bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of interleukin-6 and interleukin-10 in morphological and functional changes of the blood–brain barrier in hypertriglyceridemia
Authors: Barabási Beáta , Barna Lilla , Santa-Maria Ana Raquel , Harazin András , Molnár Réka , Kincses András , Vigh Judit P. , Dukay Brigitta , Sántha Miklós , Tóth Melinda E. , Walter Fruzsina R. , Deli Mária A. , Hoyk Zsófia 
Published: March 2023

Abstract
Background
Hypertriglyceridemia is closely linked to atherosclerosis related inflammatory processes and blood–brain barrier (BBB) dysfunction. Using apolipoprotein B-100 (APOB-100) transgenic mice, an animal model of chronic hypertriglyceridemia, we analyzed BBB function and morphology in vitro and ex vivo. Our objective was to determine which BBB characteristics are produced mainly by interleukin (IL)-6, an atherosclerosis promoting cytokine, and whether these actions can be antagonized by IL-10, an anti-inflammatory cytokine.

Methods
Brain endothelial and glial cell cultures and brain microvessels were isolated from wild type (WT) and APOB-100 transgenic mice and were treated with IL-6, IL-10 and their combination. First, IL-6 and IL-10 production was measured in WT and APOB-100 microvessels using qPCR. Then functional parameters of endothelial cell cultures were analyzed and immunocytochemistry for key BBB proteins was performed.

Results
IL-6 mRNA levels were higher in brain microvessels than in brain parenchyma of APOB-100 transgenic mice. Transendothelial electric resistance and P-glycoprotein activity were lower, and paracellular permeability was higher in cultured APOB-100 brain endothelial cells. These features were sensitive to both IL-6 and IL-10 treatments. A decreased P-glycoprotein immunostaining was measured in transgenic endothelial cells under control conditions and in WT cells after treating them with IL-6. This effect was antagonized by IL-10. Changes in immunostaining for tight junction proteins were observed after IL-6 exposure, which were in part antagonized by IL-10. In glial cell cultures an increase in aquaporin-4 immunolabeling in the transgenic group and an increase in microglia cell density in WT glia cultures was detected after IL-6 treatment, which was antagonized by IL-10. In isolated brain microvessels a decrease in P-glycoprotein immunolabeled area fraction was measured in APOB-100 microvessels under control conditions and in WT microvessels after every cytokine treatment. ZO-1 immunolabeling showed characteristics similar to that of P-glycoprotein. No change was seen in claudin-5 and occludin immunoreactive area fractions in microvessels. A decrease in aquaporin-4 immunoreactivity was measured in WT microvessels treated by IL-6, which was antagonized by IL-10.

Conclusion
IL-6 produced in microvessels contributes to BBB impairment observed in the APOB-100 mice. We showed that IL-10 partly antagonizes the effects of IL-6 at the BBB.
Latest development in the fabrication and use of lignin-derived humic acid
Authors: Sutradhar Shrikanta , Fatehi Pedram 
Published: March 2023

AbstractHumic substances (HS) are originated from naturally decaying biomass. The main products of HS are humic acids, fulvic acids, and humins. HS are extracted from natural origins (e.g., coals, lignite, forest, and river sediments). However, the production of HS from these resources is not environmentally friendly, potentially impacting ecological systems. Earlier theories claimed that the HS might be transformed from lignin by enzymatic or aerobic oxidation. On the other hand, lignin is a by-product of pulp and paper production processes and is available commercially. However, it is still under-utilized. To address the challenges of producing environmentally friendly HS and accommodating lignin in valorized processes, the production of lignin-derived HS has attracted attention. Currently, several chemical modification pathways can be followed to convert lignin into HS-like materials, such as alkaline aerobic oxidation, alkaline oxidative digestion, and oxidative ammonolysis of lignin. This review paper discusses the fundamental aspects of lignin transformation to HS comprehensively. The applications of natural HS and lignin-derived HS in various fields, such as soil enrichment, fertilizers, wastewater treatment, water decontamination, and medicines, were comprehensively discussed. Furthermore, the current challenges associated with the production and use of HS from lignin were described.
Differences in eco-physiological responses to the removal of adventitious roots between Syzygium nervosum A. Cunn. ex DC. and Syzygium cumini (L.) Skeels saplings under waterlogging
Authors: Li Dadong , Miao Lingfeng , Tian Mengjie , Zhou Jingjing , Yang Weizong , Yang Fan 
Published: March 2023

Abstract
Key message
The production of adventitious roots partially counteracts the negative effects of waterlogging on the growth of Syzygium nervosum A. Cunn. ex DC. and Syzygium cumini (L.) Skeels. S. cumini was more responsive and suffered from larger negative effects than S. nervosum after the removal of adventitious roots.

Context
Adventitious roots contain gas channels and functionally replace or compensate for the loss of primary roots that usually decay during waterlogging. However, the importance of adventitious roots on growth in waterlogged woody plants varies with species. Therefore, there has been some controversy about whether adventitious roots have beneficial effects on the growth of waterlogged plants.

Aims
We assessed whether S. nervosum and S. cumini differentially responded to the ablation of adventitious roots during waterlogging and whether compensatory responses occurred in the primary roots in both species.

Methods
S. nervosum and S. cumini saplings were subjected to waterlogging and adventitious root removal for 120 days, and morphological, physiological, biochemical parameters, and biomass were recorded.

Results
All plants survived waterlogging, and produced adventitious roots at the shoot base. Waterlogging had negative effects on the growth of both species, but the effect was more severe in S. cumini than in S. nervosum as seen from the values of comprehensive evaluation and total biomass. However, S. nervosum compensated for the ablation of adventitious roots with increased primary root dry mass, primary root activity, total root length, root tip number, and peroxidase activity.

Conclusions
S. nervosum with a high proportion of adventitious roots would be at an advantage during waterlogging. The removal of adventitious roots was detrimental to the growth of both species, but S. nervosum exhibited less damage than S. cumini due to its compensatory physiological responses and its primary roots.
A linear heuristic for multiple importance sampling
Authors: Sbert Mateu , Szirmay-Kalos László 
Published: March 2023

AbstractMultiple importance sampling combines the probability density functions of several sampling techniques into an importance function. The combination weights are the proportion of samples used for the particular techniques. This paper addresses the determination of the optimal combination weights from a few initial samples. Instead of the numerically unstable optimization of the variance, in our solution the quasi-optimal weights are obtained by solving a linear equation, which leads to simpler computations and more robust estimations. The proposed method is validated with 1D numerical examples and with the direct lighting problem of computer graphics.
Symmetrized fractional total variation for signal and image analysis
Authors: Leaci Antonio , Tomarelli Franco 
Published: March 2023

AbstractWe introduce and study a variational model for signal and image analysis based on Riemann–Liouville fractional derivatives. Both the one-dimensional and two-dimensional cases are studied. The model exploits a quadratic fitting data term together with both right and left Riemann–Liouville fractional derivatives as regularizing terms, with the aim of achieving an orientation-independent analysis.
Glycaemia in low-premixed insulin analogue type 2 diabetes patients in a real-world setting: are the CGM targets met?
Authors: Krajnc Mitja , Kravos Tramšek Nika Aleksandra 
Published: March 2023

Abstract
Background
There are insufficient data on continuous glucose monitoring (CGM) in nonintensive insulin therapy patients. Using CGM and the recommended CGM targets, we wanted to evaluate low-premix insulin analogue therapy (biphasic aspart/NovoMix 30 and biphasic lispro 25/Humalog Mix 25) in real-world type 2 diabetes patients for glycaemic efficacy and especially hypoglycaemia.

Methods
The prospective observational study was performed on 35 patients who were treated with a low-premixed insulin. We used the Dexcom G6 system for CGM (9.6 ± 1 days) to measure the clinically relevant CGM parameters: glycaemic variability (%CV), TBR (time below range) < 3.0 mmol/l = 54 mg/dl (level 2 hypoglycaemia), TBR 3.0–3.8 (= 54–69 mg/dl), TIR (time in range) 3.9–10–0 mmol/l (70–180 mg/dl), TAR (time above range) 10–13.9 mmol/l (180–250 mg/dl) and TAR > 13.9 mmol/l (250 mg/dl). We also assessed clinical and demographic characteristics, laboratory HbA1c, fasting blood glucose, peak postprandial glucose values, and the percentage of hypoglycaemia between 00:00 and 06:00.

Results
In our patients, the average ± SD age was 70.4 ± 9.2 years, diabetes duration 17.4 ± 7.1 years, 51% were females, average daily insulin dose was 46.4 units (80% received biphasic aspart). The average ± SD TIR was 62.1 ± 12.2%, TBR < 3.0 mmol/l 0.8 ± 2.0%, TBR 3.0–3.8 mmol/l 1.5 ± 1.5%, TAR 10–13.9 mmol/l 29.2 ± 12.4%, TAR > 13.9 mmol/l 6.4 ± 7.2% and %CV 29.9 ± 7.1%. The average time in hypoglycemia was 33.1 min daily in our patients (11.5 min in the level 2 range). In the older/high-risk population, the TBR/TIR/TAR/level 2 TAR targets were met in 40/80/77/80%, respectively. For the general T2D people, level 2 TBR/TBR/TIR/TAR/level 2 TAR would be met in 74/83/34/77/49%. Average fasting blood glucose was 8.0 ± 2.5 mmol/l (144 ± 45 mg/dl), BMI 31.3 ± 5.1 kg/m2, daily insulin dose 46.4 ± 12.1 units, HbA1c 57.4 ± 5.4 mmol/mol (7.4 ± 0.7%). The glycaemic variability goal was met in 80% (with 66% meeting the lower 33% CV goal). 17 ± 12% of hypoglycaemia was nocturnal. People with TBR > 4% were significantly older.

Conclusions
Most of our type 2 diabetes patients, treated with low-premixed insulin, did not meet the recommended TBR target for older/high-risk patients while meeting the TIR and TAR targets. Nevertheless, the time spent in (total and nocturnal) hypoglycemia was short. The study indicates that the general type 2 diabetes population targets would mostly be met for TBR and %CV in our patients but not the TIR and TAR targets. CGM appears to be a useful clinical tool in these patients.
Productive and physiological implications of top-dress addition of branched-chain amino acids and arginine on lactating sows and offspring
Authors: Luise Diana , Correa Federico , Stefanelli Claudio , Simongiovanni Aude , Chalvon-Demersay Tristan , Zini Maddalena , Fusco Luciano , Bosi Paolo , Trevisi Paolo 
Published: March 2023

Abstract
Background
Branched-chain amino acids (BCAAs), including L-leucine (L-Leu), L-isoleucine (L-Ile), L-valine (L-Val), and L-arginine (L-Arg), play a crucial role in mammary gland development, secretion of milk and regulation of the catabolic state and immune response of lactating sows. Furthermore, it has recently been suggested that free amino acids (AAs) can also act as microbial modulators. This study aimed at evaluating whether the supplementation of lactating sows with BCAAs (9, 4.5 and 9 g/d/sow of L-Val, L-Ile and L-Leu, respectively) and/or L-Arg (22.5 g/d/sow), above the estimated nutritional requirement, could influence the physiological and immunological parameters, microbial profile, colostrum and milk composition and performance of sows and their offspring.

Results
At d 41, piglets born from the sows supplemented with the AAs were heavier (P = 0.03). The BCAAs increased glucose and prolactin (P < 0.05) in the sows’ serum at d 27, tended to increase immunoglobulin A (IgA) and IgM in the colostrum (P = 0.06), increased the IgA (P = 0.004) in the milk at d 20 and tended to increase lymphocyte% in the sows’ blood at d 27 (P = 0.07). Furthermore, the BCAAs tended to reduce the Chao1 and Shannon microbial indices (P < 0.10) in the sows’ faeces. The BCAA group was discriminated by Prevotellaceae_UCG-004, Erysipelatoclostridiaceae UCG-004, the Rikenellaceae_RC9_gut_group and Treponemaberlinense. Arginine reduced piglet mortality pre- (d 7, d 14) and post-weaning (d 41) (P < 0.05). Furthermore, Arg increased the IgM in the sow serum at d 10 (P = 0.05), glucose and prolactin (P < 0.05) in the sow serum at d 27 and the monocyte percentage in the piglet blood at d 27 (P = 0.025) and their jejunal expression of NFKB2 (P = 0.035) while it reduced the expression of GPX-2 (P = 0.024). The faecal microbiota of the sows in Arg group was discriminated by Bacteroidales. The combination of BCAAs and Arg tended to increase spermine at d 27 (P = 0.099), tended to increase the Igs (IgA and IgG, P < 0.10) at d 20 in the milk, favoured the faecal colonisation of Oscillospiraceae UCG-005 and improved piglet growth.

Conclusion
Feeding Arg and BCAAs above the estimated requirements for milk production may be a strategy to improve sow productive performance in terms of piglet average daily gain (ADG), immune competence and survivability via modulation of the metabolism, colostrum and milk compositions and intestinal microbiota of the sows. The synergistic effect between these AAs, noticeable by the increase of Igs and spermine in the milk and in the improvement of the performance of the piglets, deserves additional investigation.
In-hospital mortality for aspiration pneumonia in a tertiary teaching hospital: A retrospective cohort review from 2008 to 2018
Authors: Shin Dongho , Lebovic Gerald , Lin R. Jun 
Published: March 2023

Background Aspiration pneumonia is a preventable condition that has higher rates of recurrence and mortality compared to non-aspiration pneumonia. The primary objective of the study was to examine independent patient factors that are associated with mortality in those requiring acute admission for aspiration pneumonia at a tertiary institution. Secondary goals of the study were to review whether factors such as mechanical ventilation and speech language pathology intervention can impact patient mortality, length of stay (LOS), and costs relating to hospitalization. Methods Patients older than 18 years of age who were admitted with a primary diagnosis of aspiration pneumonia from January 1, 2008 to December 31, 2018 at Unity Health Toronto-St. Michael's hospital in Toronto, Canada, were included in the study. Descriptive analyses were performed on patient characteristics using age as a continuous variable as well as a dichotomous variable with age 65 as a cut-off. Multivariable logistic regression was used to identify independent factors that contributed to in-hospital mortality and Cox proportional-hazard regression was used to identify independent factors that affected LOS. Results A total of 634 patients were included in this study. 134 (21.1%) patients died during hospitalization with an average age of 80.3 ± 13.4. The in-hospital mortality did not change significantly over the ten-year period ( p = 0.718). Patients who died had longer LOS with a median length of 10.5 days ( p = 0.012). Age [Odds Ratio (OR) 1.72, 95% Confidence Interval (95% CI) 1.47–2.02, p < 0.05] and invasive mechanical ventilation (OR 2.57, 95% CI 1.54–4.31, p < 0.05) were independent predictors of mortality while female gender was found to be a protective factor (OR 0.60, 95% CI 0.38–0.92, p = 0.02). Elderly patients had five times higher risk of dying during their hospital course when compared to younger patients [Hazard Ratio (HR) 5.25, 95% CI 2.99–9.23, p < 0.05). Conclusion Elderly patients are a high-risk population for developing aspiration pneumonia and are at higher risk of death when hospitalized for this condition. This warrants improved preventative strategies in the community. Further studies involving other institutions and creating a Canada-wide database are required. Graphical Abstract
Development and validation of a sensitive assay for the quantification of arachidonoylcyclopropylamide (ACPA) in cell culture by LC–MS/MS
Authors: Boyacıoğlu Özge , Reçber Tuba , Kır Sedef , Korkusuz Petek , Nemutlu Emirhan 
Published: March 2023

AbstractSynthetic and natural cannabinoid derivatives are highly investigated as drug candidates due to their antinociceptive, antiepileptic and anticancer potential. Arachidonoylcyclopropylamide (ACPA) is a synthetic cannabinoid with antiproliferative and apoptotic effects on non-small cell lung cancer and pancreatic and endometrial carcinoma. Thus, ACPA has a great potential for being used as an anticancer drug for epithelial cancers. Therefore, determining the levels of ACPA in biological fluids, cells, tissues and pharmaceutical dosage forms is crucial in monitoring the effects of various pharmacological, physiological and pathological stimuli on biological systems. However, the challenge in the quantification of ACPA is its short half-life and lack of UV signal. Therefore, we developed a liquid chromatography-tandem mass spectrometric (LC–MS/MS) method for sensitive and selective quantification of ACPA in cell culture medium and intracellular matrix. Multiple reaction monitoring in the positive ionization mode was used for detection with 344 → 203 m/z transitions. The separation of ACPA was performed on C18 column (50 × 3.0 mm, 2.1 μm) with the mobile phase run in the gradient mode with 0.1% formic acid (FA) in water and 0.1% FA in acetonitrile at a flow rate of 0.3 ml/min. The assay was linear in the concentration range of 1.8–1000 ng/mL (r = 0.999). The validation studies revealed that the method was linear, sensitive, accurate, precise, selective, repeatable, robust and rugged. Finally, the developed method was applied to quantify ACPA in cell culture medium and intracellular matrix.
An evaluation of the impact of the implementation of the Tele-ICU: a retrospective observational study
Authors: Watanabe Taro , Ohsugi Koichi , Suminaga Yuri , Somei Masayuki , Kikuyama Kazuki , Mori Maiko , Maruo Hiroko , Kono Nao , Kotani Toru 
Published: March 2023

Abstract
Background
The telemedicine intensive care unit (Tele-ICU) is defined as a system in which intensive care professionals remotely provide care to critically ill patients and support the on-site staff in the intensive care unit (ICU) using secured audio–video and electronic links. Although the Tele-ICU is expected to resolve the shortage of intensivists and reduce the regional disparities in intensive care resources, the efficacy has not yet been evaluated in Japan because of a lack of clinically available system.

Methods
This was a single-center, historical comparison study in which the impact of the Tele-ICU on ICU performance and changes in workload of the on-site staff were evaluated. The Tele-ICU system developed in the United States was used. Data for 893 adult ICU patients before the Tele-ICU implementation and for all adult patients registered in the Tele-ICU system from April 2018 to March 2020 were abstracted and included. We investigated ICU and hospital mortality and length of stay and ventilation duration after the Tele-ICU implementation in each ICU, and compared between pre and post implementation and changes over time. We also assessed physician workload as defined by the frequency and duration of access to the electronic medical record (EMR) of the targeted ICU patients.

Results
After the Tele-ICU implementation 5438 patients were included. In unadjusted data pre/post study showed significant decreases in ICU (8.5–3.8%) and hospital (12.4–7.7%) mortality and ICU length of stay (p < 0.001), and those values were maintained for 2 years. In data stratified by predicted hospital mortality, ICU and hospital actual mortality in high and medium risk patients decreased significantly after the implementation. Ventilation duration was shortened (p < 0.007). Access frequency of the on-site physicians decreased by 25%, and the decrease occurred in the daytime shift and in the physicians with 3–15 years of work experience.

Conclusions
Our study showed the Tele-ICU implementation was associated with lower mortality, especially in medium and high risk patients, and decreased EMR-related tasks of on-site physicians. These results suggest that the Tele-ICU could be a solution of the shortage of intensivists and regional disparities for intensive care.
An intensity index and its application for summertime extratropical cyclones in East Asia
Authors: Wang Sitao , Qin Yujing , Lu Chuhan , Guan Zhaoyong 
Published: March 2023

AbstractThe intensity definition and classification of the extratropical cyclone (EC) are still less studied than the tropical cyclone, due to the relatively ambiguous structure and diverse life cycle of ECs. In this study, a two-dimensional objective cyclone identification method based on outermost closed isolines is used to obtain the EC-related datasets, and the summertime ECs in East Asia are classified by the relationship between ECs of different intensities and the corresponding precipitation. The results show that compared with the cyclone mean depth, central wind and other traditional intensity indicators, the cyclone intensity index that is the maximum product of the EC-associated wind speed and specific humidity, has the highest correlation with the EC-associated maximum precipitation (r = 0.74). To simplify the definition of cyclone intensity index, the vqmax within the radius of 300 km from the cyclone center is defined as the cyclone intensity. According to the relationship between EC and precipitation intensity and the precipitation grades in China, the ECs in East Asia are classified into four levels. Accordingly, the EC-associated maximum precipitation increases substantially with the raising of cyclone level. In particular, 32.8% of heavy rain events in East Asia in summer are related to ECs of the strongest category. The results will facilitate a better understanding of the relationship between the strongest category EC and local precipitation.
Cognitive framework for blended mathematical sensemaking in science
Authors: Kaldaras Leonora , Wieman Carl 
Published: March 2023

Abstract
Background
Blended mathematical sensemaking in science (“Math-Sci sensemaking”) involves deep conceptual understanding of quantitative relationships describing scientific phenomena and has been studied in various disciplines. However, no unified characterization of blended Math-Sci sensemaking exists.

Results
We developed a theoretical cognitive model for blended Math-Sci sensemaking grounded in prior work. The model contains three broad levels representing increasingly sophisticated ways of engaging in blended Math-Sci sensemaking: (1) developing qualitative relationships among relevant variables in mathematical equations describing a phenomenon (“qualitative level”); (2) developing mathematical relationships among these variables (“quantitative level”); and (3) explaining how the mathematical operations used in the formula relate to the phenomenon (“conceptual level”). Each level contains three sublevels. We used PhET simulations to design dynamic assessment scenarios in various disciplines to test the model. We used these assessments to interview undergraduate students with a wide range of Math skills. Interview analysis provided validity evidence for the categories and preliminary evidence for the ordering of the categories comprising the cognitive model. It also revealed that students tend to perform at the same level across different disciplinary contexts, suggesting that blended Math-Sci sensemaking is a distinct cognitive construct, independent of specific disciplinary context.

Conclusion
This paper presents a first-ever published validated cognitive model describing proficiency in blended Math-Sci sensemaking which can guide instruction, curriculum, and assessment development.