bluuebunny/crossref_metadata_2025 huggingface dataset:
Towards probabilistic seismic performance of vehicle‐bridge interaction systems: From stochastic dynamic model to fragility analysis
Authors: Yuan Peng , Dong You , Feng Ruiwei , Frangopol Dan M.
Published: October 2022

This paper aims to assess the seismic fragility of vehicle‐bridge‐interaction (VBI) systems considering the effects of vehicle types, traffic conditions, and road surface qualities. A stochastic nonlinear mechanical model for the earthquake‐VBI system is developed, and the fragility functions for the proposed VBI model are derived by considering the relevant probabilistic seismic demand parameters. On the basis of a typical four‐span continuous prestressed concrete highway bridge in China, a complete numerical model for the VBI system is built considering multiple uncertainties from bridge and vehicle parameters, as well as the road surface qualities. A total of 120 real ground motion records with different combinations of magnitude‐source‐to‐site distance (M‐R) and earthquake intensity characteristics are selected. Meanwhile, 80 scenarios in terms of different combinations of vehicle types, vehicle speeds, and road surface irregularities are defined. In this context, 96,000 nonlinear time‐history analyses are performed, and the developed fragility models are applied to the VBI system at both component and system levels. Results indicate that the fragilities of pier drift, bearing shear strain, and the overall VBI system increase with the increase of the vehicle weight or the decrease of the vehicle speed, while the vertical deck displacement is dominated by the vehicle weight. It is also found that the road surface quality has a negligible effect on both component and system fragilities.
Cross‐wavelet analysis of coherent wind and saltation events
Authors: Ellis Jean T. , Sherman Douglas J.
Published: October 2022

This paper presents high‐resolution field measurements of the wind and saltation fields using miniphones and anemometers located 20–40 mm apart (bed‐parallel) and 10–40 mm above the bed. The average wind speeds at the Shoalhaven Heads, Australia and the Jericoacoara, Brazil field sites are both 4.4 m s−1, and the average saltation rates are 5.0 and 22.2 counts/mm2 s−1, respectively. Normalized cross‐covariance analysis between the wind and saltation time series indicates a dominant saltation response time of 0 s. Cross‐wavelet analysis focusing on short‐duration events characterizes statistically significant wind–sand events and intervals. In the high aeolian saltation rate environment (Brazil), the events and intervals averaged 1.9 and 12.2 s. The low transport environment (Australia) resulted in 2.1 s events and 10.8 s intervals. This study demonstrates that wind–sand events occur about 15% of the time but account for about 23% of the sand transport. These results were possible because of the presentation of a wavelet‐derived event time series. The criticality of tightly controlled field experiments to measure coincident wind and saltation fluctuations with co‐located sensors was demonstrated. This paper emphasizes the importance of the contribution of saltation events to time‐averaged transport rates, which influences sediment flux modelling.
Subduction‐related mafic to felsic magmatism in the Xiangpishan concentric calc‐alkaline complex, Northeast Tibetan Plateau
Authors: Zou Feng‐Hui , Wu Cai‐Lai , Deng Li‐Huan , Gao Dong , Gao Yuan‐Hong
Published: October 2022

The Xiangpishan complex in the Zongwulong‐Qinghainanshan Tectonic Belt, Northeast (NE) Tibetan Plateau, is a composite concentric pluton consisting of a felsic core (granodiorite) surrounded by quartz diorite in the middle to diorite and minor gabbro at the margin with locally less volume of monzogranite. Many dioritic enclaves are unevenly distributed within host granitoids. We evaluate the petrogenesis of the complex by geochemical, geochronological, and Hf isotopic data in tandem with regional data in the belt. The results show that felsic rocks were emplaced during the Late Permian (ca. 262–256 Ma); whilst gabbros yielded a younger age of ca. 249 Ma. As the hybrid phase from mixing between felsic and mafic magmas, enclaves and diorites have analogous ages (ca. 257–254 Ma) to both. Zircons from gabbro and enclaves are marked by higher εHf(t) value up to +1.82; whilst granodiorites have lower εHf(t) value of −5.48, consistent with hybrid diorites possessing intermediate εHf(t) values of −3.14 to 0.34. Furthermore, the quantitative calculation from Mass Balances Modelling suggests that the mass of mafic magma (ca. 67%–79%) is involved to achieve the hybridization. Geochemically, these rocks crystallized from calc‐alkaline magma with different sources, but demonstrated consistent arc‐like signatures, as they are enriched in large‐ion lithophile elements and light rare earth element (LREE), and depleted in high‐ field‐strength elements and heavy rare earth element (HREE). Besides, they present negative Nb–Ta anomalies together with significant P and Ti troughs. Finally, an evolutional model has been proposed that the asthenosphere‐lithosphere interaction played an important role during the emplacement of the complex, where the limited volumes of mantle‐derived melt act as the suppliers of heat and mass (mainly volatile components) to induce partial melting of the juvenile mafic lower crust and mixed (or mingled) with the produced crust‐derived magma during the oceanic subduction, which led to the generation of diorites as well as mafic microgranular enclaves.
Distinguishing apathy and depression in older adults with mild cognitive impairment using text, audio, and video based on multiclass classification and shapely additive explanations
Authors: Zhou Ying , Yao Xiuyu , Han Wei , Wang Yidan , Li Zheng , Li Yingxin
Published: October 2022

Objectives

This study aimed to develop a classification model to detect and distinguish apathy and depression based on text, audio, and video features and to make use of the shapely additive explanations (SHAP) toolkit to increase the model interpretability.

Methods

Subjective scales and objective experiments were conducted on 319 mild cognitive impairment (MCI) patients to measure apathy and depression. The MCI patients were classified into four groups, depression only, apathy only, depressed‐apathetic, and the normal group. Speech, facial and text features were extracted using the open‐source data analysis toolkits. Multiclass classification and SHAP toolkits were used to develop a classification model and explain the contribution of specific features.

Results

The macro‐averaged f1 score and accuracy for overall model were 0.91 and 0.90, respectively. The accuracy for the apathetic, depressed, depressed‐apathetic, and normal groups were 0.98, 0.88, 0.93, and 0.82, respectively. The SHAP toolkit identified speech features (Mel‐frequency cepstral coefficient (MFCC) 4, spectral slopes, F0, F1), facial features (action unit (AU) 14, 26, 28, 45), and text feature (text 6 semantic) associated with apathy. Meanwhile, speech features (spectral slopes, shimmer, F0) and facial expression (AU 2, 6, 7, 10, 14, 26, 45) were associated with depression. Apart from the shared features mentioned above, new speech (MFCC 2, loudness) and facial (AU 9) features were observed in the depressive‐apathetic group.

Conclusions

Apathy and depression shared some verbal and facial features while also exhibited distinct features. A combination of text, audio, and video could be used to improve the early detection and differential diagnosis of apathy and depression in MCI patients.
Individual functional parcellation revealed compensation of dynamic limbic network organization in healthy ageing
Authors: Liu Tiantian , Shi Zhongyan , Zhang Jian , Wang Kexin , Li Yuanhao , Pei Guangying , Wang Li , Wu Jinglong , Yan Tianyi
Published: October 2022

Using group‐level functional parcellations and constant‐length sliding window analysis, dynamic functional connectivity studies have revealed network‐specific impairment and compensation in healthy ageing. However, functional parcellation and dynamic time windows vary across individuals; individual‐level ageing‐related brain dynamics are uncertain. Here, we performed individual parcellation and individual‐length sliding window clustering to characterize ageing‐related dynamic network changes. Healthy participants (n = 637, 18–88 years) from the Cambridge Centre for Ageing and Neuroscience dataset were included. An individual seven‐network parcellation, varied from group‐level parcellation, was mapped for each participant. For each network, strong and weak cognitive brain states were revealed by individual‐length sliding window clustering and canonical correlation analysis. The results showed negative linear correlations between age and change ratios of sizes in the default mode, frontoparietal, and salience networks and a positive linear correlation between age and change ratios of size in the limbic network (LN). With increasing age, the occurrence and dwell time of strong states showed inverted U‐shaped patterns or a linear decreasing pattern in most networks but showed a linear increasing pattern in the LN. Overall, this study reveals a compensative increase in emotional networks (i.e., the LN) and a decline in cognitive and primary sensory networks in healthy ageing. These findings may provide insights into network‐specific and individual‐level targeting during neuromodulation in ageing and ageing‐related diseases.
Is HLA type a possible cancer risk modifier in Lynch syndrome?
Authors: Ahadova Aysel , Witt Johannes , Haupt Saskia , Gallon Richard , Hüneburg Robert , Nattermann Jacob , ten Broeke Sanne , Bohaumilitzky Lena , Hernandez‐Sanchez Alejandro , Santibanez‐Koref Mauro , Jackson Michael S. , Ahtiainen Maarit , Pylvänäinen Kirsi , Andini Katarina , Grolmusz Vince Kornel , Möslein Gabriela , Dominguez‐Valentin Mev , Møller Pål , Fürst Daniel , Sijmons Rolf , Borthwick Gillian M. , Burn John , Mecklin Jukka‐Pekka , Heuveline Vincent , von Knebel Doeberitz Magnus , Seppälä Toni , Kloor Matthias
Published: October 2022

Lynch syndrome (LS) is the most common inherited cancer syndrome. It is inherited via a monoallelic germline variant in one of the DNA mismatch repair (MMR) genes. LS carriers have a broad 30% to 80% risk of developing various malignancies, and more precise, individual risk estimations would be of high clinical value, allowing tailored cancer prevention and surveillance. Due to MMR deficiency, LS cancers are characterized by the accumulation of frameshift mutations leading to highly immunogenic frameshift peptides (FSPs). Thus, immune surveillance is proposed to inhibit the outgrowth of MMR‐deficient cell clones. Recent studies have shown that immunoediting during the evolution of MMR‐deficient cancers leads to a counter‐selection of highly immunogenic antigens. The immunogenicity of FSPs is dependent on the antigen presentation. One crucial factor determining antigen presentation is the HLA genotype. Hence, a LS carrier's HLA genotype plays an important role in the presentation of FSP antigens to the immune system, and may influence the likelihood of progression from precancerous lesions to cancer. To address the challenge of clarifying this possibility including diverse populations with different HLA types, we have established the INDICATE initiative (Individual cancer risk by HLA type, http://indicate-lynch.org/), an international network aiming at a systematic evaluation of the HLA genotype as a possible cancer risk modifier in LS. Here we summarize the current knowledge on the role of HLA type in cancer risk and outline future research directions to delineate possible association in the scenario of LS with genetically defined risk population and highly immunogenic tumors.
Sex and smoking differences in the association between gastroesophageal reflux and risk of esophageal squamous cell carcinoma in a high‐incidence area: Golestan Cohort Study
Authors: Soroush Ali , Malekzadeh Reza , Roshandel Gholamreza , Khoshnia Masoud , Poustchi Hossein , Kamangar Farin , Brennan Paul , Boffetta Paolo , Dawsey Sanford M. , Abnet Christian C. , Abrams Julian A. , Etemadi Arash
Published: October 2022

Prior studies have conflicting findings regarding the association between gastroesophageal reflux disease (GERD) and esophageal squamous cell carcinoma (ESCC). We examined this relationship in a prospective cohort in a region of high ESCC incidence. Baseline exposure data were collected from 50 045 individuals using in‐person interviews at the time of cohort entry. Participants were followed until they developed cancer, died, or were lost to follow up. Participants with GERD symptoms were categorized into any GERD (heartburn or regurgitation), mixed symptoms, or heartburn alone. Multivariable Cox regression was used to assess the relationship between GERD symptom group and histologically confirmed ESCC. The model was adjusted for known risk factors for GERD and ESCC. 49 559 individuals were included in this study, of which 9005 had GERD symptoms. Over 13.0 years of median follow up, 290 individuals were diagnosed with ESCC. We found no association between any GERD and risk of ESCC (aHR 0.90, 95% CI: 0.66‐1.24, P = .54). Similar findings were observed for the GERD symptom subtypes. Significant interactions between any GERD and sex (P = .013) as well as tobacco smoking (P = .028) were observed. In post‐hoc analyses, GERD was associated with a decreased risk of ESCC in men (aHR 0.51, 95% CI: 0.27‐0.98 P = .04) and in smokers (aHR 0.26, 95% CI: 0.08‐0.83 P = .02). While there was little evidence for an overall association between GERD symptoms and ESCC risk, significant interactions with sex and smoking were observed. Men and smokers with GERD symptoms had a lower risk of ESCC development.
Using the INCOSE Systems Engineering Competency Framework
Authors: Whitcomb Clifford , White Corina , Khan Rabia
Published: October 2022

This article provides examples for using the INCOSE Systems Engineering Competency Framework in practice. Background information is summarized, competency model tailoring is explained, and four usage scenarios are presented. The usage scenarios demonstrate how employers use the framework and assessment guide. The four usage scenarios are job candidate recruitment, individual competency assessment, job description tailoring for an engineering job that needs systems engineering competencies, and job description tailoring for a systems engineering job requiring an update for model‐based systems engineering and digital engineering competencies. All scenarios are based on those included in the Systems Engineering Competency Assessment Guide.
Teaching Systems Engineering Practices Using Principles from Studio Art Education
Authors: McDermott Tom , Nadolski Molly
Published: October 2022

We have created a cross‐disciplinary learning program across studio art, systems thinking, and systems architecture to improve systems competencies. Previous research produced a framework for relating learning concepts across these three domains. We describe how to apply these concepts to any learning situation to increase systems competencies using systems thinking and systems engineering tools. We have applied the framework in educational settings to teach systems thinking, critical thinking, and systems engineering using a tailored classroom approach derived from studio art classes. The studio format encourages the students to build their skills across a portfolio of work focused on creating appropriate views of a system, communicating them, and gaining critical review – three core aspects of the systems thinking process. An effective systems engineer conceptualizes and solves problems, addresses stakeholder concerns, explores and composes solutions, and manages system evolution. The use of art, as embodied in systems‐related tools, has proven to be an effective method for developing these skills. This article presents the framework and an example graduate level Systems and Critical Thinking class taught using the studio art approach.
Self‐harm, in‐person bullying and cyberbullying in secondary school‐aged children: A data linkage study in Wales
Authors: John Ann , Lee Sze Chim , Puchades Alice , Del Pozo‐Baños Marcos , Morgan Kelly , Page Nicholas , Moore Graham , Murphy Simon
Published: October 2022

Introduction

Although the evidence base on bullying victimization and self‐harm in young people has been growing, most studies were cross‐sectional, relied on self‐reported non‐validated measures of self‐harm, and did not separate effects of in‐person and cyberbullying. This study aimed to assess associations of self‐harm following in‐person bullying at school and cyberbullying victimization controlling for covariates.

Methods

School survey data from 11 to 16 years pupils collected in 2017 from 39 Welsh secondary schools were linked to routinely collected data. Inverse probability weighting was performed to circumvent selection bias. Survival analyses for recurrent events were conducted to evaluate relative risks (adjusted hazard ratios [AHR]) of self‐harm among bullying groups within 2 years following survey completion.

Results

A total of 35.0% (weighted N = 6813) of pupils reported being bullied, with 18.1%, 6.4% and 10.5% being victims of in‐person bullying at school only, cyberbullying only and both in‐person bullying at school and cyberbullying respectively. Adjusting for covariates, effect sizes for self‐harm were significant after being in‐person bullied at school only (AHR = 2.2 [1.1–4.3]) and being both in‐person bullied at school and cyberbullied (AHR = 2.2 [1.0–4.7]) but not being cyberbullied only (AHR = 1.2 [0.4–3.3]). Feeling lonely during recent summer holidays was also a robust predictor (AHR = 2.2 [1.2–4.0]).

Conclusions

We reaffirm the role of in‐person bullying victimization on self‐harm. Pupils were twice as likely to self‐harm following in‐person bullying as their nonvictimised peers. Interventions for young people that minimize the potential impacts of bullying on self‐harm should also include strategies to prevent loneliness.
Athree‐dimensionalmodel to describe complete human corneal oxygenation during contact lens wear
Authors: Aguilella‐Arzo Marcel , Compañ Vicente
Published: October 2022

We perform a novel 3D study to quantify the corneal oxygen consumption and diffusion in each part of the cornea with different contact lens materials. The oxygen profile is calculated as a function of oxygen tension at the cornea‐tear interface and the oxygen transmissibility of the lens, with values used in previous studies. We aim to determine the influence of a detailed geometry of the cornea in their modeling compared to previous low dimensional models used in the literature. To this end, a 3‐D study based on an axisymmetric volume element analysis model was applied to different contact lenses currently on the market. We have obtained that the model provides a valuable tool for understanding the flux and cornea oxygen profiles through the epithelium, stroma, and endothelium. The most important results are related to the dependence of the oxygen flux through the cornea‐lens system on the contact lens thickness and geometry. Both parameters play an important role in the corneal flux and oxygen tension distribution. The decline in oxygen consumption experienced by the cornea takes place just inside the epithelium, where the oxygen tension falls to between 95 and 16 mmHg under open eye conditions, and 30 to 0.3 mmHg under closed eye conditions, depending on the contact lens worn. This helps to understand the physiological response of the corneal tissue under conditions of daily and overnight contact lens wear, and the importance of detailed geometry of the cornea in the modeling of diffusion for oxygen and other species.
Sirt3 Promotes Chondrogenesis, Chondrocyte Mitochondrial Respiration and the Development of High-Fat Diet-Induced Osteoarthritis in Mice
Authors: Zhu Shouan , Donovan Elise L. , Makosa Dawid , Mehta-D'souza Padmaja , Jopkiewicz Anita , Batushansky Albert , Cortassa Dominic , Simmons Aaron D. , Lopes Erika Barboza Prado , Kinter Michael , Griffin Timothy M.
Published: October 2022

Understanding how obesity-induced metabolic stress contributes to synovial joint tissue damage is difficult because of the complex role of metabolism in joint development, maintenance, and repair. Chondrocyte mitochondrial dysfunction is implicated in osteoarthritis (OA) pathology, which motivated us to study the mitochondrial deacetylase enzyme sirtuin 3 (Sirt3). We hypothesized that combining high-fat-diet (HFD)-induced obesity and cartilage Sirt3 loss at a young age would impair chondrocyte mitochondrial function, leading to cellular stress and accelerated OA. Instead, we unexpectedly found that depleting cartilage Sirt3 at 5 weeks of age using Sirt3-flox and Acan-CreERT2 mice protected against the development of cartilage degeneration and synovial hyperplasia following 20 weeks of HFD. This protection was associated with increased cartilage glycolysis proteins and reduced mitochondrial fatty acid metabolism proteins. Seahorse-based assays supported a mitochondrial-to-glycolytic shift in chondrocyte metabolism with Sirt3 deletion. Additional studies with primary murine juvenile chondrocytes under hypoxic and inflammatory conditions showed an increased expression of hypoxia-inducible factor (HIF-1) target genes with Sirt3 deletion. However, Sirt3 deletion impaired chondrogenesis using a murine bone marrow stem/stromal cell pellet model, suggesting a context-dependent role of Sirt3 in cartilage homeostasis. Overall, our data indicate that Sirt3 coordinates HFD-induced changes in mature chondrocyte metabolism that promote OA. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Abstract

Cartilage-specific depletion of Sirt3 protects against osteoarthritis in adult mice fed a high-fat diet, potentially by increasing chondrocyte glycolysis and inhibiting mitochondrial metabolism. However, Sirt3 deletion impairs chondrogenesis, suggesting a context-dependent role of Sirt3 in cartilage homeostasis.
A posteriori localization of many‐body excited states through simultaneous diagonalization
Authors: Blanc Ambre , Monari Antonio , Tremblay Jean Christophe
Published: October 2022

In this paper we propose a numerical method to localize many‐electron excited states. To characterize the electronic structure of the electronic excited states of a system, quantum chemistry methods typically yield a delocalized description of the excitations. Some a priori localization methods have been developed to provide an intuitive local picture of the excited states. They typically require a good strategy to separate the system of interest from its environment, or a set of a priori localized orbitals, that may reduce their computational accuracy. Here, we introduce an a posteriori method to localize delocalized many‐body excited states directly obtained from quantum chemistry calculations. A localization metric for the excited states is defined from their representation as electron–hole pairs, which is encoded in the transition density matrix. This novel a posteriori strategy thus allows to localize excitons within a volume around selected fragments of a complex molecular system without tempering with its quantum chemical treatment. The method is tested on π‐stacked oligomers of phenanthrenes and pyrenes. It is found to efficiently localize and separate the excitons according to their character while preserving the information about delocalized many‐body states at a low computational cost.
The dark side of foetal bovine serum in extracellular vesicle studies
Authors: Urzì Ornella , Olofsson Bagge Roger , Crescitelli Rossella
Published: October 2022

Extracellular vesicles (EVs) have been shown to be involved in cell‐cell communication and to take part in both physiological and pathological processes. Thanks to their exclusive cargo, which includes proteins, lipids, and nucleic acids from the originating cells, they are gaining interest as potential biomarkers of disease. In recent years, their appealing features have been fascinating researchers from all over the world, thus increasing the number of in vitro studies focused on EV release, content, and biological activities. Cultured cell lines are the most‐used source of EVs; however, the EVs released in cell cultures are influenced by the cell culture conditions, such as the use of foetal bovine serum (FBS). FBS is the most common supplement for cell culture media, but it is also a source of contaminants, such as exogenous bovine EVs, RNA, and protein aggregates, that can contaminate the cell‐derived EVs and influence their cargo composition. The presence of FBS contaminants in cell‐derived EV samples is a well‐known issue that limits the clinical applications of EVs, thus increasing the need for standardization. In this review, we will discuss the pros and cons of using FBS in cell cultures as a source of EVs, as well as the protocols used to remove contaminants from FBS.
Increased cases of influenza C virus in children and adults in Austria, 2022
Authors: Camp Jeremy V. , Redlberger‐Fritz Monika
Published: October 2022

Sentinel surveillance of influenza‐like illnesses revealed an increase in the cases of influenza C virus in children and adults in Austria, 2022, compared to previous years, following one season (2020/2021), wherein no influenza C virus was detected. Whole‐genome sequencing revealed no obvious genetic basis for the increase. We propose that the reemergence is explained by waning immunity from lack of community exposure due to restrictions intended to limit severe acute respiratory syndrome coronavirus 2 spread in prior seasons, pending further investigation.
Real‐world treatment pattern and prognostic factors of stage IV lung squamous cell carcinoma patients
Authors: Hsu En‐Chi , Wu Kuan‐Li , Tsai Ying‐Ming , Lee Mei‐Hsuan , Tsai Ming‐Ju , Kuo Chia‐Yu , Liu Yu‐Chuan , Liang Fu‐Wen , Yang Chih‐Jen , Hung Jen‐Yu
Published: October 2022

Lung squamous cell carcinoma (LUSC) represents a minor proportion of nonsmall cell lung cancer (NSCLC) harboring a poor prognosis. Herein, retrospective medical record research was performed to investigate real‐world treatment patterns and identify the prognostic factors among LUSC patients. A total of 173 patients with a median age of 68 years were enrolled for analysis. Males were predominant (n = 143, 83%) and current or ex‐smokers contributed to 78% of the entire cohort. Pleura and lung were the most common metastatic sites, whereas brain metastasis was only 7%. After diagnosis, however, only 107 patients (62%) had received first‐line chemotherapy. In the chemotherapy cohort, median progression‐free survival (PFS) and overall survival (OS) were 3.9 and 11.1 months, respectively. After multivariable analysis, bone metastasis and the use of first‐line single‐agent chemotherapy independently predicted shorter PFS. For baseline characteristics, male sex, metastasis to lung, pleura, liver, and bone independently predicted worse OS. Regarding the treatment pattern, patients who had undergone standard first‐line doublet therapy and employed targeted therapies after disease progression linked to longer OS. In the real world, even those who underwent chemotherapy still had poor outcome. The findings may help clinicians to orchestrate the treatment strategies for LUSC patients and provide further direction of large‐scale studies.
Adlay (Coix lacryma‐jobi L.) Polyphenol Improves Hepatic Glucose and Lipid Homeostasis through Regulating Intestinal Flora via AMPK Pathway
Authors: Ma Shengsuo , Yang Bing , Shi Yucong , Du Yang , Lv Yiwen , Liu Jiarong , Liu Enyan , Xu Huachong , Deng Li , Chen Xiao‐yin
Published: October 2022

Scope

Non‐alcoholic fatty liver disease (NAFLD) is a type of metabolic syndrome characterized of abnormal lipid deposition in the liver. Adlay polyphenol (AP), an effective component extracted from Coix lacryma‐jobi L., has been reported that it can be used as a dietary supplement to prevent NAFLD. In this study, the mechanism and action of AP on lipid metabolism and regulation of intestinal flora are investigated.

Methods and results

AP significantly decreases the lipid accumulation in free fatty acid‐treated HepG2 cells. Western blot results indicate that AP improves lipid metabolism via activating the p‐AMPK/p‐ACC pathway. In vivo experiments show AP treatment significantly decreases the body weight, liver weight, hepatic triglyceride, and total cholesterol contents, as well as the serum glucose levels in high fat diet‐fed mice, which may affect lipid accumulation by activating AMPK pathway and changing intestinal bacterial communities and intestinal microbiome metabolism.

Conclusion

AP can be used as a food supplement for improving lipid metabolic dysfunction and reducing the incidence of metabolic diseases.
The role of material fabric in confined concrete
Authors: Ghosh Subha , Deb Arghya
Published: October 2022

The paper is a comparative study of the role of material fabric in unconfined concrete and in concrete subjected to external confinement. In unconfined concrete, the material fabric is the principal reason for the early onset of shear bands in specimens with rounded aggregates. Anisotropy in the material fabric also determines the strength of the “internal confinement mechanism,” and contributes to higher macro strength in specimens with angular aggregates. In contrast, in confined specimens, fabric isotropy, typical of rounded aggregates, is found to be more suited to capture the benefits of external confinement. With increase in axial strain, the fabric dependent anisotropic contribution grows more slowly in specimens with rounded aggregates. This facilitates rapid mobilization of confining pressure, and contributes to the higher confining efficiency of such specimens. However, higher confining pressure in specimens with rounded aggregates also results in such specimens being more susceptible to mortar damage and Mode II interface fracture than their angular counterparts.
An analytical model for ground support by bolting
Authors: Yasuda Naotoshi
Published: October 2022

Bolts have been used under various geological conditions as reinforcement to support underground openings. However, quantitative evaluations of the impacts of reinforcement bolts remain controversial. When a bolt is modeled explicitly, one challenge is determining the parameter that represents the interaction between the bolt and surrounding medium. This study aims to derive a simplified Winkler model for the ground support provided by a bolt, with the mutual interaction between the bolt and the surrounding ground analytically evaluated. Theoretical solutions are derived that rigorously consider the mutual interaction between a bolt and the surrounding ground based on two‐dimensional axisymmetric elasticity. The obtained solutions are compared with those from the simplified model, in which the bolt is assumed as a rod and the surrounding ground is assumed to have a constant stiffness. The numerical results show that the simplified model can evaluate the ground‐bolt interaction when the ground deformation follows the bolt. However, the model cannot accurately model pullout tests as the free surface strongly influences the result, and it is difficult to define a constant representing the surrounding ground.
A two‐grid finite element method for the Allen‐Cahn equation with the logarithmic potential
Authors: Wang Danxia , Li Yanan , Jia Hongen
Published: October 2022

In this paper, we present a two‐grid finite element method for the Allen‐Cahn equation with the logarithmic potential. This method consists of two steps. In the first step, based on a fully implicit finite element method, the Allen‐Cahn equation is solved on a coarse grid with mesh size H. In the second step, a linearized system whose nonlinear term is replaced by the value of the first step is solved on a fine grid with mesh size h. We give the energy stabilities of the traditional finite element method and the two‐grid finite element method. The optimal convergence order of the two‐grid finite element method in H1 norm is achieved when the mesh sizes satisfy h = O(H2). Numerical examples are given to demonstrate the validity of the proposed scheme. The results show that the two‐grid method can save the CPU time while keeping the same convergence rate.
Cdt1 overexpression drives colorectal carcinogenesis through origin overlicensing and DNA damage
Authors: Petropoulos Michalis , Champeris Tsaniras Spyridon , Nikou Sofia , Maxouri Styliani , Dionellis Vasilis S , Kalogeropoulou Argyro , Karamichali Angeliki , Ioannidis Konstantinos , Danalatos Iosif‐Rodolfos , Obst Mandy , Naumann Ronald , Delinasios George J , Gorgoulis Vassilis G , Roukos Vassilis , Anastassiadis Konstantinos , Halazonetis Thanos D , Bravou Vasiliki , Lygerou Zoi , Taraviras Stavros
Published: October 2022

Chromatin licensing and DNA replication factor 1 (CDT1), a protein of the pre‐replicative complex, is essential for loading the minichromosome maintenance complex (MCM) helicases onto the origins of DNA replication. While several studies have shown that dysregulation of CDT1 expression causes re‐replication and DNA damage in cell lines, and CDT1 is highly expressed in several human cancers, whether CDT1 deregulation is sufficient to enhance tumorigenesis in vivo is currently unclear. To delineate its role in vivo, we overexpressed Cdt1 in the mouse colon and induced carcinogenesis using azoxymethane/dextran sodium sulfate (AOM/DSS). Here, we show that mice overexpressing Cdt1 develop a significantly higher number of tumors with increased tumor size, and more severe dysplastic changes (high‐grade dysplasia), compared with control mice under the same treatment. These tumors exhibited an increased growth rate, while cells overexpressing Cdt1 loaded greater amounts of Mcm2 onto chromatin, demonstrating origin overlicensing. Adenomas overexpressing Cdt1 showed activation of the DNA damage response (DDR), apoptosis, formation of micronuclei, and chromosome segregation errors, indicating that aberrant expression of Cdt1 results in increased genomic and chromosomal instability in vivo, favoring cancer development. In line with these results, high‐level expression of CDT1 in human colorectal cancer tissue specimens and colorectal cancer cell lines correlated significantly with increased origin licensing, activation of the DDR, and microsatellite instability (MSI). © 2022 The Pathological Society of Great Britain and Ireland.
Role of MIF1/MIF2/CD74 interactions in bladder cancer
Authors: Woolbright Benjamin L , Rajendran Ganeshkumar , Abbott Erika , Martin Austin , Amalraj Sarah , Dennis Katie , Li Xiaogang , Warrick Joshua , Taylor John A
Published: October 2022

Macrophage migration inhibitory factor (MIF1) is a pleiotropic cytokine involved in inflammation and cancer. Genetic knockout of Mif1 in the validated N‐butyl‐N‐(4‐hydroxybutyl) nitrosamine (BBN) model of bladder cancer (BCa) resulted in stage arrest at non‐muscle‐invasive disease in prior studies. Small‐molecule inhibition of MIF1 reduced cancer‐associated outcomes, but it did not fully recapitulate genetic models. D‐dopachrome tautomerase (gene symbol DDT), commonly referred to as MIF2, is a functional homolog of MIF1, and both MIF1 and MIF2 can bind the cell surface receptor CD74 on multiple cell types to initiate a signaling cascade. It has been proposed that this interaction mediates part of the protumorigenic effects of MIF1 and MIF2 and may explain the discordance in prior studies. We hypothesized that MIF2 functions redundantly with MIF1 in BCa development and progression. The Cancer Genome Atlas (TCGA) analysis indicated MIF and DDT expression were increased in BCa patients compared to control. 4‐Iodopyridine (4‐IPP), a combined MIF1/MIF2 inhibitor, was more efficacious than ISO‐1, a MIF1‐only inhibitor, in preventing cellular proliferation in BCa cell lines. To evaluate these findings in vivo, wild‐type (WT) and Mif1−/− animals were exposed to 0.05% BBN in drinking water for 16 weeks to initiate tumorigenesis and then evaluated over the subsequent 4 weeks for tumor formation and progression in the presence or absence of 4‐IPP. 4‐IPP reduced bladder weights in WT animals and bladder weights/tumor stage in Mif1−/− animals. To determine whether MIF1/MIF2 functioned through CD74 in BCa, WT or Cd74−/− animals were used in the same BBN model. Although these animals were partially protected against BBN‐induced BCa, 4‐IPP did not enhance this effect. In conclusion, our data suggest that MIF2 mechanistically functions in a similar protumorigenic manner to MIF1, and this is at least partially through CD74. Dual inhibition of MIF homologs is more efficacious at reducing tumor burden in this model of BCa. © 2022 The Pathological Society of Great Britain and Ireland.
Retention of discharge instructions using an interdisciplinary model for at‐risk children with cancer: A quality improvement initiative
Authors: Offenbacher Rachel , Briggs Jessica , Ronca Kristen , Uong Audrey , Ogidan‐Odeseye Olamide , Kim Mimi , Weiser Daniel
Published: October 2022

Purpose

We sought to improve caregiver retention of critical initial hospital discharge instructions using a multidisciplinary, team‐based intervention for newly diagnosed pediatric cancer patients at high risk for unfavorable outcomes.

Materials and methods

A multidisciplinary team of pediatric residents, nurses, social workers, pharmacists and hematology/oncology faculty implemented practices to optimize teaching of key discharge material as part of four Plan‐Do‐Study‐Act intervention cycles. An 11‐question survey distributed at the first post‐discharge clinic visit assessed the efficacy of the intervention, as defined by caregiver retention of critical home instructions.

Results

Thirty‐nine caregivers of pediatric cancer patients in an urban academic tertiary‐care children's hospital took part in this project. Overall retention of key discharge information was greater in the post‐intervention cohort compared to the baseline cohort (median total scores: 89 and 63, respectively; p = .001). Improvements in the proportions of correct responses post‐intervention were also observed across all subject matters: from 0.57 to 0.88 for fever guidelines (p = .059), from 0.71 to 0.78 for signs of sepsis (p = .65), from 0.57 to 1.00 for accurate choice of on‐call number (p = .004), and from 0.71 to 0.94 for antiemetic management (p = .14).

Conclusion

Initiation of our comprehensive cancer‐specific program to improve caregiver retention of discharge instructions at the first post‐hospitalization clinic visit has been successful and sustainable. This project demonstrated that a multi‐disciplinary collaborative team effort increases caregiver retention of critical health information, and this has potential to lead to improved outcomes for patients.
The challenges of managing type 1 diabetes with other autoimmune diseases
Authors: Salloum Mohammed , Poole Ruth
Published: October 2022

People with type 1 diabetes have an increased risk of developing other autoimmune diseases compared to the background population and this risk has been increasing over the last 20 years. Coeliac disease affects absorption of food which can lead to hypoglycaemia in people with diabetes. Both conditions have dietary restrictions and managing the two can make food choices more difficult. Addison's disease can lead to significant challenges in managing blood glucose particularly in times of intercurrent illness and significantly increases morbidity and mortality in patients with diabetes. Thyroid disease, both hyperthyroidism (Graves’ disease) and hypothyroidism (Hashimoto's thyroiditis) can affect blood glucose levels directly by changes in glucose uptake and metabolism or indirectly through changes in weight. Management of type 1 diabetes includes being alert to the possibility of these potential additional diagnoses. Copyright © 2022 John Wiley & Sons.
Tropical medicine and diabetes: an integrative paradigm
Authors: Seewoodhary Jason , Benavides Rodrigo Ville , Silveira Angela
Published: October 2022

Recent advances in public health and preventative medicine have significantly changed the epidemiology of disease in the tropics this century. Tropical medicine has transitioned away from being a specialty honed exclusively on infectious disease to now encompassing the management and relationship of infectious diseases with increasingly prevalent non‐communicable diseases, such as diabetes mellitus, in lower‐ and middle‐income countries. This review will critically consider unique aspects of diabetes care in the tropics. Copyright © 2022 John Wiley & Sons.
American Society for Pharmacology and Experimental Therapeutics Division for Pharmacology Education at EB2022—Meeting report
Authors: Blumer Joe B. , Kruidering Marieke , Brandl Katharina , McPhail Brooks , Simmons Mark A.
Published: October 2022

The American Society for Pharmacology and Experimental Therapeutics (ASPET) held its annual meeting at the Experimental Biology 2022 conference in Philadelphia, PA on April 2–5, 2022. The authors provide a synopsis and discussion of each of the four sessions presented at the meeting under the ASPET Division for Pharmacology Education (DPE).
Impacts of model resolution and ocean coupling on mean and eddy momentum transfer during the rapid intensification of super‐typhoon Muifa (2011)
Authors: Yu Yang , Chen Shu‐Hua , Tseng Yu‐Heng , Foltz Gregory R. , Zhang Rong‐Hua , Gao Huiwang
Published: October 2022

This study uses a coupled atmosphere–ocean model with different numerical settings to investigate the mean and eddy momentum transfer processes responsible for Typhoon Muifa′s (2011) early rapid intensification (RI). Three experiments are conducted. Two use the coupled model with a horizontal resolution of either 1 km (HRL) or 3 km (LRL). The third (NoTCFB) is the same as LRL but excludes tropical cyclone (TC)‐induced sea‐surface temperature (SST) cooling. HRL reasonably reproduces Muifa′s intensity during its rapid intensification and weakening periods. The azimuthal mean tangential and radial momentum budgets are analysed before the RI rates diverge between HRL and LRL. Results show that the dominant processes responsible for Muifa′s intensification are different in HRL and LRL. For HRL, the net eddy effect intensifies the storm′s circulation and contracts the eyewall during early RI, and it dominates the net mean‐flow effect inside the radius of maximum wind (RMW), except near the surface and between 2 and 5 km close to the RMW. In contrast, the mean and eddy effects in LRL almost cancel inside the RMW, while the mean‐flow effects dominate and intensify tangential winds outside. Without TC‐induced SST cooling, Muifa in NoTCFB reaches a similar storm intensity as in HRL but its rapid weakening rate is substantially underestimated. The dominant mechanisms for tangential wind intensification in NoTCFB are similar to those in LRL, but their magnitudes are larger, implying a misrepresentation of the dominant momentum transfer processes in NoTCFB during RI. For the radial momentum budget analysis, the dominant processes are similar among the three experiments except for some differences in their locations and strengths.
Role of subtropical Rossby waves in governing the track of cyclones in the Bay of Bengal
Authors: Singh Vineet Kumar , Roxy Mathew Koll , Deshpande Medha
Published: October 2022

The cyclones during November in the Bay of Bengal follow two distinct tracks. Analysis for the period 1982–2019 shows that some cyclones move west‐northwestward and make landfall at the Odisha, Andhra Pradesh or Tamil Nadu coast of India, or the Sri Lanka coast, while others move north‐northeastwards and make landfall at the West Bengal, Bangladesh or Myanmar coast. Our analysis shows there is a significant difference in the steering winds governing these two different cyclone tracks. The north‐northeastward moving cyclones are associated with an anomalous upper‐level cyclonic circulation over India which is part of a subtropical Rossby wave train triggered by an anomalous upper‐level convergence over the Mediterranean region. This wave train propagates along the subtropical westerly jet from the east Atlantic/Mediterranean region and reaches the Indian subcontinent in 4 days. It induces an anomalous cyclonic circulation over the Indian landmass and provides south‐to‐north and west‐to‐east steering over the Bay of Bengal, causing the cyclones to move in a north‐northeastward direction. On the other hand, for west‐northwestward moving cyclones, there is no Rossby wave intrusion over the Indian subcontinent, hence the cyclones move in a west‐northwestward direction assisted by the beta effect and climatological winds which are from east to west over the south and central Bay of Bengal. This shows that the track of cyclones in the north Indian Ocean can be modulated by atmospheric changes in the extratropics and can act as a precursor for the prediction of the track of cyclones in this region.
Dynamic‐estimator‐based adaptive secure containment control for constrained nonlinear multi‐agent systems under denial‐of‐service attacks
Authors: Jiang Yuqiang , Niu Ben , Wang Xinjun , Wang Huanqing , Chen Wendi
Published: October 2022

This article concentrates upon the adaptive secure containment control problem for a class of uncertain nonlinear multi‐agent systems with the output constraint requirements under denial‐of‐service (DoS) attacks. At first, to overcome the difficulty that the tracking performance of the nonlinear multi‐agent systems under the DoS attacks is disturbed seriously, a novel adaptive secure containment control approach is presented by applying a DoS attacks detection mechanism and introducing the barrier Lyapunov functions, which enables the system to achieve the security control objective that the output of each agent eventually converges to the convex hull spanned by the dynamic leaders' outputs, while never violating the output constraints. Then, a state estimator is designed, which reconstructs the immeasurable states of the multi‐agent systems and approximates the completely unknown nonlinearities arising from the agents. In addition, the dynamic surface control technique is used to solve the “explosion of complexity” problem. It is demonstrated that the proposed anti‐attack controller ensures that all the signals of the closed‐loop system are semi‐globally uniformly ultimately bounded. Finally, a simulation example is provided to illustrate the effectiveness of the theoretical results.
Academic stars and licensing experience in university technology commercialization
Authors: Hsu David H. , Kuhn Jeffrey M.
Published: October 2022

Research Summary

We examine the process by which university technology transfer offices (TTOs) allocate internal resources, which provides insight into technologies offered for commercialization to the private sector. Using detailed administrative records of patenting decisions and outcomes by one prominent U.S. research‐based university's TTO over a 30‐year period, we analyze the performance of invention disclosures by academic stars and by inventors with prior licensing experience. We find that the lead inventor's academic prominence (but not licensing experience) predicts patent application filing, while licensing experience (but not academic prominence) predicts patent impact and commercialization success. We supplement this descriptive analysis with follow‐up interviews and empirical evaluation of possible mechanisms for this seemingly outsized role of academic stars.

Managerial Summary

Increasingly prevalent hybrid organizations are expected to fulfill multiple objectives. University technology transfer offices (TTOs) are an example of a hybrid organization and are charged with disseminating academia‐originated technology for the public good as well as for economic benefit. We study how one TTO allocates internal resources, using comprehensive in‐house administrative data over a 30‐year span. We find that while the TTO tends to put resources behind inventions by academic stars, the commercial returns from licensing inventions from such individuals are no different than inventions by non‐stars. By contrast, inventors' prior licensing experience highly predicts commercial returns. These results illustrate the challenges inherent in internal resource allocation inside a complex hybrid organization.