bluuebunny/crossref_metadata_2025_split huggingface dataset:
A benchmarked comparison of software packages for time-lapse image processing of monolayer bacterial population dynamics
Authors: Ahmadi Atiyeh , Courtney Matthew , Ren Carolyn , Ingalls Brian 
Published: December 2023

Time-lapse microscopy offers a powerful approach for analysing cellular activity. In particular, this technique is valuable for assessing the behaviour of bacterial populations, which can exhibit growth and intercellular interactions in monolayer. Such time-lapse imaging typically generates large quantities of data, limiting the options for manual investigation. Several of image processing software packages have been developed to facilitate analysis. It can thus be a challenge to identify the software package best suited to a particular research goal. Here, we compare four software packages that support analysis of 2D time-lapse images of cellular populations: CellProfiler, SuperSegger-Omnipose, DeLTA, and FAST. We compare their performance against benchmarked results on time-lapse observations ofE. colipopulations. Performance varies across the packages, with each of the four out-performing the others in at least one aspect of the analysis. Not surprisingly, the packages that have been in development for longer showed the strongest performance. We found that deep-learning based approaches to object segmentation outperformed traditional approaches, but the opposite was true for frame-to-frame object tracking. We offer these comparisons, together with insight on usability, computational efficiency, and feature availability, as a guide to researchers seeking image processing solutions.Significance StatementTime-lapse microscopy provides a detailed window into the world of bacterial behavior. However, the vast amount of data produced by these techniques is difficult to analyze manually. We have analysed four software tools designed to process such data and compared their performance, using populations of commonly studied bacterial species as our test subjects. Our findings offer a roadmap to scientists, helping them choose the right tool for their research. This comparison bridges a gap between microbiology and computational analysis, streamlining research efforts.
Single-cell profiling reveals the impact of genetic alterations on the differentiation of inflammation-induced colon tumors
Authors: Ghobashi Ahmed H. , Lanzloth Rosie , Ladaika Christopher A. , O’Hagan Heather M. 
Published: December 2023

AbstractGenetic mutations and chronic inflammation of the colon contribute to the development of colorectal cancer (CRC). Using a murine model of inflammation-induced colon tumorigenesis, we determined how genetic mutations alter colon tumor cell differentiation. Inflammation induced by enterotoxigenicBacteroides fragilis(ETBF) colonization of multiple intestinal neoplasia (MinApcΔ716/+) mice triggers loss of heterozygosity ofApccausing colon tumor formation. Here, we report that the addition ofBRAFV600Emutation (BRAFFV600ELgr5tm1(Cre/ERT2)CleMinApcΔ716/+, BLM) or knocking outMsh2(Msh2LoxP/LoxPVil1-creMinApcΔ716/+, MSH2KO) in the Min model altered colon tumor differentiation. Using single cell RNA-sequencing, we uncovered the differences between BLM, Min, and MSH2KO tumors at a single cell resolution. BLM tumors showed an increase in differentiated tumor epithelial cell lineages and a reduction in the stem cell population. In contrast, MSH2KO tumors were characterized by an increased stem cell population that had higher WNT signaling activity compared to Min tumors. Additionally, comparative analysis of single-cell transcriptomics revealed that BLM tumors had higher expression of transcription factors that drive differentiation, such asCdx2,than Min tumors. Using RNA velocity, we were able to identify additional potential regulators of BLM tumor differentiation such as NDRG1. The role of CDX2 and NDRG1 as putative regulators for BLM tumor cell differentiation was verified using organoids derived from BLM tumors. Our results demonstrate the critical connections between genetic mutations and cell differentiation in inflammation-induced colon tumorigenesis. Understanding such roles will deepen our understanding of inflammation-associated colon cancer.
Transcription factor activity profiling reveals the role of REST and LEF1 in the recovery from depression
Authors: Yamamoto Hajime , Araki Satomi , Onodera Ryoma , Go Yasuhiro , Abe Kentaro 
Published: December 2023

AbstractPsychophysiological disorders chronically impair brain functions, often accompanied by dysregulation of multiple genes, suggesting a multifaceted etiology behind the symptoms. To explore transcription factors (TFs) involved in such transcriptomic changes, we analyzed TF-activity profiles (TFAPs) from the brains of mice experienced chronic stress, and revealed alteration in TF-activity correlating with their pathophysiological phenotypes. We identified REST/NRSF and TCF/LEF associated with depressive phenotypes and discovered that neuropsychiatric drugs sertraline and lithium influence REST- and TCF/LEF-activity, both in vitro and in vivo, thereby affecting gene expression profiles. Pharmacological or genetic manipulation of REST- or TCF/LEF-activity in defeated mice impacts post-stress recovery from depressive phenotypes, with combined treatment further augmenting the outcomes. Our TFAP analysis enhances understanding of molecular mechanisms underpinning chronic diseases, aiding future therapeutic strategy development.
Multimodal generation of astrocyte by integrating single-cell multi-omics data via deep learning
Authors: Mao Jiashun , Wang Jianmin , Zeb Amir , No Kyoung Tai 
Published: December 2023

ABSTRACTObtaining positive and negative samples to examining several multifaceted brain diseases in clinical trials face significant challenges. We propose an innovative approach known as Adaptive Conditional Graph Diffusion Convolution (ACGDC) model. This model is tailored for the fusion of single cell multi-omics data and the creation of novel samples. ACGDC customizes a new array of edge relationship categories to merge single cell sequencing data and pertinent meta-information gleaned from annotations. Afterward, it employs network node properties and neighborhood topological connections to reconstruct the relationship between edges and their properties among nodes. Ultimately, it generates novel single-cell samples via inverse sampling within the framework of conditional diffusion model. To evaluate the credibility of the single cell samples generated through the new sampling approach, we conducted a comprehensive assessment. This assessment included comparisons between the generated samples and real samples across several criteria, including sample distribution space, enrichment analyses (GO term, KEGG term), clustering, and cell subtype classification, thereby allowing us to rigorously validate the quality and reliability of the single-cell samples produced by our novel sample method. The outcomes of our study demonstrated the effectiveness of the proposed method in seamlessly integrating single-cell multi-omics data and generating innovative samples that closely mirrored both the spatial distribution and bioinformatic significance observed in real samples. Thus, we suggest that the generation of these reliable control samples by ACGDC holds substantial promise in advancing precision research on brain diseases. Additionally, it offers a valuable tool for classifying and identifying astrocyte subtypes.
Fully automatic summarization of radiology reports using natural language processing with language models
Authors: Nishio Mizuho , Matsunaga Takaaki , Matsuo Hidetoshi , Nogami Munenobu , Kurata Yasuhisa , Fujimoto Koji , Sugiyama Osamu , Akashi Toshiaki , Aoki Shigeki , Murakami Takamichi 
Published: December 2023

AbstractNatural language processing using language models has yielded promising results in various fields. The use of language models may help improve the workflow of radiologists. This retrospective study aimed to construct and evaluate language models for the automatic summarization of radiology reports. Two datasets of radiology reports were used: MIMIC-CXR and the Japan Medical Image Database (JMID). MIMIC-CXR is an open dataset comprising chest radiograph reports. JMID is a large dataset of CT and MRI reports comprising reports from 10 academic medical centers in Japan. A total of 128,032 and 1,101,271 reports from the MIMIC-CXR and JMID, respectively, were included in this study. Four Text-to-Text Transfer Transformer (T5) models were constructed. Recall-Oriented Understudy for Gisting Evaluation (ROUGE), a quantitative metric, was used to evaluate the quality of text summarized from 19,205 and 58,043 test sets from MIMIC-CXR and JMID, respectively. The Wilcoxon signed-rank test was utilized to evaluate the differences among the ROUGE values of the four T5 models. In addition, subsets of automatically summarized text in the test sets were manually evaluated by two radiologists. Based on the Wilcoxon signed-rank test, the best T5 models were selected for the automatic summarization. The quantitative metrics of the best T5 models were as follows: ROUGE-1 = 57.75 ± 30.99, ROUGE-2 = 49.96 ± 35.36, and ROUGE-L = 54.07 ± 32.48 in MIMIC-CXR; ROUGE-1 = 50.00 ± 29.24, ROUGE-2 = 39.66 ± 30.21, and ROUGE-L = 47.87 ± 29.44 in JMID. The radiologists’ evaluations revealed that 86% (86/100) and 85% (85/100) of the texts automatically summarized from MIMIC-CXR and JMID, respectively, were clinically useful. The T5 models constructed in this study were capable of automatic summarization of radiology reports. The radiologists’ evaluations revealed that most of the automatically summarized texts were clinically valuable.
Acute intermittent hypoxia in people living with chronic stroke – a preliminary study to examine safety and efficacy as a neurorehabilitation intervention
Authors: Pearcey Gregory EP , Barry Alexander J , Sandhu Milap S , Carroll Timothy , Roth Elliot J , Rymer W Zev 
Published: December 2023

ABSTRACTBackground and PurposeAcute intermittent hypoxia (AIH) is a novel therapeutic intervention that has the potential to facilitate recovery of function, but its safety and efficacy have not been tested in people with stroke. The purpose here was to examine whether AIH is safe and effective in people with stroke.MethodsParticipants (n=10) with a unilateral, ischemic, hemispheric stroke were assessed before and following 4 sessions of AIH. Clinical tests and upper limb strength were assessed before, ∼15-30 minutes, and ∼60 minutes after the intervention.ResultsAIH was well-tolerated and there were no adverse events observed. Although no changes in strength were detected for the less-affected limb, grip strength and elbow flexion force of the more-affected limb was increased after AIH.ConclusionsAIH appears to be potentially safe and effective for improving strength in the more-affected limb in people with stroke. Future work should explore the use of AIH to enhance task-specific training-induced plasticity.
Connecting the Dots: Systematic Exploration of COVID-19 and Acute Kidney Injury through Meta-Analysis
Authors: Sarker Md. Safiullah , Jahan Rubiyat 
Published: December 2023

AbstractObjectiveCOVID-19 pandemic is a danger for the whole world. Also, our knowledge about acute kidney injury (AKI) in COVID-19 patients is incomplete. Few studies informed that the problem of AKI is a common complication, but other studies concluded that AKI is only an unusual event during COVID-19 infection. This study using meta-analysis tools aimed to find disease progression and mortality risk in affected population.MethodsWe systematically reviewed the literature on COVID-19 and its association with AKI as per PRISMA guideline. All authors independently performed a literature search until 8th June 2023. We included studies which reported clinical characteristics, incidence of AKI, and the death risk with AKI during COVID-19 infection.FindingsWe have included five studies and all of them reported older age (73-75) and males (67-84.2%) were risk factors for patient illness. COVID-19 patients with AKI had more than five times mortality risk of those without AKI. Diagnosis time after disease onset was 8.5 days (IQR, [4–11]). Fatality time after initial hospital admission was 13.5 days (IQR, 8–17). In non-survivors, systemic inflammation with high temperature, abnormal respiratory rate, acute myocardial injury, and acute respiratory distress syndrome (ARDS) were observed. Abnormal biochemical analytes and immunological markers were observed.ConclusionOur analyses indicate that patients experienced repeated changes in biochemical analytes and immune marker with the progression of the disease. It indicates the requirement of early management and treatment. Further study is required to conclude and to have better knowledge of AKI mechanism with COVID-19 infection.
A female-biased gene expression signature of dominance in cooperatively breeding meerkats
Authors: Ryan Campbell C. , Manser Marta , Shiratori Mari , Williams Kelly , Barreiro Luis , Clutton-Brock Tim , Tung Jenny 
Published: December 2023

AbstractDominance is a primary determinant of social dynamics and resource access in social animals. Recent studies show that dominance is also reflected in the gene regulatory profiles of peripheral immune cells. However, the strength and direction of this relationship differs across the species and sex combinations investigated, potentially due to variation in the predictors and energetic consequences of dominant status. To test this possibility, we investigated the association between social status and gene expression in the blood of wild meerkats (Suricata suricatta; n=113 unique individuals), including in response to lipopolysaccharide, Gardiquimod, and glucocorticoid stimulation. Meerkats are cooperatively breeding social carnivores in which breeding females physically outcompete other females to suppress reproduction, resulting in high reproductive skew. They therefore present an opportunity to disentangle the effects of social dominance from those of sexper se. We identify a sex-specific signature of dominance, including 1,045 differentially expressed genes in females but none in males. Dominant females exhibit elevated activity in innate immune pathways and an exacerbated response to LPS challenge. In this respect, female meerkats resemble wild male baboons (for which similar data are available), where physical competition is also central to determining rank hierarchies and mating effort is high. However, they differ from female primates in which social status is nepotistically determined. Our results support the hypothesis that the gene regulatory signature of social status depends on the determinants and energetic costs of social dominance. They also support potential life history trade-offs between investment in reproduction versus somatic maintenance.
Semantical and Geometrical Protein Encoding Toward Enhanced Bioactivity and Thermostability
Authors: Tan Yang , Zhou Bingxin , Zheng Lirong , Fan Guisheng , Hong Liang 
Published: December 2023

AbstractProtein engineering is a pivotal aspect of synthetic biology, involving the modification of amino acids within existing protein sequences to achieve novel or enhanced functionalities and physical properties. Accurate prediction of protein variant effects requires a thorough understanding of protein sequence, structure, and function. Deep learning methods have demonstrated remarkable performance in guiding protein modification for improved functionality. However, existing approaches predominantly rely on protein sequences, which face challenges in efficiently encoding the geometric aspects of amino acids’ local environment and often fall short in capturing crucial details related to protein folding stability, internal molecular interactions, and bio-functions. Furthermore, there lacks a fundamental evaluation for developed methods in predicting protein thermostability, although it is a key physical property that is frequently investigated in practice. To address these challenges, this paper introduces a novel pre-training framework that integrates sequential and geometric encoders for protein primary and tertiary structures. This framework guides mutation directions toward desired traits by simulating natural selection on wild-type proteins and evaluates variant effects based on their fitness to perform specific functions. We assess the proposed approach using three benchmarks comprising over 300 deep mutational scanning assays. The prediction results showcase exceptional performance across extensive experiments when compared to other zero-shot learning methods, all while maintaining a minimal cost in terms of trainable parameters. This study not only proposes an effective framework for more accurate and comprehensive predictions to facilitate efficient protein engineering, but also enhances thein silicoassessment system for future deep learning models to better align with empirical requirements. The PyTorch implementation are available athttps://github.com/tyang816/ProtSSN.
Conservation assessment of human splice site annotation based on a 470-genome alignment
Authors: Minkin Ilia , Salzberg Steven L. 
Published: December 2023

AbstractDespite many improvements over the years, the annotation of the human genome remains imperfect. The use of evolutionarily conserved sequences provides a strategy for selecting a high-confidence subset of the annotation. Using the latest whole genome alignment, we found that splice sites from protein-coding genes in the high-quality MANE annotation are consistently conserved across more than 350 species. We also studied splice sites from the RefSeq, GENCODE, and CHESS databases not present in MANE. In addition, we analyzed the completeness of the alignment with respect to the human genome annotations and described a method that would allow us to fix up to 50of the protein-coding exons. We trained a logistic regression classifier to distinguish between the conservation exhibited by sites from MANE versus sites chosen randomly from neutrally evolving sequences. We found that splice sites classified by our model as well-supported have lower SNP rates and better transcriptomic support. We then computed a subset of transcripts using only “well-supported” splice sites or ones from MANE. This subset is enriched in high-confidence transcripts of the major gene catalogs that appear to be under purifying selection and are more likely to be correct and functionally relevant.Graphical abstract
Adaptive stretching of representations across brain regions and deep learning model layers
Authors: Zhang Xin-Ya , Bobadilla-Suarez Sebastian , Luo Xiaoliang , Lemonari Marilena , Brincat Scott L. , Siegel Markus , Miller Earl K. , Love Bradley C. 
Published: December 2023

AbstractPrefrontal cortex (PFC) is known to modulate the visual system to favor goal-relevant information by accentuating task-relevant stimulus dimensions. Does the brain broadly re-configures itself to optimize performance by stretching visual representations along task-relevant dimensions? We considered a task that required monkeys to selectively attend on a trial-by-trial basis to one of two dimensions (color or motion direction) to make a decision. Except for V4 (color bound) and MT (motion bound), the brain radically re-configured itself to stretch representations along task-relevant dimensions in lateral PFC, frontal eye fields (FEF), lateral intraparietal cortex (LIP), and inferotemporal cortex (IT). Spike timing was crucial to this code. A deep learning model was trained on the same visual input and rewards as the monkeys. Despite lacking an explicit selective attention or other control mechanism, the model displayed task-relevant stretching as a consequence of error minimization, indicating that stretching is an adaptive strategy.
Complex sporulation-specific expression of transcription termination factor Rho highlights its involvement inBacillus subtiliscell differentiation
Authors: Bidnenko Vladimir , Chastanet Arnaud , Péchoux Christine , Redko-Hamel Yulia , Pellegrini Olivier , Durand Sylvain , Condon Ciarán , Boudvillain Marc , Jules Matthieu , Bidnenko Elena 
Published: December 2023

AbstractTranscription termination factor Rho controls pervasive, mainly antisense, transcription initiated at cryptic signals or resulting from read-through at weak terminators in various bacterial species. InBacillus subtilis, Rho is intricately involved in the regulation of phenomena associated with the adaptation to stationary phase and cell differentiation including the ultimate survival program of sporulation.While knockout or overexpression of therhogene alters global transcription and modifies cell physiology, in wild-typeB. subtiliscells, the reduction of Rho levels during the transition to stationary phase is necessary for both initiation and implementation of the sporulation program. However, the mechanisms that govern Rho expression throughout the cell cycle remain largely unknown.Here, we demonstrate that, besides the previously identified vegetative SigA-dependent promoter active during exponential growth, two distinct mechanisms ensure a spatiotemporal expression of therhogene during sporulation. In the mother cell of the sporangium,rhoexpression occurs through the read-through transcription initiated at the distal SigH-dependent and Spo0A∼P-regulated promoter of thespo0Fgene. In the forespore,rhois transcribed from a genuine promoter recognized by the alternative sigma factor SigF. These regulatory elements compensate for the inactivation of SigA-dependentrhoexpression at the end of exponential growth and allow the critical “refueling” of Rho protein in both compartments of the sporangium. We show that alteringrhoexpression in the mother cell or in the forespore affects differently the properties and the morphology of mature spores. Moreover, spores formed in the absence of Rho are impaired in their ability to revive under favorable growth conditions, exhibiting accelerated germination and slow outgrowth. Finally, we show that optimal outgrowth of the wild-type spores requires the expression ofrhoduring spore maturation and additionally after spore germination.
TheWinglessPlanar Cell Polarity pathway is essential for optimal activity-dependent synaptic plasticity
Authors: Dominicci-Cotto Carihann , Vazquez Mariam , Marie Bruno 
Published: December 2023

AbstractFrom fly to man, the Wingless (Wg) / Wnt signaling molecule is essential for both the stability and plasticity of the nervous system. TheDrosophilaneuromuscular junction(NMJ) has proven to be a useful system for deciphering the role of Wg in directing activity-dependent synaptic plasticity, which, in the motoneuron, has been shown to be dependent on both the canonical and the noncanonical calcium Wg pathways. Here we show that the noncanonical planar cell polarity (PCP) pathway is an essential component of the Wg signaling system controlling plasticity at the motoneuron synapse. We present evidence that disturbing the PCP pathway leads to a perturbation in activity-dependent synaptic plasticity (ADSP). We first show that a PCP-specific allele ofdishevelled(dsh) affects thede novosynaptic structures produced during ADSP. We then show that the Rho GTPases downstream of Dsh in the PCP pathway are also involved in regulating the morphological changes that take place after repeated stimulation. Finally, we show that Jun kinase is essential for this phenomenon, whereas we found no indication of the involvement of the transcription factor complex AP1 (Jun/Fos). This work shows the involvement of the neuronal PCP signaling pathway in supporting ADSP. Because we find that AP1 mutants can perform ADSP adequately, we hypothesize that, upon Wg activation, the Rho GTPases and Jun kinase are involved locally at the synapse, in instructing cytoskeletal dynamics responsible for the appearance of the morphological changes occurring during ADSP.