bluuebunny/crossref_metadata_2025_split huggingface dataset:
MycoPhylo experiment reveals how mycorrhiza types and phylogenetic relationships affect soil biodiversity and functioning
Authors: Tedersoo Leho , Loit Kaire , Agan Ahto , Rahimlou Saleh , Vask Annaliisa , Drenkhan Rein 
Published: April 2022

SummaryNatural forests and abandoned agricultural lands are increasingly replaced by monospecific forest plantations that have poor capacity to support biodiversity and ecosystem services. Natural forests harbour plants belonging to different mycorrhiza types that differ in their microbiome and carbon and nutrient cycling properties.Here we describe the MycoPhylo field experiment that encompasses 116 woody plant species from three mycorrhiza types and 237 plots, with plant diversity and mycorrhiza type diversity ranging from one to four and one to three per plot, respectively.The MycoPhylo experiment enables us to test hypotheses about the plant species, species diversity, mycorrhiza type, and mycorrhiza type diversity effects and their phylogenetic context on soil microbial diversity and functioning and soil processes.Alongside with other experiments in the TreeDivNet consortium, MycoPhylo will contribute to our understanding of the tree diversity effects on soil biodiversity and ecosystem functioning across biomes, especially from the mycorrhiza type and phylogenetic conservatism perspectives.
Extension of PERMANOVA to Testing the Mediation Effect of the Microbiome
Authors: Yue Ye , Hu Yi-Juan 
Published: April 2022

AbstractBackgroundRecently, we have seen a growing volume of evidence linking the microbiome and human diseases or clinical outcomes, as well as evidence linking the microbiome and environmental exposures. Now comes the time to assess whether the microbiome mediated the effects of the exposures on the outcomes, which will enable researchers to develop interventions to modulate the outcomes by modifying the microbiome composition. Use of distance matrices is a popular approach to analyzing complex microbiome data that are high-dimensional, sparse, and compositional. However, the existing distance-based methods for mediation analysis of microbiome data, MedTest and MODIMA, only work well in limited scenarios.ResultsPERMANOVA is currently the most commonly used distance-based method for testing microbiome associations. Using the idea of inverse regression, here we extend PER-MANOVA to testing microbiome mediation effects by including both the exposure and the outcome as covariates and basing the test on the product of theirF-statistics. This extension of PERMANOVA, which we call PERMANOVA-med, naturally inherits all the flexible features of PERMANOVA, e.g., allowing adjustment of confounders, accommodating continuous, binary, and multivariate exposure and outcome variables including survival outcomes, and providing an omnibus test that combines the results from analyzing multiple distance matrices. Our extensive simulations indicated that PERMANOVA-med always controlled the type I error and had compelling power over MedTest and MODIMA. Frequently, MedTest had diminished power and MODIMA had inflated type I error. Using real data on melanoma immunotherapy response, we demonstrated the wide applicability of PERMANOVA-med through 16 different mediation analyses, only 6 of which could be performed by MedTest and 4 by MODIMA.Availability and ImplementationPERMANOVA-med has been added to the existing function “permanovaFL” in our R package LDM, which is available on GitHub athttps://github.com/yijuanhu/LDM.
Optimized Repli-seq: Improved DNA Replication Timing Analysis by Next-Generation Sequencing
Authors: Rivera-Mulia Juan Carlos , Trevilla-Garcia Claudia , Martinez-Cifuentes Santiago 
Published: April 2022

AbstractThe human genome is divided into functional units that replicate at specific times during S-phase. This temporal program is known as replication timing (RT) and is coordinated with the spatial organization of the genome and transcriptional activity. RT is also cell type-specific, dynamically regulated during development, and alterations in RT are observed in multiple diseases. Thus, precise measure of RT is critical to understand the role of RT in gene function regulation. Distinct methods for assaying the RT program exist; however, conventional methods require thousands of cells as input, prohibiting its applicability to samples with limited cell numbers such as those from disease patients or from early developing embryos. Although single-cell analysis of RT has been developed as an alternative, these methods are low throughput and produce low resolution data. Here, we developed an improved method to measure RT genome-wide that enables high resolution analysis of low input samples. This method incorporates direct cell sorting into lysis buffer, as well as DNA fragmentation and library preparation in a single tube, resulting in higher yields, increased quality, and reproducibility with decreased costs. We also performed a systematic data processing analysis to provide standardized parameters for RT measurement. This optimized method facilitates RT analysis and will enable its application to a broad range of studies investigating the role of RT in gene expression, nuclear architecture, and disease.
Toward quantitative metabarcoding
Authors: Shelton Andrew Olaf , Gold Zachary J. , Jensen Alexander J. , D’Agnese Erin , Allan Elizabeth Andruszkiewicz , Van Cise Amy , Gallego Ramón , Ramón-Laca Ana , Garber-Yonts Maya , Parsons Kim , Kelly Ryan P. 
Published: April 2022

AbstractAmplicon-sequence data from environmental DNA (eDNA) and microbiome studies provides important information for ecology, conservation, management, and health. At present, amplicon-sequencing studies – known also as metabarcoding studies, in which the primary data consist of targeted, amplified fragments of DNA sequenced from many taxa in a mixture – struggle to link genetic observations to underlying biology in a quantitative way, but many applications require quantitative information about the taxa or systems under scrutiny. As metabarcoding studies proliferate in ecology following decades of microbial and microbiome work using similar techniques, it becomes more important to develop ways ot make them quantitative to ensure that their conclusions are adequately supported. Here we link previously disparate sets of techniques for making such data quantitative, showing that the underlying PCR mechanism explains observed patterns of amplicon data in a general way. By modeling the process through which amplicon-sequence data arises, rather than transforming the data post-hoc, we show how to estimate the starting DNA proportions from a mixture of many taxa. We illustrate how to calibrate the model using mock communities and apply the approach to simulated data and a series of empirical examples. Our approach opens the door to improve the use of metabarcoding data in a wide range of applications in ecology, public health, and related fields.
Museomic approaches to genotype historicCinchonabarks
Authors: Canales Nataly Allasi , Gardner Elliot M. , Gress Tobias , Walker Kim , Bieker Vanessa , Martin Michael D. , Nesbitt Mark , Antonelli Alexandre , Rønsted Nina , Barnes Christopher J. 
Published: April 2022

AbstractOver the last few centuries, millions of plant specimens have been collected and stored within herbaria and biocultural collections. They therefore represent a considerable resource for a broad range of scientific uses. However, collections degrade over time, and it is therefore increasingly difficult to characterise their genetic signatures. Here, we genotyped highly degradedCinchonabarks and leaves from herbaria using two separate high-throughput sequencing methods (HtS) and compared their performance. We subsequently genotyped specimens using genome skimming, the most commonly performed high-throughput sequencing (HtS) technique. We additionally used a recently developed capture bait set (Angiosperm353) for a target enrichment approach. Specifically, phylogenomic analyses of modern leaf and historical barks ofCinchonawere performed, including 23 historical barks and six fresh leaf specimens. We found that samples degraded over time, which directly reduced the quantity and quality of the data produced by both methodologies (in terms of reads mapped to the references). However, we found that both approaches generated enough data to infer phylogenetic relationships, even between highly degraded specimens that are over 230 years old. However, the target capture kit produced data for target nuclear loci and also chloroplast data, which allowed for phylogenies to be inferred from both genomes, whereas it was only possible to use chloroplast data using genome skimming. We therefore find the Angiosperms353 target capture kit a powerful alternative to genome skimming, which can be used to obtain more information from herbarium specimens, and ultimately additional cultural benefits.
Which life history strategy can maintain high genetic diversity in plants?
Authors: Tsuzuki Yoichi , Takada Takenori , Ohara Masashi 
Published: April 2022

AbstractClassifying a variety of plant life histories is an important step to understand ecological and evolutionary background of life history diversification in plants. Principal component analysis (PCA) of life history traits, as well as elasticity analysis using a ternary diagram, successfully categorized the diverse life histories and clarified their link to various ecological characteristics, such as population dynamics, functional traits, and conservation status. However, the relationships with population genetic properties, including genetic diversity, have not been explored very much. In this study, we overlaid annual change rate of expected heterozygosity η on life history spectrum obtained by PCA and elasticity analysis to examine which life history strategy can maintain high genetic diversity over time. We found that η gradually changed along the fast-slow continuum and that slow-paced life histories maintained high genetic diversity, probably due to generation overlap. Elasticity analysis showed that life histories that highly depend on stasis also maintained genetic diversity. As genetic diversity reflects adaptive potential to environmental changes, our study provides a new genetic perspective on adaptative evolution and population viability to life history study.
High Concentrations of floating life in the North Pacific Garbage Patch
Authors: Chong Fiona , Spencer Matthew , Maximenko Nikolai , Hafner Jan , McWhirter Andrew , Helm Rebecca R. 
Published: April 2022

AbstractFloating life (obligate neuston) is a core component of the ocean surface food web. However, only one region of high neustonic abundance is known so far, the Sargasso Sea in the Subtropical North Atlantic, where floating life provides critical habitat structure and ecosystem services. Here, we hypothesize that floating life is also concentrated in other gyres with converging surface currents. To test this hypothesis, we collected samples through the eastern North Pacific Subtropical Gyre in the area of the North Pacific “garbage patch” (NPGP) known to accumulate floating anthropogenic debris. We found that densities of floating life were significantly higher inside the central part of NPGP than on its periphery, and there was a significant positive relationship between neuston abundance and plastic abundance. This work has important implications for the ecology and human impact of subtropical oceanic gyre ecosystems.
Mortality among healthcare workers in Indonesia during 18 months of COVID-19
Authors: Ekawati Lenny L. , Arif Ahmad , Hidayana Irma , Nurhasim Ahmad , Munziri M. Zakiyuddin , Lestari Karina D. , Tan Amanda , Ferdiansyah Firdaus , Nashiruddin Fikry , Adnani Qorinah E.S. , Malik Halik , Maharani Tri , Riza Andy , Pasaribu Monalisa , Abidin Khairul , Andrianto Adhi A. , Nursalam  , Sri Suhardiningsih A.V. , Jubaedah Ade , Widodo N.S. , Surendra Henry , Sudoyo Herawati , Smith Adrian D. , Kreager Philip , Baird J. Kevin , Elyazar Iqbal R.F. 
Published: April 2022

AbstractThe impact of SARS-CoV-2 infections upon Indonesian health care workers (HCWs) remains unclear, as mortality data specific to HCWs is not systematically collected or analyzed in this setting. This report describes findings from a systematic collation, abstraction and analysis of HCW fatalities during the first 18 months of COVID-19 in Indonesia. HCW who died during the period of March 2020 to July 2021 across Indonesia were identified on Pusara Digital, a community web-based digital cemetery database dedicated to HCW. We calculated mortality rates and death risk ratio among HCWs and the general population. Qualitative methods explored concerns regarding mortality among HCWs. The analysis suggests that at least 1,545 HCWs died during the study period. The death of males and females HCWs were almost equally distributed (51% vs. 49%). Most were medical doctors and specialists (535, 35%), nurses (428, 28%), and midwives (359, 23%). Deaths most frequently occurred in the age group of 40 to 59 years old with the median age of 50 years (IQR: 39-59). At least 322 (21%) deaths occurred with pre-existing conditions, including 45 who were pregnant. We estimated a minimal HCW mortality rate in Indonesia at 1.707 deaths per 1000 HCW during the first 18 months of COVID-19. Provincial HCW mortality rates ranged from 0.136 (West Sulawesi) to 5.32 HCW deaths per 1000 HCWs (East Java). HCW had a significantly higher mortality rate than the general population (RR = 4.92, 95% CI 4.67 – 5.17). The COVID-19 event in Indonesia resulted in the loss of many hundreds of HCWs, most of them being senior physicians, nurses, and midwives. The HCW death rates is 5-times higher than everyone else. The sheer sparseness of the workforce requires more protective steps and a national systematic surveillance of occupational mortality is urgently needed in this setting.
Utilization of health insurance by patients with diabetes or hypertension in urban hospitals in Mbarara, Uganda
Authors: Kangwagye Peter , Bright Laban Waswa , Atukunda Gershom , Basaza Robert , Bajunirwe Francis 
Published: April 2022

AbstractBackgroundDiabetes and hypertension are among the leading contributors to global mortality and require life-long medical care. However, many patients cannot access quality healthcare due to high out-of-pocket expenditures, thus health insurance would help provide relief. This paper examines factors associated with utilization of health insurance by patients with diabetes or hypertension at two urban hospitals in Mbarara, southwestern Uganda.MethodsWe used a cross-sectional survey design to collect data from patients with diabetes or hypertension attending two hospitals located in Mbarara. Logistic regression models were used to examine associations between demographic factors, socio-economic factors and awareness of scheme existence and health insurance utilization.ResultsWe enrolled 370 participants, 235 (63.5%) females and 135 (36.5%) males, with diabetes or hypertension. Patients who were not members of a microfinance scheme were 76% less likely to enrol in a health insurance scheme (OR = 0.34, 95% CI: 0.15 – 0.78, p = 0.011). Patients diagnosed with diabetes/hypertension 5 – 9 years ago were more likely to enrol in a health insurance scheme (OR = 2.99, 95% CI: 1.14 – 7.87, p = 0.026) compared to those diagnosed 0 – 4 years ago. Patients who were not aware of the existing schemes in their areas were 99% less likely to take up health insurance (OR = 0.01, 95% CI: 0.0 – 0.02, p < 0.001) compared to those who knew about health insurance schemes operating in the study area. Majority of respondents expressed willingness to join the proposed national health insurance scheme although concerns were raised about high premiums and misuse of funds which may negatively impact decisions to enrol.ConclusionBelonging to a microfinance scheme positively influences enrolment by patients with diabetes or hypertension in a health insurance program. Although a small proportion is currently enrolled in health insurance, the vast majority expressed willingness to enrol in the proposed national health insurance scheme. Microfinance schemes could be used as an entry point for health insurance programs for patients in these settings.
Prior Optic Neuritis Detection on Peripapillary Ring Scans using Deep Learning
Authors: Motamedi Seyedamirhosein , Yadav Sunil Kumar , Kenney Rachel C. , Lin Ting-Yi , Kauer-Bonin Josef , Zimmermann Hanna G. , Galetta Steven L. , Balcer Laura J. , Paul Friedemann , Brandt Alexander U. 
Published: April 2022

AbstractBackgroundThe diagnosis of multiple sclerosis (MS) d requires demyelinating events that are disseminated in time and space. Peripapillary retinal nerve fiber layer (pRNFL) thickness as measured by optical coherence tomography (OCT) distinguishes eyes with a prior history of acute optic neuritis (ON) and may provide evidence to support a demyelinating attack.ObjectiveTo investigate whether a deep learning (DL)-based network can distinguish between eyes with prior ON and healthy control (HC) eyes using peripapillary ring scans.MethodsWe included 1,033 OCT scans from 415 healthy eyes (213 HC subjects) and 510 peripapillary ring scans from 164 eyes with prior acute ON (140 patients with MS). Data were split into 70% training (728 HC and 352 ON), 15% validation (152 HC and 79 ON), and 15% test data (153 HC and 79 ON). We included 102 OCT scans from 80 healthy eyes (40 HC) and 61 scans from 40 ON eyes (31 MS patients) from an independent second center. Receiver operating characteristic curve (ROC) analyses with area under the curve (AUC) were used to investigate performance.ResultsWe used a dilated residual convolutional neural network with alternating convolutional and max pooling layers for the classification. A final network using 2-factor augmentation had an accuracy of 0.85. The network achieved an area under the curve (AUC) of 0.86, whereas pRNFL only had an AUC of 0.77 in recognizing ON eyes. Using data from a second center, the network achieved an accuracy of 0.77 and an AUC of 0.90 compared to pRNFL, which had an AUC of 0.84.ConclusionDL-based disease classification of prior ON is feasible and has the potential to outperform thickness-based classification of eyes with and without history of prior ON.
Purification of mitochondria from skeletal muscle tissue for transcriptomic analyses reveals localisation of nuclear-encoded non-coding RNAs
Authors: Silver Jessica , Trewin Adam J. , Loke Stella , Croft Larry , Ziemann Mark , Soria Megan , Dillon Hayley , Nielsen Søren , Lamon Séverine , Wadley Glenn. D. 
Published: April 2022

ABSTRACTMitochondria are central to cellular function, particularly in metabolically active tissues such as skeletal muscle. Nuclear-encoded RNAs typically localise within the nucleus and cytosol but a small population may also translocate to subcellular compartments such as mitochondria. We aimed to investigate the nuclear-encoded RNAs that localise within the mitochondria of skeletal muscle cells and tissue. Intact mitochondria were isolated via immunoprecipitation (IP) followed by enzymatic treatments (RNase-A and proteinase-K) optimised to remove transcripts located exterior to mitochondria, making it amenable for high-throughput transcriptomic sequencing. Small-RNA sequencing libraries were successfully constructed from as little as 1.8 ng mitochondrial RNA input. Small-RNA sequencing of mitochondria from rat myoblasts revealed the enrichment of over 200 miRNAs. Whole-transcriptome RNA sequencing of enzymatically-purified mitochondria isolated by IP from skeletal muscle tissue showed a striking similarity in the degree of purity compared to mitoplast preparations which lack an outer mitochondrial membrane. In summary, we describe a novel, powerful sequencing approach applicable to animal and human tissues and cells that can facilitate the discovery of nuclear-encoded RNA transcripts localised within skeletal muscle mitochondria.
Computationally Guided Design of Novel Angiotensin Converting Enzyme Inhibitors
Authors: Lam Jennifer D. , Riley Mary , Siegel Justin B. 
Published: April 2022

ABSTRACTAngiotensin-converting enzyme inhibitors (ACEI) such as Moexipril, Trandolapril, Ramipril, and Perindopril are used to treat hypertension. However, these drugs have undesired side effects. Using computational studies, two new novel drug candidates were designed with improved molecular interactions, ADMET properties, and docking scores compared to Moexipril. Homology analysis was done to determine the best animal model for preclinical studies, and it revealed that Pan troglodytes (chim-panzees) and Mus musculus (house mouse) were the best candidates.
Retinotopic organization of feedback projections in primate early visual cortex: implications for active vision
Authors: Wang Mingli , Hou Yujie , Magrou Loïc , Autio Joonas A. , Misery Pierre , Coalson Tim , Reid Erin , Xu Yuanfang , Lamy Camille , Falchier Arnauld , Zhang Qi , Poo Mu-Ming , Dehay Colette , Glasser Matthew F. , Hayashi Takuya , Knoblauch Kenneth , Van Essen David , Shen Zhiming , Kennedy Henry 
Published: April 2022

AbstractFeedback connections play a major role in many theories of brain function. Previous studies of feedback connections to early visual areas have mainly concentrated on the representation of central visual fields. Here, injections of tracers at different eccentricities in areas V1 and V2 revealed retinotopically organized feedback. Peripheral injections revealed projections from 15 areas that are not labeled by central injections. Connection strengths for the majority of projections vary significantly with eccentricity in a systematic fashion with respect to distance and origin; whereas projections to central and upper visual fields are significantly stronger from ventral stream areas, peripheral and lower field projections are stronger from the dorsal stream. Non-invasive functional connectivity suggests a similar anatomical organization in humans. These features are discussed with respect to the cognitive and perceptual roles of these feedback pathways.
A reverse vaccinology approach identifies putative vaccination targets in the zoonotic nematode Ascaris
Authors: Evangelista Francisco Miguel Dias , van Vliet Arnoud H. M. , Lawton Scott P. , Betson Martha 
Published: April 2022

AbstractAscariasis is the most prevalent helminthic disease affecting both humans and pigs and is caused by the roundworms Ascaris lumbricoides and Ascaris suum. While preventive chemotherapy continues to be the most common control method, recent reports of anthelminthic resistance highlight the need for development of a vaccine against ascariasis. The aim of this study was to use a reverse vaccinology approach to identify potential vaccine candidates for Ascaris. Three Ascaris proteomes predicted from whole-genome sequences were analysed. Candidate proteins were identified using open-access bioinformatic tools (e.g. Vacceed, VaxiJen, Bepipred 2.0) which test for different characteristics such as sub-cellular location, T-cell and B-cell molecular binding, antigenicity, allergenicity and phylogenetic relationship with other nematode proteins. From over 100,000 protein sequences analysed, four transmembrane proteins were predicted to be non-allergen antigens and potential vaccine candidates. The four proteins are a Piezo protein, two voltage-dependent calcium channels and a protocadherin-like protein, are all expressed in either the muscle or ovaries of both Ascaris species, and all contained high affinity epitopes for T-cells and B-cells. The use of a reverse vaccinology approach allowed the prediction of four new potential vaccination targets against ascariasis in humans and pigs. These targets can now be further tested in in vitro and in vivo assays to prove efficacy in both pigs and humans.