bluuebunny/crossref_metadata_2025 huggingface dataset:
Head-to-head comparison of two human papillomavirus vaccines for efficacy against cervical intraepithelial neoplasia grade 3 and adenocarcinoma in situ—population-based follow-up of two cluster-randomized trials
Authors: Lehtinen Matti , Gray Penelope , Luostarinen Tapio , Eriksson Tiina , Apter Dan , Bly Anne , Harjula Katja , Heikkilä Kaisa , Hokkanen Mari , Kuortti Marjo , Nieminen Pekka , Nummela Mervi , Paavonen Jorma , Palmroth Johanna , Petäjä Tiina , Pimenoff Ville N. , Pukkala Eero , Dillner Joakim
Published: September 2024

Introduction

We report head-to-head comparison of the bivalent and quadrivalent HPV vaccine efficacies against immediate precursors of cervical cancer from 15 years’ country-wide cancer registry follow-up of phase III trial cohorts and an age-aligned cohort of unvaccinated women.

Methods

These individually and/or clusterrandomized cohorts of HPV6/11/16/18- and HPV16/18-vaccinated and unvaccinated women were enrolled, respectively, in 2002, 2004, and 2003/2005. The trial cohorts comprised initially 16- to 17-year-old HPV6/11/16/18-vaccinated FUTURE II (NCT00092534) participants (866) and HPV16/18-vaccinated PATRICIA (NCT00122681) and 012 trial (NCT00169494) participants (2,465), and 16,526 initially 16- to 19-year-old unvaccinated controls. After active 4-year clinical follow-up, passive, country-wide Finnish Cancer Registry (FCR) follow-up for cervical intraepithelial neoplasia grade 3 (CIN3) and adenocarcinoma in situ (AIS) was based on consented use of unique personal identifiers and started 6 months after the end of the FUTURE II and PATRICIA trials in 2007 and 2009, and ended at the end of 2019. The follow-up with altogether 229,020 follow-up years was age-aligned to ensure that similarly aged cohorts were passively followed up for 15 years post=vaccination for the intention-to-treat analyses of vaccine efficacy.

Results

Overall, we identified 5 and 16 CIN3 (no AIS) cases in the HPV6/11/16/18 and HPV16/18 cohorts, respectively, during the FCR-based follow-up. In the unvaccinated cohort, we identified 281 CIN3 cases, 20 AIS cases, and 13 cases with invasive cervical cancer. Vaccine efficacies against CIN3+ were 68.4% and 64.5% for the quadrivalent and the bivalent vaccines, respectively, with overlapping confidence intervals.

Discussion

Long-term follow-up of randomized, initially adolescent HPV-vaccinated and unvaccinated cohorts shows, in this head-to-head setting, that the bivalent and quadrivalent HPV vaccines are equally effective against immediate precursors of cervical cancer.
Hybrid attribute-based recommender system for personalized e-learning with emphasis on cold start problem
Authors: Butmeh Hala , Abu-Issa Abdallatif
Published: September 2024

This article introduces a recommendation system that merges a knowledge-based (attribute-based) approach with collaborative filtering, specifically addressing the challenges of the pure-cold start scenario in personalized e-learning. The system generates learning recommendations by assessing item similarities, utilizing the Rogers-Tanimoto similarity measure for materials and users, and Jaccard's similarity for user comparisons. Unlike traditional collaborative methods relying on prior ratings, this approach depends on attributes. Additionally, user and learning material profiling structures were created to serve as fundamental inputs for the recommendation algorithm. These profiles represent student and material knowledge in a two-dimensional space to facilitate matching. Our processes incorporate user learning styles, preferences, and prior knowledge as metrics for achieving the desired level of personalization. The system produces a list of top recommendations based on predicted ratings. To validate its efficacy, a website resembling our learning platform was developed and tested by users. The primary results demonstrate the system's ability to identify similar users even in a pure cold start condition without existing ratings. Consequently, the system proves its capability in recommending suitable materials, modeling students, and identifying similar user groups. The evaluation results of the proposed system showed a good level of satisfaction by the testimonials, quantified by a score of 82% for the recommended materials (16% higher than exiting cold-start systems), and an average score of 90% in terms of satisfaction about the generated student profiles. As they proved the capability of the framework in recommending suitable materials, and its capability in modeling students, finding similar groups of users.
Endoluminal rescue of false lumen graft deployment in TEVAR for type B aortic dissection: a case report and literature review
Authors: Zhu Hong Jiang , Yan Feng , Zhao Peng Peng
Published: September 2024

Background

Thoracic endovascular aortic repair (TEVAR) has increasingly become the preferred surgical intervention for Stanford type B aortic dissection (TBAD). The primary objective of this procedure is to seal the primary entry tear to promote positive aortic remodeling. However, the increased use of TEVAR has also led to a rise in surgical complications. Among these, the accidental deployment of the stent into the false lumen is a rare but serious complication that can result in aortic false lumen rupture and inadequate perfusion of abdominal organs.

Case summary

This case report described a 78-year-old man who presented to our hospital with sudden onset chest and back pain and was subsequently diagnosed with TBAD via aortic CTA. As conventional medical therapy failed to alleviate his chest pain, the patient underwent TEVAR. During the procedure, a complication arose when the distal end of the endograft was mistakenly deployed into the false lumen, leading to insufficient perfusion of the abdominal organs. Recognizing this issue intraoperatively, an additional endograft was promptly inserted at the distal end to reroute blood flow back to the true lumen of the aorta, thereby restoring visceral perfusion. Post-intervention, the patient's chest pain improved, and he was successfully discharged from the hospital.

Conclusion

Accidental deployment of a endograft into the false lumen during TEVAR is a rare but serious complication. Intraoperative angiography plays a crucial role in rapidly and accurately identifying this issue by detecting insufficient perfusion of abdominal organs. The use of intravascular ultrasound may help reduce the incidence of this complication. Endovascular repair is an effective emergency strategy to quickly redirect blood flow back to the true lumen, making it the preferred method for managing such emergencies.
Enhancing engineering students’ satisfaction with online learning: factors, framework, and strategies
Authors: Al-Khatib Maryam , Alkhatib Amira , Talhami Mohammed , Kashem Abdurahman Hafez Mohammed , Ayari Mohamed Arselene , Choe Pilsung
Published: September 2024

Introduction

The learning experience has undergone significant changes recently, particularly with the adoption of advanced technology and online lectures to address challenges such as pandemics. In fields like engineering, where hands-on classes are essential, the online learning environment plays a crucial role in shaping students’ experiences and satisfaction.

Methods

This study aimed to explore the key factors affecting engineering students’ satisfaction with online learning. A structured survey was administered to 263 students across various engineering disciplines and academic levels, all of whom had experienced both in-person learning before the pandemic and online learning during the pandemic. Factor analysis and multiple linear regression were employed to analyze the data.

Results

The analysis identified interactions, services, and technology as the main factors positively influencing online learning satisfaction. The regression analysis further revealed that students’ satisfaction is significantly dependent on the availability and quality of online learning services, assessment and interaction tools, and technology.

Discussion

This study highlights the critical factors that enhance engineering students’ satisfaction with online learning. It offers strategies for educators to improve online learning environments, emphasizing the importance of quality services, assessment, and interaction tools. These findings can guide the development of more effective online learning experiences in engineering education.
Spiral-curricular blended learning for the mathematics education in physics teacher training courses
Authors: Kämpf Lydia , Stallmach Frank
Published: September 2024

A good physics education depends on a good, transferable mathematics education. A concept for a cross-modular blended learning math course developed for the first two semesters of our physics teacher trainee study program is introduced. The course covers the important new mathematics required for the development of the conceptual understanding of the classical experimental physics mechanics and electrodynamics. It is based on three pillars: parallelism of the math topics to the physics lectures, spiral-curricularity to prior knowledge and high quality digitally available interactive materials such as interactive videos, formative tests and exercises to foster a self-regulated learning of the students in online as well as face-to-face learning environments. The blended learning math course and its face-to-face math seminars are integrated into the experimental physics modules. Results of surveys among the first two cohorts of course participants indicate that the design of the math course is well accepted and the interactive videos are very well received by the students. Initial tests on the learning effectiveness indicate a sufficient development of long term knowledge by the students.
The association between the weight-adjusted-waist index and frailty in US older adults: a cross-sectional study of NHANES 2007–2018
Authors: Jia Shanshan , Huo Xingwei , Sun Lirong , Yao Yuanyuan , Chen Xiaoping
Published: September 2024

Objective

This study aimed to evaluate the relationship between the weight-adjusted waist circumference index (WWI) and the frailty in American adults aged over 60 years.

Methods

We utilized data from the National Health and Nutrition Examination Surveys (NHANES) spanning from 2007 to 2018. WWI was calculated using the square root of waist circumference (cm) divided by body weight (kg). The frailty index ≥ 0.25 was employed to assess frailty. Weighted multivariate logistic regression was conducted to explore the association between WWI and frailty. Generalized Additive Modeling (GAM) was used to explore potential non-linear relationships. Receiver operating characteristic curve (ROC) analysis was used to assess the predictive ability of WWI for frailty.

Results

The study encompassed 7765 participants. Higher WWI was significantly associated with higher odds of frailty. In the fully adjusted model, each unit increase of WWI was associated with an 82% increased odds of frailty (OR: 1.82, 95% CI: 1.61 – 2.06; P < 0.001). GAM found significant nonlinear relationships and threshold effects.

Conclusion

The study presented a robust correlation between elevated WWI and increased odds of frailty among American older adults. However, these findings require further validation in large-scale, prospective studies.
From proteome to pathogenesis: investigating polycystic ovary syndrome with Mendelian randomization analysis
Authors: Zhang Jiaqi , Li Yuqing , Gong Aixia , Wang Jingmin
Published: September 2024

Background

Polycystic ovary syndrome (PCOS) is defined by oligo/anovulation, hyperandrogenism, and polycystic ovaries with uncertain pathogenesis. The proteome represents a substantial source of therapeutic targets, and their coding genes may elucidate the mechanisms underlying PCOS. However, reports on the profiles of the human plasma protein-coding genes and PCOS are limited. Here, we aimed to investigate novel biomarkers or drug targets for PCOS by integrating genetics and the human plasma proteome.

Methods

Our study acquired the protein quantitative trait loci from DECODE Genetics, offering 4,907 proteins in 35,559 individuals while obtaining PCOS summary statistics by accessing the FinnGen biobank (1,639 cases and 218,970 controls) and the genome-wide association study catalog (797 cases and 140,558 controls). Herein, we sequentially used two-sample Mendelian randomization (MR) analyses and colocalization to verify the causal link between candidate proteins, their coding genes, and PCOS. Further PCOS data download was conducted by accessing the Gene Expression Omnibus and Zenodo platforms. Gene expression level analysis, pathway enrichment analysis, immune cell infiltration, and transcription factor prediction were performed, aiming at detecting specific cell types with enriched expression and exploring potential optimized treatments for PCOS.

Results

MR analysis revealed 243 protein-coding genes with a causal relationship to PCOS risk, of which 12 were prioritized with the most significant evidence. Through colocalization analysis, three key genes, CUB domain-containing protein 1 (CDCP1), glutaredoxin 2 (GLRX2), and kirre-like nephrin family adhesion molecule 2 (KIRREL2), were identified. Subsequently, the three genes were strongly related to immune function and metabolism in terms of biological significance. In single-cell analysis, the expression levels of genes in ovarian theca cells were explored.

Conclusion

Overall, three protein-coding genes (CDCP1, GLRX2, and KIRREL2) may be related to a higher PCOS risk, suggesting that they may be entry points for exploration of PCOS pathogenesis and treatment, warranting further clinical investigations.
Long-term directional changes in urban bird communities of Mar del Plata City, Argentina
Authors: Leveau Lucas M.
Published: September 2024

Urban environments have been characterized by their temporal stability of resources, which could promote stability in bird composition. Several studies have found that bird communities in urban environments persist over the years, showing a similar species composition in the short term. However, studies analyzing continuous changes in urban communities over the long term are scarce. This study aimed to analyze the stability or directional changes (instability) in bird communities along an urban gradient. Bird counts were conducted in urban, suburban, and periurban areas over 8-10 years in 2002-2019. Changes in species composition were analyzed over periods ranging from one year to the next, to changes from one year to the seventeenth. Urban bird communities were more similar between years than suburban and periurban communities. Compositional changes were greater as time lags increased, indicating directional compositional shifts. The magnitude of these changes was similar across the urban gradient. The Chimango Caracara (Milvago chimango), the Picazuro Pigeon (Patagioenas picazuro), the Rufous Hornero (Furnarius rufus), and the Red-bellied Thrush (Turdus rufiventris) significantly increased their abundances during the period, while the House Sparrow (Passer domesticus) significantly decreased its abundance. Regional changes in species abundance, urban vegetation succession, and biotic interactions could explain the changes in bird communities.
Assessing Larix principis-rupprechtii productivity and its determinants based on national forest inventory data in Hebei Province, China
Authors: Wang Yiwen , Fan Niqiao , Qian Jialong , Zhang Jing , Ge Zhaoxuan , Liu Chong , Zhang Zhidong
Published: September 2024

Tree productivity is not only determined by stand structure, but also influenced by soil chemical properties, climate and topography. However, the relative importance of each indicator on larch (Larix principis-rupprechtii) productivity were uncertain. In this study, 76 pure larch forest plots were selected based on national forest inventory (NFI) data in Hebei Province, China. Structural equation model (SEM) was used to analyze the direct and indirect effects of stand structure, soil chemical properties, climate and topography on larch productivity, and to quantify the relative importance of each indicator in determining productivity. The results showed that stem volume growth (SVG) of larch was influenced by a combination of stand density, diameter at breast height (DBH), mean winter snow (PAS), annual temperature range (TD), slope, and alkali-hydrolysis nitrogen (AN). SVG tended to increase with decreasing stand density and AN content and increasing DBH. Stand density, DBH and AN were more important than PAS, TD, and slope in explaining SVG variation. The results can provide a scientific basis for adaptive management of larch forests.
Pattern and change of NDVI and their environmental influencing factors for 1986–2019 in the Qinling-Daba Mountains of central China
Authors: Yao Yonghui
Published: September 2024

Previous studies have shown that climate change and human activities play an important role in the vegetation dynamics in the Qinling-Daba Mountains of central China. However, which environmental factors including climate, topography, soil and human activities play an important role in the vegetation dynamics and its spatial pattern in the Qinling-Daba Mountains remains to be further clarified. Based on the normalized difference vegetation index (NDVI) data of the growing season from 1986 to 2019 synthesized by Landsat series satellite data on Google Earth Engine, this study aimed to further investigate the spatial pattern of NDVI and its dynamics, and clarify its environmental controlling factors in the Qinling-Daba Mountains using the methods of spatial analysis and Geodetector. The results showed that: (1) the spatial pattern of NDVI in the study area had a U-shaped NDVI distribution in latitude, anti-U-shaped patterns in longitude and with increasing altitude. (2) 2005 was the year of NDVI breakthrough increase, and the vegetation dynamics was divided into two periods according to the result of MK mutation test: the slow increasing period with an increasing rate of 0.25%/a from 1986 to 2004 (R2 0.74), and the rapid increasing period with an increasing rate of 0.30%/a from 2005 to 2019 (R2 0.92). (3) Topography regulating local hydrothermal conditions and soil enriching nutritions played more important influence on NDVI spatial pattern than climate factors (temperature and precipitation) at the regional scale. The effect of land use on NDVI change was stronger than that of climate warming (temperature), and the climate warming in recent decades played a more important role than precipitation on the NDVI dynamics. Research on vegetation patterns, changes and their environmental influencing factors will help the government and other related agencies to formulate plans or policies for infrastructure development and land management, ecological restoration.
Case report: Whole exome sequencing reveals a novel splicing variant of ANKRD17 gene in a Chinese male juvenile with developmental delay and transient tic disorder
Authors: Chen Jing , Yang Shuo , Wang He , Wang Hongjing , Xiao Yuanyuan , Liu Shanling
Published: September 2024

Background

The Ankyrin Repeat Domain Containing Protein 17 (ANKRD17, OMIM:615929) gene is a protein-coding gene associated with diseases such as Chopra-Amiel-Gordon Syndrome and Non-Specific Syndromic Intellectual Disability. The protein encoded by ANKRD17 gene belongs to the ankyrin repeat-containing protein family, which is one of the most widely existing protein domains that exclusively mediate protein-protein interactions. To date, the research and reports on the ANKRD17 gene are limited.

Case presentation

Trio whole exome sequencing (Trio-WES) was conducted on the proband and his unaffected parents to elucidate the genetic etiology in the proband, who was clinically diagnosed with developmental delay and other phenotypes. Subsequently, Sanger sequencing was employed for validation of the identified candidate variant. Furthermore, RNA analysis was utilized to ascertain the impact of the variant on splicing. The WES revealed a novel heterozygous ANKRD17 splicing variant (c.7248 + 1G>A) in the proband, but not detected in his unaffected parents. And the presence of the splicing variant of the ANKRD17 gene was valided by the Sanger sequencing subsequently. And the RNA analysis confirmed that the novel variant was predicted to result in loss of donor splice site, and the analysis at mRNA level confirmed that it leads to exon 32 skipping (r.7100_7278del179) and causes premature termination of translation to the protein (p.D2357fs), therefore is classified as pathogenic.

Conclusion

Our study reported a novel splicing variant in ANKRD17 gene, which may be associated with partial eating, frequent urination, and tic syndrome. This finding expands both the phenotypic and genotypic spectrum of ANKRD17 gene. Although there is currently no curative therapy available for ANKRD17 gene variants, a definitive diagnosis of its genetic etiology is significant for genetic counseling and family planning purposes. Furthermore, this is the first reported case of the ANKRD17 gene in China.
The role of convalescent plasma and hyperimmune immunoglobulins in the COVID-19 pandemic, including implications for future preparedness
Authors: So-Osman Cynthia , Burnouf Thierry , Al-Riyami Arwa Z. , Bloch Evan M. , Estcourt Lise , Goel Ruchika , Tiberghien Pierre , Vermeulen Marion , Wendel Silvano , Wood Erica M.
Published: September 2024

Introduction

When Coronavirus Disease-19 (COVID-19) struck the world in December 2019, initiatives started to investigate the efficacy of convalescent plasma, a readily available source of passive antibodies, collected from recovered patients as a therapeutic option. This was based on historical observational data from previous virus outbreaks.

Methods

A scoping review was conducted on the efficacy and safety of convalescent plasma and hyperimmune immunoglobulins for COVID-19 treatment. This review included the latest Cochrane systematic review update on 30-day mortality and safety. We also covered use in pediatric and immunocompromised patients, as well as the logistic challenges faced in donor recruitment and plasma collection in general. Challenges for low resource countries were specifically highlighted.

Results

A major challenge is the high donation frequency required from first-time donors to ensure a safe product, which minimizes the risk of transfusion-transmitted infectious. This is particularly difficult in low- and middle- income countries due to inadequate infrastructure and insufficient blood product supplies. High-certainty evidence indicates that convalescent plasma does not reduce mortality or significantly improve clinical outcomes in patients with moderate to severe COVID-19 infection. However, CCP may provide a viable treatment for patients unable to mount an endogenous immune response to SARS-CoV-2, based on mostly observational studies and subgroup data of published and ongoing randomized trials. Convalescent plasma has been shown to be safe in adults and children with COVID-19 infection. However, the efficacy in pediatric patients remains unclear.

Discussion

Data on efficacy and safety of CCP are still underway in ongoing (randomized) studies and by reporting the challenges, limitations and successes encountered to-date, research gaps were identified to be addressed for the future.

Conclusion

This experience serves as a valuable example for future pandemic preparedness, particularly when therapeutic options are limited, and vaccines are either being developed or ineffective due to underlying immunosuppression.
Socio-economic impacts of the recent bio-invasion of Callinectus sapidus on small-scale artisanal fishing in southern Italy and Portugal
Authors: Nardelli Ludovica , Fucilli Vincenzo , Pinto Hugo , Elston Jennifer Nicole , Carignani Annalisa , Petrontino Alessandro , Bozzo Francesco , Frem Michel
Published: September 2024

Introduction

The recent and growing bio-invasion of the Callinectes sapidus (known as blue crab) is causing damages in the European aquatic ecosystems, and affecting the livelihoods of the fishermen. In this context, this study explores the socio-economic impacts of this bio-invasion on small-scale artisanal fishermen in the Apulia (southern Italy) and Algarve (southern Portugal) regions, analyzing their perceptions and highlighting the repercussions of this bio-invasion on their livelihoods.

Methods

For this purpose, we carried out a field survey with representative small-scale artisanal fishermen based on the “Socio-economic Impact Classification of Alien Taxa” (SEICAT) approach by means of an “Exploratory Factor Analysis” (EFA), and a “Hierarchical Analysis and K-means Cluster Analysis”.

Results and discussion

The findings reveal that the two study areas, Apulia and Algarve, exhibit markedly different perceptions of the impact of the blue crab invasion on the well-being and activity of fishermen. In Apulia, the invasion has led to extensive damage to fishing nets, physical harm, a decline in other commercial species, reduced catch quantities, increased working hours, higher costs, and lower incomes. Conversely, in the Algarve, while net damage is less severe, the primary concerns are physical harm, increased working hours, higher costs, and reduced income. Consequently, this research provides an empirical basis for the adoption of management measures and interventions to mitigate the socioeconomic impacts of the blue crab on the fishing community and local economy, thereby contributing to the well-being of both individuals and the marine ecosystem.
The vicious cycle of frailty and pain: a two-sided causal relationship revealed
Authors: Zhong Ruipeng , Chen Yijian , Zhong Lanhua , Huang Guiming , Liang Weidong , Zou Yun
Published: September 2024

Background

The decline in physiological functions in the older people is frequently accompanied with pain and frailty, yet the causal connection between frailty and pain remains uncertain. In this study, we utilized a two-sample Mendelian randomization (MR) approach to investigate the potential causal association between frailty and pain.

Methods

Two-sample bidirectional MR was conducted using summary data from genome-wide association studies to examine the potential causal relationship between frailty (defined by the frailty index and frailty phenotype) and pain. Summary genome wide association statistics were extracted from populations of European ancestry. We also investigated the causal relationship between frailty and site-specific pain, including joint pain, limb pain, thoracic spine pain and low back pain. Causal effects were estimated using the inverse variance weighting method. Sensitivity analyses were performed to validate the robustness of the results.

Results

Genetic predisposition to frailty was associated with an increased risk of pain (frailty phenotype odds ratio [OR]: 1.73; P = 3.54 × 10–6, frailty index OR: 1.36; P = 2.43 × 10–4). Meanwhile, individuals with a genetic inclination toward pain had a higher risk of developing frailty. Regarding site-specific pain, genetic prediction of the frailty phenotype increased the occurrence risk of joint pain, limb pain and low back pain. Reverse MR analysis further showed that limb pain and low back pain were associated with an increased risk of frailty occurrence.

Conclusion

This study presented evidence supporting a bidirectional causal relationship between frailty and pain. We highlighted the significance of addressing pain to prevent frailty and recommend the inclusion of pain assessment in the evaluation system for frailty.
Conditional expression of flagellar motility, curli fimbriae, and biofilms in Shiga toxin- producing Escherichia albertii
Authors: Carter Michelle Qiu , Carychao Diana , Lindsey Rebecca L.
Published: September 2024

Escherichia albertii is an emerging foodborne pathogen. We previously reported that some avian Shiga toxin-producing E. albertii strains exhibited higher or comparable cytotoxicity in Vero-d2EGFP cells with several enterohemorrhagic E. coli (EHEC) outbreak strains. To better understand the environmental persistence of this pathogen, comparative genomics and phenotypic assays were applied to assess adhesion capability, motility, and biofilm formation in E. albertii. Among the 108 adherence-related genes, those involved in biogenesis of curli fimbriae, hemorrhagic E. coli pilus, type 1 fimbriae, and Sfm fimbriae were conserved in E. albertii. All 20 E. albertii strains carried a complete set of primary flagellar genes that were organized into four gene clusters, while five strains possessed genes related to the secondary flagella, also known as lateral flagella. Compared to EHEC strain EDL933, the eight chemotaxis genes located within the primary flagellar gene clusters were deleted in E. albertii. Additional deletion of motility genes flhABCD and motBC was identified in several E. albertii strains. Swimming motility was detected in three strains when grown in LB medium, however, when grown in 5% TSB or in the pond water-supplemented with 10% pigeon droppings, an additional four strains became motile. Although all E. albertii strains carried curli genes, curli fimbriae were detected only in four, eight, and nine strains following 24, 48, and 120 h incubation, respectively. Type 1 fimbriae were undetectable in any of the strains grown at 37°C or 28°C. Strong biofilms were detected in strains that produced curli fimbriae and in a chicken isolate that was curli fimbriae negative but carried genes encoding adhesive fimbriae K88, a signature of enterotoxigenic E. coli strains causing neonatal diarrhea in piglets. In all phenotypic traits examined, no correlation was revealed between the strains isolated from different sources, or between the strains with and without Shiga toxin genes. The phenotypic variations could not be explained solely by the genetic diversity or the difference in adherence genes repertoire, implying complex regulation in expression of various adhesins. Strains that exhibited a high level of cytotoxicity and were also proficient in biofilm production, may have potential to emerge into high-risk pathogens.
Identification and characterization of a small molecule BFstatin inhibiting BrpR, the transcriptional regulator for biofilm formation of Vibrio vulnificus
Authors: Lee Hojun , Hwang Seung-Ho , Shin Hyunwoo , Ha Nam-Chul , Wang Qiyao , Choi Sang Ho
Published: September 2024

Many pathogenic bacteria form biofilms that are resistant to not only host immune defenses but also antibiotics, posing a need for the development of strategies to control biofilms. In this study, to prevent biofilm formation of the fulminating foodborne pathogen Vibrio vulnificus, chemical libraries were extensively screened to identify a small molecule inhibiting the activity of BrpR, a transcriptional regulator for biofilm genes. Accordingly, the BrpR inhibitor BFstatin [N1-(2-chloro-5-fluorophenyl)-N3-propylmalonamide], with a half-maximal effective concentration of 8.01 μM, was identified. BFstatin did not interfere with bacterial growth or exhibit cytotoxicity to the human epithelial cell line. BFstatin directly bound to BrpR and interrupted its binding to the target promoter DNAs of the downstream genes. Molecular dynamics simulation of the interaction between BFstatin and BrpR proposed that BFstatin modifies the structure of BrpR, especially the DNA-binding domain. Transcriptomic analyses revealed that BFstatin reduces the expression of the BrpR regulon including the cabABC operon and brp locus which contribute to the production of biofilm matrix of V. vulnificus. Accordingly, BFstatin diminished the biofilm levels of V. vulnificus by inhibiting the matrix development in a concentration-dependent manner. Altogether, BFstatin could be an anti-biofilm agent targeting BrpR, thereby rendering V. vulnificus more susceptible to host immune defenses and antibiotics.
Exploring the causal associations between diet-derived circulating antioxidants and the risk of endometriosis: a Mendelian randomization study
Authors: Li Xiaoming , Xie Zhen , Qiu Hongbing , Xie Xiaofeng , Liu Lusha
Published: September 2024

Background

Numerous observational studies and randomized controlled trials have recently revealed the associations between circulating antioxidants and the risk of endometriosis, while the underlying causal relationship remains unclear. This study aimed to investigate the causal association between genetically determined circulating antioxidants and the risk of endometriosis using Mendelian randomization (MR).

Methods

A two-sample MR analysis was conducted using publicly available summary data from genome-wide association studies (GWAS) to investigate the causal impact of genetically determined absolute circulating antioxidants (such as ascorbate, retinol, β-carotene, and lycopene) and their metabolites (including α-and γ-tocopherol, ascorbate, and retinol) on the risk of endometriosis. The study used inverse variance weighted (IVW) or Wald ratio analyses as the primary estimation method and also conducted sensitivity analyses to assess heterogeneity and pleiotropy.

Results

No significant causality was observed for genetically determined circulating antioxidants and the risk of endometriosis. The pooled odds ratios (ORs) for absolute circulating antioxidants were 0.62 (95% CI: 0.32–1.18, retinol), 0.95 (95% CI: 0.79–1.15, β-carotene), 1.01 (95% CI: 0.95–1.08, lycopene), and 1.00 (95% CI: 0.99–1.02, ascorbate, expressed as a Wald ratio). The pooled ORs indicating the EM risk per unit increase in circulating antioxidant metabolites were 1.04 (95% CI: 0.82–1.33, γ-tocopherol), 0.91 (95% CI: 0.57–1.46, α-tocopherol), 1.03 (95% CI: 0.99–1.07, retinol), and 0.96 (95% CI: 0.87–1.06, ascorbate).

Conclusion

Our study demonstrated that increased levels of diet-derived circulating antioxidants were not significantly associated with a reduced risk of endometriosis.
Efficacy and safety evaluation of first-line systemic treatments for unresectable esophageal squamous cell carcinoma: a network meta-analysis
Authors: Shi Huiling , Tan Yong , Ma Chao , Wei Yushan , Shi Fengling , Wang Juan , Xu Caihua , Liang Rongrui
Published: September 2024

Objective

To evaluate the efficacy and safety of various first-line initial treatment systemic regimens for patients with unresectable esophageal squamous carcinoma(ESCC), utilizing a network meta-analysis approach.

Methods

A comprehensive search for randomized controlled trials focusing on the primary treatment of esophageal cancer ESCC was conducted across multiple databases including PubMed, Embase, Cochrane Library, and Web of Science, up until November 17, 2023. The quality of the included studies was rigorously assessed using Review Manager software. Subsequently, data analysis was meticulously carried out employing R software. The first-line treatment regimens examined were: CD (Cisplatin + Docetaxel), CET-CF (Cetuximab + Cisplatin + Fluorouracil), CF (Cisplatin + Fluorouracil), N-CF (Nivolumab + Cisplatin + Fluorouracil), NI (Nivolumab + Ipilimumab), Nim-CF (Nimotuzumab + Cisplatin + Fluorouracil), P-CF (Pembrolizumab + Cisplatin + Fluorouracil), and Ser-CF (Serplulimab + Cisplatin + Fluorouracil). The Primary endpoints included the overall survival(OS),progression-free survival (PFS),objective response rate (ORR) and disease control rate (DCR).The secondary endpoint was adverse effects(AEs).

Results

The analysis encompassed eight studies, incorporating a total of 3,051 patients with untreated esophageal cancer. There are 45 people in the CD regimen,32 in the CET-CF regimen,1,212 in the CF regimen,447 in the N-CF regimen,456 in the NI regimen,53 in the Nim-CF regimen,447 in the P-CF regimen and 368 in the Ser-CF regimen. The network meta-analysis revealed that, in comparison to the CF regimen, the other regimens (CD, CET-CF, N-CF, NI, Nim-CF, P-CF, and Ser-CF) did not demonstrate a statistically significant impact on overall survival (OS) or progression-free survival (PFS). However, Ser-CF potentially offers superior outcomes in terms of OS and PFS when juxtaposed with other regimens. Notably, N-CF was associated with a substantial increase in the objective response rate (ORR), and CET-CF markedly improved the disease control rate (DCR). In terms of adverse effects, N-CF was more likely to cause anorexia, whereas CET-CF was significantly associated with nausea, vomiting, neutropenia, and skin disorders.

Conclusion

The current evidence suggests that N-CF may provide the most favorable outcomes in terms of ORR, while CET-CF could be the optimal choice for enhancing DCR in patients with untreated esophageal cancer.
Association of the systemic inflammation and anthropometric measurements with cancer risk: a prospective study in MJ cohort
Authors: Bian Zilong , Xu Luopiao , Wang Yuting , Tsai Min-Kuang , Chu David Ta-Wei , Tu Huakang , Wen Chi-Pang , Wu Xifeng
Published: September 2024

Objective

To investigate the specific role of inflammation in the connection between obesity and the overall incidence of cancer.

Methods

A total of 356,554 participants in MJ cohort study were included. Systemic inflammation markers from blood samples and anthropometric measurements were determined using professional instruments. The Cox model was adopted to evaluate the association.

Results

Over a median follow-up of 8.2 years, 9,048 cancer cases were identified. For individual systemic inflammation biomarkers, the overall cancer risk significantly escalated as blood C-reactive protein (CRP) (hazard ratio (HR)=1.036 (1.017-1.054)) and globulin (GLO) (HR=1.128 (1.105-1.152)) levels increased, and as hemoglobin (HEMO) (HR=0.863 (0.842-0.884)), albumin (ALB) (HR=0.846 (0.829-0.863)) and platelets (PLA) (HR=0.842 (0.827-0.858)) levels decreased. For composite indicators, most of them existed a significant relationship to the overall cancer risk. Most indicators were correlated with the overall cancer and obesity-related cancer risk, but there was a reduction of association with non-obesity related cancer risk. Most of indicators mediated the association between anthropometric measurements and overall cancer risk.

Conclusions

Systemic inflammatory state was significantly associated with increased risks of cancer risk. Inflammation biomarkers were found to partly mediate the association between obesity and cancer risk.
Efficacy of different medications in the treatment of gynaecological tumours: a clinical meta-analysis
Authors: Chen Qiaoying
Published: September 2024

Background

A gynaecological tumour is one of the world’s leading causes of death for women globally. Among women, cancer is the 8th most common cause of death. Since there are no such programmes, the majority of women who are diagnosed with the condition are either in advanced stages or do not respond well to current treatments. Even if patients react to the treatments, they still risk having the cancer return, at which point any further medical intervention is met with resistance.

Method

For this study, we selected the systemic reviews and articles that have the use of different medications used for the treatment of gynaecological tumours.

Results

Regarding metformin use, this study found a positive relationship between higher survival and metformin use. Five of the studies that examined the use of statins revealed a link between statin use and higher overall and/or progression-free survival rates. Individuals on lipophilic and hydrophilic statins would do better. Research evaluating beta-blocker use during neoadjuvant treatment revealed a time-varying effect, with improved survival seen across all users early in the follow-up period. However, only non-selective beta-blocker users demonstrated a correlation with higher survival after five years. One study found that the benefits of aspirin use were significant, but the advantage for continuous users (both before and after diagnosis) was minimal.

Conclusion

Conclusions on the association between gynaecological tumour survival and NA-NSAIDs, metformin, beta-blockers, and aspirin cannot be drawn due to insufficient evidence. However, the vast majority of statin studies have demonstrated that users had higher rates of survival. Bias, however, bias may affect the results of the studies.
Biology-guided radiotherapy in metastatic prostate cancer: time to push the envelope?
Authors: Lancia Andrea , Ingrosso Gianluca , Detti Beatrice , Festa Eleonora , Bonzano Elisabetta , Linguanti Flavia , Camilli Federico , Bertini Niccolò , La Mattina Salvatore , Orsatti Carolina , Francolini Giulio , Abenavoli Elisabetta Maria , Livi Lorenzo , Aristei Cynthia , de Jong Dorine , Al Feghali Karine A. , Siva Shankar , Becherini Carlotta
Published: September 2024

The therapeutic landscape of metastatic prostate cancer has undergone a profound revolution in recent years. In addition to the introduction of novel molecules in the clinics, the field has witnessed a tremendous development of functional imaging modalities adding new biological insights which can ultimately inform tailored treatment strategies, including local therapies. The evolution and rise of Stereotactic Body Radiotherapy (SBRT) have been particularly notable in patients with oligometastatic disease, where it has been demonstrated to be a safe and effective treatment strategy yielding favorable results in terms of disease control and improved oncological outcomes. The possibility of debulking all sites of disease, matched with the ambition of potentially extending this treatment paradigm to polymetastatic patients in the not-too-distant future, makes Biology-guided Radiotherapy (BgRT) an attractive paradigm which can be used in conjunction with systemic therapy in the management of patients with metastatic prostate cancer.
Novel role of circRNAs in the drug resistance of gastric cancer: regulatory mechanisms and future for cancer therapy
Authors: Lu Ling , Gao Zihan , Jin Longtao , Geng Hao , Liang Zhaofeng
Published: September 2024

Cancer, including gastric cancer, has become a serious disease that jeopardizes public life. Currently, the main treatment methods are surgery, radiation therapy, and chemotherapy. One of the primary causes of death for patients with gastric cancer is drug resistance. Several mechanisms of anticancer drugs resistance have been reported, including changes in drugs transport and metabolism, mutations in drug targets, changes in DNA repair systems, inhibition of cell apoptosis and autophagy, gastric cancer stem cells, invasion and migration. It is becoming more widely known that non-coding RNAs, like circRNAs, play a critical role in the resistance of drugs used to treat gastric cancer. CircRNAs have a unique structure and function that is related to gastric cancer resistance, cell proliferation, apoptosis, autophagy, DNA repair systems, migration, and invasion. A clear understanding of the molecular mechanism of circRNAs mediated the resistance of gastric cancer drugs will open a new window for the treatment and management of gastric cancer. Therefore, in this review, we will summarize the current mechanism of drug resistance, and finally discuss the molecular mechanism of circRNAs in regulating the development of drug resistance in gastric cancer.
eXplainable artificial intelligence applied to algorithms for disruption prediction in tokamak devices
Authors: Bonalumi L. , Aymerich E. , Alessi E. , Cannas B. , Fanni A. , Lazzaro E. , Nowak S. , Pisano F. , Sias G. , Sozzi C.
Published: September 2024

Introduction: This work explores the use of eXplainable artificial intelligence (XAI) to analyze a convolutional neural network (CNN) trained for disruption prediction in tokamak devices and fed with inputs composed of different physical quantities.

Methods: This work focuses on a reduced dataset containing disruptions that follow patterns which are distinguishable based on their impact on the electron temperature profile. Our objective is to demonstrate that the CNN, without explicit training for these specific mechanisms, has implicitly learned to differentiate between these two disruption paths. With this purpose, two XAI algorithms have been implemented: occlusion and saliency maps.

Results: The main outcome of this paper comes from the temperature profile analysis, which evaluates whether the CNN prioritizes the outer and inner regions.

Discussion: The result of this investigation reveals a consistent shift in the CNN’s output sensitivity depending on whether the inner or outer part of the temperature profile is perturbed, reflecting the underlying physical phenomena occurring in the plasma.
Evolution and governance of online public opinion during COVID-19: a hybrid approach using communication visualization, SIR modeling, and simulation validation
Authors: Ren Lin , Zhang Jiehua , Su Zhongyue , Lai Fujun , Xiong Deping
Published: September 2024

Introduction

This study investigates the mechanisms of public opinion dissemination and governance strategies during public health events, using a two-stage SIR model informed by the Information Cascade Theory.

Methods

The research employs Gephi visual analysis to identify principal nodes of public opinion and combines model simulations with dynamic propagation analysis to verify the model's precision and applicability.

Results

The findings reveal that pivotal information nodes significantly accelerate the spread of public opinion, while ordinary nodes contribute to the natural attenuation of public discourse due to their strong spontaneous recovery capabilities. The simulation analysis further identifies the optimal timing for government intervention, particularly during the initial and peak phases of public opinion dissemination.

Discussion

Based on the results, the study recommends strategies to strengthen the management of key opinion nodes, enhance public information literacy, optimize policy implementation, and utilize simulation tools to assist in public opinion management. These recommendations offer valuable theoretical and practical insights for managing public opinion during public health events.
An experimental study of acoustic bird repellents for reducing bird encroachment in pear orchards
Authors: Chen Qing , Xie Jingjing , Yu Qiang , Liu Can , Ding Wenqin , Li Xiaogang , Zhou Hongping
Published: September 2024

Bird invasion will reduce the yield of high-value crops, which threatens the healthy development of agricultural economy. Sonic bird repellent has the advantages of large range, no time and geographical restrictions, and low cost, which has attracted people’s attention in the field of agriculture. At present, there are few studies on the application of sonic bird repellents in pear orchards to minimize economic losses and prolong the adaptive capacity of birds. In this paper, a sound wave bird repellent system based on computer vision is designed, which combines deep learning target recognition technology to accurately identify birds and drive them away. The neural network model that can recognize birds is first trained and deployed to the server. Live video is captured by an installed webcam, and the sonic bird repellent is powered by an ESP-8266 relay switch. In a pear orchard, two experimental areas were divided into two experimental areas to test the designed sonic bird repellent device, and the number of bad fruits pecked by birds was used as an indicator to evaluate the bird repelling effect. The results showed that the pear pecked fruit rate was 6.03% in the pear orchard area that used the acoustic bird repeller based on computer recognition, 7.29% in the pear orchard area of the control group that used the acoustic bird repeller with continuous operation, and 13.07% in the pear orchard area that did not use any bird repellent device. While acoustic bird repellers based on computer vision can be more effective at repelling birds, they can be used in combination with methods such as fruit bags to reduce the economic damage caused by birds.