bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sympathetic innervation of interscapular brown adipose tissue is not a predominant mediator of oxytocin-elicited reductions of body weight and adiposity in male diet-induced obese mice
Authors: Edwards Melise M. , Nguyen Ha K. , Dodson Andrew D. , Herbertson Adam J. , Wolden-Hanson Tami , Wietecha Tomasz , Honeycutt Mackenzie K. , Slattery Jared D. , O’Brien Kevin D. , Graham James L. , Havel Peter J. , Mundinger Thomas O. , Sikkema Carl , Peskind Elaine R. , Ryu Vitaly , Taborsky Gerald J. , Blevins James E. 
Published: June 2024

AbstractPrevious studies indicate that CNS administration of oxytocin (OT) reduces body weight in high fat diet-induced obese (DIO) rodents by reducing food intake and increasing energy expenditure (EE). We recently demonstrated that hindbrain (fourth ventricular [4V]) administration of OT elicits weight loss and elevates interscapular brown adipose tissue temperature (TIBAT, a surrogate measure of increased EE) in DIO mice. What remains unclear is whether OT-elicited weight loss requires increased sympathetic nervous system (SNS) outflow to IBAT. We hypothesized that OT-induced stimulation of SNS outflow to IBAT contributes to its ability to activate BAT and elicit weight loss in DIO mice. To test this hypothesis, we determined the effect of disrupting SNS activation of IBAT on the ability of 4V OT administration to increase TIBATand elicit weight loss in DIO mice. We first determined whether bilateral surgical SNS denervation to IBAT was successful as noted by ≥ 60% reduction in IBAT norepinephrine (NE) content in DIO mice. NE content was selectively reduced in IBAT at 1-, 6- and 7-weeks post-denervation by 95.9±2.0, 77.4±12.7 and 93.6±4.6% (P<0.05), respectively and was unchanged in inguinal white adipose tissue, pancreas or liver. We subsequently measured the effects of acute 4V OT (1, 5 µg ≈ 0.99, 4.96 nmol) on TIBATin DIO mice following sham or bilateral surgical SNS denervation to IBAT. We found that the high dose of 4V OT (5 µg ≈ 4.96 nmol) elevated TIBATsimilarly in sham mice as in denervated mice. We subsequently measured the effects of chronic 4V OT (16 nmol/day over 29 days) or vehicle infusions on body weight, adiposity and food intake in DIO mice following sham or bilateral surgical denervation of IBAT. Chronic 4V OT reduced body weight by 5.7±2.23% and 6.6±1.4% in sham and denervated mice (P<0.05), respectively, and this effect was similar between groups (P=NS). OT produced corresponding reductions in whole body fat mass (P<0.05). Together, these findings support the hypothesis that sympathetic innervation of IBAT is not necessary for OT-elicited increases in BAT thermogenesis and reductions of body weight and adiposity in male DIO mice.
Femtosecond X-ray snapshots reveal correlated displacements of specific distal atoms in a protein crystal
Authors: Gagnér Viktor Ahlberg , Jensen Maja , Olsson Torbjörn Nur , Sánchez Juan Cabello , Bengtsson Åsa U. J. , Ekström J. Carl , Zhang Zhedong , Jurgilaitis Andrius , Kroon David , Pham Van-Thai , Checchia Stefano , Coudert-Alteirac Hélène , Rodilla Helena , Stake Jan , Zhaunerchyk Vitali , Friedman Ran , Larsson Jörgen , Mezzasalma Stefano A. , Katona Gergely 
Published: June 2024

AbstractProtein dynamics is shaped by interactions between thermal fluctuations, external forces, and molecular structures. Thermal fluctuations have high frequencies and are hence very challenging to quantify. We were able to record femtosecond X-ray diffraction snapshots and determine atomic displacements of crystalline bovine trypsin atoms either in the native steady state or in a transient state initiated by a short THz pulse, the results of which were interpreted with numerical simulations. In the absence of THz pulses, specific distal atoms exhibited correlated movements. Under the influence of THz fields, numerical simulations demonstrated a slight enhancement of displacement correlations. The experimental results revealed a contrasting response to short THz pulses, where the measured displacements were not solely determined by the atom position, but also influenced by the atomic type. These findings call for a reinterpretation of the dynamic properties inherent in folded protein structures and the physical principles behind the formation of protein assemblies. To this end, a theoretical model was developed for lattice deformations and local excitations entraining a (squeezed) coherent steady state, explaining the emergence of atom correlations. The model accounts for the magnitudes of atomic displacements and fluctuations through a balance between harmonic and anharmonic coupling forces.
A Self-Supervised Learning Approach for High Throughput and High Content Cell Segmentation
Authors: Lam Van , Byers Jeff M. , Robitaille Michael , Kaler Logan , Christodoulides Joseph A. , Raphael Marc P. 
Published: June 2024

AbstractIn principle, AI-based algorithms should enable rapid and accurate cell segmentation in high-throughput settings. However, reliance on large datasets, human input, and computational expertise, along with issues of limited generalizability and the necessity for specialized training are notable drawbacks of nominally “automated” segmentation tools. To overcome this roadblock, we introduce an innovative, user-friendly self-supervised learning method (SSL) for pixel classification that requires no dataset-specific modifications or curated labelled data sets, thus providing a more streamlined cell segmentation approach for high-throughput and high-content research. We demonstrate that our algorithm meets the criteria of being fully automated with versatility across various magnifications, optical modalities and cell types. Moreover, our SSL algorithm is capable of identifying complex cellular structures and organelles which are otherwise easily missed, thereby broadening the machine learning applications to high-content imaging. Our SSL technique displayed consistent F1 scores across segmented images, with scores ranging from 0.831 to 0.876, outperforming the popular Cellpose algorithm, which showed greater variance in F1 scores from 0.645 to 0.8815, mainly due to errors in segmentation. On average, our SSL method achieved an F1 score of 0.852 ±0.017, exceeding Cellpose’s average of 0.804 ±0.08. This novel SSL method not only advances segmentation accuracy but also minimizes the need for extensive computational expertise and data security concerns, making it easier for biological researchers to incorporate automated segmentation into their studies.
Artificial Intelligence driven Benchmarking Tool for Emission Reduction in Canadian Dairy Farms
Authors: Parmar Pratik Mukund , Bi Hangqing , Neethirajan Suresh 
Published: June 2024

AbstractThis study develops an Artificial Intelligence-driven benchmarking tool to reduce methane emissions in Canadian dairy farms, responding to the urgent need to mitigate environmental impacts from agriculture. Utilizing a comprehensive dataset from over 1000 dairy farms and processors across Canada, combined with satellite-driven methane emission data, we apply advanced machine learning technologies and data analytics, including geospatial analysis and time series forecasting. This approach identifies critical emission hotspots and temporal trends. We tested several predictive models—ARIMA, LSTM, GBR, and PROPHET—with the LSTM model showing the greatest accuracy in forecasting emissions, demonstrated by the lowest Root Mean Squared Error (RMSE) of 15.40. Our results highlight the transformative potential of AI tools in agricultural environmental management by providing dairy farmers and policymakers with precise, real-time emission insights. This facilitates informed decision-making and the implementation of effective emission reduction strategies. This study not only advances understanding of emission dynamics in dairy farming but also underscores the role of technology in sustainable agricultural practices and achieving environmental targets consistent with global agreements.
SLO2.1/NALCN Functional Complex Activity in Mouse Myometrial Smooth Muscle Cells During Pregnancy
Authors: Ferreira Juan J. , Kent Lindsey N. , McCarthy Ronald , Butler Alice , Ma Xiaofeng , Peramsetty Nikita , Amazu Chinwendu , Zhang Alexander , Whitter Grace C. , England Sarah K. , Santi Celia M. 
Published: June 2024

AbstractAt the end of pregnancy, the uterus transitions from a quiescent to a highly contractile state. This is partly due to depolarization of the resting membrane potential in uterine (myometrial) smooth muscle cells (MSMCs). Experiments with human MSMCs showed that the membrane potential is regulated by a functional complex between the sodium (Na+)-activated potassium (K+) channel SLO2.1 and the Na+Leak Channel Non-Selective (NALCN). In human MSMCs, Na+entering through NALCN activates SLO2.1, leading to K+efflux, membrane hyperpolarization (cells become more negative inside), and reduced contractility. Decreased SLO2.1/NALCN activity results in reduced K+efflux, leading to membrane depolarization, Ca2+influx via voltage-dependent calcium channels, and increased MSMC contractility. However, all of these experiments were performed with MSMCs isolated from women at term, so the role of the SLO2.1/NALCN complex early in pregnancy was speculative. To address this question here, we examined the role of the SLO2.1/NALCN complex in regulating mouse MSMC membrane potential across pregnancy. We report thatSlo2.1andNalcnexpression change along pregnancy, being more highly expressed in MSMCs from non-pregnant and early pregnant mice than in those from late-pregnant mice.Functional studies revealed that SLO2.1 channels mediate a significant portion of the K+current in mouse MSMCs, particularly in cells from non-pregnant and early pregnant mice. Activation of SLO2.1 by Na+influx through NALCN led to membrane hyperpolarization in MSMCs from early pregnancy but not in MSMCs from later pregnancy. Moreover, we found that the NALCN/SLO2.1 complex regulates intracellular Ca2+responses more in MSMCs from non-pregnant and early pregnancy mice than in MSMCs from late pregnancy. Together, these findings reveal that the SLO2.1/NALCN functional complex is conserved between mouse and humans and functions throughout pregnancy. This work could open avenues for targeted pharmacological interventions in pregnancy-related complications.
L-Arginine and asymmetric dimethylarginine (ADMA) transport across the mouse blood-brain and blood-CSF barriers: evidence of saturable transport at both interfaces and CNS to blood efflux
Authors: Fidanboylu Mehmet , Thomas Sarah Ann 
Published: June 2024

ABSTRACTL-Arginine is the physiological substrate for the nitric oxide synthase (NOS) family, which synthesises nitric oxide (NO) in endothelial and neuronal cells. NO synthesis can be inhibited by endogenous asymmetric dimethylarginine (ADMA). NO has explicit roles in cellular signalling and vasodilation. Impaired NO bioavailability represents the central feature of endothelial dysfunction associated with vascular diseases. Interestingly, dietary supplementation withL-arginine has been shown to alleviate endothelial dysfunctions caused by impaired NO synthesis. In this study the transport kinetics of [3H]-arginine and [3H]-ADMA into the central nervous system (CNS) were investigated using physicochemical assessment and thein situbrain/choroid plexus perfusion technique in anesthetized mice. Results indicated thatL-arginine and ADMA are tripolar cationic amino acids and have a gross charge at pH 7.4 of 0.981.L-Arginine (0.00149±0.00016) has a lower lipophilicity than ADMA (0.00226±0.00006) as measured using octanol-saline partition coefficients. Thein situperfusion studies revealed that [3H]-arginine and [3H]-ADMA can cross the blood-brain barrier (BBB) and the blood-CSF barrier. [3H]-Arginine (11.6nM) and [3H]-ADMA (62.5nM) having unidirectional transfer constants (Kin) into the frontal cortex of 5.84±0.86 and 2.49±0.35 μl.min-1.g-1, respectively, and into the CSF of 1.08±0.24 and 2.70±0.90 μl.min-1.g-1, respectively. In addition, multiple-time uptake studies revealed the presence of CNS-to-blood efflux of ADMA. Self- and cross-inhibition studies indicated the presence of transporters at the BBB and the blood-CSF barriers for both amino acids, which were shared to some degree. Importantly, these results are the first to demonstrate: (i) saturable transport of [3H]-ADMA at the blood-CSF barrier (choroid plexus) and (ii) a significant CNS to blood efflux of [3H]-ADMA. Our results suggest that the arginine paradox, in other words the clinical observation that NO-deficient patients respond well to oral supplementation withL-arginine even though the plasma concentration is easily sufficient to saturate endothelial NOS, could be related to ADMA transport.
Serotonin-2B receptor (5-HT2BR) expression and binding in the brain of ageing APPswe/PS1de9transgenic mice and in human Alzheimer’s Disease brain tissue
Authors: Anzalone Marco , Karam Sarmad A. , Briting Sanne R. R. , Petersen Sussanne , Thomsen Majken B. , Landau Anne M. , Finsen Bente , Metaxas Athanasios 
Published: June 2024

AbstractAlthough evidence of dysregulation in central serotonergic signaling is widespread in Alzheimer’s disease (AD), relatively little is known about the specific involvement of the serotonin-2B receptor (5-HT2BR) subtype. Here, we assessed 5-HT2BR expression and binding in brain tissue fromAPPswe/PS1dE9transgenic (TG) mice and AD patients. 5-HT2BR mRNA was measured by RT-qPCR in 3-to >18-month-old TG and wild-type (WT) littermate mice (n=3-8), and in middle frontal gyrus samples from female, AD and control subjects (n=7-10). The density of 5-HT2BRs was measured by autoradiography using 1 nM [3H]RS127445 and 1 μM LY266097. In both mouse and human samples, 5-HT2BR mRNA was detectable after 33 amplification cycles. Levels in WT mice, not TG mice, increased with age, and were higher in AD patients compared to control subjects. [3H]RS127445 binding was low in the mouse brain, detected after 3 months of age. 5-HT2BR density was overall lower in the hippocampus of TG compared to WT mice. Specific binding was too low to be reliably quantified in the human samples. These data provide evidence of a different 5-HT2BR expression and binding in theAPPswe/PS1dE9TG model of AD and AD patients. Studies investigating the functional involvement of the 5-HT2BR in AD are warranted.
Arterial effects of anthracycline: structural and inflammatory assessments in non-human primates and lymphoma patients using18F-FDG positron emission tomography
Authors: Rankin Stephen , Fountain Caitlin , Gemmell Alastair J , Quinn Daire , Henderson Alasdair , McClure John , Small Sandy , Venugopal Balaji , McKay Pamela , Slomka Piotr J , Colville David , Petrie Mark C , Meléndez Giselle C. , Lang Ninian N 
Published: June 2024

ABSTRACTBackgroundAnthracyclines, such as doxorubicin, are important anti-cancer therapies but are associated with arterial injury. Histopathological insights have been limited to small animal models and the role of inflammation in the arterial toxic effects of anthracycline is unclear in humans. Our aims were: 1) To evaluate aortic media fibrosis and injury in non-human primates treated with anthracyclines; 2) To assess the effect of anthracycline on aortic inflammation in patients treated for lymphoma.Methods1) African Green monkeys (AGM) received doxorubicin (30–60 mg/m2/biweekly IV, cumulative dose: 240 mg/m2). Blinded histopathologic analyses of collagen deposition and cell vacuolization in the ascending aorta were performed 15 weeks after the last doxorubicin dose and compared to 5 age- and gender-matched healthy, untreated AGMs. 2) Analysis of the thoracic aorta of patients with diffuse large B-cell lymphoma (DLBCL), at baseline and after doxorubicin exposure, was performed using18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in this observational study. The primary outcome was change in maximal tissue-to-background ratio (TBRmax) of the thoracic aorta from baseline to their end-of-treatment clinical PET/CT.ResultsIn AGMs, doxorubicin exposure was associated with greater aortic fibrosis (collagen deposition: doxorubicin cohort 6.23±0.88% vs. controls 4.67±0.54%; p=0.01) and increased intracellular vacuolization (doxorubicin 66.3 ± 10.1 vs controls 11.5 ± 4.2 vacuoles/field, p<0.0001) than untreated controls.In 101 patients with DLBCL, there was no change in aortic TBRmax after anthracycline exposure (pre-doxorubicin TBRmax 1.46±0.16 vs post-doxorubicin TBRmax 1.44±0.14, p=0.14). The absence of change in TBRmax was consistent across all univariate analyses.ConclusionsIn a large animal model, anthracycline exposure was associated with aortic fibrosis. In patients with lymphoma, anthracycline exposure was not associated with aortic inflammation.Further research is required to elucidate the mechanisms of anthracycline-related vascular harm.
Residual immunity and seasonality of an epidemic
Authors: Chen Siyu , Sankoff David 
Published: June 2024

AbstractWe present a dynamical model of the onset and severity of cyclical epidemic disease taking account only of seasonal boosts of antibody during the infectious season and residual immunity remaining from one season to the next. We also compile data from public health sources on the annual number of cases of influenza A and peak infectivity month over a quarter century. In these data, we discover that there is a negative correlation between the change in number of cases from one year to the next and the shift of peak infectivity month between the two seasons, although this does not extend to a prediction of epidemic timing or case number based on the the previous season’s statistics. Simulating the mathematical model, we discover that there is also a negative correlation between the change in titer from one season to the next and the shift of peak infectivity month between the two seasons, suggesting that the empirical results can be explained by our minimal boost-and-wane model. In addition, the model predicts that suppressing the epidemic for one season, or witnessing a strong surge for one season, both have lasting effects for a number of successive seasons.
Evaluation of Acute Myeloid Leukemia Genomes using Genomic Proximity Mapping
Authors: Yeung Cecilia CS , Eacker Stephen M. , Sala-Torra Olga , Beppu Lan , Woolston David W. , Liachko Ivan , Malig Maika , Stirewalt Derek , Fang Min , Radich Jerald 
Published: June 2024

AbstractBackgroundCytogenetic analysis encompasses a suite of standard-of-care diagnostic testing methods that is routinely applied in cases of acute myeloid leukemia (AML) to assess chromosomal changes that are clinically relevant for risk classification and treatment decisions.ObjectiveIn this study, we assess the use of Genomic Proximity Mapping (GPM) for cytogenomic analysis of AML diagnostic specimens for detection of cytogenetic risk variants included in the European Leukemia Network (ELN) risk stratification guidelines.MethodsArchival patient samples (N=48) from the Fred Hutchinson Cancer Center leukemia bank with historical clinical cytogenetic data were processed for GPM and analyzed with the CytoTerra® cloud-based analysis platform.ResultsGPM showed 100% concordance for all specific variants that have associated impacts on risk stratification as defined by ELN 2022 criteria, and a 72% concordance rate when considering all variants reported by the FH cytogenetic lab. GPM identified 39 additional variants, including variants of known clinical impact, not observed by cytogenetics.ConclusionsGPM is an effective solution for the evaluation of known AML-associated risk variants and a source for biomarker discovery.
Prediction of chronological age from resting-state EEG power in the first three years of life
Authors: An Winko W. , Bhowmik Aprotim C. , Nelson Charles A. , Wilkinson Carol L. 
Published: June 2024

AbstractThe infant brain undergoes rapid and significant developmental changes in the first three years of life. Understanding these changes through the prediction of chronological age using neuroimaging data can provide insights into typical and atypical brain development. We utilized longitudinal resting-state EEG data from 457 typically developing infants, comprising 938 recordings, to develop age prediction models. The multilayer perceptron model demonstrated the highest accuracy with an R2of 0.82 and a mean absolute error of 92.4 days. Aperiodic offset and periodic theta, alpha, and beta power were identified as key predictors of age via Shapley values. Application of the model to EEG data from infants later diagnosed with autism spectrum disorder or Down syndrome revealed significant underestimations of chronological age. This study establishes the feasibility of using EEG to assess brain maturation in early childhood and supports its potential as a clinical tool for early identification of alterations in brain development.
Evaluation of SURUS: a Named Entity Recognition System to Extract Knowledge from Interventional Study Records
Authors: Peeters Casper , Vijverberg Koen , Pouwer Marianne , Westerman Bart , Boot Maikel , Verberne Suzan 
Published: June 2024

BACKGROUNDMedical decision-making is commonly guided by systematic analysis of peer-reviewed scientific literature, published as systematic literature reviews (SLRs). These analyses are cumbersome to conduct as they require large amounts of time and subject matter expertise to be available. Automated extraction of key datapoints from clinical publications could speed up the process of systematic literature review assembly. To this end, we built, trained and validated SURUS, a named entity recognition (NER) system comprised of a Bidirectional Encoder Representations from Transformers (BERT) model trained on a highly granular dataset. The aim of this study was to assess the quality of classification of critical elements in clinical study abstracts by SURUS, in particular the patient, intervention, comparator and outcome (PICO) elements and elements of study design.DATASET & METHODSThe PubMedBERT-based model was trained and evaluated using a dataset of 400 interventional study abstracts, manually annotated by experts using 25 labels with a total of 39,531 annotations according to a strict annotation guideline, with Cohen’s κ inter-annotator agreement of 0.81. We evaluated in-domain quality, and assessed out-of-domain quality of the system by testing it on out-of-domain abstracts of other disease areas and observational study types. Finally, we tested the utility of SURUS by comparing its predictions to expert-assigned PICO and study design (PICOS) classifications.RESULTSThe SURUS NER system achieved an overall F1 score of 0.95, with minor deviation between labels. In addition, SURUS achieved a NER F1 of 0.90 for out-of-domain therapeutic area abstracts and 0.84 for observational study abstracts. Finally, SURUS showed considerable utility when compared to expert-assigned PICOS classifications of interventional studies, with an F1 of 0.89 and a recall of 0.96.CONCLUSIONTo our knowledge, with an F1 score of 0.95, SURUS ranks among the best-performing models available to date for conducting exhaustive systematic literature analyses. A strict guideline and high inter-annotation agreement resulted in high-quality in-domain medical entity of a finetuned BERT-based model, which was largely preserved during extensive out-of-domain evaluation, indicating its utility across other indication areas and study types. Current approaches in the field lack the granularity in training data and versatility demonstrated by the SURUS approach, thereby making the latter the preferred choice for automated extraction and classification tasks in the clinical literature domain. We think that this approach sets a new standard in medical literature analysis and paves the way for creating highly granular datasets of labelled entities that can be used for downstream analysis outside of traditional SLRs.