bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid Activation of Neuroinflammation in Stroke: Plasma and Extracellular Vesicles Obtained on a Mobile Stroke Unit
Authors: Kowalski Robert G. , Ledreux Aurélie , Violette John E. , Neumann Robert T. , Ornelas David , Yu Xiaoli , Griffiths Steven G. , Lewis Scott , Nash Priscilla , Monte Andrew A. , Coughlan Christina M. , Deighan Clayton , Grotta James C. , Jones William J. , Graner Michael W. 
Published: February 2023

Background:
Neuroinflammation is ubiquitous in acute stroke and worsens outcome. However, the precise timing of the inflammatory response is unknown, hindering the design of acute anti-inflammatory therapeutic interventions. We sought to identify the onset of the neuroinflammatory cascade using a mobile stroke unit.

Methods:
The study is a proof-of-concept, cohort investigation of ultra-early blood- and extracellular vesicle–derived markers of neuroinflammation and outcome in acute stroke. Blood was obtained, prehospital, on an mobile stroke unit. Outcomes were biomarker concentrations, modified Rankin Scale score, and National Institutes of Health Stroke Scale score.

Results:
Forty-one adults were analyzed, including 15 patients treated on the mobile stroke unit between August 2021 and April 2022, and 26 healthy controls to establish biomarker reference levels. Median patient age was 74 (range, 36–97) years, 60% were female, and 80% White. Ten (67%) were diagnosed as stroke, with 8 (53%) confirmed and 2 likely transient ischemic attack or stroke averted by thrombolysis; 5 were stroke mimics. For strokes, median initial National Institutes of Health Stroke Scale score was 11 (range, 4–19) and 6 (75%) received tPA (tissue-type plasminogen activator). Blood was obtained a median of 58 (range, 36–133) minutes after symptom onset. Within 36 minutes after stroke, plasma IL-6 (interleukin-6), neurofilament light chain, UCH-L1 (ubiquitin C-terminal hydrolase L1), and GFAP (glial fibrillary acidic protein) were elevated by as much as 10 times normal. In EVs, MMP-9 (matrix metalloproteinase-9), CXCL4 (chemokine (C-X-C motif) ligand 4), CRP (C-reactive protein), IL-6, OPN (osteopontin), and PECAM1 (platelet and endothelial cell adhesion molecule 1) were elevated. Inflammatory markers increased rapidly in the first 2 hours and continued rising for 24 hours.

Conclusions:
The neuroinflammatory cascade was found to be activated within 36 to 133 minutes after stroke and progresses rapidly. This is earlier than observed previously in humans and suggests injury from neuroinflammation occurs faster than had been surmised. These findings could inform development of acute immunomodulatory stroke therapies and lead to new diagnostic tools and improved outcomes.
Association Between Hospital-Documented Atrial Fibrillation and Central Retinal Artery Occlusion
Authors: Lusk Jay B. , Song Ailin , Unnithan Shakthi , Al-Khalidi Hussein R. , Delic Alen , de Havenon Adam , Biousse Valérie , Schrag Matthew , Poli Sven , Piccini Jonathan P. , Xian Ying , O’Brien Emily C. , Mac Grory Brian 
Published: February 2023

Background:
Carotid stenosis is thought to be the primary risk factor for central retinal artery occlusion (CRAO); however, it is not known whether atrial fibrillation (AF)—a cardiac arrhythmia that underlies over 25% of cerebral ischemic strokes—predisposes patients to CRAO.

Methods:

A retrospective, observational, cohort study was performed using data from the State Inpatient Databases and State Emergency Department Databases from New York (2006–2015), California (2003–2011), and Florida (2005–2015) to determine the association between AF and CRAO. The primary exposure was hospital-documented AF. The primary end point was hospital-documented CRAO, defined as having an
International Classification of Diseases, Ninth Revision, Clinical Modification
, code 362.31 in the primary diagnosis position. Cause-specific hazard models were used to model CRAO-free survival among patients according to hospital-documented AF status.

Results:
Of 39 834 885 patients included in the study, 2 723 842 (median age, 72.7 years; 48.5% women) had AF documented during the exposure window. The median follow-up duration was 6 years and 1 month. Patients with AF were older, more likely to be of non-Hispanic White race/ethnicity, and had a higher burden of cardiovascular comorbidities compared with patients without AF. The cumulative incidence of CRAO determined prospectively after exclusions was 8.69 per 100 000 at risk in those with AF and 2.39 per 100 000 at risk in those without AF over the study period. Before adjustment, AF was associated with higher risk of CRAO (hazard ratio, 2.55 [95% CI, 2.15–3.03]). However, after adjustment for demographics, state, and cardiovascular comorbidities, there was an inverse association between AF and risk of CRAO (adjusted hazard ratio, 0.72 [95% CI, 0.60–0.87]). These findings were robust in our prespecified sensitivity analyses. By contrast, positive control outcomes of embolic and ischemic stroke showed an expected strong relationship between AF and risk of stroke.

Conclusions:
We found an inverse association between AF and CRAO in a large, representative study of hospitalized patients; however, this cohort did not ascertain AF or CRAO occurring outside of hospital or emergency department settings.
The ERA5 Extreme Seasons Explorer as a Basis for Research at the Weather and Climate Interface
Authors: Boettcher Maxi , Röthlisberger Matthias , Attinger Roman , Rieder Joëlle , Wernli Heini 
Published: February 2023

Abstract
Meteorological extremes on the seasonal time scale have received increased attention due to their relevance for society and economy. A recently developed approach to identify seasonal extremes is applied here to ERA5 reanalyses from 1950 to 2020 to identify hot and cold, wet and dry, and stormy and calm extreme seasons globally. The approach consists of (i) fitting a statistical model to seasonal mean values (of temperature, precipitation, and wind speed) at each grid point, (ii) selecting a local return period threshold above which seasonal mean values are deemed extreme, and (iii) forming spatially coherent extreme season objects. The paper introduces the ERA5 extreme season explorer, an open-access web portal enabling researchers to visualize and download extreme season objects of any of the six types in their region of interest, for further investigating their underlying dynamics, statistical properties, and impacts. To illustrate the potential of our extreme season objects, we first discuss the top 10 cold winters in ERA5 globally and then focus on an unusual triple-compound extreme season in winter 1953/54 in Europe, which was simultaneously extremely cold, dry, and calm. We show that detailed analysis of weather system dynamics, including cyclones, blocks, jets, and Rossby waves, provides important insight into the processes leading to extreme seasons. In summary, this study presents for the first time a catalogue of objectively identified extreme seasons in the last decades, shows exemplarily how large-scale dynamics can lead to such seasons, and with the help of the explorer supports the community in accelerating research in this important area at the interface of weather and climate dynamics.
Flow characteristics of a centrifugal fan with optimized edge curvatures of an impeller front disk
Authors: Zheng Shuihua , Shao Zhenghao , Liu Jianfei , Chen Jinxue , Li Yiliang , Chai Min 
Published: January 2023

In this study, the flow characteristics of different radiated impeller front disk fans were investigated by computational fluid dynamics to explore the effect of the radiated impeller front disk of the centrifugal fan on the three-dimensional flow of the volute-free centrifugal fan. Specifically, the flow-static pressure performance curve of the prototype fan was obtained to compare the numerical simulation results with the experimental results, so as to verify the accuracy of the numerical simulation. Besides, the linear fitting function of the radian edge of the front disk of the impeller was adjusted to acquire improved optimized fans. After numerical simulation analysis, the modification increases the outlet flow, static pressure at the outlet of the fan, static pressure efficiency, and total efficiency by 19 m³/h, 4.7 Pa, 5.6%, and 6.8%, respectively. The research reveals that the curvature of the front disk edge of the impeller can increase the flow channel volume between the blades and reduce the energy loss generated inside the impeller, thereby improving the static pressure and efficiency of the fan.
The ethical pathway – Does the perceived realisation of the individuals’ values change during the post-stroke time?
Authors: Rannikko Sunna Eva Erika , Leino-Kilpi Helena , Pasanen Miko , Suhonen Riitta 
Published: January 2023

Background Stroke causes ethically challenging changes in the lives of individuals with stroke (IwS). However, it is unclear whether the changes are stable or dynamic. In this study, a novel concept ‘ethical pathway’ is used to describe the potential changes in the perceived realisation of IwS’ values in temporal passage post-stroke. Ethical pathway includes three central values of nursing: dignity, privacy and autonomy. Aim of the study was to analyse the perceived ethical pathway of IwS over a non-limited post-stroke period, with the purpose to understand the existence of the IwS’ ethical pathway in theoretical level. Design A descriptive and correlational design. Methods The volunteer participants were recruited via the Finnish Brain Association. Data were collected with questions of background variables and the Ethical Pathway of Individuals with Stroke (EPIS) instrument and analysed statistically. The Ethics Committee of the University approved the study and permission for data collection was obtained from the association. Results Sixty-one IwS participated in the study. The ethical pathway varied during the post-stroke time. Of the values, dignity and privacy were realised lower with longer post-stroke time. The life situational factors were associated with the realisation of the values, but not consistently.
Standardized airway wall thickness Pi10 from routine CT scans of COPD patients as imaging biomarker for disease severity, lung function decline, and mortality
Authors: Kahnert Kathrin , Jörres Rudolf A. , Kauczor Hans-Ulrich , Alter Peter , Trudzinski Franziska C. , Herth Felix , Jobst Bertram , Weinheimer Oliver , Nauck Sebastian , Mertsch Pontus , Kauffmann-Guerrero Diego , Behr Jürgen , Bals Robert , Watz Henrik , Rabe Klaus F. , Welte Tobias , Vogelmeier Claus F. , Biederer Jürgen 
Published: January 2023

Background: Chest computed tomography (CT) is increasingly used for phenotyping and monitoring of patients with COPD. The aim of this work was to evaluate the association of Pi10 as a measure of standardized airway wall thickness on CT with exacerbations, mortality, and response to triple therapy. Methods: Patients of GOLD grades 1–4 of the COSYCONET cohort with prospective CT scans were included. Pi10 was automatically computed and analyzed for its relationship to COPD severity, comorbidities, lung function, respiratory therapy, and mortality over a 6-year period, using univariate and multivariate comparisons. Results: We included n = 433 patients (61%male). Pi10 was dependent on both GOLD grades 1–4 ( p = 0.009) and GOLD groups A–D ( p = 0.008); it was particularly elevated in group D, and ROC analysis yielded a cut-off of 0.26 cm. Higher Pi10 was associated to lower FEV1 % predicted and higher RV/TLC, moreover the annual changes of lung function parameters ( p < 0.05), as well as to an airway-dominated phenotype and a history of myocardial infarction ( p = 0.001). These associations were confirmed in multivariate analyses. Pi10 was lower in patients receiving triple therapy, in particular in patients of GOLD groups C and D. Pi10 was also a significant predictor for mortality ( p = 0.006), even after including multiple other predictors. Conclusion: In summary, Pi10 was found to be predictive for the course of the disease in COPD, in particular mortality. The fact that Pi10 was lower in patients with severe COPD receiving triple therapy might hint toward additional effects of this functional therapy on airway remodeling. Registration: ClinicalTrials.gov, Identifier: NCT01245933
Indole-3-propionic acid alleviates chondrocytes inflammation and osteoarthritis via the AhR/NF-κB axis
Authors: Zhuang Huangming , Ren Xunshan , Jiang Fuze , Zhou Panghu 
Published: January 2023

AbstractBackgroundOsteoarthritis (OA) is a common chronic disease characterized by chronic inflammation and extracellular matrix degradation. Indole-3-propionic acid (IPA) is a tryptophan metabolite secreted by intestinal flora, which can exert anti-inflammatory effects in a variety of diseases. In this study, we further investigated the potential therapeutic role of IPA in OA and the underlying mechanism.MethodsIL-1β was utilized to induce chondrocyte inflammation. Then, the cytotoxicity of IPA on rat chondrocytes was assessed. Meanwhile, RT-qPCR, Griess reaction, ELISA, Western blot and immunofluorescence were performed to evaluate the expression of inflammatory factors and stromal proteins, and the NF-κB pathway in chondrocytes treated with IL-1β alone, with IPA or with aryl hydrocarbon receptor (AhR) knockdown. An OA rat model was established by anterior cruciate ligament transection, and hematoxylin-eosin staining, Safranin-O/Fast Green staining and immunochemistry were applied to estimate OA severity.ResultsIPA did not affect cellular viability at concentrations up to 80 µM. IPA significantly inhibited the IL-1β-induced expression of inflammatory factors (Nitric oxide, PGE2, TNF-α, IL-6, iNOS and COX-2) and matrix-degrading enzymes (MMP-3, MMP-13 and ADAMTS-5), upregulated the expression of anabolic markers (aggrecan and collagen-II) and inactivated the NF-κB pathway. However, AhR knockdown could abolish the above protection capabilities and the suppression of the NF-κB pathway induced by IPA. Furthermore, IPA significantly reduced serum inflammatory cytokines expression, cartilage destruction and synovitis in vivo, demonstrating its protective role in OA progression.ConclusionIPA improved IL-1β-induced chondrocyte inflammation and extracellular matrix degradation through the AhR/NF-κB axis, which provides an innovative therapeutic strategy for OA.
Pristine/folate-functionalized graphene oxide as two intrinsically radioiodinated nano-theranostics: self/dual in vivo targeting comparative study
Authors: Swidan Mohamed M. , Essa Basma M. , Sakr Tamer M. 
Published: February 2023

Abstract
Background
Nanomedicine offers great potentials for theranostic studies via providing higher efficacy and safety levels. This work aimed to develop and evaluate a new nanoplatform as a tumor theranostic probe.

Results
Carboxyl-functionalized graphene oxide nanosheets (FGO) was well synthesized from graphite powder and then conjugated with folic acid to act as a targeted nano-probe. Full characterization and in vitro cytotoxicity evaluation were conducted; besides, in vivo bio-evaluation was attained via intrinsic radioiodination approach in both normal and tumor-bearing Albino mice. The results indicated that FGO as well as conjugated graphene oxide nanosheets (CGO) are comparatively non-toxic to normal cells even at higher concentrations. Pharmacokinetics of FGO and CGO showed intensive and selective uptake in the tumor sites where CGO showed high T/NT of 7.27 that was 4 folds of FGO at 1 h post injection. Additionally, radioiodinated-CGO (ICGO) had declared a superior prominence over the previously published tumor targeted GO radiotracers regarding the physicochemical properties pertaining ability and tumor accumulation behavior.

Conclusions
In conclusion, ICGO can be used as a selective tumor targeting agent for cancer theranosis with aid of I-131 that has a maximum beta and gamma energies of 606.3 and 364.5 keV, respectively.
Cudraflavone B induces human glioblastoma cells apoptosis via ER stress-induced autophagy
Authors: Pan Jinlin , Zhao Rongchuan , Dong Caihua , Yang Jiao , Zhang Ruobing , Sun Minxuan , Ahmad Nafees , Zhou Yuanshuai , Liu Yanxiang 
Published: January 2023

Abstract
Background
Glioblastoma (GBM) is the most common malignant intracranial tumor with a low survival rate. However, only few drugs responsible for GBM therpies, hence new drug development for it is highly required. The natural product Cudraflavone B (CUB) has been reported to potentially kill a variety of tumor cells. Currently, its anit-cancer effect on GBM still remains unknown. Herein, we investigated whether CUB could affect the proliferation and apoptosis of GBM cells to show anti-GBM potential.

Results
CUB selectively inhibited cell viability and induced cell apoptosis by activating the endoplasmic reticulum stress (ER stress) related pathway, as well as harnessing the autophagy-related PI3K/mTOR/LC3B signaling pathway. Typical morphological changes of autophagy were also observed in CUB treated cells by microscope and scanning electron microscope (SEM) examination. 4-Phenylbutyric acid (4-PBA), an ER stress inhibitor, restored the CUB-caused alteration in signaling pathway and morphological change.

Conclusions
Our finding suggests that CUB impaired cell growth and induced cell apoptosis of glioblastoma through ER stress and autophagy-related signaling pathways, and it might be an attractive drug for treatment of GBM.
Exogenous hydrogen sulfide and methylglyoxal alleviate cadmium-induced oxidative stress in Salix matsudana Koidz by regulating glutathione metabolism
Authors: Guo Long , Ling Long , Wang Xiaoqian , Cheng Ting , Wang Hongyan , Ruan Yanan 
Published: February 2023

Abstract
Background
Cadmium (Cd) is a highly toxic element for plant growth. In plants, hydrogen sulfide (H2S) and methylglyoxal (MG) have emerged as vital signaling molecules that regulate plant growth processes under Cd stress. However, the effects of sodium hydrosulfide (NaHS, a donor of H2S) and MG on Cd uptake, physiological responses, and gene expression patterns of Salix to Cd toxicity have been poorly understood. Here, Salix matsudana Koidz. seedlings were planted in plastic pot with applications of MG (108 mg kg− 1) and NaHS (50 mg kg− 1) under Cd (150 mg kg− 1) stress.

Results
Cd treatment significantly increased the reactive oxygen species (ROS) levels and malondialdehyde (MDA) content, but decreased the growth parameters in S. matsudana. However, NaHS and MG supplementation significantly decreased Cd concentration, ROS levels, and MDA content, and finally enhanced the growth parameters. Cd stress accelerated the activities of antioxidative enzymes and the relative expression levels of stress-related genes, which were further improved by NaHS and MG supplementation. However, the activities of monodehydroascorbate reductase (MDHAR), and dehydroascorbate reductase (DHAR) were sharply decreased under Cd stress. Conversely, NaHS and MG applications restored the MDHAR and DHAR activities compared with Cd-treated seedlings. Furthermore, Cd stress decreased the ratios of GSH/GSSG and AsA/DHA but considerably increased the H2S and MG levels and glyoxalase I-II system in S. matsudana, while the applications of MG and NaHS restored the redox status of AsA and GSH and further improved glyoxalase II activity. In addition, compared with AsA, GSH showed a more sensitive response to exogenous applications of MG and NaHS and plays more important role in the detoxification of Cd.

Conclusions
The present study illustrated the crucial roles of H2S and MG in reducing ROS-mediated oxidative damage to S. matsudana and revealed the vital role of GSH metabolism in regulating Cd-induced stress.
Effects of dexmedetomidine on evoked potentials in spinal surgery under combined intravenous inhalation anesthesia: a randomized controlled trial
Authors: Jiang Xinyu , Tang Xiaoning , Liu Shaoquan , Liu Ling 
Published: January 2023

Abstract
Objective
We aimed to investigate the effects of different doses of dexmedetomidine (Dex) on evoked potentials in adult patients undergoing spinal surgery under intravenous anesthesia with low-concentration desflurane.

Methods
Ninety patients were divided into three groups at random. To maintain anesthesia in the control group (group C), desflurane 0.3 MAC (minimal alveolar concentration), propofol, and remifentanil were administered. Dex (0.5 μg·kg−1) was injected for 10 min as a loading dose in the low-dose Dex group (group DL), then adjusted to 0.2 μg·kg−1·h−1 until the operation was completed. Dex (1 μg·kg−1) was injected for 10 min as a loading dose in the high-dose Dex group (group DH), then adjusted to 0.7 μg·kg−1·h−1 until the operation was completed. The additional medications were similar to those given to group C. The perioperative hemodynamics, body temperature, intraoperative drug dosages, fluid volume, urine volume, blood loss, the latency and amplitude of somatosensory evoked potentials (SEPs) at four different time points, the incidence of positive cases of SEPs and transcranial motor evoked potentials (tcMEPs), and perioperative adverse reactions were all recorded.

Results
Data from 79 patients were analyzed. The MAP measured at points T2-T4 in group DH was higher than at corresponding points in group C (P < 0.05). The MAP at point T4 in group DL was higher than at corresponding points in group C (P < 0.05). The remifentanil dosage in group DH was significantly lower than in group C (P = 0.015). The fluid volume in group DL was significantly lower than in group C (P = 0.009). There were no significant differences among the three groups in the amplitude and latency of SEP at different time points, nor in the incidence of warning SEP signals. The incidence of positive tcMEP signals did not differ significantly between groups C and DL (P > 0.05), but was significantly higher in group DH than in groups DL (P < 0.05) or C (P < 0.05). The incidence of intraoperative hypertension was significantly higher in group DH than in group C (P = 0.017).

Conclusions
Low-dose Dex has no effect on the SEPs and tcMEPs monitoring during spinal surgery. High-dose Dex has no effect on SEPs monitoring, but it may increase the rate of false positive tcMEPs signals and the incidence of intraoperative hypertension.

Trial registration
This study has completed the registration of the Chinese Clinical Trial Center at 11/09/2020 with the registration number ChiCTR2000038154.