bluuebunny/crossref_metadata_2025 huggingface dataset:
Two New Calibration Techniques of Lumped‐Parameter Mathematical Models for the Cardiovascular System
Authors: Tonini Andrea , Regazzoni Francesco , Salvador Matteo , Dede' Luca , Scrofani Roberto , Fusini Laura , Cogliati Chiara , Pontone Gianluca , Vergara Christian , Quarteroni Alfio
Published: January 2025

Cardiocirculatory mathematical models are valuable tools for investigating both physiological and pathological conditions of the circulatory system. To assess an individual's clinical condition, these models must be tailored through parameter calibration. This study introduces a novel calibration method for a lumped‐parameter cardiocirculatory model, by leveraging on the correlation matrix between model parameters and outputs to adjust the latter based on observed data. We evaluate the performance of our method, both independently and in combination with the L‐BFGS‐B optimization algorithm (Limited memory Broyden–Fletcher–Goldfarb–Shanno with Bound constraints), and we compare our results with those of L‐BFGS‐B alone. Using synthetic data, we show that both the correlation matrix calibration method and the combined one reduce the loss function of the optimization problem more effectively than L‐BFGS‐B. Moreover, the correlation matrix calibration method exhibits greater robustness to the initial parameter guess than both the combined method and L‐BFGS‐B. When applied to noisy data, all three calibration methods achieve comparable results. Although the correlation matrix calibration method yields less accurate parameter estimates than L‐BFGS‐B, in a real‐world clinical case, the two new calibration methods provide clinical insights comparable to L‐BFGS‐B. Notably, the correlation matrix calibration method is three times faster than the other two calibration methods. These findings highlight the effectiveness of our new calibration method for clinical applications.
Micropolar Elastoplasticity Using a Fast Fourier Transform‐Based Solver
Authors: Francis Noah M. , Lebensohn Ricardo A. , Pourahmadian Fatemeh , Dingreville Rémi
Published: January 2025

This work presents a micromechanical spectral formulation for obtaining the full‐field and homogenized response of elastoplastic micropolar composites. A closed‐form radial‐return mapping is derived from thermodynamics‐based micropolar elastoplastic constitutive equations to determine the increment of plastic strain necessary to return the generalized stress state to the yield surface, and the algorithm implementation is verified using the method of numerically manufactured solutions. Then, size‐dependent material response and micro‐plasticity are shown as features that may be efficiently simulated in this micropolar elastoplastic framework. The computational efficiency of the formulation enables the generation of large datasets in reasonable computing times.
Ossicular Chain Reconstruction With Glass Ionomer Cement Following Removal of Active Middle Ear Implant
Authors: McFeely William J. , McFeely Alexis E. , Shohet Jack A.
Published: January 2025

The use of bone cement in ossicular chain reconstruction (OCR) represents an area of recent interest. This multi‐institutional retrospective study assesses the efficacy of glass ionomer cement (GIC) in OCR following the explantation of a fully implantable active middle ear implant. A postoperative 4‐frequency mean air‐bone gap (ABG) was obtained for 15 subjects by averaging 0.5, 1, 2, and 4 kHz frequencies. For Group A (short‐term, N = 15), at a mean of 4.5 months postoperatively, 9 (60%) achieved an ABG between 0 and 10 dB, 5 (33%) were 11 to 20 dB, and 1 (7%) was 21 to 30 dB. For Group B (long‐term, N = 5), at a mean of 50 months postoperatively, 4 (80%) were 0 to 10 dB and 1 (20%) was 11 to 20 dB. These results suggest that GIC represents an effective means of ABG closure after device explantation.
Unsupervised machine learning analysis to identify patterns of ICU medication use for fluid overload prediction
Authors: Henry Kelli , Deng Shiyuan , Chen Xianyan , Zhang Tianyi , Devlin John W. , Murphy David J. , Smith Susan E. , Murray Brian , Kamaleswaran Rishikesan , Most Amoreena , Sikora Andrea ,   the MRC‐ICU Investigator Team
Published: January 2025

Background

Fluid overload (FO) in the intensive care unit (ICU) is common, serious, and may be preventable. Intravenous medications (including administered volume) are a primary cause for FO but are challenging to evaluate as a FO predictor given the high frequency and time‐dependency of their use and other factors affecting FO. We sought to employ unsupervised machine learning methods to uncover medication administration patterns correlating with FO.

Methods

This retrospective cohort study included 927 adults admitted to an ICU for ≥72 h. FO was defined as a positive fluid balance ≥7% of admission body weight. After reviewing medication administration record data in 3‐h periods, medication exposure was categorized into clusters using principal component analysis (PCA) and Restricted Boltzmann Machine (RBM). Medication regimens of patients with and without FO were compared within clusters to assess their temporal association with FO.

Results

FO occurred in 127 (13.7%) of 927 included patients. Patients received a median (interquartile range) of 31(13–65) discrete intravenous medication administrations over the 72‐h period. Across all 47,803 intravenous medication administrations, 10 unique medication clusters, containing 121 to 130 medications per cluster, were identified. The mean number of Cluster 7 medications administered was significantly greater in the FO cohort compared with patients without FO (25.6 vs.10.9, p < 0.0001). A total of 51 (40.2%) of 127 unique Cluster 7 medications were administered in more than five different 3‐h periods during the 72‐h study window. The most common Cluster 7 medications included continuous infusions, antibiotics, and sedatives/analgesics. Addition of Cluster 7 medications to an FO prediction model including the Acute Physiologic and Chronic Health Evaluation (APACHE) II score and receipt of diuretics improved model predictiveness from an Area Under the Receiver Operation Characteristic (AUROC) curve of 0.719 to 0.741 (p = 0.027).

Conclusions

Using machine learning approaches, a unique medication cluster was strongly associated with FO. Incorporation of this cluster improved the ability to predict FO compared to traditional prediction models. Integration of this approach into real‐time clinical applications may improve early detection of FO to facilitate timely intervention.
Interaction of an Open‐To‐Air Helium Plasma Jet, Produced by Sub‐Microsecond Discharges, With a Polystyrene Surface
Authors: Hamdan Ahmad , Zamo Aurélie
Published: January 2025

This study investigates the effects of an open‐to‐air helium plasma jet, generated by sub‐microsecond discharges, on polystyrene (PS) surfaces positioned at distances of 1 and 10 mm from the nozzle. Optical emission spectroscopy revealed that at 1 mm the plasma spectrum is dominated by N₂⁺ emission, while at 10 mm N₂ emission prevails. Surface analysis showed that at 1 mm PS surfaces developed micro‐ and nanostructures with varying compositions, particularly in the outer regions, while at 10 mm the surface exhibited a uniform nanostructure distribution. X‐ray photoelectron spectroscopy and X‐ray diffraction analyses indicated the incorporation of oxygen and nitrogen species and suggested the formation of functionalized graphene/graphite oxide microstructures.
Exogenous Treatment of Caffeic Acid and Methylglyoxal Synergistically Enhances Anticancer Effect in Prostate Cancer via Inhibition of Glyoxalase‐1
Authors: Anjaly Km , Tiku Ashu Bhan
Published: January 2025

Background

Caffeic acid (CA), a dietary compound, has been studied for its potential impact on inhibiting prostate cancer (PCa) growth. PCa is often associated with heightened expression of glyoxalase‐1 (Glo‐1), making it a target for potential therapeutic interventions. CA's mechanisms in suppressing Glo‐1 expression and its effects on PCa cell proliferation are areas of interest for understanding its potential as an anticancer agent.

Methods

Cellular viability and proliferation were evaluated through MTT and clonogenic assays. The expression levels of particular proteins were assessed using western blot analysis and immunocytochemistry.

Results

Results indicated significant reduction in PCa cell proliferation by CA, accompanied by induction of DNA double‐strand breaks, leading to apoptotic cell death through decreased pro‐caspases expression. Additionally, CA was found to inhibit Glo‐1 expression. To enhance CA's anticancer effect, a novel approach was taken by combining it with methylglyoxal (MG). Exogenous MG treatment, a glycolysis by‐product and glyoxalase enzyme substrate, exhibited dose and time‐dependent toxicity in PCa cells when combined with CA. This combination treatment showed heightened toxicity against PCa cells, attributed to CA's inhibition of Glo‐1 expression and the nontoxic doses of exogenous MG. Consequently, increased levels of endogenous MG were observed, leading to apoptosis and suggesting a promising strategy for targeting glyoxalase oncogenic signaling pathways in PCa with minimal adverse effects.

Conclusion

The study highlights the potential of CA as a therapeutic agent for inhibiting PCa growth through multiple mechanisms, including the induction of apoptotic cell death and inhibition of Glo‐1 expression. Combining CA with MG enhances its anticancer effects, offering a promising strategy for targeting glyoxalase oncogenic pathways in PCa.
Effect of the Coupling Beam with Different Intensity Profile upon Rydberg EIT and Rydberg Two‐Color Polarization Spectroscopy with Cesium Ladder‐Type Level
Authors: Chang Rui , Wang Tao , Yang Yuhui , Hao Lili , He Jun , Wang Junmin
Published: January 2025

Electromagnetically induced transparency (EIT) and two‐color polarization spectroscopy (TCPS) with Rydberg atoms are spectroscopic techniques developed based on the interaction between a ladder‐type three‐level atomic system and two light fields. The narrow linewidth and high contrast Rydberg EIT and Rydberg TCPS have important applications in laser frequency stabilization, Rydberg antennas, Rydberg radar and microwave electric fields detection. Here, the EIT and TCPS with cesium Rydberg atoms are investigated using a ladder‐type level system driven by the 509‐nm coupling beam and the 852‐nm probe beam. The 509‐nm coupling beam with three kinds of intensity spatial profile (Laguerre–Gaussian mode, Gaussian mode, Flat‐top mode) is employed one by one in experiments. Due to the different intensity spatial distributions of the three 509‐nm coupling beams, the Autler–Townes (A–T) splitting method is utilized to calibrate the Rabi frequency of the coupling beams. These results show that the linewidth is narrowest when the 509‐nm coupling beam has the Laguerre–Gaussian mode with an equal Rabi frequency among the three cases, the linewidth and contrast of the EIT and TCPS are optimized by varying the beam sizes of the 509‐nm Laguerre–Gaussian beams. The laser frequency stabilization by using of TCPS with three kinds of 509‐nm coupling beams are compared, the Laguerre–Gaussian coupling beam case is more effective for frequency stabilization because of the narrower linewidth.
A Pilot Evaluation of the Adequacy of Prenatal Vitamins to Cover Dietary Deficits During Pregnancy and Lactation
Authors: Smith Chase K. , Fay Emily E. , Moreni Sue L. , Mao Jennie , Hebert Mary F.
Published: January 2025

Objectives

The objectives of this pilot survey were (1) to compare dietary intakes during three survey windows (25–28 weeks gestation, 28–32 weeks gestation and ≥ 3 months postpartum) with the National Institutes of Health, Office of Dietary Supplements' (NIH:ODS) established recommendations for pregnant and lactating women, and (2) to evaluate the general adequacy of commonly used prenatal vitamins (PVs) to cover the identified deficits in dietary intake.

Methods

In this longitudinal pilot survey, 39 healthy consented women, aged 18–50 years with singleton pregnancies and pre‐pregnancy BMI < 30.0 kg/m2 were included. Items from self‐reported dietary intakes during three survey windows were converted to nutritional content using Fooducate (LLC), a public database. Three‐day mean intakes per survey window per subject were compared with NIH:ODS recommendations to determine dietary deficits. Eight commonly utilised PVs (identified via web searches of common prenatal vitamins and their availability in local stores) were evaluated for adequacy in correcting each dietary deficit.

Results

Nutrients that were ≥ 30% higher than the recommended RDA/AI were carbohydrates, sodium, vitamin A, and vitamin C in the first survey window; carbohydrates, sodium, and vitamin A in the second survey window; and sodium and iron in the third survey window. Nutrients that were ≥ 30% lower than the RDA/AI were potassium, vitamin D, and iron in the first survey window; potassium, vitamin D, and iron during the second survey window; and dietary fibre, potassium, vitamin C, and vitamin D in the third survey window. None of the evaluated PVs corrected all deficits, but two were close to the goal and only one corrected all vitamin D deficits.

Conclusion

Women who are or are planning to become pregnant should be educated on dietary recommendations during pregnancy and lactation, ideally such that supplements become unnecessary. However, it remains good practice to carefully consider prenatal vitamin content before selection.
Driving Sustainable Development Through CSR Leadership: Insights Into Organizational Learning and Technological Innovation
Authors: Zada Muhammad , Khan Salman , Zada Shagufta , Dhar Bablu Kumar
Published: January 2025

Corporate social responsibility (CSR) leadership is increasingly recognized as a critical enabler of sustainable development, particularly within the context of organizational transformation. By fostering organizational learning and leveraging technological innovation, CSR leadership facilitates sustainable development outcomes (SDOs). This study examines the multifaceted role of CSR leadership in advancing SDOs, emphasizing the mediating influence of organizational green learning (OGL) and the moderating role of green technological adoption (GTA). Grounded in stakeholder theory and organizational learning theory, the research employs a time‐lagged survey design involving 417 employees from diverse sectors within Chinese manufacturing firms. The findings underscore that CSR leadership significantly enhances OGL by cultivating resource integration and environmental adaptability, which are pivotal in achieving SDOs. Furthermore, GTA is shown to amplify the positive relationship between OGL and SDOs, underscoring the necessity of technological readiness in embedding sustainability within organizational strategies. This study addresses key gaps in the literature by offering a comprehensive framework that links CSR leadership with green learning and technological innovation, providing both theoretical contributions and actionable insights. The findings have practical implications for managers and policymakers, particularly in resource‐intensive and innovation‐driven industries seeking to balance sustainability with economic objectives.
Virtual Screening and Molecular Docking of Traditional Chinese Medicine Database Reveals Curculigoside as a Promising Inhibitor for Non‐Insulin‐Dependent Diabetes Mellitus
Authors: Hossain Md. Sanower , Roney Miah , Uddin Md. Nazim , Haslinda Shariffuddin Jun
Published: January 2025

Millions worldwide grapple with diabetes mellitus, a global health burden lacking a definitive cure. The DrugRep, a web program for multi‐database drug discovery, remains unexplored for antidiabetic agents in non‐insulin‐dependent diabetes mellitus (NIDDM). Therefore, this study aimed to screen the TCM database using the fit‐docking approach to identify potential antidiabetic agents targeting NIDDM through virtual screening. From a pool of 2390 monomeric compounds, 50 lead compounds were identified based on their similarity to the reference compound, nateglinide. The selected compounds underwent in silico pharmacokinetic analysis (ADMET), revealing moderate to poor water solubility and suggesting suitability for oral administration. Molecular docking experiments found that curculigoside exhibited the most significant binding properties among the four lead compounds, forming stable hydrogen bonds with the target protein. Molecular dynamics (MD) simulations, principal component analysis (PCA), and free energy landscape (FEL) confirmed the stability of the curculigoside‐protein (PDB ID: 5HHW) complex, while MM‐GBSA free energy calculations indicated a favorable binding affinity. Overall, curculigoside emerges as a promising inhibitor for NIDDM due to its strong binding properties and interactions with key residues within the active pocket of the target protein. However, further research and validation studies are warranted to explore its therapeutic potential and effectiveness for NIDDM.
Pseudo‐Multicomponent Reactions of Lawsone: Synthetic Strategies of Bis‐Lawsone
Authors: Acharya Swadhin Swaraj , Samantaray Dibyaranjan , Sibakrishna Chipuru , Parida Bibhuti Bhusan
Published: January 2025

1,4‐Naphthoquinones (1,4‐NQs) are an important class of molecules with diverse pharmaceutical applications. Lawsone, a naturally occurring molecule with a diverse range of bioactivities, falls in the class of 1,4‐NQs. It possesses 1,3‐dicarbonyl functionality, which has been utilized in the synthesis of bis‐lawsones with the reaction with aldehydes. In this review we have discussed the notable developments of bis‐lawsone synthesis from 2009 to 2023. Also, the review highlights the limitations and future perspectives in the area.
Ultrasound‐Assisted Annulation of 2‐Aminothiophenols with Aldehydes: Facile Synthesis of Benzothiazoles
Authors: Li Siqi , Chen Xuerou , Sun Shilong , Tian Xueyu , Sun Wuji
Published: January 2025

An ultrasound‐assisted facile condensation reaction was developed to synthesize the benzothiazoles. The reaction conditions are mild and do not require toxic metals or ligands, making it an efficient and mild synthesis strategy. Starting from the commercially available aldehydes and 2‐aminothiophenols, this method was found to have wide functional group compatibility, resulting in a series of benzothiazole derivates in moderate to excellent yields. Moreover, all of the benzothiazole derivatives have been characterized by the 1H NMR, 13C NMR, and HRMS.
Technology differentiation, product market rivalry, and M&A transactions
Authors: Arts Sam , Cassiman Bruno , Hou Jianan
Published: January 2025

Research Summary

We study how unique firm technology influences M&A activity. Using a text‐based network approach, we map each firm's position relative to every other firm in technology space to measure the uniqueness of its technology portfolio. Our findings indicate that firms with more unique technology portfolios become prime acquisition targets, particularly for close competitors within the same product market segments. These competitors seek to reduce competition and incorporate unique technologies to strengthen their competitive advantage. Furthermore, firms with unique technology portfolios tend to attract acquirers with closer technological proximity, facilitating the evaluation and integration of these technology assets. Our study underscores unique technology as a critical asset in the market for corporate control and a key driver of M&A transactions.

Managerial Summary

In today's high‐tech business environment, M&As are pivotal strategies not just for growth and competitiveness but often specifically aimed at acquiring the technology of target firms. By analyzing US public firms, we demonstrate that those with unique technology portfolios attract more acquisition interest, particularly from close product market rivals. These rivals aim to reduce competition and strengthen their existing product business by incorporating the unique technology. Companies with unique technology are also particularly appealing to those within closer technological proximity, easing the evaluation and integration process. Our findings emphasize that possessing a unique technology portfolio is a vital asset in the market for corporate control and a major catalyst for mergers and acquisitions activities.
Dual‐Driven Activation of High‐Valence States in Prussian Blue Analogues Via Graphene‐Quantum Dots and Ozone‐Induced Surface Restructuring for Superior Hydrogen Evolution Electrocatalyst
Authors: Tarigan Angelina Melanita , Rinawati Mia , Aulia Sofiannisa , Chang Ling‐Yu , Chang Chia‐Yu , Su Wei‐Nien , Haw Shu‐Chih , Huang Wei‐Hsiang , Setyawan Heru , Yeh Min‐Hsin
Published: January 2025

Electrochemical water splitting is a pivotal process for sustainable hydrogen energy production, relying on efficient hydrogen evolution reaction (HER) catalysts, particularly in acidic environments, where both high activity and durability are crucial. Despite the favorable kinetics of platinum (Pt)‐based materials, their performance is hindered under harsh conditions, driving the search for alternatives. Due to their unique structural characteristic, Prussian blue analogs (PBAs) emerge as attractive candidates for designing efficient HER electrocatalysts. However, modulating their properties and functionalities is crucial to overcome their conductivity issue. Herein, a reconfiguration strategy for the dual‐driven surface restructuring of the CoFe PBA involving graphene quantum dots (GQD) and UV/ozone is proposed. X‐ray absorption spectroscopy (XAS) analysis revealed that dual‐driven reconstruction plays a pivotal role in promoting the high‐valence metal ions, effectively reducing charge transfer resistance—a key limitation in HER. The optimized CoFe PBA/GQD‐UV exhibits remarkable electrocatalytic performance toward HER, with a low overpotential of 77 mV to reach a current density of 10 mA cm−2 with excellent durability for 12 h under an extremely high current density of 500 mA cm−2 in an acidic solution. This dual‐combination strategy offering a new pathway to develop highly active electrocatalysts.
Design and Implementation of Node Degree Centrality Computing of Network Security Database Based on Knowledge Graph
Authors: Wu Chao , Wu Feng
Published: January 2025

With the development and popularization of network technology, network security issues are increasingly being valued. The application of knowledge graph technology in network security can significantly enhance the level of protection, assist users and relevant departments in understanding overall trends of network security vulnerabilities, and swiftly identify and respond to security threats. To improve the analysis and response capabilities to network security threats, developing methods for identifying key nodes in the network is urgent. This research focuses on the degree centrality calculation method for nodes in a network security database based on knowledge graphs. We propose a novel approach for computing node degree centrality within a knowledge graph‐based network security database. The method comprises two main components: weight calculation and score calculation. Additionally, we have developed a node importance ranking module based on a network security knowledge graph derived from the CVE database, providing a faster and more accurate solution compared to manual methods. We then discuss the significant application value and promising development prospects of the knowledge graph‐based node degree centrality calculation method in the field of network security protection in future work.
Precast concrete sandwich panels with recycled tire crumb rubber and expanded polystyrene foam cores under low‐velocity drop weight impact
Authors: Hosan Anwar , Basir Abdul , Shaikh Faiz Uddin Ahmed , Chen Wensu
Published: January 2025

Structural behavior of precast concrete sandwich panels under low‐velocity drop weight impact is presented in this paper. Three types of concrete panels are considered namely, solid concrete panel (SCP), concrete sandwich panels containing recycled tire crumb rubber as core (CRSP), and expanded polystyrene foam as core (FSP). The panels are reinforced with steel mesh or steel fibers. A total of 12 panels are cast in this study. Six panels are reinforced using steel mesh, and the other six panels are reinforced using steel fibers. The impact test is carried out by dropping a weight from a varying height to input impact energy, which can cause various levels of damage for all specimens. The structural performance is discussed in detail, including failure modes, impact force, deflection, and strain. It is found that the core material greatly affects the structural response of the precast concrete panels. The sandwich panel containing recycled tire crumb rubber performed well in terms of rebounding force, permanent deflections, and damage behavior by partially absorbing the impact energy in both types of reinforced concrete panels. In CRSP and FSP, the maximum deflection to permanent deflection ratio rose from 1.19 in SCP to 2.67 and 2.01, respectively. A decrease of 70% in strain value from the first impact to permanent strain was recorded in CRSP when reinforced using conventional steel mesh. In comparison to its counterpart FSP, the CRSP exhibited a significantly smaller fracture width on the tension face as a result of the core's ability to dissipate impact energy, resulting in lower deflections and less damage to the panel. The CRSP reinforced with steel fibers demonstrated comparable performance to the counterpart FSP in terms of energy absorption and deflection reduction; however, it performed noticeably better than the SCP reinforced with steel fibers by reducing residual deflection by 51.8 mm. Consequently, recycled tire crumb rubber can be used as a sustainable alternative to traditional core materials in precast concrete panels.
Subanesthetic Ketamine Ameliorates Activity‐Based Anorexia of Adult Mice
Authors: Dong Yiru , Aoki Chiye
Published: January 2025

Objective

Anorexia nervosa (AN) is an eating disorder with the second highest mortality of all mental illnesses and high relapse rate, especially among adult females, yet with no accepted pharmacotherapy. A small number of studies have reported that adult females who struggled with severe and relapsing AN experienced sustained remission of the illness following ketamine infusions. Two other reports showed that 30 mg/kg IP ketamine can reduce vulnerability of adolescent mice to activity‐based anorexia (ABA), an animal model of AN. However, no study has tested the efficacy of ketamine on adult ABA mice. This study aimed to fill this gap in knowledge.

Methods

Forty‐one female mice underwent three cycles of ABA (ABA1, ABA2, and ABA3) to assess relapse vulnerability in adulthood. Of them, 13 received ketamine injections (30 mg/kg, 3 doses) during ABA2 (KET) in adulthood to assess ketamine's acute effects during ABA2 and ketamine's potential for sustained efficacy during ABA3, 10–13 days later. The remaining 28 received vehicle or no injections during ABA2 (CON).

Results

Severe weight loss (>20% of baseline) during ABA3 was observed for 89% of CON but only 69% of KET. Overall wheel running per day was significantly less for KET than CON (p < 0.01) throughout ABA2, including hours of food availability, and these reductions were sustained through ABA3. Food consumption was not altered significantly by ketamine.

Discussion

These findings suggest that ketamine may reduce adult females’ vulnerability to ABA and may protect women from AN relapse by reducing hyperactivity.
Neuroprotective Effect of Curcumin–Metavanadate in the Hippocampus of Aged Rats
Authors: Gonzalez‐Cano Sonia Irais , Peña‐Rosas Ulises , Muñoz‐Arenas Guadalupe , Torres‐Cinfuentes Diana Milena , Treviño Samuel , Moran‐Raya Carolina , Flores Gonzalo , Guevara Jorge , Diaz Alfonso
Published: January 2025

Brain aging is a multifactorial process that includes a reduction in the biological and metabolic activity of individuals. Oxidative stress and inflammatory processes are characteristic of brain aging. Given the current problems, the need arises to implement new therapeutic approaches. Polyoxidovanadates (POV), as well as curcumin, have stood out for their participation in a variety of biological activities. This work aimed to evaluate the coupling of metavanadate and curcumin (Cuma‐MV) on learning, memory, redox balance, neuroinflammation, and cell death in the hippocampal region (CA1 and CA3) and dentate gyrus (DG) of aged rats. Rats 18 months old were administered a daily dose of curcumin (Cuma), sodium metavanadate (MV), or Cuma‐MV for two months. The results demonstrated that administration of Cuma‐MV for 60 days in aged rats improved short‐ and long‐term recognition memory, decreased reactive oxygen species, and substantially improved lipoperoxidation in the hippocampus. Furthermore, the activity of superoxide dismutase and catalase increased in animals treated with Cuma‐MV. It is important to highlight that the treatment with Cuma‐MV exhibited a significantly greater effect than the treatments with MV or Cuma in all the parameters evaluated. Finally, we conclude that Cuma‐MV represents a potential therapeutic option in the prevention and treatment of cognitive decline associated with aging.
Lefebvre Visits Joyful Kolkata? The Right to the City and Migrant Laborers
Authors: Dey Biswas Sattwick
Published: January 2025

In late March 2020, with 4 h of notice, the union government of India imposed a complete nationwide lockdown, or containment measures against COVID-19 under the Disaster Management Act 2005 (especially its Sects. 8 and 10).
Urban Digital Infrastructuring and the (re)production of Privilege
Authors:   The UDI Writers Collective
Published: January 2025

A global digital and data revolution governs future urban strategies and profoundly influences the infrastructures built in cities. Numerous digital urban infrastructures remain hidden to city dwellers, all the while concurrently shaping, if not dictating, urban rhythms.
A Citizenship of Sharing: Transformations of an Urban Patron Saint
Authors: Rose Els
Published: January 2025

The question as to what makes a city prosperous, and how a city responds to crises that challenge its resilience, yields different responses in different historical periods. The city of Utrecht offers a relevant case to study these questions from a cultural perspective because of the historically layered heritage of its answers. In the course of its history, the city changed roles a number of times. Founded as an outpost of the Roman military, it developed into the most important ecclesiastical centre of the northern Low Countries in the Middle Ages as well as an important crossroads of trade routes. Throughout that period, the urban community of Utrecht identified with its local patron saint, the charitable figure of Saint-Martin who shared his cloak with a poor beggar. Through the centuries, the celebration of the urban patron saint was a continuum, while it took different appearances and performative expressions. In recent decades, newly invented Saint Martin-traditions find expression in street performances and participatory art. These new traditions focus primarily on social cohesion through involving vulnerable and marginalized neighborhoods with culturally and religiously mixed populations in the traditional celebration of the patron saint. The language expressing cultural efforts to contribute to the sustainability and resilience of the city and its urban community shows the transformative power of both the urban populace and the symbolic figure of sharing and participation. While the medieval city responded to the libertas it acquired in 1122 with the building of walls, this same event was celebrated in 2022 under the title ‘Utrecht Without Walls’. In both historical moments, the same symbol of sharing and participation imagined by the traditional patron saint played a crucial role. The present chapter discusses the transformative power of an urban community relating to its ancient patron saint in new ways to address issues of inclusion, social cohesion, and prosperity in a modern city.
Political Apathy or Political Exclusion? Malaysian Youth, Generational Barriers and Inclusive Political Participation for Urban Development Planning in Penang
Authors: van Gils Bart A. M. , Pijnacker Lisa S. , Tayeb Azmil
Published: January 2025

When a city or state government undertakes a large-scale development project, such governments may initiate or support activities that foster participation of the inhabitants.
Building Inclusive Cities for and from Undocumented Migrants? The Experiences of Madrid and Barcelona Under the Commons’ Municipalist Governments (2015–2019)
Authors: Espiñeira Keina , Fernández-Suárez Belén
Published: January 2025

Cities and their local policies possess the capacity to create more inclusive, safe, and sustainable environments than other levels of governance more distant from citizens. Consequently, urban social policies must prioritize the inclusion of vulnerable and socially excluded groups at the forefront of their initiatives.
Universal flops of length 1 and 2 from D2-branes at surface singularities
Authors: Moleti Marina , Valandro Roberto
Published: January 2025

Abstract

We study families of deformed ADE surfaces by probing them with a D2-brane in Type IIA string theory. The geometry of the total space X of such a family can be encoded in a scalar field Φ, which lives in the corresponding ADE algebra and depends on the deformation parameters. The superpotential of the probe three dimensional (3d) theory incorporates a term that depends on the field Φ. By varying the parameters on which Φ depends, one generates a family of 3d theories whose moduli space always includes a geometric branch, isomorphic to the deformed surface. By fibering this geometric branch over the parameter space, the total space X of the family of ADE surfaces is reconstructed. We explore various cases, including when X is the universal flop of length ℓ = 1, 2. The effective theory, obtained after the introduction of Φ, provides valuable insights into the geometric features of X, such as the loci in parameter space where the fiber becomes singular and, more notably, the conditions under which this induces a singularity in the total space. By analyzing the monopole operators in the 3d theory, we determine the charges of certain M2-brane states arising in M-theory compactifications on X.
Wood-fiber insulation boards produced with polylactic acid as a binder by hot press and hot air
Authors: Cárdenas-Oscanoa Aldo Joao , Tene Tayo Lawrence , Huang Caoxing , Huang Chen , Shivappa Nayaka Darshan , Euring Markus
Published: January 2025

Traditionally, there are two types of wood fiber insulation boards (WFIB), the rigid ones produced in the industry by a continuous steam process, bonded with polymer diphenylmethane diisocyanate (pMDI), with densities between 80 and 200 kg/m3, and the flexible ones with densities under 80 kg/m3 produced by hot air, usually with bicomponent fibers as a binder. In this work, wood fiber insulation boards (WFIB) were produced with polylactic acid (PLA) as a binder by hot press (HP) and hot air (HA). WFIB with densities of 60 kg/m3, 80 kg/m3, 100 kg/m3 and 5%, 10% and 15% of PLA percentage were produced by hot press (HP) and hot air (HA). Wood and PLA fibers were examined by scanning electronic microscope (SEM) and optical microscope. The WFIB were assessed for physical properties as density and short-term water absorption as well as for their resistance to compression as a mechanical property. Thermal properties such as thermal conductivity and thermogravimetric analysis (TGA) were also tested. In the produced WFIB, the values of density follow the same pattern as water absorption, compression strength, and thermal conductivity. The polylactic acid (PLA) content improves mechanical value like compression and diminishes physical value such as short-term water absorption in WFIB. In conclusion, wood fiber insulation boards (WFIB) were successfully produced with polylactic acid (PLA) as a binder, by hot press (HP) and hot air (HA), reaching remarkably lower thermal conductivity values, comparable with commercial ones.
Characterization of a Novel Col1a1G643S/+ Osteogenesis Imperfecta Mouse Model with Insights into Skeletal Phenotype, Fragility, and Therapeutic Evaluations
Authors: Saitou Hiroyuki , Ohata Yasuhisa , Takeyari Shinji , Nishizawa Chiaki , Nakayama Hirofumi , Fujiwara Makoto , Kitabatake Yasuji , Kubota Takuo , Ozono Keiichi
Published: January 2025

Osteogenesis imperfecta (OI) is an inheritable skeletal disorder characterized by bone fragility often caused by pathogenic variants in the COL1A1 gene. Current OI mouse models with a glycine substitution in Col1a1 exhibit excessive severity, thereby limiting long-term pathophysiological analysis and drug effect assessments. To address this limitation, we constructed a novel OI mouse model mimicking a patient with OI type III. This was achieved by introducing a G-to-A transversion at nucleotide position 2428 in the Col1a1 gene via CRISPR-Cas9 technology in C57BL/6 J mice. The resulting heterozygous variant mice (Col1a1G643S/+) displayed reduced body weight and pronounced skeletal abnormalities. Micro-CT analysis at 12 weeks revealed decreased vertebral bone parameters and altered cortical bone characteristics, indicative of bone fragility. Additionally, the abnormalities of the anisotropy, complexity, connectivity, and structure of trabecular bone were revealed. A three-point bending test confirmed the fragility, with reduced displacement and fracture energy in both sexes. Furthermore, we evaluated the effect of 4-phenylbutyric acid on the bone in Col1a1G643S/+ mice at 12 weeks, observing no significant effects, likely due to the absence of collagen retention in the ER in this model. Despite being a moderate OI model, Col1a1G643S/+ mice manifest a distinct and fragile bone phenotype, making them suitable for extended studies. This model offers a valuable platform for investigating long-term pathophysiological aspects of OI and assessing the efficacy of potential therapeutic interventions.
Targeted knockdown of ATM, ATR, and PDEδ increases Gag HIV-1 VLP production in HEK293 cells
Authors: Díaz-Maneh Andy , Pérez-Rubio Pol , Granes Cristina Rigau , Bosch-Molist Laia , Lavado-García Jesús , Gòdia Francesc , Cervera Laura
Published: January 2025

Several strategies have been developed in recent years to improve virus-like particle (VLP)-based vaccine production processes. Among these, the metabolic engineering of cell lines has been one of the most promising approaches. Based on previous work and a proteomic analysis of HEK293 cells producing Human Immunodeficiency Virus-1 (HIV-1) Gag VLPs under transient transfection, four proteins susceptible of enhancing VLP production were identified: ataxia telangiectasia mutated (ATM), ataxia telangiectasia and rad3-related (ATR), DNA-dependent protein kinase catalytic subunit (DNA-PKcs), and retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit delta (PDEδ). The knockdown of ATM, ATR, and PDEδ in HEK293 cells increased HIV-1 VLP titers in the supernatant by 3.4-, 2.1-, and 2.2-fold, respectively. Also, possible metabolic synergies between plasmids were investigated by statistical design of experiments (DoE), enabling us to identify the optimal production strategy, that was further demonstrated at lab-scale stirred tank bioreactor operated in perfusion, significantly increasing both VLPs specific and volumetric productivities to 8.3 × 103 VLPs/cellxday and 7.5 × 1012 VLPs/Lxday, respectively.

Key points

• ATM, ATR, and PDEδ knockdowns increased VLP production in HEK293 cells.

• Knockdown of ATM increased budding efficiency and extracellular vesicle concentration.

• ATM knockdown could be intensified to bioreactor scale operated in perfusion.

Graphical Abstract
Sex differences in immunotherapy outcomes and tumor-infiltrating immune cell profiles in patients with advanced renal cell carcinoma
Authors: Ishihara Hiroki , Fukuda Hironori , Mizoguchi Yukihiro , Yamashita Makiko , Aoki Kazunori , Ishiyama Ryo , Ikeda Takashi , Nemoto Yuki , Shimmura Hiroaki , Hashimoto Yasunobu , Yoshida Kazuhiko , Hirai Toshihito , Iizuka Junpei , Tokita Daisuke , Kondo Tsunenori , Nagashima Yoji , Takagi Toshio
Published: January 2025

Sex differences in the outcomes of advanced renal cell carcinoma (RCC) treated with immune checkpoint inhibitors (ICIs) and the profiles of tumor-infiltrating immune cells (TIICs) remain unclear. We retrospectively evaluated data from 563 patients with RCC receiving systemic therapy, including first-line dual ICI combinations (i.e., immunotherapy [IO]-IO), combinations of ICIs with tyrosine kinase inhibitors (TKIs) (i.e., IO-TKI), TKI monotherapy, and subsequent nivolumab monotherapy. Survival and tumor response were compared between the sexes in each treatment group, and TIIC profiles were compared using 116 RCC tumor samples analyzed by flow cytometry. Progression-free survival (PFS) was shorter in female than in male patients in the IO-IO (p = 0.0227) and nivolumab monotherapy (p = 0.0478) groups. Furthermore, sex remained an independent factor for shorter PFS after adjusting for covariates in the IO-IO (p = 0.0340) and nivolumab monotherapy (p = 0.0322) groups. In contrast, PFS was not significantly different between sexes in the IO-TKI or TKI monotherapy groups (p > 0.05). Overall survival and objective response rates were not significantly different between the sexes in any of the treatment groups (p > 0.05). Some TIIC populations, including that of CD8 + T cells (p = 0.0096), decreased to a greater extent in female than in male patients in the advanced-stage population. In conclusion, the effectiveness of ICIs on PFS was lower in female patients than in male patients, potentially because of the different profiles of the immune microenvironment, particularly the decreased number of CD8 + T cells in females.
Prognostic relevance of CD163+ immune cells in patients with metastatic breast cancer
Authors: Lindberg Ida , Saleh Aya , Tutzauer Julia , Gunnarsdottir Frida Björk , Rydén Lisa , Bergenfelz Caroline , Larsson Anna-Maria
Published: January 2025

Metastatic breast cancer (MBC) is generally considered an incurable disease and even though new treatments are available, the median survival is approximately three years. The introduction of immune therapies for MBC highlights the importance of the immune system in cancer progression and treatment. CD163+ anti-inflammatory myeloid cells, including tumor associated macrophages (TAMs), are known to be of relevance in early breast cancer but their role in MBC is not yet established. Here we determine the levels of CD163+ immune cells in 139 patients with newly diagnosed MBC by using Immunohistochemistry (IHC) and gene expression analyses (GEX). We aim to determine changes and distribution of CD163+ immune cells during tumor progression from primary tumors (PT) to lymph node metastases (LNM) and distant metastases (DM). In addition, we evaluate associations between CD163+ immune cells, clinicopathological factors and disease outcome (progression-free and overall survival; PFS and OS, respectively). Despite similar distribution, high levels of CD163+ immune cells in the tumor nest of PT, but not in LNM or DM, associated with adverse prognostic features including higher grade and molecular subtype, as well as with shorter PFS and OS, however this observation was not significant after adjusted multivariate analyses. Finally, high levels of CD163+ immune cells in PT, as well as GEX in PT and synchronous LNM associated with shorter OS from the initial diagnosis. These results indicate that evaluating the levels of CD163+ immune cells may identify MBC patients with a worse prognosis. Unraveling the role of CD163+ immune cells in the complex immune responses in MBC is highly relevant for improving future immune therapies.
Characterization of the adaptive immune response in a mouse model for HPV-positive head and neck squamous cell carcinoma with implications to human disease
Authors: Oliveri Franziska , Neher Linda , Pscheid Ronja , Sewald Isabel , Gowdavally Sowmya , Betzler Annika C. , Hallitsch Jaqueline , Greve Jens , Laban Simon , Schmid Sebastian , Hoffmann Thomas K. , Schuler Patrick J. , Brunner Cornelia
Published: January 2025

Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer worldwide with a poor prognosis for survival. Risk factors include alcohol and tobacco abuse and infection with human papilloma virus (HPV). To enhance anti-tumor immune responses immunotherapeutic approaches are approved for recurrent metastatic disease but only approx. 20% of patients respond to checkpoint blockade of the PD-1/PD-L1 axis. Therefore, preclinical research is needed to better understand molecular and cellular processes and to identify new therapeutic targets. Immunocompetent mouse models can serve these purposes but only few are currently available for HPV-positive HNSCC. Here, we established a mouse cell line overexpressing the oncogenes E6/E7 of the HPV16 genome as well as a constitutively active form of H-Ras and studied the anti-tumor immune response upon orthotopic tumor growth at the floor of the mouth. Moreover, we analyzed the same immunoregulatory pathways in samples of HPV-positive cancer patients. T cells in the tumor of mice and humans exhibited high expression of CD39 and CD73, two ectoenzymes involved in the production of immunosuppressive adenosine from ATP, along with increased expression of PD-1, LAG-3 and GITR. Additionally, B cell responses were elevated in tumor-bearing mice, seen as an increase of germinal center, immunoregulatory marginal zone and follicular B cell subtypes. Taken together, this study suggests that the generated mouse model shares characteristics with human disease and can thus be used as a platform to study anti-tumor responses in HPV-positive HNSCC which will help to identify novel therapeutic targets.
Identification of immune suppressor candidates utilizing comparative transcriptional profiling in histiocytic sarcoma
Authors: Lenz Jennifer A. , Peng Brandon , Assenmacher Charles‑Antoine , King Austin , Zhang Paul J. , Maki Robert G. , Blanco M. Andres , Radaelli Enrico , Atherton Matthew J.
Published: January 2025

Histiocytic sarcoma (HS) is a rare yet lethal malignancy with no established standard of care therapies. A lack of pre-clinical models limits our understanding of HS pathogenesis and identification of therapeutic targets. Canine HS shares multiple clinical and genetic similarities with human HS, supporting its use as a unique translational model. Prior studies have investigated the immunogenicity of HS. Although increased tumor infiltrating lymphocyte (TIL) density is associated with favorable outcomes in canine HS, virtually all canine patients eventually succumb to progressive disease consistent with ultimate failure of anti-tumor immunity. To investigate potential regulators of the immune tumor microenvironment (TME), we undertook a comparative transcriptional approach of three long-lived cases of canine pulmonary HS with heavy T cell infiltrate and three short-lived cases of splenic HS that lacked significant T cell inflammation and compared these data to corresponding grossly normal tissues from dogs undergoing necropsy. This comparison identified PDCD1, encoding the immune checkpoint PD-1, and SPP1, encoding the secreted pro-tumorigenic protein osteopontin, as positive differentially expressed genes (DEGs) in canine HS. TXNIP, encoding the tumor suppressor TXNIP, was the most significant negative DEG. Comparative transcriptomic studies revealed conservation of enriched (including SPP1) and depleted (including TXNIP) DEGs between canine and human HS patients. Immunohistochemistry demonstrated osteopontin in the TMEs of canine and human HS. Collectively, we uncover PD-1, osteopontin, and TXNIP as putative actionable targets in HS and further establish canine HS as a preclinical platform to screen novel immunotherapeutic approaches for this deadly disease.