bluuebunny/crossref_metadata_2025 huggingface dataset:
The status of active after-school clubs among primary school children in England (UK) after the COVD-19 lockdowns: implications for policy and practice
Authors: Walker Robert , Salway Ruth , House Danielle , Emm-Collison Lydia , Breheny Katie , Sansum Kate , Churchward Sarah , Williams Joanna G , Vocht Frank de , Hollingworth William , Jago Russell
Published: October 2023

Background

Children’s physical activity in England is more dependent on active clubs after the COVID-19 pandemic. However, it is unclear how the COVID-19 pandemic and related cost-of-living crisis have impacted on active club participation, costs and provision. This mixed-methods natural experiment explored school-based and community-based active clubs after lockdowns, using a unique combination of data sources to highlight implications for policy and practice post-COVID-19.

Methods

Cross-sectional questionnaire data on school and community active clubs were collected from 10-11-year-old children pre-COVID-19 in 2017-18 (N = 1,296; 50 schools), in 2021 (N = 393; 23 schools), and 2022 (N = 463; 27 schools). Club participation and attendance frequency were modelled using logistic and Poisson mixed effects models, adjusted for child age, gender and household education. In 2021 and 2022, parents reported expenditure on community-based clubs and schools provided data on school-based club provision, with data summarised descriptively. Qualitative data were collected in 2021 and 2022, with one-to-one interviews with school staff (N = 18) and parents (N = 43), and twelve child focus groups (N = 92), and analysed using the framework method.

Results

School-based active club participation was higher in 2022 compared to pre-pandemic (50% /43%), while community-based club participation was lower (74%/80%). Children attended 0.3 fewer clubs per week. Those from lower education households were less likely to participate in both types of active clubs, and girls less likely to attend community clubs. In 2022, the median cost of community and school club sessions were £6.67 and £3.88 respectively, with 52% of school-based clubs free to parents. Schools offered an average of 3.4 active clubs per week for 10-11-year-olds in 2022, with 34% partly/wholly subsidised. Qualitative analysis highlighted the impact of the cost-of-living crisis and COVID-19 pandemic on family resources, encouraging a shift to more affordable and convenient school-based active clubs, which negatively impacted the community-based active club environment. However, many schools struggled to meet this increased demand.

Conclusions

Findings emphasise the importance for policymakers to support schools to meet increased demand for clubs and community clubs to increase affordable and convenient physical activity opportunities. Targeted support is needed to prevent socioeconomic and gender inequalities.
Restoring natural upper limb movement through a wrist prosthetic module for partial hand amputees
Authors: Choi Seoyoung , Cho Wonwoo , Kim Keehoon
Published: October 2023

Background

Most partial hand amputees experience limited wrist movement. The limited rotational wrist movement deteriorates natural upper limb system related to hand use and the usability of the prosthetic hand, which may cause secondary damage to the musculoskeletal system due to overuse of the upper limb affected by repetitive compensatory movement patterns. Nevertheless, partial hand prosthetics, in common, have only been proposed without rotational wrist movement because patients have various hand shapes, and a prosthetic hand should be attached to a narrow space.

Methods

We hypothesized that partial hand amputees, when using a prosthetic hand with a wrist rotation module, would achieve natural upper limb movement muscle synergy and motion analysis comparable to a control group. To validate the proposed prototype design with the wrist rotation module and verify our hypothesis, we compared a control group with partial hand amputees wearing hand prostheses, both with and without the wrist rotation module prototype. The study contained muscle synergy analysis through non-negative matrix factorization (NMF) using surface electromyography (sEMG) and motion analyses employing a motion capture system during the reach-to-grasp task. Additionally, we assessed the usability of the prototype design for partial hand amputees using the Jebsen-Taylor hand function test (JHFT).

Results

The results showed that the number of muscle synergies identified through NMF remained consistent at 3 for both the control group and amputees using a hand prosthesis with a wrist rotation module. In the motion analysis, a statistically significant difference was observed between the control group and the prosthetic hand without the wrist rotation module, indicating the presence of compensatory movements when utilizing a prosthetic hand lacking this module. Furthermore, among the amputees, the JHFT demonstrated a greater improvement in total score when using the prosthetic hand equipped with a wrist rotation module compared to the prosthetic hand without this module.

Conclusion

In conclusion, integrating a wrist rotation module in prosthetic hand designs for partial hand amputees restores natural upper limb movement patterns, reduces compensatory movements, and prevent the secondary musculoskeletal. This highlights the importance of this module in enhancing overall functionality and quality of life.
Effect of urban vs. remote settings on prehospital time and mortality in trauma patients in Norway: a national population-based study
Authors: Nilsbakken Inger Marie Waal , Cuevas-Østrem Mathias , Wisborg Torben , Sollid Stephen , Jeppesen Elisabeth
Published: October 2023

Background

Norway has a diverse population pattern and often long transport distances from injury sites to hospitals. Also, previous studies have found an increased risk of trauma-related mortality in remote areas in Norway. Studies on urban vs. remote differences on trauma outcomes from other countries are sparse and they report conflicting results.The aim of the present study was to investigate differences in prehospital time intervals in urban and remote areas in Norway and assess how prehospital time and urban vs. remote settings were associated with mortality in the Norwegian trauma population.

Methods

We performed a population-based study of trauma cases included in the Norwegian Trauma Registry from 2015 to 2020. 28,988 patients met the inclusion criteria. Differences in study population characteristics and prehospital time intervals (response time, on-scene time and transport time) were analyzed. The Norwegian Centrality Index score was used for urban vs. remote classification. Descriptive statistics and relevant non-parametric tests with effect size measurements were used. A binary logistic regression model, adjusted for confounding factors, was performed.

Results

The prehospital time intervals increased significantly from urban to remote areas.Adjusted for control variables we found a significant relationship between prolonged on-scene time and higher odds of mortality. Also, suburban areas compared with remote areas were associated with higher odds of mortality.

Conclusion

In this nationwide study comparing prehospital time intervals in urban and remote areas, we found that prehospital time intervals in remote areas exceeded those in urban areas. Prolonged on-scene time was found to be associated with higher odds of mortality, but remoteness itself was not.
Smart chemometrics-assisted spectrophotometric methods for efficient resolution and simultaneous determination of paracetamol, caffeine, drotaverine HCl along with three of their corresponding related impurities
Authors: Tawfik Samia A. , Hegazy Maha A. , El-Ragehy Nariman A. , Sedik Ghada A.
Published: October 2023

Three novel, simple and accurate multivariate spectrophotometric assisted mathematical techniques were developed for determination of paracetamol, caffeine, drotaverine HCl and their related impurities. The used multivariate algorithms are principal component regression (PCR), partial least squares (PLS), and synergy intervals partial least squares (siPLS). Linearity of the suggested methods was found to be (1.00–14.60, 1.40–7.00, 1.40–3.80, 1.00–3.00, 1.50–3.50 and 2.50–4.50 µg/mL) for paracetamol, caffeine, drotaverine HCl, and their related impurities; p-aminophenol, theophylline and homoveratric acid, correspondingly. The presented methods were effectively implemented in the determination of the cited compounds in their laboratory prepared mixtures. Commercially available tablet preparation was also analyzed using the applied methods where no impurities were detected and without interference from tablet additives. Moreover, statistical analysis did not reveal any noticeable differences between the obtained results and those acquired from the reported method in terms of accuracy and precision. The developed multivariate algorithms were validated by means of internal and external validation sets. The obtained results showed the siPLS algorithm’s superiority to PCR and PLS according to the values of correlation coefficient values (r) and the lowest root mean square error of prediction (RMSEP). The combination of four subintervals [10, 12, 14, and 17] produced the highest efficiency model. Furthermore, these methods may be an applicable substitute to HPLC ones in quality control laboratories during rush of analyses where several samples have to be analyzed in a short time.
DVT: a high-throughput analysis pipeline for locomotion and social behavior in adult Drosophila melanogaster
Authors: Mi Kai , Li Yiqing , Yang Yuhang , Secombe Julie , Liu Xingyin
Published: October 2023

Background

Drosophila melanogaster is excellent animal model for understanding the molecular basis of human neurological and motor disorders. The experimental conditions and chamber design varied between studies. Moreover, most previously established paradigms focus on fly trace detection algorithm development. A comprehensive understanding on how fly behaves in the chamber is still lacking.

Results

In this report, we established 74 unique behavior metrics quantifying spatiotemporal characteristics of adult fly locomotion and social behaviors, of which 49 were newly proposed. By the aiding of the developed analysis pipeline, Drosophila video tracking (DVT), we identified siginificantly different patterns of fly behavior confronted with different chamber height, fly density, illumination and experimental time. Meanwhile, three fly strains which are widely used as control lines, Canton-S(CS), w1118 and Oregon-R (OR), were found to exhibit distinct motion explosiveness and exercise endurance.

Conclusions

We believe the proposed behavior metrics set and pipeline should help identify subtle spatial and temporal differences of drosophila behavior confronted with different environmental factors or gene variants.
Clinical Warburg effect in lymphoma patients admitted to intensive care unit
Authors: Chaba Anis , Fodil Sofiane , Lemiale Virginie , Mariotte Eric , Valade Sandrine , Azoulay Elie , Zafrani Lara
Published: October 2023

Background

The Warburg effect, characterized by elevated lactate levels without tissue hypoxia or shock, has been described in patients with aggressive lymphoproliferative malignancies. However, the clinical characteristics and long-term outcomes in this population remain poorly understood.

Methods

We retrospectively analyzed 135 patients with aggressive lymphoproliferative malignancies admitted to the ICU between January 2017 and December 2022. Patients were classified into three groups: Clinical Warburg Effect (CWE), No Warburg with High Lactate level (NW-HL), and No Warburg with Normal Lactate level (NW-NL). Clinical characteristics and outcomes were compared between the groups and factors associated with 1-year mortality and CWE were identified using multivariable analyses.

Results

Of the 135 patients, 46 (34%) had a CWE. This group had a higher proportion of Burkitt and T cell lymphomas, greater tumor burden, and more frequent bone and cerebral involvement than the other groups. At 1 year, 72 patients (53%) died, with significantly higher mortality in the CWE and NW-HL groups (70% each) than in the NW-NL group (38%). Factors independently associated with 1-year mortality were age [HR = 1.02 CI 95% (1.00–1.04)], total SOFA score at admission [HR = 1.19 CI 95% (1.12–1.25)], and CWE [HR = 3.87 CI 95% (2.13–7.02)]. The main factors associated with the CWE were tumor lysis syndrome [OR = 2.84 CI 95% (1.14–7.42)], bone involvement of the underlying malignancy [OR = 3.58 CI 95% (1.02–12.91)], the total SOFA score at admission [OR = 0.81 CI 95% (0.69–0.91)] and hypoglycemia at admission [OR = 14.90 CI 95% (5.42–47.18)].

Conclusion

CWE is associated with a higher tumor burden and increased 1-year mortality compared to patients without this condition. Our findings underscore the importance of recognizing patients with CWE as a high-risk cohort, as their outcomes closely resemble those of individuals with lymphoma and shock, despite not requiring advanced organ support. Clinicians should recognize the urgency of managing these patients and consider early intervention to improve their prognosis.
Revealing parental mosaicism: the hidden answer to the recurrence of apparent de novo variants
Authors: Lee Mianne , Lui Adrian C. Y. , Chan Joshua C. K. , Doong Phoenix H. L. , Kwong Anna K. Y. , Mak Christopher C. Y. , Li Raymond H. W. , Kan Anita S. Y. , Chung Brian H. Y.
Published: October 2023

Mosaicism refers to the presence of two or more populations of genetically distinct cells within an individual, all of which originate from a single zygote. Previous literature estimated the percentage of parental mosaicism ranged from 0.33 to 25.9%. In this study, parents whose children had previously been diagnosed with developmental disorders with an apparent de novo variant were recruited. Peripheral blood, buccal and semen samples were collected from these parents if available for the detection of potential parental mosaicism using droplet digital PCR, complemented with the method of blocker displacement amplification. Among the 20 families being analyzed, we report four families with parental mosaicism (4/20, 20%). Two families have maternal gonosomal mosaicism (EYA1 and EBF3) and one family has paternal gonadal mosaicism (CHD7) with a pathogenic/ likely pathogenic variant. One family has a paternal gonosomal mosaicism with a variant of uncertain significance (FLNC) with high clinical relevance. The detectable variant allele frequency in our cohort ranged from 8.7–35.9%, limit of detection 0.08–0.16% based on our in-house EBF3 assay. Detecting parental mosaicism not only informs family with a more accurate recurrence risk, but also facilitates medical teams to create appropriate plans for pregnancy and delivery, offering the most suitable care.
Inter-observer variation in two-dimensional and three-dimensional ultrasound measurement of papillary thyroid microcarcinoma
Authors: Yan Lin , Ren Ling , Li Yingying , Luo Yukun
Published: October 2023

Backgrounds

The reliable ultrasound (US) measurements of papillary thyroid microcarcinoma (PTMC) are very important during active surveillance. This prospective study was design to investigate the inter-observer reliability and agreement of two- dimensional ultrasound(2DUS) and three-dimensional ultrasound(3DUS) in the measurement of maximum diameter and volume for PTMC.

Methods

This prospective study included 51 consecutive patients with solitary PTMC confirmed by biopsy. Two independent observers performed measurements of each tumor using a standardized measurement protocol. The maximum diameter was the largest one of the three diameters measured on the largest transverse and longitudinal 2DUS images. 2DUS volume was calculated using ellipsoid formula method. The virtual organ computer aided analysis(VOCAL) was used to determine 3DUS volume. The inter-observer reliability was assessed using intraclass correlation coefficient(ICC) with 95% confidence intervals(CIs). Bland-Altman analysis was used to evaluate agreement, and expressed as a bias with 95% limits of agreement(LOA).

Results

The maximum diameter was 0.78 ± 0.14 cm. Volume measured by 3DUS was significantly smaller than that by 2DUS(0.163 ± 0.074 cm3 vs. 0.175 ± 0.078 cm3, P = 0.005). The ICCs of inter-observer reliability of maximum diameter, 2DUS volume and 3DUS volume was 0.922(0.864–0.955), 0.928(0.874–0.959), and 0.974(0.955–0.985), respectively. The ICCs of 2DUS and 3DUS volume was 0.955(0.909–0.976). The inter-observer agreement of maximum diameter, 2DUS volume and 3DUS volume was 1.096(0.7322 to 1.459), 1.008(0.5802–1.435), and 1.011(0.7576–1.265), respectively. The inter-observer agreement of 2DUS and 3DUS volume was 1.096(0.7322 to 1.459).

Conclusion

Maximum diameter had the lowest degree of observer variation among all the measurements. Volume measured by 3DUS had lower variability and higher repeatability than that by 2DUS, which might be helpful to provide more reliable estimates of tumor size for PTMC.
Using the kidney failure risk equation to predict end-stage kidney disease in CKD patients of South Asian ethnicity: an external validation study
Authors: Maher Francesca , Teece Lucy , Major Rupert W. , Bradbury Naomi , Medcalf James F. , Brunskill Nigel J. , Booth Sarah , Gray Laura J.
Published: October 2023

Background

The kidney failure risk equation (KFRE) predicts the 2- and 5-year risk of needing kidney replacement therapy (KRT) using four risk factors — age, sex, urine albumin-to-creatinine ratio (ACR) and creatinine-based estimated glomerular filtration rate (eGFR). Although the KFRE has been recalibrated in a UK cohort, this did not consider minority ethnic groups. Further validation of the KFRE in different ethnicities is a research priority. The KFRE also does not consider the competing risk of death, which may lead to overestimation of KRT risk. This study externally validates the KFRE for patients of South Asian ethnicity and compares methods for accounting for ethnicity and the competing event of death.

Methods

Data were gathered from an established UK cohort containing 35,539 individuals diagnosed with chronic kidney disease. The KFRE was externally validated and updated in several ways taking into account ethnicity, using recognised methods for time-to-event data, including the competing risk of death. A clinical impact assessment compared the updated models through consideration of referrals made to secondary care.

Results

The external validation showed the risk of KRT differed by ethnicity. Model validation performance improved when incorporating ethnicity and its interactions with ACR and eGFR as additional risk factors. Furthermore, accounting for the competing risk of death improved prediction. Using criteria of 5 years ≥ 5% predicted KRT risk, the competing risks model resulted in an extra 3 unnecessary referrals (0.59% increase) but identified an extra 1 KRT case (1.92% decrease) compared to the previous best model. Hybrid criteria of predicted risk using the competing risks model and ACR ≥ 70 mg/mmol should be used in referrals to secondary care.

Conclusions

The accuracy of KFRE prediction improves when updated to consider South Asian ethnicity and to account for the competing risk of death. This may reduce unnecessary referrals whilst identifying risks of KRT and could further individualise the KFRE and improve its clinical utility. Further research should consider other ethnicities.
An efficient permutation approach for SbPN-based symmetric block ciphers
Authors: Nazish Mir , Banday M. Tariq , Syed Insha , Banday Sheena
Published: October 2023

It is challenging to devise lightweight cryptographic primitives efficient in both hardware and software that can provide an optimum level of security to diverse Internet of Things applications running on low-end constrained devices. Therefore, an efficient hardware design approach that requires some specific hardware resource may not be efficient if implemented in software. Substitution bit Permutation Network based ciphers such as PRESENT and GIFT are efficient, lightweight cryptographic hardware design approaches. These ciphers introduce confusion and diffusion by employing a 4 × 4 static substitution box and bit permutations. The bit-wise permutation is realised by simple rerouting, which is most cost-effective to implement in hardware, resulting in negligible power consumption. However, this method is highly resource-consuming in software, particularly for large block-sized ciphers, with each single-bit permutation requiring multiple sub-operations. This paper proposes a novel software-based design approach for permutation operation in Substitution bit Permutation Network based ciphers using a bit-banding feature. The conventional permutation using bit rotation and the proposed approach have been implemented, analysed and compared for GIFT and PRESENT ciphers on ARM Cortex-M3-based LPC1768 development platform with KEIL MDK used as an Integrated Development Environment. The real-time performance comparison between conventional and the proposed approaches in terms of memory (RAM/ROM) footprint, power, energy and execution time has been carried out using ULINKpro and ULINKplus debug adapters for various code and speed optimisation scenarios. The proposed approach substantially reduces execution time, energy and power consumption for both PRESENT and GIFT ciphers, thus demonstrating the efficiency of the proposed method for Substitution bit Permutation Network based symmetric block ciphers.
Independent external validation of a stroke recurrence score in patients with embolic stroke of undetermined source
Authors: Ingwersen Thies , Olma Manuel C. , Schlemm Eckhard , Mayer Carola , Cheng Bastian , Tütüncü Serdar , Kirchhof Paulus , Veltkamp Roland , Röther Joachim , Laufs Ulrich , Nabavi Darius G. , Ntaios George , Endres Matthias , Haeusler Karl Georg , Thomalla Götz
Published: October 2023

Background

Embolic stroke of undetermined source (ESUS) accounts for a substantial proportion of ischaemic strokes. A stroke recurrence score has been shown to predict the risk of recurrent stroke in patients with ESUS based on a combination of clinical and imaging features. This study aimed to externally validate the performance of the ESUS recurrence score using data from a randomized controlled trial.

Methods

The validation dataset consisted of eligible stroke patients with available magnetic resonance imaging (MRI) data enrolled in the PreDAFIS sub-study of the MonDAFIS study. The score was calculated using three variables: age (1 point per decade after 35 years), presence of white matter hyperintensities (2 points), and multiterritorial ischaemic stroke (3 points). Patients were assigned to risk groups as described in the original publication. The model was evaluated using standard discrimination and calibration methods.

Results

Of the 1054 patients, 241 (22.9%) were classified as ESUS. Owing to insufficient MRI quality, three patients were excluded, leaving 238 patients (median age 65.5 years [IQR 20.75], 39% female) for analysis. Of these, 30 (13%) patients experienced recurrent ischaemic stroke or transient ischemic attack (TIA) during a follow-up period of 383 patient-years, corresponding to an incidence rate of 7.8 per 100 patient-years (95% CI 5.3–11.2). Patients with an ESUS recurrence score value of ≥ 7 had a 2.46 (hazard ratio (HR), 95% CI 1.02–5.93) times higher risk of stroke recurrence than patients with a score of 0–4. The cumulative probability of stroke recurrence in the low-(0–4), intermediate-(5–6), and high-risk group (≥ 7) was 9%, 13%, and 23%, respectively (log-rank test, χ2 = 4.2, p = 0.1).

Conclusions

This external validation of a published scoring system supports a threshold of ≥ 7 for identifying ESUS patients at high-risk of stroke recurrence. However, further adjustments may be required to improve the model’s performance in independent cohorts. The use of risk scores may be helpful in guiding extended diagnostics and further trials on secondary prevention in patients with ESUS.

Trial registration: Clinical Trials, NCT02204267. Registered 30 July 2014, https://clinicaltrials.gov/ct2/show/NCT02204267.
The AnimalAssociatedMetagenomeDB reveals a bias towards livestock and developed countries and blind spots in functional-potential studies of animal-associated microbiomes
Authors: Avila Santos Anderson Paulo , Kabiru Nata’ala Muhammad , Kasmanas Jonas Coelho , Bartholomäus Alexander , Keller-Costa Tina , Jurburg Stephanie D. , Tal Tamara , Camarinha-Silva Amélia , Saraiva João Pedro , Ponce de Leon Ferreira de Carvalho André Carlos , Stadler Peter F. , Sipoli Sanches Danilo , Rocha Ulisses
Published: October 2023

Background

Metagenomic data can shed light on animal-microbiome relationships and the functional potential of these communities. Over the past years, the generation of metagenomics data has increased exponentially, and so has the availability and reusability of data present in public repositories. However, identifying which datasets and associated metadata are available is not straightforward. We created the Animal-Associated Metagenome Metadata Database (AnimalAssociatedMetagenomeDB - AAMDB) to facilitate the identification and reuse of publicly available non-human, animal-associated metagenomic data, and metadata. Further, we used the AAMDB to (i) annotate common and scientific names of the species; (ii) determine the fraction of vertebrates and invertebrates; (iii) study their biogeography; and (iv) specify whether the animals were wild, pets, livestock or used for medical research.

Results

We manually selected metagenomes associated with non-human animals from SRA and MG-RAST.  Next, we standardized and curated 51 metadata attributes (e.g., host, compartment, geographic coordinates, and country). The AAMDB version 1.0 contains 10,885 metagenomes associated with 165 different species from 65 different countries. From the collected metagenomes, 51.1% were recovered from animals associated with medical research or grown for human consumption (i.e., mice, rats, cattle, pigs, and poultry). Further, we observed an over-representation of animals collected in temperate regions (89.2%) and a lower representation of samples from the polar zones, with only 11 samples in total. The most common genus among invertebrate animals was Trichocerca (rotifers).

Conclusion

Our work may guide host species selection in novel animal-associated metagenome research, especially in biodiversity and conservation studies. The data available in our database will allow scientists to perform meta-analyses and test new hypotheses (e.g., host-specificity, strain heterogeneity, and biogeography of animal-associated metagenomes), leveraging existing data. The AAMDB WebApp is a user-friendly interface that is publicly available athttps://webapp.ufz.de/aamdb/.
MRI features for predicting the pathological grade of HCC in patients undergoing liver transplantation
Authors: Altan Kus Aylin , Keceoglu Selim , Ozer Ali
Published: October 2023

Background

Contrast-enhanced magnetic resonance imaging (MRI) plays a crucial role in the diagnosis of hepatocellular carcinoma (HCC). This study aims to assess the performance of MRI features for evaluating hepatocellular carcinoma (HCC) aggressiveness in living liver transplantation in patients.

Material and methods

This retrospective study included patients who underwent liver transplantation in our hospital between 2015 and 2020. Abdominal contrast-enhanced MRIs of these patients were reviewed, and clinical, radiological, and histopathological findings of HCCs were recorded. The prognostic features of HCCs as determined by MRI were compared with Edmondson-Steiner (E-S) grades. Liver parenchyma fibrosis based on an apparent diffusion coefficient (ADC) map was correlated with histological subclassification of cirrhosis using the Laennec staging system.

Results

The study subjects included 37 men and 8 women with a mean age of 59.56 ± 7.81 (range: 25–72). The mean tumour size was 37.33 ± 22.27 mm (range: 10–118 mm), and nine tumours (23.1%) involved portal vein tumour thrombosis. There was a significant correlation between tumour grade and size (p = 0.007) and intratumoral fat (p = 0.014) even though no significant correlations between grade and mean ADC value, capsule appearance, presence of satellite lesions, smooth margin, imaging of the tumour feeding artery, and corona enhancement of HCC (p > 0.05) were found. There was a statistically significant correlation between mild (stage 4A) and moderate (stage 4B) fibrosis of non-tumorous liver parenchyma and ADC value (p < 0.001).

Conclusion

Our study found that ADC values can be used to distinguish mild cirrhotic livers from moderate cirrhotic livers. Diffusion MRI might be used to diagnose the degree of liver fibrosis without histopathological analysis. According to our results, only intralesional fat and tumour size correlated with tumour grade, and as such, these parameters could be used as prognostic MRI biomarkers for HCC.
Baseline and recurrent exposure to the standard dose of artemisinin-based combination therapies (ACTs) induces oxidative stress and liver damage in mice (BALB/c)
Authors: Audu David , Patel Vinood B. , Idowu Olufunmilayo A. , Mshelbwala Fakilahyel M. , Idowu Adewumi B.
Published: October 2023

Background

In malaria-endemic countries, repeated intake of artemisinin-based combination therapies (ACTs) is rampant and driven by drug resistance, improper usage, and easy accessibility. Stress effects and potential liver toxicity due to the frequent therapeutic use of ACTs have not been extensively studied. Here, we investigated the effects of repeated treatment with standard doses of the commonly used ACTs artemether/lumefantrine (A/L) and artesunate-amodiaquine (A/A) on oxidative stress and liver function markers in male mice (BALB/c).

Methods

Forty Five mice were divided into three groups: control, A/L, and A/A. The drugs were administered three days in a row per week, and the regimen was repeated every two weeks for a total of six cycles. The levels of oxidative stress and liver function markers were measured in both plasma and liver tissue after initial (baseline) and repeated exposures for the second, third, and sixth cycles.

Results

Exposure to A/L or A/A caused a significant (p < 0.001) increase in plasma malondialdehyde (MDA) levels after the first and repeated exposure periods. However, Hepatic MDA levels increased significantly (p < 0.01) only after the sixth exposure to A/A. Following either single or repeated exposure to A/L or A/A, plasma and liver glutathione peroxidase (GPx) and catalase (CAT) activities, plasma aspartate and alanine transaminase, alkaline phosphatase activity, and bilirubin levels increased, whereas total plasma protein levels decreased significantly (p < 0.001). Varying degrees of hepatocyte degeneration and blood vessel congestion were observed in liver tissues after a single or repeated treatment period.

Conclusion

Irrespective of single or repeated exposure to therapeutic doses of A/L or A/A, plasma oxidative stress and liver damage were observed. However, long-term repeated A/A exposure can led to hepatic stress. Compensatory processes involving GPx and CAT activities may help reduce the observed stress.
Rockfall alarm system for railway monitoring: Integrating seismic detection, localization, and characterization
Authors: Rebert Théo , Cai Caifang , Hallier Amélie , Bardainne Thomas
Published: October 2023

Rockfalls pose a threat to human infrastructure below cliffs. Sensitive and reactive alarm systems are needed for rail traffic safety because small rockfalls ([Formula: see text]) impacting the railroad may cause train derailment. We develop a seismic processing workflow for rockfall early warning, powered by dense arrays deployed along the track. The method is evaluated by dropping rocks from a controlled height and triggering rockfalls on a cliff. We indicate that seismic arrays are highly sensitive to small impacts and are able to detect them, locate them, and estimate their magnitude. The detection can be performed in near real-time with a simple algorithm because small-scale rockfalls produce impulsive waveforms near the impact. Precise localization with matched field processing is able to track the trajectory of a rockfall. Impacts against the steel rails may be recognized by their source signature. The seismic amplitudes are related to the rockfall volume by the Hertz law, which may be used to estimate their volume. These results indicate the potential of seismic-driven near real-time rockfall alarm systems.
Multi-image, reverse time, and Kirchhoff migrations with compact Green’s functions
Authors: Cunha Carlos , Ritter Gerson , Sardinha Alexandre , Dias Bruno Pereira , Guerra Claudio , Thedy Fernanda , Hargreaves Nelson , Coacci Rodrigo
Published: October 2023

Using compact representations of Green’s functions we derive a common framework for reverse time migration (RTM) and Kirchhoff migration. These compact Green’s functions (CGFs) are 3D volumes containing traveltimes and amplitudes for the N most representative events in the upcoming/downgoing decomposed 4D wavefields originating from a point source. Within this framework, we implement an RTM algorithm using a multivalued excitation time/amplitude imaging condition. This new approach produces four complementary imaging volumes (different combinations of source and receiver decomposed wavefields) and angle/azimuth gathers with computational effort less than 15% greater than that of plain (one image and no gathers) RTM algorithms. The advantages of separating the image volume into four complementary volumes are well established in the literature (low-frequency noise separation and turning wave imaging); however, its use has been limited by the computational cost. Despite using two source propagations to decompose the source wavefield, we reduce the computations to less than 20% of a single source propagation by performing finite-difference propagation with half the frequency limit used in the receiver wavefield propagation. The combination of CGF and an excitation time/amplitude imaging condition allows receiver wavefield decomposition with only one wavefield propagation. Our RTM algorithm constructs angle/azimuth gathers using a postmigration computation of the source and receiver wavefield’s propagation directions. To compute the propagation directions after migration, we use a new concept: the cumulative wavefield volumes, which are 3D, imaging-condition-guided compressions, of the 4D source and receiver wavefields. We also use CGF to implement a Kirchhoff migration algorithm that produces four complementary image volumes with RTM-like quality. Furthermore, we present synthetic and field data examples to clarify the new concepts and illustrate the results obtained using these methods.
Association Between Concurrent Use of Benzodiazepines and Opioids and Health Care Utilization Among Patients With Cancer in Puerto Rico
Authors: Fuentes Payán Wilmarie , González Lorenzo Keyla , Gelabert Martínez Frankie , Conte Schmidt Nelly , Tortolero-Luna Guillermo , Ramos-Fernández María R. , Gierbolini-Bérmudez Axel , Melin Kyle , Ortiz-Ortiz Karen J.
Published: October 2023

PURPOSE

To evaluate the association between concurrent use of opioids and benzodiazepines (BZDs) and emergency room (ER) visits and hospital admissions in patients with cancer.

METHODS

Data were obtained from the Puerto Rico Central Cancer Registry-Health Insurance Linkage. Odds ratios (ORs) with 95% CIs and incidence rate ratio (IRR) were estimated using logistic and negative binomial regression analyses to assess the association between concurrent use of opioids and BZDs (overlap of at least 7 days) and ER visits and hospital admissions.

RESULTS

A total of 9,259 patients were included in the main analysis. The logistic regression results showed a significant association between concurrent use of opioids and BZDs and at least one ER visit (OR, 1.28 [95% CI, 1.07 to 1.54]) or hospital admission (OR, 1.42 [95% CI, 1.18 to 1.71]) compared with individuals with BZDs alone, after adjusting for age, sex, comorbidity index, cancer stage, health insurance, and health region. Compared with individuals with opioid use alone, the association did not reach significance. In the negative binomial regression, a significant association was observed for ER visits (IRR, 1.52 [95% CI, 1.31 to 1.76]) and hospitalizations (IRR, 1.34 [95% CI, 1.20 to 1.50]) when compared with individuals with BZDs alone. Compared with individuals with opioids alone, it only reached significance for ER visits (IRR, 1.39 [95% CI, 1.20 to 1.61]).

CONCLUSION

Careful evaluation must be done before prescribing concurrent opioids and BZDs in patients with cancer, as the results suggest that coprescribing may increase the odds of ER visits and hospitalizations.
Skewness in Body fat Distribution Pattern Links to Specific Cardiometabolic Disease Risk Profiles
Authors: Linge Jennifer , Cariou Bertrand , Neeland Ian J , Petersson Mikael , Rodríguez Ángel , Dahlqvist Leinhard Olof
Published: October 2023

Objective

Fat distribution pattern could help determine cardiometabolic risk profile. This study aimed to evaluate the association of balance/imbalance between visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (aSAT), and liver fat (LF) with incident type 2 diabetes (T2D) and cardiovascular disease (CVD) in the UK Biobank prospective cohort study.

Methods

Magnetic resonance images of 40 174 participants were analyzed for VAT, aSAT, and LF using AMRA® Researcher. To assess fat distribution patterns independent of body mass index (BMI), fat z-scores (z-VAT, z-aSAT, z-LF) were calculated. Participants without prevalent T2D/CVD (N = 35 138) were partitioned based on balance between (1) z-VAT and z-LF (z-scores = 0 as cut-points for high/low), (2) z-VAT and z-aSAT, and (3) z-LF and z-aSAT. Associations with T2D/CVD were investigated using Cox regression (crude and adjusted for sex, age, BMI, lifestyle, arterial hypertension, statin treatment).

Results

T2D was significantly associated with z-LF (hazard ratio, [95% CI] 1.74 [1.52-1.98], P < .001) and z-VAT (1.70 [1.49-1.95], P < .001). Both remained significant after full adjustment. For z-scores balance, strongest associations with T2D were z-VAT > 0 and z-LF > 0 (4.61 [2.98-7.12]), z-VAT > 0 and z-aSAT < 0 (4.48 [2.85-7.06]), and z-LF > 0 and z-aSAT < 0 (2.69 [1.76-4.12]), all P < .001. CVD was most strongly associated with z-VAT (1.22 [1.16-1.28], P < .001) which remained significant after adjustment for sex, age, BMI, and lifestyle. For z-scores balance, strongest associations with CVD were z-VAT > 0 and z-LF < 0 (1.53 [1.34-1.76], P < .001) and z-VAT > 0 and z-aSAT < 0 (1.54 [1.34-1.76], P < .001). When adjusted for sex, age, and BMI, only z-VAT > 0 and z-LF < 0 remained significant.

Conclusion

High VAT in relation to BMI (z-VAT > 0) was consistently linked to both T2D and CVD; z-LF > 0 was linked to T2D only. Skewed fat distribution patterns showed elevated risk for CVD (z-VAT > 0 and z-LF < 0 and z-VAT > 0 and z-aSAT < 0) and T2D (z-VAT > 0 and z-aSAT < 0).
THU128 Transcription Factor ETV5 In POMC Neurons Regulate Energy And Glucose Homeostasis
Authors: Gahlot Surbhi , Caron Alexandre , Lee Syann , Elmquist Joel K
Published: October 2023

Disclosure: S. Gahlot: None. A. Caron: None. S. Lee: None. J.K. Elmquist: None.

Pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (ARH) are critical for the regulation of energy balance and glucose homeostasis. Pomc gene transcription is regulated by the Erythrocyte Transformation Specific (ETS)-domain transcription factors, including Etv1, Etv2, Etv4, and Etv5. Large-scale genome-wide association studies have identified ETV5 genetic variants linked with human obesity and body mass index. Histological studies in adult mouse pituitaries also show the co-localization of ETV5 with POMC and POMC-derived peptides: adrenocorticotropic hormone (ACTH) and alpha-melanocyte stimulating hormone (α-MSH). Furthermore, whole-body Etv5 knockout mice are lean, severely glucose intolerant and hypoinsulinaemic. While these findings suggest a potential role for Etv5 in the control of energy and glucose balance, the role of Etv5 remains unknown. This study aims to determine whether ETV5 binds to the Pomc promoter to alter its expression and regulate energy balance and glucose homeostasis. To assess whether ETV5 binds to the Pomc promoter, we performed chromatin immunoprecipitation with quantitative real-time PCR (ChIP-qPCR) in C57BL/6J mice. ChIP-qPCR determined that Etv5 directly binds to the Pomc promoter. We further performed luciferase reporter assay in mouse neuroblastoma N2a cell lysates to measure the Pomc promoter activity after Etv5 knockdown or overexpression. Luciferase assay revealed that Etv5 knockdown increased, while Etv5 overexpression reduced the Pomc promoter activity in N2a cells. Also, Etv5 overexpression blocked the leptin-induced POMC activation. Further, to determine the role of Etv5 in POMC neurons to regulate energy balance and glucose homeostasis, we used the Cre/loxP system to selectively delete Etv5 from POMC neurons both prenatally and postnatally. Mice were fed either a standard chow or a 60% high-fat diet (HFD), followed by serial body weight, food intake, body composition, metabolic assessment, glucose tolerance and insulin tolerance test measurements. We found that mice with a prenatal deletion of Etv5 in POMC neurons had reduced body weight, reduced lean mass, and were protected from HFD-induced insulin resistance. Similarly, postnatal deletion of Etv5 in POMC neurons resulted in reduced body weight, lean mass and fat mass, and increased insulin sensitivity and energy expenditure in mice of 8 weeks age. We also performed electrophysiological recordings in hypothalamic slices from these mice to assess POMC neuron excitability. We found that loss of Etv5 increased the activity and electrical excitability of POMC neurons. These findings highlight a previously unrecognized role of Etv5 in POMC neurons in the regulation of energy balance and glucose homeostasis. These results also point to the potential therapeutic applications for Etv5 against obesity.

Presentation: Thursday, June 15, 2023
FRI024 The Effect Of High Fat Diet On Insulin Signaling In White Adipose Tissue Of Liver Androgen Receptor Knockout In Female Mice
Authors: Young Demarrius
Published: October 2023

Disclosure: D. Young: None.

Introduction: Insulin resistance affects up to a third of the US adult population and polycystic ovary syndrome affects up to 10% of reproductive-age adult women. The liver and white adipose tissue play an essential component in the metabolism of insulin and androgen signaling. Hyperandrogenism in females can increase predisposition to insulin resistance. Andrisse et al 2021 showed that deleting the liver androgen receptor (LivARKO) prevented female mice from developing hyperandrogenemia-induced insulin resistance. We wanted to know does LivARKO prevent high fructose diet (HFrD) induced insulin resistance? In our study, we placed female LivARKO mice on high fructose diets (HFrD) to determine if they demonstrated blunted insulin resistance. We hypothesized was that HFrD LivARKO female mice would display impaired insulin action in white adipose tissue. We needed to demonstrate that insulin signaling was functional in LivARKO mice on a control and a HFrD. There are six groups in this study: wild type (WT) no treatment, WT treatment-1, WT treatment-2, LivARKO no treatment, LivARKO treatment-1, and LivARKO treatment-2. No treatment is a chow diet, treatment-1 is a control diet, and treatment-2 is HFrD. Methods: Female LivARKO mice were placed on two diets: Control (Con, Research Diets Inc, RDI D12450J and High Fructose (HFrD, RDI D02022704. The mice were sacrificed after 1 month on the diet. Half of the mice were given a dose of 0.5 U/kg insulin before sacrificing to investigate the effects of the diets on insulin signaling. Western blots were used to determine protein expression in tissue from the white adipose tissue. BCA assays were used to standardize the protein concentration in each sample. Insulin action was measured molecularly by examining p-AKT Serine 473 ( Santa Cruz sc-514032) and p-IRS1 Serine 306 ( Santa Cruz sc-33956). If p-AKT S473 levels increase in the presence of insulin, indicating that insulin is likely functioning properly. If p-IRS1 S306 are elevated, indicates malfunctioning insulin or resistance. Results: LivARKO Female mice on a control diet did not express any insulin stimulated p-AKT in WAT, LivARKO Female mice on a high fructose diet displayed increased insulin stimulated p-AKT compared to LivARKO HFrD mice not given insulin. P-IRS1 was increased in the WAT of the Control Insulin group compared to the WAT of the Control Basal group of female LivARKO mice. Once placed on a HFrD, p-IRS1 was not present in the WAT either group of LivARKO mice. Conclusion: In conclusion, the data is inconclusive. HFrD appeared to augment insulin-stimulated p-AKT but lowered p-IRS1 in WAT of female LivARKO mice. There were several limitations to this study. We do not have data for LivARKO on chow or data for WT on control diet to decipher these effects. Further research is required into what components of the Control Diet are prompting this difference in insulin action.

Presentation: Friday, June 16, 2023
FRI037 Time-restricted Feeding Prevents Progression Of Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis Through IPMK
Authors: Jung Ik-Rak , Anokye-Danso Frederick , Jin Sunghee , Ahima Rexford S , Kim Sangwon
Published: October 2023

Disclosure: I. Jung: None. F. Anokye-Danso: None. S. Jin: None. R.S. Ahima: None. S. Kim: None.

Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide, with a broad spectrum ranging from simple steatosis to advanced stage of nonalcoholic steatohepatitis (NASH). Although many clinical trials for NAFLD treatment are undergoing, there are currently no approved therapies. Insulin resistance is central to the progression of NAFLD and implicated in disease progression from steatosis to NASH. Therefore, modulation of insulin resistance represents a potential strategy for NAFLD treatment. We have reported that inositol polyphosphate multikinase (IPMK), a key enzyme in inositol polyphosphate biosynthesis, plays a role in regulating hepatic insulin signaling and gluconeogenesis both in vitro and in vivo. However, the roles of IPMK in hepatic lipid metabolism were not investigated. To determine the role of IPMK in NAFLD/NASH, we fed high fat diet (HFD) or methionine-choline deficient diet (MCDD) in both wild type (WT) and liver-specific IPMK knockout (LKO) mice. We also examined the effect of time-restricted feeding (TRF), which is known to be beneficial for metabolic disease without influencing the food intake, in NAFDL/NASH. Here, we show that hepatic IPMK protein was decreased in WT mice fed a MCDD compared to a normal chow diet (ND) and loss of IPMK in the liver augments hepatic steatosis and steatohepatitis in mice fed a HFD as well as MCDD. Compared to the WT mice, triglycerides (TG) and pro-inflammatory gene expression in the liver increase significantly in the LKO mice fed HFD. Importantly, MCDD-fed LKO mice exhibit exacerbated NAFLD/NASH accompanied by an increase in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), hepatic TG accumulation and fibrosis, and pro-inflammatory gene expression. Finally, TRF by limiting a food access only during the dark cycle led to an increase in expression hepatic IPMK protein in MCDD mice. Importantly, TRF alleviates NAFLD/NASH reflected by reduced hepatic TG accumulation, lowered serum ALT and AST levels, downregulated pro-inflammatory gene expression compared with ad libitum mice. Our results demonstrate that loss of IPMK mediates the progression of NAFLD/NASH and may be potentially targeted for treatment of NAFLD/NASH.

Presentation: Friday, June 16, 2023