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Currently, no objective method exists to measure the extent of fibrosis in swallowing musculature in head and neck cancer (HNC) patients. We developed and psychometrically tested a method of quantifying fibrosis volume using magnetic resonance imaging (MRI). The overall aim of this study was to determine if clinical MRI is a reliable tool to measure fibrosis of the pharyngeal musculature in patients with HNC managed with RT and to assess its potential to capture changes in fibrosis over time. Eligible participants were adults with HNC treated with radiation therapy (RT) who received minimally two MRIs and videofluoroscopic swallow (VFS) studies from baseline (pre-RT) up to 1-year post-RT. Two neuroradiologists independently contoured fibrosis volume in batches from MRIs using Vitrea™. Sufficient inter-rater reliability was set at Intraclass Correlation Coefficient (ICC) > 0.75. Two speech-language pathologists independently rated VFSs for swallowing impairment using standardized scales, with discrepancies resolved by consensus. MRI and VFS scores were correlated using Spearman's rank coefficient. Participants included 42 adults (male = 33); mean age 59 (SD = 8.8). ICC (95% Confidence Interval) for fibrosis volume was 0.34 (0, 0.76) for batch one and 0.43 (0, 0.82) for batch two. Consensus meetings were held after each batch. Sufficient reliability was reached by batch three (ICC = 0.95 (0.79, 0.99)). Fibrosis volume increased significantly from 3 to 12 months (mean change = 1.28 mL (SD = 5.21), p = 0.006), as did pharyngeal impairment from baseline to 12 months (mean score change = 3.05 (SD = 3.02), p = 0.003). Fibrosis volume moderately correlated with pharyngeal impairment at 3 and 12 months (0.49, p = 0.004 and 0.59, p = 0.005, respectively). We demonstrated a reliable measure of fibrosis volume in swallowing musculature from existing clinical MRIs and identified that larger fibrosis volume was associated with worse swallowing function. The reliable capture of fibrosis volume offers a pragmatic method for early detection of fibrosis and concomitant dysphagia., Competing Interests: Declarations. Conflict of interest: The authors have no relevant financial or non-financial interests to disclose., (© 2024. Crown.)

Fascinatingly, an abundance of recent studies has subscribed to the importance of cytotoxic immune mechanisms that appear to increase the risk/trigger for many progressive neurodegenerative disorders, including Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis, and multiple sclerosis. Events associated with the neuroinflammatory cascades, such as ageing, immunologic dysfunction, and eventually disruption of the blood-brain barrier and the "cytokine storm", appear to be orchestrated mainly through the activation of microglial cells and communication with the neurons. The inflammatory processes prompt cellular protein dyshomeostasis. Parkinson's and Alzheimer's disease share a common feature marked by characteristic pathological hallmarks of abnormal neuronal protein accumulation. These Lewy bodies contain misfolded α-synuclein aggregates in PD or in the case of AD, they are Aβ deposits and tau-containing neurofibrillary tangles. Subsequently, these abnormal protein aggregates further elicit neurotoxic processes and events which contribute to the onset of neurodegeneration and to its progression including aggravation of neuroinflammation. However, there is a caveat for exclusively linking neuroinflammation with neurodegeneration, since it's highly unlikely that immune dysregulation is the only factor that contributes to the manifestation of many of these neurodegenerative disorders. It is unquestionably a complex interaction with other factors such as genetics, age, and environment. This endorses the "multiple hit hypothesis". Consequently, if the host has a genetic susceptibility coupled to an age-related weakened immune system, this makes them more susceptible to the virus/bacteria-related infection. This may trigger the onset of chronic cytotoxic neuroinflammatory processes leading to protein dyshomeostasis and accumulation, and finally, these events lead to neuronal destruction. Here, we differentiate "neuroinflammation" and "inflammation" with regard to the involvement of the blood-brain barrier, which seems to be intact in the case of neuroinflammation but defect in the case of inflammation. There is a neuroinflammation-inflammation continuum with regard to virus-induced brain affection. Therefore, we propose a staging of this process, which might be further developed by adding blood- and CSF parameters, their stage-dependent composition and stage-dependent severeness grade. If so, this might be suitable to optimise therapeutic strategies to fight brain neuroinflammation in its beginning and avoid inflammation at all., (© 2024. The Author(s).)

This article deals with the interrelationship between body, mind and culture with respect to being healthy and being ill. If one wants to treat not only sickness but also sick people, it is helpful to be aware not only of the somatic and psychological dimensions of a disease but also of the "cultural" dimension of a disease. Based on personal reflections and supplemented by a focused literature search this article provides insights into how cultural influences not only affect the experience of illness but also decide how an illness is dealt with individually and socially. Furthermore, it is shown that not only being sick but also the sick body can be understood in somatic, psychological and cultural dimensions and that a distinction must be made between the body as it physically is and as it is subjectively perceived. Finally, an insight into the complexity of the somatopsychic and psychosomatic interactions is provided in order to derivatively show how mental stress can lead to physical pain and physical pain can become a mental stressor., Competing Interests: Einhaltung ethischer Richtlinien Interessenkonflikt J. Tesarz gibt an, dass kein Interessenkonflikt besteht.Für diesen Beitrag wurden von den Autor/-innen keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Aerobic exercises like running and cycling may lower cardiovascular disease (CVD) risk through favorable effects on central blood pressure and vascular function. Arm ergometry is a popular exercise modality used in rehabilitation settings, but little is known regarding the central hemodynamic and vascular effects of this form of exercise., Purpose: To compare the acute effects of leg versus arm exercise on central blood pressure and vascular function., Methods: Twenty-one participants (n = 11 female, Age 21 ± 3, BMI 24.5 ± 3.2 kg/m 2 ) completed two visits to the Human Performance Laboratory. Central systolic blood pressure (cSBP), central diastolic blood pressure (cDBP), and peripheral augmentation index (pAIx) were measured using a brachial oscillometric blood pressure cuff with measures being taken before and after 20 min of acute moderate-intensity (submaximal) arm or leg cycling exercise., Results: There was a condition-by-time interaction for pAIx (p = 0.011). pAIx slightly increased following arm exercise but significantly decreased following leg exercise. There was a condition-by-time interaction for cDBP (p = 0.011). cDBP significantly decreased following arm exercise but increased immediately following leg exercise. There was no condition-by-time interaction for cSBP (p = 0.721). There were similar acute increases in cSBP immediately post-exercise for both conditions., Conclusion: Arm exercise increased pAlx and decreased cDBP compared to leg exercise. As an increase in pAIx may increase left ventricular work and a reduction in cDBP may reduce coronary perfusion pressure, these findings suggest that a single bout of arm exercise may not have the same favorable acute effect on central hemodynamic load as a single bout of leg exercise., Competing Interests: Declarations Conflict of interest We have no conflicts of interest to disclose., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Herein, transient releases either from NADH-loaded liposomes or enzymatic reactions confined in giant liposomes were imaged by electrochemiluminescence (ECL). NADH was first encapsulated with the [Ru(bpy) 3 ] 2+ luminophore inside giant liposomes (around 100 µm in diameter) made of DOPC/DOPG phospholipids (i.e., 1,2-dioleolyl-sn-glycero-3-phosphocholine/1,2-dioleoyl-sn-glycerol-3-phospho-(1'-rac-glycerol) sodium salt) on their inner- and outer-leaflet, respectively. Then, membrane permeabilization triggered upon contact between the liposome and a polarized ITO electrode surface and ECL was locally generated. Combination of amperometry, photoluminescence, and ECL provided a comprehensive monitoring of a single liposome opening and content release. In a second part, the work is focused on the ECL characterization of NADH produced by glucose dehydrogenase (GDH)-catalyzed oxidation of glucose in the confined environment delimited by the liposome membrane. This was achieved by encapsulating both the ECL and catalytic reagents (i.e., the GDH, glucose, NAD + , and [Ru(bpy) 3 ] 2+ ) in the liposome. In accordance with the results obtained, NADH can be used as a biologically compatible ECL co-reactant to image membrane permeabilization events of giant liposomes. Under these conditions, the ECL signal duration was rather long (around 10 s). Since many enzymatic reactions involve the NADH/NAD + redox couple, this work opens up interesting prospects for the characterization of enzymatic reactions taking place notably in artificial cells and in confined environments., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Recent advancements in synthesis and sequencing techniques have made deoxyribonucleic acid (DNA) a promising alternative for next-generation digital storage. As it approaches practical application, ensuring the security of DNA-stored information has become a critical problem. Deniable encryption allows the decryption of different information from the same ciphertext, ensuring that the "plausible" fake information can be provided when users are coerced to reveal the real information. In this paper, we propose a deniable encryption method that uniquely leverages DNA noise channels. Specifically, true and fake messages are encrypted by two similar modulation carriers and subsequently obfuscated by inherent errors. Experiment results demonstrate that our method not only can conceal true information among fake ones indistinguishably, but also allow both the coercive adversary and the legitimate receiver to decrypt the intended information accurately. Further security analysis validates the resistance of our method against various typical attacks. Compared with conventional DNA cryptography methods based on complex biological operations, our method offers superior practicality and reliability, positioning it as an ideal solution for data encryption in future large-scale DNA storage applications., (© 2024. International Association of Scientists in the Interdisciplinary Areas.)

Electric stimulation (ES) is a versatile technique that uses an electric field to manipulate microorganisms individually. Over the past several decades, the capabilities of ES have expanded from bioremediation to the precise motion control of cells and microorganisms. However, there is limited information on the underlying mechanisms, latest advancement and broader microbial applications of ES in various fields, such as the production of extracellular polymers with upgraded properties. This review article summarizes recent advancements in ES and discusses it as a unique external manipulation technique for microorganisms with wide applications in bioremediation, industry, biofilm deactivation, disinfection, and controlled biosynthesis. One specific application of ES discussed in this review is the extracellular biosynthesis, regulation, and organization of extracellular polymers, such as bacterial cellulose nanofibrils, curdlan, and microbial nanowires. Overall, this review aims to provide a platform for microbial biotechnologists and synthetic biologists to leverage the manipulation of microorganisms using ES for bio-based applications, including the production of extracellular polymers with enhanced properties. Researchers can engineer, manipulate, and control microorganisms for various applications by harnessing the potential of electric fields., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Sulfite, widely used as a food additive, performs indispensable functions in the field of food sterilization, bleaching, and antisepsis. However, the overuse of sulfite may destroy food nutrition and pose health risks to people. In this work, an innovative BODIPY-based fluorescent probe (BODIPY-DBC) was constructed for highly sensitive recognition of sulfite. The BODIPY-DBC probe possessed both colorimetric and ratiometric dual mode, a low detection limit (33.12 nM), high sensitivity, a wide pH usage range (5-12), a fast response time (2 min), and superior fluorescence imaging capability for detecting sulfite. The recognition mechanism was certificated by 1 H NMR titration, HRMS analysis, and DFT calculation. The BODIPY-DBC probe was not only loaded on test strips for detecting sulfite conveniently with the naked eye, but also employed to detect sulfite content in real food samples to ensure food safety. Furthermore, it also achieved excellent performances for monitoring sulfite in dual-channel fluorescence imaging (HeLa cell and zebrafish)., Competing Interests: Declarations. Ethics declarations: All animal experiments were approved by the Animal Ethical Committee of the Nanjing University of Chinese Medicine and conducted in strict accordance with the National Care and use of Laboratory Animals by the National Animal Research Authority (China). Conflict of interest: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

A multienzyme-like L-argininemodified CeO 2  (Arg-CeO 2 ) nanozyme was prepared for accurate total antioxidant capacity (TAC) determination of Ganoderma sichuanense (G. sichuanense). It exhibits oxidase-like and peroxidase-like activities catalyzing the generation of superoxide anion free radicals and hydroxyl radicals, accelerating 3, 3', 5, 5'-tetramethylbenzidine (TMB) chromogenic reaction. Antioxidants can effectively eliminate the generated free radicals, inhibiting the TMB chromogenic reaction. Hence, TAC can be assessed by Arg-CeO 2  catalyzed TMB chromogenic reaction using ascorbic acid (AA) as a reference substance. TAC of G. sichuanense extracted using different solvents was determined, indicating the highest TAC observed in the G. sichuanense extracted by the mixture solvent (deionized water/ethanol/ethyl acetate = 1 : 1 : 1). A visual assessment platform based on Arg-CeO 2  hydrogel nanozyme utilizing a self-programmed smartphone app and a self-designed 3D printed device is established. TAC using AA as a reference substance (3.33 ~ 83.33 µM) can be detected with a detection limit as low as 0.58 µM. The platform can realize one-step quantitative determination of TAC in G. sichuanense within 40 min. The proposed visual assessment platform presented exhibits promising application prospects in the field of TAC assessment in food., Competing Interests: Declarations. Ethical approval: This research did not involve human or animal samples. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Polyethyleneimine (PEI) based fluorescent polymeric nanorods with high quantum yield (87.21%) were synthesized by crosslinking and self-assembly of PEI by vitamin B 6 cofactor pyridoxal 5'-phosphate (PLP). The fluorescent PEIPLP polymeric nanorods were employed for the ratiometric detection of doxorubicin (DOX). With the addition of DOX to the PEIPLP nanorods, the fluorescent intensity was decreased at 510 nm and concomitantly enhanced at 590 nm due to the fluorescence resonance energy transfer (FRET) process. The selective and specific ratiometric fluorescence response from the PEIPLP nanorods can be employed to detect DOX down to 10 nM. The practical utility of the PEIPLP nanorods was examined by detecting DOX in human serum., Competing Interests: Declarations. Ethics approval: Not applicable as the study does not include any use of animals and humans. Consent to participate: Not applicable. Consent to Publish: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Purpose: The aim of the current study was to determine whether gait control (muscle synergies) or gait stability (margin of stability (MoS)) were different between younger and older adults when walking on level or downhill slopes. Further, it sought to determine associations between either age or physical activity with muscle synergy widths., Methods: Ten healthy younger (28.1 ± 8.0 years) and ten healthy older (69.5 ± 6.3 years) adults walked at their preferred walking speed on a treadmill at different slopes (0˚, - 4˚ and - 8˚). Muscle synergies were extracted using non-negative matrix factorisation and compared between groups and walking slopes. Correlations between the full width at half maximum (FWHM) of the synergies' activations and weekly recreational physical activity minutes and age were also determined., Results: Younger and older adults both walked with similar muscle synergies across all tested slopes, with 4 synergies accounting for > 85% variance of overall muscle activity in both groups across all tested slopes, with high scalar products (≥ 0.86) for each synergy and slope. It was also demonstrated that physical activity and age had different associations with pooled muscle synergies across slopes, as weekly minutes spent in recreational physical activity were associated with the FWHM of a synergy activated at weight acceptance, whereas age was associated with the FWHM of synergies occurring at push off and foot clearance, respectively., Conclusion: Our results suggest that healthy older and younger adults walk with similar muscle synergies on downhill slopes, and that physical activity and age influence different muscle synergies during walking., Competing Interests: Declarations. Conflict of interest: The authors have no relevant financial or non-financial interests to disclose. Ethical approval: The project was granted ethical approval by the Western Sydney University Human Research Ethics Committee (Approval number: H11409). Consent to participate: Informed consent was obtained from all individual participants included in the study., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The synthesis of a novel bidentate ligand-protected copper nanocluster via a solid-state strategy is reported. Single-crystal X-ray diffraction analysis result reveals that the copper nanocluster features an octahedral core (Cu 6 ) coordinated by six ligands. Noncovalent interactions (C-H … π and π … π) exist between the copper nanoclusters. The copper nanocluster displays luminescence even at 250 °C. The luminescence intensity is linearly correlated with temperature changes. The copper nanocluster can assemble into luminescent nanosheets whose emission is quenched by 4-nitrophenol. Spectroscopic analysis and theoretical calculations results demonstrate that the inner filter effect and electron transfer cause the above quenching effect. A probe based on luminescent nanosheets was constructed for β-galactosidase activity determination. The linearity range is 3.3-91.8 U·L -1 , and the limit of detection is 0.45 U·L -1 . This probe was also evaluated for determination of the β-galactosidase activity in human serum via spiking experiments. The recoveries ranged from 96.2% to 101.8%., Competing Interests: Declarations. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Surface functionalization and the combined utilization of zero-dimensional and two-dimensional nanomaterials is an effective method to achieve highly sensitive detection for electrochemical analysis. Using an all-in-one strategy, phthalocyanine, gold nanoparticles, and ionic liquid were successively modified on the graphene surface as a highly integrated electrode modification material. Phthalocyanine can repair the defects of reduced graphene oxide by binding to the graphene structure surface through non-covalent functionalization. The combination of ionic liquid on the surface of gold nanoparticles can enhance their physical and chemical activity while preserving their stability. The obtained phthalocyanine-coated graphene nanosheets decorated with ionic liquid-functionalized gold nanoparticles nanocomposites had enhanced electrocatalysis and conductivity ability, and were used for highly sensitive electrochemical detection of ascorbic acid in fruit juices. Excellent results were obtained for the detection of ascorbic acid in the linear range 0.05 to 50 µmol/L with a detection limit of 6.80 nmol/L (S/N = 3) and a sensitivity of 2.68 μA μM -1  cm -2 , indicated that the proposed sensor strategy with multiple signal amplification can achieve higher detection sensitivity. Furthermore, the sensor was used to quantify ascorbic acid content in grapefruit and orange juice with good selectivity and accuracy. The highly integrated electroactive nanocomposites construction method described may also be used with other electrode modification materials and is anticipated to yield fresh perspectives on the advancement of ultrasensitive detection., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Metal ion pollution poses a global concern due to its significant risks to both human health and environmental well-being. The toxicity of these ions can increase when they coexist, interacting with each other and with other harmful substances, even at low concentrations. Therefore, an accurate, rapid, and cost-effective methodology is urgently needed for the simultaneous quantification of multiple metal ions. This study presents a new approach for the multiplexed detection of various metal ions (Ag + , Cu 2+ , Hg 2+ , Al 3+ , Pb 2+ , Fe 3+ , Fe 2+ , Zn 2+ , Ni 2+ , Cd 2+ , and Ca 2+ ) using a triple-emission nanoprobe comprising carbon dots and distinctly capped CdTe quantum dots, specifically green-emitting glutathione -quantum dots and red-emitting 3-mercaptopropionic acid-quantum dots. The method achieved high accuracy by analysing first- and second-order photoluminescence data with distinct advanced chemometric tools. R 2 P values for partial least squares and unfolded partial least square models exceeding 0.9 for several metal ions at low concentrations (mmol L -1 ) were obtained. Additionally, PL second-order data yielded significantly better results than PL first-order data, attributed to the distinct behaviour of the metal ions over time. Interestingly, it was also noted for the first time the significant contribution of the molar ratio between the metal ions on the models' accuracy. This novel method provides a highly accurate and efficient way to detect multiple metal ions simultaneously, paving the way for improved environmental monitoring and pollution assessment. The utilization of the proposed method contributes to a better understanding of the complex interactions in mixed metal ion systems, allowing for earlier detection and mitigation of metal ion contamination threats., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: Clinicians monitor scoliosis progression using radiographs during growth. Three standing positions were assessed because the arms must be elevated to visualize all vertebrae on radiographs, possibly affecting sagittal parameters. 3D Ultrasound (3DUS) is safe to assess positions without radiation, but its test-retest reliability has not been established for common radiograph positions. The aim was to determine the test-retest reliability of frontal, sagittal, and transverse measurements obtained from three positions using 3DUS imaging., Methods: Participants with AIS were recruited from a clinic in Alberta. Participants underwent 3DUS scans in habitual standing, fingers to clavicle, and hands on wall. Participants were re-scanned in the same positions 20-min following first scans. Custom software obtained measurements. Test-retest reliability (ICC 3,1 ) with standard error of measurement (SEM) was assessed by one evaluator who was blinded to the test measurement when completing retest., Results: Forty-three participants with AIS had an age, height, and weight of 15 ± 2 years, 164 ± 10 cm, and 54 ± 11 kg, respectively. Standing curve angle was 23 ± 11°. Habitual standing max curve angle, T4/T5 kyphosis, and AVR twist satisfied criteria for individual use (ICC 2,1  > 0.90). Fingers to clavicle AVR twist satisfied criteria for individual use, and all hands on wall measurements satisfied criteria for individual use (ICC > 0.90). All other parameters satisfied criteria for research use (ICC > 0.70). Range of SEM for curve angle, whole kyphosis, T4/T5 kyphosis, lordosis, and AVR twist were 3.0-4.8°, 4.0-5.1°, 3.6-5.3°, 3.9-5.6°, and 1.6-2.2°, respectively., Conclusion: 3DUS produces reliable frontal, sagittal, and transverse measurements for research use in three standing positions. Hands on wall produces reliable measurements for clinical practice., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflict of interest. Consent to participate: Written assent was obtained from all individual participants under the age of 18 included in this study. Written parental consent was obtained from the parents of participants under the age of 18. Written consent was obtained from all individual participants 18 years old. Ethical approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Health Research Ethics Board of the University of Alberta PRO00111881., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Fragile X syndrome (FXS) is the leading hereditary cause of intellectual disability and the most commonly associated genetic cause of autism. Historically, research into its pathophysiology has focused predominantly on neurons; however, emerging evidence suggests involvement of additional cell types and systems. The objective of this study was to review and synthesize current evidence regarding the pathophysiology of Fragile X syndrome. A comprehensive literature review was conducted using databases such as PubMed and Google Scholar, employing MeSH terms including "Fragile X Syndrome," "FMR1 gene," and "FMRP." Studies on both human and animal models, from inception to 2022, published in recognized journals were included. The evidence supports those neurons, glial cells, stem cells, the immune system, and lipid metabolism pathways contribute to the pathophysiology of Fragile X syndrome. Further research is necessary to explore these fields independently and to elucidate their interactions., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Declaration of AI utilization: In the preparation of this manuscript, artificial intelligence tools were utilized exclusively for tasks such as language refinement and grammar checks, while ensuring that all scientific analysis, interpretation, and conclusions remain the work of the authors., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Droplet-based bioprinting (DBB) allows for high precision, noncontact, and on-demand distribution of bioinks, hence it has been widely utilized in the preparation of bacteria-laden living materials (BLMs). Nonetheless, discontinuous ink deposition makes it challenging to fabricate large-sized intact living structures via this technique. Herein, we explore the way of using DBB to construct centimeter-scale BLMs with bespoke geometries, and further demonstrate its potential applicability in sensing-responsive device by integrating engineered bacteria. We first established a DBB method based on printing-path design, which does not require hardware modification. This strategy was able to produce customized 3D-hydrogel structures with high shape fidelity. Then, we confirmed the excellent biocompatibility of the above biofabrication approach. The Escherichia coli survived 93% ± 4.0% in printed BLMs, with uniform distribution throughout the structure. As a proof-of-concept, we finally manufactured a test strip-like heavy metal biosensor capable of plug-and-play detecting mercury (II) in water using the aforesaid approach. To our knowledge, this is the first study to employ 3D bioprinted BLMs for the detection of prevalent heavy metal pollutants. Our research shed light on the versatility of DBB in BLMs construction, which is not restricted to two-dimensional patterns. Moreover, our results are expected to innovate heavy metal biodetection and improve detection efficiency and sensitivity., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Considering the high incidence of breast cancer, a sensitive and specific approach is crucial for its early diagnosis and follow-up treatment. Folate receptors (FR), which are highly expressed on the epithelial tissue such as breast cancer cells (e.g., MCF-7), have been used in cancer diagnosis and bioimaging. This study presents an innovative colorimetric and fluorescence bioimaging platform towards MCF-7 using folic acid (FA)-conjugated iron-oxide magnetite silica-based nanocomposite (Fe 3 O 4 @SiO 2 -3-aminopropyl)triethoxysilane (APTES-NH 2 )@cysteine (Cyt)-Cyt@FA). For identification of MCF-7, the polyvinylpyrrolidone (PVP)-capped-platinum (Pt) nanoparticle was utilized as a nanozyme to catalyze the reaction between 3,3',5,5'-tetramethylbenzidine (TMB) and H 2 O 2 for visual detection of MCF-7 cells. Colorimetric changes are detectable by the naked eye and spectrophotometry at the wavelength of 450 nm, with a linear range of 50-5000 cells/mL and a detection limit of 30 cells/mL. The Fe 3 O 4 @SiO 2 -APTES-NH 2 @Cyt-Cyt@FA complex was modified with rhodamine B as a fluorescence bioimaging probe to monitor FR-overexpressed MCF-7 cells. The nanocomposite is biocompatible with a toxicity threshold of about 800 µg/mL. These methodologies facilitate bioimaging and colorimetric assays without sophisticated instrumentation, offering high specificity, sensitivity, repeatability, and stability, making them suitable as versatile methods for detecting and bioimaging cancer cells., Competing Interests: Declarations. Ethical approval: All procedures have been implemented with the permission of the “National Institutes for Medical Research Development” (License number: IR.NIMAD.REC.1400.133). Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Objectives: To determine the Incremental Cost-Utility Ratio (ICUR) of cochlear implantation in the treatment of adult patients with single-sided deafness (SSD) and asymmetric hearing loss (AHL)., Methods: This prospective multicenter pragmatic study including a randomized controlled trial (RCT) enrolled 155 subjects with SSD or AHL. Subjects chose a treatment option between: abstention, Contralateral Routing Of the Signal hearing aids, Bone Conduction Device or Cochlear Implant (CI). Participants who opted for CI were then randomized between two arms: "immediate CI" where the cochlear implantation was performed within one month and "initial observation" where subjects were first observed. The ICUR of CI was determined at 6 months follow-up by comparing the two arms. Utility was measured using EuroQoL- 5 dimensions (EQ-5D), to calculate the gain in Quality-Adjusted Life Years (QALY). Individual costs were extracted from the French National Health Insurance database. A Markovian MultiState (MMS) model assessed the ICUR evolution over the lifetime horizon., Results: Among the 155 included participants, 51 opted for a CI and were randomized. For a 6 months follow-up period, the ICUR was €422,279/QALY gained after CI. Using the MMS model, the ICUR of CI decreased to €57,561/QALY at 10 years follow-up, €38,006/QALY at 20 years, and dropped to €26,715 at 50 years. In the participants with severe tinnitus, mean ICUR was €31,105/QALY at 10 years., Conclusions: CI can be considered as an efficient treatment in SSD and AHL from 20 years follow-up in the global population, and before 10 years follow-up in patients with severe associated tinnitus., Competing Interests: Declarations Conflict of interest The authors have no conflicts of interest to declare., (© 2024. The Author(s).)

Posterior fossa anomalies are less common in prenatal diagnosis than midline anomalies or ventricular dilatations. However, they constitute an important entity, combining neurological disorders as well as normal variants that should be recognized in prenatal diagnosis because of the genetic implications and neurodevelopmental outcome of some of these conditions. Here we present some of the main imaging features enabling prenatal diagnosis of posterior fossa anomalies in a context of constantly evolving classifications, resulting from advances in genetics and neuroimaging., Competing Interests: Declarations Conflicts of interest None, (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A facile and highly specific optical sensing strategy is established for glyphosate (GLYP) detection using structure-switching signaling aptamers (F-SSSAs) with fluorescence signal reporting functionality. The strategy involves two domains: the FITC-labeled signal transduction domain for fluorescence signal reporting, while the functional domain (specific structure-switching aptamers) controls the target recognition. Graphene oxide (GO) works as a robust F-SSSAs quencher in the absence of GLYP. However, the F-SSSAs structure is switched in the presence of GLYP, prominently affecting the interaction with GO. The fluorescence of the structure-switching signaling aptamer-based sensing system is subsequently restored. The present strategy exhibits two dynamic linear relationships for GLYP detection in the ranges 0.2 to 80 ng·mL -1 and 100 to 800 ng·mL -1 , with a low detection limit (LOD) of 0.07 ng·mL -1 . Significantly, the proposed sensing system has been successfully utilized to detect GLYP in water, soil, and rice, demonstrating its potential applications in GLYP monitoring., Competing Interests: Declarations Ethical approval This research did not involve human or animal samples. Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Artificial intelligence (AI) is increasingly recognized for its transformative potential in radiology; yet, its application in pediatric radiology is relatively limited when compared to the whole of radiology. This manuscript introduces pediatric radiologists to essential AI concepts, including topics such as use case, data science, machine learning, deep learning, natural language processing, and generative AI as well as basics of AI training and validating. We outline the unique challenges of applying AI in pediatric imaging, such as data scarcity and distinct clinical characteristics, and discuss the current uses of AI in pediatric radiology, including both image interpretive and non-interpretive tasks. With this overview, we aim to equip pediatric radiologists with the foundational knowledge needed to engage with AI tools and inspire further exploration and innovation in the field., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A fluorescence (FL)-based nanosensor has been devised for creatinine (CR) detection in human urine specimens. The proposed nanosensor utilized a nanocomposite (NC) of carbon dots (CDs) and graphene oxide (GO). The formation of CDs/GO NC reduced the CD FL emission (λ excitation  = 390 nm, λ emission  = 461 nm) by ~ 75%. With the introduction of CR to the NC, the CD emission intensity was reinstated by approximately 70%. The linear detection range for CR was 10 -5 to 0.1 mg dL -1 (R 2  = 0.998), with a limit of detection of 4.3 × 10 -2  mg dL -1 . Additionally, CDs/GO NC exhibited outstanding consistency and specificity in recognizing CR within urine specimens from both healthy individuals and patients suffering from chronic kidney disease (CKD). The Bland-Altman assessment (utilizing 25 human urine specimens) displayed remarkable consensus (R 2  = 0.995) among the FL approach and the benchmark Jaffe technique. This observation indicates the hands-on usefulness of the nanosensor for identifying CR in biological specimens., Competing Interests: Declarations Ethical approval Ethical approval for collecting patient urine samples was obtained by the Institutional ethical committee and due consent was obtained from the subjects prior to sample collection. Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Purpose: Cancer outcome is dependent on multiple predetermining factors including cancer, type of cancer and its related factors. This study aims to investigate the association between COVID-19 & cancer/cancer types, focusing on risk of in-hospital mortality within 30 days of hospitalization of COVID-19 patients with cancer., Materials and Methods: We did a registry (National Clinical Registry for COVID-19) based retrospective observational study including 51,544 patients, of whom 976 were patients with cancer, admitted with COVID-19 between August 2020 and August 2023 across 42 hospitals of India., Results: Out of 51,544 patients, 976 (1.8%) had cancer. Hematological malignancies made up 15.06% (147 cases), while solid cancers accounted for 29.5% (288 cases), with genitourinary (18.4%, 80 cases), gastrointestinal (15.2%, 49 cases), and lung cancers (10.1%, 34 cases) being the most common. Solid cancers had the highest in-hospital mortality rate at 25%. Survival analysis showed that cancer-related hazards were highest at admission but decreased to levels comparable with other morbidities within nine to ten days. For each cancer type, the hazard was significantly elevated compared to that of the cancer-free (Other Comorbidities and No Comorbiditiy) groups during the initial period of hospitalization. The use of Remdesivir, steroids, and anticoagulants reduced mortality risk, and prior COVID-19 vaccination was protective against mortality across all cancer types., Conclusion: This study shows that both cancer in general and specific cancer types significantly increase the risk of severe outcomes among SARS-CoV-2-infected patients, especially immediately after hospitalization. The findings highlight the need for close monitoring and personalized interventions for COVID-19 patients with cancer for at least 10 days post-hospitalization, with a more specific high-risk period ranging from 7 to 18 days depending on the type of cancer., Competing Interests: Declarations Conflict of interest The authors declare no competing interests., (© 2024. The Author(s).)

Eating and drinking are fundamental to life. However, older patients are often restricted with oral intake due to feared risk of aspiration. Eating and Drinking with Acknowledged Risks (EDAR) is an alternative process which enables comfort, dignity, and autonomy for these patients. While national guidance has been developed for EDAR in the UK, other ageing societies such as Japan do not have such guidance. To understand the perspectives and experiences of healthcare professionals regarding the complex decision-making process around EDAR we planned a mixed methods study comparing the two countries. This was the qualitative phase of the study. Twelve healthcare professionals (two doctors, nurses and speech and language therapists each in Japan and the UK) participated in semi-structured interviews on their roles and experiences related to EDAR in older adults. We analysed the data thematically, and three themes emerged: (1) healthcare professionals and healthcare systems, (2) priorities in decision-making and (3) relationship with family and patient. There were many similarities but also differences across the countries, in the setting, training and individual experience. Decision-making was shaped by a complex combination of individual, structural and cultural factors, which indicated in the Japanese culture a greater likeliness to defer clinical decision-making and to side with families' wishes. Healthcare professionals' experiences and attitudes towards EDAR differed depending on various factors related with the individual and environment. The next quantitative phase of our research aims to establish the mechanism to increase confidence around EDAR in professionals and training options., Competing Interests: Declarations Ethical Approval Ethical approval was provided by the Ethics Committee of Hashimoto Municipal Hospital in Japan (ID R2.10-1) and the Health Research Authority and Health and Care Research Wales in the UK (ID 321158). Written informed consent was obtained from each participant. Competing Interests Yuki Yoshimatsu is supported by the Japanese Respiratory Society Fellowship Grant (2021). This study was funded by the Great Britain Sasakawa Foundation (Butterfield Award, B149). The funders had no involvement in the study design or conduction. The authors received no other financial support for the research, authorship and publication of this article. The authors declare that they have no other competing interests., (© 2024. The Author(s).)

Escherichia coli (E. coli) O157:H7 is an important food-borne pathogen that can cause hemorrhagic diarrhea and enteritis in humans and animals. Realizing the rapid quantitation of E. coli O157:H7 is of great significance for the guarantee of food safety and disease control. In this study, an electrochemical immunosensing technique based on a functionalized composite of Cu-metal organic framework (Cu-MOF) and poly (3,4-ethylenedioxythiophene)-poly (styrenesulfonate) (PEDOT:PSS) is developed, achieving rapid and sensitive quantitation of E. coli O157:H7 in food and clinical feces samples. The organic functionalization of Cu-MOF significantly improves the interface conductivity to facilitate electron transfer and provides the sulfonic groups (-SO 3 H) to conjugate bio-recognizing elements for target determination. The immunosensor delivers a linear detection range of 3 × 10 2  ~ 3 × 10 8  cfu/mL, a low limit of detection (LOD) of 7.4 cfu/mL, and a short analysis time of 40 min. In addition, it does not show any cross-reactivity with other common pathogens and exhibits high repeatability with relative standard deviations (RSDs) all lower than 2.09%, providing a promising approach for warranting  food safety and control of E. coli O157:H7 disease., Competing Interests: Declarations Ethical approval Not applicable. Conflict of interest The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Breast cancer (BC), a widespread and lethal neoplasm, is irrespective of the subtype of BC. Metastasis remains a crucial determinant for unfavorable outcome. The identification of novel diagnostic markers is instrumental in optimizing the treatment regime for BC. The direct correlation between anoikis and the progression/outcome of BC is well established. Nevertheless, the contribution of anoikis-related genes (ARGs) in BC remains obscure at present. We implemented the METABRIC dataset to scrutinize and assess differentially expressed ARGs in BC versus healthy breast tissues. An unsupervised consensus clustering approach for ARGs was employed to classify patients into diverse subtypes. ESTIMATE algorithms were utilized to assess immune infiltrative patterns. Prognostic gene expression patterns were derived from LASSO regression and univariate COX regression analysis. Subsequently, these signatures underwent examination via use of the Kaplan-Meier survival curve. 6 pairs of fresh tissue specimens (tumor and adjacent non-tumor) were employed to assess the expression of 7 ARGs genes via qPCR. Notably, DCN and FOS were not expressed in BC tissue, which had been excluded in our subsequent experiments. Also, among remaining 5 ARGs, solely the expression of ADH1A demonstrated a statistically remarkable disparity between freshly collected cancer tissues and the adjacent ones. ADH1A-overexpressed and ADH1A-sh vectors were transfected into MCF-7 and MCF-7-AR cell lines, respectively. The expression status of FABP4, CALML5, ADH1A, C1orf106, CIDEC, β-catenin, N-cadherin, and Vimentin in the clinical samples were scrutinized using RT-qPCR and western blotting techniques. Migration and invasion through transwell chambers were employed to assess the migratory and invasive potential of the cells. Detailed evaluation of cell proliferation was conducted utilizing a Cell Counting Kit-8 (CCK-8) assay. The apoptotic index of the cells was determined by flow cytometry analysis. An innovative anoikis-associated signature consisting of seven genes, namely ADH1A, DCN, CIEDC, FABP4, FOS, CALML5, and C1orf106, was devised to stratify BC patients into high- and low-risk cohorts. This unique risk assessment model, formulated via the distinctive signature approach, has been validated as an independent prognostic indicator. Additional analysis demonstrated that distinct risk subtypes manifested variances in the tumor microenvironment and drug sensitivities. Suppression of ADH1A enhanced the migratory and invasive capacities and reduced these tumorigenesis-related protein levels, underscoring the prognostic role of ADH1A in the progression of BC. Through our meticulous study, we have elucidated the possible molecular markers and clinical implications of ARGs in BC. Our model, which incorporate seven ARGs, has proven to accurately forecast the survival outcomes of BC patients. Moreover, the thorough molecular study of ADH1A has augmented our comprehension of ARGs in BC and opened a novel avenue for guiding personalized and precise therapeutic interventions for BC patients., Competing Interests: Declarations Conflict of interest The authors declare no conflicts of interest. They are solely responsible for the content and writing of this article. Ethics approval and consent to participate Authors conducting experiments on humans or using human tissue samples must ensure that all experiments were conducted in compliance with relevant guidelines and regulations. The study was approved by the Ethics Committee of the First Affiliated Hospital of Kunming Medical University, and all methods were performed in accordance with applicable guidelines and regulations. Consent for publication All authors have reviewed and approved the final manuscript for publication., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

While antineoplastic therapies aim to specifically target cancer cells, they may also exert adverse effects on healthy tissues, like healthy hematopoietic stem and progenitor cells (HSPC), leading to hematotoxicity as a common side effect. Mesenchymal stromal cells (MSC) are a major component of the bone marrow (BM) microenvironment, regulating normal hematopoiesis, while their susceptibility to anticancer therapies and contribution to therapy-related hematotoxicity remains largely unexplored. To address this, we investigated the effects of etoposide, temozolomide, 5-azacitidine, and venetoclax on healthy BM-derived MSC functionality. Doses below therapeutic effects of etoposide (0.1-0.25 µM) inhibited cellular growth and induced cellular senescence in healthy MSC, accompanied by an increased mRNA expression of CDKN1A, decreased trilineage differentiation capacity, and insufficient hematopoietic support. Pharmacological doses of 5-azacitidine (2.5 µM) shifted MSC differentiation capacity by inhibiting osteogenic capacity but enhancing the chondrogenic lineage, as demonstrated by histochemical staining and on mRNA level. At the highest clinically relevant dose, neither venetoclax (40 nM) nor temozolomide (100 µM) exerted any effects on MSC but clearly inhibited cellular growth of cancer cell lines and primary healthy HSPC, pointing to damage to hematopoietic cells as a major driver of hematotoxicity of these two compounds. Our findings show that besides HSPC, also MSC are sensitive to certain antineoplastic agents, resulting in molecular and functional alterations that may contribute to therapy-related myelosuppression. Understanding these interactions could be helpful for the development of strategies to preserve BM MSC functionality during different kinds of anticancer therapies., Competing Interests: Declarations Conflict of interest The authors declare that they have no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results., (© 2024. The Author(s).)

Effective food safety monitoring requires a multi-step approach from farm to fork, involving different methods, ranging from convenient screening devices to sophisticated laboratory confirmatory testing. However, sample transportation to routine laboratories is time-consuming and expensive. Simplified on-site sampling followed by laboratory analysis offers a potential solution. Dried blood spot (DBS) cards ensure stability and ease of sample transportation and are used in clinical testing. However, the applicability of such an approach could be broader and include the storage of dried extract from more complex (solid) matrices. Therefore, a simplified approach is presented here, using DBS cards for on-site sampling and subsequent laboratory confirmation for food contaminants. To achieve this, an analytical tool (Smartcard) was designed using 3D-printing technology. As a proof of concept, the approach was applied to detect the pesticide fipronil, which is widely used in ornamental flower production to limit pests and on poultry farms. The Smartcard can securely store the sample extracts on a DBS card (dried extract spot (DExS) card), incorporate the lateral flow immunoassay (LFIA) and immediately provide an estimate of contamination levels. After simplified in-syringe extraction of the sample, the LFIA allows direct screening of fipronil (half maximum inhibitory concentration of 6.5 µg/l with calibration standards), and the same sample extract can be directly applied to the DExS card for storage and transport to the laboratory, where analyte re-extraction and instrumental analysis is performed using ultra high-pressure liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) detecting fipronil down to 0.8 µg/kg., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

This study aimed to identify functional challenges faced by individuals with non-esophageal dysphagia and to offer a tool for quantitatively evaluating the person abilities within the framework of the International Classification of Functioning, Disability and Health (ICF). Additionally, this study attempted to differentiate the personal abilities of individuals with dysphagia and hierarchize item difficulties using the ICF-based Item Response Theory (IRT) modeling approach. This cross-sectional study enrolled a cohort of 150 patients with dysphagia (105 male and 45 female) from a tertiary hospital in China. Participants were assigned to evaluate the 114-item ICF dysphagia questionnaire. To further assess their swallowing capabilities, eating patterns, quality of life, and nutritional status, participants underwent a battery of five additional scales. The ICF qualifiers underwent data shaping including dichotomization and missing value imputation, Mokken scale analysis (MSA) for checking unidimensionality, local independence, monotonicity, and invariant item ordering (IIO), and parametric IRT modeling for identifying an optimal model from the 1-parametric logistic model (1PLM), 2PLM, 3PLM, and 4PLM. Finally, we tested the robustness of the optimal model via Monte Carlo simulation and illustrated the usefulness of the model by its person-item map. The 1PLM emerged as the optimal model with a total of 50 ICF items (12 'd-Activities and Participation', 33 'b-Body Functions', and 5 'e-environmental' items). The final scale presented strong reliability with Cronbach's Alpha = 0.967. Furthermore, the scale showed good validity with a significant positive correlation (p < 0.001, r ^ Winsorized = 0.60) between model-estimated person abilities and swallowing-quality of life (SWAL-QoL) scores. The findings also demonstrated measurement equivalence of the final model for individuals with different genders or across various age groups. The utilization of the person-item map can effectively compare the difficulty levels of items with the abilities of patients, thereby facilitating the delivery of tailored care and precise rehabilitation strategies that match the individual competency of those suffering from dysphagia. This study developed a parsimonious dysphagia-specific ICF outcomes tool derived from the IRT, named iSWAL-Performance Scale. The findings complement quantitative information on the psychometric characteristics of this 50-item scale., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

An electrochemiluminescence (ECL) detection system is presented integrated with a bipolar electrode system for sensitive cancer diagnosis. In order to achieve the highest electrical conductivity and redox-active surface area, MXene was chosen as the material for the bipolar electrode. As part of the detection process, the anodic pole of the bipolar electrode was modified with the receptor tyrosine kinase like orphan receptor 1 (ROR1) antibody, followed by an immunoassay using the ROR1 antibody-modified Ag triangle that was identified as significantly enhancing ECL. We measured the ECL of luminol using the anode pole of BPE as an analytical signal in the presence of H 2 O 2 . Additionally, 3D-printed microchannels were used to fabricate the BPE system, to reduce the quantity of sample required. It has been shown that the present immunosensors are low-cost and sensitive in detecting types of cancer, with an extended linear range of 10 fg mL -1 to 1 µg mL -1 in the analysis of synthetic samples and achieving an accuracy of ~ 90% in diagnosing ten unknown real samples., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

The instability of the signal intensity of fluorescent biosensors and the false signals have been significant factors affecting the performance of biosensors. Herein, a novel signaling system is devised through the application of reversible addition-fragmentation chain transfer (RAFT) polymerization with monomers containing the tetraphenylethylene (TPE) groups. TPE exhibits an aggregation-induced emission (AIE) phenomenon in certain solvents, mainly due to the blockage of the rotation of its four benzene rings, which also exist in the aggregated state. With this property, a series of molecules are modified based on click chemistry for RAFT polymerization using Fe 3 O 4 magnetic beads as the carriers, and stable aggregated luminescent TPE polymers are formed on the surface of magnetic beads to realize the transformation of fluorescence signal from "0" to "1". In addition, the fluorescence signal demonstrates a positive correlation with alkaline phosphatase (ALP) activity, which can be quantified by measuring the fluorescence intensity. The biosensor exhibits high sensitivity and good linearity in the range of 0.1-5 U/L, with a LOD of 0.079 U/L. Furthermore, the designed strategy demonstrated satisfactory performance in the quantitative determination of ALP activity in serum samples, indicating that the signaling system developed by combining RAFT polymerization and AIE molecules has an important application in the field of fluorescent biosensors., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Three-metal-core-shell nanoparticles (Au@Pt@PdNPs) providing excellent peroxidase-like activity were applied in lateral flow immunoassay (LFIA), designated as Au@Pt@Pd-LFIA, for detecting the nucleocapsid protein (NP) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). An Au@Pt@Pd-LFIA was developed for quantitatively testing of SARS-CoV-2 NP with a range 0.12-31.25 ng/mL. The limit of detection (LOD) of Au@Pt@Pd-LFIA strip was 0.06 ng/mL, which was 16-fold or eightfold more sensitive than that of the gold lateral flow immunoassay (Au-LFIA) and the gold flower flow immunoassay (AF-LFIA) strips, respectively. For detection of clinical samples from nasal swabs using test strips, Au@Pt@Pd-LFIA had 84.09% sensitivity, 100% specificity, and 92.55% accuracy. In terms of detection time, the testing of Au@Pt@Pd-LFIA strip was 16 min similar to Au-LFIA (15 min) and AF-LFIA (10 min), but much shorter than ELISA (2 h). In conclusion, Au@Pt@Pd-LFIA is a sensitive, rapid, and simple test for quantitative detection of SARS-CoV-2 NP in nasal swab samples., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

A highly sensitive and selective label-free impedimetric immunosensor based on AuNPs@pDA@NiCo 2 S 4 @MoS 2 nanocomposite modified on the surface of a screen-printed electrode (SPE) was designed for the detection of interleukin-6 (IL-6). The distribution of NiCo 2 S 4 nanoparticles on MoS 2 nanosheets was able to prevent them from agglomerating. The polydopamine (pDA) layer was coated on the surface of NiCo 2 S 4 @MoS 2 nanosheets by self-polymerization, which improved the stability and biocompatibility of the nanomaterial. The excellent reduction ability of pDA promoted the synthesis of gold nanoparticles (AuNPs), which increased the amount of antibody adsorption and the conductivity of the material. Finally, the antibody (Ab) of IL-6 was immobilized on the surface of AuNPs@pDA@NiCo 2 S 4 @MoS 2 nanocomposite. Electrochemical impedance spectroscopy (EIS) was used to detect the change of impedance before and after the immune response between Ab and IL-6 antigen (IL-6). Under the optimal experimental conditions, the relative change in impedance and the logarithmic concentration of IL-6 showed a good linear relationship in the range 1.00 to 1.00 × 10 6  pg/mL, with a low detection limit of 0.97 pg/mL. In addition, the proposed immunosensor performed with good reproducibility, stability, and specificity. It was successfully applied to the determination of IL-6 in patient's serum samples of head and neck carcinoma with recoveries of 98.40% to 106.5%. To sum up, the proposed label-free impedimetric immunosensor was successfully constructed for IL-6 detection in real samples., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Acute liver injury (ALI) has a clear requirement for novel therapies. One emerging option is the use of alternatively activated macrophages (AAMs); a distinct subtype of macrophage with a role in liver injury control and repair. In this comprehensive review, we provide an overview of the current limited options for ALI, and the potential advantages offered by AAMs. We describe the evidence supporting their use from in vitro studies, pre-clinical animal studies, and human clinical trials. We suggest why the first evidence for the clinical use of AAMs is likely to be found in acetaminophen toxicity, and discuss the specific evidence for AAM use in this population, as well as potential applications for AAMs in other patient populations. The key domains by which the performance of AAMs for the treatment of ALI will be assessed are identified, and remaining challenges to the successful delivery of AAMs to clinic are explored., (© 2024. The Author(s).)

Novel green-emitting fluorescent microspheres (GreFMPs) were assembled by loading highly luminescent gold nanoclusters (Arg/ATT/AuNCs) on dendritic mesoporous silica nanoparticles (DMSNs) via PEI-mediated electrostatic adsorption. The fluorescence microspheres  exhibit excellent monodispersion with average diameters about (254.5 ± 34.6 nm). Compared with free Arg/ATT/AuNCs, the GreFMPs have similar fluorescent properties and biocompatibility but superior environmental tolerance. Subsequently, an immunochromatographic assay based on GreFMPs (GreFMP-ICA) has been successfully developed, which is highly selective toward alpha fetoprotein (AFP) in human serum. Under the optimal parameters, there is a good linear range between 0.5 and 160.0 ng/mL, the limit of detection was found to be about 0.5 ng/mL, and the recovery and relative standard deviation are 81.0 ~ 100.6% and 3.5 ~ 16.6%, respectively. These results manifested that the GreFMPs are beneficial for the rational design of the ICA platform, and the proposed GreFMP-ICA has the potential to screen AFP in clinical applications., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Chiral nanoenzymes are a new type of material that possesses both chiral nanostructures and enzymatic catalytic activity. These materials exhibit selectivity in their catalytic activity towards organisms due to the introduction of chiral features in nanomaterials and have inherent chiral discrimination in organisms. As synthetic enzymes, chiral nanoenzymes offer significant advantages over natural enzymes. Due to their unique chiral structure and distinctive physicochemical properties, chiral nanoenzymes play an important role in various fields, including biology, medicine, and environmental protection. Their strong stereospecificity and biocompatibility make them useful in disease therapy, biosensing, and chiral catalysis, setting them apart from conventional and natural enzymes. In recent years, the design of synthetic methods and biological applications of chiral nanoenzymes has received significant attention and extensive research among scientists. This paper provides a systematic review of the research progress in the discovery, development, and application of chiral nanoenzymes in the last decade. Additionally, it presents various applications of chiral nanoenzymes, such as disease therapy, biosensing, and chiral catalysis. Finally, the challenges and future prospects of chiral nanoenzymes are discussed., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

The mycorrhizal fungi of cultivated Vanilla spp. have mainly been studied in America, while a recent study has investigated them on Réunion Island (Indian Ocean). However, there are many different types of cultivation on Réunion, from shade-house crops to forest farms of endemic or exotic trees. Here we fill a gap in the study of the root mycobiome of Vanilla by sampling vines in forest plantations on recent lava flows in the southeast of Réunion. Specifically, we aimed to characterize the fungal communities between terrestrial and epiphytic roots, between forest farms that differ mainly in the species of trees, and between Vanilla roots and ECM-like roots of nearby trees. By sequencing fungal ITS2, we showed that the Vanilla root mycobiome is diverse and differed between the root types and forest farms. Epiphytic and terrestrial roots host endophytic fungi, while a putative rust with visible urediniospores was abundant in terrestrial roots mainly. Other pathogens were detected in epiphytic roots (Colletotrichum) with no sign of disease. Following sequencing and electron microscopy, Tulasnellaceae, characterized by imperforate parenthesomes and cell wall expansion with an amorphous matrix, were shown to be the main mycorrhizal fungi in both vanilla root types. Interestingly, the dominant Tulasnellaceae OTU was found in ECM-type roots of trees belonging to the ectomycorrhizal family Sapotaceae. Further observations are needed to confirm the ectomycorrhizal association of endemic trees with Tulasnella. Moreover, labeling experiments will be instrumental in investigating the transfer of nutrients between the trees and the Vanilla through the network of mycorrhizal associations in the soil., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study aimed to evaluate the effects of radiotherapy (RT) and chemoradiotherapy (CRT) on the wear and surface roughness of in vitro irradiated human enamel and dentin subjected to abrasive challenge. Enamel and dentin specimens (n = 42) were prepared from teeth donated by healthy patients and those with head and neck cancer who had received radiotherapy (RT) or chemoradiotherapy (CRT). The specimens were categorized into three groups: control, RT, and CRT (n = 14 per group for both enamel and dentin). These samples were subjected to an in vitro abrasive experiment using a brushing machine, followed by wear and surface roughness assessments with a confocal laser scanning microscope conducted before and after the abrasive challenge, considering both exposed and non-exposed areas. Statistical analysis used Shapiro-Wilk tests for normality, Wilcoxon tests for comparing two means, and Kruskal-Wallis tests. A significance level of 5% was adopted. In enamel specimens, wear profile values ​​of CRT and RT groups were not different from the control (p > 0.05). The RT group presents lower step values than the CRT and control groups (p < 0.001). No significant difference in final surface roughness was observed in all groups (p > 0.05). In dentin specimens, no significant difference in wear profile and step was observed in all groups (p > 0.05). However, CRT and RT groups present higher values in final surface roughness (p < 0.001). The exposure to ionizing radiation (associated or not to chemotherapy) influenced the surface roughness of dentin and the wear (step) of enamel after the in vitro abrasive challenge.Trial registration: Ethical procedures were approved by the FORP/USP Research Ethics Committee (CAAE: 61308416.4.0000.5419), and Hospital do Câncer de Barretos/Fundação Pio XII (CAAE: 61308416.4.3001.5437)., Competing Interests: Declarations. Conflict of interest: The authors have no conflicts of interest to declare that they are relevant to the content of this article. The authors declare no competing interests. Ethical approval: This was an in vitro experimental study carried out with human teeth donated to the teeth biobank of the Faculty of Dentistry of Ribeirão Preto—University of São Paulo, Brazil (FORP/USP). All patients signed the donation term. Ethical procedures were approved by the FORP/USP Research Ethics Committee (CAAE: 61308416.4.0000.5419), and Hospital do Câncer de Barretos/Fundação Pio XII (CAAE: 61308416.4.3001.5437), as a co-participating institution in teeth donation. Furthermore, we declare that we follow all the guidelines of the Declaration of Helsinki. All eligible participants or legal guardians were informed about the nature of the study and the potential risks and benefits of their participation, signing an informed consent form., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The biuret method is currently recognized as a reference measurement procedure for serum/plasma total protein by the Joint Committee for Traceability in Laboratory Medicine (JCTLM). However, as the reaction involved in this method is highly time-dependent, to ensure identical measurement conditions for calibrator and samples for high accuracy, a fast and simple measurement procedure is critical to ensure the precision and trueness of this method. We measured serum/plasma total protein using a Cary 60 spectrophotometer coupled with a fiber optic probe, which was faster and simpler than the conventional cuvette method. The biuret method utilizing alkaline solutions of copper sulfate and potassium sodium tartrate was added to the sample and calibrator (NIST SRM 927e) incubated for 1 h before measurement. A panel of samples consisting of pooled human serum, single donor serum, and certified reference materials (CRMs) from three sources were measured for method validation. Sixteen native patient samples were measured using the newly developed biuret method and compared against clinical analyzers. Additionally, the results of three cycles of a local External Quality Assessment (EQA) Programme submitted by participating clinical laboratories were compared against the biuret method. Our biuret method using fiber optic probe demonstrated good precision with within-day relative standard deviation (RSD) of 0.04 to 0.23% and between-day RSD of 0.58%. The deviations between the obtained values and the certified values for all three CRMs ranged from -0.38 to 1.60%, indicating good method trueness. The routine methods using clinical analyzers were also found to agree well with the developed biuret method using fiber optic probe for EQA samples and native patient samples. The biuret method using a fiber optic probe represented a convenient and reliable way of measuring serum total protein. It also demonstrated excellent precision and trueness using CRMs and patient samples, which made the method a simpler candidate reference method for serum protein measurement., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Tuberculosis is a highly infectious disease caused by the bacterium Mycobacterium tuberculosis, and the spread of this agent has caused serious health problems worldwide. The rapid and accurate detection of M. tuberculosis is essential for controlling the spread of infection and for preventing the emergence of multidrug-resistant strains. In this study, the powerful trans-cleavage ability of CRISPR-Cas12a for ssDNA was combined with a surface-enhanced Raman spectroscopy (SERS)-based strategy to establish a CRISPR-SERS sensor for the hypersensitive detection of M. tuberculosis DNA. We observed a linear relationship between the concentration of M. tuberculosis DNA and the output signal over the range of 5 to 100 pM. The equation describing the standard curve was y = 24.10x + 1594, with R 2  = 0.9914. The limit of detection was as low as 4.42 pM for genomic DNA, and a plasmid containing an M. tuberculosis-specific sequence was detected at 5 copy/μL. A detection accuracy of 100% was achieved in the analysis of DNA isolated from the sputum of hospitalized patients with tuberculosis. The entire detection process is simple to deploy and only takes 50 min and results in the sensitive and specific detection of M. tuberculosis DNA. This study provides a new method for the detection of tuberculosis. The tool is stable and can be utilized on-site, and it thus broadens the diagnostic application of CRISPR-Cas12a-based sensor technology., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

In this study, xanthine oxidase was immobilized for the first time using a novel magnetic metal-organic framework material (Fe 3 O 4 -SiO 2 -NH 2 @MnO 2 @ZIF-8-NH 2 ). A ligand fishing method was established to rapidly screen XOD inhibitors from Ligusticum wallichii based on the immobilized XOD. Characterization and properties of the immobilized enzyme revealed its excellent stability and reusability. A ligand was screened from Ligusticum wallichii and identified as ligustilide by ultra-high performance liquid chromatography tandem mass spectrometry. The IC 50 value of ligustilide was determined to be 27.70 ± 0.13 μM through in vitro inhibition testing. Furthermore, molecular docking verified that ligustilide could bind to amino acid residues at the active site of XOD. This study provides a rapid and effective method for the preliminary screening of XOD inhibitors from complex natural products and has great potential for further discovery of anti-hyperuricemic compounds., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Purpose: Head and neck emergencies in children are frequent cause of visits to the hospital. Imaging plays a critical role in the management of these patients. This review article aims to familiarize radiologists with the common clinical presentations encountered, imaging characteristics of nontraumatic pediatric head and neck emergencies, and improve their ability to recognize associated complications as well as be aware of common mimics., Methods: We researched our database for commonly encountered nontraumatic head and neck emergencies in children. A literature search was done to compare and complete the list of conditions to be discussed in this review., Results: The review was organized according to anatomical location of the emergent condition. Relevant anatomy has been discussed along with clinical presentation, imaging characteristics and complications. We have presented common mimics with each set of disorders. Key imaging characteristics have been delineated using radiology images., Conclusion: Familiarity with the known complications of head and neck emergencies allows the radiologist to actively search for such findings, encourage early institution of appropriate therapy, and improve outcomes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Faced with an unprecedented demand for long-term care, European health care systems are moving towards mixed care models, where the welfare state and informal caregivers share care responsibilities. While informal care is often viewed as a means of alleviating pressure on public care, it comes with significant economic costs for caregivers, their employers, and society at large. This study uses nationally representative data to estimate the total direct (informal care time and out-of-pocket costs) and indirect (productivity) economic costs of informal care in the Netherlands in 2019. Informal care time costs are estimated using the opportunity cost and the proxy good methods. Indirect costs are estimated using the human capital and friction cost approaches. Our results reveal the considerable annual societal cost of informal care in the Netherlands, ranging between €17.5 billion and €30.1 billion, depending on the valuation approach. These costs are equivalent to 2.15% and 3.71% of Dutch GDP in 2019, comparable to the public expenditure on long-term care in that year. Female caregivers account for slightly more than half (53%-57%) of the total costs. Around 57%-88% of these costs are in the form of informal care time. The main driver of indirect costs is the temporary cessation of work, which comprises 12%-17% of the total costs. Findings corroborate that substantial resources, yet thus far largely disregarded, are spent on informal care even in a country with a relatively generous public long-term care system., (© 2024. The Author(s).)

Our objective was to compare AOTMiT (Polish: Agencja Oceny Technologii Medycznych i Taryfikacji) recommendations to other HTA (Health Technology Assessment) agencies for newly registered drugs and new registration indications issued by the European Medicines Agency between 2014 and 2019. The study aims to assess the consistency and justifications of AOTMiT recommendations compared to that of other HTA agencies in 11 countries. A total of 2496 reimbursement recommendations published by 12 HTA agencies for 464 medicinal products and 525 indications were analyzed. Our analysis confirmed that the Polish AOTMiT agency seems to bear the closest resemblance to the corresponding HTA agencies from Canada (CADTH) and New Zealand (PHARMAC), when it comes to the outcome of HTA recommendations (positive or negative). Poland had a general scheme for justifying recommendations, similar to that of Ireland-four aspects (i.e., clinical efficacy, safety profile, cost-effectiveness, and impact on the payer's budget) are important for Poland when formulating the final decision. Compared to other countries, Poland shows a noticeably different pattern of justifying reimbursement recommendations, as revealed primarily in terms of budget impact and somewhat less so for cost-effectiveness rationales., (© 2024. The Author(s).)

Accumulating evidence have documented sex differences in brain anatomy from early childhood to late adulthood. However, whether sex difference of brain structure emerges in the neonatal brain and how sex modulates the development of cortical morphology during the perinatal stage remains unclear. Here, we utilized T2-weighted MRI from the Developing Human Connectome Project (dHCP) database, consisting of 41 male and 40 female neonates born between 35 and 43 postmenstrual weeks (PMW). Neonates of each sex were arranged in a continuous ascending order of age to capture the progressive changes in cortical thickness and curvature throughout the developmental continuum. The maturational covariance network (MCN) was defined as the coupled developmental fluctuations of morphology measures between cortical regions. We constructed MCNs based on the two features, respectively, to illustrate their developmental interdependencies, and then compared the network topology between sexes. Our results showed that cortical structural development exhibited a localized pattern in both males and females, with no significant sex differences in the developmental trajectory of cortical morphology, overall organization, nodal importance, and modular structure of the MCN. Furthermore, by merging male and female neonates into a unified cohort, we identified evident dependencies influences in structural development between different brain modules using the Granger causality analysis (GCA), emanating from high-order regions toward primary cortices. Our findings demonstrate that the maturational pattern of cortical morphology may not differ between sexes during the perinatal period, and provide evidence for the developmental causality among cortical structures in perinatal brains., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Microplastics (MPs) have attracted significant attention due to their global distribution in living environments. Although some studies have reported MP-induced hepatotoxicity in mouse models, a systematic approach to MP-mediated liver toxicity was still lacking. Therefore, we used a mouse model to study the sub-chronic effects of MP exposure on the liver. Female C57BL/6 mice, aged 6 weeks, received an oral administration of 0.3 mg of Nile Red-labeled polystyrene (PS) microplastics, with particle sizes of 0.5 µm (submicron) and 5 µm (micron), via gavage, while control mice received vehicle only. Each mouse was exposed to MPs twice a week for 12 weeks. After sacrifice, the levels of MP accumulation, oxidative stress, inflammation, and pathological changes were measured in the mouse liver, and blood samples were collected for serum biochemistry analysis. Our results demonstrated that 0.5 µm PS-MPs were accumulated in mouse livers post-MP exposure, but not in the 5 µm MP exposure group. Simultaneously, increased levels of glucose, triglyceride, alanine transaminase (ALT), aspartate transaminase (AST), superoxide dismutase, 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA), interleukin-6, and lipid droplets were found in the 0.5 µm MP exposure group, while the fewer responses, including elevated liver weight index, glucose, high-density lipoprotein, AST, and decreased HNE-MA were observed in 5 µm MP exposure group. These results indicate that sub-chronic exposure to submicron MPs causes MP deposition in mouse livers, which further induces oxidative stress, increases inflammatory cytokines and perturbs glucose and lipid homeostasis, which might trigger more severe metabolic dysfunction or non-alcoholic steatohepatitis-like hepatotoxicity., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The proliferation of multidrug-resistant and biofilm-forming pathogenic bacteria poses a serious threat to public health. The limited effectiveness of current antibiotics motivates the search for new antibacterial compounds. In this study, a novel strain, RG-5, was isolated from desert soil. This strain exhibited potent antibacterial and antibiofilm properties against multidrug-resistant and biofilm-forming pathogenic bacteria. Through phenotypical characterizations, 16S rRNA gene sequence and phylogenetic analysis, the strain was identified as Streptomyces pratensis with 99.8% similarity. The active compound, RG5-1, was extracted, purified by reverse phase silica column HPLC, identified by ESI-MS spectrometry, and confirmed by 1 H and 13 C NMR analysis as 2,5-Piperazinedione, 3,6-bis(2-methylpropyl), belonging to cyclic peptides. This compound showed interesting minimum inhibitory concentrations (MICs) of 04 to 15 µg/mL and minimum biofilm inhibitory concentrations (MBICs 50%) of ½ MIC against the tested bacteria. Its molecular mechanism of action was elucidated through a molecular docking study against five drug-protein targets. The results demonstrated that the compound RG5-1 has a strong affinity and interaction patterns with glucosamine-6-phosphate synthase at - 6.0 kcal/mol compared to reference inhibitor (- 5.4 kcal/mol), medium with penicillin-binding protein 1a (- 6.1 kcal/mol), and LasR regulator protein of quorum sensing (- 5.4 kcal/mol), confirming its antibacterial and antibiofilm activities. The compound exhibited minimal toxicity and favorable physicochemical and pharmacological properties. This is the first report that describes its production from Streptomyces, its activities against biofilm-forming and multidrug-resistant bacteria, and its mechanism of action. These findings indicate that 2,5-piperazinedione, 3,6-bis(2-methylpropyl) has the potential to be a promising lead compound in the treatment of antibiotic-resistant and biofilm-forming pathogens., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A novel portable cotton swab based on nitrogen-doped carbon dots (NCDs) for Al 3+ detection was constructed for the first time. NCDs with bright green fluorescence were prepared by hydrothermal method with phenylhydrazine hydrochloride and 3-hydroxy-2-naphthoic acid hydrazide as precursors. The surface of NCDs was exposed to abundant functional groups (such as amino, carboxyl, hydroxyl, etc.), which was helpful for the formation of complexes between NCDs and Al 3+ . In the presence of Al 3+ , the aggregation of NCDs obviously induced their fluorescence enhancement due to the aggregation-induced emission (AIE) of NCDs. Furthermore, the quantum yield (QY) of NCDs was enhanced by 12 times with Al 3+ , and the fluorescence lifetime was increased by 7.54 ns. The fluorescence intensity was linearly correlated with the concentration of Al 3+ (2.5-300 μM), and the limit of detection was 0.76 μM. Moreover, for the portable way, cotton swabs were successfully employed to construct the sensors for the detection of Al 3+ in food samples. This proposal has potential for the application in food analysis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Dysphagia is defined as difficulty in swallowing, while presbyphagia is described as a change in swallowing process in healthy older adults, which is a compensable physiological impairment and synonymous with dysphagia. Aging is a well-known risk factor for Alzheimer's disease (AD), and oropharyngeal dysphagia (OD) is a common condition in AD. Our study aims to compare OD in AD patients and older adults with presbyphagia (OAwP). 65 older adults (AD = 32, mean age:76.5 ± 6; OAwP = 33, mean age:71.1 ± 4) were included. Swallowing disorders were evaluated by Flexible Endoscopic Evaluation Study, which scored by Penetration Aspiration Scale (PAS) that scores other than 1 indicate dysphagia, Murray Secretion Severity Scale (MSSS), and Eating Assessment Tool-10 (EAT-10). Neurologist determined Clinical Dementia Rating (CDR) scores of AD patients. AD and OAwP groups had OD, respectively, 96.87% vs. 81.81% by PAS, 87.5% vs. 60.60% by MSSS, and 56.25% vs. 18.18% by EAT-10. No statistical differences were observed between AD and OAwP in terms of gender, age, PAS, and MSSS values (p > 0.05). There was a significant difference in EAT-10 total scores (p = 0.000), and had OD by EAT-10 (p = 0.024). No differences were found in age, time elapsed since diagnosis, PAS, and EAT-10 scores based on CDR, but there was a difference in MSSS scores (p = 0.013). CDR in AD were associated with gender, time elapsed since diagnosis, and MSSS scores (p < 0.05). OAwP experience swallowing problems at least as much as those with AD. Evaluation of swallowing disorders after diagnosis is essential for both AD and OAwP. Early-stage management of disease with preventive treatment approaches can delay onset of symptoms., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)