
Authors: Gamisch Alexander , Klaus Winter , Fischer Gunter A. , Peter Comes Hans 
Published: January 2021

Introductory paragraphDespite growing evidence that niche shifts are more common in flowering plants than previously thought, still little is known about the key physiological (e.g. photosynthesis) traits underlying such niche shifts. To address this question, we here combine a comprehensively sampled phylogeny for mostly epiphytic MalagasyBulbophyllumorchids (c. 210 spp.) with climatic niche and carbon isotope-derived photosynthesis data to infer the groups’ spatial-temporal history and to test the role of Crassulacean Acid Metabolism (CAM), a highly water-use efficient type of photosynthesis, in facilitating niche shifts and diversification. We find that most extant species still retain niche (Central Highland) and photosynthesis (C3) states as likely present in the single mid-Miocene (c.12.70 Ma) ancestor colonizing Madagascar. However, we also infer a major transition to CAM, linked to a late Miocene (c. 7.36 Ma) invasion of species from the sub-humid highland niche first into the island’s humid eastern coastal, and then into the seasonally dry ‘Northwest Sambirano’ rainforests, yet without significant effect on diversification rates. These findings support the rarely recognized hypothesis that CAM in tropical epiphytes may be selectively advantageous even in high rainfall habitats, rather than presenting a mere adaptation to dry environments or epiphytismper se. Overall, our study qualifies CAM as an evolutionary ‘gateway’ trait that considerably widened the spatial-ecological amplitude of Madagascar’s most species-rich orchid genus.