bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intestelligence: A pharmacological neural network using intestine data
Authors: Watanabe Yusuke , Ban Hiroshi , Hagura Nobuhiro , Ikegaya Yuji 
Published: April 2023

AbstractA neural network is a machine learning algorithm that can learn and make predictions by adjusting the strength of the connections between nodes. The sigmoid function is commonly used as an activation function in these nodes. This study explores the potential applicability of biological materials in the development of alternative activation functions. Inspired by the fact that acetylcholine induces intestinal contractions that follow a sigmoid function, we used pharmacological data obtained from guinea pig ilea in a layered neural network for image classification tasks. We found that the intestinal data-based neural network with the same structure as a conventional three-layer perceptron achieved an impressive classification accuracy of 85.7% ± 0.6% based on the MNIST handwritten digit dataset (chance = 10%). Additionally, the neural network was trained to determine whether objects in photographs collected from the internet were digestible, achieving an accuracy of 88.5% ± 0.9% (chance = 50%). Our approach highlights the potential applicability of intestine data in neural computations based on pharmacological mechanisms.
Neoadjuvant systemic oncolytic vesicular stomatitis virus is safe and may enhance long-term survivorship in dogs with naturally occurring osteosarcoma
Authors: Makielski Kelly M. , Sarver Aaron L. , Henson Michael S. , Stuebner Kathleen M. , Borgatti Antonella , Suksanpaisan Lukkana , Preusser Caitlin , Tabaran Alexandru-Flaviu , Cornax Ingrid , O’Sullivan M. Gerard , Chehadeh Andrea , Groschen Donna , Bergsrud Kelly , Pracht Sara , Winter Amber , Mills Lauren J. , Schwabenlander Marc D. , Wolfe Melissa , Farrar Michael A. , Cutter Gary R. , Koopmeiners Joseph S. , Russell Stephen J. , Modiano Jaime F. , Naik Shruthi 
Published: April 2023

AbstractOsteosarcoma is a devastating bone cancer that disproportionally afflicts children, adolescents, and young adults. Standard therapy includes surgical tumor resection combined with multiagent chemotherapy, but many patients still suffer from metastatic disease progression. Neoadjuvant systemic oncolytic virus (OV) therapy has the potential to improve clinical outcomes by targeting primary and metastatic tumor sites and inducing durable antitumor immune responses. Here we described the first evaluation of neoadjuvant systemic therapy with a clinical-stage recombinant oncolytic Vesicular stomatitis virus (VSV), VSV-IFNβ-NIS, in naturally occurring cancer, specifically appendicular osteosarcoma in companion dogs. Canine osteosarcoma has a similar natural disease history as its human counterpart. VSV-IFNβ-NIS was administered prior to standard of care surgical resection, permitting microscopic and genomic analysis of tumors. Treatment was well-tolerated and a “tail” of long-term survivors (∼35%) was apparent in the VSV-treated group, a greater proportion than observed in two contemporary control cohorts. An increase in tumor inflammation was observed in VSV-treated tumors and RNAseq analysis showed that all the long-term responders had increased expression of a T-cell anchored immune gene cluster. We conclude that neoadjuvant VSV-IFNβ-NIS is safe and may increase long-term survivorship in dogs with naturally occurring osteosarcoma, particularly those that exhibit pre-existing antitumor immunity.
Neurodevelopmental disorders and cancer networks share pathways; but differ in mechanisms, signaling strength, and outcome
Authors: Yavuz Bengi Ruken , Arici M Kaan , Demirel Habibe Cansu , Tsai Chung-Jung , Jang Hyunbum , Nussinov Ruth , Tuncbag Nurcan 
Published: April 2023

AbstractNeurodevelopmental disorders (NDDs) and cancer are connected, with immunity as their common factor. Their clinical presentations differ; however, individuals with NDDs are more likely to acquire cancer. Schizophrenia patients have ∼50% increased risk; autistic individuals also face an increased cancer likelihood. NDDs are associated with specific brain cell types at specific locations, emerging at certain developmental time windows during brain evolution. Their related mutations are germline; cancer mutations are sporadic, emerging during life. At the same time, NDDs and cancer share proteins, pathways, and mutations. Here we ask exactly which features they share, and how despite their commonality, they differ in outcomes. Our pioneering bioinformatics exploration of the mutations, reconstructed disease-specific networks, pathways, and transcriptome profiles of autism spectrum disorder (ASD) and cancers, points to elevated signal strength in pathways related to proliferation in cancer, and differentiation in ASD. Signaling strength, not the activating mutation, is the key factor in deciding cancer versus NDDs.
A Machine Learning-optimized system for on demand, pulsatile, photo- and chemo-therapeutic treatment using near-infrared responsive MoS2-based microparticles in a breast cancer model
Authors: Kanelli Maria , Bardhan Neelkanth M. , Sarmadi Morteza , Alsaiari Shahad , Rothwell William T. , Pardeshi Apurva , De Fiesta Dominique C. , Mak Howard , Spanoudaki Virginia , Henning Nicole , Han Jooli , Belcher Angela M. , Langer Robert S. , Jaklenec Ana 
Published: April 2023

ABSTRACTCancer therapy research is of high interest because of the persistence and mortality of the disease and the side effects of traditional therapeutic methods, while often multimodal treatments are necessary based on the patient’s needs. The development of less invasive modalities for recurring treatment cycles is thus of critical significance. Herein, a light-activatable microparticle system was developed for localized, pulsatile delivery of anticancer drugs with simultaneous thermal ablation, by applying controlled ON-OFF thermal cycles using near-infrared laser irradiation. The system is composed of poly(caprolactone) microparticles of 200 μm size with incorporated molybdenum disulfide (MoS2) nanosheets as the photothermal agent and hydrophilic doxorubicin or hydrophobic violacein, as model drugs. Upon irradiation the nanosheets heat up to ≥50 °C leading to polymer matrix melting and release of the drug. MoS2nanosheets exhibit high photothermal conversion efficiency and allow for application of low power laser irradiation for the system activation. A Machine Learning algorithm was applied to acquire optimal laser operation conditions; 0.4 W/cm2laser power at 808 nm, 3-cycle irradiation, for 3 cumulative minutes. In a mouse subcutaneous model of 4T1 triple-negative breast cancer, 25 microparticles were intratumorally administered and after 3-cycle laser treatment the system conferred synergistic phototherapeutic and chemotherapeutic effect. Our on-demand, pulsatile synergistic treatment resulted in increased median survival up to 40 days post start of treatment compared to untreated mice, with complete eradication of the tumors at the primary site. Such a system could have potential for patients in need of recurring cycles of treatment on subcutaneous tumors.GRAPHICAL ABSTRACT
Information storage across a microbial community using universal RNA memory
Authors: Kalvapalle Prashant B. , Staubus August , Dysart Matthew J. , Gambill Lauren , Reyes Gamas Kiara , Chieh Lu Li , Silberg Jonathan J. , Stadler Lauren B. , Chappell James 
Published: April 2023

ABSTRACTBiological recorders can code information in DNA, but they remain challenging to apply in complex microbial communities. To program microbiome information storage, a synthetic catalytic RNA (cat-RNA) was used to write information in ribosomal RNA (rRNA) about gene transfer host range. By reading out native and modified rRNA using amplicon sequencing, we find that 140 out of 279 wastewater microbial community members from twenty taxonomic orders participate in conjugation and observe differences in information storage across amplicon sequence variants. Twenty of the variants were only observed in modified rRNA amplicons, illustrating information storage sensitivity. This autonomous and reversible RNA-addressable memory (RAM) will enable biosurveillance and microbiome engineering across diverse ecological settings and studies of environmental controls on gene transfer and cellular uptake of extracellular materials.One-Sentence SummaryRibosomal RNA sequencing detects cellular events recorded across a wastewater microbial community using synthetic biology.
Multidimensional responses of ecological stability to eutrophication in grasslands
Authors: Chen Qingqing , Wang Shaopeng , Borer Elizabeth T. , Bakker Jonathan D. , Seabloom Eric W. , Harpole W. Stanley , Eisenhauer Nico , Lekberg Ylva , Buckley Yvonne M. , Catford Jane A. , Roscher Christiane , Donohue Ian , Power Sally A. , Daleo Pedro , Ebeling Anne , Knops Johannes M. H. , Martina Jason P. , Eskelinen Anu , Morgan John W. , Risch Anita C. , Caldeira Maria C. , Bugalho Miguel N , Virtanen Risto , Barrio Isabel C , Niu Yujie , Jentsch Anke , Stevens Carly J. , Alberti Juan , Hautier Yann 
Published: April 2023

AbstractEutrophication usually impacts biodiversity, species composition, and functioning of grassland communities. Whether such effects propagate to influence the stability of these community aspects is unknown. Using standardized experiments across 55 global grasslands, we quantified the effects of nutrient addition on five stability facets (i.e., temporal invariability and resistance during and recovery after dry and wet growing seasons) for three community aspects (i.e., aboveground biomass, community composition, and species richness). Nutrient addition reduced the temporal invariability and resistance of species richness and community composition, but not biomass, during dry and wet growing seasons. Temporal invariability and resistance during, but not recovery after, dry and wet growing seasons were strongly positively correlated in both ambient and eutrophic conditions. This indicates that maintaining and restoring the stability of plant communities requires increasing resistance rather than recovery. Harnessing the complexity of ecological stability provides new insights for grassland ecosystem sustainability in a changing world.
Proliferative response of ERα-positive breast cancer cells to 10 μM enterolactone, and the associated alteration in the transcriptomic landscape
Authors: Hatwik Juana , Patil Hrishikesh Nitin , Limaye Anil Mukund 
Published: April 2023

AbstractEnterolactone (EL) is a product of gut-microbial metabolism of dietary plant lignans. Studies linking EL with breast cancer risk have bolstered investigations into its effects on the mammary epithelial cells, and the mechanisms thereof. While it binds to the estrogen receptor α; ERα, its effect on the proliferation of mammary tumor cell lines is reportedly ambivalent; depending on its concentration. The genomic correlates of EL actions also remain unexplored. Here we have elaborately studied the effect of EL on proliferation of ERα-positive, and ERα-negative cell lines. 10 µM EL significantly enhanced the growth of the ERα-positive MCF-7 or T47D breast cancer cells, but not the ERα-negative MDA-MB-231 or MDA-MB-453 cells. In MCF-7 cells, it significantly increased the expression ofTFF1mRNA, an estrogen-induced transcript. The binding of ERα to the estrogen response element within theTFF1locus further demonstrates the pro-estrogenic effect of 10 µM EL. We further explored the genome-wide transcriptomic effect of 10 µM EL. Analysis of RNA-seq data obtained from control- or 10 µM EL treated-MCF-7 cells revealed modulation of expression of diverse sets of functionally related genes, which reflected cell cycle progression, rather than cell cycle arrest or apoptosis. The manner in which 10 µM EL regulated the hallmark G2/M checkpoint, and estrogen-response-late genes correlated with proliferation inducing, and estrogen-like effects of EL on MCF-7 cells.
Multipotent Progenitors Instruct Ontogeny of the Superior Colliculus
Authors: Cheung Giselle , Pauler Florian M. , Koppensteiner Peter , Krausgruber Thomas , Streicher Carmen , Schrammel Martin , Gutmann-Özgen Natalie , Ivec Alexis E. , Bock Christoph , Shigemoto Ryuichi , Hippenmeyer Simon 
Published: April 2023

SUMMARYThe superior colliculus (SC) in the mammalian midbrain is essential for multisensory integration, attention, and complex behavior (Basso and May, 2017; Cang et al., 2018). The mature SC cytoarchitecture is organized into distinct laminae and composed of a rich variety of neuronal and glial cell types (Ayupe et al., 2023; Edwards et al., 1986; May, 2006; Xie et al., 2021; Zeisel et al., 2018). Precise execution of the developmental programs regulating the generation of SC cell-type diversity is essential, because deficits due to genetic mutations have been associated with neurodevelopmental diseases and SC dysfunction (Jure, 2018; McFadyen et al., 2020). However, the fundamentals directing the ontogeny of the SC are not well understood. Here we pursued systematic lineage tracing at the single progenitor cell level in order to decipher the principles instructing the generation of cell-type diversity in the SC. We combinedin silicolineage reconstruction with a novel genetic MADM (Mosaic Analysis with Double Markers)-CloneSeq approach. MADM-CloneSeq enables the unequivocal delineation of cell lineagesin situ, and cell identity based on global transcriptome, of individual clonally-related cells. Our systematic reconstructions of cell lineages revealed that all neuronal cell types in SC emerge from local progenitors without any extrinsic source. Strikingly, individual SC progenitors are exceptionally multipotent with the capacity to produce all known excitatory and inhibitory neuron types of the prospective mature SC, with individual clonal units showing no pre-defined composition. At the molecular level we identified an essential role for PTEN signaling in establishing appropriate proportions of specific inhibitory and excitatory neuron types. Collectively, our findings demonstrate that individual multipotent progenitors generate the full spectrum of excitatory and inhibitory neuron types in the developing SC, providing a novel framework for the emergence of cell-type diversity and thus the ontogeny of the mammalian SC.
SHARPIN enhances ferroptosis in synovial sarcoma cells via NF-κB- and PRMT5-mediated PGC1α reduction
Authors: Tamiya Hironari , Urushihara Naoko , Shizuma Kazuko , Ogawa Hisataka , Nakai Sho , Wakamatsu Toru , Takenaka Satoshi , Kakunaga Shigeki 
Published: April 2023

AbstractSarcoma is a rare type of cancer for which new therapeutic agents are required. Ferroptosis is a nonapoptotic cell death triggered by iron-mediated lipid peroxidation. We found that transferrin receptor 1 (TFRC), an iron uptake protein, was expressed at higher levels in sarcoma cell lines than in noncancer and carcinoma cell lines. Glutathione peroxidase 4 (GPX4) protects cells against ferroptosis, and its inhibition using RAS-selective lethal 3 (RSL3) had an antitumor effect that was more pronounced in sarcoma cell lines, particularly synovial sarcoma cells, than in non-sarcoma cells. Because NF-κB can provoke ferroptosis, we examined the role of SHARPIN, an activator of NF-κB, in sarcoma. We found that SHARPIN expression is significantly associated with reduced survival in cohorts of patients with cancer, including sarcoma. In addition, SHARPIN promotes the sensitivity of sarcoma cells to ferroptosis. Further analyses revealed that the PGC1α/NRF2/SLC7A11 axis and BNIP3L/NIX-mediated mitophagy are regulated through NF-κB and PRMT5 downstream of SHARPIN. Our findings suggest that ferroptosis could have a therapeutic effect in sarcoma, particularly in subpopulations with high TFRC and SHARPIN expression.
A Hidden Proportional Feedback Mechanism Underlies Enhanced Dynamic Performance and Noise Rejection in Sensor-Based Antithetic Integral Control
Authors: Filo Maurice , Hou Mucun , Khammash M. 
Published: April 2023

AbstractEfficient regulation of cellular processes is essential for both endogenous and synthetic biological processes. The design of biomolecular feedback controllers that achieve robust and timely regulation is the subject of considerable research at the interface between synthetic biology and control theory. Integral feedback controllers, known for their ability to confer the property of Robust Perfect Adaptation (RPA), are increasingly becoming common features in biological control design. Antithetic integral feedback (AIF) controllers, in particular, have enabled effective chemical reaction realizations of integral controllers that deliver RPA in both deterministic and stochastic settings. This paved the way to experimental implementations of integral controllers in bacterial and mammalian cells. While AIF controllers deliver favorable adaptation properties, they do not necessarily lead to good transient performance or noise reduction properties and may in some cases lead to increased overshoot or cell-to-cell variability. These limitations are commonly circumvented by augmenting new circuitry that realize proportional or derivative feedback mechanisms to enhance dynamic and noise rejection features without affecting the AIF controller’s adaptation properties. In this paper, we report that a sensor-based variant of the basic AIF motif exhibits favorable transient dynamic properties and (as reported elsewhere) reduced noise variance. We show that these features are attributed to a “hidden” proportional feedback component that is inherent in the controller structure and that such mechanism is solely responsible for the controller’s underlying enhanced dynamic performance and noise rejection properties. This sensor-based AIF controller hence offers a minimal biomolecular realization of Proportional-Integral (PI) control, whereby both integral and proportional feedback mechanisms are achieved through a single actuation reaction.
Systemic inflammation modulates the levels of EBI2 and 7α,25-OHC synthesizing (CH25H, CYP7B1) and degrading (HSD3B7) enzymes in brain microvascular cells
Authors: Caratis Fionä , Karaszewski Bartosz , Klejbor Ilona , Furihata Tomomi , Rutkowska Aleksandra 
Published: April 2023

ABSTRACTThe endogenous ligand for the EBI2 receptor, oxysterol 7α,25OHC, crucial for immune responses, is finely regulated by CH25H, CYP7B1 and HSD3B7 enzymes. Lymphoid stromal cells and follicular dendritic cells within T cell follicles maintain a gradient of 7α,25OHC, with stromal cells increasing and dendritic cells decreasing its concentration. This gradient is pivotal for proper B cell positioning in lymphoid tissue. In the animal model of multiple sclerosis, the experimental autoimmune encephalomyelitis, the levels of 7α,25OHC rapidly increase in the central nervous system driving the migration of EBI2 expressing immune cells through the blood-brain barrier (BBB). To explore if blood vessel cells in the brain express these enzymes, we examined normal mouse brain microvessels and studied their expression changes during inflammation. EBI2 was abundantly expressed in endothelial cells, pericytes/smooth muscle cells, and astrocytic endfeet. CH25H, CYP7B1, and HSD3B7 were variably detected in each cell type, suggesting their active involvement in oxysterol 7α,25OHC synthesis and gradient maintenance under normal conditions. Under acute inflammatory conditions, EBI2 and synthesizing enzyme modulation occurred in brain vasculature, with variations based on the enzyme and cell type. Significant species-specific differences emerged in EBI2 and enzyme levels between mouse and human BBB-forming cells. Overall, our investigation suggest a direct role of the brain microvascular cells in regulating 7α,25OHC levels, shedding light on potential therapeutic targets for neuroinflammatory disorders.
Post COVID-19 Condition, Work Ability and Occupational Changes: Results from a Population-based Cohort
Authors: Kerksieck Philipp , Ballouz Tala , Haile Sarah R. , Schumacher Celine , Lacy Joanne , Domenghino Anja , Fehr Jan S. , Bauer Georg F. , Dressel Holger , Puhan Milo A. , Menges Dominik 
Published: April 2023

AbstractBackgroundEvidence from population-based studies on the impact of post COVID-19 condition (PCC) on ability to work is limited but critical due to its high prevalence among individuals of working-age.ObjectiveTo evaluate the association between PCC, work ability, and occupational changes.DesignPopulation-based, longitudinal cohort.SettingGeneral population, Canton of Zurich, Switzerland.Participants672 adults of working-age with SARS-CoV-2 infection.MeasurementsCurrent work ability, work ability related to physical and mental demands, and estimated future work ability in 2 years (assessed using Work Ability Index), as well as PCC-related occupational changes at one year after infection.ResultsThere was very strong evidence that current work ability scores were 0.62 (95% confidence interval (CI) 0.30 to 0.95) points lower among those with PCC compared to those without. Similarly, there was very strong evidence for lower odds of reporting higher work ability with respect to physical (odds ratio (OR) 0.30, 95% CI 0.20 to 0.46) and mental (OR 0.40, 0.27 to 0.62) demands among those with PCC compared to those without. Higher age and history of psychiatric diagnosis were associated with a more substantial reduction in current work ability. 5.8% of those with PCC reported direct effects of PCC on their occupational situation, with 1.6% of those with PCC completely dropping out of the workforce and 43% of those with PCC-related occupational changes reporting financial difficulties as a result.LimitationsSelection, use of self-reported outcome measures, and limited generalizability to individuals with most severe COVID-19 or following vaccination.ConclusionsThese findings highlight the need for providing support and interdisciplinary interventions to individuals affected by PCC to help them maintain or regain their work ability and productivity.Primary Funding SourceFederal Office of Public Health, Department of Health of the Canton of Zurich, University of Zurich Foundation, Switzerland.Study RegistrationISRCTN14990068.
Finding the right tool: a comprehensive evaluation of microglial inducible cre mouse models
Authors: Bedolla Alicia , Mckinsey Gabriel , Ware Kierra , Santander Nicolas , Arnold Thomas , Luo Yu 
Published: April 2023

SummaryThe recent proliferation of newCreandCreERrecombinase lines provides researchers with a diverse toolkit to study microglial gene function. To determine how best to apply these lines in studies of microglial gene function, a thorough and detailed comparison of their properties is needed. Here, we examined four different microglialCreERlines (Cx3cr1CreER(Litt),Cx3cr1CreER(Jung),P2ry12CreER,Tmem119CreER), focusing on (1) recombination specificity; (2) leakiness - degree of non-tamoxifen recombination in microglia and other cells; (3) efficiency of tamoxifen-induced recombination; (4) extra-neural recombination -the degree of recombination in cells outside the CNS, particularly myelo/monocyte lineages (5) off-target effects in the context of neonatal brain development. We identify important caveats and strengths for these lines which will provide broad significance for researchers interested in performing conditional gene deletion in microglia. We also provide data emphasizing the potential of these lines for injury models that result in the recruitment of splenic immune cells.