bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short‐term high‐fat diet feeding of mice suppresses catecholamine‐stimulated Ca2+ signalling in hepatocytes and intact liver
Authors: Brumer Robert P. , Corrêa‐Velloso Juliana C. , Thomas Samantha J. , Sandiford Oleta A. , Thomas Andrew P. , Bartlett Paula J. 
Published: March 2023

AbstractExcess consumption of carbohydrates, fat and calories leads to non‐alcoholic fatty liver disease (NAFLD) and hepatic insulin resistance; these are major factors in the pathogenesis of type II diabetes. Hormones and catecholamines acting through G‐protein coupled receptors (GPCRs) linked to phospholipase C (PLC) and increases in cytosolic Ca2+ ([Ca2+]c) regulate many metabolic functions of the liver. In the intact liver, catabolic hormones such as glucagon, catecholamines and vasopressin integrate and synergize to regulate the frequency and extent to which [Ca2+]c waves propagate across hepatic lobules to control metabolism. Dysregulation of hepatic Ca2+ homeostasis has been implicated in the development of metabolic disease, but changes in hepatic GPCR‐dependent Ca2+ signalling have been largely unexplored in this context. We show that short‐term, 1‐week, high‐fat diet (HFD) feeding of mice attenuates noradrenaline‐stimulated Ca2+ signalling, reducing the number of cells responding and suppressing the frequency of [Ca2+]c oscillations in both isolated hepatocytes and intact liver. The 1‐week HFD feeding paradigm did not change basal Ca2+ homeostasis; endoplasmic reticulum Ca2+ load, store‐operated Ca2+ entry and plasma membrane Ca2+ pump activity were unchanged compared to low‐fat diet (LFD)‐fed controls. However, noradrenaline‐induced inositol 1,4,5‐trisphosphate production was significantly reduced after HFD feeding, demonstrating an effect of HFD on receptor‐stimulated PLC activity. Thus, we have identified a lesion in the PLC signalling pathway induced by short‐term HFD feeding, which interferes with hormonal Ca2+ signalling in isolated hepatocytes and the intact liver. These early events may drive adaptive changes in signalling, which lead to pathological consequences in fatty liver disease.
imageKey points
Non‐alcoholic fatty liver disease (NAFLD) is a growing epidemic.
In healthy liver, the counteracting effects of catabolic and anabolic hormones regulate metabolism and energy storage as fat. Hormones and catecholamines promote catabolic metabolism via increases in cytosolic Ca2+ ([Ca2+]c).
We show that 1 week high‐fat diet (HFD) feeding of mice attenuated the Ca2+ signals induced by physiological concentrations of noradrenaline. Specifically, HFD suppressed the normal pattern of periodic [Ca2+]c oscillations in isolated hepatocytes and disrupted the propagation of intralobular [Ca2+]c waves in the intact perfused liver.
Short‐term HFD inhibited noradrenaline‐induced inositol 1,4,5‐trisphosphate generation, but did not change basal endoplasmic reticulum Ca2+ load or plasma membrane Ca2+ fluxes.
We propose that impaired Ca2+ signalling plays a key role in the earliest phases of the etiology of NAFLD, and is responsible for many of the ensuing metabolic and related dysfunctional outcomes at the cellular and whole tissue level.
Effect of Force Field on Deformation and Migration of Single Cell With Orientation Controlled by Micro-Striped Topography Patterns
Authors: Hashimoto Shigehiro , Kishimoto Kazuya 
Published: March 2023

AbstractThe effect of the force field parallel to the surface of the scaffold plate on cell activity (deformation, migration) has been studied in vitro. Cell orientation was aligned by microtopography patterns (striped ridgelines; height 0.7 μm, width 3 μm, spacing 3 μm) on the scaffold plane. Three compartments were designed with different angles (0 deg, 45 deg, and 90 deg) between the longitudinal direction of the ridge and the direction of the force field. Osteoblasts (MC3T3-E1; osteoblast precursor cell line derived from mouse calvaria) were used in the experiment. After applying a force field for 5 h, the position and contour of each cell were tracked on time-lapse microscopy images for 48 h. Experimental results show that force fields not parallel to the major axis of the cell activate subsequent actions (deformation, migration) of the cell. The effect is maintained for 48 h even if the cells move to different areas of the topography pattern.
Onto Quantifying Unsteady Propulsion Characteristics Using Momentum and Energy Control Volume Assessments
Authors: Loubimov George , Kinzel Michael 
Published: March 2023

AbstractThis effort presents a novel approach to interrogate efficiency for unsteady, undulating propulsion using variable momentum and energy conservation (VMEC) assessments. These integral approaches utilize large amounts of data from computational fluid dynamics (CFD) to address present difficulties associated with separating thrust from drag associated with propelling bodies as well as potentially resolve issues associated with defining a nonzero efficiency for a body in self-propulsion. Such a fundamental issue is addressed through strategic control volume assessments of the momentum and energy conservation equations. In this work, the Method of Manufactured Solutions (MMS) is used to verify the integral-based evaluation approach and better quantify output. The MMS results indicate the method is valid and that one can separate work associated with lift and drag from the energy budget. This separation procedure provides a means to separate propulsive and drag forces. The effort then studies previously validated CFD simulations of heaving and pitching foils to provide insight associated with separating axial forces into their thrust and drag components for highly complex systems. The effort then presents a new efficiency metric that can obtain nonzero efficiencies in self-propulsion. Overall, the results indicate that energy-based assessments provide insight that is a step forward toward isolating loss from propulsive mechanisms and developing proper metrics of efficiency.
The Continued Olympic Agenda Shift: A Case Study of the Time on Camera for Men and Women During the 2022 Beijing Olympics on NBC
Authors: Arth Zachary W. , Angelini James R. , Gentile Patrick C. , Hard Andrew W. 
Published: March 2023

This case study assessed the differences in time on camera dedicated to men and women athletes at the 2022 Beijing Winter Olympics. An analysis of the entirety of the programming on the the American broadcast television company NBC, including the prime-time broadcasts, the daytime programming, and the additional nightly content, yielded nearly 185 hr of coded Olympic content. When excluding mixed-sex events, in the 61.5 hr of prime-time coverage, women received 60.05% of the time on camera. During the non-prime-time coverage, which spanned 123 hr, men received the majority of clock time, accounting for 51.6% of coverage. In addition, differences by sport were uncovered, with the major differences occurring in alpine skiing, which saw more women’s coverage regardless of broadcast. In contrast, women received more coverage in freestyle skiing and snowboarding during the prime-time broadcast, but men were more emphasized in these competitions during the non-prime-time content. Utilizing agenda setting as the theoretical framework for this case study, ramifications for these broadcast trends and differences are discussed.
Effects of Gluteus Medius and Biceps Femoris Stimulation on Reduction of Knee Abduction Moment During a Landing Task
Authors: Wang Dan , Wang Man , Chu Vikki Wing-Shan , Yung Patrick Shu-Hang , Fong Daniel T.P. 
Published: March 2023

Anterior cruciate ligament injury prevention should focus primarily on reduction of the knee abduction moment (KAM) in landing tasks. Gluteus medius and hamstring forces are considered to decrease KAM during landing. The effects of different muscle stimulations on KAM reduction were compared using 2 electrode sizes (standard 38 cm2 and half size 19 cm2) during a landing task. Twelve young healthy female adults (22.3 [3.6] y, 1.62 [0.02] m, 50.2 [4.7] kg) were recruited. KAM was calculated under 3 conditions of muscle stimulation (gluteus medius, biceps femoris, and both gluteus medius, and biceps femoris) using 2 electrode sizes, respectively versus no stimulation during a landing task. A repeated-measures analysis of variance determined that KAM differed significantly among stimulation conditions and post hoc analysis revealed that KAM was significantly decreased in conditions of stimulating either the gluteus medius (P < .001) or the biceps femoris (P < .001) with the standard electrode size, and condition of stimulating both gluteus medius and biceps femoris with half-size electrode (P = .012) when compared with the control condition. Therefore, stimulation on the gluteus medius, the biceps femoris, or both muscles could be implemented for the examination of anterior cruciate ligament injury potential.
Prefrontal Cortex Activity in Siblings With and Without Developmental Coordination Disorder: An Exploratory Study
Authors: Plumb Mandy S. , Charity Megan , Milla Kimberly , Bodt Barry , Getchell Nancy 
Published: March 2023

Background: Previous research suggests that children with or at risk of probable developmental coordination disorder (pDCD) activate different areas of the brain when performing certain motor skills compared with typically developing (TD) children. This study used functional near-infrared spectroscopy to compare prefrontal cortex (PFC) activity in TD and pDCD during the completion of manual (three-dimensional [3D]) and computerized versions (two-dimensional) of the Tower of Hanoi (ToH) puzzle. Method: A total of 12 children (TD and pDCD; one female/11 male, , SD ± 1.52 years) performed the two-dimensional and 3D conditions of the ToH disk tasks, with equivalent executive function but different motor requirements, with functional near-infrared spectroscopy to compare PFC activity. Results: Interestingly, brain oxygenation levels were more apparent in the 3D versus two-dimensional ToH. In the 3D, there were large differences between pairs of discordant sibling sets and this was located to the right medial PFC, with pDCD exhibiting less activation in this region. Conclusion: While only exploratory, we have identified potential differences in the right medial PFC region, which differs within sibling sets with different pDCD status. These results concur with previous studies and are an area that needs to be explored further with a larger cohort of TD and pDCD.
Diagnostic accuracy of point-of-care lung ultrasound for COVID-19: a systematic review and meta-analysis
Authors: Matthies Ashley , Trauer Michael , Chopra Karl , Jarman Robert David 
Published: March 2023

BackgroundPoint-of-care (POC) lung ultrasound (LUS) is widely used in the emergency setting and there is an established evidence base across a range of respiratory diseases, including previous viral epidemics. The necessity for rapid testing combined with the limitations of other diagnostic tests has led to the proposal of various potential roles for LUS during the COVID-19 pandemic. This systematic review and meta-analysis focused specifically on the diagnostic accuracy of LUS in adult patients presenting with suspected COVID-19 infection.MethodsTraditional and grey-literature searches were performed on 1 June 2021. Two authors independently carried out the searches, selected studies and completed the Quality Assessment Tool for Diagnostic Test Accuracy Studies (QUADAS-2). Meta-analysis was carried out using established open-source packages inR. We report overall sensitivity, specificity, positive and negative predictive values, and the hierarchical summary receiver operating characteristic curve for LUS. Heterogeneity was determined using the I2statistic.ResultsTwenty studies were included, published between October 2020 and April 2021, providing data from a total of 4314 patients. The prevalence and admission rates were generally high across all studies. Overall, LUS was found to be 87.2% sensitive (95% CI 83.6 to 90.2) and 69.5% specific (95% CI 62.2 to 72.5) and demonstrated overall positive and negative likelihood ratios of 3.0 (95% CI 2.3 to 4.1) and 0.16 (95% CI 0.12 to 0.22), respectively. Separate analyses for each reference standard revealed similar sensitivities and specificities for LUS. Heterogeneity was found to be high across the studies. Overall, the quality of studies was low with a high risk of selection bias due to convenience sampling. There were also applicability concerns because all studies were undertaken during a period of high prevalence.ConclusionDuring a period of high prevalence, LUS had a sensitivity of 87% for the diagnosis of COVID-19 infection. However, more research is required to confirm these results in more generalisable populations, including those less likely to be admitted to hospital.PROSPERO registration numberCRD42021250464
Emergency physician gender is associated with early pregnancy loss management: a multisite retrospective cohort study
Authors: Srajer Amelia , Wylie Megg , Zaver Fareen , Lonergan Kevin , Brain Philippa , Lang Eddy 
Published: March 2023

BackgroundPatients experiencing early pregnancy loss often first present to the emergency department (ED) where they can be managed non-operatively through expectant or medical management, or surgically by the obstetrical team. Studies have reported that physician gender can influence clinical decision making, but there is limited research on this phenomenon in the ED. The objective of this study was to determine whether emergency physician gender is associated with early pregnancy loss management.MethodsData were retrospectively collected from patients who presented to Calgary EDs with a non-viable pregnancy from 2014 to 2019. Pregnancies>12 weeks gestational age were excluded. The emergency physicians included saw at least 15 cases of pregnancy loss over the study period. The primary outcome was obstetrical consult rates by male versus female emergency physicians. Secondary outcomes included rates of initial surgical evacuation via dilation and curettage (D&C) procedures, ED returns, returns to care for D&Cs and total D&C rates. Data were analysed using χ2, Fisher’s exact and Mann-Whitney U tests, as appropriate. Multivariable logistic regression models accounted for physician age, years of practice, training programme and type of pregnancy loss.Results98 emergency physicians and 2630 patients from 4 ED sites were included. 76.5% of the physicians were male accounting for 80.4% of pregnancy loss patients. Patients seen by female physicians were more likely to receive an obstetrical consultation (adjusted OR (aOR) 1.50, 95% CI 1.22 to 1.83) and initial surgical management (aOR 1.35, 95% CI 1.08 to 1.69). ED return rates and total D&C rates were not associated with physician gender.ConclusionPatients seen by female emergency physicians had higher rates of obstetrical consultation and initial operative management compared with those seen by male emergency physicians, but outcomes were similar. Additional research is required to determine why these gender differences exist and how these discrepancies may impact the care of early pregnancy loss patients.
Predictors of cognitive deterioration in subjective cognitive decline: evidence from longitudinal studies and implications for SCD-plus criteria
Authors: Li Han , Tan Chen-Chen , Tan Lan , Xu Wei 
Published: March 2023

BackgroundSubjective cognitive decline (SCD) is an early manifestation of cognitive deterioration (CD) in some individuals. Therefore, it is worthwhile to conduct a systematic review and meta-analysis to summarise predictors of CD among individuals with SCD.MethodPubMed, Embase, and Cochrane Library were searched until May 2022. Longitudinal studies that assessed factors associated with CD in SCD population were included. Multivariable-adjusted effect estimates were pooled using random-effects models. The credibility of evidence was assessed. The study protocol was registered with PROSPERO.ResultsA total of 69 longitudinal studies were identified for systematic review, of which 37 were included for the meta-analysis. The mean conversion rate of SCD to any CD was 19.8%, including all-cause dementia (7.3%) and Alzheimer’s disease (4.9%). Sixteen factors (66.67%) were found as predictors, including 5 SCD features (older age at onset, stable SCD, both self- and informant-reported SCD, worry and SCD in the memory clinic), 4 biomarkers (cerebral amyloid β-protein deposition, lower scores of Hulstaert formula, higher total tau in the cerebrospinal fluid and hippocampus atrophy), 4 modifiable factors (lower education, depression, anxiety and current smoking), 2 unmodifiable factors (apolipoprotein E4 and older age) and worse performance on Trail Making Test B. The robustness of overall evidence was impaired by risk of bias and heterogeneity.ConclusionThis study constructed a risk factor profile for SCD to CD conversion, supporting and supplementing the existing list of features for identifying SCD populations at high risk of objective cognitive decline or dementia. These findings could promote early identification and management of high-risk populations to delay dementia onset.PROSPERO registration numberCRD42021281757.
VulANalyzeR: Explainable Binary Vulnerability Detection with Multi-task Learning and Attentional Graph Convolution
Authors: Li Litao , Ding Steven H. H. , Tian Yuan , Fung Benjamin C. M. , Charland Philippe , Ou Weihan , Song Leo , Chen Congwei 
Published: March 2023

Software vulnerabilities have been posing tremendous reliability threats to the general public as well as critical infrastructures, and there have been many studies aiming to detect and mitigate software defects at the binary level. Most of the standard practices leverage both static and dynamic analysis, which have several drawbacks like heavy manual workload and high complexity. Existing deep learning-based solutions not only suffer to capture the complex relationships among different variables from raw binary code but also lack the explainability required for humans to verify, evaluate, and patch the detected bugs.We propose VulANalyzeR, a deep learning-based model, for automated binary vulnerability detection, Common Weakness Enumeration-type classification, and root cause analysis to enhance safety and security. VulANalyzeR features sequential and topological learning through recurrent units and graph convolution to simulate how a program is executed. The attention mechanism is integrated throughout the model, which shows how different instructions and the corresponding states contribute to the final classification. It also classifies the specific vulnerability type through multi-task learning as this not only provides further explanation but also allows faster patching for zero-day vulnerabilities. We show that VulANalyzeR achieves better performance for vulnerability detection over the state-of-the-art baselines. Additionally, a Common Vulnerability Exposure dataset is used to evaluate real complex vulnerabilities. We conduct case studies to show that VulANalyzeR is able to accurately identify the instructions and basic blocks that cause the vulnerability even without given any prior knowledge related to the locations during the training phase.
Novel Calmodulin Variant p.E46K Associated With Severe Catecholaminergic Polymorphic Ventricular Tachycardia Produces Robust Arrhythmogenicity in Human Induced Pluripotent Stem Cell–Derived Cardiomyocytes
Authors: Gao Jingshan , Makiyama Takeru , Yamamoto Yuta , Kobayashi Takuya , Aoki Hisaaki , Maurissen Thomas L. , Wuriyanghai Yimin , Kashiwa Asami , Imamura Tomohiko , Aizawa Takanori , Huang Hai , Kohjitani Hirohiko , Nishikawa Misato , Chonabayashi Kazuhisa , Fukuyama Megumi , Manabe Hiromi , Nakau Kouichi , Wada Tsutomu , Kato Koichi , Toyoda Futoshi , Yoshida Yoshinori , Makita Naomasa , Woltjen Knut , Ohno Seiko , Kurebayashi Nagomi , Murayama Takashi , Sakurai Takashi , Horie Minoru , Kimura Takeshi 
Published: March 2023

Background:

CaM (calmodulin) is a ubiquitously expressed, multifunctional Ca
2+
sensor protein that regulates numerous proteins. Recently, CaM missense variants have been identified in patients with malignant inherited arrhythmias, such as long QT syndrome and catecholaminergic polymorphic ventricular tachycardia (CPVT). However, the exact mechanism of CaM-related CPVT in human cardiomyocytes remains unclear. In this study, we sought to investigate the arrhythmogenic mechanism of CPVT caused by a novel variant using human induced pluripotent stem cell (iPSC) models and biochemical assays.

Methods:

We generated iPSCs from a patient with CPVT bearing
CALM2
p.E46K. As comparisons, we used 2 control lines including an isogenic line, and another iPSC line from a patient with long QT syndrome bearing
CALM2
p.N98S (also reported in CPVT). Electrophysiological properties were investigated using iPSC-cardiomyocytes. We further examined the RyR2 (ryanodine receptor 2) and Ca
2+
affinities of CaM using recombinant proteins.

Results:

We identified a novel de novo heterozygous variant,
CALM2
p.E46K, in 2 unrelated patients with CPVT accompanied by neurodevelopmental disorders. The E46K-cardiomyocytes exhibited more frequent abnormal electrical excitations and Ca
2+
waves than the other lines in association with increased Ca
2+
leakage from the sarcoplasmic reticulum via RyR2. Furthermore, the [
3
H]ryanodine binding assay revealed that E46K-CaM facilitated RyR2 function especially by activating at low [Ca
2+
] levels. The real-time CaM-RyR2 binding analysis demonstrated that E46K-CaM had a 10-fold increased RyR2 binding affinity compared with wild-type CaM which may account for the dominant effect of the mutant CaM. Additionally, the E46K-CaM did not affect CaM-Ca
2+
binding or L-type calcium channel function. Finally, antiarrhythmic agents, nadolol and flecainide, suppressed abnormal Ca
2+
waves in E46K-cardiomyocytes.

Conclusions:
We, for the first time, established a CaM-related CPVT iPSC-CM model which recapitulated severe arrhythmogenic features resulting from E46K-CaM dominantly binding and facilitating RyR2. In addition, the findings in iPSC-based drug testing will contribute to precision medicine.
Interdecadal Change of Tropical Cyclone Translation Speed during Peak Season in South China Sea: Observed Evidence, Model Results, and Possible Mechanism
Authors: Shan Kaiyue , Chu Pao-Shin , Yu Xiping 
Published: March 2023

Abstract
Long-term variations in the translation speed of tropical cyclones (TCs) in the South China Sea (SCS) are examined based on five TC datasets from different institutions. TC translation speed during the TC peak season in the SCS shows an evident rhythm of interdecadal change throughout 1977–2020. This interdecadal change in TC translation speed in the SCS can be well reproduced by a newly developed trajectory model. The model results indicate that the interdecadal change in TC translation speed is primarily due to an interdecadal change in the steering flow in the SCS. Such an interdecadal change in the steering flow is closely related to an east–west shift of the subtropical high in the western North Pacific (WNP) ocean basin, which may be driven by the zonal sea surface temperature (SST) gradient between the north Indian (NI) and WNP ocean basins. A new index of the zonal SST gradient is proposed, which is shown to be effective for indicating the interdecadal change in east–west shift of subtropical high, and thus, the TC translation speed in the SCS.

Significance Statement
Identification of the prevailing trend of tropical cyclone activities due to climate change has been a challenging subject of scientific studies in recent years. This research focuses on the long-term variability of the tropical cyclone translation speed in the South China Sea. It is demonstrated that there is evidently an interdecadal rhythm for variation of the tropical cyclone translation speed in the South China Sea, and this variation can be well reproduced using a newly developed trajectory model. Based on the simulation results, the possible mechanism for this variation is also elucidated.