bluuebunny/crossref_metadata_2025 huggingface dataset:
1. Europe
Authors: Brasili Andrea , Kolev Atanas , Revoltella Debora , Schantz Jochen , Tueske Annamaria
Published: December 2023

This chapter describes the dynamics of public investment over the review period and its likely path ahead. In 2022, public investment growth largely exceeded total expenditures growth, and it is set to increase further. The reinstatement of fiscal rules (after the deactivation of the General Escape Clause) would not necessarily lead to a decline in public investment thanks to the financial resources provided by the RRF. Meanwhile, there is some tentative evidence that high inflation and capacity constraints in the public administration are slowing the implementation of the RRF. Improving implementation capacity is key for the success of the existing plans and preserving absorption capacity for future investments is crucial for Europe to maintain a leading role in the needed digital, green, and energy transitions.
4. Italy’s Public Investments
Authors: Barbieri Giovanni , Cerniglia Floriana , Dia Enzo
Published: December 2023

This chapter provides the country report on Italy with an analysis of the role the Italian National Recovery and Resilience Plan in boosting public investment up to and beyond 2026. Italy’s NRRP has more than 235 billion euros available for investments and reforms, making it one of the most remarkable modernization initiatives in the last seventy years. The impact of the NRRP is assessed and specific implementation challenges are highlighted, some of which have been caused by factors such as fragmented governance, a lack of effective monitoring, and compliance issues. Overcoming these difficulties is crucial for continuing to receive disbursements from the Commission. The effectiveness of its governance is examined. An open question is how to ensure a positive capital-spending trajectory in Italy (especially after 2026) in compliance with the new rules set out in the Stability and Growth Pact.
8. Making Green Public Investments a Reality in the EU Fiscal Framework and the EU Budget
Authors: Pekanov Atanas , Schratzenstaller-Altzinger Margit
Published: December 2023

Additional green public investment at the Member-State level will be needed to address the climate emergency as a central priority in the EU. This chapter discusses two paths to enable increased green public investments in the EU: through possible amendments to the current EU fiscal framework or through funding from the EU budget. The Commission’s proposal from November 2022 regarding orientations for a reform of the EU-governance framework widens the leeway for debt-financed public investment. However, existing green public investment needs are not considered sufficiently. Therefore, we discuss several options to enable the flexibility of national budgets to ensure a level of green public investment which―together with private resources―is sufficient to close the existing green investment gaps. In addition, the use of the lever the EU budget theoretically offers to contribute to green public investment in the EU needs to be intensified. At about 1% of EU GNI (1.7% of EU GNI including NGEU) the overall volume of the EU budget is limited. The more important are steps to strengthen spending in policies that create EU value added, inter alia green public investment.
Optimum Estimation of Coastal Currents Using Moving Vehicles
Authors: Chen KuanYu , Huang Chen-Fen , Zheng Zhe-Wen , Lin Sheng-Fong , Liu Jin-Yuan , Guo Jenhwa
Published: December 2023

Ocean acoustic tomography (OAT) deploys most moored stations on the periphery of the tomographic region to sense the solenoidal current field. Moving vehicle tomography (MVT), an advancement of OAT, not only samples the region from various angles for improving the resolution of mapped currents but also acquires information about the irrotational flow due to the sampling points inside the region. To reconstruct a complete two-dimensional current field, the spatial modes derived from the open-boundary modal analysis (OMA) are preferable to the conventional truncated Fourier series since the OMA technique describes the solenoidal and irrotational flows efficiently in which all modes satisfy the coastline and open boundary conditions. Comparisons of the reconstructions are presented using three different representations of currents. The first two representations explain only the solenoidal flow: the truncated Fourier series and the OMA Dirichlet modes. The third representation, accounting for the solenoidal and irrotational flows, uses all the OMA modes. For reconstructing the solenoidal flow, the OMA representation with the Dirichlet modes performs better than the Fourier series. A large difference appears near the bay mouth, where the OMA-Dirichlet reconstruction shows a better fit to the uniform currents. However, considerable uncertainty exists outside the bay mouth where the irrotational currents dominate. This can be improved by the third representation with the inclusion of the Neumann and boundary modes. The reconstruction results using field data were validated against the acoustic Doppler current profiler (ADCP) measurements. Additionally, incorporating constraints from ADCP measurements enhances the accuracy of the reconstruction.

Significance Statement

This study contributes toward improving our understanding of accurately measuring oceanic circulation patterns over large areas without relying solely upon stationary sensors or satellite imagery. The study combines multiple sources, such as shipboard ADCP and tomographic techniques, to obtain a complete picture of what is happening beneath surface waters across entire regions under investigation. It has important implications for fields such as climate science, marine biology, and fisheries management, where accurate knowledge of the movement and distribution of water masses is crucial for predicting future trends and making informed decisions.
Urinary metabolite of pesticide, 3,5,6-trichloropyridinol, is associated with all-cause but not with cancer mortality
Authors: Qiao Fulu , Ma Teng , Wang Xia , Zhang Feng , Wan Long
Published: December 2023

3,5,6-trichloropyridinol (TCPY) is a metabolite of chlorpyrifos and chlorpyrifos-methyl, whose presence in the environment is of potential toxicity to human. So, it is need to monitor and regualte TCPY levels to protect human health. However, it is not known whether TCPY is associated with all-cause and cancer mortality and to which degree its levels contributed to hazard risk. The study enrolled 3951 participants from the National Health and Nutrition Examination Surveys (NHANES). Ultra-high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry was used to measure urinary TCPY. Cox proportional hazards regression analysis was performed to explore the associations between TCPY and all-cause and cancer mortality. The study found that the average level of TCPY in the cohort was 1.79 μg/L and was higher in those who had passed away. Individuals in the highest quartile had a 1.56-fold independent increase in rate for all-cause mortality compared to those in the lowest quartile (hazard ratio [HR] 1.56, 95% confidence interval 1.09–2.24, p = 0.002). However, while the univariate model showed a hazard ratio of 2.37 (1.19–4.71) for the highest quartile in regards to cancer mortality, this association disappeared after adjusting for demographics, lifestyles, and comorbidities. Exposure to urinary 3,5,6-trichloropyridinol, as a result of insecticide exposure, increased the rate of all-cause mortality but was not independently associated with cancer mortality.
Transcriptomic analysis reveals the early body wall regeneration mechanism of the sea cucumber Holothuria leucospilota after artificially induced transverse fission
Authors: Liu Renhui , Ren Xinyue , Wang Junyan , Chen Ting , Sun Xinyu , Lin Tiehao , Huang Jiasheng , Guo Zhengyan , Luo Ling , Ren Chunhua , Luo Peng , Hu Chaoqun , Cao Xudong , Yan Aifen , Yuan Lihong
Published: December 2023

Background

Sea cucumbers exhibit a remarkable ability to regenerate damaged or lost tissues and organs, making them an outstanding model system for investigating processes and mechanisms of regeneration. They can also reproduce asexually by transverse fission, whereby the anterior and posterior bodies can regenerate independently. Despite the recent focus on intestinal regeneration, the molecular mechanisms underlying body wall regeneration in sea cucumbers still remain unclear.

Results

In this study, transverse fission was induced in the tropical sea cucumber, Holothuria leucospilota, through constrainment using rubber bands. Histological examination revealed the degradation and loosening of collagen fibers on day-3, followed by increased density but disorganization of the connective tissue on day-7 of regeneration. An Illumina transcriptome analysis was performed on the H. leucospilota at 0-, 3- and 7-days after artificially induced fission. The differential expression genes were classified and enriched by GO terms and KEGG database, respectively. An upregulation of genes associated with extracellular matrix remodeling was observed, while a downregulation of pluripotency factors Myc, Klf2 and Oct1 was detected, although Sox2 showed an upregulation in expression. In addition, this study also identified progressively declining expression of transcription factors in the Wnt, Hippo, TGF-β, and MAPK signaling pathways. Moreover, changes in genes related to development, stress response, apoptosis, and cytoskeleton formation were observed. The localization of the related genes was further confirmed through in situ hybridization.

Conclusion

The early regeneration of H. leucospilota body wall is associated with the degradation and subsequent reconstruction of the extracellular matrix. Pluripotency factors participate in the regenerative process. Multiple transcription factors involved in regulating cell proliferation were found to be gradually downregulated, indicating reduced cell proliferation. Moreover, genes related to development, stress response, apoptosis, and cell cytoskeleton formation were also involved in this process. Overall, this study provides new insights into the mechanisms of whole-body regeneration and uncover potential cross-species regenerative-related genes.
Targeting antimalarial metabolites from the actinomycetes associated with the Red Sea sponge Callyspongia siphonella using a metabolomic method
Authors: Gamaleldin Noha M. , Bahr Hebatallah S. , Millán-Aguiñaga Natalie , Danesh Mahshid , Othman Eman M. , Dandekar Thomas , Hassan Hossam M. , Abdelmohsen Usama Ramadan
Published: December 2023

Malaria is a persistent illness that is still a public health issue. On the other hand, marine organisms are considered a rich source of anti‑infective drugs and other medically significant compounds. Herein, we reported the isolation of the actinomycete associated with the Red Sea sponge Callyspongia siphonella. Using "one strain many compounds" (OSMAC) approach, a suitable strain was identified and then sub-cultured in three different media (M1, ISP2 and OLIGO). The extracts were evaluated for their in-vitro antimalarial activity against Plasmodium falciparum strain and subsequently analyzed by Liquid chromatography coupled with high-resolution mass spectrometry (LC-HR-MS). In addition, MetaboAnalyst 5.0 was used to statistically analyze the LC-MS data. Finally, Molecular docking was carried out for the dereplicated metabolites against lysyl-tRNA synthetase (PfKRS1). The phylogenetic study of the 16S rRNA sequence of the actinomycete isolate revealed its affiliation to Streptomyces genus. Antimalarial screening revealed that ISP2 media is the most active against Plasmodium falciparum strain. Based on LC-HR-MS based metabolomics and multivariate analyses, the static cultures of the media, ISP2 (ISP2-S) and M1 (M1-S), are the optimal media for metabolites production. OPLS-DA suggested that quinone derivatives are abundant in the extracts with the highest antimalarial activity. Fifteen compounds were identified where eight of these metabolites were correlated to the observed antimalarial activity of the active extracts. According to molecular docking experiments, saframycin Y3 and juglomycin E showed the greatest binding energy scores (-6.2 and -5.13) to lysyl-tRNA synthetase (PfKRS1), respectively. Using metabolomics and molecular docking investigation, the quinones, saframycin Y3 (5) and juglomycin E (1) were identified as promising antimalarial therapeutic candidates. Our approach can be used as a first evaluation stage in natural product drug development, facilitating the separation of chosen metabolites, particularly biologically active ones.
Stress-related cellular pathophysiology as a crosstalk risk factor for neurocognitive and psychiatric disorders
Authors: Palamarchuk Iryna S. , Slavich George M. , Vaillancourt Tracy , Rajji Tarek K.
Published: December 2023

In this narrative review, we examine biological processes linking psychological stress and cognition, with a focus on how psychological stress can activate multiple neurobiological mechanisms that drive cognitive decline and behavioral change. First, we describe the general neurobiology of the stress response to define neurocognitive stress reactivity. Second, we review aspects of epigenetic regulation, synaptic transmission, sex hormones, photoperiodic plasticity, and psychoneuroimmunological processes that can contribute to cognitive decline and neuropsychiatric conditions. Third, we explain mechanistic processes linking the stress response and neuropathology. Fourth, we discuss molecular nuances such as an interplay between kinases and proteins, as well as differential role of sex hormones, that can increase vulnerability to cognitive and emotional dysregulation following stress. Finally, we explicate several testable hypotheses for stress, neurocognitive, and neuropsychiatric research. Together, this work highlights how stress processes alter neurophysiology on multiple levels to increase individuals’ risk for neurocognitive and psychiatric disorders, and points toward novel therapeutic targets for mitigating these effects. The resulting models can thus advance dementia and mental health research, and translational neuroscience, with an eye toward clinical application in cognitive and behavioral neurology, and psychiatry.
The creation and validation of predictive models to assess the risk of unfavorable outcomes following hybrid total arch repair for Stanford type A aortic dissection
Authors: Liu Xinyi , Liu Xing , Yang Yuehang , Zhang Ai , Shi Jiawei , Li Huadong , Liu Junwei , Jiang Xionggang , Wang Zhiwen
Published: December 2023

Background

The objective of this study was to develop and validate a nomogram for the individualized prediction of adverse events in patients with Stanford type A aortic dissection (TAAD) undergoing hybrid total aortic arch repair.

Methods

From April 2019 to April 2022, we conducted a comprehensive review of the medical records of Stanford type A aortic dissection patients who underwent hybrid total aortic arch repair surgery at our hospital. Patients were separated into two groups based on whether or not a composite adverse event occurred following surgery. Using univariate and multivariate analyses of logistic regression, the prediction model was created. Construct risk prediction models utilizing nomograms and evaluate their precision, discrimination, and clinical utility.

Results

Age, platelets, serum blood urea nitrogen, and ascending aortic diameter were the variables included in the nomogram by univariate and multivariate analysis. The risk model performed well in internal validation, with an area under the curve (AUC) of 0.829. The calibration curve demonstrated good agreement between predicted and actual probabilities (Hosmer-Lemeshow test, P = 0.22). Clinical decision analysis curves demonstrate predictive nomograms’ clinical utility.

Conclusion

This study created and validated a nomogram for predicting the risk of composite endpoint events in TAAD patients undergoing hybrid total aortic arch repair. The nomogram can help determine the severity of a patient’s condition and provide a more personalized diagnosis and treatment.
Use of a combination of diaphragmatic ultrasound and muscle relaxation monitoring in predicting post-extubation adverse respiratory events among elderly patients in an anesthesia intensive care unit
Authors: Huang Lun , Xia Bo , Cheng Lei , Hu Xian-Wen , Zheng Li-Dong , Cheng Feng
Published: December 2023

Objective

The purpose of this study was to examine the feasibility of using a combination of diaphragmatic ultrasound and muscle relaxation monitoring in predicting adverse respiratory events after extubation among elderly patients in an anesthetic intensive care unit (AICU).

Methods

The study participants were 120 elderly patients who were in the AICU after laparoscopic radical resection for colorectal cancer. Based on whether there were critical respiratory events (CREs) after extubation, they were divided into the adverse event group and the non-adverse event group. We used logistic regression to identify factors influencing the occurrence of CREs post-extubation in elderly patients. Using the receiver operating characteristic (ROC) curve, we analyzed the value of each indicator in predicting CREs post-extubation.

Results

We included 109 patients in the final analysis. In the adverse event group (n = 19), the age, proportion of females, and proportion of preoperative respiratory diseases were higher than in the non-adverse event group (n = 90). The muscle relaxation value, quiet breathing diaphragmatic excursion during extubation (DE-QB), deep breathing diaphragmatic excursion during extubation (DE-DB), and deep breathing diaphragmatic thickening fraction during extubation (DTF-DB) of patients in the adverse event group were significantly lower than those in the non-adverse event group (P < 0.05). Using binary logistic regression analysis, we identified muscle relaxation value, DE-DB, and DTF-DB during extubation as significant predictors of CREs post-extubation in elderly patients (P < 0.05). The area under the curve (AUC) of the combination of the muscle relaxation value, DE-DB, and DTF-DB during extubation for predicting CREs after extubation in elderly patients was 0.949, which was higher than that of any single indicator.

Conclusion

The combination of diaphragmatic ultrasound and muscle relaxation monitoring was more accurate in predicting CREs post-extubation among elderly patients in the AICU.
“Salivary LINC00657 and miRNA-106a as diagnostic biomarkers for oral squamous cell carcinoma, an observational diagnostic study”
Authors: Tarrad Nayroz Abdel Fattah , Hassan Sandy , Shaker Olfat Gamil , AbdelKawy Maha
Published: December 2023

Background

Early detection and diagnosis of malignant tumors is critical for improving the survival rate and treatment outcomes of oral cancer. Thus, the current prospective investigation was designed to verify the role, sensitivity, and specificity of salivary LINC00657 and miRNA-106a as diagnostic markers in oral squamous cell carcinoma patients as compared to oral lichen planus (as an example of oral potentially malignant disorders) and normal individuals, and to show LINC00657 relation to miR-106a.

Methods

A total of 36 participants were included, subdivided into 3 groups: Group I: 12 patients diagnosed with oral squamous cell carcinoma (OSCC). Group II: 12 patients diagnosed with oral lichen planus (OLP). Group III: 12 systemically free individuals with no oral mucosal lesions. Unstimulated salivary samples were collected from all participants to evaluate level of LINC00657 and miR-106a in different groups using quantitative real-time PCR.

Results

OSCC showed the highest LINC00657 and lowest miR-106a fold change among included groups. Receiver Operating Characteristic (ROC) curve analysis of the two biomarkers for detecting OSCC revealed that LINC00657 had higher diagnostic accuracy (DA) (83.3%) compared to miR-106a (80.4%). As for detecting OLP, ROC analysis showed that miR-106a had higher (DA) (61%) compared to LINC00657 (52.5%). To discriminate OSCC from OLP, the diagnostic accuracy of both markers is the same (75%). Moreover, differentiating OSCC grades II and III, ROC analysis showed that miR-106a had lower (DA) (60%) compared to LINC00657 (DA) (83.3%).

Conclusions

Salivary LINC00657 and miR-106a could be promising diagnostic markers for oral squamous cell carcinoma. Salivary LINC00657 may differentiate oral squamous cell carcinoma from oral potentially malignant disorders with considerable diagnostic accuracy. Moreover, low levels of salivary miR-106a could have the potential to indicate malignancy.

Trial registration

The study was retrospectively registered on clinicaltrial.gov with NCT05821179 (first trial registration in 26/3/2023), date of registration: 19/4/2023.
The role of patients’ stories in medicine: a systematic scoping review
Authors: Quah Elaine Li Ying , Chua Keith Zi Yuan , Lin Casper Keegan Ronggui , Vijayan Andrew Vimal , Abdul Hamid Nur Amira Binte , Owyong Jasmine Lerk Juan , Satku Neeta , Woong Natalie , Lim Crystal , Phua Gillian Li Gek , Ong Eng Koon , Fong Warren , Krishna Lalit Kumar Radha
Published: December 2023

Background

Patients’ stories provide Palliative Care physicians with a glimpse into the former’s lives and their psycho-emotional, sociocultural, and contextual considerations. Yet, few physicians are trained to interpret and apply patients’ stories in their practice. Inherent variability in how stories are transmitted and interpreted raises questions over their potential effects on care. Amidst a dearth of accounts in Palliative Care, we map current use of patient stories to guide the training, assessment, and oversight of this ‘care influencing’ practice in medicine.

Methods

This systematic scoping review was guided by the Systematic Evidence-Based Approach (SEBA) to ensure a reproducible and structured approach. The themes and categories identified through the Split Approach’s concurrent and independent thematic and directed content analyses provided a comprehensive sketch of the included articles. The Jigsaw Perspective combined the themes and categories identified. The last stage of SEBA compared these results with two recent reviews of storytelling to ensure consistency of the domains created that guided the discussion.

Results

Ten thousand two hundred seven articles were reviewed, 963 full text articles were evaluated, and 199 articles were included. The four domains identified were study characteristics, benefits, approaches, and positive effects and concerns.

Conclusion

Stories support patient-centered, personalized, and holistic clinical care. However, variability in the stories, their interpretations and use in care decisions underscore the need for further study on the structuring, teaching, assessing, and delivery of this ‘care influencing’ practice.
Network pharmacology combined with metabolomics to explore the mechanism for Lonicerae Japonicae flos against respiratory syncytial virus
Authors: Ding Jie , Li Jing , Zhang Zhe , Du Yaxuan , Liu Yuhong , Wang Ping , Du Haitao
Published: December 2023

Background

Respiratory Syncytial Virus (RSV) stands out as a primary contributor to lower respiratory tract infections and hospitalizations, particularly in infants. Lonicerae japonicae flos (LJF), a traditional Chinese medicine renowned for its efficacy against various viral infections, including RSV, has been widely employed. Despite its common use, the precise therapeutic mechanism of LJF against RSV remains elusive. This study aimed to investigate the underlying mechanism of LJF against RSV through network pharmacology and metabolomics.

Methods

In this study, based on network pharmacology, potential targets related to LJF and RSV were obtained from PubChem and Swiss Target Prediction. The core targets and pathways were established and verified by enrichment analysis and molecular docking. The anti-RSV efficacy of LJF was determined by in vitro experiments. Additionally, metabolomics analysis was integrated, allowing for the identification of differential metabolites and their correlation with targets following LJF treatment in the context of RSV infection.

Results

A total of 23 active ingredients and 780 targets were obtained, of which 102 targets were associated with LJF anti-RSV. The construction of the corresponding Protein–Protein Interaction (PPI) network unveiled potential core targets, including STAT3, TNF, and AKT1. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that LJF's anti-RSV effects primarily involve key pathways such as the PI3K-Akt signaling pathway, EGFR tyrosine kinase inhibitor resistance, and FoxO signaling pathway. Molecular docking showed that ZINC03978781, 4,5'-Retro-.beta.,.beta.-Carotene -3,3'-dione, 4',5'-didehydro and 7-epi-Vogeloside had better binding ability. The cellular assay showed that the therapeutic index of LJF against RSV was 4.79. Furthermore, 18 metabolites were screened as potential biomarkers of LJF against RSV, and these metabolites were mainly involved in the pathways of purine metabolism, linoleic acid metabolism, alpha-linolenic acid metabolism, and other related pathways.

Conclusions

The intergration of network pharmacology and metabolomics can clarify the active targets and related pathways of LJF against RSV, which could provide a valuable reference for further research and clinical application of LJF.
Undergraduate oncology education in Sudanese public medical schools; a national cross-sectional study
Authors: Alrawa Salma S. , Elgadi Ammar , Alfadul Esraa S. A. , Alshikh Shahd , Hammad Nazik , Abdelhafeez Abdelhafeez
Published: December 2023

Background

Cancer was the fifth leading cause of death in Sudan general hospitals in 2020, and its incidence is increasing. Medical students’ cancer education is key in cancer control. Evaluating the current education is the first step in optimizing it. The aim of this study was to assess undergraduate oncology education in Sudan public medical schools as reflected by the graduates of the year 2021–2022.

Method

This was a cross-sectional institution-based study. A validated online questionnaire was sent between 8 September and 11 November 2022 to graduates who were selected using a stratified random sampling technique from 17 Sudan public medical schools. The data were collected using Google Forms and analyzed using R software version 4.2.2 and Microsoft Excel 2022.

Results

A total of 707 graduates completed the questionnaire. They reported generally poor exposure to oncology. Palliative and radiation oncology in addition to chemotherapy daycare units were never attended by 76.0%, 72.0%, and 72.0% of graduates, respectively. The massed oncology curriculum was associated with increased hours of lectures dictated to medical (p = 0.005), radiation (p < 0.001), and palliative oncology (0.035). It was associated with an increased likelihood of assessment in breaking bad news (p < 0.001), counseling cancer patients (p = 0.015), and oncology-related knowledge (p < 0.001). The massed curriculum was associated with a decrease in interest in pursuing an oncology career (p = 0.037). Students were generally confident in their oncology competencies, and no difference was observed in relation to the curriculum approach (p > 0.05).

Conclusion

This study reflected poor exposure to oncology at the undergraduate level in Sudanese public medical schools. The massed oncology curriculum was associated with formal assessment of oncology-related competencies and better exposure to some disciplines, such as radiation and palliative oncology. Nonetheless, it was associated with decreased interest in an oncology career. In spite of the poor exposure, graduates were confident in their skills in oncology-related competencies. Further objective analysis of competence is needed.
Biomechanical stimulation promotes blood vessel growth despite VEGFR-2 inhibition
Authors: Johnson Bronte Miller , Johnson Allison McKenzie , Heim Michael , Buckley Molly , Mortimer Bryan , Berry Joel L. , Sewell-Loftin Mary Kathryn
Published: December 2023

Background

Angiogenesis, or the growth of new vasculature from existing blood vessels, is widely considered a primary hallmark of cancer progression. When a tumor is small, diffusion is sufficient to receive essential nutrients; however, as the tumor grows, a vascular supply is needed to deliver oxygen and nutrients into the increasing mass. Several anti-angiogenic cancer therapies target VEGF and the receptor VEGFR-2, which are major promoters of blood vessel development. Unfortunately, many of these cancer treatments fail to completely stop angiogenesis in the tumor microenvironment (TME). Since these therapies focus on the biochemical activation of VEGFR-2 via VEGF ligand binding, we propose that mechanical cues, particularly those found in the TME, may be a source of VEGFR-2 activation that promotes growth of blood vessel networks even in the presence of VEGF and VEGFR-2 inhibitors.

Results

In this paper, we analyzed phosphorylation patterns of VEGFR-2, particularly at Y1054/Y1059 and Y1214, stimulated via either VEGF or biomechanical stimulation in the form of tensile strains. Our results show prolonged and enhanced activation at both Y1054/Y1059 and Y1214 residues when endothelial cells were stimulated with strain, VEGF, or a combination of both. We also analyzed Src expression, which is downstream of VEGFR-2 and can be activated through strain or the presence of VEGF. Finally, we used fibrin gels and microfluidic devices as 3D microtissue models to simulate the TME. We determined that regions of mechanical strain promoted increased vessel growth, even with VEGFR-2 inhibition through SU5416.

Conclusions

Overall, understanding both the effects that biomechanical and biochemical stimuli have on VEGFR-2 activation and angiogenesis is an important factor in developing effective anti-angiogenic therapies. This paper shows that VEGFR-2 can be mechanically activated through strain, which likely contributes to increased angiogenesis in the TME. These proof-of-concept studies show that small molecular inhibitors of VEGFR-2 do not fully prevent angiogenesis in 3D TME models when mechanical strains are introduced.
Pandemic disruptions in vaccine uptake in a low-income setting: a qualitative inquiry
Authors: Malik Fauzia Aman , Ahsan Nazia , Jabeen Rawshan , Afzal Osama , Siddiqi Alysha , Khan Ayub , Hopkins Kathryn L. , Kazi Abdul Momin
Published: December 2023

Background

While the COVID-19 pandemic has exposed the vulnerabilities of immunization delivery systems globally, the devastating impact of the pandemic on immunization delivery is most pronounced in low and middle-income countries like Pakistan. We conducted a qualitative study to capture the views and experiences of parents and healthcare workers (HWs) and assess the impact of the COVID-19 pandemic on childhood routine immunization (CRI) and COVID-19 vaccination in Pakistan.

Methods

We used a qualitative research design with a purposive sampling approach. Semi-structured interviews (via telephone) and focus group discussions (via Zoom) were conducted with parents/child caregivers and HWs, respectively. All qualitative interviews were conducted between February and July 2021 from three sites (two urban and one rural) in Sindh, Pakistan. Interviews were audio-recorded, transcribed, and coded for a team-based thematic analysis.

Results

Overall, most parents and HWs indicated a strong trust in the benefits of CRI; nonetheless, a substantial disruption in the delivery and uptake of these services was also reported. The barriers towards CRI included closed vaccination centers, drastic reduction in outreach programs, lack of information for parents/child caregivers on vaccine availability, fear in the community regarding vaccine safety, limited vaccine supply, and a lack of healthcare staff. For COVID-19 vaccines, challenges cited included skepticism about the reality of the pandemic and confusion over COVID-19 vaccines due to conflicting (or mis-or-dis) information. Both participant groups showed a willingness to integrate COVID-19 vaccination into Pakistan’s Expanded Program for Immunization if required in the future.

Conclusion

During the COVID-19 pandemic, disruptions of regular immunization delivery in Pakistan were not due to parental unwillingness to vaccinate, but rather to social and logistical challenges caused by a rapidly changing context and difficulties in providing vaccination services safely. Barriers to vaccine access and concerns about COVID-19 exposure during clinic visits also contributed to uncertainty regarding immunization services early in the pandemic. For catchup campaigns and future pandemics, more than focusing interventions on persuading people, strategic approaches to building resilience through system-based interventions, such as investing in surge capacity in the immunization workforce to bounce back quickly after the first shock are required.
Unveiling the role of miR-137-3p/miR-296-5p/SERPINA3 signaling in colorectal cancer progression: integrative analysis of gene expression profiles and in vitro studies
Authors: Liu Huimin , Wu Xingxing , Wang Dandan , Li Quanxi , Zhang Xin , Xu Liang
Published: December 2023

Background

Colorectal cancer (CRC) is a prevalent malignancy worldwide, with increasing incidence and mortality rates. Although treatment options have improved, CRC remains a leading cause of death due to metastasis. Early intervention can significantly improve patient outcomes, making it crucial to understand the molecular mechanisms underlying CRC metastasis. In this study, we performed bioinformatics analysis to identify potential genes associated with CRC metastasis.

Methods

We downloaded and integrated gene expression datasets (GSE89393, GSE100243, and GSE144259) from GEO database. Differential expression analysis was conducted, followed by Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The hub gene SERPINA3 was selected for further in vitro functional studies. Additionally, the role of miR-137-3p/miR-296-5p/ Serpin family A member 3 (SERPINA3) in CRC cell function was investigated using in vitro assays.

Results

Analysis of the gene expression datasets revealed differentially expressed genes (DEGs) associated with CRC metastasis. GO analysis showed enrichment in biological processes such as blood coagulation regulation and wound healing. Cellular component analysis highlighted extracellular matrix components and secretory granules. Molecular function analysis identified activities such as serine-type endopeptidase inhibition and lipoprotein receptor binding. KEGG analysis revealed involvement in pathways related to complement and coagulation cascades, cholesterol metabolism, and immune responses. The common DEGs among the datasets were further investigated. We identified SERPINA3 as a hub gene associated with CRC metastasis. SERPINA3 exerted enhanced effects on migration, proliferation and epithelial-mesenchymal transition (EMT) and inhibitory effects on caspase-3/-9 activities in HT29 and SW620 cells. MiR-137-3p overexpression increased activities of caspase-3/-9, decreased migration and proliferation, and also repressed EMT in HT29 cells, which were obviously attenuated by SERPINA3 enforced overexpression. Consistently, SERPINA3 enforced overexpression also largely reversed miR-296-5p mimics-induced increased in activities of caspase-3/-9, decrease in migration, proliferation and EMT in HT29 cells.

Conclusion

Through bioinformatics analysis, we identified potential genes associated with CRC metastasis. The functional studies focusing on SERPINA3/miR-137-3p/miR-296-5p further consolidated its role in regulating CRC progression. Our findings provide insights into novel mechanisms underlying CRC metastasis and might contribute to the development of effective treatment strategies. However, the role of SERPINA3/miR-137-3p/miR-296-5p signaling in CRC still requires further investigation.
Understanding the spread of infectious diseases in edge areas of hotspots: dengue epidemics in tropical metropolitan regions
Authors: Lee Ya-Peng , Wen Tzai-Hung
Published: December 2023

Identifying clusters or hotspots from disease maps is critical in research and practice. Hotspots have been shown to have a higher potential for transmission risk and may be the source of infections, making them a priority for controlling epidemics. However, the role of edge areas of hotspots in disease transmission remains unclear. This study aims to investigate the role of edge areas in disease transmission by examining whether disease incidence rate growth is higher in the edges of disease hotspots during outbreaks. Our data is based on the three most severe dengue epidemic years in Kaohsiung city, Taiwan, from 1998 to 2020. We employed conditional autoregressive (CAR) models and Bayesian areal Wombling methods to identify significant edge areas of hotspots based on the extent of risk difference between adjacent areas. The difference-in-difference (DID) estimator in spatial panel models measures the growth rate of risk by comparing the incidence rate between two groups (hotspots and edge areas) over two time periods. Our results show that in years characterized by exceptionally large-scale outbreaks, the edge areas of hotspots have a more significant increase in disease risk than hotspots, leading to a higher risk of disease transmission and potential disease foci. This finding explains the geographic diffusion mechanism of epidemics, a pattern mixed with expansion and relocation, indicating that the edge areas play an essential role. The study highlights the importance of considering edge areas of hotspots in disease transmission. Furthermore, it provides valuable insights for policymakers and health authorities in designing effective interventions to control large-scale disease outbreaks.
Perioperative, function, and positive surgical margin in extraperitoneal versus transperitoneal single port robot-assisted radical prostatectomy: a systematic review and meta-analysis
Authors: Jiang Yu , Liu Yang , Qin Shize , Zhong Shuting , Huang Xiaohua
Published: December 2023

Background

Extraperitoneal and transperitoneal approaches are two common modalities in single-port (SP) robot-assisted radical prostatectomy (RARP), but differences in safety and efficacy between the two remain controversial. This study aimed to compare the perioperative, function, and positive surgical margin of extraperitoneal with transperitoneal approaches SP-RARP.

Methods

Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, this study is registered with PROSPERO (CRD 42023409667). We systematically searched databases including PubMed, Embase, Web of Science, and Cochrane Library to identify relevant studies published up to February 2023. Stata 15.1 software was used to analyze and calculate the risk ratio (RR) and weighted mean difference (WMD).

Results

A total of five studies, including 833 participants, were included in this study. The SP-TPRP group is superior to the SP-EPRP group in intraoperative blood loss (WMD: − 43.92, 95% CI − 69.81, − 18.04; p = 0.001), the incidence of postoperative Clavien-Dindo grade II and above complications (RR: 0.55, 95% CI − 0.31, 0.99; p = 0.04), and postoperative continence recovery (RR: 1.23, 95% CI 1.05, 1.45; p = 0.04). Conversely, the hospitalization stays (WMD: 7.88, 95% confidence interval: 0.65, 15.1; p = 0.03) for the SP-EPRP group was shorter than that of the SP-TPRP group. However, there was no significant difference in operation time, postoperative pain score, total incidence of postoperative complications, and positive surgical margin (PSM) rates between the two groups (p > 0.05).

Conclusions

This study demonstrates that both extraperitoneal and extraperitoneal SP-RARP approaches are safe and effective. SP-TPRP is superior to SP-EPRP in postoperative blood loss, the incidence of postoperative Clavien-Dindo grade II and above complications, and postoperative continence recovery, but it is accompanied by longer hospital stays.
Down-regulated TAB1 suppresses the replication of Coxsackievirus B5 via activating the NF-κB pathways through interaction with viral 3D polymerase
Authors: Zhang Jiayu , Teng Peiying , Sun Bo , Zhang Jihong , Zhou Xiaoshuang , Chen Wei
Published: December 2023

Coxsackievirus Group B type 5 (CVB5), an important pathogen of hand-foot-mouth disease, is also associated with neurological complications and poses a public health threat to young infants. Among the CVB5 proteins, the nonstructural protein 3D, known as the Enteroviral RNA-dependent RNA polymerase, is mainly involved in viral genome replication and transcription. In this study, we performed immunoprecipitation coupled with liquid chromatography-tandem mass spectrometry (LC–MS/MS) to identify host proteins that interacted with CVB5 3D polymerase. A total of 116 differentially expressed proteins were obtained. Gene Ontology analysis identified that the proteins were involved in cell development and cell adhesion, distributed in the desmosome and envelope, and participated in GTPase binding. Kyoto Encyclopedia of Genes and Genomes analysis further revealed they participated in nerve diseases, such as Parkinson disease. Among them, 35 proteins were significantly differentially expressed and the cellular protein TGF-BATA-activated kinase1 binding protein 1 (TAB1) was found to be specifically interacting with the 3D polymerase. 3D polymerase facilitated the entry of TAB1 into the nucleus and down-regulated TAB1 expression via the lysosomal pathway. In addition, TAB1 inhibited CVB5 replication via inducing inflammatory factors and activated the NF-κB pathway through IκBα phosphorylation. Moreover, the 90-96aa domain of TAB1 was an important structure for the function. Collectively, our findings demonstrate the mechanism by which cellular TAB1 inhibits the CVB5 replication via activation of the host innate immune response, providing a novel insight into the virus-host innate immunity.
Real-world predictors of divorce among outpatients with bipolar disorder: sex differences and clinical implications
Authors: Tokumitsu Keita , Sugawara Norio , Adachi Naoto , Kubota Yukihisa , Watanabe Yoichiro , Miki Kazuhira , Azekawa Takaharu , Edagawa Koji , Katsumoto Eiichi , Hongo Seiji , Goto Eiichiro , Ueda Hitoshi , Kato Masaki , Yoshimura Reiji , Nakagawa Atsuo , Kikuchi Toshiaki , Tsuboi Takashi , Watanabe Koichiro , Yasui-Furukori Norio
Published: December 2023

Background

Bipolar disorder is a mental illness characterized by recurring episodes of mania and depression and is known to cause social impairment. Additionally, it has been revealed that bipolar disorder increases the risk of divorce and loss of family member support, which can worsen the prognosis. However, there is limited evidence regarding the predictive factors of divorce among patients with bipolar disorder in real-world settings.

Methods

This study utilized an observational approach and involved psychiatrists from 176 member clinics of the Japanese Association of Neuro-Psychiatric Clinics. They were requested to conduct a retrospective review of medical records and complete a questionnaire focused on patients diagnosed with bipolar disorder. The data collection period for baseline patient characteristics spanned from September to October 2017. Next, we investigated the incidence of divorce over a 2-year period, ranging from baseline to September to October 2019.

Results

A total of 1071 outpatients with bipolar disorder were included in the analysis, and 2.8% (30/1071) experienced divorce during the first 2 years of observation. The incidence of divorce in this population was considerably higher than that in the general Japanese population. Binomial logistic regression analysis confirmed that a younger baseline age and lower BMI values were statistically significant predictors of divorce occurrence for all study participants. The predictors of divorce were then examined separately by sex. The results revealed that for men, a younger age at baseline and having bipolar I disorder compared to bipolar II disorder were statistically significant predictors of divorce. In contrast, for women, having a lower BMI and using anxiolytics emerged as statistically significant predictors of divorce.

Conclusions

In this study, a younger baseline age and lower BMI values were statistically significant predictors of divorce in patients with bipolar disorder. Notably, the predictors of divorce varied significantly between men and women. These findings provide important insights from a family perspective regarding social support for individuals with bipolar disorder in real-world clinical settings.
Biomechanical insights into ankle instability: a finite element analysis of posterior malleolus fractures
Authors: Ying Jichong , Liu Jianlei , Wang Hua , Zhuang Yunqiang , Yu Tianming , Wang Shuaiyi , Huang Dichao
Published: December 2023

Background

Posterior malleolus fractures are known to be associated with ankle instability. The complexities involved in obtaining precise laboratory-based spatial pressure measurements of the ankle highlight the significance of exploring the biomechanical implications of these fractures.

Methods

Finite element analysis was utilized to examine the stress distribution across the contact surface of the ankle joint, both in its natural state and under varied sagittal fracture line angles. The study aimed to identify stress concentration zones and understand the influence of sagittal angles on stress distribution.

Results

Three distinct stress concentration zones were identified on the ankle's contact surface: the anterolateral tibia, the anteromedial tibia, and the fracture line. The most significant stress was observed at the fracture line when a fracture occurs. Stress at the fracture line notably spikes as the sagittal angle decreases, which can potentially compromise ankle stability. Larger sagittal angles exhibited only minor stress variations at the contact surface's three vertices. It was inferred that sagittal angles below 60° might pose risks to ankle stability.

Conclusions

The research underscores the potential implications of fractures on the stress profile of the ankle joint, emphasizing the role of the contact surface in ensuring stability. The identification of three zones of stress concentration and the influence of sagittal angles on stress distribution offers a valuable reference for therapeutic decision-making. Further, the study reinforces the importance of evaluating sagittal fracture angles, suggesting that angles below 60° may compromise ankle stability.