bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Overnight Storage of Human Atrial Myocytes on Intracellular Calcium Homeostasis and Electrophysiological Utility
Authors: Aceituno Cristina , Revuelta David , Jiménez-Sábado Verónica , Ginel Antonino , Molina Cristina E. , Hove-Madsen Leif
Published: November 2024

Human atrial myocytes afford an attractive experimental model to investigate mechanisms underlying electrophysiological alterations in cardiovascular disease. However, this model presents limitations, such as the availability of human atrial tissue and a variable yield of myocytes isolation. Therefore, we aimed to determine whether overnight storage can increase the time window where the electrophysiological properties of human atrial myocytes can be determined. To address this issue, human atrial myocytes isolated from patients undergoing cardiac surgery were used for patch-clamp experiments on the day of cell isolation (Day 1) and the following day (Day 2). The shape of the current–voltage (I–V) relationship for the calcium current (ICa) depended on the access resistance and the cell capacitance, with large cells (>75 pF) requiring a lower access resistance (<15 MΩ) than small cells (<40 pF) to avoid distortion of the I–V curve. Importantly, overnight storage did not significantly affect (1) the ICa amplitude or properties, (2) sarcoplasmic reticulum calcium homeostasis or (3) the frequency-dependency of the beat-to-beat response. In conclusion, overnight storage of isolated human atrial myocytes at 4 °C does not affect essential features of intracellular calcium homeostasis and, therefore, affords a simple protocol to extend the experimental lifetime of human atrial myocytes.
A Simple and Efficient One-Step Synthesis System for Flexible Production of Circular RNA in E. coli
Authors: Zhao Xiayang , Liu Yiqing , Huang Huanhui , Sun Yue , Wu Fangli , Jin Weibo
Published: November 2024

Circular RNA (circRNA) exhibits a higher stability and intracellular half-life than linear RNA and has better potential in the fields of RNA vaccines and RNAi drugs. The current strategies for circRNA preparation have low efficiency, high costs, and high complexity, which significantly limits their applications. In this paper, we propose a one-step synthesis of circRNA based on E. coli. The four RNA sequence lengths of 1700, 1400, 500, and 64 nt were connected to group II intron elements from the surface protein region of Clostridium tetani and then inserted downstream of the T7 promoter in the pET28a plasmid to assist in cyclization. Then, circRNA was produced in HT115, where the yields of pET28-1700, pET28-1400, pET28-500, and pET28-64 were improved to 820, 783, 691, and 460 ng/1 mL, respectively. Consequently, this system could achieve the mass production of circRNA using only a simple E. coli culture and inducible expression. Meanwhile, the overexpressed circRNA and small circular interference RNA (sciRNA) maintained their biological functions in the protein translation and RNAi. Therefore, this simple and efficient one-step synthesis system can be applied to the functional study and preparation of circRNA in the future.
Advances in the Synthesis and Biological Applications of Enoxacin-Based Compounds
Authors: Suleiman Garba , El Brahmi Nabil , Guillaumet Gérald , El Kazzouli Saïd
Published: November 2024

A comprehensive review of advances in the synthesis and biological applications of enoxacin (1, referred to as ENX)-based compounds is presented. ENX, a second-generation fluoroquinolone (FQ), is a prominent 1,8-naphthyridine containing compounds studied in medicinal chemistry. Quinolones, a class of synthetic antibiotics, are crucial building blocks for designing multi-biological libraries due to their inhibitory properties against DNA replication. Chemical modifications at positions 3 and 7 of the quinolone structure can transform antibacterial FQs into anticancer analogs. ENX and its derivatives have been examined for various therapeutic applications, including anticancer, antiviral, and potential treatment against COVID-19. Several synthetic methodologies have been devised for the efficient and versatile synthesis of ENX and its derivatives. This review emphasizes all-inclusive developments in the synthesis of ENX derivatives, focusing on modifications at C3 (carboxylic acid, Part A), C7 (piperazinyl, Part B), and other modifications (Parts A and B). The reactions considered were chosen based on their reproducibility, ease of execution, accessibility, and the availability of the methodology reported in the literature. This review provides valuable insights into the medicinal properties of these compounds, highlighting their potential as therapeutic agents in various fields.
The Quest for Eternal Youth: Hallmarks of Aging and Rejuvenating Therapeutic Strategies
Authors: Nunkoo Vharoon Sharma , Cristian Alexander , Jurcau Anamaria , Diaconu Razvan Gabriel , Jurcau Maria Carolina
Published: November 2024

The impressive achievements made in the last century in extending the lifespan have led to a significant growth rate of elderly individuals in populations across the world and an exponential increase in the incidence of age-related conditions such as cardiovascular diseases, diabetes mellitus type 2, and neurodegenerative diseases. To date, geroscientists have identified 12 hallmarks of aging (genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, impaired macroautophagy, mitochondrial dysfunction, impaired nutrient sensing, cellular senescence, stem cell exhaustion, defective intercellular communication, chronic inflammation, and gut dysbiosis), intricately linked among each other, which can be targeted with senolytic or senomorphic drugs, as well as with more aggressive approaches such as cell-based therapies. To date, side effects seriously limit the use of these drugs. However, since rejuvenation is a dream of mankind, future research is expected to improve the tolerability of the available drugs and highlight novel strategies. In the meantime, the medical community, healthcare providers, and society should decide when to start these treatments and how to tailor them individually.
Decreased Expression of the EAAT5 Glutamate Transporter at Photoreceptor Synapses in Early, Pre-Clinical Experimental Autoimmune Encephalomyelitis, a Mouse Model of Multiple Sclerosis
Authors: El Samad Ali , Jaffal Julia , Ibrahim Dalia R. , Schwarz Karin , Schmitz Frank
Published: November 2024

Background: Multiple sclerosis is a frequent neuroinflammatory and neurodegenerative disease of the central nervous system that includes alterations in the white and gray matter of the brain. The visual system is frequently affected in multiple sclerosis. Glutamate excitotoxicity might play a role in disease pathogenesis. Methodology: In the present study, we analyzed with qualitative and quantitative immunofluorescence microscopy and Western blot analyses whether alterations in the EAAT5 (SLC1A7) glutamate transporter could be involved in the previously observed alterations in structure and function of glutamatergic photoreceptor ribbon synapses in the EAE mouse model of MS. EAAT5 is a presynaptic glutamate transporter located near the presynaptic release sites. Results: We found that EAAT5 was strongly reduced at the photoreceptor synapses of EAE retinas in comparison to the photoreceptor synapses of the respective control retinas as early as day 9 post-immunization. The Western blot analyses demonstrated a decreased EAAT5 expression in EAE retinas. Conclusions: Our data illustrate early alterations of the EAAT5 glutamate transporter in the early pre-clinical phase of EAE/MS and suggest an involvement of EAAT5 in the previously observed early synaptic changes at photoreceptor synapses. The precise mechanisms need to be elucidated by future investigations.
Childhood Maltreatment and Adolescent Risky Behavior: Mediating the Effect of Parent–Adolescent Conflict and Violent Tendencies
Authors: Özdemir Bişkin Serap
Published: November 2024

Childhood maltreatment experiences are an important public health issue associated with a variety of short- and long-term social and psychological outcomes. Despite the negative impact of these experiences, little research has examined the mechanisms underlying the relationship between childhood maltreatment and adolescent risky behavior, which is a critical step in developing intervention services to prevent such behavior during adolescence. The present study aimed to examine the mediating role of parent–adolescent conflict and violent tendency in the relationships between childhood maltreatment and adolescent risky behavior in adolescence. Participants were 303 high school students, 60.1% female (n = 182) and 39.9% (n = 121) male, from four different high schools in Türkiye. It was found that childhood maltreatment was significantly and positively associated with adolescent risky behavior. In addition, that parent–adolescent conflict and violent tendencies mediated the relationship between childhood maltreatment and adolescent risky behavior. And also parent–adolescent conflict mediated the relationship between childhood maltreatment and violent tendencies and adolescent risky behavior. The results of this study suggest that parent–adolescent conflict and violent tendencies are important in increasing the impact of childhood maltreatment on adolescent risky behavior. In order to reduce the impact of maltreated childhood experiences on risky behavior, interventions can be designed to increase positive adolescent–parent relationships and reduce violent tendencies.
Developmental Trajectories of Loneliness Among Chinese Early Adolescents: The Roles of Early Peer Preference and Social Withdrawal
Authors: Chen Wanfen , Xiao Bowen
Published: November 2024

This study aimed to examine distinct loneliness trajectories and to explore the roles of group-level peer preference and individual-level social withdrawal (i.e., unsociability and shyness) as predictors of these trajectories. Participants were 1134 Chinese elementary school students (Mage = 10.44 years; 565 boys). Data were collected from self-reports and peer nominations. Latent class growth analysis (LCGA) was employed to identify distinct trajectories of loneliness, and multinomial logistic regression was subsequently used to examine the relationships between these trajectories and their predictors. Results showed that three loneliness trajectories were identified: high increasing, moderate decreasing, and low decreasing. Participants at baseline with higher peer preference were more likely to belong to the low decreasing trajectory subgroup rather than the other two subgroups. Furthermore, those at Time 1 with higher unsociability had lower odds of being classified into the moderate or low decreasing trajectory subgroup compared to the high increasing trajectory subgroup. Additionally, participants at baseline with higher shyness had reduced likelihoods of following the low decreasing trajectory subgroup as opposed to the other two subgroups. These results have implications for how we understand both the different subgroups of loneliness trajectories and the predictions of peer preference and social withdrawal on these trajectories in Chinese early adolescents.
Do Boys Empathize Less than Girls? Exploring the Links Among Empathy, Gender and Sexist Attitudes in Adolescents
Authors: García-Senlle Magaly Luisina , Martín-Fernández Manuel , Conchell Raquel , Arrojo Sara , Lila Marisol
Published: November 2024

(1) Background: Intimate partner violence (IPV) remains a pervasive issue, particularly among adolescents. Its prevalence is still high despite intervention efforts, especially for younger generations. Empathy and sexism are factors linked with IPV that have shown gender differences. This study focuses on how gender moderates the association of empathy and sexist attitudes among adolescents in Spain; (2) Methods: A two-stage stratified cluster sampling method for collecting data from 516 adolescents (219 boys, 297 girls) aged 12–18 years was used. Participants completed the Ambivalent Sexism Inventory and the Interpersonal Reactivity Index. Hierarchical multiple regression analyzed the moderating role of gender in the relation between empathy and ambivalent sexism; (3) Results: Boys exhibited higher sexism levels than girls. Perspective taking negatively predicted hostile sexism. Empathic concern positively predicted hostile and benevolent sexism. Significant gender-specific patterns emerged: more empathic concern was linked with increased hostile sexism in boys; higher perspective taking was linked with increased benevolent sexism in boys, but was lower in girls; (4) Conclusions: There is a complex interplay among empathy, gender, and sexism, suggesting that IPV prevention programs should be tailored differently for boys and girls by considering broader socio-political contexts, addressing traditional gender norms, and promoting gender equality.
Different Deeds, Different Needs—Types of Violence Against Women and Social Support Sought Online
Authors: Pavšič Mrevlje Tinkara , Erčulj Vanja Ida
Published: November 2024

Women, as victims of violence, among which intimate partner violence prevails, venture online to seek a supportive community. Members of online support groups differ in the experiences and needs they have and support they seek. The objective of this research was to explore the difference in types of support sought and support received between women who self-report having been a witness/victim of violence and others who directly ask for help without explaining their circumstances. For this purpose, content analysis of 600 randomly selected starting posts from an online support community was performed. The results reveal an association between the needs expressed and the experience of violence described. Although users most frequently sought informational support, those recounting sexual violence more often asked for emotional support or were looking for an emotional release. Posts describing a different kind of violence were more likely to bring more support than short posts directly asking for help. The findings are important since women in a violent relationship tend to become more isolated or controlled by their partners, pointing to the crucial role of online support in helping and encouraging those women to take the first step in seeking help from formal institutions.
Impact of Teleworking Practices on Presenteeism: Insights from a Cross-Sectional Study of Japanese Teleworkers During COVID-19
Authors: Otsuka Yuichiro , Itani Osamu , Nakajima Suguru , Matsumoto Yuuki , Kaneita Yoshitaka
Published: November 2024

Few studies have examined the relationship between teleworking practices and presenteeism. This study determined the association between teleworking practices and presenteeism among teleworkers in Japan. A cross-sectional online survey was administered to 2687 teleworkers from five companies in Japan, collecting data on demographic variables, teleworking practices, frequency and duration of teleworking, presenteeism, and various lifestyle- and health-related factors. A logistic regression analysis was performed. Teleworkers with full-time employment and less teleworking experience exhibited higher presenteeism rates. Key practices negatively associated with presenteeism included creating a dedicated workspace, chatting with colleagues, and setting daily work goals. Gender differences were significant: for men, additional practices, such as determining their work hours, were beneficial; while for women, chatting with colleagues was particularly important. A sensitivity analysis indicated that specific teleworking practices can mitigate presenteeism. Certain teleworking practices, such as creating a workspace, chatting with colleagues, and setting work goals, were associated with lower presenteeism among teleworkers. These findings highlight the need for organizations to support telework ergonomics, promote social interaction, and encourage goal setting to enhance teleworker productivity and health. Training for employees and supervisors to raise awareness of their own and their subordinates’ health while teleworking is advised.
Fluid Flow Modeling and Experimental Investigation on a Shear Thickening Fluid Damper
Authors: Chen Shiwei , Fu Xiaojiao , Meng Peiling , Cheng Lei , Wang Lifang , Yuan Jing
Published: November 2024

Shear Thickening Fluid (STF) is a specialized high-concentration particle suspension capable of rapidly and reversibly altering its viscosity when exposed to sudden impacts. Consequently, STF-based dampers deliver a self-adaptive damping force and demonstrate significant potential for applications in structural vibration control. This study presents both a modeling and experimental investigation of a novel double-rod structured STF damper. Initially, a compound STF is formulated using silica particles as the dispersed phase and polyethylene glycol solution as the dispersing medium. The rheological properties of the STF are then experimentally evaluated. The STF’s constitutive rheological behavior is described using the G-R model. Following this, the flow behavior of the STF within the damper’s annular gap is explored, leading to the development of a two-dimensional axisymmetric fluid simulation model for the damper. Based on this model, the dynamic mechanism of the proposed STF damper is analyzed. Subsequently, the STF damper is optimally designed and subjected to experimental investigation using a dynamic testing platform under different working conditions. The experimental results reveal that the proposed STF damper, whose equivalent stiffness can achieve a nearly threefold change with excitation frequency and amplitude, exhibits good self-adaptive capabilities. By dividing the damper force into two parts: the frictional damping pressure drop, and the osmotic pressure drop generated by the “Jamming effect”. A fitting model is proposed, and it aligns closely with the nonlinear performance of the STF damper.
Agile Project Management in the Pre-Construction Stage: Facing the Challenges of Projectification in the Construction Industry
Authors: Moreno Francisco , Forcael Eric , Romo Rubén , Orozco Francisco , Moroni Ginnia , Baesler Felipe
Published: November 2024

Given the complex and dispersed nature of construction projects, which demand collaboration among varied experts, it is crucial to reevaluate project management and execution approaches to enhance their performance. Agile principles offer a path towards heightened responsiveness within tasks and processes, addressing the construction industry’s fast-paced nature and growing client demands for timely project completion. However, adopting new management methodologies, such as Agile, needs a significant cultural shift, enabling the cultivation of multi-skilled and self-managing teams. Projectification, a growing trend in contemporary society where more activities are managed as projects, has gained significant relevance in recent years. This study examines the application of Agile project management (specifically Agile Scrum methodology) during the pre-construction phase of a construction project through the lens of Projectification. As evidenced by the research results, applying the Agile methodology in the pre-construction phase may help enhance flexibility and collaboration, enabling teams to adapt quickly to evolving project requirements and unforeseen challenges. The findings demonstrate that Agile methodologies offer numerous benefits, including enhanced adaptability, flexibility, accountability, transparency, and teamwork. Additionally, there were significant reductions in time and costs, emphasizing the value of Agile practices in construction project management.
A Comparative Study of the Design of East Asian Royal Gardens
Authors: Liang Yuehui , He Songfei
Published: November 2024

The current research methods employed in the study of gardens are largely concentrated in the fields of landscape architecture, architecture, and ecology. However, there is a paucity of analytical methods dedicated to the domain of garden design. However, the design content of gardens is within the scope of design studies. It is therefore imperative to develop or refine research methods for the analysis of gardens that are firmly grounded in design principles. The primary contribution of this study is the development of a design analysis framework, centered on the interrelationships between ‘user–garden–environment’, which can be applied to the analysis and investigation of gardens from a ‘people, objects, and environment’ perspective, in alignment with design studies. Influenced by similar geography, environment, culture, customs, etc., the garden design of China, Japan, and South Korea presents a very East Asian design style of forms, elements, features, etc., but also formed the differences of each characteristic. This paper takes China’s Chengde Mountain Resort, Japan’s Shugakuin Imperial Villa, and South Korea’s Changdeokgung, which are listed on the World Heritage List, as examples Based on the design analysis method proposed in this paper, a relevant design comparative study is conducted in three aspects: users of East Asia’s royal gardens, the design object—the gardens—and the external environment, and the similarities and differences between the Chinese, Japanese, and Korean royal gardens are analyzed. This study aims to verify the feasibility of the analytical framework of ‘user–garden–environment’ design by analyzing typical cases of royal gardens in China, Japan, and South Korea. This will enable the creation of multiple values conducive to the development of gardens. Furthermore, the analytical framework of ‘user–garden–environment’ is subjected to a process of deconstruction through the case studies of typical royal gardens in the three East Asian countries. This is done to overcome the limitations of existing research methodologies, provide a novel systematic research methodology for garden research, and facilitate the protection and inheritance of the historical and cultural heritage of gardens in East Asia. Additionally, this approach offers a reference point for related garden research in the context of modern lifestyles.
The Effect of CeO2 on the Catalytic Activity and SO2 Resistance of the V2O5-MoO3/TiO2 Catalyst Prepared Using the Ball Milling Method for the NH3-SCR of NO
Authors: Zi Xuehong , Ye Jingtong , Cheng Yao , Li Shuangye , Li Xiangru , Li Xingtong , Qiu Wenge , Song Liyun
Published: November 2024

V2O5-WO3(MoO3)/TiO2 catalysts are widely used in industrial denitrification (deNOx) processes based on the selective catalytic reduction (SCR) technique. To lower their cost and shorten the production cycle, V2O5-MoO3/TiO2 catalysts with and without CeO2 modification were prepared using the ball milling method. This study demonstrates that the CeO2-modified catalyst has high NO conversion and a broader temperature window due to the decreased amount of easily reducible vanadium species and the enhanced property of oxygen species activation in CeO2. Meanwhile, the SO2 resistance of the catalyst is restrained due to the strong adsorption and oxidation of SO2 over CeO2 in the catalyst.
Facile Construction of Supported Polyoxometalate Ionic Liquids for Deep Oxidative Desulfurization of Fuel
Authors: Tong Shuang , Huang Tianqi , Chen Mengyue , Zhu Zidan , Wang Chao , Li Hongping , Zhang Ming
Published: November 2024

A series of commercial silica-supported polyoxometalate ionic liquids ([Cnmim]3PMo12O40) with different substitutes in the imidazole ring were prepared via a facile ball milling method and employed as catalysts in the oxidative desulfurization of organosulfur compounds. The experimental results demonstrated that the active polyoxometalate center was successfully immobilized with a highly uniform dispersion on the silica. Without any organic solvent as the extractant, sulfur removal with the sample C16PMo/SiO2-BM reached 99.5% in 30 min under the optimal condition, which was ascribed to the high specific surface area and lipophilicity. In addition, the active site was verified by a free radical trapping experiment and an ESR spin capture experiment. In addition, the oxidative product was confirmed by GC-MS analysis.
Copper-Catalyzed Trifluoromethylthiolaton and Radical Cyclization of N-Phenylpent-4-Enamides to Construct SCF3-Substituted γ-Lactams
Authors: Zhang Hanyang , Liu Wen , Hu Jiale , Zhang Qian , Fang Zeguo , Li Dong
Published: November 2024

An efficient method involving copper-catalyzed trifluoromethylthiolation and radical cyclization of N-phenylpent-4-enamides using readily available and stable AgSCF3 as the trifluoromethylthiolating reagent is described. The method enables the synthesis of a series of potential medicinally valuable trifluoromethylthio-substituted γ-lactams and relative 2-oxazolidinone derivatives with broad functional group compatibility. Mechanistic investigations indicated that this reaction involved amidyl radical-initiated cascade 5-exo-trig cyclization followed by trifluoromethylthiolation, resulting in the formation of new C-N and C-S bonds.
Association of Genomic Alterations with the Presence of Serum Monoclonal Proteins in Chronic Lymphocytic Leukemia
Authors: Piñeyroa Juan A. , López-Oreja Irene , Nadeu Ferran , Martínez-Farran Ares , Aróstegui Juan Ignacio , López-Guerra Mónica , Correa Juan Gonzalo , Fabregat Aleix , Villamor Neus , Monge-Escatín Ines , Albiol Nil , Costa Dolors , Aymerich Marta , Beà Sílvia , Campo Elías , Delgado Julio , Colomer Dolors , Mozas Pablo
Published: November 2024

The presence of a monoclonal protein detected by serum immunofixation electrophoresis (sIFE) has been reported as an adverse prognostic factor in chronic lymphocytic leukemia (CLL). However, the genetic underpinning of this finding has not been studied. We retrospectively studied 97 CLL patients with simultaneous information on sIFE and genetic alterations detected by next-generation sequencing. sIFE was positive in 49 patients. The most common isotypes were IgG κ (27%) and bi/triclonal (25%). A +sIFE was associated with a higher number of mutated genes [median 2 (range 0–3) vs. 0 (range 0–2), p = 0.006], and a higher frequency of unmutated IGHV status (60 vs. 29%, p = 0.004). An IgM monoclonal protein was associated with TP53 mutations (36% in IgM +sIFE vs. 12% in non-IgM +sIFE or –sIFE, p = 0.04), and bi/triclonal proteins with NOTCH1 mutations (33% in bi/triclonal vs. 9% in monoclonal +sIFE or –sIFE, p = 0.04). These data suggest an association between a +sIFE and a higher mutational burden, and some monoclonal isotypes with specific mutations.
Enhancing Proton Therapy Efficacy Through Nanoparticle-Mediated Radiosensitization
Authors: Ma Jie , Shen Hao , Mi Zhaohong
Published: November 2024

Proton therapy, characterized by its unique Bragg peak, offers the potential to optimize the destruction of cancer cells while sparing healthy tissues, positioning it as one of the most advanced cancer treatment modalities currently available. However, in comparison to heavy ions, protons exhibit a relatively lower relative biological effectiveness (RBE), which limits the efficacy of proton therapy. The incorporation of nanoparticles for radiosensitization presents a novel approach to enhance the RBE of protons. This review provides a comprehensive discussion of the recent advancements in augmenting the biological effects of proton therapy through the use of nanoparticles. It examines the various types of nanoparticles that have been the focus of extensive research, elucidates their mechanisms of radiation sensitization, and evaluates the factors influencing the efficiency of this sensitization process. Furthermore, this review discusses the latest synergistic therapeutic strategies that integrate nanoparticle-mediated radiosensitization and outlines prospective directions for the future application of nanoparticles in conjunction with proton therapy.
Does Incretin Agonism Have Sustainable Efficacy?
Authors: Janket Sok-Ja , Chatanaka Miyo K. , Sohaei Dorsa , Tamimi Faleh , Meurman Jukka H. , Diamandis Eleftherios P.
Published: November 2024

Recent clinical trials using synthetic incretin hormones, glucagon-like peptide 1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists have demonstrated that these treatments ameliorated many complications related to obesity, emphasizing the significant impact of body weight on overall health. Incretins are enteroendocrine hormones secreted by gut endothelial cells triggered by nutrient ingestion. The phenomenon that oral ingestion of glucose elicits a much higher insulin secretion than intra-venous injection of equimolar glucose is known as the incretin effect. This also alludes to the thesis that food intake is the root cause of insulin resistance. Synthetic GLP-1 and GIP agonists have demonstrated unprecedented glucoregulation and body weight reduction. Also, randomized trials have shown their ability to prevent complications of obesity, including development of diabetes from prediabetes, reducing cardiovascular disease risks and renal complications in diabetic patients. Moreover, the benefits of these agonists persist among the patients who are already on metformin or insulin. The ultimate question is “Are these benefits of incretin agonism sustainable?” Chronic agonism of pancreatic β-cells may decrease the number of receptors and cause β-cell exhaustion, leading to β-cell failure. Unfortunately, the long-term effects of these drugs are unknown at the present because the longest duration in randomized trials is 3 years. Additionally, manipulation of the neurohormonal axis to control satiety and food intake may hinder the long-term sustainability of these treatments. In this review, we will discuss the incretins’ mechanism of action, challenges, and future directions. We will briefly review other molecules involved in glucose homeostasis such as amylin and glucagon. Amylin is co-expressed with insulin from the pancreas β-cells but does not have insulinotropic function. Amylin suppresses glucagon secretion, slowing gastric emptying and suppressing the reward center in the central nervous system, leading to weight loss. However, amylin can self-aggregate and cause serious cytotoxicity and may cause β-cell apoptosis. Glucagon is secreted by pancreatic α-cells and participates in glucose homeostasis in a glucose-dependent manner. In hypoglycemia, glucagon increases the blood glucose level by glycogenolysis and gluconeogenesis and inhibits glycogenesis in the liver. Several triple agonists, in combination with dual incretins and glucagon, are being developed.
Impact of Climate Change on Biodiversity and Implications for Nature-Based Solutions
Authors: Schipper Cor A. , Hielkema Titus W. , Ziemba Alexander
Published: November 2024

The Intergovernmental Panel on Climate Change (IPCC) provides regular scientific assessments on climate change, its implications, and potential future risks based on estimated energy matrixes and policy pathways. The aim of this publication is to assess the risks climate change poses to biodiversity using projected IPCC climate scenarios for the period 2081–2100, combined with key species-sensitivity indicators and variables as a response to climate change projections. In doing so, we address how climate-change-driven pressures may affect biodiversity. Additionally, a novel causal relationship between extreme ambient temperature exposure levels and the corresponding effects on individual species, noted in this paper as the Upper Thermal-Tolerance Limit and Species Sensitivity Distribution (UTTL-SSD), provides a compelling explanation of how global warming affects biodiversity. Our study indicates that North American and Oceanian sites with humid continental and subtropical climates, respectively, are poised to realize temperature shifts that have been identified as potential key tipping-point triggers. Heat stress may significantly affect approximately 60–90% of mammals, 50% of birds, and 50% of amphibians in North American and Oceanian sites for durations ranging from 5 to 84 days per year from 2080. In the humid temperate oceanic climate of European sites, the climate conditions remain relatively stable; however, moderate cumulative effects on biodiversity have been identified, and additional biodiversity-assemblage threat profiles exist to represent these. Both the integration of IPCC-IUCN profiles and the UTTL-SSD response relationship for the species communities considered have resulted in the identification of the projected threats that climate pressures may impose under the considered IPCC scenarios, which would result in biodiversity degradation. The UTTL-SSD responses developed can be used to highlight potential breakdowns among trophic levels in food web structures, highlighting an additional critical element when addressing biodiversity and ecosystem concerns.
Exploring Machine Learning Methods for Aflatoxin M1 Prediction in Jordanian Breast Milk Samples
Authors: Aref Abdullah , Omar Eman , Alseidi Eman , Alqudah Nour Elhuda A. , Omar Sharaf
Published: November 2024

The presence of aflatoxin M1 in breast milk poses a serious risk to the health of infants because of its potential to cause cancer and have negative effects on development. Detecting AFM1 in milk samples using conventional methods is often time-consuming and may not provide real-time monitoring capabilities. The use of machine learning techniques to forecast aflatoxin M1 levels in breast milk samples is examined in this study. To develop predictive models of aflatoxin M1 in breast milk, we employed well-known supervised machine learning algorithms such as Random Forest and Gradient Boosting. The findings show that machine learning can be used for the identification of aflatoxin M1 in breast milk. By actively monitoring breast quality, this research highlights the significance of machine learning in protecting babies’ health and advances the prediction skills in food safety.
The Conservation of Biodiverse and Threatened Dry Rainforest Plant Communities Is Vital in a Changing Climate
Authors: Howard Marion , Pearl Hilary , McDonald Bill , Shimizu Yoko , Srivastava Sanjeev Kumar , Shapcott Alison
Published: November 2024

Dry rainforest communities are globally threatened by anthropogenic pressures and climatic change but are less well researched and more poorly conserved than mesic rainforests. In response to the increasing loss of biodiversity, the Australian Government joined other international signatory parties to adopt the Kunming-Montreal Global Biodiversity Framework (GBF). The GBF emphasises the maintenance of connectivity and genetic diversity of whole ecosystems via landscape-scale conservation initiatives. Rainforest plant diversity, distinctiveness, and the current level of conservation of seasonal rainforest regional ecosystems of the Central Queensland Coast region in Australia were evaluated. Our three-marker DNA barcode dated phylogeny of rainforest plant taxa together with community species lists were used to calculate phylogenetic diversity (PD) estimates and species composition. Levels of rainforest ecosystem protection were assessed using Queensland government data. This study found selection pressures for moisture and geology significantly influence rainforest distribution and species diversity and evidence of a high degree of variability in terms of conservation. While some phylogenetically distinctive rainforest community types were well conserved, restricted or endangered communities were very poorly protected. Additionally, we found smaller dry rainforests in the Central Queensland Coast represent regional plant migration but are inadequately protected, highlighting the need for a revision of conservation objectives within the region.
Student Perceptions of Academic Functioning During the COVID-19 Pandemic in Germany
Authors: Hendriksen Pauline A. , Koyun Anna H. , Garssen Johan , Stock Ann-Kathrin , Verster Joris C.
Published: November 2024

Background: The COVID-19 pandemic posed unprecedented challenges to higher education in Germany, necessitating a rapid transition to remote learning. This study evaluates the impact of the pandemic on academic functioning among German university students. Methods: An online survey was conducted with 207 students aged 18 to 35. Results: Significantly poorer academic functioning was evident during the pandemic, particularly in academic output and role satisfaction. Younger students (18 to 24 years) experienced a greater decrease in contact with teachers and lower academic output compared to older students (25 to 35 years). These findings suggest that younger students may struggle more with remote learning due to challenges in self-regulation and time management. Additionally, pandemic-induced disruptions blurred the boundaries between work and personal life, increasing stress and adversely affecting academic performance. No significant differences were found based on sex or living situation. Conclusion: Academic functioning was significantly poorer during the COVID-19 pandemic. This finding highlights the need for targeted support strategies to mitigate the negative effects of the pandemic on students’ academic performance and well-being. Further research is recommended to explore the long-term implications of the pandemic on academic outcomes and student well-being.
Specific Quality of Life Questionnaire Validation in Patients with Colorectal Cancer
Authors: Mihăileanu Florin , Cismaru Cosmin Andrei , Cordoș Ariana Anamaria , Ciocan Răzvan Alexandru , Chiorescu Stefan , Constantinescu Ioana , Stancu Bogdan , Breazu Caius , Coman Horațiu , Berindan Neagoe Ioana , Gherman Claudia Diana
Published: November 2024

(1) Background: The quality of life of cancer patients is not only important for their well-being, but it has great influence on the overall survival and response to therapy, considering the adherence to treatment and follow-up. (2) Methods: This research is a prospective study conducted over a period of 6 months involving patients admitted in the Department of Surgery II, Cluj County Emergency Clinical Hospital. The specific questionnaire designed by us for patients with colorectal cancer contains questions about the quality of life and symptoms such as weight loss, pain, constipation, and diarrhoea. (3) Results: Our prospective study included in the analysis 50 patients with colorectal cancer. The CR 29 questionnaire outlined scores below 30 for sore skin, urinary incontinence, dysuria, faecal incontinence, flatulence, discomfort from bowel movement, sexual dysfunction and hair loss. The CR 30 functioning scale depicted high scores for cognitive (100%, 95% CI [0.91–1]), physical (88%, 95% CI [0.75–0.95]), and functional (88%, 95% CI [0.39–0.68]) domains and low scores (<50) for emotional (98%, 95% CI [0.88–0.99]) and social (100%, 95% CI [0.91–1]) functions. (4) Conclusions: The quality of life of patients with colorectal cancer was influenced by socio-economic status, smoking, surgical procedure, and neoplastic pathology.
Radiomics Feature Stability in True and Virtual Non-Contrast Reconstructions from Cardiac Photon-Counting Detector CT Datasets
Authors: Canalini Luca , Becker Elif G. , Risch Franka , Bette Stefanie , Hellbrueck Simon , Becker Judith , Rippel Katharina , Scheurig-Muenkler Christian , Kroencke Thomas , Decker Josua A.
Published: November 2024

Objectives: Virtual non-contrast (VNC) series reconstructed from contrast-enhanced cardiac scans acquired with photon counting detector CT (PCD-CT) systems have the potential to replace true non-contrast (TNC) series. However, a quantitative comparison of the image characteristics of TNC and VNC data is necessary to determine to what extent they are interchangeable. This work quantitatively evaluates the image similarity between VNC and TNC reconstructions by measuring the stability of multi-class radiomics features extracted in intra-patient TNC and VNC reconstructions. Methods: TNC and VNC series of 84 patients were retrospectively collected. For each patient, the myocardium and epicardial adipose tissue (EAT) were semi-automatically segmented in both VNC and TNC reconstructions, and 105 radiomics features were extracted in each mask. Intra-feature correlation scores were computed using the intraclass correlation coefficient (ICC). Stable features were defined with an ICC higher than 0.75. Results: In the myocardium, 41 stable features were identified, and the three with the highest ICC were glrlm_GrayLevelVariance with ICC3 of 0.98 [0.97, 0.99], ngtdm_Strength with ICC3 of 0.97 [0.95, 0.98], firstorder_Variance with ICC3 of 0.96 [0.94, 0.98]. For the epicardial fat, 40 stable features were found, and the three highest ranked are firstorder_Median with ICC3 of 0.96 [0.93, 0.97], firstorder_RootMeanSquared with ICC3 of 0.95 [0.92, 0.97], firstorder_Mean with ICC3 of 0.95 [0.92, 0.97]. A total of 24 features (22.8%; 24/105) showed stability in both anatomical structures. Conclusions: The significant differences in the correlation of radiomics features in VNC and TNC volumes of the myocardium and epicardial fat suggested that the two reconstructions may differ more than initially assumed. This indicates that they may not be interchangeable, and such differences could have clinical implications. Therefore, care should be given when selecting VNC as a substitute for TNC in radiomics research to ensure accurate and reliable analysis. Moreover, the observed variations may impact clinical workflows, where precise tissue characterization is critical for diagnosis and treatment planning.
Anti-Modified Peptide Antibodies (AMPAs) in Rheumatoid Arthritis: Study of the Diagnostic Value of Citrullinated, Homocitrullinated, and Acetylated Fibrin/Filaggrin Chimeric Peptides
Authors: Haro Isabel , Castellanos-Moreira Raul , Sanmartí Raimon , Gómara María José
Published: November 2024

Background/Objectives. The presence of anti-citrullinated peptide/protein antibodies (ACPAs), anti-carbamylated peptide/protein antibodies (anti-CarPs), and anti-acetylated peptide/protein antibodies (AAPAs), collectively termed as anti-modified peptide/protein antibodies (AMPAs), is a hallmark of rheumatoid arthritis. These autoantibodies play a crucial role in the complex autoimmune responses observed in patients. Understanding the interplay between them is essential for early diagnosis and effective management of the disease. Methods. In this work, we investigate IgG, IgM, and IgA levels of ACPAs, anti-CarPs, and AAPAs in two cohorts: patients with established RA disease and healthy blood donors, using a unique peptide antigenic backbone. Results. Our results showed that antibody levels of anti-citrullinated peptide (CFFCP) and anti-homocitrullinated peptide (CFFHP) were significantly higher in RA patients compared to healthy blood donors in the three isotypes analyzed, IgG, IgA, and IgM. Fine specificities were more frequent when using the CFFCP antigen. Regarding the reactivity to the acetyl-lysine modified peptide (CFFAP), the correlation between IgA and IgG/IgM was very weak. CCFAP was highly specific for isotypes IgG and IgA, but its sensitivity was low for both isotypes. Anti-CarP and AAPA are significant in the context of RA, particularly concerning their IgA isotypes. Conclusions. Their inclusion in diagnostics assessments for RA, especially for anti-citrulline negative cases, presents a potential advance in the field; however, they do not replace yet traditional markers like rheumatoid factor (RF) and ACPAs.
Predicting Dysglycemia in Patients with Diabetes Using Electrocardiogram
Authors: Song Ho-Jung , Han Ju-Hyuck , Cho Sung-Pil , Im Sung-Il , Kim Yong-Suk , Park Jong-Uk
Published: November 2024

Background: In this study, we explored the potential of predicting dysglycemia in patients who need to continuously manage blood glucose levels using a non-invasive method via electrocardiography (ECG). Methods: The data were collected from patients with diabetes, and heart rate variability (HRV) features were extracted via ECG processing. A residual block-based one-dimensional convolution neural network model was used to predict dysglycemia. Results: The dysglycemia prediction results at each time point, including at the time of blood glucose measurement, 15 min prior to measurement, and 30 min prior to measurement, exhibited no significant differences compared with the blood glucose measurement values. This result confirmed that the proposed artificial intelligence model for dysglycemia prediction performed well at each time point. Additionally, to determine the optimal number of features required for predicting dysglycemia, 77 HRV features were individually eliminated in the order of decreasing importance with respect to the prediction accuracy; the optimal number of features for the model to predict dysglycemia was determined to be 12. The dysglycemia prediction results obtained 30 min prior to measurement, which exhibited the highest prediction range in this study, were as follows: accuracy = 90.5, sensitivity = 87.52, specificity = 92.74, and precision = 89.86. Conclusions: Furthermore, we determined that no significant differences exist in the blood glucose prediction results reported in previous studies, wherein various vital signs and blood glucose values were used as model inputs, and the results obtained in this study, wherein only ECG data were used to predict dysglycemia.
Clinical Comparison of OC-Sensor Pledia and Phadia 250 for Fecal Calprotectin Testing
Authors: Shin Eunju , Seo Jong Do , Shim Hee Sook , Kim Hanah , Hur Mina , Yun Yeo-Min , Moon Hee-Won
Published: November 2024

Background: The fecal calprotectin (f-Cal) test is a convenient method used for differentiating inflammatory bowel disease (IBD) from functional bowel disorders. The OC-Sensor Pledia (OC-FCa; Eiken Chemical Co., Tokyo, Japan) is a latex agglutination turbidimetric immunoassay used for f-Cal measurements. We evaluated the clinical performance of OC-FCa and compared the f-Cal levels between OC-FCa and Phadia 250 (Thermo Fisher Scientific, Freiburg, Germany). Methods: We collected 278 stool samples; of these, 158 were taken from patients with suspected IBD, and 120 were taken from healthy individuals. We analyzed the f-Cal distribution in each group and compared the clinical performance and agreement between OC-FCa and Phadia 250. Results: The f-Cal of patients with IBD was significantly different from that of patients without IBD for both OC-FCa and Phadia 250 (p < 0.0001 and p < 0.001, respectively). The concordance between OC-FCa and Phadia 250 was 82.3%, with moderate agreement (kappa = 0.644, 95% confidence interval = 0.525–0.763). OC-FCa and Phadia 250 showed a high correlation (r = 0.90); their diagnostic performance showed moderate accuracy (AUC = 0.873 and 0.866, respectively) and had no significant difference (p = 0.616). Conclusions: Both OC-FCa and Phadia 250 showed a high correlation and good clinical performance. F-Cal measured using OC-FCa was reliable for initial differentiation between patients with IBD and without IBD. Therefore, OC-FCa and Phadia 250 could be alternative devices for measuring f-Cal depending on the laboratory situation.