Tyrosine hydroxylase inhibits HCC progression by downregulating TGFß/Smad signaling.

The alteration of metabolic processes has been found to have significant impacts on the development of hepatocellular carcinoma (HCC). Nevertheless, the effects of dysfunction of tyrosine metabolism on the development of HCC remains to be discovered. This research demonstrated that tyrosine hydroxylase (TH), which responsible for the initial and limiting step in the bio-generation of the neuro-transmitters dopamine and adrenaline, et al. was shown to be reduced in HCC. Increased expression of TH was found facilitates the survival of HCC patients. In addition, decreased TH indicated larger tumor size, much more numbers of tumor, higher level of AFP, and the presence of cirrhosis. TH effectively impairs the growth and metastasis of HCC cells, a process dependent on the phosphorylation of serine residues (S19/S40). TH directly binds to Smad2 and hinders the cascade activation of TGFß/Smad signaling with the treatment of TGFß1. In summary, our study uncovered the non-metabolic functions of TH in the development of HCC and proposes that TH might be a promising biomarker for diagnosis as well as an innovative target for metastatic HCC.

Evaluation of modified clear Twin Block aligner in treating adolescents with skeletal class II malocclusion: A two-centre cephalometric study.

INTRODUCTION: The purpose of this study was to evaluate the therapeutic effect of modified clear Twin Block (CTB) aligner and traditional twin block (TB) appliance from skeletal, dentoalveolar and soft tissue changes in adolescents with skeletal class II malocclusion. METHODS: A total of 80 adolescents, included in this study from two medical centres, were distributed into CTB group, TB group and control group based on the treatment they received. Lateral cephalograms at pre-treatment (T1) and post-treatment (T2) were measured by modified Pancherz's cephalometric analysis, and dentoskeletal and soft tissue changes were analysed by independent-sample t-test, paired-sample t-test, ANOVA test and Scheffe's Post Hoc test. RESULTS: Seventy-five adolescents completed the study, including 32 in the CTB group, 32 in the TB group and 11 in the control group. Both CTB and TB treatment showed significant differences in most dentoskeletal and soft tissue measurements. Compared with the control group, improvements were observed in class II molar relationship through significant different in S Vert/Ms-S Vert/Mi in the CTB group (P < .01) and the TB group (P < .001), as well as deep overjet through significant different in S Vert/Is-S Vert/Ii in the CTB group (P < .001) and the TB group (P < .001). Besides, the CTB group also showed less protrusion of lower incisors and resulted in a more significant improvement in profile with fewer adverse effects on speaking, eating and social activities. CONCLUSIONS: For adolescents with skeletal class II malocclusion, CTB appliance was as effective as TB on improving dentoskeletal and soft tissue measurements, featuring more reliable teeth control and patient acceptance.

Molecular phylogeny and morphology of Sporodiniella sinensis sp. nov. (Syzygitaceae, Mucorales), an invertebrate-associated species from Yunnan, China.

During investigations of invertebrate-associated fungi in Yunnan Province of China, a new species, Sporodiniella sinensis sp. nov., was collected. Morphologically, S. sinensis is similar to Sporodiniella umbellata; however, it is distinguished from S. umbellata by its greater number of sporangiophore branches, longer sporangiophores, larger sporangiospores, and columellae. The novel species exhibits similarities of 91.62 % for internal transcribed spacer (ITS), 98.66-99.10 % for ribosomal small subunit (nrSSU), and 96.36-98.22 % for ribosomal large subunit (nrLSU) sequences, respectively, compared to S. umbellata. Furthermore, phylogenetic analyses based on combined sequences of ITS, nrLSU and nrSSU show that it forms a separate clade in Sporodiniella, and clusters closely with S. umbellata with high statistical support. The phylogenetic and morphological evidence support S. sinensis as a distinct species. Here, it is formally described and illustrated, and compared with other relatives.

Enhancing the Electrochemical Performances of Disordered Li1.23Ni0.3Nb0.3Fe0.16O0.85F0.15 Cathode Material for Lithium-Ion Batteries by LiNbOx Coating.

For the next generation of lithium-ion batteries (LIBs), it is primary to seek high capacity and long-lifetime electrode materials. Li-excess disordered rock-salt structure (DRS) cathodes have gained much attention due to their high specific capacity. However, Li-excess can lead to a decrease in the structural stability of an electrode material. A new Li-rich DRS oxyfluorides, Li1.23Ni0.3Nb0.3Fe0.16O0.85F0.15 (F0.15) with a series amounts of LiNbOx (LN) coating (0, 5, 10, and 15 wt % denoted as F0.15-LN0, F0.15-LN5, F0.15-LN10, and F0.15-LN15, respectively), are successfully synthesized and evaluated as cathode materials in LIBs. Among them, F0.15-LN10 exhibits the highest initial discharge specific capacity of 296.1 mAh g-1 (at a current density of 20 mA g-1) with the capacity retention rate of 14% higher than that of the uncoated F0.15 after 80 cycles. Even at 300 mA g-1, F0.15-LN10 still delivers the highest discharge specific capacity of 130 mAh g-1. After 20 cycles, the charge-transfer impedance of F0.15-LN10 remained the smallest. The characterizations indicate that LN coating reduces the surface polarization of the cathode materials, slows the interfacial side reactions between the electrolyte and the electrode, and speeds up the Li+ diffusion. These results demonstrate that LN coating is an effective strategy to improve the electrochemical performance.

Molecular phylogeny and morphology reveal two new entomopathogenic species of Ophiocordyceps (Ophiocordycipitaceae, Hypocreales) parasitic on termites from China.

Two new termite-pathogenic species, Ophiocordycepsglobiperitheciata and O.longistipes, are described from Yunnan Province, China. Six-locus (ITS, nrSSU, nrLSU, tef-1α, rpb1 and rpb2) phylogenetic analyses in combination with morphological observations were employed to characterize these two species. Phylogenetically, O.globiperitheciata is most closely related to Hirsutellacryptosclerotium and O.communis, whereas O.longistipes shares a sister relationship with O.fusiformis. However, O.globiperitheciata differs from H.cryptosclerotium by parasitizing Blattodea and producing clavate, unbifurcated stromata. Ophiocordycepsglobiperitheciata is distinguished from O.communis by multiple stromata, shorter asci and ascospores. Ophiocordycepslongistipes differs from O.fusiformis in producing larger stromata, perithecia, asci and ascospores, as well as smaller citriform or oval conidia. Morphological descriptions of the two new species and a dichotomous key to the 19 termite-pathogenic Ophiocordyceps species are presented.

Social Bonding, Risky Lifestyle, and Polyvictimization Among a Sample of Chinese Adolescents.

Polyvictimization has received substantial scholarly attention globally since it has been put forward two decades ago. However, the current lack of understanding of the causes of polyvictimization hinders the design of intervention programs. This study aims to integrate social bonding theory and lifestyle-routine activity theory to understand the etiology of polyvictimization in the Chinese context. Our results suggest that social bonding exerted not only a direct effect on polyvictimization (ß = -.030, p < .001) but also an indirect effect through delinquency and association with delinquent peers. Surprisingly, we found that the pathways linking social bonding and polyvictimization do not differ across genders. Implications for practice and theories are discussed.

Performance of metagenomic next-generation sequencing in cerebrospinal fluid for diagnosis of tuberculous meningitis.

Purpose. Metagenomic next-generation sequencing (mNGS) has been widely used in the diagnosis of infectious diseases, while its performance in diagnosis of tuberculous meningitis (TBM) is incompletely characterized. The aim of this study was to assess the performance of mNGS in the diagnosis of TBM, and illustrate the sensitivity and specificity of different methods.Methods. We retrospectively recruited TBM patients between January 2021 and March 2023 to evaluate the performance of mNGS on cerebrospinal fluid (CSF) samples, in comparison with conventional microbiological testing, including culturing of Mycobacterium tuberculosis (MTB), acid-fast bacillus (AFB) stain, reverse transcription PCR and Xpert MTB/RIF.Results. Of the 40 enrolled, 34 participants were diagnosed with TBM, including 15(44.12 %) definite and 19(55.88 %) clinical diagnosis based upon clinical manifestations, CSF parameters, brain imaging, pathogen evidence and treatment response. The mNGS method identified sequences of Mycobacterium tuberculosis complex (MTBC) in 11 CSF samples. In patients with definite TBM, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of mNGS were 78.57, 100, 100, 66.67 and 85 %, respectively. Compared to conventional diagnostic methods, the sensitivity of mNGS (78.57 %) was higher than AFB (0 %), culturing (0 %), RT-PCR (60 %) and Xpert MTB/RIF (14.29 %).Conclusions. Our study indicates that mNGS of CSF exhibited an overall improved sensitivity over conventional diagnostic methods for TBM and can be considered a front-line CSF test.

Spectral encoder to extract the efficient features of Raman spectra for reliable and precise quantitative analysis.

Raman spectroscopy has become a powerful analytical tool highly demanded in many applications such as microorganism sample analysis, food quality control, environmental science, and pharmaceutical analysis, owing to its non-invasiveness, simplicity, rapidity and ease of use. Among them, quantitative research using Raman spectroscopy is a crucial application field of spectral analysis. However, the entire process of quantitative modeling largely relies on the extraction of effective spectral features, particularly for measurements on complex samples or in environments with poor spectral signal quality. In this paper, we propose a method of utilizing a spectral encoder to extract effective spectral features, which can significantly enhance the reliability and precision of quantitative analysis. We built a latent encoded feature regression model; in the process of utilizing the autoencoder for reconstructing the spectrometer output, the latent feature obtained from the intermediate bottleneck layer is extracted. Then, these latent features are fed into a deep regression model for component concentration prediction. Through detailed ablation and comparative experiments, our proposed model demonstrates superior performance to common methods on single-component and multi-component mixture datasets, remarkably improving regression precision while without needing user-selected parameters and eliminating the interference of irrelevant and redundant information. Furthermore, in-depth analysis reveals that latent encoded feature possesses strong nonlinear feature representation capabilities, low computational costs, wide adaptability, and robustness against noise interference. This highlights its effectiveness in spectral regression tasks and indicates its potential in other application fields. Sufficient experimental results show that our proposed method provides a novel and effective feature extraction approach for spectral analysis, which is simple, suitable for various methods, and can meet the measurement needs of different real-world scenarios.

Modeling the precise interaction of glioblastoma with human brain region-specific organoids.

Glioblastoma is a highly aggressive malignant tumor of the central nervous system, but the interaction between glioblastoma and different types of neurons remains unclear. Here, we established a co-culture model in vitro using 3D printed molds with microchannels, in which glioblastoma organoids (GB), dorsal forebrain organoids (DO, mainly composed of excitatory neurons), and ventral forebrain organoids (VO, mainly composed of inhibitory neurons) were assembled. Our results indicate that DO has a greater impact on altered gene expression profiles of GB, resulting in increased invasive potential. GB cells preferentially invaded DO along axons, whereas this phenomenon was not observed in VO. Furthermore, GB cells selectively inhibited neurite outgrowth in DOs and reduced the expression of the vesicular GABA transporter (VGAT), leading to neuronal hyperexcitability. By revealing how glioblastoma interacts with brain cells, our study provides a more comprehensive understanding of this disease.

The power and the promise of synthetic lethality for clinical application in cancer treatment.

Synthetic lethality is a phenomenon wherein the simultaneous deficiency of two or more genes results in cell death, while the deficiency of any individual gene does not lead to cell death. In recent years, synthetic lethality has emerged as a significant topic in the field of targeted cancer therapy, with certain drugs based on this concept exhibiting promising outcomes in clinical trials. Nevertheless, the presence of tumor heterogeneity and the intricate DNA repair mechanisms pose challenges to the effective implementation of synthetic lethality. This review aims to explore the concepts, development, and ethical quandaries surrounding synthetic lethality. Additionally, it will provide an in-depth analysis of the clinical application and underlying mechanism of synthetic lethality.

Tetherless Optical Neuromodulation: Wavelength from Orange-red to Mid-infrared.

Optogenetics, a technique that employs light for neuromodulation, has revolutionized the study of neural mechanisms and the treatment of neurological disorders due to its high spatiotemporal resolution and cell-type specificity. However, visible light, particularly blue and green light, commonly used in conventional optogenetics, has limited penetration in biological tissue. This limitation necessitates the implantation of optical fibers for light delivery, especially in deep brain regions, leading to tissue damage and experimental constraints. To overcome these challenges, the use of orange-red and infrared light with greater tissue penetration has emerged as a promising approach for tetherless optical neuromodulation. In this review, we provide an overview of the development and applications of tetherless optical neuromodulation methods with long wavelengths. We first discuss the exploration of orange-red wavelength-responsive rhodopsins and their performance in tetherless optical neuromodulation. Then, we summarize two novel tetherless neuromodulation methods using near-infrared light: upconversion nanoparticle-mediated optogenetics and photothermal neuromodulation. In addition, we discuss recent advances in mid-infrared optical neuromodulation.

The Mitogenomic Characterization and Phylogenetic Analysis of the Plant Pathogen Phyllosticta yuccae.

Phyllosticta yuccae is an important plant pathogen causing leaf spot disease in Yucca gigantea Lem. It is imperative to note that the amount of information available about the mitogenome of this subject is severely limited. This must be addressed immediately, as it is crucial to our understanding and progress in this field. To better understand the mitogenomic characteristics of P. yuccae, we conducted its sequencing by MGISEQ. Afterwards, the mitogenome was assembled and annotated. The mitogenomic characteristics and phylogenetic placement of the P. yuccae strain KUMCC 6213 were analyzed. The study revealed that the mitogenome of P. yuccae is a circular DNA molecule, consisting of 178,540 base pairs. It contains a total of 64 genes, including 14 protein-coding genes (PCGs), 26 transfer RNA genes (tRNA), 2 ribosomal RNA genes (rRNA), and 22 open reading frame genes (ORF), accounting for 80.98% of the total size. Repetitive sequences accounted for 15.42% of the mitogenome. The analysis of codon usage indicated that the codon UUA was the most commonly utilized, whereas the amino acid Leu was the most frequently employed. A comparative analysis of mitogenomes between P. yuccae and Macrophomina phaseolina (Tassi) Goid. showed notable variations in the position and size of gene clusters, with cox1, nad4, and nad4L genes exhibiting relatively low conservation. Phylogenetic analysis based on the 14 PCGs revealed that P. yuccae has the closest genetic relationship with M. phaseolina (Botryosphaeriaceae, Botryosphaeriales). This study first reports the mitogenome of P. yuccae and validates its phylogenetic placement. The findings enhance the knowledge of mitogenomes in Botryosphaeriales, offering novel perspectives on the genetics and evolution of the plant pathogen P. yuccae. This is crucial for the accurate prevention and management of leaf spot disease in Y. gigantea.

An individualized stemness-related signature to predict prognosis and immunotherapy responses for gastric cancer using single-cell and bulk tissue transcriptomes.

BACKGROUND: Currently, many stemness-related signatures have been developed for gastric cancer (GC) to predict prognosis and immunotherapy outcomes. However, due to batch effects, these signatures cannot accurately analyze patients one by one, rendering them impractical in real clinical scenarios. Therefore, we aimed to develop an individualized and clinically applicable signature based on GC stemness. METHODS: Malignant epithelial cells from single-cell RNA-Seq data of GC were used to identify stemness-related signature genes based on the CytoTRACE score. Using two bulk tissue datasets as training data, the enrichment scores of the signature genes were applied to classify samples into two subtypes. Then, using the identified subtypes as criteria, we developed an individualized stemness-related signature based on the within-sample relative expression orderings of genes. RESULTS: We identified 175 stemness-related signature genes, which exhibited significantly higher AUCell scores in poorly differentiated GCs compared to differentiated GCs. In training datasets, GC samples were classified into two subtypes with significantly different survival times and genomic characteristics. Utilizing the two subtypes, an individualized signature was constructed containing 47 gene pairs. In four independent testing datasets, GC samples classified as high risk exhibited significantly shorter survival times, higher infiltration of M2 macrophages, and lower immune responses compared to low-risk samples. Moreover, the potential therapeutic targets and corresponding drugs were identified for the high-risk group, such as CD248 targeted by ontuxizumab. CONCLUSIONS: We developed an individualized stemness-related signature, which can accurately predict the prognosis and efficacy of immunotherapy for each GC sample.

Systemic and cerebrospinal fluid biomarkers for tuberculous meningitis identification and treatment monitoring.

IMPORTANCE: Tuberculous meningitis is a life-threatening infection with high mortality and disability rates. Current diagnostic methods using cerebrospinal fluid (CSF) samples have limited sensitivity and lack predictive biomarkers for evaluating prognosis. This study's findings reveal excessive activation of the immune response during tuberculous meningitis (TBM) infection. Notably, a strong negative correlation was observed between CSF levels of monokine induced by interferon-γ (MIG) and the CSF/blood glucose ratio in TBM patients. MIG also exhibited the highest area under the curve with high sensitivity and specificity. This study suggests that MIG may serve as a novel biomarker for differentiating TBM infection in CSF or serum, potentially leading to improved diagnostic accuracy and better patient outcomes.

Intercalation of Metal into Transition Metal Dichalcogenides in Molten Salts.

Van der Waals (vdW)-layered materials have drawn tremendous interests due to their unique properties. Atom intercalation in the vdW gap of layered materials can tune their electronic structure and generate unexpected properties. Here a chemical-scissor-mediated method that enables metal intercalation into transition metal dichalcogenides (TMDCs) in molten salts is reported. By using this approach, various guest metal atoms (Mn, Fe, Co, Ni, Cu, and Ag) are intercalated into various TMDC hosts (such as TiS2 , NbS2 , TaS2 , TiSe2 , NbSe2 , TaSe2 , and Ti0.5 V0.5 S2 ). The structure of the intercalated compound and intercalation mechanism are investigated. The results indicate that the vdW gap and valence state of TMDCs can be modified through metal intercalation, and the intercalation behavior is dictated by the electron work function. The adjustable charge transfer and intercalation endow a channel for rapid mass transfer to enhance the electrochemical performances. Such a chemical-scissor-mediated intercalation provides an approach to tune the physical and chemical properties of TMDCs, which may open an avenue in functional application ranging from energy conversion to electronics.

Radical-Dearomative Generation of Cyclohexadienyl Pd(II) toward the 3D Transformation of Nonactivated Phenyl Rings.

Traditional palladium-catalyzed dearomatization of (hetero)arenes takes place via an ionic pathway and usually requires elevated temperatures to overcome the energy barrier of the dearomative insertion step. Herein, a combination of the radical and two-electron pathways is disclosed, which enables room temperature dearomative 3D transformations of nonactivated phenyl rings with Pd(0) as the catalyst. Experimental results together with density functional theory (DFT) calculations indicate a versatile π-allyl Pd(II) species, cyclohexadienyl Pd(II), possibly is involved in the dearomatization. This species is generated by combining the cyclohexadienyl radical and Pd(I). The cyclohexadienyl Pd(II) provides chemoselective (carboamination and trieneylation), regioselective (1,2-carboamination), and diastereoselective (carbonyl-group directed face selectivity) conversions.

Interleukin-33/serum stimulation-2 pathway: Regulatory mechanisms and emerging implications in immune and inflammatory diseases.

Interleukin (IL)- 33, a nuclear factor and pleiotropic cytokine of the IL-1 family, is gaining attention owing to its important role in chronic inflammatory and autoimmune diseases. This review extends our knowledge of the effects exerted by IL-33 on target cells by binding to its specific receptor serum stimulation-2 (ST2). Depending on the tissue context, IL-33 performs multiple functions encompassing host defence, immune response, initiation and amplification of inflammation, tissue repair, and homeostasis. The levels and activity of IL-33 in the body are controlled by complex IL-33-targeting regulatory pathways. The unique temporal and spatial expression patterns of IL-33 are associated with host homeostasis and the development of immune and inflammatory disorders. Therefore, understanding the origin, function, and processes of IL-33 under various conditions is crucial. This review summarises the regulatory mechanisms underlying the IL-33/ST2 signalling axis and its potential role and clinical significance in immune and inflammatory diseases, and discusses the current complex and conflicting findings related to IL-33 in host responses.

Case report: Transcatheter edge-to-edge repair with MitraClip for acute mitral regurgitation after myocardial infarction.

INTRODUCTION: Acute mitral regurgitation (MR) due to papillary muscle rupture (PMR) is a rare but lethal mechanical complication of acute myocardial infarction (MI). The treatment of patients with post-MI PMR, especially those with cardiogenic shock, presents great challenges due to the high surgical risk. PATIENT CONCERNS: We report an 80-year-old woman with a history of hypertension and diabetes mellitus, presented with chest pain. Despite an early percutaneous coronary intervention and transfer to the intensive care unit, her general condition and hemodynamic parameters continued to deteriorate rapidly. DIAGNOSIS: Evidenced by electrocardiogram, echocardiogram and coronary angiography, the patient was diagnosed with acute lateral and posterior ST-segment elevation MI, cardiogenic shock, PMR, severe MR, and pulmonary edema. INTERVENTIONS: The patient received percutaneous mitral valve repair with MitraClip (Abbott Vascular, Santa Clara, CA, USA) supported by extracorporeal membranous oxygenation and intra-aortic balloon pump. OUTCOMES: The patient was discharged with relief of heart failure symptoms, reduced MR, and recovery of cardiac function, remaining in a stable condition in New York Heart Association class I after 15-month outpatient follow up. CONCLUSION: Transcatheter edge-to-edge repair with MitraClip can serve as a viable alternative to surgery in reducing MR in post-MI PMR patients at high surgical risk.

The effect of health literacy on early postoperative recovery of patients undergoing outpatient surgery.

BACKGROUND: The measurement of the health literacy level of patients undergoing outpatient surgery has become a major challenge in perioperative nursing of outpatient surgery. OBJECTIVE: To analyze the effect of health literacy on early postoperative recovery of patients undergoing outpatient surgery by developing a health literacy assessment tool for this population. METHODS: A scale for the assessment of health literacy was established based on Nutbeam's health literacy model. From April to September 2021, 264 patients were selected in the daytime operating rooms of six Class A tertiary hospitals in Kunming, Yunnan Province to investigate health literacy and early postoperative rehabilitation quality, and the influencing factors of the two variables were analyzed. RESULTS: An assessment scale of health literacy of patients undergoing outpatient surgery was developed, including 3 dimensions and 24 items. The Cronbach's α coefficient of the total scale was 0.944, the split-half reliability was 0.902, and the content validity was 0.920. Exploratory factor analysis showed that the cumulative variance contribution rate was 66.37%, and the scale had good structural validity. Multiple linear regression analysis showed that age, functional health literacy, interactive health literacy, and critical health literacy could explain 60.4% of the variation (adjusted R2= 0.583) of postoperative recovery quality of patients undergoing outpatient surgery. CONCLUSION: Health literacy of patients undergoing outpatient surgery is an important factor that affects the quality of early postoperative recovery. The health literacy assessment scale can assist medical staff in implementing personalized perioperative nursing and health education.

Machine learning analysis with the comprehensive index of corneal tomographic and biomechanical parameters in detecting pediatric subclinical keratoconus.

Background: Keratoconus (KC) occurs at puberty but diagnosis is focused on adults. The early diagnosis of pediatric KC can prevent its progression and improve the quality of life of patients. This study aimed to evaluate the ability of corneal tomographic and biomechanical variables through machine learning analysis to detect subclinical keratoconus (SKC) in a pediatric population. Methods: Fifty-two KC, 52 SKC, and 52 control pediatric eyes matched by age and gender were recruited in a case-control study. The corneal tomographic and biomechanical parameters were measured by professionals. A linear mixed-effects test was used to compare the differences among the three groups and a least significant difference analysis was used to conduct pairwise comparisons. The receiver operating characteristic (ROC) curve and the Delong test were used to evaluate diagnostic ability. Variables were used in a multivariate logistic regression in the machine learning analysis, using a stepwise variable selection to decrease overfitting, and comprehensive indices for detecting pediatric SKC eyes were produced in each step. Results: PE, BAD-D, and TBI had the highest area under the curve (AUC) values in identifying pediatric KC eyes, and the corresponding cutoff values were 12 µm, 2.48, and 0.6, respectively. For discriminating SKC eyes, the highest AUC (95% CI) was found in SP A1 with a value of 0.84 (0.765, 0.915), and BAD-D was the best parameter among the corneal tomographic parameters with an AUC (95% CI) value of 0.817 (0.729, 0.886). Three models were generated in the machine learning analysis, and Model 3 (y = 0.400*PE + 1.982* DA ratio max [2 mm]-0.072 * SP A1-3.245) had the highest AUC (95% CI) value, with 90.4% sensitivity and 76.9% specificity, and the cutoff value providing the best Youden index was 0.19. Conclusion: The criteria of parameters for diagnosing pediatric KC and SKC eyes were inconsistent with the adult population. Combined corneal tomographic and biomechanical parameters could enhance the early diagnosis of young patients and improve the inadequate representation of pediatric KC research.