bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comparison of short-read, HiFi long-read, and hybrid strategies for genome-resolved metagenomics
Authors: Eisenhofer Raphael , Nesme Joseph , Santos-Bay Luisa , Koziol Adam , Sørensen Søren Johannes , Alberdi Antton , Aizpurua Ostaizka 
Published: October 2023

AbstractShotgun metagenomics enables the reconstruction of complex microbial communities at a high level of detail. Such an approach can be conducted using both short-read and long-read sequencing data, as well as a combination of both. To assess the pros and cons of these different approaches, we used 22 faecal DNA extracts collected weekly for 11 weeks from two respective lab mice to study seven performance metrics over four combinations of sequencing depth and technology: i) 20 Gbp of Illumina short-read data, ii) 40 Gbp of short-read data, iii) 20 Gbp of PacBio HiFi long-read data, and iv) 40 Gbp of hybrid (20 Gbp of short-read + 20 Gbp of long-read) data. No strategy was best for all metrics, but instead, each one excelled across different metrics. The long-read approach yielded the best assembly statistics, with the highest N50 and lowest number of contigs. The 40 Gbp short-read approach yielded the highest number of refined bins. Finally, the hybrid approach yielded the longest assemblies, and the highest mapping rate to the bacterial genomes. Our results suggest that while long-read sequencing significantly improves the quality of reconstructed bacterial genomes, it is more expensive and requires deeper sequencing than short-read approaches to recover a comparable amount of reconstructed genomes. The most optimal strategy is study-specific, and depends on how researchers assess the tradeoff between the quantity and quality of recovered genomes.ImportanceOur understanding of microbial communities is limited by the technologies we employ. Here, we test several different DNA sequencing techniques to better understand the pros and cons of each. Long read DNA sequencing allowed for the reconstruction of higher quality and even complete microbial genomes, however, the cost was greater than commonly used short-read DNA sequencing. We suggest researchers consider the trade-offs between each method and decide based on the goals of their research question/s.
Pumping the brakes: rostromedial tegmental inhibition of compulsive cocaine seeking
Authors: Vento Peter J. , Watson Jacob R. , Pullmann Dominika , Black Samantha L. , Tomberlin Jensen S. , Jhou Thomas C. 
Published: October 2023

AbstractAddiction is marked by aberrant decision-making and an inability to suppress inappropriate and often dangerous behaviors. We previously demonstrated that inactivation of the rostromedial tegmental nucleus (RMTg) in rats causes persistent food seeking despite impending aversive footshock, an effect strikingly similar to the punishment resistance observed in people with a history of protracted drug use [1]. Here, we extend these studies to demonstrate chemogenetic silencing of RMTg axonal projections to the ventral tegmental area (VTA) (RMTg◊VTA pathway) causes rats to endure significantly more footshock to receive cocaine infusions. To further test whether activation of this circuit is sufficient to suppress reward seeking in the absence of an overtly aversive stimulus, we used temporally specific optogenetic stimulation of the RMTg◊VTA pathway as a “punisher” in place of footshock following lever pressing for either food or cocaine reward. While optical stimulation of the RMTg◊VTA pathway robustly suppressed lever pressing for food, we found that stimulation of this circuit had only modest effects on suppressing responding for cocaine infusions. Even though optical RMTg◊VTA stimulation was not particularly effective at reducingongoingcocaine use, this experience nevertheless had long-lasting consequences, as reinstatement of drug seeking in response to cocaine-associated cues was profoundly suppressed when tested nearly two weeks later. These results suggest the RMTg may serve as a useful target for producing enduring reductions in drug craving, particularly during periods of abstinence from drug use.
Single nuclei chromatin accessibility and transcriptomic map of breast tissues of women of diverse genetic ancestry
Authors: Bhat-Nakshatri Poornima , Gao Hongyu , Khatpe Aditi S. , McGuire Patrick C. , Erdogan Cihat , Chen Duojiao , Jiang Guanglong , New Felicia , German Rana , Storniolo Anna Maria , Liu Yunlong , Nakshatri Harikrishna 
Published: October 2023

AbstractSingle nuclei analysis is allowing robust classification of cell types in an organ that helps to establish relationships between cell-type specific gene expression and chromatin accessibility status of gene regulatory regions. Using breast tissues of 92 healthy donors of various genetic ancestry, we have developed a comprehensive chromatin accessibility and gene expression atlas of human breast tissues. Integrated analysis revealed 10 distinct cell types in the healthy breast, which included three major epithelial cell subtypes (luminal hormone sensing, luminal adaptive secretory precursor, and basal-myoepithelial cells), two endothelial subtypes, two adipocyte subtypes, fibroblasts, T-cells, and macrophages. By integrating gene expression signatures derived from epithelial cell subtypes with spatial transcriptomics, we identify specific gene expression differences between lobular and ductal epithelial cells and age-associated changes in epithelial cell gene expression patterns and signaling networks. Among various cell types, luminal adaptive secretory cells and fibroblasts showed genetic ancestry dependent variability. A subpopulation of luminal adaptive secretory cells with alveolar progenitor (AP) cell state were enriched in Indigenous American (IA) ancestry and fibroblast populations were distinct in African ancestry. ESR1 expression pattern was distinctly different in cells from IA compared to the rest, with a high level of ESR1 expression extending to AP cells and crosstalk between growth factors and Estrogen Receptor signaling being evident in these AP cells. In general, cell subtype-specific gene expression did not uniformly correlate with cell-specific chromatin accessibility, suggesting that transcriptional regulation independent of chromatin accessibility governs cell type-specific gene expression in the breast.
A portable, easy-to-use paper-based biosensor for rapid in-field detection of fecal contamination on fresh produce farms
Authors: Wang Jiangshan , Kaur Simerdeep , Kayabasi Ashley , Ranjbaran Mohsen , Rath Ishaan , Benschikovski Ilan , Raut Bibek , Ra Kyungyeon , Rafiq Nafisa , Verma Mohit S. 
Published: October 2023

AbstractLaboratory-based nucleic acid amplification tests (NAATs) are highly sensitive and specific, but they require the transportation of samples to centralized testing facilities and have long turnaround times. During the Coronavirus Disease 2019 (COVID-19) pandemic, substantial advancement has been achieved with the development of paper-based point-of-care (POC) NAATs, offering features such as low cost, being easy to use, and providing rapid sample-to-answer times. Although most of the POC NAATs innovations target clinical settings, we have developed a portable, paper-based loop-mediated isothermal amplification (LAMP) testing platform for on-farm applications, capable of detectingBacteroidalesas a fecal contamination biomarker. Our integrated platform includes a drop generator, a heating and imaging unit, and paper-based biosensors, providing sensitive results (limit of detection 3 copies ofBacteroidalesper cm2) within an hour of sample collection. We evaluated this integrated platform on a commercial lettuce farm with a concordance of 100% when compared to lab-based tests. Our integrated paper-based LAMP testing platform holds great promise as a reliable and convenient tool for on-site NAATs. We expect that this innovation will encourage the fresh produce industry to adopt NAATs as a complementary tool for decision-making in growing and harvesting. We also hope that our work can stimulate further research in the development of on-farm diagnostic tools for other agricultural applications, leading to improved food safety and technology innovation.
Grove-level analysis of titer and prevalence of “CandidatusLiberibacter asiaticus” andWolbachiainDiaphorina citri,vector of citrus Huanglongbing
Authors: Mann Marina , Thompson Luke , Johnson Lynn , Heck Michelle 
Published: October 2023

AbstractHuanglongbing (HLB, or citrus greening disease) affects all citrus varieties world-wide. In the USA, Asia, and South America the causal agent is “CandidatusLiberibacter asiaticus” (CLas), a phloem-limited, uncultured, alphaproteobacterium. The hemipteran insect vector,Diaphorina citri(Asian citrus psyllid) acquires and transmitsCLas in a circulative, propagative manner. In addition toCLas,D. citrihosts multiple symbiotic bacterial species includingWolbachia(wDi). InD. citri, wDi has been sequenced and studied but specific roles inD. citribiology are unknown. Using well established quantitative PCR methods we measuredCLas titer inD. citricollected from four groves in central Florida with distinct HLB management strategies and tested whetherCLas and wDi titer were correlated in a sub-set of these insects. Grove site had the largest effect onCLas titer. Sex had no effect onCLas titer, while higher wDi titer was correlated with non-infected insects. Our results suggest that more directed follow-up research is necessary and important to clarify whether field management tactics influenceCLas titer inD. citriand to better understand gene-by-environment interactions amongD. citri, wDi andCLas. Now that millions of trees in Florida have been treated with injectable formulations of oxytetracycline, which is likely to decrease bacterial populations inD. citri, this study may represent the last biologically meaningful snapshot of grove-level vector-pathogen ecology in the state during the HLB epidemic.
Dedifferentiated early postnatal lung myofibroblasts redifferentiate in adult disease
Authors: Chandran Rachana R. , Adams Taylor , Kabir Inamul , Gallardo Eunate , Kaminski Naftali , Gomperts Brigitte , Greif Daniel M. 
Published: October 2023

AbstractAlveolarization ensures sufficient lung surface area for gas exchange, and during bulk alveolarization in mice (postnatal day [P] 4.5-14.5), alpha-smooth muscle actin (SMA)+myofibroblasts accumulate, secrete elastin, and lay down alveolar septae. Herein, we delineate the dynamics of the lineage of early postnatal SMA+myofibroblasts during and after bulk alveolarization and in response to lung injury. SMA+lung myofibroblasts first appear at ∼P2.5 and proliferate robustly. Lineage tracing shows that, at P14.5 and over the next few days, the vast majority of SMA+myofibroblasts downregulate smooth muscle cell markers and undergo apoptosis. Of note, ∼8% of these dedifferentiated cells and another ∼1% of SMA+myofibroblasts persist to adulthood. Single cell RNA sequencing analysis of the persistent SMA-cells and SMA+myofibroblasts in the adult lung reveals distinct gene expression profiles. For instance, dedifferentiated SMA-cells exhibit higher levels of tissue remodeling genes. Most interestingly, these dedifferentiated early postnatal myofibroblasts re-express SMA upon exposure of the adult lung to hypoxia or the pro-fibrotic drug bleomycin. However, unlike during alveolarization, these cells that re-express SMA do not proliferate with hypoxia. In sum, dedifferentiated early postnatal myofibroblasts are a previously undescribed cell type in the adult lung and redifferentiate in response to injury.
A phylogenetic method linking nucleotide substitution rates to rates of continuous trait evolution
Authors: Gemmell Patrick , Sackton Timothy B. , Edwards Scott V. , Liu Jun S. 
Published: October 2023

AbstractGenomes contain conserved non-coding sequences that perform important biological functions, such as gene regulation. We present a phylogenetic method, PhyloAcc-C, that associates nucleotide substitution rates with changes in a continuous trait of interest. The method takes as input a multiple sequence alignment of conserved elements, continuous trait data observed in extant species, and a background phylogeny and substitution process. Gibbs sampling is used to assign rate categories (background, conserved, accelerated) to lineages and explore whether the assigned rate categories are associated with increases or decreases in the rate of trait evolution. We test our method using simulations and then illustrate its application using mammalian body size and lifespan data previously analyzed with respect to protein coding genes. Like other studies, we find processes such as tumor suppression, telomere maintenance, and p53 regulation to be related to changes in longevity and body size. In addition, we also find that skeletal genes, and developmental processes, such as sprouting angiogenesis, are relevant. The R/C++ software package implementing our method is available under an open source license fromhttps://github.com/phyloacc/PhyloAcc-C.
Neuroprotective Effects of Naltrexone in a Mouse Model of Post-Traumatic Epilepsy
Authors: Rodriguez Saul , Sharma Shaunik , Tiarks Grant , Peterson Zeru , Jackson Kyle , Thedens Daniel , Wong Angela , Keffala-Gerhard David , Mahajan Vinit B. , Ferguson Polly J. , Newell Elizabeth A. , Glykys Joseph , Nickl-Jockschat Thomas , Bassuk Alexander G. 
Published: October 2023

AbstractTraumatic Brain Injury (TBI) induces neuroinflammatory responses that can initiate epileptogenesis, which develops into epilepsy. Recently, we identified the anti-convulsive effects of naltrexone, a mu-opioid receptor (MOR) antagonist. While blocking opioid receptors can reduce inflammation, it is unclear if post-TBI epileptogenesis can be prevented by blocking MORs. Here, we tested if naltrexone prevents neuroinflammation and epileptogenesis post-TBI. TBI was induced by a modified Marmarau Weight-Drop (WD) method applied to four-week-old C57BL/6J male mice. Mice were given the pro-convulsant pentylenetetrazol (PTZ) on day two post-injury while telemetry-monitored mice received PTZ on day five. Naltrexone/vehicle treatment started two hours after PTZ. Integrated EEG-video (vEEG) recorded interictal events and spontaneous seizures for three months. Molecular, histological and neuroimaging techniques were used to evaluate neuroinflammation and neurodegeneration both acutely and chronically. Peripheral immune responses were assessed through serum chemokine/cytokine measurements. We observed increases in MOR expression, nitro-oxidative stress, mRNA expression of inflammatory cytokines, microgliosis, neurodegeneration, and white matter damage in the neocortex of TBI mice. vEEG revealed increased interictal events in TBI mice, with 71% developing epilepsy. Naltrexone ameliorated neuroinflammation and neurodegeneration, reduced interictal events and prevented epilepsy, illustrating that naltrexone is a promising drug to prevent TBI-associated neuroinflammation and epileptogenesis in post-traumatic epilepsy.
Activity-dependent survival of odorant receptor neurons in ants
Authors: Sieriebriennikov Bogdan , Sieber Kayli R , Kolumba Olena , Mlejnek Jakub , Jafari Shadi , Yan Hua 
Published: October 2023

ABSTRACTOlfaction is essential for complex social behavior in eusocial insects. To discriminate complex social cues, ants evolved an expanded number ofodorant receptor(Or) genes. Unlike most insect species, mutations in the obligate odorant co-receptor geneorcolead to loss of ∼80% antennal lobe glomeruli in ants. However, its cellular mechanism remains unclear. Here we demonstrate that this surprising neuronal phenotype results from massive apoptosis of odorant receptor neurons (ORNs) in the mid- to late-stages of pupal development. Further bulk and single-nucleus transcriptome analysis show that, although the majority oforco-expressing ORNs die inorcomutants, a small proportion of them survive: they expressionotropic receptor(Ir) genes that form IR complexes. In addition, we found that someOrgenes are expressed in mechanosensory neurons as well as non-neuronal cells, possibly due to the leaky regulation from nearby non-Orgenes. Our findings suggest that chemosensory receptors are required for activity-dependent survival of developing ORNs in ants.
Multimodal joint deconvolution and integrative signature selection in proteomics
Authors: Pan Yue , Wang Xusheng , Liu Chunyu , Peng Junmin , Li Qian 
Published: October 2023

AbstractDeconvolution is an efficient approach for detecting cell-type-specific (cs) transcriptomic signals without cellular segmentation. However, this type of methods have not been extended to the proteomics research. Here we present a novel algorithm and tool to dissect bulk proteome by leveraging the information shared between transcriptome-proteome. Our tool first identifies potential cell marker proteins by integrating RNA and protein bulk expression profiles and then jointly quantifies the cell abundance in mixture proteomes without using a reference signature matrix, enabling the downstream analyses such as cs-protein Quantitative Trait Loci (cspQTL) mapping. This new method and the cspQTL analysis are implemented in the R package MIC-SQTL that also provides integrative visualization of bulk multimodal samples, available athttps://bioconductor.org/packages/MICSQTL.
Kombucha Tea-associated Microbes Remodel Host Metabolic Pathways to Suppress Lipid Accumulation
Authors: DuMez-Kornegay Rachel N. , Morris Alexis J. , Dowen Robert H. 
Published: October 2023

ABSTRACTThe popularity of the ancient, probiotic-rich beverage Kombucha Tea (KT) has surged in part due to its purported health benefits, which include protection against metabolic diseases; however, these claims have not been rigorously tested and the mechanisms underlying host response to the probiotics in KT are unknown. Here, we establish a reproducible method to maintainC. eleganson a diet exclusively consisting of Kombucha Tea-associated microbes (KTM), which mirrors the microbial community found in the fermenting culture. KT microbes robustly colonize the gut of KTM-fed animals and confer normal development and fecundity. Intriguingly, animals consuming KTMs display a marked reduction in total lipid stores and lipid droplet size. We find that the reduced fat accumulation phenotype is not due to impaired nutrient absorption, but rather it is sustained by a programed metabolic response in the intestine of the host. KTM consumption triggers widespread transcriptional changes within core lipid metabolism pathways, including upregulation of a suite of lysosomal lipase genes that are induced during lipophagy. The elevated lysosomal lipase activity, coupled with a decrease in lipid droplet biogenesis, is partially required for the reduction in host lipid content. We propose that KTM consumption stimulates a fasting- like response in theC. elegansintestine by rewiring transcriptional programs to promote lipid utilization. Our results provide mechanistic insight into how the probiotics in Kombucha Tea reshape host metabolism and how this popular beverage may impact human metabolism.
Participant Flow Diagrams for Health Equity in AI Research
Authors: Ellen Jacob G. , Matos João , Viola Martin , Gallifant Jack , Quion Justin , Celi Leo Anthony , Hussein Nebal S. Abu 
Published: October 2023

AbstractBiases in sample creation can arise at any study phase, including initial patient recruitment, exclusion criteria, input-level exclusion and outcome-level exclusion, and often reflect the underrepresentation or exclusion of demographic groups historically disadvantaged in medical research. The use of non-representative samples to construct clinical algorithms in artificial intelligence (AI) and machine learning (ML) applications may further amplify this selection bias. Building on the “Data Cards” initiative for transparency in AI research, we advocate for the addition of a detailed participant flow diagram for AI studies, emphasizing the need to detail excluded participant demographic characteristics at every study phase. This tracking of excluded participants enhances understanding of potential algorithmic biases before their clinical implementation, and thus deserves to be detailed in any medical AI study. We include both a model for this flow diagram as well as a brief case study explaining how it could be implemented in practice. Through standardized reporting of participant flow diagrams, we can better gauge the potential inequity embedded in AI applications, facilitating more reliable and equitable clinical algorithms.
Enhancing immunotherapy outcomes in glioblastoma through predictive machine learning
Authors: Mestrallet Guillaume 
Published: October 2023

AbstractGlioblastoma is a highly aggressive cancer associated with a dismal prognosis, with a mere 5% of patients surviving beyond five years post-diagnosis. Current therapeutic modalities encompass surgical intervention, radiotherapy, chemotherapy, and immune checkpoint inhibitors (ICB). However, the efficacy of ICB remains limited in glioblastoma patients, necessitating a proactive approach to anticipate treatment response and resistance.In this comprehensive study, we conducted a rigorous analysis involving two distinct glioblastoma patient cohorts subjected to PD-1 blockade treatments. Our investigation unveiled that a significant portion, 60%, of patients exhibit persistent disease progression despite ICB intervention. To elucidate the underpinnings of resistance, we characterized the immune profiles of glioblastoma patients with continued cancer progression following anti-PD1 therapy. These profiles revealed multifaceted defects, encompassing compromised macrophage, monocyte, and T follicular helper responses, impaired antigen presentation, aberrant regulatory T cell (Tregs) responses, and heightened expression of immunosuppressive molecules (TGFB, IL2RA, and CD276). Building upon these resistance profiles, we leveraged cutting-edge machine learning algorithms to develop predictive models and accompanying software. This innovative computational tool achieved remarkable success, accurately forecasting the progression status of 82.82% of glioblastoma patients following ICB, based on their unique immune characteristics.In conclusion, our pioneering approach advocates for the personalization of immunotherapy in glioblastoma patients. By harnessing patient-specific attributes and computational predictions, we offer a promising avenue for the enhancement of clinical outcomes in the realm of immunotherapy. This paradigm shift towards tailored therapies underscores the potential to revolutionize the management of glioblastoma, opening new horizons for improved patient care.