bluuebunny/crossref_metadata_2025 huggingface dataset:
Olive leaf extract prevents obesity, cognitive decline, and depression and improves exercise capacity in mice
Authors: Mikami Toshio , Kim Jimmy , Park Jonghyuk , Lee Hyowon , Yaicharoen Pongson , Suidasari Sofya , Yokozawa Miki , Yamauchi Ken
Published: June 2021

Obesity is a risk factor for development of metabolic diseases and cognitive decline; therefore, obesity prevention is of paramount importance. Neuronal mitochondrial dysfunction induced by oxidative stress is an important mechanism underlying cognitive decline. Olive leaf extract contains large amounts of oleanolic acid, a transmembrane G protein-coupled receptor 5 (TGR5) agonist, and oleuropein, an antioxidant. Activation of TGR5 results in enhanced mitochondrial biogenesis, which suggests that olive leaf extract may help prevent cognitive decline through its mitochondrial and antioxidant effects. Therefore, we investigated olive leaf extract’s effects on obesity, cognitive decline, depression, and endurance exercise capacity in a mouse model. In physically inactive mice fed a high-fat diet, olive leaf extract administration suppressed increases in fat mass and body weight and prevented cognitive declines, specifically decreased working memory and depressive behaviors. Additionally, olive leaf extract increased endurance exercise capacity under atmospheric and hypoxic conditions. Our study suggests that these promising effects may be related to oleanolic acid’s improvement of mitochondrial function and oleuropein’s increase of antioxidant capacity.
Childhood overeating is associated with adverse cardiometabolic and inflammatory profiles in adolescence
Authors: Hübel Christopher , Herle Moritz , Santos Ferreira Diana L. , Abdulkadir Mohamed , Bryant-Waugh Rachel , Loos Ruth J. F. , Bulik Cynthia M. , Lawlor Deborah A. , Micali Nadia
Published: June 2021

Childhood eating behaviour contributes to the rise of obesity and related noncommunicable disease worldwide. However, we lack a deep understanding of biochemical alterations that can arise from aberrant eating behaviour. In this study, we prospectively associate longitudinal trajectories of childhood overeating, undereating, and fussy eating with metabolic markers at age 16 years to explore adolescent metabolic alterations related to specific eating patterns in the first 10 years of life. Data are from the Avon Longitudinal Study of Parents and Children (n = 3104). We measure 158 metabolic markers with a high-throughput (1H) NMR metabolomics platform. Increasing childhood overeating is prospectively associated with an adverse cardiometabolic profile (i.e., hyperlipidemia, hypercholesterolemia, hyperlipoproteinemia) in adolescence; whereas undereating and fussy eating are associated with lower concentrations of the amino acids glutamine and valine, suggesting a potential lack of micronutrients. Here, we show associations between early behavioural indicators of eating and metabolic markers.
Severe protein deficiency induces hepatic expression and systemic level of FGF21 but inhibits its hypothalamic expression in growing rats
Authors: Moro Joanna , Chaumontet Catherine , Even Patrick C. , Blais Anne , Piedcoq Julien , Gaudichon Claire , Tomé Daniel , Azzout-Marniche Dalila
Published: June 2021

To study, in young growing rats, the consequences of different levels of dietary protein deficiency on food intake, body weight, body composition, and energy balance and to assess the role of FGF21 in the adaptation to a low protein diet. Thirty-six weanling rats were fed diets containing 3%, 5%, 8%, 12%, 15% and 20% protein for three weeks. Body weight, food intake, energy expenditure and metabolic parameters were followed throughout this period. The very low-protein diets (3% and 5%) induced a large decrease in body weight gain and an increase in energy intake relative to body mass. No gain in fat mass was observed because energy expenditure increased in proportion to energy intake. As expected, Fgf21 expression in the liver and plasma FGF21 increased with low-protein diets, but Fgf21 expression in the hypothalamus decreased. Under low protein diets (3% and 5%), the increase in liver Fgf21 and the decrease of Fgf21 in the hypothalamus induced an increase in energy expenditure and the decrease in the satiety signal responsible for hyperphagia. Our results highlight that when dietary protein decreases below 8%, the liver detects the low protein diet and responds by activating synthesis and secretion of FGF21 in order to activate an endocrine signal that induces metabolic adaptation. The hypothalamus, in comparison, responds to protein deficiency when dietary protein decreases below 5%.
Major ocean currents may shape the microbiome of the topshell Phorcus sauciatus in the NE Atlantic Ocean
Authors: Sousa Ricardo , Vasconcelos Joana , Vera-Escalona Iván , Delgado João , Freitas Mafalda , González José A. , Riera Rodrigo
Published: June 2021

Studies on microbial communities are pivotal to understand the role and the evolutionary paths of the host and their associated microorganisms in the ecosystems. Meta-genomics techniques have proven to be one of the most effective tools in the identification of endosymbiotic communities of host species. The microbiome of the highly exploited topshell Phorcus sauciatus was characterized in the Northeastern Atlantic (Portugal, Madeira, Selvagens, Canaries and Azores). Alpha diversity analysis based on observed OTUs showed significant differences among regions. The Principal Coordinates Analysis of beta-diversity based on presence/absence showed three well differentiated groups, one from Azores, a second from Madeira and the third one for mainland Portugal, Selvagens and the Canaries. The microbiome results may be mainly explained by large-scale oceanographic processes of the study region, i.e., the North Atlantic Subtropical Gyre, and specifically by the Canary Current. Our results suggest the feasibility of microbiome as a model study to unravel biogeographic and evolutionary processes in marine species with high dispersive potential.
Inter-vendor performance of deep learning in segmenting acute ischemic lesions on diffusion-weighted imaging: a multicenter study
Authors: Alis Deniz , Yergin Mert , Alis Ceren , Topel Cagdas , Asmakutlu Ozan , Bagcilar Omer , Senli Yeseren Deniz , Ustundag Ahmet , Salt Vefa , Dogan Sebahat Nacar , Velioglu Murat , Selcuk Hakan Hatem , Kara Batuhan , Oksuz Ilkay , Kizilkilic Osman , Karaarslan Ercan
Published: June 2021

There is little evidence on the applicability of deep learning (DL) in the segmentation of acute ischemic lesions on diffusion-weighted imaging (DWI) between magnetic resonance imaging (MRI) scanners of different manufacturers. We retrospectively included DWI data of patients with acute ischemic lesions from six centers. Dataset A (n = 2986) and B (n = 3951) included data from Siemens and GE MRI scanners, respectively. The datasets were split into the training (80%), validation (10%), and internal test (10%) sets, and six neuroradiologists created ground-truth masks. Models A and B were the proposed neural networks trained on datasets A and B. The models subsequently fine-tuned across the datasets using their validation data. Another radiologist performed the segmentation on the test sets for comparisons. The median Dice scores of models A and B were 0.858 and 0.857 for the internal tests, which were non-inferior to the radiologist’s performance, but demonstrated lower performance than the radiologist on the external tests. Fine-tuned models A and B achieved median Dice scores of 0.832 and 0.846, which were non-inferior to the radiologist's performance on the external tests. The present work shows that the inter-vendor operability of deep learning for the segmentation of ischemic lesions on DWI might be enhanced via transfer learning; thereby, their clinical applicability and generalizability could be improved.
Author Correction: Genetic Factors and Genotype-Environment Interactions Contribute to Variation in Melanin Production in the Fungal Pathogen Cryptococcus neoformans
Authors: Samarasinghe Himeshi , Aceituno-Caicedo David , Cogliati Massimo , Kwon-Chung Kyung J. , Rickerts Volker , Velegraki Aristea , Akcaglar Sevim , Xu Jianping
Published: June 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Extraction of Preisach model parameters for fluorite-structure ferroelectrics and antiferroelectrics
Authors: Wang Zheng , Hur Jae , Tasneem Nujhat , Chern Winston , Yu Shimeng , Khan Asif
Published: June 2021

Flourite-structure ferroelectrics (FEs) and antiferroelectrics (AFEs) such as HfO2 and its variants have gained copious attention from the semiconductor community, because they enable complementary metal-oxide-semiconductor (CMOS)-compatible platforms for high-density, high-performance non-volatile and volatile memory technologies. While many individual experiments have been conducted to characterize and understand fluorite-structure FEs and AFEs, there has been little effort to aggregate the information needed to benchmark and provide insights into their properties. We present a fast and robust modeling framework that automatically fits the Preisach model to the experimental polarization ($$Q_{FE}$$

Q

FE

) versus electric field ($$E_{FE}$$

E

FE

) hysteresis characterizations of fluorite-structure FEs. The modifications to the original Preisach model allow the double hysteresis loops in fluorite-structure antiferroelectrics to be captured as well. By fitting the measured data reported in the literature, we observe that ferroelectric polarization and dielectric constant decrease as the coercive field rises in general.
Neuroprotective effect of selumetinib on acrolein-induced neurotoxicity
Authors: Huang Hui-Ju , Wang Hsiang-Tsui , Yeh Ting-Yu , Lin Bo-Wei , Shiao Young-Ji , Lo Yu-Li , Lin Anya Maan-Yuh
Published: June 2021

Abnormal accumulation of acrolein, an α, β unsaturated aldehyde has been reported as one pathological cause of the CNS neurodegenerative diseases. In the present study, the neuroprotective effect of selumetinib (a MEK–ERK inhibitor) on acrolein-induced neurotoxicity was investigated in vitro using primary cultured cortical neurons. Incubation of acrolein consistently increased phosphorylated ERK levels. Co-treatment of selumetinib blocked acrolein-induced ERK phosphorylation. Furthermore, selumetinib reduced acrolein-induced increases in heme oxygenase-1 (a redox-regulated chaperone protein) and its transcriptional factor, Nrf-2 as well as FDP-lysine (acrolein-lysine adducts) and α-synuclein aggregation (a pathological biomarker of neurodegeneration). Morphologically, selumetinib attenuated acrolein-induced damage in neurite outgrowth, including neuritic beading and neurite discontinuation. Moreover, selumetinib prevented acrolein-induced programmed cell death via decreasing active caspase 3 (a hallmark of apoptosis) as well as RIP (receptor-interacting protein) 1 and RIP3 (biomarkers for necroptosis). In conclusion, our study showed that selumetinib inhibited acrolein-activated Nrf-2-HO-1 pathway, acrolein-induced protein conjugation and aggregation as well as damage in neurite outgrowth and cell death, suggesting that selumetinib, a MEK–ERK inhibitor, may be a potential neuroprotective agent against acrolein-induced neurotoxicity in the CNS neurodegenerative diseases.
Mantle-derived helium released through the Japan trench bend-faults
Authors: Park Jin-Oh , Takahata Naoto , Jamali Hondori Ehsan , Yamaguchi Asuka , Kagoshima Takanori , Tsuru Tetsuro , Fujie Gou , Sun Yue , Ashi Juichiro , Yamano Makoto , Sano Yuji
Published: June 2021

Plate bending-related normal faults (i.e. bend-faults) develop at the outer trench-slope of the oceanic plate incoming into the subduction zone. Numerous geophysical studies and numerical simulations suggest that bend-faults play a key role by providing pathways for seawater to flow into the oceanic crust and the upper mantle, thereby promoting hydration of the oceanic plate. However, deep penetration of seawater along bend-faults remains controversial because fluids that have percolated down into the mantle are difficult to detect. This report presents anomalously high helium isotope (3He/4He) ratios in sediment pore water and seismic reflection data which suggest fluid infiltration into the upper mantle and subsequent outflow through bend-faults across the outer slope of the Japan trench. The3He/4He and4He/20Ne ratios at sites near-trench bend-faults, which are close to the isotopic ratios of bottom seawater, are almost constant with depth, supporting local seawater inflow. Our findings provide the first reported evidence for a potentially large-scale active hydrothermal circulation system through bend-faults across the Moho (crust-mantle boundary) in and out of the oceanic lithospheric mantle.
Systematic analysis of safety profile for darunavir and its boosted agents using data mining in the FDA Adverse Event Reporting System database
Authors: Tian Xiaojiang , Yao Yao , He Guanglin , Jia Yuntao , Wang Kejing , Chen Lin
Published: June 2021

This current investigation was aimed to generate signals for adverse events (AEs) of darunavir-containing agents by data mining using the US Food and Drug Administration Adverse Event Reporting System (FAERS). All AE reports for darunavir, darunavir/ritonavir, or darunavir/cobicistat between July 2006 and December 2019 were identified. The reporting Odds Ratio (ROR), proportional reporting ratio (PRR), and Bayesian confidence propagation neural network (BCPNN) were used to detect the risk signals. A suspicious signal was generated only if the results of the three algorithms were all positive. A total of 10,756 reports were identified commonly observed in hepatobiliary, endocrine, cardiovascular, musculoskeletal, gastrointestinal, metabolic, and nutrition system. 40 suspicious signals were generated, and therein 20 signals were not included in the label. Severe high signals (i.e. progressive extraocular muscle paralysis, acute pancreatitis, exfoliative dermatitis, acquired lipodystrophy and mitochondrial toxicity) were identified. In pregnant women, umbilical cord abnormality, fetal growth restriction, low birth weight, stillbirth, premature rupture of membranes, premature birth and spontaneous abortion showed positive signals. Darunavir and its boosted agents induced AEs in various organs/tissues, and were shown to be possibly associated with multiple adverse pregnant conditions. This study highlighted some novel and severe AEs of darunavir which need to be monitored prospectively.
Natural human postural oscillations enhance the empathic response to a facial pain expression in a virtual character
Authors: Treal Thomas , Jackson Philip L. , Jeuvrey Jean , Vignais Nicolas , Meugnot Aurore
Published: June 2021

Virtual reality platforms producing interactive and highly realistic characters are being used more and more as a research tool in social and affective neuroscience to better capture both the dynamics of emotion communication and the unintentional and automatic nature of emotional processes. While idle motion (i.e., non-communicative movements) is commonly used to create behavioural realism, its use to enhance the perception of emotion expressed by a virtual character is critically lacking. This study examined the influence of naturalistic (i.e., based on human motion capture) idle motion on two aspects (the perception of other’s pain and affective reaction) of an empathic response towards pain expressed by a virtual character. In two experiments, 32 and 34 healthy young adults were presented video clips of a virtual character displaying a facial expression of pain while its body was either static (still condition) or animated with natural postural oscillations (idle condition). The participants in Experiment 1 rated the facial pain expression of the virtual human as more intense, and those in Experiment 2 reported being more touched by its pain expression in the idle condition compared to the still condition, indicating a greater empathic response towards the virtual human’s pain in the presence of natural postural oscillations. These findings are discussed in relation to the models of empathy and biological motion processing. Future investigations will help determine to what extent such naturalistic idle motion could be a key ingredient in enhancing the anthropomorphism of a virtual human and making its emotion appear more genuine.
A genome-wide portrait of pervasive drug contaminants
Authors: Ogbede Joseph Uche , Giaever Guri , Nislow Corey
Published: June 2021

Using a validated yeast chemogenomic platform, we characterized the genome-wide effects of several pharmaceutical contaminants, including three N-nitrosamines (NDMA, NDEA and NMBA), two related compounds (DMF and 4NQO) and several of their metabolites. A collection of 4800 non-essential homozygous diploid yeast deletion strains were screened in parallel and the strain abundance was quantified by barcode sequencing. These data were used to rank deletion strains representing genes required for resistance to the compounds to delineate affected cellular pathways and to visualize the global cellular effects of these toxins in an easy-to-use searchable database. Our analysis of the N-nitrosamine screens uncovered genes (via their corresponding homozygous deletion mutants) involved in several evolutionarily conserved pathways, including: arginine biosynthesis, mitochondrial genome integrity, vacuolar protein sorting and DNA damage repair. To investigate why NDMA, NDEA and DMF caused fitness defects in strains lacking genes of the arginine pathway, we tested several N-nitrosamine metabolites (methylamine, ethylamine and formamide), and found they also affected arginine pathway mutants. Notably, each of these metabolites has the potential to produce ammonium ions during their biotransformation. We directly tested the role of ammonium ions in N-nitrosamine toxicity by treatment with ammonium sulfate and we found that ammonium sulfate also caused a growth defect in arginine pathway deletion strains. Formaldehyde, a metabolite produced from NDMA, methylamine and formamide, and which is known to cross-link free amines, perturbed deletion strains involved in chromatin remodeling and DNA repair pathways. Finally, co-administration of N-nitrosamines with ascorbic or ferulic acid did not relieve N-nitrosamine toxicity. In conclusion, we used parallel deletion mutant analysis to characterize the genes and pathways affected by exposure to N-nitrosamines and related compounds, and provide the data in an accessible, queryable database.
Musical novices perform with equal accuracy when learning to drum alone or with a peer
Authors: Schiavio Andrea , Stupacher Jan , Xypolitaki Elli , Parncutt Richard , Timmers Renee
Published: June 2021

The capacity of expert musicians to coordinate with each other when playing in ensembles or rehearsing has been widely investigated. However, little is known about the ability of novices to achieve satisfactory coordinated behaviour when making music together. We tested whether performance accuracy differs when novices play a newly learned drumming pattern with another musically untrained individual (duo group) or alone (solo group). A comparison between musical outcomes of the two groups revealed no significant differences concerning performative accuracy. An additional, exploratory examination of the degree of mutual influence between members of the duos suggested that they reciprocally affected each other when playing together. These findings indicate that a responsive auditory feedback involving surprises introduced by human errors could be part of pedagogical settings that employ repetition or imitation, thereby facilitating coordination among novices in a less prescribed fashion.
Sensitive detection and quantification of SARS-CoV-2 in saliva
Authors: Abasiyanik Mustafa Fatih , Flood Blake , Lin Jing , Ozcan Sefika , Rouhani Sherin J. , Pyzer Athalia , Trujillo Jonathan , Zhen Chaojie , Wu Ping , Jumic Stephen , Wang Andrew , Gajewski Thomas F. , Wang Peng , Hartley Madeline , Ameti Bekim , Niemiec Rachael , Fernando Marian , Mishra Vasudha , Savage Peter , Aydogan Bulent , Bethel Cindy , Matushek Scott , Beavis Kathleen G. , Agrawal Nishant , Segal Jeremy , Tay Savaş , Izumchenko Evgeny
Published: June 2021

Saliva has significant advantages as a test medium for detection of SARS-CoV-2 infection in patients, such as ease of collection, minimal requirement of supplies and trained personnel, and safety. Comprehensive validation in a large cohort of prospectively collected specimens with unknown SARS-CoV-2 status should be performed to evaluate the potential and limitations of saliva-based testing. We developed a saliva-based testing pipeline for detection of SARS-CoV-2 nucleic acids using real-time reverse transcription PCR (RT-PCR) and droplet digital PCR (ddPCR) readouts, and measured samples from 137 outpatients tested at a curbside testing facility and 29 inpatients hospitalized for COVID-19. These measurements were compared to the nasal swab results for each patient performed by a certified microbiology laboratory. We found that our saliva testing positively detects 100% (RT-PCR) and 93.75% (ddPCR) of curbside patients that were identified as SARS-CoV-2 positive by the Emergency Use Authorization (EUA) certified nasal swab testing assay. Quantification of viral loads by ddPCR revealed an extremely wide range, with 1 million-fold difference between individual patients. Our results demonstrate for both community screening and hospital settings that saliva testing reliability is on par with that of the nasal swabs in detecting infected cases, and has potential for higher sensitivity when combined with ddPCR in detecting low-abundance viral loads that evade traditional testing methods.
Diverse and nonlinear influences of built environment factors on COVID-19 spread across townships in China at its initial stage
Authors: Ma Shuang , Li Shuangjin , Zhang Junyi
Published: June 2021

The built environment can contribute to the spread of the novel coronavirus disease (COVID-19) by facilitating human mobility and social contacts between infected and uninfected individuals. However, mobility data capturing detailed interpersonal transmission at a large scale are not available. In this study, we aimed to objectively assess the influence of key built environment factors, which create spaces for activities—“inferred activity” rather than “actually observed activity”—on the spread of COVID-19 across townships in China at its initial stage through a random forest approach. Taking data for 2994 township-level administrative units, the spread is measured by two indicators: the ratio of cumulative infection cases (RCIC), and the coefficient of variation of infection cases (CVIC) that reflects the policy effect in the initial stage of the spread. Accordingly, we selected 19 explanatory variables covering built environment factors (urban facilities, land use, and transportation infrastructure), the level of nighttime activities, and the inter-city population flow (from Hubei Province). We investigated the spatial agglomerations based on an analysis of bivariate local indicators of spatial association between RCIC and CVIC. We found spatial agglomeration (or positive spatial autocorrelations) of RCIC and CVIC in about 20% of all townships under study. The density of convenience shops, supermarkets and shopping malls (DoCSS), and the inter-city population flow (from Hubei Province) are the two most important variables to explain RCIC, while the population flow is the most important factor in measuring policy effects (CVIC). When the DoCSS gets to 21/km2, the density of comprehensive hospitals to 0.7/km2, the density of road intersections to 72/km2, and the density of gyms and sports centers to 2/km2, their impacts on RCIC reach their maximum and remain constant with further increases in the density values. Stricter policy measures should be taken at townships with a density of colleges and universities higher than 0.5/km2 or a density of comprehensive hospitals higher than 0.25/km2 in order to effectively control the spread of COVID-19.
Evaluation of the Intel RealSense T265 for tracking natural human head motion
Authors: Hausamann Peter , Sinnott Christian B. , Daumer Martin , MacNeilage Paul R.
Published: June 2021

Accurate and robust tracking of natural human head motion in natural environments is important for a number of applications including virtual and augmented reality, clinical diagnostics, as well as basic scientific research. IMU provide a versatile solution for recording inertial data including linear acceleration and angular velocity, but reconstructing head position is difficult or impossible. This problem can be solved by incorporating visual data using a technique known as visual-inertial simultaneous localization and mapping (VI-SLAM). A recently released commercial solution, the Intel RealSense T265, uses a proprietary VI-SLAM algorithm to estimate linear and angular position and velocity, but the performance of this device for tracking of natural human head motion in natural environments has not yet been comprehensively evaluated against gold-standard methods. In this study, we used a wide range of metrics to evaluate the performance of the T265 with different walking speeds in different environments, both indoor and outdoor, against two gold-standard methods, an optical tracking system and a so-called perambulator. Overall, we find that performance of the T265 relative to these gold-standard methods is most accurate for slow to normal walking speeds in small- to medium-sized environments. The suitability of this device for future scientific studies depends on the application; data presented here can be useful in making that determination.
Immune modulation via adipose derived Mesenchymal Stem cells is driven by donor sex in vitro
Authors: Mckinnirey Flyn , Herbert Benjamin , Vesey Graham , McCracken Sharon
Published: June 2021

Mesenchymal stromal/stem cells (MSCs) are currently being used in clinical trials as proposed treatments for a large range of genetic, immunological, orthopaedic, cardiovascular, endocrine and neurological disorders. MSCs are potent anti-inflammatory mediators which are considered immune evasive and employ a large range of secreted vesicles to communicate and repair damaged tissue. Despite their prolific use in therapy, sex specific mechanism of action is rarely considered as a potential confounding factor for use. The purpose of this study was to examine the potency and functionality of both female and male adipose derived MSCs in order to gain further insights into donor selection. Methods MSC were expanded to passage 4, secretome was harvested and stored at − 80c. To assess potency MSC were also primed and assessed via functional immune assays, ELISA, multiplex and immunophenotyping. Results Female MSCs (fMSC), consistently suppressed Peripheral blood mononuclear cell (PBMC) proliferation significantly (p < 0.0001) more than male MSC (mMSC). In co-culture mPBMCs, showed 60.7 ± 15.6% suppression with fMSCs compared with 22.5 ± 13.6% suppression with mMSCs. Similarly, fPBMCs were suppressed by 67.9 ± 10.4% with fMSCs compared to 29.4 ± 9.3% with mMSCs. The enhanced immunosuppression of fMSCs was attributed to the production of higher concentrations of the anti-inflammatory mediators such as IDO1 (3301 pg/mL vs 1699 pg/mL) and perhaps others including IL-1RA (1025 pg/mL vs 701 pg/mL), PGE-2 (6142 pg/mL vs 2448 pg/mL) and prolonged expression of VCAM-1 post activation relative to mMSCs. In contrast, mMSCs produces more inflammatory G-CSF than fMSCs (806 pg/mL vs 503 pg/mL). Moreover, IDO1 expression was correlated to immune suppression and fMSCs, but not mMSCs induced downregulation of the IL-2 receptor and sustained expression of the early T cell activation marker, CD69 in PBMCs further highlighting the differences in immunomodulation potentials between the sexes. Conclusion In conclusion, our data shows that female MSC are more potent in vitro than their male counterparts. The inability of male MSC to match female MSC driven immunomodulation and to use the inflammatory microenvironment to their advantage is evident and is likely a red flag when using allogeneic male MSC as a therapeutic for disease states.
Thermal injury induces early blood vessel occlusion in a porcine model of brass comb burn
Authors: Wang Jing , Wang Cheng Z. , Salsbury John R. , Zhang Jianzi , Enkhbaatar Perenlei , Herndon David N. , El Ayadi Amina , Ansari Naseem H.
Published: June 2021

Burn wound progression is an important determinant of patient morbidity and mortality after injury. In this study, we used the brass comb contact burn to determine burn wound vertical injury progression with a focus on blood vessel occlusion and endothelial cell death. Class A 3-month-old Yorkshire pigs received a brass comb contact burn. Burn wounds were sampled at 0, 30 min, 1, 2, 4, and 24 h. Hematoxylin Phloxin Saffron staining and vimentin immunostaining were performed to determine the depth of blood vessel occlusion and endothelial cell death, respectively. The depth of blood vessel occlusion increased by 30 min (p < 0.005) and peaked by 1 to 4 h (p > 0.05). The depth of endothelial cell death risen to a plateau at 30 min (p < 0.005) to 2 h and then peaked at 24 h (p < 0.03). We observed a progression of blood vessel occlusion and vascular endothelial cell death from the middle of the dermis to the hypodermis within 2 h to 4 h after the initial injury, namely a progression from a second-degree (partial thickness) to third-degree (full thickness) burn. These data suggest that therapeutic interventions during this time window may provide a better outcome by reducing or preventing vertical progression of blood vascular occlusion or endothelial cell death.
Embedding supervised exercise training for men on androgen deprivation therapy into standard prostate cancer care: a feasibility and acceptability study (the STAMINA trial)
Authors: Reale Sophie , Turner Rebecca R. , Sutton Eileen , Steed Liz , Taylor Stephanie J. C. , Morrissey Dylan , Doherty Patrick , Greenfield Diana M. , Collinson Michelle , Hewison Jenny , Brown Janet , Ibeggazene Saïd , Mason Malcolm , Rosario Derek J. , Bourke Liam
Published: June 2021

Lifestyle interventions involving exercise training offset the adverse effects of androgen deprivation therapy in men with prostate cancer. Yet provision of integrated exercise pathways in cancer care is sparse. This study assessed the feasibility and acceptability of an embedded supervised exercise training intervention into standard prostate cancer care in a single-arm, multicentre prospective cohort study. Feasibility included recruitment, retention, adherence, fidelity and safety. Acceptability of behaviourally informed healthcare and exercise professional training was assessed qualitatively. Despite the imposition of lockdown for the COVID-19 pandemic, referral rates into and adherence to, the intervention was high. Of the 45 men eligible for participation, 79% (n = 36) received the intervention and 47% (n = 21) completed the intervention before a government mandated national lockdown was enforced in the United Kingdom. Patients completed a mean of 27 min of aerobic exercise per session (SD = 3.48), at 77% heart rate maximum (92% of target dose), and 3 sets of 10 reps of 3 resistance exercises twice weekly for 12 weeks, without serious adverse event. The intervention was delivered by 26 healthcare professionals and 16 exercise trainers with moderate to high fidelity, and the intervention was deemed highly acceptable to patients. The impact of societal changes due to the pandemic on the delivery of this face-to-face intervention remain uncertain but positive impacts of embedding exercise provision into prostate cancer care warrant long-term investigation.
Independent duplications of the Golgi phosphoprotein 3 oncogene in birds
Authors: Opazo Juan C. , Vandewege Michael W. , Gutierrez Javier , Zavala Kattina , Vargas-Chacoff Luis , Morera Francisco J. , Mardones Gonzalo A.
Published: June 2021

Golgi phosphoprotein 3 (GOLPH3) was the first reported oncoprotein of the Golgi apparatus. It was identified as an evolutionarily conserved protein upon its discovery about 20 years ago, but its function remains puzzling in normal and cancer cells. The GOLPH3 gene is part of a group of genes that also includes the GOLPH3L gene. Because cancer has deep roots in multicellular evolution, studying the evolution of the GOLPH3 gene family in non-model species represents an opportunity to identify new model systems that could help better understand the biology behind this group of genes. The main goal of this study is to explore the evolution of the GOLPH3 gene family in birds as a starting point to understand the evolutionary history of this oncoprotein. We identified a repertoire of three GOLPH3 genes in birds. We found duplicated copies of the GOLPH3 gene in all main groups of birds other than paleognaths, and a single copy of the GOLPH3L gene. We suggest there were at least three independent origins for GOLPH3 duplicates. Amino acid divergence estimates show that most of the variation is located in the N-terminal region of the protein. Our transcript abundance estimations show that one paralog is highly and ubiquitously expressed, and the others were variable. Our results are an example of the significance of understanding the evolution of the GOLPH3 gene family, especially for unraveling its structural and functional attributes.
Species variations in tenocytes’ response to inflammation require careful selection of animal models for tendon research
Authors: Oreff Gil Lola , Fenu Michele , Vogl Claus , Ribitsch Iris , Jenner Florien
Published: June 2021

For research on tendon injury, many different animal models are utilized; however, the extent to which these species simulate the clinical condition and disease pathophysiology has not yet been critically evaluated. Considering the importance of inflammation in tendon disease, this study compared the cellular and molecular features of inflammation in tenocytes of humans and four common model species (mouse, rat, sheep, and horse). While mouse and rat tenocytes most closely equalled human tenocytes’ low proliferation capacity and the negligible effect of inflammation on proliferation, the wound closure speed of humans was best approximated by rats and horses. The overall gene expression of human tenocytes was most similar to mice under healthy, to horses under transient and to sheep under constant inflammatory conditions. Humans were best matched by mice and horses in their tendon marker and collagen expression, by horses in extracellular matrix remodelling genes, and by rats in inflammatory mediators. As no single animal model perfectly replicates the clinical condition and sufficiently emulates human tenocytes, fit-for-purpose selection of the model species for each specific research question and combination of data from multiple species will be essential to optimize translational predictive validity.
Well-scale demonstration of distributed pressure sensing using fiber-optic DAS and DTS
Authors: Ekechukwu Gerald K. , Sharma Jyotsna
Published: June 2021

In this study, we used data from optical fiber-based Distributed Acoustic Sensor (DAS) and Distributed Temperature Sensor (DTS) to estimate pressure along the fiber. A machine learning workflow was developed and demonstrated using experimental datasets from gas–water flow tests conducted in a 5163-ft deep well instrumented with DAS, DTS, and four downhole pressure gauges. The workflow is successfully demonstrated on two experimental datasets, corresponding to different gas injection volumes, backpressure, injection methods, and water circulation rates. The workflow utilizes the random forest algorithm and involves a two-step process for distributed pressure prediction. In the first step, single-depth predictive modeling is performed to explore the underlying relationship between the DAS (in seven different frequency bands), DTS, and the gauge pressures at the four downhole locations. The single-depth analysis showed that the low-frequency components (< 2 Hz) of the DAS data, when combined with DTS, consistently demonstrate a superior capability in predicting pressure as compared to the higher frequency bands for both the datasets achieving an average coefficient of determination (or R2) of 0.96. This can be explained by the unique characteristic of low-frequency DAS which is sensitive to both the strain and temperature perturbations. In the second step, the DTS and the low-frequency DAS data from two gauge locations were used to predict pressures at different depths. The distributed pressure modeling achieved an average R2 of 0.95 and an average root mean squared error (RMSE) of 24 psi for the two datasets across the depths analyzed, demonstrating the distributed pressure measurement capability using the proposed workflow. A majority of the current DAS applications rely on the higher frequency components. This study presents a novel application of the low-frequency DAS combined with DTS for distributed pressure measurement.
Integrating spatial analysis and questionnaire survey to better understand human-onager conflict in Southern Iran
Authors: Mohammadi Alireza , Almasieh Kamran , Wan Ho Yi , Nayeri Danial , Alambeigi Amir , Ransom Jason I. , Cushman Samuel A.
Published: June 2021

Southern Iran is a conservation priority area for the endangered Persian onager (Equus hemionus onager), which is threatened by habitat fragmentation and conflict with local communities. To better understand factors that influence onager conservation, we administered a questionnaire in local communities to survey their ecological knowledge, personal experience related to onager, and attitudes toward traditional solutions for reducing crop damage by onager. In addition, we used resistant kernel and factorial least-cost path analyses to identify core areas and corridors for onager movement, and spatial randomization of vehicle collisions and crossing locations to test the predictive ability of resistant kernel and factorial least-cost path predictions of movement. We found that local communities that were knowledgeable about onagers experienced less crop damage from onager compared with those who used traditional methods. Habitat connectivity models revealed that core areas of movement are highly concentrated at the center of protected areas. Some sections of core areas have been cut off by roads where most vehicle collisions with onagers occurred. We propose that effective onager conservation will require integrated landscape-level management to reduce mortality risk, protection of core areas and corridors, development of mitigation strategies to reduce vehicle collisions, and conflict mediation between local communities and onagers.
Impaired regulation of heart rate and sinoatrial node function by the parasympathetic nervous system in type 2 diabetic mice
Authors: Liu Yingjie , Jansen Hailey J. , Krishnaswamy Pooja S. , Bogachev Oleg , Rose Robert A.
Published: June 2021

Heart rate (HR) and sinoatrial node (SAN) function are modulated by the autonomic nervous system. HR regulation by the parasympathetic nervous system (PNS) is impaired in diabetes mellitus (DM), which is denoted cardiovascular autonomic neuropathy. Whether blunted PNS effects on HR in type 2 DM are related to impaired responsiveness of the SAN to PNS agonists is unknown. This was investigated in type 2 diabetic db/db mice in vivo and in isolated SAN myocytes. The PNS agonist carbachol (CCh) had a smaller inhibitory effect on HR, while HR recovery time after CCh removal was accelerated in db/db mice. In isolated SAN myocytes CCh reduced spontaneous action potential firing frequency but this effect was reduced in db/db mice due to blunted effects on diastolic depolarization slope and maximum diastolic potential. Impaired effects of CCh occurred due to enhanced desensitization of the acetylcholine-activated K+ current (IKACh) and faster IKACh deactivation. IKACh alterations were reversed by inhibition of regulator of G-protein signaling 4 (RGS4) and by the phospholipid PIP3. SAN expression of RGS4 was increased in db/db mice. Impaired PNS regulation of HR in db/db mice occurs due to reduced responsiveness of SAN myocytes to PNS agonists in association with enhanced RGS4 activity.
The effect of congenital blindness on resting-state functional connectivity revisited
Authors: Guerreiro Maria J. S. , Linke Madita , Lingareddy Sunitha , Kekunnaya Ramesh , Röder Brigitte
Published: June 2021

Lower resting-state functional connectivity (RSFC) between ‘visual’ and non-‘visual’ neural circuits has been reported as a hallmark of congenital blindness. In sighted individuals, RSFC between visual and non-visual brain regions has been shown to increase during rest with eyes closed relative to rest with eyes open. To determine the role of visual experience on the modulation of RSFC by resting state condition—as well as to evaluate the effect of resting state condition on group differences in RSFC—, we compared RSFC between visual and somatosensory/auditory regions in congenitally blind individuals (n = 9) and sighted participants (n = 9) during eyes open and eyes closed conditions. In the sighted group, we replicated the increase of RSFC between visual and non-visual areas during rest with eyes closed relative to rest with eyes open. This was not the case in the congenitally blind group, resulting in a lower RSFC between ‘visual’ and non-‘visual’ circuits relative to sighted controls only in the eyes closed condition. These results indicate that visual experience is necessary for the modulation of RSFC by resting state condition and highlight the importance of considering whether sighted controls should be tested with eyes open or closed in studies of functional brain reorganization as a consequence of blindness.
Association between aphasia severity and brain network alterations after stroke assessed using the electroencephalographic phase synchrony index
Authors: Kawano Teiji , Hattori Noriaki , Uno Yutaka , Hatakenaka Megumi , Yagura Hajime , Fujimoto Hiroaki , Nagasako Michiko , Mochizuki Hideki , Kitajo Keiichi , Miyai Ichiro
Published: June 2021

Electroencephalographic synchrony can help assess brain network status; however, its usefulness has not yet been fully proven. We developed a clinically feasible method that combines the phase synchrony index (PSI) with resting-state 19-channel electroencephalography (EEG) to evaluate post-stroke motor impairment. In this study, we investigated whether our method could be applied to aphasia, a common post-stroke cognitive impairment. This study included 31 patients with subacute aphasia and 24 healthy controls. We assessed the expressive function of patients and calculated the PSIs of three motor language-related regions: frontofrontal, left frontotemporal, and right frontotemporal. Then, we evaluated post-stroke network alterations by comparing PSIs of the patients and controls and by analyzing the correlations between PSIs and aphasia scores. The frontofrontal PSI (beta band) was lower in patients than in controls and positively correlated with aphasia scores, whereas the right frontotemporal PSI (delta band) was higher in patients than in controls and negatively correlated with aphasia scores. Evaluation of artifacts suggests that this association is attributed to true synchrony rather than spurious synchrony. These findings suggest that post-stroke aphasia is associated with alternations of two different networks and point to the usefulness of EEG PSI in understanding the pathophysiology of aphasia.
Multiplex protein profiling method for extracellular vesicle protein detection
Authors: Sun Li , Meckes David G.
Published: June 2021

Extracellular vesicles (EVs) are small nanometer-sized membrane sacs secreted into biological fluids by all cells. EVs encapsulate proteins, RNAs and metabolites from its origin cell and play important roles in intercellular communication events. Over the past decade, EVs have become a new emerging source for cancer diagnostics. One of the challenges in the study of EVs and there utility as diagnostic biomarkers is the amount of EVs needed for traditional protein analysis methods. Here, we present a new immuno-PCR method that takes advantage of commercially available TotalSeq antibodies containing DNA conjugated oligos to identify immobilized protein analysts using real-time qPCR. Using this method, we demonstrate that multiple EV surface proteins can be profiled simultaneously with high sensitivity and specificity. This approach was also successfully applied to similar protocol using cell and serum samples. We further described the development of a micro-size exclusion chromatography method, where we were able to detect EV surface proteins with as little as 10 μL of human serum when combined with immuno-PCR. Overall, these results show that the immuno-PCR method results in rapid detection of multiple EV markers from small sample volumes in a single tube.
On the permittivity of titanium dioxide
Authors: Bonkerud Julie , Zimmermann Christian , Weiser Philip Michael , Vines Lasse , Monakhov Eduard V.
Published: June 2021

Conductive rutile TiO2 has received considerable attention recently due to multiple applications. However, the permittivity in conductive, reduced or doped TiO2 appears to cause controversy with reported values in the range 100–10,000. In this work, we propose a method for measurements of the permittivity in conductive, n-type TiO2 that involves: (i) hydrogen ion-implantation to form a donor concentration peak at a known depth, and (ii) capacitance–voltage measurements for donor profiling. We cannot confirm the claims stating an extremely high permittivity of single crystalline TiO2. On the contrary, the permittivity of conductive, reduced single crystalline TiO2 is similar to that of insulating TiO2 established previously, with a Curie–Weiss type temperature dependence and the values in the range 160–240 along with the c-axis.
Swedish intrauterine growth reference ranges for estimated fetal weight
Authors: Lindström Linda , Ageheim Mårten , Axelsson Ove , Hussain-Alkhateeb Laith , Skalkidou Alkistis , Wikström Anna-Karin , Bergman Eva
Published: June 2021

Fetal growth restriction is a strong risk factor for perinatal morbidity and mortality. Reliable standards are indispensable, both to assess fetal growth and to evaluate birthweight and early postnatal growth in infants born preterm. The aim of this study was to create updated Swedish reference ranges for estimated fetal weight (EFW) from gestational week 12–42. This prospective longitudinal multicentre study included 583 women without known conditions causing aberrant fetal growth. Each woman was assigned a randomly selected protocol of five ultrasound scans from gestational week 12 + 3 to 41 + 6. Hadlock’s 3rd formula was used to estimate fetal weight. A two-level hierarchical regression model was employed to calculate the expected median and variance, expressed in standard deviations and percentiles, for EFW. EFW was higher for males than females. The reference ranges were compared with the presently used Swedish, and international reference ranges. Our reference ranges had higher EFW than the presently used Swedish reference ranges from gestational week 33, and higher median, 2.5th and 97.5th percentiles from gestational week 24 compared with INTERGROWTH-21st. The new reference ranges can be used both for assessment of intrauterine fetal weight and growth, and early postnatal growth in children born preterm.