bluuebunny/crossref_metadata_2025 huggingface dataset:
Effective description of sub-maximal chaos: stringy effects for SYK scrambling
Authors: Choi Changha , Haehl Felix M. , Mezei Márk , Sárosi Gábor
Published: March 2023

Abstract

It has been proposed that the exponential decay and subsequent power law saturation of out-of-time-order correlation functions can be universally described by collective ‘scramblon’ modes. We develop this idea from a path integral perspective in several examples, thereby establishing a general formalism. After reformulating previous work on the Schwarzian theory and identity conformal blocks in two-dimensional CFTs relevant for systems in the infinite coupling limit with maximal quantum Lyapunov exponent, we focus on theories with sub-maximal chaos: we study the large-q limit of the SYK quantum dot and chain, both of which are amenable to analytical treatment at finite coupling. In both cases we identify the relevant scramblon modes, derive their effective action, and find bilocal vertex functions, thus constructing an effective description of chaos. The final results can be matched in detail to stringy corrections to the gravitational eikonal S-matrix in holographic CFTs, including a stringy Regge trajectory, bulk to boundary propagators, and multi-string effects that are unexplored holographically.
Pharmacological and mechanistic study of PS1, a Pdia4 inhibitor, in β-cell pathogenesis and diabetes in db/db mice
Authors: Tseng Hui-Ju , Chen Wen-Chu , Kuo Tien-Fen , Yang Greta , Feng Ching-Shan , Chen Hui-Ming , Chen Tzung-Yan , Lee Tsung-Han , Yang Wen-Chin , Tsai Keng-Chang , Huang Wei-Jan
Published: March 2023

Pdia4 has been characterized as a key protein that positively regulates β-cell failure and diabetes via ROS regulation. Here, we investigated the function and mechanism of PS1, a Pdia4 inhibitor, in β-cells and diabetes. We found that PS1 had an IC50 of 4 μM for Pdia4. Furthermore, PS1 alone and in combination with metformin significantly reversed diabetes in db/db mice, 6 to 7 mice per group, as evidenced by blood glucose, glycosylated hemoglobin A1c (HbA1c), glucose tolerance test, diabetic incidence, survival and longevity (P < 0.05 or less). Accordingly, PS1 reduced cell death and dysfunction in the pancreatic β-islets of db/db mice as exemplified by serum insulin, serum c-peptide, reactive oxygen species (ROS), islet atrophy, and homeostatic model assessment (HOMA) indices (P < 0.05 or less). Moreover, PS1 decreased cell death in the β-islets of db/db mice. Mechanistic studies showed that PS1 significantly increased cell survival and insulin secretion in Min6 cells in response to high glucose (P < 0.05 or less). This increase could be attributed to a reduction in ROS production and the activity of electron transport chain complex 1 (ETC C1) and Nox in Min6 cells by PS1. Further, we found that PS1 inhibited the enzymatic activity of Pdia4 and mitigated the interaction between Pdia4 and Ndufs3 or p22 in Min6 cells (P < 0.01 or less). Taken together, this work demonstrates that PS1 negatively regulated β-cell pathogenesis and diabetes via reduction of ROS production involving the Pdia4/Ndufs3 and Pdia4/p22 cascades.
Development of a diagnostic tool for product circularity: a redesign approach
Authors: Mesa Jaime A. , González-Quiroga Arturo
Published: March 2023

The design of circular products is gaining relevance among academics, practitioners, and industry as a critical step to face material scarcity, the unsustainability of industrial processes, and excessive waste generation. Therefore, product design is a powerful research field to promote material, component, and product circularity throughout several lifecycles. However, there is a lack of formal methods to measure the circularity of products, especially from the early design stages. Therefore, this paper proposes a diagnostic tool for measuring circularity, identifying potential improvement opportunities, and redesigning interventions in the conceptual design phase. The tool consists of eight single indicators that measure disassemblability, reassemblability, durability, modularity, simplicity, standardization, commonality, relative costs, and the number of secondary functions of products. A case study is presented to validate the tool, considering several improvement scenarios around the 6R strategies. Finally, a list of redesign interventions for each improvement scenario was assembled as a primary output of the proposed tool.
Optimisation of scan duration and image quality in oncological 89Zr immunoPET imaging using the Biograph Vision PET/CT
Authors: van Sluis Joyce , Boellaard Ronald , Dierckx Rudi A. J. O. , van Esch Evelien L. M. , Croes Demi A. , de Ruijter Laura Kist , van de Donk Pim P. , de Vries Elisabeth G. E. , Noordzij Walter , Brouwers Adrienne H.
Published: March 2023

Purpose

Monoclonal antibody (mAb)-based PET (immunoPET) imaging can characterise tumour lesions non-invasively. It may be a valuable tool to determine which patients may benefit from treatment with a specific monoclonal antibody (mAb) and evaluate treatment response. For 89Zr immunoPET imaging, higher sensitivity of state-of-the art PET/CT systems equipped with silicon photomultiplier (SiPM)-based detector elements may be beneficial as the low positron abundance of 89Zr causes a low signal-to-noise level. Moreover, the long physical half-life limits the amount of activity that can be administered to the patients leading to poor image quality even when using long scan durations. Here, we investigated the difference in semiquantitative performance between the PMT-based Biograph mCT, our clinical reference system, and the SiPM-based Biograph Vision PET/CT in 89Zr immunoPET imaging. Furthermore, the effects of scan duration reduction using the Vision on semiquantitative imaging parameters and its influence on image quality assessment were evaluated.

Methods

Data were acquired on day 4 post 37 MBq 89Zr-labelled mAb injection. Five patients underwent a double scan protocol on both systems. Ten patients were scanned only on the Vision. For PET image reconstruction, three protocols were used, i.e. one camera-dependent protocol and European Association of Nuclear Medicine Research Limited (EARL) standards 1 and 2 compliant protocols. Vision data were acquired in listmode and were reprocessed to obtain images at shorter scan durations. Semiquantitative PET image parameters were derived from tumour lesions and healthy tissues to assess differences between systems and scan durations. Differently reconstructed images obtained using the Vision were visually scored regarding image quality by two nuclear medicine physicians.

Results

When images were reconstructed using 100% acquisition time on both systems following EARL standard 1 compliant reconstruction protocols, results regarding semiquantification were comparable. For Vision data, reconstructed images that conform to EARL1 standards still resulted in comparable semiquantification at shorter scan durations (75% and 50%) regarding 100% acquisition time.

Conclusion

Scan duration of 89Zr immunoPET imaging using the Vision can be decreased up to 50% compared with using the mCT while maintaining image quality using the EARL1 compliant reconstruction protocol.
A phase I prospective, non-randomized trial of autologous dendritic cell-based cryoimmunotherapy in patients with metastatic castration-resistant prostate cancer
Authors: Thomsen Liv Cecilie Vestrheim , Honoré Alfred , Reisæter Lars Anders Rokne , Almås Bjarte , Børretzen Astrid , Helle Svein Inge , Førde Kristina , Kristoffersen Einar Klæboe , Kaada Silje Helland , Melve Guro Kristin , Haslerud Torjan Magne , Biermann Martin , Bigalke Iris , Kvalheim Gunnar , Azeem Waqas , Olsen Jan Roger , Gabriel Benjamin , Knappskog Stian , Halvorsen Ole Johan , Akslen Lars Andreas , Bahn Duke , Pantel Klaus , Riethdorf Sabine , Ragde Haakon , Gjertsen Bjørn Tore , Øyan Anne Margrete , Kalland Karl-Henning , Beisland Christian
Published: March 2023

Metastatic castration-resistant prostate cancer (mCRPC) is an immunologically cold disease with dismal outcomes. Cryoablation destroys cancer tissue, releases tumor-associated antigens and creates a pro-inflammatory microenvironment, while dendritic cells (DCs) activate immune responses through processing of antigens. Immunotherapy combinations could enhance the anti-tumor efficacy. This open-label, single-arm, single-center phase I trial determined the safety and tolerability of combining cryoablation and autologous immature DC, without and with checkpoint inhibitors. Immune responses and clinical outcomes were evaluated. Patients with mCRPC, confirmed metastases and intact prostate gland were included. The first participants underwent prostate cryoablation with intratumoral injection of autologous DCs in a 3 + 3 design. In the second part, patients received cryoablation, the highest acceptable DC dose, and checkpoint inhibition with either ipilimumab or pembrolizumab. Sequentially collected information on adverse events, quality of life, blood values and images were analyzed by standard descriptive statistics. Neither dose-limiting toxicities nor adverse events > grade 3 were observed in the 18 participants. Results indicate antitumor activity through altered T cell receptor repertoires, and 33% durable (> 46 weeks) clinical benefit with median 40.7 months overall survival. Post-treatment pain and fatigue were associated with circulating tumor cell (CTC) presence at inclusion, while CTC responses correlated with clinical outcomes. This trial demonstrates that cryoimmunotherapy in mCRPC is safe and well tolerated, also for the highest DC dose (2.0 × 108) combined with checkpoint inhibitors. Further studies focusing on the biologic indications of antitumor activity and immune system activation could be considered through a phase II trial focusing on treatment responses and immunologic biomarkers.
An SIR model with viral load-dependent transmission
Authors: Della Marca Rossella , Loy Nadia , Tosin Andrea
Published: March 2023

The viral load is known to be a chief predictor of the risk of transmission of infectious diseases. In this work, we investigate the role of the individuals’ viral load in the disease transmission by proposing a new susceptible-infectious-recovered epidemic model for the densities and mean viral loads of each compartment. To this aim, we formally derive the compartmental model from an appropriate microscopic one. Firstly, we consider a multi-agent system in which individuals are identified by the epidemiological compartment to which they belong and by their viral load. Microscopic rules describe both the switch of compartment and the evolution of the viral load. In particular, in the binary interactions between susceptible and infectious individuals, the probability for the susceptible individual to get infected depends on the viral load of the infectious individual. Then, we implement the prescribed microscopic dynamics in appropriate kinetic equations, from which the macroscopic equations for the densities and viral load momentum of the compartments are eventually derived. In the macroscopic model, the rate of disease transmission turns out to be a function of the mean viral load of the infectious population. We analytically and numerically investigate the case that the transmission rate linearly depends on the viral load, which is compared to the classical case of constant transmission rate. A qualitative analysis is performed based on stability and bifurcation theory. Finally, numerical investigations concerning the model reproduction number and the epidemic dynamics are presented.
Optical pressure sensing at MHz rates via collisional line broadening of carbon monoxide: uncertainty quantification in reacting flows
Authors: Nair Anil P. , Minesi Nicolas Q. , Kuenning Nicholas M. , Keller Alex R. , Spearrin R. Mitchell
Published: March 2023

An optical method for high-speed line-of-sight pressure measurements using infrared laser absorption spectroscopy is presented with detailed uncertainty analysis related to thermodynamic and compositional variation in combustion environments. The technique exploits simultaneous sub-microsecond sensing of temperature and mole fraction to extract pressure from collisional line broadening at MHz rates. A distributed-feedback quantum-cascade laser near 5 $$\upmu $$
μ
m in a bias-tee circuit is used to spectrally resolve multiple rovibrational transitions in the P-branch of the fundamental band of carbon monoxide, which may be seeded or nascent to reacting flows. A comprehensive approach for estimating collisional line broadening in complex combustion gas mixtures is presented. Uncertainty is quantified for a wide range of conditions, reflecting different fuels, equivalence ratios, reaction progress, and combustion modes (deflagration and detonation), which influence gas composition and temperature. The sensor was evaluated for accuracy and precision in both a high-enthalpy shock-tube facility in hydrocarbon–air ignition experiments and behind ethylene–oxygen detonation waves in a detonation-impulse tube facility at temperatures from 1500 to 3000 K and pressures from 0.5 to 10 bar. Pressure measurements were compared to measurements by piezoelectric pressure transducers and to theoretical estimates from normal-shock and Chapman-Jouguet simulations. The high-speed path-integrated optical pressure measurement offers an alternative to traditional electromechanical transducers that are constrained to values at wall boundaries and have proven unreliable in some harsh reacting flows.
Assessing phosphorus availability in paddy soils: the importance of integrating soil tests and plant responses
Authors: Martinengo Sara , Schiavon Michela , Santoro Veronica , Said-Pullicino Daniel , Romani Marco , Miniotti Eleonora Francesca , Celi Luisella , Martin Maria
Published: March 2023

Phosphorus (P) cycling in paddy soil is closely related to iron (Fe) redox wheel; its availability to rice has thus generally been ascribed to Fe minerals reductive dissolution. However, the literature aimed to identify the best method for predicting rice available P does not uniformly point to Fe reductants. Rice plants can indeed solubilize and absorb P through many strategies as a function of P supply, modifying the chemical environment. Therefore, this study aims to estimate P availability in paddy soils coupling the redox mechanisms driving P cycling with concurrent plant responses. Soil available P was estimated in three groups of paddy soils with low, medium, or high P content assessing easily desorbable pools (0.01 M calcium chloride, Olsen, Mehlich-III, anion exchanging resins) and Fe-bound P pools (EDTA, citrate-ascorbate, and oxalate). Rice P uptake and responses to P availability were assessed by a mesocosm cultivation trial. Although P released in porewater positively correlated with dissolved Fe(II), it did not with plant P uptake, and readily desorbable P pools were better availability predictors than Fe-bound pools, mainly because of the asynchrony observed between Fe reduction and plant P demand. Moreover, in low P soils, plants showed higher Fe(II) oxidation, enhanced root growth, and up-regulation of P root transporter encoding genes, plant responses being related with changes in P pools. These results indicate the generally assumed direct link between Fe reduction and rice P nutrition in paddy soils as an oversimplification, with rice P nutrition appearing as the result of a complex trade-off between soil redox dynamics, P content, and plant responses.
Impact of progesterone on the immune system in women: a systematic literature review
Authors: Zwahlen Michelle , Stute Petra
Published: March 2023

Purpose

The immune system is influenced by many factors, including female sex hormones. The extent of this influence, however, is not completely understood so far. This systematic literature review aims at giving an overview of the existing concepts on how endogenous progesterone influences the female immune system along the menstrual cycle.

Methods

The inclusion criteria were healthy female subjects in their reproductive age with a regular menstrual cycle. The exclusion criteria were exogenous progesterone, animal models, nonhealthy study populations and pregnancy. This led to 18 papers covered in this review. The search was performed using the databases EMBASE, Ovid MEDLINE and Epub, and the last search was conducted on September 18, 2020. Our findings were analyzed in four categories: cellular immune defense, humoral immune defense, objective and subjective clinical parameters.

Results

We demonstrated that progesterone acts in an immunosuppressive way, favoring a Th-2-like cytokine profile. Further, we showed that progesterone inhibits mast cell degranulation and relaxes smooth muscle cells. Furthermore, we found supporting evidence for a so-called window of vulnerability after ovulation, where immune functions are lowered and mediated through progesterone.

Conclusion

The clinical relevance of these findings is not completely understood yet. As the sample sizes of included studies were rather small and the content of them was broad, further investigations are needed to define to which extent the described changes actually clinically meaningful, whether they are capable of influencing the female health and how these findings can be used to increase well-being.
The first rib as a method of adult age-at-death estimation in a modern South African sample
Authors: Jooste Nicolene , Steyn Maryna
Published: March 2023

An age-at-death estimation method using the first rib may be particularly advantageous as this rib is relatively easy to identify, not easily damaged postmortem, and associated with less mechanical stresses compared to other age indicators. Previously, mixed results have been achieved using the first rib to estimate age-at-death. This study aimed to develop and test an age-at-death estimation method using the first rib. An identified modern black South African sample of 260 skeletons were used to collect age-related data from the first rib. Multiple linear regression analysis equations were created from this data for male, female, and combined samples. When tested on a hold-out sample, equations generated mean inaccuracies of 7–13 years for point estimates. The 95% confidence intervals contained the true age in 11–33% of individuals depending on the equation used, but wider intervals generated using 95% prediction intervals contained true ages for 100% of individuals. Point estimate inaccuracies are comparable to other age-at-death estimation methods and may be useful if single indicator estimation is unavoidable in the case of missing or damaged bones. However, combined methods that use indicators from many areas of the skeleton are preferable and may reduce interval widths.
Summer weather perception and preferences in Powsin Culture Park (Warsaw, Poland)
Authors: Rozbicka Katarzyna , Rozbicki Tomasz
Published: March 2023

Green areas situated inside the city play a very important role for many aspects. Among other, from the social point of view, they have a positive impact on the life of city habitants: directly improve well-being and health, reduce noise, provide opportunities for activity and recreation, improve the tourist attractiveness of the city, etc. The objective of this study was to assess thermal sensations and preferences of people staying outdoors for recreational purposes in the area of the city park during summer 2019, as well as to identify how bioclimate perceptions are modified by personal factors (physical and physiological). In order to determine the optimum thermal zone for recreation and urban tourism during the summer, the regression model for mean thermal preferences (MTPV) every 1 °C in PET value intervals was calculated, and according to this procedure, the preferable spectrum of thermal conditions for tourism and recreation in Warsaw which is related to the PET value range between 27.3 and 31.7 °C. All age groups indicated the highest frequency of neutral thermal sensation vote, which decreased with feeling more extreme thermal conditions. In the case of classification by the gender, the men more than the women indicated the thermal conditions as neutral, “slightly warm,” and “warm.” Studies have shown that women were more sensitive than men to extreme thermal sensations especially “hot” and men more often than women indicated greater acceptance for comfortable and warmer thermal conditions.
Searching for nothing: placing zero on the temporal continuum
Authors: Pinto Carlos , Salgado Sara
Published: March 2023

Generalization allows responses acquired in one situation to be transferred to similar situations. For temporal stimuli, a discontinuity has been found between zero and non-zero durations: responses in trials with no (or 0-s) stimuli and in trials with very short stimuli differ more than what would be expected by generalization. This discontinuity may happen because 0-s durations do not belong to the same continuum as non-zero durations. Alternatively, the discontinuity may be due to generalization decrement effects: a 0-s stimulus differs from a short stimulus not only in duration, but also in its presence, thus leading to greater differences in performance. Aiming to reduce differences between trials with and without a stimulus, we used two procedures to test whether a potential reduction in generalization decrement would bring performance following zero and non-zero durations closer. In both procedures, there was a reduction in the discontinuity between 0-s and short durations, supporting the hypothesis that 0-s durations are integrated in the temporal subjective continuum.
The influence of different storage media on Vickers hardness and surface roughness of CAD/CAM resin composites
Authors: Fuchs Florian , Schmidtke Julius , Hahnel Sebastian , Koenig Andreas
Published: March 2023

Introduction

This study examined Vickers hardness as well as surface characteristics of different computer-aided design/computer-aided manufacturing (CAD/CAM) resin composites prior to and after storage in various media.

Materials and methods

CAD/CAM resin composite blocks (Grandio Blocs (GB), Lava Ultimate (LU), Brilliant Crios (BC), Cerasmart (GC), Shofu Block HC (SB), Tetric CAD (TC), Luxacam Composite (LC); incl. different translucency variants) were prepared, polished and surface free energy was determined. The specimens were divided into four groups: dry conditions for 24 h (25 °C), demineralized water (37 °C), Pepsi Cola (37 °C) and 75% ethanol (37 °C). After seven and 28 days of storage, Vickers hardness was determined. Surface roughness was measured after the entire storage period.

Results and discussion

Vickers hardness was in the range of about 150 HV for GB, around 115 HV for LU, and 80–100 HV for BC, GC, SB, TC and LC. Only minor differences (total: 50.2 (6.4)–56.2 (3.2) mN/m) in surface free energy could be detected. No relationship was observed between surface free energy and filler content. However, a correlation between filler content and Vickers hardness was evident. Artificial aging caused a decrease of Vickers hardness (up to −40 HV or 35%) depending on storage media, duration and material. The changes in surface texture after immersion in different media were below a value of ΔSa = 0.015 µm.

Conclusion

Artificial aging of CAD/CAM resin composites leads to a significant decrease of Vickers hardness for most materials, while only small changes in surface roughness were identified.

Graphical Abstract
The In-Vitro Effect of Silver and Zinc Oxide Nanoparticles on Fluoride Release and Microhardness of a Resin-Modified Glass Ionomer Cement
Authors: AlMatar Dalal , AlSanousi Shaikha , Ahmed Jasim , Saad Bin Qasim Syed
Published: March 2023

Reinforcement of nanoparticles into existing restorative biomaterials in dentistry is an area of interest. The aim of the current investigation was to incorporate silver nanoparticles (SNP) and zinc oxide nanoparticles (ZnONP) into a commercially available resin-modified glass ionomer cement (RMGIC). Their effects on the fluoride (F-) release from RMGIC were also investigated over a period of 14-days. Nanoparticles were incorporated at a loading concentration of 5 wt%, either individually or in a combination of both. Scanning electron microscopy (SEM), Fourier Transform infrared spectroscopy (FTIR), Nanocomputerized tomography (NanoCT), and the Vickers microhardness tester were used to examine the specimens. The fluoride release was analyzed by high performance liquid chromatography (HPLC). Data were analysed using ANOVA and Tukey’s test. RMGIC containing 5% ZnONP and 5% SNP + 5% ZnONP showed significant alterations in the surface ultrastructure with pores being evident in the surface. Fluoride release in parts per million (ppm) was highest in the 5% SNP and 5% ZnO-NP incorporated RMGIC compared to the control group and 5% SNP-incorporated RMGIC. RMGIC, as well as change in color observed in the 5% SNP incorporated RMGIC.
Strong Pairs of Periodic Segments
Authors: Wójcik Klaudiusz
Published: March 2023

We introduce the notion of a strong pair of periodic segments over [0, T] and we show its applications in detecting chaotic dynamics. We prove a various number of fixed point index formulas concerning periodic points of the Poincaré map.
Instructional design of virtual patients in dental education through a 4C/ID lens: a narrative review
Authors: Janesarvatan Fatemeh , Van Rosmalen Peter
Published: March 2023

Although VPs have been applied in various medical and dental education programmes, it remains uncertain whether their design was based on specific instructional design (ID) principles, and therefore, how to improve on them. In this study, we evaluated the extent to which ID principles have played a role in the development of VPs for clinical skills training purposes in dental education. First, as frame of reference we mapped key ID principles identified in VPs and medical simulations on the widely used four-component instructional design (4C/ID) model. Next, a literature search was conducted using Libsearch, a single search tool accessing databases such as MEDLINE, PubMed, Embase, CINAHL, ERIC, PsycInfo and Scopus. Following the PRISMA framework for systematic reviews, we selected 21 studies that used screen-based VP simulations for undergraduate dental students. The data analysis consisted of a review of each study analysing the key instructional design features connected to the components of the 4C/ID model. Overall, the results indicate that a structured approach to the design and implementation of VPs likely will have a positive effect on their use. While some ID-principles are shared such as the importance of clinical task variation to improving the transfer of learning. Others, however, such as the choice of learning mode or the use of cognitive feedback are ambiguous. Given its impact on students’ ability to establish effective cognitive schemas and the option to compare and study designs we recommend a more rigorous approach such as 4C/ID for the design of VPs.
Integrated Influence Zone Calculation Method for the Existing Metro Tunnel Under the Influence of Adjacent Construction
Authors: Han Yuzhen , Nie Xiaofan , Chen Xiangsheng
Published: March 2023

Adjacent construction around metro tunnels is a common situation in urban cities, which usually leads to the disturbance of surrounding soils and existing tunnels. Based on the influence zone theory, construction risks can be described in a graded manner. However, the calculation of the influence zone in existing research is mostly based on a single indicator, which is difficult to adapt to the increasingly stringent requirements of real projects. To address this limitation, a normalized method for the influence function and a weighted combination method for multi-indicators were proposed. These methods can combine any number of indicators to obtain an integrated result of the influence zone, facilitating direct guidance of engineering. Based on a case study of the Metro construction in Qingdao, a series of numerical simulations and calculations of the integrated influence zone was carried out. The results show that the shape of the integrated influence zone in this case is a necked bottle, i.e., the new tunnel causes a greater influence when it is below the existing tunnel. The change of soil layer and the weight of indicators both play important roles on the shape of the influence zone. The relevant conclusions and methods provide a basis for the safety assessment of similar projects.
Bone Marrow Mesenchymal Stem Cells Expanded Inside the Nichoid Micro-Scaffold: a Focus on Anti-Inflammatory Response
Authors: Barzaghini Bianca , Carelli Stephana , Messa Letizia , Rey Federica , Avanzini Maria Antonietta , Jacchetti Emanuela , Maghraby Erika , Berardo Clarissa , Zuccotti Gianvincenzo , Raimondi Manuela Teresa , Cereda Cristina , Calcaterra Valeria , Pelizzo Gloria
Published: March 2023

Purpose

Mesenchymal stem cells (MSCs) represent a promising source for stem cell therapies in numerous diseases, including pediatric respiratory system diseases. Characterized by low immunogenicity, high anti-inflammatory, and immunoregulatory features, MSCs demonstrated an excellent therapeutic profile in numerous in vitro and preclinical models. MSCs reside in a specialized physiologic microenvironment, characterized by a unique combination of biophysical, biochemical, and cellular properties. The exploitation of the 3D micro-scaffold Nichoid, which simulates the native niche, enhanced the anti-inflammatory potential of stem cells through mechanical stimulation only, overcoming the limitation of biochemical and xenogenic growth factors application.

Materials and Methods

In this work, we expanded pediatric bone marrow MSCs (BM-MSCs) inside the Nichoid and performed a complete cellular characterization with different approaches including viability assays, immunofluorescence analyses, RNA sequencing, and gene expression analysis.

Results

We demonstrated that BM-MSCs inside the scaffold remain in a stem cell quiescent state mimicking the condition of the in vivo environment. Moreover, the gene expression profile of these cells shows a significant up-regulation of genes involved in immune response when compared with the flat control.

Conclusion

The significant changes in the expression profile of anti-inflammatory genes could potentiate the therapeutic effect of BM-MSCs, encouraging the possible clinical translation for the treatment of pediatric congenital and acquired pulmonary disorders, including post-COVID lung manifestations.

Lay Summary

Regenerative medicine is the research field integrating medicine, biology, and biomedical engineering. In this context, stem cells, which are a fundamental cell source able to regenerate tissues and restore damage in the body, are the key component for a regenerative therapeutic approach. When expanded outside the body, stem cells tend to differentiate spontaneously and lose regenerative potential due to external stimuli. For this reason, we exploit the scaffold named Nichoid, which mimics the in vivo cell niche architecture. In this scaffold, mesenchymal stem cells “feel at home” due to the three-dimensional mechanical stimuli, and our findings could be considered as an innovative culture system for the in vitro expansion of stem cells for clinical translation.

Future Perspective

The increasing demand of safe and effective cell therapies projects our findings toward the possibility of improving cell therapies based on the use of BM-MSCs, particularly for their clinical translation in lung diseases.

Graphical Abstract
Mechanical behavior of coal under true triaxial loading test connecting the effect of excavation- and mining-induced disturbances
Authors: Gao Mingzhong , Zhou Xuemin , Wang Xuan , Xie Jing , Wang Chen , Zhang Qi , Lv Heqiang , Guo Chenchen
Published: March 2023

In order to understand the mechanical behavior of a stope and analyse the stress conditions of surrounding rocks after ventilation shaft excavation and the abutment stresses of the top coal mining layout. In situ uniaxial stress monitoring tests were performed to understand the field abutment pressure evolution. Furthermore, the variation of the stress concentration factor was studied using the Tongxin Mine 8309 mining face of the TongMei Group, China, as a case study. A loading model of coal rock under excavation- and mining-induced disturbances was proposed, and the stress path and experimental method were designed to investigate the high excavation-damaged zone (HDZ), excavation-damaged zone (EDZ), and undisturbed zone (UZ). Moreover, the mechanical characteristics and failure characteristics of coal rock in different zones under site disturbance were obtained and the mesoscopic analysis is carried out by acoustic emission test. The results indicated that the strengths of the UZ, EDZ, and HDZ samples declined gradually. The volume of the UZ sample continuously expanded. However, the volumes of the EDZ and HDZ samples were compressed first and then expanded. Furthermore, the shear bands presented in all three samples resulted in failure. The cubic triaxial tests performed without considering mining-induced pressure produced higher strengths and less damage compared with the results of the true triaxial tests. The stress path used in the laboratory with the mining-induced stress throughout the stope could optimally reproduce the in situ mining process, which is significantly safe and efficient for the mining of deep resources.
Challenges and opportunities in the implementation of an antimicrobial stewardship program in Nepal
Authors: Khanal Sushil , Acharya Upasana , Trotter Andrew B. , Tripathi Prashant , Koirala Sabin , Pahari Bishnu , Acharya Subhash P.
Published: March 2023

Antimicrobial resistance (AMR) continues to be a serious global public issue. Unnecessary and inappropriate use of antimicrobials has been identified as a major contributing factor for AMR. Implementation of antimicrobial stewardship programs (ASPs) is valued as a key strategy to combat AMR. Although ASP is a key intervention to improve appropriate use of antibiotics, there is limited experience and research to describe its implementation in low-income countries such as Nepal. Grande International Hospital (GIH) is the first health organization in Nepal to implement and sustain a multidisciplinary ASP and infection control program. Challenges faced in implementing ASP include lack of acceptance from physicians, lack of knowledge regarding antibiotic prescribing, lack of staff for ASP activities, limitations in diagnostic testing to inform ASP, and limitations in antibiotic choice due to antibiotic unavailability. Our ASP includes the following components: an ASP committee, an antibiotic prescribing reference guide with dosage recommendations, inpatient formulary restriction system, educational outreach and programming for physicians and other stakeholders, and periodic review and revision of the program and reference guide. The ASP provided opportunities to address several knowledge gaps across our healthcare institution including improved knowledge and competency regarding rational use of antibiotics, access to quality medicines and better care to patients. It is our hope that, by describing the challenges and opportunities we experienced while implementing our ASP, we can support and encourage other institutions to adapt and implement ASPs in Nepal and other resource-limited settings.
Internal and External Paternalism
Authors: Ben-Moshe Nir
Published: March 2023

I introduce a new distinction between two types of paternalism, which I call ‘internal’ and ‘external’ paternalism. The distinction pertains to the question of whether the paternalized subject’s current evaluative judgments are mistaken relative to a standard of correctness that is internal to her evaluative point of view—which includes her ‘true’ or ‘ideal’ self—as opposed to one that is wholly external. I argue that this distinction has important implications for (a) the distinction between weak and strong paternalism; (b) the distinction between soft and hard paternalism; and (c) medical practice, where internal paternalism can, and probably often does, occur.
Lessons Learned: Community Engagement in Emergencies in Puerto Rico
Authors: Lafarga Previdi Irene , Vélez Vega Carmen M. , Guzzi Vasques Ana C. , Fernández Repollet Emma , Torres Zayas Héctor R. , Alshawabkeh Akram , Cordero José F.
Published: March 2023

Objective:

To describe the importance of community engagement from research projects and research centers in times of disasters or emergencies, using the case of Puerto Rico in recent years (2017 - 2022) as an example.

Methods:

First, research participants and stakeholders from local community and health organizations were contacted via email and phone calls after each emergency to assess their immediate needs. Second, needs were classified in categories (materials, educational resources, service referrals, and collaborations). Finally, delivery of support was coordinated in a timely manner whether in person or online.

Results:

Activities were conducted such as handing out materials, providing educational resources, contacting participants, and stakeholders, as well as coordinating collaboration with community and organizations.

Conclusion:

Several lessons were learned from our experiences related to Puerto Rico’s recent emergencies as well as some relevant recommendations for future disasters. The efforts presented illustrate the importance of community engagement from academic institutions in disasters. Research centers and research projects, particularly those with community engagement components, should consider providing support in the preparedness phase as well as the recovery phase if necessary. Community engagement in emergencies is crucial to recovery efforts as well as fostering empowerment and making an impact on individual and societal levels.
Microbiota and probiotics: chances and challenges – a symposium report
Authors: Ruxton Carrie Helen Stevenson , Kajita Chiyuki , Rocca Paola , Pot Bruno
Published: March 2023

The 10th International Yakult Symposium was held in Milan, Italy, on 13–14 October 2022. Two keynote lectures covered the crewed journey to space and its implications for the human microbiome, and how current regulatory systems can be adapted and updated to ensure the safety of microorganisms used as probiotics or food processing ingredients. The remaining lectures were split into sections entitled “Chances” and “Challenges.” The “Chances” section explored opportunities for the science of probiotics and fermented foods to contribute to diverse areas of health such as irritable bowel syndrome, major depression, Parkinson’s disease, immune dysfunction, infant colic, intensive care, respiratory infections, and promoting healthy longevity. The “Challenges” section included selecting appropriate clinical trial participants and methodologies to minimise heterogeneity in responses, how to view probiotics in the context of One Health, adapting regulatory frameworks, and understanding how substances of bacterial origin can cross the blood–brain barrier. The symposium provided evidence from cutting-edge research that gut eubiosis is vital for human health and, like space, the microbiota deserves further exploration of its vast potential.
Resolution ES-11/4 Territorial Integrity of Ukraine: Defending the Principles of the Charter of the United Nations (U.N.G.A.)
Authors: Mälksoo Lauri
Published: March 2023

The resolution “Territorial Integrity of Ukraine: Defending the Principles of the Charter of the United Nations” was adopted by the UN General Assembly (UNGA) on October 12, 2022, with 143 UN member states in favor, five against, thirty-five abstentions, and ten not voting. It is another important UNGA resolution on Ukraine, after the UNGA qualified as aggression Russia's invasion of Ukraine since February 24, 2022 in its resolution of 2 March 2022. That resolution had 141 states voting in favor, thus a slight increase in votes supporting Ukraine's rights under international law can be seen in the resolution at issue.
Nationalist Memory Narratives and the Politics of History in Ukraine since the 1990s
Authors: Kasianov Georgiy
Published: March 2023

This essay focuses on analyzing the history of the evolution of the nationalist memory narrative in recent memory politics in Ukraine. It observes the political rehabilitation of the radical nationalist movement and its leaders and organizations, followed by public recognition and glorification, and the evolution of this memory narrative since the beginning of the 1990s from local memory to the centerpiece of the state politics of memory. This article examines the memorialization and commemoration of the nationalist movement at regional and national levels (sites of memory, memorial dates, renaming of topographical objects, movies, TV series, etc.), policies aimed at the promotion of the nationalist historical myth, political controversies, roles of major actors, public debates on these issues, societal responses, and international disputes.
The role of HM Coastguard with particular reference to helicopters
Authors: Hammond G. E.
Published: March 2023

HM Coastguard's main function is the co-ordination of all civil marine search and rescue operations around the coast of the United Kingdom—the area limits corresponding to those set out in the ICAO SAR Plan. To achieve this task the coastguards are so disposed around our coast, on a 24 hour watchkeeping basis, to best receive the distress information and vector the appropriate rescue facility to the scene. There are 550 regular coastguards maintaining 150 regular stations (see map) backed up by over 7000 auxiliary coastguards and 214 auxiliary stations. All regular Coastguard Stations maintain watch on MF and VHF marine distress frequencies, are netted in to their local 999 emergency telephone system and are interconnected by VHF radio and telephone. All Rescue HQs and some strategically placed constantly manned stations are addtionally connected to the PO Telex system with direct lines to their adjacent PO Coast Radio Stations. CG Auxiliary stations, provided with VHF radio and telephone facilities, are only manned at times of casualty risk.
Evaluation of the overall fuel mass penalty of an aircraft system
Authors: Le Claire R.
Published: March 2023

The purpose of this note is:

(a)

to provide a method for evaluating the fuel mass penalty incurred in flight after fitment of a system to an aircraft. The method relies only on a limited number of parameters and should prove particularly useful in the early design stages of a new project.

(b)

to show the relative importance of the parameters involved, in particular the relationship between the fuel penalty due to system basic mass and that due to system drag (other than mass drag) which, depending on the flight conditions, could be significant or even greater.
The Common Market and the Regulation of Air Transport
Authors: Allott P. J.
Published: March 2023

The EEC Treaty gives a good deal of prominence to transport policy. Among the activities of the Community specifically listed in Article 3 is Article 3(e)—‘the adoption of a common policy in the sphere of transport’.

There is a whole Title devoted to it, consisting of 11 articles (Articles 74-84), and the title is included in Part Two of the Treaty which is entitled ‘Foundations of the Community’. Yet on 5th June 1973, speaking in the European Parliament, the Commissioner responsible for transport (Mr. Scarascia Mugnozza) said:

‘… without wishing to detract from the progress already achieved, particularly when it is viewed in relation to existing difficulties, we must nevertheless frankly and objectively admit that very few of the aims of the common transport policy have been achieved.’
The balance of time and cost
Authors: Brown D. G.
Published: March 2023

During the preparation of this paper within the present stringent financial climate in the industry I have been deeply conscious of time and cost, since it is much more difficult these days to give the time and also to justify the cost of an activity of this nature.

Initially it was intended to examine the contribution of the aircraft designer to the improvement of those phases of the total journey over which the designer could have a direct influence. However, the organising committee had other thoughts and has requested that I should point up those aspects where, despite the efforts of the aircraft manufacturers to improve their product by reducing airborne times and real costs, many of the resulting benefits appear to have been frittered away and lost within the surface phases of the total system.
Royal Air Force experience of the Harrier
Authors: Wade Ruthven
Published: March 2023

No one who has served in the Royal Air Force for any length of time can be anything but vividly aware of the intimate connection of Sir Sydney Camm with the Service, and the profound effect that he and his aircraft have had upon us. The list of military aircraft for which he was responsible from 1925 onwards reads almost like a history of the Royal Air Force: Hornbill, Hart, Fury, Hurricane, Typhoon, Tempest, Hunter, P.1127 and the Hawk.
A note on fully developed turbulent flow down a circular pipe
Authors: Patel Rajni P.
Published: March 2023

This investigation originated when some difficulties were experienced in establishing good flow conditions in a circular pipe to study the effects of longitudinal cooling on slanted hot-wires.

In the past many investigators have presented results on turbulent flow through pipes and it is now generally assumed that this flow field is known in sufficient detail. For example, Schlichting has given a through description of the mean velocity distribution for turbulent flow through pipes based on the experimental results of Nikuradse. On the other hand Townsend describes the structure of the flow based on the results of Laufer. Although the investigation of Nikuradse and Laufer are classical works there appears to be some uncertainty in whether or not their turbulent flows down pipes were really fully developed.
The operation of the Bell 212 under instrument flight rules
Authors: Ginn M. C.
Published: March 2023

It is my very great honour to be asked as an operator to cover the Bell 212s part in the story of IFR operation of medium helicopters.

None of us should forget that two great British companies have for years been blazing a trail in the IFR operation of two helicopters, the S-61 and the Wessex 60, and I can only assume that it was because Irish Helicopters was, I understand, the first operator to put the CAA approved Bell 212/IFR into operation that the privilege of giving this talk has come my way, and I speak humbly and mindful of the invaluable efforts of others before us.
The evolution of army aviation
Authors: Richardson T. A.
Published: March 2023

The important thing in the land battle is to overpower your opponent by out-manoeuvring him and then hitting him with all the weapons at your disposal. Clubs, swords, spears, brickbats and arrows, or rifles, machine guns and artillery or nuclear, chemical and guided weapons, the principles are the same:

(a) Seek the enemy out.

(b) Move into position.

(c) Destroy him in battle.

The first task is therefore surveillance and target acquisition. This is a task which requires a soldier to get into a position to observe and discover where your enemy is and what he is doing. Most sensible enemies hide behind hills to keep out of harm's way, in order to conceal their future intentions. Therefore one of our basic problems is to find out what goes on behind the hill.
Concorde and safety: design, testing and certification
Authors: Chevalier R.
Published: March 2023

For the engineer, the “Concorde challenge” could be defined as follows:

A passenger carrying aircraft twice as fast as the existing aircraft and at least as safe.

When the jets came out 20 years ago, there was a sudden increase of the speeds used up to then, but their envelope stopped at the limit where the difficulties associated with very high speeds start