bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytotoxic study against L20B cell line, spectral characterizations and DFT theoretical calculations for new dioxidovanadium(V) complexes with dinitrogen donor ligands
Authors: Alajrawy othman , Hadi Huda A. , Al-Luhaibi Roaa S. Awad , Sabar Sarah S. , Ahmed Mohammed , Dawood Ashour
Published: March 2024

Two dioxidovanadium(V) complexes have been prepared with dinitrogen atoms donor (o-phenylenediamine (OPD) and dithiooxamide (DTO)) ligands. The cytotoxicity studies of the prepared complexes against the L20B cell line showed that they have moderated activity against the L20B cell line. The complexes were characterized by different spectral techniques such as FT-IR, UV-Vis., mass, 1H-NMR spectroscopy, magnetic susceptibility, molar conductivity, and finally the spectral data were compared with the data obtained by the DFT theoretical calculations. The obtained spectroscopic data confirmed that the two ligands are coordinated from the two amine groups and in cis-conformation with the two oxygen atoms. The experimental and theoretical calculations showed that the two complexes are mononuclear with proposed distorted octahedral structures. The complexes are very stable, the electronic energies are (-773.10 and − 907.56 a.u.), the HOMO orbitals energies are (-0.386 and − 0.504 a.u.), and the LUMO orbitals energies are (-0.213 and − 0.421 a.u.) for the complexes; respectively. The bond angles around the vanadium(V) atoms are in the range (69.44–91.36 A°), and the dihedral angles are in the range (111.22-161.94 °). Calculations explained the complexes are polarized (3.39–5.28) more than the free ligands (0.002-3.00). The electronic transition in the complex (2) (0.083) is less than for the complex (1) (0.173). The complexes showed good solubility in water. Finally, the best cytotoxic result is for the complex (1) against the L20B cell lines and this open the door to use this complex with oral administration in future studies.
Life skills development of students in Japanese high schools: What is underpinning whole-person education by homeroom teachers?
Authors: Kassai Haruna
Published: March 2024

Homeroom teachers in Japan are responsible for the whole-person education of students, which includes fostering students’ life skills. They provide their teaching based on their own beliefs because there are no official guidelines for homeroom teaching. Since there are very few previous studies on homeroom teachers’ beliefs, this research aims to understand homeroom teachers’ beliefs, which underpin their teaching, and establish a foothold for future research. In order to explore what kinds of students’ life skills homeroom teachers wish to foster through their teaching, data were collected through a questionnaire from 42 homeroom teachers in three different Japanese high schools. Moreover, online interviews were conducted with 16 teachers of the 42 participants to gain insights about factors that affect the formation of their beliefs. According to the findings, homeroom teachers especially emphasise fostering skills to build relationships with others and attitudes to follow rules in society. Furthermore, rather than teacher education, the personal experiences of each teacher affect the formation of these beliefs. These results suggest that to maintain the quality of whole-person education by homeroom teachers, it would be effective to provide teacher trainings focusing on homeroom teaching or opportunities to share beliefs with other teachers.
The Effects of Tetrahydrocurcumin on Adriamycin and Taxane resistance in Anaplastic Thyroid Cancer Cells
Authors: KOCDOR Mehmet Ali , KAYA Yagmur , ATES Halil , BILDIK Ezel , KOCDOR Hilal
Published: March 2024

Purpose Anaplastic thyroid cancer (ATC) is rare but one of the most lethal human malignancy. Despite the advances in cancer treatments, ATC remained incurable due to a lack of effective treatments. ATC cells display resistance against all cytostatics. Adriamycin and taxanes have been used with limited efficacy. There is an urgent need for new treatments and less toxic substances that will enhance the effectiveness of current treatments. One of the most effective curcumin derivative, tetrahydrocurcumin (THC), appears to have several anti-cancer and anti-MDR (multidrug resistance) actions. Thus, we aimed to compare the anti-cancer efficacy of THC with adriamycin and docetaxel, as well as evaluate the anti-MDR action of two drugs in ATC cell lines, if any. Methods We used MTT test to find the IC50 values for Adriamycin (Adr), docetaxel (Doce) and THC (Cur). The cells were treated with IC50 and half-IC50 (IC25) doses. IC25 doses were also used for drug combinations. Wound healing assay, spheroid formation in soft agar, oxidative stress analysis, flow-cytometrically apoptosis, and multidrug resistance activity factor analysis (MAF) for MDR1 (P-gp), MRP1/2, BCRP expressions were performed in both cell lines. Results THC was more potent than docetaxel and adriamycin on cell migration, spheroid formation, anti-oxidant capacity, and apoptosis induction at LD50 dose in both cell lines. THC-induced MAF suppression was found particularly for MDR1 in both cell lines. Whereas adriamycin and docetaxel treatments lead to increased MRP1/2 and BCRP expressions. THC suppressed these actions dose dependent manner. Conclusion THC can modify MDR protein expressions and stem cell properties, which can increase the efficacy of doxorubicin and adriamycin in treating anaplastic thyroid cancer. THC has anti-cancer potential that is comparable to these two cytostatics. Curcumin could be considered an adjunctive component of the ATC treatment.
Systematical comparison reveals distinct brain transcriptomic features in models of depression induced by gut microbiota dysbiosis and chronic stress
Authors: Gui Siwen , Liu Yiyun , Pu Juncai , Wang Dongfang , Zhong Xiaogang , Chen Weiyi , Chen Xiaopeng , Chen Yue , Chen Xiang , Tao Wei , Xie Peng
Published: March 2024

Major depressive disorder (MDD) is a devastating psychiatric illness caused by various etiologies. Both chronic stress and gut microbiome dysbiosis are implicated in the pathogenesis of MDD. However, limited research was undertaken to delineate the distinct effects of these two pathogenic factors on the brain transcriptome. We generated and compared transcriptomic features of anterior cingulate cortex (ACC) from depressive-like mice induced by gut microbiome dysbiosis and canonical chronic stress paradigms, including gene expression pattern and network characteristics. The data derived from MDD patients served as a reference standard to filter the molecular alterations associated with the disorder. Chronic stress induced a plethora of altered genes and biological functions associated with depression, central to which are mitochondrial dysfunction. However, gut microbiota dysbiosis specifically regulated a limited scope of genes and biological mechanisms, targeting the aberrations in vesicular transport systems and the perturbation of autophagy pathways. Network analysis revealed that hierarchical gene co-expression specifically affected by gut microbiota dysbiosis, rather than chronic stress. The further functional clustering analysis and the central distribution of the inflammation-related differentially expressed genes suggested the intricate interplay between disrupted autophagy processes, microglia-mediated inflammation, and synaptic dysfunctions in the network influenced by gut microbiota dysbiosis. Our findings revealed the distinctive transcriptomic alterations of brain shaped by gut microbiota and chronic stress in development of MDD and contributed to understanding the heterogeneity of depression. Additionally, we have provided a valuable data resource and bioinformatic analysis template for further studies.
Top-level para-karate: kata competition performance analysis
Authors: Augustovicova Dusana , Hadza Radovan , Hruby Michal , Magyar Adrian , Biesen Debbie Van
Published: March 2024

Purpose:Para-karate has been gaining popularity at a rapid pace; however, it appears that there is currently limited scientific research on the subject. This study aims to examine the preference of katas performed at para-karate top-level events and investigate a connection between the sport class (type of impairment) and the kata selection.
Methods:Data includes information on katas from 9 events- 4 World Para-karate Championships (2016, 2018, 2021, 2023) and 5 European Para-Karate Championships (2018, 2019, 2021, 2022, 2023). Altogether 906 katas were performed - 567 by males, 339 by females. Data was analysed using descriptive statistics and chi-square test.
Results:During the competition, top para-karate athletes used 61% of the official WKF kata list (62 katas out of 102). The most popular katas were Gojushiho Sho (selected in 19.9% of all performances), Unsu (11.5%), Kanku Sho (9.5%), Suparinpei (6.7%), Jion (6.2%) and others. There was a significant relationship between sport class and the selected katas (p≤0.05). For K30 the most popular kata was Unsu (15%), and for K10 and K21+K22 Gojushiho Sho (16.6% and 30.3% respectively).
Conclusions: The choice of kata for para-karate athletes depends on their impairment, severity of the impairment, and years of experience. Most intellectually impaired athletes individually used only one and the most challenging type of kata for them with a proven lower fast-slow ratio of movement to succeed.
Decoding public’s real-time emotional and cognitive responses to the changing climate on social media
Authors: Liao Qiuyan , Xu Yucan , YUAN Jiehu , Li Sijia
Published: March 2024

The existing research on the associations between climate change-related events and mental well-being outcomes warrants several gaps. These studies either used a mono approach such as cross-sectional surveys or focused on clinical mental health outcomes. Moreover, the underlying mechanism channelling changing climate and real-time emotional well-being as well as their pro-environmental action were seldom studied. This study aimed to address these gaps by integrating multiple data sources, including social media posts about climate change on Weibo (n = 76,514), regional meteorological data (n(records) = 216,476), and regional vulnerability data in China. This study proposed and tested a novel mechanism linking meteorological factors and emotional well-being through three cognitive responses (thinking styles, social affiliations, and somatosensory experiences), and explored their relationships with individuals’ pro-environmental tendencies. Additionally, this study examined the moderating role of regional vulnerability and seasonal effects in the impact of climate change on public emotional well-being. The results revealed that extreme hot days and hotter temperatures were associated with more negative emotional well-being and lower pro-environmental tendencies and that these effects were mediated by individuals’ analytical-intuitive thinking style, social affiliations, and somatosensory experiences and moderated by seasons and regional population density. The implications of these findings for climate change communication and intervention were discussed, emphasizing the role of cognitive responses of the public to enhance coping abilities for climate change and promote pro-environmental behaviours.
Piloting a Community Health and Well-being Worker Model in Cornwall: a guide for implementation and spread
Authors: Tredinnick-Rowe John , Byng Richard , Brown Tamsyn , Chapman Donna
Published: March 2024

Background
This paper evaluates the introduction of ten Community Health and Well-being Workers (CHWW) in four pilot sites across Cornwall. The period evaluated was from the initial start in June 2022 until June 2023, covering the project setup and implementation across a range of Primary Care Networks (PCNs) and Voluntary sector partners (VSCO).
Methods
All ten CHWWs and their managers at each site were interviewed to understand the barriers and enablers to implementation and wider learning that could be captured around the project setup. Qualitative methods were used for data collection, including semi-structured interviews and focus groups. Transcripts were thematically analysed for cross-cutting themes, as well as site-specific effects.
Results
In terms of learning, we cover the following key areas, which were of most importance to the successful implementation of the pilot:
The CHWW's were introduced into an already established, successful social prescribing (SP) system by the time the CHWW project began. CHWWs can access some of the same training and office space as SPs, with overlapping meeting schedules allowing them joint input on some topics. It seemed that all the pre-work in terms of relationships and learning about a similar role helped a rapid implementation.
Each site's CHWW management structure uses the same line management as the SPs. Roles were clustered together to remove duplication, maximise coverage and triaging of residents.
The largest barrier to overcome was integrating VSCO staff into NHS systems. Conversely, hosting CHWWs within an NHS organisation has pros and cons, namely better access to NHS data and staff, but longer lead-in time for registration on systems, and more bureaucracy for procurement/spend.
Conclusions
Looking to the future, the pilot’s success has spread the programme to the other integrated care areas in the country, with ongoing plans for further roll out and evaluation in the coming years.
Expression profile analysis and the role of miRNA in breast adenocarcinoma
Authors: Zhang Ming-Yang , Huang Yi-Min , Lv Xiang , Yang Xingxia , Shen Si-Jia , Wang Jian-Guo , Zhu Juan-Yin
Published: March 2024

To search for hub microRNAs (miRNAs) that might serve as biomarkers for breast cancer (BC), we conducted out comprehensive analysis of data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and whole transcriptome profiling (WT). For overall sample analysis, we found 3 differently expressed miRNA in BC tissues compared to para-carcinoma tissues (PT). Subtype analysis showed that 19, 36 and 19 miRNAs were respectively specific differently expressed in early-stage breast cancer (EBC), advanced stage breast cancer (ABC) and Triple-negative breast cancer (TNBC) compared to PT. Multivariate Cox regression analysis showed that hsa-miR-342-3p and hsa-miR-7705 were independent prognostic factors for overall BC and EBC, respectively. And we found hsa-miR-181b-5p, hsa-miR-3200-3p and hsa-miR-4789-3p were all independent prognostic factors for ABC. Moreover, Kaplan-Meier survival analysis showed that hsa-miR-160b-5p significantly affected the survival of patients in ABC. GSEA demonstrated that tumor related KEGG items (such as cell cycle, ERBB signaling pathway, Wnt signaling pathway, etc.) were differentially enriched in BC. The results of qPCR showed that the expression status of hsa-miR-342-3p, hsa-miR-7705 hsa-miR-160b-5p and hsa-miR-3200-3p were consistent with the results of comprehensive analysis. Finally, this study revealed hsa-miR-342-3p, hsa-miR-7705, hsa-miR-160b-5p and hsa-miR-3200-3p can be used as prognostic biomarkers for BC.
Cyberbullying and mental distress among adolescents in secondary school: Tunisian cross sectional study
Authors: Touhemi Donia Ben , Maryam Chaabane , Khaoula Khemakhem , khadija Chiha , Hela Ayadi , Yousr Moalla
Published: March 2024

Purpose: Ours study aimed to describe the characteristics of adolescents who are victims of cyberbullying and to evaluate the psychological state of these victims.
Methods: This is a cross-sectional, descriptive, and analytical study conducted with a representative sample of adolescents attending 6 schools in the Sfax region during the month of February 2022. The pre-established form containing socio-demographic and family information was used. Cyberbullying was assessed using the "Cyber-Harassment Student Survey". Mental distress was evaluated using the Depression Anxiety Stress Scales (DASS-21), validated in Arabic.
Results: Data was collected data from 396 adolescents, of which 54.8% were female. The average age of participants was 16.65 years.
Cyberbullying was reported by 47% of the surveyed adolescents.
Factors associated with cyberbullying in these adolescents included residing in urban areas (p = 0.017), experiencing relational problems with parents (p = 0.001) and siblings (p = 0.002), the presence of behavioral problems in school (p = 0.009), and low academic performance (p = 0.000)
Among cyberbullying victims, 41.3% reported moderate to severe depressive symptoms; 47.8% had moderate to severe anxiety levels, and 29.5% had moderate to severe stress levels. Cyberbullying was strongly correlated with depression (p < 0.0001), anxiety (p = 0.00), and stress (p = 0.00).
Conclusion: The results of this study indicate that cyberbullying is widespread within schools and has negative consequences on the mental health of young individuals. Recognizing this prevalence is essential and calls for a prevention strategy against cyber-related issues.
Do residents in proximity to blue spaces exhibit lower emotion-related impulsivity? The mediating role of perceived crowdedness
Authors: Liu Jia , Liu Siyi , Meng Jiahui , Meng Yilin , Yang Zhihui
Published: March 2024

Background
Emotion-related impulsivity (ERI) is a significant predisposing factor for various mental health issues and is influenced by individuals' immediate environment. Previous research has largely focused on mitigating ERI through individual-level interventions without extensively considering the role of the external environment. This study explores the impact of passive blue space exposure (PBSE) on ERI, considering both subjective and objective measures of PBSE and investigating the mediating role of perceived crowdedness.
Methods
Two studies were conducted using online platforms to collect data from Chinese residents. Study 1 (n = 369) examined the predictive effect of objective PBSE, as assessed by the normalized difference water index (NDWI), on ERI. Study 2 (n = 374) focused on subjective PBSE and the mediating effect of perceived crowdedness on ERI. Descriptive statistics, correlational analyses, and path analyses were employed to evaluate the relationships between PBSE, perceived crowdedness, and ERI.
Results
Study 1 demonstrated a negative correlation between objective PBSE and ERI, with marginal significance in predictive analysis after controlling for covariates. Study 2 revealed that subjective PBSE was significantly negatively associated with ERI, and perceived crowdedness significantly mediated this relationship. Subjective PBSE reduced perceived crowdedness, which in turn decreased ERI, accounting for 20% of the total effect. The findings suggest that PBSE, both objective and subjective, may serve as a protective factor against ERI.
Conclusions
This research highlights the negative association between PBSE and ERI, extending the understanding of environmental influences on impulsive behavior. It emphasizes the potential of utilizing blue spaces in urban planning and individual exposure to alleviate impulsivity. The study also sheds light on the importance of considering both subjective and objective environmental factors in psychological research and interventions. Future studies should consider a comprehensive approach to measuring PBSE and explore causal relationships through experimental designs.
A Trust-region Framework for Iteration Solution of the Direct INDSCAL Problem in Metric Multidimensional Scaling
Authors: Zhou Xue-lin L. , Li Chao-qian
Published: March 2024

The well-known INdividual Differences SCALing (INDSCAL) model is intended for the simultaneous metric multidimensional scaling (MDS) of several doubly centered matrices of squared dissimilarities. An alternative approach, called for short DINDSCAL (direct INDSCAL), is proposed for analyzing directly the input matrices of squared dissimilarities. In the present work, the problem of fitting the DINDSCAL model to the data is formulated as a Riemannian optimization problem on a product matrix manifold comprised of the Stiefel sub-manifold of zero-sum matrices and non-negative diagonal matrices. A practical algorithm, based on the generic Riemannian trust-region method by Absil et al., is presented to address the underlying problem, which is characterized by global convergence and local superlinear convergence rate. Numerical experiments are conducted to illustrate the efficiency of the proposed method. Furthermore, comparisons with the existing projected gradient approach and some classical methods in the MATLAB toolbox Manopt are also provided to demonstrate the merits of the proposed approach.
Mathematics subject classification: 15A24; 15A57; 65F10; 65F30
The Utilization of Psychosocial Oncology Services by Oral Cancer Patients According to their Language Profile in the Montreal Area: a Real-Word Observational Study Protocol
Authors: Janati Amal Idrissi , Gigliotti Jordan , Sanders Justin , Makhoul Nicholas , Emami Elham , Martel Marc O. , Gosselin Nathalie , Cailhol Lionel , Brown-Johnson Anita , Karra Nour , Ramanakumar Agnihotram V.
Published: March 2024

Background
Many oral cancer patients experience psychosocial distress during their care trajectory. In recent years, psychosocial oncology services have been established in numerous hospitals to support cancer patients with emotional, psychological, or social needs. The use of psychosocial oncology services by oral cancer patients has not been documented, which hinders monitoring and continuous improvement of care. In Quebec, the shortage of care personnel, persistent barriers to screening for distress, and the stigma of using mental health services influence the use of psychosocial oncology services in oral oncology. This impact is particularly highlighted among the English-speaking minority, where challenges in accessing health and mental health services have been reported. Thus, this study aims to generate surveillance data on the use of psychosocial oncology services by oral cancer patients and survivors, according to their official language status in Quebec.
Methods
We will conduct a retrospective cross-sectional study based on real-world data from oral cancer patients who are followed at one of Montreal's major hospital centers. In addition to sociodemographic and clinical data, French-speaking and English-speaking patients will be compared regarding the referral rate to the psychosocial oncology department, the delay and response rate to these requests, and the type of psychosocial oncology services received. Analyses will be conducted to explore factors related to possible differences in the use of psychosocial oncological services between French- and English-speaking patients.
Discussion
Communicating our data to healthcare providers and decision-makers will allow them to review their policies and strategies to promote comprehensive care for oral oncology patients while ensuring equity of access to services between the linguistic minority and majority.
Efficacy and prognosis of surgical treatment for burning hands syndrome patients
Authors: Liu Yapu , Su Yuanyuan , Wang Songmao , Gao Lifeng , Zheng Xiaochen , Ge Hailong , Hou Xiuwei , Wu Guangliang
Published: March 2024

Purpose: Few reports have discussed surgical treatment of patients with burning hands syndrome, a mild variant of traumatic central spinal cord syndrome (TCCS). In this report, we characterized the role of surgical treatment for patients with burning hands syndrome.
Methods: A total of 32 cases from August 2013 to August 2018 met the inclusion criteria, including 26 males and 6 females aged 55.7±10.8 years. All patients complained of burning, numbness, and tingling in hands after cervical hyperextension injury, and no sensory or motor dysfunction of the lower limbs. The graded redefined assessment of strength, sensibility, and prehension (GRASSP) scoring system was used to evaluate upper limb neurological function preoperatively, 1 week after surgery, and at the last follow-up.
Results: All patients were followed up for more than 24 months, with an average follow-up of 50.4±18.4 months. The nerve function of the upper limbs had recovered significantly after 1 week and at the last follow-up. The percentage of patients showing improvement at 1 week after surgery was 44.7±2.6% for dorsal sensory function, 44.8±2.7% for palmar sensory function, 46.4±3.4% for strength, 44.3±4.1% for prehension ability, and 48.7±3.6% for prehension performance. The percentage of patients showing improvement at the last follow-up period was 90.2±2.5% for dorsal sensory function, 89.0±2.5% for palmar sensory function, 93.3±2.5% for strength, 91.3±2.8% for prehension ability, and 91.4±2.5% for prehension performance.
Conclusions: Our results show that surgical decompression and internal fixation in patients with burning hands syndrome can achieve good neurological recovery.
Open Innovation and Regulatory Challenges in New Modality Development: The Pivotal Role of CDMOs in Advancing Antibody Drugs
Authors: Yoshiura Hiromu , Kawata Yayoi , Sengoku Shintaro
Published: March 2024

Background Ensuring regulatory-compliant manufacturing capability is an essential challenge for new treatment modalities, but its internalisation is not easy for pharmaceutical companies, especially start-ups. This study examines the functions and requirements of contracted development and manufacturing organisations (CDMOs) using the development process of antibody medicines as a case study.
Methods Utilizing PubMed, Cortellis and Patent Integration databases, this study delves into publication and contractual trends in monoclonal antibody drugs (mAbs) development, alongside an analysis of patent filings by CDMOs, offering a comprehensive overview of the evolving landscape in mAbs innovation.
Results In the early stages of mAbs development, dedicated bio firms (DBFs) led R&D with superior drug discovery technology but lacked manufacturing capability, which was complemented by CDMOs. This collaboration was an opportunity for CDMOs to expand their capabilities beyond manufacturing technology into antibody drug candidate discovery and structural optimisation technology. From mid-development onwards, it established a technology platform based on these capabilities and developed and established partnerships with existing pharmaceutical companies, including mega pharma.
Conclusions The impact of institutions and regulations on the innovation process was assessed during this development process. These findings are expected to provide valuable insights into the innovation system for new modalities.
Comparison of Subjective and Objective Visual Quality of Two Main Types of Refractive Surgeries in Early Postoperative Stage
Authors: Zou Zongyin , Li Hui , He Runzhang , Nong Yating , Zhou Sheng , Yang Jing
Published: March 2024

Purpose:
To explore subjective and objective visual quality of patients who underwent laser refractive surgery and ICL implantation in early postoperative stage after adjusting the imbalance of the baseline characteristics.
Methods:
This retrospective study included 58eyes with myopia and myopic astigmatism who underwent ICL V4c implantation or laser refractive surgery (including SMILE and FS-LASIK) in our hospital from July 2022 to December 2021. Objective visual quality mainly including higher-order aberrations (HOAs) were measured using an OPD-Scan III aberrometer (Nidek Co., Ltd., Gamagori, Japan) preoperatively and 1 week postoperatively. The subjective visual quality was obtained through the Quality of Vision (QoV) questionnaire. The propensity score inverse probability of treatment weighting (PS-IPTW) was used to balance the baseline characteristics.
Results:
After IPTW, the confounding factors with statistical significance between laser refractive surgery group and ICL implantation group. Before IPTW, the objective visual quality of laser refractive surgery was better than ICL implantation. However, after IPTW, only spherical aberration(p＝0.023) is statistically different between two groups. The patients who underwent laser refractive surgery reported better subjective visual quality in frequency(p＝0.020), severity(p＝0.043) and bothersome(p＝0.002). But two groups showed no significant difference after IPTW.
Conclusion:
The subjective and objective visual quality of patients who underwent laser refractive surgery and ICL implantation are relatively similar in early postoperative stage. The better subjective and objective visual quality in laser refractive surgery than ICL implantation could be influenced by imbalanced baseline characteristics.
Identification of plasma exosomal lncRNA as a biomarker for early diagnosis of gastric cancer
Authors: wei ye , Hu Xuming , Yuan Shuai , Zhao Yue , Zhu Chunhui , Guo Mingzhou , Cui Hengmi
Published: March 2024

Background,
there were about 1,090,000 gastric cancer(GC) cases in 2020 in China. The incidence and mortality rates ranked the fifth and third among all kinds of cancers in China. Early diagnosis plays an important role in the treatment and prognosis of gastric cancer. In recent years, noninvasive diagnosis, especially plasma exosome lncRNAs, has become a promissing biomarkers with high specificity and sensitivity for early diagnosis of cancers.
Methods, in this study, the exosomes in the plasma of patients with early gastric cancer were isolated by a commercial kit. After identified by electron microscopy observation, particle size analysis and western-blot verification, the lncRNAs in the exosomes were extracted. The lncRNAs differentially expressed in the plasma exosomes of patients with gastric cancer were analysized by high-throughput RNA sequencing(RNA-Seq). The differentially expressed lncRNAs were verified by RT-qPCR in 93 patients with early gastric cancer and 49 normal controls.
Results, Electron microscopy, particle size analysis and western blot showed that exosomes were successfully isolated from plasma. RNA-Seq results show that 76 lncRNAs were up-regulated and 260 lncRNAs were down regulated in plasma exosomes of early gastric cancer patients compared with normal controls. RT-qPCR analysis indicated that a total of 6 lncRNAs were significantly and differentially expressed in gastric cancer patients compared to normal controls, with 2 (lncmstrg. 1319590,Lncmstrg. 2312697) highly expressed and 4 lowly expressed (lncmstr-g.1004024.1, lncmstrg. 2441832.8, lncmstrg. 315376.1, lncmstrg. 907985.2,)(p < 0.05). The survival curve analysis indicated that lncmstrg.2441832.8 and lncmstrg.2312697 had higher sensitivity and specificity for the diagnosis of gastric cancer, respectively and AUC curve areas were 0.6211 and 0.631, p < 0.05, respectively, which were greater than the traditional clinical detection indexes CEA (0.61) and AFP (0.57). When combined lncmstrg.2441832.8 and lncmstrg.2312697 in gastric cancer diagnosis, AUC curve area reached 0.73, which was greater than CA199 (0.71).
Conclusion, lncmstrg.2441832.8 and lncmstrg.2312697 may be a potential and promissing biomarkers for early diagnosis of gastric cancer.
A novel structure of vehicle motion cueing algorithm for a pneumatic motion simulation platform
Authors: Liu Chao , Li Li , Zhao Ling
Published: March 2024

In this paper, a novel structure of motion cueing algorithm (MCA) is proposed to simulate translational accelerations and angular velocities of vehicles on a pneumatic motion simulation platform (PMSP). The designed MCA includes nonlinear scaling algorithm, linear quadraticregulator (LQR), low pass filter and data fusion algorithm.Taking into account absolute sensory thresholds of human vestibular organ, the nonlinear scaling algorithm is designed to scale the translational accelerations and angular velocities of vehicles for ensuring the outputs of the MCA are inangular displacement ranges of the PMSP. According to the model of otolith organ and semicirular canal, the LQR ispresented to constrain the perception errors between the vehicles and PMSP. The data fusion algorithm is proposed to obtain desired angular displacement of the PMSP from the outputs of the nonlinear scaling algorithm for reducing perception errors. Considering the ranges of deflection angleand angular velocity on the PMSP, perception errors and absolute sensory thresholds, gains of the MCA are optimized by genetic algorithm. Note that the designed MCA can notonly be applied to the PMSP, but also be extended to the classical 6-degree-of-freedom platform for improving simulation performance. Finally, the effectiveness of the proposed algorithm is verified by real experiment using an active disturbance rejection controller.
A systematic computational DFT study for the phosphorus based drug-carrier mechanism for heparin a life-saving anticoagulant for cardiovascular diseases
Authors: Ahmad A. , Abahussain A. A.M , Nazir M. H. , Zaidi S. Z.J.
Published: March 2024

Cardiovascular diseases (CVDs) are the major cause of global morbidity and mortality, representing a substantial burden on global healthcare. Thrombotic events serve as major determinants of patient outcomes. Heparin, an anticoagulant drug, is crucial in treating thrombotic disorders. Its clinical utility is limited due to the challenges related to targeted delivery. In this study, we employed computational material modeling techniques using DFT calculations to investigate the potential of black phosphorus as drug carrier for heparin drug delivery. Thermodynamic favorability of interaction between drug and carrier is investigated by adsorption energies calculations. Molecular orbital analysis reveals the electron transfer process and potential reactivity of drug, carrier and their complexes, important for understanding the drug delivery mechanism. The properties such as chemical potential, chemical hardness, chemical softness and global electrophilicity index are computed to study the stability of drug delivery complexes. Weak intermolecular interactions between heparin and black phosphorus are highlighted by non-covalent interaction (NCI) analysis. UV-vis analysis was employed to generate UV-vis spectra of drug delivery complexes. These spectra reveal the potential photochemical properties of complexes, crucial for triggering drug delivery mechanism. This study presents the valuable insights into the therapeutic potential of black phosphorus as drug carrier for heparin drug delivery to treat cardiovascular diseases such as thrombotic events.
The cerebral blood flow response to neuroactivation is reduced in cognitively normal men with β-amyloid accumulation
Authors: Vestergaard Mark Bitsch , Bakhtiari Aftab , Osler Merete , Mortensen Erik Lykke , Lindberg Ulrich , Law Ian , Lauritzen Martin , Benedek Krisztina , Larsson Henrik Bo Wiberg
Published: March 2024

Background
Accumulation of β-amyloid (Aβ) in the brain is a hallmark of Alzheimer’s Disease (AD). Cerebral deposition of Aβ initiates deteriorating pathways which eventually can lead to AD. However, the exact mechanisms are not known. A possible pathway could be that Aβ affects the cerebral vessels, causing inadequate cerebrovascular function. In the present study, we examined if Aβ accumulation is associated with a reduced cerebral blood flow response (CBF) to neuronal activation by visual stimulation (DCBFVis.Act) in cognitively normal subjects from the Metropolit Danish Male Birth Cohort.
Methods
64 subjects participated in the present study. DCBFVis.Act was measured using arterial spin labelling (ASL) combined with blood-oxygen-level-dependent (BOLD) MRI. Neuronal activation was obtained by visual stimulation by a flickering checkerboard presented on a screen in the MRI-scanner. Brain Aβ accumulation and cerebral glucose metabolism were assessed by PET imaging using the radiotracers [11C]Pittsburgh Compound-B (PiB) and [18F]Fluorodeoxyglucose (FDG), respectively. Cortical thickness was measured from structural MRI.
Results
DCBFVis.Act correlated negatively (\(\beta\) = -32.1 [95% confidence interval (CI): -60.2 ; -4.1], r = -0.30, p = 0.025) with PiB standardized uptake value ratio (SUVr) in the brain regions activated by visual stimulation. DCBFVis.Act did not correlate with FDG SUVr (\(\beta\) = 1.9 [CI: -23.8 ; 27.6], r = 0.02, p = 0.88) or cortical thickness (\(\beta\) = 10.3 [CI: -8.4 ; 29.0], r = 0.15, p = 0.27) in the activated brain regions. Resting CBF did not correlate with PiB SUVr neither in the regions activated by visual stimulation (\(\beta\) = -17.8 [CI:-71.9 ; 36.2], r = 0.09, p = 0.51) nor in the remaining cortex (\(\beta\) = 5.2 [CI:-3.9 ; 14.2], r = 0.15, p = 0.26).
Conclusion
We found a correlation between high PiB SUVr and reduced CBF response to neuronal activation, indicating a link between Aβ accumulation and impaired cerebrovascular function. The impairment was not associated with cortical thinning or hypometabolism, suggesting that Aβ accumulation affecting brain vessel function could be a very early pathology leading to neurodegenerative disease.
Contrasting metabolic responses of two chickpea varieties to root infection by Phytophthora are influenced by arbuscular mycorrhizal inoculation
Authors: Weinberger Natascha V. , Powell Jeff R. , Mikhael Meena , Plett Krista L. , Plett Jonathan M.
Published: March 2024

Most terrestrial plants, including important crop plants like chickpea (Cicer arietinum), benefit from mutualistic symbiosis with arbuscular mycorrhizal (AM) fungi due to enhanced nutrition and improved immune responses. Although this latter phenomenon, so-called Mycorrhiza Induced Resistance (MIR), is well-reported and metabolic adjustments have been observed, the diversity of mechanisms by which AM fungi prime disease resistance are still poorly understood. Using two chickpea varieties (Sonali and Kyabra) we investigated how differential host genotypes may impact AM-mediated defence responses against a root rot pathogen, Phytophthora medicaginis. Inoculation with Rhizophagus irregularis significantly inhibited disease-related biomass losses in Kyabra, while no impact on plant biomass was observed in Sonali. Using root metabolomic profiling, we detected 143 metabolic features which exhibited significant variation between at least two experimental conditions. Most noteable, the two chickpea varieties tested largely showed opposing metabolomic responses to microbial exposure. Furthermore, co-innoculation of pathogenic and beneficial microbes led to a core set of differentially expressed metabolomic features in Kyabra and Sonali. These results demonstrate contrasting levels of metabolomic responses to microbial inoculation and reveal potential molecular features involved in MIR in a globally relevant crop.
Salidroside alleviates inflammatory reaction and sciatic nerve injury by inhibiting AKT/NF-κB pathway
Authors: Chen Linyan , Meng Yun , Shao Xiaoyu , Song Qimin , Che Fengyuan
Published: March 2024

Background
Peripheral nerve injury is a common traumatic nerve injury disease with poor prognosis. Salidroside is a natural compound extracted from the plant Rhodiola, which has been proved to have neuroprotective effect. This experiment studied the therapeutic effect of salidroside on peripheral nerve injury.
Methods
Establishment of sciatic nerve injury model in Sprague-Dawley adult rats by arterial compression. Bsso-Beattie-Bresnahan(BBB score, F-wave and Tce-MEP were used to compare the motor and nerve conduction functions of rats. Histological differences were observed by Histological assessments and transmission electron microscopy. The rat model of sciatic nerve injury was selected and salidroside injection was injected for 14 consecutive days. The effects of salidroside on motor and nerve conduction function of SNI rats were evaluated by behavioral and electrophysiological monitoring. Histological changes were observed by HE staining and transmission electron microscope. Establishment of Schwann cell inflammation model. The expression of ROS was detected. The expressions of inflammatory factors and nerve growth factors in sciatic nerve tissue and RSC96 cells of rats were detected by QRT-PCR and western blotting.
Results
The compression of arteries causes sciatic nerve injury in different degrees. The motor and nerve conduction function of rats decreased, myelin sheath and axon were damaged, and the level of inflammation increased. Salidroside improved the nerve function and morphology of rats, reduced neuroinflammation and promoted the expression of nerve growth factor. Salidroside down-regulated the expression of inflammation in Schwann cells treated with LPS, reduced the production of ROS and promoted the secretion of nerve growth factor.
Conclusion
Sciatic nerve injury caused by arterial entrapment produces persistent neuroinflammatory reaction. Salidroside reduces the expression of inflammatory factor TNF-α through AKT/NF-κB pathway, up-regulates the expression of NGF, promotes myelin sheath growth and axon regeneration, and improves the neurological function of SNI rats.
Bile acid metabolism Modulate intestinal immunity involved in ulcerative colitis progression
Authors: Huang Hua , Yan Shuai , Guo Tianwei , Hua Qiuwen , Wang Yongtong , Ji Lijiang
Published: March 2024

Background: Bile acid is an important participant in intestinal immunity and inflammation, which exert their immune regulatory effects by interacting with immune cells in the intestine，many immune cells are involved in the pathogenesis of ulcerative colitis (UC), but the underlying mechanisms between Bile acid and immunity are unknown.
Object: The aim of this study was to investigate the relationship between Bile acid metabolism (BCM) and inflammation in colonic tissues and to identify potential therapeutic targets for modulating immune responses.
Methods: A total of 2,318 differentially expressed genes (DEGs) and 35 BCM-associated DEGs were obtained, and the results of gene ontology analysis showed that DEGs were significantly enriched in the positive regulation of NK cell and T cell activation. Fifteen types of immune cells were identified in inflamed colon tissues.
Results: Five BCM-associated DEGs (APOA1, AMACR, PEX19, CH25H, and AQP9) were highly correlated with immune-associated DEGs and all were significantly up/down-regulated in immune cells. And we further found at the cellular level that AQP9 gene expression may be regulated by IFN-γ- JAK signaling pathway promotes CD8+T cell activation.
Conclusion: This study contributes to the understanding of the pathogenesis and the mechanism of BCM in UC immune cells.
Predictors of flares in recent-onset psoriatic arthritis. Results of a multivariable model based on machine learning
Authors: Queiro Rubén , Seoane-Mato Daniel , Agirregoikoa Eva Galindez , Cañete Juan D. , Gratacós Jordi , Juanola Xavier , Fiter Jordi , Marcos Ana González , Laiz Ana
Published: March 2024

Background
Predicting the occurrence of a flare using tools and information that are readily available in daily clinical practice would provide added value in disease management. Scarcely any studies address this issue. The aim was to identify patient- and disease-related characteristics predicting flares in recent-onset PsA.
Methods
We performed a multicenter observational prospective study (2-year follow-up, regular annual visits). The study population comprised patients aged ≥ 18 years, fullfilling the CASPAR criteria and less than 2 years since the onset of symptoms. Flares were defined as inflammatory episodes affecting the axial skeleton and/or peripheral joints (joints, digits or entheses), diagnosed by a rheumatologist. The dataset contained data for the independent variables from the baseline visit and from follow-up visit number 1. These were matched with the outcome measures from follow-up visits 1 and 2, respectively. We trained a logistic regression model and random forest–type and XGBoost machine learning algorithms to analyze the association between the outcome measure and the variables selected in the bivariate analysis. A k-fold cross-validation with k = 5 was performed.
Results
At the first follow-up visit, 37.6% of the patients who attended the clinic had experienced flares since the baseline visit. Of those who attended the second visit, 27.4% had experienced flares since the first visit. The number of observations for the multivariate analysis was 295.The variables predicting flares between visits were PsAID, number of digits with onychopathy, age-adjusted Charlson comorbidity index and level of physical activity. The mean values of the measures of validity of the machine learning algorithms were all high, especially sensitivity (95.71%. 95% CI: 79.84–100.00).
Conclusions
These findings provide guidance not only on general measures (regular physical activity), but also on therapy (drugs addressing nail disease).
Enhancing Class Diagram Dynamics: A Natural Language Approach with ChatGPT
Authors: Djaber ROUABHIA
Published: March 2024

The present research introduces an innovative methodology, assisted by artificial intelligence, aimed at enhancing the dynamics of class diagrams within the field of software engineering. This methodology employs advanced language models, such as ChatGPT, to address the limitations inherent in traditional manual methods, particularly when dealing with complex systems. The approach is iterative, analyzing natural language use cases in detail and extracting key insights through the language understanding capabilities of ChatGPT. These insights are then integrated into a UML class diagram, resulting in demonstrable improvements in both accuracy and completeness. The updated diagram, supplemented with explicit methods derived from use cases, offers a more precise delineation of functional responsibilities and improved class relationships. This leads to a more comprehensive understanding of system interactions. This methodology, which is both versatile and efficient, aligns with UML best practices and holds significant value for Agile development. While further evaluation is necessary, preliminary findings suggest that AI-driven approaches hold considerable potential for enhancing the dynamics of class diagrams and advancing software development practices.
Tracking The Molecular Dynamics of Lineage Switch Under CD19 CAR-T Treatment in Non-KMT2A Rearranged B-ALL Patients
Authors: Wang Jianxiang , Qiu Shaowei , Mei Yihan , Gu Runxia , Liu Yu , Chen Manling , Xing Haiyan , Tang Kejing , Tian Zheng , Rao Qing , Yang Donglin , Pang Aiming , Wei Shuning , Jia Yujiao , Wang Huijun , Feng Sizhou , Wei Hui , Zhu Ping , Wang Min , Wang Ying , Liu Wenbing
Published: March 2024

Lineage switch in B-acute lymphoblastic leukemia (B-ALL) patients is a rare event during CD19 chimeric antigen receptor (CAR)-T treatment. Some studies have reported KMT2A rearrangements (KMT2A-r) as a risk factor in lineage switch, but the underlying mechanism of non-KMT2A-r cases remains unclear. Here, we described two young adult B-ALL lineage switch cases without KMT2A-r. Our analysis revealed lineage-specific transcription factors and surface markers related alterations, while major gene mutations remain unchanged. By reconstructing developmental trajectories, B-progenitor-like blasts were found to be reprogrammed into myeloid blasts after CAR-T treatment. Interestingly, we observed the increase of BCOR/BCORL1 truncating mutation burden at myeloid relapse in both cases. By retrospective analysis, we found that BCOR/BCORL1 gene mutated patients possessed myeloid-related features, indicating it as a potential risk factor for lineage switch. In summary, we established a study paradigm about lineage switch by single-cell technologies, which may be applied to clinical practice.