bluuebunny/crossref_metadata_2025 huggingface dataset:
Bovine milk‐derived extracellular vesicles enhance doxorubicin sensitivity in triple negative breast cancer cells by targeting metabolism and STAT signalling
Authors: Sanwlani Rahul , Kang Taeyoung , Gummadi Sriram , Nedeva Christina , Ang Ching‐Seng , Mathivanan Suresh
Published: June 2023

Metastatic triple‐negative breast cancer (TNBC) has a low 5‐year survival rate of below 30% with systemic chemotherapy being the most widely used treatment. Bovine milk‐derived extracellular vesicles (MEVs) have been previously demonstrated to have anti‐cancer attributes. In this study, we isolated bovine MEVs from commercial milk and characterised them according to MISEV guidelines. Bovine MEVs sensitised TNBC cells to doxorubicin, resulting in reduced metabolic potential and cell‐viability. Label‐free quantitative proteomics of cells treated with MEVs and/or doxorubicin suggested that combinatorial treatment depleted various pro‐tumorigenic interferon‐inducible gene products and proteins with metabolic function, previously identified as therapeutic targets in TNBC. Combinatorial treatment also led to reduced abundance of various STAT proteins and their downstream oncogenic targets with roles in cell‐cycle and apoptosis. Taken together, this study highlights the ability of bovine MEVs to sensitise TNBC cells to standard‐of‐care therapeutic drug doxorubicin, paving the way for novel treatment regimens.
Recent advances in covalent organic polymers‐based thin films as memory devices
Authors: Zhou Pan‐Ke , Yu Hongling , Li Yiping , Yu Hong , Chen Qian , Chen Xiong
Published: June 2023

Covalent organic polymers (COPs) have emerged as a promising class of materials for memory devices due to their unique electronic properties and potential for tunability. This review highlights recent advances in the field of COPs‐based thin films for memory applications, with a focus on the synthesis and characterization of COP thin films, their electronic properties, and their performance as memory devices. The potential of COPs‐based thin films as flexible memory devices is also discussed. Overall, the recent progress in COPs‐based thin films for memory applications suggests that these materials may have a significant impact on the development of next‐generation memory technologies.
Disparities in prevalence and outcomes of respiratory disease in low‐ and middle‐income countries
Authors: Rodriguez‐Martinez Carlos E. , Sossa‐Briceño Monica P.
Published: June 2023

Objectives

To provide a comprehensive overview of disparities in prevalence and outcomes of respiratory diseases and notable challenges for providing optimal treatment to pediatric patients with respiratory diseases living in low‐ and middle‐income countries (LMICs), as an input to help better understand the roots of respiratory health disparities.

Methods

We conducted a narrative review of relevant literature published in electronic databases from inception to February 2023 that present data on disparities in prevalence and outcomes of respiratory disease in LMICs. Additionally, we included studies that describe and discuss challenges for providing optimal treatment to pediatric patients with respiratory diseases living in LMICs.

Results

A number of early life exposures have been associated with adverse respiratory outcomes in later life. Several studies have shown marked geographical variations in the prevalence and burden of pediatric asthma, with consistently lower prevalence rates but significantly higher burdens and worse outcomes in LMICs. There is a wide range of challenges that adversely affect the efficient care of children with respiratory diseases that can be classified into three categories: patient‐related factors, social/environmental factors, and factors related to healthcare providers or the healthcare system.

Conclusions

Respiratory health disparities in children living in LMICs represent a global public health issue mainly explained by an unequal distribution of preventable and modifiable risk factors for respiratory diseases across different demographic groups.
Exposure to outdoor air pollution and risk of hospitalization for bronchiolitis in an urban environment: A 9‐year observational study
Authors: Dondi Arianna , Manieri Elisa , Betti Ludovica , Dormi Ada , Carbone Claudio , Biagi Carlotta , Pierantoni Luca , Zama Daniele , Paglione Marco , Lanari Marcello
Published: June 2023

Background

Outdoor air pollution is supposed to influence the course of bronchiolitis, but the evidence is limited. The present study aimed at evaluating the role of outdoor air pollutants on hospitalization for bronchiolitis.

Methods

Infants aged ≤12 months referred for bronchiolitis to our Pediatric Emergency Department in Bologna, Italy, from 1 October 2011 to 16 March 2020 (nine epidemic seasons) were retrospectively included. Daily concentrations of benzene (C6H6), nitrogen dioxide (NO2), particulate matter ≤2.5 μm (PM2.5), and ≤10 μm (PM10), and the mean values of individual patient exposure in the week and the 4 weeks before hospital access were calculated. The association between air pollutants exposure and hospitalization was evaluated through logistic regression analysis.

Results

A total of 2902 patients were enrolled (59.9% males; 38.7% hospitalized). Exposure to PM2.5 in the 4 weeks preceding bronchiolitis was identified as the main parameter significantly driving the risk of hospitalization (odds ratio [95% confidence interval]: 1.055 [1.010–1.102]). After stratifying by season, higher values of other outdoor air pollutants were found to significantly affect hospitalization: 4‐week exposure to C6H6 (Season 2011–2012, 4.090 [1.184–14.130]) and PM2.5 (Season 2017–2018, 1.282 [1.032–1.593]), and 1‐week exposure to C6H6 (Season 2012–2013, 6.193 [1.552–24.710]), NO2 (Season 2013–2014, 1.064 [1.009–1.122]), PM2.5 (Season 2013–2014, 1.080 [1.023–1.141]), and PM10 (Season 2018–2019, 1.102 [0.991–1.225]).

Conclusion

High levels of PM2.5, C6H6, NO2, and PM10 may increase the risk of hospitalization in children affected by bronchiolitis. Open‐air exposure of infants during rush hours and in the most polluted areas should be avoided.
Controlling the TiO2–Dye Nanomolecular Interactions for Improving the Photoconversion in Transparent Dye‐Sensitized Solar Cells
Authors: Roy Pritha , Kurokawa Yuki , Pandey Shyam S.
Published: June 2023

Herein, transparent dye‐sensitized solar cells (DSSCs) are fabricated using two sensitizing dyes aiming toward panchromatic photon harvesting following two different approaches of dye adsorption such as using dye cocktail and sequential dye adsorption. A combination of complementary yellow‐colored dye (D‐131) and green‐colored far‐red‐sensitive squaraine dye (SQ‐140) is judiciously selected not only for panchromatic light absorption but also for bypassing the absorption in the high eye‐sensitivity wavelength region (500–600 nm) region to improve the transparency. The DSSC fabricated using a dye cocktail of D‐131 and SQ‐140 in a 9:1 molar ratio exhibits a photoconversion efficiency (PCE) and average visible transparency (AVT) of 3.89% and 36.9%, respectively. In contrast, stepwise and controlled dye adsorption of SQ‐140 followed by D‐131 on mesoporous TiO2 leads to further improvement in the PCE from 3.89% to 4.50%, while AVT is reduced from 36.9% to 15.6%. This marked improvement in the PCE for the stepwise co‐sensitized transparent DSSCs is attributed to the suppression of unfavorable inter‐dye interaction leading to synergistic photon harvesting by both of the constituent sensitizing dyes.
Binary Addressable Optical Multiplexing Waveguides via Electrochromic Switching
Authors: Rhim Seon-Young , Heyl Max , Busch Kurt , List-Kratochvil Emil J.W.
Published: June 2023

Photonic circuits attract much attention as promising candidates to overcome the drawbacks of their electronic counterparts. By utilizing the broad bandwidth and low energy consumption of optical communication, hybrid circuits can provide a comprehensive platform for the era beyond Moore's law. In particular, parallel matrix operations, the heavy lifting behind neural networks, remain challenging for traditional electronics due to high heat dissipation. To enable these parallel computations optically, (de‐)multiplexing is crucial to address the different channels. Previously this has been accomplished with complex spectral or time encodings in wave division or time division methods. However, herein, a simple method to address parallel optical channels exclusively with 2‐bit signals is presented. By using PEDOT:PSS as electrochromic material for intensity modulation, light transmission or absorption is controlled by oxidation and reduction with an electrolyte. Y‐branch structures are used to design the multiplexing layout and to assign the 2‐bit states to the channels. This binary addressable optical multiplexer, therefore, combines optical communication with electronic signals into a hybrid circuit.
Influence of New Glass Phase Structure on the Mechanical Properties of Composite Ceramic SiC/Si3N4
Authors: Wang Qiang , Zhou Cunlong , Yang Chao
Published: June 2023

Though the addition of a second phase is an effective method for toughening silicon nitride (Si3N4) ceramics, certain residual thermal stress is generated at the phase interface. In case of a large value of residual thermal stress, a weak interface forms between the second phase and the matrix material, reducing the strength of the material. Herein, a new type of core–shell structure silicon carbide SiC–glass phase is produced inside the material by adding a presintering process into the traditional SiC–Si3N4 sintering process. The radial and tangential thermal stresses around the core–shell structural SiC–glass phase and SiC particle are compared by using the finite element method. The results indicate that the core–shell structural SiC–glass phase inhibits the interfacial debonding. Compared with the introduction of SiC particle alone, the core–shell structural SiC–glass phase optimizes the mechanical properties of SiC/Si3N4 composite ceramic, with the fracture toughness reduced by 9.6%, the bending strength increased by 12.3%, and the friction coefficient reduced by 8.5% for the SiC/Si3N4 ceramics with SiC content of 5%.
Defect‐Engineered ZIF‐Derived Non‐Pt Cathode Catalyst at 1.5 mg cm−2 Loading for Proton Exchange Membrane Fuel Cells
Authors: Zhu Weikang , Liu Haotian , Pei Yabiao , Liu Tao , Zhang Junfeng , Liu Xin , Wang Lianqin , Feng Yingjie , Yin Yan , Guiver Michael D.
Published: June 2023

Due to the sluggish kinetics of the oxygen reduction reaction (ORR) by non‐Pt based catalyst, high loading of catalyst is required to achieve satisfactory fuel cell performance, which inevitably leads to the increase of the catalyst layer thickness with serious mass transport resistance. Herein, a defective zeolitic imidazolate framework (ZIF) derived Co/Fe‐N‐C catalyst with small mesopores (2–4 nm) and high density of CoFe atomic active sites are prepared by regulating the Fe dosage and pyrolysis temperature. Molecular dynamics simulation and electrochemical tests indicate that > 2 nm mesopores show insignificant influence on the diffusion process of O2 and H2O molecules, leading to the high utilization of active sites and low mass transport resistance. The proton exchange membrane fuel cell (PEMFC) shows a high‐power density of 755 mW cm−2 with only 1.5 mg cm−2 of non‐Pt catalyst in the cathode. No apparent performance loss caused by concentration difference can be observed, in particular in the high current density region (1 A cm−2). This work emphasizes the importance of small mesopore design in the Co/Fe‐N‐C catalyst, which is anticipated to provide essential guidance for the application of non‐Pt catalysts.
Thickness‐Controlled Synthesis of Compact and Uniform MOF Protective Layer for Zinc Anode to Achieve 85% Zinc Utilization
Authors: Xiang Yang , Zhong Yi , tan Pingping , Zhou Liyuan , Yin Guijie , pan Hongwei , Li Xu , Jiang Yinzhu , Xu Maowen , Zhang Xuan
Published: June 2023

Zinc anode‐based aqueous batteries have attracted considerable interest for large‐scale energy storage and wearable devices. Unfortunately, the formation of Zn dendrite, parasitic hydrogen evolution reaction (HER), and irreversible by‐products, seriously restrict their practical applications. Herein, a series of compact and uniform metal‐organic frameworks (MOFs) films with precisely controlled thickness (150–600 nm) are constructed by a pre‐oxide gas deposition (POGD) method on Zn foil. Under the protection of MOF layer with optimum thickness, the corrosion of zinc, the side reaction of hydrogen evolution, and the growth of dendrites on the zinc surface are suppressed. The symmetric cell based on Zn@ZIF‐8 anode exhibits exceptional cyclicality for over 1100 h with low voltage hysteresis of≈38 mV at 1 mA cm−2. Even at current densities of 50 mA cm−2 with an area capacity of 50 mAh cm−2 (85% Zn utilization), the electrode can keep cycling for >100 h. Besides, this Zn@ZIF‐8 anode also delivers a high average CE of 99.4% at 1 mA cm−2. Moreover, a rechargeable Zn ion battery is fabricated based on the Zn@ZIF‐8 anode and MnO2 cathode, which presents an exceptionally long lifespan with no capacity attenuation for 1000 cycles.
Facile Synthesis of Self‐Targeted Zn2+‐Gallic acid Nanoflowers for Specific Adhesion and Elimination of Gram‐Positive Bacteria
Authors: Huang Yue , Chen Yongcheng , Lu Zhouyu , Yu Bo , Zou Lingyun , Song Xiaohui , Han Haijie , Jin Qiao , Ji Jian
Published: June 2023

Transition metal ions are served as disinfectant thousand years ago. However, the in vivo antibacterial application of metal ions is strongly restricted due to its high affinity with proteins and lack of appropriate bacterial targeting method. Herein, for the first time, Zn2+‐gallic acid nanoflowers (ZGNFs) are synthesized by a facile one‐pot method without additional stabilizing agents. ZGNFs are stable in aqueous solution while can be easily decomposed in acidic environments. Besides, ZGNFs can specifically adhere onto Gram‐positive bacteria, which is mediated by the interaction of quinone from ZGNFs and amino groups from teichoic acid of Gram‐positive bacteria. ZGNFs exhibit high bactericidal effect toward various Gram‐positive bacteria in multiple environments, which can be ascribed to the in situ Zn2+ release on bacterial surface. Transcriptome studies reveal that ZGNFs can disorder basic metabolic processes of Methicillin‐resistant Staphylococcus aureus (MRSA). Moreover, in a MRSA‐induced keratitis model, ZGNFs exhibit long‐term retention in the infected corneal site and prominent MRSA elimination efficacy due to the self‐targeting ability. This research not only reports an innovative method to prepare metal‐polyphenol nanoparticles, but also provides a novel nanoplatform for targeted delivery of Zn2+ in combating Gram‐positive bacterial infections.
A High‐Nickel Layered Double Hydroxides Cathode Boosting the Rate Capability for Chloride Ion Batteries with Ultralong Cycling Life
Authors: Song Zhihao , Yin Qing , Yang Shuhan , Miao Yidong , Wu Yunjia , Li Yong‐Zhi , Ren Yaojian , Sui Yanwei , Qi Jiqiu , Han Jingbin
Published: June 2023

Chloride‐ion batteries (CIBs) have drawn growing attention in large‐scale energy storage applications owing to their comprehensive merits of high theoretical energy density, dendrite‐free characteristic, and abundance of chloride‐containing materials. Nonetheless, cathodes for CIBs are plagued by distinct volume effect and sluggish Cl− diffusion kinetics, leading to inferior rate capability and short cycling life. Herein, an unconventional Ni5Ti‐Cl LDH is reported with a high nickel ratio as a cathode material for CIB. The reversible capacity of Ni5Ti‐Cl LDH retains 127.9 mAh g−1 over 1000 cycles at a large current density of 1000 mA g−1, which exceeds that of ever reported CIBs, with extraordinary low volume change of 1.006% during a whole charge/discharge process. Such superior Cl‐storage performance is attributed to synergetic contributions consisting of high redox activity from Ni2+/Ni3+ and pinning Ti that restrains local structural distortion of LDH host layers and enhances adsorption intensity of chloride atoms during the reversible Cl− intercalation/de‐intercalation in LDH gallery, which are revealed by a comprehensive study including X‐ray photoelectron spectroscopy, kinetic investigations, and DFT calculations. This work provides an effective strategy to design low‐cost LDHs materials for high‐performance CIBs, which are also applicable to other types of halide‐ion batteries (e.g., fluoride‐ion and bromide‐ion batteries).
Simultaneous High Ionic Conductivity and Lithium‐Ion Transference Number in Single‐Ion Conductor Network Polymer Enabling Fast‐Charging Solid‐State Lithium Battery
Authors: Wang Yongyin , Sun Qiyue , Zou Junlong , Zheng Yansen , Li Jiashen , Zheng Mingtao , Liu Yingliang , Liang Yeru
Published: June 2023

Developing solid‐state electrolyte with sufficient ionic conduction and flexible‐intimate interface is vital to advance fast‐charging solid‐state lithium batteries. Solid polymer electrolyte yields the promise of interfacial compatibility, yet its critical bottleneck is how to simultaneously achieve high ionic conductivity and lithium‐ion transference number. Herein, single‐ion conducting network polymer electrolyte (SICNP) enabling fast charging is proposed to positively realize fast lithium‐ion locomotion with both high ionic conductivity of 1.1 × 10−3 S cm−1 and lithium‐ion transference number of 0.92 at room temperature. Experimental characterization and theoretical simulations demonstrate that the construction of polymer network structure for single‐ion conductor not only facilitates fast hopping of lithium ions for boosting ionic kinetics, but also enables a high dissociation level of the negative charge for lithium‐ion transference number close to unity. As a result, the solid‐state lithium batteries constructed by coupling SICNP with lithium anodes and various cathodes (e.g., LiFePO4, sulfur, and LiCoO2) display impressive high‐rate cycling performance (e.g., 95% capacity retention at 5 C for 1000 cycles in LiFePO4|SICNP|lithium cell) and fast‐charging capability (e.g., being charged within 6 min and discharged over than 180 min in LiCoO2|SICNP|lithium cell). Our study provides a prospective direction for solid‐state electrolyte that meets the lithium‐ion dynamics for practical fast‐charging solid‐state lithium batteries.
Mimicking evasive behavior in wavelength‐dependent reconfigurable phototransistors with ultralow power consumption
Authors: Shao He , Li Yueqing , Chen Jiefeng , Yang Wei , Wang Le , Fu Jingwei , Wang Yiru , Ling Haifeng , Xie Linghai , Huang Wei
Published: June 2023

Retinal‐inspired synaptic phototransistors, which integrate light signal detection, preprocessing, and memory functions, show promising applications in artificial vision sensors. In recent years, it has been reported to construct heterojunction in phototransistors to realize positive photoconductance (PPC) and negative photoconductance (NPC) modulations, thereby achieving visible and infrared wavelength discrimination and various visual functions. However, relatively little attention has been paid to wavelength‐dependent switching and reconfigurability between two states (PPC and NPC), limiting further applications for complex simulations of biological visual functions. Here, a mixed organic–inorganic heterojunction synaptic phototransistor was constructed by integrating CsPbBr3 nanoplates (NPLs) with strong blue‐light absorption and poly(3‐hexylthiophene‐2,5‐diyl) (P3HT) with strong red‐light absorption. Compared with the three‐dimensional (3D) structure CsPbBr3 nanocubes (NCs), the two‐dimensional (2D) CsPbBr3 NPLs exhibited more efficient charge transfer with P3HT. Based on the individual optical absorption properties in organic–inorganic heterojunction, the device exhibited wavelength‐selective and reconfigurable behavior between PPC and NPC. A low power consumption of 0.053 fJ per synaptic event was achieved, which is comparable to a biological synapse. Finally, Drosophila's evasive behavior to food under red and blue light can be successfully demonstrated. This work demonstrates the future potential of synaptic phototransistors for visuomorphic computing.
CoFe2O4@rGO as a Separator Coating for Advanced Lithium–Sulfur Batteries
Authors: Li Yan , Liu Jiabing , Wang Xingbo , Zhang Xiaomin , Chen Ning , Qian Lanting , Zhang Yongguang , Wang Xin , Chen Zhongwei
Published: June 2023

Lithium–sulfur (Li–S) batteries are hindered by the undesired shuttle effect and sluggish electrochemical conversion kinetics. Herein, a well‐designed CoFe2O4@reduced graphene oxide (CFO@rGO) composite is used to modify the separator to develop a multifunctional polysulfide barrier. Density functional theory (DFT) calculations confirm that highly electronegative oxygen ions in CFO tend to bond with transition metal (TM) ions at octahedral (Oh) sites, which induces the formation of FeS and CoS bonds between CFO and polysulfides. This indicates that CFO can effectively anchor polysulfides. Furthermore, the low Li2S decomposition energy barrier and Li+ diffusion energy barrier reveal that CFO can accelerate the redox reaction kinetics of sulfur species. Electronic structure calculations speculate that the low‐energy barrier can be attributed to the electron‐hopping phenomenon between TM ions of different valence states at Oh sites. Benefiting from these advantages, a CFO@rGO/PP separator demonstrates satisfactory cycling performance (0.087% capacity decay rate at 2C with 500 cycles) and superb rate performance (686 mAh g−1 at 5C). This work provides a valuable reference for future research on spinel‐type materials as electrocatalysts for Li–S batteries.
Seed‐Assisted Cu‐Doped Chemical Bath Deposition for Preparing High‐Quality NiOx Hole‐Transport Layers in Perovskite Solar Cells
Authors: Liao Yunxiao , Fei Fei , Li Bairu , Li Yue , Xu Yibo , Wang Shubo , Fang Xiang , Li Lvzhou , Yuan Ningyi , Ding Jianning
Published: June 2023

P‐type NiOx films are widely used as hole‐transport layers (HTLs) in p–i–n perovskite solar cells (PSCs) owing to their wide bandgap, stability, and optical transmittance. Chemical bath deposition (CBD) is an effective method for growing metal oxide HTLs. However, NiOx films prepared by the CBD method have pinholes because of their small grain size, which makes it difficult to cover the substrate in all directions, leading to severe carrier recombination at the interface between NiOx and perovskite. Herein, the device efficiency is improved from 18.13% to 22.51% using NiOx prepared by CBD with seed‐assisted growth and Cu‐ion doping as the HTL. The addition of crystal seeds significantly enhances the grain size, resulting in better substrate coverage by the prepared NiOx films. Cu‐ion doping improves the conductivity of the film and enhances its ability to extract holes. In addition, the results confirm that this method is suitable for the manufacturing of large‐area modules and has good reproducibility. This research demonstrates an effective CBD method for creating NiOx films for use in PSCs and offers a new approach for preparing inorganic HTLs using CBD.
Exploring nonintrusive measurements of spatio‐temporal portrait of microservices
Authors: Zeng Tao , Xu Zichen , Wu Dan , Li Xiaoling , Liu Biyong , Hu Haichuan , Tan Shuang , Tan Yusong , Xu Chenren , Stewart Christopher , Zhou Qihe , Cao Ye
Published: June 2023

As cloud native technology advances, the scale and complexity of applications built on microservice architecture continue to expand, leading to increasingly intricate differences between software within the same application. Microservice applications, offering high flexibility, are deployed in data centers as black boxes from the users' perspective, leaving them with no insight into the orchestration of cloud service providers. Consequently, users face challenges in promptly recognizing performance imbalances within their deployed applications. Meanwhile, cloud service providers may cut costs by offering a mix of qualified and unqualified services, potentially deceiving users. To enhance the understanding of microservice application organization, we propose a non‐intrusive measurement framework, termed NMPI. NMPI facilitates rapid identification of microservice application defects, offering insights into cloud services and detecting fraudulent behavior in microservice‐based applications. We model microservice applications using a queue analysis‐based approach and filter the dominant frequency components of average response time signals by employing k‐means on the fast fourier transform (FFT). Our model constructs a library of performance portraits for various software, with these portraits resembling human fingerprints that carry and mark the software's internal information. Utilizing a two‐tier microservices‐based application incorporating a database as a case study allows us to demonstrate the effectiveness of NMPI. Our experimental results show that NMPI can produce differentiable profiles of data service performance portraits across a diverse and extensive range of workloads, enabling the identification of software types and the analysis of performance conditions.
Determination of Valbenazine related substances by liquid chromatography method complying with the current regulatory guidelines. Method robustness evaluation by Design of Experiments software
Authors: Deshmukh Balasaheb R. , Akshinthala Parameswari , Katari Naresh Kumar , Deshpande Girish K. , Kowtharapu Leela Prasad , Battula Sreenivas Rao , Gundla Rambabu
Published: June 2023

A simple, specific, rapid, sensitive reversed‐phase high‐performance liquid chromatography method was developed and validated for the determination of Valbenazine, impurities, and its degradation products. The proposed high‐performance liquid chromatography method showed optimum separation in 60 min using potassium dihydrogen phosphate buffer and ACN in the ratio of 90:10 (V/V) as mobile phase‐A whereas ACN and methanol in the ratio of 60:40 (V/V) as mobile phase‐B. YMC‐Pack ODS‐AQ (150 × 4.6 mm, 3.0 μm), column used along with security guard cartridge C18, (4.0 × 3.0 mm) at 1.1 ml/min flow. The injection volume was 10 μl and detection was carried out at 285 nm. The drug was degraded under different stress conditions and the method was validated as per International Conference on Harmonization guidelines on the basis of accuracy, precision, linearity, and robustness. A degradation study indicates that Valbenazine is prone to oxidative degradation. The method was linear over the concentration range of limit of quantitation to 200% for impurities and drug substances. The method was found robust and was studied by the design of experiments. The proposed method is applicable for the determination of the stability of Valibenazine and was successfully used in the quality control of bulk drug manufacturing and pharmaceuticals.
Upgrading the Metsähovi Geodetic Research Station
Authors: Poutanen Markku , Bilker-Koivula Mirjam , Eskelinen Joona , Kallio Ulla , Kareinen Niko , Koivula Hannu , Lahtinen Sonja , Näränen Jyri , Peltoniemi Jouni , Raja-Halli Arttu , Rouhiainen Paavo , Zubko Nataliya
Published: June 2023

Metsähovi Geodetic Research Station (MGRS) of the National Land Survey of Finland, has undergone a major upgrade. The first observations at MGRS were started in 1978. A decade-long reform began in 2012, during which all major systems were renewed. This included Global Navigation Satellite System (GNSS) station, Satellite Laser Ranging (SLR) system, and a dedicated geodetic Very Long Baseline Interferometer (VLBI) system. Furthermore, the absolute gravimeter (AG) was upgraded, the superconducting gravimeter (SG) was renewed, and the station infrastructure was completely refurbished. When completed, MGRS will be one of the northernmost stations in the core network of the Global Geodetic Observing System (GGOS) of the International Association of Geodesy (IAG). MGRS has a full suite of co-located major geodetic instrumentation, and local geodetic networks and facilities to connect various observing techniques (local ties). Together, the core stations form the solid backbone for maintaining the International Terrestrial Reference Frame (ITRF) and monitoring the orientation of the Earth in space and producing information for computing precise satellite orbits, including GNSS. The stability of the stations and their long and consistent series of measurements is paramount both for global and regional networks. We present recent developments at MGRS and introduce the instrumentation that already contributes and will contribute in the future to various IAG services.
Black Holes and Analogy
Authors: Mathie Alex
Published: June 2023

It is generally accepted that science sometimes involves reasoning with analogies. Often, this simply means that analogies between disparate objects of study might be used as heuristics to guide theory development. Contemporary black hole physics, however, deploys analogical reasoning in a way that seems to overreach this traditional heuristic role. In this chapter, I describe two distinct pieces of analogical reasoning that are quite central to the contemporary study of black holes. The first underpins arguments for the existence of astrophysical Hawking radiation, and the second underpins arguments for black holes being ‘genuinely’ thermodynamical in nature. I argue that while these are distinct analogical arguments, they depend on one another in an interesting way: the success of the second analogical argument presupposes the success of the first. This induces a tension for those who wish to take black hole thermodynamics seriously, but who are sceptical of the evidence provided for astrophysical Hawking radiation by the results of analogue gravity. I consider three ways to resolve this tension, and show that each fails.
Research Assessments Should Recognize Responsible Research Practices. Narrative Review of a Lively Debate and Promising Developments
Authors: Aubert Bonn Noémie , Bouter Lex
Published: June 2023

Research assessments have been under growing scrutiny in the past few years. The way in which researchers are assessed has a tangible impact on decisions and practices in research. Yet, there is an emerging understanding that research assessments as they currently stand might hamper the quality and the integrity of research. In this chapter, we provide a narrative review of the shortcomings of current research assessments and showcase innovative actions that aim to address these. To discuss these shortcomings and actions, we target five different dimensions of research assessment. First, we discuss the content of research assessment, thereby introducing the common indicators used to assess researchers and the way these indicators are being used. Second, we address the procedure of research assessments, describing the resources needed for assessing researchers in an ever-growing research system. Third, we describe the crucial role of assessors in improving research assessments. Fourth, we present the broader environments in which researchers work, explaining that omnipresent competition and employment insecurity also need to be toned down substantially to foster high quality and high integrity research. Finally, we describe the challenge of coordinating individual actions to ensure that the problems of research assessments are addressed tangibly and sustainably.
Black hole entropy from quantum mechanics
Authors: Dorey Nick , Mouland Rishi , Zhao Boan
Published: June 2023

Abstract

We provide evidence for a holographic duality between superconformal quantum mechanics on the moduli space of Yang-Mills instantons and M-theory in certain asymptotically AdS7 × S4 backgrounds with a plane-wave boundary metric. We show that the gravitational background admits a supersymmetric black hole solution whose entropy is precisely reproduced by the superconformal index of the dual quantum mechanics.
Classical limit of higher-spin string amplitudes
Authors: Cangemi Lucile , Pichini Paolo
Published: June 2023

Abstract

It has been shown that a special set of three-point amplitudes between two massive spinning states and a graviton reproduces the linearised stress-energy tensor for a Kerr black hole in the classical limit. In this work we revisit this result and compare it to the analysis of the amplitudes describing the interaction of leading Regge states of the open and closed superstring. We find an all-spin result for the classical limit of two massive spinning states interacting with a photon or graviton. This result differs from Kerr and instead matches the current four-vector and the stress-energy tensor generated by a classical string coupled to electromagnetism and gravity respectively. For the superstring amplitudes, contrary to the black-hole case, we find that the spin to infinity limit is necessary to reproduce the classical spin multipoles.
Human pancreatic ductal organoids with controlled polarity provide a novel ex vivo tool to study epithelial cell physiology
Authors: Varga Árpád , Madácsy Tamara , Görög Marietta , Kiss Aletta , Susánszki Petra , Szabó Viktória , Jójárt Boldizsár , Dudás Krisztina , Farkas Gyula , Szederkényi Edit , Lázár György , Farkas Attila , Ayaydin Ferhan , Pallagi Petra , Maléth József
Published: June 2023

Epithelial ion and fluid secretion determine the physiological functions of a broad range of organs, such as the lung, liver, or pancreas. The molecular mechanism of pancreatic ion secretion is challenging to investigate due to the limited access to functional human ductal epithelia. Patient-derived organoids may overcome these limitations, however direct accessibility of the apical membrane is not solved. In addition, due to the vectorial transport of ions and fluid the intraluminal pressure in the organoids is elevated, which may hinder the study of physiological processes. To overcome these, we developed an advanced culturing method for human pancreatic organoids based on the removal of the extracellular matrix that induced an apical-to-basal polarity switch also leading to reversed localization of proteins with polarized expression. The cells in the apical-out organoids had a cuboidal shape, whereas their resting intracellular Ca2+ concentration was more consistent compared to the cells in the apical-in organoids. Using this advanced model, we demonstrated the expression and function of two novel ion channels, the Ca2+ activated Cl− channel Anoctamin 1 (ANO1) and the epithelial Na+ channel (ENaC), which were not considered in ductal cells yet. Finally, we showed that the available functional assays, such as forskolin-induced swelling, or intracellular Cl− measurement have improved dynamic range when performed with apical-out organoids. Taken together our data suggest that polarity-switched human pancreatic ductal organoids are suitable models to expand our toolset in basic and translational research.

Graphical abstract
Comparison of six different CAD/CAM retainers vs. the stainless steel twistflex retainer: an in vitro investigation of survival rate and stability
Authors: Roser Christoph J. , Bauer Carolien , Hodecker Lutz , Zenthöfer Andreas , Lux Christopher J. , Rues Stefan
Published: June 2023

Purpose

To compare failure rates and maximum load capacity (Fmax) of six different computer-aided design/computer-aided manufacturing (CAD/CAM) retainers with those of the hand-bent five-stranded stainless steel twistflex retainer.

Materials and methods

Six groups (n = 8 per group) of commercially available CAD/CAM retainers (cobalt–chromium [CoCr], titanium grade 5 [Ti5], nickel–titanium [NiTi], zirconia [ZrO2], polyetheretherketone [PEEK], and gold) and twistflex retainers were tested for long-term sufficiency and for Fmax using a self-developed in vitro model. All retainer models underwent a simulated ageing process of about 15 years (1,200,000 chewing cycles with a force magnitude of 65 N at 45° followed by storage in water at 37 °C for 30 days). If retainers did not debond or break during ageing, their Fmax was determined in a universal testing machine. Data were statistically analysed using Kruskal–Wallis and Mann–Whitney U‑tests.

Results

Twistflex retainers did not fail (0/8) during ageing and had the highest Fmax (445 N ± 51 N). Ti5 retainers were the only CAD/CAM retainers that also did not fail (0/8) and had similar Fmax values (374 N ± 62 N). All other CAD/CAM retainers had higher failure rates during ageing and significantly lower Fmax values (p < 0.01; ZrO2: 1/8, 168 N ± 52 N; gold: 3/8, 130 N ± 52 N; NiTi: 5/8, 162 N ± 132 N; CoCr: 6/8, 122 N ± 100 N; PEEK: 8/8, 65 ± 0 N). Failure was due to breakage in the NiTi retainers and debonding in all other retainers.

Conclusion

Twistflex retainers remain the gold standard regarding biomechanical properties and long-term sufficiency. Of the CAD/CAM retainers tested, Ti5 retainers seem to be the most suitable alternative. In contrast, all other CAD/CAM retainers investigated in this study showed high failure rates and had significantly lower Fmax values.
Sepsis and underlying comorbidities in intensive care unit patients
Authors: Thomas-Rüddel Daniel O. , Fröhlich Holger , Schwarzkopf Daniel , Bloos Frank , Riessen Reimer
Published: June 2023

Background

There is an ongoing debate as to whether death with sepsis is primarily caused by sepsis or, more often, by the underlying disease. There are no data on the influence of a researcher’s background on such an assessment. Therefore, the aim of this analysis was to assess the cause of death in sepsis and the influence of an investigator’s professional background on such an assessment.

Materials and methods

We performed a retrospective observational cohort study of sepsis patients treated in the medical intensive care unit (ICU) of a tertiary care center. For deceased patients, comorbidities and severity of illness were documented. The cause of death (sepsis or comorbidities or both combined) was independently assessed by four assessors with different professional backgrounds (medical student, senior physician in the medical ICU, anesthesiological intensivist, and senior physician specialized in the predominant comorbidity).

Results

In all, 78 of 235 patients died in hospital. Agreement between assessors about cause of death was low (κ 0.37, 95% confidence interval 0.29–0.44). Depending on the assessor, sepsis was the sole cause of death in 6–12% of cases, sepsis and comorbidities in 54–76%, and comorbidities alone in 18–40%.

Conclusions

In a relevant proportion of patients with sepsis treated in the medical ICU, comorbidities contribute significantly to mortality, and death from sepsis without relevant comorbidities is a rare event. Designation of the cause of death in sepsis patients is highly subjective and may be influenced by the professional background of the assessor.
Retrospective observational study on the use of acetyl-l-carnitine in ALS
Authors: Sassi Serena , Bianchi Elisa , Diamanti Luca , Tornabene Danilo , Sette Elisabetta , Medici Doriana , Matà Sabrina , Leccese Deborah , Sperti Martina , Martinelli Ilaria , Ghezzi Andrea , Mandrioli Jessica , Iuzzolino Valentina Virginia , Dubbioso Raffaele , Trojsi Francesca , Passaniti Carla , D’Alvano Giulia , Filosto Massimiliano , Padovani Alessandro , Mazzini Letizia , De Marchi Fabiola , Zinno Lucia , Nuredini Andi , Bongioanni Paolo , Dolciotti Cristina , Canali Elena , Toschi Giulia , Petrucci Antonio , Perna Alessia , Riso Vittorio , Inghilleri Maurizio , Libonati Laura , Cambieri Chiara , Pupillo Elisabetta
Published: June 2023

ALCAR (Acetyl-L-carnitine) is a donor of acetyl groups and increases the intracellular levels of carnitine, the primary transporter of fatty acids across the mitochondrial membranes. In vivo studies showed that ALCAR decrease oxidative stress markers and pro-inflammatory cytokines. In a previous double-blind placebo-controlled phase II trial showed positive effects on self-sufficiency (defined as a score of 3+ on the ALSFRS-R items for swallowing, cutting food and handling utensils, and walking) ALSFRS-R total score and FVC. We conducted an observational, retrospective, multicentre, case–control study to provide additional data on the effects of ALCAR in subjects with ALS in Italy. Subjects treated with ALCAR 1.5 g/day or 3 g/day were included and matched with not treated subjects by sex, age at diagnosis, site of onset, and time from diagnosis to baseline, (45 subjects per group). ALCAR 3 g/day vs not treated: 22 not treated subjects (48.9%) were still alive at 24 months after baseline, compared to 23 (51.1%) treated subjects (adj. OR 1.18, 95% CI 0.46–3.02). No statistically significant differences were detected in ALSFRS nor FVC nor self-sufficiency. ALCAR 1.5 g/day vs not treated: 22 not treated subjects (48.9%) were still alive at 24 months after baseline, compared to 32 (71.1%) treated subjects (adj. OR 0.27, 95% CI 0.10–0.71). For ALSFRS-R, a mean slope of − 1.0 was observed in treated subjects compared to − 1.4 in those not treated (p = 0.0575). No statistically significant difference was detected in the FVC nor self-sufficiency. Additional evidence should be provided to confirm the efficacy of the drug and provide a rationale for the dosage.
Neurochemistry of the mammillary body
Authors: Żakowski Witold , Zawistowski Piotr
Published: June 2023

The mammillary body (MB) is a component of the extended hippocampal system and many studies have shown that its functions are vital for mnemonic processes. Together with other subcortical structures, such as the anterior thalamic nuclei and tegmental nuclei of Gudden, the MB plays a crucial role in the processing of spatial and working memory, as well as navigation in rats. The aim of this paper is to review the distribution of various substances in the MB of the rat, with a description of their possible physiological roles. The following groups of substances are reviewed: (1) classical neurotransmitters (glutamate and other excitatory transmitters, gamma-aminobutyric acid, acetylcholine, serotonin, and dopamine), (2) neuropeptides (enkephalins, substance P, cocaine- and amphetamine-regulated transcript, neurotensin, neuropeptide Y, somatostatin, orexins, and galanin), and (3) other substances (calcium-binding proteins and calcium sensor proteins). This detailed description of the chemical parcellation may facilitate a better understanding of the MB functions and its complex relations with other structures of the extended hippocampal system.
Deep embeddings and Graph Neural Networks: using context to improve domain-independent predictions
Authors: Sola Fernando , Ayala Daniel , Hernández Inma , Ruiz David
Published: June 2023

Graph neural networks (GNNs) are deep learning architectures that apply graph convolutions through message-passing processes between nodes, represented as embeddings. GNNs have recently become popular because of their ability to obtain a contextual representation of each node taking into account information from its surroundings. However, existing work has focused on the development of GNN architectures, using basic domain-specific information about the nodes to compute embeddings. Meanwhile, in the closely-related area of knowledge graphs, much effort has been put towards developing deep learning techniques to obtain node embeddings that preserve information about relationships and structure without relying on domain-specific data. The potential application of deep embeddings of knowledge graphs in GNNs remains largely unexplored. In this paper, we carry out a number of experiments to answer open research questions about the impact on GNNs performance when combined with deep embeddings. We test 7 different deep embeddings across several attribute prediction tasks in two state-of-art attribute-rich datasets. We conclude that, while there is a significant performance improvement, its magnitude varies heavily depending on the specific task and deep embedding technique considered.
Performance based probabilistic seismic risk assessment for urban heritage. An example in Pla del Remei Area (Valencia)
Authors: Guardiola-Víllora Arianna , Molina Sergio , D’Ayala Dina
Published: June 2023

The assessment of the seismic behaviour of historic residential buildings and the estimation of their possible losses in the event of an earthquake, is a must for defining strategic mitigation plans to prevent irreplaceable heritage losses. In this study an integrated performance based probabilistic risk assessment methodology is developed. An archival study and a field survey allow to identify architectural and construction characteristics of heritage residential buildings in urban areas and determine realistic structural models. These are analysed by using a limit state approach, coded in the FaMIVE method, considering different construction hypotheses, to produce capacity curves which support the identification of a discrete number of typologies representative of the entire building stock in the area. Their fragility functions are then derived using the modified N2 method. Because of the difficulty in quantifying the expected probable losses in purely economic terms, given the heritage value of these assets, losses are computed in terms of damaged floor surface area and mean damage ratio. These have been obtained through the earthquake loss estimation platform SELENA, considering different possible seismic scenarios. The procedure is applied to masonry residential buildings in Pla del Remei area of Valencia, Spain, built between the end of the 19th Century and the end of the Spanish War (1939). This neighbourhood embodies the cultural values, construction techniques and historic legacy of a new and brief era of modernity, inspired by the new urban theories and architectural styles of Eclecticism and Modernism. Despite Valencia being located in an area of low to moderate seismicity, the results show that the maximum percentage of built damaged area ranges from 5.8 to 11.6% for 475 years return period, increasing to 33.59–51.59% for 975 years return period. The high level of resolution of the study allows mapping and identifying the structures at higher risk and is therefore a valuable tool to support sensitive and targeted retrofitting policies.