bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polymer-based dual drug delivery system for targeted treatment of fluoroquinolone-resistant Staphylococcus aureus mediated infections
Authors: Thamilselvan Gopalakrishnan , David Helma , Sajeevan Anusree , Rajaramon Shobana , Solomon Adline Princy , D Ramyadevi , Narayanan Vedha Hari B 
Published: March 2023

Abstract
The present study attempts to treat S. aureus-induced soft skin infections using a novel combinatorial therapy with an antibiotic, Ciprofloxacin (CIP), and an efflux pump inhibitor 5-Nitro-2-(3-phenylpropoxy) pyridine (5-NPPP) through a smart hydrogel delivery system. The study aims to reduce the increasing rates of infections and antimicrobial resistance; therefore, a novel efflux pump inhibitor molecule is synthesised and delivered along with an antibiotic to re-sensitize the pathogen towards antibiotics and treat the infections. CIP loaded polyvinyl alcohol (PVA) hydrogels at varying concentrations were fabricated and optimized by a chemical cross-linking process, which exhibited sustained release of the drug for 5 days. The compound 5-NPPP loaded hydrogels provided linear drug release for 2 days, necessitating the need for the development of polymeric nanoparticles to alter the release drug pattern. 5-NPPP loaded Eudragit RSPO nanoparticles were prepared by modified nanoprecipitation - solvent evaporation method, which showed optimum average particle size of 230–280 nm with > 90% drug entrapment efficiency. The 5-NPPP polymeric nanoparticles loaded PVA hydrogels were fabricated to provide a predetermined sustained release of the compound to provide synergistic effect. The selected 7% PVA hydrogels loaded with the dual drugs were evaluated using Balb/c mice models induced with S. aureus soft skin infections. The results of in vivo studies were evidenced that the dual drugs loaded hydrogels were non-toxic and reduced the bacterial load causing re-sensitization towards antibiotics, which could initiate re-epithelization. Overall, the research concluded that the PVA hydrogels loaded with CIP and 5-NPPP nanoparticles could be an ideal and promising drug delivery system to treat S. aureus induced skin infections.
Metformin ameliorates peripheral neuropathy in diabetic rats by downregulating autophagy via the AMPK pathway
Authors: Liu Fengmin , Li Wei , Xie Diya , Du Xiaojuan , Chen Xiaole 
Published: March 2023

Abstract
Aims
Diabetic neuropathy (DN) represents an important complication of diabetes mellitus. Autophagy is considered to be potentially involved in the regulation of DN. Metformin is broadly utilized in the first-line treatment of diabetes. The present work aimed to assess whether and how metformin exerts protective effects in DN.
Methods
A diabetic neuropathy rat model induced by STZ was established. Metformin was administered to examine its effect on sciatic nerve pathology, and the possible mechanism was explored.
Results
Morphological damage was observed in sciatic nerve samples from diabetic animals, accompanied by decreased p-AMPK expression and increased LC-3 levels. Notably, metformin ameliorated the morphological changes in the sciatic nerve by downregulating autophagy via p-AMPK upregulation.
Conclusions
These results indicate that metformin attenuates peripheral neuropathy in diabetic rats by regulating autophagy.
Feasible intervention combinations for achieving a safe exit of the Zero-COVID policy in China and its determinants: an individual- based model study
Authors: Cheng Qu , Hao Xingjie , Wu Degang , Wang Qi , Spear Robert C. , Wei Sheng 
Published: March 2023

Abstract
Background
Although several pathways have been proposed as the prerequisite for a safe phase-out in China, it is not clear which of them are the most important for keeping the mortality rate low, what thresholds should be achieved for these most important interventions, and how do the thresholds change with the assumed key epidemiological parameters and population characteristics.
Methods
We developed an individual-based model (IBM) to simulate the transmission of the Omicron variant in the synthetic population, accounting for the age-dependent probabilities of severe clinical outcomes, waning vaccine-induced immunity, increased mortality rates when hospitals are overburdened, and reduced transmission when self-isolated at home after testing positive. We applied machine learning algorithms on the simulation outputs to examine the importance of each intervention parameter and the feasible intervention parameter combinations for safe exits, which is defined as having mortality rates lower than that of influenza in China (14.3 per 100, 000 persons).
Results
We identified vaccine coverage in those above 70 years old, number of ICU beds per capita, and the availability of antiviral treatment as the most important interventions for safe exits across all studied locations, although the thresholds of them required for safe exits vary remarkably with the assumed vaccine effectiveness, as well as the age structure, age-specific vaccine coverage, community healthcare capacity of the studied locations.
Conclusions
The analytical framework developed here can provide the basis for further policy decisions that incorporate considerations about economic costs and societal impacts. Achieving safe exits from the Zero-COVID policy is possible, but challenging for China’s cities. When planning for safe exits, local realities such as the age structure and current age-specific vaccine coverage must be taken into consideration.
The risk of hospitalization for psychotic disorders following hospitalization for COVID-19: a French nationwide longitudinal study
Authors: Pignon Baptiste , Decio Valentina , Pirard Philippe , Bouaziz Olivier , Corruble Emmanuelle , Geoffroy Pierre , Kovess-Masfety Viviane , Leboyer Marion , Lemogne Cédric , Messika Jonathan , Perduca Vittorio , Schurhof Franck , Regnault Nolwenn , Tebeka Sarah 
Published: March 2023

Abstract
COVID-19, like other infectious diseases, may be a risk factor for a first episode of psychosis or psychotic relapse. We aimed to compare the proportions of hospitalizations for psychotic disorders in the 12 months following discharge from hospital for either COVID-19 or for another reason in the adult general population in France during the first wave of the pandemic.
We conducted a retrospective longitudinal nationwide study using the national French administrative healthcare database. Psychotic disorders were first studied as a whole, and then chronic and acute disorders separately. The role of several adjustment factors, including sociodemographics, a history of psychotic disorder, the duration of the initial hospitalization, and the level of care received during that hospitalization, were also analyzed.
Between 1 January 2020 and 30 June 2020, a total of 14,622 patients were hospitalized for psychotic disorders in the 12 months following discharge from hospital for either COVID-19 or another reason. Initial hospitalization for COVID-19 (vs. another reason) was associated with a lower rate of subsequent hospitalization for psychotic disorders (0.31 % vs. 0.51 %, OR = 0.60, 95% CI [0.53-0.67]). This was true for both chronic and acute disorders, even after adjusting for the various study variables. Importantly, a history of psychotic disorder was a major determinant of hospitalization for psychotic disorders (aOR = 126.56, 95% CI [121.85-131.46]).
Our results suggest that individuals initially hospitalized for COVID-19 (vs. another reason) present a lower risk of hospitalization for first episodes of psychotic symptoms/disorders or for psychotic relapse in the 12 months following discharge. This finding contradicts invalidates the hypothesis that there is a higher risk of psychotic disorders after a severe COVID-19.
A hydrodynamic interaction between gas bubbles departed in liquid and gas supply system
Authors: Dzienis Pawel , Golak Karol , Konopka Mateusz , Mosdorf Romuald , Bazienė Kristina , Gargasas Justinas 
Published: March 2023

Abstract
In the present paper the hydrodynamic interactions between bubble - bubble and bubble-gas supply system to the needle were experimentally and numerically investigated. In an experiment in one of the needles, the air volume flow rate was constant and in the neighbouring needle, it was changed. Despite setting the constant air flow rate supply to the needle, the frequency of bubble departures fluctuated, with a change in the flow rate in the neighbouring needle. In order to identify the occurrence of hydrodynamic interaction the methods of nonlinear data analysis - wavelet analysis and FFT were used. It can be concluded that the synchronised or alternative bubble departures from twin neighbouring needles, (occurring due to hydrodynamic interaction) are possible by modifying the bubble waiting time. Moreover modification of hydrodynamic interaction between bubble – bubble actually bubble – gas supply system can be used to control the bubble departure process.
Apremilast reverses the profibrotic phenotype of dermal fibroblasts derived from patients with systemic sclerosis and prevents the progression of bleomycin-induced dermal fibrosis in mice
Authors: Higuchi Tomoaki , Takagi Kae , Tochimoto Akiko , Ichimura Yuki , Hirose Hikaru , Sawada Tatsuo , Shibata Nobuyuki , Harigai Masayoshi , Kawaguchi Yasushi 
Published: March 2023

Abstract
Phosphodiesterase (PDE) 4 inhibitors have been reported to suppress the progression of dermal fibrosis in patients with systemic sclerosis (SSc); however, the precise mechanisms remain to be elucidated. Therefore, we conducted experiments focusing on the antifibrotic and anti-inflammatory effects of apremilast using dermal fibroblasts derived from patients with SSc and an SSc mouse model. Dermal fibroblasts derived from healthy controls and patients with SSc were incubated with apremilast in the presence or absence of 10 ng/ml transforming growth factor (TGF)-β1 for the measurement of intracellular cAMP levels and evaluation of mRNA and protein expression. A bleomycin-induced skin fibrosis mouse model was used to evaluate the inhibitory effects of apremilast on the progression of dermal fibrosis. Intracellular cAMP levels were significantly reduced in dermal fibroblasts derived from patients with SSc compared with those derived from healthy controls. Apremilast reduced the mRNA expression of COL1A1, COL1A2, CTGF, and ACTA2 and the protein expression of type I collagen and Cellular Communication Network Factor 2 (CCN2) in dermal fibroblasts. Additionally, apremilast inhibited the progression of dermal fibrosis in mice, partly by acting on macrophages. These results suggest that apremilast may be a potential candidate for treating dermal fibrosis in SSc.
Inflammatory bowel disease has a negative causal effect on chronic obstructive pulmonary disease: A two-sample bidirectional mendelian randomization study
Authors: Tian Li , Yang Xiaobin , Zheng Yansen , Peng Chaosheng 
Published: March 2023

Abstract
Background
Inflammatory bowel disease (IBD) and its main subtypes, including Crohn's disease (CD) and ulcerative colitis (UC), have been suggested to be linked with chronic obstructive pulmonary disease (COPD) progression, but the potential bidirectional causal association between them remains unclear.
Methods
We drew on summary statistics from the large-scale genome-wide association studies and adopted the inverse variance weighting (IVW)method as the main mendelian randomization analysis method to estimate the causal effect.
Results
There was no evidence support that COPD was associated with increased risk of IBD and two main subtypes (UC and CD) (IBD: odds ratio (OR) [95% confidence interval (CI)] = 0.99[0.90–1.09], P = 8.63×10− 1; UC: OR [95% CI] = 0.96[0.86–1.07], P = 4.70×10− 1; CD: OR [95% CI] = 1.10[0.89–1.35], P = 3.81×10− 1;). The IVW method provided evidence for a negative causal effect of IBD and two main subtypes (UC and CD) on COPD (IBD: OR [95% CI] = 0.93[0.89–0.97], P = 4.86×10− 4; UC: OR [95% CI] = 0.94[0.90–0.98], P = 6.57×10− 3; CD: OR [95% CI] = 0.96[0.94–0.99], P = 4.92×10− 3). The results of the sensitivity analyses were robust and no evidence of heterogeneity and horizontal pleiotropy was observed.
Conclusions
The present study showed that COPD does not affect IBD, but IBD and its main subtypes (UC and CD) have a negative causal effect on COPD. And understanding the confounding factors that affect clinical research will help the clinical treatment and management of the two diseases.
Changes in Cerebral Connectivity and Brain Tissue Pulsations with the Antidepressant Response to an Equimolar Mixture of Oxygen and Nitrous Oxide: an MRI and Ultrasound study
Authors: Desmidt Thomas , Dujardin Paul-Armand , Andersson Frédéric , Brizard Bruno , Remeniéras Jean-Pierre , Gissot Valérie , Arlicot Nicolas , Barantin Laurent , Espitalier Fabien , Belzung Catherine , Tanti Arnaud , robert gabriel , Bulteau Samuel , Gallet Quentin , Kazour François , Cognet Sandrine , Camus Vincent , El-Hage Wissam , Poupin Pierre , Karim Helmet 
Published: March 2023

Abstract
Nitrous oxide (N2O) has recently emerged as a potential fast-acting antidepressant but the cerebral mechanisms involved in this effect remain speculative. We hypothesized that the antidepressant response to an Equimolar Mixture of Oxygen and Nitrous Oxide (EMONO) would be associated with changes in cerebral connectivity and brain tissue pulsations (BTP).
Thirty participants (20 depressed and 10 healthy controls - HC) were exposed to a one-hour single session of EMONO and followed for one week. Cerebral connectivity of the Anterior Cingulate Cortex (ACC, seed based resting state blood oxygen level dependent) and BTP (as assessed with ultrasound Tissue Pulsatility Imaging) were compared before and after exposure (as well as during exposure for BTP) among HC, non-responders and responders. Response was defined as a reduction of at least 50% in the MADRS score one week after exposure.
Nine (45%) depressed participants were considered responders and eleven (55%) non-responders. In responders, we observed a significant reduction in the connectivity of the subgenual ACC with the precuneus. Connectivity of the supracallosal ACC with the mid-cingulate also significantly decreased after exposure in HC and in non-responders. BTP significantly increased in the 3 groups between baseline and gas exposure, but the increase in BTP within the first ten minutes was only significant in responders.
We found that a single session of EMONO can rapidly modify the functional connectivity in the ACC, especially in the subgenual region, which appears to contribute to the antidepressant response. In addition, larger increases in BTP, associated with a significant rise in cerebral blood flow, appear to promote the antidepressant response, possibly by facilitating optimal drug delivery to the brain. Our study identified potential cerebral mechanisms related to the antidepressant response of N2O, as well as potential markers for treatment response with this fast-acting antidepressant.
Metabolomic profiles in serum predict global functional neurological outcome at 3 and 12 months and death at 3 months following severe traumatic brain injury
Authors: Banoei Mohammad Mehdi , Lee Chel Hee , Hutchison James , Panenka William , Wellington Cheryl , Wishart David S , Winston Brent W. 
Published: March 2023

Abstract
Background
Prognostication is very important to clinicians and families during the early management of severe traumatic brain injury (sTBI), however, there are no gold standard biomarkers to determine prognosis in sTBI. As has been demonstrated in several diseases, early measurement of serum metabolomic profiles can be used as sensitive and specific biomarkers to predict outcome.
Methods
We prospectively enrolled adults with sTBI (Glasgow coma scale, GCS ≤ 8) in a multicenter Canadian TBI (CanTBI) study. Serum samples were drawn on the 1st and 4th day following injury for metabolomic profiling. The Glasgow outcome scale extended (GOSE) was collected at 3- and 12-months post-injury. Targeted direct infusion liquid chromatography tandem mass spectrometry (DI/LC-MS/MS) and untargeted proton nuclear magnetic resonance spectroscopy (1H-NMR) were used to profile serum metabolites. Multivariate analysis was used to determine the association between serum metabolomics and GOSE, dichotomized into favorable (GOSE 5–8) and unfavorable (GOSE 1–4), outcomes.
Results
Serum metabolic profiles on days 1 and 4 post-injury were highly predictive (Q2 > 0.4–0.5) and highly accurate (AUC > 0.99) to predict GOSE outcome at 3- and 12-months post-injury and mortality at 3 months. The metabolic profiles on day 4 were more predictive (Q2 > 0.55) than those measured on day 1 post-injury. Unfavorable outcomes were associated with considerable metabolite changes from day 1 to day 4 compared to favorable outcomes. Increased lysophosphatidylcholines, acylcarnitines, energy-related metabolites (glucose, lactate), aromatic amino acids and glutamate were associated with poor outcome and mortality.
Discussion
Metabolomic profiles were strongly associated with prognosis of GOSE outcome at 3 and 12 months and mortality following sTBI in adults. The current findings strongly support the use of serum metabolomics, which are shown to be better than clinical data, in determining prognosis in adults with sTBI in the early days post-injury. Our findings, however, require validation in a larger cohort of adults with sTBI before using in clinical practice.
Size-dependent active site and its catalytic mechanism for CO2 hydrogenation reactivity and selectivity over Re/TiO2
Authors: Yang Bin , Wang Yifu , Gao Biao , Zhang lingxia , Guo Limin 
Published: March 2023

Abstract
The relationship of structure sensitive between metal size and CO2 hydrogenation performance are still unclear. Herein, using a unique set of well-defined TiO2-support rhenium (Re) catalysts and systematical characterizations, we clearly demonstrate the size-dependent active site and reaction mechanism is closely related to size effect. A wave-like size dependent activity of CO2 conversion is also identified. In the size range from single atom to 1.0 nm, reverse water gas shift (RWGS) reaction controls CO2 hydrogenation and its turn over frequency decrease with the size increasing. Whereas, over 1.0 nm cluster, CO2 methanation is the main reaction and exhibits a volcano-like size dependent performance. Mechanistic studies reveal the perimeter sites in single atom catalysts dictate RWGS reaction via formate pathways. In contrast, the active site in Re cluster is edge site, where CO2 reduce to CO via redox pathway and subsequently hydrogenate to methane over edge site. This discovery may deepen the mechanistic understanding of structure sensitive.
PPARα and PPARγ are expressed in midbrain dopamine neurons and modulate dopamine- and cannabinoid-mediated behavior in mice
Authors: Xi Zheng-Xiong , Hempel Briana , Crissman Madeline , Pari Sruti , Klein Benjamin , Bi Guo-Hua , Alton Hannah 
Published: March 2023

Abstract
Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear receptors that regulate gene expression. Δ9-tetrahydrocannabinol (Δ9-THC) is a PPARg agonist and some endocannabinoids are natural activators of PPARa and PPARg. Therefore, both the receptors are putative cannabinoid receptors. However, little is known regarding their cellular distributions in the brain and functional roles in cannabinoid action. Here we first used RNAscope in situ hybridization and immunohistochemistry assays to examine the cellular distributions of PPARα and PPARγ expression in the mouse brain. We found that PPARα and PPARγ are highly expressed in ~70% midbrain dopamine (DA) neurons and in ~50% GABAergic and ~50% glutamatergic neurons in the amygdala. However, no PPARα/γ signal was detected in GABAergic neurons in the nucleus accumbens. We then used a series of behavioral assays to determine the functional roles of PPARα/γ in the CNS effects of Δ9-THC. We found that optogenetic stimulation of midbrain DA neurons was rewarding as assessed by optical intracranial self-stimulation (oICSS) in DAT-cre mice. Δ9-THC and a PPARγ (but not PPARα) agonist dose-dependently inhibited oICSS, suggesting that dopaminergic PPARγ modulates DA-dependent behavior. Surprisingly, pretreatment with PPARα or PPARγ antagonists dose-dependently attenuated the Δ9-THC-induced reduction in oICSS and anxiogenic effects. In addition, a PPARγ agonist increased, while PPARa or PPARγ antagonists decreased open-field locomotion. Pretreatment with PPARa or PPARγ antagonists potentiated Δ9-THC-induced hypoactivity and catalepsy but failed to alter Δ9-THC-induced analgesia, hypothermia and immobility. These findings provide the first anatomical and functional evidence supporting an important role of PPARa/g in DA-dependent behavior and cannabinoid action.
Neurokinin-1 receptor antagonist aprepitant regulates autophagy and apoptosis through ROS/JNK pathway in intrahepatic cholangiocarcinoma
Authors: Yang Yang , Cao Xueyan , Wang Yuting , Wu Xinyu , Zhou Ping , Miao Lin , Deng Xueting 
Published: March 2023

Abstract
Intrahepatic cholangiocarcinoma (iCCA) has a poor prognosis and limited treatment options. Aprepitant, a selective NK-1R antagonist, is capable of inhibiting the growth of various tumors in vitro and in vivo. To investigate the cytotoxic effects of aprepitant on the intrahepatic cholangiocarcinoma, we confirmed the expression of SP/NK-1R in clinical samples of iCCA by immunohistochemistry. MTT test showed that aprepitant could suppress cell viability of RBE and HCCC-9810. Meanwhile, aprepitant induced mitochondria-dependent apoptosis through ROS/JNK pathway in a dose-dependent manner. Additionally, anti-apoptotic drug z-VAD-fmk pretreatment could partly improve the decrease of cell viability induced by aprepitant, while ROS scavenger, NAC could cancel the cytotoxic effects of aprepitant in vitro. Therefore, these results indicated that autophagy is another downstream process of aprepitant-induced ROS accumulation. Changes in the expression of autophagy-related proteins and number of autophagosomes were detected by western blotting and electron microscopy, respectively. Furthermore, we observed the dynamic changes of autophagosome in RBE and HCCC-9810 treated with aprepitant by using mRFP-eGFP-LC3 adenovirus transfection. Moreover, aprepitant significantly inhibited the growth of iCCA xenografts. These findings reveal NK-1R as an potential therapeutic target against iCCA and highlight the anti-cancer ability of NK-1R antagonist aprepitant in iCCA.