bluuebunny/crossref_metadata_2025_split huggingface dataset:
Calretinin-expressing islet cells: a source of pre- and post-synaptic inhibition of non-peptidergic nociceptor input to the mouse spinal cord
Authors: Davis Olivia C. , Dickie Allen C. , Mustapa Marami B. , Boyle Kieran A. , Browne Tyler J. , Gradwell Mark A. , Smith Kelly M. , Polgár Erika , Bell Andrew M. , Kókai Éva , Watanabe Masahiko , Wildner Hendrik , Zeilhofer Hanns Ulrich , Ginty David D. , Callister Robert J. , Graham Brett A. , Todd Andrew J. , Hughes David I. 
Published: June 2023

ABSTRACTUnmyelinated non-peptidergic nociceptors (NP afferents) arborise in lamina II of the spinal cord and receive GABAergic axoaxonic synapses, which mediate presynaptic inhibition. However, until now the source of this axoaxonic synaptic input was not known. Here we provide evidence that it originates from a population of inhibitory calretinin-expressing interneurons (iCRs), which correspond to lamina II islet cells. The NP afferents can be assigned to 3 functionally distinct classes (NP1-3). NP1 afferents have been implicated in pathological pain states, while NP2 and NP3 afferents also function as pruritoceptors. Our findings suggest that all 3 of these afferent types innervate iCRs and receive axoaxonic synapses from them, providing feedback inhibition of NP input. The iCRs also form axodendritic synapses, and their targets include cells that are themselves innervated by the NP afferents, thus allowing for feedforward inhibition. The iCRs are therefore ideally placed to control the input from non-peptidergic nociceptors and pruritoceptors to other dorsal horn neurons, and thus represent a potential therapeutic target for the treatment of chronic pain and itch.
Environmental life cycle assessment of recombinant growth factor production for cultivated meat applications
Authors: Trinidad Kirsten , Ashizawa Reina , Nikkhah Amin , Semper Cameron , Casolaro Christian , Kaplan David L. , Savchenko Alexei , Blackstone Nicole Tichenor 
Published: June 2023

AbstractGrowth factors are critical components of current serum-supplemented and serum-free media formulations for cultivated meat production. However, growth factors have been excluded, estimated using proxies, or modeled using proprietary data in existing environmental assessments of cultivated meat products. Cell culture media has been identified as a hotspot in such studies, therefore it is important to accurately quantify the environmental impacts of growth factor supplementation. To address this gap, this study applied life cycle assessment (LCA) methodology to comparatively assess the environmental impacts of recombinant growth factor production for cultivated meat applications. Life cycle inventories were developed for four recombinant growth factors (IGF-1, FGF, TGF-ß, and PDGF) produced using a novel bench- scale process. The functional unit of the product output was selected as 1 mg of produced growth factor. The results indicate that recombinant growth factors can have significant environmental impacts within cultivated meat systems, despite being used in very small quantities. For example, the global warming potential of production of 1 mg of IGF-1, FGF, TGF-ß, and PDGF was estimated to be 0.1, 0.04, 0.2 and 0.2 kg CO2eq, respectively. Future research should explore the sustainability of producing these growth factors at scale to meet the needs of the expanding cultivated meat industry or identifying alternatives to these growth factors that have a lower impact on the environment.Nomenclature
Computational Studies of Human Sodium/glucose cotransporters: (SGLT1), (SGLT2) and investigation of Human Sirtuins together with Polydatin
Authors: Ferrari Ivan Vito , De Gregorio Alex , Fuggetta Maria Pia , Ravagnan Giampietro 
Published: June 2023

AbstractFor the first time, we investigated through molecular docking analysis with Autodock Vina and Autodock 4 the Polydatin, a derivative of resveratrol, with Sodium/glucose cotransporter 2 (SGLT1) and Sodium/glucose cotransporter 2(SGLT2) and with Sirtuins proteins, reporting excellent results both in terms of binding energies scores and inhibition constant Ki. In particular, from our analyses, Polydatin appears to have an excellent energetic affinity with human SGLT2 on the one hand, and with the human Sirtuin6, even though, comparing the binding energy values with all the investigated proteins, no significant differences were found in termins of binding energies scores. An important aspect that we want to underline is that our computational analyzes, although very accurate, require investigations in Vitro, in Vivo, and clinical studies to confirm that Polydatin has a key role with SGLT2, SGLT1, and with the Sirtuin family.
Species-Specific Responses Drive Browsing Impacts on Physiological and Functional Traits inQuercus agrifoliaandUmbellularia californica
Authors: Leonard Hugh E. , Ciambrone Mary , Pittermann Jarmila 
Published: June 2023

AbstractHerbivory is a fundamental ecological force in the evolution of plant physiological, morphological, and chemical attributes. In this study, we explored how browsing pressure by local deer populations affected leaf form and function in two California native tree species, coast live oak (Quercus agrifolia) and bay laurel (Umbellularia californica). Specifically, we investigated how leaf and stem vascular attributes shifted between browsed and non-browsed zones of each species and tested for differences in trait coordination as well as stem-leaf function. Browsing significantly altered traits such as leaf to phloem ratios and leaf area, but we observed few meaningful differences in leaf and stem anatomy between browsed and non-browsed material. We discuss these results in the context of such additional ecological factors and explore future research considerations for investigating leaf and stem vascular trait development with herbivore presence.
Utilizing Aggregated Molecular Phenotype (AMP) Scores to Visualize Simultaneous Molecular Changes in Mass Spectrometry Imaging Data
Authors: Chappel Jessie R. , King Mary E. , Fleming Jonathon , Eberlin Livia S. , Reif David M. , Baker Erin S. 
Published: June 2023

ABSTRACTMass spectrometry imaging (MSI) has gained increasing popularity for tissue-based diagnostics due to its ability to identify and visualize molecular characteristics unique to different phenotypes within heterogeneous samples. Data from MSI experiments are often visualized using single ion images and further analyzed using machine learning and multivariate statistics to identifym/z features of interest and create predictive models for phenotypic classification. However, often only a single molecule orm/zfeature is visualized per ion image, and mainly categorical classifications are provided from the predictive models. As an alternative approach, we developed an aggregated molecular phenotype (AMP) scoring system. AMP scores are generated using an ensemble machine learning approach to first select features differentiating phenotypes, weight the features using logistic regression, and combine the weights and feature abundances. AMP scores are then scaled between 0 and 1, with lower values generally corresponding to class 1 phenotypes (typically control) and higher scores relating to class 2 phenotypes. AMP scores therefore allow the evaluation of multiple features simultaneously and showcase the degree to which these features correlate with various phenotypes, leading to high diagnostic accuracy and interpretability of predictive models. Here, AMP score performance was evaluated using metabolomic data collected from desorption electrospray ionization (DESI) MSI. Initial comparisons of cancerous human tissues to normal or benign counterparts illustrated that AMP scores distinguished phenotypes with high accuracy, sensitivity, and specificity. Furthermore, when combined with spatial coordinates, AMP scores allow visualization of tissue sections in one map with distinguished phenotypic borders, highlighting their diagnostic utility.
A Novel Angiogenesis Role of GLP-1(32-36) to Rescue Diabetic Ischemic Lower Limbs via GLP-1R-Dependent Glycolysis
Authors: Zhang Yikai , Wang Shengyao , Zhou Qiao , Hu Yepeng , Xie Yi , Fang Weihuan , Yang Changxin , Wang Zhe , Ye Shu , Wang Xinyi , Zheng Chao 
Published: June 2023

AbstractGlucagon-like peptide 1 (GLP-1) improves angiogenesis, but the mechanism remains unclear. To address this question, we conducted a metabolomics analysis in bone marrow-derived endothelial progenitor cells (EPCs) isolated from T1DM mice treated with or without GLP-1(32-36) amide, an end-product of GLP-1. GLP-1(32-36) treatment recovered glycolysis. In addition, GLP-1(32-36) treatment rescued diabetic ischemic lower limbs and EPCs dysfunction by regulating PFKFB3-driven glycolytic flux capacity and mitochondrial dynamics. The effects of GLP-1(32-36) were abolished in mice lacking a functional GLP-1 receptor (Glp1r-/-), which could be partially rescued in EPCs transiently expressing GLP-1R. GLP-1(32-36) treatment activated the eNOS/cGMP/PKG pathway, increased glycolysis, and enhanced EPCs angiogenesis. Taken together, these findings suggest that GLP-1(32-36) could be used as a monotherapy or add-on therapy with existing treatments for DPAD.Graphical abstract
ENPP1 is an innate immune checkpoint of the anticancer cGAMP-STING pathway
Authors: Wang Songnan , Böhnert Volker , Joseph Alby J. , Sudaryo Valentino , Swinderman Jason , B.Yu Feiqiao , Lyu Xuchao , Skariah Gemini , Subramanyam Vishvak , Gilbert Luke A. , Goodarzi Hani , Li Lingyin 
Published: June 2023

AbstractENPP1 expression correlates with poor prognosis in many cancers, and we previously discovered that ENPP1 is the dominant hydrolase of extracellular cGAMP: a cancer-cell-produced immunotransmitter that activates the anticancer STING pathway. However, ENPP1 has other catalytic activities and the molecular and cellular mechanisms contributing to its tumorigenic effects remain unclear. Here, using single cell RNA-seq (scRNA-seq), we show that ENPP1 overexpression drives primary breast tumor growth and metastasis by synergistically dampening extracellular cGAMP-STING mediated antitumoral immunity and activating immunosuppressive extracellular adenosine (eADO) signaling. In addition to cancer cells, stromal and immune cells in the tumor microenvironment (TME) also express ENPP1 that restrains their response to tumor-derived cGAMP.Enpp1loss-of-function in both cancer cells and normal tissues slowed primary tumor initiation and growth and prevented metastasis in an extracellular cGAMP- and STING-dependent manner. Selectively abolishing the cGAMP hydrolysis activity of ENPP1 phenocopied total ENPP1 knockout, demonstrating that restoration of paracrine cGAMP-STING signaling is the dominant anti-cancer mechanism of ENPP1 inhibition. Strikingly, we find that breast cancer patients with lowENPP1expression have significantly higher immune infiltration and improved response to therapeutics impacting cancer immunity upstream or downstream of the cGAMP-STING pathway, like PARP inhibitors and anti-PD1. Altogether, selective inhibition of ENPP1’s cGAMP hydrolase activity alleviates an innate immune checkpoint to boost cancer immunity and is therefore a promising therapeutic approach against breast cancer that may synergize with other cancer immunotherapies.
Gestational exposure to bisphenol S induces microvesicular steatosis by promoting lipogenesis and inflammation in male rat offspring
Authors: Molangiri Archana , Varma Saikanth , Hridayanka Kota Sri Naga , Srinivas Myadara , Kona Suryam Reddy , Ibrahim Ahamed , Duttaroy Asim K , Basak Sanjay 
Published: June 2023

AbstractFetal exposure to endocrine-disrupting bisphenol A (BPA) showed a long-lasting programming effect on organ development and predisposed to the metabolic risk of adult diseases. However, limited data on developmental exposure to BPA-substitute bisphenol S (BPS) in predisposing liver metabolic disease is available. Here, the effects of BPS exposure were assessed on hepatic metabolism by examining adiposity and inflammation in the adipose and liver of the 90-day male offspring. Pregnant Wistar rats were exposed to BPA and BPS (0.0, 0.4, 4.0 µg/kg bw) via gavage from gestational day 4 to 21. Prenatal BPS-exposed offspring exhibited a higher obesogenic effect than BPA, including changes in body weight, body fat, feed efficiency, and leptin signalling. The fasting blood glucose did not change, but BPS exposure elevated plasma corticosterone levels and adipocyte hypertrophy of the visceral adipose tissue (VAT) to a greater extent than BPA. Adipocyte hypertrophy was augmented by modulated expression of lipid uptake (PPARγ, FABP4), glucocorticoid (HSD11β1), inflammation (IL6, IL1β, CRP, COX2), oxidative stress (CHOP) and apoptotic (Caspase 3) mediators. Liver histology showed numerous lipid droplets, and hepatocyte ballooning, associated with upregulated expression of cholesterol, lipid biogenesis and glucocorticoid activators, indicating microvesicular steatosis in the prenatally BPS-exposed adult offspring. The upregulated PPARα, ADRP, and FGF21 expression and increased lipid peroxidation in the offspring’s liver suggest metaflammation due to fetal exposure to BPS. Fetal BPS exposure demonstrated a more significant disruption in metabolism involving adiposity, liver fat, inflammation in excess, and predisposition to hepatic steatosis in the male offspring.HighlightsFetal BPS exposure exhibited enlarged and inflamed adipocytes more than BPAPrenatal BPS exposure induced excess lipid droplets & hepatocyte ballooning in liverIn utero exposure to BPS induces microvesicular steatosis in adult rats
Spatial redundancy transformer for self-supervised fluorescence image denoising
Authors: Li Xinyang , Hu Xiaowan , Chen Xingye , Fan Jiaqi , Zhao Zhifeng , Wu Jiamin , Wang Haoqian , Dai Qionghai 
Published: June 2023

AbstractFluorescence imaging with high signal-to-noise ratios has become the foundation of accurate visualization and analysis of biological phenomena. However, the inevitable photon shot noise poses a formidable challenge on imaging sensitivity. In this paper, we provide a spatial redundancy denoising transformer (SRDTrans) to remove noise from fluorescence images in a self-supervised manner. First, a sampling strategy based on spatial redundancy is proposed to extract adjacent orthogonal training pairs, which eliminates the dependence on high imaging speed. Secondly, to break the performance bottleneck of convolutional neural networks (CNNs), we designed a lightweight spatiotemporal transformer architecture to capture long-range dependencies and high-resolution features at a low computational cost. SRDTrans can overcome the inherent spectral bias of CNNs and restore high-frequency information without producing over-smoothed structures and distorted fluorescence traces. Finally, we demonstrate the state-of-the-art denoising performance of SRDTrans on single-molecule localization microscopy and two-photon volumetric calcium imaging. SRDTrans does not contain any assumptions about the imaging process and the sample, thus can be easily extended to a wide range of imaging modalities and biological applications.
Shared genetic risk factors and their implications for treatment of IPF and systemic hypertension
Authors: Parcesepe Gina , Allen Richard J , Guillen-Guio Beatriz , Moss Samuel , Jenkins R Gisli , Wain Louise V 
Published: June 2023

AbstractMore than 50% of individuals with idiopathic pulmonary fibrosis (IPF) have co-morbid hypertension. High blood pressure can lead to organ fibrosis or can be a consequence of artery stiffening due to fibrosis. Studies have implicated common processes, such as TGF-β signalling, in both traits’ regulation. Our goal is to identify shared genetic risk factors for IPF and hypertension.We analysed the genome-wide genetic correlation using LD Score Regression and the largest available genome-wide association studies of clinically defined IPF, and systolic and diastolic blood pressure (SBP and DBP, respectively). We then conducted a genome-wide colocalisation analysis to identify regions with a shared signal at P<10−5between IPF and either SBP or DBP.There was no genome-wide correlation between IPF and SBP (correlation (95% CI) -0.077(−0.142, -0.011), P=0.022) or DBP (correlation (95% CI) -0.027(−0.093, 0.039), P=0.427). The genome-wide colocalisation identified 8 shared signals, 3 (nearMAD1L1, GOLPH3L/HORMAD1, and at 17q21.31) had the same direction of effect on risk of IPF and hypertension and 5 (nearTERC, OBFC1, DEPTOR, and at 7q22.1 and 6p21.2) had opposite effects.These findings support that there may be shared fibrotic mechanisms between IPF and hypertension. The opposite effects of variants at specific loci highlight the need for caution when considering therapeutic targeting of these shared pathways for either disease.
Circulating H3K27 Methylated Nucleosome plasma concentration: a synergistic information with ctDNA Molecular Profiling
Authors: Grolleau Emmanuel , Candiracci Julie , Lescuyer Gaelle , Barthelemy David , Benzerdjeb Nazim , Haon Christine , Geiguer Florence , Raffin Margaux , Hardat Nathalie , Balandier Julie , Rabeuf Rémi , Chalabreysse Lara , Wozny Anne-Sophie , Rommelaere Guillaume , Rodriguez-Lafrasse Claire , Subtil Fabien , Couraud Sébastien , Herzog Marielle , Payen-Gay Lea 
Published: June 2023

ABSTRACTBackgroundMolecular profiling of circulating tumor DNA (ctDNA) is a helpful tool for cancer treatment indication or for the early detection of relapse. A subset of patients with advanced lung adenocarcinoma cancers (NSCLC)can be cured by immunotherapy, radiotherapy, and/or chemotherapy combined regimens, or targeted therapies depending on their ctDNA molecular profile. However, clinical interpretation of ctDNA negative result remains challenging. Cell-free DNA (cfDNA) in association with nucleosomes are released into the bloodstream upon cell death therefore the characterization of both may provide useful information for patient management., Dysregulations of epigenetic modifications, such as histone methylation, are found to play a key role in tumorigenesis of different cancers. However, the concentration of circulating nucleosomes in blood, as a biomarker of the contributive value of ctDNA molecular profiling in patient management at diagnosis or during patient follow-up has not previously been investigated.ResultsSignificantly elevated concentrations of H3K27Me3-nucleosomes were found in plasmas at diagnosis and during the follow-up of NSCLC patients compared to healthy donors (median: 24ng/ml; 16.9ng/ml vs 8ng/ml, p-value<0.0001, respectively). Interestingly, by combining H3K27Me3 level and ctDNA molecular profile, we found that 25.5% of the patients had high levels of H3K27Me3 (above cut-off level at 22.5 ng/ml) and no somatic alteration detected at diagnosis. This strongly supports the presence of non-mutated ctDNA in the corresponding plasma. During patient follow-up, H3K27Me3 level was lower in ctDNA-negative group compared to ctDNA-positive group (medianctDNA-= 13.4 ng/mL vs medianctDNA+ = 26.1 ng/mL, respectively, p_value<0.0001). In 41.8% of the samples, no somatic mutation and low level of H3K27Me3-nucleosomes were observed suggesting molecular indicator of treatment response. In contrast, high H3K27Me3-nucleosome level was found in 15.1% of the sample despite no somatic mutations being detected allowing the identification of disease progression from 43.1% to 58.2% over molecular profiling alone.ConclusionMeasuring H3K27Me3-nucleosome levels in combination with ctDNA molecular profiling may not only improve confidence in the negative molecular result in cfDNA in lung cancer at diagnosis, it may also be a promising biomarker for Molecular Residual Disease (MRD) monitoring during and/or after treatment.
The Medical Knowledge Oligarchies
Authors: Matos João , Nakayama Luis , Charpignon Marie-Laure , Gallifant Jack , Kashkooli Mohammad , Carli Francesco , Celi Leo Anthony 
Published: June 2023

AbstractIntroductionHealthcare policies and clinical decisions heavily rely on research publications from high-impact medical journals. A lack of author diversity in medical publications poses a risk to underrepresented groups. To promote equity in healthcare medical decisions, fostering collaborations within research groups is crucial. This study integrates scientometrics with network analysis to uncover intricate co-authorship networks and examine diversity and inclusion in scientific collaboration.MethodsThe authors’ metadata from five high-impact medical journals were collected, and a weighted graph of co-authorships was constructed. The study addresses four research questions: identifying influential authors, exploring research output communities, analyzing collaboration patterns, and examining the evolution of collaboration over time.ResultsCentral nodes are significantly more likely to be male or from high-income countries. Further, when evaluated over time, the graph reveals concerning trends in diversity where collaboration with authors from lower income countries is not growing. All code is publicly available on GitHub.DiscussionThe findings underscore the need to promote diversity within research niches and question the role of gatekeepers in facilitating inclusivity. Future studies should expand the scope of network analysis and explore additional factors such as funding sources and guidelines.ConclusionOverall, this study contributes a framework for auditing diversity and inclusion in scientific collaboration, aiming to promote transparency and a more equitable medical knowledge production system.
Cardioprotective effect of the low energy extracorporeal shock wave on the doxorubicin-induced cardiomyopathy in breast cancer patients
Authors: Song Shinjeong , Woo Joohyun , Kim HyunGoo , Lee Jun Woo , Lim Woosung , Moon Byung-In , Kwon Kihwan 
Published: June 2023

AbstractBackgroundDoxorubicin is a highly effective anti-cancer drug but causes left ventricular (LV) dysfunction, and also induces late-onset cardiomyopathy. Extensive research has been done and is being done to discover preventive treatments. However, an effective and clinically applicable preventive treatment is yet to be discovered. Cardiac Extracorporeal shock waves therapy (C-ESWT) has been suggested to treat inflammatory and ischemic diseases and protect cardiomyocytes from doxorubicin-induced cardiomyopathy. The aim of this study is to assess the safety and efficacy of C-ESWT in treating patients with doxorubicin.MethodsA single-center, randomized, prospective controlled study to evaluate the prevention and safety of doxorubicin-induced cardiomyopathy using C-ESWT was performed. We enrolled 64 breast cancer patients. C-ESWT group 33 patients were treated with our cardiac shock wave therapy (200 shots/spot at 0.09mJ/mm2 for 20 spots, 3 times a week every two-chemotherapy cycles). Efficacy endpoints were LVGLS by 2D speckle tracking echocardiography using Tomtec software and CTRCD. Echocardiography should be performed on the baseline line and every 4 cycles of chemotherapy, followed by a follow-up 3,6 months after chemotherapy to compare the incidence of cardiomyopathy of subclinical LV dysfunction due to chemotherapy between the two groups. CTRCD was defined as a reduction in LV ejection fraction (EF) from a baseline greater than 10% to less than 55% and subclinical CTRCD was defined as a GLS reduction of ≥ 15% compared to the baseline value.ResultsParticipants averaged 50±9 years in age, 100% female. In the results of follow-up 6 months after the end of chemotherapy, there was a significant difference in delta LVGLS between the ESW group and the control group (EF; -0.2±7.7% vs. -3.7±14.2 p-value; 0.076, GLS; -1.2±9.3% vs. -11.2±9.5% p-value; <0.001). In the control group, 2 patients developed CTRCD. A total of 27% (14 patients) of patients developed subclinical LV dysfunction (Control group; 11 vs. ESW group; 3). ESW therapy was performed safely without any serious adverse events.ConclusionIn this prospective study, C-ESWT established efficacy in preventing CRTCD as well as chemotherapy-induced cardiomyopathy using doxorubicin chemotherapy and the safety of C-ESWT use in breast cancer patients.