A Randomized Comparison Between Anterior Talofibular Ligament Repair Using Broström Operation with and without an Internal Brace.

The aim of the study was to compare the intermediate-term (>24 months) clinical outcomes between anterior talofibular ligament repair using Broström operation with and without an internal brace. Nineteen patients underwent surgery using an arthroscopic traditional Broström repair with an internal brace technique (IB) and Eighteen patients underwent surgery using an arthroscopic traditional Broström repair without an internal brace technique (TB) . All patients were evaluated clinically using the Foot and Ankle Outcome Score (FAOS) and Foot and Ankle Ability Measure (FAAM). According to FAAM, sports activity scores of TB and IB groups were 83.33 ± 5.66 and 90.63 ± 6.21 at the final follow-up (p = .02). There were no significant differences in preoperative and postoperative stress radiographs between the two groups. Total medical expense was more in the IB group (p < .001). It also has a significant superiority in the terms of FAAM scores at sports activity. However, there was no difference during daily life.

Enhanced control of periodontitis by an artificial intelligence-enabled multimodal-sensing toothbrush and targeted mHealth micromessages: A randomized trial.

AIM: Treatment of periodontitis, a chronic inflammatory disease driven by biofilm dysbiosis, remains challenging due to patients' poor performance and adherence to the necessary oral hygiene procedures. Novel, artificial intelligence-enabled multimodal-sensing toothbrushes (AI-MST) can guide patients' oral hygiene practices in real-time and transmit valuable data to clinicians, thus enabling effective remote monitoring and guidance. The aim of this trial was to assess the effect of such a system as an adjunct to clinical practice guideline-conform treatment. MATERIALS AND METHODS: This was a single-centre, double-blind, standard-of-care controlled, randomized, parallel-group, superiority trial. Male and female adults with generalized Stage II/III periodontitis were recruited at the Shanghai Ninth People's Hospital, China. Subjects received a standard-of-care oral hygiene regimen or a technology-enabled, theory-based digital intervention consisting of an AI-MST and targeted doctor's guidance by remote micromessaging. Additionally, both groups received guideline-conform periodontal treatment. The primary outcome was the resolution of inflamed periodontal pockets (≥4 mm with bleeding on probing) at 6 months. The intention-to-treat (ITT) analysis included all subjects who received the allocated treatment and at least one follow-up. RESULTS: One hundred patients were randomized and treated (50 tests/controls) between 1 February and 30 November 2022. Forty-eight tests (19 females) and 47 controls (16 females) were analysed in the ITT population. At 6 months, the proportion of inflamed periodontal pockets decreased from 80.7% (95% confidence interval [CI] 76.5-84.8) to 52.3% (47.7-57.0) in the control group, and from 81.4% (77.1-85.6) to 44.4% (39.9-48.9) in the test group. The inter-group difference was 7.9% (1.6-14.6, p < .05). Test subjects achieved better levels of oral hygiene (p < .001). No significant adverse events were observed. CONCLUSIONS: The tested digital health intervention significantly improved the outcome of periodontal therapy by enhancing the adherence and performance of self-performed oral hygiene. The model breaks the traditional model of oral health care and has the potential to improve efficiency and reduce costs (NCT05137392).

GDF-15 Suppresses Puromycin Aminonucleoside-Induced Podocyte Injury by Reducing Endoplasmic Reticulum Stress and Glomerular Inflammation.

GDF15, also known as MIC1, is a member of the TGF-beta superfamily. Previous studies reported elevated serum levels of GDF15 in patients with kidney disorder, and its association with kidney disease progression, while other studies identified GDF15 to have protective effects. To investigate the potential protective role of GDF15 on podocytes, we first performed in vitro studies using a Gdf15-deficient podocyte cell line. The lack of GDF15 intensified puromycin aminonucleoside (PAN)-triggered endoplasmic reticulum stress and induced cell death in cultivated podocytes. This was evidenced by elevated expressions of Xbp1 and ER-associated chaperones, alongside AnnexinV/PI staining and LDH release. Additionally, we subjected mice to nephrotoxic PAN treatment. Our observations revealed a noteworthy increase in both GDF15 expression and secretion subsequent to PAN administration. Gdf15 knockout mice displayed a moderate loss of WT1+ cells (podocytes) in the glomeruli compared to wild-type controls. However, this finding could not be substantiated through digital evaluation. The parameters of kidney function, including serum BUN, creatinine, and albumin-creatinine ratio (ACR), were increased in Gdf15 knockout mice as compared to wild-type mice upon PAN treatment. This was associated with an increase in the number of glomerular macrophages, neutrophils, inflammatory cytokines, and chemokines in Gdf15-deficient mice. In summary, our findings unveil a novel renoprotective effect of GDF15 during kidney injury and inflammation by promoting podocyte survival and regulating endoplasmic reticulum stress in podocytes, and, subsequently, the infiltration of inflammatory cells via paracrine effects on surrounding glomerular cells.

Unveiling unique microbial nitrogen cycling and nitrification driver in coastal Antarctica.

Largely removed from anthropogenic delivery of nitrogen (N), Antarctica has notably low levels of nitrogen. Though our understanding of biological sources of ammonia have been elucidated, the microbial drivers of nitrate (NO3-) cycling in coastal Antarctica remains poorly understood. Here, we explore microbial N cycling in coastal Antarctica, unraveling the biological origin of NO3- via oxygen isotopes in soil and lake sediment, and through the reconstruction of 1968 metagenome-assembled genomes from 29 microbial phyla. Our analysis reveals the metabolic potential for microbial N2 fixation, nitrification, and denitrification, but not for anaerobic ammonium oxidation, signifying a unique microbial N-cycling dynamic. We identify the predominance of complete ammonia oxidizing (comammox) Nitrospira, capable of performing the entire nitrification process. Their adaptive strategies to the Antarctic environment likely include synthesis of trehalose for cold stress, high substrate affinity for resource utilization, and alternate metabolic pathways for nutrient-scarce conditions. We confirm the significant role of comammox Nitrospira in the autotrophic, nitrification process via 13C-DNA-based stable isotope probing. This research highlights the crucial contribution of nitrification to the N budget in coastal Antarctica, identifying comammox Nitrospira clade B as a nitrification driver.

Design and demonstration of high efficiency perfectly vertical grating couplers with a random structure.

Utilizing an automated optimization method, we propose a perfectly vertical grating coupler (PVGC) characterized by random structure, superior performance, simplified fabrication process, and increased minimum feature size (MFS). Within the range of MFS from 60 to 180 nm, the optimized PVGC exhibited a simulated coupling efficiency of approximately -2.0 dB at 1550 nm with a 34 nm 1-dB bandwidth. Experimental results for the PVGCs fabricated by electron beam lithography (EBL) demonstrated coupling efficiencies ranging from -2.5 to -2.8 dB with a 32 nm 1-dB bandwidth while maintaining high manufacturing tolerances. This represents the most outstanding experimental outcome to date regarding the coupling performance of a PVGC fabricated on a 220 nm silicon on insulator (SOI), without requiring any complex processes as reported in the existing literature.

Cyclodextrin-conjugated low-molecular-weight polyethyleneimine as a macromolecular contrast agent for tumor-targeted magnetic resonance imaging.

Macromolecular contrast agents (CAs) usually possess excellent contrast ability and tumor-targeting ability in comparison with small-molecule CAs, especially for early tumor detection. Herein, cyclodextrin-conjugated low-molecular-weight polyethyleneimine was synthesized as a macromolecular backbone. Afterward, a linear polymer with adamantane terminal and Gd chelates was synthesized, followed by conjugating with the backbone via host-guest interaction. Finally, folic acid was conjugated onto the as-prepared CAs through bioorthogonal chemistry, which endowed the CAs with the capability to accumulate into the tumor region. Compared to Magnevist (r1 = 4.25 mM-1 s-1) used in clinic, the PC/Ad-PEG2000-PLL(DTPA-Gd)-FA exhibited higher longitudinal relaxivity (r1 = 11.62 mM-1 s-1) with excellent biocompatibility. Furthermore, in vivo experiments demonstrated that PC/Ad-PEG2000-PLL(DTPA-Gd)-FA could effectively accumulate in the tumor region and produce a brighter image than that of Magnevist. The H&E staining and metabolic data further illustrated that this CA possessed excellent biocompatibility in vivo. Finally, these results above suggest that this macromolecular CA could be a potential candidate as a MRI CA for tumor-targeted diagnosis.

Influence of motor capacity of the lower extremity and mobility performance on foot plantar pressures in community-dwelling older women.

Objectives: To investigate the associations of motor capacity of the lower extremity and mobility performance in daily physical activities with peak foot plantar pressures during walking among older women. Methods: Using the data collected among 58 community-dwelling older women (68.66 ± 3.85 years), Pearson correlation and multiple linear regression analyses were performed to analyze the associations of motor capacity of the lower extremity (the 30-s chair stand test, the timed one-leg stance with eyes closed, and the Fugl-Meyer assessment of lower extremity), mobility performance in daily physical activities (the average minutes of moderate to vigorous physical activity every day and the metabolic equivalents), and foot plantar pressures (peak force and peak pressure) with the age and body fat percentage as covariates. Results: (1) The motor capacity of the lower extremity has higher explanatory power for peak foot plantar pressures compared with the mobility performance in daily physical activities. (2) Higher body fat percentage was positively associated with peak force and pressure, while a lower score on the Fugl-Meyer assessment of lower extremity was negatively associated with both of them. (3) The metabolic equivalents were positively associated with the peak force, while the 30-s chair stand test was negatively associated with it. Conclusions: Mobility performance in daily physical activities can be significant predictors for peak foot plantar pressures among older women. The significant predictor variables include the Fugl-Meyer assessment of lower extremity, the 30-s chair stand test, and metabolic equivalents.

Design, synthesis, and evaluation of a carboxylesterase detection probe with therapeutic effects.

In this study, a lysosomal targeting fluorescent probe recognition on CEs was designed and synthesized. The obtained probe BF2-cur-Mor demonstrated excellent selectivity, sensitivity, pH-independence, and enzyme affinity towards CEs within 5 min. BF2-cur-Mor could enable recognition of intracellular CEs and elucidate that the CEs content of different cancer cells follows the rule of HepG2 > HCT-116 > A549 > HeLa, and the CEs expression level of hepatoma cancer cells far exceeds that of normal hepatic cells, being in good agreement with the previous reports. The ability of BF2-cur-Mor to monitor CEs in vivo was confirmed by zebrafish experiment. BF2-cur-Mor exhibits some pharmacological activity in that it can induce apoptosis in hepatocellular carcinoma cells but is weaker in normal hepatocyte cells, being expected to be a potential "diagnostic and therapeutic integration" tool for the clinical diagnosis of CEs-related diseases.

Theoretical investigation on action mechanism and mollifying efficacy of propellant stabilizers.

CONTEXT: This project performed quantum chemical computation, through kinetic and thermodynamic analyses to compare relative reactivity, reaction rate, and equilibrium composition from the possible pathways in connection with stabilizer-nitrodioxide reactions to determine the stability of the materials for practical application. Corresponding achievements have promoted the use of N-methyl-p-nitroaniline (MNA) and dinitrophenyl malonamide series (M3, M4, and M5) stabilizers as high priorities for selection. METHODS: The Gaussian 09 program (G09) (Frisch et al 2009) and density functional theory (DFT) calculations with the B3LYP/6-31G(d,p) function were performed to obtain related geometric and thermodynamic energy data for the molecular systems in this study. The synchronous transit-guided quasi-Newton method (STQN) (Peng and Schlegel Isr J Chem 33:49, 1993) was applied through the QST3 procedure to identify single imaginary frequency-valued transition-state species. The related reaction rate constant (k) and pre-exponential factor (A) were obtained, based on transition state theory (Su 2008), using Eqs. 11 and 12.

Wickerhamomyces corioli f.a., sp. nov., a novel yeast species discovered in two mushroom species.

Two yeast strains, designated as 19-39-3 and 19-40-2, obtained from the fruiting bodies of Trametes versicolor and Marasmius siccus collected in Yunwu Mountain Forest Park, PR China, have been identified as representing a novel asexual ascomycetous yeast species. From the results of phylogenetic analyses of the sequences of the D1/D2 domains of the large subunit (LSU) rRNA, small subunit (SSU) rRNA and translation elongation factor 1-α (TEF1) genes, it was determined that these strains represent a member of the genus Wickerhamomyces, with Wickerhamomyces alni and Candida ulmi as the closest relatives. The novel species exhibited 6.6 and 6.7% differences in the D1/D2 domains compared with W. alni and C. ulmi, respectively. Additionally, distinct biochemical and physiological differences were observed between the novel species and its related counterparts. No sexual reproduction was observed in these strains, leading to the proposal of the name Wickerhamomyces corioli f.a., sp. nov. for this newly discovered species.

Safflower polysaccharide ameliorates acute ulcerative colitis by regulating STAT3/NF-κB signaling pathways and repairing intestinal barrier function.

This study is to investigate the effect of SPS on the UC model. An animal model of UC induced by DSS was developed using C57BL/6 mice. The body weight was recorded every day, and the symptoms related to UC were detected. H&E staining, AB-PAS staining and PSR staining were used to evaluate the histopathological changes of the colon. Inflammation and mucosal barrier indicators were detected by qRT-PCR, and the 16 S rRNA sequence was used to detect the intestinal flora. SPS can significantly prevent and treat DSS-induced ulcerative colitis in animals. SPS significantly improved clinical symptoms, alleviated pathological damage, inhibited the infiltration of intestinal inflammatory cells. SPS treatment can protect goblet cells, enhance the expression of tight junction proteins and mucins, inhibit the expression of antimicrobial peptides, thereby improving intestinal barrier integrity. The prevention and treatment mechanism of SPS may be related to the inhibition of STAT3/NF-κB signaling pathway to regulate intestinal barrier function. In particular, SPS also significantly adjusted the structure of intestinal flora, significantly increasing the abundance of Akkermansia and Limosilactobacillus and inhibiting the abundance of Bacteroides. Overall, SPS has a significant therapeutic effect on ulcerative colitis mice, and is expected to play its value effectively in clinical treatment.

Characteristics of the complete mitochondrial genome of Gerres limbatus (Cuvier, 1830) (Perciformes: Gerreidae).

The saddleback silver-biddy Gerres limbatus (Cuvier 1830) is distributed in Indo-West Pacific Oceans and associated with shallow coastal marine waters and estuaries. In this study, the complete mitochondrial genome of G. limbatus was firstly documented, which is 16,730 bp in length, including 13 protein-coding genes, 22 transfer RNA genes and 2 ribosomal RNA genes. The overall base composition of the mitochondrial genome is 26.42% A, 28.68% C, 27.32% T, and 17.58% G. The Maximum Likelihood phylogenetic tree was constructed based on COI gene of the 31 species from the family Gerreidae, with Heteroclinus puellarum and Hypopterus macropterus as outgroups. It revealed that G. erythrourus was placed as the sister group to G. limbatus.

Landslide hazard cascades can trigger earthquakes.

While earthquakes are well-known to trigger surface hazards and initiate hazard cascades, whether surface hazards can instead trigger earthquakes remains underexplored. In 2018, two landslides on the Tibetan plateau created landslide-dammed lakes which subsequently breached and caused catastrophic outburst floods. Here we build an earthquake catalog using machine-learning and cross-correlation-based methods which shows there was a statistically significant increase in earthquake activity (local magnitude ≤ 2.6) as the landslide-dammed lake approached peak water level which returned to the background level after dam breach. We further find that ~90% of the seismicity occurred where Coulomb stress increased due to the combined effect of direct loading and pore pressure diffusion. The close spatial and temporal correlation between the calculated Coulomb stress increase and earthquake activity suggests that the earthquakes were triggered by these landslide hazard cascades. Finally, our Coulomb stress modeling considering the properties of landslide-dammed lakes and reservoir-induced earthquakes globally suggests that earthquake triggering by landslide-dammed lakes and similar structures may be a ubiquitous phenomenon. Therefore, we propose that earthquake-surface hazard interaction can include bidirectional triggering which should be properly accounted for during geological hazard assessment and management in mountainous regions.

Soft interface confined DNA walker for sensitive and specific detection of SARS-CoV-2 variants.

Nucleic acid detection is conducive to preventing the spread of COVID-19 pandemic. In this work, we successfully designed a soft interface confined DNA walker by anchoring hairpin reporter probes on cell membranes for the detection of SARS-CoV-2 variants. In the presence of target RNA, the cyclic self-assembly reaction occurred between hairpin probes H1 and H2, and the continuous walking of target RNA on cell membranes led to the gradual amplification of fluorescence signal. The enrichment of H1 on membranes and the unique fluidity of membranes promoted the collision efficiency between DNA strands in the reaction process, endowing this method with high sensitivity. In addition, the double-blind test of synthetic RNA in 5% normal human serum demonstrated the good stability and anti-interference in complex environment of this method, which exhibited great potential in clinical diagnostics.

A novel framework for high resolution air quality index prediction with interpretable artificial intelligence and uncertainties estimation.

Accurate air quality index (AQI) prediction is essential in environmental monitoring and management. Given that previous studies neglect the importance of uncertainty estimation and the necessity of constraining the output during prediction, we proposed a new hybrid model, namely TMSSICX, to forecast the AQI of multiple cities. Firstly, time-varying filtered based empirical mode decomposition (TVFEMD) was adopted to decompose the AQI sequence into multiple internal mode functions (IMF) components. Secondly, multi-scale fuzzy entropy (MFE) was applied to evaluate the complexity of each IMF component and clustered them into high and low-frequency portions. In addition, the high-frequency portion was secondarily decomposed by successive variational mode decomposition (SVMD) to reduce volatility. Then, six air pollutant concentrations, namely CO, SO2, PM2.5, PM10, O3, and NO2, were used as inputs. The secondary decomposition and preliminary portion were employed as the outputs for the bidirectional long short-term memory network optimized by the snake optimization algorithm (SOABiLSTM) and improved Catboost (ICatboost), respectively. Furthermore, extreme gradient boosting (XGBoost) was applied to ensemble each predicted sub-model to acquire the consequence. Ultimately, we introduced adaptive kernel density estimation (AKDE) for interval estimation. The empirical outcome indicated the TMSSICX model achieved the best performance among the other 23 models across all datasets. Moreover, implementing the XGBoost to ensemble each predicted sub-model led to an 8.73%, 8.94%, and 0.19% reduction in RMSE, compared to SVM. Additionally, by utilizing SHapley Additive exPlanations (SHAP) to assess the impact of the six pollutant concentrations on AQI, the results reveal that PM2.5 and PM10 had the most notable positive effects on the long-term trend of AQI. We hope this model can provide guidance for air quality management.

Sex- and Age-Specific Prevalence of Osteopenia and Osteoporosis: Sampling Survey.

BACKGROUND: Osteopenia and osteoporosis are posing a long-term influence on the aging population's health contributing to a higher risk of mortality, loss of autonomy, hospitalization, and huge health system costs and social burden. Therefore, more pertinent data are needed to demonstrate the current state of osteoporosis. OBJECTIVE: This sampling survey seeks to assess the trends in the prevalence of osteopenia and osteoporosis in a Chinese Han population. METHODS: A community-based cross-sectional study involving 16,377 participants used a multistage sampling method. Bone mineral density was measured using the quantitative ultrasonic densitometry. Student t test and Mann-Whitney U test were used to test the difference between normally and nonnormally distributed quantitative variables between male and female participants. A chi-square (χ2) test was used to compare categorized variables. Stratified analysis was conducted to describe the prevalence rates of osteoporosis (T score ≤-2.5) and osteopenia (T score -2.5 to -1.0) across age, sex, calcium intake, and menopause. A direct standardization method was used to calculate the age-standardized prevalence rates of osteoporosis and osteopenia. T-score was further categorized into quartiles (T1-T4) by age- and sex-specified groups. RESULTS: The prevalence rates of osteopenia and osteoporosis were 40.5% (6633/16,377) and 7.93% (1299/16,377), respectively, and the age-standardized prevalence rates were 27.32% (287,877,129.4/1,053,861,940) and 3.51% (36,974,582.3/1,053,861,940), respectively. There was an increase in osteopenia and osteoporosis prevalence from 21.47% (120/559) to 56.23% (754/1341) and 0.89% (5/559) to 17.23% (231/1341), respectively, as age increased from 18 years to 75 years old. The prevalence rates of osteopenia and osteoporosis were significantly higher in female participants (4238/9645, 43.94% and 1130/9645, 11.72%) than in male participants (2395/6732, 35.58% and 169/6732, 2.51%; P<.001), and in postmenopausal female participants (3638/7493, 48.55% and 1053/7493, 14.05%) than in premenopausal female participants (538/2026, 26.55% and 53/2026, 2.62%; P<.001). In addition, female participants with a history of calcium intake had a lower osteoporosis prevalence rate than female participants without any history of calcium intake in all age groups (P=.004). From low quartile to high quartile of T-score, the prevalence of diabetes mellitus (752/4037, 18.63%; 779/4029, 19.33%; 769/3894, 19.75%; and 869/3879, 22.4%) and dyslipidemia (2228/4036, 55.2%; 2304/4027, 57.21%; 2306/3891, 59.26%; and 2379/3878, 61.35%) were linearly increased (P<.001), while the prevalence of cancer (112/4037, 2.77%; 110/4029, 2.73%; 103/3894, 2.65%; and 77/3879, 1.99%) was decreased (P=.03). CONCLUSIONS: Our data imply that as people age, osteopenia and osteoporosis are more common in females than in males, particularly in postmenopausal females than in premenopausal females, and bone mineral density significantly affects the prevalence of chronic diseases. These findings offer information that can be applied to intervention programs meant to prevent or lessen the burden of osteoporosis in China.

N6-methyladenosine-dependent signaling in colorectal cancer: Functions and clinical potential.

Colorectal cancer (CRC) ranks as the third most prevalent malignancy worldwide. Despite the gradual expansion of therapeutic options for CRC, its clinical management remains a formidable challenge. And, because of the current dearth of technical means for early CRC screening, most patients are diagnosed at an advanced stage. Therefore, it is imperative to develop novel diagnostic and therapeutic tools for this disease. N6-methyladenosine (m6A), the predominant RNA modification in eukaryotes, can be recognized by m6A-specific methylated reading proteins to modulate gene expression. Studies have revealed that CRC disrupts m6A homeostasis through various mechanisms, thereby sustaining aberrant signal transduction and promoting its own progression. Consequently, m6A-based diagnostic and therapeutic strategies have garnered widespread attention. Although utilizing m6A as a biomarker and drug target has demonstrated promising feasibility, existing observations primarily stem from preclinical models; henceforth necessitating further investigation and resolution of numerous outstanding issues.

Systemic investigation of di-isobutyl phthalate (DIBP) exposure in the risk of cardiovascular via influencing the gut microbiota arachidonic acid metabolism in obese mice model.

Phthalate esters (PE), a significant class of organic compounds used in industry, can contaminate humans and animals by entering water and food chains. Recent studies demonstrate the influence of PE on the development and progression of heart diseases, particularly in obese people. Di-isobutyl phthalate (DIBP) was administered orally to normal and diet-induced obese mice in this research to assess cardiovascular risk. The modifications in the microbial composition and metabolites were examined using RNA sequencing and mass spectrometry analysis. Based on the findings, lean group rodents were less susceptible to DIBP exposure than fat mice because of their cardiovascular systems. Histopathology examinations of mice fed a high-fat diet revealed lesions and plagues that suggested a cardiovascular risk. In the chronic DIBP microbial remodeling metagenomics Faecalibaculum rodentium was the predominant genera in obese mice. According to metabolomics data, arachidonic acid (AA) metabolism changes caused by DIBP were linked to unfavorable cardiovascular events. Our research offers new understandings of the cardiovascular damage caused by DIBP exposure in obese people and raises the possibility that arachidonic acid metabolism could be used as a regulator of the gut microbiota to avert related diseases.

Epidemiological study of pediatric nutritional deficiencies: an analysis from the global burden of disease study 2019.

BACKGROUND: Nutritional deficiencies (ND) continue to threaten the lives of millions of people around the world, with children being the worst hit. Nevertheless, no systematic study of the epidemiological features of child ND has been conducted so far. Therefore, we aimed to comprehensively assess the burden of pediatric ND. METHODS: We analyzed data on pediatric ND between 1990 and 2019 from the Global Burden of Disease study (GBD) 2019 at the global, regional, and national levels. In addition, joinpoint regression models were used to assess temporal trends. RESULTS: In 2019, the number of prevalent cases of childhood malnutrition increased to 435,071,628 globally. The global age-standardized incidence, prevalence, and DALY rates showed an increasing trend between 1990 and 2019. Meanwhile, the burden of child malnutrition was negatively correlated with sociodemographic index (SDI). Asia and Africa still carried the heaviest burden. The burden and trends of child malnutrition varied considerably across countries and regions. At the age level, we found that malnutrition was significantly more prevalent among children < 5 years of age. CONCLUSION: Pediatric ND remains a major public health challenge, especially in areas with low SDI. Therefore, primary healthcare services in developing countries should be improved, and effective measures, such as enhanced pre-school education, strengthened nutritional support, and early and aggressive treatment, need to be developed.