bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of LXR controls the polarization of human inflammatory macrophages through upregulation of MAFB
Authors: de la Aleja Arturo González , Herrero Cristina , Torres-Torresano Mónica , Schiaffino María Teresa , del Castillo Alejandro , Alonso Bárbara , Vega Miguel A. , Puig-Kröger Amaya , Castrillo Antonio , Corbí Ángel L. 
Published: March 2023

AbstractMonocyte-derived macrophages contribute to pathogenesis in inflammatory diseases and their effector functions greatly depend on the prevailing extracellular milieu. Whereas M-CSF primes macrophages for acquisition of an anti-inflammatory profile, GM-CSF drives the generation of T cell-stimulatory and pro-inflammatory macrophages. Liver X Receptors (LXRα and LXRβ) are nuclear receptors that control cholesterol metabolism and regulate differentiation of tissue-resident macrophages. Macrophages from rheumatoid arthritis and other inflammatory pathologies exhibit an enriched LXR pathway, and recent reports have shown that LXR activation raises pro-inflammatory effects and impairs the acquisition of the anti-Inflammatory profile of M-CSF-dependent monocyte-derived macrophages (M-MØ). We now report that LXR inhibition prompts the acquisition of an anti-inflammatory gene and functional profile of macrophages generated within a pathological environment (synovial fluid from Rheumatoid Arthritis patients) as well as during the GM-CSF-dependent differentiation of human monocyte-derived macrophages (GM-MØ). Mechanistically, inhibition of LXR results in macrophages with higher expression of the v-Maf Avian Musculoaponeurotic Fibrosarcoma Oncogene Homolog B (MAFB) transcription factor, which governs the macrophage anti-inflammatory profile, as well as over-expression of MAFB-regulated genes. Indeed, gene silencing experiments on human macrophages evidenced that MAFB is required for the LXR inhibitor to enhance the anti-inflammatory nature of human macrophages. As a whole, our results demonstrate that LXR inhibition prompts the acquisition of an anti-inflammatory transcriptional and functional profile of human macrophages in a MAFB-dependent manner, and propose the use of LXR antagonists as potential therapeutic alternatives in macrophage re-programming strategies during inflammatory responses.
Significant impact of time-of-day variation on metformin pharmacokinetics
Authors: Türk Denise , Scherer Nina , Selzer Dominik , Dings Christiane , Hanke Nina , Dallmann Robert , Schwab Matthias , Timmins Peter , Nock Valerie , Lehr Thorsten 
Published: March 2023

Abstract
Aims/hypothesis
The objective was to investigate if metformin pharmacokinetics is modulated by time-of-day in humans using empirical and mechanistic pharmacokinetic modelling techniques on a large clinical dataset. This study also aimed to generate and test hypotheses on the underlying mechanisms, including evidence for chronotype-dependent interindividual differences in metformin plasma and efficacy-related tissue concentrations.

Methods
A large clinical dataset consisting of individual metformin plasma and urine measurements was analysed using a newly developed empirical pharmacokinetic model. Causes of daily variation of metformin pharmacokinetics and interindividual variability were further investigated by a literature-informed mechanistic modelling analysis.

Results
A significant effect of time-of-day on metformin pharmacokinetics was found. Daily rhythms of gastrointestinal, hepatic and renal processes are described in the literature, possibly affecting drug pharmacokinetics. Observed metformin plasma levels were best described by a combination of a rhythm in GFR, renal plasma flow (RPF) and organic cation transporter (OCT) 2 activity. Furthermore, the large interindividual differences in measured metformin concentrations were best explained by individual chronotypes affecting metformin clearance, with impact on plasma and tissue concentrations that may have implications for metformin efficacy.

Conclusions/interpretation
Metformin’s pharmacology significantly depends on time-of-day in humans, determined with the help of empirical and mechanistic pharmacokinetic modelling, and rhythmic GFR, RPF and OCT2 were found to govern intraday variation. Interindividual variation was found to be partly dependent on individual chronotype, suggesting diurnal preference as an interesting, but so-far underappreciated, topic with regard to future personalised chronomodulated therapy in people with type 2 diabetes.

Graphical abstract
Non-isothermal thin-film flow of a viscoplastic material over topography: critical Bingham number for a partial slump
Authors: Moyers-Gonzalez Miguel , Hewett James N. , Cusack Dale R. , Kennedy Ben M. , Sellier Mathieu 
Published: March 2023

Abstract
This paper considers the non-isothermal flow of a viscoplastic fluid on a horizontal or an inclined surface with a flat, a step-up and a step-down topography. A particular application of interest is the spread of a fixed mass—a block—of material under its own weight. The rheology of the fluid is described by the Bingham model which includes the effect of yield stress, i.e. a threshold stress which must be exceeded before flow can occur. Both the plastic viscosity and the yield stress are modelled with temperature-dependent parameters. The flow is described by a reduced model with a thin-film equation for the height of the block and a depth-averaged energy conservation equation for the heat transfer. Results show that for large values of the yield stress, only the outer fraction of the fluid spreads outward, the inner fraction remaining unyielded, hence the block only partially slumps. Conversely, for small values of the yield stress, the entire block of fluid becomes yielded and therefore slumps. We present an analysis which predicts the critical value of the yield stress for which partial slump occurs and how it depends on temperature.

Graphical abstract
Piezoresistive behavior of DLP 3D printed CNT/polymer nanocomposites under monotonic and cyclic loading
Authors: Saadi Omar Waqas , Schiffer Andreas , Kumar S. 
Published: March 2023

AbstractThis study examines the piezoresistive behavior of MWCNT/polymer composites fabricated by the digital light processing (DLP) technique. A photocurable nanocomposite resin feedstock possessing low viscosity with excellent printability and high conductivity was developed for DLP 3D printing of bulk and cellular geometries. By optimizing the resin composition and synthesis route, electrical percolation was achieved at an ultra-low MWCNT loading of 0.01 phr (parts per hundred resin), providing a conductivity of 3.5 × 10−5 S m−1, which is significantly higher than the values reported in the extant works for similar nanocomposites. Reducing the MWCNT content also enhanced the piezoresistivity of the nanocomposite due to longer inter-MWCNT distances in the percolating conductive network. Under quasi-static tensile loading, the nanocomposite with 0.01 phr MWCNT loading showed gauge factors of 2.40 and 4.78, corresponding to the elastic and inelastic regime, respectively. Quasi-static cyclic tensile tests with constant strain amplitudes (within elastic regime) revealed that the response of the nanocomposite was affected by viscoelastic deformation, which caused significant changes in the material’s strain sensing performance between consecutive load cycles. Finally, the developed resin was used to realize a self-sensing gyroid lattice structure, and its strain and damage sensing capabilities were demonstrated.
Preclinical development and evaluation of nanobody-based CD70-specific CAR T cells for the treatment of acute myeloid leukemia
Authors: Cheng Jiali , Ge Tong , Zhu Xiaojian , Wang Jue , Zeng Yuhao , Mu Wei , Cai Haodong , Dai Zhenyu , Jin Jin , Yang Yongkun , Hu Guang , Mao Xia , Zhou Jianfeng , Zhu Li , Huang Liang 
Published: March 2023

Abstract
Background
Acute myeloid leukemia (AML) treatment remains challenging. CD70 was reported as a promising AML-specific antigen. Preclinically, CAR T-cell with single-chain-variable fragment (scFv) or truncated CD27 targeting CD70 has been reported to treat AML. However, various disadvantages including spontaneous exhaustion, proteinase-mediated loss of functional receptors, and high immunogenicity, limited its further application to clinical settings. Alternatively, the single-variable domain on heavy chain (VHH), also known as nanobodies, with comparable binding ability and specificity, provides an optional solution.

Method
We generated CD70 knocked-out novel nanobody-based anti-CD70-CAR T-cells (nb70CAR-T) with two different VHHs for antigen detection. Next, we detected the CD70 expression on primary AML blasts by flow cytometry and associated the efficacy of nb70CAR-T with the target antigen density. Finally, epigenetic modulators were investigated to regulate the CD70 expression on AML cells to promote the functionality of nb70CAR-T.

Results
Our nb70CAR-T exhibited expected tumoricidal functionality against CD70-expressed cell lines and primary AML blasts. However, CD70 expression in primary AML blasts was not consistently high and nb70CAR-T potently respond to an estimated 40.4% of AML patients when the CD70 expression level was over a threshold of 1.6 (MFI ratio). Epigenetic modulators, Decitabine and Chidamide can up-regulate CD70 expression on AML cells, enhancing the treatment efficacy of nb70CAR-T.

Conclusion
CD70 expression in AML blasts was not fully supportive of its role in AML targeted therapy as reported. The combinational use of Chidamide and Decitabine with nb70CAR-T could provide a new potential for the treatment of AML.
The impact of pre-transplantation nephrectomy on quality of life in patients with autosomal dominant polycystic kidney disease
Authors: Geertsema Paul , Gansevoort Ron T. , Brenkman Lisanne P. J. , Dekker Shosha E. I. , Eleveld Damia V. P. , de Fijter Johan W. , Leliveld Anna M. , Levy Maya , Meijer Esther , Pol Robert A. , Schillern Emmelien E. M. , Sanders Jan-Stephan F. , Casteleijn Niek F. 
Published: March 2023

Abstract
Purpose
In selected ADPKD patients, a nephrectomy is required in the work-up for a kidney transplantation. Because the impact of this procedure is unknown, we investigated the effect of pre-transplantation nephrectomy on quality of life in this group.

Methods
In this retrospective cohort study all ADPKD patients, ≥ 18 years, who received a kidney transplantation in 2 ADPKD expertise centers between January 2000 and January 2016, were asked to participate. Quality of life was assessed using three validated questionnaires on three time points. Nephrectomy was performed in preparation for transplantation.

Results
Two hundred seventy-six ADPKD patients (53 ± 9 years, 56.2% male) were included. 98 patients (35.5%) underwent native nephrectomy in preparation for transplantation, of which 43 underwent bilateral nephrectomy. Pre-transplantation, ADPKD-IS scores were worse in the nephrectomy group vs. no-nephrectomy group (physical: 2.9 vs. 2.3, p < 0.001; emotional: 2.0 vs. 1.8, p = 0.03; fatigue: 3.0 vs. 2.3, p = 0.01). Post-transplantation and post-nephrectomy, ADPKD-IS scores improved significantly in both groups, with a significantly higher improvement in the nephrectomy group. During follow-up, all scores were still better compared to pre-transplantation. Observed physical QoL (ADPKD-IS physical 1.3 vs. 1.7, p = 0.04; SF-36 physical 50.0 vs. 41.3, p = 0.03) was better post-transplantation after bilateral nephrectomy compared to unilateral nephrectomy. In retrospect, 19.7% of patients would have liked to undergo a nephrectomy, while the decision not to perform nephrectomy was made by the treating physician.

Conclusion
This study shows that pre-transplantation nephrectomy improves quality of life in selected ADPKD patients. Bilateral nephrectomy may be preferred, although the risk of additional complications should be weighted.
Spinal astrocyte dysfunction drives motor neuron loss in late-onset spinal muscular atrophy
Authors: Schmitt Linda-Isabell , David Christina , Steffen Rebecca , Hezel Stefanie , Roos Andreas , Schara-Schmidt Ulrike , Kleinschnitz Christoph , Leo Markus , Hagenacker Tim 
Published: March 2023

AbstractSpinal muscular atrophy (SMA) is a progressive neuromuscular disorder caused by a loss of the survival of motor neuron 1 (SMN1) gene, resulting in a loss of spinal motor neurons (MNs), leading to muscle weakness and wasting. The pathogenesis of MN loss in SMA and the selective vulnerability in different cellular populations are not fully understood. To investigate the role of spinal astrocytes in the pathogenesis of late-onset SMA, we used a mouse model in addition to in vitro approaches. Immunostaining, Western blot analysis, small interfering ribonucleic acid (siRNA) transfections, functional assays, enzyme-linked immunosorbent assay (ELISA), behavioral tests, and electrophysiological measurements were performed. Early activation of spinal astrocytes and a reduction of the excitatory amino acid transporter 1 (EAAT1) on postnatal day (P) 20 preceded the loss of spinal MNs in SMA mice occurring on P42. EAAT1 reduction resulted in elevated glutamate levels in the spinal cord of SMA mice at P20 and P42. SMA-like astrocytes generated by siRNA and an ex vivo model of glutamate excitotoxicity involving organotypic spinal cord slice cultures revealed the critical role of glutamate homeostasis in the degeneration of MNs. The pre-emptive administration of arundic acid (AA), as an inhibitor of astrocyte activation, to SMA mice prior to the loss of motor neurons (P28) resulted in elevated EAAT1 protein levels compared to vehicle-treated SMA mice and prevented the increase of glutamate in the spinal cord and the loss of spinal MNs. Furthermore, AA preserved motor functions during behavioral experiments, the electrophysiological properties, and muscle alteration of SMA mice. In a translational approach, we transfected healthy human fibroblasts with SMN1 siRNA, resulting in reduced EAAT1 expression and reduced uptake but increased glutamate release. These findings were verified by detecting elevated glutamate levels and reduced levels of EAAT1 in cerebrospinal fluid of untreated SMA type 2 and 3 patients. In addition, glutamate was elevated in serum samples, while EAAT1 was not detectable. Our data give evidence for the crucial role of spinal astrocytes in the pathogenesis of late-onset SMA, a potential driving force for MN loss by glutamate excitotoxicity caused by EAAT1 reduction as an early pathophysiological event. Furthermore, our study introduces EAAT1 as a potential therapeutic target for additional SMN-independent therapy strategies to complement SMN-enhancing drugs.
The effects of standardised versus individualised seat height on 1-minute sit-to-stand test performance in healthy individuals: a randomised crossover trial
Authors: Kuhn Manuel , Vollenweider Sibylle , Clarenbach Christian F. , Kohlbrenner Dario 
Published: March 2023

Abstract
Purpose
We aimed to (i) investigate differences in 1-minute sit-to-stand test (1MSTST) performance (i.e., the number of repetitions) between a standardised modality (i.e., starting from a conventional chair with 46 cm seat height) and an individualised modality (i.e., starting with a knee joint flexion angle of 90°), and to (ii) quantify the influence of tibia and femur length on 1MSTST performance.

Methods
Healthy participants were recruited for this randomised crossover study, performing each 1MSTST modality twice in a randomised order. The primary outcome was the number of repetitions in the 1MSTST. Secondary endpoints were the acute responses in peripheral oxygen saturation, heart rate, and leg fatigue and dyspnoea. Additionally, we investigated correlations of performance with knee extensor strength in both modalities.

Results
Thirty participants were recruited and completed the study. They achieved significantly less repetitions in the standardised 1MSTST compared to the individualised 1MSTST (B = − 12.1, 95% confidence interval [95% CI] =  − 14.8/− 9.4, p < 0.001). We found a significant effect of femur length on 1MSTST performance (B = − 1.6, 95% CI = − 2.6/− 0.7, p = 0.01), tibia length showed significant interaction with the 1MSTST modality (B = 1.2, 95% CI = 0.2/2.2, p = 0.03).

Conclusion
An individualisation of the 1MSTST starting position to 90° knee flexion angle leads to more repetitions compared to the traditional starting position. The higher repetition count is explained by controlling for differences in tibia length. We recommend individualisation of the 1MSTST, enabling more valid comparisons across populations and study samples.

Trial registration number
http://www.ClinicalTrials.gov, NCT04772417.

Trial registration date
February 26, 2021.
Quality of life changes over time and predictors in a large head and neck patients’ cohort: secondary analysis from an Italian multi-center longitudinal, prospective, observational study—a study of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) head and neck working group
Authors: Viganò Anna , De Felice Francesca , Iacovelli Nicola Alessandro , Alterio Daniela , Ingargiola Rossana , Casbarra Alessia , Facchinetti Nadia , Oneta Olga , Bacigalupo Almalina , Tornari Elena , Ursino Stefano , Paiar Fabiola , Caspiani Orietta , Di Rito Alessia , Musio Daniela , Bossi Paolo , Steca Patrizia , Jereczek-Fossa Barbara Alicja , Caso Letizia , Palena Nicola , Greco Andrea , Orlandi Ester 
Published: March 2023

Abstract
Purpose
The present study examined the longitudinal trajectories, through hierarchical modeling, of quality of life among patients with head and neck cancer, specifically symptoms burden, during radiotherapy, and in the follow-up period (1, 3, 6, and 12 months after completion of radiotherapy), through the M.D. Anderson Symptom Inventory Head and Neck questionnaire, formed by three factors. Furthermore, analyses were conducted controlling for socio-demographic as well as clinical characteristics.

Methods
Multi-level mixed-effects linear regression was used to estimate the association between quality of life and time, age, gender, household, educational level, employment status, ECOG performance status, human papilloma virus (HPV) status, surgery, chemotherapy, alcohol intake, and smoking.

Results
Among the 166 participants, time resulted to be a predictor of all the three questionnaire factors, namely, general and specific related symptoms and interference with daily life. Moreover, regarding symptom interference with daily activities factor, HPV-positive status played a significant role. Considering only HPV-negative patients, only time predicted patients’ quality of life. Differently, among HPV-positive patients, other variables, such as gender, educational level, alcohol use, surgery, age at diagnosis, employment status, and ECOG status, resulted significant.

Conclusion
It was evident that quality of life of patients with head and neck cancer declined during RT, whereas it slowly improved after ending treatment. Our results clarified the role of some socio-demographic and clinical variables, for instance, HPV, which would allow to develop treatments tailored to each patient.
Microscopic synchrotron X-ray analysis of mercury waste in simulated landfill experiments
Authors: Takaoka Masaki , Kusakabe Taketoshi , Shiota Kenji , Hirata Osamu , Kawase Keizou , Yanase Ryuji , Nitta Kiyofumi 
Published: March 2023

AbstractMercury enters into the environment or waste streams because it is present as an impurity in natural minerals. Mercury must be appropriately managed as an hazardous waste. In this study, a waste layer of artificial mercury sulfide mixed with incinerator ash and sewage sludge compost in a simulated landfill experiment for 5 years was analyzed using microscopic synchrotron X-ray to obtain basic knowledge of mercury behavior in a landfill. Mapping by synchrotron X-ray revealed the distribution of mercury-containing particles in the waste layer. In most cases, the movement of mercury sulfide was not considered significant even within a microscopic range; however, water flows could enhance the movement of mercury sulfide particles. When disposing of mercury sulfide, “concentrated placement” or solidification, rather than mixing with other wastes, was more effective at preventing mercury leaching in lysimeters. The chemical form of mercury sulfide in each lysimeter was confirmed by X-ray absorption fine structure (XAFS) analysis, which showed that most of the mercury was present as metacinnabar and had not undergone any changes, indicating that it was extremely stable. The microscopic synchrotron X-ray analysis proved very useful for studying the behavior of mercury waste in a simulated landfill experiment.
The behaviour of selected rare-earth elements during the conversion of phosphogypsum to calcium sulphide and residue
Authors: Christophe Nsaka Ntumba , McCrindle Rob , Maree Jannie , Ngole-Jeme Veronica 
Published: March 2023

AbstractPhosphogypsum (PG) is a large hazardous waste from fertiliser and phosphoric acid industries from which useful products including rare-earth elements (REEs) can be recovered depending on the treatment process. Its conversion to calcium sulphide (CaS) which was achieved at 95% followed by the formation of S, CaCO3 and residue is one of the plausible treatment processes leading to economic and environmental benefits. This study aimed at monitoring selected REEs behaviour during the conversion of (PG) to (CaS). The concentrations of REEs in the raw PG, the produced CaS and the obtained residue were determined after digestion (microwave and traditional acid leaching) using ICP-OES. The effect of CO2 and H2S used in the process of forming CaCO3 and S from PG on the concentrations of REEs was also investigated. Microwave digestion proved to be more effective than traditional acid leaching in the recovery of REEs. Microwave digestion using 3 mL HNO3 + 1 mL HCl was more effective than 1 mL HNO3 + 3 mL in REEs recovery. CaS contained the highest amount of Ce, Pr, Nd, Sm, Eu, Gd, Dy, Ho, Er, La and Y with values of 2646, 476, 2255, 320, 60.5, 376, 79.8, 1.24, 476, 1185 and 318 µg/g respectively. Based on these findings, the residue could be further processed to recover REEs despite less than 40% decrease in concentration for the majority of REEs observed due to the use of H2S and CO2. CO2 was found to be more suitable as fewer REEs were leached as compared to H2S. All things considered, the obtained residue could be a good secondary source of REEs as it is easier to leach, retained good amount of REEs and lesser impurities.
A developed distributed ledger technology architectural layer framework for decentralized governance implementation in virtual enterprise
Authors: Anthony Jnr. Bokolo 
Published: March 2023

AbstractDistributed Ledger technology (DLT) has recently emerged as a disruptive system with a wide range of applicability, with prospect to improve societal interactions at large. In virtual enterprise (VE) context researchers and practitioners have started to investigate the deployment of DLT to automate the processing of data and implementation of decisions to support the provision of digital services. Although academic interest in this domain is growing, a practical analysis of DLT from a governance perspective is still lacking to date. Accordingly, this study aims to fill this gap and provide implications related to decentralized governance of DLT. This article develops an architectural governance-by-design framework that defines the governance of DLT as a combination of architectural layers and governance of DLT dimensions. Design science is employed, and IOTA tangle an open-source DLT which employs a decentralized asynchronous network is deployed to evaluate the applicability of the developed architectural governance-by-design framework through qualitative interviews and literature inquiry. The findings confirm the developed architectural governance-by-design framework and offer a shared discussion and insight surrounding the topic of governance of DLT. The findings also identify limitations associated with governance of DLT solutions and proposes policy recommendations to be used as guidelines for practitioners to improve the adoption of DLT to accelerate VE digitalization.