bluuebunny/crossref_metadata_2025 huggingface dataset:
Impacts, Potential Benefits and Eradication Feasibility of Aquatic Alien Species in an Integral Natural State Reserve
Authors: Paganelli Daniele , Bellati Adriana , Gazzola Andrea , Bracco Francesco , Pellitteri-Rosa Daniele
Published: January 2024

Riverine wetlands are stepping-stone environments for the protection of local biodiversity, but they are particularly vulnerable to biological invasions. In order to take action against biological invasions, it is crucial to assess the impacts of alien species. However, it is also important to assess the potential benefits on ecosystem services that alien species could have. Once it has been verified that negative impacts are higher than potential benefits, it is important to propose feasible actions to contrast them. In this study, we assessed eight freshwater alien species recorded in an integral protected wetland using the Invasive Species Effects Assessment Tool (INSEAT) to quantify their negative impacts and potential benefits on ecosystem services. Moreover, for each species, we evaluated the feasibility of the main eradication techniques currently proposed in the literature using the Non-Native Risk Management scheme (NNRM), with the final aim of suggesting effective actions for their management. The INSEAT results indicated that all the assessed species had more impacts than benefits while NNRM provided useful indications on the best practical conservation actions to use for reducing the density, and therefore, the negative impacts on ecosystem services and the local biodiversity of the assessed alien species.
Molecular Mechanisms and the Significance of Synonymous Mutations
Authors: Oelschlaeger Peter
Published: January 2024

Synonymous mutations result from the degeneracy of the genetic code. Most amino acids are encoded by two or more codons, and mutations that change a codon to another synonymous codon do not change the amino acid in the gene product. Historically, such mutations have been considered silent because they were assumed to have no to very little impact. However, research in the last few decades has produced several examples where synonymous mutations play important roles. These include optimizing expression by enhancing translation initiation and accelerating or decelerating translation elongation via codon usage and mRNA secondary structures, stabilizing mRNA molecules and preventing their breakdown before translation, and faulty protein folding or increased degradation due to enhanced ubiquitination and suboptimal secretion of proteins into the appropriate cell compartments. Some consequences of synonymous mutations, such as mRNA stability, can lead to different outcomes in prokaryotes and eukaryotes. Despite these examples, the significance of synonymous mutations in evolution and in causing disease in comparison to nonsynonymous mutations that do change amino acid residues in proteins remains controversial. Whether the molecular mechanisms described by which synonymous mutations affect organisms can be generalized remains poorly understood and warrants future research in this area.
Salmonella typhimurium Vaccine Candidate Delivering Infectious Bronchitis Virus S1 Protein to Induce Protection
Authors: Liu Kaihui , Li Zewei , Li Quan , Wang Shifeng , Curtiss Roy , Shi Huoying
Published: January 2024

Infectious bronchitis (IB) is a highly infectious viral disease of chickens which causes significant economic losses in the poultry industry worldwide. An effective vaccine against IB is urgently needed to provide both biosafety and high-efficiency immune protection. In this study, the S1 protein of the infectious bronchitis virus was delivered by a recombinant attenuated Salmonella typhimurium vector to form the vaccine candidate χ11246(pYA4545-S1). S. typhimurium χ11246 carried a sifA− mutation with regulated delayed systems, striking a balance between host safety and immunogenicity. Here, we demonstrated that S1 protein is highly expressed in HD11 cells. Immunization with χ11246(pYA4545-S1) induced the production of antibody and cytokine, leading to an effective immune response against IB. Oral immunization with χ11246(pYA4545-S1) provided 72%, 56%, and 56% protection in the lacrimal gland, trachea, and cloaca against infectious bronchitis virus infection, respectively. Furthermore, it significantly reduced histopathological lesions in chickens. Together, this study provides a new idea for the prevention of IB.
Antibacterial Metabolites Produced by Limonium lopadusanum, an Endemic Plant of Lampedusa Island
Authors: Gargiulo Ernesto , Roscetto Emanuela , Galdiero Umberto , Surico Giuseppe , Catania Maria Rosaria , Evidente Antonio , Taglialatela-Scafati Orazio
Published: January 2024

Lampedusa, the largest island of the Pelagie archipelago, Sicily, Italy, has proven to be a rich source of plants and shrubs used in folk medicine. These plants, often native to the island, have been very poorly investigated for their phytochemical composition and biological potential to be translated into pharmacological applications. To start achieving this purpose, a specimen of Limonium lopadusanum, a plant native to Lampedusa, was investigated for the first time. This manuscript reports the results of a preliminary biological assay, focused on antimicrobial activity, carried out using the plant organic extracts, and the isolation and chemical and biological characterization of the secondary metabolites obtained. Thus 3-hydroxy-4-methoxybenzoic acid methyl ester (syn: methyl isovanillate, (1), methyl syringate (2), pinoresinol (3), erythrinassinate C (4) and tyrosol palmitate (5) were isolated. Their antimicrobial activity was tested on several strains and compound 4 showed promising antibacterial activity against Enterococcus faecalis. Thus, this metabolite has antibiotic potential against the drug-resistant opportunistic pathogen E. faecalis.
Deciphering the Calcium Code: A Review of Calcium Activity Analysis Methods Employed to Identify Meaningful Activity in Early Neural Development
Authors: Paudel Sudip , Yue Michelle , Nalamalapu Rithvik , Saha Margaret S.
Published: January 2024

The intracellular and intercellular flux of calcium ions represents an ancient and universal mode of signaling that regulates an extensive array of cellular processes. Evidence for the central role of calcium signaling includes various techniques that allow the visualization of calcium activity in living cells. While extensively investigated in mature cells, calcium activity is equally important in developing cells, particularly the embryonic nervous system where it has been implicated in a wide variety array of determinative events. However, unlike in mature cells, where the calcium dynamics display regular, predictable patterns, calcium activity in developing systems is far more sporadic, irregular, and diverse. This renders the ability to assess calcium activity in a consistent manner extremely challenging, challenges reflected in the diversity of methods employed to analyze calcium activity in neural development. Here we review the wide array of calcium detection and analysis methods used across studies, limiting the extent to which they can be comparatively analyzed. The goal is to provide investigators not only with an overview of calcium activity analysis techniques currently available, but also to offer suggestions for future work and standardization to enable informative comparative evaluations of this fundamental and important process in neural development.
The Role of Chorein Deficiency in Late Spermatogenesis
Authors: Arai Kaoru , Nishizawa Yoshiaki , Nagata Omi , Sakimoto Hitoshi , Sasaki Natsuki , Sano Akira , Nakamura Masayuki
Published: January 2024

VPS13A, also known as chorein, whose loss of function causes chorea-acanthocytosis (ChAc), is characterized by Huntington’s-disease-like neurodegeneration and neuropsychiatric symptoms in addition to acanthocytosis in red blood cells. We previously reported that ChAc-model mice with a loss of chorein function exhibited male infertility, with asthenozoospermia and mitochondrial dysmorphology in the spermatozoa. Here, we report a novel aspect of chorein dysfunction in male fertility, particularly its role in spermatogenesis and mitochondrial integrity. An increase in anti-malondialdehyde antibody immunoreaction within the testes, predominantly observed at the advanced stages of sperm formation in chorein-deficient mice, suggests oxidative stress as a contributing factor to mitochondrial dysfunction and impaired sperm maturation. The chorein immunoreactivity in spermatids of wild-type mice accentuates its significance in sperm development. ChAc-model mice exhibit mitochondrial ultrastructural abnormalities, specifically during the late stages of sperm maturation, suggesting a critical timeframe for chorein’s action in spermiogenesis. We observed an increase in TOM20 protein levels, indicative of disrupted mitochondrial import mechanisms. The concurrent decrease in metabolic enzymes such as IDH3A, LDHC, PGK2, and ACAT1 suggests a complex chorein-mediated metabolic network that is essential for sperm vitality. Additionally, heightened separation of cytoplasmic droplets from sperm highlights the potential membrane instability in chorein-deficient spermatozoa. Metabolomic profiling further suggests a compensatory metabolic shift, with elevated glycolytic and TCA-cycle substrates. Our findings suggest that chorein is involved in anti-ferroptosis and the maturation of mitochondrial morphology in the late stages of spermatogenesis, and its deficiency leads to asthenozoospermia characterized by membrane instability, abnormal cytosolic glycolysis, abnormal mitochondrial function, and a disrupted TCA cycle. Further analyses are required to unravel the molecular mechanisms that directly link these findings and to elucidate the role of chorein in spermatogenesis as well as its broader implications.
Sulfated CXCR3 Peptide Trap Use as a Promising Therapeutic Approach for Age-Related Macular Degeneration
Authors: Jo Gukheui , Chae Jae-Byoung , Jung Sun-Ah , Lyu Jungmook , Chung Hyewon , Lee Joon H.
Published: January 2024

Background and Objectives: Chemokines have various biological functions and potential roles in the development or progression of neuroinflammatory diseases. However, the specific pathogenic roles of chemokines in the major cause for vision loss among the elderly, the leading cause of blindness in older individuals, remain elusive. Chemokines interact with their receptors expressed in the endothelium and on leukocytes. The sulfation of tyrosine residues in chemokine receptors increases the strength of ligand–receptor interaction and modulates signaling. Therefore, in the present study, we aimed to construct a human recombinant sulfated CXCR3 peptide trap (hCXCR3-S2) and mouse recombinant sulfated CXCR3 peptide trap (mCXCR3-S2) to demonstrate in vivo effects in preventing choroidal neovascularization (CNV) and chemotaxis. Materials and Methods: We generated expression vectors for mCXCR3-S2 and hCXCR3-S2 with GST domains and their respective cDNA sequences. Following overexpression in E. coli BL21 (DE3), we purified the fusion proteins from cell lysates using affinity chromatography. First, the impact of hCXCR3-S2 was validated in vitro. Subsequently, the in vivo efficacy of mCXCR3-S2 was investigated using a laser-induced CNV mouse model, a mouse model of neovascular age-related macular degeneration (AMD). Results: hCXCR3-S2 inhibited the migration and invasion of two human cancer cell lines. Intravitreal injection of mCXCR3-S2 attenuated CNV and macrophage recruitment in neovascular lesions of mouse models. These in vitro and in vivo effects were significantly stronger with CXCR3-S2 than with wild-type CXCR3 peptides. Conclusion: These findings demonstrate that the sulfated form of the CXCR3 peptide trap is a valuable tool that could be supplemented with antivascular endothelial growth factors in AMD treatment.
Identification of a Novel Germline PPP4R3A Missense Mutation Asp409Asn on Familial Non-Medullary Thyroid Carcinoma
Authors: Hu Yixuan , Han Zhuojun , Guo Honghao , Zhang Ning , Shen Na , Jiang Yujia , Huang Tao
Published: January 2024

Familial non-medullary thyroid carcinoma (FNMTC) accounts for 3% to 9% of all thyroid cancer cases, yet its genetic mechanisms remain unknown. Our study aimed to screen and identify novel susceptibility genes for FNMTC. Whole-exome sequencing (WES) was conducted on a confirmed FNMTC pedigree, comprising four affected individuals across two generations. Variants were filtered and analyzed using ExAC and 1000 Genomes Project, with candidate gene pathogenicity predicted using SIFT, PolyPhen, and MutationTaster. Validation was performed through Sanger sequencing in affected pedigree members and sporadic patients (TCGA database) as well as general population data (gnomAD database). Ultimately, we identified the mutant PPP4R3A (NC_000014.8:g.91942196C>T, or NM_001366432.2(NP_001353361.1):p.(Asp409Asn), based on GRCH37) as an FNMTC susceptibility gene. Subsequently, a series of functional experiments were conducted to investigate the impact of PPP4R3A and its Asp409Asn missense variant in thyroid cancer. Our findings demonstrated that wild-type PPP4R3A exerted tumor-suppressive effects via the Akt-mTOR-P70 S6K/4E-BP1 axis. However, overexpression of the PPP4R3A Asp409Asn mutant resulted in loss of tumor-suppressive function, ineffective inhibition of cell invasion, and even promotion of cell proliferation and migration by activating the Akt/mTOR signaling pathway. These results indicated that the missense variant PPP4R3A Asp409Asn is a candidate susceptibility gene for FNMTC, providing new insights into the diagnosis and intervention of FNMTC.
Association between Psoriasis and Renal Functions: An Integration Study of Observational Study and Mendelian Randomization
Authors: Tan Yuxuan , Huang Zhizhuo , Li Haiying , Yao Huojie , Fu Yingyin , Wu Xiaomei , Lin Chuhang , Lai Zhengtian , Yang Guang , Jing Chunxia
Published: January 2024

Psoriasis is an autoimmune-mediated disease with several comorbidities in addition to typical skin lesions. Increasing evidence shows the relationships between psoriasis and renal functions, but the relationship and causality remain unclear. We aimed to investigate the associations and causality between psoriasis and four renal functions, including the estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), urine albumin to creatinine ratio (UACR), and chronic kidney disease (CKD). For the population-based study, we analyzed the National Health and Nutrition Examination Survey (NHANES) data from five cycles (2003–2006 and 2009–2014) on psoriasis and renal functions. Subgroup analyses were conducted among different categories of participants. Meanwhile, a bidirectional two-sample Mendelian randomization (TSMR) study in European populations was also performed using summary-level genetic datasets. Causal effects were derived by conducting an inverse-variance weighted (MR-IVW) method. A series of pleiotropy-robust MR methods was employed to validate the robustness. Multivariable MR (MVMR) was conducted to complement the result when five competing risk factors were considered. A total of 20,244 participants were enrolled in the cross-sectional study, where 2.6% of them had psoriasis. In the fully adjusted model, participants with psoriasis had significantly lower eGFR (p = 0.025) compared with the healthy group. Individuals who are nonoverweight are more likely to be affected by psoriasis, leading to an elevation of BUN (Pint = 0.018). In the same line, TSMR showed a negative association between psoriasis and eGFR (p = 0.016), and sensitive analysis also consolidated the finding. No causality was identified between psoriasis and other renal functions, as well as the inverse causality (p > 0.05). The MVMR method further provided quite consistent results when adjusting five confounders (p = 0.042). We detected a significant negative effect of psoriasis on eGFR, with marginal association between BUN, UACR, and CKD. The adverse of psoriasis on the renal should merit further attention in clinical cares.
Microfluidics in High-Throughput Drug Screening: Organ-on-a-Chip and C. elegans-Based Innovations
Authors: Yoon Sunhee , Kilicarslan You Dilara , Jeong Uiechan , Lee Mina , Kim Eunhye , Jeon Tae-Joon , Kim Sun Min
Published: January 2024

The development of therapeutic interventions for diseases necessitates a crucial step known as drug screening, wherein potential substances with medicinal properties are rigorously evaluated. This process has undergone a transformative evolution, driven by the imperative need for more efficient, rapid, and high-throughput screening platforms. Among these, microfluidic systems have emerged as the epitome of efficiency, enabling the screening of drug candidates with unprecedented speed and minimal sample consumption. This review paper explores the cutting-edge landscape of microfluidic-based drug screening platforms, with a specific emphasis on two pioneering approaches: organ-on-a-chip and C. elegans-based chips. Organ-on-a-chip technology harnesses human-derived cells to recreate the physiological functions of human organs, offering an invaluable tool for assessing drug efficacy and toxicity. In parallel, C. elegans-based chips, boasting up to 60% genetic homology with humans and a remarkable affinity for microfluidic systems, have proven to be robust models for drug screening. Our comprehensive review endeavors to provide readers with a profound understanding of the fundamental principles, advantages, and challenges associated with these innovative drug screening platforms. We delve into the latest breakthroughs and practical applications in this burgeoning field, illuminating the pivotal role these platforms play in expediting drug discovery and development. Furthermore, we engage in a forward-looking discussion to delineate the future directions and untapped potential inherent in these transformative technologies. Through this review, we aim to contribute to the collective knowledge base in the realm of drug screening, providing valuable insights to researchers, clinicians, and stakeholders alike. We invite readers to embark on a journey into the realm of microfluidic-based drug screening platforms, fostering a deeper appreciation for their significance and promising avenues yet to be explored.
Sensing Levofloxacin with an RNA Aptamer as a Bioreceptor
Authors: Kramat Janice , Kraus Leon , Gunawan Vincent J. , Smyej Elias , Froehlich Philipp , Weber Tim E. , Spiehl Dieter , Koeppl Heinz , Blaeser Andreas , Suess Beatrix
Published: January 2024

To combat the growing threat of antibiotic resistance, environmental testing for antibiotic contamination is gaining an increasing role. This study aims to develop an easy-to-use assay for the detection of the fluoroquinolone antibiotic levofloxacin. Levofloxacin is used in human and veterinary medicine and has been detected in wastewater and river water. An RNA aptamer against levofloxacin was selected using RNA Capture-SELEX. The 73 nt long aptamer folds into three stems with a central three-way junction. It binds levofloxacin with a Kd of 6 µM and discriminates the closely related compound ciprofloxacin. Furthermore, the selection process was analyzed using a next-generation sequencing approach to better understand the sequence evolution throughout the selection. The aptamer was used as a bioreceptor for the development of a lateral flow assay. The biosensor exploited the innate characteristic of RNA Capture-SELEX to select aptamers that displace a complementary DNA oligonucleotide upon ligand binding. The lateral flow assay achieved a limit of visual detection of 100 µM. While the sensitivity of this assay constrains its immediate use in environmental testing, the present study can serve as a template for the selection of RNA aptamer-based biosensors.
Crime Risk and Depression Differentially Relate to Aspects of Sleep in Patients with Major Depression or Social Anxiety
Authors: Klumpp Heide , Feurer Cope , Chang Fini , Kapella Mary C.
Published: January 2024

Individuals with internalizing conditions such as depression or anxiety are at risk of sleep difficulties. Social–ecological models of sleep health propose factors at the individual (e.g., mental health) and neighborhood (e.g., crime risk) levels that contribute to sleep difficulties. However, these relationships have been under-researched in terms of internalizing conditions. Therefore, the current study comprised participants diagnosed with major depression (n = 24) or social anxiety (n = 35). Sleep measures included actigraphic variables (i.e., total sleep time, waking after sleep onset, sleep onset latency) and subjective sleep quality. Geocoding was used to assess nationally-normed crime risk exposure at the person level (e.g., murder, assault) and property level (e.g., robbery, burglary). Analyses consisted of independent t-tests to evaluate potential differences between diagnostic groups. To examine relationships, multiple regressions were used with internalizing symptoms, crime risk, and age as independent variables and sleep measures as the dependent variable. The t-test results revealed that groups differed in symptoms and age but not sleep or neighborhood crime. Regression results revealed crime risk positively corresponded with sleep onset latency but no other sleep measures. Also, only depression positively corresponded with total sleep time. Preliminary findings suggest exposure to crime and depression relate differentially to facets of sleep in individuals with internalizing conditions.
The Story behind the Mask: A Narrative Review on Hypomimia in Parkinson’s Disease
Authors: Bianchini Edoardo , Rinaldi Domiziana , Alborghetti Marika , Simonelli Marta , D’Audino Flavia , Onelli Camilla , Pegolo Elena , Pontieri Francesco E.
Published: January 2024

Facial movements are crucial for social and emotional interaction and well-being. Reduced facial expressions (i.e., hypomimia) is a common feature in patients with Parkinson’s disease (PD) and previous studies linked this manifestation to both motor symptoms of the disease and altered emotion recognition and processing. Nevertheless, research on facial motor impairment in PD has been rather scarce and only a limited number of clinical evaluation tools are available, often suffering from poor validation processes and high inter- and intra-rater variability. In recent years, the availability of technology-enhanced quantification methods of facial movements, such as automated video analysis and machine learning application, led to increasing interest in studying hypomimia in PD. In this narrative review, we summarize the current knowledge on pathophysiological hypotheses at the basis of hypomimia in PD, with particular focus on the association between reduced facial expressions and emotional processing and analyze the current evaluation tools and management strategies for this symptom, as well as future research perspectives.
Flood Risk and Preventive Choices: A Framework for Studying Human Behaviors
Authors: Sapienza Alessandro , Falcone Rino
Published: January 2024

The topic of flood phenomena has always been of considerable importance due to the high risks it entails, both in terms of potential economic and social damage and the jeopardizing of human lives themselves. The spread of climate change is making this topic even more relevant. This work aims to contribute to evaluating the role that human factors can play in responding to critical hydrogeological phenomena. In particular, we introduce an agent-based platform for analyzing social behaviors in these critical situations. In our experiments, we simulate a population that is faced with the risk of a potentially catastrophic event. In this scenario, citizens (modeled through cognitive agents) must assess the risk they face by relying on their sources of information and mutual trust, enabling them to respond effectively. Specifically, our contributions include (1) an analysis of some behavioral profiles of citizens and authorities; (2) the identification of the “dissonance between evaluation and action” effect, wherein an individual may behave differently from what their information sources suggest, despite having full trust in them in situations of particular risk; (3) the possibility of using the social structure as a “social risk absorber”, enabling support for a higher level of risk. While the results obtained at this level of abstraction are not exhaustive, they identify phenomena that can occur in real-world scenarios and can be useful in defining general guidelines.
“Knowing I Had Someone to Turn to Was a Great Feeling”: Mentoring Rural-Appalachian STEM Students
Authors: Gantt Henrietta S. , Cain Leia K. , Gibbons Melinda M. , Thomas Cherish F. , Wynn Mary K. , Johnson Betsy C. , Hardin Erin E.
Published: January 2024

Post-secondary students benefit from mentorships, which provide both emotional and academic support tailored to the unique challenges they face. STEM students, and, in particular, those with historically marginalized identities, have unique strengths and face distinct barriers that can be ameliorated by careful, knowledgeable, and well-situated mentoring relationships. With that in mind, we conducted a narrative case study with 10 rural-Appalachian STEM majors enrolled in an NSF-funded mentoring program, intending to collect stories of their impactful experiences with their mentors. We utilized the narrative reconstruction process, and, in so doing, identified five major themes related to the importance of mentor assignment and the impact of mentors’ characteristics and skills related to empathy, consistency, active listening, and teaching. We situate our findings within the existing literature and provide implications for scholars and practitioners who work with mentoring programs dedicated to working with Appalachian communities.
Attachment Orientation and Preferences for Partners’ Emotional Responses in Stressful and Positive Situations
Authors: Chin Brian N. , Kim Lauryn , Parsons Shelby M. , Feeney Brooke C.
Published: January 2024

Attachment theory proposes that close relationships help us to regulate our emotions in stressful and positive situations. However, no previous studies have examined preferences for a partner’s emotional response to one’s own stressful and positive situations or tested whether these preferences differ based on attachment orientation. This study examines the association of attachment orientation and preferences for partners’ emotional responses relative to one’s own emotional responses in stressful and positive contexts among 425 United States adults who were currently in a committed relationship of ≥6 months. Data were collected in 2020. Overall, participants preferred their partners to feel and express less distress, less worry, more calm, and more hope than themselves during stressful situations and for their partners to feel and express more excitement, pride, and hope than themselves during positive situations. Higher attachment anxiety predicted preferences for partners to feel and express more distress/worry in stressful situations, whereas higher attachment avoidance predicted preferences for partners to feel and express less hope in stressful situations. Statistical interactions of attachment anxiety × attachment avoidance indicated that the combination of low attachment anxiety and high attachment avoidance (dismissing avoidance) was associated with preferences for partners to feel and express less positive emotions in positive situations, whereas the combination of high attachment anxiety and high attachment avoidance (fearful avoidance) was associated with preferences for partners to feel and express more negative emotions in stressful situations and less positive emotions in positive situations. This investigation provides novel evidence for links between attachment orientation and preferences for partners’ emotional responses in two theoretically important contexts, which has implications for the nature and function of emotion regulation in close relationships. Future research is needed to determine the generalizability of these findings to more collectivist cultural contexts.
Trade-Off Judgement for Daylighting and Energy Consumption in the High and Large Space of the University Gymnasium in Beijing
Authors: Wu Yanpeng , Jin Meitong , Zhang Tianhu
Published: January 2024

Taking the high and large space of the University of Science and Technology Beijing Gymnasium as this research object, this paper analyzes the influence of different window positions, window-to-wall ratio (WWR), solar heat gain coefficient (SHGC), heat transfer coefficient (K), and visible light transmittance (VT) on the total indoor energy consumption in winter and summer and obtains the relationship between the daylight factor and VT formed when the window is opened per unit area. Through energy consumption simulation, the variation law and calculation formula for indoor total energy consumption are obtained. The results show that the SHGC and K of the exterior window have a significant influence on the total energy consumption. By using the energy consumption simulation of different types of exterior windows, it is concluded that the SHGC of the south-facing window is negatively correlated with the variation of air conditioning energy consumption per unit area Δe1,w, while the others are positively correlated. Moreover, the SHGC and K of the skylight have the most significant influence on the Δe1,w. The total energy consumption decreases and then increases with the increase in the window area, and there is a lowest point, so the right side of the lowest point is less than or equal to 105% of the lowest total energy consumption as a reasonable window area zone. Finally, a progressive optimization method for weighing daylighting and energy consumption in university gymnasiums in Beijing is proposed.
International Comparison of Weather and Emission Predictive Building Control
Authors: Hepf Christian , Gottkehaskamp Ben , Miller Clayton , Auer Thomas
Published: January 2024

Building operational energy alone accounts for 28% of global carbon emissions. A sustainable building operation promises enormous savings, especially under the increasing concern of climate change and the rising trends of the digitalization and electrification of buildings. Intelligent control strategies play a crucial role in building systems and electrical energy grids to reach the EU goal of carbon neutrality in 2050 and to manage the rising availability of regenerative energy. This study aims to prove that one can create energy and emission savings with simple weather and emission predictive control (WEPC). Furthermore, this should prove that the simplicity of this approach is key for the applicability of this concept in the built world. A thermodynamic simulation (TRNSYS) evaluates the performance of different variants. The parametrical study varies building construction, location, weather, and emission data and gives an outlook for 2050. The study showcases five different climate locations and reveals heating and cooling energy savings of up to 50 kWh/(m2a) and emission savings between 5 and 25% for various building types without harming thermal comfort. This endorses the initial statement to simplify building energy concepts. Furthermore, it proposes preventing energy designers from overoptimizing buildings with technology as the solution to a climate-responsible energy concept.
Impact of Variable Parameters of Expansion Joints and Bearing Supports on the Vehicle-Induced Vibration of Curved Girder Bridges
Authors: Zheng Yu , Lu Chunfang , Huang Xiaomin , Xu Weibing , Zhou Daxing , Li Jin , Li Jianxiang , Hou Liqun , Wang Kuan , Sun Yulong
Published: January 2024

To study how varying the parameters of expansion joints and bearing supports (E-B parameters) affects the dynamic response of a coupled vehicle–bridge system for curved girder bridges, a dynamic response analysis method for the coupled vehicle–joint (bearing)–bridge system, which takes into account centrifugal forces, was proposed and verified. Subsequently, taking a continuous curved box girder bridge as the prototype, the influence of the E-B parameters on the vehicle-induced dynamic response of the curved girder bridge was explored. The results showed that the dynamic amplification factor (DAF) of the middle beam of the expansion joint (DAF-EJ) and the main girder of the curved bridge (DAF-MG) were both significantly influenced by the E-B parameters. When there were height differences between the middle beam and side beam in the EJ, the DAF-EJ obviously varied, and the DAF-MG increased. When the EJ was damaged, the impact effect of the vehicle on the bearing support increased. The DAF-EJ and DAF-MG both increased with the decrease of the vertical support stiffness of the bearing support. The DAF-EJ was greatly affected by the single-support void at the near-slit end of the lane. The DAF-MGs at the beam end, the 1/4 point and 1/2 point of the first span, and the 1/2 point of the second span, were significantly affected by the single-support void near the measuring point. Compared with the single-support void, the DAF-EJ and DAF-MG more significantly increased under the double-support void. Variation in the height difference of the EJ had a more significant effect on the DAF-EJ and DAF-MG at the beam end, while a vertical stiffness reduction in the bearing support had a more significant effect on the DAF-MG.
OpenSeismoMatlab: New Features, Verification and Charting Future Endeavors
Authors: Papazafeiropoulos George , Plevris Vagelis
Published: January 2024

To facilitate the precise design of earthquake-resistant structures, it is imperative to accurately evaluate the impact of seismic events on these constructions and predict their responses. OpenSeismoMatlab, a robust, free ground motion data processing software, plays a pivotal role in this endeavor. It empowers users to compute a wide array of outcomes using input acceleration time histories, encompassing time histories themselves, as well as linear and nonlinear spectra. These capabilities are instrumental in supporting structural design initiatives. This study provides a comprehensive exposition of the latest version (v 5.05) of OpenSeismoMatlab. It delves into intricate facets of the software, encompassing a detailed exploration of the input and output variables integral to each operational category. Comprehensive calculation flowcharts are presented to elucidate the software’s organizational structure and operational sequences. Furthermore, a meticulous verification assessment is conducted to validate OpenSeismoMatlab’s performance. This verification entails a rigorous examination of specific cases drawn from existing literature, wherein the software’s outcomes are rigorously compared against corresponding results from prior studies. The examination not only underscores the reliability of OpenSeismoMatlab but also emphasizes its ability to generate outcomes that closely align with findings documented in the established body of literature. Concluding the study, the paper outlines potential directions for future research, shedding light on avenues where further development and exploration can enhance the utility and scope of OpenSeismoMatlab in advancing seismic engineering and structural design practices.
The Transabdominal Lumbar Approach (TALA) for Robotic Renal Surgery—A Retrospective Single-Center Comparative Study and Step-by-Step Description of a Novel Approach
Authors: Heining Franziska Maria , Bieri Uwe , Niemann Tilo , Maletzki Philipp , Tschung Christopher , Adank Jean-Pascal , Rössler Fabian , Nocito Antonio , Hefermehl Lukas John
Published: January 2024

The transperitoneal approach (TP) and the retroperitoneal approach (RP) are two common methods for performing nephrectomy or partial nephrectomy. However, both approaches face difficulties, such as trocar placement and limited working space (RP). TP is impaired in the case of dorsal tumors and dissection of the renal artery can be challenging due to the anatomic localization dorsally to the renal vein. A hybrid approach that combines both methods has been previously reported in a case series, but not evaluated systematically. This study proposes a modified hybrid approach, which we call the transabdominal lumbar approach (TALA), involving late robotic docking after elaborating the retroperitoneum using conventional laparoscopy. The study compares the last 20 consecutive patients who underwent RP and the last 20 patients who underwent TALA at our institution. The investigated variables include operative time and amount of blood loss, hospitalization duration, postoperative analgesia requirement, and postoperative complications. The study found no significant difference in operative time, blood loss, ischemia time, or hospital stay between the two groups. The TALA group had fewer complications regarding Clavien–Dindo category 3, but one complication of category 4. In Conclusion, TALA is a safe and promising approach that combines the advantages of RP and TP.
Antibody–Drug Conjugates: The Dynamic Evolution from Conventional to Next-Generation Constructs
Authors: Metrangolo Virginia , Engelholm Lars H.
Published: January 2024

Introduced almost two decades ago, ADCs have marked a breakthrough in the targeted therapy era, providing clinical benefits to many cancer patients. While the inherent complexity of this class of drugs has challenged their development and broad application, the experience gained from years of trials and errors and recent advances in construct design and delivery have led to an increased number of ADCs approved or in late clinical development in only five years. Target and payload diversification, along with novel conjugation and linker technologies, are at the forefront of next-generation ADC development, renewing hopes to broaden the scope of these targeted drugs to difficult-to-treat cancers and beyond. This review highlights recent trends in the ADC field, focusing on construct design and mechanism of action and their implications on ADCs’ therapeutic profile. The evolution from conventional to innovative ADC formats will be illustrated, along with some of the current hurdles, including toxicity and drug resistance. Future directions to improve the design of next-generation ADCs will also be presented.
Tumor Suppression by Anti-Fibroblast Activation Protein Near-Infrared Photoimmunotherapy Targeting Cancer-Associated Fibroblasts
Authors: Glabman Raisa A. , Olkowski Colleen P. , Minor Hannah A. , Bassel Laura L. , Kedei Noemi , Choyke Peter L. , Sato Noriko
Published: January 2024

Cancer-associated fibroblasts (CAFs) constitute a prominent cellular component of the tumor stroma, with various pro-tumorigenic roles. Numerous attempts to target fibroblast activation protein (FAP), a highly expressed marker in immunosuppressive CAFs, have failed to demonstrate anti-tumor efficacy in human clinical trials. Near-infrared photoimmunotherapy (NIR-PIT) is a highly selective tumor therapy that utilizes an antibody-photo-absorbing conjugate activated by near-infrared light. In this study, we examined the therapeutic efficacy of CAF depletion by NIR-PIT in two mouse tumor models. Using CAF-rich syngeneic lung and spontaneous mammary tumors, NIR-PIT against FAP or podoplanin was performed. Anti-FAP NIR-PIT effectively depleted FAP+ CAFs, as well as FAP+ myeloid cells, and suppressed tumor growth, whereas anti-podoplanin NIR-PIT was ineffective. Interferon-gamma production by CD8 T and natural killer cells was induced within hours after anti-FAP NIR-PIT. Additionally, lung metastases were reduced in the treated spontaneous mammary cancer model. Depletion of FAP+ stromal as well as FAP+ myeloid cells effectively suppressed tumor growth in bone marrow chimeras, suggesting that the depletion of both cell types in one treatment is an effective therapeutic approach. These findings highlight a promising therapy for selectively eliminating immunosuppressive FAP+ cells within the tumor microenvironment.
Major Stressful Life Events and the Risk of Pancreatic, Head and Neck Cancers: A Case–Control Study
Authors: Sridhar Arthi , Sekhon Vishaldeep Kaur , Nguyen Chandler , Abushalha Kamelah , Tahanan Amirali , Rahbar Mohammad Hossein , Jafri Syed Hasan
Published: January 2024

Background: Major stressful life events have been shown to be associated with an increased risk of lung cancer, breast cancer and the development of various chronic illnesses. The stress response generated by our body results in a variety of physiological and metabolic changes which can affect the immune system and have been shown to be associated with tumor progression. In this study, we aim to determine if major stressful life events are associated with the incidence of head and neck or pancreatic cancer (HNPC). Methods: This is a matched case–control study. Cases (CAs) were HNPC patients diagnosed within the previous 12 months. Controls (COs) were patients without a prior history of malignancy. Basic demographic data information on major stressful life events was collected using the modified Holmes–Rahe stress scale. A total sample of 280 was needed (79 cases, 201 controls) to achieve at least 80% power to detect odds ratios (ORs) of 2.00 or higher at the 5% level of significance. Results: From 1 January 2018 to 31 August 2021, 280 patients were enrolled (CA = 79, CO = 201) in this study. In a multivariable logistic regression analysis after controlling for potential confounding variables (including sex, age, race, education, marital status, smoking history), there was no difference between the lifetime prevalence of major stressful event in cases and controls. However, patients with HNPC were significantly more likely to report a major stressful life event within the preceding 5 years when compared to COs (p = 0.01, OR = 2.32, 95% CI, 1.18–4.54). Conclusions: Patients with head, neck and pancreatic cancers are significantly associated with having a major stressful life event within 5 years of their diagnosis. This study highlights the potential need to recognize stressful life events as risk factors for developing malignancies.
Complete Primary Pathological Response Following Neoadjuvant Treatment and Radical Resection for Pancreatic Ductal Adenocarcinoma
Authors: Yeung Kai Tai Derek , Doyle Joseph , Kumar Sacheen , Aitken Katharine , Tait Diana , Cunningham David , Jiao Long R. , Bhogal Ricky Harminder
Published: January 2024

Introduction: Neoadjuvant treatment (NAT) for borderline (BD) or locally advanced (LA) primary pancreatic cancer (PDAC) is now a widely adopted approach. We present a case series of patients who have achieved a complete pathological response of the primary tumour on final histology following neoadjuvant chemotherapy +/− chemoradiation and radical surgery. Methods: Patients who underwent radical pancreatic resection following neoadjuvant treatment between March 2006 and March 2023 at a single institution were identified by retrospective case note review of a prospectively maintained database. Results: Ten patients were identified to have a complete primary pathological response (ypT0) on postoperative histology. Before treatment, five patients were considered BD and five were LA according to National Comprehensive Cancer Network guidelines. All patients underwent staging Computed Tomography (CT) and nine underwent 18Fluorodeoxyglucose Positron Emission Tomography (18FDG-PET/CT) imaging, with a mean maximum standardized uptake value (SUVmax) of the primary lesion at 6.14 ± 1.98 units. All patients received neoadjuvant chemotherapy, and eight received further chemoradiotherapy prior to resection. Mean pre- and post-neoadjuvant treatment serum Ca19-9 was 148.0 ± 146.3 IU/L and 18.0 ± 18.7 IU/L, respectively (p = 0.01). The mean duration of NAT was 5.6 ± 1.7 months. The mean time from completion of NAT to surgery was 13.1 ± 8.3 weeks. The mean lymph node yield was 21.1 ± 10.4 nodes, with one patient found to have 1 lymph node involved. All resections were reported to be R0. The mean length of stay was 11.8 ± 6.2 days. At the time of analysis, one death was reported at 35 months postoperatively. Two cases of recurrence were reported at 16 months (surgical bed) and 33 months (pulmonary). All other patients remain alive and under active surveillance. The current overall survival is 26.6 ± 20.7 months and counting. Conclusions: Complete primary pathological response is uncommon but possible following neoadjuvant treatment in patients with PDAC. Further work to identify the common denominator within this unique cohort may lead to advances in the therapeutic approach and offer hope for patients diagnosed with borderline or locally advanced pancreatic ductal adenocarcinoma.
Caring for Pregnant Patients with Cancer: A Framework for Ethical and Patient-Centred Care
Authors: Linkeviciute Alma , Canario Rita , Peccatori Fedro Alessandro , Dierickx Kris
Published: January 2024

(1) Background: Caring for pregnant cancer patients is clinically and ethically complex. There is no structured ethical guidance for healthcare professionals caring for these patients. (2) Objective: This concept paper proposes a theoretically grounded framework to support ethical and patient-centred care of pregnant cancer patients. (3) Methodological approach: The framework development was based on ethical models applicable to cancer care during pregnancy—namely principle-based approaches (biomedical ethics principles developed by Beauchamp and Childress and the European principles in bioethics and biolaw) and relational, patient-focused approaches (relational ethics, ethics of care and medical maternalism)—and informed by a systematic review of clinical practice guidelines. (4) Results: Five foundational discussion themes, summarising the key ethical considerations that should be taken into account by healthcare professionals while discussing treatment and care options with these patients, were identified. This was further developed into a comprehensive ethics checklist that can be used during clinical appointments and highlights the need for a holistic view to patient treatment, care and counselling while providing ethical, patient-centric care. (5) Conclusion: The proposed framework was further operationalised into an ethics checklist for healthcare professionals that aims to help them anticipate and address ethical concerns that may arise when attending to pregnant cancer patients. Further studies exploring clinicians’ attitudes towards cancer treatment in the course of pregnancy and patient experiences when diagnosed with cancer while pregnant and wider stakeholder engagement are needed to inform the development of further ethical, patient-centred guidance.
Novel Insights in Venous Thromboembolism Risk Assessment Methods in Ambulatory Cancer Patients: From the Guidelines to Clinical Practice
Authors: Drăgan Anca , Drăgan Adrian Ştefan
Published: January 2024

Many cancer patients will experience venous thromboembolism (VTE) at some stage, with the highest rate in the initial period following diagnosis. Novel cancer therapies may further enhance the risk. VTE in a cancer setting is associated with poor prognostic, a decreased quality of life, and high healthcare costs. If thromboprophylaxis in hospitalized cancer patients and perioperative settings is widely accepted in clinical practice and supported by the guidelines, it is not the same situation in ambulatory cancer patient settings. The guidelines do not recommend primary thromboprophylaxis, except in high-risk cases. However, nowadays, risk stratification is still challenging, although many tools have been developed. The Khrorana score remains the most used method, but it has many limits. This narrative review aims to present the current relevant knowledge of VTE risk assessment in ambulatory cancer patients, starting from the guideline recommendations and continuing with the specific risk assessment methods and machine learning models approaches. Biomarkers, genetic, and clinical features were tested alone or in groups. Old and new models used in VTE risk assessment are exposed, underlining their clinical utility. Imaging and biomolecular approaches to VTE screening of outpatients with cancer are also presented, which could help clinical decisions.