bluuebunny/crossref_metadata_2025 huggingface dataset:
Soft, miniaturized, wireless olfactory interface for virtual reality
Authors: Liu Yiming , Yiu Chun Ki , Zhao Zhao , Park Wooyoung , Shi Rui , Huang Xingcan , Zeng Yuyang , Wang Kuan , Wong Tsz Hung , Jia Shengxin , Zhou Jingkun , Gao Zhan , Zhao Ling , Yao Kuanming , Li Jian , Sha Chuanlu , Gao Yuyu , Zhao Guangyao , Huang Ya , Li Dengfeng , Guo Qinglei , Li Yuhang , Yu Xinge
Published: May 2023

Recent advances in virtual reality (VR) technologies accelerate the creation of a flawless 3D virtual world to provide frontier social platform for human. Equally important to traditional visual, auditory and tactile sensations, olfaction exerts both physiological and psychological influences on humans. Here, we report a concept of skin-interfaced olfactory feedback systems with wirelessly, programmable capabilities based on arrays of flexible and miniaturized odor generators (OGs) for olfactory VR applications. By optimizing the materials selection, design layout, and power management, the OGs exhibit outstanding device performance in various aspects, from response rate, to odor concentration control, to long-term continuous operation, to high mechanical/electrical stability and to low power consumption. Representative demonstrations in 4D movie watching, smell message delivery, medical treatment, human emotion control and VR/AR based online teaching prove the great potential of the soft olfaction interface in various practical applications, including entertainment, education, human machine interfaces and so on.
Molecular mechanisms of tubulogenesis revealed in the sea star hydro-vascular organ
Authors: Perillo Margherita , Swartz S. Zachary , Pieplow Cosmo , Wessel Gary M.
Published: May 2023

A fundamental goal in the organogenesis field is to understand how cells organize into tubular shapes. Toward this aim, we have established the hydro-vascular organ in the sea star Patiria miniata as a model for tubulogenesis. In this animal, bilateral tubes grow out from the tip of the developing gut, and precisely extend to specific sites in the larva. This growth involves cell migration coupled with mitosis in distinct zones. Cell proliferation requires FGF signaling, whereas the three-dimensional orientation of the organ depends on Wnt signaling. Specification and maintenance of tube cell fate requires Delta/Notch signaling. Moreover, we identify target genes of the FGF pathway that contribute to tube morphology, revealing molecular mechanisms for tube outgrowth. Finally, we report that FGF activates the Six1/2 transcription factor, which serves as an evolutionarily ancient regulator of branching morphogenesis. This study uncovers distinct mechanisms of tubulogenesis in vivo and we propose that cellular dynamics in the sea star hydro-vascular organ represents a key comparison for understanding the evolution of vertebrate organs.
Skin basal cell carcinomas assemble a pro-tumorigenic spatially organized and self-propagating Trem2+ myeloid niche
Authors: Haensel Daniel , Daniel Bence , Gaddam Sadhana , Pan Cory , Fabo Tania , Bjelajac Jeremy , Jussila Anna R. , Gonzalez Fernanda , Li Nancy Yanzhe , Chen Yun , Hou JinChao , Patel Tiffany , Aasi Sumaira , Satpathy Ansuman T. , Oro Anthony E.
Published: May 2023

Cancer immunotherapies have revolutionized treatment but have shown limited success as single-agent therapies highlighting the need to understand the origin, assembly, and dynamics of heterogeneous tumor immune niches. Here, we use single-cell and imaging-based spatial analysis to elucidate three microenvironmental neighborhoods surrounding the heterogeneous basal cell carcinoma tumor epithelia. Within the highly proliferative neighborhood, we find that TREM2+ skin cancer-associated macrophages (SCAMs) support the proliferation of a distinct tumor epithelial population through an immunosuppression-independent manner via oncostatin-M/JAK-STAT3 signaling. SCAMs represent a unique tumor-specific TREM2+ population defined by VCAM1 surface expression that is not found in normal homeostatic skin or during wound healing. Furthermore, SCAMs actively proliferate and self-propagate through multiple serial tumor passages, indicating long-term potential. The tumor rapidly drives SCAM differentiation, with intratumoral injections sufficient to instruct naive bone marrow-derived monocytes to polarize within days. This work provides mechanistic insights into direct tumor-immune niche dynamics independent of immunosuppression, providing the basis for potential combination tumor therapies.
Zinc homeostasis governed by Golgi-resident ZnT family members regulates ERp44-mediated proteostasis at the ER-Golgi interface
Authors: Amagai Yuta , Yamada Momo , Kowada Toshiyuki , Watanabe Tomomi , Du Yuyin , Liu Rong , Naramoto Satoshi , Watanabe Satoshi , Kyozuka Junko , Anelli Tiziana , Tempio Tiziana , Sitia Roberto , Mizukami Shin , Inaba Kenji
Published: May 2023

Many secretory enzymes acquire essential zinc ions (Zn2+) in the Golgi complex. ERp44, a chaperone operating in the early secretory pathway, also binds Zn2+ to regulate its client binding and release for the control of protein traffic and homeostasis. Notably, three membrane transporter complexes, ZnT4, ZnT5/ZnT6 and ZnT7, import Zn2+ into the Golgi lumen in exchange with protons. To identify their specific roles, we here perform quantitative Zn2+ imaging using super-resolution microscopy and Zn2+-probes targeted in specific Golgi subregions. Systematic ZnT-knockdowns reveal that ZnT4, ZnT5/ZnT6 and ZnT7 regulate labile Zn2+ concentration at the distal, medial, and proximal Golgi, respectively, consistent with their localization. Time-course imaging of cells undergoing synchronized secretory protein traffic and functional assays demonstrates that ZnT-mediated Zn2+ fluxes tune the localization, trafficking, and client-retrieval activity of ERp44. Altogether, this study provides deep mechanistic insights into how ZnTs control Zn2+ homeostasis and ERp44-mediated proteostasis along the early secretory pathway.
Resistance to anti-HER2 therapy associated with the TSC2 nonsynonymous variant c.4349 C > G (p.Pro1450Arg) is reversed by CDK4/6 inhibitor in HER2-positive breast cancer
Authors: Yang Ziyan , Feng Jianguo , Jing Ji , Huang Yuan , Ye Wei-Wu , Lei Lei , Wang Xiao-Jia , Cao Wen-Ming
Published: May 2023

HER2-positive breast cancer patients carrying the germline TSC2 nonsynonymous variant c.4349 C > G (p.Pro1450Arg) are resistant to anti-HER2 therapy. Multi-predictor in silico analysis reveals that this variant is deleterious. We explore the potential mechanism of this TSC2 variant and investigate methods for overcoming anti-HER2 resistance. TSC2 c.4349 C > G reverses the inhibitory effect on mTOR and downstream signaling by increasing TSC2 phosphorylation at Thr1462 and confers significant lapatinib resistance in vitro and in vivo. The combination of lapatinib and the CDK4/6 inhibitor palbociclib inhibits cyclin D1/CDK4/Rb alternative pathway and TSC2 phosphorylation, thereby partially attenuating mTOR activity and inducing TSC2-mutant cell blockage at G1/G0. In in vitro and xenograft models, palbociclib+lapatinib shows higher anti-tumor activity than monotherapy and overcomes the resistance of the TSC2 c.4349 C > G-related variant to anti-HER2 therapy. We reveal a new mechanism of resistance to anti-HER2 therapy and provide a strategy to increase the efficiency of anti-HER2 therapy in HER2-positive breast cancer.
Shared molecular genetic factors influence subcortical brain morphometry and Parkinson’s disease risk
Authors: García-Marín Luis M. , Reyes-Pérez Paula , Diaz-Torres Santiago , Medina-Rivera Alejandra , Martin Nicholas G. , Mitchell Brittany L. , Rentería Miguel E.
Published: May 2023

Parkinson’s disease (PD) is a late-onset and genetically complex neurodegenerative disorder. Here we sought to identify genes and molecular pathways underlying the associations between PD and the volume of ten brain structures measured through magnetic resonance imaging (MRI) scans. We leveraged genome-wide genetic data from several cohorts, including the International Parkinson’s Disease Genomics Consortium (IPDG), the UK Biobank, the Adolescent Brain Cognitive Development (ABCD) study, the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE), the Enhancing Neuroimaging Genetics through Meta-Analyses (ENIGMA), and 23andMe. We observed significant positive genetic correlations between PD and intracranial and subcortical brain volumes. Genome-wide association studies (GWAS) - pairwise analyses identified 210 genomic segments with shared aetiology between PD and at least one of these brain structures. Pathway enrichment results highlight potential links with chronic inflammation, the hypothalamic-pituitary-adrenal pathway, mitophagy, disrupted vesicle-trafficking, calcium-dependent, and autophagic pathways. Investigations for putative causal genetic effects suggest that a larger putamen volume could influence PD risk, independently of the potential causal genetic effects of intracranial volume (ICV) on PD. Our findings suggest that genetic variants influencing larger intracranial and subcortical brain volumes, possibly during earlier stages of life, influence the risk of developing PD later in life.
Incentives and barriers to private finance for forest and landscape restoration
Authors: Löfqvist Sara , Garrett Rachael D. , Ghazoul Jaboury
Published: May 2023

Increased private finance can accelerate forest and landscape restoration globally. Here we conduct semi-structured interviews with asset managers, corporations and restoration finance experts to examine incentives and barriers to private restoration finance. Next, we assess what type of restoration projects and regions appeal to different private funders and how current financial barriers can be overcome. We show that market incentives for corporations include meeting net-emission-reduction commitments, impact and sustainable branding opportunities, and promotion of sustainability in supply chains. Conversely, asset managers face stronger barriers to investing in restoration as it is deemed a high-risk, unknown investment with low profitability. We find that investment finance biases towards restoration projects in low-risk areas and corporate finance towards areas with business presence. Both private finance types tend to omit projects focusing on natural regeneration. Through expanded and diversified markets for restoration benefits, strong public policy support and new financial instruments, private finance for restoration can be scaled for a wider variety of restoration projects in more diverse geographical contexts.
Chromosome-level genome assembly of Microplitis manilae Ashmead, 1904 (Hymenoptera: Braconidae)
Authors: Shu Xiaohan , Yuan Ruizhong , Zheng Boying , Wang Zhizhi , Ye Xiqian , Tang Pu , Chen Xuexin
Published: May 2023

Microplitis manilae Ashmead (Hymenoptera: Braconidae) is an important parasitoid of agricultural pests in lepidopteran species. So far, two extant genome assembles from the genus Microplitis are fragmented. Here, we offered a high-quality genome assembly of M. manilae at the chromosome level with high accuracy and contiguity, assembled by ONT long-read, MGI-SEQ short-read, and Hi-C sequencing methods. The final assembled genome size was 282.85 Mb, with 268.17 Mb assigned to 11 pseudochromosomes. The scaffold N50 length was 25.23 Mb, and the complete BUSCO score was 98.61%. The genome contained 152.37 Mb of repetitive elements, representing 53.87% of the total genome size. We predicted 15,689 protein-coding genes, of which 13,580 genes were annotated functionally. Gene family evolution investigations of M. manilae revealed 615 expanded and 635 contracted gene families. The high-quality genome of M. manilae reported in this paper will be a useful genomic resource for research on parasitoid wasps in the future.
RGN as a prognostic biomarker with immune infiltration and ceRNA in lung squamous cell carcinoma
Authors: Liao Yang , Cheng Wen , Mou Ruiyu , Li Xiaojiang , Jia Yingjie
Published: May 2023

Regucalcin (RGN) is a potent inhibitory protein of calcium signaling and expresses in various tissues. However, the role of RGN in the tumor immunological microenvironment in lung squamous cell carcinoma (LUSC) remains unclear. This study identified the expression of RGN from public databases and immunohistochemistry with clinical specimen. The association between RGN and the tumor immune microenvironment (TIME) was investigated in LUSC by ESTIMATE and CIBERSORT algorithms. Similarly, the Tumor IMmune Estimation Resource (TIMER) database was used to identify the correlation between RGN and immune cells. The ceRNA network was established based on the data obtained from public databases. Finally, prediction of drug response to chemotherapy and immunotherapy was performed to evaluate clinical significance. This study found that RGN expression was significantly downregulated in tumor tissues and closely related to clinical factors and prognosis of LUSC patients. Differentially expressed genes (DEGs) grouped by the expression of RGN were mostly involved in immunobiological processes such as humoral immune response and leukocyte mediated immunity. RGN and its related miRNA (has-miR-203a-3p) and lncRNAs (ZNF876P and PSMG3-AS1) constructed the novel prognosis-related ceRNA network. Plasma cells, T cells CD4 memory resting, Macrophages M0, Macrophages M1, Mast cells resting, Mast cells activated and Neutrophils showed significantly different levels of infiltration between high and low RGN expression groups. The TIMER database showed that RGN expression was positively correlated with certain immune infiltrating cells. High RGN expression group showed a higher TIDE score, a higher dysfunction score and a lower MSI score, presenting a possible lower efficacy after accepting the immunotherapy than low RGN expression group. RGN expression was closely associated with prognosis of LUSC patients and played an important role in tumor microenvironment. This suggests that RGN could be a promising biomarker for assessing immunotherapy efficacy and prognosis.
Influence of maternal psychological distress during COVID-19 pandemic on placental morphometry and texture
Authors: Saeed Haleema , Lu Yuan-Chiao , Andescavage Nickie , Kapse Kushal , Andersen Nicole R. , Lopez Catherine , Quistorff Jessica , Barnett Scott , Henderson Diedtra , Bulas Dorothy , Limperopoulos Catherine
Published: May 2023

The Coronavirus Disease 2019 (COVID-19) pandemic has been accompanied by increased prenatal maternal distress (PMD). PMD is associated with adverse pregnancy outcomes which may be mediated by the placenta. However, the potential impact of the pandemic on in vivo placental development remains unknown. To examine the impact of the pandemic and PMD on in vivo structural placental development using advanced magnetic resonance imaging (MRI), acquired anatomic images of the placenta from 63 pregnant women without known COVID-19 exposure during the pandemic and 165 pre-pandemic controls. Measures of placental morphometry and texture were extracted. PMD was determined from validated questionnaires. Generalized estimating equations were utilized to compare differences in PMD placental features between COVID-era and pre-pandemic cohorts. Maternal stress and depression scores were significantly higher in the pandemic cohort. Placental volume, thickness, gray level kurtosis, skewness and run length non-uniformity were increased in the pandemic cohort, while placental elongation, mean gray level and long run emphasis were decreased. PMD was a mediator of the association between pandemic status and placental features. Altered in vivo placental structure during the pandemic suggests an underappreciated link between disturbances in maternal environment and perturbed placental development. The long-term impact on offspring is currently under investigation.
A possible new cardiac heterogeneity as an arrhythmogenic driver
Authors: Rabinovitch A. , Rabinovitch R. , Biton Y. , Braunstein D. , Thieberger R.
Published: May 2023

Atrial fibrillation (AF) is the commonest cardiac arrhythmia, affecting 3 million people in the USA and 8 million in the EU (according to the European Society of Cardiology). So, why is it that even with the best medical care, around a third of the patients are treatment resistant. Extensive research of its etiology showed that AF and its mechanisms are still debatable. Some of the AF origins are ascribed to functional and ionic heterogeneities of the heart tissue and possibly to additional triggering agents. But, have all AF origins been detected? Are all accepted origins, in fact, arrhythmogenic? In order to study these questions and specifically to check our new idea of intermittency as an arrhythmogenesis agent, we chose to employ a mathematical model which was as simple as possible, but which could still be used to observe the basic network processes of AF development. At this point we were not interested in the detailed ionic propagations nor in the actual shapes of the induced action potentials (APs) during the AF outbreaks. The model was checked by its ability to exactly recapture the basic AF developmental stages known from experimental cardiac observations and from more elaborate mathematical models. We use a simple cellular automata 2D mathematical model of N × N matrices to elucidate the field processes leading to AF in a tissue riddled with randomly distributed heterogeneities of different types, under sinus node operation, simulated by an initial line of briefly stimulated cells inducing a propagating wave, and with or without an additional active ectopic action potential pulse, in turn simulated by a transitory operation of a specific cell. Arrhythmogenic contributions, of three different types of local heterogeneities in myocytes and their collaborations, in inducing AF are examined. These are: a heterogeneity created by diffuse fibrosis, a heterogeneity created by myocytes having different refractory periods, and a new heterogeneity type, created by intermittent operation of some myocytes. The developmental stages (target waves and spirals) and the different probabilities of AF occurring under each condition, are shown. This model was established as being capable of reproducing the known AF origins and their basic development stages, and in addition has shown: (1) That diffuse fibrosis on its own is not arrhythmogenic but in combination with other arrhythmogenic agents it can either enhance or limit AF. (2) In general, combinations of heterogeneities can act synergistically, and, most importantly, (3) The new type of intermittency heterogeneity proves to be extremely arrhythmogenic. Both the intermittency risk and the fibrosis role in AF generation were established. Knowledge of the character of these arrhythmogenesis agents can be of real importance in AF treatment.
4,6-Diamino-2-thiopyrimidine-based Cobalt Metal Organic Framework (Co-DAT‐MOF): green, efficient, novel and reusable nanocatalyst for synthesis of multicomponent reactions
Authors: Ghorbani-Choghamarani Arash , Kakakhani Zahra , Taherinia Zahra
Published: May 2023

In this study, Co-DAT‐MOF powder was prepared via the solvothermal method using 4, 6-diamino-2-thiopyrimidine as the organic linker and Co(NO3)2·6H2O. The synthesized catalysts are characterized using XRD, FT-IR, TGA, SEM, BET, NH3-TPD, and ICP-OES techniques. SEM analysis clearly indicated the formation of nanosheet microspheres. NH3-TPD-MS was employed as a means of identifying the various strengths of acid sites and their relative abundance in an attempt to explain the effect of the catalyst surface acid sites. We identified a new acidic feature in Co-DAT‐MOF catalyst, related to the presence of desorption peaks in the NH3-TPD profiles. The activity of Co-DAT‐MOF catalyst for the synthesis of multicomponent reactions correlates with lewis acidity. In addition, Co-DAT‐MOF exhibited excellent performance for the synthesis of pyrroloacridine-1(2H)-one and chromeno [2, 3- d] pyrimidin-8-amines, as well as good reusability and recyclability.
Risk analysis for patients with arterial thromboembolic events after intravitreal ranibizumab or aflibercept injections
Authors: Chou Yun-I. , Chang Hao-Yun , Lin Meng-Yin , Tseng Ching-Han , Wang Tsung-Jen , Lin I-Chan
Published: May 2023

Intravitreal anti–vascular endothelial growth factor (anti-VEGF) agents have been increasingly applied in the treatment of retinal neovascular diseases. Concerns have arisen that these intravitreal agents may be associated with a potential risk of arterial thromboembolic (ATE) events. We conducted a retrospective, nationwide population‐based cohort study to analyze the risks for ATE events in patients receiving intravitreal ranibizumab (IVR) or intravitreal aflibercept (IVA). Data (2011–2018) were obtained from Taiwan’s National Health Insurance Research Database. Cox proportional-hazards model was used to identify the risk factors for ATEs. Of the total 3,469 patients, 1393 and 2076 patients received IVR and IVA, respectively. In our result, 38 ATEs occurred within 6 months after IVR or IVA. The risk of ATEs was lower in patients receiving IVR than in those receiving IVA (adjusted hazard ratio [aHR], 0.27; 95% confidence interval [CI], 0.11–0.66). Patients with coronary artery disease (CAD) exhibited a higher risk of ATEs than did those without CAD (aHR, 3.47; 95% CI, 1.41–8.53). The risk of ATEs was higher in patients with an event of acute myocardial infarction (AMI) or ischemic stroke (IS) within 6 months prior to index IVI than in those without recent AMI/IS events (aHR, 23.8; 95% CI, 7.35–77.2 and IS: aHR, 290.2; 95% CI, 103.1–816.4). In conclusion, compared with IVA, IVR was associated with a lower risk of ATEs. When strategies for anti-VEGF agents are devised, risk factors, such as CAD and a history of AMI or IS within 6 months should be considered. Further large-scale studies are warranted to elucidate the safety of anti-VEGF injections.
Prediction of clinically relevant postoperative pancreatic fistula using radiomic features and preoperative data
Authors: Bhasker Nithya , Kolbinger Fiona R. , Skorobohach Nadiia , Zwanenburg Alex , Löck Steffen , Weitz Jürgen , Hoffmann Ralf-Thorsten , Distler Marius , Speidel Stefanie , Leger Stefan , Kühn Jens-Peter
Published: May 2023

Clinically relevant postoperative pancreatic fistula (CR-POPF) can significantly affect the treatment course and outcome in pancreatic cancer patients. Preoperative prediction of CR-POPF can aid the surgical decision-making process and lead to better perioperative management of patients. In this retrospective study of 108 pancreatic head resection patients, we present risk models for the prediction of CR-POPF that use combinations of preoperative computed tomography (CT)-based radiomic features, mesh-based volumes of annotated intra- and peripancreatic structures and preoperative clinical data. The risk signatures were evaluated and analysed in detail by visualising feature expression maps and by comparing significant features to the established CR-POPF risk measures. Out of the risk models that were developed in this study, the combined radiomic and clinical signature performed best with an average area under receiver operating characteristic curve (AUC) of 0.86 and a balanced accuracy score of 0.76 on validation data. The following pre-operative features showed significant correlation with outcome in this signature ($$p < 0.05$$p<0.05) - texture and morphology of the healthy pancreatic segment, intensity volume histogram-based feature of the pancreatic duct segment, morphology of the combined segment, and BMI. The predictions of this pre-operative signature showed strong correlation (Spearman correlation co-efficient,$$\rho = 0.7$$ρ=0.7) with the intraoperative updated alternative fistula risk score (ua-FRS), which is the clinical gold standard for intraoperative CR-POPF risk stratification. These results indicate that the proposed combined radiomic and clinical signature developed solely based on preoperatively available clinical and routine imaging data can perform on par with the current state-of-the-art intraoperative models for CR-POPF risk stratification.
Analysis of the correlation between climatic variables and Dengue cases in the city of Alagoinhas/BA
Authors: Figueredo Marcos Batista , Monteiro Roberto Luiz Souza , do Nascimento Silva Alexandre , de Araújo Fontoura José Roberto , da Silva Andreia Rita , Alves Carolina Aparecida Pereira
Published: May 2023

The Aedes aegypti mosquito is the main vector of dengue and is a synanthropic insect and due to its anthropophilic nature, it has specific reproductive needs. In addition to that, it also needs tropical regions that provide climate-prone conditions that favor vector development. In this article, we propose the cross-correlation analysis between the climatic variables air temperature, relative humidity, weekly average precipitation and dengue cases in the period from 2017 to early 2021 in the municipality of Alagoinhas, Bahia, Brazil. To do so, we apply the trend-free cross-correlation, $$\rho DCCA$$

ρ
D
C
C
A

, being a generalization of the fluctuation analysis without trend, where we calculate the cross correlation between time series to establish the influence of these variables on the occurrence of dengue disease. The results obtained here were a moderate correlation between relative humidity and the incidence of dengue cases, and a low correlation for relative air temperature and precipitation. However, the predominant factor in the incidence of dengue cases in the city of Alagoinhas is relative humidity and not air temperature and precipitation.
Building performance simulations can inform IoT privacy leaks in buildings
Authors: Wang Alan , Campbell Bradford , Heydarian Arsalan
Published: May 2023

As IoT devices become cheaper, smaller, and more ubiquitously deployed, they can reveal more information than their intended design and threaten user privacy. Indoor Environmental Quality (IEQ) sensors previously installed for energy savings and indoor health monitoring have emerged as an avenue to infer sensitive occupant information. For example, light sensors are a known conduit for inspecting room occupancy status with motion-sensitive lights. Light signals can also infer sensitive data such as occupant identity and digital screen information. To limit sensor overreach, we explore the selection of sensor placements as a methodology. Specifically, in this proof-of-concept exploration, we demonstrate the potential of physics-based simulation models to quantify the minimal number of positions necessary to capture sensitive inferences. We show how a single well-placed sensor can be sufficient in specific building contexts to holistically capture its environmental states and how additional well-placed sensors can contribute to more granular inferences. We contribute a device-agnostic and building-adaptive workflow to respectfully capture inferable occupant activity and elaborate on the implications of incorporating building simulations into sensing schemes in the real world.
Traumatic brain injury related deaths in residents and non-residents of 30 European countries: a cross-sectional study
Authors: Sivco Patrik , Plancikova Dominika , Melichova Juliana , Rusnak Martin , Hereitova Iva , Beranek Vaclav , Cibulka Roman , Majdan Marek
Published: May 2023

The incidence and mortality of traumatic brain injuries (TBI) among non-residents to countries where they occur remains unknown, warranting epidemiological research. Epidemiological data are key to inform prevention and public health policies related to TBI, as well as to help promote safe travelling practice. The aim of this study was to analyse the epidemiological patterns of TBI-related deaths among residents and non-residents in 30 European countries in 2015 using standardised European level data on causes of death. A large-scale cross-sectional study analysing TBI-related deaths in 30 European countries in 2015 among residents and non-residents to the country of occurrence of the death was conducted. Data from death certificates collected on European level by Eurostat were used to calculate the numbers of TBI-related deaths and estimate crude and age-standardised mortality rates. Rates were stratified by country, sex, age-group and by resident status. External causes of the injury were determined using the provided ICD-10 codes. 40,087 TBI-related deaths were identified; overall about 3% occurred among non-residents with highest proportions in Turkey (11%), Luxembourg (9%) and Cyprus (5%). Taking into account tourism intensity in the countries, Bulgaria, Greece and Austria showed highest rates of TBI-related deaths in non-residents: 0.7,0.5 and 0.5 per million overnight stays, respectively. The pooled age-standardised TBI-related mortality in non-residents was 0.2 (95% CI 0.1–0.3), among residents 10.4 (95% CI 9.4–11.5) per 100,000. In non-residents, TBI-related deaths were shifted to younger populations (86% in < 35 years); in non-residents 78% were 15–64 years old. Falls were predominant among residents (47%), and traffic accidents among non-residents (36%). Male:female ratio was higher among non-residents (3.9), compared to residents (2.1). Extrapolating our findings, we estimate that annually 1022 TBI-related deaths would occur to non-residents in the EU-27 + UK and 1488 in Europe as a continent. We conclude, that the primary populations at risk of TBI-related deaths in European countries differ in several characteristics between residents and non-residents to the country of the occurrence of death, which warrants for different approaches in prevention and safety promotion. Our findings suggest that TBI occurring in European countries among non-residents present a problem worthy of attention from public health and travel medicine professionals and should be further studied.
Risk factors for patients with acute hospital-acquired symptomatic pulmonary thromboembolism
Authors: Ye Lujuan , Xie Hailiang , Lai Minggui , Zheng Guofu , Xie Yuancai , Liu Xiaochun
Published: May 2023

This study aimed to identify independent risk factors for acute hospital-acquired symptomatic pulmonary embolism (HA-SPE) by comparing the clinical data of HA-SPE and acute nonhospital-acquired symptomatic pulmonary embolism (NHA-SPE). A total of 292 patients were included in the analysis and divided into two groups: 191 patients had acute NHA-SPE, and 101 patients had acute HA-SPE. The average age of these 292 patients was 63.2 years, and the sample included 145 males. Multivariate analysis showed that malignant tumour (OR, 3.811; 95% CI [1.914–7.586], P = 0.000), recent surgery (OR, 7.310; 95% CI 3.392–15.755], P = 0.000), previous VTE (OR, 5.973; 95% CI 2.194 16.262], P = 0. 000), and the length of stay (LOS) (OR, 1.075; 95% CI [1.040–1.111], P = 0.000) were independent risk factors for acute HA-AEP. The c-statistic for this model was 0.758 (95% CI [0.698–0.800], P < 0.0001). The K-M curve showed that the hazard ratio (HR) of the HA group to the NHA group in all-cause mortality was 3.807 (95% CI [1.987, 7.295], P = 0.0061). Strengthening the prevention and control of patients with these risk factors may reduce the incidence of acute HA-SPE.
Study on the emergency capacity of coal mine enterprises in Longdong Area based on D-FAHP method
Authors: Yang Fengfeng , Zhang Jufeng , Jin Bangxin , Wang Siyang , Xi Caixia
Published: May 2023

Emergency capability assessment is a complex system with multiple factors, variables and levels. Incomplete and uncertain assess information often occurs during assessment. Based on this, a method combining D-number theory and fuzzy analytic Hierarchy process (FAHP) is proposed to study the emergency capacity of coal enterprises in Longdong area. On the basis of analyzing the limitation of D-S evidence theory, the D-number theory was optimized and improved. According to the principles of systematicness, feasibility, scientificity and timeliness, a hierarchical structure model of enterprise emergency capability assessment was constructed from the perspective of pre-incident, mid-incident and post-incident, which consisted of 4 first-level indicators and 18 s-level indicators. The weight and importance of the assessment index of emergency response capability are calculated by organically integrating the D-number preference relation with the hierarchy structure. Combined with the assessment results of experts, a quantitative analysis and evaluation of the emergency response capacity of a coal enterprise was conducted by using FAHP. The comprehensive score of the enterprise's emergency response capability was 80.45, and the level of emergency response capacity was "good". The research results show that the D-FAHP method has high reliability in evaluating the emergency response capability of coal enterprises, avoiding the impact of uncertain and incomplete information on the assessment results. This can not only effectively identify the weak links in emergency management, but also meet the emergency decision-making needs of enterprises in the emergency state, which has important guiding significance to improve the ability and level of enterprise emergency management.
Percutaneous transluminal angioplasty and stenting vs aggressive medical management on stroke or intracranial atherosclerotic stenosis: a systematic review and meta-analysis
Authors: Lai Zhiyu , Peng Mingqiang , He Haoming , Li Yingbin , Bai Xiaoxin , Cai Jun
Published: May 2023

There are currently two main treatment strategies mainly for high-risk patients: percutaneous transluminal angioplasty and stenting (PTAS) and aggressive medical management (AMM). However, the choice between PTAS or AMM remains controversial for patients with stroke or intracranial atherosclerotic stenosis (ICAS). The investigators searched the PubMed, Web of Science, Embase, Scopus, and Cochrane library databases. Randomized controlled trial (RCT) comparing PTAS and AMM for patients with stroke or ICAS were selected. RevMan 5.3 was used to analyze the results and assess risk of bias. The primary endpoints are stroke and death within 30 days after enrollment, or ischemic stroke in the territory of the qualifying artery beyond 30 days, and entire follow-up endpoints. The secondary outcomes were the disabling or fatal stroke, and incidence of death within 3 years. Four studies, 989 patients were included in this article. The AMM group was superior in the entire follow-up endpoint (OR 0.56; 95% CI 0.40, 0.79). The AMM also better in primary endpoint within 30 days (OR 0.32; 95% CI 0.17, 0.61). There was no significant difference beyond 30 days (OR 1.08; 95% CI 0.63, 1.86). The remaining outcomes, such as stroke and death, were not significantly different (P > 0.05). This meta-analysis shows AMM is significantly more effective than PTAS in subjects with ICAS due to the high rate of periprocedural stroke (OR 0.32; 95% CI 0.17, 0.61) and stroke during the entire follow-up (OR 0.56; 95% CI 0.40, 0.79) associated with PTAS. Furthermore, PTAS offers no additional benefits over AMM beyond 30 days (OR 1.08; 95% CI 0.63, 1.86).
Comprehensive analysis of mitophagy in HPV-related head and neck squamous cell carcinoma
Authors: Yanan Li , Hui Liang , Zhuo Cheng , Longqing Ding , Ran Sun
Published: May 2023

Head and neck squamous cell carcinoma (HNSCC) is a common tumour type in otorhinolaryngology, and its occurrence is related to long-term exposure to tobacco and alcohol. Recently, HPV infection has become an increasingly important contributor to HNSCC, and HPV-associated HNSCC has a different clinical course and better prognosis than non-HPV-associated HNSCC. However, the exact molecular mechanism of HNSCC is unclear. Here, we obtained data from The Cancer Genome Atlas (TCGA) and gene expression omnibus (GEO) to analyse the mitophagy process and related influencing factors of HPV-associated HNSCC via the integration of bioinformatics analysis and experimental validation. We found that in HPV-associated HNSCC, process of mitophagy affects tumour development, immune cell infiltration and prognosis. In the mitophagy process of HPV-related HNSCC: NOS2, IL17REL, TMSB15A, TUBB4A and other hub genes showed significantly higher expression levels than in non-HPV-related HNSCC. Furthermore, this was also confirmed by quantitative real-time PCR (qRT‒PCR), which was used to detect the expression of differentially expressed genes in HNSCC tissues. Furthermore, we found that the unique immunological characteristics by expressing CD8+ T cell in a high level in HPV-related HNSCC, and the scores obtained from the score model affected the prognosis of patients. In conclusion, our study revealed the unique biomolecular signature of mitophagy in HPV-associated HNSCC, which may contribute to the development of precise treatment regimens for HPV-associated HNSCC patients.
A hybrid approach to full-scale reconstruction of renal arterial network
Authors: Xu Peidi , Holstein-Rathlou Niels-Henrik , Søgaard Stinne Byrholdt , Gundlach Carsten , Sørensen Charlotte Mehlin , Erleben Kenny , Sosnovtseva Olga , Darkner Sune
Published: May 2023

The renal vasculature, acting as a resource distribution network, plays an important role in both the physiology and pathophysiology of the kidney. However, no imaging techniques allow an assessment of the structure and function of the renal vasculature due to limited spatial and temporal resolution. To develop realistic computer simulations of renal function, and to develop new image-based diagnostic methods based on artificial intelligence, it is necessary to have a realistic full-scale model of the renal vasculature. We propose a hybrid framework to build subject-specific models of the renal vascular network by using semi-automated segmentation of large arteries and estimation of cortex area from a micro-CT scan as a starting point, and by adopting the Global Constructive Optimization algorithm for generating smaller vessels. Our results show a close agreement between the reconstructed vasculature and existing anatomical data obtained from a rat kidney with respect to morphometric and hemodynamic parameters.
Two legume fatty acid amide hydrolase isoforms with distinct preferences for microbial- and plant-derived acylamides
Authors: Arias-Gaguancela Omar , Herrell Emily , Aziz Mina , Chapman Kent D.
Published: May 2023

Fatty acid amide hydrolase (FAAH) is a widely conserved amidase in eukaryotes, perhaps best known for inactivating N-acylethanolamine lipid mediators. However, FAAH enzymes hydrolyze a wide range of acylamide substrates. Analysis of FAAHs from multiple angiosperm species revealed two conserved phylogenetic groups that differed in key conserved residues in the substrate binding pocket. While the foundation group of plant FAAHs, designated FAAH1, has been studied at the structural and functional level in Arabidopsis thaliana, nothing is known about FAAH2 members. Here, we combined computational and biochemical approaches to compare the structural and enzymatic properties of two FAAH isoforms in the legume Medicago truncatula designated MtFAAH1 and MtFAAH2a. Differences in structural and physicochemical properties of the substrate binding pockets, predicted from homology modeling, molecular docking, and molecular dynamic simulation experiments, suggested that these two FAAH isoforms would exhibit differences in their amidohydrolase activity profiles. Indeed, kinetic studies of purified, recombinant MtFAAHs indicated a reciprocal preference for acylamide substrates with MtFAAH1 more efficiently utilizing long-chain acylamides, and MtFAAH2a more efficiently hydrolyzing short-chain and aromatic acylamides. This first report of the enzymatic behavior of two phylogenetically distinct plant FAAHs will provide a foundation for further investigations regarding FAAH isoforms in legumes and other plant species.
Telemedicine and the environment: life cycle environmental emissions from in-person and virtual clinic visits
Authors: Thiel Cassandra L. , Mehta Natasha , Sejo Cory Sean , Qureshi Lubna , Moyer Meagan , Valentino Vincent , Saleh Jason
Published: May 2023

Concern over climate change is growing in the healthcare space, and telemedicine has been rapidly expanding since the start of the COVID19 pandemic. Understanding the various sources of environmental emissions from clinic visits—both virtual and in-person—will help create a more sustainable healthcare system. This study uses a Life Cycle Assessment with retrospective clinical data from Stanford Health Care (SHC) in 2019–2021 to determine the environmental emissions associated with in-person and virtual clinic visits. SHC saw 13% increase in clinic visits, but due to the rise in telemedicine services, the Greenhouse Gas emissions (GHGs) from these visits decreased 36% between 2019 and 2021. Telemedicine (phone and video appointments) helped SHC avoid approximately 17,000 metric tons of GHGs in 2021. Some departments, such as psychiatry and cancer achieved greater GHG reductions, as they were able to perform more virtual visits. Telemedicine is an important component for the reduction of GHGs in healthcare systems; however, telemedicine cannot replace every clinic visit and proper triaging and tracking systems should be in place to avoid duplicative care.
Light-sheets and smart microscopy, an exciting future is dawning
Authors: Daetwyler Stephan , Fiolka Reto Paul
Published: May 2023

Light-sheet fluorescence microscopy has transformed our ability to visualize and quantitatively measure biological processes rapidly and over long time periods. In this review, we discuss current and future developments in light-sheet fluorescence microscopy that we expect to further expand its capabilities. This includes smart and adaptive imaging schemes to overcome traditional imaging trade-offs, i.e., spatiotemporal resolution, field of view and sample health. In smart microscopy, a microscope will autonomously decide where, when, what and how to image. We further assess how image restoration techniques provide avenues to overcome these tradeoffs and how “open top” light-sheet microscopes may enable multi-modal imaging with high throughput. As such, we predict that light-sheet microscopy will fulfill an important role in biomedical and clinical imaging in the future.
Scale-free dynamics in the core-periphery topography and task alignment decline from conscious to unconscious states
Authors: Klar Philipp , Çatal Yasir , Langner Robert , Huang Zirui , Northoff Georg
Published: May 2023

Scale-free physiological processes are ubiquitous in the human organism. Resting-state functional MRI studies observed the loss of scale-free dynamics under anesthesia. In contrast, the modulation of scale-free dynamics during task-related activity remains an open question. We investigate scale-free dynamics in the cerebral cortex’s unimodal periphery and transmodal core topography in rest and task states during three conscious levels (awake, sedation, and anesthesia) complemented by computational modelling (Stuart-Landau model). The empirical findings demonstrate that the loss of the brain’s intrinsic scale-free dynamics in the core-periphery topography during anesthesia, where pink noise transforms into white noise, disrupts the brain’s neuronal alignment with the task’s temporal structure. The computational model shows that the stimuli’s scale-free dynamics, namely pink noise distinguishes from brown and white noise, also modulate task-related activity. Together, we provide evidence for two mechanisms of consciousness, temporo-spatial nestedness and alignment, suggested by the Temporo-Spatial Theory of Consciousness (TTC).
Non-thermal evolution of dense plasmas driven by intense x-ray fields
Authors: Ren Shenyuan , Shi Yuanfeng , van den Berg Quincy Y. , Kasim Muhammad F. , Chung Hyun-Kyung , Fernandez-Tello Elisa V. , Velarde Pedro , Wark Justin S. , Vinko Sam M.
Published: May 2023

The advent of x-ray free-electron lasers has enabled a range of new experimental investigations into the properties of matter driven to extreme conditions via intense x-ray-matter interactions. The femtosecond timescales of these interactions lead to the creation of transient high-energy-density plasmas, where both the electrons and the ions may be far from local thermodynamic equilibrium. Predictive modelling of such systems remains challenging because of the different timescales at which electrons and ions thermalize, and because of the vast number of atomic configurations required to describe highly-ionized plasmas. Here we present CCFLY, a code designed to model the time-dependent evolution of both electron distributions and ion states interacting with intense x-ray fields on ultra-short timescales, far from local thermodynamic equilibrium. We explore how the plasma relaxes to local thermodynamic equilibrium on femtosecond timescales in terms of the charge state distribution, electron density, and temperature.
Human metabolome variation along the upper intestinal tract
Authors: Folz Jacob , Culver Rebecca Neal , Morales Juan Montes , Grembi Jessica , Triadafilopoulos George , Relman David A. , Huang Kerwyn Casey , Shalon Dari , Fiehn Oliver
Published: May 2023

Most processing of the human diet occurs in the small intestine. Metabolites in the small intestine originate from host secretions, plus the ingested exposome1and microbial transformations. Here we probe the spatiotemporal variation of upper intestinal luminal contents during routine daily digestion in 15 healthy male and female participants. For this, we use a non-invasive, ingestible sampling device to collect and analyse 274 intestinal samples and 60 corresponding stool homogenates by combining five mass spectrometry assays2,3and 16S rRNA sequencing. We identify 1,909 metabolites, including sulfonolipids and fatty acid esters of hydroxy fatty acids (FAHFA) lipids. We observe that stool and intestinal metabolomes differ dramatically. Food metabolites display trends in dietary biomarkers, unexpected increases in dicarboxylic acids along the intestinal tract and a positive association between luminal keto acids and fruit intake. Diet-derived and microbially linked metabolites account for the largest inter-individual differences. Notably, two individuals who had taken antibiotics within 6 months before sampling show large variation in levels of bioactive FAHFAs and sulfonolipids and other microbially related metabolites. From inter-individual variation, we identifyBlautiaspecies as a candidate to be involved in FAHFA metabolism. In conclusion, non-invasive, in vivo sampling of the human small intestine and ascending colon under physiological conditions reveals links between diet, host and microbial metabolism.
Strong and tough magnesium-MAX phase composites with nacre-like lamellar and brick-and-mortar architectures
Authors: Liu Yanyan , Xie Xi , Liu Zengqian , Yu Qin , Wang Xuegang , Wang Shaogang , Jia Qing , Zhang Zhefeng , Yang Rui , Ritchie Robert O.
Published: May 2023

Bioinspired nacre-like structures are effective in toughening materials, yet are difficult to construct in magnesium-ceramic systems. Here, a set of magnesium-MAX phase composites with nacre-like lamellar and brick-and-mortar architectures are fabricated by pressureless infiltration of the magnesium melt into ice-templated Ti3AlC2 ceramic scaffolds. The structure and mechanical properties of the composites are elucidated with a special focus on the effects of the types of architectures (lamellar or brick-and-mortar) and matrices (pure magnesium or AZ91D alloy) on the toughening mechanisms. The nacre-like architectures are found to play a role in blunting the cracks via plastic deformation and microcracking, and shielding the cracks from applied stress by promoting crack deflection and uncracked-ligament bridging mechanisms. These composites achieve a good combination of specific strength and fracture toughness, which are superior to many other reported magnesium-ceramic and nacre-like metal-ceramic composite materials.