bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Chinese herbal medicine on Patients with AECOPD Risk Window: study protocol for a Randomized Controlled Trial
Authors: Hailong Zhang , Huanrong Ruan , guixiang Zhao , Li ya , Jiansheng Li
Published: September 2023

Background
Chronic Obstructive Pulmonary Disease (COPD) is a major chronic disease with high incidence, mortality, and prevalence. Acute exacerbations mostly occur in a centralized period after an acute exacerbation, during which are extremely easy to occur again. We call this “high-risk period” as the “AECOPD risk window” (AECOPD-RW). At present, Western medicine lacks specific guidance on the medication of AECOPD-RW. Chinese herbal medicine has good efficacy and advantages in the treatment of COPD. Based on the clear distribution of syndrome in the previous period, this study aims to evaluate the clinical efficacy and safety of Chinese herbal medicine on AECOPD-RW.
Methods
This proposed study is a multi-center, double-blind, randomized controlled trial (RCT) to compare the efficacy of two therapies for patients with AECOPD-RW. 336 subjects will be randomly assigned in a 1:1 ratio to experimental group or control group for 8 weeks treatment and 18 weeks follow-up. Based on health education and conventional treatment, the experimental group will receive Chinese herbal medicine granule according to Chinese medicine syndrome types, while the control group will receive Chinese herbal medicine placebo granule according to Chinese medicine syndrome types. The primary outcomes are acute exacerbation rate in the AECOPD-RW, COPD Assessment Test (CAT) in the AECOPD-RW, and secondary outcomes include time to the first acute exacerbation, degree of acute exacerbation in the AECOPD-RW, acute exacerbation rate in the follow-up period, degree of acute exacerbation in the follow-up period, lung function, mMRC, quality of life and index of security. Outcome measurements will be evaluated at week 0, 8 of the treatment period and at week 16, 26 of the follow-up period. The results will provide evidence for the clinical efficacy and safety of traditional Chinese medicine in the treatment of AECOPD RW, and provide a reliable scheme for the treatment of AECOPD-RW.
Discussion
This is the first multicenter, randomized, double-blind, placebo-controlled parallel trial designed to investigate the efficacy of Chinese herbal medicine in the treatment of AECOPD-RW. The result of this RCT may help effectively reduce the possibility of AECOPD recurrence, change the course of disease deterioration, and provide evidence-based evidence for Chinese herbal medicine prevention and treatment of AECOPD-RW.
Trial registration
This trial was registered in ClinicalTrials.gov, NCT04851093. Registered on 14 April 2021.
CYTL1 induces cell proliferation to modulate gastric cancer progression
Authors: Bai Weisong , Zhao Lizhi , Qian Weikun , Shang Peiqiang , Ma Qingyong , Ma Zhenhua
Published: September 2023

Background
Cytokine-like protein 1 (CYTL1) is ubiquitously expressed in multiple human cancers, including gastric cancer (GC). However, its physiological role in GC is unknown. Herein, we elucidated the importance of CYTL1 in GC and assessed its association with GC progression.
Methods
The Cancer Genome Atlas (TCGA) was used to obtain clinical data for GC patients. Next, we investigated the associations among the CYTL1 expression level, pathological features, and patient prognosis. Finally, we examined the relationships among the CYTL1 level, immune cell invasion (CI), and GC progression.
Results
The CYTL1 level was elevated in GC tissues compared to surrounding normal tissues. Moreover, enhanced CYTL1 expression in GCs was intricately linked to worse prognosis. Based on univariate and multivariate Cox regression analyses, the CYTL1 level, along with age, residual tumor status, N stage, and primary therapeutic outcome, was an independent indicator of disease-specific survival (DSS), overall survival (OS), and progression-free interval (PFI) in GC patients. Furthermore, an elevated CYTL1 level was associated with tumor infiltration of pDCs, mast cells, macrophages, DCs, Tem cells, NK cells, Th2 cells, and Th17 cells. Using gene set enrichment analysis (GSEA), we revealed that an elevated CYTL1 level was intricately linked to cell proliferation (CP) and the glycolytic network. Finally, CYTL1 knockdown in GC cell lines drastically reduced CP, cell migration (CM), and CI in both in vitro and in vivo studies.
Conclusion
CYTL1 expression correlates with GC progression and glycolysis, indicating that it may be a strong prognostic indicator in GC.
The Effect of Build Orientation on the Mechanical Properties of a Variety of Polymer AM-Created Triply Periodic Minimal Surface Structures
Authors: Temiz Abdurrahim
Published: September 2023

This research aimed to determine how different pattern types (TPMS) and build orientations affected the mechanical properties of test specimens made with masked stereolithography (MSLA) and a commercially available gray resin. Moreover, the study aimed to determine the best TPMS pattern type and build orientation to enhance both UTS and elongation at break. For the purpose of experimental assessment of their tensile qualities, samples of the Gyroid lattice, Schwarz Primitive lattice, and Schwarz Diamond lattice structures were 3D printed using SLA technology. The results of producing on the on edge, upright and flat orientations of a building were compared. The results showed that across all three building orientations, the D-shaped component produced the highest UTS and the P-shaped component produced the largest elongation. It's apparent that the upright position produced the smallest UTS. When comparing the UTS and elongation at break between the flat and on-edge constructed orientations, it is clear that the former is lower.
Magmatism Controls Global Oceanic Transform Fault Topography
Authors: Tian Xiaochuan , Behn Mark , Ito Garrett , Schierjott Jana , Kaus Boris , Popov Anton
Published: September 2023

Oceanic transform faults are fundamental features of plate tectonics, accommodating strike-slip motion between two adjacent mid-ocean ridge segments. The continuations of these faults form tectonically inactive fracture zones, creating the longest ‘scars’ on the Earth’s surface. Yet, despite the relatively simple kinematic and thermal structures, oceanic transform faults display an enigmatic continuum of morphologies ranging from deep valleys to small ridges. Here, through three-dimensional numerical modeling of two mid-ocean ridge segments separated by a transform fault, we find that the rate of magma intrusion within the transform domain exerts a first-order control on transform topography. Low-rate magmatism results in transform-parallel tectonic stretching, generating deep transform valleys and fracture zones. Intermediate-rate magmatism fully accommodates far-field stretching, but strike-slip motion induces across-transform tension, producing shallow valleys whose depth increases with the shear strength of the fault. High-rate magmatism leads to local compression that generates fault-parallel ridges. The models not only reproduce the observed global transform valley depths but also predict the observation that fracture zones are consistently shallower than their adjacent transform valleys. These results suggest that plate motion changes are not a necessary condition for generating oceanic transform topography and that oceanic transform faults are not simple conservative strike-slip plate boundaries.
From remains to results: assessing the feasibility of free DNA for disaster victim identification and forensic applications
Authors: Worrapitirungsi Wikanda , Sathirapatya Tikumphorn , Sukawutthiya Poonyapat , Vongpaisarnsin Kornkiat , Varrarthyarom Pagparpat
Published: September 2023

In tropical disaster victim identification (DVI) scenarios, challenging environmental conditions lead to accelerated DNA degradation in remains. To further enhance the utilization of leached DNA from tissue in the preservative solution (termed "free DNA") as an alternative source, we incorporated new results by assessing its integrity in postmortem and decomposing cadavers preserved in DNA/RNA Shield™ and modified TENT, with silica-based purification (QIAquick®) for faster processing. The psoas muscle tissues of one decomposed and ten cadavers were preserved in each solution at 25°C and 35°C for three months. Free DNA efficiency was compared with individual reference samples for reliable results in quantity, quality, and STR profiles. The findings revealed that DNA/RNA Shield™ effectively preserves free DNA integrity for extended storage, while modified TENT is more suitable for short-term storage due to higher degradation levels. Moreover, the use of free DNA samples with massive parallel sequencing displays potential for forensic DNA analysis. Successful amplification of the mtDNA control region enables variant calling and heteroplasmy analysis, while also serving for quality control using ACTB and enabling differentiation within the 16S rRNA region for microbiome analysis. The simplicity of handling free DNA for PCR-based forensic analysis adds to its potential for various applications, including DVI and field-based analysis of biological evidence.
Ensemble of Self-supervised Learning Methods for Robust Skin Disease Image Diagnosis Leveraging Unlabeled Data
Authors: Kojima Kaname , Tadokoro Ryu , Kinoshita Kengo , Asano Yoshihide , Yamasaki Kenshi , Shido Kosuke
Published: September 2023

Deep learning technologies have led to remarkable improvements in medical image analysis, but the collection and annotation of medical data remain challenging. This study leverages self-supervised learning and unlabeled images from the National Skin Disease Database of Japan (NSDD) to enhance skin disease classification. By generating pre-trained models using three self-supervised learning methods, and comparing them to a baseline pre-trained model on ImageNet, we found that pre-training with unlabeled images increased transfer learning performance by 1-2% on labeled images in the NSDD. We also demonstrated the effectiveness of the pre-trained models across four public dermatological image datasets. We further implemented a hybrid pre-training approach that combines self-supervised and supervised learning, and observed accuracy improvements in certain datasets. Since the optimal strategy is task and dataset-specific, we proposed an ensemble of transfer learned models from diverse pre-training methods for robust classification. The ensemble approach consistently enhanced accuracy across various datasets, with an improvement by up to 8.3% from the baseline, confirming the effectiveness of self-supervised pre-training with unlabeled dermatological images even when the images are mainly from one ethnic group.
Impact of familiarity with the format of the exam on performance in the OSCE of 5th undergraduate medical students – an interventional study
Authors: Neuwirt Hannes , Eder Iris Elisabeth , Gauckler Philipp , Horvath Lena , Koeck Stefan , Noflatscher Maria , Schaefer Benedikt , Simeon Anja , Petzer Venera , Prodinger Wolfgang , Berendonk Christoph
Published: September 2023

Background: Assessments aim to verify whether students have acquired the necessary competencies. These assessments are typically carried out as summative structured examinations. It is important not only to establish a constructive alignment between teaching and assessment but also to familiarize students with the examination format prior to the assessment. The latter point is intended to ensure that true competency is measured. Regarding practical examinations such as objective structured clinical examinations (OSCEs), this is often not the case. Therefore, it is unclear whether students can demonstrate their true potential or possibly perform less effectively due to the unfamiliar examination format. Hence, we questioned whether a 10-minute active familiarization in the form of simulation improved medical students´ OSCE performance. Next, we wanted to elucidate whether the effect depends on whether the familiarization procedure is active or passive. Methods: We implemented an intervention consisting of a 10-minute active simulation to prepare the students for the OSCE setting. We compared the impact of this intervention on performance to no intervention in 5th-year medical students (n=1284) from 2018 until 2022. Recently, a passive lecture, in which the OSCE setting is explained without active participation of the students, was introduced as a comparator group. Students who participated in neither the intervention nor the passive lecture group formed the control group. The OSCE performance between the groups and the impact of gender was assessed using X2, nonparametric tests and regression analysis (total n=362). Results: We found that active familiarization of students in the exam setting yields significantly better performance compared to the passive comparator (Cohen´s d=0.857, p<0.001)) and control group (Cohen´s d=0.473, p<0.001). In multivariate regression analysis, active intervention remained the only significant variable with a 2.945-fold increase in the probability of passing the exam (p=0.018). Conclusions: A short 10-minute active intervention to familiarize students with the OSCE setting significantly improved student performance. We suggest that curricula should include simulations on the exam setting in addition to courses that increase knowledge or skills to mitigate the negative effect of nonfamiliarity with the OSCE exam setting on the student.
Coupling normothermic machine perfusion with mesenchymal stem cell bioreactors: benefits exerted on the rat liver
Authors: Lonati Caterina
Published: September 2023

Administration of mesenchymal-stem-cells (MSCs) during Normothermic-Machine-Perfusion (NMP) reduces ischemia/reperfusion injury, but the strategy to apply cell-based therapies ex-situ can hamper their effectiveness. To fully harness MSCs potential, we developed an advanced perfusion system equipped with a MSCs-bioreactor and investigated its benefits on the rat liver.
The study involved two work packages: 1) Development: bioreactors seeded with 2x107 human adipose tissue-derived MSCs were connected to the NMP circuit and subjected to 4h-liverless perfusion (Liverless-NMP,n=5); 2) MSCs-bioreactor-based liver NMP: rat livers were perfused for 4h on the NMP circuit coupled with the MSCs-bioreactor (NMP+bioreactor,n=5) or without it (NMP,n=5).
MSCs remained metabolically active during liverless-NMP and showed a preserved expression of stemness-related markers. When used for liver NMP, MSCs changed their secretome in a liver-tailored manner. Organs exposed to the MSCs-bioreactor-based perfusion produced more bile, released less damage biomarkers, and showed higher ATP content with reduced succinate accumulation than those subjected to NMP alone. A lower release of pro-inflammatory mediators and the induction of factors involved in resolution/regeneration were also observed.
This proof-of-concept study provides a novel MSCs-based protocol for liver NMP, thereby creating a modern perfusion platform able to preserve mitochondrial function, sustain hepatic cell viability, reduce inflammation, and trigger healing processes.
Synthetic rescue of XPC phenotype via PIK3C3 downregulation
Authors: Gidrol Xavier , Kobaisi Farah , Sulpice Eric , Nasrallah Ali , Fayyad-kazan Hussein , Rachidi Walid
Published: September 2023

Xeroderma Pigmentosum C is a dermal hereditary disease. It is caused by a mutation in the DNA damage recognition protein XPC that belongs to the Nucleotide excision repair pathway. XPC patients exhibit a photosensitive phenotype and fail to repair UV induced DNA lesions leading to their accumulation and ultimate conversion to mutations and carcinomas. In an attempt to normalize this phenotype, we screened a library of siRNAs targeting the human kinases, given their role in different DNA repair pathways. WT and XPC immortalized patient fibroblasts were transfected with the library then irradiated with UVB to induce DNA damage. XPC phenotypic reversal was monitored by the quantification of decreased photosensitivity and increased DNA damage repair. Out of the 1292 kinase siRNAs tested, twenty-eight were selected cellular survival compared to cells transfected with non-targeting siRNA in XP-C irradiated cells. Out of the selected hits, two kinases, PIK3C3 and LATS1, induce more than 20% repair of 6-4PP DNA lesions. The down regulation of autophagy-related protein PIK3C3 alone had an exclusive photo protective effect on XP-C irradiated cells validated these effects also on primary XP-C patient fibroblasts and CRISPR-Cas9 generated XPC-KO keratinocytes. PIK3C3 knock down in XP-C cells ameliorated in UVB dose response analysis, decreased apoptosis and lowered phosphorylation of P53 with no effect on proliferation. More importantly, PIK3C3 knock down induced an increase in UVRAG expression, a previously reported cDNA conveying lower photosensitivity in XP-C cells. Attempts to improve the XPC photosensitive and deficient repair phenotype using PIK3C3 inhibitors could thus pave a way for new therapeutic approaches delaying or preventing tumor initiation.
Prediction of Adverse Events Risk in Patients with Comorbid Post- Traumatic Stress Disorder and Alcohol Use Disorder Using Electronic Medical Records by Deep Learning Models
Authors: Miranda Oshin , Fan Peihao , Qi Xiguang , Wang Haohan , Brannock M Daniel , Kosten Thomas , Ryan Neal David , Kirisci Levent , Wang LiRong
Published: September 2023

Background Prediction of high-risk events in mental disorder patients is crucial. In our previous study, we developed a deep learning model: DeepBiomarker by using electronic medical records (EMR) to predict suicide related event (SRE) risk in post-traumatic stress disorder (PTSD) patients. Methods We applied DeepBiomarker2 through data integration of multimodal information: lab test, medication, co-morbidities, and social determinants of health. We analyzed EMRs of 5,565 patients from University of Pittsburgh Medical Center with a diagnosis of PTSD and alcohol use disorder (AUD) on risk of developing an adverse event (opioid use disorder, SREs, depression and death). Results DeepBiomarker2 predicted whether a PTSD + AUD patient will have a diagnosis of any adverse events (SREs, opioid use disorder, depression, death) within 3 months with area under the receiver operator curve (AUROC) of 0.94. We found piroxicam, vilazodone, dronabinol, tenofovir, suvorexant, empagliflozin, famciclovir, veramyst, amantadine, sulfasalazine, and lamivudine to have potential to reduce risk. Conclusions DeepBiomarker2 can predict multiple adverse event risk with high accuracy and identify potential risk and beneficial factors. Our results offer suggestions for personalized interventions in a variety of clinical and diverse populations.
Assessment of outdoor thermal human comfort over Houche Al-Oumara, North Lebanon
Authors: ELCHAAR ALI ADNAN , Hewehy Mahmoud Ahmed , Abbas Ismail Ibrahim , Robaa El-Sayed Mohamed Abdel-Hamid , Mostafa Mohammed Salah El-din Mostafa Mohammed Salah El-din Mostafa
Published: September 2023

This study investigated thermal discomfort in Houche Al-Oumara from 1994 to 2021 using different discomfort indices and analyzed data on temperatures, relative humidity, and rainfall. It was found that July and August had significantly higher mean temperatures compared to other months, with the highest temperature occurring in July. Conversely, January was the coldest month. The study observed a linear increase in mean air temperature from January to July, followed by a linear decrease from July to December. Similar patterns were observed for relative humidity, but in the opposite direction. Less than half of the population experienced thermal discomfort during July and August. The study emphasized the importance of understanding long-term thermal discomfort trends, considering global warming, urbanization, and population growth. Rainfall data analysis revealed significant variability in the annual average rainfall over the years, without a clear trend. Periods of consecutive years with above-average or below-average rainfall were identified. These findings are valuable for policymakers in managing human thermal comfort in rural areas. They provide insights into the influence of environmental factors such as air temperature, relative humidity, and rainfall. The results can assist in developing strategies to address heat stress-related health risks and plan for sustainable development in North Lebanon.
Free particles beyond fermions and bosons
Authors: Wang Zhiyuan , Hazzard Kaden
Published: September 2023

It is commonly believed that there are only two types of particle exchange statistics in quantum mechanics, fermions and bosons, with the exception of anyons in two dimension [1-4]. In principle, a second exception known as parastatistics, which extends outside of two dimensions, has been considered [5] but was believed to be physically equivalent to fermions and bosons [6, 7]. In this paper we show that nontrivial parastatistics inequivalent to either fermions or bosons can exist in physical systems. These new types of identical particles obey generalized exclusion principles, leading to exotic free-particle thermodynamics distinct from any system of free fermions and bosons. We formulate our theory by developing a second quantization of paraparticles, which naturally includes exactly solvable non-interacting theories, and incorporates physical constraints such as locality. We then construct a family of one-dimensional quantum spin models where free parastatistical particles emerge as quasiparticle excitations. This demonstrates the possibility of a new type of quasiparticle in condensed matter systems, and, more speculatively, the potential for previously unconsidered types of elementary particles.
Near full-length genome analysis of two novel HIV second recombinant forms in Hebei, China.
Authors: FENG YUXIN , Lu Jianhua , Wang LiJing , Han Jingwan , Wang Yuling , Li Chen , Wang Xiaolin , Li Beilei , Liu Yongjian , Xiaojing Qu , Jia Lei , Chen Qian , Yao Ru , Li Yingxia , Feng Fumin , Li Jingyun , Li Hanping , Li Lin , DAI ERHEI
Published: September 2023

Individuals infected with HIV-1 among men who have sex with men (MSM) rose rapidly in recent years in China, and such subtypes as CRF01_AE, CRF07_BC, B, and some novel URFs were prevalent among them. Co-circulation of strains among MSM populations allows the development of CRFs and URFs. In the study, we reported two new URFs from two HIV-1-positive subjects infected through homosexual contact routes in Hebei, China. Two URFs originated from CRF01_AE, CRF07_BC, and B through analysis of near full-Length genome (NFLG) using phylogenetic tree and recombinant analysis, and CRF01_AE segments in the backbone of URFs derived from cluster 4 of CRF01_AE. The CRF07_BC segments of two URFs were clustered with 07BC_N. The development of novel URFs with complicated genomic structures continually indicated that it was necessary to strengthen the survey of the HIV-1 prevalence and new URFs among the MSM populations in this region.
Genetically encoded transcriptional plasticity underlies stress adaptation in Mycobacterium tuberculosis
Authors: Liu Qingyun , Bei Cheng , Zhu Junhao , Culviner Peter , Rubin Eric , Fortune Sarah , Gao Qian
Published: September 2023

Transcriptional regulation is a critical adaptive mechanism that allows bacteria to respond to changing environments, yet the concept of transcriptional plasticity (TP) remains largely unexplored. In this study, we investigate the genome-wide TP profiles of Mycobacterium tuberculosis (Mtb) genes by analyzing 894 RNA sequencing samples derived from 73 different environmental conditions. Our data reveal that Mtb genes exhibit significant TP variation that correlates with gene function and gene essentiality. We also found that critical genetic features, such as gene length, GC content, and operon size independently impose constraints on TP, beyond trans-regulation. By extending our analysis to include two other Mycobacterium species -- M. smegmatis and M. abscessus -- we demonstrate a striking conservation of the TP landscape. This study provides a comprehensive understanding of the TP exhibited by mycobacteria genes, shedding light on this significant, yet understudied, genetic feature encoded in bacterial genomes.
Diagnostic value of cuproptosis-related genes in sepsis: A novel model based on bioinformatics screening
Authors: Jia Xuan , Tian Yuan , Zhang Dian , Chen Siqia , Meng Dongmei
Published: September 2023

Background: Sepsis is a life-threatening functional disorder of the organs resulting from a dysregulated host immune response to infection and is a leading cause of death and critical illness worldwide. Genetic diagnosis combined with big data analysis of existing biomarkers has great potential in the diagnosis and prognosis prediction of sepsis, and there is an urgent need to construct prognostic models that will improve the effectiveness of treatment decisions. Methods: We used data from the Gene Expression Omnibus (GEO) (https://www.ncbi.nlm.nih.gov/geo/) database to perform a comprehensive analysis of differential gene expression profiles associated with cuproptosis in sepsis. Combining the sepsis datasets (GSE131761 and GSE54514) as test sets, a total of 208 sepsis samples and 69 normal samples were used for the analysis of cuproptosis-related differentially expressed genes (CRDEGs), weighted gene co-expression network analysis (WGCNA), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The gene sets from the Molecular Signatures Database (MSigDB) and were used to perform GSVA (Gene Set Variation Analysis) and GSEA (Gene-set Enrichment Analysis). The prognostic performance of the hub genes in the CRDEGs diagnostic model was examined in the validation set (GSE25504 and GSE26378), and receiver operating characteristic curves (ROC) were plotted. We constructed a Cox regression model and drew a nomogram based on the final screened CRDEGs. The prognostic Calibration and decision curve analysis were used to evaluate the model. Finally, we constructed a protein-protein interaction network (PPI network) and performed ceRNA network analysis and immune cell infiltration abundance correlation analysis. Results: We obtained two sepsis disease subtype groups based on clustering analysis of differentially expressed cuproptosis hub genes (LIPT1, PDHB, MTF1, GLS, SLC31A1). GO and KEGG analyses indicated that sepsis-related cuproptosis alterations were primarily enriched in cellular copper ion homeostasis, regulation of respiratory gaseous exchange by neurological system process, suckling behavior, protein-cofactor linkage. WGCNA yielded six cuproptosis-related gene co-expression modules and 202 CRDEGs between subgroups of sepsis. A total of 32 CRDEGs were extracted additionally based on LASSO analysis calculations, of which 23 CRDEGs were included in the optimized diagnostic gene labels used for constructing Cox regression models and plotting nomogram. Finally, in the immune infiltration analysis, there was a statistically significant relationship between the abundance of immune infiltration of 16 immune cells and the expression of CRDEGs. Conclusions: The diagnostic model we constructed on CRDEGs has promising predictive power, paving the way for further exploration of the mechanisms related to cuproptosis in sepsis and providing new ideas for discovering potential biomarkers and diagnostic patterns for sepsis.
Graphene oxide/copper nanosheet-integrated hydrogel platform as a bioactive and biocompatible scaffold to accelerate calvarial defect restoration
Authors: Yang Ying , Zhou Bixia , Li Min , Jiang Xulei , Zhou Xinxin , Hu Chengjun , Zhang Dou , Luo Hang , Tan Wuyuan , Yang Xinghua , Lei Shaorong
Published: September 2023

Background
The treatment of craniofacial bone defects caused by trauma, tumors, and infectious and degenerative diseases is a significant issue in current clinical practice. Following the rapid development of bone tissue engineering (BTE) in the last decade, bioactive scaffolds coupled with multifunctional properties are in high demand with regard to effective therapy for bone defects.
Methods
In this study, motivated by the versatile biological functions of nanomaterials and synthetic hydrogels, copper nanoparticle (CuNP)-decorated graphene oxide (GO) nanosheets (GO/Cu) were combined with methacrylated gelatin (GelMA)-based organic-inorganic hybrids to construct porous bone scaffolds that mimic the extracellular matrix (ECM) of bone tissues by photocrosslinking. The material characterizations, in vitro cytocompatibility and osteogenesis of the biohybrid hydrogel scaffolds were investigated, and two different animal models were established to further confirm the in vivo neovascularization, macrophage recruitment, biocompatibility, biosafety and bone regenerative potential.
Results
It found that GO/Cu-functionalized GelMA/β-TCP hydrogel scaffolds exhibited evidently promoted osteogenic activities and excellent cytocompatibility, with favorable surface characteristics and sustainable release of Cu2+. Additionally, improved neovascularization, macrophage recruitment and tissue integration were found in mice implanted with the bioactive hydrogels. More importantly, the observations of microCT reconstruction and histological analysis in a calvarial bone defect model in rats treated with GO/Cu-incorporated hydrogel scaffolds, demonstrated significantly accelerated bone healing.
Conclusions
Taken together, this BTE-based bone repair strategy provides a promising and feasible method for constructing multifunctional GO/Cu nanocomposite- incorporated biohybrid hydrogel scaffolds with facilitated osteogenesis, angiogenesis and immunoregulation in one system, thereby demonstrating the great application potential for correcting craniofacial bone defects in future clinical scenarios.
Carrier-free low-molecular-weight heparin and lipid conjugate-based nano-anticoagulant with an albumin shuttling effect
Authors: Park Jooho , Lee Jae-Hyeon , Lim Hansol , Ma Gaeun , Seo Minho , Lee Jun-Hyuck , Yang Seong-Bin , Jeong Han-Gil , Kweon Seho
Published: September 2023

The potential for polysaccharides to have long-term effects in the body is restricted by their naturally large molecular size and flexibility. In particular, patients receiving the anticoagulant heparin in preventive therapies would strongly benefit from an extended (long-term) effect of administered heparin, but the related technology has hardly been developed. Here, we have newly designed and evaluated a nanoengineered low-molecular-weight heparin (LMWH) and octadecylamine conjugate (LMHO) that can act for a long time while maintaining close to 97 ± 3% of heparin activity via end-specific conjugation of the reducing end of heparin. It generates self-assembled nanoparticles (NP) with an average size of 105 ± 1.7 nm in water without any nanocarrier and, further, can be combined with serum albumin, resulting in a lipid-based albumin shuttling effect such that the resulting molecules can circulate in the bloodstream for 4–5 days. We substantiate the self-assembly capability of LMHO and its interaction with albumin through molecular dynamics (MD) simulations and transmission electron microscopy (TEM) analysis, offering novel insights. This innovative approach to carrier-free polysaccharide delivery, enhanced by nanoengineered albumin shuttling, represents a promising platform to address limitations in conventional therapies.
Beneficial effects of the extracts and fractions of Dendranthema zawadskii and quantitative analysis of phenolic compounds by HPLC/UV
Authors: So Jeong , Lee Hak-Dong , Lee Sullim , Lee Sanghyun , Lim Jin Hee
Published: September 2023

Dendranthema spp. are good sources of phenolic compounds with pharmacological effects. To improve industrial material efficiency and economic feasibility, Dendranthema zawadskii (DZ) was fractionated, and its functional substances and biological activities were evaluated. The linarin contents in the butanol (Bu) and ethyl acetate (EtOAc) fractions were 77.360 mg/g and 70.603 mg/g, respectively, which were approximately 3.4 times higher than those in the methanol extract. In the EtOAc fraction, the luteolin content was 52.135 mg/g (6.4 times higher than that in the methanol extract) and the 3,5-DCQA content was 184.704 mg/g (9.7 times higher than that in the methanol extract). Excluding the hexane (He) and chloroform (Ch) fractions, cell viability was 80% or higher at concentrations of ≤200 μg/mL for HaCaT cells and 25 μg/mL for B16F10 cells, indicating a lack of toxicity. The total polyphenol content of the EtOAc fraction was 370.50 mg/g and the total flavonoid content was 947.47 mg/g, which were significantly higher than those of the other fractions. As a result, the antioxidant activity of the EtOAc fraction at a low concentration of 25 μg/mL was 92.47%, similar to that of the control, and at 100 μg/mL, the He and Bu fractions exhibited high antioxidant activity (>90%). The EtOAc fraction had the highest tyrosinase inhibitory activity (33.33%) and inhibited melanin formation by 37.12% compared with that in the α-MSH treatment group. The antibacterial activities of 100 mg/mL He, Ch, and EtOAc fractions against Staphylococcus aureus were higher than that of the positive control, and the antibacterial activity against Pseudomonas aeruginosawas higher than that of the positive control for all fractions (100 mg/mL). The Ch fraction had the strongest activity against Candida albicans. Overall, the EtOAc fraction of DZ has a high potential as an industrial material, as it can be safely used with high functionality and polyphenol and flavonoid contents, with extensive potential applications in cosmetics, functional foods, and pharmaceuticals.
Distance-edge-monitoring sets of networks
Authors: Yang Gang , Zhou Jiannan , He Changxiang , Mao Yaping
Published: September 2023

It is important to be able to monitor the network and detect this failure when a connection (an edge) fails. For a vertex set $M$ and an edge $e$ of the graph $G$, let $P(M, e)$ be the set of pairs $(x, y)$ with a vertex $x$ of$M$ and a vertex $y$ of $V(G)$ such that $e$ belongs to all shortest paths between $x$ and $y$. A vertex set $M$ of the graph $G$ is \emph{distance-edge-monitoring set} if every edge $e$ of $G$ is monitored by some vertex of $M$,that is, the set $P(M, e)$ is nonempty. The distance-edge-monitoring number of a graph $G$, recently introduced by Foucaud, Kao, Klasing, Miller, and Ryan, is defined as the smallest size of distance-edge-monitoring sets of $G$.In this paper, we determine the bounds of the distance-edge-monitoring number of grid-based pyramids and the exact value of distance-edge-monitoring number for $M(t)$-graph and Sierpi{\'n}ski-type graphs.We also compare the distance-edge-monitoring set with average degree, the size of edge set and the size of vertex set of $G$, where $G$ is $M(t)$-graph or Sierpi{\'n}ski-type graphs.
A Crosswalk Study of Law Enforcement Agency Records of Nonfatal Shootings with Aggravated Assaults captured in NIBRS
Authors: De Biasi Alaina , McGarrell Edmund , Wolfe Scott
Published: September 2023

Despite being more prevalent, national efforts to provide a valid and reliable source of data on nonfatal shooting injuries lag behind those focused on fatal shooting injuries. Even more, national data systems that do collect data on nonfatal shooting injuries have severe shortcomings that place limits on their usefulness to inform firearm violence research, including intervention and prevention efforts. Our study focuses on one common source of firearm violence data that is supported by law enforcement agencies (LEAs): The National Incident-Based Reporting System (NIBRS). Recognizing the limitations of NIBRS and to inform internal practices, some LEAs keep records on nonfatal shooting injuries. These records prevent a natural opportunity to compare known incidents of nonfatal shootings to aggravated assaults involving a firearm and injury to the victim, a NIBRS proxy measure for nonfatal shootings. To this end, the purpose of our study is to assess the ability of NIBRS to identify nonfatal shooting incidents through a comparison of known nonfatal shooting incidents identified by the Detroit Police Department from 2017 through 2020. Our findings demonstrate the value of expanding NIBIRS to improve the measurement of nonfatal shooting injuries and the importance of LEAs in driving this change and supporting firearm violence research.
A non-antibiotic erythromycin derivative improves muscle endurance by regulating endogenous anti-fatigue protein orosomucoid
Authors: Feng Jiayi , Wan Jingjing , Sun Yang , Chen Fei , Chen Yi , Guo Pengyue , Sun Qingyan , Zhang Weidong , Liu Xia
Published: September 2023

Background
At present, there is no official approved drug for improving muscle endurance. Our previous research found that acute phase protein Orosomucoid was an endogenous anti-fatigue protein, elevated by erythromycin to promote muscle bioenergetics and endurance. Here, we try to find a non-antibiotic erythromycin derivative improving muscle endurance.
Methods
The antibacterial activity was evaluated by bacterial inhibition ring test and 16S rRNA sequencing of the feces. Mice muscle endurance was evaluated by forced-swimming and treadmill-running. Fatigue index of isolated soleus muscle was evaluated by electrically evoked contraction. Glycogen content and mitochondrial number were tested by glycogen assay kit and transmission electron microscope. The expression of Orosomucoid in tissues and cells was detected by western blotting. Orosomucoid-targeting activity of HMS-01 was evaluated on Orosomucoid-deficient mice.
Results
HMS-01 is a novel erythromycin derivative, which lost antibacterial activity and could time- and dose-dependently prolong mice force-swimming and running time, improving fatigue index of soleus muscle. Moreover, HMS-01 increased glycogen content and mitochondria numbers in liver and muscle, and Orosomucoid level in vivo and in vitro. In Orosomucoid-deficient mice, the anti-fatigue and glycogen-elevation activity of HMS-01 disappeared.
Conclusions
HMS-01 may be a promising small molecule drug targeting Orosomucoid to enhance muscle endurance.
Low Prevalence of Ideal Cardiovascular Health Metrics in Nigerians: a cross sectional study
Authors: Amadi Casmir , Lawal Folasade , Akinsola Clement , Udenze Ifeoma , Mbakwem Amam , Ajuluchukwu Jayne , Oke David
Published: September 2023

Background: Ideal cardiovascular health (ICH) is a metrics for primordial prevention of cardiovascular disease (CVD). Its prevalence in Nigerians is not known.
Methods
This cross-sectional study assessed the seven American Heart Association’s ICH metrics of 889 Nigerians. The metrics included non-smoking, healthy diet, physical activity, body mass index (<25 kg/m2), untreated blood pressure <120/<80 mmHg, untreated total cholesterol <200 mg/dL, and untreated fasting blood glucose <100 mg/dL). Logistic regressions were used to estimate associations between sociodemographic factors (age and sex) and meeting 5–7 CVH metrics.
Results: No one met all 7 of ICH metrics while 70 (7.8%) had 5-7metrics. The most prevalent and least prevalent ideal biological factors were ideal fasting plasma cholesterol (62.8%) and ideal blood pressure (31.5%) respectively. The most prevalent and least prevalent behavioural factors were ideal smoking status (86.2%) and ideal diet (6.5%) respectively. Compared to males, females had better ideal BP, p=0.005; better ideal fasting plasma glucose, p=0.031; better ideal fasting plasma cholesterol, p<0.001 and ideal smoking status, p<0.001. Ages 45 to 64 had better ideal smoking status and ideal physical activity (p<0.001 and p=0.001 respectively).
Conclusion: There is a low prevalence of ICHamong Nigerians. Concerted efforts should be made to improve healthy living among Nigerians.
Comprehensive identification of potentially active transposon-mobility genes in C. elegans genome
Authors: Arata Yukinobu , Jurica Peter , Parrish Nicholas , Sako Yasushi
Published: September 2023

Transposons are the mobile DNA that itself encodes genes for their own mobility. During evolution, transposons accumulated their copies on genomic DNA, whereas many of them lost their mobile activity due to deletion or point mutations on the DNA elements required for their mobility. Here, we focused on the transposon-encoded genes which are directly involved in replication, excision, and integration of transposon DNA, i.e. transposon-mobility genes in the C. elegans genome. Among the 62,773 copies of retro- and DNA transposons in the latest assembly of the C. elegans genome (VC2010), 290 transposon-mobility genes conserved the complete open reading frame (ORF) structure. Among them, only 145 genes conserved the critical amino acids at the catalytic core. In contrast to the huge number of transposon copies in the genome, a limited number of genes encoded potentially functional enzymes for transposon mobility. Our finding indicates that a handful number of transposon copies can autonomously transpose in the C. elegansgenome.
WITHDRAWN: Evaluating Patient and Public Involvement (PPI) in NHS Talking Therapies for Anxiety and Depression: A Framework Analysis of PPI Experience and Development of Good Practice Guidelines
Authors: Verbist Irini , Fabian Hannah , Huey Dale , Brooks Helen , Blakemore Amy
Published: September 2023

Background
Patient and public involvement (PPI) in research is increasingly growing. Despite the potential benefits of receiving service-user feedback within healthcare services, PPI remains limited in the context of psychological therapies services. Six PPI meetings, aiming to improve treatment engagement, were held in an NHS Talking Therapies service in Northwest England. The aim of the study is to evaluate the PPI experience and to develop good practice guidelines, hoping to encourage PPI activity within Talking Therapies services.
Methods
The study adopted a qualitative focus group design using a semi-structured topic guide. Five participants were recruited from the PPI meetings, all of whom were ex-service users. Framework analysis, incorporating both inductive and deductive coding, was applied to the transcript. The National Institute of Health Research (NIHR) INVOLVE standards were used as the predetermined themes, namely, respect, support, transparency, responsiveness, fairness of opportunity and accountability.
Results
The members reported an overall positive PPI experience. Acknowledgement of PPI contribution, receiving adequate guidance and flexibility, and acquiring new knowledge increased members’ feelings of empowerment. It was also emphasised that being provided with detailed information about the process and role expectations, as well as enabling inclusivity, encouraged engagement and active participation. The members also offered some suggestions for future involvement, such as ensuring diverse recruitment and discretion. In addition, a new standard was added, “Safe Space”, underscoring the importance of creating a welcoming environment when involving people with past or present mental health difficulties.
Conclusions
To the best of our knowledge, this is the first study presenting good practice guidelines to facilitate the recruitment, engagement, empowerment, and impact of PPI activity in Talking Therapies services. By providing this guidance, we hope that researchers and clinical staff will be encouraged to involve service users in the decision-making of Talking Therapies service improvement.
Single-Atom Tailored Atomically-Precise Nanoclusters for Enhanced Electrochemical CO2 Reduction Activity
Authors: Zang Shuang-Quan , Wang Shan , Wang Yi-Man , Yan Fang-Qin , Wang Qian-You , Du Chen-Xia
Published: September 2023

The development of facile tailoring approach to adjust the intrinsic activity and stability of atomically-precise metal nanoclusters (NCs) catalysts is of great interest but remians challenging. Herein, the well-defined Au8 NCs modified by single-atom (SA) sites were rationally synthesized via a co-eletropolymerization strategy, in which uniformly dispersed metal NC and SA co-entrenched on the poly-carbazole matrix. Systematic characterization and theoretical modeling reveal that functionalizing SAs enable altering the electronic structures of Au8 clusters, which amplifies their electrocatalytic CO2 reduction reaction (CO2RR) activity by ~18.07 fold compared to isolated Au8 metal clusters. The rearrangements of the electronic structure not only strengthen the adsorption of the key intermediates *COOH, but also establish a favorable reaction pathway for the CO2RR. Moreover, this strategy fixing NCs and SAs on cross-linked polymer networks efficiently deduce the performance deactivation caused by agglomeration during the catalytic process. This work contribute to explore the intrinsic activity and stability improvement of metal clusters.
Underwater Image Processing and Target Detection from Particle Swarm Optimization Algorithm
Authors: Zhang Yangmei , Bi Yang , Li Junfang
Published: September 2023

The underwater image obtained is difficult to satisfy human visual perception because of the particle scattering and water absorption phenomena when visible light propagates underwater. In underwater images, light absorption easily leads to image distortion and reduction of image contrast and brightness. Therefore, this work aims to improve the quality of underwater image processing, reduce the distortion rate of underwater images, and further improve the efficiency of underwater image extraction, processing, and tracking. This work combines intelligent blockchain technology in emerging multimedia industries with existing image processing technology to improve the target detection capability of image processing algorithms. Firstly, the theory of visual saliency analysis (VSA) is studied. The steps of image processing using VSA are analyzed. Based on the original Itti model, the visual significance detection step is optimized. Then, the theoretical basis and operation steps of particle swarm optimization (PSO) algorithm in intelligent blockchain technology are studied. VSA theory is combined with PSO to design underwater image processing algorithms and target detection optimization algorithms for underwater images. The experimental results show that: (1) the method has a higher F value and lower Mean Absolute Error. (2) Compared with the original image, the restored image entropy through this method is greatly improved, and the information in the image increases. Therefore, this method has good performance. Besides, this method performs well in image definition, color, and brightness. The quality of the restored image through this method is better than that of other algorithms. (3) Compared with similar algorithms, the relative errors of this method are reduced by 2.56%, 3.24% and 3.89%, respectively. The results show that the method has high accuracy. The research results can provide a reference for future underwater image processing and target detection research. In addition, the designed underwater image processing and target detection and tracking algorithms can improve the detection efficiency and accuracy of underwater targets and help to accurately obtain underwater target images.