bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-modal profiling identifies CD4+CXCR5+PD-1- Tfh cells as prognostic and predictive biomarkers for response to R-CHOP therapy in human DLBCL
Authors: Yu Sisi , Kong Hao , Luo Huaichao , Zhao Xingzhong , Zhu Guanghui , Feng Xiuqin , Yang Jie , Wu Xiangji , Dai Yu , Wu Chunwei , Wang James Q. , Cao Dan , Xu Yang , Jiang Hong , Wang Ping 
Published: October 2024

SummaryDespite the improvements in clinical outcomes for patients with Diffuse Large B-Cell Lymphoma (DLBCL), a significant proportion of those patients still face challenges with refractory/relapsed (R/R) disease after receiving first-line R-CHOP treatment. Characterizing the heterogeneity of the tumor microenvironment (TME) in diffuse large B cell lymphoma (DLBCL) is crucial for understanding relapsed/refractory disease. However, the complex and diverse nature of the TME has impeded progress. Here, using single-cell RNA sequencing(scRNA-seq), we explored the DLBCL landscape at single-cell resolution, profiling 77,344 cells from both primary and relapsed DLBCL patients. We further investigated the shared and distinct molecular and cellular features of tumor microenvironment in both primary and relapsed DLBCL tumors by integrating next-generation DNA sequencing data and multiple scRNA-seq datasets from total 72,351 cells. Our results demonstrated that there was a significant decrease of CD4+CXCR5+PD-1- Tfh cells, along with excessive activation of the TNF-NFκB signaling pathways in malignant B cells in R/R disease. Furthermore, by using multiplex IHC, we confirmed that CD4+CXCR5+PD-1- Tfh cells are prognostic and predictive biomarkers for response to R-CHOP treatment. As a proof of concept, we successfully generated mutilplexed images of CD4+CXCR5+PD-1- Tfh cells from a single DAPI staining in human DLBCL tissues through using generative artificial intelligence. Our study offers critical insights into the heterogeneity and molecular features of DLBCL, shedding light on the crucial role of CD4+CXCR5+PD-1- Tfh cells in the recurrent process.HighlightsShared and distinct molecular and cellular features of tumor microenvironment in both primary and relapsed DLBCL tumors;The characteristic of relapsed DLBCL TME is a dysfunctional immune microenvironment with a significant decrease of CD4+CXCR5+PD-1- Tfh cells.CD4+CXCR5+PD-1- Tfh cells are prognostic and predictive biomarkers for response to R-CHOP treatmentDetermination of CD4+CXCR5+PD-1- Tfh cells in human DLBCL tissues through using generative artificial intelligence.
Testing for age- and sex- specific mitonuclear epistasis inDrosophila
Authors: Garlovsky Martin D. , Dobler Ralph , Guo Ruijian , Voigt Susanne , Dowling Damian K. , Reinhardt Klaus 
Published: October 2024

ABSTRACTThe need for efficient ATP production is predicted to result in the evolution of cooperation between the mitochondrial and nuclear encoded components of the electron transport system. Novel (i.e., mismatched) mitonuclear genotype combinations are therefore predicted to result in negative fitness consequences, which may become more prevalent with ageing. Such negative fitness effects are expected to be prominent in males, since maternal inheritance of mitochondria is predicted to lead to accumulation of male-harming mutations (the mother’s curse hypothesis). To test these predictions, we measured female and male fertility traits using a genetically diverse panel of 27 mitonuclear populations ofDrosophila melanogasterwith matched or experimentally mismatched mitonuclear genomes at different ages. We found no overall effect of mitonuclear mismatch. In females, we found no effect of mitonuclear epistasis. In males, we found limited evidence of mitonuclear epistasis affecting fitness in old age, however, not in the direction predicted. Experimentally mismatched males sired more offspring in one comparison. Sex-specific advantages of mismatched males might arise if novel nuclear alleles compensate for deleterious mitochondrial alleles that have accumulated. If such compensatory effects of novel mitonuclear combinations increasing fitness occur in nature, they could represent a possible counterforce to the mother’s curse.
WITHDRAWN: A comparative analysis of salt stress adaptiveness between two flax (Linum usitatissimumL.) genotypes, Flanders and Astella, having contrasting lignan contents
Authors: Debnath Anirban Jyoti , Harenčár Ľubomír , Kučka Matúš , Kovár Marek , Ivanišová Eva , Mistríková Veronika , Gažo Ján , Ražná Katarína 
Published: October 2024

WITHDRAWAL STATEMENTThe authors have withdrawn their manuscript because of the necessary revisions to the manuscript that may reorient the study findings. Its publication will be possible only after the peer review process in a scientific journal. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author
Benchmarking Cell Type Annotation by Large Language Models with AnnDictionary
Authors: Crowley George ,   Tabula Sapiens Consortium, Quake Stephen R. 
Published: October 2024

AbstractWe developed an open-source package called AnnDictionary (https://github.com/ggit12/anndictionary/) to facilitate the parallel, independent analysis of multiple anndata. AnnDictionary is built on top of LangChain and Scanpy and supports all common large language model (LLM) providers. AnnDictionary only requires 1 line of code to configure or switch the LLM backend and it contains numerous multithreading optimizations to support the analysis of many anndata and large anndata. We used AnnDictionary to benchmark all major LLMs at de novo cell-type annotation in Tabula Sapiens. We found that cell type annotation with AnnDictionary outperformed previous annotation with the same LLM by ∼20% (58% vs 77%), and with other LLMs by ∼25%. LLMs varied greatly in absolute agreement with manual annotation based on model size. Inter-LLM agreement also varied with model size. We find that LLM annotation of most major cell types to be more than 80-90% accurate, and will maintain a leaderboard of LLM cell type annotation athttps://singlecellgpt.com/celltype-annotation-leaderboard.
Do flowers with specialized morphologies produce more nectar and pollen?
Authors: Keasar Tamar , Bodner Levona 
Published: October 2024

ABSTRACTPremise of the studyFlower morphology influences the wiring of plant-pollinator interaction networks. Flowers with deep corolla tubes and bilateral symmetry have a narrower pollinator range, hence are considered more specialized than shallow radial flowers. Past inter-specific comparisons revealed positive correlations between flower depth and nectar production rates in a few plant communities, suggesting that specialized flowers may allocate more resources into food rewards for pollinators.MethodsTo evaluate this hypothesis, we compiled a global dataset of flower morphology vs. nectar sugar production rates (n = 494 plant species) and per-flower pollen counts (n = 164 species). We applied phylogenetically controlled mixed models to examine the effects of symmetry and tube length on floral rewards.Key resultsCorolla tube lengths, symmetry type and their interaction significantly predicted nectar production rates, with the larger effect attributed to tube length. Neither tube length nor symmetry predicted pollen number. Both nectar and pollen production were affected by phylogeny in a larger dataset that included 854 nectar-producing and 1040 pollen-producing species. Plant genus explained more of the variation in nectar production, and less of the variation in pollen production, than plant family.ConclusionsOur findings suggest that visual signals associated with specialized flowers honestly advertise nectar production, but not pollen rewards. Other visual and chemical family-specific floral displays potentially advertise pollen availability to pollinators. We propose experiments to test whether nectar foragers indeed use flower depth as a visual signal that guides their choices of nectar sources.
Identifying potential dopamine receptor D2 antagonist from Rauwolfia serpentina – An in-silico virtual screening approach
Authors: Chakraborty Souvik , Bhowmick Sushmita , Maiti Tarasankar 
Published: October 2024

AbstractBackgroundTo combat the alarming rise of neuropsychiatric diseases like Schizophrenia, new drugs with fewer side effects have to be identified and characterized for the symptomatic treatment of Scz. Positive symptoms associated with Scz are hallucinations and delusions mainly due to the overactivation of the D2 dopaminergic receptors in the cortical pathways. D2 receptor antagonists identified fromRauwolfia serpentinaare employed for controlling positive symptoms.Materials and methodsThe IMPPAT database was used to identify phytoconstituents from the root ofRauwolfia serpentinathat can be used for antagonizing D2 dopaminergic receptor. 39 compounds were identified and SDF files were obtained from the PubChem database molecular docking with the modelled dopamine D2 receptor was used as a virtual screening tool followed by ADMET screening of the potential lead compound.ResultsAfter docking analysis, 11 compounds having binding affinity ≥ -9 kcal/mol were shortlisted for ADMET analysis. After analysis, 4 compounds (1,2-dihydrovomilenine, Corynanthine, Rauwolscine, and Yohimbine) were identified as potential leads. Among these 4 compounds, 1,2-dihydrovomelenine has been identified as the lead compound.ConclusionThe present study identified a potential new therapeutic compound that can be used for controlling the positive symptoms of Scz patients in vitro as well as in vivo.
Dual-Approach Co-expression Analysis Framework (D-CAF) Enables Identification of Novel Circadian Regulation From Multi-Omic Timeseries Data
Authors: Chuah Joshua , Cordi Carmalena , Hahn Juergen , Hurley Jennifer 
Published: October 2024

AbstractThe circadian clock is a central driver of many biological and behavioral processes, regulating the levels of many genes and proteins, termed clock controlled genes and proteins (CCGs/CCPs), to impart biological timing at the molecular level. While transcriptomic and proteomic data has been analyzed to find potential CCGs and CCPs, multi-omic modeling of circadian data, which has the potential to enhance the understanding of circadian control of biological timing, remains relatively rare due to several methodological hurdles. To address this gap, a Dual-approach Co-expression Analysis Framework (D-CAF) was created to perform perturbation-robust co-expression analysis on time-series measurements of both transcripts and proteins. Applying this D-CAF framework to previously gathered transcriptomic and proteomic data from mouse macrophages gathered over circadian time, we identified small, highly significant clusters of oscillating transcripts and proteins in the unweighted similarity matrices and larger, less significant clusters of of oscillating transcripts and proteins using the weighted similarity network. Functional enrichment analysis of these clusters identified novel immunological response pathways that appear to be under circadian control. Overall, our findings suggest that D-CAF is a tool that can be used by the circadian community to integrate multi-omic circadian data to improve our understanding of the mechanisms of circadian regulation of molecular processes.
Population genomics reveals strong impacts of genetic drift without purging and guides conservation of bull and giant kelp
Authors: Bemmels Jordan B. , Starko Samuel , Weigel Brooke L. , Hirabayashi Kaede , Pinch Alex , Elphinstone Cassandra , Dethier Megan N. , Rieseberg Loren H. , Page Jonathan E. , Neufeld Christopher J. , Owens Gregory L. 
Published: October 2024

SummaryKelp forests are declining in many parts of the northeast Pacific1–4. In small populations, genetic drift can reduce adaptive variation and increase fixation of recessive deleterious alleles5–7, but natural selection may purge harmful variants8–10. To understand evolutionary dynamics and inform restoration strategies, we investigated genetic structure and the outcomes of genetic drift and purging by sequencing the genomes of 429 bull kelp (Nereocystis luetkeana) and 211 giant kelp (Macrocystis pyriferasensu lato11; cf.12) from the coastlines of British Columbia and Washington. We identified 6-7 geographically and genetically distinct clusters in each species. Low effective population size was associated with low genetic diversity and high inbreeding coefficients (including increased selfing rates), with extreme variation in these genetic health indices among bull kelp populations but more moderate variation in giant kelp. We found no evidence that natural selection is purging putative recessive deleterious alleles in either species. Instead, genetic drift has fixed many such alleles in small populations of bull kelp, leading us to predict (1) reduced within-population inbreeding depression in small populations, which may be associated with an observed shift toward increased selfing rate, and (2) hybrid vigour in crosses between small populations. Our genomic findings imply several strategies for optimal sourcing and crossing of populations for restoration and aquaculture, but which require experimental validation. Overall, our work reveals strong genetic structure and suggests that conservation strategies should consider the multiple health risks faced by small populations whose evolutionary dynamics are dominated by genetic drift.
Biodiversity forecasting in natural plankton communities reveals temperature and biotic interactions as key predictors
Authors: Merz Ewa , Pomati Francesco , Saavedra Serguei , Gilarranz Luis J. 
Published: October 2024

SummaryAs natural ecosystems experience unprecedented human-made degradation, it is urgent to deliver quantitative anticipatory forecasts of biodiversity change and identify relevant biotic and abiotic predictors. Forecasting natural ecosystems has been challenging due to their complexity, chaotic nonlinear nature and the availability of adequate data. Here, we use four years of daily abundance of a complex lake planktonic ecosystem and its abiotic environment to model and forecast biodiversity metrics. Using a state-of-the-art equation-free modelling technique, we forecast community richness and turnover with a proficiency greater than the constant predictor several generations ahead (30 days). Short-term forecasts improve substantially using biotic predictors (i.e., autoregressive term or community richness). Long-term forecasts require a more complex set of variables (i.e., biotic interactions), and the forecast proficiency depends strongly on including abiotic predictors such as water temperature. Depending on the forecast horizon, biotic and abiotic predictors can interact nonlinearly and synergistically, enhancing each other’s effects on biodiversity metrics. Our findings showcase the challenges of forecasting biodiversity in natural ecosystems and stress the importance of monitoring focal biotic and abiotic predictors to anticipate undesired changes.
MicrobiomeKG: Bridging Microbiome Research and Host Health Through Knowledge Graphs
Authors: Goetz Skye L. , Glen Amy K. , Glusman Gwênlyn 
Published: October 2024

AbstractThe microbiome represents a complex community of trillions of microorganisms residing in various body parts, and plays critical roles in maintaining host health and well-being. Understanding the interactions between microbiota and host offers valuable insights into potential strategies to promote health, including microbiome-targeted interventions. We have created MicrobiomeKG, a Knowledge Graph for microbiome research, bridging various taxa and microbial pathways with host health. This novel knowledge graph derives algorithmically-generated knowledge assertions from the supplemental tables supporting published microbiome papers, and is deployed for integrative analysis and hypothesis generation via the Biomedical Data Translator ecosystem.
Gamma Knife Stereotactic radiotherapy combined with tislelizumab as later-line therapy in pMMR/MSS/MSI-L metastatic colorectal cancer: A Phase II Trial Analysis
Authors: Zhang Yiran , Guan Hanyang , Liu Shijin , Li Haoquan , Bian Zili , He Jiashuai , Zhao Zhan , Qiu Shenghui , Mo Tianmu , Zhang Xiangwei , Chen Zuyang , Ding Hui , Zhao Xiaoxu , Wang Liang , Pan Yunlong , Pan Jinghua 
Published: October 2024

AbstractAn immunosuppressive tumor microenvironment limits the efficacy of immunotherapy, thus patients with MSS and pMMR mCRC often face great challenges.In this phase II trial, patients received Gamma Knife SBRT combined with Tislelizumab. P Biomarker analysis was performed pre- and post-treatment. From November 2022 to July 2024, 13 of 20 patients achieved PR, 6 achieved SD. mPFS was 10.7 months (95% CI, 6.4-15.0). With no grade 4 events noted, common adverse events included nausea (65%), anemia (55%), and fatigue (45%). For patients who had not responded to first and second-line therapies, the combo of Gamma Knife SBRT and tislelizumab showed high efficacy and reasonable safety. Significant post-radiotherapy improvements in the tumor’s immunosuppressive microenvironment. These results imply that patients with pMMR/MSS/MSI-L mCRC who were unresponsive to the first and second-line chemotherapy, Gamma Knife SBRT with tislelizumab provides a safe and powerful later-line treatment alternative.Statement of significanceThis study offers a safe and powerful option for pMMR/MSS/MSI-L mCRC patients fail to first and second-line chemotherapy. And discover Gamma Knife SBRT contributed to potentially converting the suppressive “cold” tumor immune microenvironment into an activated “hot” microenvironment conducive to immunotherapy efficacy in pMMR CRC.
Early establishment and life course stability of sex biases in the human brain transcriptome
Authors: Benoit-Pilven Clara , Asteljoki Juho V. , Leinonen Jaakko , Karjalainen Juha , Daly Mark J. , Tukiainen Taru 
Published: October 2024

AbstractTo elaborate on the origins of the established male-female differences in several brain-related phenotypes, we assessed the patterns of transcriptomic sex biases in the developing and adult human forebrain. We find an abundance of sex differences in expression (sex-DE) in the prenatal brain, driven by both hormonal and sex-chromosomal factors, and considerable consistency in the sex effects between the developing and adult brain, with little sex-DE exclusive to the adult forebrain. Sex-DE was not enriched in genes associated with brain disorder, consistent with systematic differences in the characteristics of these genes (e.g. constraint). Yet, the genes with persistent sex-DE across lifespan were overrepresented in disease gene co-regulation networks, pointing to their potential to mediate sex biases in brain phenotypes. Altogether, our work highlights the prenatal development as a crucial timepoint for the establishment of brain sex differences.
Colorimetric detection methods of pH-sensing wound dressing for point-of-care wound diagnostics
Authors: Cherifi Katia , Toupchinejad Farnoush , Christodoulopoulos Katerina , Kizilkaya Aylin , Matoori Simon 
Published: October 2024

AbstractChronic lower extremity wounds like diabetic foot ulcers (DFUs) are a major complication of diabetes and the leading cause of lower limb amputations worldwide. Currently, DFUs are diagnosed through macroscopic evaluation, and molecular diagnostics are lacking for the disease staging, treatment selection, and evaluation of treatment success. There is a need for new diagnostic technologies combined with detection methods for point-of-care use. Preclinical and clinical data support the importance of wound pH as a biomarker in chronic wound healing, with DFUs typically exhibiting more alkaline pH values when compared to normal healing wounds. In a previous study, we developed a pH-sensing fluorescent bandage based on pyranine-loaded microparticles that were physically immobilized in an alginate hydrogel. Here, we present a second-generation pH-sensing bandage for colorimetric wound diagnostics. Pyranine was adsorbed at high concentrations onto microparticles to enable colorimetric signal detection. This approach leverages pyranine’s ability to change color in response to pH variations through proton exchange properties with the wound fluid. The colorimetric properties of our bandage enable signal detection by two methods suited for point-of-care use: a smartphone camera and a cost-effective homebuilt RGB detector. Analyzing the color intensity of the bandage with Red, Green and Blue absorbance values, it is possible to correlate the RGB absorbance to a pH value in the clinically-relevant range to 6.0 to 9.0in vitroandex vivo, as the B values decreased with the increase in pH levels, as associated with DFUs. These findings indicate the potential of colorimetric detection using smartphone cameras or home-built absorbance detectors for rapid wound diagnostics at the point-of-care.Graphical AbstractA pH-sensing bandage enables colorimetric detection of chronic wounds. The bandage absorbs wound exudate, triggering proton exchange with dye-loaded microparticles in an alginate matrix. Chronic wounds with high pH values induce strong fluorescence and yellow coloration. The signal is quantified through RGB colorimetry analysis using a smartphone camera or a homebuilt RGB detector, enabling point-of-care diagnostics for chronic wounds.
High-Resolution Genome-Wide Maps Reveal Widespread Presence of Torsional Insulation
Authors: Hall Porter M. , Mayse Lauren A. , Bai Lu , Smolka Marcus B. , Pugh B. Franklin , Wang Michelle D. 
Published: October 2024

AbstractTorsional stress in chromatin plays a fundamental role in cellular functions, influencing key processes such as transcription, replication, and chromatin organization. Transcription and other processes may generate and be regulated by torsional stress. In the genome, the interplay of these processes creates complicated patterns of both positive (+) and negative (-) torsion. However, a challenge in generating an accurate torsion map is determining the zero-torsion baseline signal, which is conflated with chromatin accessibility. Here, we introduce a high-resolution method based on the intercalator trimethylpsoralen (TMP) to address this challenge. We describe a method to establish the zero-torsion baseline while preserving the chromatin state of the genome ofS. cerevisiae. This approach enables both high-resolution mapping of accessibility and torsional stress in chromatin in the cell. Our analysis shows transcription-generated torsional domains consistent with the twin-supercoiled-domain model of transcription and suggests a role for torsional stress in recruiting topoisomerases and in regulating 3D genome architecture via cohesin. Significantly, we reveal that insulator sequence-specific transcription factors decouple torsion between divergent promoters, whereas torsion spreads between divergent promoters lacking these factors, suggesting that torsion serves as a regulatory mechanism in these regions. Although insulators are known to decouple gene expression, our finding provides a physical explanation of how such decoupling may occur. This new method provides a potential path forward for using TMP to measure torsional stress in the genome without the confounding contribution of accessibility in chromatin.