bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early Detection of Novel SARS-CoV-2 Variants from Urban and Rural Wastewater through Genome Sequencing and Machine Learning
Authors: Zhuang Xiaowei , Vo Van , Moshi Michael A. , Dhede Ketan , Ghani Nabih , Akbar Shahraiz , Chang Ching-Lan , Young Angelia K. , Buttery Erin , Bendik William , Zhang Hong , Afzal Salman , Moser Duane , Cordes Dietmar , Lockett Cassius , Gerrity Daniel , Kan Horng-Yuan , Oh Edwin C. 
Published: April 2024

AbstractGenome sequencing from wastewater has emerged as an accurate and cost-effective tool for identifying SARS-CoV-2 variants. However, existing methods for analyzing wastewater sequencing data are not designed to detect novel variants that have not been characterized in humans. Here, we present an unsupervised learning approach that clusters co-varying and time-evolving mutation patterns leading to the identification of SARS-CoV-2 variants. To build our model, we sequenced 3,659 wastewater samples collected over a span of more than two years from urban and rural locations in Southern Nevada. We then developed a multivariate independent component analysis (ICA)-based pipeline to transform mutation frequencies into independent sources with co-varying and time-evolving patterns and compared variant predictions to >5,000 SARS-CoV-2 clinical genomes isolated from Nevadans. Using the source patterns as data-driven reference “barcodes”, we demonstrated the model’s accuracy by successfully detecting the Delta variant in late 2021, Omicron variants in 2022, and emerging recombinant XBB variants in 2023. Our approach revealed the spatial and temporal dynamics of variants in both urban and rural regions; achieved earlier detection of most variants compared to other computational tools; and uncovered unique co-varying mutation patterns not associated with any known variant. The multivariate nature of our pipeline boosts statistical power and can support accurate and early detection of SARS-CoV-2 variants. This feature offers a unique opportunity for novel variant and pathogen detection, even in the absence of clinical testing.
Asymptomatic seroconversion in healthy people against dengue and chikungunya in Kandy district of Sri Lanka
Authors: Edirisinghe L.E.A.D.A. , Mahakapuge T.A.N. , Kularatne S.A.M. , Kularatne S.A.M.D.A. , Rajapakse R.P.V.J. 
Published: April 2024

AbstractBackgroundBoth dengue and chikungunya are transmitted byAedes aegyptiand have many similarities in epidemiology and clinical manifestations. These two viruses are known to cause asymptomatic infection, however, studies to assess the seroprevalence in healthy individuals are limited. Our objective is to estimate the asymptomatic seroconversion status of both these infections Sri Lanka where dengue has been endemic and the last notable outbreak of chikungunya occurred in 2007.MethodsThe study was performed using venous blood samples of 454 healthy individuals (age range 11-78) in Kandy district, who had no known history of dengue or chikungunya infections in the past or present. Samples were tested for dengue NS1 antigen, dengue IgM, dengue IgG, Chikungunya IgM and Chikungunya IgG by using commercially available ELISA kits. Statistical data analysis was performed using SPSS software version 16.0 (SPSS, Inc., Chicago, IL, USA).Pvalue <0.05 was considered statistically significant.ResultsOf the 454 healthy individuals, 287 (63.2%) were positive for dengue IgG indicating a past infection and 18 (4%) were positive for dengue-specific IgM. Of the same total, 82 (18.1%) were positive chikungunya chikungunya-specific IgM and only 6 (1.3%) were positive for chikungunya-specific IgM. The number of individuals positive for both dengue IgG and Chikungunya IgG, indicating dual antibody prevalence or exposure to both diseases asymptomatically was 61(13.43%). For dengue specific IgG, the highest sero-conversion rate (80.4%) was observed in 51-60 year age group whilst the lowest (50%) in the age group 11-20. Out of the MOH areas, the highest prevalence (71.4%) of positives were observed in Bambaradeniya and the lowest prevalence (53.1%) in Yatinuwara suburbs in Kandy. The highest percentage of dengue IgM prevalence (6.3%) was observed in the age group 21-30 years and the lowest percentage (1.5%) was observed in the age group 11-20.ConclusionsAn asymptomatic seroconversion rate was observed in both dengue and Chikungunya infections. Dengue records a high rate due to its endemicity and periodic outbreaks. It is interesting to note the low-grade prevalence of Chikungunya infection contrary to the belief itsnon-existence in the island currently.
Whole-genome duplication in the Multicellularity Long Term Evolution Experiment
Authors: Tong Kai , Datta Sayantan , Cheng Vivian , Haas Daniella J. , Gourisetti Saranya , Yopp Harley L. , Day Thomas C. , Lac Dung T. , Conlin Peter L. , Bozdag G. Ozan , Ratcliff William C. 
Published: April 2024

ABSTRACTWhole-genome duplication (WGD) is widespread across eukaryotes and can promote adaptive evolution1–4. However, given the instability of newly-formed polyploid genomes5–7, understanding how WGDs arise in a population, persist, and underpin adaptations remains a challenge. Using our ongoing Multicellularity Long Term Evolution Experiment (MuLTEE)8, we show that diploid snowflake yeast (Saccharomyces cerevisiae) under selection for larger multicellular size rapidly undergo spontaneous WGD. From its origin within the first 50 days of the experiment, tetraploids persist for the next 950 days (nearly 5,000 generations, the current leading edge of our experiment) in ten replicate populations, despite being genomically unstable. Using synthetic reconstruction, biophysical modeling, and counter-selection experiments, we found that tetraploidy evolved because it confers immediate fitness benefits in this environment, by producing larger, longer cells that yield larger clusters. The same selective benefit also maintained tetraploidy over long evolutionary timescales, inhibiting the reversion to diploidy that is typically seen in laboratory evolution experiments. Once established, tetraploidy facilitated novel genetic routes for adaptation, playing a key role in the evolution of macroscopic multicellular size via the origin of evolutionarily conserved aneuploidy. These results provide unique empirical insights into the evolutionary dynamics and impacts of WGD, showing how it can initially arise due to its immediate adaptive benefits, be maintained by selection, and fuel long-term innovations by creating additional dimensions of heritable genetic variation.
Evaluating the Role of Endophyte-Rich Leaves in Protecting Tropical Trees Against a Generalist Herbivore and a Pathogen
Authors: Rolón Bolívar Aponte , Arnold A. Elizabeth , Juliá Mareli Sánchez , Van Bael Sunshine A. 
Published: April 2024

1.AbstractPlants use chemical compounds and physical barriers to defend themselves against natural enemies. For instance, tough leaves are considered to be better defended than soft leaves and we can measure this spectrum of defenses via leaf functional traits. Leaf traits such as leaf chemistry, lifespan, toughness, and leaf mass per area often are a plant’s first line of defense. Plants with longer lifespans that invest more in leaf tissue and higher leaf mass per area (LMA) typically feature robust constitutive defenses (e.g., leaf toughness, thickness, and dense cell walls) as well. In contrast, plants that invest more in leaf nutrients and have low LMA often invest more in induced defenses. Whether constitutive or induced, leaf traits represent an environmental filter for foliar endophytic fungi (FEF), which may play an additional role in plant defense. Our overarching assumption is that FEF alter leaf fate by interacting directly or indirectly with leaf traits, thus reshaping successive FEF colonization, development of leaf traits and response to plant enemies. To evaluate this hypothesis, we inoculated seedlings of seven tropical tree species that varied in leaf traits with natural and diverse endophyte communities. We confirmed the success of our inoculations of low FEF load (E-) and high FEF load (E+) treatment groups via culturing and culture-free amplicon sequencing. We then measured leaf removal by leaf-cutter ants and leaf necrosis due to a generalist fungal pathogen. Across the experiment, we observed greater herbivory in theE-treatment compared to theE+treatment, but no difference in pathogen damage. However, withinE-andE+treatment groups, leaves exposed to pathogen had greater leaf damage than non-exposed leaves. Dimensionality reduction of leaf functional traits (i.e., LMA, toughness, thickness, and anthocyanin levels) revealed relationships among traits and distinct host species characteristics. All leaf functional traits had significant correlations with FEF community composition. In turn, indicator species analyses reveal functional traits and taxonomic identities of FEF associated with high- and low leaf damage by natural enemies, suggesting new insights into cryptic roles of foliar symbionts in extending and modifying plant defenses in tropical forests.
Large-scale single-virus genomics uncovers hidden diversity of river water viruses and diversified gene profiles
Authors: Nishikawa Yohei , Wagatsuma Ryota , Tsukada Yuko , Chia-ling Lin , Chijiiwa Rieka , Hosokawa Masahito , Takeyama Haruko 
Published: April 2024

AbstractEnvironmental viruses (primarily bacteriophages) are widely recognized as playing an important role in ecosystem homeostasis through the infection of host cells. However, the majority of environmental viruses are still unknown as their mosaic structure and frequent mutations in their sequences hinder genome construction in current metagenomics. To enable the large-scale acquisition of environmental viral genomes, we developed a new single-viral genome sequencing platform with microfluidic-generated gel beads. Amplification of individual DNA viral genomes in mass-produced gel beads allows high-throughput genome sequencing compared to conventional single-virus genomics. The sequencing analysis of river water samples yielded 1431 diverse viral single-amplified genomes, while viral metagenomics recovered 100 viral metagenome-assembled genomes at the comparable sequence depth. The 99.5% of viral single-amplified genomes were determined novel at the species level, most of which could not be recovered by a metagenomic assembly. The large-scale acquisition of diverse viral genomes identified protein clusters commonly detected in different viral strains, allowing the gene transfer to be tracked. Moreover, comparative genomics within the same viral species revealed that the profiles of various methyltransferase subtypes were diverse, suggesting an enhanced escape from host bacterial internal defense mechanisms. Our use of gel bead-based single-virus genomics will contribute to exploring the nature of viruses by accelerating the accumulation of draft genomes of environmental DNA viruses.
Computational stabilization of a non-heme iron enzyme enables efficient evolution of new function
Authors: King Brianne R. , Sumida Kiera H. , Caruso Jessica L. , Baker David , Zalatan Jesse G. 
Published: April 2024

AbstractDirected evolution has emerged as a powerful tool for engineering new biocatalysts. However, introducing new catalytic residues can be destabilizing, and it is generally beneficial to start with a stable enzyme parent. Here we show that the deep learning-based tool ProteinMPNN can be used to redesign Fe(II)/αKG superfamily enzymes for greater stability, solubility, and expression while retaining both native activity and industrially-relevant non-native functions. For the Fe(II)/αKG enzyme tP4H, we performed site-saturation mutagenesis with both the wild-type and stabilized design variant and screened for activity increases in a non-native C-H hydroxylation reaction. We observed substantially larger increases in non-native activity for variants obtained from the stabilized scaffold compared to those from the wild-type enzyme. ProteinMPNN is user-friendly and widely-accessible, and straightforward structural criteria were sufficient to obtain stabilized, catalytically-functional variants of the Fe(II)/αKG enzymes tP4H and GriE. Our work suggests that stabilization by computational sequence redesign could be routinely implemented as a first step in directed evolution campaigns for novel biocatalysts.
Novel multiparametric bulk and single extracellular vesicle pipeline for adipose cell-specific biomarker discovery in paired human biospecimens
Authors: Hade Mangesh Dattu , Greenwald Jacelyn , Palacio Paola Loreto , Nguyen Kim Truc , Shantaram Dharti , Butsch Bradley L. , Kim Yongseok , Noria Sabrena , Brethauer Stacy A. , Needleman Bradley J. , Hsueh Willa , Wysocki Vicki H. , Reátegui Eduardo , Magaña Setty M. 
Published: April 2024

AbstractObesity remains a growing and global public health burden across a broad spectrum of metabolic, systemic, and neurodegenerative diseases. Previously considered merely a fat storage depot, adipose tissue is now recognized as an active endocrine organ crucial for metabolic and systemic regulation of local and distant organs. A burgeoning line of investigation centers on adipose-derived extracellular vesicles (ADEVs) and their pivotal role in obesity-associated pathobiology. However, robust methodologies are lacking for specifically isolating and characterizing human ADEVs. To bridge this gap, we have developed a robust multiparametric framework incorporating bulk and single EV characterization, proteomics, and mRNA phenotyping. EVs from matched human visceral adipose tissue, mature adipocyte-conditioned media, and plasma collected from the same individual bariatric surgical patients were analyzed and subjected to bottom-up proteomics analysis. This framework integrates bulk EV proteomics for cell-specific marker identification and subsequent single EV interrogation with single-particle interferometric reflectance imaging (SP-IRIS) and total internal reflection fluorescence (TIRF) microscopy. Our proteomics analysis revealed 76 unique proteins from adipose tissue-derived EVs (ATEVs), 512 unique proteins from adipocyte EVs (aEVs), and 1003 shared proteins. Prominent pathways enriched in ATEVs included lipid metabolism, extracellular matrix organization, and immune modulation, while aEVs exhibited enhanced roles in chromatin remodeling, oxidative stress responses, and metabolic regulation. Notably, adipose tissue-specific proteins such as adiponectin and perilipin were highly enriched in ADEVs and confirmed in circulating plasma EVs. Colocalization of key EV and adipocyte markers, including CD63 and PPARG, were validated in circulating plasma EVs. In summary, our study paves the way toward a tissue and cell-specific, multiparametric framework for an ‘adiposity EV signature’ in obesity-driven diseases.
The causal role of adiposity in mental illness: A systematic review and meta-analysis of Mendelian randomization studies
Authors: Gao Min , Doody Paul J , Koutoukidis Dimitrios A , Yu Yebo , Aveyard Paul , Stevens Richard , Dixon Padraig C 
Published: April 2024

AbstractImportanceExcess adiposity is associated with mental illnesses, but the causality of these associations remains equivocal.ObjectiveTo examine the causal effect of adiposity on mental illnesses by summarizing and assessing evidence from Mendelian randomization (MR) studies.Study SelectionSearches were conducted on Embase, Medline, and Web of Science from database inception to January 8th2024.Data Extraction and SynthesisStudies using MR study designs that estimated adiposity measures including body mass index, abdominal adiposity, peripheral adiposity, or body composition in relation to mental illnesses were included. Study quality was assessed with a scoring system reflecting MR study guidelines. Data were pooled in meta-analyses using random-effects models. Subgroup analyses were conducted by sex.Main Outcomes and MeasuresOutcomes were the presence or severity of depression, anxiety, eating disorders, bipolar disorder, obsessive compulsive disorder, post-traumatic stress disorder, schizophrenia, and related psychotic disorders.ResultsForty-one studies with 184 MR estimates were included in the systematic review; and 16 studies with 30 MR estimates were included in meta-analysis. Pooled estimates suggested that general adiposity was causally associated with depression (OR: 1.05, 95% CI, 1.00-1.10, p<0.001; I2=82.8%), though the effect size was modest and there was high heterogeneity. Subgroup difference by sex in the causal relationship was notobserved(p=0.382). No evidence of causal associations was found between adiposity and other mental illnesses, though these analyses were characterized by high imprecision and heterogeneity.Conclusion and RelevanceGeneral adiposity appears to be causally associated with depression, suggesting psychological benefits of weight management. Evidence for causal associations between adiposity and other mental illnesses remains uncertain.Key PointsQuestionIs adiposity causally associated with mental illnesses?FindingsIn this systematic review of 41 Mendelian randomization studies, with 184 MR estimates, and meta-analysis of 30 MR estimates, general adiposity was causally associated with depression. There was no evidence of sex differences. Evidence of causal associations between adiposity and other mental illnesses was unclear.MeaningThe findings suggest that higher adiposity can cause depression, which highlights the psychological importance of weight management.
Evaluation of a participatory approach to stratifying neighbourhoods across the Tanzanian city of Dar es Salaam in terms of income by comparing with latent profile analysis of deprivation based on national census data
Authors: Msuya Ibrahim , Boudou Martin , Levira Francis , Moshi Irene , O’Dwyer Jean , Killeen Gerard 
Published: April 2024

AbstractStudying geographic heterogeneities in the characteristics of city neighbourhoods, such as population income and deprivation, has been a common practice in urban health studies for tailored and targeted interventions, especially in highly developed and diversified cities. While a range of different approaches has been applied to classify different parts of towns and cities, participatory stratification approaches (PSAs) have become popular despite their subjective basis because of their affordability, simplicity and practicality, all of which allow them to be frequently updated. While more objective statistical approaches, such as latent profile analysis (LPA), can also be used to stratify neighbourhoods using formal socio-economic and demographic data, these rely on the availability of rich datasets and advanced analytical capacities that are not always available in low and middle-income countries. This study assessed a PSA to stratify neighbourhoods across the Tanzania city of Dar es Salaam in terms of income, by comparing it with a complementary LPA using national census data from 2012 to stratify them in terms of deprivation. A consultative community-based workshop was used for the PSA, while 15 selected deprivation indicators from the census data were used to profile them using LPA. While the PSA allocated neighbourhoods to five income strata, six clear deprivation strata could be distinguished by LPA. A strong positive correlation was observed between the stratum identified by the LPA and that obtained through the PSA (ρ = 0.739, p < 0.0001). Furthermore, paired comparison of the two sets of correlation coefficients between each deprivation indicator and the stratum assigned by each stratification approach revealed no difference (V = 33, p-value = 0.1354), confirming that the two approaches yielded very similar patterns of stratification., Also, the two approaches yielded broadly comparable cartographic pictures of the city, depicting similar spatial distribution of wealth and poverty. Overall, this evidence indicates that subjective community knowledge and lived experience may be invaluable for understanding the built environment and for mapping out pockets of poverty and affluence at fine scales with minimum resources.
Analyzing Predictors and Geospatial Trends of the Number of Visits and Timing of Antenatal Care in Zambia: A Generalized Linear Mixed Model (GLMM) Investigation from 1992 to 2018
Authors: Shumba Samson , Fwemba Isaac , kaymba Violet 
Published: April 2024

AbstractAntenatal care (ANC) plays a crucial role in preventing and detecting pregnancy risks, facilitating prompt treatment, and disseminating essential information to expectant mothers. This role is particularly vital in developing countries, where a 4.65% rise in maternal mortality rate was observed in 2022, with 800 maternal and 7,700 perinatal deaths reported. The study aims to analyse the predictors and geospatial trends of the number of visits and timing of antenatal care in Zambia from 1992 to 2018, utilizing a generalised linear mixed model approach. The analysis utilized the Zambia Demographic Health Survey (ZDHS) database. The relationship between dependent and independent variables was examined using the Rao-Scott Chi-square test. Predictors of inadequate utilisation of ANC were identified through the multilevel generalised linear model. Spatial effects were modeled using Quantum Geographic Information System (QGIS) version 3.34.1 to develop univariate choropleth maps. A total of 45, 140 (31, 482 women had less than 8 ANC visits and 2, 004 had 8 or more ANC visits) women with a prior childbirth were included in the study. The findings in the study revealed that among women aged 15 to 19 years in 1992, 1996 and 2013/14, the rates of inadequate antenatal care utilization (less than eight ANC visits) was 90.87%, 90.99%, and 99.63%, respectively. Lack of formal education was associated with inadequate ANC from 1992 to 2018, with percentages ranging from 91.12% to 99.64%. They were notable geospatial variations in the distribution of ANC underutilization across provinces with Luapula, Muchinga, Northwestern, Northern and Eastern recording higher proportions. Furthermore, the study showed that age (25 to 29 and 30 to 34) was associated with increased risk of inadequacy ANC utilization (AOR, 2.94; 95% CI, 1.20 – 7.19 and AOR, 2.65; 95% CI, 1.05 – 6.65 respectively). Higher education and wealth index correlated with reduced odds of inadequate ANC utilization. In conclusion, this study highlights worrisome trends in ANC utilization in Zambia, with a significant rise in inadequacy, especially in adhering to the WHO’s recommended eight ANC visits. Over the period from 1996 to 2018, there was a discernible decline in the prevalence of delayed initiation of ANC. The findings underscore a notable disparity between current ANC practices and established guidelines. Additionally, various factors predicting suboptimal ANC attendance have been identified. These insights call for targeted interventions to address the identified challenges and improve the overall quality and accessibility of ANC services in Zambia.