The inflammasome regulates the innate inflammatory response and is involved in autoimmune diseases. In this study, we explored the levels of IL-18 and IL-1β in serum and urine and the influence of various single-nucleotide polymorphisms (SNPs) on kidney lesions at diagnosis in patients with ANCA-associated vasculitis (AAV) and their clinical outcomes. Ninety-two patients with renal AAV were recruited, and blood and urine were collected at diagnosis. Serum and urine cytokine levels were measured by ELISA. DNA was extracted and genotyped using TaqMan assays for SNPs in several inflammasome genes. Lower serum IL-18 (p = 0.049) and the IL-18 rs187238 G-carrier genotype (p = 0.042) were associated with severe fibrosis. The IL-18 rs1946518 TT genotype was associated with an increased risk of relapse (p = 0.05), whereas GG was related to better renal outcomes (p = 0.031). The rs187238 GG genotype was identified as a risk factor for mortality within the first year after AAV diagnosis, independent of the requirement for dialysis or lung involvement (p = 0.013). We suggest that decreased cytokine levels could be a surrogate marker of scarring and chronicity of the renal lesions, together with the rs187238 GG genotype. If our results are validated, the rs1946518 TT genotype predicts the risk of relapse and renal outcomes during follow-up. Full article

Sepsis is a life-threatening condition with a rising disease burden worldwide. It is a multifactorial disease and is defined as a dysregulated host response to infection. Neutrophils have been shown to be involved in the pathogenesis of sepsis by exacerbating inflammation. However, the exact effector mechanism of action still remains a mystery. Changes in the glycosylation pattern of the immunoglobulin G (IgG) Fc region are described for several diseases including meningococcal sepsis. In this study, we investigated the possible contribution of neutrophils and neutrophil implication, potentially related to degranulation or neutrophil extracellular trap (NET) formation in changing the IgG Fc N-glycosylation pattern in a murine sepsis model. We have measured the serum level of cytokines/chemokines and immunoglobulins, the serum activity of neutrophil elastase (NE), and analyzed the IgG Fc glycosylation pattern by Liquid Chromatography-Electrospray Ionization-Mass Spectrometry (LC-ESI-MS) and Lectin enzyme-linked immunosorbent assay (ELISA). We observed an increased activity of NE- and neutrophil-associated cytokines such as keratinocyte chemoattractant (KC) with the development of sepsis. Regarding the IgG Fc N-glycosylation, we observed an increase in fucosylation and α1,3-galactosylation and a decrease for sialyation. Interestingly, these changes were not uniform for all IgG subclasses. After depletion of neutrophils, we saw a change in the exposure of fucose and α2,6-linked sialic acid during the time course of our experimental sepsis model. In conclusion, neutrophils can influence changes in the IgG glycosylation pattern in experimental sepsis. Full article

Enantioseparation of nineteen liquid crystalline racemic mixtures obtained based on (R,S)-2-octanol was studied in reversed-phase mode on an amylose tris(3-chloro-5-methylphenylcarbamate) (ReproSil Chiral-MIG) and a cellulose tris(3,5-dichlorophenylcarbamate) (ReproSil Chiral-MIC). These polysaccharide-based chiral stationary phase (CSP) columns for High-Performance Liquid Chromatography (HPLC) were highly effective in recognizing isomers of minor structural differences. The mobile phase (MP), which consists of acetonitrile (ACN)/water (H₂O) at different volume ratios, was used. The mobile phases were pumped at a flow rate of 0.3, 0.5, or 1 mL·min⁻¹ with a column temperature of 25 °C, using a UV detector at 254 nm. The order of the elution was also determined. The chromatographic parameters, such as resolution (R_s), selectivity (α), and the number of theoretical plates, i.e., column efficiency (N), were determined. The polysaccharide-based CSP columns have unique advantages in separation technology, and this study has shown the potential usefulness of the CSP columns in separating liquid crystalline racemic mixtures belonging to the same homologous series. Full article

Simple and efficient sample pretreatment methods are important for analysis and detection of chemical warfare agents (CWAs) in environmental and biological samples. Despite many commercial materials or reagents that have been already applied in sample preparation, such as SPE columns, few materials with specificity have been utilized for purification or enrichment. In this study, ionic magnetic mesoporous nanomaterials such as poly(4-VB)@M-MSNs (magnetic mesoporous silicon nanoparticles modified by 4-vinyl benzene sulfonic acid) and Co²⁺@M-MSNs (magnetic mesoporous silicon nanoparticles modified by cobalt ions) with high absorptivity for ethanol amines (EAs, nitrogen mustard degradation products) and cyanide were successfully synthesized. The special nanomaterials were obtained by modification of magnetic mesoporous particles prepared based on co-precipitation using -SO₃H and Co²⁺. The materials were fully characterized in terms of their composition and structure. The results indicated that poly(4-VB)@M-MSNs or Co²⁺@M-MSNs had an unambiguous core-shell structure with a BET of 341.7 m²·g⁻¹ and a saturation magnetization intensity of 60.66 emu·g⁻¹ which indicated the good thermal stability. Poly(4-VB)@M-MSNs showed selective adsorption for EAs while the Co²⁺@M-MSNs were for cyanide, respectively. The adsorption capacity quickly reached the adsorption equilibrium within the 90 s. The saturated adsorption amounts were MDEA = 35.83 mg·g⁻¹, EDEA = 35.00 mg·g⁻¹, TEA = 17.90 mg·g⁻¹ and CN⁻= 31.48 mg·g⁻¹, respectively. Meanwhile, the adsorption capacities could be maintained at 50–70% after three adsorption–desorption cycles. The adsorption isotherms were confirmed as the Langmuir equation and the Freundlich equation, respectively, and the adsorption mechanism was determined by DFT calculation. The adsorbents were applied for enrichment of targets in actual samples, which showed great potential for the verification of chemical weapons and the destruction of toxic chemicals. Full article

The epidermal growth factor receptor (EGFR) is a pivotal target in cancer therapy due to its significance within the tyrosine kinase family. EGFR inhibitors like AG-1478 and PD153035, featuring a 4-anilinoquinazoline moiety, have garnered global attention for their potent therapeutic activities. While pre-clinical studies have highlighted the significant impact of halogen substitution at the C3’-anilino position on drug potency, the underlying mechanism remains unclear. This study investigates the influence of halogen substitution (X = H, F, Cl, Br, I) on the structure, properties, and spectroscopy of halogen-substituted 4-anilinoquinazoline tyrosine kinase inhibitors (TKIs) using time-dependent density functional methods (TD-DFT) with the B3LYP functional. Our calculations revealed that halogen substitution did not induce significant changes in the three-dimensional conformation of the TKIs but led to noticeable alterations in electronic properties, such as dipole moment and spatial extent, impacting interactions at the EGFR binding site. The UV–visible spectra show that more potent TKI-X compounds typically have shorter wavelengths, with bromine’s peak wavelength at 326.71 nm and hydrogen, with the lowest IC50 nM, shifting its lambda max to 333.17 nm, indicating a correlation between potency and spectral characteristics. Further analysis of the four lowest-lying conformers of each TKI-X, along with their crystal structures from the EGFR database, confirms that the most potent conformer is often not the global minimum structure but one of the low-lying conformers. The more potent TKI-Cl and TKI-Br exhibit larger deviations (RMSD > 0.65 Å) from their global minimum structures compared to other TKI-X (RMSD < 0.15 Å), indicating that potency is associated with greater flexibility. Dipole moments of TKI-X correlate with drug potency (ln(IC50 nM)), with TKI-Cl and TKI-Br showing significantly higher dipole moments (>8.0 Debye) in both their global minimum and crystal structures. Additionally, optical spectral shifts correlate with potency, as TKI-Cl and TKI-Br exhibit blue shifts from their global minimum structures, in contrast to other TKI-X. This suggests that optical reporting can effectively probe drug potency and conformation changes. Full article

In Pinus massoniana, the methyl-D-erythritol-4-phosphate (MEP) pathway plays a crucial role in the biosynthesis of terpenoids. The fourth step of this pathway is specifically regulated by 4-(cytidine 5′-diphospho)-2-C-methyl-D-erythritol kinase (CMK). In this study, PmCMK (MW892445.1) was isolated. As a member of the GHMP kinase family, PmCMK exhibits homology with CMK genes across diverse species. The examination of relative expression patterns revealed that PmCMK exhibited higher expression levels in tissues of P. massoniana that are rich in resin. We successfully cloned the PmCMK promoter (1654 bp) and integrated it into a GUS reporter vector. This construct was then transformed into the leaves of tobacco (Nicotiana × sanderae) to assess transient expression patterns. The results demonstrated that the promoter was active not only in the roots, leaves, and stems of the tobacco plants but also exhibited varying expression levels in response to treatments with IAA, SA, MeJA, and PEG6000. This suggested that PmCMK expression was modulated by a variety of signals. It revealed that the expression of PmCMK was affected by different treatments. Further allogeneic expression studies showed that tobacco overexpressing PmCMK exhibited increased levels of chlorophyll and carotene compared to the wild type. This enhancement in content indicates that PmCMK has a significant role in isoprene biosynthesis. These findings provide valuable insights for future research aimed at elucidating the biosynthetic pathways of terpenoids and developing breeding strategies to enhance resin production in P. massoniana. Full article

In-line digital holography is a powerful tool widely used for microscopic object imaging. Usually, in-line and out-line configurations are used to implement holographic systems, but in-line-based set-ups are preferable as they are less sensitive to mechanical vibrations and refraction index variations. However, non-desired blurred conjugate images are superposed to the reconstructed object image by using in-line systems. One strategy to remove the conjugate image contribution is to include a double-sideband filter at the Fourier plane of the system. After using the filter, data obtained at the CCD are processed to retrieve the magnitude and phase (hologram) of the diffracted wavefront while removing the conjugated image. Afterwards, a diffraction integral equation is used to digitally propagate the hologram. Despite the above-mentioned factors, there is not a thorough analysis in the literature of magnification parameters associated with the final reconstructed image, this aspect being crucial for the experimental application of the above-stated approach. Under this scenario, a theoretical analysis of the longitudinal and transverse magnifications of the reconstructed images is provided in this work. The method is validated through the simulation and experimental results of different microscopic objects: glass microspheres, a micrometric reticle, and a resolution test chart USAF 1951. The obtained results provide that the combination of magnification relations with methods for hologram propagation and optimal focused image identification is effective for object position determination. This approach could be useful for 3D microparticle localization and monitoring with optimized magnification within real-time applications. Full article

Combining organometallic frameworks with graphene oxide presents a fresh strategy to enhance the electrochemical capabilities of supercapacitors, contributing to the advancement of sustainable energy solutions. Continued refinement of materials and device design holds promise for broader applications across energy storage and conversion systems. This featured application underscores the inventive utilization of organometallic frameworks on graphene oxide, shedding light on the creation of superior energy storage devices for eco-friendly solutions. This review article delves into the synergistic advancements resulting from the fusion of organometallic frameworks with graphene oxide, offering a thorough exploration of their utility in sustainable eco-energy solutions. This review encompasses various facets, including synthesis methodologies, amplified catalytic performances, and structural elucidations. Through collaborative efforts, notable progressions in photocatalysis, photovoltaics, and energy storage are showcased, illustrating the transformative potential of these hybrids in reshaping solar energy conversion and storage technologies. Moreover, the environmentally conscious features of organometallic–graphene oxide hybrids are underscored through their contributions to environmental remediation, addressing challenges in pollutant elimination, water purification, and air quality enhancement. The intricate structural characteristics of these hybrids are expounded upon to highlight their role in tailoring material properties for specific eco-energy applications. Despite promising advancements, challenges such as scalability and stability are candidly addressed, offering a pragmatic view of the current research landscape. The manuscript concludes by providing insights into prospective research avenues, guiding the scientific community towards surmounting hurdles and fully leveraging the potential of organometallic–graphene oxide hybrids for a sustainable and energy-efficient future. Full article

Extracellular vesicles (EVs) are “micro-shuttles” that play a role as mediators of intercellular communication. Cells release EVs into the extracellular environment in both physiological and pathological conditions and are involved in intercellular communication, due to their ability to transfer proteins, lipids, and nucleic acids, and in the modulation of the immune system and neuroinflammation. Because EVs can penetrate the blood–brain barrier and move from the central nervous system to the peripheral circulation, and vice versa, recent studies have shown a substantial role for EVs in several neurological diseases, including multiple sclerosis (MS). MS is a demyelinating disease where the main event is caused by T and B cells triggering an autoimmune reaction against myelin constituents. Recent research has elucidate the potential involvement of extracellular vesicles (EVs) in the pathophysiology of MS, although, to date, their potential role both as agents and therapeutic targets in MS is not fully defined. We present in this review a summary and comprehensive examination of EVs’ involvement in the pathophysiology of multiple sclerosis, exploring their potential applications as biomarkers and indicators of therapy response. Full article

Avian leukosis virus (ALV) is an avian oncogenic retrovirus that can impair immunological function, stunt growth and decrease egg production in avian flocks. The capsid protein (P27) is an attractive candidate for ALV diagnostics. In the present study, a new hybridoma cell (1F8) stably secreting an anti-P27 monoclonal antibody (mAb) was developed. The mAb exhibited a high affinity constant (Ka) of 8.65 × 10^6.0 L/mol, and it could be used for the detection of ALV-A/B/J/K strains. Moreover, a total of eight truncated recombinant proteins and five synthetic polypeptides were utilized for the identification of the B-cell epitopes present on P27. The results revealed that ²¹⁸IIKYVLDRQK²²⁷ was the minimal epitope recognized by 1F8, which had never been reported before. Additionally, the epitopes could strongly react with different ALV subgroup’s specific positive serum and had a complete homology among all the ALV subgroups strains. Finally, a new sandwich ELISA method was created for the detection of ALV antigens, demonstrating increased sensitivity compared to a commercially available ELISA kit. These results offer essential knowledge for further characterizing the antigenic composition of ALV P27 and will facilitate the development of diagnostic reagents for ALV. Full article

External corrosion poses a significant threat to the integrity and lifespan of buried pipelines. Accurate prediction of corrosion rates is important for the safe and efficient transportation of oil and natural gas. However, limited data availability often impacts the performance of conventional predictive models. This study proposes a novel composite modeling approach integrating kernel principal component analysis (KPCA), particle swarm optimization (PSO), and extreme learning machine (ELM). The key innovation lies in using KPCA for reducing the dimensionality of complex input data combined with PSO for optimizing the parameters of the ELM network. The model was rigorously trained on 12 different datasets and comprehensively evaluated using metrics such as the coefficient of determination (R²), standard deviation (SD), mean relative error (MRE), and root mean square error (RMSE). The results show that KPCA effectively extracted four primary components, accounting for 91.33% of the data variability. The KPCA-PSO-ELM composite model outperformed independent models with a higher accuracy, achieving an R² of 99.59% and an RMSE of only 0.0029%. The model comprehensively considered various indicators under the conditions of limited data. The model significantly improved the prediction accuracy and provides a guarantee for the safety of oil and gas transport. Full article

Diagnosis of pulmonary embolism remains a challenge for clinicians as its differential diagnosis is wide. The use of sequential diagnostic strategies based on the assessment of clinical probability, D-dimer measurement, and computed tomography pulmonary angiography have been validated in large prospective outcome studies. D-dimer measurement at a standard cutoff of 500 μg/L has gained wide acceptance to rule out pulmonary embolism in around 20 to 30% of patients with a clinically suspected pulmonary embolism. To improve the efficiency of D-dimer measurement, different ways of selecting a higher, albeit safe cutoff were explored: the age-adjusted D-dimer cutoff and the clinical adapted D-dimer cutoff. While both have been prospectively validated in large studies, some differences do exist. In particular, the prevalence of pulmonary embolism in these different validation studies was very different. Overall, the age-adjusted cutoff seems to be safer and less efficient, while the clinical probability adapted cutoff seems more efficient and less safe. Here, we report the available data regarding these two different ways to increase the diagnostic yield of D-dimer. Also, well beyond the accuracy of these adjusted/adapted cutoffs, some external factors, such as the prevalence of pulmonary embolism in the tested population and the clinical setting, have an important impact of the negative predictive value and on the overall efficiency of these cutoffs. Therefore, we also discuss which cutoff should be used according to the expected prevalence of the disease and according to the clinical setting. Full article

Fish growth is a fundamental biological process driven by a multitude of intrinsic (within-individual) and extrinsic (environmental) factors that underpin individual fitness and population dynamics. Interannual variability in river hydrology regarding the intensity and duration of floods and droughts can induce interannual variations in the biotic and abiotic variables that regulate fish growth. However, the understanding of how interannual variability in river hydrology affects fish growth remains limited for most species and ecosystems. We evaluated how inter-annual hydrological variations within the Amazon River basin influence the growth of the catfish Pseudoplaystoma fasciatum. Our research questions were as follows: Do floods lead to the faster growth of P. fasciatum and droughts lead to the slower growth? And do floods and droughts affect all age classes in the same manner? We sampled 364 specimens of P. fasciatum from five sites in the Amazon basin, estimated their growth rates, and related the growth rates to indices of the intensity of floods and droughts. We fitted linear mixed-effects models to test the relationship between growth increments and hydrological indices (with F and D quantifying the intensities of floods and droughts, respectively), age as fixed effects, and basins and Fish ID as random effects. We found an inverse relationship between the increment width in the fish hard parts and hydrological indices. That is, intense floods and droughts negatively affected the growth rates. We also found that the growth of P. fasciatum was no different in years with intense and mild floods across age classes 1–5, although was different for age class 6. However, the growth of P. fasciatum was faster in years of mild droughts for all age classes. Our results showing that the growth of P. fasciatum was slower in years of intense droughts are supported by those of previous studies in the Amazon basin and elsewhere. However, our results showing for the first time that the growth of P. fasciatum is slower in years of intense flooding is the opposite of patterns found in other studies. These results thus suggest that the growth of P. fasciatum is maximized within an optimum range of hydrological conditions, where neither floods nor droughts are intense. Full article

This work examines the beneficial role of an unsteady stenosis, not driven by any external energy source, as a means for augmenting the flow rate of a valveless pump in a hydraulic loop, including an open tank. In contrast to our previous work, in which the concept of the latter stenosis was introduced for the first time in a horizontal closed loop, here, gravity was taken into account. The stenosis neck cross-sectional area was controlled by the fluid pressure and the opposing force applied externally by a spring of adjustable tension. A pincher compressed and decompressed a part of the pump’s flexible tube periodically, with frequencies from 5 Hz to 11 Hz and compression ratios A_b from 24% to 65%. The presence of the stenosis increased the net flow rate by 19 times for A_b = 24% and 6.3 times for A_b = 38%; whereas for A_b = 65%, the flow rates were comparable. The volumetric efficiency varied from 30% to 40% under the presence of the stenosis, and from 2% to 20% without the stenosis. The role of the stenosis was to cause a unidirectional flow, opening during tube compression and closing during decompression. The pressure amplitudes along the flexible tube increased towards the rigid–flexible tube junction (as a result of the wave reflections), which were found to be significantly attenuated by the presence of the stenosis, whereas the flow rate pulsations did not exceed 10% of the mean at the peak net flow rates. Full article

As transportation evolves with greater adoption of electric vehicles (EVs), vehicle-to-vehicle (V2V) energy trading stands out as an important innovation for managing energy resources more effectively as it reduces dependency on traditional energy infrastructures and, hence, alleviates the pressure on the power grid during peak demand times. Thus, this paper conducts a systematic review of the V2V energy trading frameworks. Through the included article analysis (n = 61), this paper discusses the state-of-the-art energy trading frameworks’ structure, employed methodologies, encountered challenges, and potential directions for future research. To the best of the authors’ knowledge, this is the first review explicitly focused on V2V energy trading. We detail four critical challenges to face while establishing the framework in current research, providing an overview of various methodologies, including auctions, blockchain, game theory, optimisation, and demand forecasting, that are used to address these challenges and explore their integration within the research landscape. Additionally, this paper forecasts the evolution of V2V energy trading, highlighting the potential incorporation of advanced and established technologies like artificial intelligence (AI), digital twins, and smart contracts. This review aims to encapsulate the existing state of V2V energy trading research and stimulate future advancements and technological integration within the field. Full article

Background: The Mediterranean Diet (MedDiet) has long been recognized for its health-promoting attributes, with proven benefits in preventing cardiovascular and metabolic diseases. During the global COVID-19 pandemic, MedDiet’s potential to mitigate the impact of SARS-CoV-2 infection gained attention. This study aims to investigate the interplay among MedDiet adherence, immune system response to SARS-CoV-2 vaccines, and potential sex-related variations. Methods: A retrospective observational study was conducted through collecting data from a web survey for the Italian population. Adherence to the MedDiet was assessed using the Mediterranean Diet Adherence Screener (MEDAS); in addition, COVID-19 symptoms and vaccination details were also obtained. Results: Significant associations between MedDiet adherence, COVID-19 symptoms, and vaccine-related side effects were observed. Notably, females demonstrated distinct responses, reporting lymph node enlargement and a different prevalence and severity of vaccine side effects compared to males. Conclusions: This study highlights the protective role of the MedDiet against COVID-19 and emphasizes the relevance of sex-specific responses in vaccination outcomes according to MEDAS score. Full article

Hypoxia-inducible factor 1-alpha (HIF1A) is a key transcription factor aiding tumor cells’ adaptation to hypoxia, regulated by the prolyl hydroxylase family (EGLN1-3) by directing toward degradation pathways. DNA methylation potentially influences EGLN and HIF1A levels, impacting cellular responses to hypoxia. We examined 96 HNSCC patients and three cell lines, analyzing gene expression of EGLN1-3, HIF1A, CA9, VEGF, and GLUT1 at the mRNA level and EGLN1 protein levels. Methylation levels of EGLNs and HIF1A were assessed through high-resolution melting analysis. Bioinformatics tools were employed to characterize associations between EGLN1-3 and HIF1A expression and methylation. We found significantly higher mRNA levels of EGLN3, HIF1A, GLUT1, VEGF, and CA9 (p = 0.021; p < 0.0001; p < 0.0001; p = 0.004, and p < 0.0001, respectively) genes in tumor tissues compared to normal ones and downregulation of the EGLN1 mRNA level in tumor tissues (p = 0.0013). In HNSCC patients with hypermethylation of HIF1A in normal tissue, we noted a reduction in HIF1A mRNA levels compared to tumor tissue (p = 0.04). In conclusion, the differential expression of EGLN and HIF1A genes in HNSCC tumors compared to normal tissues influences patients’ overall survival, highlighting their role in tumor development. Moreover, DNA methylation could be responsible for HIF1A suppression in the normal tissues of HNSCC patients. Full article

In this paper, based on Meyerhof’s theory of homogeneous foundation, the limit equilibrium analysis method and unified logarithmic spiral sliding surface assumption are used to derive the theoretical formula for the ultimate bearing capacity of a layered foundation when the foundation is completely rough. It should be noted that this formula is only applicable to strip foundations of upper soft clay and lower sandy soil. In addition, a comparative analysis is conducted between theoretical formulas and semiempirical formulas for layered foundations. On the basis of verifying the reliability of the theoretical formula results, numerical simulation is carried out to further explore and analyze the influence of the width to depth ratio of the foundation, the strength parameters of the double-layer soil, and the thickness of the upper soft soil on the bearing capacity of the foundation. Research has shown that the formula for the bearing capacity of a layered foundation derived in this paper has a certain degree of error compared to Meyerhof’s semiempirical formula, but it is in good agreement with numerical simulation results and Hansen’s weighted average method results. The ratio of the width to depth of the foundation, the ratio of the cohesive force of the double-layer soil, and the tangent ratio of the internal friction angle have a significant positive correlation with the ultimate bearing capacity of the foundation. The increase in thickness of the overlying cohesive soil has a negative impact on the ultimate bearing capacity of the foundation, and the thicker the soil, the smaller the foundation’s bearing capacity. Full article

Maritime transportation plays a pivotal role in global trade and international supply chains. However, the sector is also a significant source of emissions. One of the most promising technologies for reducing these emissions is air lubrication, which involves installing bubbles along the hull of a ship. Despite its potential, the design of cost-effective bubble-installation plans for ship fleets over the planning horizon remains unexplored in the literature. This paper addresses this gap by proposing a mathematical programming model designed to optimize the installation of bubble-based systems. We present several propositions concerning the model’s properties, supported by rigorous proofs. To validate the model’s effectiveness, we conduct a series of computational experiments. The findings demonstrate that our optimization model enables shipping companies to devise bubble-installation plans that are cost-effective. This contribution not only extends the current understanding of emission reduction technologies in maritime transportation, but also offers practical insights for their implementation. Full article

The dissolved gas analysis of insulating oil in power transformers can provide valuable information about fault diagnosis. Power transformer datasets are often imbalanced, worsening the performance of machine learning-based fault classifiers. A critical step is choosing the proper evaluation metric to select features, models, and oversampling techniques. However, no clear-cut, thorough guidance on that choice is available to date. In this work, we shed light on this subject by introducing new tailored evaluation metrics. Our results and discussions bring fresh insights into which learning setups are more effective for imbalanced datasets. Full article

Tomato fruit ripening is accompanied by carotenoid accumulation and color changes. To elucidate the regulatory mechanisms underlying carotenoid synthesis during fruit ripening, a combined transcriptomic and metabolomic analysis was conducted on red-fruited tomato (WP190) and orange-fruited tomato (ZH108). A total of twenty-nine (29) different carotenoid compounds were identified in tomato fruits at six different stages. The abundance of the majority of the carotenoids was enhanced significantly with fruit ripening, with higher levels of lycopene; (E/Z)-lycopene; and α-, β- and γ-carotenoids detected in the fruits of WP190 at 50 and 60 days post anthesis (DPA). Transcriptome analysis revealed that the fruits of two varieties exhibited the highest number of differentially expressed genes (DEGs) at 50 DPA, and a module of co-expressed genes related to the fruit carotenoid content was established by WGCNA. qRT-PCR analysis validated the transcriptome result with a significantly elevated transcript level of lycopene biosynthesis genes (including SlPSY2, SlZCIS, SlPDS, SlZDS and SlCRTSO2) observed in WP190 at 50 DPA in comparison to ZH108. In addition, during the ripening process, the expression of ethylene biosynthesis (SlACSs and SlACOs) and signaling (SlEIN3 and SlERF1) genes was also increased, and these mechanisms may regulate carotenoid accumulation and fruit ripening in tomato. Differential expression of several key genes in the fruit of two tomato varieties at different stages regulates the accumulation of carotenoids and leads to differences in color between the two varieties of tomato. The results of this study provide a comprehensive understanding of carotenoid accumulation and ethylene biosynthesis and signal transduction pathway regulatory mechanisms during tomato fruit development. Full article

Background: Complications are an inevitable part of orthopaedic surgery, and how one defines complications can have an impact on the ability to learn from them. There have been issues with a commonly used classification system first outlined by Clavien and Dindo. Our aim was to evaluate a modification of this classification system developed for use in our department, with our hypothesis being that this could make our audit presentations more efficient. Methods: A modified Clavien–Dindo Classification was prospectively applied to all complications recorded in the orthopaedic departmental audits at our institution for a 12-month period. The audit discussion was recorded and analysed and compared with the complication audits for the preceding 12-month period. Results: We analysed eight audit presentations before and eight audit presentations after the introduction of a modified Clavien–Dindo classification to our orthopaedic complications over a 2-year period. The number of PowerPoint™ slides (103 vs. 84, p = 0.03) and the time spent on each presentation (88 vs. 71 min, p = 0.02) decreased significantly with the introduction of the modified classification. The novel system was found to have high inter-observer reliability. Conclusions: The modified Clavien–Dindo classification system is a reproducible classification system for orthopaedic complications. It made our audit presentations more efficient. Full article