bluuebunny/crossref_metadata_2025 huggingface dataset:
Hollow fiber bioreactor allows sustained production of immortalized mesenchymal stromal cell-derived extracellular vesicles
Authors: Garcia Sergio G , Sanroque-Muñoz Marta , Clos-Sansalvador Marta , Font-Morón Miriam , Monguió-Tortajada Marta , Borràs Francesc E. , Franquesa Marcella
Published: May 2024

Aim: Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) have been reported to hold great potential as cell-free therapies due to their low immunogenicity and minimal toxicity. However, the large doses of MSC-EVs that are required for their clinical application highlight the urgency of finding a large-scale system for MSC-EV manufacture. In this study, we aimed to set up a hollow fiber bioreactor system for the continuous homogenous production of functional and high-quality MSC-EVs.

Methods: MSC lines from two donors were immortalized (iMSC) and inoculated into hollow fiber bioreactors. Throughout 4 weeks, conditioned medium was daily harvested. iMSC-EVs were purified and characterized for content, immunophenotype, size, and functionality and compared to 2D cultured iMSC.

Results: The iMSC inoculated into the bioreactor remained viable during the whole culture period, and they maintained their MSC phenotype at the end of EV production. Our results showed that the bioreactor system allows to obtain 3D-cultured iMSC-derived EVs (3D-EVs) that are comparable to flask (2D)-cultured iMSC-derived EVs (2D-EVs) in terms of protein and lipid content, size, and phenotype. We also confirm that 3D-derived EVs exhibit comparable functionality to 2D-EVs, showing pro-angiogenic potential in a dose-dependent manner.

Conclusions: These findings suggest that setting up a hollow fiber bioreactor system inoculating immortalized MSC lines facilitates the large-scale, functional, and high-quality production of iMSC-EVs. Our results emphasize the great potential of this production methodology to standardize EV production in the pursuit of clinical applications.
Exploring Extravasation in Cancer Patients
Authors: Pham Tuan D. , Tsunoyama Taichiro
Published: May 2024

Extravasation, the unintended leakage of intravenously administered substances, poses significant challenges in cancer treatment, particularly during chemotherapy and radiotherapy. This comprehensive review explores the pathophysiology, incidence, risk factors, clinical presentation, diagnosis, prevention strategies, management approaches, complications, and long-term effects of extravasation in cancer patients. It also outlines future directions and research opportunities, including identifying gaps in current knowledge and proposing areas for further investigation in extravasation prevention and management. Emerging technologies and therapies with the potential to improve extravasation prevention and management in both chemotherapy and radiotherapy are highlighted. Such innovations include advanced vein visualization technologies, smart catheters, targeted drug delivery systems, novel topical treatments, and artificial intelligence-based image analysis. By addressing these aspects, this review not only provides healthcare professionals with insights to enhance patient safety and optimize clinical practice but also underscores the importance of ongoing research and innovation in improving outcomes for cancer patients experiencing extravasation events.
The ‘Radiant Effect’: Recent Sonographic Image-Enhancing Technique and Its Impact on Nuchal Translucency Measurements
Authors: Bergsch Arne , Degenhardt Jan , Stressig Rüdiger , Dudwiesus Heiko , Graupner Oliver , Ritgen Jochen
Published: May 2024

Background: This study assesses the effects of the ‘Radiant’ image enhancement technique on fetal nuchal translucency (NT) measurements during first trimester sonographic ex-ams.

Methods: A retrospective analysis of 263 ultrasound images of first trimester midsagittal sections was conducted. NT measurements were obtained using a semi-automatic tool. Statistical methods were applied to compare NT measurements with and without ‘Radi-ant’ enhancement. An in-vitro setup with predefined line distances provided additional data.

Results: Incremental increases in NT measurements were observed with varying levels of ‘Radiant’ application: An average increase of 0.19 mm with ‘Radiant min’, 0.24 mm with ‘Radiant mid’ and 0.30 mm with ‘Radiant max.’ The in-vitro results supported these findings, showing consistent effects on line thickness and measurement accuracy, with the smallest mean deviation occurring at the ‘Radiant mid’ setting.

Conclusions: ‘Radiant’ image enhancement leads to significant increases in NT measure-ments. To avoid systematic biases in clinical assessments, it is advisable to disable ‘Radi-ant’ during NT measurement procedures. Further studies are necessary to corroborate these findings and to consider updates to the NT reference tables based on this technology.
In-Depth Analysis of Disaster (Risk) Management System in Serbia: A Critical Examination of Systemic Strengths and Weaknesses
Authors: Cvetković Vladimir M.
Published: May 2024

This study comprehensively explores Serbia's Disaster (Risk) Management System, aiming to critically evaluate its inherent strengths and weaknesses. Using descriptive-analytical methods and qualitative interpretation, SWOT analysis was applied to collect data from scientific papers, books, and institutional reports. This study delves deeply into the nuances of Serbia's Disaster Management Framework, revealing a nuanced landscape of strengths, weaknesses, and strategic improvement opportunities. Identified strengths underscore a robust foundation characterized by proficient professionals, state-of-the-art technology, and cohesive teamwork, all pivotal for effective emergency preparedness and response. Conversely, weaknesses underscore pressing imperatives for enhancements in regulatory enforcement, resource allocation, and infrastructure upgrades, presently hampering the framework's efficacy and response readiness. This research contributes to the ongoing discourse on disaster risk management and serves as a catalyst for further scholarly inquiry and policy formulation. By mapping out the structure of Serbia’s Disaster (Risk) Management Framework and integrating diverse data sources, the study enriches theoretical models and lays the groundwork for practical policy interventions. Its findings, including precise recommendations for policy reform and strategic improvements, provide valuable insights for policymakers, emergency management experts, and stakeholders seeking to enhance disaster preparedness and response capabilities on both national and global scales.
Unveiling the Antitumor Mechanism of 7α-Acetoxy-6β-Hydroxyroyleanone from Plectranthus hadiensis in Glioblastoma
Authors: Magalhães Mariana , Domínguez-Martín Eva María , Jorge Joana , Gonçalves Ana Cristina , Massenzio Francesca , Spigarelli Renato , Ribeiro-Rodrigues Teresa , Catarino Steve , Girão Henrique , Monti Barbara , Spisni Enzo , Ferreira Lino , Oliveira Paulo J. , Efferth Thomas , Rijo Patrícia , Cabral Célia
Published: May 2024

Glioblastoma (GB) is the most aggressive and prevalent glioma within the Central Nervous System. GB exhibit a dismal 5-year survival rate (~6%) due to unfavorable prognosis and lack of viable treatment options. Therefore, novel therapies with plant-derived compounds emerge as very promising. This study aims to investigate the antitumor activity of 7α-acetoxy-6β-hydroxyroyleanone (Roy) in GB cell lines. Roy was isolated from Plectranthus hadiensis Schweinf. and its antitumor mechanism was assessed in a panel of five GB cell lines to mimic tumor heterogeneity. Metabolic activity was evaluated by Alamar Blue® assay, while cell death, cell cycle regulation, mitochondrial membrane potential, and activated caspase-3 were evaluated by flow cytometry. mRNA levels of target genes were measured by qPCR and protein expression was assessed by Western blotting. Cell uptake and impact on mitochondrial morphology were evaluated by confocal microscopy. Roy induced G2/M cell cycle arrest, mitochondrial fragmentation, and apoptosis by inhibiting the expression of anti-apoptotic proteins and increasing activated caspase-3 levels with concentration 6-9 fold lower than those of temozolomide, the first-line treatment. Roy demonstrated a robust antitumor activity against GB cells, without affecting non tumoral cells (microglia and astrocytes), being a promising natural lead compound for the development of novel chemotherapeutic approaches.
Integration of Laban Movement System’s Effort Theory in Biomechanical Analysis of Golf Swing: A Focus on the Initiation of the Downswing and Hip Turn Dynamics
Authors: Kim Wangdo , Vette Albert H. , Ottes Wanda , Wahl Colleen
Published: May 2024

This study explores the application of the Laban/Bartenieff Movement System (® LBMS), particularly its Effort component, to analyze the biomechanical dynamics of the golf swing. Focusing on the initiation of the downswing, this paper investigates how the instantaneous screw axis (ISA) with rotational and linear motions contributes to subsequent movements, such as the hip turn. We propose that the physical forces generated by the golf club, characterized by mass moment inertia, extend beyond the body's boundaries, such as through the hand grip. A skilled golfer’s ability to 'allow' these forces to influence body dynamics without opposing them is analyzed through the lens of LBMS's Free Flow Effort, suggesting an indulgent and expansive use of movement energy.
Ergonomic Analysis of Working Postures Using OWAS In Scaffold Activities and Recommendations at Refinery Construction
Authors: Erdoğan Hakan , Yağımlı Mustafa , Tozan Hakan
Published: May 2024

Workers involved in scaffolding erection and dismantling activities are exposed to various physical risk factors. However, no existing study indicates that awkward working postures in scaffolding activities lead to musculoskeletal system disorders (MSDs). This study explores the ergonomic risks intrinsic to scaffolding tasks in refinery construction using the Ovako Working Posture Analysing System (OWAS).In the refinery, the utilized scaffolding encompasses an area of 319674 square meters and a volumetric extent of 603294 cubic meters. Observations were conducted on the postures of 500 scaffolding group workers across 5210 locations within the site, culminating in capturing 2000 photographic records. The mass of each scaffolding component was meticulously determined. After three months of observation, medical records were consulted for further insights. A statistical analysis employing the Pearson correlation technique was conducted to scrutinize the relationship between the ages of the scaffolding workers and the incidence of MSDs, alongside patterns of absenteeism. This analysis elucidated a robust and statistically significant correlation between the age of the workers and the prevalence of MSD associated with their occupational activities.As a result of the results of the OWAS ergonomic risk assessment, a number of regulatory changes were made to the scaffolding workforce, and then medical records were looked over again. This re-evaluation revealed a marked reduction in MSDs. The OWAS method's reliance on simple observational techniques holds substantial merit for its application within construction environments. Our research underscores the exposure of workers engaged in scaffolding tasks within continuous projects, such as refinery construction, to substantial ergonomic risks.
A Comprehensive Review on Various Techniques Used for Synthesizing Graphene Quantum Dots
Authors: singh laxmi , shukla hemant , Gupta Gopal
Published: May 2024

Graphene quantum dots (GQDs) have garnered significant attention in recent years due to their unique properties and promising applications in various fields such as electronics, optoelectronics, bioimaging, and sensing. The synthesis of GQDs is a critical step in harnessing their potential, and numerous methods have been developed to produce GQDs with specific properties. This review provides an overview of the different techniques employed for synthesizing GQDs, including top-down and bottom-up approaches. Furthermore, it discusses the advantages, limitations, and potential applications of each method, offering insights into the future direction of GQD synthesis research.
Methodological Rigor in Laboratory Education Research
Authors: Agustian Hendra Y.
Published: May 2024

Despite the growing number of published studies on student learning in the laboratory, there is a critical need to improve methodological rigor. Resonating with discussions on research methods, this paper outlines the importance of theory-informed research questions, the minimization of researcher and participant biases, and the use of triangulation and iteration in data collection to establish rigor. An illustrative case is presented within the context of a large interdisciplinary research project aimed at improving laboratory learning at the university level. The project incorporates two research avenues: one focusing on literature and faculty perspectives, and the other on a comprehensive assessment of multidimensional learning in the laboratory. The project employs a mixed methods paradigm and is grounded in a conceptual framework that conceptualizes laboratory work as epistemic practice, requiring a holistic analysis of student learning. The article concludes by discussing the results and implications of the project's findings, which are synthesized to highlight aspects of establishing methodological rigor. The overarching goal is to develop a comprehensive assessment instrument that captures the complexity and richness of the laboratory learning environment. The findings from this research are expected to contribute to the advancement of laboratory education research by providing a model for methodological rigor that can be applied across various scientific and interdisciplinary contexts.
Genetic Architecture of CHD in NICU patients – UMC Ljubljana Experience
Authors: Peterlin Ana , Bertok Sara , Writzl Karin , Lovrečić Luca , Maver Aleš , Debeljak Maruša , Nosan Gregor
Published: May 2024

Congenital heart disease (CHD) is the most commonly detected congenital anomaly and affects up to 1 % of all live-born neonates. Current guidelines support the use of Chromosomal Microarray Analysis (CMA) and Next Generation Sequencing (NGS) as diagnostic approaches to identify genetic causes. The aim of our study was to evaluate the diagnostic yield of CMA and NGS in a cohort of neonates with both isolated and syndromic CHD. The present study included 188 infants under 28 days of age with abnormal echocardiography findings hospitalized at the Department of Neonatology, UMC Ljubljana, between January 2014 and December 2023. Phenotypic data were obtained for each infant by retrospective medical chart review. We established the genetic diagnosis of 22 distinct syndromes in 17% of neonates. The most common genetic diagnoses were 22q11.2 microdeletion (22.7%) and CHARGE syndromes (22.7%), Noonan syndrome (9.1%), and Williams syndrome (9.1%). In addition, we detected variants of uncertain significance in 4.8% of neonates. Timely genetic diagnosis is important for the detection of syndrome-related comorbidities, prognosis, reproductive genetic risks and, when appropriate, genetic testing of other family members.
Real-World Efficacy and Safety of Paclitaxel-Gemcitabine in Relapsed Small-Cell Lung Cancer
Authors: Dantoing Edouard , Demontrond Pierre , Léturgie Bénédicte , Curcio Hubert , Orsini Charlotte , Coquard Aude , Tillon-Strozyk Julie , Gervais Radj , Thiberville Luc , Bota Suzanna , Guisier Florian
Published: May 2024

Small-cell lung cancer (SCLC) is a cancer with poor prognosis. For relapsed extensive-stage (ES) SCLC, second-line treatment options are scarce. Topotecan was the only approved treatment in this setting until 2020. Since topotecan induces significant toxicities, alternative off-label regimens are being used. This study evaluated real-world efficacy and safety of Paclitaxel Gemcitabine chemotherapy in patients with relapsed ES-SCLC. We retrospectively reviewed data from all consecutive patients with relapsed ES-SCLC who received Paclitaxel Gemcitabine chemotherapy from september 2008 to january 2022 in two centers. Patient characteristics (n=188) were: PS≥2: 24.5%; brain metastasis: 42%; platinum-sensitive disease: 41%. Patients received Paclitaxel Gemcitabine as second- (77%) third (18%) or fourth (6%) line of therapy. Median progression-free and overall survival were 2.1 (95CI 1.8–2.4) and 3.8 (95CI 3.3–4.8) months in the overall population, respectively, with 17% response rate (RR) and 28% disease-control rate. PS, history of brain radiation, platinum-sensitive disease, liver, and adrenal gland metastasis were associated with longer survival in univariate analysis. PS was the only prognostic factor in multivariate analysis, with 21% RR and 4.1 months median DOR in PS 0-1 patients.
Paclitaxel Gemcitabine chemotherapy may represent a treatment option in PS0-1 relapsed SCLC.
Cognitive Strategy Instruction in Vocabulary Learning Task: the Role of Intelligence
Authors: Izmalkova Anna
Published: May 2024

In paired-associate vocabulary learning task, second language learners employ different cognitive strategies, associated with either elaborative or rote rehearsal, resulting in different recall performance. The current study investigated the role of intelligence, measured with Raven’s Advanced Progressive Matrices, in strategy effects on performance and eye movement parameters. The Keyword method, which is regarded as a more effective cognitive strategy in paired-associate task, was induced on a sample of 32 healthy participants with normal or corrected to normal vision. Effective cognitive strategy use, mentioned in a structured post-hoc report, was found to improve performance after strategy induction. Higher intelligence score was associated with higher recall performance in case the Keyword method was reported, but not in the cases when no rote rehearsal was reported. No effect of cognitive strategy use on eye movement measures after explicit cognitive strategy instruction was revealed, which is supposed to be connected with lack of self-sustained strategy use immediately after strategy instruction. The findings emphasize the role of intelligence in cognitive strategy instruction.
Feasible Actuator Range Modifier (FARM), a Tool Aiding the Solution of Unit Dispatch Problems for Advanced Energy Systems
Authors: Wang Haoyu , Ponciroli Roberto , Alfonsi Andrea , Talbot Paul W. , Elmer Thomas W. , Epiney Aaron S. , Vilim Richard B.
Published: May 2024

Integrated energy systems (IES) seek to minimize power generating costs in future power grids through the dynamic coupling of different energy technologies. To accommodate fluctuations in load demand due to the penetration of renewable energy sources, flexible operation capabilities must be fully exploited, i.e., even power plants that are traditionally considered as base-load units need to be operated according to unconventional paradigms. Thermomechanical loads induced by frequent power adjustments can accelerate the wear and tear of components. If a unit is flexibly operated without respecting limits on materials and components, the risk of failures of expensive components will eventually increase, nullifying the additional profits ensured by flexible operation. In addition to the limits on power variations (explicit constraints), the solution of the unit dispatch problem needs to meet the limits on temperature, pressure and flow rate variations (implicit constraints). The FARM (Feasible Actuator Range Modifier) module was developed to enable existing optimization algorithms to identify solutions to the unit dispatch problem that are both economically favorable and technologically sustainable. Thanks to the iterative dispatcher-validator scheme, FARM permits addressing all the imposed constraints without excessively increasing the computational costs. In this work, the algorithms constituting the module are described, and the performance was assessed by solving the unit dispatch problem for an IES composed of three units, i.e., Balance of Plant, Gas Turbine, High-Temperature Steam Electrolysis. Finally, FARM module provides dedicated tools for visualizing the response of the process variables of interest during operation transients and a tool aiding the operator at making decisions. These techniques might represent the first step towards the deployment of an Ecological Interface Design (EID) for IES units.
Novel Diagnostic and Immunotherapeutic Approaches for Wheat Allergy
Authors: Zheng Wanqi , Wai Christine Yee Yan , Sit Jason Ka Chun , Cheng Nam Sze , Leung Christy Wing Man , Leung Ting Fan
Published: May 2024

Wheat, a component of the staple diet globally, is a common food allergen in children. The symptoms of wheat allergy (WA) range from skin rash to shortness of breath, significantly impairing quality of life. Following initial clinical suspicion, individuals may undergo wheat allergen-specific skin prick test (SPT), blood test for serum immunoglobulin E (sIgE) levels or oral food challenge. Conventional management of WA lies in wheat avoidance, yet accidental consumption may be inevitable owing to the ubiquity of wheat in various food products. This article aims to provide an overview of the immunologic pathway of WA, followed by its novel diagnostic methods, namely alcohol-soluble SPT extracts, component-resolved diagnosis and basophil activation test (BAT). The mechanisms underlying wheat allergen-specific oral immunotherapy (OIT) as well as a summary of the efficacy, tolerability and safety of related clinical trials will then be discussed.
Properties and mechanisms for PFAS adsorption to aqueous clay and humic soil components
Authors: Luft Charles , Schutt Timothy , Shukla Manoj
Published: May 2024

The proliferation of poly- and perfluorinated alkyl substances (PFASs) has resulted in global concerns over contamination and bioaccumulation. PFAS compounds tend to remain in the environment indefinitely, and research is needed to elucidate the ultimate fate of these molecules. We have investigated the model humic substance and model clay surfaces as a potential environmental sink for the adsorption and retention of three representative PFAS molecules with varying chain length and head groups. Utilizing molecular dynamics simulation, we quantify the ability of pyrophyllite and the humic substance to favorably adsorb these PFAS molecules from aqueous solution. We have observed that the hydrophobic nature of the pyrophyllite surface makes the material well suited for the sorption of medium- and long-tail PFAS moieties. Similarly, we find a preference for the formation of a monolayer on the surface for long-chain PFAS molecules at high concentration. Furthermore, we discussed trends in the adsorption mechanisms for the fate and transport of these compounds, as well as potential approaches for their environmental remediation.
Análise de custo de sequência de tratamento de câncer de ovário avançado, HRD/ BRCAwt, sob a perspectiva do sistema de saúde suplementar brasileiro
Authors: Bernardino Graziela , Samora Michelle , Reis Fabiana , Meirelles Isandra , Rodrigues Larissa , Alemar Marcella de , Tanaka Straus
Published: May 2024

Objetivo: Estimar o custo da sequência de tratamento considerando as terapias com niraparibe e bevacizumabe, respectivamente, como terapias de manutenção de 1L e 2L para pacientes com câncer de ovário (CO) epitelial com deficiência de recombinação homóloga (HRD) e BRCA selvagem (BRCAwt) em um horizonte temporal de cinco anos, sob a perspectiva do sistema de saúde suplementar brasileiro. Métodos: Foi desenvolvido um modelo de sobrevida particionado com três transições de estados de saúde, considerando os seguintes regimes em 1L e 2L, respectivamente: carboplatina + paclitaxel seguido de terapia de manutenção com niraparibe; carboplatina + gencitabina + bevacizumabe seguido pela continuação de bevacizumabe. As posologias em bula e as curvas de sobrevida livre de progressão dos respectivos estudos pivotais em cada uma das linhas terapêuticas foram utilizadas naanálise, e o custo de tratamento foi calculado a partir da lista oficial de preços de medicamentos da CMED de abril de 2023. Resultados: O custo em 1L e 2L foi de BRL 868.830 e BRL 403.407, totalizando BRL 1.272.237 em um horizonte temporal de cinco anos, com 2,28 e 0,52 anos de vida livre de progressão, respectivamente, na 1L e 2L, com o total de 2,8 anos. Conclusões: O resultado da análise de custo de sequência de tratamento de câncer de ovário HRD/BRCAwt apresentou um custo total estimado de BRL 1.272.237, com 2,8 anos de vida livre de progressão. Essa análise contribui no entendimento dos custos e da eficácia esperada com o uso da terapia de manutenção de niraparibe em 1L e bevacizumabe em 2L em um horizonte temporal de cinco anos.
Custo-utilidade da utilização de teste farmacogenético como guia para o tratamento de depressão sob a perspectiva do Sistema de Saúde Suplementar
Authors: Andrade-Silva Jessica , May Guido , Gueuvoghlanian-Lopes Bárbara , Freitas Isabela , Souza Bruna , May Paula , Teich Vanessa
Published: May 2024

Objetivo: Desenvolver uma análise de custo-utilidade da implementação do teste farmacogenético como uma ferramenta adicional para orientar a escolha do melhor tratamento medicamentoso para indivíduos com depressão. Métodos: Para a realização desta análise, criou-se um modelo analítico de decisão baseado em um modelo de Markov. A avaliação foi realizada sob a perspectiva do Sistema de Saúde Suplementar brasileiro, com horizonte temporal de 10 anos, incluindo custos médicos diretos e custos da tecnologia utilizada, além de ter como comparador o tratamento empírico tradicional para a depressão. As probabilidades de transição foram obtidas por meio de análise da literatura disponível. Também foram realizadas análises de sensibilidade probabilística e univariada. Adicionalmente, foi realizada uma avaliação sob a perspectiva da sociedade, incluindo os custosde tratamento medicamentoso realizados pelos pacientes. Resultados: De acordo com a análise realizada, o emprego do teste farmacogenético como guia do tratamento para depressão mostrou-se favorável, proporcionando economia de -R$ 3.439,97 por paciente e aumento de 0,39 QALY ao longo do horizonte temporal. Assim, evidencia-se uma economia significativa a favor do testefarmacogenético, correspondendo a -R$ 8.776,78 por QALY salvo. Além disso, a robustez do modelo foi comprovada por meio das análises de sensibilidade. No cenário sob perspectiva da sociedade, o resultado foi ainda mais favorável, proporcionando economia de -R$ 9.381,49 por paciente e aumento de 0,39 QALY, correspondendo a -R$ 23.936,05 por QALY salvo. Conclusão: Os resultadosencontrados neste estudo demonstraram que o uso de testes farmacogenéticos no tratamento da depressão é economicamente vantajoso, com aumento no valor de QALY e redução nos custos médicos diretos, em comparação ao tratamento empírico tradicional. Essa descoberta alinha-se à tendência atual de personalização no cuidado da saúde mental, sugerindo implicações práticas na reavaliação de protocolos, com potencial incorporação dos testes farmacogenéticos como padrãode cuidado.
Identification of Fake Messages Using Two PKCs
Authors: Dissanayake W.D.M.G.M.
Published: May 2024

In this paper, two public key cryptosystems are presented and analyzed. The first cryptosystem is an improvement of the RSA public key cryptosystem. The second cryptosystem is a novel public key cryptosystem. The encryption/decryption moduli of the second scheme are quite different from widely used encryption/decryption moduli by other public key cryptosystems. This cryptosystem is based on the exponentiation congruence and use an interesting, computer-friendly modulus: 2^n. These primitives can be used in protocols for authentication, key exchanges, and digital signatures. These two public key cryptosystems are more suitable for highly confidential digital transactions. Both of the cryptosystems are strongly IND secure. The most important thing is, that the both of the public key cryptosystems can identify whether a message is fake. The second public key cryptosystem is more secure for quantum attacks than the RSA. It is also very collaborative with hash functions such as Whirlpool and SHA-512, because of the modulus 2^n.
The transcriptional landscape underlying larval development and metamorphosis in the Malabar grouper (Epinephelus malabaricus)
Authors: Huerlimann Roger , Roux Natacha , Maeda Ken , Pilieva Polina , Miura Saori , Chen Hsiao-chian , Izumiyama Michael , Laudet Vincent , Ravasi Timothy
Published: May 2024

Most teleost fishes exhibit a biphasic life history with a larval oceanic phase that is transformed into morphologically and physiologically different demersal, benthic or pelagic juveniles. This process of transformation is characterized by a myriad of hormone induced changes, during the often abrupt transition between larval and juvenile phases called metamorphosis. Thyroid hormones (TH) are known to be instrumental for triggering and coordinating this transformation but other hormonal systems such as corticoids, might be also involved as it is the case in amphibians. In order to investigate the potential involvement of these two hormonal pathways in marine fish post-embryonic development, we used the Malabar grouper (Epinephelus malabaricus) as a model system. We assembled a chromosome-scale genome sequence and conducted a transcriptomic analysis of nine larval developmental stages. We studied the expression patterns of genes involved in TH and corticoid pathways, as well as four biological processes known to be regulated by TH in other teleost species: ossification, pigmentation, visual perception, and metabolism. Surprisingly, we observed an activation of many of the same pathways involved in metamorphosis also at an early stage of the larval development, suggesting an additional implication of these pathways in the formation of early larval features. Overall, our data brings new evidence to the controversial interplay between corticoids and thyroid hormones during metamorphosis as well as, surprisingly, during the early larval development. Further experiments will be needed to investigate the precise role of both pathways during these two distinct periods and whether an early activation of both corticoid and thyroid hormone pathways occur in other teleost species.
Mixed methods analysis of medical students' symptoms and feelings during a catastrophic period
Authors: Felix Soraia Nogueira , Costa Anna Paula Lima , Andrade Juliana Matsumoto , Correia Aristides Tadeu , Costa Fernanda Magalhães Arantes , Kobayasi Renata , Garcia Maria Lúcia Bueno , Martins Milton de Arruda , Tempski Patrícia Zen , Tibério Iolanda de Fátima Lopes Calvo , Romanholo Beatriz Mangueira Saraiva
Published: May 2024

Background: Social restrictions and isolation during pandemic may have contributed to various physical and emotional disorders. We aimed to assess the perceptions of medical students regarding their emotions, anxiety and depression symptoms, and daily experiences during the pandemic.
Methods: a prospective mixed methods study involving students in their 1st to 4th years of medicine at a university in São Paulo, Brazil(2020-2021). Participants completed standardized questionnaires online about anxiety, depression, happiness, and quality of life, and participated in an online focus group.
Results: A total of 313 students completed the questionnaires, 200 were involved in the focus group. Women exhibited higher scores for anxiety (p=0.002) and depression (p=0.007); men demonstrated better quality of life (p=0.042). Younger students presented better quality of life (p=0.048) and lower anxiety (p=0.001). The focus groups revealed recurring negative feelings: anxiety, depression, tiredness, loneliness, difficulty managing time and others, resulting in reduced mental and physical health during the pandemic. Coping strategies were discussed, including the adoption of new healthy habits, religious practices, and reconnection with family.
Limitations:while there are moderate correlations, the instruments utilized do not provide diagnoses and do not suggest a causal link. Nonparametric processes can cause bias in a correlational study like this one.
Conclusion: Depression and anxiety symptoms were more prevalent among females, while quality of life improved for younger and male students. The qualitative analysis enhanced our understanding of the determinants and consequences of students' recurring negative feelings and revealed positive aspects such asgreater proximity to family and religiosity.
Towards net-zero emissions in global residential heating and cooling: a global scenario analysis
Authors: Mastrucci Alessio , Boza-Kiss Benigna , Ruijven Bas van
Published: May 2024

Accounting for 21% of global greenhouse gas (GHG) emissions, buildings play a crucial role in climate change mitigation. Demand-side interventions entail large energy and GHG emission reduction potentials. The effects of broader mitigation policies at the global level beyond energy efficiency improvements, including sufficiency and structural changes, and their interaction with cross-sectoral climate policies are, however, still unclear. Here, we assess a comprehensive set of scenarios to reduce residential space heating and cooling emissions towards net-zero targets. We find that activity reductions, fuel shifts, and technological improvements can reduce current global residential space heating and cooling CO2 emissions by 61% until 2050. Combining these demand-side interventions and stringent climate policies entails up to 96% reduction of current CO2 emissions by 2050. Neutralizing residual direct CO2 emissions due to fossil fuels for space heating would require additional interventions.
Introducing gene-edited copies of BrSOC1 genes into late-bolting inbred Chinese cabbage lines effectively delays bolting
Authors: Jung Haemyeong , Park Hyun Ji , Jo Seung Hee , Lee Areum , Jung Min , Kim Youn-Sung , Cho Hye Sun
Published: May 2024

Background
Late bolting occurs when a plant inherits two recessive late-bolting alleles at the same locus, requiring time and effort for sustainable cultivar development.
Results
We generated late-bolting F1 hybrids by crossing Chinese cabbage (Brassica rapa) lines genome-edited in SUPPRESSOR OF OVEREXPRESSION OF CO1 (BrSOC1) with late-bolting inbred lines. We generated F1 hybrids by crossing Cas9-free lines with knockouts in two or three BrSOC1 genes to early- or late-bolting inbred lines. Crossing brsoc1 knockout lines with the early-bolting 20 inbred line delayed bolting compared with parental lines. However, the extent of delayed bolting was more pronounced when using late-bolting inbred lines as parents. We selected JN06 and JN08 as late-bolting inbred lines with low expression of BrSOC1s: F1 hybrids derived from crosses between brsoc1s and JN06 or JN08 showed significantly improved late-bolting traits, with more days after bolting and more leaves produced, surpassing those of the parental lines. Notably, F1 hybrids carrying one gene-edited copy of each BrSOC1 exhibited a greater delay in bolting, of up to 12 days, compared with F1 hybrids carrying fewer gene-edited brsoc1 copies. The expression levels of genes downstream of SOC1 were also significantly lower in the F1 hybrids compared with the parental lines. Furthermore, these F1 hybrids demonstrated greater resistance to bolting than commercial varieties.
Conclusions
Our findings highlight the efficacy of generating F1 hybrids using genome-edited brsoc1s as a parent to inhibit bolting in Chinese cabbage and expedite the breeding of cultivars with improved traits.
A Nomogram model for predicting early hyperglycemia in premature infants
Authors: Wang Yongming , Xu Fengzhi , Yin Huijuan , Xu Wang , Luo Jingxia , He Jianping , Wu Shasha
Published: May 2024

BACKGROUND/AIMS: Hyperglycemia in preterm infants is likely to lead to severe complications and higher mortality. Timely identification of hyperglycemia in preterm infants is vital for the prognosis of patients. We developed and validated predictive models for hyperglycemia in preterm infants < 32 weeks of gestational age to aid in the early detection of these patients.
METHODS:A retrospective analysis was performed on 460 premature infants to examine the association of various clinical variables with hyperglycemia. We collected data from June 1, 2021, to May 31, 2023. clinical and demographic parameters were analyzed using univariable and multivariable logistic regression analysis(backward method). We constructed a nomogram to assess the risk of hyperglycemia. The model's accuracy was validated using bootstrap resampling (n=500), and the POC curve was used for discrimination analysis to calibrate function and value. Calibration was evaluated via a calibration curve. The model's clinical utility was evaluated through decision curve analysis.
RESULTS: Of the 29 potential predictors analyzed in 460 premature infants, the incidence of hyperglycemia was 24.1%. Multivariable logistic regression analysis identified birth weight, invasive ventilation, and Intraventricular hemorrhage as independent risk factors for premature infants with hyperglycemia. The resulting nomogram accurately predicted hyperglycemia risk with an area under the curve of 0.735(95%CI: 0.685-0.786). The bootstrap-validated area under the curve remained at 0.735(95%CI: 0.687-0.785). This model exhibited excellent calibration and demonstrated greater predictive efficacy and clinical utility for hyperglycemia. CONCLUSIONS: We have developed a prediction nomogram of hyperglycemia that can assist clinical treatment decision-making.
The teaching of Pediatric Palliative Care in medical residencies
Authors: Peripolli Marcelle , Okamoto Cristina Terumy , Coelho Izabel Cristina Meister Martins , Melo Fernanda Pegoraro de Godoi , Kojo Maria Vitoria Mesquita , de Almeida Marcio José
Published: May 2024

Objective: The aim of this study was to understand the perceptions of newly graduated pediatricians in medical residency programs regarding palliative care education, seeking potential gaps in training and comprehending whether professionals feel equipped to manage these patients.
Method: This is an exploratory and descriptive study with a qualitative approach. Semistructured interviews were conducted in a virtual environment with 15 pediatricians who graduated from three pediatric medical residency programs in a capital city. The information was processed according to the content analysis method proposed by Bardin with the support of ATLAS.ti software.
Results: Respondents reported a lack of theoretical and practical preparation regarding palliative care education and did not feel qualified to manage these patients. They also highlight the importance of the palliative care physician, not only for the appropriate treatment of patients but also as a facilitator of teaching during medical residency. Participants noted the need for greater knowledge about the bioethical and legal aspects of pediatric palliative care and for adequate time to address the subject with the patient and their families.
Conclusions: Despite the relevance of this topic, there are still gaps in the teaching-learning process of pediatric palliative care, from undergraduate to postgraduate education. It is necessary to invest in more research to develop a suitable curriculum that favors education through specific and mandatory spaces for palliative care within residency programs.
A Novel Approach to Engineering Three-dimensional Bladder Tumor Models for Drug Testing.
Authors: Monjaras-Avila Cesar Ulises , Luque-Badillo Ana Cecilia , Bacon Jack , Wyatt Alexander , So Alan , Chavez-Munoz Claudia
Published: May 2024

Bladder cancer (BCa) poses a significant health challenge, particularly affecting men with higher incidence and mortality rates. Addressing the need for improved predictive models in BCa treatment, this study introduces an innovative 3D in vitro patient-derived bladder cancer tumor model, utilizing decellularized pig bladders as scaffolds. Traditional 2D cell cultures, insufficient in replicating tumor microenvironments, have driven the development of sophisticated 3D models. In the development of the in vitro bladder cancer model, muscle invasive bladder cancer patients' cells were cultured within decellularized pig bladders, yielding a three-dimensional cancer model. To demonstrate the 3D cancer model's effectiveness as a drug screening platform, the 3D models were treated with Cisplatin (Cis), Gemcitabine (Gem), and a combination of both drugs. Comprehensive cell viability assays and histological analyses illustrated changes in cell survival and proliferation. The model exhibited promising correlations with clinical outcomes, boasting an 83.3% reliability rate in predicting treatment responses. Comparison with traditional 2D cultures and spheroids underscored the 3D model's superiority in reliability, with an 83.3% predictive capacity compared to 50% for spheroids and 33.3% for 2D culture. Acknowledging limitations, such as the absence of immune and stromal components, the study suggests avenues for future improvements. In conclusion, this 3D bladder cancer model, combining decellularization and patient-derived samples, marks a significant advancement in preclinical drug testing. Its potential for predicting treatment outcomes and capturing patient-specific responses opens new avenues for personalized medicine in bladder cancer therapeutics. Future refinements and validations with larger patient cohorts hold promise for revolutionizing BCa research and treatment strategies.
CHAMP1 premature termination codon mutations found in individuals with intellectual disability cause a homologous recombination defect through haploinsufficiency
Authors: Yoshizaki Yujiro , Ouchi Yunosuke , Kurniawan Dicky , Yumoto Eisuke , Yoneyama Yuki , Rizqullah Faiza Ramadhani , Sato Hiyori , Sarholz Mirjam Hanako , Natsume Toyoaki , Kanemaki Masato T. , Ikeda Masanori , Ui Ayako , Iemura Kenji , Tanaka Kozo
Published: May 2024

CHAMP1 (chromosome alignment-maintaining phosphoprotein 1) plays a role in the repair of DNA double-strand breaks (DSBs) by homologous recombination (HR). The CHAMP1 gene is one of the genes mutated in individuals with intellectual disability. The majority of the mutations are premature termination codon (PTC) mutations, while missense mutations have also been reported. How these mutations affect the functions of CHAMP1 has not been clarified yet. Here we investigated the effects of the CHAMP1 mutations on HR. In B lymphocytes and fibroblasts derived from individuals with CHAMP1 PTC mutations, truncated CHAMP1 proteins of the expected sizes were detected. When DSBs were induced in fibroblasts with PTC mutations, a defect in HR was detected. U2OS cells expressing the CHAMP1 mutants did not show an HR defect in the presence of endogenous wild-type (WT) CHAMP1, whereas they were unable to restore HR activity when WT CHAMP1 was depleted, suggesting that the PTC mutations are loss-of-function mutations. On the other hand, the CHAMP1 mutants with missense mutations restored HR activity when WT CHAMP1 was depleted. In DLD-1 cells, heterozygous depletion of CHAMP1 resulted in an HR defect, indicating haploinsufficiency. These results suggest that CHAMP1 PTC mutations cause an HR defect through a haploinsufficient mechanism, while CHAMP1 missense mutations do not affect the HR function of CHAMP1.
Physical pressure resistance of gastrointestinal anastomotic site via polyglycolic acid promoting fibrosis
Authors: Tanda Hideki , Shibutani Masatsune , Natsuki Seiji , Kasashima Hiroaki , Fukuoka Tatsunari , Maeda Kiyoshi
Published: May 2024

Anastomotic-leakage incidence has been reported to be reduced on using polyglycolic acid (PGA) sheets as reinforcing materials; however, there is insufficient evidence regarding the reinforcement mechanism. Therefore, we investigated effects of PGA sheets on gastrointestinal anastomoses in rats. In the first approach, five rats underwent laparotomy; the PGA sheet was pasted onto the normal cecal wall. After five days, the cecum was removed and histologically evaluated. In the second approach, ten rats were randomly divided into two groups of five animals each. The rats underwent laparotomy; the cecal wall was sutured after a full-thickness incision. In the PGA group, a PGA sheet was used to cover the suture area. After 5 days, the cecum was removed, and the physical pressure resistance was evaluated. We confirmed the growth of a fibrous capsule measuring 855 (648–1048) µm outside the cecal serosa in the first approach. The median pressure resistance in the second approach was 57 (45.0–90.0) and 90 (82.5–94.5) mmHg in Control and PGA groups, respectively. The pressure resistance was significantly higher in the PGA group (p = 0.046). In summary, the PGA sheet may form a barrier of fibrosis on the intestinal wall and provide reinforcement to prevent anastomotic leakage.
Research on sorting reinforcement and repair order of ancient timber buildings based on an ordered fractile weight method
Authors: Gao Zhongwei , Du Yue , Zhang Jinfang , Zhang Yingda , Zhao Shiyu , Yang Xiaobing
Published: May 2024

Ancient timber buildings have existed for a long time. However, due to wood’s natural characteristics, it is prone to damage such as insect infestation, decay, and cracking, resulting in structural unsafety. Therefore, partial and intermittent reinforcement and repair are essential for maintaining ancient timber buildings. Due to limited financial and material resources, it is critical to determine and sort the priority order of reinforcing and repairing ancient timber buildings. In this study, an ordered fractile weighted method was adopted to establish a sorting method that reviews the incentive preferences of decision-makers during the information aggregation process and measures the development levels of the evaluated objects on various indicators. A case study was also used to trial the sorting method. By using the weighted sum with weights not equal to 1 in the information aggregation process, the aggregation values were reduced, thereby further highlighting the differences between the evaluated objects. The method was concluded to be flexible in application and could address the rational sorting of reinforcement and repair order for ancient timber buildings. Thus, it provides a basis for decision-making for the protection and management of ancient buildings.
Cytomegalovirus Results in Poor Graft Function via Bone Marrow-Derived Endothelial Progenitor Cells
Authors: Lv Weiran , Zhou Ya , Zhao Ke , Li Xuan , Huang Fen , Fan Zhiping , Chang Yuan , Yi Zhengshan , Jin Hua , Liang Yang , Liu Qifa
Published: May 2024

Poor graft function (PGF), characterized by myelosuppression, represents a significant challenge following allogeneic hematopoietic stem cell transplantation (allo-HSCT) with human cytomegalovirus (HCMV) being established as a risk factor for PGF. However, the underlying mechanism remains unclear. Bone marrow endothelial progenitor cells (BM-EPCs) can support hematopoiesis. We aim to explore the effects of CMV on BM-EPCs and its underlying mechanism. We investigated the compromised functionality of EPCs derived from individuals diagnosed with HCMV viremia (HCMV-emia) accompanied by PGF as well as after infected by HCMV AD 169 strain in vitro. We found dysfunction of HCMV-infected EPCs was characterized by decreased cell proliferation, tube formation, migration and hematopoietic support, and increased apoptosis and secretion of TGF-β1. We demonstrated that HCMV-induced TGF-β1 secretion by BM-EPCs played a dominant role in hematopoiesis suppression in vitro experiment. Moreover, HCMV up-regulates the p38 MAPK and its downstream transcription factor AP-1 to induce myelosuppression through promoting TGF-β1 secretion. In conclusion, HCMV could infect BM-EPCs and lead to their dysfunction. Enhanced secretion of TGF-β1 by BM-PECs is induced by HCMV through the up-regulation of p38 MAPK and its downstream transcription factor AP-1, resulting in myelosuppression, which might make a substantial contribution to the pathogenesis of PGF after allo-HSCT.