bluuebunny/crossref_metadata_2025 huggingface dataset:
SIRT2 regulates oxidative stress response in liver fibrosis mice through the NLRP3 inflammasome pathway
Authors: Guo Jingru , Nie Junshu , Li Dongni , Zhang Shoufeng , Ma Li , Lu Jingjing , Ji Hong , Li Shize , xu bin
Published: October 2023

Liver fibrosis is a crucial step in the progression of various chronic liver diseases to cirrhosis, which can affect the prognosis of chronic liver diseases. The NAD+ dependent deacetylase sirtuins family member SIRT2 can regulate the inflammatory corpuscular pathway in pathological processes, but its related mechanism is not yet clear. This study established liver fibrosis models in wild-type and SIRT2 knockout mice, and evaluated their effects on liver homeostasis using immunoblotting, immunofluorescence, and histopathological staining methods. The results indicate that the deletion of the SIRT2 gene enhances NLRP3 acetylation, activates the NLRP3 inflammasome pathway, and accelerates oxidative stress. These findings suggest that SIRT2 may be a potential target for regulating liver fibrosis and restoring health.
In vivo pharmacodynamics of lactoferrin-coupled lipid nanocarriers for lung carcinoma: intravenous versus powder for inhalation
Authors: Gaber Dina M. , Nafee Noha , Elzoghby Ahmed O. , Helmy Maged W. , Abdallah Osama Y.
Published: October 2023

Lung carcinoma characterized by high mortality rate and poor prognosis; the efficacy of drug delivery should improve drug exposure at the targeted site. this study aims at evaluating lactoferrin role as targeting ligand besides the administration route impact on tissue deposition and organ distribution.
Lactoferrin (Lf)-coupled/uncoupled solid lipid nanoparticles (SLNs) were loaded with myricetin-phospholipid-complex (MYR-PH-CPX). Following physicochemical characterization, in-vitro antitumor activity and cellular uptake were investigated in A549-cell line. In-vivo deposition and biodistribution of fluorescently-labeled inhalable microparticles (with/without-Lf) were compared to intravenously administered fluorescently-labeled-SLNs (with/without-Lf) in mice.
Lf-coupled-SLNs (98.59±0.47 nm), showed high entrapment efficiency (95.3±0.5%) and prolonged drug release. The in-vitro antitumor study showed reduction in IC50 for Lf-coupled-SLNs by ~2-and 3.5-fold relative to uncoupled-SLNs and MYR-PH-CPX, respectively confirming Lf role in enhancing antitumor activity by boosting cells internalization in shorter time. Furthermore, 3D-time laps confocal imaging showed that labeled-Lf-coupled-SLNs had a higher rate and extent of uptake in A549-cells compared to uncoupled-SLNs and free dye. In-vivo biodistribution proved that Lf enhanced pulmonary deposition of inhaled SLNs (~1.5 fold) and limited migration to the other organs within 6h relative to intravenous. Conclusively, local administration is superior due to less drug clearance resulting in lower toxicity accompanied by systemic application.
Study on industrial carbon emissions in China based on GDIM decomposition method and two decoupling effects
Authors: Shen Chaofeng , Zhang Jun , Pang Jianfei , Xu Haifeng
Published: October 2023

The driving factors of China's industrial carbon emissions are decomposed by GDIM, so as to explore the reasons for the change of China's industrial carbon emissions. The decoupling effect of China's industrial carbon emissions and economic growth is studied by speed decoupling and quantity decoupling. The speed decoupling is measured by Tapio decoupling elasticity and emission reduction effort function, and the quantity decoupling is measured by environmental Kuznets curve (EKC). The results show that the positive driving factors are output size effect > industrial energy consumption effect > population size effect, and the negative driving factors are investment carbon emission effect > output carbon intensity effect > per capita output effect > economic efficiency effect > energy intensity effect. The elasticity of emission reduction is basically greater than that of energy conservation, indicating that there is still much room for efforts in emission reduction. The overall decoupling effect of carbon emissions is undecoupling - strong decoupling - undecoupling. The shape of quadratic EKC curve is "U" type, and the shape of cubic EKC curve is "N" type, which satisfies the EKC curve hypothesis.
Multi-Category Prediction of Students’ Academic Performance Using Machine Learning: For Students Joining Higher Educational Institution in Ethiopia
Authors: Ahmed Abdulkadir , Tolera Daniel , shebera wondimagegn
Published: October 2023

Following the deployment of the Learning Management System (LMS) platform in higher educational institutions in Ethiopia, a massive amount of potentially helpful but as-yet untapped educational data has been generated. Despite the fact that the data is powerful enough to contribute to reducing student dropout rates through the application of modern educational data mining techniques such as machine learning, it has not been successfully employed to tackle student academic performance problems in higher education institutions(HEIs). As a result, a machine learning model was proposed based on data from three semesters of undergraduate students at Bule Hora University. To predict students' academic achievement, five machine learning methods (SVM, Random Forest, KNN, Gradient Boosting, and Decision Tree) were used. The Decision Tree model outperformed other models with a promising result of 97.3% on test accuracy and was selected as a proposed model. Moreover, our findings suggest that academic factors (entrance result, study time, attendance, and Internet access) and socio-demographic factors (age, gender, father job, mother job, family size, and address) had a greater impact on students' academic success. However, the academic performance of students was less affected by additional features like extra classes, another job, and guidance and counselling. Moreover, we are working on improving the accuracy of the proposed model. In this study, the student entrance result is the only variable used from the pre-university data. However, a CGPA result is not sufficient to qualify a student. Therefore, in the future, the exit exam results of the students will be incorporated.
Investment funds are responsible for substantial environmental and social impacts with trade-offs
Authors: Popescu Ioana , Schaubroeck Thomas , Gibon Thomas , Petucco Claudio , Benetto Enrico
Published: October 2023

As finance takes on a pivotal role in sustainability transitions, regulations that mandate impact reporting at financial product level are emerging worldwide. Without standardized and reliable indicators, sustainable investing risks being watered down by greenwashing. We show that life-cycle-based, ready-to-use impact indicators can be adapted for sustainability assessment of financial products. We designate 13 environmental and 13 social impact indicators aligned primarily with the EU Sustainable Finance Disclosure Regulation, one of the first pieces of regulation mandating sustainability reporting for financial products. Two major advancements of our framework are the coverage of social impacts and the direct policy relevance. As practical application, we estimate the impacts of a sample of 230 self-labelled sustainable investment funds for all indicators. We show that these investment funds are exposed to significant environmental and social impacts via their investee companies. Total estimated impacts vary between 2.1 and 28.4 times the impacts associated with the consumption of a one million EU citizens, depending on the indicator. Trade-offs could be signalled between and within environmental and social indicators. Finally, most impacts can be traced to a small number of publicly listed companies, which investors could engage with, in order to drive change.
The sex-specific difference in age-related aortic regional morphological changes
Authors: meng zixuan , Cheng Lele , Liu wenjun , Yu yue , Liu hui , Yao guo , Yang jian , Wu Yue , Jian Zhijie
Published: October 2023

Aim
To investigate the sex differences in age-related changes in aortic morphology.
Method
A cross-sectional study screened patients with chest and abdomen contrast CT images from July 2021 to April 2022. The aortic morphological values were compared by sex in different ages to analyze their correlation with age. To validate the coherence of sex differences in age-related arterial changes in morphology, data from a previously published article was extracted to examine the correlation between age and branchial ankle pulse wave velocity (baPWV) in different sexes.
Results
208 participants (59.6% males, mean age 60.13±16.33 years old) were enrolled. The BSA-adjusted diameters are positively correlated with age in both sexes with females experiencing a more rapid increase throughout lifespan than males. The BSA-adjusted aortic diameters at different segments of females were smaller than males earlier on, however, this trend was reversed with age. The tortuosity of the aorta and descending thoracic aorta increased significantly with age, especially in females. Furthermore, baPWV showed the same variation tendency that baPWV increased with age and even more rapidly in females.
Conclusion
Throughout life course, the rate of aortic morphological aging differs between the sexes, with more significant changes in aortic tortuosity in females, especially in older age groups.
The use of healthcare systems data for RCTs
Authors: Toader Alice-Maria , Gamble Carrol , Dodd Susanna , Williamson Paula
Published: October 2023

Background:
Healthcare systems data (HSD) has the potential to optimize efficiency of randomized controlled trials (RCTs), by decreasing trial specific data demands. Therefore, use of HSD in trials is expected to increase. In 2019, it was estimated that 47% of NIHR funded trials were planning to use HSD. We aim to understand the extent and nature of its current use and its evolution over time.
Methods:
We identified a cohort of RCTs within the NIHR Journals Library that commenced after 2019 and were described as being in progress at 6th June 2022. Details on the source and use of HSD were extracted from eligible RCTs. The use of HSD was categorised according to whether it was used as the sole data source for outcomes and whether the outcomes were primary or secondary. HSD is often insufficient for patient reported outcomes (PROs). We aimed to determine methods used by trialists for collecting PRO data alongside HSD.
Results:
Of the 84 eligible studies, 52 (62%) used HSD, and 79 (94%) collected PROs. The number of RCTs using HSD for at least one outcome was 28 (54%) with 24 of these using HSD as the sole data source for at least one outcome.
The number of studies using HSD for primary and secondary outcomes were 10 (20%) and 21 (40%) respectively. The sources of HSD were National Health Service (NHS) Digital 37 (79%), patient registries 7 (29%), primary care 5 (21%), The Office for National Statistics (ONS) 3 (13%), and other 2 (8%).
PROs were collected for 92% of the trials using HSD. Methods for collection of PROs included in-person 26 (54%), online 22 (46%), postal 18 (38%), phone 14 (29%), app 2 (4%).
Conclusions:
HSD is being used in around two thirds of the studies but cannot yet be used to support PRO data collection within the cohort we examined. Comparison with an earlier cohort demonstrates an increase in the number of RCTs planning to use HSD.
Mapping protein binding sites by photoreactive fragment pharmacophores
Authors: Keseru Gyorgy , Ábrányi-Balogh Peter , Bajusz Dávid , Orgovan Zoltan , Keeley Aaron , Petri Laszlo , Peczka Nikolett , Szalay Tibor , Palfy Gyula , Gadanecz Marton , Perczel Andras , Grant Emma , Bush Jacob , Takács Tamás , Buday Laszlo , Ranđelović Ivan , Baranyi Marcel , Marton Andras , Karancsi Tamas , Schlosser Gitta , Ashraf Qirat , de Araujo Elvin , Imre Tímea , Tovari Jozsef
Published: October 2023

Fragment screening is a popular strategy of generating viable chemical starting points especially for challenging targets. Although fragments provide a better coverage of chemical space and they have typically higher chance of binding, their weak affinity necessitates highly sensitive and often resource-intensive biophysical assays. Here, we introduce a new screening concept that combines evolutionary optimized fragment pharmacophores with the use of a photoaffinity handle that enables high hit rates by LC-MS-based detection. The sensitivity of our screening protocol was further improved by a target-conjugated photocatalyst. We have assembled, synthesized, and screened 100 diazirine-tagged fragments against three protein targets of different tractability. Our targets included a conventional enzyme, the first bromodomain of BRD4, a protein-protein interaction represented by the oncogenic KRasG12D protein, and the yet unliganded N-terminal domain of the STAT5B transcription factor. We have discovered several new fragment hits against all three targets and identified their binding sites via enzymatic digestion, structural studies and modelling. Our results revealed that this protocol outperforms screening traditional photoaffinity fragments in better exploration of the available binding sites and higher hit rates observed for even difficult targets.
TNFSF15 Inhibits Progression of Diabetic Retinopathy by Blocking Pyroptosis via Interacting with GSDME
Authors: Li Hua , Zhao Hongkun , Dai Yating , Li Yunqin
Published: October 2023

Diabetic retinopathy is a common microvascular complication of diabetes and a leading cause of blindness. Pyroptosis has emerged as a mechanism of cell death involved in DR pathology. This study explored the role of GSDME-mediated pyroptosis and its regulation by TNFSF15 in DR. We found GSDME was upregulated in the progression of DR. High glucose promoted GSDME-induced pyroptosis in retinal endothelial cells and retinal pigment epithelial cells, attributable to activation of caspase-3 which cleaves GSDME to generate the pyroptosis-executing N-terminal fragment. TNFSF15 was identified as a binding partner and inhibitor of GSDME-mediated pyroptosis. TNFSF15 expression was increased by high glucose but suppressed by the caspase-3 activator Raptinal. Moreover, TNFSF15 inhibited high glucose- and Raptinal-induced pyroptosis by interacting with GSDME in retinal cells. Collectively, our results demonstrate TNFSF15 inhibits DR progression by blocking GSDME-dependent pyroptosis of retinal cells, suggesting the TNFSF15-GSDME interaction as a promising therapeutic target for DR.
Adipocyte Enhancer Binding Protein 1 (AEBP1) Inhibition as a Potential Anti-Fibrotic Therapy in Heart Failure.
Authors: Drakos Stavros , Shankar Thirupura Sundari , Visker Joseph , Amrute Junedh , Polishchuk Georgiy , Lunde Ty , Ling Jing , Ferrin Peter , Hamouche Rana , Feigle Dominik , Calder Dallen , Sachse Frank , Kyriakopoulos Christos , Maneta Eleni , Tseliou Eleni , Navankasattusas Sutip , Selzman Craig , Seidel Thomas , Lavine Kory
Published: October 2023

Persistent activation of fibroblasts to myofibroblasts leads to increased myocardial fibrosis which is often detrimental to cardiac function and leads to heart failure (HF). Adipocyte enhancer binding protein (AEBP1) plays a crucial role in fibroblast activation following injury in the kidney, liver, and lungs. AEBP1 inhibition resulted in fibrosis attenuation in these organs. AEBP1 has been reported to be upregulated in the HF myocardium, however, its role in cardiac fibrosis progression is not well understood. In this study, we show that AEBP1 is crucial for cardiac fibroblast activation and AEBP1 inhibition prevents cardiac fibroblast differentiation in vitro. AEBP1 knock-down (KD) in mouse models of acute cardiac fibrosis improved cardiac structure and function. Tissue culture studies of non-failing donor myocardium resulted in increased cellular hypertrophy and tissue remodeling following AEBP1 overexpression. Contrarily, a significant improvement in cardiac structure evident from reduced cardiomyocyte hypertrophy and reduced fibrosis was observed in chronic HF myocardium following AEBP1 KD. Overall, we show that AEBP1 plays a critical role in fibrogenesis, and its inhibition has the potential to attenuate fibrosis in acute and chronic HF.
Evaluating Oviposition Deterrent, Larvicidal and Repellent Effects of Different Plant Extracts and Their Combinations against Aedes aegypti
Authors: Majeed Shahid , Ishaq Amna , Javaid Rameen , Sharif Rao Muhammad Sajjad , Iftikhar Sana , Akbar Rabia , Rahman Abdur
Published: October 2023

Mosquitoes are significantly important in public health as they transmit many vector-borne diseases like dengue fever (DF), malaria, and filariasis to millions of people worldwide. Although there is no effective vaccination for the prevention of dengue, avoiding mosquito bites is one method to control mosquito populations. Due to the extensive uses of synthetic repellent,’ mosquitoes established resistance against them. The plant-based extracts are used as an alternative to targeted insecticides. Therefore, current study aimed to examine the oviposition-deterrent, larvicidal and repellent efficacy of plant-based extracts Clove (Syzygium aromaticum), Cinnamon (Cinnamomum verum), Lemon (Citrus limon), Orange (Citrus sinensis), Onion (Allium cepa), Garlic (Allium sativum), Lemon grass (Cymbopogon citratus), and Aloe vera (Aloe barbadensis Miller) against Aedes aegypti under laboratory conditions. The maximum repellency was observed by clove, and lemon peel plant extract compared to all other botanical plants. However, lemon, clove, garlic, onion, and garlic with lemongrass are promising for oviposition control. While, clove, lemon peel, orange and lemon peels, and lemongrass combination for larvicidal control. In terms of repellents, the most suspected repellent plants showed by the combinations of (Olive oil, lemon peel, citrus peel, lemongrass, Aloe vera), (Olive oil, lemon peel, citrus peel, lemongrass), (Olive oil, lemon peels, citrus peels, Aloe vera), such as 19.85, 19.85,19.84 repellency value along with 100% protection time up to 1 h. The establishment of plant-based products against Aedes aegypti, complemented with insecticidal activity, could lead to an innovative approach to managing mosquito populations and disease vectors.
Modelling impacts to water quality in salmonid-bearing waterways following the introduction of Emerald Ash Borer in the Pacific Northwest, USA.
Authors: Maze Dominic , Bond Julia , Mattsson Monte
Published: October 2023

Oregon ash (Fraxinus latifolia Benth.) wetlands and riparian forests are an important economic, cultural, and ecological resource in the Pacific Northwest, USA, and are threatened by the invasive insect, emerald ash borer (Agrilus planipennis Fairmmaire) (EAB). Following the discovery of EAB in Forest Grove, Oregon in June of 2022, concern has focused on EAB-induced ash mortality that has the potential to alter vegetation communities and modify wetland hydrology by elevating the water table. Of primary concern is an increase in solar loading of waterways and wetlands that are already degraded beyond meeting their beneficial uses for Endangered Species Act-listed salmonids and other cold-water species following canopy dieback of Oregon ash. Our study, begun before the first detection of EAB on the West Coast, models potential impacts of EAB-mediated Oregon ash canopy loss to temperature-related water quality on two waterways in the vicinity of Portland, Oregon. Our results indicate a significant increase in solar loading with likely negative impacts to aquatic Endangered Species Act-listed salmonids, other aquatic wildlife, and associated habitat. We forecast greater impacts to these resources outside our study scope and include management considerations and recommendations for entities with water quality-related regulatory obligations.
The Identification and Characterization of a New Species, Neopestalotiopsis Strain CP1, a Pathogen Causing Leaf Blight on Curcuma phaeocaulis in Guangxi, China
Authors: Li Shanshan , Long Meimei , Guo Lulu , Luo Yaqi , Sun Xianchao , Qian Kun , He Lin , Ma Guanhua
Published: October 2023

Zedoary turmeric (Curcuma phaeocaulis), a cornerstone of traditional Chinese medicines in Guangxi Province, holds immense significance. Regrettably, the emergence of a novel leaf wilt in October 2017 has cast a pall over its production, leading to detrimental impacts on both yield and quality. By meticulous single-conidial isolation, this new pathogen was successfully extracted from ten diseased leaves. Subsequent confirmation of pathogenicity was achieved via the meticulous execution of Koch's postulates. In pursuit of accurate identification, morphological data were harmonized with a concatenated sequence analysis of the rDNA internal transcribed spacer (ITS), β-tubulin (TUB), and translation elongation factor 1 (TEF) regions. This rigorous approach unveiled the pathogen as an entirely novelNeopestalotiopsis species, warranting the nomenclature Neopestalotiopsis strain CP1. The optimum pH of conidial germination was between 5.0 and 5.5. Among the 665 different metabolites of the Neopestalotiopsis strain CP1, 60 carbon sources, 35 nitrogen sources, 4 phosphate sources, 8 sulfur sources, and 1 biometabolic pathway, effectively promoted the growth and development of conidia. The optimum pH of conidial germination was between 5.0 and 5.5. Among the 665 different metabolites of the Neopestalotiopsis strain CP1, 60 carbon sources, 35 nitrogen sources, 4 phosphate sources, 8 sulfur sources, and 1 biometabolic pathway, effectively promoted the growth and development of conidia. The ramifications of this pathogen's definitive identification and ongoing surveillance cannot be overstated, signifying a pivotal alert to zedoary turmeric cultivators in confronting this newfound peril.
Estimating the prevalence of symptomatic and asymptomatic dengue fever among adults in the Central Health Region - Burkina Faso: a protocol for field study
Authors: Ouédraogo Jean Claude Romaric Pingdwindé , Ilboudo Sylvain , Compaoré Tegwinde Rebeca , Tougma Alix , Bado Prosper , Nitiéma Mathieu , Zeba Mohamadi , Ouédraogo Wendlasida Thomas , Ouédraogo Salfo , Lougué Siaka , Tarnagda Grissoum , Kini Bondo Félix , Ouédraogo Sylvin , Savadogo Léon Gueswendé Blaise
Published: October 2023

Background: Dengue fever is misdiagnosed as malaria in Africa and underreported. In Burkina Faso, specific data on dengue fever are lacking on adults. This study aims to estimate the prevalence of symptomatic and asymptomatic dengue fever and to assess their determinants among adults over two years in the Central Health Region of Burkina Faso.
Methods: An analytical cross-sectional study will be conducted with repetitive quantitative data collection in 2022 and 2023. It will include adults suspected of dengue from health facilities of the 5 districts - Central Health Region, and adult contacts of dengue probable cases from households. Participants will undergo rapid diagnosis tests for dengue fever and malaria, with dengue-positive cases to be confirmed by Real-Time Polymerase Chain Reaction. The main objectives are: i) To compare the prevalence of symptomatic dengue fever among adults suspected of dengue between 2022 and 2023. ii) To compare the prevalence of symptomatic and asymptomatic dengue fever among contact adults between 2022 and 2023. iii) To evaluate the sociodemographic and bio-clinical determinants of symptomatic dengue fever among suspected cases. iv) To evaluate the sociodemographic, bio-clinical, and environmental determinants of asymptomatic dengue fever among the contacts.
Conclusions: This study will generate comprehensive data on symptomatic and asymptomatic dengue fever among adults in Burkina Faso. Such data will drive strategies in responding to dengue epidemics in the country.
The impact of elevated sulfur and nitrogen levels on cadmium tolerance in Euglena species
Authors: Saville Barry J. , Kennedy Victoria , Kaszecki Emma , Donaldson Michael E.
Published: October 2023

Heavy metal (HM) pollution threatens human and ecosystem health. Current methods for remediating water contaminated with HMs are expensive and have limited effect. Therefore, bioremediation is being investigated as an environmentally and economically viable alternative. Freshwater protists Euglena gracilis and Euglena mutabilis were investigated for their tolerance to cadmium (Cd). A greater increase in cell numbers under Cd stress was noted for E. mutabilis but only E. gracilis showed an increase in Cd tolerance following pre-treatment with elevated concentrations of S or N. To gain insight regarding the nature of the increased tolerance RNA-sequencing was carried out on E. gracilis. This revealed transcript level changes among pretreated cells, and additional differences among cells exposed to CdCl2. Gene ontology (GO) enrichment analysis reflected changes in S and N metabolism, transmembrane transport, stress response, and physiological processes related to metal binding. Identifying these changes enhances our understanding of how these organisms adapt to HM polluted environments and allows us to target development of future pre-treatments to enhance the use of E. gracilis in bioremediation relating to heavy metals.
The study of the relationship between moderate to severe Sleep Obstructive Apnea and cognitive impairment, anxiety, and depression
Authors: HONG Yanan , PEI Chong , HAO Lingli , XU Kang , LIU Feifei , DING Zhen
Published: October 2023

Objective
The present study endeavored to investigate the interconnection between obstructive sleep apnoea (OSA) and cognitive function, alongside the manifestations of depression and anxiety. Simultaneously, an analysis was conducted to discern the factors exerting influence upon cognitive function.
Methods
A cohort of 102 patients, who had undergone polysomnography (PSG) at Binhu Hospital, Anhui Medical University, between January 2022 and June 2023, was encompassed in the study. Employing the PSG findings, these individuals were classified into two distinct categories: the grouping consisted of those with either negligible or mild OSA, and the other comprised individuals with moderate to severe OSA. Utilizing the Montreal Cognitive Assessment (MoCA-Beijing), Stroop Color and Word Test (SCWT), Digit Span Test (DST), Self-rating Depression Scale (SDS), and Self-rating Anxiety Scale (SAS), scores were recorded and analysed for each of the respective assessments. Additionally, discrepancies and associations between these groups were also scrutinised.
Results
The group exhibiting moderate to severe OSA demonstrated significantly elevated measurements in parameters such as neck circumference, BMI, completion times for SCWT-A, B, C, Sleep Inefficiency Index (SIE), SAS, and SDS, in comparison to the no or mild OSA group. Furthermore, the moderate-severe OSA group manifested notably diminished MoCA scores in areas of visual-spatial and executive function, memory, language, abstraction, delayed recall, orientation, total MoCA score, lowest oxygen saturation (LSaO2), average oxygen saturation, DST-b, and DST-f, as contrasted with the no-mild OSA group. These inter-group disparities exhibited statistical significance (P < 0.05). The MoCA total score portrayed inverse correlations with age, Apnea-Hypopnea Index (AHI), BMI, SIE, SAS, SDS, CT90%, AHT90%, and Hypoxic Apnea Duration (HAD) (ranging from − 0.380 to -0.481, P < 0.05). Conversely, it displayed positive correlations with DST-f, DST-b, LSaO2, and average oxygen saturation (ranging from 0.414 to 0.744, P < 0.05). Neck circumference, AHI, and SAS were autonomously linked to MoCA scores (OR = 1.401, 1.028, 1.070, P < 0.05), whilst AHI exhibited an independent correlation with SDS and SAS scores (OR = 1.001, P = 0.003).
Conclusion
Patients grappling with moderate to severe OSA frequently reveal cognitive impairment and concomitant emotional predicaments encompassing depression and anxiety. These manifestations share an intimate association with AHI, LSaO2, and average oxygen saturation. Notably, anxiety, when coupled with OSA, emerges as an autonomous influential element impinging upon cognitive impairment.
PLGA fine nanoparticle for drug delivery systems: experimental and simulation
Authors: MOHAMMADIKHAH RASOOL , ABOLGHASEMI HOSSEIN , RASHIDI ALI-MORAD , ESMAEILI MOHAMMAD
Published: October 2023

In this work, PLGA copolymers/polymers with high molecular weight (up to 100000) become synthesised using ring opening method to be suitable for drug delivery systems. Two drugs namely (Tamoxifen citrate, cisplatin) were encapsulated into nanoPLGA copolymer capsules. Drugs were differently loaded according to their solvability (i.e. hydrophilic or hydrophobic status). After characterisation copolymer 75:25 PLGA was the best sample because of DSC analysis showing. One of PLGA copolymer (75:25 PLGA) was candidate to play the role of capsule for drug loading process that has more stability and maximum half time in the in-vivo environment. This work presents all steps to get new cancerthrap nanoparticles, from copolymer synthesis to drug encapsulation. Copolymer/polymer with molecular weight above 100000 which is very expensive and rare as a result was synthesised. Average diameter of nanoparticles shows 40–60 nm to promote much drug loading into encapsulating process, with the help of double emulsion method. Characteristics tests like TGA, DSC, DLS, SEM and TEM are accomplished to verify average size distribution as key factor and other parameters. Some key parameters to reduce size such as surfactant type are investigated. Simulations equipped by high performance computers are done which are strong devices to reproduce experimental results with low relative error. Maximum relative error is below 13 ℅. Double micro emulsion technique was successful to drug encapsulation in nano scale as we do in this work. The novelty comes from very fine nano capsules production and high loading drug in comparison with other works. Molecular dynamics simulation was accomplished by FORTRAN handy coding (with parallel computations) to give us a superior understanding of micelle formation, critical micelle concentration and size distribution or other critical parameters. Both simulation results and experimental data agree whether qualitatively and quantitatively. Results agree with experimental data and also with others reported results.
Differences in proportions and characteristics of malignant tumours by lung lobe
Authors: Nilssen Yngvar , Brustugun Odd Terje , Fjellbirkeland Lars , Helland Åslaug , Møller Bjørn , Wahl Sissel Gyrid Freim , Solberg Steinar
Published: October 2023

Background
The main focus on the characteristics of malignant lung tumours has been the size, position within the lobe, and infiltration into neighbouring structures. The aim of this study was to investigate the distribution and characteristics of malignant tumours between the lung lobes and whether the diagnosis, treatment, and outcome differed based on location.
Methods
This study is based on 10,849 lung cancer patients diagnosed in 2018–2022 with complete data on the location and characteristics of the tumours. The proportions of tumours in each lobe divided by its volume were termed the relative proportion.
Results
The right upper lobe comprised 31.2% of the tumours and 17.6% of the lung volume. The relative proportion of 1.77 was higher than in the other lobes (p < 0.001). The right middle lobe had a relative proportion of 0.64 but the highest proportion of neuroendocrine tumours (26.1% vs 15.3 on average). Surgical resection was more often performed in patients with tumours in the lower lobes, and curative radiotherapy was more often performed in the upper lobes. After adjusting for age, sex, stage, and histology, the location of the tumour was found to be a significant independent predictor for resection but not for survival.
Conclusion
The main finding of the right upper lobe as a site of predilection for lung cancer is similar to tuberculosis and pneumoconiosis. This may be explained that most of the inhaled air, containing bacilli, inorganic particles or tobacco smoke goes to the upper and right parts of the lung.
Microsurgical denervation of the spermatic cord with tunica vaginalis fenestration: results of a case series with a review of the literature
Authors: Almekaty Khaled , AbdelRahman Islam , Moubasher Amr , Abdel-Raheem Tarek , Zeidan Ashraf , Raheem Amr Abdel
Published: October 2023

Microsurgical denervation of the spermatic cord (MDSC) is one of the lines of management of chronic orchialgia, but it has not been fully adopted by different centers. This article reviews a case series experience with a review of the literature. Eighteen patients (18 testicular units) with chronic orchialgia, unresponsive to medical treatment were prospectively enrolled in this study. All underwent unilateral MDSC with a slight modification in the technique (tunica vaginalis fenestration). Efficacy of the technique was evaluated by the degree of pain improvement using the Visual Analogue Scale (VAS) which was done preoperatively and 6 months postoperatively. Safety was assessed by reporting any intra- or post-operative complications. Available literature was reviewed looking at safety and efficacy of the technique. Six patients had complete pain resolution, 11 had partial but significant resolution of their pain and the pain remained the same in one patient following MDSC. The VAS pain score significantly improved from a median (IQR) of 8(7.25-9) to 2(2-4.75) postoperatively (p=0.0029). No significant complications have been encountered in this study. So, MDSC seems to be a safe and efficacious surgical option for the treatment of resistant chronic scrotal pain (CSP) and should be more widely adopted by specialized centers.
Improving Attitudes Toward Trauma-Informed Care in the Neonatal Intensive Care Unit Through Comprehensive Multi-Disciplinary Education
Authors: Davis Patricia , Hubbard Dena , Gladdis Tiffany , Nitkin Christopher , Hansen Kara , Keith-Chancy Erin , Godwin Jennifer , Staggs Vincent , Babbar Shilpa , Hardy Michelle , Ashbaugh Jacqulin , Carter Brian
Published: October 2023

Objective: This study measured staff understanding and integration of trauma-informed care following comprehensive education.
Study Design: This mixed method design used the validated Attitudes Related to Trauma-Informed Care (ARTIC) scale and open-ended survey questions via REDCap optional surveys. Trauma-informed care education was made available to staff members in a level IV NICU. Pre- and post-intervention ARTIC scores were compared and post-intervention REDCap surveys were analyzed.
Result: There were 245 multi-disciplinary NICU team members who completed the ARTIC survey before and/or after the educational intervention; and 764 REDCap surveys were completed throughout the study time. ARTIC scores increased from pre- to post-training both for participants with data at both time points (0.5 SD mean increase) and among those with data at only one time point (0.4 SD mean increase). Content analysis of the REDCap survey corroborated the ARTIC results.
Conclusion: System-wide trauma-informed education can achieve measurable effect in a NICU setting.
Efficacy and safety of individualized rituximab in proliferative lupus nephritis
Authors: Hao Yingxuan , Guo Yanhong , Yu Lu , Wang Liuwei , Zhai Zihan , Lin Tang
Published: October 2023

The dosage, efficacy and safety of Rituximab (RTX) in the treatment of proliferative lupus nephritis (PLN) have not been fully investigated. We collected the data episodes from January 2017 to July 2023 of patients with PLN who were hospitalized in the Department of Nephrology of the First Affiliated Hospital of Zhengzhou University and treated with RTX, and the renal remission, recurrence and adverse reactions after RTX treatment were analyzed retrospectively. A total of 22 patients were enrolled, including 7 patients who were treated as a naive and 15 relapsed/refractory patients, 4 patients required hemodialysis on admission. After the first treatment of RTX, a total of 21(95.45%) patients achieved B cell depletion, and a total of 15 patients (68.18%) achieved complete response (CR). The annual average frequency of relapse per individual in the maintenance remission period in 15 refractory/relapsing patients decreased from (0.494±0.346) times to (0.026±0.010) time (P＜0.001), and the maintenance doses of prednisone decreased from (14.17±9.39) mg/day [ 20.0（12.3，40.0）months] to (8.67±5.97) mg/d[ 12.0（10.0,15.0）months] (P=0.040). Infection occurred in 3 patient within the first 3 months after RTX treatment and recovered after treatment, 3 cases were removed from hemodialysis, and no patient died. In conclusion, RTX can effectively treat PLN, reduce frequency of recurrences and decrease the dose of glucocorticoids, without increasing the occurrence of increased infection risks.
Long-term outcomes of patients with embolic stroke of undetermined source according to subtype
Authors: Lee Il Hyung , Heo JoonNyung , Lee Hyungwoo , Jeong JaeWook , Kim Joon Ho , Han Minho , Yoo Joonsang , Kim Jinkwon , Baik Minyoul , Park Hyungjong , Kim Young Dae , Nam Hyo Suk
Published: October 2023

Background and Aims: The prognosis of patients with embolic stroke of undetermined source (ESUS) may vary according to the underlying cause. Therefore, we aimed to divide ESUS into subtypes and assess the long-term outcomes.
Methods: Consecutive patients with acute ischemic stroke who underwent a comprehensive workup, including transesophageal echocardiography and prolonged electrocardiography monitoring, were enrolled. We classified ESUS into minor cardioembolic (CE) ESUS, arteriogenic ESUS, two or more causes ESUS, and no cause ESUS. Arteriogenic ESUS was sub-classified into complex aortic plaque (CAP) ESUS and non-stenotic (<50%) relevant artery plaque (NAP) ESUS.
Results: A total of 775 patients were enrolled. During 1286 ± 748 days follow-up, 116 major adverse cardiovascular events (MACE) occurred (4.2 events/100 patient-years). Among the ESUS subtypes, CAP ESUS was associated with the highest MACE frequency (9.7/100 patient-years, p=0.021). Cox regression analyses showed that CAP ESUS was an independent predictor of MACE (hazard ratio 2.466, 95% confidence interval 1.305–4.660) and any stroke recurrence (hazard ratio 2.470, 95% confidence interval, 1.108–5.508).
Conclusions:The prognosis of ESUS varies according to the subtype, with CAP ESUS having the worst prognosis. Categorizing ESUS into subtypes could improve patient care and refine clinical trials.
Mechanisms of action of berberine hydrochloride in planktonic cells and biofilms of Pseudomonas aeruginosa
Authors: Liu Qingyu , Tang Yongxue , Jiang Siyu , Yu Xiao , Zhu Huibin , Xie Xiaobing , Ning Xingwang
Published: October 2023

The growing prevalence of extensive drug-resistant and pan-drug resistant Pseudomonas aeruginosa (P. aeruginosa) has become a significant concern for global public health, particularly due to the formation of biofilms. Consequently, it is crucial to explore the development of novel antimicrobials that specifically target P. aeruginosa and its biofilms. Here we found a natural compound named berberine hydrochloride, subsequently, Crystalline violet staining and Confocal laser scanning microscope further demostrated that berberine hydrochloride suppress biofilm. Additionally, it was found that the expression of pslA and other biofilm-related genes were downregulated. Compared with available antibiotics, berberine hydrochloride has multiple modes of action in P. aeruginosa. The antimicrobial mechanism showed that berberine hydrochloride might have antimicrobial effects by damaging bacterial cell membranes, generating reactive oxygen species (ROS) and lowering intracellular adenosine triphosphate (ATP). Futhermore, berberine hydrochloride possesses various attributes, including minimal cytotoxicity and reduced susceptibility to drug resistance. In a mice peritonitis model, it was reported to inhibit the growth of P. aeruginosa significantly and displayed high bacteriostatic action. Collectively, the berberine hydrochloride is a safe and effective antibacterial agent for inhibiting P. aeruginosa.
Bacterial Peptidoglycan as a Food Digestive Signal that Facilitates Adaptation of Animals in Nature
Authors: Qi Bin , Hao Fanrui , Liu Huimin
Published: October 2023

Food availability and usage is a major adaptive force for the successful survival of animals in nature. However, very little is known about the signal from food to activate the hosts digestive system, which facilitates animals to digest more diverse food in nature. Here, by using a food digestion system in C. elegans, we discover that bacterial peptidoglycan (PGN) is a unique food signal that activates animals to digest inedible food. We identified that a glycosylated protein BCF-1 in the gut that interacts directly with bacterial peptidoglycan. This interaction inhibits mitochondrial UPR (UPRmt) by regulating the release of a neuropeptide (NLP-3). Moreover, constitutive activation of UPRmt is sufficient to inhibit food digestion, which depends on innate immune PMK-1. Addition, inhibition of innate immune PMK-1 can counter the digest defects of bcf-1 mutants. Finally, we demonstrate that natural adaptation is reduced in animals with digestion defects. Thus, our study reveals that bacterial PGN-glycosylated protein interaction is essential for digestion though cell-non-autonomous UPRmt inhibition, which facilitates adaptation of the host animals by increasing ability to consume a wide range of foods in their natural environment.
Prolyl hydroxylase domain inhibitor: a potential pre-hospital pharmaceutical intervention for trauma and hemorrhagic shock
Authors: Wu Xiaowu , Cap Andrew P. , Bynum James A. , Chance Tiffani C. , Darlington Daniel N. , Meledeo Michael A.
Published: October 2023

Trauma and hemorrhagic shock-associated pre-hospital deaths are mainly due to hypoperfusion-induced tissue hypoxia leading to irreversible organ dysfunction at or near the point of injury or during transportation prior to receiving definitive therapy. The prolyl hydroxylase domain (PHD) is an oxygen sensor that regulates tissue adaptation to hypoxia by stabilizing hypoxia inducible factor (HIF). The benefit of PHD inhibitors (PHDi) in the treatment of anemia and lactatemia arises from HIF stabilization, which stimulates endogenous production of erythropoietin and activates lactate recycling through gluconeogenesis. The results of this study provide insight into the therapeutic roles of MK-8617, a pan-inhibitor of PHD-1, 2, and 3, in the mitigation of lactatemia in anesthetized rats with polytrauma and hemorrhagic shock. Additionally, in an anesthetized rat model of lethal decompensated hemorrhagic shock (65% of estimated blood volume (EBV)), acute administration of MK-8617 significantly improves one-hour survival and maintains survival at least until 4 hours following limited resuscitation with whole blood (20% EBV) at one hour after hemorrhage. This study suggests that pharmaceutical interventions to inhibit prolyl hydroxylase activity can be used as a potential pre-hospital countermeasure for trauma and hemorrhage at or near the point of injury.
Study on "pull-shear" material removal principle and novel compound structure tool design during cutting KFRP
Authors: Su Fei , Liu Guangtao , Zhang Ke , Ding Xun , Gong Changliang
Published: October 2023

The Kevlar fiber-reinforced polymer (KFRP) is widely used in various fields due to its excellent mechanical and physical properties. However, the material is prone to processing defects such as burring and furry during secondary processing. In this paper, based on the cutting removal mechanism of KFRP, a "pull-shear" material removal principle for the residual fibers was proposed and analyzed. Then, a novel compound structure milling tool was designed. Theoretical and experimental analyses of the milling tests were carried out on the plain-woven KFRP composites. The result indicates that when the fibers are subjected to tension, the cutting surface quality is significantly improved. Therefore, when the "pull-shear" removal principle can be implemented effectively, the fibers can be effectively cut off in time. The "pulling-shearing" effect can be effectively implemented by the novel compound structure milling tool. The milling surface quality of the novel compound structure milling tool is better than the conventional tools. The burrs defect factor gradually decreases with the increase of the feed speed. The burrs defect factors tend to increase with the increase in cutting speed.
Comprehensive Bioinformatic Investigation of TP53 Dysregulation in Diverse Cancer Landscapes
Authors: Khan Ruby , Puszynski Krzysztof , Kozłowska Emilia
Published: October 2023

In this study, we present a comprehensive analysis of the role of TP53 in various cancers, its impact on disease-free survival (DFS), and the mathematical models used to understand TP53 protein network dynamics.
TP53 Analysis: We analyzed a diverse set of cancers, including BLCA, BRCA, CESC, CHOL, COAD, DLBC, ESCA, HNSC, KICH, KIRC, LIHC, LUAD, LUSC, and UCEC, and identified TP53 overexpression as a significant prognostic factor in PRAD. The analysis, supported by a significant p-value (p < 0.05), revealed the distinctive influence of TP53 overexpression on DFS outcomes in PRAD. Our study includes graphical representations of overall survival (OS) analysis, vividly illustrating the stark contrast in OS time between tumors with higher TP53 expression (depicted by the red line) and those with lower TP53 expression (indicated by the blue line). Additionally, the hazard ratio (HR) underscores the impact of TP53 on overall survival.
TP53 Protein Network Analysis: Furthermore, we investigate the TP53 protein network, identifying genes with strong positive correlations with TP53 expression in 13 out of 27 cancers, along with some negative correlations with important tumor suppressor genes. This network analysis revealed key proteins such as SIRT1, CBP, p300, ATM, DAXX, HSP 90-alpha, Mdm2, RPA70, 14-3-3 protein sigma, p53, and ASPP2, which play critical roles in cell cycle regulation, DNA damage response, and transcriptional control.
Mathematical Models: We also describe mathematical models used to simulate TP53 protein network dynamics. These models consider variables such as protein concentrations (Pi ), correlation coefficients (Cij ), rate constants (kij ), and degradation rate constants (λi ). The models’ equations capture the dynamics of protein concentrations influenced by correlations and rate constants specific to different cancer types. Our findings provide compelling evidence of the pivotal roles played by TP53 and TP53 overexpression in shaping cancer prognosis across various tumor types. These results carry significant implications for clinical management and underscore the need for further research into the underlying molecular mechanisms driving these associations.