bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crosstalk of hepatocyte nuclear factor 4a and glucocorticoid receptor in the regulation of lipid metabolism in mice fed a high-fat-high-sugar diet
Authors: Lu Hong , Lei Xiaohong , Winkler Rebecca , John Savio , Kumar Devendra , Li Wenkuan , Alnouti Yazen 
Published: May 2022

Abstract
Background
Hepatocyte nuclear factor 4α (HNF4α) and glucocorticoid receptor (GR), master regulators of liver metabolism, are down-regulated in fatty liver diseases. The present study aimed to elucidate the role of down-regulation of HNF4α and GR in fatty liver and hyperlipidemia.

Methods
Adult mice with liver-specific heterozygote (HET) and knockout (KO) of HNF4α or GR were fed a high-fat-high-sugar diet (HFHS) for 15 days. Alterations in hepatic and circulating lipids were determined with analytical kits, and changes in hepatic mRNA and protein expression in these mice were quantified by real-time PCR and Western blotting. Serum and hepatic levels of bile acids were quantified by LC-MS/MS. The roles of HNF4α and GR in regulating hepatic gene expression were determined using luciferase reporter assays.

Results
Compared to HFHS-fed wildtype mice, HNF4α HET mice had down-regulation of lipid catabolic genes, induction of lipogenic genes, and increased hepatic and blood levels of lipids, whereas HNF4α KO mice had fatty liver but mild hypolipidemia, down-regulation of lipid-efflux genes, and induction of genes for uptake, synthesis, and storage of lipids. Serum levels of chenodeoxycholic acid and deoxycholic acid tended to be decreased in the HNF4α HET mice but dramatically increased in the HNF4α KO mice, which was associated with marked down-regulation of cytochrome P450 7a1, the rate-limiting enzyme for bile acid synthesis. Hepatic mRNA and protein expression of sterol-regulatory-element-binding protein-1 (SREBP-1), a master lipogenic regulator, was induced in HFHS-fed HNF4α HET mice. In reporter assays, HNF4α cooperated with the corepressor small heterodimer partner to potently inhibit the transactivation of mouse and human SREBP-1C promoter by liver X receptor. Hepatic nuclear GR proteins tended to be decreased in the HNF4α KO mice. HFHS-fed mice with liver-specific KO of GR had increased hepatic lipids and induction of SREBP-1C and PPARγ, which was associated with a marked decrease in hepatic levels of HNF4α proteins in these mice. In reporter assays, GR and HNF4α synergistically/additively induced lipid catabolic genes.

Conclusions
induction of lipid catabolic genes and suppression of lipogenic genes by HNF4α and GR may mediate the early resistance to HFHS-induced fatty liver and hyperlipidemia.

Graphical abstract
Magnetic resonance guided adaptive stereotactic body radiotherapy for lung tumors in ultracentral location: the MAGELLAN trial (ARO 2021-3)
Authors: Regnery Sebastian , Ristau Jonas , Weykamp Fabian , Hoegen Philipp , Sprengel Simon David , Paul Katharina Maria , Buchele Carolin , Klüter Sebastian , Rippke Carolin , Renkamp Claudia Katharina , Pohl Moritz , Meis Jan , Welzel Thomas , Adeberg Sebastian , Koerber Stefan Alexander , Debus Jürgen , Hörner-Rieber Juliane 
Published: May 2022

Abstract
Background
Stereotactic Body Radiotherapy (SBRT) is a standard treatment for inoperable primary and secondary lung tumors. In case of ultracentral tumor location, defined as tumor contact with vulnerable mediastinal structures such as the proximal bronchial tree (PBT) or esophagus, SBRT is associated with an increased risk for severe complications. Magnetic resonance (MR)-guided SBRT can mitigate this risk based on gated dose delivery and daily plan adaptation. The MAGELLAN trial aims to find the maximum tolerated dose (MTD) of MR-guided SBRT of ultracentral lung tumors (ULT).

Patients and methods
MAGELLAN is a prospective phase I dose escalation trial. A maximum of 38 patients with primary and secondary ULT with a tumor size ≤ 5 cm will be enrolled. Ultracentral location is defined as an overlap of the planning target volume (PTV) with the PBT or esophagus. Patients are treated at a 0.35 Tesla MR-linac (MRIdian® Linac, ViewRay Inc.
) employing a gating strategy and daily plan adaptation. Dose escalation starts at 10 × 5.5 Gy (biologically effective dose BED3/10: 155.83 Gy/85.25 Gy), may proceed up to 10 × 6.5 Gy (BED3/10: 205.83 Gy/107.25 Gy) and is guided by a customized time-to-event continual reassessment method (TITE CRM) with backup element, which alternately assigns patients to dose escalation and backup cohorts.

Discussion
The results of the MAGELLAN trial will guide further research and clinical implementation of MR-guided SBRT as ablative treatment of ULT.
Moreover, the combination of MR-guided radiotherapy with TITE-CRM including a backup element may serve as blueprint for future radiation dose escalation studies in critical locations.

Trial Registration

Registered at ClinicalTrials.gov: NCT04925583 on 14th June 2021.
Targeting TROY-mediated P85a/AKT/TBX3 signaling attenuates tumor stemness and elevates treatment response in hepatocellular carcinoma
Authors: Liu Beilei , Fang Xiaona , Kwong Dora Lai-Wan , Zhang Yu , Verhoeft Krista , Gong Lanqi , Zhang Baifeng , Chen Jie , Yu Qianqian , Luo Jie , Tang Ying , Huang Tuxiong , Ling Fei , Fu Li , Yan Qian , Guan Xin-Yuan 
Published: May 2022

AbstractBackgroundPrevious in vitro hepatocyte differentiation model showed that TROY was specifically expressed in liver progenitor cells and a small proportion of hepatocellular carcinoma cells, suggesting that TROY may participate in hepatocellular carcinoma (HCC) stemness regulation. Here, we aim to investigate the role and mechanism of TROY in HCC pathogenesis.MethodBioinformatics analysis of the TCGA dataset has been used to identify the function and mechanism of TROY. Spheroid, apoptosis, and ALDH assay were performed to evaluate the stemness functions. Validation of the downstream pathway was based on Western blot, co-immunoprecipitation, and double immunofluorescence.ResultsHCC tissue microarray study found that a high frequency of TROY-positive cells was detected in 53/130 (40.8%) of HCC cases, which was significantly associated with poor prognosis and tumor metastasis. Functional studies revealed that TROY could promote self-renewal, drug resistance, tumorigenicity, and metastasis of HCC cells. Mechanism study found that TROY could interact with PI3K subunit p85α, inducing its polyubiquitylation and degradation. The degradation of p85α subsequently activate PI3K/AKT/TBX3 signaling and upregulated pluripotent genes expression including SOX2, NANOG, and OCT4, and promoted EMT in HCC cells. Interestingly, immune cell infiltration analysis found that upregulation of TROY in HCC tissues was induced by TGF-β1 secreted from CAFs. PI3K inhibitor wortmannin could effectively impair tumor stemness to sorafenib.ConclusionWe demonstrated that TROY is an HCC CSC marker and plays an important role in HCC stemness regulation. Targeting TROY-positive CSCs with PI3K inhibitor wortmannin combined with chemo- or targeted drugs might be a novel therapeutic strategy for HCC patients.Graphical abstract
Recreational climbers are more conscientious than recreational athletes–a case control study
Authors: Steinmetz Gino , Assmann Mara , Hubert Jan , Saul Dominik 
Published: May 2022

Abstract
Background
Physiological characteristics of climbers have been extensively studied, while the personality of climbers remains poorly understood. Personality research in sports is an established field, predicting long-term success as well as short-term behavior. The goal of our study was to examine recreational climbers’ personality and gain a better understanding of what makes them reach new heights.

Methods
We analyzed a cohort of 50 recreational climbers and 50 non-climbing athletes (control) regarding their personality characteristics. We assessed the BMI, the self-reported climbing grade, and the years of climbing experience. To evaluate the personality of recreational climbers and athletes, we used the German version of the Big Five Inventory (BFI-2), which summarizes the personality in five main categories.

Results
Recreational climbers scored significantly higher in conscientiousness than non-climbing athletes (p = 0.04), there was no significant difference between the other four main personality traits. Female climbers scored significantly higher in conscientiousness than male climbers (p = 0.02), while female athletes scored higher in openness than male athletes (p < 0.01). The climbing group displayed a small but significant negative correlation between conscientiousness and BMI (r = -0.39; p < 0.01).

Conclusion
In conclusion, the personality of recreational climbers and recreational athletes differs in conscientiousness, with the climbers showing higher scores. Regarding gender, we found higher levels of conscientiousness in female climbers and higher openness in female athletes in comparison to their male counterparts. A negative correlation between BMI and conscientiousness of the climbers was detected.
Does caffeine ingestion affect the lower-body post-activation performance enhancement in female volleyball players?
Authors: Filip-Stachnik Aleksandra , Spieszny Michał , Stanisz Lidia , Krzysztofik Michał 
Published: May 2022

Abstract
Background
Post-activation performance enhancement (PAPE) is a physiological phenomenon that acutely improves voluntary muscular performance following a conditioning activity. A large and growing body of literature has investigated different strategies to induce a PAPE stimulus; however, little attention has been given to whether acute caffeine ingestion could augment the effect of PAPE on subsequent performance. This study evaluated the acute effects of caffeine ingestion and back squat conditioning activity on subsequent countermovement jump (CMJ) performance in female semi-professional volleyball players.

Methods
Fourteen resistance-trained female volleyball players (26 ± 3 years) performed 3 different testing conditions in randomized order: where each ingested 6 mg/kg of caffeine (CAF) or placebo (PLAC) and performed a single set of back squats at 80%1RM until mean movement velocity dropped by 10% as the conditioning activity or a control (CTRL) condition where participants did not ingest any supplement and did not perform the conditioning activity. CMJ height was examined at baseline and in 2 min intervals until 10 min postconditioning activity. Furthermore, due to the wide inter-individual variation in optimal recovery time of PAPE response, the baseline and best post-conditioning activity performance were also analyzed.

Results
The Friedman test revealed a significant difference in jump height within CTRL (p = 0.002) and CAF (p = 0.001) conditions, but no significant difference was found within the PAP condition. The post hoc showed a significant decrease in jump height in 8th min in CTRL condition (p = 0.022, effect size [ES] = −0.31), a significant increase in jump height in 2nd min in CAF condition (p = 0.013, ES = 0.3), without differences in PLAC condition in comparison to baseline values. Moreover, a significant jump height increases from baseline to best performance post conditioning activity value for CAF (p = 0.001, ES = 0.39) and PLAC (p = 0.001, ES = 0.3) condition, but no significant difference was found for the CTRL condition.

Conclusions
The single set of heavy-loaded back squats with controlled velocity used as a conditioning activity in the current study enhanced subsequent CMJ performance in female volleyball players with no additional effect of caffeine.
Ischemic stroke and intestinal flora: an insight into brain–gut axis
Authors: Hu Wenjie , Kong Xiangyi , Wang Hui , Li Yunqing , Luo Yimin 
Published: May 2022

AbstractStroke is a type of cerebrovascular disease that significantly endangers human health and lowers quality of life. This understandably places a heavy burden on society and families. In recent years, intestinal flora has attracted increasing attention from scholars worldwide, and its association with ischemic stroke is becoming a hot topic of research amongst researchers in field of stroke. After suffering from a stroke, intestinal microbial dysbiosis leads to increased intestinal permeability and activation of the intestinal immune system, which in turn leads to ectopic intestinal bacteria and pro-inflammatory cells that enter brain tissue through the damaged blood-brain barrier. This exacerbates ischemia-reperfusion injury. Interestingly, after a stroke, some metabolites produced by the intestinal flora attenuate ischemia-reperfusion injury by suppressing the post-stroke inflammatory response and promotes the repair of neurological function. Here we elucidate the changes in gut flora after occurrence of a stroke and highlight the immunomodulatory processes of the post-stroke gut flora.
Cardioprotective effects of sodium thiosulfate against doxorubicin-induced cardiotoxicity in male rats
Authors: Shekari Maryam , Gortany Narges Khalilian , Khalilzadeh Mina , Abdollahi Alireza , Ghafari Homanaz , Dehpour Ahmad Reza , Ghazi-Khansari Mahmoud 
Published: May 2022

Abstract
Background
Doxorubicin (DOX) is an effective antitumor agent, but its clinical usage is limited due to adverse cardiotoxic effects. Several compounds have been studied to reduce DOX cardiotoxicity to improve its therapeutic index. This study was aimed to investigate the protective effects of sodium thiosulfate (STS) pre-treatment against DOX-induced cardiomyopathy in rats.

Methods
Male Wistar rats were randomized into 4 groups: control (saline), DOX (2.5 mg/kg, 3 times per week, intraperitoneal [i.p.]), STS (300 mg/kg, 3 times per week, i.p), and DOX + STS (30 min prior to DOX injection, 3 times per week, i.p.) over a period of 2 weeks. The body weight, electrocardiography, histopathology, papillary muscle contractility, and oxidative stress biomarkers in heart tissues were assessed.

Results
The results indicated that STS significantly improved the body weight (P < 0.01), decreased QRS complex and QT interval on ECG (P < 0.05 and P < 0.001, respectively), as well as declined the papillary muscle excitation, and increased its contraction (P < 0.01) compared to DOX-treated rats. STS strongly suppressed oxidative stress induced by DOX through the significant improvement of the cardiac tissue antioxidant capacity by increasing glutathione, superoxide dismutase (P < 0.001), and decreasing the level of lipid peroxidation (P < 0.01).

Conclusion
Taken together, the results of this study demonstrated that STS showed potent cardioprotective effects against DOX-induced cardiotoxicity by suppressing oxidative stress.
Strategies of visibility in the smart city
Authors: Torisson Fredrik 
Published: May 2022

AbstractCities across the world are increasingly labelling themselves as smart in one way or another. At the same time, this smartness appears amorphous or invisible in its built urban environment. Critical researchers writing on the smart city regularly express confusion or exasperation about precisely the difficulty to locate the smart in the city. Visibility of the smart city is not a given. This article argues that visibility in the case of the smart city is instead strategically produced, and that the strategy opted for tells us something about the kind of urban imaginary put forward. The article introduces a provisional and non-exhaustive taxonomy of strategies of visibility based on analyses of three different cases of smart city projects (in Brazil, Sweden and Canada) and identifies the ways in which the smart city is made visible (or not)—symbolic presence of smart, modelling smart and ubiquitous invisible smart—and discusses what kind of city is envisioned based on each strategy.
Recent trends in movement ecology of animals and human mobility
Authors: Joo Rocío , Picardi Simona , Boone Matthew E. , Clay Thomas A. , Patrick Samantha C. , Romero-Romero Vilma S. , Basille Mathieu 
Published: May 2022

AbstractMovement is fundamental to life, shaping population dynamics, biodiversity patterns, and ecosystem structure. In 2008, the movement ecology framework (MEF Nathan et al. in PNAS 105(49):19052–19059, 2008) introduced an integrative theory of organismal movement—linking internal state, motion capacity, and navigation capacity to external factors—which has been recognized as a milestone in the field. Since then, the study of movement experienced a technological boom, which provided massive quantities of tracking data of both animal and human movement globally and at ever finer spatio-temporal resolutions. In this work, we provide a quantitative assessment of the state of research within the MEF, focusing on animal movement, including humans and invertebrates, and excluding movement of plants and microorganisms. Using a text mining approach, we digitally scanned the contents of$$>8000$$>8000papers from 2009 to 2018 available online, identified tools and methods used, and assessed linkages between all components of the MEF. Over the past decade, the publication rate has increased considerably, along with major technological changes, such as an increased use of GPS devices and accelerometers and a majority of studies now using the R software environment for statistical computing. However, animal movement research still largely focuses on the effect of environmental factors on movement, with motion and navigation continuing to receive little attention. A search of topics based on words featured in abstracts revealed a clustering of papers among marine and terrestrial realms, as well as applications and methods across taxa. We discuss the potential for technological and methodological advances in the field to lead to more integrated and interdisciplinary research and an increased exploration of key movement processes such as navigation, as well as the evolutionary, physiological, and life-history consequences of movement.
Physical growth and social prognosis of esophageal atresia after 15 years of age
Authors: Masuya Ryuta , Muto Mitsuru , Sugita Koshiro , Murakami Masakazu , Yano Keisuke , Harumatsu Toshio , Onishi Shun , Yamada Koji , Yamada Waka , Matsukubo Makoto , Kawano Takafumi , Machigashira Seiro , Nakame Kazuhiko , Torikai Motofumi , Mukai Motoi , Kaji Tatsuru , Ieiri Satoshi 
Published: May 2022

Abstract
Background
The mortality rate of esophageal atresia (EA) has significantly improved, but late complications remain problematic. We evaluated the physical growth, late complications, and social prognosis of postoperative patients with EA who have reached 15 years of age.

Methods
EA patients who were treated at our institution from 1984 to 2003 were enrolled. The follow-up, physical growth at the last visit, late complications and treatment, academic status, and employment situation were evaluated.

Results
Twenty-nine EA patients were registered, and the 23 surviving patients (79.3%) were followed. Anthropometry at the latest visit tended to be below the standard values. Fundoplication was performed in 6 (26.1%) of 9 (39.1%) patients with gastroesophageal reflux. Anastomotic stenosis was found in 12 patients (52.2%), and 2 (8.7%) were treated with re-anastomosis. Thirteen patients were attending a regular school, and one was attending a school for disabled children. Four had jobs from 18 years of age. Follow-up was aborted during early childhood in nine patients.

Conclusions
The physical size of EA was smaller than in the healthy population of the same age. Late complications had not affected the physical growth but were sometimes recognized in adolescence. The social prognosis of the patients was largely favorable.
The integrity of the research record: a mess so big and so deep and so tall
Authors: Lee William , Casey Patricia , Poole Norman , Kaufman Kenneth R. , Lawrie Stephen M. , Malhi Gin , Petkova Eva , Siddiqi Najma , Bhui Kamaldeep 
Published: May 2022

SummaryPoor research integrity is increasingly recognised as a serious problem in science. We outline some evidence for this claim and introduce the Royal College of Psychiatrists (RCPsych) journals’ Research Integrity Group, which has been created to address this problem.
Convolutional neural network-based automatic cervical vertebral maturation classification method
Authors: Li Haizhen , Chen Yanlong , Wang Qing , Gong Xu , Lei Yi , Tian Jialiang , Gao Xuemei 
Published: May 2022

Objectives: This study aimed to develop a fully automated artificial intelligence-aided cervical vertebral maturation (CVM) classification method based on convolutional neural networks (CNNs) to provide an auxiliary diagnosis for orthodontists. Methods: This study consisted of cephalometric images from patients aged between 5 and 18 years. After grouping them into six cervical stages (CSs) by orthodontists, a data set was constructed for analyzing CVM using CNNs. The data set was divided into training, validation, and test sets in the ratio of 70, 15, and 15%. Four CNN models namely, VGG16, GoogLeNet, DenseNet161, and ResNet152 were selected as the candidate models. After training and validation, the models were evaluated to determine which of them is most suitable for CVM analysis. Heat maps were analyzed for a deeper understanding of what the CNNs had learned. Results: The final classification accuracy ranking was ResNet152>DenseNet161>GoogLeNet>VGG16, as evaluated on the test set. ResNet152 proved to be the best model among the four models for CVM classification with a weighted κ of 0.826, an average AUC of 0.933 and total accuracy of 67.06%. The F1 score rank for each subgroup was: CS6>CS1>CS4>CS5>CS3>CS2. The area of the third (C3) and fourth (C4) cervical vertebrae were activated when CNNs were assessing the images. Conclusion: CNN models proved to be a convenient, fast and reliable method for CVM analysis. CNN models have the potential to provide automatic auxiliary diagnostic tools in the future.
Intelligent digital twins and the development and management of complex systems
Authors: Grieves Michael 
Published: May 2022

The interest in defining and implementing Digital Twins (DT) is at the forefront of today’s product organizations. The evolution of increasingly complex systems requires that their information be organized and managed via digital twins. In addition, the development of Artificial Intelligence (AI) will result in an increasing degree of system complexity. These complex systems will exhibit true emergent behavior as AIs modify system aspects as the result of goal seeking and learning. DTs will need to increase in capability, becoming intelligent in their approach. This article presents a discussion on how these Intelligent Digital Twins (IDTs) will evolve and assist in developing and managing complex systems.