bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tissue factor links inflammation, thrombosis, and senescence in COVID-19
Authors: Nguyen Dayna , Jeon Hye-Min , Lee Jeongwu 
Published: November 2022

AbstractCOVID-19 is a highly contagious respiratory infection caused by the SARS-CoV-2 virus. The infected lung epithelial cells secrete a group of chemokines and cytokines, which triggers harmful cytokine storms and hyper-thrombotic responses. Recent studies have proposed that viral-induced senescence is responsible for cytokine release and inflammation in COVID-19 patients. However, it is unknown whether cellular senescence is commonly triggered after viral infection and how inflammation and thrombosis, hyper-activated in these patients, are functionally connected. To address these questions, we conducted a bioinformatics-based meta-analysis using single-cell and bulk RNA sequencing datasets obtained from human patient studies, animal models, and cell lines infected with SARS-CoV-2 and other respiratory viruses. We found that the senescence phenotype is robustly upregulated in most SARS-CoV-2-infected patients, especially in the infected lung epithelial cells. Notably, the upregulation of Tissue factor (F3), a key initiator of the extrinsic blood coagulation pathway, occurs concurrently with the upregulation of the senescence-associated secretory phenotype (SASP) factors. Furthermore, F3 levels are positively correlated with the senescence and hyper-coagulation gene signatures in COVID-19 patients. Together, these data demonstrate the prevalence of senescence in respiratory viral infection and suggest F3 as a critical link between inflammation, thrombosis, and senescence in these disease states.
Comparison of two isolation methods of tobacco-derived extracellular vesicles, their characterization and uptake by plant and rat cells
Authors: Kocholata Michaela , Prusova Michaela , Auer Malinska Hana , Maly Jan , Janouskova Olga 
Published: November 2022

AbstractPlant extracellular vesicles (pEVs) derived from numerous edible sources gain a lot of attention in recent years, mainly due to the potential to efficiently carry bioactive molecules into mammalian cells. In the present study, we focus on isolation of PDNVs (plant-derived nanovesicles) and pEVs from callus culture and from BY-2 culture of Nicotiana tabacum (tobacco). Tobacco was selected as a source of plant vesicles, as it is commonly used by human, moreover it is a model organism with established techniques for cultivation of explant cultures in vitro. Explant cultures are suitable for the isolation of pEVs in large quantities, due to their fast growth in sterile conditions. As the efficiency of isolation methods varies, we were comparing two methods of isolation. We evaluated biophysical and biochemical properties of plant vesicles, as well as differences between isolates. We encountered difficulties in the form of vesicles aggregation, which is often described in publications focused on mammalian nanovesicles. In an effort to prevent vesicle aggregation, we used trehalose in different stages of isolation. We show tobacco-derived vesicles successfully enter tobacco and mesenchymal cell lines. We observed that tobacco-nanovesicles isolated by different methods incorporated fluorescent dye with different efficiency. The results of our study show tobacco-derived vesicles isolated by various isolation methods are able to enter plant, as well as mammalian cells.
The diagnostic and prognostic potential of the EGFR/MUC4/MMP9 axis in glioma patients
Authors: Quesnel Agathe , Coles Nathan , Polvikoski Tuomo M. , Karagiannis George S. , Angione Claudio , Islam Meez , Khundakar Ahmad A. , Filippou Panagiota S. 
Published: November 2022

AbstractGlioblastoma is the most aggressive form of brain cancer, presenting poor prognosis despite current advances in treatment. There is therefore an urgent need for novel biomarkers and therapeutic targets. Interactions between mucin 4 (MUC4) and the epidermal growth factor receptor (EGFR) are involved in carcinogenesis, and may lead to matrix metalloproteinase-9 (MMP9) overexpression, exacerbating cancer cell invasiveness. In this study, the role of MUC4, MMP9, and EGFR in the progression and clinical outcome of glioma patients was investigated. Immunohistochemistry (IHC) and immunofluorescence (IF) in fixed tissue samples of glioma patients were used to evaluate the expression and localization of EGFR, MMP9, and MUC4. Kaplan–Meier survival analysis was also performed to test the prognostic utility of the proteins for glioma patients. The protein levels were assessed with enzyme-linked immunosorbent assay (ELISA) in serum of glioma patients, to further investigate their potential as non-invasive serum biomarkers. We demonstrated that MUC4 and MMP9 are both significantly upregulated during glioma progression. Moreover, MUC4 is co-expressed with MMP9 and EGFR in the proliferative microvasculature of glioblastoma, suggesting a potential role for MUC4 in microvascular proliferation and angiogenesis. The combined high expression of MUC4/MMP9, and MUC4/MMP9/EGFR was associated with poor overall survival (OS). Finally, MMP9 mean protein level was significantly higher in the serum of glioblastoma compared with grade III glioma patients, whereas MUC4 mean protein level was minimally elevated in higher glioma grades (III and IV) compared with control. Our results suggest that MUC4, along with MMP9, might account for glioblastoma progression, representing potential therapeutic targets, and suggesting the ‘MUC4/MMP9/EGFR axis’ may play a vital role in glioblastoma diagnostics.
Modeling and characteristic analysis of roadway profile under the influence of multiple factors
Authors: Liu Zhixiang , Zou Kang , Xie Miao , Xie Chunxue , Sun Zhan 
Published: November 2022

AbstractConsidering that the movement trajectory of roadheader cutting head directly affects the surface morphology characteristics of roadway forming, the creation mechanism of roadway contour obtained by cutting head cutting roadway is analyzed. The robot kinematics analysis method was used to determine the coordinates of the roadheader cutting head in the roadway space coordinate system, and the mathematical model of the cutting head cutting the roadway contour was constructed. Through numerical calculation, the differences of roadway morphology characteristics formed by three different types of cutting heads are analyzed. The orthogonal experiment was designed, and the regression equation under multiple factors was solved with the experimental results. The influence of cutting feed rate, cutting Angle, cutting head radius and cutting head cone Angle on the morphology characteristics of cutting surface was analyzed by regression calculation and theoretical calculation. The research results show that the roadway surface obtained by "spherical crown + cylinder" cutting head is the most uneven, and the roadway surface obtained by "spherical crown + cone + cylinder" cutting head is the most flat. With the decrease of cutting lifting Angle, cutting feed, cutting head cone Angle and the increase of cutting head crown radius, the smoothness of roadway obtained by cutting is higher.
Exactly solving the Kitaev chain and generating Majorana-zero-modes out of noisy qubits
Authors: Rančić Marko J. 
Published: November 2022

AbstractMajorana-zero-modes (MZMs) were predicted to exist as edge states of a physical system called the Kitaev chain. MZMs should host particles that are their own antiparticles and could be used as a basis for a qubit which is robust-to-noise. However, all attempts to prove their existence gave inconclusive results. Here, the Kitaev chain is exactly solved with a quantum computing methodology and properties of MZMs are probed by generating eigenstates of the Kitev Hamiltonian on 3 noisy qubits of a publicly available quantum computer. After an ontological elaboration I show that two eigenstates of the Kitaev Hamiltonian exhibit eight signatures attributed to MZMs. The results presented here are a most comprehensive set of validations of MZMs ever conducted in an actual physical system. Furthermore, the findings of this manuscript are easily reproducible for any user of publicly available quantum computers, solving another important problem of research with MZMs—the result reproducibility crisis.
Using model explanations to guide deep learning models towards consistent explanations for EHR data
Authors: Watson Matthew , Awwad Shiekh Hasan Bashar , Al Moubayed Noura 
Published: November 2022

AbstractIt has been shown that identical deep learning (DL) architectures will produce distinct explanations when trained with different hyperparameters that are orthogonal to the task (e.g. random seed, training set order). In domains such as healthcare and finance, where transparency and explainability is paramount, this can be a significant barrier to DL adoption. In this study we present a further analysis of explanation (in)consistency on 6 tabular datasets/tasks, with a focus on Electronic Health Records data. We propose a novel deep learning ensemble architecture that trains its sub-models to produce consistent explanations, improving explanation consistency by as much as 315% (e.g. from 0.02433 to 0.1011 on MIMIC-IV), and on average by 124% (e.g. from 0.12282 to 0.4450 on the BCW dataset). We evaluate the effectiveness of our proposed technique and discuss the implications our results have for both industrial applications of DL and explainability as well as future methodological work.
Multi-decadal oscillations of surface temperatures and the impact on temperature increases
Authors: Kalicinsky Christoph , Koppmann Ralf 
Published: November 2022

AbstractThe last IPCC assessment report indicated that natural climate variability could temporarily amplify or obscure anthropogenic climate change on decadal time scales. Here we analyse global mean surface temperatures in terms of such long-period variations. We find two main oscillations, a strong oscillation with a period of about 70 years and an amplitude of about 0.09 K and a quasi-bidecadal oscillation with an amplitude of about 0.06 K. The strong oscillation shows large hemispheric differences. In the Northern hemisphere the period is longer and the amplitude is larger (about 82 years and 0.18 K) compared to the Southern hemisphere (about 47 years and 0.065 K). No obvious hemispheric differences are observed for the quasi-bidecadal oscillation. Such long-period oscillations can strengthen or weaken the temperature increase if the oscillation positively or negatively adds to the underlying long-term trend.
Laser-optics-based method to suppress Mikania micrantha growth
Authors: Lan Yu-Pin 
Published: November 2022

AbstractMikania micrantha is an exotic and aggressive species that can reproduce asexually and sexually through its germinative stem and its featherlike seeds. Present weeding methods cannot effectively or economically control the spread of Mikania micrantha. In this article, we propose a method to suppress the growth and spread of Mikania micrantha by applying a high-energy laser beam to penetrate its stem. The threshold penetrating optical intensity is 3.1 W/mm2. To optimize the damage to the inner tissue of the stem, which includes the vascular bundle and medulla for transporting organic nutrients, water, and inorganic salt, the absorption spectrum of the tissue and laser beam size are analyzed. According to the absorption spectrum of the tissue and growth mechanism of Mikania micrantha, a 455 nm blue laser is used as an irradiated light source. A single beam with two different beam sizes or two laser beams with the same beam size is used to optimize the stem damage. By the time the cumulative energy reaches 15 Joules for a single laser beam with dimensions of 0.81 mm × 0.74 mm, the inner tissue will be damaged 97.5%. We perform laser irradiation on the fresh Mikania micrantha grown hydroponically, with the result that all samples withered in 30 days. Therefore, using the method before the flowering season of Mikania micrantha can effectively inhibit its reproduction.
Delivery of the reduced form of vitamin K2(20) to NIH/3T3 cells partially protects against rotenone induced cell death
Authors: Toki Erina , Goto Shotaro , Setoguchi Shuichi , Terada Kazuki , Watase Daisuke , Yamakawa Hirofumi , Yamada Ayano , Koga Mitsuhisa , Kubota Kaori , Iwasaki Katsunori , Karube Yoshiharu , Matsunaga Kazuhisa , Takata Jiro 
Published: November 2022

AbstractMitochondria generate energy through the action of the electron transport chain (ETC) and ATP synthase. Mitochondrial malfunction can lead to various disorders, including neurodegenerative diseases. Several reports have shown that menaquinone-4 (MK-4, vitamin K2(20)), a safe drug for osteoporosis, may improve mitochondrial function. Here, we hypothesized that the efficient delivery of menahydroquinone-4 (MKH), an active form of MK-4, could exert a supporting effect. We verified the effects of MKH delivery on mitochondrial dysfunction by using MK-4 and MKH ester derivatives in NIH/3T3 mouse fibroblast cells treated with mitochondrial inhibitors. MK-4 and MKH derivatives suppressed cell death, the decline in mitochondrial membrane potential (MMP), excessive reactive oxygen species (ROS) production, and a decrease in intrinsic coenzyme Q9 (CoQ9) induced by rotenone (ROT, complex I inhibitor). MK-4 and MKH derivatives delivered MKH to NIH/3T3 cells, acting as an effective MKH prodrug, proving that the delivered MKH may reflect the mitigation effects on ROT-induced mitochondrial dysfunction. MKH prodrugs are also effective against 3-nitropropionic acid (3-NP, complex II inhibitor) and carbonyl cyanide-m-chlorophenylhydrazone (CCCP, uncoupler)-induced cell death. In conclusion, MKH delivery may mitigate mitochondrial dysfunction by maintaining MMP, ROS, and CoQ9, indicating that MKH prodrugs may be good candidates for treating mitochondrial disorders.
Retrospective analysis and prospective validation of an AI-based software for intracranial haemorrhage detection at a high-volume trauma centre
Authors: Zia Adil , Fletcher Calvin , Bigwood Shalini , Ratnakanthan Prasanna , Seah Jarrel , Lee Robin , Kavnoudias Helen , Law Meng 
Published: November 2022

AbstractRapid detection of intracranial haemorrhage (ICH) is crucial for assessing patients with neurological symptoms. Prioritising these urgent scans for reporting presents a challenge for radiologists. Artificial intelligence (AI) offers a solution to enable radiologists to triage urgent scans and reduce reporting errors. This study aims to evaluate the accuracy of an ICH-detection AI software and whether it benefits a high-volume trauma centre in terms of triage and reducing diagnostic errors. A peer review of head CT scans performed prior to the implementation of the AI was conducted to identify the department’s current miss-rate. Once implemented, the AI software was validated using CT scans performed over one month, and was reviewed by a neuroradiologist. The turn-around-time was calculated as the time taken from scan completion to report finalisation. 2916 head CT scans and reports were reviewed as part of the audit. The AI software flagged 20 cases that were negative-by-report. Two of these were true-misses that had no follow-up imaging. Both patients were followed up and exhibited no long-term neurological sequelae. For ICH-positive scans, there was an increase in TAT in the total sample (35.6%), and a statistically insignificant decrease in TAT in the emergency (− 5.1%) and outpatient (− 14.2%) cohorts. The AI software was tested on a sample of real-world data from a high-volume Australian centre. The diagnostic accuracy was comparable to that reported in literature. The study demonstrated the institution’s low miss-rate and short reporting time, therefore any improvements from the use of AI would be marginal and challenging to measure.
Observation of hapten-induced sensitization responses for the development of a mouse skin sensitization test, including the elicitation phase
Authors: Kamata Ryo , Okawa Yukiko , Hamaguchi Yuto , Tabata Soma , Terasaki Masanori , Takeda Kazuki 
Published: November 2022

AbstractThe only official method that can detect the skin sensitizing potential of chemicals, including the elicitation response, is the OECD test guideline (TG) 406. However, this guideline uses guinea pigs, which requires complex procedures. Since a simple and complete test method for evaluating skin sensitization is needed, especially for mechanistic studies of skin sensitization, this study confirmed the reactivity of mice to skin sensitizing substances. We set up a protocol involving one induction exposure of the test substance to the back skin, followed by three challenge exposures to the auricle (Protocol 2), and compared their skin sensitization responses with the results of two exposures to the auricle and back skin every 2 weeks (Protocol 1) and a local lymph node assay (TG442B). A hapten 2,4-dinitrofluorobenzene caused significant auricular thickening, skin inflammation, and enlarged auricular lymph nodes in Protocols 1 and 2. These changes were more pronounced in Protocol 2. Plasma IgE and IgG1 and gene expression of IL4, IFNγ, and perforin were significantly increased in Protocol 2. Cell proliferation in the auricular lymph nodes was observed in both protocols as in TG442B. These results indicate that Protocol 2 can be a good candidate for a relatively simple skin sensitization test.
The relationship between islet β-cell function and metabolomics in overweight patients with Type 2 diabetes
Authors: Lv You , Zheng Yuanyuan , Zhao Xue , Li Zhuo , Wang Guixia 
Published: November 2022

Abstract
A cross-sectional study was performed using metabolomics in overweight patients with Type 2 diabetes (T2D) at different stages of the disease. We aimed to identify potential metabolites for assessing islet β-cell function in order to investigate the correlation between islet β-cell dysfunction and metabolite changes in overweight patients with T2D. We selected 60 overweight adults (24 ≤ body mass index [BMI] &lt; 28 kg/m2) with T2D who had been admitted to our hospital. The participants were equally divided into three groups according to disease duration: H1 (duration ≤ 5 years), H2 (5 years &lt; duration ≤ 10 years), and H3 (duration &gt; 10 years). Questionnaires, physical examinations, laboratory tests, and imaging studies were administered to all participants. The modified homeostasis model of assessment (HOMA) index was calculated using fasting C-peptide levels, and metabolite assays were performed using mass spectrometry. The results showed that HOMA-β and visceral fat area (VFA) were negatively correlated with diabetes duration. The VFA was positively correlated with arginine, cysteine, methionine, proline, and succinyl/methylmalonylcarnitine levels. The HOMA-β was negatively correlated with the serine and tetradecanoyldiacylcarnitine levels, and positively correlated with the aspartic acid, cysteine, homocysteine, piperamide, proline, and valine levels. The HOMA-IR was negatively correlated with hydroxypalmitoylcarnitine levels and positively correlated with the myristoylcarnitine levels. Thus, at different stages of T2D progression in overweight patients, serine, aspartic acid, cysteine, homocysteine, piperamide, proline, valine, and tetradecanoyldiacylcarnitine may be associated with HOMA-β and represent potential novel biomarkers for evaluating islet β-cell function.
Quantifying muscle blood flow: a transformative breakthrough in the science of human exercise physiology
Authors: Olson Thomas P. , Smith Joshua R. , Curry Timothy B. 
Published: November 2022

Abstract
Over 50 years ago, John Wahren and Lennart Jorfeldt published a manuscript in Clinical Science where they detailed a series of studies of leg blood flow during exercise. They used a novel approach to indicator dye dilution: continuous arterial infusions of dye using venous samples. This technique allowed them to describe for the first time the fundamental relationships between large muscle group exercise, muscle blood flow, and pulmonary and muscle oxygen uptake. They also defined mechanical efficiency, a key measurement of muscle function. This paper formed the basis for research into muscle blood flow and exercise in health and disease and continued to be cited by modern research. In this commentary, we describe the innovations they made, the key observations that came out of their results, and the importance of this manuscript to current research.
Comprehensive configuration strategy of energy storage allocation and line upgrading for distribution networks considering a high proportion of integrated photovoltaics
Authors: Zhang Xiaohui , Wang Liang , Zhang Bo , Li Jia , Pan Yongchao , Zhang Lu , Tang Wei 
Published: November 2022

AbstractThe rapid development of photovoltaics (PVs) and load caused a significant increase in peak loads and peak‐valley differences in rural distribution networks, which require load peak shifting and line upgrading. Large peak‐valley differences also bring challenges on the safe operation of the utility power grid. Considering the integration of a high proportion of PVs, this study establishes a bilevel comprehensive configuration model for energy storage allocation and line upgrading in distribution networks, which can reduce peak loads and peak‐valley differences. In the upper level, a minimum annual planning cost is obtained by developing the installation capacity of centralised energy storage in transformer stations, the installation location and capacity of decentralised energy storage on lines and a scheme of line upgrading. In the lower level, the minimum total annual operation cost of the distribution network is obtained by developing an optimal scheduling for the centralised energy storage in transformer stations and decentralised energy storage on lines. Simulation results show that compared with the conventional energy storage planning strategy, the configuration investment can be reduced by 467.66 million yuan at least with the proposed strategy.
Eosinophile Granulomatose mit Polyangiitis – ein
Übersichtsartikel
Authors: Schindler Viktoria , Venhoff Nils 
Published: November 2022

ZusammenfassungDie eosinophile Granulomatose mit Polyangiitis (EGPA) ist eine seltene Form der
ANCA-assoziierten Vaskulitiden (AAV) aus der Gruppe der
Kleingefäßvaskulitiden. Sie ist definiert als eine Vaskulitis
kleiner und mittelgroßer Gefäße mit
granulomatöser Entzündung sowie Blut- und Gewebseosinophilie.
Fast alle Patienten haben allergische Symptome mit Asthma bronchiale und
rhinosinusitischen Beschwerden. Das sonstige klinische Spektrum variiert je nach
Lokalisation, Schweregrad und Art der Krankheitsmanifestation. Durch die
eosinophile Infiltration und Inflammation kann es zu Rhinosinusitis,
Pneumonitis, gastrointestinaler Beteiligung und Kardiomyopathie kommen.
Insbesondere Letztere ist mit einer schlechteren Prognose assoziiert. Als
nekrotisierende pauci-immune Kleingefäßvaskulitis kann die EGPA,
ähnlich wie die anderen AAV, pulmonale Infiltrate mit alveolärer
Hämorrhagie, eine Glomerulonephritis, kutane Vaskulitis mit Purpura,
sowie zentrale und periphere neurologische Schädigungen verursachen. Das
Auftreten perinukleärer ANCA (pANCA), mit Spezifität gegen die
Myeloperoxidase (MPO) wird in etwa einem Drittel der Fälle beobachtet,
ist allerdings nicht spezifisch für die EGPA. MPO-ANCA-positive
Patienten haben häufiger eine periphere neurologische Beteiligung und
eine Glomerulonephritis, während ANCA-negative Patienten
häufiger eine kardiale und pulmonale Beteiligung aufweisen. Eine
differentialdiagnostische Herausforderung im klinischen Alltag stellt die
Abgrenzung zum hypereosinophilen Syndrom (HES) dar. Das Therapiekonzept der EGPA
hängt davon ab, ob der Schweregrad der Erkrankung potentiell Organ- oder
lebensbedrohlich ist. Bei schweren Formen der EGPA werden in der Akuttherapie
hauptsächlich Glukokortikoide in Kombination mit Cyclophosphamid
eingesetzt. Rituximab wird mittlerweile als alternative Behandlungsoption in den
Leitlinien genannt. Zur Remissionserhaltung stehen verschiedene immunsuppressive
Therapien zur Verfügung. Bei EGPA ohne schwere Organbeteiligung ist die
IL-5 Blockade mit Mepolizumab zugelassen.