bluuebunny/crossref_metadata_2025_split huggingface dataset:
Green Heart Louisville: Intra-urban, hyperlocal land-use regression modeling of ultrafine particles
Authors: Prathibha Pradeep , Yeager Raymond , Bhatnagar Aruni , Turner Jay 
Published: March 2023

AbstractExposure to ultrafine particles (UFP) is increasingly linked to adverse health outcomes. While nation-wide air monitoring networks in the United States do not measure UFP, small-scale measurements have revealed persistent patterns in urban UFP. This project maps hyperlocal UFP in a 12 km2study area of a health effects study in Louisville, KY, through mobile measurements to elucidate the relationship between the urban landscape and UFP exposures. We measured UFP number concentration along all drivable streets (∼340 km) during daytime and nighttime on both weekdays and weekends. After deconvoluting UFP levels to isolate local signals from neighborhood and urban signals, we fitted a land-use regression (LUR) model to explain differences in local UFP as a function of characteristics of the built and natural environment.Median UFP in the study domain was 6,850 #/cm3, which is comparable to urban background measured or estimated for other U.S. cities. UFP was higher during the weekend than on weekdays, potentially due to changes in local activity (e.g. increased restaurant hours) apparent at fine spatial scales. The final LUR model explained 61% of the spatial heterogeneity in log(UFP). Leave-one-area-out cross validation revealed overprediction in regions farther from highways and underprediction in regions with dense food service locations and major roads. This suggests that additional mobile measurements to capture longer-term, robust UFP may yield improved models.
MOVER: Medical Informatics Operating Room Vitals and Events Repository
Authors: Samad Muntaha , Rinehart Joseph , Angel Mirana , Kanomata Yuzo , Baldi Pierre , Cannesson Maxime 
Published: March 2023

AbstractArtificial Intelligence (AI) holds great promise for transforming the healthcare industry. However, despite its potential, AI is yet to see widespread deployment in clinical settings in significant part due to the lack of publicly available clinical data and the lack of transparency in the published AI algorithms. There are few clinical data repositories publicly accessible to researchers to train and test AI algorithms, and even fewer that contain specialized data from the perioperative setting. To address this gap, we present and release the Medical Informatics Operating Room Vitals and Events Repository, which includes data from 58,799 unique patients and 83,468 surgeries collected from the UCI Medical Center over a period of seven years. MOVER is freely available to all researchers who sign a data usage agreement, and we hope that it will accelerate the integration of AI into healthcare settings, ultimately leading to improved patient outcomes.
Pharmacological characterization of the endocannabinoid sensor GRABeCB2.0
Authors: Singh Simar , Sarroza Dennis , English Anthony , McGrory Maya , Dong Ao , Zweifel Larry , Land Benjamin B. , Li Yulong , Bruchas Michael R. , Stella Nephi 
Published: March 2023

AbstractIntroductionThe endocannabinoids (eCBs), 2-arachidonoylglycerol (2-AG) and arachidonoyl ethanolamine (AEA), are produced by separate enzymatic pathways, activate cannabinoid receptors with distinct pharmacology, and differentially regulate pathophysiological processes. The genetically encoded sensor, GRABeCB2.0, detects real-time changes in eCB levels in cells in culture and preclinical model systems; however, its activation by eCB analogues produced by cells and by phyto-cannabinoids remains uncharacterized, a current limitation when interpreting changes in its response. This information could provide additional utility for the tool in in vivo pharmacology studies of phyto-cannabinoid action.MethodsGRABeCB2.0was expressed in cultured HEK293 cells. Live cell confocal microscopy and high-throughput fluorescent signal measurements.Results2-AG increased GRABeCB2.0fluorescent signal (EC50= 85 nM), and the cannabinoid 1 receptor (CB1R) antagonist, SR141617, decreased GRABeCB2.0signal (SR1, IC50= 3.3 nM), responses that mirror their known potencies at cannabinoid 1 receptors (CB1R). GRABeCB2.0fluorescent signal also increased in response to AEA (EC50= 815 nM), the eCB analogues 2-linoleoylglycerol and 2-oleoylglycerol (2-LGand2-OG, EC50s = 1.5 and 1.0 μM, respectively), Δ9-tetrahydrocannabinol (Δ9-THC) andΔ8-THC(EC50s = 1.6 and 2.0 μM, respectively), and the artificial CB1R agonist, CP55,940 (CP, EC50= 82 nM); however their potencies were less than what has been described at CB1R. Cannabidiol (CBD) did not affect basal GRABeCB2.0fluorescent signal and yet reduced the 2-AG stimulated GRABeCB2.0responses (IC50= 8.8 nM).Conclusions2-AG and SR1 modulate the GRABeCB2.0fluorescent signal with EC50s that mirror their potencies at CB1R whereas AEA, eCB analogues, THC and CP increase GRABeCB2.0fluorescent signal with EC50s significantly lower than their potencies at CB1R. CBD reduces the 2-AG response without affecting basal signal, suggesting that GRABeCB2.0retains the negative allosteric modulator (NAM) property of CBD at CB1R. This study describes the pharmacological profile of GRABeCB2.0to improve interpretation of changes in fluorescent signal in response to a series of known eCBs and CB1R ligands.
Mitochondrial translation regulates terminal erythroid differentiation by maintaining iron homeostasis
Authors: Morishima Tatsuya , Fakruddin Md. , Masuda Takeshi , Wang Yuxin , Schoonenberg Vivien A. C. , Butter Falk , Arima Yuichiro , Akaike Takaaki , Tomizawa Kazuhito , Wei Fan-Yan , Suda Toshio , Takizawa Hitoshi 
Published: March 2023

AbstractA lack of the mitochondrial tRNA taurine modifications mediated by mitochondrial tRNA translation optimization 1 (Mto1) was recently shown to induce proteostress in embryonic stem cells. Since erythroid precursors actively synthesize the hemoglobin protein, we hypothesized thatMto1dysfunctions may result in defective erythropoiesis. Hematopoietic-specificMto1conditional knockout (cKO) mice were embryonic lethal due to niche-independent defective terminal erythroid differentiation. Mechanistically, mitochondrial oxidative phosphorylation complex-I was severely defective in theMto1cKO fetal liver and this was followed by cytoplasmic iron accumulation. Overloaded cytoplasmic iron promoted heme biosynthesis and enhanced the expression of embryonic hemoglobin proteins, which induced an unfolded protein response via the IRE1α-Xbp1 signaling pathway inMto1cKO erythroblasts. An iron chelator rescued erythroid terminal differentiation in theMto1cKO fetal liverin vitro. The new point of view provided by this novel non-energy-related molecular mechanism may lead to a breakthrough in mitochondrial research.
A Systematic Investigation of Detectors for Low Signal-to-Noise Ratio EMG Signals
Authors: Yuvaraj Monisha , Raja Priyanka , David Ann , Burdet Etienne , SKM Varadhan , Balasubramanian Sivakumar 
Published: March 2023

AbstractActive participation of stroke survivors during robot-assisted movement therapy is essential for sensorimotor recovery. Robot-assisted therapy contingent on movement intention is an effective way to encourage patients’ active engagement. For severely impaired stroke patients with no residual movements, a surface electromyogram (EMG) has been shown to be a viable option for detecting movement intention. Although numerous algorithms for EMG detection exist, the detector with the highest accuracy and lowest latency for low signal-to-noise ratio (SNR) remains unknown. This study, therefore, investigates the performance of thirteen existing EMG detection algorithms on simulated low SNR (0dB and -3dB) EMG signals generated using three different EMG signal models: gaussian, laplacian, and biophysical model. The detector performance was quantified using the false positive rate (FPR), false negative rate (FNR), and detection latency. Any detector that consistently showed FPR and FNR of no more than 20%, and latency of no more than 50ms, was considered an appropriate detector for use in robot-assisted therapy. The results indicate that the Modified Hodges detector – a simplified version of the threshold-based Hodges detector introduced in the current study – was the most consistent detector across the different signal models and SNRs. It consistently performed for ∼90% and ∼40% of the tested trials for 0dB and -3dB SNR, respectively. The two statistical detectors (Gaussian and Laplacian Approximate Generalized Likelihood Ratio) and the Fuzzy Entropy detectors have a slightly lower performance than Modified Hodges. Overall, the Modified Hodges, Gaussian and Laplacian Generalized Likelihood ratio, and the Fuzzy Entropy detectors were identified as the potential candidates that warrant further investigation with real surface EMG data since they had consistent detection performance on low SNR EMG data.
Endothelial cell-derived lactate triggers mesenchymal stem cell histone lactylation to attenuate osteoporosis
Authors: Wu Jinhui , Hu Miao , Jiang Heng , Ma Jun , Xie Chong , Zhang Zheng , Zhou Xin , Zhao Jianquan , Tao Zhengbo , Meng Yichen , Cai Zhuyun , Song Tengfei , Zhang Chenglin , Gao Rui , Song Hongyuan , Gao Yang , Lin Tao , Wang Ce , Zhou Xuhui 
Published: March 2023

AbstractBlood vessels play a role in osteogenesis and osteoporosis; however, the role of vascular metabolism is unclear. The present study found that ovariectomized mice exhibit reductions in bone blood vessel density and expression of endothelial glycolytic regulator pyruvate kinase M2 (PKM2). Additional data showed that endothelial cell (EC)-specific deletion of Pkm2 impair osteogenesis and worsen osteoporosis in mice. This was attributed to the impaired differentiation ability toward osteoblast of bone mesenchymal stem cells (BMSCs). Mechanistically, EC-specific deletion of Pkm2 reduce serum lactate levels secreted by ECs, which affect histone lactylation of BMSCs. We identified collagen type I alpha 2 chain, cartilage oligomeric matrix protein, ectonucleotide pyrophosphatase/phosphodiesterase 1, and transcription factor 7 like 2 as histone H3K18 lactylation-regulated osteogenic genes using joint CUT&Tag and RNA-sequencing analyses. The overexpression of PKM2 in ECs, addition of lactate, and exercise were observed to restore the phenotype of endothelial Pkm2-deficient mice. Furthermore, metabolomics of the serum indicated that osteoporosis patients showed a relatively low lactate level. The histone lactylation and related osteogenic genes of BMSCs in osteoporosis patients also decreased. In conclusion, the glycolysis of ECs fuels the differentiation of BMSCs into osteoblasts through histone lactylation, and exercise partially ameliorates osteoporosis through increased serum lactate.
RNA Sensing and Innate Immunity Constitutes a Barrier for Interspecies Chimerism
Authors: Hu Yingying , Sun Hai-Xi , Sakurai Masahiro , Jones Amanda E. , Liu Lizhong , Cheng Tianlei , Zheng Canbin , Li Jie , Ravaux Benjamin , Luo Zhou , Ding Yi , Liu Tianbin , Wu Yan , Chen Elizabeth H. , Chen Zhijian J. , Abrams John M. , Gu Ying , Wu Jun 
Published: March 2023

AbstractInterspecies chimera formation with human pluripotent stem cells (PSCs) holds great promise to generate humanized animal models and provide donor organs for transplant. However, the approach is currently limited by low levels of human cells ultimately represented in chimeric embryos. Different strategies have been developed to improve chimerism by genetically editing donor human PSCs. To date, however, it remains unexplored if human chimerism can be enhanced in animals through modifying the host embryos. Leveraging the interspecies PSC competition model, here we discovered retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) signaling, an RNA sensor, in “winner” cells plays an important role in the competitive interactions between co-cultured mouse and human PSCs. We found that genetic inactivation ofDdx58/Ifih1-Mavs-Irf7axis compromised the “winner” status of mouse PSCs and their ability to outcompete PSCs from evolutionarily distant species during co-culture. Furthermore, by usingMavs-deficient mouse embryos we substantially improved unmodified donor human cell survival. Comparative transcriptome analyses based on species-specific sequences suggest contact-dependent human-to-mouse transfer of RNAs likely plays a part in mediating the cross-species interactions. Taken together, these findings establish a previously unrecognized role of RNA sensing and innate immunity in “winner” cells during cell competition and provides a proof-of-concept for modifying host embryos, rather than donor PSCs, to enhance interspecies chimerism.
Sustained improvements in brain health and metabolic markers 24 months following bariatric surgery
Authors: Legault Marianne , Pelletier Mélissa , Lachance Amélie , Lachance Marie-Ève , Zeighami Yashar , Gauthier Marie-Frédérique , Iceta Sylvain , Biertho Laurent , Fulton Stephanie , Richard Denis , Dagher Alain , Tchernof André , Dadar Mahsa , Michaud Andréanne 
Published: March 2023

AbstractBackgroundObesity and its metabolic complications are associated with lower gray matter (GM) and white matter (WM) density, whereas weight loss after bariatric surgery leads to an increase in both measures. These increases of GM and WM density are significantly associated with post-operative weight loss and improvement of the metabolic/inflammatory profiles. While our recent studies demonstrated widespread increases in WM density 4 and 12 months after bariatric surgery, it is not clear if theses changes persist over time. The underlying mechanisms also remain unknown. In this regard, numerous studies demonstrate that the enlargement or hypertrophy of mature adipocytes, particularly in the visceral fat compartment, is an important marker of adipose tissue dysfunction and obesity-related cardiometabolic abnormalities.ObjectiveTo assess whether the previously observed increases in WM and GM densities are maintained 24 months post-surgery, and to examine if pre-operative abdominal omental (OM) and subcutaneous (SC) adipocyte diameters are associated with WM and GM changes after bariatric surgery.Methods32 participants undergoing bariatric surgery were recruited. WM and GM densities were assessed from T1-weighted MRIs acquired prior to and 4-, 12-, and 24-months post-surgery using voxel-based morphometry. OM and SC adipose tissue samples were collected during the surgical procedure. OM and SC adipocyte diameters were measured by microscopy of fixed adipose tissue samples. Linear mixed-effects models were performed controlling for age, sex, surgery type, initial BMI, and diabetic status.ResultsThe average weight loss at 24 months was 33.5±7.2%. A widespread increase in WM density was observed 24 months post-surgery mainly in the cerebellum, brainstem, and corpus callosum (p<0.05, FDR) as well as some regions in GM density. Greater baseline OM adipocyte diameter was associated with greater changes in total WM density at 24 months (p=0.008). A positive trend was observed between SC adipocyte diameter and changes in total WM density at 24 months (p=0.05).ConclusionOur results show prolonged increases of WM and GM densities up to 24 months post-bariatric surgery. Greater preoperative OM adipocyte diameter is associated with greater increases in WM density at 24 months, suggesting that individuals with excess visceral adiposity might benefit the most from surgery.
HIVtat Alters Epithelial Differentiation State and Increases HPV16 Infectivity in Oral Keratinocytes
Authors: Seaman William T , Madden Victoria , Webster-Cyriaque Jennifer 
Published: March 2023

AbstractHuman Papillomavirus (HPV)-associated oral disease has increased during the era of HIV antiretroviral therapy. HPV and HIV proteins may be co-present at mucosal surfaces. Recent published studies have determined that HIVtat is secreted in the saliva and has been detected in oral mucosa even in the context of antiretroviral therapy. We hypothesized that HIVtat promoted oral HPV pathogenesis. Clinical HPV16 cloned episomes were introduced into differentiated oral epithelial cells (OKF6tert1). HIVtat mediated transactivation, DNA damage, oxidative stress, and effects on cellular differentiation were assessed. Detection of keratin 10 and of loricrin confirmed terminal differentiation. Sodium butyrate-treated (NaB) cells demonstrated an eight-fold increase in cross-linked involucrin, suggesting full terminal differentiation. HIVtat modulated this differentiation both in the presence and absence of NaB. Later viral events, including E6* and E1^E4 gene expression were assessed. HIVtat mediated relief of repressed L1 expression that mapped to a known inhibitory region (nucleotides 5561-6820). Viruses from HIVtat co-expressing cells exhibited robust de novo HPV16 infection. In conclusion, a novel oral keratinocyte monolayer system supported replication of an HPV16 clinical isolate where direct HIVtat and oral HPV interactions enhanced HPV de novo infection.
Differentiated Oral Epithelial Cells Support the HPV Life Cycle
Authors: Seaman William T , Saladyanant Thatsanee , Madden Victoria , Webster-Cyriaque Jennifer 
Published: March 2023

AbstractHuman Papillomavirus (HPV) associated oral disease continues to increase, both in the context of immune competence and of immune suppression. There are few models of oral HPV infection and current models are laborious. We hypothesized that differentiated oral epithelial cells could support the HPV life cycle. Clinical HPV16 cloned episomes were introduced into differentiated oral epithelial cells (OKF6tert1). Viral and cellular gene expression was assessed in the presence or absence of sodium butyrate, a differentiating agent that moved the cells to full terminal differentiation. Detection of keratin 10, cross-linked involucrin, and loricrin in the presence and absence of sodium butyrate confirmed terminal differentiation. Increasing sodium butyrate concentrations in the absence of HPV, were associated with decreased suprabasal markers and increased terminal differentiation markers. However, in the presence of HPV and of increasing sodium butyrate concentrations, both mitotic and suprabasal markers were increased and the terminal differentiation marker, loricrin, decreased. In this unique differentiated state, early and late viral gene products were detected including spliced mRNAs for E6*, E1^E4, and L1. E7 and L1 proteins were detected. The ratio of late (E1^E4) to early (E6/E7) transcripts in HPV16+ OKF6tert1 cells was distinct compared to HPV16+ C33a cells. Consistent with permissive HPV replication, DNA damage responses (phospho-chk2, gamma-H2AX), HPV E2-dependent LCR transactivation, and DNase-resistant particles were detected and visualized by transmission electron microscopy. In sum, monolayers of differentiated immortalized oral epithelial cells supported the full HPV life cycle. HPV may optimize the differentiation state of oral epithelial cells to facilitate its replication.
Standing wave mesoscopy
Authors: Foylan Shannan , Schniete Jana Katharina , Kölln Lisa Sophie , Dempster John , Hansen Carsten Gram , Shaw Michael , Bushell Trevor John , McConnell Gail 
Published: March 2023

AbstractStanding wave (SW) microscopy is a method that uses an interference pattern to excite fluorescence from labelled cellular structures and produces high-resolution images of three-dimensional objects in a two-dimensional dataset. SW microscopy is performed with high magnification, high numerical aperture objective lenses, and while this results in high resolution images, the field of view is very small. Here we report upscaling of this interference imaging method from the microscale to the mesoscale using the Mesolens, which has the unusual combination of a low magnification and high numerical aperture. With this method, we produce SW images within a field of view of 4.4 mm x 3.0 mm that can readily accommodate over 16,000 cells in a single dataset. We demonstrate the method using both single-wavelength excitation and the multi-wavelength SW method TartanSW. We show application of the method for imaging of fixed and living cells specimens, with the first application of SW imaging to study cells under flow conditions.
Host plant affects the larval gut microbial communities of the generalist herbivoresHelicoverpa armigeraandSpodoptera frugiperda
Authors: Rodrigues Pedro A. P. , Cavichiolli de Oliveira Nathalia , Omoto Celso , Girke Thomas , Cônsoli Fernando L. 
Published: March 2023

SummaryInvestigations on symbiotic associations between Lepidoptera and bacteria have been inconclusive as to whether these microorganisms represent transient or persistent associations. One reason for this is that most studies have sampled the microbiota from only a few species and frequently from laboratory-reared animals. We sequenced the 16S rRNA gene to profile the gut microbiome of the field collected, agricultural pestsHelicoverpa armigeraandSpodoptera frugiperda. We found that variation in the structure of bacterial communities is in great part associated with their host diet. Moreover,Enterococcus, among a few other taxa, is consistently present in all samples regardless of the plant hosts were collected. The larval gut bacteria composition matches previously published data in the same or related species, indicating that associations with bacteria taxa such asEnterococcusare persistent despite geographical variation and sampling techniques. Based on our phylogenetic analysis it is not clear, however, ifEnterococciassociated with Lepidoptera are necessarily different from environmental bacteria. We conclude that to fully understand the nature of Lepidoptera - gut bacteria associations it will be necessary to conduct larger sampling efforts and combine them with identification methods of bacterial strains that go beyond screening of the 16S rRNA gene.
Ambient temperature crystal structure ofEscherichia coliCyaY protein displays alternate conformation
Authors: Shafiei Alaleh , Baldir Nilufer , Na Jongbum , Kim Jin Hae , DeMirci Hasan 
Published: March 2023

AbstractFrataxin is a 23 KDa mitochondrial iron-binding protein that is involved in biogenesis of iron sulfur clusters. A deficiency in frataxin leads to Friedreich’s ataxia, a progressive neurodegenerative disorder. The bacterial ortholog of eukaryotic mitochondrial frataxin, CyaY, is thought to play a role in iron sulfur cluster assembly as an iron supplier, making it an important target for study. Here, we present the first ambient temperature crystal structure of CyaY protein fromEscherichia coli, obtained using the Turkish Light Source “Turkish DeLight”. This study reveals the dynamic structural characteristics of CyaY at near-physiological temperature and displays an alternate conformation, highlighting the importance of temperature considerations in protein structure characterization and providing new insights into the protein’s flexibility.